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PMID:22535
|
gltB gene and regulation of nitrogen metabolism by glutamine synthetase in Escherichia coli.
|
A mutant (gltB) of Escherichia coli lacking glutamate synthase (GOGAT) was unable to utilize a wide variety of compounds as sole nitrogen source (e.g., arginine, proline, gamma-aminobutyrate, and glycine). Among revertants of these Asm- strains selected on one of these compounds (e.g., arginine, proline, or gamma-aminobutyrate) were those that produce glutamine synthetase (GS) constitutively (GlnC phenotype). These revertants had a pleiotropically restored ability to grow on compounds that are metabolized to glutamate. This suggested that the expression of the genes responsible for the metabolism of these nitrogen sources was regulated by GS. An examination of the regulation of proline oxidase confirmed this hypothesis. The differential sensitivities of GlnC and wild-type strains to low concentrations (0.1 mM) of the glutamine analog L-methionine-DL-sulfoximine supported the conclusion that the synthesis of a glutamine permease was also positively controlled by GS. During the course of this study we found that the reported position of the locus (gltB) for glutamate synthase is incorrect. We have relocated this gene to be 44% linked to the argG locus by P1 transduction. Further mapping has shown that the locus previously called aspB is in reality the gltB locus and that the "suppressor" of the aspB mutation (A. M. Reiner, J. Bacteriol. 97:1431-1436, 1969) is the locus for glutamate dehydrogenase (gdhA).
|
gltB gene and regulation of nitrogen metabolism by glutamine synthetase in Escherichia coli. A mutant (gltB) of Escherichia coli lacking glutamate synthase (GOGAT) was unable to utilize a wide variety of compounds as sole nitrogen source (e.g., arginine, proline, gamma-aminobutyrate, and glycine). Among revertants of these Asm- strains selected on one of these compounds (e.g., arginine, proline, or gamma-aminobutyrate) were those that produce glutamine synthetase (GS) constitutively (GlnC phenotype). These revertants had a pleiotropically restored ability to grow on compounds that are metabolized to glutamate. This suggested that the expression of the genes responsible for the metabolism of these nitrogen sources was regulated by GS. An examination of the regulation of proline oxidase confirmed this hypothesis. The differential sensitivities of GlnC and wild-type strains to low concentrations (0.1 mM) of the glutamine analog L-methionine-DL-sulfoximine supported the conclusion that the synthesis of a glutamine permease was also positively controlled by GS. During the course of this study we found that the reported position of the locus (gltB) for glutamate synthase is incorrect. We have relocated this gene to be 44% linked to the argG locus by P1 transduction. Further mapping has shown that the locus previously called aspB is in reality the gltB locus and that the "suppressor" of the aspB mutation (A. M. Reiner, J. Bacteriol. 97:1431-1436, 1969) is the locus for glutamate dehydrogenase (gdhA).
|
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] |
PMID:22536
|
Purification and properties of an extracellular protease from Myxococcus virescens.
|
An extracellular protease from Myxococcus virescens was purified by phosphate precipitation, gel exclusion, and ion-exchange chromatography. The enzyme appeared homogeneous upon disc electrophoresis. The molecular weight of the protease was estimated to be 26,000. The enzyme was rapidly inactivated by ethylenediaminetetraacetate, but the activity could be partially restored by divalent cations. Diisopropylphosphorofluoridate inhibited enzyme activity completely. Michaelis-Menten kinetics were obeyed with casein and hemoglobin as substrates. First-order kinetics were obtained with elastin as the substrate, provided trypsin was in excess. Petidolytic activity indicated that the peptide bonds hydrolyzed by the enzyme were mainly those involving amino acids with nonpolar side chains.
|
Purification and properties of an extracellular protease from Myxococcus virescens. An extracellular protease from Myxococcus virescens was purified by phosphate precipitation, gel exclusion, and ion-exchange chromatography. The enzyme appeared homogeneous upon disc electrophoresis. The molecular weight of the protease was estimated to be 26,000. The enzyme was rapidly inactivated by ethylenediaminetetraacetate, but the activity could be partially restored by divalent cations. Diisopropylphosphorofluoridate inhibited enzyme activity completely. Michaelis-Menten kinetics were obeyed with casein and hemoglobin as substrates. First-order kinetics were obtained with elastin as the substrate, provided trypsin was in excess. Petidolytic activity indicated that the peptide bonds hydrolyzed by the enzyme were mainly those involving amino acids with nonpolar side chains.
|
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] |
PMID:22537
|
Ammonia assimilation and glutamate formation in Caulobacter crescentus.
|
In the dimorphic bacterium Caulobacter crescentus, ammonia assimilation occurs only via the combined action of the enzymes glutamine synthetase and glutamate synthase. Mutants auxotrophic for glutamate lacked glutamate synthase activity, and the mutations leading to the glutamate auxotrophy appeared to lie at two distinct genetic loci. Both glutamate synthase and glutamine synthetase activities were subject to regulation by repression. Glutamate synthase activity was highest in cultures grown in minimal medium with ammonia as sole nitrogen source and was about fivefold lower in rich broth. Glutamine synthetase activity was highest in cells grown with growth-rate-limiting amounts of ammonia as nitrogen source and was about fourfold lower in rich broth. In addition, glutamine synthetase activity appeared to be regulated by an adenylylation system like that described for Escherichia coli.
|
Ammonia assimilation and glutamate formation in Caulobacter crescentus. In the dimorphic bacterium Caulobacter crescentus, ammonia assimilation occurs only via the combined action of the enzymes glutamine synthetase and glutamate synthase. Mutants auxotrophic for glutamate lacked glutamate synthase activity, and the mutations leading to the glutamate auxotrophy appeared to lie at two distinct genetic loci. Both glutamate synthase and glutamine synthetase activities were subject to regulation by repression. Glutamate synthase activity was highest in cultures grown in minimal medium with ammonia as sole nitrogen source and was about fivefold lower in rich broth. Glutamine synthetase activity was highest in cells grown with growth-rate-limiting amounts of ammonia as nitrogen source and was about fourfold lower in rich broth. In addition, glutamine synthetase activity appeared to be regulated by an adenylylation system like that described for Escherichia coli.
|
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-0.018776165321469307,
0.05477890744805336,
-0.028196532279253006
] |
PMID:22538
|
Purification and properties of nitroalkane oxidase from Fusarium oxysporum.
|
A nitroalkane-oxidizing enzyme, which was inducibly formed by addition of nitroethane to the medium was purified to homogeneity from an extract of Fusarium oxysporum (IFO 5942) with an overall yield of about 20%. The enzyme catalyzed the oxidative denitrification of 1-nitropropane as follows: CH2(NO2)CH2CH3 + O2 + H2O leads to OHCCH2CH3 + HNO2 + H2O2. In addition to 1-nitropropane, 3-nitro-2-pentanol, 2-nitropropane, and nitrocyclohexane are good substrates; the enzyme is designated "nitroalkane oxidase" (EC class 1.7.3). The enzyme has a molecular weight of approximately 185,000 and consists of four subunits identical in molecular weight (47,000). Flavin adenine dinucleotide was required for the enzyme activity and could be replaced in part by riboflavin 5'-phosphate. The maximum reactivity was found at about pH 8.0. The enzyme was inhibited significantly by HgCl2, KCN, p-chloromercuribenzoate, and N-ethylmaleimide. The Michaelis constants are as follows: 1-nitropropane, 1.54 mM; 2-nitropropane, 7.40 mM; nitroethane, 1.00 mM; 3-nitro-2-pentanol, 3.08 mM; nitrocyclohexane, 0.90 mM; and flavin adenine dinucleotide, 1.33 micrometer.
|
Purification and properties of nitroalkane oxidase from Fusarium oxysporum. A nitroalkane-oxidizing enzyme, which was inducibly formed by addition of nitroethane to the medium was purified to homogeneity from an extract of Fusarium oxysporum (IFO 5942) with an overall yield of about 20%. The enzyme catalyzed the oxidative denitrification of 1-nitropropane as follows: CH2(NO2)CH2CH3 + O2 + H2O leads to OHCCH2CH3 + HNO2 + H2O2. In addition to 1-nitropropane, 3-nitro-2-pentanol, 2-nitropropane, and nitrocyclohexane are good substrates; the enzyme is designated "nitroalkane oxidase" (EC class 1.7.3). The enzyme has a molecular weight of approximately 185,000 and consists of four subunits identical in molecular weight (47,000). Flavin adenine dinucleotide was required for the enzyme activity and could be replaced in part by riboflavin 5'-phosphate. The maximum reactivity was found at about pH 8.0. The enzyme was inhibited significantly by HgCl2, KCN, p-chloromercuribenzoate, and N-ethylmaleimide. The Michaelis constants are as follows: 1-nitropropane, 1.54 mM; 2-nitropropane, 7.40 mM; nitroethane, 1.00 mM; 3-nitro-2-pentanol, 3.08 mM; nitrocyclohexane, 0.90 mM; and flavin adenine dinucleotide, 1.33 micrometer.
|
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0.07547732442617416,
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] |
PMID:22539
|
Association-dissociation of the flavoprotein hog kidney D-amino acid oxidase. Determination of the monomer-dimer equilibrium constant and the energetics of subunit association.
|
The enzyme concentration dependence of spectrophotometric titrations of hog kidney D-amino acid oxidase [EC 1.4.3.3] with p-aminobenzoate was studied. The monomer-dimer equilibrium constant of the oxidized holoenzyme at 25 degrees C was estimated to be 7 X 10(5)M-1 at pH 7.5 and 4X 10(6)M-1 at pH 8.3. The energetics of subunit association are discussed.
|
Association-dissociation of the flavoprotein hog kidney D-amino acid oxidase. Determination of the monomer-dimer equilibrium constant and the energetics of subunit association. The enzyme concentration dependence of spectrophotometric titrations of hog kidney D-amino acid oxidase [EC 1.4.3.3] with p-aminobenzoate was studied. The monomer-dimer equilibrium constant of the oxidized holoenzyme at 25 degrees C was estimated to be 7 X 10(5)M-1 at pH 7.5 and 4X 10(6)M-1 at pH 8.3. The energetics of subunit association are discussed.
|
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] |
PMID:22540
|
Light-induced pH changes and changes in absorbance of pH indicators in Rhodospirillum rubrum chromatophores.
|
1. The light-induced pH change of chromatophore suspensions from Rhodospirillum rubrum was stimulated significantly and similarly by KCl, NaCl, LiCl, RbCl, CsCl, MgCl2, MnCl2, and CaCl2. In the dark, the pH of chromatophore suspensions decreased immediately and markedly on adding these salts. 2. The light-induced pH change stimulated by KCl plus valinomycin was inhibited by LiCl and NaCl, but not by RbCl. 3. The optimum pH values for light-induced pH change and photosynthetic ATP formation were around 5 and 8, respectively. The amount of chromatophore-bound ubiquinone-10 reduced in the light was independent of pH from 5 to 9. At pH 8, the number of protons incorporated into chromatophores in the light was one-half of the number of ubiquinone-10 molecules reduced in the light. 4. Among several pH indicators tested, bromothymol blue (BTB) and neutral red (NR) showed absorbance changes on illumination of chromatophores. Although the pH change indicated by the absorbance change was opposite to the light-induced pH change of the medium, the effect of KCl on the absorbance changes of BTB and NR, and the effect of valinomycin on that of NR, but not on that of BTB, were similar to those on the light-induced pH change. 5. The light-induced absorbance change of BTB was significantly inhibited by NR, whereas that of NR was hardly influenced by BTB. 6. Oligomycin stimulated the light-induced absorbance change of BTB under either non-phosphorylating or phosphorylating conditions. On the other hand, that of NR under phosphorylating conditions was 50% of that under non-phosphorylating conditions, and was increased by oligomycin.
|
Light-induced pH changes and changes in absorbance of pH indicators in Rhodospirillum rubrum chromatophores. 1. The light-induced pH change of chromatophore suspensions from Rhodospirillum rubrum was stimulated significantly and similarly by KCl, NaCl, LiCl, RbCl, CsCl, MgCl2, MnCl2, and CaCl2. In the dark, the pH of chromatophore suspensions decreased immediately and markedly on adding these salts. 2. The light-induced pH change stimulated by KCl plus valinomycin was inhibited by LiCl and NaCl, but not by RbCl. 3. The optimum pH values for light-induced pH change and photosynthetic ATP formation were around 5 and 8, respectively. The amount of chromatophore-bound ubiquinone-10 reduced in the light was independent of pH from 5 to 9. At pH 8, the number of protons incorporated into chromatophores in the light was one-half of the number of ubiquinone-10 molecules reduced in the light. 4. Among several pH indicators tested, bromothymol blue (BTB) and neutral red (NR) showed absorbance changes on illumination of chromatophores. Although the pH change indicated by the absorbance change was opposite to the light-induced pH change of the medium, the effect of KCl on the absorbance changes of BTB and NR, and the effect of valinomycin on that of NR, but not on that of BTB, were similar to those on the light-induced pH change. 5. The light-induced absorbance change of BTB was significantly inhibited by NR, whereas that of NR was hardly influenced by BTB. 6. Oligomycin stimulated the light-induced absorbance change of BTB under either non-phosphorylating or phosphorylating conditions. On the other hand, that of NR under phosphorylating conditions was 50% of that under non-phosphorylating conditions, and was increased by oligomycin.
|
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] |
PMID:22543
|
Calf liver nuclear N-acetyltransferases. Purification and properties of two enzymes with both spermidine acetyltransferase and histone acetyltransferase activities.
|
Calf liver contains two nuclear N-acetyltransferases which are separated by chromatography on hydroxylapatite. Both acetyltransferase A and acetyltransferase B will transfer acetate from acetyl-CoA to either histone or spermidine. The same protein catalyzes the reaction with both substrates; this is shown by a constant ratio of spermidine to histone activity over a 5,000-fold purification and identical heat denaturation kinetics for both spermidine and histone acetyltransferase activity with each enzyme. Histone is preferentially acetylated when both acceptors are present. Both enzymes preferentially acetylate polyamines (spermidine, spermine, and diaminodipropylamine) to diamines. Acetyltransferase A acetylates histones in the order: whole histone greater than H4 greater than H2A greater than H3 greater than H2B greater than H1; acetyltransferase B in the order: whole histone greater than H4 = H3 greater than H2A greater than H2B greater than H1. Michaelis constants are 2 X 10(-4)M for spermidine and 9 X 10(-6)M for acetyl-CoA. Acetyltransferase A has a molecular weight of 150,000; acetyltransferase B 175,000. Both enzymes are strongly inhibited by p-chloromercuribenzoate and weakly inhibited by EDTA.
|
Calf liver nuclear N-acetyltransferases. Purification and properties of two enzymes with both spermidine acetyltransferase and histone acetyltransferase activities. Calf liver contains two nuclear N-acetyltransferases which are separated by chromatography on hydroxylapatite. Both acetyltransferase A and acetyltransferase B will transfer acetate from acetyl-CoA to either histone or spermidine. The same protein catalyzes the reaction with both substrates; this is shown by a constant ratio of spermidine to histone activity over a 5,000-fold purification and identical heat denaturation kinetics for both spermidine and histone acetyltransferase activity with each enzyme. Histone is preferentially acetylated when both acceptors are present. Both enzymes preferentially acetylate polyamines (spermidine, spermine, and diaminodipropylamine) to diamines. Acetyltransferase A acetylates histones in the order: whole histone greater than H4 greater than H2A greater than H3 greater than H2B greater than H1; acetyltransferase B in the order: whole histone greater than H4 = H3 greater than H2A greater than H2B greater than H1. Michaelis constants are 2 X 10(-4)M for spermidine and 9 X 10(-6)M for acetyl-CoA. Acetyltransferase A has a molecular weight of 150,000; acetyltransferase B 175,000. Both enzymes are strongly inhibited by p-chloromercuribenzoate and weakly inhibited by EDTA.
|
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] |
PMID:22545
|
Tyrosine hydroxylase. Activation by protein phosphorylation and end product inhibition.
|
Protein phosphorylation activates tyrosine hydroxylase in crude extracts of rat striatum, hypothalamus, and adrenal glands by a reduction in the apparent Km value for 6-methyltetrahydropterin. Removal of endogenous catecholamines by gel filtration or cation exchange results in a similar activation. Phosphorylation causes only a small additional reduction in the apparent Km for reduced pterin in striatal extracts from which catecholamines have been removed. Kinetic analysis indicates that protein phosphorylation causes a significant increase in the Ki for end product dopamine, whereas gel filtration or cation exchange treatment has little effect on the dopamine Ki value. None of the above treatments appears to change the molecular weight of the enzyme. At physiological concentrations of dopamine, the increase in Ki by phosphorylation would effectively release tyrosine hydroxylase from end product feedback inhibition.
|
Tyrosine hydroxylase. Activation by protein phosphorylation and end product inhibition. Protein phosphorylation activates tyrosine hydroxylase in crude extracts of rat striatum, hypothalamus, and adrenal glands by a reduction in the apparent Km value for 6-methyltetrahydropterin. Removal of endogenous catecholamines by gel filtration or cation exchange results in a similar activation. Phosphorylation causes only a small additional reduction in the apparent Km for reduced pterin in striatal extracts from which catecholamines have been removed. Kinetic analysis indicates that protein phosphorylation causes a significant increase in the Ki for end product dopamine, whereas gel filtration or cation exchange treatment has little effect on the dopamine Ki value. None of the above treatments appears to change the molecular weight of the enzyme. At physiological concentrations of dopamine, the increase in Ki by phosphorylation would effectively release tyrosine hydroxylase from end product feedback inhibition.
|
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] |
PMID:22546
|
Oxalate and spin-labeled oxalate as probes of the anion binding site of human transferrin. Metal to anion distance.
|
The spin-labeled anion N-[4-(2,2,6,6-tetramethylpiperidin-1-oxyl)] oxamate has been synthesized and characterized. In the presence of this compound, a specific iron-transferrin-anion complex is formed, as evidenced by the development of a characteristic red color. No EPR signal was observed for the nitroxyl radical in the protein complex, presumably due to broadening of the signal by the paramagnetic metal ion. Failure to observe a signal implies that the metal to nitroxyl distance is less than or equal to 6 A. This suggests that the anion is directly attached to the metal ion in the protein. The pH dependence of iron dissociation from iron-transferrin-oxalate is also reported. This complex is more stable at low pH than iron-transferrin-carbonate.
|
Oxalate and spin-labeled oxalate as probes of the anion binding site of human transferrin. Metal to anion distance. The spin-labeled anion N-[4-(2,2,6,6-tetramethylpiperidin-1-oxyl)] oxamate has been synthesized and characterized. In the presence of this compound, a specific iron-transferrin-anion complex is formed, as evidenced by the development of a characteristic red color. No EPR signal was observed for the nitroxyl radical in the protein complex, presumably due to broadening of the signal by the paramagnetic metal ion. Failure to observe a signal implies that the metal to nitroxyl distance is less than or equal to 6 A. This suggests that the anion is directly attached to the metal ion in the protein. The pH dependence of iron dissociation from iron-transferrin-oxalate is also reported. This complex is more stable at low pH than iron-transferrin-carbonate.
|
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0.04561571031808853
] |
PMID:22547
|
Quaternary states of methemoglobin and its valence-hybrid. A pulse radiolysis study.
|
Using the pulse radiolysis technique on solutions of stripped adult human methemoglobin, we found that the heme-iron within a single subunit in the tetramer was reduced to iron(II). The valence-hybrid thus formed was reacted with oxygen and with carbon monoxide. Kinetics of the reactions were studied. The effects of pH, inositol hexaphosphate, and temperature on these reactions were examined. The kinetics of the ligation of O2 and CO were used to characterize the affinity states of the valence-hybrid and its parent methemoglobin. Our results support the description of stripped methemoglobin A as residing in an R state. In the presence of inositol hexaphosphate methemoglobin is stabilized in a T state, but it switches into a high affinity state when the pH is raised a0ove 8.0. This structural transition was not found to coincide with the switch of spin state of the heme-iron that accompanies the ionization of water in aquomethemoglobin A.
|
Quaternary states of methemoglobin and its valence-hybrid. A pulse radiolysis study. Using the pulse radiolysis technique on solutions of stripped adult human methemoglobin, we found that the heme-iron within a single subunit in the tetramer was reduced to iron(II). The valence-hybrid thus formed was reacted with oxygen and with carbon monoxide. Kinetics of the reactions were studied. The effects of pH, inositol hexaphosphate, and temperature on these reactions were examined. The kinetics of the ligation of O2 and CO were used to characterize the affinity states of the valence-hybrid and its parent methemoglobin. Our results support the description of stripped methemoglobin A as residing in an R state. In the presence of inositol hexaphosphate methemoglobin is stabilized in a T state, but it switches into a high affinity state when the pH is raised a0ove 8.0. This structural transition was not found to coincide with the switch of spin state of the heme-iron that accompanies the ionization of water in aquomethemoglobin A.
|
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] |
PMID:22549
|
Increase in hepatic tyrosine aminotransferase mRNA during enzyme induction by N6,O2'-dibutyryl cyclic AMP.
|
Tyrosine aminotransferase mRNA was quantitated by translation in a cell-free system derived from wheat germ followed by specific immunoprecipitation of the newly synthesized enzyme subunit. Hepatic poly(A)-containg RNA prepared from rats treated for 4 h with N6, O2'-dibutyryl cyclic AMP and theophylline was approximately 5.6 times more active in directing the synthesis of the tyrosine aminotransferase subunit relative to untreated controls. The overall template activity of the RNA prepared from control and cyclic AMP-treated animals was virtually identical, demonstrating that the cyclic nucleotide effect was specific for the tyrosine aminotransferase mRNA. At all times, after a single injection of dibutyryl cyclic AMP and theophylline, the increase in hepatic enzyme activity was accompanied by corresponding induction in the level of functional tyrosine aminotransferase mRNA. Other inducers of tyrosine aminotransferase, such as glucagon and hydrocortisone, also increased the level of tyrosine aminotransferase mRNA in proportion to their effect on enzyme activity. The RNA polymerase II inhibitor, alpha-amanitin, completely blocked the dibutyryl cyclic AMP-mediated increase in tyrosine aminotransferase mRNA activity. These studies demonstrate that, in intact animals, the induction of tyrosine aminotransferase activity by dibutyryl cyclic AMP can be completely accounted for by a corresponding increase in the level of functional mRNA coding for the enzyme.
|
Increase in hepatic tyrosine aminotransferase mRNA during enzyme induction by N6,O2'-dibutyryl cyclic AMP. Tyrosine aminotransferase mRNA was quantitated by translation in a cell-free system derived from wheat germ followed by specific immunoprecipitation of the newly synthesized enzyme subunit. Hepatic poly(A)-containg RNA prepared from rats treated for 4 h with N6, O2'-dibutyryl cyclic AMP and theophylline was approximately 5.6 times more active in directing the synthesis of the tyrosine aminotransferase subunit relative to untreated controls. The overall template activity of the RNA prepared from control and cyclic AMP-treated animals was virtually identical, demonstrating that the cyclic nucleotide effect was specific for the tyrosine aminotransferase mRNA. At all times, after a single injection of dibutyryl cyclic AMP and theophylline, the increase in hepatic enzyme activity was accompanied by corresponding induction in the level of functional tyrosine aminotransferase mRNA. Other inducers of tyrosine aminotransferase, such as glucagon and hydrocortisone, also increased the level of tyrosine aminotransferase mRNA in proportion to their effect on enzyme activity. The RNA polymerase II inhibitor, alpha-amanitin, completely blocked the dibutyryl cyclic AMP-mediated increase in tyrosine aminotransferase mRNA activity. These studies demonstrate that, in intact animals, the induction of tyrosine aminotransferase activity by dibutyryl cyclic AMP can be completely accounted for by a corresponding increase in the level of functional mRNA coding for the enzyme.
|
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] |
PMID:22550
|
Molecular weights of aggregation states of Busycon hemocyanin.
|
Molecular weights of all hemocyanin aggregates which can be homogeneously isolated have been measured by sedimentation equilibrium. The larger aggregates, which are the ones present under physiological conditions, are, to a very close approximation, integral multiples of a 4.4 x 10(6)-dalton, 60 S species. Dissociation of the 60 S species at high pH gives heterogeneous samples in which the smallest species has a molecular weight of 300,000. The smallest subunit which can be produced in denaturing solvents also has a molecular weight of 300,000.
|
Molecular weights of aggregation states of Busycon hemocyanin. Molecular weights of all hemocyanin aggregates which can be homogeneously isolated have been measured by sedimentation equilibrium. The larger aggregates, which are the ones present under physiological conditions, are, to a very close approximation, integral multiples of a 4.4 x 10(6)-dalton, 60 S species. Dissociation of the 60 S species at high pH gives heterogeneous samples in which the smallest species has a molecular weight of 300,000. The smallest subunit which can be produced in denaturing solvents also has a molecular weight of 300,000.
|
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] |
PMID:22551
|
The inhibition by 6-diazo-5-oxo-l-norleucine of glutamine catabolism of the cultured human lymphoblast.
|
The rapid catabolism of glutamine by the cultured human lymphoblast line WI-L2 can be inhibited greater than 95% by incubation of cell suspensions with 6-diazo-5-oxo-L-norleucine (DON). The inhibition persists for at least four hours after removal of DON from the cell suspension. The exposure of cells to DON ihibits over 95% of the glutaminase activity measured in lysates in the presence of either phosphate or maleate. Similarly, gamma-glutamyl transpeptidase, assayed with gamma-glutamyl-p-nitroanilide as substrate and glycyglycine as acceptor, is inhibited over 90%. DON-treated and control cells accumulated radioactive material from suspensions containing [14C]-L-glutamine at similar initial rates; the radioactive material accumulated by the DON-treated cells is all recoverable as glutamine while the radioactive material accumulated by untreated cells is principally recovered as glutamate.
|
The inhibition by 6-diazo-5-oxo-l-norleucine of glutamine catabolism of the cultured human lymphoblast. The rapid catabolism of glutamine by the cultured human lymphoblast line WI-L2 can be inhibited greater than 95% by incubation of cell suspensions with 6-diazo-5-oxo-L-norleucine (DON). The inhibition persists for at least four hours after removal of DON from the cell suspension. The exposure of cells to DON ihibits over 95% of the glutaminase activity measured in lysates in the presence of either phosphate or maleate. Similarly, gamma-glutamyl transpeptidase, assayed with gamma-glutamyl-p-nitroanilide as substrate and glycyglycine as acceptor, is inhibited over 90%. DON-treated and control cells accumulated radioactive material from suspensions containing [14C]-L-glutamine at similar initial rates; the radioactive material accumulated by the DON-treated cells is all recoverable as glutamine while the radioactive material accumulated by untreated cells is principally recovered as glutamate.
|
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] |
PMID:22552
|
Role of the vacuolar apparatus in augmented protein degradation in cultured fibroblasts.
|
Rat embryo fibroblasts, grown in Eagle's MEM with 10% serum, showed a rapid increase in autophagic vacuoles when placed in MEM with 0-1% serum. Concurrent with this response, degradation of cellular proteins showed a 2-fold increase. We did not find any increases in cathepsin D, beta-glucuronidase, beta-galactosidase, and beta-glucosidase, or proteolytic activity of cell homogenates at pH 3.7 towards endogenous substrates. Homogenates prepared in 250 mM sucrose at pH 7.0 showed a 40% increase in protein breakdown. These data support the hypothesis that the induced increase in proteolysis, characteristic of cells placed in a nutritionally deficient medium, is effected by an activated vacuolar apparatus (lysosomes and autophagic vacuoles). We suggest, however, that this mechanism is distinct from normal protein turnover in the cell, but can be rapidly induced by appropriate alterations in the cellular environment. Finally, this induced proteolytic mechanism is not dependent upon an increase in lysosomal enzymes, but rather a structural alteration within the cell which effects a transfer of cellular proteins into the vacuolar apparatus.
|
Role of the vacuolar apparatus in augmented protein degradation in cultured fibroblasts. Rat embryo fibroblasts, grown in Eagle's MEM with 10% serum, showed a rapid increase in autophagic vacuoles when placed in MEM with 0-1% serum. Concurrent with this response, degradation of cellular proteins showed a 2-fold increase. We did not find any increases in cathepsin D, beta-glucuronidase, beta-galactosidase, and beta-glucosidase, or proteolytic activity of cell homogenates at pH 3.7 towards endogenous substrates. Homogenates prepared in 250 mM sucrose at pH 7.0 showed a 40% increase in protein breakdown. These data support the hypothesis that the induced increase in proteolysis, characteristic of cells placed in a nutritionally deficient medium, is effected by an activated vacuolar apparatus (lysosomes and autophagic vacuoles). We suggest, however, that this mechanism is distinct from normal protein turnover in the cell, but can be rapidly induced by appropriate alterations in the cellular environment. Finally, this induced proteolytic mechanism is not dependent upon an increase in lysosomal enzymes, but rather a structural alteration within the cell which effects a transfer of cellular proteins into the vacuolar apparatus.
|
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] |
PMID:22553
|
Lectin-mediated agglutination of amphibian embryonic cells.
|
Dissociated blastula cells of Xenopus laevis are agglutinated with wheat germ agglutinin (WGA), Ricinus communis agglutinin (RCA), concanavalin A (Con A) and, to a lesser extent with soya bean agglutinin (SBA). They are not agglutinated with fucose-binding protein. Neuraminidase treatment of cells enhances their agglutinability with RCA and SBA, but has no effect on Con A- and WGA-mediated agglutinability. Treatment of cells with procaine, or xylocaine, has no effect on the cells' agglutinability or on the extrusion of lobopodia. Treatment with colchicine or cytochalasin B either separately or simultaneously has no effect on lectin-mediated agglutinability. Cells treated with cytochalasin B or colchicine and cytochalasin B simultaneously lack lobopodial extensions, while colchicine alone has no effect on these structures. Phenothiazine tranquillizers inhibit agglutination mediated by all of the above mentioned lectins. Lobopodial extensions are absent in cells treated with these compounds. Glutaraldehyde fixation inhibits RCA and WGA mediated agglutinability and reduces the Con A-mediated agglutinability. Results suggest that in this system microtubules and microfilaments are not involved in lectin-mediated agglutination.
|
Lectin-mediated agglutination of amphibian embryonic cells. Dissociated blastula cells of Xenopus laevis are agglutinated with wheat germ agglutinin (WGA), Ricinus communis agglutinin (RCA), concanavalin A (Con A) and, to a lesser extent with soya bean agglutinin (SBA). They are not agglutinated with fucose-binding protein. Neuraminidase treatment of cells enhances their agglutinability with RCA and SBA, but has no effect on Con A- and WGA-mediated agglutinability. Treatment of cells with procaine, or xylocaine, has no effect on the cells' agglutinability or on the extrusion of lobopodia. Treatment with colchicine or cytochalasin B either separately or simultaneously has no effect on lectin-mediated agglutinability. Cells treated with cytochalasin B or colchicine and cytochalasin B simultaneously lack lobopodial extensions, while colchicine alone has no effect on these structures. Phenothiazine tranquillizers inhibit agglutination mediated by all of the above mentioned lectins. Lobopodial extensions are absent in cells treated with these compounds. Glutaraldehyde fixation inhibits RCA and WGA mediated agglutinability and reduces the Con A-mediated agglutinability. Results suggest that in this system microtubules and microfilaments are not involved in lectin-mediated agglutination.
|
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] |
PMID:22554
|
Studies on human alpha-lactalbumin: radioimmunoassay measurements in normal human breast and breast cancer.
|
A sensitive and specific radioimmunoassay for human alpha-lactalbumin, a milk protein, has been developed in order to examine the effect of prolactin on the human breast in normal and diseased states. Samples of milk from nursing mothers and from men and women with galactorrhea were found to contain milligram concentrations of this protein. In serum, 8 of 25 normal men and 18 of 44 normal women had detectable concentrations of alpha-lactalbumin. Significantly higher levels of alpha-lactalbumin were found in 17 of 19 women during pregnancy who were not actively lactating. All nursing mothers were found to have distinctly elevated serum alpha-lactalbumin concentrations. In a group of 17 female patients with phenothiazine induced prolactin elevations (mean 29.4 ng/ml), the mean serum alpha-lactalbumin of 17.3 ng/ml was significantly higher than in normal female volunteers. Patients with gynecomastia were not noted to have elevated alpha-lactalbumin. In vitro, homogenates of normal breast and carcinoma tissue from the same individuals revealed that in 9 of 17 patients alpha-lactalbumin was present in higher concentrations in normal than in cancerous tissue. Overall, alpha-lactalbumin was found in 48.5% of homogenates and 41% of organ cultures of normal breast tissue from cancer patients. In contrast, it was present in only 19% of homogenates and 21% of cultures of carcinoma tissue, indicating that the cancer tissue may lose its ability to produce alpha-lactalbumin. Differences in biologic behavior were found in some tumors. In 2 cases homogenates of breast cancer tissue had much higher concentrations of alpha-lactalbumin than the normal tissue, and in 3 of 33 tumors studied in organ culture prolactin increased alpha-lactalbumin output.
|
Studies on human alpha-lactalbumin: radioimmunoassay measurements in normal human breast and breast cancer. A sensitive and specific radioimmunoassay for human alpha-lactalbumin, a milk protein, has been developed in order to examine the effect of prolactin on the human breast in normal and diseased states. Samples of milk from nursing mothers and from men and women with galactorrhea were found to contain milligram concentrations of this protein. In serum, 8 of 25 normal men and 18 of 44 normal women had detectable concentrations of alpha-lactalbumin. Significantly higher levels of alpha-lactalbumin were found in 17 of 19 women during pregnancy who were not actively lactating. All nursing mothers were found to have distinctly elevated serum alpha-lactalbumin concentrations. In a group of 17 female patients with phenothiazine induced prolactin elevations (mean 29.4 ng/ml), the mean serum alpha-lactalbumin of 17.3 ng/ml was significantly higher than in normal female volunteers. Patients with gynecomastia were not noted to have elevated alpha-lactalbumin. In vitro, homogenates of normal breast and carcinoma tissue from the same individuals revealed that in 9 of 17 patients alpha-lactalbumin was present in higher concentrations in normal than in cancerous tissue. Overall, alpha-lactalbumin was found in 48.5% of homogenates and 41% of organ cultures of normal breast tissue from cancer patients. In contrast, it was present in only 19% of homogenates and 21% of cultures of carcinoma tissue, indicating that the cancer tissue may lose its ability to produce alpha-lactalbumin. Differences in biologic behavior were found in some tumors. In 2 cases homogenates of breast cancer tissue had much higher concentrations of alpha-lactalbumin than the normal tissue, and in 3 of 33 tumors studied in organ culture prolactin increased alpha-lactalbumin output.
|
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] |
PMID:22555
|
Inhibition of folate enzymes by sulfasalazine.
|
Sulfasalazine (salicylazosulfapyridine), an agent widely used for the treatment of ileitis and colitis, is also a competitive inhibitor of intestinal folate transport (1, 2). The mechanism of action of sulfasalazine remains uncertain. To further explore the mechanism of sulfasalazine action, the interaction of the drug with the folate recognition site was tested with three enzymes: dihydrofolate reductase, methylenetetrahydrofolate reductase, and serine transhydroxymethylase, each catalyzing a reaction involving a different folate derivative. Each of these enzymes was inhibited by sulfasalazine in the same concentration range as that previously observed to inhibit intestinal folate transport; the kinetic data are consistent with a competitive mode of inhibition. Specificity of inhibition was demonstrated by the finding that the reduction of the pteridine ring of pteroylheptaglutamic acid by dihydrofolate reductase was subject to inhibition, whereas the hydrolysis of the gamma-glutamyl peptide side chain by chicken pancreas conjugase was not affected. These results are interpreted to indicate that sulfasalazine interferes with a folate recognition site which is common to these enzymes and to the intestinal transport system. Sulfasalazine, therefore, has certain properties of an antifolate drug.
|
Inhibition of folate enzymes by sulfasalazine. Sulfasalazine (salicylazosulfapyridine), an agent widely used for the treatment of ileitis and colitis, is also a competitive inhibitor of intestinal folate transport (1, 2). The mechanism of action of sulfasalazine remains uncertain. To further explore the mechanism of sulfasalazine action, the interaction of the drug with the folate recognition site was tested with three enzymes: dihydrofolate reductase, methylenetetrahydrofolate reductase, and serine transhydroxymethylase, each catalyzing a reaction involving a different folate derivative. Each of these enzymes was inhibited by sulfasalazine in the same concentration range as that previously observed to inhibit intestinal folate transport; the kinetic data are consistent with a competitive mode of inhibition. Specificity of inhibition was demonstrated by the finding that the reduction of the pteridine ring of pteroylheptaglutamic acid by dihydrofolate reductase was subject to inhibition, whereas the hydrolysis of the gamma-glutamyl peptide side chain by chicken pancreas conjugase was not affected. These results are interpreted to indicate that sulfasalazine interferes with a folate recognition site which is common to these enzymes and to the intestinal transport system. Sulfasalazine, therefore, has certain properties of an antifolate drug.
|
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] |
PMID:22556
|
Effect of proteolytic enzymes on the binding of cobalamin to R protein and intrinsic factor. In vitro evidence that a failure to partially degrade R protein is responsible for cobalamin malabsorption in pancreatic insufficiency.
|
Cobalamin (Cbl; vitamin B(12)) malabsorption in pancreatic insufficiency can be partially corrected by bicarbonate and completely corrected by pancreatic proteases but the mechanisms involved are unknown. Because saliva contains enough R-type Cbl-binding protein (R protein) to bind all of the dietary and biliary Cbl, it is possible that R protein acts as an inhibitor of Cbl absorption and that pancreatic proteases are required to alter R protein and prevent such inhibition. To test this hypothesis we studied the ability of R protein and intrinsic factor (IF) to compete for Cbl binding and ability of pancreatic proteases to alter this competition. Human salivary R protein bound Cbl with affinities that were 50- and 3-fold higher than those of human IF at pH 2 and 8, respectively. Cbl bound to IF was transferred to an equal amount of R protein with t((1/2))'s of 2 and 90 min at pH 2 and 8, respectively, and within several hours respective ratios of R protein-Cbl/IF-Cbl of 50 and 2 were observed. Cbl bound to R protein was not transferred to IF at either pH 2 or 8. Incubation of R protein with pancreatic proteases at pH 8 led to a 150-fold decrease in its affinity for Cbl. Incubation of R protein-Cbl with pancreatic proteases led to complete transfer of Cbl to IF within 10 min. Gel filtration studies with R protein-[(57)Co]Cbl and (125)I-R protein showed that pancreatic proteases partially degraded R protein. Pancreatic proteases differed in their ability to effect these changes with trypsin > chymotrypsin > elastase. Pancreatic proteases did not alter IF in any of the parameters mentioned above. Pepsin failed to alter either R protein or IF. THESE STUDIES SUGGEST THE FOLLOWING: (a) that Cbl is bound almost exclusively to R protein in the acid milieu of the stomach, rather than to IF as has been assumed previously; (b) that Cbl remains bound to R protein in the slightly alkaline environment of the intestine until pancreatic proteases partially degrade R protein and enable Cbl to become bound exclusively to IF; and (c) that the primary defect in Cbl absorption in pancreatic insufficiency is a lack of pancreatic proteases and a failure to alter R protein and effect the transfer of Cbl to IF. These studies also suggest that the partial correction of Cbl malabsorption observed with bicarbonate is due to neutralization of gastric HCl, since at slightly alkaline, pH IF can partially compete with R protein for the initial binding and retention of Cbl.
|
Effect of proteolytic enzymes on the binding of cobalamin to R protein and intrinsic factor. In vitro evidence that a failure to partially degrade R protein is responsible for cobalamin malabsorption in pancreatic insufficiency. Cobalamin (Cbl; vitamin B(12)) malabsorption in pancreatic insufficiency can be partially corrected by bicarbonate and completely corrected by pancreatic proteases but the mechanisms involved are unknown. Because saliva contains enough R-type Cbl-binding protein (R protein) to bind all of the dietary and biliary Cbl, it is possible that R protein acts as an inhibitor of Cbl absorption and that pancreatic proteases are required to alter R protein and prevent such inhibition. To test this hypothesis we studied the ability of R protein and intrinsic factor (IF) to compete for Cbl binding and ability of pancreatic proteases to alter this competition. Human salivary R protein bound Cbl with affinities that were 50- and 3-fold higher than those of human IF at pH 2 and 8, respectively. Cbl bound to IF was transferred to an equal amount of R protein with t((1/2))'s of 2 and 90 min at pH 2 and 8, respectively, and within several hours respective ratios of R protein-Cbl/IF-Cbl of 50 and 2 were observed. Cbl bound to R protein was not transferred to IF at either pH 2 or 8. Incubation of R protein with pancreatic proteases at pH 8 led to a 150-fold decrease in its affinity for Cbl. Incubation of R protein-Cbl with pancreatic proteases led to complete transfer of Cbl to IF within 10 min. Gel filtration studies with R protein-[(57)Co]Cbl and (125)I-R protein showed that pancreatic proteases partially degraded R protein. Pancreatic proteases differed in their ability to effect these changes with trypsin > chymotrypsin > elastase. Pancreatic proteases did not alter IF in any of the parameters mentioned above. Pepsin failed to alter either R protein or IF. THESE STUDIES SUGGEST THE FOLLOWING: (a) that Cbl is bound almost exclusively to R protein in the acid milieu of the stomach, rather than to IF as has been assumed previously; (b) that Cbl remains bound to R protein in the slightly alkaline environment of the intestine until pancreatic proteases partially degrade R protein and enable Cbl to become bound exclusively to IF; and (c) that the primary defect in Cbl absorption in pancreatic insufficiency is a lack of pancreatic proteases and a failure to alter R protein and effect the transfer of Cbl to IF. These studies also suggest that the partial correction of Cbl malabsorption observed with bicarbonate is due to neutralization of gastric HCl, since at slightly alkaline, pH IF can partially compete with R protein for the initial binding and retention of Cbl.
|
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] |
PMID:22569
|
Comparison of the ribonucleoproteins of different rabies virus serotypes by radioimmunoassay.
|
Radioimmunoassay (RIA) provides a sensitive serological procedure for detecting rabies virus ribonucleoprotein (RNP) as well as its specific antibodies, RIA was carried out using highly purified RNPs labelled by the chloramine-T method. This paper describes optimal conditions for iodination of RNP with high specific activity. The optimal concentrations of 125I, RNP, chloramine-T, and reducing agent as well as the effect of pH on the reaction were investigated. RIA proved to be extremely sensitive for detection of homologous antibodies. In competition experiments the part-relationship of the group-specific RNPs of the three rabies virus serotypes (HEP, MOK and LBV) was confirmed.
|
Comparison of the ribonucleoproteins of different rabies virus serotypes by radioimmunoassay. Radioimmunoassay (RIA) provides a sensitive serological procedure for detecting rabies virus ribonucleoprotein (RNP) as well as its specific antibodies, RIA was carried out using highly purified RNPs labelled by the chloramine-T method. This paper describes optimal conditions for iodination of RNP with high specific activity. The optimal concentrations of 125I, RNP, chloramine-T, and reducing agent as well as the effect of pH on the reaction were investigated. RIA proved to be extremely sensitive for detection of homologous antibodies. In competition experiments the part-relationship of the group-specific RNPs of the three rabies virus serotypes (HEP, MOK and LBV) was confirmed.
|
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] |
PMID:22573
|
A simple method to determine gammaglutamyl-cyclotransferase activity in erythrocytes.
|
A new method for the determination of erythrocyte gammaGCT is described. The method follows the release of alanine from gammaglutamyl alanine by a series of linked reactions that result in the oxidation of NADH to NAD. The pH optimum for human erythrocyte gammaGCT was found to be 9.0, and the Km for gammaglutamyl alanine was found to be 2.3 X 10(-3) M. Human erythrocytes had the highest activity of all the species studied (human, rabbit, dog, sheep, cattle, chicken).
|
A simple method to determine gammaglutamyl-cyclotransferase activity in erythrocytes. A new method for the determination of erythrocyte gammaGCT is described. The method follows the release of alanine from gammaglutamyl alanine by a series of linked reactions that result in the oxidation of NADH to NAD. The pH optimum for human erythrocyte gammaGCT was found to be 9.0, and the Km for gammaglutamyl alanine was found to be 2.3 X 10(-3) M. Human erythrocytes had the highest activity of all the species studied (human, rabbit, dog, sheep, cattle, chicken).
|
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] |
PMID:22574
|
Hyperlipidemia in renal failure: studies of plasma lipoproteins, hepatic triglyceride production, and tissue lipoprotein lipase in a chronically uremic rat moedl.
|
To determine whether hypertriglyceridemia in chronic renal failure resulted from altered production and/or removal, Sprague-Dawley rats in which chronic uremia had been induced by five-sixths nephrectomy were studied. In this model, basal plasma TG levels were higher than in controls (uremic 141 +/- 52 mg/100 ml; control 83 +/- 25; mean +/- SD; p less than 0.001) at 1 month after nephrectomy and remained significantly elevated throughout the 10-week duration of study. In the uremic animals hepatic TGSR's (Triton) were not increased (uremic 0.56 +/- 0.11 mg/min; control 0.63 +/- 0.13) and AcCoAc, the rate-limiting enzyme in hepatic lipogenesis, was significantly reduced (control 24.5 +/- 3.8 nM/min/mg protein; uremic 18.2 +/- 1.1; p less than 0.005). The TG removal system--heparin-elutable LPL activities--was similar in control and uremic animals in heart, diaphragm, and adipose tissue. However, serum from both acute and chronically uremic rats lowered adipose LPL activity (P less than 0.01). These observations suggest that in uremia (1) TG production is not increased and (2) the clearance of TG-rich lipoprotein from the circulation is reduced because of a functional impairment in LPL.
|
Hyperlipidemia in renal failure: studies of plasma lipoproteins, hepatic triglyceride production, and tissue lipoprotein lipase in a chronically uremic rat moedl. To determine whether hypertriglyceridemia in chronic renal failure resulted from altered production and/or removal, Sprague-Dawley rats in which chronic uremia had been induced by five-sixths nephrectomy were studied. In this model, basal plasma TG levels were higher than in controls (uremic 141 +/- 52 mg/100 ml; control 83 +/- 25; mean +/- SD; p less than 0.001) at 1 month after nephrectomy and remained significantly elevated throughout the 10-week duration of study. In the uremic animals hepatic TGSR's (Triton) were not increased (uremic 0.56 +/- 0.11 mg/min; control 0.63 +/- 0.13) and AcCoAc, the rate-limiting enzyme in hepatic lipogenesis, was significantly reduced (control 24.5 +/- 3.8 nM/min/mg protein; uremic 18.2 +/- 1.1; p less than 0.005). The TG removal system--heparin-elutable LPL activities--was similar in control and uremic animals in heart, diaphragm, and adipose tissue. However, serum from both acute and chronically uremic rats lowered adipose LPL activity (P less than 0.01). These observations suggest that in uremia (1) TG production is not increased and (2) the clearance of TG-rich lipoprotein from the circulation is reduced because of a functional impairment in LPL.
|
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] |
PMID:22576
|
Cholesterol ester hydrolysis by homogenates of whole testis, seminiferous tubules and interstitial cells of mature rats.
|
The characteristics and localization of a cholesterol ester hydrolase enzyme in homogenates of whole testis and in isolated seminiferous tubules and interstitial cells of mature rats have been investigated. Hydrolysis of cholesteryl [1(-14)C]oleate occurred at an optimum pH of 7.0, was linearly related to time up to 5--6 h of incubation and increased linearly up to 0.25 mg protein/incubation. Hydrolytic activity was inhibited by increasing the incubation temperature from 29 to 41 degrees C and by sonication. Cholesterol ester hydrolase activity/mg protein was three times greater in homogenates of seminiferous tubules than in interstitial cells. Cholesterol ester hydrolase may function to provide precursors for use in seminiferous tubular steroid hormone biosynthesis or germ cell maturation.
|
Cholesterol ester hydrolysis by homogenates of whole testis, seminiferous tubules and interstitial cells of mature rats. The characteristics and localization of a cholesterol ester hydrolase enzyme in homogenates of whole testis and in isolated seminiferous tubules and interstitial cells of mature rats have been investigated. Hydrolysis of cholesteryl [1(-14)C]oleate occurred at an optimum pH of 7.0, was linearly related to time up to 5--6 h of incubation and increased linearly up to 0.25 mg protein/incubation. Hydrolytic activity was inhibited by increasing the incubation temperature from 29 to 41 degrees C and by sonication. Cholesterol ester hydrolase activity/mg protein was three times greater in homogenates of seminiferous tubules than in interstitial cells. Cholesterol ester hydrolase may function to provide precursors for use in seminiferous tubular steroid hormone biosynthesis or germ cell maturation.
|
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] |
PMID:22579
|
Energetics of biological nitrogen fixation: determination of the ratio of formation of H2 to NH4+ catalysed by nitrogenase of Klebsiella pneumoniae in vivo.
|
Nitrogen fixation (Nif)-derepressed mutants of Klebsiella pneumoniae consumed, under optimum conditions, 7.5 to 8.5 mol glucose per mol N2 fixed. The nitrogenase system of these mutants catalysed the production of about 1.3 mol H2 per mol N2 reduced. Almost one-third of the energy as ATP and reductant used by nitrogenase in vivo may be lost in H2 production, since an ATP/2e ratio of approximately 4 was obtained. Nitrogenase-catalysed H2 production was not substantially suppressed by increasing the partial pressure of N2 from 0.2 atm (20 kPa) to 1 atm (101 kPa). In the absence of N2, H2 production catalysed by nitrogenase increased about threefold. It is concluded that nitrogenase-catalysed H2 production is of major importance in the overall efficiency of biological N2 fixation in vivo.
|
Energetics of biological nitrogen fixation: determination of the ratio of formation of H2 to NH4+ catalysed by nitrogenase of Klebsiella pneumoniae in vivo. Nitrogen fixation (Nif)-derepressed mutants of Klebsiella pneumoniae consumed, under optimum conditions, 7.5 to 8.5 mol glucose per mol N2 fixed. The nitrogenase system of these mutants catalysed the production of about 1.3 mol H2 per mol N2 reduced. Almost one-third of the energy as ATP and reductant used by nitrogenase in vivo may be lost in H2 production, since an ATP/2e ratio of approximately 4 was obtained. Nitrogenase-catalysed H2 production was not substantially suppressed by increasing the partial pressure of N2 from 0.2 atm (20 kPa) to 1 atm (101 kPa). In the absence of N2, H2 production catalysed by nitrogenase increased about threefold. It is concluded that nitrogenase-catalysed H2 production is of major importance in the overall efficiency of biological N2 fixation in vivo.
|
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] |
PMID:22590
|
Aerobic and anaerobic bacteriology of acute otitis media in children.
|
Tympanocentesis and aerobic and anaerobic cultivation of the middle-ear fluid obtained was performed through one or both tympanic membranes of 62 children with acute otitis media. Aerobic bacteria alone, predominantely pneumococcus and Hemophilus influenzae, were isolated from 57% of patients; anaerobic organisms alone, most commonly Propionibacterium acnes and Peptococcus, from 15%. Thirteen percent yielded mixtures of aerobes and anaerobes, and several had multiple aerobic or anaerobic agents. The isolation of only anaerobic bacteria, supported in some patients by gram-stain observations of middle-ear fluid, suggest that these bacteria, especially Petococcus, may occasionally play a direct role in acute otitis media.
|
Aerobic and anaerobic bacteriology of acute otitis media in children. Tympanocentesis and aerobic and anaerobic cultivation of the middle-ear fluid obtained was performed through one or both tympanic membranes of 62 children with acute otitis media. Aerobic bacteria alone, predominantely pneumococcus and Hemophilus influenzae, were isolated from 57% of patients; anaerobic organisms alone, most commonly Propionibacterium acnes and Peptococcus, from 15%. Thirteen percent yielded mixtures of aerobes and anaerobes, and several had multiple aerobic or anaerobic agents. The isolation of only anaerobic bacteria, supported in some patients by gram-stain observations of middle-ear fluid, suggest that these bacteria, especially Petococcus, may occasionally play a direct role in acute otitis media.
|
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] |
PMID:22591
|
The pharmacologic effects of furosemide therapy in the low-birth-weight infant.
|
The pharmacologic effects of furosemide were studied in six infants (mean gestation 30.7 weeks; mean birth weight 1,490 gm) at ages 10 to 57 days. Furosemide (for clinical indication, standardized at 1 mg/kg) was given intravenously over one minute; data were collected over the ensuing 24 hours. For three hours following furosemide administration, a significant diuresis was observed. Sodium excretion, percent fractional sodium excretion, and potassium excretion were significantly increased and urinary pH significantly decreased for six hours following the administration of furosemide. Creatinine and free water clearances were slightly elevated, although not significantly. Furosemide is an effective diuretic, the onset of pharmacologic action was within one hour, the peak action was sustained for three hours, and the duration of action was six hours. The net fluid, sodium, and potassium losses following a 1 mg/kg single dose were 28 ml, and 3.6 and 0.3 mEq/kg, respectively.
|
The pharmacologic effects of furosemide therapy in the low-birth-weight infant. The pharmacologic effects of furosemide were studied in six infants (mean gestation 30.7 weeks; mean birth weight 1,490 gm) at ages 10 to 57 days. Furosemide (for clinical indication, standardized at 1 mg/kg) was given intravenously over one minute; data were collected over the ensuing 24 hours. For three hours following furosemide administration, a significant diuresis was observed. Sodium excretion, percent fractional sodium excretion, and potassium excretion were significantly increased and urinary pH significantly decreased for six hours following the administration of furosemide. Creatinine and free water clearances were slightly elevated, although not significantly. Furosemide is an effective diuretic, the onset of pharmacologic action was within one hour, the peak action was sustained for three hours, and the duration of action was six hours. The net fluid, sodium, and potassium losses following a 1 mg/kg single dose were 28 ml, and 3.6 and 0.3 mEq/kg, respectively.
|
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] |
PMID:22592
|
Physiologic changes induced by theophylline in the treatment of apnea in preterm infants.
|
Ten preterm infants (birth weight 0.970 to 2.495 kg) with apnea due to periodic breathing (apneic interval = 5 to 10 seconds) or with "serious apnea" (greater than or equal to 20 seconds) were studied before and after the administration of theophylline. We determined the incidence of apnea, respiratory minute volume, alveolar gases, arterial gases and pH, "specific" compliance, functional residual capacity, and work of breathing. Theophylline decreased the incidence of apnea (P less than .05), increased respiratory minute volume (P less than 0.001), decreased (PACO2 (and PaCO2 P less than 0.001), increased the slope of the CO2 response curve (P less than 0.02) with a significant shift to the left (P less than 0.02). These findings suggest that the decreased incidence of apnea after theophylline is associated with an increase in alveolar ventilation and increased sensitivity to CO2 with a pronounced shift of the CO2 response curve to the left. These data are consistent with the idea that apnea is a reflection of a depressed respiratory system.
|
Physiologic changes induced by theophylline in the treatment of apnea in preterm infants. Ten preterm infants (birth weight 0.970 to 2.495 kg) with apnea due to periodic breathing (apneic interval = 5 to 10 seconds) or with "serious apnea" (greater than or equal to 20 seconds) were studied before and after the administration of theophylline. We determined the incidence of apnea, respiratory minute volume, alveolar gases, arterial gases and pH, "specific" compliance, functional residual capacity, and work of breathing. Theophylline decreased the incidence of apnea (P less than .05), increased respiratory minute volume (P less than 0.001), decreased (PACO2 (and PaCO2 P less than 0.001), increased the slope of the CO2 response curve (P less than 0.02) with a significant shift to the left (P less than 0.02). These findings suggest that the decreased incidence of apnea after theophylline is associated with an increase in alveolar ventilation and increased sensitivity to CO2 with a pronounced shift of the CO2 response curve to the left. These data are consistent with the idea that apnea is a reflection of a depressed respiratory system.
|
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] |
PMID:22593
|
The microfilaria of Brugia timori (Partono et al. 1977 = Timor microfilaria, David and Edeson, 1964): morphologic description with comparison to Brugia malayi of Indonesia.
|
The microfilaria of Brugia timori was compared with microfilariae of Indonesian strains of periodic and subperiodic Brugia malayi using alcohol-fixed (stained) and formalin-fixed (unstained) preparations. As noted by other observers of the Timor microfilaria, the absence of a stained sheath in Giemsa preparations, a long cephalic space with a length-to-width ratio of about 3:1, and a great overall body length are features which most readily distinguish this parasite. Additionally, B. timori has greater numbers of single row nuclei in the terminal column of body cells and a lesser bulge of the cuticle surrounding nuclei in the distal portion of the tail than does B. malayi. About 60% of B. timori microfilariae were exsheathed in haemalum-stained thick blood films. Brugia timori microfilariae were found to be distinct from microfilariae of B. malayi by comparing percentages of total body length included between the cephalic tip and major internal anatomic markers.
|
The microfilaria of Brugia timori (Partono et al. 1977 = Timor microfilaria, David and Edeson, 1964): morphologic description with comparison to Brugia malayi of Indonesia. The microfilaria of Brugia timori was compared with microfilariae of Indonesian strains of periodic and subperiodic Brugia malayi using alcohol-fixed (stained) and formalin-fixed (unstained) preparations. As noted by other observers of the Timor microfilaria, the absence of a stained sheath in Giemsa preparations, a long cephalic space with a length-to-width ratio of about 3:1, and a great overall body length are features which most readily distinguish this parasite. Additionally, B. timori has greater numbers of single row nuclei in the terminal column of body cells and a lesser bulge of the cuticle surrounding nuclei in the distal portion of the tail than does B. malayi. About 60% of B. timori microfilariae were exsheathed in haemalum-stained thick blood films. Brugia timori microfilariae were found to be distinct from microfilariae of B. malayi by comparing percentages of total body length included between the cephalic tip and major internal anatomic markers.
|
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] |
PMID:22594
|
Total surgical reconstruction for patients with abdominal muscular deficiency ("prune-belly") syndrome.
|
In the past decade, seven children with the prune-belly syndrome have been seen. Their management has consisted of immediate high tubeless urinary diversion, usually pyelostomy. Thereafter, total reconstruction has been carried out, preferably at one stage. This consists of (1) bilateral shortening, tapering and reimplantation of the ureters, (2) reduction cystoplasty, (3) bilateral orchiopexy, and (4) excision of that part of the abdominal wall that is most redundant and least endowed with musculature. This early effort at mechanical reconstruction has led to gratifying progress in six of the seven children.
|
Total surgical reconstruction for patients with abdominal muscular deficiency ("prune-belly") syndrome. In the past decade, seven children with the prune-belly syndrome have been seen. Their management has consisted of immediate high tubeless urinary diversion, usually pyelostomy. Thereafter, total reconstruction has been carried out, preferably at one stage. This consists of (1) bilateral shortening, tapering and reimplantation of the ureters, (2) reduction cystoplasty, (3) bilateral orchiopexy, and (4) excision of that part of the abdominal wall that is most redundant and least endowed with musculature. This early effort at mechanical reconstruction has led to gratifying progress in six of the seven children.
|
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] |
PMID:22595
|
Technique and experience with 24-hour esophageal pH monitoring in children.
|
The technique and scoring system of 24-hr pH esophageal monitoring has been modified to evaluate gastroesophageal reflux in infants and children. The data from two pediatric controls and five clinical cases are presented and compared to normal adult values. This test has better objectivity, precision, sensitivity, and reliability than contrast studies, endoscopy, esophageal biopsy, acid perfusion, or acid reflux tests. The 24-hr pH monitoring assists the evaluation of sphincter maturation, pulmonary disease, and the significance of body position. With more experience, this technique could identify children at risk fo developing severe complications of reflux esophagitis and aid in the selection of candidates for surgical intervention.
|
Technique and experience with 24-hour esophageal pH monitoring in children. The technique and scoring system of 24-hr pH esophageal monitoring has been modified to evaluate gastroesophageal reflux in infants and children. The data from two pediatric controls and five clinical cases are presented and compared to normal adult values. This test has better objectivity, precision, sensitivity, and reliability than contrast studies, endoscopy, esophageal biopsy, acid perfusion, or acid reflux tests. The 24-hr pH monitoring assists the evaluation of sphincter maturation, pulmonary disease, and the significance of body position. With more experience, this technique could identify children at risk fo developing severe complications of reflux esophagitis and aid in the selection of candidates for surgical intervention.
|
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] |
PMID:22596
|
Physostigmine's effect on diminished fetal heart rate variability caused by scopolamine, meperidine and propiomazine.
|
Physostigmine was given to 17 patients in labor, previously given scopolamine alone or meperidine and propiomazine in combination, to ascertain its effect on reversing the loss of fetal heart rate variability caused by the administration of these drugs. The results of the study indicated that scopolamine in doses of 0.65 to 1.08 milligrams diminished fetal heart rate variability in all 7 patients and physostigmine reversed this loss of fetal heart rate variability in all 7 patients within 4 to 17 minutes after injection of the first dose of physostigmine. Similar results were noted in 10 patients with the combination of meperidine, 50 mg, and propiomazine, 20 mg. It seems tenable from this study that physostigmine does cross the placental barrier and enters the fetal circulation and that this usually occurs within 3 to 17 minutes with an average of approximately 9 minutes. In the healthy fetus the loss of fetal heart rate variability caused by scopolamine, meperidine or propiomazine can be reversed by the use of physostigmine and this reversal seems abrupt and clinically measurable on the fetal monitor print out.
|
Physostigmine's effect on diminished fetal heart rate variability caused by scopolamine, meperidine and propiomazine. Physostigmine was given to 17 patients in labor, previously given scopolamine alone or meperidine and propiomazine in combination, to ascertain its effect on reversing the loss of fetal heart rate variability caused by the administration of these drugs. The results of the study indicated that scopolamine in doses of 0.65 to 1.08 milligrams diminished fetal heart rate variability in all 7 patients and physostigmine reversed this loss of fetal heart rate variability in all 7 patients within 4 to 17 minutes after injection of the first dose of physostigmine. Similar results were noted in 10 patients with the combination of meperidine, 50 mg, and propiomazine, 20 mg. It seems tenable from this study that physostigmine does cross the placental barrier and enters the fetal circulation and that this usually occurs within 3 to 17 minutes with an average of approximately 9 minutes. In the healthy fetus the loss of fetal heart rate variability caused by scopolamine, meperidine or propiomazine can be reversed by the use of physostigmine and this reversal seems abrupt and clinically measurable on the fetal monitor print out.
|
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] |
PMID:22598
|
The influence of adrenalectomy on monoamine oxidase and NADH cytochrome c reductase in the rat heart.
|
The effect of adrenalectomy on the activities of monoamine oxidase (MAO), NADH cytochrome c reductase (NCR), succinate dehydrogenase, malate dehydrogenase, fumarase, NAD+ nucleosidase and acid phosphatase in homogenates of rat hearts was examined. Besides MAO only the NCR activity increased. However, both the total and the rotenone-insensitive NCR activities increased, with that of the rotenone-insensitive being about half of the total, which indicated that the effect of adrenalectomy was exerted on components of this enzyme localized on both the inner and outer membranes of the mitochondrion. The lack of effect on the other enzymes suggests that adrenalectomy has a relatively selective action on MAO and NCR, and does not work by a generalized increase in protein synthesis or by an effect on the FAD cofactor. The MAO increase was seen with a variety of substrates, and was due to a rise in Vmax without change in Km. The response to adrenalectomy in the summer differed from that seen in the winter. The possible reasons for these effects of adrenalectomy are discussed.
|
The influence of adrenalectomy on monoamine oxidase and NADH cytochrome c reductase in the rat heart. The effect of adrenalectomy on the activities of monoamine oxidase (MAO), NADH cytochrome c reductase (NCR), succinate dehydrogenase, malate dehydrogenase, fumarase, NAD+ nucleosidase and acid phosphatase in homogenates of rat hearts was examined. Besides MAO only the NCR activity increased. However, both the total and the rotenone-insensitive NCR activities increased, with that of the rotenone-insensitive being about half of the total, which indicated that the effect of adrenalectomy was exerted on components of this enzyme localized on both the inner and outer membranes of the mitochondrion. The lack of effect on the other enzymes suggests that adrenalectomy has a relatively selective action on MAO and NCR, and does not work by a generalized increase in protein synthesis or by an effect on the FAD cofactor. The MAO increase was seen with a variety of substrates, and was due to a rise in Vmax without change in Km. The response to adrenalectomy in the summer differed from that seen in the winter. The possible reasons for these effects of adrenalectomy are discussed.
|
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] |
PMID:22600
|
The effect of metyrapone on granuloma induced by carrageenan-impregnated sponges in normal and essential fatty acid deficient rats.
|
Treatment of normal rats with metyrapone (20 mg kg-1 day-1, s.c.) for 5 days, starting on the day before implantation, inhibited the production of granuloma, induced by carrageenan-impregnated sponges, determined 8 days after implantation. Exudate volume and prostaglandin (PG) production were unaffected. In essential fatty acid deficient (EFAD) rats, metyrapone did not alter the already existing adrenal hyperplasia due to EFAD and did not affect either granuloma formation or exudate production. The results are discussed in relation to earlier work using adrenalectomy and with regard to the effect of EFA deficiency on adrenal corticosteroid production. It is suggested that metyrapone is a more useful tool than adrenalectomy in studying the role of endogenous corticosteroids.
|
The effect of metyrapone on granuloma induced by carrageenan-impregnated sponges in normal and essential fatty acid deficient rats. Treatment of normal rats with metyrapone (20 mg kg-1 day-1, s.c.) for 5 days, starting on the day before implantation, inhibited the production of granuloma, induced by carrageenan-impregnated sponges, determined 8 days after implantation. Exudate volume and prostaglandin (PG) production were unaffected. In essential fatty acid deficient (EFAD) rats, metyrapone did not alter the already existing adrenal hyperplasia due to EFAD and did not affect either granuloma formation or exudate production. The results are discussed in relation to earlier work using adrenalectomy and with regard to the effect of EFA deficiency on adrenal corticosteroid production. It is suggested that metyrapone is a more useful tool than adrenalectomy in studying the role of endogenous corticosteroids.
|
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] |
PMID:22601
|
Platelets in inflammatory exudates.
|
In exudates of implanted sponges in the rat there are apparent accumulations of blood platelets, assessed by the light microscope, and of radioactivity from labelled platelets administered systemically. The use of more specific techniques for platelet detection showed no evidence of intact blood platelets in the exudate and the radioactivity was not associated preferentially with cellular components in the exudate.
|
Platelets in inflammatory exudates. In exudates of implanted sponges in the rat there are apparent accumulations of blood platelets, assessed by the light microscope, and of radioactivity from labelled platelets administered systemically. The use of more specific techniques for platelet detection showed no evidence of intact blood platelets in the exudate and the radioactivity was not associated preferentially with cellular components in the exudate.
|
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] |
PMID:22603
|
Estimation of the degree of crystallinity in digoxin by X-ray and infrared methods.
|
The X-ray procedure for estimation of the degree of crystallinity in digoxin is based upon measurement of the total X-ray scattering and the scattering from crystalline regions of the drug. The infrared procedures are based upon measurement of the peak height ratios, 1775/1618 and 3095/1618 cm-1. Correlation between results obtained by the two methods is good. These methods are of value in the physico-chemical characterization of digoxin, particularly as the properties may be altered by comminution.
|
Estimation of the degree of crystallinity in digoxin by X-ray and infrared methods. The X-ray procedure for estimation of the degree of crystallinity in digoxin is based upon measurement of the total X-ray scattering and the scattering from crystalline regions of the drug. The infrared procedures are based upon measurement of the peak height ratios, 1775/1618 and 3095/1618 cm-1. Correlation between results obtained by the two methods is good. These methods are of value in the physico-chemical characterization of digoxin, particularly as the properties may be altered by comminution.
|
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] |
PMID:22604
|
The effect of composition and ageing on the dissolution rates of chlorpropamide-urea solid dispersions.
|
Discs of chlorpropamide and urea have been prepared by (a) melting and (b) compression. Intrinsic and relative dissolution rates of the discs have been measured and the dissolution process investigated microscopically. Higher dissolution rates were found from melts than from physical mixes. The optimum dissolution rate composition found was for a melt composed of 30% w/w chlorpropamide which possessed an intrinsic dissolution rate 930 times greater than for the pure drug. Sphere formation, during dissolution rate measurement has been observed and a likely mechanism proposed to account for its occurrence. Dissolution rates generally increased with age for most melt compositions.
|
The effect of composition and ageing on the dissolution rates of chlorpropamide-urea solid dispersions. Discs of chlorpropamide and urea have been prepared by (a) melting and (b) compression. Intrinsic and relative dissolution rates of the discs have been measured and the dissolution process investigated microscopically. Higher dissolution rates were found from melts than from physical mixes. The optimum dissolution rate composition found was for a melt composed of 30% w/w chlorpropamide which possessed an intrinsic dissolution rate 930 times greater than for the pure drug. Sphere formation, during dissolution rate measurement has been observed and a likely mechanism proposed to account for its occurrence. Dissolution rates generally increased with age for most melt compositions.
|
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] |
PMID:22616
|
Loss of antibacterial preservatives from contact lens solutions during storage.
|
The preservative content of 34 commercially available contact lens solutions has been determined. Over half of the solutions contained less than 90% of the stated preservative content. Storage tests conducted at 40 degrees, using both simulated and commercially available contact lens solutions in plastics containers of the type used to present these products showed that thiomersal and chlorbutol appeared to be sorbed by these containers in contrast to benzalkonium chloride and chlorhexidine gluconate which interacted mainly by a surface adsorption process. The extent of any interactions was dependent upon the type of plastics material used to fabricate the container.
|
Loss of antibacterial preservatives from contact lens solutions during storage. The preservative content of 34 commercially available contact lens solutions has been determined. Over half of the solutions contained less than 90% of the stated preservative content. Storage tests conducted at 40 degrees, using both simulated and commercially available contact lens solutions in plastics containers of the type used to present these products showed that thiomersal and chlorbutol appeared to be sorbed by these containers in contrast to benzalkonium chloride and chlorhexidine gluconate which interacted mainly by a surface adsorption process. The extent of any interactions was dependent upon the type of plastics material used to fabricate the container.
|
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] |
PMID:22617
|
The adhesion of film coatings to tablet surfaces--the effect of some direct compression excipients and lubricants.
|
The effect of some direct compression excipients and lubricants on the adhesion of hydroxypropyl methyl cellulose films has been examined using a specially designed tensile testing apparatus (Fisher & Rowe, 1976). The adhesion was found to be influenced by both the roughness, including microporosity, of the tablet surface and its polarity. Tablets prepared from microcrystalline cellulose showed very high adhesions despite having relatively smooth surfaces, owing to the surface being saturated with hydroxyl groups able to form hydrogen bonds with the corresponding groups on the polymer. The addition of magnesium or calcium stearate to the tablet was found to decrease the adhesion, but the addition of stearic acid caused a significant increase. The effect of lubricant concentration on the adhesion could be expressed by an equation similar to that proposed by Hofrichter & McLaren (1948) for the adhesion of vinyl chloride/vinyl acetate copolymers to regenerated cellulose.
|
The adhesion of film coatings to tablet surfaces--the effect of some direct compression excipients and lubricants. The effect of some direct compression excipients and lubricants on the adhesion of hydroxypropyl methyl cellulose films has been examined using a specially designed tensile testing apparatus (Fisher & Rowe, 1976). The adhesion was found to be influenced by both the roughness, including microporosity, of the tablet surface and its polarity. Tablets prepared from microcrystalline cellulose showed very high adhesions despite having relatively smooth surfaces, owing to the surface being saturated with hydroxyl groups able to form hydrogen bonds with the corresponding groups on the polymer. The addition of magnesium or calcium stearate to the tablet was found to decrease the adhesion, but the addition of stearic acid caused a significant increase. The effect of lubricant concentration on the adhesion could be expressed by an equation similar to that proposed by Hofrichter & McLaren (1948) for the adhesion of vinyl chloride/vinyl acetate copolymers to regenerated cellulose.
|
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] |
PMID:22619
|
The effects of p-chlorophenylalanine and ethanolamine-O-sulphate in an animal test of anxiety.
|
p-Chlorophenylalanine, which produces a depletion of brain 5-HT concentration, had effects qualitatively similar to those previously found with chronic chlordiazepoxide and with acute ethanol in the social interaction test of anxiety. This result is compatible with the idea that a reduced turnover of 5-HT is important in anxiety reduction. On the same test, ethanolamine-O-sulphate, which raises brain gamma-aminobutyric acid, was without effect, suggesting raised concentrations of this acid are not essential for anxiety reduction.
|
The effects of p-chlorophenylalanine and ethanolamine-O-sulphate in an animal test of anxiety. p-Chlorophenylalanine, which produces a depletion of brain 5-HT concentration, had effects qualitatively similar to those previously found with chronic chlordiazepoxide and with acute ethanol in the social interaction test of anxiety. This result is compatible with the idea that a reduced turnover of 5-HT is important in anxiety reduction. On the same test, ethanolamine-O-sulphate, which raises brain gamma-aminobutyric acid, was without effect, suggesting raised concentrations of this acid are not essential for anxiety reduction.
|
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] |
PMID:22621
|
Renal clearance procedure for the rat: effect of dopamine and standard saluretics.
|
Four standard diuretic compounds were evaluated for electrolyte output, effects on glomerular filtration rate (GFR), and effective renal plasma flow (RPF) in an anaesthetized rat preparation. Triamterene, hydrochlorothiazide, acetazoleamide and furosemide exerted their characteristic diuretic effects at doses which did not significantly change GFR or RPF. Regulation of the rate of a 3% mannitol-0.9% NaCl infusion to rats permitted the establishment of GFR and RPF values which were approximately in the middle of the reported range for this species. A significant increase in RPF without a concurrent rise in GFR was produced with dopamine. This was effectively blocked by the peripheral dopamine inhibitor, bulbocapnine.
|
Renal clearance procedure for the rat: effect of dopamine and standard saluretics. Four standard diuretic compounds were evaluated for electrolyte output, effects on glomerular filtration rate (GFR), and effective renal plasma flow (RPF) in an anaesthetized rat preparation. Triamterene, hydrochlorothiazide, acetazoleamide and furosemide exerted their characteristic diuretic effects at doses which did not significantly change GFR or RPF. Regulation of the rate of a 3% mannitol-0.9% NaCl infusion to rats permitted the establishment of GFR and RPF values which were approximately in the middle of the reported range for this species. A significant increase in RPF without a concurrent rise in GFR was produced with dopamine. This was effectively blocked by the peripheral dopamine inhibitor, bulbocapnine.
|
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0.01900189369916916,
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0.07857135683298111,
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] |
PMID:22622
|
Effect of drugs on rats exposed to cold--restraint stress.
|
The extent of protection afforded by over 40 drugs of various pharmacological groups against the development of gastric erosions induced in rats by a combination of cold and restraint has been investigated. Some drugs offered good protection, others had no effect on, or exacerbated, the lesions. Attempts are made to explain the mode of action of the protective drugs.
|
Effect of drugs on rats exposed to cold--restraint stress. The extent of protection afforded by over 40 drugs of various pharmacological groups against the development of gastric erosions induced in rats by a combination of cold and restraint has been investigated. Some drugs offered good protection, others had no effect on, or exacerbated, the lesions. Attempts are made to explain the mode of action of the protective drugs.
|
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] |
PMID:22623
|
Effects of pulmonary metabolites of prostaglandins E2 and F2alpha on guinea-pig respiratory tract.
|
The effects of three pulmonary metabolites of prostaglandins E2 and F2alpha on the guinea-pig tracheal muscle in vitro and on lung resistance in vivo were investigated. Prostaglandin F2alpha, 13,14-dihydro PGF2alpha and 13,14-dihydro 15-oxo PGF2alpha produced contractions on the tracheal muscle in vitro. 15-oxo PGF2alpha relaxed some tracheal preparations but stimulated others, the stimulant action having a threshold dose range some 10-25 times lower than the relaxant doses. Prostaglandin F2alpha and 13,14-dihydro PGF2alpha increased lung resistance in anaesthetized guinea-pigs. Prostaglandin E2 and its three pulmonary metabolites produced relaxation of guinea pig trachea in vitro and decreased lung resistance in vivo. All three metabolites were less active than PGE2 in both the systems. The in vitro effects of PGF2alpha and its metabolites were selectively blocked by polyphloretin phosphate.
|
Effects of pulmonary metabolites of prostaglandins E2 and F2alpha on guinea-pig respiratory tract. The effects of three pulmonary metabolites of prostaglandins E2 and F2alpha on the guinea-pig tracheal muscle in vitro and on lung resistance in vivo were investigated. Prostaglandin F2alpha, 13,14-dihydro PGF2alpha and 13,14-dihydro 15-oxo PGF2alpha produced contractions on the tracheal muscle in vitro. 15-oxo PGF2alpha relaxed some tracheal preparations but stimulated others, the stimulant action having a threshold dose range some 10-25 times lower than the relaxant doses. Prostaglandin F2alpha and 13,14-dihydro PGF2alpha increased lung resistance in anaesthetized guinea-pigs. Prostaglandin E2 and its three pulmonary metabolites produced relaxation of guinea pig trachea in vitro and decreased lung resistance in vivo. All three metabolites were less active than PGE2 in both the systems. The in vitro effects of PGF2alpha and its metabolites were selectively blocked by polyphloretin phosphate.
|
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] |
PMID:22624
|
Identification of the in vitro N-oxidized metabolites of (+)- and (-)-N-benzylamphetamine.
|
This study has identified (+)- and (-)-N-benzyl-N-hydroxyamphetamine as metabolites after incubation of both (+)- and (-)-N-benzylamphetamine with fortified rabbit liver homogenates. The isomeric hydroxylamine metabolites were identified using the techniques of g.l.c., t.l.c. and combined g.l.c.-mass spectrometry (ms) and by comparison with results from reference samples. An additional novel metabolic product was identified after incubation of N-benzylamphetamine which had properties consistent with that of N-benzyl-amphetamine nitrone.
|
Identification of the in vitro N-oxidized metabolites of (+)- and (-)-N-benzylamphetamine. This study has identified (+)- and (-)-N-benzyl-N-hydroxyamphetamine as metabolites after incubation of both (+)- and (-)-N-benzylamphetamine with fortified rabbit liver homogenates. The isomeric hydroxylamine metabolites were identified using the techniques of g.l.c., t.l.c. and combined g.l.c.-mass spectrometry (ms) and by comparison with results from reference samples. An additional novel metabolic product was identified after incubation of N-benzylamphetamine which had properties consistent with that of N-benzyl-amphetamine nitrone.
|
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] |
PMID:22717
|
Temperature dependence of the disintegration times of compressed tablets containing hydroxypropylcellulose as binder.
|
The dependence of the disintegration times of placebo and active tablets containing hydroxypropylcellulose (HPC), as binder on the temperature of the test medium in the region of 37 degrees is reported. The degree of temperature dependence varied with the HPC lot and concentration in the formulation of certain drugs, such as caffeine. The extent of the temperature dependence could be diminished by reducing the HPC concentration in the formulations. Corresponding trends were observed in drug release behaviour from some of these formulations. The effects observed were interpreted in terms of the thermodynamic behaviour of HPC systems and a specific drug-HPC interaction.
|
Temperature dependence of the disintegration times of compressed tablets containing hydroxypropylcellulose as binder. The dependence of the disintegration times of placebo and active tablets containing hydroxypropylcellulose (HPC), as binder on the temperature of the test medium in the region of 37 degrees is reported. The degree of temperature dependence varied with the HPC lot and concentration in the formulation of certain drugs, such as caffeine. The extent of the temperature dependence could be diminished by reducing the HPC concentration in the formulations. Corresponding trends were observed in drug release behaviour from some of these formulations. The effects observed were interpreted in terms of the thermodynamic behaviour of HPC systems and a specific drug-HPC interaction.
|
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] |
PMID:22718
|
A model for short term drug absorption studies; comparison of sulphadiazine tablets.
|
The four parameter equation, applicable to drug absorption kinetics over a limited time period, has been used to interpret plasma concentration, time results following oral dosage with three different formulations of sulphadiazine tablets, to each of five subjects. Assessment parameters for the formulations, the time for ten percent absorption, the time interval between 10-90% absorption and the plasma concentration with no disposition (relative availability) have been estimated. Intersubject variation obscured many of the differences between formulations. To blank off this variation, plasma concentrations at each time were averaged and then random variation corresponding to the error of the assay method was applied so as to generate a number of sets of data which including the mean concentrations was equal to the number of sets in the original measurements. Kinetic analysis of these sets indicated a number of significant differences between the formulations.
|
A model for short term drug absorption studies; comparison of sulphadiazine tablets. The four parameter equation, applicable to drug absorption kinetics over a limited time period, has been used to interpret plasma concentration, time results following oral dosage with three different formulations of sulphadiazine tablets, to each of five subjects. Assessment parameters for the formulations, the time for ten percent absorption, the time interval between 10-90% absorption and the plasma concentration with no disposition (relative availability) have been estimated. Intersubject variation obscured many of the differences between formulations. To blank off this variation, plasma concentrations at each time were averaged and then random variation corresponding to the error of the assay method was applied so as to generate a number of sets of data which including the mean concentrations was equal to the number of sets in the original measurements. Kinetic analysis of these sets indicated a number of significant differences between the formulations.
|
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] |
PMID:22719
|
Degradation of (--)-ephedrine in solution and during extraction with diethyl ether.
|
Significant losses occurred during the extraction of small quantities of ephedrine from aqueous media using either regular or analytical grades of diethyl ether. The losses were, at least in part, caused by reaction of the ephedrine with aldehydic impurities in the ether; three substituted oxazolidines were identified, using g.l.c. and g.l.c-ms. These and one other oxazolidine were synthesized and characterized by g.l.c., g.l.c.-ms, nmr and infrared spectroscopy. Alternative mechanisms for ephedrine breakdown were considered. Ephedrine was separately oxidized by three different oxidizing agents and also irradiated by ultraviolet light; the products were characterized by g.l.c., g.l.c.-ms. A method for the purification of diethyl ether is recommended to minimize ephedrine breakdown.
|
Degradation of (--)-ephedrine in solution and during extraction with diethyl ether. Significant losses occurred during the extraction of small quantities of ephedrine from aqueous media using either regular or analytical grades of diethyl ether. The losses were, at least in part, caused by reaction of the ephedrine with aldehydic impurities in the ether; three substituted oxazolidines were identified, using g.l.c. and g.l.c-ms. These and one other oxazolidine were synthesized and characterized by g.l.c., g.l.c.-ms, nmr and infrared spectroscopy. Alternative mechanisms for ephedrine breakdown were considered. Ephedrine was separately oxidized by three different oxidizing agents and also irradiated by ultraviolet light; the products were characterized by g.l.c., g.l.c.-ms. A method for the purification of diethyl ether is recommended to minimize ephedrine breakdown.
|
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] |
PMID:22720
|
Red cell cyanide.
|
The amount of cyanide released on acidifying whole blood was much greater than the total from the plasma and red cells assayed separately, and varied directly with plasma thiocyanate concentrations. This artifactual formation of cyanide by whole blood was reduced by exposure to carbon monoxide. Incubation of haemolysates of washed red blood cells showed that optimum cyanide production from thiocyanate occurred at pH 4.5 with none at pH 7.4; spectrophotometric study confirmed the involvement of haemoglobin. It is doubtful whether this activity of haemoglobin is of normal physiological importance and it is probable that the evidence for the enzyme, 'thiocyanate oxidase' was based on this artifact of assay. Plasma cyanide is probably the metabolically relevant measurement, since the red blood cells act as a 'cyanide sink'. Where values for whole blood cyanide are required we recommend separate assay of plasma and saline washed red blood cells.
|
Red cell cyanide. The amount of cyanide released on acidifying whole blood was much greater than the total from the plasma and red cells assayed separately, and varied directly with plasma thiocyanate concentrations. This artifactual formation of cyanide by whole blood was reduced by exposure to carbon monoxide. Incubation of haemolysates of washed red blood cells showed that optimum cyanide production from thiocyanate occurred at pH 4.5 with none at pH 7.4; spectrophotometric study confirmed the involvement of haemoglobin. It is doubtful whether this activity of haemoglobin is of normal physiological importance and it is probable that the evidence for the enzyme, 'thiocyanate oxidase' was based on this artifact of assay. Plasma cyanide is probably the metabolically relevant measurement, since the red blood cells act as a 'cyanide sink'. Where values for whole blood cyanide are required we recommend separate assay of plasma and saline washed red blood cells.
|
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] |
PMID:22721
|
Changes in muscarinic ligand binding to intestinal muscle strips produced by pre-exposure to hypotonic conditions.
|
The extent of the binding of [3H]propylbenzilylcholine mustard (3H-PrBCM) to muscarinic receptors in longitudinal muscle strips from guinea-pig small intestine is increased by nearly 50% when the strips are preexposed to distilled water before measurement of 3H-PrBCM binding in Krebs-Henseleit solution. The apparent rate constant for 3H-PrBCM-receptor complex formation is more than double that of intact strips. The curves for the inhibition of 3H-PrBCM binding by methylatropinium bromide in normal and treated strips are superimposable, but, in contrast, distilled water pretreatment shifts the inhibition curve for carbachol to lower concentrations by a factor of 5-6. The inhibition curve for methylfurmethide is also shifted, by a factor of approximately 4, but the effect on the curve for hexyltrimethylammonium (C6TMA) is slight. The relative inhibition produced by benzhexol in the two preparations was variable. Comparison of the rate of equilibration of benzhexol with muscarinic receptors in intact and in distilled water pretreated muscle indicates that this inconsistency is unlikely to be due to incomplete equilibration.
|
Changes in muscarinic ligand binding to intestinal muscle strips produced by pre-exposure to hypotonic conditions. The extent of the binding of [3H]propylbenzilylcholine mustard (3H-PrBCM) to muscarinic receptors in longitudinal muscle strips from guinea-pig small intestine is increased by nearly 50% when the strips are preexposed to distilled water before measurement of 3H-PrBCM binding in Krebs-Henseleit solution. The apparent rate constant for 3H-PrBCM-receptor complex formation is more than double that of intact strips. The curves for the inhibition of 3H-PrBCM binding by methylatropinium bromide in normal and treated strips are superimposable, but, in contrast, distilled water pretreatment shifts the inhibition curve for carbachol to lower concentrations by a factor of 5-6. The inhibition curve for methylfurmethide is also shifted, by a factor of approximately 4, but the effect on the curve for hexyltrimethylammonium (C6TMA) is slight. The relative inhibition produced by benzhexol in the two preparations was variable. Comparison of the rate of equilibration of benzhexol with muscarinic receptors in intact and in distilled water pretreated muscle indicates that this inconsistency is unlikely to be due to incomplete equilibration.
|
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] |
PMID:22722
|
Modification by monoamine oxidase inhibitors of the analgesic, hypothermic and toxic actions of morphine and pethidine in mice.
|
A single injection of phenelzine 100 mg kg-1 given 18 h before, decreased the analgesia and hypothermia induced by morphine, but potentiated the analgesic and hypothermic effects of pethidine, when the analgesics were administered either intraperitoneally, or intracerebroventricularly. The modification of pethidine analgesia and hypothermia, but not morphine analgesia, was antagonized by methysergide (10 mg lg-1, s.c.). The LD50 of pethidine, but not that of morphine, was 30-40% lower in mice treated with phenelzine tranylcypromine or iproniazid 6 h before the test. The increased lethality of a single dose of pethidine induced by phenelzine was also prevented by methysergide. Pretreatment of mice with 100 mg kg-1 phenelzine was followed by a significant rise in both brain tryptophan and 5-hydroxytryptamine (5-HT) concentrations which lasted for 24 h. Therefore, the changes in pethidine effects could have been due to raised brain tryptophan and 5-HT concentrations.
|
Modification by monoamine oxidase inhibitors of the analgesic, hypothermic and toxic actions of morphine and pethidine in mice. A single injection of phenelzine 100 mg kg-1 given 18 h before, decreased the analgesia and hypothermia induced by morphine, but potentiated the analgesic and hypothermic effects of pethidine, when the analgesics were administered either intraperitoneally, or intracerebroventricularly. The modification of pethidine analgesia and hypothermia, but not morphine analgesia, was antagonized by methysergide (10 mg lg-1, s.c.). The LD50 of pethidine, but not that of morphine, was 30-40% lower in mice treated with phenelzine tranylcypromine or iproniazid 6 h before the test. The increased lethality of a single dose of pethidine induced by phenelzine was also prevented by methysergide. Pretreatment of mice with 100 mg kg-1 phenelzine was followed by a significant rise in both brain tryptophan and 5-hydroxytryptamine (5-HT) concentrations which lasted for 24 h. Therefore, the changes in pethidine effects could have been due to raised brain tryptophan and 5-HT concentrations.
|
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] |
PMID:22723
|
Delay of castor oil diarrhoea in rats: a new way to evaluate inhibitors of prostaglandin biosynthesis.
|
Forty-four non-steroidal anti-inflammatory compounds were tested for possible effects on castor oil-induced diarrhoea in rats. A small but significant delay of intestinal evacuations was found with all compounds. Quantitatively, the oral doses required to delay diarrhoea beyond the first hour after castor oil challenge reflected the acute anti-inflammatory potency of the tested compounds. Qualitatively, the evolution of the effective doses with increasing delay was linear for potent inhibitors of prostaglandin biosynthesis. The evolution for less potent compounds was markedly different and suggested the earlier occurrence of non-specific drug effects. Suprofen, the most potent of the series of compounds, produced the 1 h delay at an oral dose of 1.11 mg kg-1; the ED50 increased linearly to 115 mg kg-1 for a 4 h delay. Compared with other compounds the activity pattern of suprofen was consistent with that of a very potent, short-acting inhibitor of prostaglandin biosynthesis, which maintains its specific action over a wide dose range. It is concluded that delay of castor oil-induced diarrhoea in rats allows a detailed characterization of aspirin-like compounds, and that inhibition of prostaglandin biosynthesis is insufficient to suppress the intestinal effects of the oil.
|
Delay of castor oil diarrhoea in rats: a new way to evaluate inhibitors of prostaglandin biosynthesis. Forty-four non-steroidal anti-inflammatory compounds were tested for possible effects on castor oil-induced diarrhoea in rats. A small but significant delay of intestinal evacuations was found with all compounds. Quantitatively, the oral doses required to delay diarrhoea beyond the first hour after castor oil challenge reflected the acute anti-inflammatory potency of the tested compounds. Qualitatively, the evolution of the effective doses with increasing delay was linear for potent inhibitors of prostaglandin biosynthesis. The evolution for less potent compounds was markedly different and suggested the earlier occurrence of non-specific drug effects. Suprofen, the most potent of the series of compounds, produced the 1 h delay at an oral dose of 1.11 mg kg-1; the ED50 increased linearly to 115 mg kg-1 for a 4 h delay. Compared with other compounds the activity pattern of suprofen was consistent with that of a very potent, short-acting inhibitor of prostaglandin biosynthesis, which maintains its specific action over a wide dose range. It is concluded that delay of castor oil-induced diarrhoea in rats allows a detailed characterization of aspirin-like compounds, and that inhibition of prostaglandin biosynthesis is insufficient to suppress the intestinal effects of the oil.
|
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] |
PMID:22731
|
Particle slippage and rearrangement during compression of pharmaceutical powders.
|
Compression data from different size fractions of lactose, chloroquine diphosphate, stearic acid and calcium carbonate have been analysed using the Walker and the Heckel compression equations. Points of inflection in graphs of log applied pressure vs the reciprocal of the packing fraction at low pressures corresponded closely to figures for theoretical packing conditions for equisized spheres and are attributed to a change in the stage of compression. The degree of particle slippage and rearrangement taking place during compression has been shown to increase as the particle size of the powder decreases and to be more extensive for powders composed of non-spherical particles. In addition, three types of compression behaviour have been distinguished for the four powders studied.
|
Particle slippage and rearrangement during compression of pharmaceutical powders. Compression data from different size fractions of lactose, chloroquine diphosphate, stearic acid and calcium carbonate have been analysed using the Walker and the Heckel compression equations. Points of inflection in graphs of log applied pressure vs the reciprocal of the packing fraction at low pressures corresponded closely to figures for theoretical packing conditions for equisized spheres and are attributed to a change in the stage of compression. The degree of particle slippage and rearrangement taking place during compression has been shown to increase as the particle size of the powder decreases and to be more extensive for powders composed of non-spherical particles. In addition, three types of compression behaviour have been distinguished for the four powders studied.
|
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] |
PMID:22737
|
Solid dispersions of nitrofurantoin, ethotoin, and coumarin with polyethylene glycol 6000 and their coprecipitates with providone 25,000.
|
The influence of two linear polymers, polyethylene glycol 6000 and povidone 25,000, on the dissolution rate of three poorly soluble drugs, nitrofurantoin, ethotoin, and coumarin, was studied. Povidone 25,000 produced better drug solubilization than polyethylene glycol 6000 with the drug-polymer ratios studied, and an increase in the weight fraction of either polymer gave more rapid dissolution. TLC and IR studies ruled out any interaction between the drugs and polyethylene glycol 6000. IR spectrophotometry provided evidence that there was complex formation between nitrofurantoin and povidone 25,000, probably via hydrogen bonding.
|
Solid dispersions of nitrofurantoin, ethotoin, and coumarin with polyethylene glycol 6000 and their coprecipitates with providone 25,000. The influence of two linear polymers, polyethylene glycol 6000 and povidone 25,000, on the dissolution rate of three poorly soluble drugs, nitrofurantoin, ethotoin, and coumarin, was studied. Povidone 25,000 produced better drug solubilization than polyethylene glycol 6000 with the drug-polymer ratios studied, and an increase in the weight fraction of either polymer gave more rapid dissolution. TLC and IR studies ruled out any interaction between the drugs and polyethylene glycol 6000. IR spectrophotometry provided evidence that there was complex formation between nitrofurantoin and povidone 25,000, probably via hydrogen bonding.
|
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] |
PMID:22738
|
General method for determining macrodissociation constants of polyprotic, amphoteric compounds from solubility measurements.
|
Equilibrium solubility and pH measurements can be used to determine macrodissociation constants of weak acids and bases of some highly insoluble substances. Equations are derived extending solubility, pH, and pKa (macroscopic) relationships to polyprotic, amphoteric substances. A general method for estimating pKa values, given a set of solubility and pH measurements, is presented. Included in the estimation procedure is a subroutine for approximating thermodynamic pKa values. The method was tested on two data sets (tyrosine and 2,3-dihydroxyadenine) and rendered pKa (thermodynamic) estimates in close agreement with those using other methods.
|
General method for determining macrodissociation constants of polyprotic, amphoteric compounds from solubility measurements. Equilibrium solubility and pH measurements can be used to determine macrodissociation constants of weak acids and bases of some highly insoluble substances. Equations are derived extending solubility, pH, and pKa (macroscopic) relationships to polyprotic, amphoteric substances. A general method for estimating pKa values, given a set of solubility and pH measurements, is presented. Included in the estimation procedure is a subroutine for approximating thermodynamic pKa values. The method was tested on two data sets (tyrosine and 2,3-dihydroxyadenine) and rendered pKa (thermodynamic) estimates in close agreement with those using other methods.
|
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] |
PMID:22739
|
l-Bunolol and propranolol: oral and intravenous beta-adrenoceptor blocking activity in rats compared to dogs and humans.
|
To determine the pharmacological significance of reported differences between species in l-bunolol metabolism, oral and intravenous beta-adrenoceptor blocking activity against an isoproterenol-induced tachycardia was compared in dogs, rats, and humans. Propranolol was similarly studied in rats and dogs. Species differences in intravenous potency were minimal for both compounds in contrast to oral dose studies. Oral to intravenous ratios of doses causing a comparable degree of beta-adrenoceptor blockade after l-bunolol were: rat, 212; dog 4; and human, 5. For propranolol, the oral to intravenous dose ratios were 210 and 32 for the rat and dog, respectively. These pharmacological findings show major differences in the rat compared to dogs and humans and may be explained in part by differences in the urinary excretion patterns of l-bunolol in the various species.
|
l-Bunolol and propranolol: oral and intravenous beta-adrenoceptor blocking activity in rats compared to dogs and humans. To determine the pharmacological significance of reported differences between species in l-bunolol metabolism, oral and intravenous beta-adrenoceptor blocking activity against an isoproterenol-induced tachycardia was compared in dogs, rats, and humans. Propranolol was similarly studied in rats and dogs. Species differences in intravenous potency were minimal for both compounds in contrast to oral dose studies. Oral to intravenous ratios of doses causing a comparable degree of beta-adrenoceptor blockade after l-bunolol were: rat, 212; dog 4; and human, 5. For propranolol, the oral to intravenous dose ratios were 210 and 32 for the rat and dog, respectively. These pharmacological findings show major differences in the rat compared to dogs and humans and may be explained in part by differences in the urinary excretion patterns of l-bunolol in the various species.
|
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] |
PMID:22740
|
Stability of tetrahydrocannabinols II.
|
The biphasic degradation of delta9-tetrahydrocannabinol (I), as monitored by flame-ionization GLC, produced delta8-tetrahydrocannabinol (II), cannabidiol (X), 9-hydroxyhexahydrocannabinol (VI), 9,10-dihydro-9-hydroxyisocannabidiol (VI), and and 6,12-dihydro-6-hydroxycannabidiol (VIII) in acidic solutions. Further identification was made by GLC, mass spectrometry, and comparison with authentic samples. Only II and IV were produced above pH 4 in the neutral region by first-order kinetics. The acidic degradation of cannabidiol (X) gave I and the products of the acidic degradation of I. The initial phase of acidic I degradation was assigned to the development of solvolytic equilibria among I, VIII, X, and, possibly, isocannabidiol (IX), with the concomitant production of II and IV. Compounds VIII, IX, and X did not appear in the neutral region since ether cleavage occurred only in strong mineral acids. Hydration of the delta9-double bond resulted only in acid-catalyzed equilibria of cleaved ethers with the delta8-configurations and characterized the second phase of acid degradation of I. Cannabinol and hexahydrocannabinol were found together in several cases due to the disproportionation of I as catalyzed by silicic acid, silica gel, and chloroform.
|
Stability of tetrahydrocannabinols II. The biphasic degradation of delta9-tetrahydrocannabinol (I), as monitored by flame-ionization GLC, produced delta8-tetrahydrocannabinol (II), cannabidiol (X), 9-hydroxyhexahydrocannabinol (VI), 9,10-dihydro-9-hydroxyisocannabidiol (VI), and and 6,12-dihydro-6-hydroxycannabidiol (VIII) in acidic solutions. Further identification was made by GLC, mass spectrometry, and comparison with authentic samples. Only II and IV were produced above pH 4 in the neutral region by first-order kinetics. The acidic degradation of cannabidiol (X) gave I and the products of the acidic degradation of I. The initial phase of acidic I degradation was assigned to the development of solvolytic equilibria among I, VIII, X, and, possibly, isocannabidiol (IX), with the concomitant production of II and IV. Compounds VIII, IX, and X did not appear in the neutral region since ether cleavage occurred only in strong mineral acids. Hydration of the delta9-double bond resulted only in acid-catalyzed equilibria of cleaved ethers with the delta8-configurations and characterized the second phase of acid degradation of I. Cannabinol and hexahydrocannabinol were found together in several cases due to the disproportionation of I as catalyzed by silicic acid, silica gel, and chloroform.
|
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] |
PMID:22741
|
The pH of brain extracellular fluid in the cat.
|
1. The blood supply to the medulla was determined by the injection of indian ink via the vertebral arteries. Virtually the whole medulla was supplied by penetrating vessels from the ventral surface. The highest density of small arterioles and venules was found close to the roots of XII and on the ventrolateral surface.2. The pH of extracellular fluid (pH(e.c.f.)) was measured with pH microelectrodes of tip size 1-3 mum in cortex and medulla in seventeen cats, anaesthetized with pentobarbitone or a chloralose-urethane mixture. Parallel measurements were made of the pH of c.s.f. and plasma, the DC potential between plasma and brain and ventilation or phrenic nerve discharge.3. In the majority of tests under steady conditions, the pH of e.c.f. was found to be lower than that of c.s.f. by between 0.03 and 0.08 units. No systematic pH gradients could be found to a depth of 5 mm beneath the surface of either medulla or cortex.4. When plasma P(CO2) was altered, pH(e.c.f.) changed with a latent period and speed of response related to the density of blood vessels. In vascular areas of the medulla and in the cortex, the latent period of 4 sec and the change of pH(e.c.f.) coincided with changes in ventilation. Changes in pH(c.s.f.) over the same areas were invariably slower.5. CO(2) buffering capacities were in the order plasma > e.c.f. > c.s.f. Typical values were respectively, -2.2, -2.1 and -1.6.6. The pH of e.c.f. was unaffected by the intravenous injection of H+ and only slowly by the injection of HCO(3)-. Only up to a depth of 1 mm beneath the surface was pH(e.c.f.) affected by superfusion of mock c.s.f. in the range 6.8-8.0 units. This response had a latent period of 2-3 min and was complete in 15 min.7. The pH of e.c.f. fell with hypoxia after a latent period of > 1 min and if all vasosensory nerves had been cut, pH(e.c.f.) was markedly affected by changes of blood pressure.8. These results indicate that even under steady conditions, the pH of e.c.f. and c.s.f. is not identical, that pH(e.c.f.) is more obviously affected by changes in P(a, CO2) than pH(c.s.f.) and that putative H+ sensors which drive respiratory neurones are likely to be similarly affected.
|
The pH of brain extracellular fluid in the cat. 1. The blood supply to the medulla was determined by the injection of indian ink via the vertebral arteries. Virtually the whole medulla was supplied by penetrating vessels from the ventral surface. The highest density of small arterioles and venules was found close to the roots of XII and on the ventrolateral surface.2. The pH of extracellular fluid (pH(e.c.f.)) was measured with pH microelectrodes of tip size 1-3 mum in cortex and medulla in seventeen cats, anaesthetized with pentobarbitone or a chloralose-urethane mixture. Parallel measurements were made of the pH of c.s.f. and plasma, the DC potential between plasma and brain and ventilation or phrenic nerve discharge.3. In the majority of tests under steady conditions, the pH of e.c.f. was found to be lower than that of c.s.f. by between 0.03 and 0.08 units. No systematic pH gradients could be found to a depth of 5 mm beneath the surface of either medulla or cortex.4. When plasma P(CO2) was altered, pH(e.c.f.) changed with a latent period and speed of response related to the density of blood vessels. In vascular areas of the medulla and in the cortex, the latent period of 4 sec and the change of pH(e.c.f.) coincided with changes in ventilation. Changes in pH(c.s.f.) over the same areas were invariably slower.5. CO(2) buffering capacities were in the order plasma > e.c.f. > c.s.f. Typical values were respectively, -2.2, -2.1 and -1.6.6. The pH of e.c.f. was unaffected by the intravenous injection of H+ and only slowly by the injection of HCO(3)-. Only up to a depth of 1 mm beneath the surface was pH(e.c.f.) affected by superfusion of mock c.s.f. in the range 6.8-8.0 units. This response had a latent period of 2-3 min and was complete in 15 min.7. The pH of e.c.f. fell with hypoxia after a latent period of > 1 min and if all vasosensory nerves had been cut, pH(e.c.f.) was markedly affected by changes of blood pressure.8. These results indicate that even under steady conditions, the pH of e.c.f. and c.s.f. is not identical, that pH(e.c.f.) is more obviously affected by changes in P(a, CO2) than pH(c.s.f.) and that putative H+ sensors which drive respiratory neurones are likely to be similarly affected.
|
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] |
PMID:22746
|
Effect of 4-aminopyridine on release of noradrenaline from the perfused cat spleen by nerve stimulation.
|
1. 4-aminopyridine (4-AP, 1 mM) increased noradrenaline (NA) output from the perfused cat spleen at 5 Hz by about fivefold. Enhancement of NA release by 4-AP was reversible. Output of NA induced by potassium was not affected. 2. NA output was doubled at low concentrations (0.1--0.3 mM) of 4-AP, but maximal effect was obtained at 1--3 mM. At 10 mM, it induced spontaneous release of NA which was insensitive to calcium. 3. Insignificant outputs obtained at 5 Hz in 0.1 and 0.3 mM calcium-Krebs solution were markedly enhanced by 4-AP. 4-AP enhanced release at all calcium concentrations up to 5 mM, but maximum output was obtained at 2.5 mM. 4. 4-AP at pH 8.5 was more effective in enhancing NA release than at pH 7.4. 5. 4-AP increased the recovery of intra-arterially infused NA from the control 26 to 47%. 6. 4-AP did not affect release of catecholamines (CA) from the perfused cat adrenal gland by acetylcholine (ACh). 7. It is suggested that 4-AP inactivates potassium current in sympathetic nerves and prolongs the duration of the action potential, thereby allowing a greater influx of calcium ions into the neurone to enhance release of NA.
|
Effect of 4-aminopyridine on release of noradrenaline from the perfused cat spleen by nerve stimulation. 1. 4-aminopyridine (4-AP, 1 mM) increased noradrenaline (NA) output from the perfused cat spleen at 5 Hz by about fivefold. Enhancement of NA release by 4-AP was reversible. Output of NA induced by potassium was not affected. 2. NA output was doubled at low concentrations (0.1--0.3 mM) of 4-AP, but maximal effect was obtained at 1--3 mM. At 10 mM, it induced spontaneous release of NA which was insensitive to calcium. 3. Insignificant outputs obtained at 5 Hz in 0.1 and 0.3 mM calcium-Krebs solution were markedly enhanced by 4-AP. 4-AP enhanced release at all calcium concentrations up to 5 mM, but maximum output was obtained at 2.5 mM. 4. 4-AP at pH 8.5 was more effective in enhancing NA release than at pH 7.4. 5. 4-AP increased the recovery of intra-arterially infused NA from the control 26 to 47%. 6. 4-AP did not affect release of catecholamines (CA) from the perfused cat adrenal gland by acetylcholine (ACh). 7. It is suggested that 4-AP inactivates potassium current in sympathetic nerves and prolongs the duration of the action potential, thereby allowing a greater influx of calcium ions into the neurone to enhance release of NA.
|
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] |
PMID:22748
|
Pyrazolodiazepines. 2. 4-Aryl-1,3-dialkyl-6,8-dihydropyrazolo[3,4-e] [1,4]diazepin-7(1H)-ones as antianxiety and anticonvulsant agents.
|
A series of 4-aryl-1,3-dialkyl-6,8-dihydropyrazolo[3,4-e] [1,4]diazepin-7(1H)-ones was synthesized and screened for psychotropic activity. In animals, a number of these pyrazolodiazepinones had strong CNS effects similar to diazepam. One compound, 4-(2-fluorophenyl)-6,8-dihydro-1,3,8-trimethylpyrazolo[3,4-e] [1,4]diazepin-7(1H)-one (54), is being studied in the clinic as a component of a new animal anesthetic, Tilazol.
|
Pyrazolodiazepines. 2. 4-Aryl-1,3-dialkyl-6,8-dihydropyrazolo[3,4-e] [1,4]diazepin-7(1H)-ones as antianxiety and anticonvulsant agents. A series of 4-aryl-1,3-dialkyl-6,8-dihydropyrazolo[3,4-e] [1,4]diazepin-7(1H)-ones was synthesized and screened for psychotropic activity. In animals, a number of these pyrazolodiazepinones had strong CNS effects similar to diazepam. One compound, 4-(2-fluorophenyl)-6,8-dihydro-1,3,8-trimethylpyrazolo[3,4-e] [1,4]diazepin-7(1H)-one (54), is being studied in the clinic as a component of a new animal anesthetic, Tilazol.
|
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] |
PMID:22749
|
Synthetic models of deoxyribonucleic acid complexes with antimalarial compounds. 3. Forces involved in the stacking interaction between aminoquinoline and the nucleotide bases.
|
As an approach to the problem of the nature of the forces responsible for the stacking interactions between the aminoquinoline ring of the antimalarial chloroquine and the monomeric nucleotide bases, we have examined models in which the aromatic nucleus of the drug is linked to the nucleotide bases by a trimethylene chain. The degree of stacking of the models was determined in different conditions of solvent, pH, and temperature by hypochromism measurement in the UV. The results show that forces of the donor-acceptor type, due to the presence of a positive charge on the quinoline ring at neutral pH, do not bring an important contribution to the stacking interaction between the aminoquinoline and the nucleotide bases, while the influence of the solvent water is fundamental.
|
Synthetic models of deoxyribonucleic acid complexes with antimalarial compounds. 3. Forces involved in the stacking interaction between aminoquinoline and the nucleotide bases. As an approach to the problem of the nature of the forces responsible for the stacking interactions between the aminoquinoline ring of the antimalarial chloroquine and the monomeric nucleotide bases, we have examined models in which the aromatic nucleus of the drug is linked to the nucleotide bases by a trimethylene chain. The degree of stacking of the models was determined in different conditions of solvent, pH, and temperature by hypochromism measurement in the UV. The results show that forces of the donor-acceptor type, due to the presence of a positive charge on the quinoline ring at neutral pH, do not bring an important contribution to the stacking interaction between the aminoquinoline and the nucleotide bases, while the influence of the solvent water is fundamental.
|
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] |
PMID:22750
|
beta-Adrenergic blocking agents. 17. 1-Phenoxy-3-phenoxyalkylamino-2-propanols and 1-alkoxyalkylamino-3-phenoxy-2-propanols.
|
The synthesis is described of a series of derivatives of 1-phenoxy-3-phenoxyalkylamino-2-propanols and 1-alkoxyalkylamino-3-phenoxy-2-propranols. The compounds were investigated for their beta-adrenoceptor blocking properties and many showed a surprising degree of cardioselectivity when tested in vivo in anesthetized cats for their effects on an isoproterenol-induced tachycardia and depressor response. The structure-activity relationship shown by this series of compounds is related to that of known cardioselective analogues and a possible reason for their cardioselectivity is discussed.
|
beta-Adrenergic blocking agents. 17. 1-Phenoxy-3-phenoxyalkylamino-2-propanols and 1-alkoxyalkylamino-3-phenoxy-2-propanols. The synthesis is described of a series of derivatives of 1-phenoxy-3-phenoxyalkylamino-2-propanols and 1-alkoxyalkylamino-3-phenoxy-2-propranols. The compounds were investigated for their beta-adrenoceptor blocking properties and many showed a surprising degree of cardioselectivity when tested in vivo in anesthetized cats for their effects on an isoproterenol-induced tachycardia and depressor response. The structure-activity relationship shown by this series of compounds is related to that of known cardioselective analogues and a possible reason for their cardioselectivity is discussed.
|
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] |
PMID:22751
|
Synthesis and beta-adrenergic blocking activity of a novel class of aromatic oxime ethers.
|
A new series of beta-adrenergic blocking amines containing an oximino-propanolic chain linked to an aromatic nucleus was synthesized. Most of the derivatives are characterized by beta2-selectivity. The structure-activity relationship are discussed. One of the compounds, selected for further studies, was more active on the trachea than on the atria of guinea pig, 155 times in vitro and 26 times in vivo. In comparison, butoxamine's beta2-selectivity is 13 in vitro and only 2 in vivo. With a series of 30 acetophenone oxime derivatives, no quantitative structure-activity relationships could be detected.
|
Synthesis and beta-adrenergic blocking activity of a novel class of aromatic oxime ethers. A new series of beta-adrenergic blocking amines containing an oximino-propanolic chain linked to an aromatic nucleus was synthesized. Most of the derivatives are characterized by beta2-selectivity. The structure-activity relationship are discussed. One of the compounds, selected for further studies, was more active on the trachea than on the atria of guinea pig, 155 times in vitro and 26 times in vivo. In comparison, butoxamine's beta2-selectivity is 13 in vitro and only 2 in vivo. With a series of 30 acetophenone oxime derivatives, no quantitative structure-activity relationships could be detected.
|
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] |
PMID:22752
|
Synthesis of heteroaromatic potential beta-adrenergic antagonists by the glycidol route.
|
The synthesis of several 3-alkylamino-2-hydroxypropyl heteroaryl ethers (13-15, 17, and 18) is described. These compounds were prepared by the alkylamination of the corresponding glycidyl ethers (6-8, 10, and 11), which in turn were obtained from the requisite heteroaryl halides and the sodium salt of glycidol. The above basic ethers exhibited beta-blocking activity, but the potency of the tested compounds was considerably less than that of propanolol. Only 3-tert-butylamino-2-hydroxyl-1-(1,2,4-thiadiazol-5-yl) propyl ether (13) showed some selective myocardial beta-blocking activity.
|
Synthesis of heteroaromatic potential beta-adrenergic antagonists by the glycidol route. The synthesis of several 3-alkylamino-2-hydroxypropyl heteroaryl ethers (13-15, 17, and 18) is described. These compounds were prepared by the alkylamination of the corresponding glycidyl ethers (6-8, 10, and 11), which in turn were obtained from the requisite heteroaryl halides and the sodium salt of glycidol. The above basic ethers exhibited beta-blocking activity, but the potency of the tested compounds was considerably less than that of propanolol. Only 3-tert-butylamino-2-hydroxyl-1-(1,2,4-thiadiazol-5-yl) propyl ether (13) showed some selective myocardial beta-blocking activity.
|
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] |
PMID:22753
|
(1-(3-(Phenothiazin-10-yl)propyl)-4-piperidinyl)phenylmethanones, a novel class of long-acting neuroleptic agents.
|
In previous studies the phenyl-4-piperidinylmethanone moiety was shown to be a neuroleptic pharmacophore. A short series of [1-[3-(phenothiazin-10-yl)propyl]-4-piperidinyl]phenylmethanones was prepared and tested for neuroleptic activity using the blockade of d-amphetamine lethality in aggregated mice and suppression of conditioned avoidance behavior as the end points. Most compounds were shown to be potent neuroleptic agents and two were found to possess a long duration of action.
|
(1-(3-(Phenothiazin-10-yl)propyl)-4-piperidinyl)phenylmethanones, a novel class of long-acting neuroleptic agents. In previous studies the phenyl-4-piperidinylmethanone moiety was shown to be a neuroleptic pharmacophore. A short series of [1-[3-(phenothiazin-10-yl)propyl]-4-piperidinyl]phenylmethanones was prepared and tested for neuroleptic activity using the blockade of d-amphetamine lethality in aggregated mice and suppression of conditioned avoidance behavior as the end points. Most compounds were shown to be potent neuroleptic agents and two were found to possess a long duration of action.
|
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] |
PMID:22754
|
Potential inhibitors of L-asparagine biosynthesis. 4. Substituted sulfonamide and sulfonylhydrazide analogues of L-asparagine.
|
Several N-substituted sulfonamides and N'-substituted sulfonylhydrazides have been prepared as sulfur analogues of L-asparagine with the potential of acting as inhibitors of L-asparagine synthetase (ASase, from Novikoff hepatoma). L-Cysteine was converted in known steps to N-carboxy-3-(sulfonylchloro)-L-alanine dibenzyl ester (1). Condensation of 1 with O-benzylhydroxylamine, p-(fluorosulfonyl)benzylamine, or monoethyl fumarylhydrazide (9), followed by deblocking with HF, gave 3-(hydroxysulfamoyl)-L-alanine (3a), 3-[p-(fluorosulfonylbenzyl)]sulfamoyl-L-alanine (3c), and 3-sulfo-L-alanine S-[2-[(E)-3-(ethoxycarbonyl)acryloyl]hydrazide] (3e), respectively. Similarly, 1 with 2-chloroethylamine and deblocking with H2-Pd gave 3-[(2-chloroethyl)sulfamoyl]-L-alanine (3b). tert-Butyl carbazate was allowed to react with 1 and the tert-butyl group was removed with HCl. The resulting sulfonylhydrazide 7 was condensed with p-(fluorosulfonyl)benzoyl chloride and then deblocked with HF to give 3-sulfo-L-alanine S-[2-[P-(fluorosulfonyl)benzoyl]hydrazide] (3d). The inhibition of ASase by 3a-e at 2 mM was 97, 0, 30, 43, and 37%, respectively, and 3a was competitive with L-aspartic acid. Neither 3a nor 3e was effective in increasing the life span of mice bearing P-388 lymphocytic leukemia.
|
Potential inhibitors of L-asparagine biosynthesis. 4. Substituted sulfonamide and sulfonylhydrazide analogues of L-asparagine. Several N-substituted sulfonamides and N'-substituted sulfonylhydrazides have been prepared as sulfur analogues of L-asparagine with the potential of acting as inhibitors of L-asparagine synthetase (ASase, from Novikoff hepatoma). L-Cysteine was converted in known steps to N-carboxy-3-(sulfonylchloro)-L-alanine dibenzyl ester (1). Condensation of 1 with O-benzylhydroxylamine, p-(fluorosulfonyl)benzylamine, or monoethyl fumarylhydrazide (9), followed by deblocking with HF, gave 3-(hydroxysulfamoyl)-L-alanine (3a), 3-[p-(fluorosulfonylbenzyl)]sulfamoyl-L-alanine (3c), and 3-sulfo-L-alanine S-[2-[(E)-3-(ethoxycarbonyl)acryloyl]hydrazide] (3e), respectively. Similarly, 1 with 2-chloroethylamine and deblocking with H2-Pd gave 3-[(2-chloroethyl)sulfamoyl]-L-alanine (3b). tert-Butyl carbazate was allowed to react with 1 and the tert-butyl group was removed with HCl. The resulting sulfonylhydrazide 7 was condensed with p-(fluorosulfonyl)benzoyl chloride and then deblocked with HF to give 3-sulfo-L-alanine S-[2-[P-(fluorosulfonyl)benzoyl]hydrazide] (3d). The inhibition of ASase by 3a-e at 2 mM was 97, 0, 30, 43, and 37%, respectively, and 3a was competitive with L-aspartic acid. Neither 3a nor 3e was effective in increasing the life span of mice bearing P-388 lymphocytic leukemia.
|
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] |
PMID:22755
|
Selective monoamine oxidase inhibitors. 1. Compounds related to 4-aminophenethylamine.
|
A series of derivatives of 4-aminophenethylamine was synthesized and their effect on monoamine oxidase (MAO) activity in the brain was evaluated. Several of the new compounds were potent and selective inhibitors of the A form of MAO but were poor inhibitors of the B form. The most active compounds were the 2,6-dichloro-(9) and the 2-halogeno-4-dimethylaminophenethylamines (5, 6, and 8). Some of the compounds also strongly antagonized aggressive behavior in isolated male mice. This effect was correlated to the MAO inhibition when tyramine was used as substrate. Significant correlations between MAO inhibition in vivo and potentiation of the syndromes produced by 5-hydroxytryptophan and tryptamine and antagonism of reserpine sedation were obtained.
|
Selective monoamine oxidase inhibitors. 1. Compounds related to 4-aminophenethylamine. A series of derivatives of 4-aminophenethylamine was synthesized and their effect on monoamine oxidase (MAO) activity in the brain was evaluated. Several of the new compounds were potent and selective inhibitors of the A form of MAO but were poor inhibitors of the B form. The most active compounds were the 2,6-dichloro-(9) and the 2-halogeno-4-dimethylaminophenethylamines (5, 6, and 8). Some of the compounds also strongly antagonized aggressive behavior in isolated male mice. This effect was correlated to the MAO inhibition when tyramine was used as substrate. Significant correlations between MAO inhibition in vivo and potentiation of the syndromes produced by 5-hydroxytryptophan and tryptamine and antagonism of reserpine sedation were obtained.
|
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] |
PMID:22756
|
Adrenoceptor blocking agents. 2. 2-(alpha-Hydroxyarylmethyl)-3,3-dimethylaziridines, a new class of selective beta2-adrenoceptor antagonists.
|
Threo- and erythro-2-(alpha-hydroxybenzyl)-3,3-dimethylaziridines (1a and 1b) and threo-2-[alpha-hydroxy(2-naphthyl)methyl]- and 2-[alpha-hydroxy(3,4-dichlorobenzyl)]-3,3-dimethylaziridines (1d and 1c) have been prepared as conformationally restricted analogues of beta-adrenoceptor blocking agents like dichloroisoproterenol (DCI) and pronethalol. The aziridine analogues 1 except possibly 1c are competitive antagonists of isoproterenol-induced response on a guinea pig tracheal chain preparation and the order of potency is 1d greater than 1a greater than or equal to 1b greater than propranolol greater than 1c. Unlike propranolol, these compounds have no effect on the isoproterenol-induced response on guinea pig auricles and no significant local anesthetic and antiarrhythmic activity. The aziridine analogues 1 represent the first of a new class of selective beta2-adrenoceptor blocking agents.
|
Adrenoceptor blocking agents. 2. 2-(alpha-Hydroxyarylmethyl)-3,3-dimethylaziridines, a new class of selective beta2-adrenoceptor antagonists. Threo- and erythro-2-(alpha-hydroxybenzyl)-3,3-dimethylaziridines (1a and 1b) and threo-2-[alpha-hydroxy(2-naphthyl)methyl]- and 2-[alpha-hydroxy(3,4-dichlorobenzyl)]-3,3-dimethylaziridines (1d and 1c) have been prepared as conformationally restricted analogues of beta-adrenoceptor blocking agents like dichloroisoproterenol (DCI) and pronethalol. The aziridine analogues 1 except possibly 1c are competitive antagonists of isoproterenol-induced response on a guinea pig tracheal chain preparation and the order of potency is 1d greater than 1a greater than or equal to 1b greater than propranolol greater than 1c. Unlike propranolol, these compounds have no effect on the isoproterenol-induced response on guinea pig auricles and no significant local anesthetic and antiarrhythmic activity. The aziridine analogues 1 represent the first of a new class of selective beta2-adrenoceptor blocking agents.
|
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] |
PMID:22757
|
Antidepressant agents. 9. 3,3-Diphenylcyclobutylamines, a new class of central stimulants.
|
3,3-Diphenylcyclobutylamine (4), N-methyl-3,3-diphenylcyclobutylamine (6), and N,N-dimethyl-3,3-diphenyl-cyclobutylamine (7) have been prepared and tested as potential antidepressant agents. The secondary (6) and tertiary (7) amines strongly decrease the accumulation of NA and 5-HT in brain slices in vitro and in vivo. The cyclobutylamines also cause motor stimulation. The most potent compound in this respect is the tertiary amine 7. The increase in locomotion is not blocked by pretreatment with phenoxybenzamine, methergoline, or alpha-methyltyrosine. Pretreatment with pimozide or reserpine reduces the hyperactivity induced by 7. This hyperstimulation seems to be caused by a mechanism of action which differs from that of amphetamine. 7 may cause increase in locomotion by release of dopamine from granular stores.
|
Antidepressant agents. 9. 3,3-Diphenylcyclobutylamines, a new class of central stimulants. 3,3-Diphenylcyclobutylamine (4), N-methyl-3,3-diphenylcyclobutylamine (6), and N,N-dimethyl-3,3-diphenyl-cyclobutylamine (7) have been prepared and tested as potential antidepressant agents. The secondary (6) and tertiary (7) amines strongly decrease the accumulation of NA and 5-HT in brain slices in vitro and in vivo. The cyclobutylamines also cause motor stimulation. The most potent compound in this respect is the tertiary amine 7. The increase in locomotion is not blocked by pretreatment with phenoxybenzamine, methergoline, or alpha-methyltyrosine. Pretreatment with pimozide or reserpine reduces the hyperactivity induced by 7. This hyperstimulation seems to be caused by a mechanism of action which differs from that of amphetamine. 7 may cause increase in locomotion by release of dopamine from granular stores.
|
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] |
PMID:22758
|
Disseminated intravascular coagulopathy during experimental pneumococcal sepsis: studies in normal and asplenic rhesus monkeys.
|
Disseminated intravascular coagulation (DIC) was induced in both normal and asplenic rhesus monkeys by intravenous challenge with Streptococcus pneumoniae. Our observations in the infected monkeys have led us to conclude that (1) pneumococcal capsular polysaccharide (PCP), immune complexes and complement may not have primary roles in the initiation of DIC; (2) intact pneumococci may be catalysts for the development of DIC; (3) the initial event in DIC may be activation of Hageman factor; and (4) evidence of activation of Hageman factor-dependent systems is present regardless of severity of infection.
|
Disseminated intravascular coagulopathy during experimental pneumococcal sepsis: studies in normal and asplenic rhesus monkeys. Disseminated intravascular coagulation (DIC) was induced in both normal and asplenic rhesus monkeys by intravenous challenge with Streptococcus pneumoniae. Our observations in the infected monkeys have led us to conclude that (1) pneumococcal capsular polysaccharide (PCP), immune complexes and complement may not have primary roles in the initiation of DIC; (2) intact pneumococci may be catalysts for the development of DIC; (3) the initial event in DIC may be activation of Hageman factor; and (4) evidence of activation of Hageman factor-dependent systems is present regardless of severity of infection.
|
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] |
PMID:22764
|
A sexual-enhancement workshop: beyond group systematic desensitization for women's sexual anxiety.
|
This study investigated whether six women who previously had received 15 sessions of group systematic desensitization (SD) for their sexual anxiety would report additional treatment gains from participation in a sexual-enhancement workshop with their partners. After group SD six couples participated in six, 1 1/2 hour weekly group sessions. The women reported a significant increase in marital adjustment and a significant decrease in sexual anxiety. A significant decrease was found in the women's sexual nonresponsiveness as perceived by their partners. Future studies should (1) contrast the effects of group SD with women alone versus couple group treatment, (2) determine which treatment components are most influential for defined subject types, and (3) obtain data on men's sexual functioning.
|
A sexual-enhancement workshop: beyond group systematic desensitization for women's sexual anxiety. This study investigated whether six women who previously had received 15 sessions of group systematic desensitization (SD) for their sexual anxiety would report additional treatment gains from participation in a sexual-enhancement workshop with their partners. After group SD six couples participated in six, 1 1/2 hour weekly group sessions. The women reported a significant increase in marital adjustment and a significant decrease in sexual anxiety. A significant decrease was found in the women's sexual nonresponsiveness as perceived by their partners. Future studies should (1) contrast the effects of group SD with women alone versus couple group treatment, (2) determine which treatment components are most influential for defined subject types, and (3) obtain data on men's sexual functioning.
|
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] |
PMID:22766
|
Transcriptase activity associated with rabies virion.
|
Rabies virion-associated transcriptase activity was investigated in vitro and compared with that of the New Jersey serotype of vesicular stomatitis virus. The concentration of detergent that affected [3H]GMP incoporation into acid-insoluble material was significantly different for both viruses. Vesicular stomatitis virus New Jersey required 0.05 to 0.1% nonionic detergent, whereas rabies virion could not be fully activated unless 4 to 5% detergent was used. Other optimal conditions were as follows: 40 mM NaCl, 5 mM Mg2+, 40 mM Tris-hydrochloride (pH 7.4), 5 mM dithiothreitol, and 30 degrees C. The reaction required four nucleoside triphosphates. The initial rate of RNA synthesis by rabies virion enzyme was 140 pmol of GMP incorporated/mg of viral protein per h and linearly increased until about 8 h, with a slight initial lag phase. The enzyme activity that correlated with the content of L protein was highest when rabies virions were grown at 33 degrees C. The product was single-stranded RNA, which was complementary in base sequences to rabies viral RNA. Most of the RNA synthesized sedimented at 6-16S.
|
Transcriptase activity associated with rabies virion. Rabies virion-associated transcriptase activity was investigated in vitro and compared with that of the New Jersey serotype of vesicular stomatitis virus. The concentration of detergent that affected [3H]GMP incoporation into acid-insoluble material was significantly different for both viruses. Vesicular stomatitis virus New Jersey required 0.05 to 0.1% nonionic detergent, whereas rabies virion could not be fully activated unless 4 to 5% detergent was used. Other optimal conditions were as follows: 40 mM NaCl, 5 mM Mg2+, 40 mM Tris-hydrochloride (pH 7.4), 5 mM dithiothreitol, and 30 degrees C. The reaction required four nucleoside triphosphates. The initial rate of RNA synthesis by rabies virion enzyme was 140 pmol of GMP incorporated/mg of viral protein per h and linearly increased until about 8 h, with a slight initial lag phase. The enzyme activity that correlated with the content of L protein was highest when rabies virions were grown at 33 degrees C. The product was single-stranded RNA, which was complementary in base sequences to rabies viral RNA. Most of the RNA synthesized sedimented at 6-16S.
|
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] |
PMID:22767
|
The increasing incidence of Ampicillin-resistant Haemophilus influenzae. A cause of otitis media.
|
Middle ear exudate was obtained by myringotomy or aspiration from 625 suburban children, aged 1 month to 12 years, who had acute otitis media; bacterial pathogens were isolated from 71%. Haemophilus species were isolated from 212 (29%), and Streptococcus pneumoniae from 205 (28%). From 1975 to August 1977, the number of Haemophilus isolates found to be resistant to ampicillin has appreciably increased. Currently, 8% of all cases of acute otitis media in the Washington, DC, area are due to H influenzae resistant to ampicillin. Thirty-one of 35 patients with resistant H influenzae otitis were treated with an erythromycin/sulfisoxazole combination with an impressive clinical response. Twenty-six of these 31 cases had failed to have H influenzae eradicated by an average of ten days of oral ampicillin in recommended doses.
|
The increasing incidence of Ampicillin-resistant Haemophilus influenzae. A cause of otitis media. Middle ear exudate was obtained by myringotomy or aspiration from 625 suburban children, aged 1 month to 12 years, who had acute otitis media; bacterial pathogens were isolated from 71%. Haemophilus species were isolated from 212 (29%), and Streptococcus pneumoniae from 205 (28%). From 1975 to August 1977, the number of Haemophilus isolates found to be resistant to ampicillin has appreciably increased. Currently, 8% of all cases of acute otitis media in the Washington, DC, area are due to H influenzae resistant to ampicillin. Thirty-one of 35 patients with resistant H influenzae otitis were treated with an erythromycin/sulfisoxazole combination with an impressive clinical response. Twenty-six of these 31 cases had failed to have H influenzae eradicated by an average of ten days of oral ampicillin in recommended doses.
|
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] |
PMID:22768
|
Inhibition by cyanide of drug oxidations in rat liver microsomes.
|
Cyanide inhibited microsomal activities of aniline hydroxylation and aminopyrine, ethylmorphine and codeine demethylations and produced a modified type II difference spectrum of cytochrome P-450 to give two spectral dissociation constants, 0.21mM and 1.05 mM. The binding of cyanide to cytochrome P-450 resulted in innhibition of NADPH-cytochrome P-450 reductase activity. The cyanide inhibition of drug oxidations was partially avoided by increasing oxygen tension. A possible mechanism for the inhibition of drug oxidations by cyanide is discussed.
|
Inhibition by cyanide of drug oxidations in rat liver microsomes. Cyanide inhibited microsomal activities of aniline hydroxylation and aminopyrine, ethylmorphine and codeine demethylations and produced a modified type II difference spectrum of cytochrome P-450 to give two spectral dissociation constants, 0.21mM and 1.05 mM. The binding of cyanide to cytochrome P-450 resulted in innhibition of NADPH-cytochrome P-450 reductase activity. The cyanide inhibition of drug oxidations was partially avoided by increasing oxygen tension. A possible mechanism for the inhibition of drug oxidations by cyanide is discussed.
|
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] |
PMID:22769
|
Impaired maturation of pre-synaptic cholinergic nerve terminals in the superior cervical ganglia after administration of guanethidine and dexamethasone.
|
The role of post-synaptic cells in the development of pre-synaptic cholinergic nerve terminals has been investigated in immature rat superior cervical ganglia (SCG) and adrenals employing chemical agents which prevent the normal maturation of post-synaptic cells. A marked atrophy of ganglion adrenergic neurons after guanethidine administration was accompanied by the complete failure of normal maturation of choline acetyltransferase (ChAc) activity in the presynaptic endings. However, the same treatment failed to alter the levels of ChAc in the mature ganglia despite the marked atrophy of adrenergic neurons. Administration of dexamethasone resulted in a growth retardation of ganglion neurons as well as adrenal chromaffin cells reflected by the lower levels of tyrosine hydroxylase and dopamine-beta-hydroxylase than those in untreated tissues. The levels of ChAc were significantly lower in the ganglia, but not in the adrenals when treatment was started immediately after birth. These results support the view that the normal synapse formation in the SCG depends on the normal maturation of adrenergic neurons, and suggest that this dependence is detectable only during a limited period of life.
|
Impaired maturation of pre-synaptic cholinergic nerve terminals in the superior cervical ganglia after administration of guanethidine and dexamethasone. The role of post-synaptic cells in the development of pre-synaptic cholinergic nerve terminals has been investigated in immature rat superior cervical ganglia (SCG) and adrenals employing chemical agents which prevent the normal maturation of post-synaptic cells. A marked atrophy of ganglion adrenergic neurons after guanethidine administration was accompanied by the complete failure of normal maturation of choline acetyltransferase (ChAc) activity in the presynaptic endings. However, the same treatment failed to alter the levels of ChAc in the mature ganglia despite the marked atrophy of adrenergic neurons. Administration of dexamethasone resulted in a growth retardation of ganglion neurons as well as adrenal chromaffin cells reflected by the lower levels of tyrosine hydroxylase and dopamine-beta-hydroxylase than those in untreated tissues. The levels of ChAc were significantly lower in the ganglia, but not in the adrenals when treatment was started immediately after birth. These results support the view that the normal synapse formation in the SCG depends on the normal maturation of adrenergic neurons, and suggest that this dependence is detectable only during a limited period of life.
|
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] |
PMID:22771
|
Enhancement of NADPH-dependent lipid peroxidation activity by ethylene-diamineteraacetic acid (EDTA) in the presence of ferrous ion in rabbit liver microsomes.
|
The addition of EDTA to the incubation mixture containing rabbit liver microsomes and ferrous ion resulted in 2-fold increase of lipid peroxidation activity. Such an enhancement was not observed in rat liver microsomes. The maximum lipid peroxidation activity seen in rabbit microsomes in the presence of EDTA and ferrous ion was about 80% that seen in rat liver microsomes. From these results, it is likely that low lipid peroxidation activity in rabbit liver microsomes may account for the insufficiency of an EDTA-LIKE FACTORS(S) IN RABBIT LIVER MICROSOMES.
|
Enhancement of NADPH-dependent lipid peroxidation activity by ethylene-diamineteraacetic acid (EDTA) in the presence of ferrous ion in rabbit liver microsomes. The addition of EDTA to the incubation mixture containing rabbit liver microsomes and ferrous ion resulted in 2-fold increase of lipid peroxidation activity. Such an enhancement was not observed in rat liver microsomes. The maximum lipid peroxidation activity seen in rabbit microsomes in the presence of EDTA and ferrous ion was about 80% that seen in rat liver microsomes. From these results, it is likely that low lipid peroxidation activity in rabbit liver microsomes may account for the insufficiency of an EDTA-LIKE FACTORS(S) IN RABBIT LIVER MICROSOMES.
|
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] |
PMID:22774
|
[Psychotropic drugs--real progress or danger? (author's transl)].
|
Three types of modern psychotropic drugs strongly influenced the practice of psychiatric therapy during the past 25 years: Minor tranquilizers, Antidepressants, and Neuroleptics. 1. From the clinical point of view the effects of tranquilizers are more unspecific as compared to those of neuroleptic and antidepressant drugs. Only with the latter two it is possible to treat manifestations of endogenous psychoses (schizophrenic and affective psychoses). The appraisal of both, the advantages (e.g. effectiveness on the symptomatology of acute psychotic manifestations or prophylactic effect in longtime application) and the risks (e.g. side-effects) have to be the basis of treatment of each single patient. 2. The recovery of biochemical mechanisms of neuroleptic and antidepressant drugs (especially of the effects on biogenic amines in CNS) is the most important advance in clearing up the biochemical disturbances in endogenous psychoses.
|
[Psychotropic drugs--real progress or danger? (author's transl)]. Three types of modern psychotropic drugs strongly influenced the practice of psychiatric therapy during the past 25 years: Minor tranquilizers, Antidepressants, and Neuroleptics. 1. From the clinical point of view the effects of tranquilizers are more unspecific as compared to those of neuroleptic and antidepressant drugs. Only with the latter two it is possible to treat manifestations of endogenous psychoses (schizophrenic and affective psychoses). The appraisal of both, the advantages (e.g. effectiveness on the symptomatology of acute psychotic manifestations or prophylactic effect in longtime application) and the risks (e.g. side-effects) have to be the basis of treatment of each single patient. 2. The recovery of biochemical mechanisms of neuroleptic and antidepressant drugs (especially of the effects on biogenic amines in CNS) is the most important advance in clearing up the biochemical disturbances in endogenous psychoses.
|
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] |
PMID:22778
|
Effects of sodium ions on the electrical and pH gradients across the membrane of Streptococcus lactis cells.
|
Energized cells of Streptococcus lactis conserve and transduce energy at the plasma membrane in the form of an electrochemical gradient of hydrogen ions (deltap). An increase in energy-consuming processes, such as cation transport, would be expected to result in a change in the steady state deltap. We determined the electrical gradient (deltapsi) from the fluorescence of a membrane potential-sensitive cyanine dye, and the chemical H+ gradient (deltaph) from the distribution of a weak acid. In glycolyzing cells incubated at pH5 the addition of NaCl to 200 mM partially dissipated the deltap by decreasing deltapsi, while the delta pH was constant. The deltap was also determined independently from the accumulation levels of thiomethyl-beta-galactoside. The deltap values decreased in cells fermenting glucose at pH 5 or pH 7 when NaCl was added, while the deltapH values were unaffected; cells fermenting arginine at pH 7 showed similar effects. Thus, these nongrowing cells cannot fully compensate for the energy demand of cation transport.
|
Effects of sodium ions on the electrical and pH gradients across the membrane of Streptococcus lactis cells. Energized cells of Streptococcus lactis conserve and transduce energy at the plasma membrane in the form of an electrochemical gradient of hydrogen ions (deltap). An increase in energy-consuming processes, such as cation transport, would be expected to result in a change in the steady state deltap. We determined the electrical gradient (deltapsi) from the fluorescence of a membrane potential-sensitive cyanine dye, and the chemical H+ gradient (deltaph) from the distribution of a weak acid. In glycolyzing cells incubated at pH5 the addition of NaCl to 200 mM partially dissipated the deltap by decreasing deltapsi, while the delta pH was constant. The deltap was also determined independently from the accumulation levels of thiomethyl-beta-galactoside. The deltap values decreased in cells fermenting glucose at pH 5 or pH 7 when NaCl was added, while the deltapH values were unaffected; cells fermenting arginine at pH 7 showed similar effects. Thus, these nongrowing cells cannot fully compensate for the energy demand of cation transport.
|
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] |
PMID:22779
|
Energetics of galactose, proline, and glutamine transport in a cytochrome-deficient mutant of Salmonella typhimurium.
|
The effect of inhibitors and uncouplers on the osmotic shock-sensitive transport systems for glutamine and galactose (by the beta-methyl galactoside permease) was compared to their effect on the osmotic shock-resistant proline and galactose permease systems in cytochrome-deficient cells of Salmonella typhimurium SASY28. Both osmotic shock-sensitive and -resistant systems were sensitive to uncouplers and to inhibitors of the membrane-bound Ca2+, Mg2+-activated adenosine triphosphatase. This suggests that uptake by both types of systems is energized in these cells by an electrochemical gradient of protons formed by ATP hydrolysis through the ATPase.
|
Energetics of galactose, proline, and glutamine transport in a cytochrome-deficient mutant of Salmonella typhimurium. The effect of inhibitors and uncouplers on the osmotic shock-sensitive transport systems for glutamine and galactose (by the beta-methyl galactoside permease) was compared to their effect on the osmotic shock-resistant proline and galactose permease systems in cytochrome-deficient cells of Salmonella typhimurium SASY28. Both osmotic shock-sensitive and -resistant systems were sensitive to uncouplers and to inhibitors of the membrane-bound Ca2+, Mg2+-activated adenosine triphosphatase. This suggests that uptake by both types of systems is energized in these cells by an electrochemical gradient of protons formed by ATP hydrolysis through the ATPase.
|
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] |
PMID:22775
|
[Model of motion sickness in dogs for assessing the effectiveness of pharmacological substances].
|
The paper describes a model of motion sickness for dogs. The method is based on the simultaneous use of vertical and rotatory movement of the device with a continuously varying angular velocity of rotation to generate Coriolis acceleration. The exposure increases significantly the number of sick animals to be used in the selection of antimotion drugs. Diphenidol, marezine, tigane, bromotigane and metachloropromide were tested. Diphenidol and to a lesser extent marezine and metachloropromide proved effective. Tigane and bromotigane were ineffective against motion sickness.
|
[Model of motion sickness in dogs for assessing the effectiveness of pharmacological substances]. The paper describes a model of motion sickness for dogs. The method is based on the simultaneous use of vertical and rotatory movement of the device with a continuously varying angular velocity of rotation to generate Coriolis acceleration. The exposure increases significantly the number of sick animals to be used in the selection of antimotion drugs. Diphenidol, marezine, tigane, bromotigane and metachloropromide were tested. Diphenidol and to a lesser extent marezine and metachloropromide proved effective. Tigane and bromotigane were ineffective against motion sickness.
|
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] |
PMID:22776
|
[Hygienic evaluation of the water reclaimed from various moisture-containing wastes].
|
The paper reviews 5 experiments on 25 healthy male test subjects, aged 20-36. For drinking and cooking they used water reclaimed from various water-containing wastes (atmospheric condensate, urine, fluids used in engineering processes and biological wastes) by the oxidation-catalytic and sorption techniques. The resultant water was saturated with salts and decontaminated by ionic silver at a dose of 0.1 mg/l. The experimental data on the excretion of water and minerals allow the conclusion that reclaimed and conditioned water is physiologically adequate and that the human body reacts to its intake as it does to normal potable water.
|
[Hygienic evaluation of the water reclaimed from various moisture-containing wastes]. The paper reviews 5 experiments on 25 healthy male test subjects, aged 20-36. For drinking and cooking they used water reclaimed from various water-containing wastes (atmospheric condensate, urine, fluids used in engineering processes and biological wastes) by the oxidation-catalytic and sorption techniques. The resultant water was saturated with salts and decontaminated by ionic silver at a dose of 0.1 mg/l. The experimental data on the excretion of water and minerals allow the conclusion that reclaimed and conditioned water is physiologically adequate and that the human body reacts to its intake as it does to normal potable water.
|
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] |
PMID:22780
|
Pilot open-label study of triazolam in the treatment of insomnia following alcohol withdrawal.
|
Insomnia and anxiety decreased in 12 outpatients taking triazolam following alcohol withdrawal.
|
Pilot open-label study of triazolam in the treatment of insomnia following alcohol withdrawal. Insomnia and anxiety decreased in 12 outpatients taking triazolam following alcohol withdrawal.
|
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] |
PMID:22777
|
[Variants of the control over a gas-exchange closed ecosystem with a periodically operating autotrophic component].
|
The paper discusses the problem of how to control a gas exchange closed ecosystem that consists of autotrophic and heterotrophic components and operates periodically in the light or in the dark. The purpose of the control is to maintain the steady state of an ecosystem with a man-oriented atmosphere. This problem of control has different solutions each of which is characterized by a set of six dimensionless variables associated with three equations--steady-state conditions. The physical characteristics of the variables and conditions of similarity of ecosystems are described. The resultant methods of control are evaluated from the point of view of economic operation of the ecosystem and the level of stability of its amosphere. The class of ecosystems for which the results obtained are valid in the event of accidental perturbations is presented.
|
[Variants of the control over a gas-exchange closed ecosystem with a periodically operating autotrophic component]. The paper discusses the problem of how to control a gas exchange closed ecosystem that consists of autotrophic and heterotrophic components and operates periodically in the light or in the dark. The purpose of the control is to maintain the steady state of an ecosystem with a man-oriented atmosphere. This problem of control has different solutions each of which is characterized by a set of six dimensionless variables associated with three equations--steady-state conditions. The physical characteristics of the variables and conditions of similarity of ecosystems are described. The resultant methods of control are evaluated from the point of view of economic operation of the ecosystem and the level of stability of its amosphere. The class of ecosystems for which the results obtained are valid in the event of accidental perturbations is presented.
|
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] |
PMID:22783
|
[Diagnosis and treatment of postoperative infections following hip injuries].
|
The authors studied the diagnosis and treatment of posttraumatic infections of the hip joint, based on their own material. In case of latent infection the increased sedimentation rate and taking of comparative X-ray films are held important, that shows a narrowing and disappearance of the sclerosed edge of the acetabulum. Following dislocation of the hip joint ankylosis may be attained, but after fractures of the proximal and of the femur the infection cannot be cured, unless the nail and the head of the femur are removed.
|
[Diagnosis and treatment of postoperative infections following hip injuries]. The authors studied the diagnosis and treatment of posttraumatic infections of the hip joint, based on their own material. In case of latent infection the increased sedimentation rate and taking of comparative X-ray films are held important, that shows a narrowing and disappearance of the sclerosed edge of the acetabulum. Following dislocation of the hip joint ankylosis may be attained, but after fractures of the proximal and of the femur the infection cannot be cured, unless the nail and the head of the femur are removed.
|
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] |
PMID:22785
|
[Treatment of childhood humeral fractures by wire fixation].
|
Out of 526 upper limb fractures treated in the Pediatric Surgery Department of the Péterfy Sándor Hospital between 1970-1975, 63 patients were operated on. (11.9%). Fractures in childhood are generally treated by closed methods because healing of the growing bone is favourable. If it is reasonable, fractures of the forearm bones are successfully treated by means of intramedullary wire fixation, fractures of the elbow by means of transfixation. No septic complication occured following operation. Growth disturbancies were not observed in the affected bones after the operative intervention in the course of 1 to 5 years. On this ground the author recommends the adaptational "minimal" osteosynthesis in the treatment of fractures in infancy, if closed methods do not promise optimal results.
|
[Treatment of childhood humeral fractures by wire fixation]. Out of 526 upper limb fractures treated in the Pediatric Surgery Department of the Péterfy Sándor Hospital between 1970-1975, 63 patients were operated on. (11.9%). Fractures in childhood are generally treated by closed methods because healing of the growing bone is favourable. If it is reasonable, fractures of the forearm bones are successfully treated by means of intramedullary wire fixation, fractures of the elbow by means of transfixation. No septic complication occured following operation. Growth disturbancies were not observed in the affected bones after the operative intervention in the course of 1 to 5 years. On this ground the author recommends the adaptational "minimal" osteosynthesis in the treatment of fractures in infancy, if closed methods do not promise optimal results.
|
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] |
PMID:22787
|
[The role of orthopedic surgery in the treatment of spastic patients].
|
The authors performed 958 operations on spastic patients. Based on this clinical material, they introduce the possibilities and principles of operative treatment. Position of joints in the lower limb, their synergism and compensatory changes in a closed kinetic chain are analysed in the article. These factors must be attended to carefully if one should decide the site and variety of operation to be performed. The authors suggest that patients should be operated on early, in certain cases even preventive operation is necessary. Results are better if children who already can stand and walk are operated on, but in many cases operation itself is needed to enable them to these activities. Results were good in 83,2%, no changes in 3,4%, worse in 4,2 out of the 716 operations evaluated. Operative treatment along with conductive pedagogy and other methods of physiotherapy help these patients to be able to take care of themselves and to become useful members of society.
|
[The role of orthopedic surgery in the treatment of spastic patients]. The authors performed 958 operations on spastic patients. Based on this clinical material, they introduce the possibilities and principles of operative treatment. Position of joints in the lower limb, their synergism and compensatory changes in a closed kinetic chain are analysed in the article. These factors must be attended to carefully if one should decide the site and variety of operation to be performed. The authors suggest that patients should be operated on early, in certain cases even preventive operation is necessary. Results are better if children who already can stand and walk are operated on, but in many cases operation itself is needed to enable them to these activities. Results were good in 83,2%, no changes in 3,4%, worse in 4,2 out of the 716 operations evaluated. Operative treatment along with conductive pedagogy and other methods of physiotherapy help these patients to be able to take care of themselves and to become useful members of society.
|
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] |
PMID:22788
|
[Possibilities of treatment of open fractures of the tibia].
|
Results of healing in 477 cases of open leg fractures treated in the Central Institut of Traumatology in Budapest are analysed in the article. 47,2% of cases were treated by closed methods. The authors are convinced that careful conservative management leads to good results, if the type of the fracture is suitable. Conditions of operative treatment are outlined. In favourable circumstances a stable internal fixation should be performed, otherwise inramedullary wiring and plaster may hold the fragments until healing occurs. Soft tissues should be handled carefully and placing sutures under tension must be avoided, by all means.
|
[Possibilities of treatment of open fractures of the tibia]. Results of healing in 477 cases of open leg fractures treated in the Central Institut of Traumatology in Budapest are analysed in the article. 47,2% of cases were treated by closed methods. The authors are convinced that careful conservative management leads to good results, if the type of the fracture is suitable. Conditions of operative treatment are outlined. In favourable circumstances a stable internal fixation should be performed, otherwise inramedullary wiring and plaster may hold the fragments until healing occurs. Soft tissues should be handled carefully and placing sutures under tension must be avoided, by all means.
|
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] |
PMID:22789
|
[Stable osteosynthesis on the hand].
|
The authors write on the usefulness of the A.S.I.F. Small Fragment Instrumentary, its possible ways of application in the treatment of fractures of bones of the hand. The operative techniques is introduced, indication and contraindications based on the clinical material of the authors are discussed in the article. Limitations to the application of this method are also included.
|
[Stable osteosynthesis on the hand]. The authors write on the usefulness of the A.S.I.F. Small Fragment Instrumentary, its possible ways of application in the treatment of fractures of bones of the hand. The operative techniques is introduced, indication and contraindications based on the clinical material of the authors are discussed in the article. Limitations to the application of this method are also included.
|
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] |
PMID:22790
|
[Syringomyelia with severe osteo-articular changes].
|
Attention was drawn to a patient after admission to the Central Institute of Oncology, and syringomyelia was diagnosed on the basis of X-ray films taken by the author. The deformations were symmetrical and they were localized in the area of innervation of the C VI, VII, D I segment. The radiological diagnosis was proved by the neurological examinations.
|
[Syringomyelia with severe osteo-articular changes]. Attention was drawn to a patient after admission to the Central Institute of Oncology, and syringomyelia was diagnosed on the basis of X-ray films taken by the author. The deformations were symmetrical and they were localized in the area of innervation of the C VI, VII, D I segment. The radiological diagnosis was proved by the neurological examinations.
|
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] |
PMID:22792
|
Evidence for inhibition of dopamine-beta-hydroxylase in vivo after sub-acute pyrazole treatment in rats.
|
Pyrazole, a widely used inhibitor of alcohol dehydrogenase, has been shown to cause a decrease of brain and heart noradrenaline (NA). An attempt to explain the mechanism of this effect is now described. L-DOPA (50-200 mg/kg, s.c.) was unable to restore brain or heart noradrenaline levels in pyrazole pre-treated rats. After monoamine oxidase inhibition with tranylcypromine or pargyline there was a slight increase in brain NA in these rats but no further increase was observed in response to L-DOPA (30 mg/kg). Brain dopamine levels were relatively higher in pyrazole pre-treated rats. This difference was particularly clear in the hypothalamus but not present at all in striatum. It was impossible to duplicate the above results using nialamide as the monoamine oxidase inhibitor. After depletion of monoamine stores by reserpine (2 x 2 mg/kg) or oxypertine (75 mg/kg) and treatment with tranylcypromine and L-DOPA it is possible to get an indication of the maximal rate of synthesis of NA. In pyrazole treated rats synthesis of NA in brain was 70% reduced and about 50% reduced in heart. Synthesis of dopamine from L-DOPA was unimpaired. Dopamine-beta-hydroxylase activity in the hypothalamus of rats treated for four days with pyrazole (100 mg/kg i.p.) was more than 40% reduced. This inhibition could not be obtained by addition of pyrazole to samples of purified dopamine-beta-hydroxylase. The results strongly suggest that the reason for the decrease in brain and peripheral NA seen after pyrazole administration in rats is due to inhibition of dopamine-beta-hydroxylase.
|
Evidence for inhibition of dopamine-beta-hydroxylase in vivo after sub-acute pyrazole treatment in rats. Pyrazole, a widely used inhibitor of alcohol dehydrogenase, has been shown to cause a decrease of brain and heart noradrenaline (NA). An attempt to explain the mechanism of this effect is now described. L-DOPA (50-200 mg/kg, s.c.) was unable to restore brain or heart noradrenaline levels in pyrazole pre-treated rats. After monoamine oxidase inhibition with tranylcypromine or pargyline there was a slight increase in brain NA in these rats but no further increase was observed in response to L-DOPA (30 mg/kg). Brain dopamine levels were relatively higher in pyrazole pre-treated rats. This difference was particularly clear in the hypothalamus but not present at all in striatum. It was impossible to duplicate the above results using nialamide as the monoamine oxidase inhibitor. After depletion of monoamine stores by reserpine (2 x 2 mg/kg) or oxypertine (75 mg/kg) and treatment with tranylcypromine and L-DOPA it is possible to get an indication of the maximal rate of synthesis of NA. In pyrazole treated rats synthesis of NA in brain was 70% reduced and about 50% reduced in heart. Synthesis of dopamine from L-DOPA was unimpaired. Dopamine-beta-hydroxylase activity in the hypothalamus of rats treated for four days with pyrazole (100 mg/kg i.p.) was more than 40% reduced. This inhibition could not be obtained by addition of pyrazole to samples of purified dopamine-beta-hydroxylase. The results strongly suggest that the reason for the decrease in brain and peripheral NA seen after pyrazole administration in rats is due to inhibition of dopamine-beta-hydroxylase.
|
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] |
PMID:22793
|
Physicians, physicians' assistants, and the social characteristics of patients in southern Appalachia.
|
A focus on health care delivery systems and the emergence of New Health Practitioners, particularly Physicians' Assistants (PAs), represents one of the more significant nonbiomedical developments in American medicine since World War II. Much discussion about PAs revolves around the kinds of illnesses they are qualified to treat which then permits physicians to concentrate on patients with other types of illnesses. Ignored in this focus on illness characteristics is the possibility that physicians and PAs may treat patients with different social characteristics. That issue is the topic of this paper. Differences between the status characteristics of physician and PA patients are reported for a rural community where PAs and physicians work side by side in the same offices. The relationships observed in this rural community suggest that the higher a patient's socioeconomic status, the more likely (s)he is to be treated by the physician.
|
Physicians, physicians' assistants, and the social characteristics of patients in southern Appalachia. A focus on health care delivery systems and the emergence of New Health Practitioners, particularly Physicians' Assistants (PAs), represents one of the more significant nonbiomedical developments in American medicine since World War II. Much discussion about PAs revolves around the kinds of illnesses they are qualified to treat which then permits physicians to concentrate on patients with other types of illnesses. Ignored in this focus on illness characteristics is the possibility that physicians and PAs may treat patients with different social characteristics. That issue is the topic of this paper. Differences between the status characteristics of physician and PA patients are reported for a rural community where PAs and physicians work side by side in the same offices. The relationships observed in this rural community suggest that the higher a patient's socioeconomic status, the more likely (s)he is to be treated by the physician.
|
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] |
PMID:22794
|
The distribution of physician extenders.
|
As part of the Medicare Physician Extender Reimbursement Study, a mail survey was conducted of 5,572 physician extenders (PEs) to identify potential study participants. Analysis of survey results indicates that PEs are distributed disproportionately more often than physicians to primary care practices and to rural low income areas. However, there are substantial differences among types of PEs with regard to practice location and practice arrangement. The relationship between these findings and the distribution of other medical manpower and innovations is then discussed.
|
The distribution of physician extenders. As part of the Medicare Physician Extender Reimbursement Study, a mail survey was conducted of 5,572 physician extenders (PEs) to identify potential study participants. Analysis of survey results indicates that PEs are distributed disproportionately more often than physicians to primary care practices and to rural low income areas. However, there are substantial differences among types of PEs with regard to practice location and practice arrangement. The relationship between these findings and the distribution of other medical manpower and innovations is then discussed.
|
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] |
PMID:22795
|
Physician assistants: an overview of an emerging health profession.
|
This article describes the background characteristics, work environments, and job characteristics of the physician assistant profession as they existed in late 1974 and early 1975. Of the 939 physician assistants participating in this study, three-fourths were working in primary care specialties and half were located in communities having fewer than 50,000 persons. Favorable levels of responsibility for patient care, supervisory support, and role acceptance were reported by respondents. The mean income was $14,285. Job opportunities appeared plentiful, but career opportunities were considered by most to be either limited or nonexistent. Physician assistants are providing important additional medical manpower in primary care fields and in smaller communities, but the preceived lack of opportunities for career advancement may prove to be a significant problem for this emerging health profession in the years ahead.
|
Physician assistants: an overview of an emerging health profession. This article describes the background characteristics, work environments, and job characteristics of the physician assistant profession as they existed in late 1974 and early 1975. Of the 939 physician assistants participating in this study, three-fourths were working in primary care specialties and half were located in communities having fewer than 50,000 persons. Favorable levels of responsibility for patient care, supervisory support, and role acceptance were reported by respondents. The mean income was $14,285. Job opportunities appeared plentiful, but career opportunities were considered by most to be either limited or nonexistent. Physician assistants are providing important additional medical manpower in primary care fields and in smaller communities, but the preceived lack of opportunities for career advancement may prove to be a significant problem for this emerging health profession in the years ahead.
|
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] |
PMID:22796
|
The effectiveness and cost of acute respiratory illness medical care provided by physicians and algorithm-assisted physicians' assistants.
|
The medical management of patients with acute respiratory illnesses was analyzed at two different clinics during a 14- to 21-month period. Patients received care from either physicians or physician-supervised physician's assistants (PA). The PAs used respiratory illness clinical algorithms to guide their choice of diagnostic tests and treatment. Illness outcome, patient satisfaction, and medical care cost data were obtained for all patients approximately two weeks after the index illness. Despite significant differences in patient population characteristics, illness outcomes were similar, regardless of the provider's educational background. Medical care costs, however, were highest for the physician's patients. For all patients, diagnostic tests contributed about one-third of the total direct costs, mainly because of chest x-ray and throat culture use. Sixty to eighty per cent of medication costs were due to nonprescription drugs used principally for symptom relief. The data demonstrate that the medical care delivered by these physician's assistants was as effective and less costly than the care provided by physicians. Reducing chest x-ray and throat culture use would have a significant economic impact, without adversely affecting medical care effectiveness.
|
The effectiveness and cost of acute respiratory illness medical care provided by physicians and algorithm-assisted physicians' assistants. The medical management of patients with acute respiratory illnesses was analyzed at two different clinics during a 14- to 21-month period. Patients received care from either physicians or physician-supervised physician's assistants (PA). The PAs used respiratory illness clinical algorithms to guide their choice of diagnostic tests and treatment. Illness outcome, patient satisfaction, and medical care cost data were obtained for all patients approximately two weeks after the index illness. Despite significant differences in patient population characteristics, illness outcomes were similar, regardless of the provider's educational background. Medical care costs, however, were highest for the physician's patients. For all patients, diagnostic tests contributed about one-third of the total direct costs, mainly because of chest x-ray and throat culture use. Sixty to eighty per cent of medication costs were due to nonprescription drugs used principally for symptom relief. The data demonstrate that the medical care delivered by these physician's assistants was as effective and less costly than the care provided by physicians. Reducing chest x-ray and throat culture use would have a significant economic impact, without adversely affecting medical care effectiveness.
|
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] |
PMID:22797
|
[Changes of serum and urinary uric-acid levels after portacaval anastomosis in the rat].
|
Significantly higher levels of uric acid in serum and urine together with increased urine volume and pH were observed in rats after portacaval end-to-side anastomosis in comparison to sham-operated and non-operated pair-fed controls. An increased supply of endogenous uric acid by reduced transformation of uric acid to allantoin and decreased uricase activity in the liver was assumed. Adaptation of enzyme activities of other metabolic pathways of the liver after PCA due to diminished blood and oxygen supply were described in previous experiments. This model seems suitable for other studies on hyperuricemia, hyperuricosuria and uric acid lithiasis.
|
[Changes of serum and urinary uric-acid levels after portacaval anastomosis in the rat]. Significantly higher levels of uric acid in serum and urine together with increased urine volume and pH were observed in rats after portacaval end-to-side anastomosis in comparison to sham-operated and non-operated pair-fed controls. An increased supply of endogenous uric acid by reduced transformation of uric acid to allantoin and decreased uricase activity in the liver was assumed. Adaptation of enzyme activities of other metabolic pathways of the liver after PCA due to diminished blood and oxygen supply were described in previous experiments. This model seems suitable for other studies on hyperuricemia, hyperuricosuria and uric acid lithiasis.
|
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] |
PMID:22798
|
The dietary regulation of stearyl coenzyme A desaturase activity and membrane fluidity in the rat aorta.
|
Numerous studies have demonstrated that alterations in membrane composition or fluidity are often associated with alterations in the properties of membrane-bound enzymes. In order to obtain membranes of varying fluidity, rats were fed diets that were either fat-free or supplemented with 15% safflower oil, and two properties associated with aorta and liver microsomal membranes were selected for study: stearyl CoA desaturase activity, and fluidity as monitored by fatty acid composition and microviscosity (measured by fluorescence depolarization). If fluidity directly modulates desaturase activity, one would predict that a low fluidity would stimulate the desaturase activity. Ten times more desaturase activity is present in aorta microsomes from rats on a fat-free diet than in microsomes from rats on a safflower oil supplemented diet. However, on the fat-free diet, these aorta microsomes were more fluid than those of rats fed safflower oil supplemented diet. The fluidity of liver microsomal membranes was not altered in response to diet, despite significant changes in desaturase enzyme content. The contrasting evidence presented here suggests that no correlation exists between desaturase enzyme activity and membrane fluidity in the two tissues studies. We have demonstrated that the aorta has appreciable capacity to desaturate stearyl CoA and that dietary manipulation causes significant changes in aorta membrane fluidity that may be of sufficient magnitude to affect the overall metaboism of aorta cells.
|
The dietary regulation of stearyl coenzyme A desaturase activity and membrane fluidity in the rat aorta. Numerous studies have demonstrated that alterations in membrane composition or fluidity are often associated with alterations in the properties of membrane-bound enzymes. In order to obtain membranes of varying fluidity, rats were fed diets that were either fat-free or supplemented with 15% safflower oil, and two properties associated with aorta and liver microsomal membranes were selected for study: stearyl CoA desaturase activity, and fluidity as monitored by fatty acid composition and microviscosity (measured by fluorescence depolarization). If fluidity directly modulates desaturase activity, one would predict that a low fluidity would stimulate the desaturase activity. Ten times more desaturase activity is present in aorta microsomes from rats on a fat-free diet than in microsomes from rats on a safflower oil supplemented diet. However, on the fat-free diet, these aorta microsomes were more fluid than those of rats fed safflower oil supplemented diet. The fluidity of liver microsomal membranes was not altered in response to diet, despite significant changes in desaturase enzyme content. The contrasting evidence presented here suggests that no correlation exists between desaturase enzyme activity and membrane fluidity in the two tissues studies. We have demonstrated that the aorta has appreciable capacity to desaturate stearyl CoA and that dietary manipulation causes significant changes in aorta membrane fluidity that may be of sufficient magnitude to affect the overall metaboism of aorta cells.
|
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] |
PMID:22803
|
Biochemical properties of a penicillinase from Escherichia coli carrying Rms 298.
|
We obtained two R plasmids, i.e., Rms195 and Rms298, from a clinical isolate, E. coli GN5503. Penicillin beta-lactamase (PCase) was extracted from ML1410 Rms195+ and Rms298+, and was purified by chromatography. Rms195 PCase was identical to the type I PCase mediated by R-TEM, RI and Rms212. The isoelectric point of Rms298 PCase was 5.9 and its molecular weight was 21,000 +/- 1,000. The substrate profile and physiochemical properties indicate that Rms298 PCase belongs to the type IV PCase mediated by Rms139 isolated from Pseudomonas aeruginosa.
|
Biochemical properties of a penicillinase from Escherichia coli carrying Rms 298. We obtained two R plasmids, i.e., Rms195 and Rms298, from a clinical isolate, E. coli GN5503. Penicillin beta-lactamase (PCase) was extracted from ML1410 Rms195+ and Rms298+, and was purified by chromatography. Rms195 PCase was identical to the type I PCase mediated by R-TEM, RI and Rms212. The isoelectric point of Rms298 PCase was 5.9 and its molecular weight was 21,000 +/- 1,000. The substrate profile and physiochemical properties indicate that Rms298 PCase belongs to the type IV PCase mediated by Rms139 isolated from Pseudomonas aeruginosa.
|
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] |
PMID:22810
|
[Neurological complications following whooping-cough vaccination (author's transl)].
|
The clinical symptoms, frequency, etiology, pathogenesis and differential diagnosis of neurological complications following immunisation against pertussis are being discussed. Guide lines are presented for the evaluation of the causal connection between the observed complications and the vaccination.
|
[Neurological complications following whooping-cough vaccination (author's transl)]. The clinical symptoms, frequency, etiology, pathogenesis and differential diagnosis of neurological complications following immunisation against pertussis are being discussed. Guide lines are presented for the evaluation of the causal connection between the observed complications and the vaccination.
|
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] |
PMID:22812
|
Mutagenic and recombinogenic action of pesticides in Aspergillus nidulans.
|
Thirteen pesticides, aminotriazole, benomyl, captafol, captan, dalapon-Na, dichlorvos, dinobuton, dodine, ioxynil, mecoprop, neburon, picloram and tordon were tested for ability to induce (1) point mutations to 8-azaguanine resistance, (2) mitotic crossing-over, and (3) mitotic non-disjunction and haploidization in Aspergillus nidulans. Tests were performed at three different pHs, i.e. 4.5, 7, 8.2. Three of the pesticides, captan , captafol and dichlorvos induced point mutations; dichlorvos also induced a high frequency of mitotic crossing-over and non-disjunction; benomyl induced a very high frequency of non-disjunction whereas aminotriazole induced weakly both types of somatic segregation.
|
Mutagenic and recombinogenic action of pesticides in Aspergillus nidulans. Thirteen pesticides, aminotriazole, benomyl, captafol, captan, dalapon-Na, dichlorvos, dinobuton, dodine, ioxynil, mecoprop, neburon, picloram and tordon were tested for ability to induce (1) point mutations to 8-azaguanine resistance, (2) mitotic crossing-over, and (3) mitotic non-disjunction and haploidization in Aspergillus nidulans. Tests were performed at three different pHs, i.e. 4.5, 7, 8.2. Three of the pesticides, captan , captafol and dichlorvos induced point mutations; dichlorvos also induced a high frequency of mitotic crossing-over and non-disjunction; benomyl induced a very high frequency of non-disjunction whereas aminotriazole induced weakly both types of somatic segregation.
|
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] |
PMID:22823
|
Differentiation of cardiac chronotropic and inotropic effects of beta-adrenoceptor agonists.
|
The relative inotropic and chronotropic activity of beta-adrenoceptor agonists was studied in the noradrenaline-depleted, anaesthetized cat. Terbutaline, a selective beta2-adrenoceptor agonist, gave at a certain dose a more pronounced chronotropic than inotropic response, while a new beta1-selective adrenoceptor agonist (-)-H 80/62 produced the same degree of chronotropic and inotropic stimulation. The results indicate that there is some difference between the beta-adrenoceptors in the sinus node mediating chronotropic stimulation and beta-adrenoceptors in the ventricular myocardium mediating stimulation of the contractile force. It has been shown that there are both beta1- and beta2-adrenoceptors in the heart (Carlsson et al., 1972). In the light of this finding it is hypothetized that there are differences in the relative distribution of beta1- and beta2-adrenoceptors in the sinus node and in the myocardium. Athough beta1 is the predominant type of beta-adrenoceptor in both regions, the beta1:beta2 concentration ratio seems to be higher in the myocardium, than in the sinus node.
|
Differentiation of cardiac chronotropic and inotropic effects of beta-adrenoceptor agonists. The relative inotropic and chronotropic activity of beta-adrenoceptor agonists was studied in the noradrenaline-depleted, anaesthetized cat. Terbutaline, a selective beta2-adrenoceptor agonist, gave at a certain dose a more pronounced chronotropic than inotropic response, while a new beta1-selective adrenoceptor agonist (-)-H 80/62 produced the same degree of chronotropic and inotropic stimulation. The results indicate that there is some difference between the beta-adrenoceptors in the sinus node mediating chronotropic stimulation and beta-adrenoceptors in the ventricular myocardium mediating stimulation of the contractile force. It has been shown that there are both beta1- and beta2-adrenoceptors in the heart (Carlsson et al., 1972). In the light of this finding it is hypothetized that there are differences in the relative distribution of beta1- and beta2-adrenoceptors in the sinus node and in the myocardium. Athough beta1 is the predominant type of beta-adrenoceptor in both regions, the beta1:beta2 concentration ratio seems to be higher in the myocardium, than in the sinus node.
|
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] |
PMID:22824
|
Regulation of nerve growth factor content in C6 glioma cells by beta-adrenergic receptor stimulation.
|
The C6 glioma cell line contains nerve growth factor (NGF) which can be released into the medium. Treatment of the cells with beta-adrenoceptor agonists resulted in increased content of NGF in both the cells and the medium within a few hours, whereas alpha-adrenoceptor agonists were ineffective. The response was blocked by beta- but not alpha-adrenoceptor antagonists. The increase of the NGF content of glioma cells appeared to be mediated by an elevation of cyclic AMP or GMP. The addition to the cell cultures of other putative neurotransmitters failed to change the content of either NGF or cyclic AMP. These results are discussed with respect to a model for adrenergic neuron-glial interactions.
|
Regulation of nerve growth factor content in C6 glioma cells by beta-adrenergic receptor stimulation. The C6 glioma cell line contains nerve growth factor (NGF) which can be released into the medium. Treatment of the cells with beta-adrenoceptor agonists resulted in increased content of NGF in both the cells and the medium within a few hours, whereas alpha-adrenoceptor agonists were ineffective. The response was blocked by beta- but not alpha-adrenoceptor antagonists. The increase of the NGF content of glioma cells appeared to be mediated by an elevation of cyclic AMP or GMP. The addition to the cell cultures of other putative neurotransmitters failed to change the content of either NGF or cyclic AMP. These results are discussed with respect to a model for adrenergic neuron-glial interactions.
|
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] |
PMID:22825
|
Effects of medium pH on p-aminohippurate transport in rat kidney fragments.
|
Addition of many oxidizable substrates to medium often enhances p-aminohippurate (PAH) transport by incubating renal tissue. Since the oxidation of various substrates by rat kidney tissue may change medium pH and this pH change has not been considered by many in conclusions, we followed the effects of medium pH on the magnitude and kinetics of in vitro PAH transport. Two previous studies employing rat kidney slices reported different optimal medium pH for PAH accumulation, i.e. pH 6.5 and pH 8.0. By repeating these studies over a wide range of medium pH, we confirmed the presence of enhanced steady state accumulation relative to pH 7.4 at two separate pH ranges, one at pH 6.7--6.9 (+ 15%), and the other at pH 7.7--7.9 (+ 22%). PAH influx, as measured by early tissue accumulation, was not different at pH 7.4 and 7.8; while at pH 6.8, it actually decreased. It was only later in the incubation that accumulation was greater at pH 6.8 and 7.8. Probably due to the small stimulation in steady state accumulation at either pH, we could not discern, by the methodology currently available, if this was secondary to augmented influx, decreased efflux, or a combination of both in the latter part of incubation. We conclude that the contribution secondary to medium pH changes must be considered when evaluating the effects of various substrates on PAH accumulation by kidney slices.
|
Effects of medium pH on p-aminohippurate transport in rat kidney fragments. Addition of many oxidizable substrates to medium often enhances p-aminohippurate (PAH) transport by incubating renal tissue. Since the oxidation of various substrates by rat kidney tissue may change medium pH and this pH change has not been considered by many in conclusions, we followed the effects of medium pH on the magnitude and kinetics of in vitro PAH transport. Two previous studies employing rat kidney slices reported different optimal medium pH for PAH accumulation, i.e. pH 6.5 and pH 8.0. By repeating these studies over a wide range of medium pH, we confirmed the presence of enhanced steady state accumulation relative to pH 7.4 at two separate pH ranges, one at pH 6.7--6.9 (+ 15%), and the other at pH 7.7--7.9 (+ 22%). PAH influx, as measured by early tissue accumulation, was not different at pH 7.4 and 7.8; while at pH 6.8, it actually decreased. It was only later in the incubation that accumulation was greater at pH 6.8 and 7.8. Probably due to the small stimulation in steady state accumulation at either pH, we could not discern, by the methodology currently available, if this was secondary to augmented influx, decreased efflux, or a combination of both in the latter part of incubation. We conclude that the contribution secondary to medium pH changes must be considered when evaluating the effects of various substrates on PAH accumulation by kidney slices.
|
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] |
PMID:22826
|
Further evidence on the role of the hypothalamic afferents on the estrogen-induced prolactin release.
|
Serum prolactin (Prl) concentrations in ovariectomized rats were low without significant differences between morning and afternoon values. These levels were not affected by either frontal or caudal hypothalamic deafferentation. However, they increased after lesioning the hypothalamic median eminence (ME). Three days after the injection of 20 microgram estradiol benzoate (EB) into ovariectomized non-lesioned rats, a rise in serum Prl occurred in the afternoon but not in the morning. In animals with ME lesions estrogen enhanced both morning and afternoon values. The animals with caudal hypothalamic deafferentation and those which had undergone sham operation showed the same pattern as the normal animals. On the contrary, after estrogen treatment of rats with frontal hypothalamic deafferentation high serum Prl concentration during the morning and low levels in the afternoon were observed. It is concluded that estrogen effects on Prl secretion are in part mediated by frontal neural afferents to the hypothalamus. They would facilitate Prl inhibiting factor (PIF) secretion in the morning and inhibit PIF secretion in the afternoon.
|
Further evidence on the role of the hypothalamic afferents on the estrogen-induced prolactin release. Serum prolactin (Prl) concentrations in ovariectomized rats were low without significant differences between morning and afternoon values. These levels were not affected by either frontal or caudal hypothalamic deafferentation. However, they increased after lesioning the hypothalamic median eminence (ME). Three days after the injection of 20 microgram estradiol benzoate (EB) into ovariectomized non-lesioned rats, a rise in serum Prl occurred in the afternoon but not in the morning. In animals with ME lesions estrogen enhanced both morning and afternoon values. The animals with caudal hypothalamic deafferentation and those which had undergone sham operation showed the same pattern as the normal animals. On the contrary, after estrogen treatment of rats with frontal hypothalamic deafferentation high serum Prl concentration during the morning and low levels in the afternoon were observed. It is concluded that estrogen effects on Prl secretion are in part mediated by frontal neural afferents to the hypothalamus. They would facilitate Prl inhibiting factor (PIF) secretion in the morning and inhibit PIF secretion in the afternoon.
|
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] |
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