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PMID:6719 | The effects of angiotensin I and angiotensin II on the isolated tracheal muscle of the cat. | The effects of Asp1-beta-amide-Val5-angiotensin II (A II) and Asp1-Ile5-angiotensin I (A I) have been studied on the isolated continuously superfused cat tracheal muscle contracted by 5-hydroxytryptamine (5-HT). Both peptides have been shown to induce dose-dependent relaxation on this muscle. Similar effects have been obtained with synthetic bradykinin, prostaglandin E2 (PGE2), noradrenaline and histamine. The effects of bradykinin, A I and A II have been shown to be inhibited by aspirin but not by propranolol, metiamide, SC 19220 or a specific, competitive antagonist of A II. The relaxing effect of A I is not due to the conversion of decapeptide to octapeptide A II. The possible mechanism of the relaxing effects of A I and A II on the cat isolated tracheal muscle is discussed. | The effects of angiotensin I and angiotensin II on the isolated tracheal muscle of the cat. The effects of Asp1-beta-amide-Val5-angiotensin II (A II) and Asp1-Ile5-angiotensin I (A I) have been studied on the isolated continuously superfused cat tracheal muscle contracted by 5-hydroxytryptamine (5-HT). Both peptides have been shown to induce dose-dependent relaxation on this muscle. Similar effects have been obtained with synthetic bradykinin, prostaglandin E2 (PGE2), noradrenaline and histamine. The effects of bradykinin, A I and A II have been shown to be inhibited by aspirin but not by propranolol, metiamide, SC 19220 or a specific, competitive antagonist of A II. The relaxing effect of A I is not due to the conversion of decapeptide to octapeptide A II. The possible mechanism of the relaxing effects of A I and A II on the cat isolated tracheal muscle is discussed. | [
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PMID:6720 | Anticholinergic activity of antipsychotic drugs in relation to their extrapyramidal effects. | Antipsychotic drugs were evaluated with two indices of anticholinergic activity, mydriasis in mice in vivo and antagonism of carbamylcholine-induced contractions of guinea-pig tracheal strips in vitro. The drugs from most to least potent as oral mydriatic agents were mepazine, clozapine, thioridazine, promazine and chlorpromazine. Trifluoperazine, pimozide and haloperidol were inactive. These results were consistent with the hypothesis that anticholinergic activity of antipsychotic drugs is inversely related to their propensity to produce extrapyramidal effects in man. In vitro results appeared to predict the incidence of extraphyramidal effects less accurately than in vivo results. | Anticholinergic activity of antipsychotic drugs in relation to their extrapyramidal effects. Antipsychotic drugs were evaluated with two indices of anticholinergic activity, mydriasis in mice in vivo and antagonism of carbamylcholine-induced contractions of guinea-pig tracheal strips in vitro. The drugs from most to least potent as oral mydriatic agents were mepazine, clozapine, thioridazine, promazine and chlorpromazine. Trifluoperazine, pimozide and haloperidol were inactive. These results were consistent with the hypothesis that anticholinergic activity of antipsychotic drugs is inversely related to their propensity to produce extrapyramidal effects in man. In vitro results appeared to predict the incidence of extraphyramidal effects less accurately than in vivo results. | [
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PMID:6721 | Some factors influencing dissolution from salicylic acid-urea solid dispersions. | Solid dispersion systems of salicylic acid-urea have been prepared using a fusion method. Two different methods of cooling the melt were employed, rapid cooling in liquid nitrogen and slow cooling in air. Differential scanning calorimetry and an X-ray diffraction technique were employed to investigate the nature of the fused mixture. Evidence was found of compound formation between the constituents. Dissolution rates of drug from non-disintegrating discs of solid dispersion systems were measured. Rapid cooling of the melt resulted in a much faster drug dissolution rate than from a corresponding mixture prepared by a slow cooling method. This phenomenon is explained by a difference in the sizes of drug particles produced under the different cooling conditions. Rapid cooling favoured the generation of many nucleation sites for the solid drug particles as the liquid was cooled, and hence many small particles were obtained. Conversely, slow cooling favoured the growth of the first few nuclei or solid drug particles, rather than the production of new nuclei, and hence large drug particles were obtained. | Some factors influencing dissolution from salicylic acid-urea solid dispersions. Solid dispersion systems of salicylic acid-urea have been prepared using a fusion method. Two different methods of cooling the melt were employed, rapid cooling in liquid nitrogen and slow cooling in air. Differential scanning calorimetry and an X-ray diffraction technique were employed to investigate the nature of the fused mixture. Evidence was found of compound formation between the constituents. Dissolution rates of drug from non-disintegrating discs of solid dispersion systems were measured. Rapid cooling of the melt resulted in a much faster drug dissolution rate than from a corresponding mixture prepared by a slow cooling method. This phenomenon is explained by a difference in the sizes of drug particles produced under the different cooling conditions. Rapid cooling favoured the generation of many nucleation sites for the solid drug particles as the liquid was cooled, and hence many small particles were obtained. Conversely, slow cooling favoured the growth of the first few nuclei or solid drug particles, rather than the production of new nuclei, and hence large drug particles were obtained. | [
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PMID:6747 | Aggregation of antiacetylcholine drugs in aqueous solution: micellar properties of some diphenylmethane derivatives. | Light scattering methods have been used to examine the aggregation in aqueous solution of a series of antiacetylcholine drugs based on the diphenylmethane nucleus. The drugs investigated included adiphenine hydrochloride, piperidolate hydrochloride, benztropine mesylate, orphenadrine hydrochloride, chlorphenoxamine hydrochloride, lachesine hydrochloride, poldine methylsulphate, pipenzolate bromide, clidinium bromide, benzilonium bromide and ambutonium bromide. A micellar pattern of association was established for all compounds and critical micellar concentrations and aggregation numbers have been determined. | Aggregation of antiacetylcholine drugs in aqueous solution: micellar properties of some diphenylmethane derivatives. Light scattering methods have been used to examine the aggregation in aqueous solution of a series of antiacetylcholine drugs based on the diphenylmethane nucleus. The drugs investigated included adiphenine hydrochloride, piperidolate hydrochloride, benztropine mesylate, orphenadrine hydrochloride, chlorphenoxamine hydrochloride, lachesine hydrochloride, poldine methylsulphate, pipenzolate bromide, clidinium bromide, benzilonium bromide and ambutonium bromide. A micellar pattern of association was established for all compounds and critical micellar concentrations and aggregation numbers have been determined. | [
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PMID:6748 | The crystallization behaviour of sulphathiazole. | Previous investigations into the dissolution kinetics of sulphathiazole Form 1 have shown the process to be first order with respect to driving force. However, below 37 degrees first order kinetics did not apply, due to the surface reaction becoming the rate controlling factor. The present study examines the kinetics of crystallization over the temperature range 25 to 50 degrees. Crystallization is a process greatly dependent upon the high-entropy surface integration step which, unlike the dissolution process, is much more sensitive to crystal growth inhibitors. In the absence of inhibitors crystallization above 34 degrees follows first order kinetics but below 34 degrees the process changes to third order. Similar temperature effects on the dissolution of sulphathiazole have been previously reported. | The crystallization behaviour of sulphathiazole. Previous investigations into the dissolution kinetics of sulphathiazole Form 1 have shown the process to be first order with respect to driving force. However, below 37 degrees first order kinetics did not apply, due to the surface reaction becoming the rate controlling factor. The present study examines the kinetics of crystallization over the temperature range 25 to 50 degrees. Crystallization is a process greatly dependent upon the high-entropy surface integration step which, unlike the dissolution process, is much more sensitive to crystal growth inhibitors. In the absence of inhibitors crystallization above 34 degrees follows first order kinetics but below 34 degrees the process changes to third order. Similar temperature effects on the dissolution of sulphathiazole have been previously reported. | [
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PMID:6749 | Anomalies in some properties of powder mixtures. | Mixtures of lactose and paracetamol and of lactose and oxytetracycline exhibit anomalous properties. The mean particle sizes, tensile strengths and flow properties of the mixtures are not proportionally intermediate between those of the constituents. The results are ascribed to changes that occur in the packing arrangements of the particles. These changes could have practical consequences in monitoring the progress of a mixing operation by measuring apparent particle size and in controlling the properties of granules, capsules and tablets prepared from the mixtures. | Anomalies in some properties of powder mixtures. Mixtures of lactose and paracetamol and of lactose and oxytetracycline exhibit anomalous properties. The mean particle sizes, tensile strengths and flow properties of the mixtures are not proportionally intermediate between those of the constituents. The results are ascribed to changes that occur in the packing arrangements of the particles. These changes could have practical consequences in monitoring the progress of a mixing operation by measuring apparent particle size and in controlling the properties of granules, capsules and tablets prepared from the mixtures. | [
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PMID:6750 | Fluorimetric assay of tetracycline mixtures. | A simple and precise fluorimetric method is described for the simultaneous assay in plasma of a mixture containing chlortetracycline, demethylchlortetracycline and tetracycline. Assay within the therapeutic ranges of 0-5 mg litre(-1) is achieved by formation of strongly fluorescent aluminum/tetracycline complexes, without prior extraction or separation of the individual antibiotics. This is performed by determinations at the peak excitation and fluorescence emission wavelengths of each tetracycline chelate. The method can be similarly applied to the assay of oxytetracycline, rolitetracycline and minocycline. | Fluorimetric assay of tetracycline mixtures. A simple and precise fluorimetric method is described for the simultaneous assay in plasma of a mixture containing chlortetracycline, demethylchlortetracycline and tetracycline. Assay within the therapeutic ranges of 0-5 mg litre(-1) is achieved by formation of strongly fluorescent aluminum/tetracycline complexes, without prior extraction or separation of the individual antibiotics. This is performed by determinations at the peak excitation and fluorescence emission wavelengths of each tetracycline chelate. The method can be similarly applied to the assay of oxytetracycline, rolitetracycline and minocycline. | [
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PMID:6751 | Preliminary investigations of the metabolism and pharmacological activity of beta-hydroxytryptamines in mammals. | beta-Hydroxytryptamine and beta-hydroxy-5-hydroxytryptamine were incubated with rat liver slices and oxidative deamination was established as the main route of metabolism: in both instances the corresponding indole-3-glycollic acids and indole-3-ethane diols were the major metabolites. However, the rates of deamination of beta-hydroxylated tryptamines, as measured manometrically, were found to be much slower than those of tryptamines nonhydroxylated in the side chain. The pharmacological activities of beta-hydroxylated tryptamines were tested in guinea-pigs on resistance of respiratory pathways, spontaneous respiration, electrocardiogram, blood pressure and isolated ileum, using tryptamine and 5-HT as reference substances. The effects of tryptamines hydroxylated in the side chain were in general similar to those of corresponding tryptamines but of much lower intensities; only in increasing the blood pressure was beta-hydroxytryptamine as active as tryptamine. The different reactions of these two groups of substances in the presence of some antagonists indicate that the receptors are probably not the same. | Preliminary investigations of the metabolism and pharmacological activity of beta-hydroxytryptamines in mammals. beta-Hydroxytryptamine and beta-hydroxy-5-hydroxytryptamine were incubated with rat liver slices and oxidative deamination was established as the main route of metabolism: in both instances the corresponding indole-3-glycollic acids and indole-3-ethane diols were the major metabolites. However, the rates of deamination of beta-hydroxylated tryptamines, as measured manometrically, were found to be much slower than those of tryptamines nonhydroxylated in the side chain. The pharmacological activities of beta-hydroxylated tryptamines were tested in guinea-pigs on resistance of respiratory pathways, spontaneous respiration, electrocardiogram, blood pressure and isolated ileum, using tryptamine and 5-HT as reference substances. The effects of tryptamines hydroxylated in the side chain were in general similar to those of corresponding tryptamines but of much lower intensities; only in increasing the blood pressure was beta-hydroxytryptamine as active as tryptamine. The different reactions of these two groups of substances in the presence of some antagonists indicate that the receptors are probably not the same. | [
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PMID:6752 | Differential effect of neuroleptic drugs on dopamine turnover in the extrapyramidal and limbic system. | In gallamine-immobilized cats, the caudate nucleus and the nucleus accumbens septi were perfused by means of a push-pull cannula and dopamine was measured in the perfusate. Chlorpromazine (10 mg kg(-1)) and clozapine (20 mg kg(-1)), administered intravenously, enhanced the release of dopamine. The effect of chlorpromazine was similar in both regions whereas that of clozapine was more pronounced in the nucleus accumbens than in the caudate nucleus. Furthermore, in the rat, sulpiride, clozapine and thioridazine increased the homovanillic acid concentration in striatum and limbic system to a similar extent. However, following probenecid administration, the net effect of these drugs on homovanillic acid accumulation was more marked in the limbic system than in the striatum whereas haolperidol and chlorpromazine had a similar effect in the two regions. It is concluded that, in contrast to haloperidol and chlorpromazine, sulpiride, clozapine and thioridazine may preferentially affect the limbic dopaminergic transmission. This possibly accounts for the fact that sulpiride, clozapine and thioridazine display an antipsychotic action and yet cause less extrapyramidal side effects than haloperidol and chlorpromazine. | Differential effect of neuroleptic drugs on dopamine turnover in the extrapyramidal and limbic system. In gallamine-immobilized cats, the caudate nucleus and the nucleus accumbens septi were perfused by means of a push-pull cannula and dopamine was measured in the perfusate. Chlorpromazine (10 mg kg(-1)) and clozapine (20 mg kg(-1)), administered intravenously, enhanced the release of dopamine. The effect of chlorpromazine was similar in both regions whereas that of clozapine was more pronounced in the nucleus accumbens than in the caudate nucleus. Furthermore, in the rat, sulpiride, clozapine and thioridazine increased the homovanillic acid concentration in striatum and limbic system to a similar extent. However, following probenecid administration, the net effect of these drugs on homovanillic acid accumulation was more marked in the limbic system than in the striatum whereas haolperidol and chlorpromazine had a similar effect in the two regions. It is concluded that, in contrast to haloperidol and chlorpromazine, sulpiride, clozapine and thioridazine may preferentially affect the limbic dopaminergic transmission. This possibly accounts for the fact that sulpiride, clozapine and thioridazine display an antipsychotic action and yet cause less extrapyramidal side effects than haloperidol and chlorpromazine. | [
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PMID:6753 | An in vitro method for the study of beta-receptor mediated effects on slow contracting skeletal muscle. | The soleus muscle of a guinea-pig was dissected out under pentobarbitone anaesthesia and mounted on a holder in an organ bath containing Krebs solution. The tendon was attached to a force transducer and subtetanic contractions were evoked by electrical field stimulation (0.5 ms pulses at 10-12 Hz for 1.5 or 3 s every 22 s). The experiments were performed at 37 degrees. Terbutaline, a selective agonist at beta2-adrenoceptors, reduced the force of subtetanic contractions in a dose-dependent manner, the EC50 being 0.2 muM. The reduction was due to a lessened degree of fusion. The results conform to previous in vivo studies. | An in vitro method for the study of beta-receptor mediated effects on slow contracting skeletal muscle. The soleus muscle of a guinea-pig was dissected out under pentobarbitone anaesthesia and mounted on a holder in an organ bath containing Krebs solution. The tendon was attached to a force transducer and subtetanic contractions were evoked by electrical field stimulation (0.5 ms pulses at 10-12 Hz for 1.5 or 3 s every 22 s). The experiments were performed at 37 degrees. Terbutaline, a selective agonist at beta2-adrenoceptors, reduced the force of subtetanic contractions in a dose-dependent manner, the EC50 being 0.2 muM. The reduction was due to a lessened degree of fusion. The results conform to previous in vivo studies. | [
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PMID:6754 | Effects of alpha-methyldopa on blood pressure in the anaesthetized dog. | Intravenous infusion over 1 h of 20 mg kg(-1) of alpha-methyldopa produced hypotension in the anaesthetized dog. The magnitude of this effect was, however, inversely correlated with bodyweight. Either rapid intravenous injection of alpha-methyldopa or slow infusion of alpha-methyldopate, was less effective in lowering blood pressure than infusion of free alpha methyldopa in dogs of equivalent bodyweight. Infusion of alpha-methyldopa into a vertebral or internal carotid artery produced hypotensive responses but these were no greater and generally less than those obtained to intravenous infusion. alpha-Methyldopa was therefore capable of producing hypotension in the dog but no evidence was obtained for this being the result of an action within the brain. | Effects of alpha-methyldopa on blood pressure in the anaesthetized dog. Intravenous infusion over 1 h of 20 mg kg(-1) of alpha-methyldopa produced hypotension in the anaesthetized dog. The magnitude of this effect was, however, inversely correlated with bodyweight. Either rapid intravenous injection of alpha-methyldopa or slow infusion of alpha-methyldopate, was less effective in lowering blood pressure than infusion of free alpha methyldopa in dogs of equivalent bodyweight. Infusion of alpha-methyldopa into a vertebral or internal carotid artery produced hypotensive responses but these were no greater and generally less than those obtained to intravenous infusion. alpha-Methyldopa was therefore capable of producing hypotension in the dog but no evidence was obtained for this being the result of an action within the brain. | [
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PMID:6755 | The effect of cholinesterase inhibitors on the antimuscarinic effect of hemicholinium-3 (HC-3) in the rat. | The effect of hemicholinium-3 (HC-3) on responses of the rat isolated bladder and ileum to acetylcholine and carbachol was investigated in the absence and presence of a number of anticholinesterases. Responses of the bladder to acetylcholine were potentiated by DFP, edrophonium, BW284C51 and physostigmine but were unaffected by the specific butyrylcholinesterase inhibitor iso-OMPA. Responses to carbachol were not potentiated by the anticholinesterases. HC-3 (1.7 X 10(-4) M) inhibited responses to carbachol without affecting those to acetylcholine. In the presence of physostigmine or DFP responses to acetylcholine were inhibited by HC-3 but no such inhibition was observed in the presence of BW284C51, edrophonium or iso-OMPA or a combination of the latter two anticholinesterases. Responses to carbachol were also inhibited to a greater extent in the presence of DFP. In the ileum, responses to acetylcholine were increased in the presence of DFP, edrophonium and physostigmine but were unaffected by iso-Ompa. responses to carbachol were not increased by any of the anticholinesterases. HC-3 (2.8 X 10(-4) M) inhibited responses to both acetylcholine and carbachol in the ileum and the degree of inhibition was not significantly altered by the presence of any of the anticholinesterases used. Although a weak anticholinesterase, HC-3 was also found to decrease the inhibitory action of physostigmine on the hydrolysis of acetylcholine by homogenates of rat ileum. A similar effect was noted with DFP but not with edrophonium. The results obtained do not support a prejunctional action for HC-3 in antagonizing responses to carbachol. It is concluded that in addition to an inhibitory action on the post-junctional muscarinic receptor HC-3 may interfere with the anticholinesterase activity of some cholinesterase inhibitors such as physostigmine and DFP but not edrophonium. | The effect of cholinesterase inhibitors on the antimuscarinic effect of hemicholinium-3 (HC-3) in the rat. The effect of hemicholinium-3 (HC-3) on responses of the rat isolated bladder and ileum to acetylcholine and carbachol was investigated in the absence and presence of a number of anticholinesterases. Responses of the bladder to acetylcholine were potentiated by DFP, edrophonium, BW284C51 and physostigmine but were unaffected by the specific butyrylcholinesterase inhibitor iso-OMPA. Responses to carbachol were not potentiated by the anticholinesterases. HC-3 (1.7 X 10(-4) M) inhibited responses to carbachol without affecting those to acetylcholine. In the presence of physostigmine or DFP responses to acetylcholine were inhibited by HC-3 but no such inhibition was observed in the presence of BW284C51, edrophonium or iso-OMPA or a combination of the latter two anticholinesterases. Responses to carbachol were also inhibited to a greater extent in the presence of DFP. In the ileum, responses to acetylcholine were increased in the presence of DFP, edrophonium and physostigmine but were unaffected by iso-Ompa. responses to carbachol were not increased by any of the anticholinesterases. HC-3 (2.8 X 10(-4) M) inhibited responses to both acetylcholine and carbachol in the ileum and the degree of inhibition was not significantly altered by the presence of any of the anticholinesterases used. Although a weak anticholinesterase, HC-3 was also found to decrease the inhibitory action of physostigmine on the hydrolysis of acetylcholine by homogenates of rat ileum. A similar effect was noted with DFP but not with edrophonium. The results obtained do not support a prejunctional action for HC-3 in antagonizing responses to carbachol. It is concluded that in addition to an inhibitory action on the post-junctional muscarinic receptor HC-3 may interfere with the anticholinesterase activity of some cholinesterase inhibitors such as physostigmine and DFP but not edrophonium. | [
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PMID:6771 | Rapid and sensitive colorimetric determination of cobalt(II). | A highly selective and sensitive spectrophotometric determination of cobalt (II) was developed. 7-Nitroso-8-hydroxyquinoline-5-sulfonic acid sodium salt was used as the chromogenic reagent for color development. Although other metals form colored chelates with the ligand, it was possible to develop a selective method using McIlvaine's pH 8 citric acid-phosphate buffer. Under these conditions, iron(II), iron (III), copper (II), zinc (II), and manganese (II), minerals likely to be compounded with cobalt (II) in geriatric formulations, do not interfere with the precision of the method or the color development. Calcium (II) and magnesium (II) do not form colored chelates with the used ligand. Hormones, vitamins, and additives likely to be present along with the cobalt ion in pharmaceutical formulations do not interfere. The sensitivity is 0.37 mug of cobalt (II)/ml of sample solution. | Rapid and sensitive colorimetric determination of cobalt(II). A highly selective and sensitive spectrophotometric determination of cobalt (II) was developed. 7-Nitroso-8-hydroxyquinoline-5-sulfonic acid sodium salt was used as the chromogenic reagent for color development. Although other metals form colored chelates with the ligand, it was possible to develop a selective method using McIlvaine's pH 8 citric acid-phosphate buffer. Under these conditions, iron(II), iron (III), copper (II), zinc (II), and manganese (II), minerals likely to be compounded with cobalt (II) in geriatric formulations, do not interfere with the precision of the method or the color development. Calcium (II) and magnesium (II) do not form colored chelates with the used ligand. Hormones, vitamins, and additives likely to be present along with the cobalt ion in pharmaceutical formulations do not interfere. The sensitivity is 0.37 mug of cobalt (II)/ml of sample solution. | [
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PMID:6772 | High-pressure liquid chromatographic determination of the 15-epimer of dinoprost in bulk drug. | The p-nitrophenacyl esters of dinoprost and its 15-epimer are well resolved using high-pressure liquid chromatography. Quantitation was achieved using the internal standard technique. The specially synthesized diphenylurea ester of cholic acid was found to be a model internal standard. Graphs of peak height ratios of the prostaglandin to the internal standard were linear with respect to the amount of prostaglandin injected, with the lower detection limit of the 15-epimer being about 0.5%. Data are presented that demonstrate the usefulness of this analytical technique in determining the concentration of the 15-epimer present during studies on the kinetics of decomposition of dinoprost. | High-pressure liquid chromatographic determination of the 15-epimer of dinoprost in bulk drug. The p-nitrophenacyl esters of dinoprost and its 15-epimer are well resolved using high-pressure liquid chromatography. Quantitation was achieved using the internal standard technique. The specially synthesized diphenylurea ester of cholic acid was found to be a model internal standard. Graphs of peak height ratios of the prostaglandin to the internal standard were linear with respect to the amount of prostaglandin injected, with the lower detection limit of the 15-epimer being about 0.5%. Data are presented that demonstrate the usefulness of this analytical technique in determining the concentration of the 15-epimer present during studies on the kinetics of decomposition of dinoprost. | [
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PMID:6773 | Effect of edetate disodium and reduced glutathione on absorption of acetazolamide from GI tract of rats. | The absorption of acetazolamide suspensions from in situ rat gastric and intestinal loop segments was studied. In 1 hr, 66.2 and 64.3% remained unabsorbed from the rat stomach and intestine, respectively. Although 1% (w/v) reduced glutathione and 1% (w/v) (24 mM) edetate disodium had no effect on gastric absorption, drug absorption from the rat intestine (1 hr) was increased 1.5 and 2 times, respectively. It was hypothesized that the relatively poor intestinal absorption was due primarily to the formation of a pH-dependent (pH 4.5-10), nonabsorbable complex between acetazolamide and carbonic anhydrase present in the gut and that reduced glutathione acted as an inhibitor to promote intestinal absorption. Equilibrium dialysis studies showed that reduced glutathion could reduce the fraction of drug bound to human carbonic anhydrase B by one-half when present in a molar ratio 10 times that of acetazolamide; edetate disodium had no effect on the in vitro binding. It was, therefore, assumed that edetate disodium promoted an increase in intestinal absorption by altering the permeability of intestinal epithelium. Based upon present experimentation, however, the alteration of intestinal epithelium by reduced glutathione cannot be ruled out. | Effect of edetate disodium and reduced glutathione on absorption of acetazolamide from GI tract of rats. The absorption of acetazolamide suspensions from in situ rat gastric and intestinal loop segments was studied. In 1 hr, 66.2 and 64.3% remained unabsorbed from the rat stomach and intestine, respectively. Although 1% (w/v) reduced glutathione and 1% (w/v) (24 mM) edetate disodium had no effect on gastric absorption, drug absorption from the rat intestine (1 hr) was increased 1.5 and 2 times, respectively. It was hypothesized that the relatively poor intestinal absorption was due primarily to the formation of a pH-dependent (pH 4.5-10), nonabsorbable complex between acetazolamide and carbonic anhydrase present in the gut and that reduced glutathione acted as an inhibitor to promote intestinal absorption. Equilibrium dialysis studies showed that reduced glutathion could reduce the fraction of drug bound to human carbonic anhydrase B by one-half when present in a molar ratio 10 times that of acetazolamide; edetate disodium had no effect on the in vitro binding. It was, therefore, assumed that edetate disodium promoted an increase in intestinal absorption by altering the permeability of intestinal epithelium. Based upon present experimentation, however, the alteration of intestinal epithelium by reduced glutathione cannot be ruled out. | [
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PMID:6774 | Chlorpromazine metabolism VIII: blood levels of chlorpromazine and its sulfoxide in schizophrenic patients. | A procedure was standardized for extracting chloropromazine and its sulfoxide from the blood and for applying a recently developed fluorometric assay method to determine blood levels of these two compounds in schizophrenic patients receiving chlorpromazine therapy. The described methodology opens avenues for performing bioavailability and generic equivalence studies in humans. | Chlorpromazine metabolism VIII: blood levels of chlorpromazine and its sulfoxide in schizophrenic patients. A procedure was standardized for extracting chloropromazine and its sulfoxide from the blood and for applying a recently developed fluorometric assay method to determine blood levels of these two compounds in schizophrenic patients receiving chlorpromazine therapy. The described methodology opens avenues for performing bioavailability and generic equivalence studies in humans. | [
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PMID:6775 | Effects of various hydrodynamic conditions on dissolution rate determinations. | An automated potentiometric procedure was used in dissolution rate studies to determine the effects of various hydrodynamic conditions on dissolution rate determinations. Changes in the hydrodynamics of the system resulted from using various sizes and shapes of dissolution vessels. Dissolution rate constants for benzoic acid prills in distilled water at pH-stat 6.2 were used as a measure of the agitation intensities present in the different shaped vessels. Great variations in the dissolution rates occurred in vessels with the same diameter and stirrer blade position when the shapes of the bottom of the vessel were varied. A similar order of dissolution rates was obtained at 100 and 150 rpm for the individual vessels at various propeller heights. The order differed from one vessel to another, depending on the shape of the bottom (concave, convex, or flat) of the vessel. In some cases, a change in the type of bottom resulted in the opposite order of rates for vessels with the same diameter. | Effects of various hydrodynamic conditions on dissolution rate determinations. An automated potentiometric procedure was used in dissolution rate studies to determine the effects of various hydrodynamic conditions on dissolution rate determinations. Changes in the hydrodynamics of the system resulted from using various sizes and shapes of dissolution vessels. Dissolution rate constants for benzoic acid prills in distilled water at pH-stat 6.2 were used as a measure of the agitation intensities present in the different shaped vessels. Great variations in the dissolution rates occurred in vessels with the same diameter and stirrer blade position when the shapes of the bottom of the vessel were varied. A similar order of dissolution rates was obtained at 100 and 150 rpm for the individual vessels at various propeller heights. The order differed from one vessel to another, depending on the shape of the bottom (concave, convex, or flat) of the vessel. In some cases, a change in the type of bottom resulted in the opposite order of rates for vessels with the same diameter. | [
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PMID:6776 | Determination of tinidazole in tablets by dc polarography. | A polarographic method was developed for determining tinidazole in tablets. The substance is extracted from the sample with water, pH 6.8 Britton-Robinson buffer is added to an aliquot, and the solution is polarographed at the dropping mercury electrode versus the saturated calomel electrode. The polarographic wave is well developed and enables a fairly precise quantitative determination. The method of standard addition is used. | Determination of tinidazole in tablets by dc polarography. A polarographic method was developed for determining tinidazole in tablets. The substance is extracted from the sample with water, pH 6.8 Britton-Robinson buffer is added to an aliquot, and the solution is polarographed at the dropping mercury electrode versus the saturated calomel electrode. The polarographic wave is well developed and enables a fairly precise quantitative determination. The method of standard addition is used. | [
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PMID:6777 | Spectrophotometric determination of diphenhydramine hydrochloride using dipicrylamine. | A spectrophotometric procedure for the determination of diphenhydramine hydrochloride based on the reaction with dipicrylamine was developed. A yellow complex forms and is easily extractable by chloroform at pH 5. The mole ratio of diphenydramine hydrochloride to dipicrylamine in the complex is 1:3. The absorbance of the complex obeys Beer's law over the concentration range of 3-10 mug of diphenhydramine hydrochloride per ml of chloroform. This procedure can be carried out in the presence of other compounds without interference. | Spectrophotometric determination of diphenhydramine hydrochloride using dipicrylamine. A spectrophotometric procedure for the determination of diphenhydramine hydrochloride based on the reaction with dipicrylamine was developed. A yellow complex forms and is easily extractable by chloroform at pH 5. The mole ratio of diphenydramine hydrochloride to dipicrylamine in the complex is 1:3. The absorbance of the complex obeys Beer's law over the concentration range of 3-10 mug of diphenhydramine hydrochloride per ml of chloroform. This procedure can be carried out in the presence of other compounds without interference. | [
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PMID:6778 | Application of trihydroxyindole reaction to methanesulfonanilides: fluorometric analysis for soterenol and mesuprine. | Methanesulfonanilides, like soterenol and mesuprine, which are bioisosteric with adrenergic catecholamines, form fluorescent species when subjected to the trihydroxyindole reaction. Presumably, the fluorescence is due to adrenolutin-like species formed from aminochrome intermediates. Fluorescence was not induced in a relative of soterenol where a methyl group was added to the sulfonamido nitrogen, a fact that suggests the presence of a quinoid intermediate in the reaction scheme of soterenol. A ring isomer of soterenol, where the methanesulfonamido and hydroxyl groups were interchanged, produced only about 5% as much fluorescence response as soterenol. The sterenol counterparts to isoproterenol and isoproterenol sulfonic acid did not produce fluorescence when treated like soterenol. This finding and the fact that response was linear with concentration for soterenol and mesuprine suggest that a fluorometric analysis could be developed for these methanesulfonanilides. | Application of trihydroxyindole reaction to methanesulfonanilides: fluorometric analysis for soterenol and mesuprine. Methanesulfonanilides, like soterenol and mesuprine, which are bioisosteric with adrenergic catecholamines, form fluorescent species when subjected to the trihydroxyindole reaction. Presumably, the fluorescence is due to adrenolutin-like species formed from aminochrome intermediates. Fluorescence was not induced in a relative of soterenol where a methyl group was added to the sulfonamido nitrogen, a fact that suggests the presence of a quinoid intermediate in the reaction scheme of soterenol. A ring isomer of soterenol, where the methanesulfonamido and hydroxyl groups were interchanged, produced only about 5% as much fluorescence response as soterenol. The sterenol counterparts to isoproterenol and isoproterenol sulfonic acid did not produce fluorescence when treated like soterenol. This finding and the fact that response was linear with concentration for soterenol and mesuprine suggest that a fluorometric analysis could be developed for these methanesulfonanilides. | [
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PMID:6779 | Continuous dissolution rate determination as a function of the pH of the medium. | A method was developed for varying the pH of the medium during dissolution rate studies of timed-release tablets with the aid of compressed, totally soluble, alkaline powder mixtures. Commercial as well as experimental timed-release capsules or tablets were used as models, and dissolution rates were determined at pH 1.1, 2.4, and 7.4. The system can be applied to other pH values or other variations of the dissolution medium (e.g., ionic strength) to: (a) correlate in vitro release rates with bioavailability data, (b) discriminate between alternative formulations during dosage form development, or (c) serve as a selective control procedure for a series of sustanined-release dosage forms. | Continuous dissolution rate determination as a function of the pH of the medium. A method was developed for varying the pH of the medium during dissolution rate studies of timed-release tablets with the aid of compressed, totally soluble, alkaline powder mixtures. Commercial as well as experimental timed-release capsules or tablets were used as models, and dissolution rates were determined at pH 1.1, 2.4, and 7.4. The system can be applied to other pH values or other variations of the dissolution medium (e.g., ionic strength) to: (a) correlate in vitro release rates with bioavailability data, (b) discriminate between alternative formulations during dosage form development, or (c) serve as a selective control procedure for a series of sustanined-release dosage forms. | [
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PMID:6780 | Controlled flocculation of coarse suspensions by colloidally dispersed solids I: Interaction of bismuth subnitrate with bentonite. | Deflocculated suspensions of coarse powders tend to cake as the individual particles settle out and form compact, cohesive sediments. Limited flocculation results in looser sediments because the settled-out flocs incorporate large amounts of the liquid suspending medium. Controlled flocculation of bismuth subnitrate suspensions was achieved by the addition of small amounts of bentonite. The interaction of the coarse, positively charge bismuth subnitrate particles in aqueous suspension with negatively charged, colloidally dispersed bentonite was investigated by measuring electrophoretic mobility, sedimentation volume, and viscosity. Gradual addition of bentonite dispersion to bismuth subnitrate suspensions first reduced the zeta-potential of the bismuth subnitrate particles from +28 mv to zero, then inverted it, and finally caused it to level off at -20 mv for bismuth subnitrate-bentonite weight ratios below 200. Owing to the much greater specific surface area of bentonite, the surface of the bismuth subnitrate lath-shaped crystals was completely covered by 0.5% of its weight in clay platelets. Adhesion was promoted by electrovalences between surface bismuthyl ions and cation-exchange sites of the clay and by secondary valences. The charge neutralization of bismuth subnitrate by bentonite was a heterocoagulation process: the addition of small amounts of the clay flocculated the bismuth subnitrate suspensions and eliminated caking. While the zeta-potential of the bismuth subnitrate particles leveled off when their surface was saturated with bentonite platelets, sedimentation volume and viscosity continued to increase when the clay concentration was increased further while maintaining the bismuth subnitrate concentration constant. The excess, nonadsorbed bentonite formed the characteristic house-of-cards structure, incorporating the bentonite-coated bismuth subnitrate particles as cornerstones. | Controlled flocculation of coarse suspensions by colloidally dispersed solids I: Interaction of bismuth subnitrate with bentonite. Deflocculated suspensions of coarse powders tend to cake as the individual particles settle out and form compact, cohesive sediments. Limited flocculation results in looser sediments because the settled-out flocs incorporate large amounts of the liquid suspending medium. Controlled flocculation of bismuth subnitrate suspensions was achieved by the addition of small amounts of bentonite. The interaction of the coarse, positively charge bismuth subnitrate particles in aqueous suspension with negatively charged, colloidally dispersed bentonite was investigated by measuring electrophoretic mobility, sedimentation volume, and viscosity. Gradual addition of bentonite dispersion to bismuth subnitrate suspensions first reduced the zeta-potential of the bismuth subnitrate particles from +28 mv to zero, then inverted it, and finally caused it to level off at -20 mv for bismuth subnitrate-bentonite weight ratios below 200. Owing to the much greater specific surface area of bentonite, the surface of the bismuth subnitrate lath-shaped crystals was completely covered by 0.5% of its weight in clay platelets. Adhesion was promoted by electrovalences between surface bismuthyl ions and cation-exchange sites of the clay and by secondary valences. The charge neutralization of bismuth subnitrate by bentonite was a heterocoagulation process: the addition of small amounts of the clay flocculated the bismuth subnitrate suspensions and eliminated caking. While the zeta-potential of the bismuth subnitrate particles leveled off when their surface was saturated with bentonite platelets, sedimentation volume and viscosity continued to increase when the clay concentration was increased further while maintaining the bismuth subnitrate concentration constant. The excess, nonadsorbed bentonite formed the characteristic house-of-cards structure, incorporating the bentonite-coated bismuth subnitrate particles as cornerstones. | [
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PMID:6781 | Urinary excretion of probenecid and its metabolites in humans as a function of dose. | A GLC assay was used to study the excretion of probenecid and its metabolites in the urine of human subjects following oral doses of 0.5, 1, and 2 g. From 75 to 88% of the dose was found in the urine. The major metabolite, probenecid acyl glucuronide, accounted for 34-47% of the dose. Approximately equal amounts (10-15%) of the mono-N-propyl, secondary alcohol, and carboxylic acid metabolites were excreted in the unconjugated from with only traces in the conjugated form. The primary alcohol metabolite was not found in measurable amounts. The terminal half-lives for excretion of all metabolites were in the range of 4-6 hr, were independent of dose, and were limited by their rates of formation. A prolonged time course of excretion of the metabolites, particularly at higher doses, suggests that probenecid, being poorly soluble in water, precipitates from solution in the GI tract, forming a depot of drug from which absorption is dissolution rate limited. The urinary excretion of unchanged probenecid, which accounts for 4-13% of the dose, is dependent on both the pH and flow rate of urine. | Urinary excretion of probenecid and its metabolites in humans as a function of dose. A GLC assay was used to study the excretion of probenecid and its metabolites in the urine of human subjects following oral doses of 0.5, 1, and 2 g. From 75 to 88% of the dose was found in the urine. The major metabolite, probenecid acyl glucuronide, accounted for 34-47% of the dose. Approximately equal amounts (10-15%) of the mono-N-propyl, secondary alcohol, and carboxylic acid metabolites were excreted in the unconjugated from with only traces in the conjugated form. The primary alcohol metabolite was not found in measurable amounts. The terminal half-lives for excretion of all metabolites were in the range of 4-6 hr, were independent of dose, and were limited by their rates of formation. A prolonged time course of excretion of the metabolites, particularly at higher doses, suggests that probenecid, being poorly soluble in water, precipitates from solution in the GI tract, forming a depot of drug from which absorption is dissolution rate limited. The urinary excretion of unchanged probenecid, which accounts for 4-13% of the dose, is dependent on both the pH and flow rate of urine. | [
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PMID:6782 | Nitrofurantoin solubility in aqueous urea and creatinine solutions. | Experiments were carried out to determine the effect of urea and creatinine on the solubility of nitrofurantoin in water at different temperature and pH conditions. The addition of urea to aqueous media increased nitrofurantoin solubility up to a maximum concentration level and then decreased solubility at higher urea concentrations. The amount of urea needed to bring about maximum nitrofurantoin solubility was dependent on temperature and ranged between 1.75 and 2.50%. Spectral studies suggest a possible interaction between urea and nitrofurantoin molecules. Nitrofurantoin solubility increased with an increasing creatinine concentration ranging from 0.05 to 1.6%. Spectral studies indicate a strong interaction between creatinine and nitrofurantoin molecules in solution. The combined effect of urea and creatinine of the solubility of nitrofurantoin could account for the absence of crystalluria with this drug, even though unusually high concentrations in urine have been reported. | Nitrofurantoin solubility in aqueous urea and creatinine solutions. Experiments were carried out to determine the effect of urea and creatinine on the solubility of nitrofurantoin in water at different temperature and pH conditions. The addition of urea to aqueous media increased nitrofurantoin solubility up to a maximum concentration level and then decreased solubility at higher urea concentrations. The amount of urea needed to bring about maximum nitrofurantoin solubility was dependent on temperature and ranged between 1.75 and 2.50%. Spectral studies suggest a possible interaction between urea and nitrofurantoin molecules. Nitrofurantoin solubility increased with an increasing creatinine concentration ranging from 0.05 to 1.6%. Spectral studies indicate a strong interaction between creatinine and nitrofurantoin molecules in solution. The combined effect of urea and creatinine of the solubility of nitrofurantoin could account for the absence of crystalluria with this drug, even though unusually high concentrations in urine have been reported. | [
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PMID:6783 | Influence of pH and route of injection on acute toxicity of tetracycline in mice. | Some LD50 determinations for tetracycline hydrochloride in mice were carried out over a range of pH values, using both the intraperitoneal and the subcutaneous routes of injection. Depending on the pH of the formulation, either water or a solvent system of water and 60% (v/v) propylene glycol was employed thus ensuring complete solution of the drug at all pH values tested. Higher LD50 values were obtained with the subcutaneous route than with the intraperitoneal route. With either route of administration, there was a trend toward lowest LD50 value occurrence at the isoelectric pH of tetracycline. Actual statistical significance was achieved for the intraperitoneal route only when LD50 values obtained at the isoelectric pH were compared with either of the more acidic pH values. | Influence of pH and route of injection on acute toxicity of tetracycline in mice. Some LD50 determinations for tetracycline hydrochloride in mice were carried out over a range of pH values, using both the intraperitoneal and the subcutaneous routes of injection. Depending on the pH of the formulation, either water or a solvent system of water and 60% (v/v) propylene glycol was employed thus ensuring complete solution of the drug at all pH values tested. Higher LD50 values were obtained with the subcutaneous route than with the intraperitoneal route. With either route of administration, there was a trend toward lowest LD50 value occurrence at the isoelectric pH of tetracycline. Actual statistical significance was achieved for the intraperitoneal route only when LD50 values obtained at the isoelectric pH were compared with either of the more acidic pH values. | [
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PMID:6784 | Monoamine oxidase inhibition and the induction of ponto-geniculo-occipital wave activity by reserpine in the cat. | Reserpine induces ponto-geniculo-occipital wave activity similar to that seen in the cat during the rapid eye movement phase of sleep. This action of reserpine was blocked by the monoamine oxidase inhibitors, pheniprazine, harmaline and clorgyline, but not deprenyl or its demethylated analog. After a single dose (20 mg/kg) of either pheniprazine or harmaline, the time course of antagonism of the effect of reserpine was in good correspondence with inhibition of monoamine oxidase but not with restoration of the serotonin content of several regions of the brain. Harmaline had a reversible effect while that of pheniprazine persisted for weeks. Clorgyline in low doses (0.5-1.0 mg/kg), at which it is a specific inhibitor of type A monoamine oxidase, antagonized the action of reserpine for over 2 weeks. Deprenyl and its demethylated analog failed to suppress the reserpine-induced waves even at 10 times the dose of clorgyline when they should have completely inhibited type B monoamine oxidase. In contrast to antagonism of reserpine, suppression of rapid eye movement sleep by these monoamine oxidase inhibitors could be temporally dissociated from their inhibition of the enzyme. It is concluded that suppression of the induction of ponto-geniculo-occipital waves by reserpine after administration of the monoamine oxidase inhibitors is a specific effect of these drugs and is related to inhibition of type A monoamine oxidase. Suppression of rapid eye movement sleep is probably a nonspecific effect and not related to inhibition of the enzyme. | Monoamine oxidase inhibition and the induction of ponto-geniculo-occipital wave activity by reserpine in the cat. Reserpine induces ponto-geniculo-occipital wave activity similar to that seen in the cat during the rapid eye movement phase of sleep. This action of reserpine was blocked by the monoamine oxidase inhibitors, pheniprazine, harmaline and clorgyline, but not deprenyl or its demethylated analog. After a single dose (20 mg/kg) of either pheniprazine or harmaline, the time course of antagonism of the effect of reserpine was in good correspondence with inhibition of monoamine oxidase but not with restoration of the serotonin content of several regions of the brain. Harmaline had a reversible effect while that of pheniprazine persisted for weeks. Clorgyline in low doses (0.5-1.0 mg/kg), at which it is a specific inhibitor of type A monoamine oxidase, antagonized the action of reserpine for over 2 weeks. Deprenyl and its demethylated analog failed to suppress the reserpine-induced waves even at 10 times the dose of clorgyline when they should have completely inhibited type B monoamine oxidase. In contrast to antagonism of reserpine, suppression of rapid eye movement sleep by these monoamine oxidase inhibitors could be temporally dissociated from their inhibition of the enzyme. It is concluded that suppression of the induction of ponto-geniculo-occipital waves by reserpine after administration of the monoamine oxidase inhibitors is a specific effect of these drugs and is related to inhibition of type A monoamine oxidase. Suppression of rapid eye movement sleep is probably a nonspecific effect and not related to inhibition of the enzyme. | [
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PMID:6785 | Further studies on angiotensin tachyphylaxis. | Rabbit aorta and rat fundus do not display tachyphylaxis to angiotensin II (Asp1)angiotensin II) at 37 degrees C. These tissues do, however, display tachyphylaxis to [Sar1]angiotensin II (N-methylglycine 1 angiotensin II) and [dimethylglycine angiotensin II, respectively, at this temperature. At 22 degrees C, both tissues displayed rapid tachyphylaxis to [Asp1]angiotensin II which was reversed on prolonged incubation in peptide-free medium. At 37 degrees C, but at a lower than normal pH (pH 6.5 instead of 7.4), the rabbit aorta developed rapid tachyphylaxis to [Asp1)angiotensin II; this effect also was reversed on prolonged incubation in peptide-free medium. The rat uterus, at 30 degrees C, displayed tachyphylaxis to [Asp1]angiotensin II and analogs in order of rate of onset: [Sar1]angiotensin II greater than [Asp1]angiotensin II greater than [des-Asp1]angiotensin II. Over half of the individual uterine strips tested displayed no tachyphylaxis to [des-Asp1]angiotensin II. However, at 22 degrees C tachyphylaxis to all three compounds was rapid on onset and was reversed on prolonged incubation. The results indicate a correlation between affinity of the peptide analog for angiotensin receptor and its ability to induce tachyphylaxis. A possible involvement of membrane-bound enzymes in the onset and duration of tachyphylaxis is suggested. | Further studies on angiotensin tachyphylaxis. Rabbit aorta and rat fundus do not display tachyphylaxis to angiotensin II (Asp1)angiotensin II) at 37 degrees C. These tissues do, however, display tachyphylaxis to [Sar1]angiotensin II (N-methylglycine 1 angiotensin II) and [dimethylglycine angiotensin II, respectively, at this temperature. At 22 degrees C, both tissues displayed rapid tachyphylaxis to [Asp1]angiotensin II which was reversed on prolonged incubation in peptide-free medium. At 37 degrees C, but at a lower than normal pH (pH 6.5 instead of 7.4), the rabbit aorta developed rapid tachyphylaxis to [Asp1)angiotensin II; this effect also was reversed on prolonged incubation in peptide-free medium. The rat uterus, at 30 degrees C, displayed tachyphylaxis to [Asp1]angiotensin II and analogs in order of rate of onset: [Sar1]angiotensin II greater than [Asp1]angiotensin II greater than [des-Asp1]angiotensin II. Over half of the individual uterine strips tested displayed no tachyphylaxis to [des-Asp1]angiotensin II. However, at 22 degrees C tachyphylaxis to all three compounds was rapid on onset and was reversed on prolonged incubation. The results indicate a correlation between affinity of the peptide analog for angiotensin receptor and its ability to induce tachyphylaxis. A possible involvement of membrane-bound enzymes in the onset and duration of tachyphylaxis is suggested. | [
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PMID:6786 | Studies on adrenal phenylethanolamine N- methyltransferase (PNMT) with S K & F 64139, a selective inhibitor. | SK&F 64139 is a potent, reversible inhibitor of phenylethanolamine N-methyltransferase; its IC50 concentration in our standard assay system was 1 X 10(-7) M. Kinetically, the compound is a competitive inhibitor with respect to norepinephrine but is uncompetitive when S-adenosylmethionine is the variable substrate. In contrast to a previously reported compound (SK&F 7698), the drug is only a weak alpha receptor antagonist (KB = 6 X 10(-6) M). In both the rat and squirrel monkey, SK&F 64139 produced dose-dependent decreases in the adrenal epinephrine content coupled with stoichiometrically equivalent increases in the norepinephrine pool(s). Further evidence for in vivo phenylethanolamine N-methyltransferase inhibitory activity was that the drug markedly inhibited the conversion of a tracer dose of 3H-norepinephrine to 3H-epinephrine in the rat adrenal gland after unit oral doses as low as 5 mg/kg. | Studies on adrenal phenylethanolamine N- methyltransferase (PNMT) with S K & F 64139, a selective inhibitor. SK&F 64139 is a potent, reversible inhibitor of phenylethanolamine N-methyltransferase; its IC50 concentration in our standard assay system was 1 X 10(-7) M. Kinetically, the compound is a competitive inhibitor with respect to norepinephrine but is uncompetitive when S-adenosylmethionine is the variable substrate. In contrast to a previously reported compound (SK&F 7698), the drug is only a weak alpha receptor antagonist (KB = 6 X 10(-6) M). In both the rat and squirrel monkey, SK&F 64139 produced dose-dependent decreases in the adrenal epinephrine content coupled with stoichiometrically equivalent increases in the norepinephrine pool(s). Further evidence for in vivo phenylethanolamine N-methyltransferase inhibitory activity was that the drug markedly inhibited the conversion of a tracer dose of 3H-norepinephrine to 3H-epinephrine in the rat adrenal gland after unit oral doses as low as 5 mg/kg. | [
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PMID:6787 | The effects of metoclopramide in modifying the response of isolated guinea-pig ileum to various agonists. | Metoclopramide has a dual effect on intestinal smooth muscle. Low concentrations of metoclopramide cause potentiation of the responses to substance P, acetylcholine, histamine and barium chloride on the guinea-pig ileum. Higher concentrations produce a depression of smooth muscle responses which is characteristic of the tertiary amine local anesthetics. Neural pathways are involved in the mechanism of potentiation, since the enhancement of the responses to the agonists is abolished by tetrodotoxin. Atropine partially antagonizes the potentiating effect of metoclopramide implying that activation of muscarinic receptors is a contributing factor, but this does not fully explain the potentiation. | The effects of metoclopramide in modifying the response of isolated guinea-pig ileum to various agonists. Metoclopramide has a dual effect on intestinal smooth muscle. Low concentrations of metoclopramide cause potentiation of the responses to substance P, acetylcholine, histamine and barium chloride on the guinea-pig ileum. Higher concentrations produce a depression of smooth muscle responses which is characteristic of the tertiary amine local anesthetics. Neural pathways are involved in the mechanism of potentiation, since the enhancement of the responses to the agonists is abolished by tetrodotoxin. Atropine partially antagonizes the potentiating effect of metoclopramide implying that activation of muscarinic receptors is a contributing factor, but this does not fully explain the potentiation. | [
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PMID:6788 | Statistical parameters of transmitter release at frog neuromuscular junctions treated with guanidine or tetraethylammonium. | Transmitter release at Mg++ -depressed frog neuromuscular junctions can be described using binomial statistics. The number of quanta (m) released by the nerve terminal action potential is directly proportional to the mean probability (p) that a quantum will be released and the number of quanta available for release (n). Guanidine or tetraethylammonium (TEA) increased m and n, but had no effect on p. At junctions depressed by d-tubocurarine, both compounds enhanced the amplitude of the initial end-plate potential, caused an accelerated rate of fade of end-plate potential amplitudes and raised the steady-state level of end-plate potential amplitude. This finding was interpreted to mean that guanidine and TEA increased transmitter mobilization and may be related to the increase by the compounds of the parameters n. If so, then the data support the idea that n represents the number of quanta available for release rather than the number of transmitter release sites in the terminal membrane. Neither compound affected the power relationship between [Ca++]o and transmitter release. When plotted on a double logarithmic basis, the slope of the line relating [Ca++]o to increased transmitter release was 3.7, a relationship not altered by the drugs. Thus, the compounds had no effect on the fundamental interaction between Ca++ and transmitter release sites. In contrast to [Ca++]o, the power relationship between increased transmitter release and the concentration of drug in the bathing solution was 0.69 for guanidine and 0.84 for TEA. Because of this finding, it was concluded that the compounds increased transmitter release by mechanisms other than or in addition to increasing Ca++ conductance. | Statistical parameters of transmitter release at frog neuromuscular junctions treated with guanidine or tetraethylammonium. Transmitter release at Mg++ -depressed frog neuromuscular junctions can be described using binomial statistics. The number of quanta (m) released by the nerve terminal action potential is directly proportional to the mean probability (p) that a quantum will be released and the number of quanta available for release (n). Guanidine or tetraethylammonium (TEA) increased m and n, but had no effect on p. At junctions depressed by d-tubocurarine, both compounds enhanced the amplitude of the initial end-plate potential, caused an accelerated rate of fade of end-plate potential amplitudes and raised the steady-state level of end-plate potential amplitude. This finding was interpreted to mean that guanidine and TEA increased transmitter mobilization and may be related to the increase by the compounds of the parameters n. If so, then the data support the idea that n represents the number of quanta available for release rather than the number of transmitter release sites in the terminal membrane. Neither compound affected the power relationship between [Ca++]o and transmitter release. When plotted on a double logarithmic basis, the slope of the line relating [Ca++]o to increased transmitter release was 3.7, a relationship not altered by the drugs. Thus, the compounds had no effect on the fundamental interaction between Ca++ and transmitter release sites. In contrast to [Ca++]o, the power relationship between increased transmitter release and the concentration of drug in the bathing solution was 0.69 for guanidine and 0.84 for TEA. Because of this finding, it was concluded that the compounds increased transmitter release by mechanisms other than or in addition to increasing Ca++ conductance. | [
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PMID:6789 | Effect of fatty acids on the disposition of ammonia. | Subcoma doses of fatty acids and ammonium salts injected intraperitoneally at the same time into rats or cats act synergistically to produce coma. Under these circumstances, the blood ammonia, is more than double that when the NH4+ is given alone. After these observations a rat liver homogenate system was utilized to study the effect of fatty acids on ammonia utilization in urea, glutamate and glutamine synthesis in vitro. Acetylglutamate-catalyzed urea synthesis was completely inhibited by 45 mM octanoate and was depressed 46% by 9.5 mM octanoate. Citrulline synthesis was similarly inhibited 86 and 28%, respectively. The concentration of liver octanoate at the moment of occurrence of coma after an in vivo injection was approximately 10 mM. The inhibitory effect of fatty acids on the utilization of NH4+ in the urea cycle was greater the longer the fatty acid chain. The critical step in this interference with ammonia metabolism was the inhibition of carbamyl phosphate synthetase. Argininosuccinate synthetase activity was also inhibited to a lesser degree, but ornithine transcarbamylase, argininosuccinate lyase and arginase were unaffected. Glutamate dehydrogenase was likewise inhibited in liver (83%) and brain (43%) by 13 mM octanoate, whereas glutamine synthetase was unaffected. Thus, the two main processes whereby ammonia is metabolized were inhibited by fatty acids at concentrations that exist pathologically, which accounts, at least in part, for the rise in blood ammonia in vivo. | Effect of fatty acids on the disposition of ammonia. Subcoma doses of fatty acids and ammonium salts injected intraperitoneally at the same time into rats or cats act synergistically to produce coma. Under these circumstances, the blood ammonia, is more than double that when the NH4+ is given alone. After these observations a rat liver homogenate system was utilized to study the effect of fatty acids on ammonia utilization in urea, glutamate and glutamine synthesis in vitro. Acetylglutamate-catalyzed urea synthesis was completely inhibited by 45 mM octanoate and was depressed 46% by 9.5 mM octanoate. Citrulline synthesis was similarly inhibited 86 and 28%, respectively. The concentration of liver octanoate at the moment of occurrence of coma after an in vivo injection was approximately 10 mM. The inhibitory effect of fatty acids on the utilization of NH4+ in the urea cycle was greater the longer the fatty acid chain. The critical step in this interference with ammonia metabolism was the inhibition of carbamyl phosphate synthetase. Argininosuccinate synthetase activity was also inhibited to a lesser degree, but ornithine transcarbamylase, argininosuccinate lyase and arginase were unaffected. Glutamate dehydrogenase was likewise inhibited in liver (83%) and brain (43%) by 13 mM octanoate, whereas glutamine synthetase was unaffected. Thus, the two main processes whereby ammonia is metabolized were inhibited by fatty acids at concentrations that exist pathologically, which accounts, at least in part, for the rise in blood ammonia in vivo. | [
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PMID:6790 | Microsomal reductive glycosidase. | Rat liver microsomes contain a phenobarbital inducible, NADPH dependent, reductive glycosidase capable of cleaving several anthracycline antibiotics, including adriamycin and daunorubicin, to deoxyaglycone products. The pH optimum for the reaction ranges from 7 to 7.4, and no metal requirements are noted. Molecular oxygen reversibly inhibits the microsomal enzyme greater than 95% at 20% oxygen partial pressure. Carbon monoxide, SKF 525A and sulfhydryl reagents are not inhibitory to the reaction, but the enzyme is sensitive to Cu++ and Zn++. Since the intact glycoside is necessary for conversion to the deoxyaglycone and a possible intermediate hydroxylated aglycone is not reduced to the deoxyaglycone, a concerted reaction mechanism is proposed. The reductive glycosidase activity is also present in rat brain, kidney and other tissues. Sensitivity of this enzyme to molecular oxygen suggests a possible regulatory role for the enzyme in vivo. | Microsomal reductive glycosidase. Rat liver microsomes contain a phenobarbital inducible, NADPH dependent, reductive glycosidase capable of cleaving several anthracycline antibiotics, including adriamycin and daunorubicin, to deoxyaglycone products. The pH optimum for the reaction ranges from 7 to 7.4, and no metal requirements are noted. Molecular oxygen reversibly inhibits the microsomal enzyme greater than 95% at 20% oxygen partial pressure. Carbon monoxide, SKF 525A and sulfhydryl reagents are not inhibitory to the reaction, but the enzyme is sensitive to Cu++ and Zn++. Since the intact glycoside is necessary for conversion to the deoxyaglycone and a possible intermediate hydroxylated aglycone is not reduced to the deoxyaglycone, a concerted reaction mechanism is proposed. The reductive glycosidase activity is also present in rat brain, kidney and other tissues. Sensitivity of this enzyme to molecular oxygen suggests a possible regulatory role for the enzyme in vivo. | [
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PMID:6791 | Neutral protease activity and erythropoietin production in the rat after cobalt administration. | The generation of erythropoietin purportedly involves the interaction of an enzyme, of renal origin, and a circulating plasma protein substrate. Cobalt, which has the capacity to stimulate erythropoietin formation, was evaluated for its effects on renal and plasma protease activity; in addition, the nature of the erythrogenic mechanism was investigated. Rats receiving one s.c. injection of cobalt demonstrated significant increases in activity of renal cathepsins A and B. The activity of a plasma protease was also elevated in rats after cobalt treatment. Cathepsins A and B and plasma protease were sensitive to the same enzymatic inhibitory agents, and all three enzymes demonstrated activity patterns similar to that of the renal erythropoietic factor [enzyme(s) presumed responsible for generating erythropoietin] in rats treated with cobalt. These data may help to elucidate the mechanism of erythropoiesis. | Neutral protease activity and erythropoietin production in the rat after cobalt administration. The generation of erythropoietin purportedly involves the interaction of an enzyme, of renal origin, and a circulating plasma protein substrate. Cobalt, which has the capacity to stimulate erythropoietin formation, was evaluated for its effects on renal and plasma protease activity; in addition, the nature of the erythrogenic mechanism was investigated. Rats receiving one s.c. injection of cobalt demonstrated significant increases in activity of renal cathepsins A and B. The activity of a plasma protease was also elevated in rats after cobalt treatment. Cathepsins A and B and plasma protease were sensitive to the same enzymatic inhibitory agents, and all three enzymes demonstrated activity patterns similar to that of the renal erythropoietic factor [enzyme(s) presumed responsible for generating erythropoietin] in rats treated with cobalt. These data may help to elucidate the mechanism of erythropoiesis. | [
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PMID:6792 | Cholestyramine-induced inhibition of salicylazosulfapyridine (sulfasalazine) metabolism by rat intestinal microflora. | The effect of multiple oral administration of the hypocholesterolemic agent cholestyramine (a strongly basic anion-exchange resin) on the metabolism of salicylazosulfapyridine by microflora present in the colon and cecum was assessed in conventional rats by following the time course of salicylazosulfapyridine and its metabolites in the urine and feces. The intestinal metabolism of salicylazosulfapyridine (a single 100 mg/kg oral dose), which involves reduction of the azo linkage by bacterial azo reductases and the liberation of sulfapyridine and 5-aminosalicylic acid (potential active metabolites of the drug), was markedly inhibited by the resin (250 mg/kg oral doses at -2, +2 and +6 hours), resulting in an enhanced fecal excretion of intact salicylazosulfapyridine. The existence of a rank-order correlation between the in vitro binding of salicylazosulfapyridine, sulfapyridine and 5-aminosalicylic acid to the resin and their fecal excretion pattern in resin-treated animals suggests that a direct cholestyramine-salicylazosulfapyridine interaction occurred within the intestinal tract and that in the bound state, the azo bond of the drug was inaccessible to bacterial azo reductases. These findings suggest that chronic oral administration of cholestyramine to patients with ulcerative colitis who are receiving salicylazosulfapyridine could result in a significant reduction in the absorption and metabolism of the drug and hence, in its therapeutic efficacy. | Cholestyramine-induced inhibition of salicylazosulfapyridine (sulfasalazine) metabolism by rat intestinal microflora. The effect of multiple oral administration of the hypocholesterolemic agent cholestyramine (a strongly basic anion-exchange resin) on the metabolism of salicylazosulfapyridine by microflora present in the colon and cecum was assessed in conventional rats by following the time course of salicylazosulfapyridine and its metabolites in the urine and feces. The intestinal metabolism of salicylazosulfapyridine (a single 100 mg/kg oral dose), which involves reduction of the azo linkage by bacterial azo reductases and the liberation of sulfapyridine and 5-aminosalicylic acid (potential active metabolites of the drug), was markedly inhibited by the resin (250 mg/kg oral doses at -2, +2 and +6 hours), resulting in an enhanced fecal excretion of intact salicylazosulfapyridine. The existence of a rank-order correlation between the in vitro binding of salicylazosulfapyridine, sulfapyridine and 5-aminosalicylic acid to the resin and their fecal excretion pattern in resin-treated animals suggests that a direct cholestyramine-salicylazosulfapyridine interaction occurred within the intestinal tract and that in the bound state, the azo bond of the drug was inaccessible to bacterial azo reductases. These findings suggest that chronic oral administration of cholestyramine to patients with ulcerative colitis who are receiving salicylazosulfapyridine could result in a significant reduction in the absorption and metabolism of the drug and hence, in its therapeutic efficacy. | [
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PMID:6793 | The correlation between antinociceptive activity of narcotics and their antagonists as measured in the mouse tail-flick test and increased synthesis of brain catecholamines. | The effects of several narcotics, narcotic antagonists-analgesics and narcotic antagonists on the synthesis of dopamine and norepinephrine in mouse brain were estimated and related to their activity in the tail-flick test. Catecholamine synthesis was estimated by measuring the accumulation of 3H-dopamine and 3H-norepinephrine formed from an injection of 3H-tyrosine. Morphine produced dose-related increases in both tail-flick activity and catecholamine synthesis. Each of the narcotic analgesics produced a significant increase in catecholamine synthesis 30 minutes after the subcutaneous injection of an antinociceptive dose (ED80). Under these same conditions, drugs which are inactive in the tail-flick test, such as pentazocine, produced a decrease in catecholamine synthesis and cyclazocine; naloxone and naltrexone were without significant effect. However, cyclazocine, which was inactive in the tail-flick test and did not alter catecholamine synthesis 30 minutes after administration, demonstrated tail-flick activity and produced increased catecholamine synthesis 2 minutes after its administration. Morphine was devoid of either activity 2 minutes after administration. Similarly, at 2 hours after the administration of a dose of morphine (10 mg/kg) that was active in the tail-flick test and increased catecholamine synthesis at 30 minutes, neither tail-flick activity nor increased catecholamine synthesis was observed. Naloxone blocked both the antinociceptive action and the increased catecholamine synthesis produced by both morphine and methadone. The results of these studies indicate that a correlation exists between tail-flick activity of narcotic-like drugs and their ability to increase catecholamine synthesis. These data support the hypothesis that brain catecholamines may be involved in the central mediation of the tail-flick response and other actions of the narcotic analgesics. | The correlation between antinociceptive activity of narcotics and their antagonists as measured in the mouse tail-flick test and increased synthesis of brain catecholamines. The effects of several narcotics, narcotic antagonists-analgesics and narcotic antagonists on the synthesis of dopamine and norepinephrine in mouse brain were estimated and related to their activity in the tail-flick test. Catecholamine synthesis was estimated by measuring the accumulation of 3H-dopamine and 3H-norepinephrine formed from an injection of 3H-tyrosine. Morphine produced dose-related increases in both tail-flick activity and catecholamine synthesis. Each of the narcotic analgesics produced a significant increase in catecholamine synthesis 30 minutes after the subcutaneous injection of an antinociceptive dose (ED80). Under these same conditions, drugs which are inactive in the tail-flick test, such as pentazocine, produced a decrease in catecholamine synthesis and cyclazocine; naloxone and naltrexone were without significant effect. However, cyclazocine, which was inactive in the tail-flick test and did not alter catecholamine synthesis 30 minutes after administration, demonstrated tail-flick activity and produced increased catecholamine synthesis 2 minutes after its administration. Morphine was devoid of either activity 2 minutes after administration. Similarly, at 2 hours after the administration of a dose of morphine (10 mg/kg) that was active in the tail-flick test and increased catecholamine synthesis at 30 minutes, neither tail-flick activity nor increased catecholamine synthesis was observed. Naloxone blocked both the antinociceptive action and the increased catecholamine synthesis produced by both morphine and methadone. The results of these studies indicate that a correlation exists between tail-flick activity of narcotic-like drugs and their ability to increase catecholamine synthesis. These data support the hypothesis that brain catecholamines may be involved in the central mediation of the tail-flick response and other actions of the narcotic analgesics. | [
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PMID:6794 | Evaluation of the discriminative effects of morphine in the rat. | The discriminative effects produced by morphine in the rat were evaluated using a two-choice, discrete trial avoidance task. Stimulus control of behavior was attained with a dose of morphine one-third to one-tenth of that used in previous studies. Morphine produced dose-related discriminative effects over a 100-fold dose range. The stimulus control produced by the discriminative effects of morphine met the following criteria for classification as a specific narcotic effect: 1) oxymorphone, levorphanol, methadone and meperidine, narcotic analgesics from diverse chemical families, also produced dose-related morphine-like discriminative effects; 2) dextrorphan and thebaine, compounds structurally related to the narcotics but lacking narcotic activity, failed to produce morphine-like discriminative effects; 3) effects were blocked by the narcotic antagonist naloxone; and 4) tolerance to the discriminative effects developed upon the repeated administration of morphine and cross-tolerance extended to methadone. The discriminative effects produced by morphine were further characterized by evaluating the capacity of prototypes of other classes of psychoactive drugs to produce morphine-like discriminative effects. Profadol and pentazocine, euphorogenic analgesics with mixed agonist and narcotic antagonist properties, produced dose-related morphine-like discriminative effects whereas cyclazocine, a dysphorogenic analgesic with mixed agonist and narcotic-antagonist properties, did not. In addition, the nonopioid psychoactive drugs d-amphetamine, pentobarbital and chlorpromazine also failed to produce morphine-like discriminative effects. Thus, morphine-like discriminative effects were produced uniquely by the narcotic analgesics and euophorogenic analgesics with mixed agonist and narcotic antagonist properties. These results suggest that the component of action of morphine that enables it to function as a discriminative stimulus in the rat is analogous to the component of action of morphine responsible for producing subjective effects in man. | Evaluation of the discriminative effects of morphine in the rat. The discriminative effects produced by morphine in the rat were evaluated using a two-choice, discrete trial avoidance task. Stimulus control of behavior was attained with a dose of morphine one-third to one-tenth of that used in previous studies. Morphine produced dose-related discriminative effects over a 100-fold dose range. The stimulus control produced by the discriminative effects of morphine met the following criteria for classification as a specific narcotic effect: 1) oxymorphone, levorphanol, methadone and meperidine, narcotic analgesics from diverse chemical families, also produced dose-related morphine-like discriminative effects; 2) dextrorphan and thebaine, compounds structurally related to the narcotics but lacking narcotic activity, failed to produce morphine-like discriminative effects; 3) effects were blocked by the narcotic antagonist naloxone; and 4) tolerance to the discriminative effects developed upon the repeated administration of morphine and cross-tolerance extended to methadone. The discriminative effects produced by morphine were further characterized by evaluating the capacity of prototypes of other classes of psychoactive drugs to produce morphine-like discriminative effects. Profadol and pentazocine, euphorogenic analgesics with mixed agonist and narcotic antagonist properties, produced dose-related morphine-like discriminative effects whereas cyclazocine, a dysphorogenic analgesic with mixed agonist and narcotic-antagonist properties, did not. In addition, the nonopioid psychoactive drugs d-amphetamine, pentobarbital and chlorpromazine also failed to produce morphine-like discriminative effects. Thus, morphine-like discriminative effects were produced uniquely by the narcotic analgesics and euophorogenic analgesics with mixed agonist and narcotic antagonist properties. These results suggest that the component of action of morphine that enables it to function as a discriminative stimulus in the rat is analogous to the component of action of morphine responsible for producing subjective effects in man. | [
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PMID:6795 | Protein synthesis by a cell-free preparation from the bird malaria, Plasmodium lophurae. | Cytoplasmic polyribosomes were isolated from the avian malaria parasite Plasmodium lophurae by lysis with 0.15% Triton X-100 followed by high speed centrifugation through a discontinuous sucrose gradient. Polyribosomes were protected from nuclease degradation using 100 mug/ml heparin or 50 mug/ml dextran sulfate. Cell-free incorporation of radioisotope-labeled amino acids required a pH 5 fraction (duck reticulocyte), Mg2+, and an energy-generating system. The protein synthesizing system was stimulated by the addition of polyuridylic acid. Optimum conditions for protein synthesis by the plasmodial system are described. The effects of drugs on the cell-free protein synthesizing system using duck reticulocyte and plasmodial ribosomes are reported. | Protein synthesis by a cell-free preparation from the bird malaria, Plasmodium lophurae. Cytoplasmic polyribosomes were isolated from the avian malaria parasite Plasmodium lophurae by lysis with 0.15% Triton X-100 followed by high speed centrifugation through a discontinuous sucrose gradient. Polyribosomes were protected from nuclease degradation using 100 mug/ml heparin or 50 mug/ml dextran sulfate. Cell-free incorporation of radioisotope-labeled amino acids required a pH 5 fraction (duck reticulocyte), Mg2+, and an energy-generating system. The protein synthesizing system was stimulated by the addition of polyuridylic acid. Optimum conditions for protein synthesis by the plasmodial system are described. The effects of drugs on the cell-free protein synthesizing system using duck reticulocyte and plasmodial ribosomes are reported. | [
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PMID:6796 | The serine hydroxymethyltransferase of Plasmodium lophurae. | Plasmodium lophurae serine hydroxymethyltransferase (EC 2.1.2.1) was partially purified and characterized by (NH4)2SO4 fractionation and chromatography on Sephadex G-100. The enzyme, precipitated by 3.0.3.3 M (NH4)2SO4, had a molecular weight of 68,300 as estimated by exclusion chromatography on G-100. The pH optimum of the enzyme was 6.8-7.6 in sodium phosphate-citrate buffer. Citrate stabilized the enzyme during storage in phosphate buffer at 4 C. The Km was 4.3 X 10(-3) M for L-serine and 2.5 X 10(-4) M for tetrahydrofolate. | The serine hydroxymethyltransferase of Plasmodium lophurae. Plasmodium lophurae serine hydroxymethyltransferase (EC 2.1.2.1) was partially purified and characterized by (NH4)2SO4 fractionation and chromatography on Sephadex G-100. The enzyme, precipitated by 3.0.3.3 M (NH4)2SO4, had a molecular weight of 68,300 as estimated by exclusion chromatography on G-100. The pH optimum of the enzyme was 6.8-7.6 in sodium phosphate-citrate buffer. Citrate stabilized the enzyme during storage in phosphate buffer at 4 C. The Km was 4.3 X 10(-3) M for L-serine and 2.5 X 10(-4) M for tetrahydrofolate. | [
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PMID:6797 | Pentamidine transport and sensitivity in brucei-group trypanosomes. | Sensitivity to pentamidine of bloodstream forms and culture forms of Trypanosoma brucei brucei, strains of this subspecies, and strains of T. brucei rhodesiense characteristically differs in vitro. Analyses of transport parameters for pentamidine uptake in these organisms show differences that correspond with drug sensitivity. Long slender bloodstream forms of T. b. brucei have a high affinity for the drug and high rates of uptake at indicated by Km and Vmax values for [3H]pentamidine transport. Although pentamidine and stilbamidine resistance is associated with dyskinetoplasty, this condition does not itself confer resistance to pentamidine nor does it affect pentamidine transport. However, drug-resistant strains show lower rates for pentamidine transport as does T. b. rhodesiense, which is characteristically less sensitive to the drug. Of all the forms and strains studied, procyclic trypomastigotes were least sensitive to pentamidine and had a remarkable ability to exclude the drug. | Pentamidine transport and sensitivity in brucei-group trypanosomes. Sensitivity to pentamidine of bloodstream forms and culture forms of Trypanosoma brucei brucei, strains of this subspecies, and strains of T. brucei rhodesiense characteristically differs in vitro. Analyses of transport parameters for pentamidine uptake in these organisms show differences that correspond with drug sensitivity. Long slender bloodstream forms of T. b. brucei have a high affinity for the drug and high rates of uptake at indicated by Km and Vmax values for [3H]pentamidine transport. Although pentamidine and stilbamidine resistance is associated with dyskinetoplasty, this condition does not itself confer resistance to pentamidine nor does it affect pentamidine transport. However, drug-resistant strains show lower rates for pentamidine transport as does T. b. rhodesiense, which is characteristically less sensitive to the drug. Of all the forms and strains studied, procyclic trypomastigotes were least sensitive to pentamidine and had a remarkable ability to exclude the drug. | [
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PMID:6798 | The influence of growth medium on the interactions between Bordetella pertussis and Staphylococcus aureus. | Previous observers showed that many strains of Staphylococcus aureus stimulated the growth of Bordetella pertussis but we have found the reverse: the growth of all available strains of B. pertussis on charcoal-agar medium was inhibited by a standard strain of S. aureus; and 17 of 18 strains of S. aureus (as well as several other organisms) inhibited the growth of a standard strain of B. pertussis. All inhibiting colonies had an unusual brown colouration on the charcoal agar used in the investigation. Both the brown colouration and the inhibitory property were caused by acid production, probably from the starch in the medium. We therefore suggest that media containing starch and blood should not be used in studies of bacterial interference. | The influence of growth medium on the interactions between Bordetella pertussis and Staphylococcus aureus. Previous observers showed that many strains of Staphylococcus aureus stimulated the growth of Bordetella pertussis but we have found the reverse: the growth of all available strains of B. pertussis on charcoal-agar medium was inhibited by a standard strain of S. aureus; and 17 of 18 strains of S. aureus (as well as several other organisms) inhibited the growth of a standard strain of B. pertussis. All inhibiting colonies had an unusual brown colouration on the charcoal agar used in the investigation. Both the brown colouration and the inhibitory property were caused by acid production, probably from the starch in the medium. We therefore suggest that media containing starch and blood should not be used in studies of bacterial interference. | [
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PMID:6799 | Localization of calcium binding sites associated with the calcium spike in barnacle muscle. | La ion behaves as a competitive inhibitor of Ca ions on the calcium spike in the giant muscle fiber of the barnacle, Balanus nubilus. La-treated muscle fibers, in which the rate of rise of the spike was diminished to a known degree, have been examined with the electron-microscope. In such fibers dense particles are seen in association with the surface membrane and external lamina of the cell. La particles are not seen in association with fibers that have been allowed to recover from La inhibition before fixation. The number of La particles seen in association with the muscle fiber increases with increasing La concentration when the Ca and Mg concentrations are held constant and decreases with increasing Ca and Mg concentration when the La concentration is held constant. The results suggest that the La visible in the electron-microscope under the conditions of these experiments is bound to a class of sites similar to those involved in the Ca spike. | Localization of calcium binding sites associated with the calcium spike in barnacle muscle. La ion behaves as a competitive inhibitor of Ca ions on the calcium spike in the giant muscle fiber of the barnacle, Balanus nubilus. La-treated muscle fibers, in which the rate of rise of the spike was diminished to a known degree, have been examined with the electron-microscope. In such fibers dense particles are seen in association with the surface membrane and external lamina of the cell. La particles are not seen in association with fibers that have been allowed to recover from La inhibition before fixation. The number of La particles seen in association with the muscle fiber increases with increasing La concentration when the Ca and Mg concentrations are held constant and decreases with increasing Ca and Mg concentration when the La concentration is held constant. The results suggest that the La visible in the electron-microscope under the conditions of these experiments is bound to a class of sites similar to those involved in the Ca spike. | [
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PMID:6801 | Characterization of Whitney's Clethrionomy gapperi virus isolates from Massachusetts. | Six strains of virus were recovered from the blood and/or liver of five Clethrionomys gapperi ochraceus trapped in southeastern Massachusetts during 1969. Biological, antigenic and physiochemical properties of these isolates are reported. USA M-2268a was selected as the reference strain. This strain was identical by complement-fixation and neutralization tests to Whitneys C. gapperie virus (USA 64-7855) from New York State and was related to, but distinct from, an unpublished agent (Johnson's Microtus montanus enterovirus USA M-1146) isolated in June, 1962 from voles trapped in Klamath County, Oregon. USA M-2268a was resistant to lipid solvents and acid pH and was stable at temperatures of 4 C, 22 C, and 37 C. Virus was detected over a 10-day observation period in four species of mosquitoes inoculated with USA M-2268a, although there was no evidence of infection or replication, and transmission attempts by bite failed. Neutralizing antibody was detected in C.g. gapperi and C. g. ochraceus in various habitats throughout the state. | Characterization of Whitney's Clethrionomy gapperi virus isolates from Massachusetts. Six strains of virus were recovered from the blood and/or liver of five Clethrionomys gapperi ochraceus trapped in southeastern Massachusetts during 1969. Biological, antigenic and physiochemical properties of these isolates are reported. USA M-2268a was selected as the reference strain. This strain was identical by complement-fixation and neutralization tests to Whitneys C. gapperie virus (USA 64-7855) from New York State and was related to, but distinct from, an unpublished agent (Johnson's Microtus montanus enterovirus USA M-1146) isolated in June, 1962 from voles trapped in Klamath County, Oregon. USA M-2268a was resistant to lipid solvents and acid pH and was stable at temperatures of 4 C, 22 C, and 37 C. Virus was detected over a 10-day observation period in four species of mosquitoes inoculated with USA M-2268a, although there was no evidence of infection or replication, and transmission attempts by bite failed. Neutralizing antibody was detected in C.g. gapperi and C. g. ochraceus in various habitats throughout the state. | [
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PMID:6802 | Sea-blue histiocytes in a case of Takayasu arteritis. | Arteriographic, immunological, and bone marrow studies of a young woman with Takayasu arteritis disclosed the presence of sea-blue histiocytes in her bone marrow. We know of no other similar reports. | Sea-blue histiocytes in a case of Takayasu arteritis. Arteriographic, immunological, and bone marrow studies of a young woman with Takayasu arteritis disclosed the presence of sea-blue histiocytes in her bone marrow. We know of no other similar reports. | [
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PMID:6805 | Quantitative and qualitative determinations of the combined effect of tetracycline and oleandomycin. I. In vitro effect. | Growth inhibitory effect of combined treatment of tetracycline (TC) and oleandomycin (OM), at a ratio of 2:1, on certain species of pathogenic bacteria including drug-resistant ones was examined. By the crossed paper strip method, synergistic effects were demonstrated against 9 of the 16 strains of Staphylococcus aureus, and all of the 5 strains of Escherichia coli studied. Antagonism was observed with none of the strains and with 2 strains of Streptococcus pyogenes and 2 strains of Streptococcus pneumoniae tested in the present experiments. The MICs determined by the agar dilution method, also gave similar results, although synergism was not conclusively demonstrated by this method. With representative strains of S. aureus, synergism was evidenced by quantitative measurement of growth inhibition. In some strains, 1.0 mug of one drug per ml of medium inhibited the induction of resistance to the second drug. Such a small dose of one drug also inhibited the development of a mutant resistant to the second drug. These inhibitory actions were thought to be one of the important factors causing the synergistic effect of TC and OM on drug resistant bacteria. | Quantitative and qualitative determinations of the combined effect of tetracycline and oleandomycin. I. In vitro effect. Growth inhibitory effect of combined treatment of tetracycline (TC) and oleandomycin (OM), at a ratio of 2:1, on certain species of pathogenic bacteria including drug-resistant ones was examined. By the crossed paper strip method, synergistic effects were demonstrated against 9 of the 16 strains of Staphylococcus aureus, and all of the 5 strains of Escherichia coli studied. Antagonism was observed with none of the strains and with 2 strains of Streptococcus pyogenes and 2 strains of Streptococcus pneumoniae tested in the present experiments. The MICs determined by the agar dilution method, also gave similar results, although synergism was not conclusively demonstrated by this method. With representative strains of S. aureus, synergism was evidenced by quantitative measurement of growth inhibition. In some strains, 1.0 mug of one drug per ml of medium inhibited the induction of resistance to the second drug. Such a small dose of one drug also inhibited the development of a mutant resistant to the second drug. These inhibitory actions were thought to be one of the important factors causing the synergistic effect of TC and OM on drug resistant bacteria. | [
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PMID:6806 | Elevated plasma renin activity in aortitis syndrome. | Plasma renin activity (PRA) was measured in 38 cases of aortitis syndrome. The values of resting peripheral vein blood PRA were 32.2 +/- 4.2 (SE) mmug/ml. These values were 3 times higher than those of normal subjects. Hypertension due to renal arterial stenosis was observed in 18 cases. Their resting PRA values were 41.2 +/- 6.0 mmug/ml, while in the remaining 20 patients without renovascular hypertension those values were 24.2 +/- 5.4 mmug/ml. The patients belonging to aortic arch type or extensive type had 2 times higher PRA values than those of abdominal type. The patients with stenosis or obstruction of common carotid arteries had significantly higher PRA values than the patients without these lesions. Hyperresponse of renin secretion to upright posture was also observed in the same patients with carotid artery stenosis. Abnormal renin release in Takayasu's arteritis disappeared after denervation of the carotid sinus nerve. The present study suggests that the unstable state of carotid sinus reflex is the main cause for the hypersecretion of renin. | Elevated plasma renin activity in aortitis syndrome. Plasma renin activity (PRA) was measured in 38 cases of aortitis syndrome. The values of resting peripheral vein blood PRA were 32.2 +/- 4.2 (SE) mmug/ml. These values were 3 times higher than those of normal subjects. Hypertension due to renal arterial stenosis was observed in 18 cases. Their resting PRA values were 41.2 +/- 6.0 mmug/ml, while in the remaining 20 patients without renovascular hypertension those values were 24.2 +/- 5.4 mmug/ml. The patients belonging to aortic arch type or extensive type had 2 times higher PRA values than those of abdominal type. The patients with stenosis or obstruction of common carotid arteries had significantly higher PRA values than the patients without these lesions. Hyperresponse of renin secretion to upright posture was also observed in the same patients with carotid artery stenosis. Abnormal renin release in Takayasu's arteritis disappeared after denervation of the carotid sinus nerve. The present study suggests that the unstable state of carotid sinus reflex is the main cause for the hypersecretion of renin. | [
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PMID:6807 | Perinephritis hypertension in monkeys. I. An increase of plasma renin activity associated with increased permeability of retinal vessels and angionecrosis. | The renal parenchyma of 5 crub-eating monkeys (Macaca irus) was wrapped by cellophane, and plasma renin activity, blood pressure and vascular permeability of ocular ground were measured in comparison with 5 unoperated control monkeys. The results demonstrated that increases of systolic arterial pressure, plasma renin activity, and permeability of the retinal vessels were found in 4 operated monkeys. There was no such abnormal finding in the unoperated control monkeys. Generally there was a rough parallelism among levels of plasma renin activity and systolic blood pressure, an increase of permeability of retinal vessels and fibrinoid angionecrosis and/or necrotizing angitis similar to polyarteritis nodosa. | Perinephritis hypertension in monkeys. I. An increase of plasma renin activity associated with increased permeability of retinal vessels and angionecrosis. The renal parenchyma of 5 crub-eating monkeys (Macaca irus) was wrapped by cellophane, and plasma renin activity, blood pressure and vascular permeability of ocular ground were measured in comparison with 5 unoperated control monkeys. The results demonstrated that increases of systolic arterial pressure, plasma renin activity, and permeability of the retinal vessels were found in 4 operated monkeys. There was no such abnormal finding in the unoperated control monkeys. Generally there was a rough parallelism among levels of plasma renin activity and systolic blood pressure, an increase of permeability of retinal vessels and fibrinoid angionecrosis and/or necrotizing angitis similar to polyarteritis nodosa. | [
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PMID:6808 | Hemodynamics of experimentally hypertensive rats in conscious and anesthetized states. | Cardiac output was measured by a pulse contour method in reno-vascular hypertensive rats, deoxycorticosterone (DOC) hypertensive rats and normotensive control Wistar rats in the conscious state. All rats were male in sex and 12-13 weeks of age (2-3 weeks after operation in the hypertensive rats). Cardiac output per body weight was not significantly different among the groups. Therefore, the hypertension in the experimentally hypertensive rats in the conscious state was ascribable to an increased total peripheral resistance. After anesthesia with pentobarbital and thoracotomy, the DOC rats were no longer hypertensive. However, in the renovascular hypertensive rats, the hypertensive state due to an increase in vascular resistance persisted after anesthesia, thoracotomy, and even ganglion blockade with hexamethonium bromide, indicating the importance of non-neural factors in the renovascular hypertension. Aortic compliance measured in vivo under anesthesia was smaller in either the renovascular or DOC hypertensive rats than in the control rats before and after ganglion blockade, which suggests a non-neural hardening of elastic vessels in the experimental hypertensions. | Hemodynamics of experimentally hypertensive rats in conscious and anesthetized states. Cardiac output was measured by a pulse contour method in reno-vascular hypertensive rats, deoxycorticosterone (DOC) hypertensive rats and normotensive control Wistar rats in the conscious state. All rats were male in sex and 12-13 weeks of age (2-3 weeks after operation in the hypertensive rats). Cardiac output per body weight was not significantly different among the groups. Therefore, the hypertension in the experimentally hypertensive rats in the conscious state was ascribable to an increased total peripheral resistance. After anesthesia with pentobarbital and thoracotomy, the DOC rats were no longer hypertensive. However, in the renovascular hypertensive rats, the hypertensive state due to an increase in vascular resistance persisted after anesthesia, thoracotomy, and even ganglion blockade with hexamethonium bromide, indicating the importance of non-neural factors in the renovascular hypertension. Aortic compliance measured in vivo under anesthesia was smaller in either the renovascular or DOC hypertensive rats than in the control rats before and after ganglion blockade, which suggests a non-neural hardening of elastic vessels in the experimental hypertensions. | [
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PMID:6813 | Enhancement of sulphatide metabolism in the hypertrophied kidney of C3H/He mouse with reference to [Na+, K+]-dependent ATPase. | Sulphatide (cerebroside sulphate) metabolism of C3H/He mouse kidney was investigated in the course of compensatory renal hypertrophy in association with the change of [Na+,K+]-dependent ATPase, arylsulfatase A and beta-galactosidase activity. A remarkable increase in 35S incorporation into kidney sulphatide was observed 24 hours and especially 7 days after unilateral nephrectomy. In contrast, no significant alteration of 32P incorporation into major phospholipids such as phosphatidylcholine, phosphatidylethanolamine and sphingomyelin was demonstrated in the compensatory hypertrophied mouse kidney. [Na+, K+]-dependent ATPase increased to 126% of control in the remaining kidneys on 7 days after operation. Specific increase in 35S specific activity of kidney sulphatide suggests its possible link with the process of active ion transport through membrane-bound [Na+,K+]-dependent ATPase. Arylsulphatase A activity increased to 151% of control on days, while little change was observed in beta-galactosidase activity. These results suggest a sole concern of a turnover of sulphate moiety of sulphatide molecule in the elevated metabolism. | Enhancement of sulphatide metabolism in the hypertrophied kidney of C3H/He mouse with reference to [Na+, K+]-dependent ATPase. Sulphatide (cerebroside sulphate) metabolism of C3H/He mouse kidney was investigated in the course of compensatory renal hypertrophy in association with the change of [Na+,K+]-dependent ATPase, arylsulfatase A and beta-galactosidase activity. A remarkable increase in 35S incorporation into kidney sulphatide was observed 24 hours and especially 7 days after unilateral nephrectomy. In contrast, no significant alteration of 32P incorporation into major phospholipids such as phosphatidylcholine, phosphatidylethanolamine and sphingomyelin was demonstrated in the compensatory hypertrophied mouse kidney. [Na+, K+]-dependent ATPase increased to 126% of control in the remaining kidneys on 7 days after operation. Specific increase in 35S specific activity of kidney sulphatide suggests its possible link with the process of active ion transport through membrane-bound [Na+,K+]-dependent ATPase. Arylsulphatase A activity increased to 151% of control on days, while little change was observed in beta-galactosidase activity. These results suggest a sole concern of a turnover of sulphate moiety of sulphatide molecule in the elevated metabolism. | [
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PMID:6814 | Effect of taurine on alteration in adrenal functions induced by stress. | When rats were exposed to immobilized cold stress, adrenaline content in the adrenal gland as well as noradrenaline content in the brain stem were reduced drastically, while noradrenaline content in the atria was not altered by the application of stress. Oral administrations of taurine (4-7 g/kg/day, for 3 days) prevented the stress-induced decline of adrenaline in the adrenal gland and this preventive effect could not be duplicated by the administration of L-isoleucine or DL-methionine. In hypophysectomized rats, the stress also induced a significant fall in adrenaline content of the adrenal gland, however taurine administration did not show significant preventive effects on the decline in adrenal catecholamines. The immobilized cold stress induced a significant increase in blood sugar and this increase was antagonized by pretreatment with taurine. Taurine had no significant effects on the stress-induced increase in the activity of adrenal tyrosine hydroxylase and the turnover rate of adrenaline in the adrenal gland measured by the rate of decline of this amine following alpha-methyl-tyrosine administration. The administration of taurine, in both in vivo and in vitro, inhibited the release of adrenaline from adrenal medullary granules, but that of dopamine-beta-hydroxylase was not significantly affected. The stress-induced elevation of the blood level of corticosterone was not affected by taurine administration. These findings indicate that taurine antagonizes the stress-induced elevation of blood sugar by reducing adrenaline output from the adrenal gland. The regulatory mechanism most likly involves the inhibition of adrenaline release from adrenal medullary granules, possibly by stabilizing the membrane of the granules. | Effect of taurine on alteration in adrenal functions induced by stress. When rats were exposed to immobilized cold stress, adrenaline content in the adrenal gland as well as noradrenaline content in the brain stem were reduced drastically, while noradrenaline content in the atria was not altered by the application of stress. Oral administrations of taurine (4-7 g/kg/day, for 3 days) prevented the stress-induced decline of adrenaline in the adrenal gland and this preventive effect could not be duplicated by the administration of L-isoleucine or DL-methionine. In hypophysectomized rats, the stress also induced a significant fall in adrenaline content of the adrenal gland, however taurine administration did not show significant preventive effects on the decline in adrenal catecholamines. The immobilized cold stress induced a significant increase in blood sugar and this increase was antagonized by pretreatment with taurine. Taurine had no significant effects on the stress-induced increase in the activity of adrenal tyrosine hydroxylase and the turnover rate of adrenaline in the adrenal gland measured by the rate of decline of this amine following alpha-methyl-tyrosine administration. The administration of taurine, in both in vivo and in vitro, inhibited the release of adrenaline from adrenal medullary granules, but that of dopamine-beta-hydroxylase was not significantly affected. The stress-induced elevation of the blood level of corticosterone was not affected by taurine administration. These findings indicate that taurine antagonizes the stress-induced elevation of blood sugar by reducing adrenaline output from the adrenal gland. The regulatory mechanism most likly involves the inhibition of adrenaline release from adrenal medullary granules, possibly by stabilizing the membrane of the granules. | [
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PMID:6815 | A clinical comparison of syrup of ipecac and apomorphine use in adults. | A prospective, randomized study was performed to compare syrup of ipecac to apomorphine as the emetic of choice in poisoning cases. Of the 28 adults studied, 15 patients (54%) received 30 ml of ipecac orally and 13 received 0.1 mg/kg apomorphine subcutaneously. Emesis was successfully induced with initial therapy in 13 of 15 (87%) ipecac-treated patients and 10 of 13 (77%) apomorphine-treated patients. In the ipecac group the mean latency period before onset of vomiting was 11.6 minutes (range 4 to 26 min) and in the apomorphine group, 5.3 minutes (range 2 to 13 min) (P less than .01). In the ipecac group, one patient suffered moderate central nervous system (CNS) depression. No hypotension or respiratory depression was observed in this group. In the apomorphine group significant CNS depression developed in eight patients (62%), hypotension developed in five (38%) and respiratory depression in one. There was no consistent relationship between type of poison ingested and occurrence of side effects. | A clinical comparison of syrup of ipecac and apomorphine use in adults. A prospective, randomized study was performed to compare syrup of ipecac to apomorphine as the emetic of choice in poisoning cases. Of the 28 adults studied, 15 patients (54%) received 30 ml of ipecac orally and 13 received 0.1 mg/kg apomorphine subcutaneously. Emesis was successfully induced with initial therapy in 13 of 15 (87%) ipecac-treated patients and 10 of 13 (77%) apomorphine-treated patients. In the ipecac group the mean latency period before onset of vomiting was 11.6 minutes (range 4 to 26 min) and in the apomorphine group, 5.3 minutes (range 2 to 13 min) (P less than .01). In the ipecac group, one patient suffered moderate central nervous system (CNS) depression. No hypotension or respiratory depression was observed in this group. In the apomorphine group significant CNS depression developed in eight patients (62%), hypotension developed in five (38%) and respiratory depression in one. There was no consistent relationship between type of poison ingested and occurrence of side effects. | [
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PMID:6816 | Monitoring resuscitation of primates from hemorrhagic and septic shock. | Monitoring data in 16 primates subjected to septic or hemorrhagic shock and resuscitated with various solutions is presented. From a paractical standpoint, central venous pressure and urine output appear to be the best indices to use in the emergency department for resuscitation of the shock victim. The sophisticated measurements such as cardiac output, thermodye volumes, pulmonary artery wedge pressure and oxygen consumption should be reserved for the individual with depressed cardiovascular reserves and who needs "fine tuning" of his volume status. | Monitoring resuscitation of primates from hemorrhagic and septic shock. Monitoring data in 16 primates subjected to septic or hemorrhagic shock and resuscitated with various solutions is presented. From a paractical standpoint, central venous pressure and urine output appear to be the best indices to use in the emergency department for resuscitation of the shock victim. The sophisticated measurements such as cardiac output, thermodye volumes, pulmonary artery wedge pressure and oxygen consumption should be reserved for the individual with depressed cardiovascular reserves and who needs "fine tuning" of his volume status. | [
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PMID:6819 | [Fertility after treatment with HCG for undescended testes (author's tranls)]. | 151 out of 212 adolescents having had been treated by human chorionic gonadotrophin (HCG) before puberty because of undescended testes, were re-examined 7 to 12 years later at an individual age of at least 17 years. In 121 of them a semen specimen for sperm counts could be obtained. In 10 patients, however, no ejaculate could be collected because of their hypogonadism. 78 of these 121 patients examined by sperm count had a sufficient testicular descensus after HCG treatment. In 43 adolescents HCG therapy failed, therefore subsequent orchidopexy was performed. A normal sperm count was seen in only 39 per cent of the 121 patients. After unilateral testicular maldescensus 18%, after bilateral maldescensus 43% of the patients had to be evaluated as prospectively infertile. Maier and Spann reported sperm counts below 10(6)/ml in 9 out of 17 patients with bilateral maldescensus who had been treated by surgery alone. In the present study, however, only 9 out of 35 individuals treated for bilateral maldescensus by HCG alone showed sperm counts below 10(6)/ml. Plasma LH and FSH concentrations were determined in 93 patients, 6 out of which showed hypergonadotrophic values of FSH and sperm counts below 10(7)/ml. Subsequently, 3 cases of Klinefelter's syndrome could be diagnosed among the total group of 121 patients. The etiology of testicular maldescensus is by no means uniform since anatomical, endocrine and/or chromosomal factors are involved. | [Fertility after treatment with HCG for undescended testes (author's tranls)]. 151 out of 212 adolescents having had been treated by human chorionic gonadotrophin (HCG) before puberty because of undescended testes, were re-examined 7 to 12 years later at an individual age of at least 17 years. In 121 of them a semen specimen for sperm counts could be obtained. In 10 patients, however, no ejaculate could be collected because of their hypogonadism. 78 of these 121 patients examined by sperm count had a sufficient testicular descensus after HCG treatment. In 43 adolescents HCG therapy failed, therefore subsequent orchidopexy was performed. A normal sperm count was seen in only 39 per cent of the 121 patients. After unilateral testicular maldescensus 18%, after bilateral maldescensus 43% of the patients had to be evaluated as prospectively infertile. Maier and Spann reported sperm counts below 10(6)/ml in 9 out of 17 patients with bilateral maldescensus who had been treated by surgery alone. In the present study, however, only 9 out of 35 individuals treated for bilateral maldescensus by HCG alone showed sperm counts below 10(6)/ml. Plasma LH and FSH concentrations were determined in 93 patients, 6 out of which showed hypergonadotrophic values of FSH and sperm counts below 10(7)/ml. Subsequently, 3 cases of Klinefelter's syndrome could be diagnosed among the total group of 121 patients. The etiology of testicular maldescensus is by no means uniform since anatomical, endocrine and/or chromosomal factors are involved. | [
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PMID:6820 | [Carbromal intoxication: influence of hemodialysis and hemoperfusion]. | It has been demonstrated with an in vitro model that hemoperfusion through Amberlite XAD4 or coated charcoal containing cartridges eliminates carbromal and its ureid derivatives more efficiently than hemodialysis. The following clearancs were measured in vitro (blood flow: 200 ml/min): Coil dialyser (1 m2): 55-85 ml/min, charcoal hemoperfusion 100-125 ml/min, Amberlite XAD4 hemoperfusion: 200 ml/min. The data of one patient who had been hemoperfused after the ingestion of 35 g Carbromal with the Haemocol cartridge (SMith & Nephews) are depicted. Our results permit to draw the conclusion that hemoperfusion at this time is the most efficient means to eliminate Carbromal from intoxicated patients. | [Carbromal intoxication: influence of hemodialysis and hemoperfusion]. It has been demonstrated with an in vitro model that hemoperfusion through Amberlite XAD4 or coated charcoal containing cartridges eliminates carbromal and its ureid derivatives more efficiently than hemodialysis. The following clearancs were measured in vitro (blood flow: 200 ml/min): Coil dialyser (1 m2): 55-85 ml/min, charcoal hemoperfusion 100-125 ml/min, Amberlite XAD4 hemoperfusion: 200 ml/min. The data of one patient who had been hemoperfused after the ingestion of 35 g Carbromal with the Haemocol cartridge (SMith & Nephews) are depicted. Our results permit to draw the conclusion that hemoperfusion at this time is the most efficient means to eliminate Carbromal from intoxicated patients. | [
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PMID:6826 | Monitoring of midmyocardial and subendocardial pH in normal and ischemic ventricles. | Midmyocardial and subendocardial pH monitoring was used as an indirect method for continuous evaluation of regional canine myocardial ischemia. Left ventricular midmyocardial pH (pHm) at 4 mm. depth was monitored in 10 dogs, under resting conditions, by means of a 5 mm. Beckman pH probe. pHm was 6.96 +/- 0.03, recorded at myocardial temperatures of 35 to 37 degrees C. Ischemia was then produced by snare occlusion of the proximal left main coronary artery for 2 minutes. pHm decreased to 6.87 +/- 0.03 (p less than 0.01) at 1 minute and 6.80 +/- 0.04 (p less than 0.005) in 2 minutes. When flow was restored, pHm returned toward normal within 2 minutes (pH 6.86 +/- 0.03) and at 5 minutes had returned to control values (pH 6.93 +/- 0.03). In another 5 dogs under similar conditions, pHm at 4 mm. and subendocardial pH (pHe at 8 mm.) were measured. Baseline pHm (6.97 +/- 0.01) and pHe (6.84 +/- 0.02) levels were significantly different (p less than 0.0005). After 2 minutes of ischemia, pHm was 6.82 +/- 0.03, whereas pHe decreased to 6.78 +/- 0.04 (p less than 0.1). Five minutes after snare release, pHe remained at 6.73 +/- 0.07; pHm (6.93 +/- 0.03) returned to control values. Both pHm (6.93 +/- 0.02) and pHe (6.84 +/- 0.09) levels were normal 15 minutes after release of the snare. The midmyocardium and subendocardium have different pH levels which can be monitored. Ischemia produces different pH patterns in these layers. pHm returns to control values within 5 minutes after 2 minutes of ischemia, whereas pHe remains depressed for at least 5 minutes. pH monitoring provides an accurate and simple method for on-line evaluation of endocardial ischemia. | Monitoring of midmyocardial and subendocardial pH in normal and ischemic ventricles. Midmyocardial and subendocardial pH monitoring was used as an indirect method for continuous evaluation of regional canine myocardial ischemia. Left ventricular midmyocardial pH (pHm) at 4 mm. depth was monitored in 10 dogs, under resting conditions, by means of a 5 mm. Beckman pH probe. pHm was 6.96 +/- 0.03, recorded at myocardial temperatures of 35 to 37 degrees C. Ischemia was then produced by snare occlusion of the proximal left main coronary artery for 2 minutes. pHm decreased to 6.87 +/- 0.03 (p less than 0.01) at 1 minute and 6.80 +/- 0.04 (p less than 0.005) in 2 minutes. When flow was restored, pHm returned toward normal within 2 minutes (pH 6.86 +/- 0.03) and at 5 minutes had returned to control values (pH 6.93 +/- 0.03). In another 5 dogs under similar conditions, pHm at 4 mm. and subendocardial pH (pHe at 8 mm.) were measured. Baseline pHm (6.97 +/- 0.01) and pHe (6.84 +/- 0.02) levels were significantly different (p less than 0.0005). After 2 minutes of ischemia, pHm was 6.82 +/- 0.03, whereas pHe decreased to 6.78 +/- 0.04 (p less than 0.1). Five minutes after snare release, pHe remained at 6.73 +/- 0.07; pHm (6.93 +/- 0.03) returned to control values. Both pHm (6.93 +/- 0.02) and pHe (6.84 +/- 0.09) levels were normal 15 minutes after release of the snare. The midmyocardium and subendocardium have different pH levels which can be monitored. Ischemia produces different pH patterns in these layers. pHm returns to control values within 5 minutes after 2 minutes of ischemia, whereas pHe remains depressed for at least 5 minutes. pH monitoring provides an accurate and simple method for on-line evaluation of endocardial ischemia. | [
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PMID:6827 | [The use of "mesh graft" in traumatology]. | Vandeput and J. Tanner's method for the reconstruction of the reticular grafting skin has been used and is recommended by the authors for the treatment of not only the thermic--, but of the mechanis lesions. The author has obtained very good results. The method is discussed and its advantages are pointed out. | [The use of "mesh graft" in traumatology]. Vandeput and J. Tanner's method for the reconstruction of the reticular grafting skin has been used and is recommended by the authors for the treatment of not only the thermic--, but of the mechanis lesions. The author has obtained very good results. The method is discussed and its advantages are pointed out. | [
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PMID:6828 | [Solitary tuberculoma in the tendonous section of the m. quadriceps]. | A case of isolated tuberculosis observed in the tensinous part of the quadriceps muscle is reported by the authors. The rarity of the case is pointed out. A few possibilities of the development of this tuberculoma are dealt with. In the authors' case the focus developed probably after haematogenous generalization. One year after the operation the patient is symptomfree and has no complaints. | [Solitary tuberculoma in the tendonous section of the m. quadriceps]. A case of isolated tuberculosis observed in the tensinous part of the quadriceps muscle is reported by the authors. The rarity of the case is pointed out. A few possibilities of the development of this tuberculoma are dealt with. In the authors' case the focus developed probably after haematogenous generalization. One year after the operation the patient is symptomfree and has no complaints. | [
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PMID:6829 | [The effect of chitin powder on the healing of skin wounds]. | Locally administered chitin powder has influences favourably the healing of the circular, open skin wounds on the dorsum. The tensil strength of the 7 days' incised skin wounds on the dorsum has increased under the effect of chitin powder suspension administered 3 days before the incision. The total hydroxyproline content was not influenced significantly by the chitin powder either in the case of circular open skin wounds or of incised dorsal skin wounds. | [The effect of chitin powder on the healing of skin wounds]. Locally administered chitin powder has influences favourably the healing of the circular, open skin wounds on the dorsum. The tensil strength of the 7 days' incised skin wounds on the dorsum has increased under the effect of chitin powder suspension administered 3 days before the incision. The total hydroxyproline content was not influenced significantly by the chitin powder either in the case of circular open skin wounds or of incised dorsal skin wounds. | [
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] |
PMID:6830 | [Constitution and structure of human tendons]. | In this introductory study our actual knowledge on the tendons is resumed and it is pointed out that on the basis of this knowledge no explanation is given as regards the pathomechanism of the "spontaneous" tendon ruptures. The authors' concept on the tendons as motor units is discussed. The examinations are dealt with, by which the authors intend to revise the conventional static tendon model. | [Constitution and structure of human tendons]. In this introductory study our actual knowledge on the tendons is resumed and it is pointed out that on the basis of this knowledge no explanation is given as regards the pathomechanism of the "spontaneous" tendon ruptures. The authors' concept on the tendons as motor units is discussed. The examinations are dealt with, by which the authors intend to revise the conventional static tendon model. | [
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PMID:6831 | [Incidence of blood aspiration in fatal fractures of the base of the skull]. | The frequency of blood inhalation has been examined by the authors in the 15 years' material of the Institute of Forensic Medicine of the "Semmelweis" University Medical School. Out of 51.308 post mortem examinations 487 cases of isolated basicranial fractures were found. Out of them in 265 cases (=54%) blood inhalation as cause of death was verified. Attention is called to the importance of prompt blood aspiration in patients with basicranial fracture. | [Incidence of blood aspiration in fatal fractures of the base of the skull]. The frequency of blood inhalation has been examined by the authors in the 15 years' material of the Institute of Forensic Medicine of the "Semmelweis" University Medical School. Out of 51.308 post mortem examinations 487 cases of isolated basicranial fractures were found. Out of them in 265 cases (=54%) blood inhalation as cause of death was verified. Attention is called to the importance of prompt blood aspiration in patients with basicranial fracture. | [
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PMID:6832 | [Open fractures of the hand joints]. | In the authors' opinion the optimal treatment of the open fractures of the hand articulations is the internal fixation offering the best fixation possible--this being the best antidote of the inflammatory complications and assuring the satisfactory late functional results. The splinting (stabliizing) methods known so far--as well as the preventive measures applied by the authors against inflammatory complications are discussed. | [Open fractures of the hand joints]. In the authors' opinion the optimal treatment of the open fractures of the hand articulations is the internal fixation offering the best fixation possible--this being the best antidote of the inflammatory complications and assuring the satisfactory late functional results. The splinting (stabliizing) methods known so far--as well as the preventive measures applied by the authors against inflammatory complications are discussed. | [
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PMID:6833 | [Superficial tendoplasty after injury of the intrinsic muscle]. | In 6 fingers of two injured patients, after the lesion of the intrinsic musculature of the finger with three phalanges Bunnell's sublime tendoplasty has been performed by the authors. Satisfactory functional results have been obtained, therefore the method is recommended by the authors for the treatment of similar lesions. | [Superficial tendoplasty after injury of the intrinsic muscle]. In 6 fingers of two injured patients, after the lesion of the intrinsic musculature of the finger with three phalanges Bunnell's sublime tendoplasty has been performed by the authors. Satisfactory functional results have been obtained, therefore the method is recommended by the authors for the treatment of similar lesions. | [
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PMID:6834 | [Experimental tendon sheath formation by free transplantation of a long vein segment (comparative study of adhesions formed around free grafts and pedicled grafts)]. | In dog experiments, in order to improve the functions after tendinous injuries diphasic operations have been performed by the authors. In the first phase, after the extirpation of the tendon of the 2nd finger its area has been bridged over by a 5-6 cm long autologous vein transplant, cannulated with a silicone rubber bar. After 4 weeks, after the vascularization of the vein transplant the silicone bar has been removed from a new approach, and through the "tunnel" formed in this way and padded with silicone a tendon has been pulled through with two different methods: 1. according to the method of Paneva-Holevitch a diphasic pedicled tendon transplant and 2. a free tendon transplant. No differences were found as regards the adhesions, the vascularization and the tissular structure of the tendon. It may be presumed that also the distal portion of the pedicled tendon transplant is really a free tendon transplant. | [Experimental tendon sheath formation by free transplantation of a long vein segment (comparative study of adhesions formed around free grafts and pedicled grafts)]. In dog experiments, in order to improve the functions after tendinous injuries diphasic operations have been performed by the authors. In the first phase, after the extirpation of the tendon of the 2nd finger its area has been bridged over by a 5-6 cm long autologous vein transplant, cannulated with a silicone rubber bar. After 4 weeks, after the vascularization of the vein transplant the silicone bar has been removed from a new approach, and through the "tunnel" formed in this way and padded with silicone a tendon has been pulled through with two different methods: 1. according to the method of Paneva-Holevitch a diphasic pedicled tendon transplant and 2. a free tendon transplant. No differences were found as regards the adhesions, the vascularization and the tissular structure of the tendon. It may be presumed that also the distal portion of the pedicled tendon transplant is really a free tendon transplant. | [
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PMID:6835 | [Pig skin xenograft in burns. I. Technology, laboratory studies. II. Clinical experience]. | The technology of the preparation of certainly sterile xenograft--pig's skin has been examined by the authors before the therapeutical use. On the basis of their examinations it was found by the authors that 2500 krad gamma radiation is suitable for the sterilization of the pig's skin--for the preparation of both the nature or lyophilized skin--since at this radiation value the pig's skin suffers no injury. After the preparation of the xenograft its clinical use has been initiated with certainly sterile material in children with burns. Xenograft has been used on 50 occasions, chiefly after surgical necrectomy, as provisional biological dressing. On the basis of their satisfactors results the authors advocate the use of the xenograft in burns, in certain skin affections, in clinical pictures concomitant with skinning and cutaneous necrosis and generally in all cases, in which skin grafting in necessary. | [Pig skin xenograft in burns. I. Technology, laboratory studies. II. Clinical experience]. The technology of the preparation of certainly sterile xenograft--pig's skin has been examined by the authors before the therapeutical use. On the basis of their examinations it was found by the authors that 2500 krad gamma radiation is suitable for the sterilization of the pig's skin--for the preparation of both the nature or lyophilized skin--since at this radiation value the pig's skin suffers no injury. After the preparation of the xenograft its clinical use has been initiated with certainly sterile material in children with burns. Xenograft has been used on 50 occasions, chiefly after surgical necrectomy, as provisional biological dressing. On the basis of their satisfactors results the authors advocate the use of the xenograft in burns, in certain skin affections, in clinical pictures concomitant with skinning and cutaneous necrosis and generally in all cases, in which skin grafting in necessary. | [
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PMID:6836 | [Radioisotopes used in the diagnosis of bone diseases]. | The radiopharmacons produced in Hungary and suitable for the demonstration of reactive bone alterations are discussed by the authors. These pharmacons are the following: 85ScCl2=Strontiumchloride, 153Sm-EDTA=Samarium ethylendiamintetraacetate, 169Yb-citrate=Ytterbium-citrate, 99mTc-HEDSPA=Technetium-hydroxy-ethylene-diphosphonate, 99mTc-pyrophosphate. The scintigraphic pictures obtained by the use of these radiopharmacons are presented. On the basis of their experimental examinations the numerous advantages of the use of 99mTc-HEDSPA are pointed out and the possibilities are outlines, which are to be obtained in the detection of occult bone alterations, in the examination of juvenile patients and perhaps in the case of osteotransplantation. | [Radioisotopes used in the diagnosis of bone diseases]. The radiopharmacons produced in Hungary and suitable for the demonstration of reactive bone alterations are discussed by the authors. These pharmacons are the following: 85ScCl2=Strontiumchloride, 153Sm-EDTA=Samarium ethylendiamintetraacetate, 169Yb-citrate=Ytterbium-citrate, 99mTc-HEDSPA=Technetium-hydroxy-ethylene-diphosphonate, 99mTc-pyrophosphate. The scintigraphic pictures obtained by the use of these radiopharmacons are presented. On the basis of their experimental examinations the numerous advantages of the use of 99mTc-HEDSPA are pointed out and the possibilities are outlines, which are to be obtained in the detection of occult bone alterations, in the examination of juvenile patients and perhaps in the case of osteotransplantation. | [
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PMID:6838 | [Surgical treatment of knee joint ligaments]. | Because injuries of the ligaments of the knee joint, during 11 years 58 operations have been performed by the authors. In order to evaluate the late results, all patients have been reexamined 1 to 10 years after the operation. In more than the half of the cases at the least 2 ligament injuries have been operated on. 31 patients underwent the operation within two weeks after the injury, and the other patients later on. The authors' material and results are compared also with the data of the literature. In the authors' opinion the result of the surgical treatment is not decisively depending on the chosen operative method. The early and exact diagnosis--forming the basis of the suitable treatment--are of far greater importance. The perfect operative technique and the consequent rehabilitation are indispensable requirements of all surgical interventions. After severe ligament injury of the knee joint the surgical intervention allowed to 2/3 or 3/4 of the injured patients to return to work with stabilized knee. In younger patients also sporting may be possible. Therefore the surgical treatment of the knees, which became unstable because of ligament injury, is absolutely indicated in patients in working age. | [Surgical treatment of knee joint ligaments]. Because injuries of the ligaments of the knee joint, during 11 years 58 operations have been performed by the authors. In order to evaluate the late results, all patients have been reexamined 1 to 10 years after the operation. In more than the half of the cases at the least 2 ligament injuries have been operated on. 31 patients underwent the operation within two weeks after the injury, and the other patients later on. The authors' material and results are compared also with the data of the literature. In the authors' opinion the result of the surgical treatment is not decisively depending on the chosen operative method. The early and exact diagnosis--forming the basis of the suitable treatment--are of far greater importance. The perfect operative technique and the consequent rehabilitation are indispensable requirements of all surgical interventions. After severe ligament injury of the knee joint the surgical intervention allowed to 2/3 or 3/4 of the injured patients to return to work with stabilized knee. In younger patients also sporting may be possible. Therefore the surgical treatment of the knees, which became unstable because of ligament injury, is absolutely indicated in patients in working age. | [
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PMID:6839 | [The so-called "intact" side in Perthes' disease]. | Out of the 32 patients treated with Perthes' disease in the Orthopaedic Department of the University Medical School, PECS, in 9 cases bilateral course has been observed. Out of 23 children with Perthes' disease and unilateral, typical course the authors have observed in 12 patients pathological X-ray signs on the "intact" side--which were more distinct on the epiphyseal center, but chiefly on the growth intervertebral disk and on the metaphysis. In the same time, no subjective complaints and no other objective clinical symptoms pointed to Perthes' disease. It is supposed by the authors that transient ischaemic state may occur also on the side classified as "intact", but with reversible consequences, thus, the alterations of the epiphyseal center do not display the typical course of the Perthes' disease. | [The so-called "intact" side in Perthes' disease]. Out of the 32 patients treated with Perthes' disease in the Orthopaedic Department of the University Medical School, PECS, in 9 cases bilateral course has been observed. Out of 23 children with Perthes' disease and unilateral, typical course the authors have observed in 12 patients pathological X-ray signs on the "intact" side--which were more distinct on the epiphyseal center, but chiefly on the growth intervertebral disk and on the metaphysis. In the same time, no subjective complaints and no other objective clinical symptoms pointed to Perthes' disease. It is supposed by the authors that transient ischaemic state may occur also on the side classified as "intact", but with reversible consequences, thus, the alterations of the epiphyseal center do not display the typical course of the Perthes' disease. | [
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PMID:6840 | [Alloplastic reconstruction of the proximal third of the femur. Case report]. | The case of a woman, aged 51, is reported. In this patient, in 1961, because of an alteration developed in the right neck of the femur--and trochanter area--diagnosed for osteoclastoma--irradiation treatment has been performed. After steadily increasing complaints the patient suffered in 1965 a pathological fracture. In 1966 after resection of the proximal third of the femurametallic prosthesis have been used. With a satisfactory hip function the patient is--even 8 and a half years after the operation--able to walk and at work again. | [Alloplastic reconstruction of the proximal third of the femur. Case report]. The case of a woman, aged 51, is reported. In this patient, in 1961, because of an alteration developed in the right neck of the femur--and trochanter area--diagnosed for osteoclastoma--irradiation treatment has been performed. After steadily increasing complaints the patient suffered in 1965 a pathological fracture. In 1966 after resection of the proximal third of the femurametallic prosthesis have been used. With a satisfactory hip function the patient is--even 8 and a half years after the operation--able to walk and at work again. | [
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PMID:6841 | Program for managing chronic pain. II. Short-term results. | A program for treating inpatients who had chronic pain resulted in significant improvement in 79% of them by the time of their dismissal. At the time of short-term follow-up (6 months), however, this improvement rate had diminished to 50%. It was observed that this type of chronically disabled person can return home and increase work-related activity without returning to previous patterns of drug use and repeated hospitalizations. | Program for managing chronic pain. II. Short-term results. A program for treating inpatients who had chronic pain resulted in significant improvement in 79% of them by the time of their dismissal. At the time of short-term follow-up (6 months), however, this improvement rate had diminished to 50%. It was observed that this type of chronically disabled person can return home and increase work-related activity without returning to previous patterns of drug use and repeated hospitalizations. | [
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PMID:6856 | Enzymatic hydrolysis of 1-monoacyl-SN-glycerol-3-phosphoryl-choline (1-lysolecithin) by phospholipases from peanut seeds. | Hydrolysis of 1-lysolecithin (1-acyl glycerophosphorylcholine [1-acyl GPC]) by preparations of phospholipase D from peanut seeds was investigated. 1-Lysolecithin was hydrolyzed at a much slower rate than phosphatidylcholine (lecithin). Although Ca+2 ions are required for the cleavage of lecithin by the enzyme, their effect on the hydrolysis of lysolecithin depended upon the concentration of the substrate: at 0.2 mM 1-lysolecithin, Ca+2 ions increased the reaction rates, whereas at concentrations of the substrate lower than 0.1 mM, Ca+2 ions were inhibitory. A broad pH activity curve between 5 and 8 was obtained with higher rates in the alkaline range, both in the absence and presence of Ca+2 ions. The increased hydrolysis of lysolecithin due to Ca+2 was noticed over the entire pH range. Upon storage of the enzyme solutions at 4 C, decreased rates of hydrolysis of lecithin were observed, with t 1/2 values of ca. 50 and 100 days depending on the purity of the preparation. During the same period, no reduction occurred in the activity of these preparations on lysolecithin as substrate. The effects of Ca+2 ions and the analysis of the products of 1-acyl GPC cleavage by the enzyme preparations revealed the presence of more than one enzyme and the formation of the following compounds: lysophosphatidic acids (1 acyl glycerophosphoric acids), free fatty acids, glycerophosphorylcholine, and choline. The possible pathways leading to the degradation of lysolecithin and the formation of these products include reactions catalyzed by lysophospholipase A1 (lysophosphatidylcholine 1-acyl hydrolase, E.C. 3.1.1.5) and a phosphodiesterase (L-3-glycerylphosphorylcholine glycerophosphohydrolase, E.C.3.1.4.2), in addition to phospholipase D (phosphatidyl-choline phosphatidohydrolase, E.C. 3.1.4.4). | Enzymatic hydrolysis of 1-monoacyl-SN-glycerol-3-phosphoryl-choline (1-lysolecithin) by phospholipases from peanut seeds. Hydrolysis of 1-lysolecithin (1-acyl glycerophosphorylcholine [1-acyl GPC]) by preparations of phospholipase D from peanut seeds was investigated. 1-Lysolecithin was hydrolyzed at a much slower rate than phosphatidylcholine (lecithin). Although Ca+2 ions are required for the cleavage of lecithin by the enzyme, their effect on the hydrolysis of lysolecithin depended upon the concentration of the substrate: at 0.2 mM 1-lysolecithin, Ca+2 ions increased the reaction rates, whereas at concentrations of the substrate lower than 0.1 mM, Ca+2 ions were inhibitory. A broad pH activity curve between 5 and 8 was obtained with higher rates in the alkaline range, both in the absence and presence of Ca+2 ions. The increased hydrolysis of lysolecithin due to Ca+2 was noticed over the entire pH range. Upon storage of the enzyme solutions at 4 C, decreased rates of hydrolysis of lecithin were observed, with t 1/2 values of ca. 50 and 100 days depending on the purity of the preparation. During the same period, no reduction occurred in the activity of these preparations on lysolecithin as substrate. The effects of Ca+2 ions and the analysis of the products of 1-acyl GPC cleavage by the enzyme preparations revealed the presence of more than one enzyme and the formation of the following compounds: lysophosphatidic acids (1 acyl glycerophosphoric acids), free fatty acids, glycerophosphorylcholine, and choline. The possible pathways leading to the degradation of lysolecithin and the formation of these products include reactions catalyzed by lysophospholipase A1 (lysophosphatidylcholine 1-acyl hydrolase, E.C. 3.1.1.5) and a phosphodiesterase (L-3-glycerylphosphorylcholine glycerophosphohydrolase, E.C.3.1.4.2), in addition to phospholipase D (phosphatidyl-choline phosphatidohydrolase, E.C. 3.1.4.4). | [
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PMID:6857 | The potentialities of some antihistaminics in preanaesthetic medication. | A detailed study has been carried out on the potentialities of antazoline and chlorpheneramine (C.P.M.) in preanaesthetic medication. It included a determination of their sedative action, effects on cardiovascular system and any possible anticholinergic and antiarrhythmic properties. Both drugs depressed spontaneous activity in mice. Antazoline produced hypotension in chloralosed dogs and spinal cats (a peripheral action). Both produced a negative inotropic action on isolated rabbit's heart. On rat's auricle antazoline produced a positive chronotropic action while C.P.M. produced a negative chronotropic action. Both drugs could protect the heart against adrenaline induced arrhythmias during chloroform and halothane anaesthesia. Their anticholinergic properties were demonstrated by studies on isolated rabbit's heart and intestine as well as on isolated guinea pig's ileum. | The potentialities of some antihistaminics in preanaesthetic medication. A detailed study has been carried out on the potentialities of antazoline and chlorpheneramine (C.P.M.) in preanaesthetic medication. It included a determination of their sedative action, effects on cardiovascular system and any possible anticholinergic and antiarrhythmic properties. Both drugs depressed spontaneous activity in mice. Antazoline produced hypotension in chloralosed dogs and spinal cats (a peripheral action). Both produced a negative inotropic action on isolated rabbit's heart. On rat's auricle antazoline produced a positive chronotropic action while C.P.M. produced a negative chronotropic action. Both drugs could protect the heart against adrenaline induced arrhythmias during chloroform and halothane anaesthesia. Their anticholinergic properties were demonstrated by studies on isolated rabbit's heart and intestine as well as on isolated guinea pig's ileum. | [
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PMID:6862 | [Classification of acute bacterial meningitis cases according to their etiology, seen in a children's hospital in Ankara from March 1973 to April 1974]. | In a 14 months period, as from March 1973 to April 1974 468 cases of acute bacterial meningitis have been diagnosed by C.S.F. findings; namely by examining the protein and sugar content, by the cell counts, Gram's staining and culturing of the sediments of C.S.F. 188 cases were proven by culturing to be meningococcic meningitis. All these cases are from the families living in suburban areas of the city under crowded circumstances, which show the importance of population density in the epidemiology of this particular disease. | [Classification of acute bacterial meningitis cases according to their etiology, seen in a children's hospital in Ankara from March 1973 to April 1974]. In a 14 months period, as from March 1973 to April 1974 468 cases of acute bacterial meningitis have been diagnosed by C.S.F. findings; namely by examining the protein and sugar content, by the cell counts, Gram's staining and culturing of the sediments of C.S.F. 188 cases were proven by culturing to be meningococcic meningitis. All these cases are from the families living in suburban areas of the city under crowded circumstances, which show the importance of population density in the epidemiology of this particular disease. | [
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PMID:6860 | [Yeast cell wall-dissolving enzymes of the thermotolerant actinomycete Thermoactinomyces vulgaris]. | The thermotolerant culture of Thermoactinomyces vulgaris PA II-4A was cultivated in the Biotec fermenter to obtain the enzyme preparation with a high proteolytic and lytic activity. Resistance of the cells of Candida utilis and Saccharomyces fragilis (mesophilic and thermotolerant strains) to the lytic action of the enzyme preparation was different. Preliminary treatment of the yeast cells by L-cysteine increased their susceptibility to the lytic action of the preparation. The degree of lysis of the cells depended also on their age: the cells growing during 10-12 hours were lysed easier than the cells cultivated during 24 hours. | [Yeast cell wall-dissolving enzymes of the thermotolerant actinomycete Thermoactinomyces vulgaris]. The thermotolerant culture of Thermoactinomyces vulgaris PA II-4A was cultivated in the Biotec fermenter to obtain the enzyme preparation with a high proteolytic and lytic activity. Resistance of the cells of Candida utilis and Saccharomyces fragilis (mesophilic and thermotolerant strains) to the lytic action of the enzyme preparation was different. Preliminary treatment of the yeast cells by L-cysteine increased their susceptibility to the lytic action of the preparation. The degree of lysis of the cells depended also on their age: the cells growing during 10-12 hours were lysed easier than the cells cultivated during 24 hours. | [
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] |
PMID:6861 | [Cholesterol breakdown by enzyme preparations extracted from Streptomyces lavendulae]. | Cholesterol was decomposed by 75-90% during two hours by enzyme preparations from the disintegrated mycelium of Streptomyces lavendulae. The effect of concentrations of cholesterol and protein on the decomposition of cholesterol by the enzyme was studied; the higher the content of protein in a sample, the more rapidly cholesterol is decomposed; the rate of cholesterol decomposition increases with a decrease of its concentration. The optimum pH is 7.5-9.0. After dialysis and lyophilization, the activity of the enzyme preparations remains the same during two weeks, and then decreases by a factor of 1.5-2 in the course of the following thirty days. | [Cholesterol breakdown by enzyme preparations extracted from Streptomyces lavendulae]. Cholesterol was decomposed by 75-90% during two hours by enzyme preparations from the disintegrated mycelium of Streptomyces lavendulae. The effect of concentrations of cholesterol and protein on the decomposition of cholesterol by the enzyme was studied; the higher the content of protein in a sample, the more rapidly cholesterol is decomposed; the rate of cholesterol decomposition increases with a decrease of its concentration. The optimum pH is 7.5-9.0. After dialysis and lyophilization, the activity of the enzyme preparations remains the same during two weeks, and then decreases by a factor of 1.5-2 in the course of the following thirty days. | [
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PMID:6865 | Sulphasalazine lung. | A patient developed the rare complication of pulmonary eosinophilia whilst receiving sulphasalazine. A review of the world literature on sulphasalazine-induced lung disease is presented. | Sulphasalazine lung. A patient developed the rare complication of pulmonary eosinophilia whilst receiving sulphasalazine. A review of the world literature on sulphasalazine-induced lung disease is presented. | [
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PMID:6863 | A tentative transmission mechanism for the twitch elicited in guinea-pig vas deferens by field stimulation. | The twitch response to nerve activity in the vas deferens does not behave as if it were adrenergic since it is enhanced by adrenoceptor blockers and often inhibited by noradrenaline and other sympathomimieic amines. Potassium (K+) ions have a strong reinforcing action on the twitch and easily restore it after blockade by lanthanum. The hypothesis is advanced that K+ ions have a transmitter function in the vas deferens and that K+ ions released in conjunction with the nerve stimulus may reach a concentration at the postsynaptic membrane sufficient to excite the muscle cell and produce a twitch. | A tentative transmission mechanism for the twitch elicited in guinea-pig vas deferens by field stimulation. The twitch response to nerve activity in the vas deferens does not behave as if it were adrenergic since it is enhanced by adrenoceptor blockers and often inhibited by noradrenaline and other sympathomimieic amines. Potassium (K+) ions have a strong reinforcing action on the twitch and easily restore it after blockade by lanthanum. The hypothesis is advanced that K+ ions have a transmitter function in the vas deferens and that K+ ions released in conjunction with the nerve stimulus may reach a concentration at the postsynaptic membrane sufficient to excite the muscle cell and produce a twitch. | [
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PMID:6867 | [On the significance of beta-adrenergic stimuli for the gastric secretion in humans]. | In adults of both sexes, the influence on the basal and the maximal by means of pentagastrin stimulated gastric secretion of a single intravenous injection of 8 mg (0.09 to 0.16 mg/kg) oxyfedrine or of two intramuscular injections of 1 mg (0.014 to 0.016 mg/kg) or of 2.5 mg (0.033 to 0.045 mg/kg) in each case isoproterenol, consecutively administered at an interval of 15 minutes, was studied. At a dose which evokes cardiovascular responses isoproterenol does not produce a significant change of the secretory rates of H+, C1-, Na+, K+, Ca++ and Mg++ or of the ionic composition of gastric juice both during basal and maximal acid output. Oxyfedrine shows only during maximal acid stimulation some effects on gastric secretion: a significant rise of the concentration and secretory rate of H+ and of the secretory rate of C1- and a significant decline of the concentration of Na+ and of both the concentration and secretory rate of Mg++. Beta-adrenergic receptors seem not to play any part in the regulation of the production of gastric juice. Possibly, the action of oxyfedrine on the stimulated gastric mucosa may be mediated by a stimulation of alpha-adrenergic receptors or by inhibition of the activity of 3',5'-AMP-phosphodiesterase. | [On the significance of beta-adrenergic stimuli for the gastric secretion in humans]. In adults of both sexes, the influence on the basal and the maximal by means of pentagastrin stimulated gastric secretion of a single intravenous injection of 8 mg (0.09 to 0.16 mg/kg) oxyfedrine or of two intramuscular injections of 1 mg (0.014 to 0.016 mg/kg) or of 2.5 mg (0.033 to 0.045 mg/kg) in each case isoproterenol, consecutively administered at an interval of 15 minutes, was studied. At a dose which evokes cardiovascular responses isoproterenol does not produce a significant change of the secretory rates of H+, C1-, Na+, K+, Ca++ and Mg++ or of the ionic composition of gastric juice both during basal and maximal acid output. Oxyfedrine shows only during maximal acid stimulation some effects on gastric secretion: a significant rise of the concentration and secretory rate of H+ and of the secretory rate of C1- and a significant decline of the concentration of Na+ and of both the concentration and secretory rate of Mg++. Beta-adrenergic receptors seem not to play any part in the regulation of the production of gastric juice. Possibly, the action of oxyfedrine on the stimulated gastric mucosa may be mediated by a stimulation of alpha-adrenergic receptors or by inhibition of the activity of 3',5'-AMP-phosphodiesterase. | [
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PMID:6900 | [Beta-lactoglobulin AB fluorescence under different physico-chemical conditions. Denaturation by urea and organic solvents]. | Dependences of different fluorescence parameters of bovine beta-lactoglobulin AB on the concentrations of urea (pH 2.8-8.8), ethanol (pH 2.1-10.2), and dioxane (pH 5.3) have been investigated. The denaturation properties (the free energy and the stoichiometry of denaturative interaction) are highly dependent on pH values. The data obtained indicate that the hydrophobic interactions are the determining forces in the stabilization process of the beta-lactoglobulin molecule. The relative contribution of these interactions lowers with pH rise. The denaturation of beta-lactoglobulin AB proceeds through two stages under conditions when the protein octamer exists. Up to 30 vol.% of ethanol and dioxane, the penetration of the organic molecules into the external parts of the protein globule takes place. At the concentration of the solvent exceeding 50 vol.% structural transitions are observed. The comparison of fluorescence and perturbation spectral data enables one to localise tryptophan residues in the protein more precisely. The results of this and former reports lead to hypothesis that beta-lactoglobulin may serve as a transporter of some substances which are unstable to acidic media. | [Beta-lactoglobulin AB fluorescence under different physico-chemical conditions. Denaturation by urea and organic solvents]. Dependences of different fluorescence parameters of bovine beta-lactoglobulin AB on the concentrations of urea (pH 2.8-8.8), ethanol (pH 2.1-10.2), and dioxane (pH 5.3) have been investigated. The denaturation properties (the free energy and the stoichiometry of denaturative interaction) are highly dependent on pH values. The data obtained indicate that the hydrophobic interactions are the determining forces in the stabilization process of the beta-lactoglobulin molecule. The relative contribution of these interactions lowers with pH rise. The denaturation of beta-lactoglobulin AB proceeds through two stages under conditions when the protein octamer exists. Up to 30 vol.% of ethanol and dioxane, the penetration of the organic molecules into the external parts of the protein globule takes place. At the concentration of the solvent exceeding 50 vol.% structural transitions are observed. The comparison of fluorescence and perturbation spectral data enables one to localise tryptophan residues in the protein more precisely. The results of this and former reports lead to hypothesis that beta-lactoglobulin may serve as a transporter of some substances which are unstable to acidic media. | [
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PMID:6901 | [The compact form of DNA in solution. IV. The effect of secondary structure defectiveness on the arrangement of double-chained DNA molecules into compact particles]. | Influence of pH on absorbance and CD-spectra of DNA in PEG-containing water-salt solutions has been studied. The changes in the spectra appeared due to disturbance of the DNA secondary structure upon acidification of the medium proir to or after DNA compactization. If acidification preceeds DNA compactization an intense negative band in the CD spectrum inherent to the compact particles is observed at pH values 7-4. The intensity of the band decreases with an increase of the acidity. The size of the compact particles as evaluated from the dependence of the apparent optical density on the wavelength value remains unchanged (about 1200 A). If the solution is strongly acidified (pH 4.0-2.8) and a considerable disturbance in the DNA secondary structure takes place a negative band in the CD spectrum completely disappears. If one acidifies a solution containing preformed DNA compact particles a decrease of the intensity of the CD negative band starts at lower pH values (less than 2.8). This process is accompanied by an increase of the size of the particles. Acidic "denaturation" of DNA within the compact particles (pH approximately 2.5) is followed by a dissappearance of the CD negative band and a considerable increase of the particle size. The data obtained indicate that the specific arrangement of DNA strands manifested in a CD negative band depends on the defects in the DNA secondary structure. | [The compact form of DNA in solution. IV. The effect of secondary structure defectiveness on the arrangement of double-chained DNA molecules into compact particles]. Influence of pH on absorbance and CD-spectra of DNA in PEG-containing water-salt solutions has been studied. The changes in the spectra appeared due to disturbance of the DNA secondary structure upon acidification of the medium proir to or after DNA compactization. If acidification preceeds DNA compactization an intense negative band in the CD spectrum inherent to the compact particles is observed at pH values 7-4. The intensity of the band decreases with an increase of the acidity. The size of the compact particles as evaluated from the dependence of the apparent optical density on the wavelength value remains unchanged (about 1200 A). If the solution is strongly acidified (pH 4.0-2.8) and a considerable disturbance in the DNA secondary structure takes place a negative band in the CD spectrum completely disappears. If one acidifies a solution containing preformed DNA compact particles a decrease of the intensity of the CD negative band starts at lower pH values (less than 2.8). This process is accompanied by an increase of the size of the particles. Acidic "denaturation" of DNA within the compact particles (pH approximately 2.5) is followed by a dissappearance of the CD negative band and a considerable increase of the particle size. The data obtained indicate that the specific arrangement of DNA strands manifested in a CD negative band depends on the defects in the DNA secondary structure. | [
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PMID:6902 | [Kinetics and mechanism of inactivation of isolated chloroplasts]. | A detailed kinetic analysis has been performed of a multistep inactivation of chloroplasts. The kinetic model suggested involves the formation of chloroplast forms differing in stability and activity. A comparison of the kinetic model with the experimental data shows that the mechanism of inactivation of isolated pea chloroplasts consists of at least two forms displaying different activity in the Hill reaction and different stability in solution. The effect was studied of the nature of the buffer and destruction products on the kinetics of chloroplast inactivation in the process of "ageing". In phosphate buffer, where the concentration of phosphate exceeds 40 mM, the effect of the destruction products of chloroplasts on their inactivation is insignificant. The pH dependence on the inactivation kinetics suggests that the pH region from 6 to 9 affects only the rapid kinetic process resulting in the increase in the chloroplast activity; irreversible inactivation of chloroplasts is pH-independent. The temperature dependence of the irreversible inactivation kinetics has been studied and the activation parametres of this stage have been determined. Possible molecular mechanism of the limiting stages of the inactivation of isolated chloroplasts are discussed, which can explain the kinetic data obtained. | [Kinetics and mechanism of inactivation of isolated chloroplasts]. A detailed kinetic analysis has been performed of a multistep inactivation of chloroplasts. The kinetic model suggested involves the formation of chloroplast forms differing in stability and activity. A comparison of the kinetic model with the experimental data shows that the mechanism of inactivation of isolated pea chloroplasts consists of at least two forms displaying different activity in the Hill reaction and different stability in solution. The effect was studied of the nature of the buffer and destruction products on the kinetics of chloroplast inactivation in the process of "ageing". In phosphate buffer, where the concentration of phosphate exceeds 40 mM, the effect of the destruction products of chloroplasts on their inactivation is insignificant. The pH dependence on the inactivation kinetics suggests that the pH region from 6 to 9 affects only the rapid kinetic process resulting in the increase in the chloroplast activity; irreversible inactivation of chloroplasts is pH-independent. The temperature dependence of the irreversible inactivation kinetics has been studied and the activation parametres of this stage have been determined. Possible molecular mechanism of the limiting stages of the inactivation of isolated chloroplasts are discussed, which can explain the kinetic data obtained. | [
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PMID:6909 | Methylmalonic aciduria without vitamin B12 deficiency in an adult sibship. | Two brothers 62 and 70 years old, without evidence of vitamin B12 lack, excreted 12 to 115 mg of methylmalonic acid daily (normal, less than 9 mg per day). Neither had anemia or hepatic dysfunction, and serum vitamin B12 concentrations ranged from 369 to 800 pg per milliliter. The propositus, the younger brother, continued to excrete excessive methylmalonate, 103 to 115 mg per day, after 2000 mug of parenterally administered vitamin B12 at the fifth and 11th months of study. Leukocyte activities of the cobalamin-linked enzyme methylmalonyl coenzyme A mutase were respectively reduced in the propositus and his brother, to 0.04 and 0.11 nmoles of 3-(14)-C Ls methylmalonyl coenzyme A metabolized per hour per milligram of leukocyte protein (normal, 0.286 +/- 0.079 [S.D.]). These activities were not enhanced by 2 mug of 5'-deoxyadenosylcobalamin added to the assays. A heritable benign form of adult methylmalonic aciduria rather than vitamin B12 lack best explains these findings. | Methylmalonic aciduria without vitamin B12 deficiency in an adult sibship. Two brothers 62 and 70 years old, without evidence of vitamin B12 lack, excreted 12 to 115 mg of methylmalonic acid daily (normal, less than 9 mg per day). Neither had anemia or hepatic dysfunction, and serum vitamin B12 concentrations ranged from 369 to 800 pg per milliliter. The propositus, the younger brother, continued to excrete excessive methylmalonate, 103 to 115 mg per day, after 2000 mug of parenterally administered vitamin B12 at the fifth and 11th months of study. Leukocyte activities of the cobalamin-linked enzyme methylmalonyl coenzyme A mutase were respectively reduced in the propositus and his brother, to 0.04 and 0.11 nmoles of 3-(14)-C Ls methylmalonyl coenzyme A metabolized per hour per milligram of leukocyte protein (normal, 0.286 +/- 0.079 [S.D.]). These activities were not enhanced by 2 mug of 5'-deoxyadenosylcobalamin added to the assays. A heritable benign form of adult methylmalonic aciduria rather than vitamin B12 lack best explains these findings. | [
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PMID:6918 | Different alpha-adrenoreceptors in the central nervous system mediating biochemical and functional effects of clonidine and receptor blocking agents. | The influence of clonidine on alpha-adrenoreceptors in the central nervous system of rats and mice has been investigated. Both functional events due to postsynaptic receptor stimulation (flexor reflex activity, motor activity) and biochemical changes have been considered. 1. Clonidine was less potent in stimulating the hindlimb flexor reflex activity of spinal rats than in inhibiting the alpha-methyltyrosine-induced disappearance of noradrenaline in the spinal cord and in the whole brain of rats. 2. The increase in flexor reflex activity due to clonidine (0.4 mg/kg) was virtually completely inhibited by phenoxybenzamine (20 mg/kg) and haloperidol (10 mg/kg), was partially inhibited by yohimbine (10 mg/kg) and piperoxan (60 mg/kg) and was not significantly inhibited by yohimbine (3 mg/kg) and tolazoline (50 mg/kg). 3. The potentiation by clonidine of the apomorphine-induced locomotor stimulation of reserpine-treated mice was almost completely inhibited by phenoxybenzamine (20 mg/kg) but was not significantly affected by yohimbine (10 or 3 mg/kg) and only slightly inhibited by tolazoline (50 mg/kg). 4. Clonidine (0.1 mg/kg) caused a considerable inhibition of the alpha-methyltyrosine-induced disappearance of noradrenaline in the spinal cord and brain or rats and in the brain of mice. This effect of clonidine was completely antagonized by yohimbine (10 mg/kg). It was markedly antagonized by yohimbine (3 mg/kg), piperoxan (60 mg/kg) or tolazoline (50 mg/kg) but not by phenoxybenzamine (20 mg/kg) or haloperidol (10 mg/kg). 5. Clonidine (0.1 mg/kg) caused an inhibition of the accumulation of Dopa after decarboxylase inhibition in the noradrenaline-rich regions of the rat central nervous system. This effect was counteracted by yohimbine (10 mg/kg), piperoxan (60 mg/kg) or tolazoline (50 mg/kg) but not by phenoxybenzamine (20 mg/kg). 6. The postsynaptic functional effects and the biochemical effects of clonidine may be due to stimulation of different alpha-adrenoreceptors since the two effects were inhibited differently by various alpha-adrenoreceptor blocking agents and since the two effects were produced by different doses of clonidine. The alpha-adrenoreceptors mediating the biochemical changes might be located on the noradrenergic neurones. | Different alpha-adrenoreceptors in the central nervous system mediating biochemical and functional effects of clonidine and receptor blocking agents. The influence of clonidine on alpha-adrenoreceptors in the central nervous system of rats and mice has been investigated. Both functional events due to postsynaptic receptor stimulation (flexor reflex activity, motor activity) and biochemical changes have been considered. 1. Clonidine was less potent in stimulating the hindlimb flexor reflex activity of spinal rats than in inhibiting the alpha-methyltyrosine-induced disappearance of noradrenaline in the spinal cord and in the whole brain of rats. 2. The increase in flexor reflex activity due to clonidine (0.4 mg/kg) was virtually completely inhibited by phenoxybenzamine (20 mg/kg) and haloperidol (10 mg/kg), was partially inhibited by yohimbine (10 mg/kg) and piperoxan (60 mg/kg) and was not significantly inhibited by yohimbine (3 mg/kg) and tolazoline (50 mg/kg). 3. The potentiation by clonidine of the apomorphine-induced locomotor stimulation of reserpine-treated mice was almost completely inhibited by phenoxybenzamine (20 mg/kg) but was not significantly affected by yohimbine (10 or 3 mg/kg) and only slightly inhibited by tolazoline (50 mg/kg). 4. Clonidine (0.1 mg/kg) caused a considerable inhibition of the alpha-methyltyrosine-induced disappearance of noradrenaline in the spinal cord and brain or rats and in the brain of mice. This effect of clonidine was completely antagonized by yohimbine (10 mg/kg). It was markedly antagonized by yohimbine (3 mg/kg), piperoxan (60 mg/kg) or tolazoline (50 mg/kg) but not by phenoxybenzamine (20 mg/kg) or haloperidol (10 mg/kg). 5. Clonidine (0.1 mg/kg) caused an inhibition of the accumulation of Dopa after decarboxylase inhibition in the noradrenaline-rich regions of the rat central nervous system. This effect was counteracted by yohimbine (10 mg/kg), piperoxan (60 mg/kg) or tolazoline (50 mg/kg) but not by phenoxybenzamine (20 mg/kg). 6. The postsynaptic functional effects and the biochemical effects of clonidine may be due to stimulation of different alpha-adrenoreceptors since the two effects were inhibited differently by various alpha-adrenoreceptor blocking agents and since the two effects were produced by different doses of clonidine. The alpha-adrenoreceptors mediating the biochemical changes might be located on the noradrenergic neurones. | [
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PMID:6919 | Noradrenaline synthesis and utilization: control by nerve impulse flow under normal conditions and after treatment with alpha-adrenoreceptor blocking agents. | The changes in the synthesis and utilization or noradrenaline cranial and caudal to an acute section of the rat spinal cord have been used to investigate the importance of nerve impulses for these processes. 1. Cranial to a lesion of the spinal cord, the alpha-methyltyrosine-induced disappearance of noradrenaline was accelerated by the alpha-adrenoreceptor blocking agents yohimbine (10 mg/kg), piperoxan (60 mg/kg) and tolazoline (50 mg/kg). In the absence of nerve impulses caudal to a lesion of the spinal cord, this disappearance was decelerated as compared to that cranial to the lesion and it was not influenced by the three alpha-adrenoreceptor blocking agents. 2. The nialamide-induced accumulation of normetanephrine in the whole brain was increased by phenoxybenzamine (20 mg/kg) and yohimbine whereas it was decreased by the alpha-adrenoreceptor stimulating agent clonidine (0.1 mg/kg). The effect of clonidine was completely antagonized by yohimbine, but not by phenoxybenzamine, giving further evidence for the view that clonidine and yohimbine have a stronger effect than phenoxybenzamine on the alpha-adrenoreceptors regulating the release of noradrenaline induced by nerve impluses. 3. The accumulation of Dopa after decarboxylase inhibition cranial to a lesion of the spinal cord was accelerated by yohimbine, piperoxan and tolazoline, but not significantly affected by phenoxybenzamine and haloperidol (10 mg/kg). In the absence of nerve impulses caudal to a lesion of the spinal cord, the popa accumulation was decelerated as compared to that cranial to the lesion and it was not influenced by the former three alpha--adrenoreceptor blocking agents as well as by clonidine. 4. The results show that the synthesis and the utilization noradrenaline normally, as well as the accelerations of these processes by alpha-adrenoreceptor blocking agents, are dependent on nerve impulses. The stimulation of the synthesis and utilization of noradrenaline by nerve impulses might by influenced via the activity of teh alpha-adrenoreceptors located either on the nerve terminals or on the cell bodies or on both parts of the noradrenergic neurones. In the absence of nerve impulses, a receptor-mediated feedback mechanism similar to that described for the synthesis of dopamine does not appear to regulate the synthesis of noradrenaline. | Noradrenaline synthesis and utilization: control by nerve impulse flow under normal conditions and after treatment with alpha-adrenoreceptor blocking agents. The changes in the synthesis and utilization or noradrenaline cranial and caudal to an acute section of the rat spinal cord have been used to investigate the importance of nerve impulses for these processes. 1. Cranial to a lesion of the spinal cord, the alpha-methyltyrosine-induced disappearance of noradrenaline was accelerated by the alpha-adrenoreceptor blocking agents yohimbine (10 mg/kg), piperoxan (60 mg/kg) and tolazoline (50 mg/kg). In the absence of nerve impulses caudal to a lesion of the spinal cord, this disappearance was decelerated as compared to that cranial to the lesion and it was not influenced by the three alpha-adrenoreceptor blocking agents. 2. The nialamide-induced accumulation of normetanephrine in the whole brain was increased by phenoxybenzamine (20 mg/kg) and yohimbine whereas it was decreased by the alpha-adrenoreceptor stimulating agent clonidine (0.1 mg/kg). The effect of clonidine was completely antagonized by yohimbine, but not by phenoxybenzamine, giving further evidence for the view that clonidine and yohimbine have a stronger effect than phenoxybenzamine on the alpha-adrenoreceptors regulating the release of noradrenaline induced by nerve impluses. 3. The accumulation of Dopa after decarboxylase inhibition cranial to a lesion of the spinal cord was accelerated by yohimbine, piperoxan and tolazoline, but not significantly affected by phenoxybenzamine and haloperidol (10 mg/kg). In the absence of nerve impulses caudal to a lesion of the spinal cord, the popa accumulation was decelerated as compared to that cranial to the lesion and it was not influenced by the former three alpha--adrenoreceptor blocking agents as well as by clonidine. 4. The results show that the synthesis and the utilization noradrenaline normally, as well as the accelerations of these processes by alpha-adrenoreceptor blocking agents, are dependent on nerve impulses. The stimulation of the synthesis and utilization of noradrenaline by nerve impulses might by influenced via the activity of teh alpha-adrenoreceptors located either on the nerve terminals or on the cell bodies or on both parts of the noradrenergic neurones. In the absence of nerve impulses, a receptor-mediated feedback mechanism similar to that described for the synthesis of dopamine does not appear to regulate the synthesis of noradrenaline. | [
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] |
PMID:6925 | [Takayasu-Onishi arteritis. II. Relations of Takayasu-Onishi arteritis with other non-specific arteritides]. | Takayasu-Onishi arteritis (T.O.) is similar to Hutchison-Horton arteritis (H.H.) on histological, clinical, laboratory, and pathogenetic grounds. Both probably depend on immunitary dysreactivity, their different clinical expression being attributable to differences in the district involved and the age of the subject. Both are preceded or accompanied by rheumatism. An interesting relation can be made out between temporal arteritis and "rheumatic polymyalgia" or, more aptly, "rhizomelic polymyalgia" (Ballabio, 1975). The latter (of rheumatic origin) may accompany arteritis - Hamrin, indeed, has suggested their unification in the description "arteritic polymyalgia". It is uncertain whether vasculopathy in the course of collagen disease, rheumatic arteritis, and polyarteritis nodosa can be identified with T.O., even though a common immunological basis can be made out. The difference between T.O. and thromboangiitis obliterans, on the other hand, is quite clear at the present time. | [Takayasu-Onishi arteritis. II. Relations of Takayasu-Onishi arteritis with other non-specific arteritides]. Takayasu-Onishi arteritis (T.O.) is similar to Hutchison-Horton arteritis (H.H.) on histological, clinical, laboratory, and pathogenetic grounds. Both probably depend on immunitary dysreactivity, their different clinical expression being attributable to differences in the district involved and the age of the subject. Both are preceded or accompanied by rheumatism. An interesting relation can be made out between temporal arteritis and "rheumatic polymyalgia" or, more aptly, "rhizomelic polymyalgia" (Ballabio, 1975). The latter (of rheumatic origin) may accompany arteritis - Hamrin, indeed, has suggested their unification in the description "arteritic polymyalgia". It is uncertain whether vasculopathy in the course of collagen disease, rheumatic arteritis, and polyarteritis nodosa can be identified with T.O., even though a common immunological basis can be made out. The difference between T.O. and thromboangiitis obliterans, on the other hand, is quite clear at the present time. | [
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PMID:6924 | [Takayasu-Onishi arteritis. Current etiopathogenetic aspects]. | By Takayasu-Onishi's arteritis is meant an arteritic process with unknown aetiology which electively affects young women, seemingly of prevalently Asiatic stock. The disease concerns almost exclusively large elastic arteries and presents clinically with early preocclusive symptomatology followed, after a varying period, by a picture of obstructive angiopathy. Here, the most recent aetiopathogenetic findings are considered. The disease's predilection for the young female, together with certain clinical and experimental observations, suggest that a dysendocrine condition may have some pathogenetic responsibility, at least in a favourable sense; this responsibility is documented by the finding of high levels of oestrogenuria during the entire cycle in patients suffering from the disease. On the other hand, the angiopathy localization in the large elastic arteries and in certain segments of the aortic arch and epiaortic trunks means that the role of topographic moments whould not be underestimated. As regards infectious factors, the tubercular and streptococcic continue to be of great importance even today. Neither acts directly, however, but by way of an abnormal immunitary reaction which they seem able to trigger off. The infectious moment would thus appear to be related to the immunitary moment, and the latter would seem to play the part of perpetuating the pathological vascular involvement promoted by contact of the organism with the aetiological agent. | [Takayasu-Onishi arteritis. Current etiopathogenetic aspects]. By Takayasu-Onishi's arteritis is meant an arteritic process with unknown aetiology which electively affects young women, seemingly of prevalently Asiatic stock. The disease concerns almost exclusively large elastic arteries and presents clinically with early preocclusive symptomatology followed, after a varying period, by a picture of obstructive angiopathy. Here, the most recent aetiopathogenetic findings are considered. The disease's predilection for the young female, together with certain clinical and experimental observations, suggest that a dysendocrine condition may have some pathogenetic responsibility, at least in a favourable sense; this responsibility is documented by the finding of high levels of oestrogenuria during the entire cycle in patients suffering from the disease. On the other hand, the angiopathy localization in the large elastic arteries and in certain segments of the aortic arch and epiaortic trunks means that the role of topographic moments whould not be underestimated. As regards infectious factors, the tubercular and streptococcic continue to be of great importance even today. Neither acts directly, however, but by way of an abnormal immunitary reaction which they seem able to trigger off. The infectious moment would thus appear to be related to the immunitary moment, and the latter would seem to play the part of perpetuating the pathological vascular involvement promoted by contact of the organism with the aetiological agent. | [
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PMID:6926 | [Comparative evaluation of local 02 consumption in lumbar sympathetic infiltration as compared with acupuncture]. | The effectiveness of acupuncture in the treatment of lower limb obliterating arteritis as an alternative to pharmacological sympatheticolumbar block was assessed by comparing local O2 consumption in the ischaemic extremity. It was found that both techniques lead to vasodilation sufficient to normalise local values. Acupuncture, however, has a more protracted effect up to 24 hr., as compared with only 12 hr after pharmacological block. | [Comparative evaluation of local 02 consumption in lumbar sympathetic infiltration as compared with acupuncture]. The effectiveness of acupuncture in the treatment of lower limb obliterating arteritis as an alternative to pharmacological sympatheticolumbar block was assessed by comparing local O2 consumption in the ischaemic extremity. It was found that both techniques lead to vasodilation sufficient to normalise local values. Acupuncture, however, has a more protracted effect up to 24 hr., as compared with only 12 hr after pharmacological block. | [
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PMID:6927 | A survey of isolates of Streptococcus pneumoniae. | Over eight months 130 isolates of Streptococcus pneumoniae were examined for sensitivity to penicillin, tetracycline, cephalosporin and co-trimoxozole. Except in one doubtful case all isolates were sensitive to penicillin. All were sensitive to cephalosporin. 6.9 percent is isolates were resistant to co-trimoxozole. It is suggested that penicillin remains the drug of choice in the treatment of pneumococcal infections. | A survey of isolates of Streptococcus pneumoniae. Over eight months 130 isolates of Streptococcus pneumoniae were examined for sensitivity to penicillin, tetracycline, cephalosporin and co-trimoxozole. Except in one doubtful case all isolates were sensitive to penicillin. All were sensitive to cephalosporin. 6.9 percent is isolates were resistant to co-trimoxozole. It is suggested that penicillin remains the drug of choice in the treatment of pneumococcal infections. | [
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PMID:6929 | [Acute hepatic porphyria as diagnostic problem in childhood (author's transl)]. | Case report of a 12 year old girl with acute hepatic porphyria. The difficulties of diagnosis in childhood are discussed. No effective treatment is known. The importance of early diagnosis is emphasized, in order to avoid certain medicaments, stress situations etc., which can cause an acute attack of porphyria. | [Acute hepatic porphyria as diagnostic problem in childhood (author's transl)]. Case report of a 12 year old girl with acute hepatic porphyria. The difficulties of diagnosis in childhood are discussed. No effective treatment is known. The importance of early diagnosis is emphasized, in order to avoid certain medicaments, stress situations etc., which can cause an acute attack of porphyria. | [
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PMID:6928 | Dibenzepin and amitriptyline in depressive states: comparative double-blind trial. | Dibenzepin and amitriptyline appeared to be equally efficacious in controlling target symptoms of depressive reactions. These results appear to be consistent with pharmacological profiles of the two drugs which are both tricylic compounds. Control of target symptoms occurred in an undulating and non-progressive manner in both groups. Aggravation of depressive symptomatology in the third week of treatment was noted in both groups and appeared to be clinically very important in the management of depressed patients. Dibenzepin caused relatively fewer side effects which appears to be an advantage over amitriptyline. Dibenzepin appeared to be a suitable alternative for amitriptyline intolerant patients, with moderately severe depression associated with anxiety, especially patients who demonstrated emotional sensitivity or passive dependent personality, and psychosomatic symptoms. | Dibenzepin and amitriptyline in depressive states: comparative double-blind trial. Dibenzepin and amitriptyline appeared to be equally efficacious in controlling target symptoms of depressive reactions. These results appear to be consistent with pharmacological profiles of the two drugs which are both tricylic compounds. Control of target symptoms occurred in an undulating and non-progressive manner in both groups. Aggravation of depressive symptomatology in the third week of treatment was noted in both groups and appeared to be clinically very important in the management of depressed patients. Dibenzepin caused relatively fewer side effects which appears to be an advantage over amitriptyline. Dibenzepin appeared to be a suitable alternative for amitriptyline intolerant patients, with moderately severe depression associated with anxiety, especially patients who demonstrated emotional sensitivity or passive dependent personality, and psychosomatic symptoms. | [
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PMID:6940 | Acid-base curve nomogram for dog blood. | Pooled canine blood of different hemoglobin concentration was equilibrated with two carbon dioxide tensions and the resulting pH's of the samples were measured at 38 degrees C. Readings obtained provided data for the construction of a cartesian nomogram for the dog, based on the pH/log pCO2 coordinate system. The nomogram can be used to evaluate both respiratory and non-respiratory acid-base parameters. For contrast, a control nomogram on human blood was also constructed. Both nomograms show broad similarity. This is to be expected as the normal criteria used to define base excess relating to dog blood are the same as those used for human blood. Nonetheless, base excess and buffer base calculations using the nomogram for the dog and that for man show a deviation of 2.5-10%, and we consider this deviation to be more due to a species difference than to any summated experimental error. | Acid-base curve nomogram for dog blood. Pooled canine blood of different hemoglobin concentration was equilibrated with two carbon dioxide tensions and the resulting pH's of the samples were measured at 38 degrees C. Readings obtained provided data for the construction of a cartesian nomogram for the dog, based on the pH/log pCO2 coordinate system. The nomogram can be used to evaluate both respiratory and non-respiratory acid-base parameters. For contrast, a control nomogram on human blood was also constructed. Both nomograms show broad similarity. This is to be expected as the normal criteria used to define base excess relating to dog blood are the same as those used for human blood. Nonetheless, base excess and buffer base calculations using the nomogram for the dog and that for man show a deviation of 2.5-10%, and we consider this deviation to be more due to a species difference than to any summated experimental error. | [
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PMID:6950 | The influence of neuromediators injected into nucleus caudatus on bioelectrical seizure activity of amygdala. | The influence of electrical and chemical stimulation of nucleus caudatus (NC) on bioelectrical seizure activity of amygdala (Am) was studied in rabbits. The electrical stimulation of NC inhibits seizures in Am induced by the administration of picrotoxin into this nucleus. Dopamine (DA) and cholinomimetics-metacholine and neostygmine-applied into NC inhibit seizures in Am. Noradrenaline (NA) acts biphasically, first potentiating and then inhibiting seizures in Am. Serotonin (5-HT) and glutamic acid (GA) administered to NC do not affect the seizures. In the case of seizures excited by electrical stimulation, DA and neostygmine possessed inhibiting action; NA, too, inhibited seizures without, however, inducing primary stimulation. Similarly as in the case of picrotoxin-stimulated seizures, neither 5-HT nor GA brought about the effects. The present study deals with the correlation of dopaminergic anc cholinergic systems in NC. | The influence of neuromediators injected into nucleus caudatus on bioelectrical seizure activity of amygdala. The influence of electrical and chemical stimulation of nucleus caudatus (NC) on bioelectrical seizure activity of amygdala (Am) was studied in rabbits. The electrical stimulation of NC inhibits seizures in Am induced by the administration of picrotoxin into this nucleus. Dopamine (DA) and cholinomimetics-metacholine and neostygmine-applied into NC inhibit seizures in Am. Noradrenaline (NA) acts biphasically, first potentiating and then inhibiting seizures in Am. Serotonin (5-HT) and glutamic acid (GA) administered to NC do not affect the seizures. In the case of seizures excited by electrical stimulation, DA and neostygmine possessed inhibiting action; NA, too, inhibited seizures without, however, inducing primary stimulation. Similarly as in the case of picrotoxin-stimulated seizures, neither 5-HT nor GA brought about the effects. The present study deals with the correlation of dopaminergic anc cholinergic systems in NC. | [
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PMID:6952 | Changes in plasma electrolytes, acid-base balance and other physiological parameters of adult female turkeys under conditions of acute hyperthermia. | The effects of acute hyperthermia on certain physiological parameters of turkey hens was studied. It was found that the response of the turkey to hyperthermia is similar to the reported response of the chicken. The birds began panting and the average body temperature increased 0.1 degrees C. as the ambient temperature reached 32 degrees C. The panting or polypnea induced a profound respiratory alkalosis in the turkeys. The acute hyperthermia also caused a significant (P less than 0.05) decrease in plasma levels of sodium, total calcium, magnesium and inorganic phosphorus. The plasma level of potassium was significantly (P less than 0.05) increased. | Changes in plasma electrolytes, acid-base balance and other physiological parameters of adult female turkeys under conditions of acute hyperthermia. The effects of acute hyperthermia on certain physiological parameters of turkey hens was studied. It was found that the response of the turkey to hyperthermia is similar to the reported response of the chicken. The birds began panting and the average body temperature increased 0.1 degrees C. as the ambient temperature reached 32 degrees C. The panting or polypnea induced a profound respiratory alkalosis in the turkeys. The acute hyperthermia also caused a significant (P less than 0.05) decrease in plasma levels of sodium, total calcium, magnesium and inorganic phosphorus. The plasma level of potassium was significantly (P less than 0.05) increased. | [
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PMID:6953 | Acid-base balance, plasma electrolytes and production performance of adult turkey hens under conditions of increasing ambient temperature. | Turkey hens were exposed to stepwise increases in ambient temperature from 21 degrees C. to 25 degrees C. to 30 degrees C. to 35 degrees C. at two-week intervals. Dietary calcium levels to 1.54, 2.01 and 2.48 percent were fed. Acid-base balance, plasma electrolytes and production performance were studied. The temperature increase caused a significant (P less than 0.05) decrease in plasma sodium, calcium, and magnesium, and in egg production, shell thickness and egg weight and a significant (P less than 0.05) increase in plasma potassium. There was no significant change in the acid-base balance of the blood as measured by blood PO2, PCO2 and pH. Egg production was not significantly correlated to blood gas activitelated to plasma calcium and magnesium levels. Dietary calcium levels had no influence on the parameters measured. | Acid-base balance, plasma electrolytes and production performance of adult turkey hens under conditions of increasing ambient temperature. Turkey hens were exposed to stepwise increases in ambient temperature from 21 degrees C. to 25 degrees C. to 30 degrees C. to 35 degrees C. at two-week intervals. Dietary calcium levels to 1.54, 2.01 and 2.48 percent were fed. Acid-base balance, plasma electrolytes and production performance were studied. The temperature increase caused a significant (P less than 0.05) decrease in plasma sodium, calcium, and magnesium, and in egg production, shell thickness and egg weight and a significant (P less than 0.05) increase in plasma potassium. There was no significant change in the acid-base balance of the blood as measured by blood PO2, PCO2 and pH. Egg production was not significantly correlated to blood gas activitelated to plasma calcium and magnesium levels. Dietary calcium levels had no influence on the parameters measured. | [
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PMID:6958 | beta-Adrenergic blockade reduces the severity of acute renal failure in rats. | Propranolol administration in the hypoxic model of acute renal failure (ARF) in rats has reduced plasma renin activity (PRA) and uraemia as compared to untreated controls. P113 has no effect on uraemia but increased PRA in ARF. A combination of both drugs is no more effective in reducing uraemia than propranolol alone. These results support the view that beta-adrenergic blockade by propranolol reduces the severity of ARF by preventing the post-hypoxic release of renin. | beta-Adrenergic blockade reduces the severity of acute renal failure in rats. Propranolol administration in the hypoxic model of acute renal failure (ARF) in rats has reduced plasma renin activity (PRA) and uraemia as compared to untreated controls. P113 has no effect on uraemia but increased PRA in ARF. A combination of both drugs is no more effective in reducing uraemia than propranolol alone. These results support the view that beta-adrenergic blockade by propranolol reduces the severity of ARF by preventing the post-hypoxic release of renin. | [
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PMID:6954 | [The effect of ACTH and several antimetabolites of vitamin B6 on the activity of tyrosine aminotransferase in the liver of intact and hypophysectomized rats]. | ACTH injected intraperitoneally in a dose of 140 Units per 1 kg of body weight to intact rats or to rats subjected to hypophysectomy 24 hours before the experiment produced an increase in the activity of tyrosine-aminotrasferase in the liver (4.5 or 2.5 times, respectively) in comparison with the normal. D-cycloserine and its dimere injected intraperitoneally to the intact starving rats in a dose of 2.0-2.5 g per 1 kg of body weight produced in 4 hours a sharp elevation in the liver of the activity of tyrosine-amino transferase, whose induction constituted 75 and 180%, respectively. 24 hours after hypophysectomy D-cycloserine produced no induction of this enzyme in the rat liver; in difference from this, the D-cycloserine dimere produced an induced formation of tyrosine-aminotransferase (comparable with ACTH) in the liver of hypophysectomized rats. This indicated that the induction mechanism of tyrosine-aminotransferase in the liver of rats under the effect of D-cycloserine and its dimere differed. | [The effect of ACTH and several antimetabolites of vitamin B6 on the activity of tyrosine aminotransferase in the liver of intact and hypophysectomized rats]. ACTH injected intraperitoneally in a dose of 140 Units per 1 kg of body weight to intact rats or to rats subjected to hypophysectomy 24 hours before the experiment produced an increase in the activity of tyrosine-aminotrasferase in the liver (4.5 or 2.5 times, respectively) in comparison with the normal. D-cycloserine and its dimere injected intraperitoneally to the intact starving rats in a dose of 2.0-2.5 g per 1 kg of body weight produced in 4 hours a sharp elevation in the liver of the activity of tyrosine-amino transferase, whose induction constituted 75 and 180%, respectively. 24 hours after hypophysectomy D-cycloserine produced no induction of this enzyme in the rat liver; in difference from this, the D-cycloserine dimere produced an induced formation of tyrosine-aminotransferase (comparable with ACTH) in the liver of hypophysectomized rats. This indicated that the induction mechanism of tyrosine-aminotransferase in the liver of rats under the effect of D-cycloserine and its dimere differed. | [
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PMID:6959 | Acute renal effects of new beta-adrenergic receptor site blocking agents on renal function. | The effects of two new beta blockers on renal function have been studied. There were significant decreases in urine flow, urea clearance, sodium and chloride excretion rates after acute administration. Fractional excretion of sodium (FeNa) fell significantly but did not continue to fall during chronic administration. Blood pressure and plasma renin activity decreased significantly after two months' therapy. These findings suggest that beta blockers in patients with unstable cardiovascular function increase the need for concomitant diuretic therapy. | Acute renal effects of new beta-adrenergic receptor site blocking agents on renal function. The effects of two new beta blockers on renal function have been studied. There were significant decreases in urine flow, urea clearance, sodium and chloride excretion rates after acute administration. Fractional excretion of sodium (FeNa) fell significantly but did not continue to fall during chronic administration. Blood pressure and plasma renin activity decreased significantly after two months' therapy. These findings suggest that beta blockers in patients with unstable cardiovascular function increase the need for concomitant diuretic therapy. | [
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PMID:6960 | Interrelationships between Ca2+ and adenylate and guanylate cyclases in the control of platelet secretion and aggregation. | Ca2+ is a powerful inhibitor (Ki is congruent to 16 muM) of basal and prostaglandin E1 (PGE1)-stimulated adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1] activity in membranes obtained from homogenized human platelets. Ca2+ (but not the ionophore A23,187) decreased V(max) of the reaction without an effect on the Ks for ATP. Neither ATP nor PGE1 affected Ki for Ca2+. In intact platelets A23,187 induced Ca2+ influx and markedly inhibited PGE1-stimulated rise in adenosine 3':5'-cyclic monophosphate (cAMP) levels. Guanylate cyclase [GTP pyrophosphate-lyase (cyclizing); EC 4.6.1.2] activity was mainly found in the soluble fraction (greater than 90%). Both soluble and membrane bound enzymes were stimulated by Mn2+ and Ca2+ and inhibited by Zn2+. Adenylate and guanylate cyclase activity were both present in a membrane fraction cyclase activity were both present in a membrane fraction which contained Ca2+ activated ATPase activity, and accumulated Ca2+ from the medium in the presence of ATP and oxalate. Other evidence indicates that these membranes originated in large part from the dense tubular system of the platelets. It is proposed that concurrent inhibition of adenylate cyclase and stimulation of guanylate cyclase facilitates the direct initiating effect of Ca2+ on platelet secretion and aggregation. | Interrelationships between Ca2+ and adenylate and guanylate cyclases in the control of platelet secretion and aggregation. Ca2+ is a powerful inhibitor (Ki is congruent to 16 muM) of basal and prostaglandin E1 (PGE1)-stimulated adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1] activity in membranes obtained from homogenized human platelets. Ca2+ (but not the ionophore A23,187) decreased V(max) of the reaction without an effect on the Ks for ATP. Neither ATP nor PGE1 affected Ki for Ca2+. In intact platelets A23,187 induced Ca2+ influx and markedly inhibited PGE1-stimulated rise in adenosine 3':5'-cyclic monophosphate (cAMP) levels. Guanylate cyclase [GTP pyrophosphate-lyase (cyclizing); EC 4.6.1.2] activity was mainly found in the soluble fraction (greater than 90%). Both soluble and membrane bound enzymes were stimulated by Mn2+ and Ca2+ and inhibited by Zn2+. Adenylate and guanylate cyclase activity were both present in a membrane fraction cyclase activity were both present in a membrane fraction which contained Ca2+ activated ATPase activity, and accumulated Ca2+ from the medium in the presence of ATP and oxalate. Other evidence indicates that these membranes originated in large part from the dense tubular system of the platelets. It is proposed that concurrent inhibition of adenylate cyclase and stimulation of guanylate cyclase facilitates the direct initiating effect of Ca2+ on platelet secretion and aggregation. | [
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PMID:6961 | The electrochemical gradient of protons and its relationship to active transport in Escherichia coli membrane vesicles. | Membrane vesicles isolated from E. coli generate a trans-membrane proton gradient of 2 pH units under appropriate conditions when assayed by flow dialysis. Using the distribution of weak acids to measure the proton gradient (deltapH) and the distribution of the lipophilic cation triphenyl-methylphosphonium to measure the electrical potential across the membrane (delta psi), the vesicles are shown to generate an electrochemical proton gradient (deltamuH+) of approximately-180 mV at pH 5.5 in the presence of ascorbate and phenazine methosulfate, the major component of which is a deltapH of about -110mV. As external pH is increased, deltapH decreases, reaching 0 at pH 7.5 and above, while delta psi remains at about-75 mV and internal pH remains at pH 7.5. Moreover, the ability of various electron donors to drive transport is correlated with their ability to generate deltamuH+. In addition, deltapH and delta psi can be varied reciprocally in the presence of valinomycin and nigericin. These data and others (manuscript in preparation) provide convincing support for the role of chemiosmotic phenomena in active transport. | The electrochemical gradient of protons and its relationship to active transport in Escherichia coli membrane vesicles. Membrane vesicles isolated from E. coli generate a trans-membrane proton gradient of 2 pH units under appropriate conditions when assayed by flow dialysis. Using the distribution of weak acids to measure the proton gradient (deltapH) and the distribution of the lipophilic cation triphenyl-methylphosphonium to measure the electrical potential across the membrane (delta psi), the vesicles are shown to generate an electrochemical proton gradient (deltamuH+) of approximately-180 mV at pH 5.5 in the presence of ascorbate and phenazine methosulfate, the major component of which is a deltapH of about -110mV. As external pH is increased, deltapH decreases, reaching 0 at pH 7.5 and above, while delta psi remains at about-75 mV and internal pH remains at pH 7.5. Moreover, the ability of various electron donors to drive transport is correlated with their ability to generate deltamuH+. In addition, deltapH and delta psi can be varied reciprocally in the presence of valinomycin and nigericin. These data and others (manuscript in preparation) provide convincing support for the role of chemiosmotic phenomena in active transport. | [
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PMID:6962 | Observation of individual carboxyl groups in hen egg-white lysozyme by use of high field 13C-nuclear magnetic resonance. | Several of the carboxyl carbon atom resonances of hen egg-white lysozyme (mucopeptide N-acetylmuramoyl hydrolase, EC 3.2.1.17) have been resolved by 13C-nuclear magnetic resonance (NMR) at 68 MHz. The change in chemical shift of the carboxyl carbon atom resonances, as a function of pH, has enabled the distinction of these resonances against the background of many nontitrating carbonyl group resonances. Several apparent microscopic ionization constants have been determined from the carboxyl group NMR titration curves, and possible assignments are discussed. Preliminary experiments were carried out in the presence of cobaltous ion, and selective shifts of several resonances were observed. Our results indicate the possibility of the direct observation of a wide range of single functional groups of proteins in solution by NMR techniques. | Observation of individual carboxyl groups in hen egg-white lysozyme by use of high field 13C-nuclear magnetic resonance. Several of the carboxyl carbon atom resonances of hen egg-white lysozyme (mucopeptide N-acetylmuramoyl hydrolase, EC 3.2.1.17) have been resolved by 13C-nuclear magnetic resonance (NMR) at 68 MHz. The change in chemical shift of the carboxyl carbon atom resonances, as a function of pH, has enabled the distinction of these resonances against the background of many nontitrating carbonyl group resonances. Several apparent microscopic ionization constants have been determined from the carboxyl group NMR titration curves, and possible assignments are discussed. Preliminary experiments were carried out in the presence of cobaltous ion, and selective shifts of several resonances were observed. Our results indicate the possibility of the direct observation of a wide range of single functional groups of proteins in solution by NMR techniques. | [
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PMID:6963 | Markedly elevated angiotensin converting enzyme in lymph nodes containing non-necrotizing granulomas in sarcoidosis. | Sarcoidosis is a disease of unknown etiology that is characterized by the generalized formation of granulomas and is accompanied by elevation in the serum in less than half the patients of angiotensin converting enzyme, a dipeptidyl carboxypeptidase that catalyzes the conversion of the decapeptide, angiotensin I, to the pressor octapeptide, angiotensin II, and L-histidyl-L-leucine. Mean activity of angiotensin converting enzyme was elevated generally more than 10-fold in granuloma-containing lymph nodes, but not in lung in which normally it is abundant, in 19 of 20 patients with sarcoidosis. Angiotensin converting enzyme in lymph nodes from subjects with sarcoidosis was similar to the enzyme from normal lung and lymph node with respect to activity as a function of pH, inhibition of activity by EDTA and o-phenanthroline, gel filtration on Sephadex G-200, and requirement for chloride for activity, but appeared to be more heat labile. The data suggest that the granulomas in sarcoidosis may be the source of the elevated serum enzyme and that cells of the granulomas, particularly the epitheloid cells which appear by electron microscopy to have active protein biosynthesis, may be actively synthesizing the enzyme. | Markedly elevated angiotensin converting enzyme in lymph nodes containing non-necrotizing granulomas in sarcoidosis. Sarcoidosis is a disease of unknown etiology that is characterized by the generalized formation of granulomas and is accompanied by elevation in the serum in less than half the patients of angiotensin converting enzyme, a dipeptidyl carboxypeptidase that catalyzes the conversion of the decapeptide, angiotensin I, to the pressor octapeptide, angiotensin II, and L-histidyl-L-leucine. Mean activity of angiotensin converting enzyme was elevated generally more than 10-fold in granuloma-containing lymph nodes, but not in lung in which normally it is abundant, in 19 of 20 patients with sarcoidosis. Angiotensin converting enzyme in lymph nodes from subjects with sarcoidosis was similar to the enzyme from normal lung and lymph node with respect to activity as a function of pH, inhibition of activity by EDTA and o-phenanthroline, gel filtration on Sephadex G-200, and requirement for chloride for activity, but appeared to be more heat labile. The data suggest that the granulomas in sarcoidosis may be the source of the elevated serum enzyme and that cells of the granulomas, particularly the epitheloid cells which appear by electron microscopy to have active protein biosynthesis, may be actively synthesizing the enzyme. | [
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PMID:6970 | Nucleation of microbiologic calcification by proteolipid. | The component of crude phospholipid responsible for B. matruchotii calcification was isolated. Crude phospholipid, extracted from the microorganism, was separated into five fractions by column chromatography. A single, protein-containing fraction catalyzed apatite formation in a metastable calcium phosphate solution. The nucleating fraction was identified as a proteolipid. | Nucleation of microbiologic calcification by proteolipid. The component of crude phospholipid responsible for B. matruchotii calcification was isolated. Crude phospholipid, extracted from the microorganism, was separated into five fractions by column chromatography. A single, protein-containing fraction catalyzed apatite formation in a metastable calcium phosphate solution. The nucleating fraction was identified as a proteolipid. | [
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