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PMID:17715 | Recording pH method of characterizing composition and monitoring dissolution profile of an anhydride-acid copolymer and its salt derivatives. | A sensitive potentiometric monitoring method was developed that permits the continuous measurement of the disolution profiles of methyl vinyl ether-maleic anhydride-acid copolymers and salt derivatives. Three distinct rate periods were observed in the dissolution rate of the anhydride copolymer, expressed as percent anhydride dissolved, was independent of sample weight over the weight range studied. The acid form of the copolymer showed only one dissolution rate period, with dissolution being very rapid. The rapid initial pH decrease observed during the first stage of dissolution for a series of anhydride-acid copolymer powder samples correlated closely with the anhydride-acid ratio, permitting chemical characterization of the copolymer functionality simultaneously with the analysis of dissolution profiles. Similarly, the extent of copolymer alkaline salt conversion was inversely proportional to the initial maximum pH increase observed during the first stage of dissolution of these salts. Mechanisms of dissolution of copolymer powder materials are discussed and compared to the dissolution of compressed disks and films reported previously. | Recording pH method of characterizing composition and monitoring dissolution profile of an anhydride-acid copolymer and its salt derivatives. A sensitive potentiometric monitoring method was developed that permits the continuous measurement of the disolution profiles of methyl vinyl ether-maleic anhydride-acid copolymers and salt derivatives. Three distinct rate periods were observed in the dissolution rate of the anhydride copolymer, expressed as percent anhydride dissolved, was independent of sample weight over the weight range studied. The acid form of the copolymer showed only one dissolution rate period, with dissolution being very rapid. The rapid initial pH decrease observed during the first stage of dissolution for a series of anhydride-acid copolymer powder samples correlated closely with the anhydride-acid ratio, permitting chemical characterization of the copolymer functionality simultaneously with the analysis of dissolution profiles. Similarly, the extent of copolymer alkaline salt conversion was inversely proportional to the initial maximum pH increase observed during the first stage of dissolution of these salts. Mechanisms of dissolution of copolymer powder materials are discussed and compared to the dissolution of compressed disks and films reported previously. | [
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PMID:17716 | Systems approach to vaginal delivery of drugs IV: methodology for determination of membrane surface pH. | A physical model including a diffusional layer in series with the membrane was developed for studying the possible differences between the pH at the membrane surface and that in the bulk solution. Both the membrane-secreted substances (acids and bases) and buffer constituents in the bulk solutions are assumed to contribute to the surface pH. Equations derived for this situation, together with experimental determinations of the acidic dissociation constant of the secreted material, the total secretion flux, the flux of total secreted acidic species, and the diffusion layer thickness, allow estimates to be made of the pH at the membrane surface. With the rabbit vagina, the membrane surface pH was close to that of the bulk solution in most cases. These results were supported by the fact that the absorption of 1-alkanoic acids in pH 2.2 phosphate buffers was relatively constant over the buffer concentration range of 0.003-0.1 M phosphate. | Systems approach to vaginal delivery of drugs IV: methodology for determination of membrane surface pH. A physical model including a diffusional layer in series with the membrane was developed for studying the possible differences between the pH at the membrane surface and that in the bulk solution. Both the membrane-secreted substances (acids and bases) and buffer constituents in the bulk solutions are assumed to contribute to the surface pH. Equations derived for this situation, together with experimental determinations of the acidic dissociation constant of the secreted material, the total secretion flux, the flux of total secreted acidic species, and the diffusion layer thickness, allow estimates to be made of the pH at the membrane surface. With the rabbit vagina, the membrane surface pH was close to that of the bulk solution in most cases. These results were supported by the fact that the absorption of 1-alkanoic acids in pH 2.2 phosphate buffers was relatively constant over the buffer concentration range of 0.003-0.1 M phosphate. | [
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PMID:17717 | Systems approach to vaginal delivery of drugs V: in situ vaginal absorption of 1-alkanoic acids. | The vaginal absorption of a homologous series of ionizable compounds, the 1-alkanoic acids, was studied using a perfusion method with a rib-cage cell surgically implanted in the rabbit vagina. The absorption rates of these compounds followed first-order kinetics. The physical model previously used for the 1-alkanols, but accounting for the pKa and pH effects in the present case was employed in the analysis of the carboxylic acid data. The aqueous diffusion layer thickness was 0.031 cm. The permeability coefficient for the lipoidal pathway increased 3.5-fold per methylene group. Both values agree reasonably well with those obtained in the alcohol study. | Systems approach to vaginal delivery of drugs V: in situ vaginal absorption of 1-alkanoic acids. The vaginal absorption of a homologous series of ionizable compounds, the 1-alkanoic acids, was studied using a perfusion method with a rib-cage cell surgically implanted in the rabbit vagina. The absorption rates of these compounds followed first-order kinetics. The physical model previously used for the 1-alkanols, but accounting for the pKa and pH effects in the present case was employed in the analysis of the carboxylic acid data. The aqueous diffusion layer thickness was 0.031 cm. The permeability coefficient for the lipoidal pathway increased 3.5-fold per methylene group. Both values agree reasonably well with those obtained in the alcohol study. | [
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|
PMID:17718 | Kinetics and mechanisms of hydrolysis of 1,4-benzodiazepines III: nitrazepam. | The hydrolysis of nitrazepam involves a two-step sequential mechanism. The intermediate is the ring-opened compound resulting from scission of the azomethine bond. The final products are glycine and 2-amino-5-ni-robenzophenone. Recyclization of the intermediate to nitrazepam occurs at pH values above the pKa of the intermediate, in the pH region where the amino group of the intermediate is not protonated. As opposed to chlordiazepoxide and oxazepam, the initial hydrolysis step occurs at the 4,5-bond, not at the 1,2-amide linkage. This difference is attributed to a preferential activation for hydrolysis of the azomethine linkage by the nitro group. The hydrolysis involves an uncatalyzed reaction, specific acid-base catalysis, and general acid-base catalysis for acetate and phosphate buffers. | Kinetics and mechanisms of hydrolysis of 1,4-benzodiazepines III: nitrazepam. The hydrolysis of nitrazepam involves a two-step sequential mechanism. The intermediate is the ring-opened compound resulting from scission of the azomethine bond. The final products are glycine and 2-amino-5-ni-robenzophenone. Recyclization of the intermediate to nitrazepam occurs at pH values above the pKa of the intermediate, in the pH region where the amino group of the intermediate is not protonated. As opposed to chlordiazepoxide and oxazepam, the initial hydrolysis step occurs at the 4,5-bond, not at the 1,2-amide linkage. This difference is attributed to a preferential activation for hydrolysis of the azomethine linkage by the nitro group. The hydrolysis involves an uncatalyzed reaction, specific acid-base catalysis, and general acid-base catalysis for acetate and phosphate buffers. | [
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|
PMID:17719 | UV spectrophotometric determination of aminophylline, amobarbital, and ephedrine hydrochloride in an antiasthma capsule preparation. | A simple and rapid procedure for the determination of aminophylline, amobarbital, and ephedrine hydrochloride in a capsule preparation is described. Aminophylline and amobarbital are determined simultaneously using differential UV spectrophotometry; ephedrine hydrochloride is determined separately after elution from an alginic acid column with 0.1 N hydrochloric acid. | UV spectrophotometric determination of aminophylline, amobarbital, and ephedrine hydrochloride in an antiasthma capsule preparation. A simple and rapid procedure for the determination of aminophylline, amobarbital, and ephedrine hydrochloride in a capsule preparation is described. Aminophylline and amobarbital are determined simultaneously using differential UV spectrophotometry; ephedrine hydrochloride is determined separately after elution from an alginic acid column with 0.1 N hydrochloric acid. | [
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|
PMID:17720 | Stability of aqueous solutions of pirbuterol. | The hydrolytic degradation of pirbuterol was investigated under saturated oxygen conditions over a wide range of pH values and at different temperatures. Two of the five observed breakdown products were positively identified. The first-order decomposition rate appeared to depend on the rate constants of the four dissociated ionic species. The most stable region for the drug was pH 1-2, where the diprotonated molecule predominated; appropriate thermodynamic parameters were calculated. | Stability of aqueous solutions of pirbuterol. The hydrolytic degradation of pirbuterol was investigated under saturated oxygen conditions over a wide range of pH values and at different temperatures. Two of the five observed breakdown products were positively identified. The first-order decomposition rate appeared to depend on the rate constants of the four dissociated ionic species. The most stable region for the drug was pH 1-2, where the diprotonated molecule predominated; appropriate thermodynamic parameters were calculated. | [
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|
PMID:17721 | Micellar distribution equilibria: ultracentrifugal study of apparent partition coefficients. | Ultracentrifugation was used for the partial isolation of polysorbate 80 micelles in aqueous media to determine the apparent partition coefficients of various drug species between water and the micellar pseudophase. The ratio of solute concentration in the micelles to that in water was measured for procaine, salicylic acid, sulfapyridine, sulfisoxazole, and sodium 2-naphthalensulfonate over ranges of pH, surfactant concentration, drug concentration, and micelle sedimentation. Apparent partition coefficients for the systems investigated were independent of both drug concentration and surfactant concentration, indicating that the mode(s) of surfactant-drug interaction are essentially invariant over the ranges of systematic variables studied. The method provides a relatively simple and rapid means of quantitatively evaluating drug-surfactant interactions above the CMC, when surfactant and solute can be assayed in mixtures without interference. | Micellar distribution equilibria: ultracentrifugal study of apparent partition coefficients. Ultracentrifugation was used for the partial isolation of polysorbate 80 micelles in aqueous media to determine the apparent partition coefficients of various drug species between water and the micellar pseudophase. The ratio of solute concentration in the micelles to that in water was measured for procaine, salicylic acid, sulfapyridine, sulfisoxazole, and sodium 2-naphthalensulfonate over ranges of pH, surfactant concentration, drug concentration, and micelle sedimentation. Apparent partition coefficients for the systems investigated were independent of both drug concentration and surfactant concentration, indicating that the mode(s) of surfactant-drug interaction are essentially invariant over the ranges of systematic variables studied. The method provides a relatively simple and rapid means of quantitatively evaluating drug-surfactant interactions above the CMC, when surfactant and solute can be assayed in mixtures without interference. | [
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|
PMID:17722 | Physicochemical properties of beta-lactam antibacterials: deuterium solvent isotope effect on penicillin G degradation rate. | To obtain kinetic evidence on the degradation mechanism of penicillin in aqueous solution, degradation rates of penicillin G in water and deuterium oxide were measured in the pH (pD) range of 4-10. The solvent isotope effect (kH2O/kD2O) of 1.53 below pH (pD) 6 supports the mechanism of water-catalyzed rearrangement of undissociated penicillin G to benzylpenicillenic acid. The spontaneous degradation at neutral pH (pD) and the hydroxide-ion-catalyzed degradation in the alkaline pH (pD) range progress with a deuterium solvent isotope effect (kH2O/kD2O) of 4.5 and 0.59, respectively. This finding indicates the mechanisms of general base-catalyzed hydrolysis by water in the neutral pH range and of nucleophilic attack of the hydroxide ion on the beta-lactam in the alkaline pH range. No significant side-chain dependency was observed in the reaction of penicillins with bases. The solvent isotope studies led to the conclusion that penicillin degradation is catalyzed by a series of bases via general base-catalyzed and nucleophilic mechanisms, depending on their basicity. | Physicochemical properties of beta-lactam antibacterials: deuterium solvent isotope effect on penicillin G degradation rate. To obtain kinetic evidence on the degradation mechanism of penicillin in aqueous solution, degradation rates of penicillin G in water and deuterium oxide were measured in the pH (pD) range of 4-10. The solvent isotope effect (kH2O/kD2O) of 1.53 below pH (pD) 6 supports the mechanism of water-catalyzed rearrangement of undissociated penicillin G to benzylpenicillenic acid. The spontaneous degradation at neutral pH (pD) and the hydroxide-ion-catalyzed degradation in the alkaline pH (pD) range progress with a deuterium solvent isotope effect (kH2O/kD2O) of 4.5 and 0.59, respectively. This finding indicates the mechanisms of general base-catalyzed hydrolysis by water in the neutral pH range and of nucleophilic attack of the hydroxide ion on the beta-lactam in the alkaline pH range. No significant side-chain dependency was observed in the reaction of penicillins with bases. The solvent isotope studies led to the conclusion that penicillin degradation is catalyzed by a series of bases via general base-catalyzed and nucleophilic mechanisms, depending on their basicity. | [
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PMID:17723 | GI pharmacology of polyethyleneimine II: motor activity in anesthetized dogs. | The effects of orally and intravenously administered doses of polyethyleneimine were observed in 18 chloralose-urethan-anesthetized dogs. Polyethyleneimine produced an initial augmentation of rhythmic segmenting gastric antral contractions, a copious flow of gastric mucus, increased segmenting and propulsive activities of the small and large intestines, and occasional micturition and defecation. The gastric corpus and fundic regions became relaxed and enlarged. These events were associated with the prompt appearance of retching. The retching response to oral administration could only be abolished by bilateral vagotomy or bilateral sympathectomy. The skeletal muscle component of retching was blocked by tubocurarine. Intravenous administration of chlorpromazine blocked the retching response and gastric corporal atonia to either intravenous or oral doses of polyethyleneimine. Either oral or intravenous administration of polyethyleneimine produced no detectable changes in the lead II ECG but was associated with marked transient reductions in both mean and pulsatile arterial blood pressures. These depressor effects showed clear tachyphylaxis. In all cases where GI effects were noted, respiration was augmented and erratic in a manner associated with the retching responses. | GI pharmacology of polyethyleneimine II: motor activity in anesthetized dogs. The effects of orally and intravenously administered doses of polyethyleneimine were observed in 18 chloralose-urethan-anesthetized dogs. Polyethyleneimine produced an initial augmentation of rhythmic segmenting gastric antral contractions, a copious flow of gastric mucus, increased segmenting and propulsive activities of the small and large intestines, and occasional micturition and defecation. The gastric corpus and fundic regions became relaxed and enlarged. These events were associated with the prompt appearance of retching. The retching response to oral administration could only be abolished by bilateral vagotomy or bilateral sympathectomy. The skeletal muscle component of retching was blocked by tubocurarine. Intravenous administration of chlorpromazine blocked the retching response and gastric corporal atonia to either intravenous or oral doses of polyethyleneimine. Either oral or intravenous administration of polyethyleneimine produced no detectable changes in the lead II ECG but was associated with marked transient reductions in both mean and pulsatile arterial blood pressures. These depressor effects showed clear tachyphylaxis. In all cases where GI effects were noted, respiration was augmented and erratic in a manner associated with the retching responses. | [
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|
PMID:17729 | Association of in vivo and in vitro propranolol levels in canine Purkinje fibers with antiarrhythmic effects. | This study has determined the propranolol content of Purkinje fibers associated with antiarrhythmic and electrophysiological actions of the drug both in vivo and in vitro. The minimum effective tissue content of propranolol that consistently reversed a sustained ouabain-induced ventrivular tachycardia in vivo after i.v. propranolol was between 6.7 and 11.1 micron g/g of tissue. Propranolol doses producing Purkinje fiber contents of less than 6.7 micron g/g failed to revert the arrhythmia but did ponotropic responses to 0.5 micron g/kg of isoproterenol. The in vivo minimum effective tissue content was produced in isolated Purkinje fibers perfused with Tyrode's solution containing 1.7 X 10(-6) M propranolol. In Purkinje fibers this concentration of propranolol depressed the rate of phase 4 depolarization previously enhanced by ouabain 2.1 X 10(-7) M. Propranolol, 1.7 X 10(-6) M, did not alter membrane responsiveness and only slightly accelerated repolarization at 5 minutes. Propranolol, 0.85 X 10(-6) M, did not significantly depress the ouabain-enhanced rate of phase 4 depolarization but did attenuate the response to epinephrine through beta blockade. This study indicated that the initial direct action of propranolol in reverting a ouabain-induced ventricular tachycardia to a sinus rhythm in the dog is depression of automaticity. | Association of in vivo and in vitro propranolol levels in canine Purkinje fibers with antiarrhythmic effects. This study has determined the propranolol content of Purkinje fibers associated with antiarrhythmic and electrophysiological actions of the drug both in vivo and in vitro. The minimum effective tissue content of propranolol that consistently reversed a sustained ouabain-induced ventrivular tachycardia in vivo after i.v. propranolol was between 6.7 and 11.1 micron g/g of tissue. Propranolol doses producing Purkinje fiber contents of less than 6.7 micron g/g failed to revert the arrhythmia but did ponotropic responses to 0.5 micron g/kg of isoproterenol. The in vivo minimum effective tissue content was produced in isolated Purkinje fibers perfused with Tyrode's solution containing 1.7 X 10(-6) M propranolol. In Purkinje fibers this concentration of propranolol depressed the rate of phase 4 depolarization previously enhanced by ouabain 2.1 X 10(-7) M. Propranolol, 1.7 X 10(-6) M, did not alter membrane responsiveness and only slightly accelerated repolarization at 5 minutes. Propranolol, 0.85 X 10(-6) M, did not significantly depress the ouabain-enhanced rate of phase 4 depolarization but did attenuate the response to epinephrine through beta blockade. This study indicated that the initial direct action of propranolol in reverting a ouabain-induced ventricular tachycardia to a sinus rhythm in the dog is depression of automaticity. | [
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PMID:17732 | Detection of light-induced changes of intracellular ionized calcium concentration in Limulus ventral photoreceptors using arsenazo III. | 1. The metallochromic indicator dye, arsenazo III, was injected intracellularly into Limulus ventral photoreceptor cells to concentrations greater than 1 mM.2. The absorption spectrum (450-750 nm) of the dye in single dark-adapted cells was measured by a scanning microspectrophotometer. When a cell was light-adapted, the absorption of the dye changed; the difference spectrum had two maxima at about 610 and 660 nm, a broad minimum at about 540 nm and an isosbestic point at about 585 nm.3. When intracellular calcium concentration was raised in dark-adapted cells previously injected with arsenazo III, the difference spectum had two maxima at about 610 and 660 nm, a broad minimum at about 530 nm and an isosbestic point at about 585 nm. The injection of Mg(2+) into dark-adapted cells previously injected with the dye induced a difference spectrum that had a single maximum at about 620 nm. Also, decreasing the intracellular pH of cells previously injected with the dye induced a difference spectrum that had a minimum at about 620 nm. The evidence suggests that there is a rise of intracellular ionized calcium when a Limulus ventral photoreceptor is light-adapted.4. The intracellular calcium concentration, [Ca(2+)](1), in light-adapted photoreceptors was estimated to reach at least 10(-4)M by compaing the light-induced difference spectra measured in ventral photoreceptors with a standard curve determined in microcuvettes containing 2mM arsenazo III in 400 mM-KCl, 1 mM-MgCl(2) and 25 mM MOPS at pH 7.0.5. In cells injected to less than 3 mM arsenazo III, light induced a transient decrease in optical transmission at 660 nm (T(660)). This decrease in T(660) indicates that illumination of a ventral photoreceptor normally causes a transient increase of [Ca(2+)](1).6. Arsenazo III was found to be sensitive, selective and rapid enough to measure light-induced changes of intracellular ionized calcium in Limulus ventral photoreceptor cells. | Detection of light-induced changes of intracellular ionized calcium concentration in Limulus ventral photoreceptors using arsenazo III. 1. The metallochromic indicator dye, arsenazo III, was injected intracellularly into Limulus ventral photoreceptor cells to concentrations greater than 1 mM.2. The absorption spectrum (450-750 nm) of the dye in single dark-adapted cells was measured by a scanning microspectrophotometer. When a cell was light-adapted, the absorption of the dye changed; the difference spectrum had two maxima at about 610 and 660 nm, a broad minimum at about 540 nm and an isosbestic point at about 585 nm.3. When intracellular calcium concentration was raised in dark-adapted cells previously injected with arsenazo III, the difference spectum had two maxima at about 610 and 660 nm, a broad minimum at about 530 nm and an isosbestic point at about 585 nm. The injection of Mg(2+) into dark-adapted cells previously injected with the dye induced a difference spectrum that had a single maximum at about 620 nm. Also, decreasing the intracellular pH of cells previously injected with the dye induced a difference spectrum that had a minimum at about 620 nm. The evidence suggests that there is a rise of intracellular ionized calcium when a Limulus ventral photoreceptor is light-adapted.4. The intracellular calcium concentration, [Ca(2+)](1), in light-adapted photoreceptors was estimated to reach at least 10(-4)M by compaing the light-induced difference spectra measured in ventral photoreceptors with a standard curve determined in microcuvettes containing 2mM arsenazo III in 400 mM-KCl, 1 mM-MgCl(2) and 25 mM MOPS at pH 7.0.5. In cells injected to less than 3 mM arsenazo III, light induced a transient decrease in optical transmission at 660 nm (T(660)). This decrease in T(660) indicates that illumination of a ventral photoreceptor normally causes a transient increase of [Ca(2+)](1).6. Arsenazo III was found to be sensitive, selective and rapid enough to measure light-induced changes of intracellular ionized calcium in Limulus ventral photoreceptor cells. | [
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|
PMID:17733 | Regulation of cerebrospinal fluid bicarbonate by the cat choroid plexus. | 1. The regulation of cerebrospinal fluid (c.s.f.) bicarbonate concentration was studied using the cat choroid plexus isolated in a chamber in situ. 2. Decreases in plasma bicarbonate concentration caused relatively small changes in the c.s.f. bicarbonate concentration. 3. Alterations in c.s.f. bicarbonate concentration (c.s.f. HCO3-=9 or 28 m-equiv/l.) were countered by changes in the bicarbonate concentration of the fluid produced by the plexus or in the rate of bicarbonate transport which returned c.s.f. bicarbonate towards normal. 4. There was significant regulation of pH in the choroid plexus fluid during hypocapnia and hypercapnia. 5. Alterations of plasma acid-base status did not significantly alter the potential difference across the choroid plexus. However, the potential difference increased when c.s.f. bicarbonate was increased and decreased when c.s.f. bicarbonate was decreased. 6. The data indicate that the bicarbonate concentration in the c.s.f. is actively regulated by the choroid plexus during acid-base disturbances occurring either systemically or in the c.s.f. | Regulation of cerebrospinal fluid bicarbonate by the cat choroid plexus. 1. The regulation of cerebrospinal fluid (c.s.f.) bicarbonate concentration was studied using the cat choroid plexus isolated in a chamber in situ. 2. Decreases in plasma bicarbonate concentration caused relatively small changes in the c.s.f. bicarbonate concentration. 3. Alterations in c.s.f. bicarbonate concentration (c.s.f. HCO3-=9 or 28 m-equiv/l.) were countered by changes in the bicarbonate concentration of the fluid produced by the plexus or in the rate of bicarbonate transport which returned c.s.f. bicarbonate towards normal. 4. There was significant regulation of pH in the choroid plexus fluid during hypocapnia and hypercapnia. 5. Alterations of plasma acid-base status did not significantly alter the potential difference across the choroid plexus. However, the potential difference increased when c.s.f. bicarbonate was increased and decreased when c.s.f. bicarbonate was decreased. 6. The data indicate that the bicarbonate concentration in the c.s.f. is actively regulated by the choroid plexus during acid-base disturbances occurring either systemically or in the c.s.f. | [
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|
PMID:17734 | Surface potential reflected in both gating and permeation mechanisms of sodium and calcium channels of the tunicate egg cell membrane. | 1. Threshold changes of Na and Ca currents due to various polyvalent cations (stabilizing cations) or H(+) ions were studied in the egg cell membrane of a tunicate, Halocynthia roretzi, by using the voltage-clamp technique.2. With an increase in [Ca](o) or a decrease in pH in the external solution, the current-voltage (I-V) relations for the peak of the Na and Ca currents shifted along the voltage axis in the positive direction. These voltage shifts in the I-V relations, measured at a potential of V((1/2)) where inward current attains its half-maximum, were shown to be identical to shifts in voltage-dependence of the time courses of Na and Ca currents, and also identical to shifts in the inactivation curves of Na current along the voltage axis.3. The shifts in V((1/2)) produced by various polyvalent cations or H(+) ions were analysed by the Gouy-Chapman equation for the diffuse double layer, by assuming that a change in V((1/2)) directly corresponds to a change in the surface double layer potential.4. The V((1/2))-divalent cation concentration relations of Na current were exactly described by the predictions of the theory with a constant value of the surface charge density of 1e(-)/(9 A)(2). The weak stabilizing effects of Mg(2+), Sr(2+) and Ba(2+) were quite similar to each other and were explained in terms of a ;screening' effect. Other divalent cations, such as Ca(2+), Mn(2+) and Ni(2+), showed various different stabilizing effects which were explained in terms of a ;binding' effect. The binding constants (K(1)'s) for Ca(2+), Mn(2+) and Ni(2+) were 0.21, 0.45 and 0.94 M(-1), respectively.5. H(+) ions showed a powerful stabilizing effect upon the Na current with a K(H) of 6 x 10(4)M(-1). This value indicates that the acidic sites around Na channels have a pK(a) of 4.78. La(3+) ions also acted as a strong stabilizer upon the Na current with a K(La) of 15 M(-1). For both H(+) and La(3+), the V((1/2))-concentration relations were also exactly described by the Gouy-Chapman equation with the same charge density of 1e(-)/(9 A)(2) as estimated by varying divalent cations.6. The stabilizing effect of permeant cations such as Ca(2+), Sr(2+) and Ba(2+) on Ca channel currents was analysed. The effect of lowering pH was also studied. It was found that the surface charge density of 1e(-)/(9 A)(2) estimated by Na current is also applicable to the explanation for the V((1/2))-divalent cation concentration or - pH relationships. The estimated binding constants for H(+), Ca(2+) and Sr(2+) were 1.2x10(5), 0.58 and 0.035 M(-1), respectively. Ba(2+) does not bind to charged sites near to the Ca channels.7. It was noticed that a considerable reduction in the conductances of Na and Ca currents occurred in parallel with a stabilizing effect. This reduction was ascribed to a decrease in the concentration of permeant cations at the external surface of the cell membrane, as predicted by the theory of the diffuse double layer. The Goldman, Hodgkin-Katz equation for ionic currents was applied to explain the conductance suppression.8. The conductance suppressions of Na and Ca channel currents due to Ca(2+), Sr(2+) and Ba(2+) were found to be apparent ones, only reflecting decreases in the surface concentration of permeant cations without any changes in the permeability. After correction for the apparent suppression, the real permeability ratio among Ca(2+), Sr(2+) and Ba(2+) for Ca channels was determined as 1.00, 0.56 and 0.21 respectively.9. The conductance suppression of Na current by lowering pH was explained in terms of a real suppression or blocking which is superimposed on the apparent suppression. Considering the surface [Na](o), the plot of P(Na) against the surface pH yielded a blocking curve of Na channel by H(+) ions, which implies that two H(+) ions are necessary to block each Na channel. For Ca channels no real blockage was observed in acidic pH.10. It was concluded from the present experiment that there exists a surface potential capable of affecting both gating and permeation mechanisms of ionic channels in this tunicate egg cell membrane. | Surface potential reflected in both gating and permeation mechanisms of sodium and calcium channels of the tunicate egg cell membrane. 1. Threshold changes of Na and Ca currents due to various polyvalent cations (stabilizing cations) or H(+) ions were studied in the egg cell membrane of a tunicate, Halocynthia roretzi, by using the voltage-clamp technique.2. With an increase in [Ca](o) or a decrease in pH in the external solution, the current-voltage (I-V) relations for the peak of the Na and Ca currents shifted along the voltage axis in the positive direction. These voltage shifts in the I-V relations, measured at a potential of V((1/2)) where inward current attains its half-maximum, were shown to be identical to shifts in voltage-dependence of the time courses of Na and Ca currents, and also identical to shifts in the inactivation curves of Na current along the voltage axis.3. The shifts in V((1/2)) produced by various polyvalent cations or H(+) ions were analysed by the Gouy-Chapman equation for the diffuse double layer, by assuming that a change in V((1/2)) directly corresponds to a change in the surface double layer potential.4. The V((1/2))-divalent cation concentration relations of Na current were exactly described by the predictions of the theory with a constant value of the surface charge density of 1e(-)/(9 A)(2). The weak stabilizing effects of Mg(2+), Sr(2+) and Ba(2+) were quite similar to each other and were explained in terms of a ;screening' effect. Other divalent cations, such as Ca(2+), Mn(2+) and Ni(2+), showed various different stabilizing effects which were explained in terms of a ;binding' effect. The binding constants (K(1)'s) for Ca(2+), Mn(2+) and Ni(2+) were 0.21, 0.45 and 0.94 M(-1), respectively.5. H(+) ions showed a powerful stabilizing effect upon the Na current with a K(H) of 6 x 10(4)M(-1). This value indicates that the acidic sites around Na channels have a pK(a) of 4.78. La(3+) ions also acted as a strong stabilizer upon the Na current with a K(La) of 15 M(-1). For both H(+) and La(3+), the V((1/2))-concentration relations were also exactly described by the Gouy-Chapman equation with the same charge density of 1e(-)/(9 A)(2) as estimated by varying divalent cations.6. The stabilizing effect of permeant cations such as Ca(2+), Sr(2+) and Ba(2+) on Ca channel currents was analysed. The effect of lowering pH was also studied. It was found that the surface charge density of 1e(-)/(9 A)(2) estimated by Na current is also applicable to the explanation for the V((1/2))-divalent cation concentration or - pH relationships. The estimated binding constants for H(+), Ca(2+) and Sr(2+) were 1.2x10(5), 0.58 and 0.035 M(-1), respectively. Ba(2+) does not bind to charged sites near to the Ca channels.7. It was noticed that a considerable reduction in the conductances of Na and Ca currents occurred in parallel with a stabilizing effect. This reduction was ascribed to a decrease in the concentration of permeant cations at the external surface of the cell membrane, as predicted by the theory of the diffuse double layer. The Goldman, Hodgkin-Katz equation for ionic currents was applied to explain the conductance suppression.8. The conductance suppressions of Na and Ca channel currents due to Ca(2+), Sr(2+) and Ba(2+) were found to be apparent ones, only reflecting decreases in the surface concentration of permeant cations without any changes in the permeability. After correction for the apparent suppression, the real permeability ratio among Ca(2+), Sr(2+) and Ba(2+) for Ca channels was determined as 1.00, 0.56 and 0.21 respectively.9. The conductance suppression of Na current by lowering pH was explained in terms of a real suppression or blocking which is superimposed on the apparent suppression. Considering the surface [Na](o), the plot of P(Na) against the surface pH yielded a blocking curve of Na channel by H(+) ions, which implies that two H(+) ions are necessary to block each Na channel. For Ca channels no real blockage was observed in acidic pH.10. It was concluded from the present experiment that there exists a surface potential capable of affecting both gating and permeation mechanisms of ionic channels in this tunicate egg cell membrane. | [
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|
PMID:17735 | Effects of prostaglandin antagonism on sodium arachidonate fever in rabbits. | 1. Sodium arachidonate, the prostaglandin precursor substance, when injected intraventricularly into rabbits, results in dose-dependent hyperthermia, which is rapid in onset and of several hours duration. 2. Arachidonate fever was inhibited by intraventricular injection of indomethacin, but not by the simultaneous intraventricular injection of either of the two prostaglandin antagonists SC 19220 or HR 546. 3. Both antagonists effectively inhibited the fever induced by the intraventricular injection of an equipotent dose of PGE1. 4. Our results show that a derivative of arachidonic acid other than prostaglandin is pyrogenic. | Effects of prostaglandin antagonism on sodium arachidonate fever in rabbits. 1. Sodium arachidonate, the prostaglandin precursor substance, when injected intraventricularly into rabbits, results in dose-dependent hyperthermia, which is rapid in onset and of several hours duration. 2. Arachidonate fever was inhibited by intraventricular injection of indomethacin, but not by the simultaneous intraventricular injection of either of the two prostaglandin antagonists SC 19220 or HR 546. 3. Both antagonists effectively inhibited the fever induced by the intraventricular injection of an equipotent dose of PGE1. 4. Our results show that a derivative of arachidonic acid other than prostaglandin is pyrogenic. | [
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|
PMID:17736 | Kinetics of luminal acidification in cortical tubules of the rat kidney. | 1. Some kinetic aspects of renal tubular acidification were studied in proximal and distal tubules of the rat kidney by combining stationary microperfusion methods and continuous measurements of luminal pH changes of phosphate or bicarbonate buffers by means of antimony electrodes. The analysis included the measurement of steady-state pH, steady-state buffer concentrations and acidification half-times. From these data, net rates of tubular bicarbonate reabsorption and of H ion secretion were obtained since it was shown that the rate of phosphate acidification provides a realistic estimate of H ion secretion. 2. Experiments were performed in control rats, in animals undergoing metabolic acidosis or alkalosis and in control and acidotic rats receiving the carbonic anydrase inhibitor Diamox. 3. In all experiments, the rates of tubular bicarbonate reabsorption and of phosphate acidification (H ion secretion) were proportional to luminal buffer levels. The changes of luminal acid concentrations followed first-order kinetics. 4. Steady-state transepithelial pH differences were reduced in metabolic alkalosis and after diamox but augmented during metabolic acidosis. 5. Acidification half-times were prolonged in metabolic acidosis and after Diamox but remained similar to control levels in metabolic alkalosis. 6. From the observation that both bicarbonate reabsorption and phosphate acidification are similarly affected by these experimental manoeuvres, it is concluded that H ion secretion plays a key role in both transport processes. | Kinetics of luminal acidification in cortical tubules of the rat kidney. 1. Some kinetic aspects of renal tubular acidification were studied in proximal and distal tubules of the rat kidney by combining stationary microperfusion methods and continuous measurements of luminal pH changes of phosphate or bicarbonate buffers by means of antimony electrodes. The analysis included the measurement of steady-state pH, steady-state buffer concentrations and acidification half-times. From these data, net rates of tubular bicarbonate reabsorption and of H ion secretion were obtained since it was shown that the rate of phosphate acidification provides a realistic estimate of H ion secretion. 2. Experiments were performed in control rats, in animals undergoing metabolic acidosis or alkalosis and in control and acidotic rats receiving the carbonic anydrase inhibitor Diamox. 3. In all experiments, the rates of tubular bicarbonate reabsorption and of phosphate acidification (H ion secretion) were proportional to luminal buffer levels. The changes of luminal acid concentrations followed first-order kinetics. 4. Steady-state transepithelial pH differences were reduced in metabolic alkalosis and after diamox but augmented during metabolic acidosis. 5. Acidification half-times were prolonged in metabolic acidosis and after Diamox but remained similar to control levels in metabolic alkalosis. 6. From the observation that both bicarbonate reabsorption and phosphate acidification are similarly affected by these experimental manoeuvres, it is concluded that H ion secretion plays a key role in both transport processes. | [
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|
PMID:17737 | Mechansims and components of renal tubular acidification. | 1. Renal cortical tubules of control and acetazolamide infused rats were perfused with 100 mM phosphate buffer at pH 5-5. The rate of alkalinization was measured by means of antimony micro-electrodes and was used to compute passive H ion fluxes from lumen to blood across the proximal and distal tubular epithelium. 2. The importance of other ionic movements that might contribute to pH changes of luminal buffers (chloride inflow into the lumen and bicarbonate diffusion across the epithelium) was assessed but found to be minor. H ion movements accounted for the majority of the observed pH changes. 3. H ion permeability of the tubular wall was calculated from the measured H fluxes and transepithelial concentration differences. It was 1-10 cm/sec, several orders of magnitude larger than those for other ions. However, such values are compatible with the mobility of protons in a medium of structure water within the limiting membrane. 4. A kinetic analysis of the mechanism of movement of H ions across the renal tubule is presented on the basis of experiments in which acidification and alkalinization of luminal buffers was followed in stationary microperfusions. The data are compatible with a pump-leak system in the proximal tubule, and with a model with low H ion permeability and a gradient dependent pump in the distal tubule. | Mechansims and components of renal tubular acidification. 1. Renal cortical tubules of control and acetazolamide infused rats were perfused with 100 mM phosphate buffer at pH 5-5. The rate of alkalinization was measured by means of antimony micro-electrodes and was used to compute passive H ion fluxes from lumen to blood across the proximal and distal tubular epithelium. 2. The importance of other ionic movements that might contribute to pH changes of luminal buffers (chloride inflow into the lumen and bicarbonate diffusion across the epithelium) was assessed but found to be minor. H ion movements accounted for the majority of the observed pH changes. 3. H ion permeability of the tubular wall was calculated from the measured H fluxes and transepithelial concentration differences. It was 1-10 cm/sec, several orders of magnitude larger than those for other ions. However, such values are compatible with the mobility of protons in a medium of structure water within the limiting membrane. 4. A kinetic analysis of the mechanism of movement of H ions across the renal tubule is presented on the basis of experiments in which acidification and alkalinization of luminal buffers was followed in stationary microperfusions. The data are compatible with a pump-leak system in the proximal tubule, and with a model with low H ion permeability and a gradient dependent pump in the distal tubule. | [
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|
PMID:17738 | A mathematical model for counter-current multiplications in the swim-bladder. | 1. A computer model for swim-bladder gas filling has been developed. Phenomenological descriptions of the Root effect (pH-dependent O2 capacity of fish haemoglobin), of the lactic acid production in the gas gland and of the geometry of the rete mirabile are incorporated in the general counter-current equations to give a comprehensive model of gas filling. 2. It is known that pH along the rete is not constant, as supposed in an earlier gas-filling model. It is also known that the Root shift reaction has a different half-time model. It is also known that the Root shift reaction has a different half-time depending on whether the haemoglobin absorbs or releases O2. These particular effects are accounted for in the present model. 3. The model gives gas filling rate and maximum swim-bladder pressure for CO2, O2 and N2. The partial pressure of these gases as well as the concentration of lactic acid and the pH along the rete are also calculated. 4. The model reproduces quite accurately experimental values for gas-filling rate in eel, together with lactic acid, CO2 and O2 concentrations measured at the rete end-points. There is also good correlation between maximum predicted stable swim-bladder pressure and maximum recorded depth for four fishes investigated (r=0-937; P=0-06). 5. The model predicts an enhancement of O2 filling rate and maximum swim-bladder pressure of at least 4 when the reaction rates of the Root shift in eel haemoglobin are 0-2 sec (Root-off) and 10 sec (Root-on), as compared to an instantaneous Root shift. 6. With a swim-bladder pressure of 1 atm and Root-shift reaction rates of equal magnitude, the po2-profile along the rete is nearly linear. When the reaction rates are such as found experimentally in eel haemoglobin, the po2 along the rete is non-linear, with a maximum of approximately 2 atm near the bladder pole of the rete. An experimental verification of this maximum will constitute a crucial test of the model. 7. The calculations show that blood flow through rete can regulate both gas-filling rate and stable swim-bladder pressure. At high pressure, the main factor limiting gas filling is loss of gas through back diffusion along the rete. 8. Maximum po2 in the swim-bladder is highly dependent upon the Root effect. If the Root effect persists up to about 100 atm, as seems to be the case blue hake, maximum po2 is more than 200 atm. When the Root effect is abolished at 10 atm, as is expected in eel, the maximum po2 drops to about 30 atm. 9. The pN2 in the bladder can reach 10-15 atm depending on blood flow, whereas PCO2 will not exceed 1 atm. | A mathematical model for counter-current multiplications in the swim-bladder. 1. A computer model for swim-bladder gas filling has been developed. Phenomenological descriptions of the Root effect (pH-dependent O2 capacity of fish haemoglobin), of the lactic acid production in the gas gland and of the geometry of the rete mirabile are incorporated in the general counter-current equations to give a comprehensive model of gas filling. 2. It is known that pH along the rete is not constant, as supposed in an earlier gas-filling model. It is also known that the Root shift reaction has a different half-time model. It is also known that the Root shift reaction has a different half-time depending on whether the haemoglobin absorbs or releases O2. These particular effects are accounted for in the present model. 3. The model gives gas filling rate and maximum swim-bladder pressure for CO2, O2 and N2. The partial pressure of these gases as well as the concentration of lactic acid and the pH along the rete are also calculated. 4. The model reproduces quite accurately experimental values for gas-filling rate in eel, together with lactic acid, CO2 and O2 concentrations measured at the rete end-points. There is also good correlation between maximum predicted stable swim-bladder pressure and maximum recorded depth for four fishes investigated (r=0-937; P=0-06). 5. The model predicts an enhancement of O2 filling rate and maximum swim-bladder pressure of at least 4 when the reaction rates of the Root shift in eel haemoglobin are 0-2 sec (Root-off) and 10 sec (Root-on), as compared to an instantaneous Root shift. 6. With a swim-bladder pressure of 1 atm and Root-shift reaction rates of equal magnitude, the po2-profile along the rete is nearly linear. When the reaction rates are such as found experimentally in eel haemoglobin, the po2 along the rete is non-linear, with a maximum of approximately 2 atm near the bladder pole of the rete. An experimental verification of this maximum will constitute a crucial test of the model. 7. The calculations show that blood flow through rete can regulate both gas-filling rate and stable swim-bladder pressure. At high pressure, the main factor limiting gas filling is loss of gas through back diffusion along the rete. 8. Maximum po2 in the swim-bladder is highly dependent upon the Root effect. If the Root effect persists up to about 100 atm, as seems to be the case blue hake, maximum po2 is more than 200 atm. When the Root effect is abolished at 10 atm, as is expected in eel, the maximum po2 drops to about 30 atm. 9. The pN2 in the bladder can reach 10-15 atm depending on blood flow, whereas PCO2 will not exceed 1 atm. | [
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|
PMID:17739 | Contraction and recovery of living muscles studies by 31P nuclear magnetic resonance. | 1. Phosphorus nuclear magnetic resonance ((31)P NMR) can be used to measure the concentrations of phosphorus-containing metabolites within living tissue. We have developed methods for maintaining muscles in physiological condition, stimulating them and recording tension while at the same time accumulating their (31)P NMR spectra. Experiments were performed on frog sartorii and frog and toad gastrocnemii at 4 degrees C.2. The NMR signals from (31)P (the naturally occurring phosphorus) is weak, and signal averaging is required. In order to follow the time course of reactions it is necessary to maintain the muscles in a steady state for many hours while they are undergoing repeated contractions. Signals were accumulated in separate computer bins according to time after initiation of contraction. By these means spectra were obtained which corresponded to the different intervals during the contraction and recovery cycle.3. In the absence of stimulation, the spectra of frog sartorius muscles and of their extracts indicated concentrations of adenosine triphosphate (ATP), phosphoryl creatine (PCr), inorganic orthophosphate (P(i)) and sugar phosphates (sugar P) which are in reasonable agreement with the values obtained by chemical analysis.4. We have confirmed that unidentified resonances representing unknown compounds appear in the spectra of both frog and toad muscle; one of these is much larger in spectra from toad than from frog. We have found an additional small, unidentified resonance which appears to be specific to toad muscle.5. Spectra accumulated during actual contractions (1 s tetani every 2 min) did not differ dramatically from those accumulated throughout the 2 min cycle of contraction and partial recovery.6. Following 25 s tetanii, approximately 20% of the PCr had been hydrolysed; it was then rebuilt exponentially with a half-time of about 10 min. The increase in [P(i)] immediately after contraction and the time course of its disappearance corresponded to the changes in [PCr]. During the later half of the recovery period the concentration of P(i) was reduced to below that in resting muscle. The [sugar P] remained very high ( approximately 4 mmol kg(-1)) throughout the 56 min interval between contractions.7. When frog sartorii were tetanized for 1 s every 2 min, the changes in [PCr] and [P(i)] between contractions could not be observed because too little signal was obtained from these small muscles. However, when toad gastrocnemii were similarly stimulated, the changes in these compounds could be readily detected and were even greater than expected.8. The position of the P(i) resonance can be used to monitor intracellular pH and changes in pH. Under the conditions of our experiments the average intracellular pH in unstimulated frog sartorius muscles was 7.5. After a 25 s tetanus this was observed to move in the acid direction by a few tenths of a pH unit and to return to its pre-stimulation value before the end of the recovery period. After a 1 s contraction of toad gastrocnemius the environment of P(i) became slightly more alkaline for the first few seconds. | Contraction and recovery of living muscles studies by 31P nuclear magnetic resonance. 1. Phosphorus nuclear magnetic resonance ((31)P NMR) can be used to measure the concentrations of phosphorus-containing metabolites within living tissue. We have developed methods for maintaining muscles in physiological condition, stimulating them and recording tension while at the same time accumulating their (31)P NMR spectra. Experiments were performed on frog sartorii and frog and toad gastrocnemii at 4 degrees C.2. The NMR signals from (31)P (the naturally occurring phosphorus) is weak, and signal averaging is required. In order to follow the time course of reactions it is necessary to maintain the muscles in a steady state for many hours while they are undergoing repeated contractions. Signals were accumulated in separate computer bins according to time after initiation of contraction. By these means spectra were obtained which corresponded to the different intervals during the contraction and recovery cycle.3. In the absence of stimulation, the spectra of frog sartorius muscles and of their extracts indicated concentrations of adenosine triphosphate (ATP), phosphoryl creatine (PCr), inorganic orthophosphate (P(i)) and sugar phosphates (sugar P) which are in reasonable agreement with the values obtained by chemical analysis.4. We have confirmed that unidentified resonances representing unknown compounds appear in the spectra of both frog and toad muscle; one of these is much larger in spectra from toad than from frog. We have found an additional small, unidentified resonance which appears to be specific to toad muscle.5. Spectra accumulated during actual contractions (1 s tetani every 2 min) did not differ dramatically from those accumulated throughout the 2 min cycle of contraction and partial recovery.6. Following 25 s tetanii, approximately 20% of the PCr had been hydrolysed; it was then rebuilt exponentially with a half-time of about 10 min. The increase in [P(i)] immediately after contraction and the time course of its disappearance corresponded to the changes in [PCr]. During the later half of the recovery period the concentration of P(i) was reduced to below that in resting muscle. The [sugar P] remained very high ( approximately 4 mmol kg(-1)) throughout the 56 min interval between contractions.7. When frog sartorii were tetanized for 1 s every 2 min, the changes in [PCr] and [P(i)] between contractions could not be observed because too little signal was obtained from these small muscles. However, when toad gastrocnemii were similarly stimulated, the changes in these compounds could be readily detected and were even greater than expected.8. The position of the P(i) resonance can be used to monitor intracellular pH and changes in pH. Under the conditions of our experiments the average intracellular pH in unstimulated frog sartorius muscles was 7.5. After a 25 s tetanus this was observed to move in the acid direction by a few tenths of a pH unit and to return to its pre-stimulation value before the end of the recovery period. After a 1 s contraction of toad gastrocnemius the environment of P(i) became slightly more alkaline for the first few seconds. | [
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|
PMID:17740 | Micro-electrode measurement of the intracellular pH and buffering power of mouse soleus muscle fibres. | 1. The intracellular pH (pHi) of surface fibres of the mouse soleus muscle has been measured in vitro using recessed-tip pH-sensitive microelectrodes. 2. In 5% CO2 and pH 7-40, the mean pHi was 7-07 +/- 0-007 (S.E. of mean) at 37 degrees C and 7-23 +/- 0-01 at 28 degrees C. The difference between these tow values is the same as the change in neutral pH between 37 and 28 degrees C. 3. Alteration of the CO2 level at constant external pH caused a biphasic change in pHi with a rapid displacement followed by a slower partial recovery. Because the recovery was incomplete, different stable pHi values were recorded at different CO2 levels, the higher the CO2 the lower the pHi. The differences in pHi were highly significant both at 37 and 28 degrees C. 4. Alteration of the CO2 level at constant external pH also changed the membrane potential (Em), an increase in CO2 leading to an increased Em. The dependence of Em on the CO2 level was much smaller in the fast-twitch muscle, extensor digitorum longus, than in soleus. 5. Changing external pH, either by alteration of the bicarbonate or CO2 level of the Ringer solution, caused pHi to change by a mean 38-7% of the external pH change. The change in pHi was accomplished about 10 times more rapidly, and in the same direction, by altering CO2 than by altering the bicarbonate. 6. Application of external NH3 and NH+4 caused a rapid intracellular alkalinization followed by a slower acidification. On removal of external NH3 and NH+4, there was a large and rapid acdification, followed by a fairly rapid recovery in pHi. 7. The size of the pHi changes occurring on alteration of the CO2 level at both constant external pH and constant external bicarbonate, and on removal of external NH3 and NH+4, suggests a non-CO2 buffering power of 45m-equiv H+ ions/pH unit per litre and a constant-CO2 buffering power of 58 m-equiv H+ ions/pH unit per litre. The buffering power was apparently unaffected by a change in temperature between 37 and 28 degrees C. 8. It was concluded that H+ ions are not passively distributed across the muscle cell membrane, and that the pHi is closely controlled by the active transport of H+, OH- or HCO-3 ions. | Micro-electrode measurement of the intracellular pH and buffering power of mouse soleus muscle fibres. 1. The intracellular pH (pHi) of surface fibres of the mouse soleus muscle has been measured in vitro using recessed-tip pH-sensitive microelectrodes. 2. In 5% CO2 and pH 7-40, the mean pHi was 7-07 +/- 0-007 (S.E. of mean) at 37 degrees C and 7-23 +/- 0-01 at 28 degrees C. The difference between these tow values is the same as the change in neutral pH between 37 and 28 degrees C. 3. Alteration of the CO2 level at constant external pH caused a biphasic change in pHi with a rapid displacement followed by a slower partial recovery. Because the recovery was incomplete, different stable pHi values were recorded at different CO2 levels, the higher the CO2 the lower the pHi. The differences in pHi were highly significant both at 37 and 28 degrees C. 4. Alteration of the CO2 level at constant external pH also changed the membrane potential (Em), an increase in CO2 leading to an increased Em. The dependence of Em on the CO2 level was much smaller in the fast-twitch muscle, extensor digitorum longus, than in soleus. 5. Changing external pH, either by alteration of the bicarbonate or CO2 level of the Ringer solution, caused pHi to change by a mean 38-7% of the external pH change. The change in pHi was accomplished about 10 times more rapidly, and in the same direction, by altering CO2 than by altering the bicarbonate. 6. Application of external NH3 and NH+4 caused a rapid intracellular alkalinization followed by a slower acidification. On removal of external NH3 and NH+4, there was a large and rapid acdification, followed by a fairly rapid recovery in pHi. 7. The size of the pHi changes occurring on alteration of the CO2 level at both constant external pH and constant external bicarbonate, and on removal of external NH3 and NH+4, suggests a non-CO2 buffering power of 45m-equiv H+ ions/pH unit per litre and a constant-CO2 buffering power of 58 m-equiv H+ ions/pH unit per litre. The buffering power was apparently unaffected by a change in temperature between 37 and 28 degrees C. 8. It was concluded that H+ ions are not passively distributed across the muscle cell membrane, and that the pHi is closely controlled by the active transport of H+, OH- or HCO-3 ions. | [
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PMID:17741 | The effect of temperature on the potential difference and input resistance of rat seminiferous tubules. | 1. The p.d. of rat seminiferous tubules was 5.86 +/- 0.15 mV, lumen negative, at 33 degrees C and varied linearly with temperature between 24 and 37 degrees C, exhibiting an apparent Q(10) (25-35 degrees C) of 2.0 with a slope of 0.43 mV/ degrees C. Exposing testes to a temperature of 37-43 degrees C resulted in an initial hyperpolarization followed by depolarization of the tubules. These changes were more rapid in testes exposed to 41-43 degrees C than in testes exposed to 37-39 degrees C.2. The R(in) of seminiferous tubules was 198 +/- 7.8 kOmega at a testis temperature of 33 degrees C. The R(in) decreased when testes were maintained at 37 and 41 degrees C, the rate of decrease being similar to the rate of depolarization.3. Exposing testes to deep body temperature by unilateral surgical cryptorchidism caused a reduction of 30 and 64% in tubular p.d. and R(in) respectively when measured 24 hr after surgery. Exposure to deep body temperature for up to 4 days did not cause any further change in either parameter.4. There was no evidence that lanthanum penetrated through the Sertoli cell tight junctions after exposing testes to 41 degrees C for up to 30 min.5. The results indicate that the seminiferous tubule p.d. is maintained by a temperature-sensitive, cellular mechanism. Exposing testes to deep body temperature or above depolarized the tubules and increased their permeability. | The effect of temperature on the potential difference and input resistance of rat seminiferous tubules. 1. The p.d. of rat seminiferous tubules was 5.86 +/- 0.15 mV, lumen negative, at 33 degrees C and varied linearly with temperature between 24 and 37 degrees C, exhibiting an apparent Q(10) (25-35 degrees C) of 2.0 with a slope of 0.43 mV/ degrees C. Exposing testes to a temperature of 37-43 degrees C resulted in an initial hyperpolarization followed by depolarization of the tubules. These changes were more rapid in testes exposed to 41-43 degrees C than in testes exposed to 37-39 degrees C.2. The R(in) of seminiferous tubules was 198 +/- 7.8 kOmega at a testis temperature of 33 degrees C. The R(in) decreased when testes were maintained at 37 and 41 degrees C, the rate of decrease being similar to the rate of depolarization.3. Exposing testes to deep body temperature by unilateral surgical cryptorchidism caused a reduction of 30 and 64% in tubular p.d. and R(in) respectively when measured 24 hr after surgery. Exposure to deep body temperature for up to 4 days did not cause any further change in either parameter.4. There was no evidence that lanthanum penetrated through the Sertoli cell tight junctions after exposing testes to 41 degrees C for up to 30 min.5. The results indicate that the seminiferous tubule p.d. is maintained by a temperature-sensitive, cellular mechanism. Exposing testes to deep body temperature or above depolarized the tubules and increased their permeability. | [
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PMID:17742 | Hyperpolarizing effects of dopamine on chemoreceptor nerve endings from cat and rabbit carotid bodies in vitro. | 1. The effects of dopamine on DC potential changes recorded from the carotid sinus nerve were studied in vitro using carotid bodies and associated sinus nerves removed from anaesthetized cats and rabbits.2. The carotid body was placed in one compartment of a superfusion chamber and was superfused with buffered salt solution. The carotid sinus nerve was led into an adjoining compartment, containing lightweight mineral oil, for recording DC potential changes with chlorided silver electrodes.3. Dopamine injected into the superfusing solution in amounts of 50-250 mug caused hyperpolarization of the DC potential. This effect occurred repeatedly in each preparation, the maximum number of tests in any one preparation being twenty-seven.4. In the same preparations, acetylcholine (50-100 mug) and NaCN (10-20 mug) caused depolarizations of the DC potential, effects that have been described by others.5. The hyperpolarizing effects of dopamine were reduced or abolished by the alpha-adrenergic antagonists, dihydroergotamine (10-100 mug/ml.) and phenoxybenzamine (5 mug/ml.) and the dopamine antagonist droperidol (10-25 mug/ml.).6. The results indicate that the inhibitory effects of dopamine on the frequency of carotid body chemosensory discharges in cats and rabbits are due to hyperpolarization of chemoreceptor afferent nerve endings and not necessarily to local vascular effects in the carotid body. | Hyperpolarizing effects of dopamine on chemoreceptor nerve endings from cat and rabbit carotid bodies in vitro. 1. The effects of dopamine on DC potential changes recorded from the carotid sinus nerve were studied in vitro using carotid bodies and associated sinus nerves removed from anaesthetized cats and rabbits.2. The carotid body was placed in one compartment of a superfusion chamber and was superfused with buffered salt solution. The carotid sinus nerve was led into an adjoining compartment, containing lightweight mineral oil, for recording DC potential changes with chlorided silver electrodes.3. Dopamine injected into the superfusing solution in amounts of 50-250 mug caused hyperpolarization of the DC potential. This effect occurred repeatedly in each preparation, the maximum number of tests in any one preparation being twenty-seven.4. In the same preparations, acetylcholine (50-100 mug) and NaCN (10-20 mug) caused depolarizations of the DC potential, effects that have been described by others.5. The hyperpolarizing effects of dopamine were reduced or abolished by the alpha-adrenergic antagonists, dihydroergotamine (10-100 mug/ml.) and phenoxybenzamine (5 mug/ml.) and the dopamine antagonist droperidol (10-25 mug/ml.).6. The results indicate that the inhibitory effects of dopamine on the frequency of carotid body chemosensory discharges in cats and rabbits are due to hyperpolarization of chemoreceptor afferent nerve endings and not necessarily to local vascular effects in the carotid body. | [
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PMID:17743 | Interacting effects of temperature and extracellular calcium on the spontaneous release of transmitter at the frog neuromuscular junction. | 1. Temperature has a characteristic effect on the frequency of m.e.p.p.s at the frog neuromuscular junction; the spontaneous release of transmitter is not affected by temperature changes below 10 degrees C whereas the system is highly temperature-sensitive above 20 degrees C.2. A very similar result is obtained when the experiment is repeated in saline containing Ca(2+) buffered at 5 x 10(-7)M, suggesting that it is unlikely that the major action of temperature is to cause an increase in Ca(2+) influx.3. It is suggested that the main effect of temperature at the presynaptic terminals is a modification of [Ca(2+)](i) by an action on intracellular Ca(2+) stores.4. The interacting effects of theophylline and the divalent cation ionophore A23187 on m.e.p.p. frequency suggest that intracellular Ca(2+) stores, in addition to the mitochondria, may well be of importance in controlling [Ca(2+)](i).5. Changes in [Ca(2+)](o) produce a modification of m.e.p.p. frequency, but the details of the response are dependent on temperature. The spontaneous release of transmitter is most sensitive to an increase in [Ca(2+)](o) at 23 degrees C, whereas the greater effect is found at 13 degrees C when [Ca(2+)](o) is lowered.6. It is suggested (i) that m.e.p.p. frequency is primarily determined by [Ca(2+)](i) at the presynaptic terminals, (ii) that the presynaptic terminals are normally able to maintain [Ca(2+)](i) almost constant in spite of increases in Ca influx associated with ionophore treatment or with a rise in [Ca(2+)](o). However, if the steady-state position of [Ca(2+)](i) is previously raised by an increased efflux from intracellular stores (produced by elevated temperature or theophylline pre-treatment), increased influx causes a rise in both [Ca(2+)](i) and in m.e.p.p. frequency. | Interacting effects of temperature and extracellular calcium on the spontaneous release of transmitter at the frog neuromuscular junction. 1. Temperature has a characteristic effect on the frequency of m.e.p.p.s at the frog neuromuscular junction; the spontaneous release of transmitter is not affected by temperature changes below 10 degrees C whereas the system is highly temperature-sensitive above 20 degrees C.2. A very similar result is obtained when the experiment is repeated in saline containing Ca(2+) buffered at 5 x 10(-7)M, suggesting that it is unlikely that the major action of temperature is to cause an increase in Ca(2+) influx.3. It is suggested that the main effect of temperature at the presynaptic terminals is a modification of [Ca(2+)](i) by an action on intracellular Ca(2+) stores.4. The interacting effects of theophylline and the divalent cation ionophore A23187 on m.e.p.p. frequency suggest that intracellular Ca(2+) stores, in addition to the mitochondria, may well be of importance in controlling [Ca(2+)](i).5. Changes in [Ca(2+)](o) produce a modification of m.e.p.p. frequency, but the details of the response are dependent on temperature. The spontaneous release of transmitter is most sensitive to an increase in [Ca(2+)](o) at 23 degrees C, whereas the greater effect is found at 13 degrees C when [Ca(2+)](o) is lowered.6. It is suggested (i) that m.e.p.p. frequency is primarily determined by [Ca(2+)](i) at the presynaptic terminals, (ii) that the presynaptic terminals are normally able to maintain [Ca(2+)](i) almost constant in spite of increases in Ca influx associated with ionophore treatment or with a rise in [Ca(2+)](o). However, if the steady-state position of [Ca(2+)](i) is previously raised by an increased efflux from intracellular stores (produced by elevated temperature or theophylline pre-treatment), increased influx causes a rise in both [Ca(2+)](i) and in m.e.p.p. frequency. | [
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|
PMID:17744 | The effects on breathing of alternate breaths of air and a carbon dioxide rich gas mixture in anaesthetized cats. | 1. An in vivo pH electrode was used to assess the effect in anaesthetized cats of the administration of 5% CO(2) (21% O(2), balance N(2)) and air as alternate inspirates upon the time course of the carotid arterial pH, and by inference, the P(CO2).2. This method of administration of CO(2) and air resulted in a lowering of the recorded pH with the production of oscillations of twice the duration seen on air alone. These larger oscillations had a period of two respiratory cycles and their amplitude was approximately twice that of normal oscillations.3. The respiratory response consisted in all cases of an increase in mean tidal volume and ventilation, and in 50-60% of recorded runs, of a highly specific sequence of tidal volume changes. The specific sequence was composed of alternately larger and smaller breaths which persisted while the larger oscillations continued.4. The use of the in vivo pH electrode made it possible to determine whether or not the tidal volume alternation was a result of sensitivity to carotid arterial P(CO2) oscillations. By diverting the carotid arterial blood through a mixing chamber the amplitude of the double (respiratory) period oscillations was, in some cases, reduced but not eliminated. In these cases the specific pattern of tidal volume changes was still present in 60% of trials. In the cases where the pH fluctuations were completely eliminated the specific respiratory pattern was never present.5. Average breath to breath differences in tidal volume seen during control runs with large oscillations present ranged in size from 3.6 to 8.6% of the mean tidal volume. When the oscillations were completely eliminated by means of the mixing chamber the breath by breath differences only ranged from 0.2 to 2.7% of mean tidal volume. The change was highly significant.6. Mean tidal volume and ventilation were not altered by eliminating the large (double period) oscillations.7. It has been shown that the tidal volume is made to change from breath to breath in a persistent manner when there are recurrent changes in carotid arterial blood chemistry. The effects on respiration involve vascular receptors above the mid carotid arterial region. It is argued that the effects involve the sensitivity of the carotid bodies to rapid (within breath) changes in P(a, CO2). There appears to be no significant effect on mean ventilation of the dynamic component of the arterial P(CO2) changes produced in these experiments. | The effects on breathing of alternate breaths of air and a carbon dioxide rich gas mixture in anaesthetized cats. 1. An in vivo pH electrode was used to assess the effect in anaesthetized cats of the administration of 5% CO(2) (21% O(2), balance N(2)) and air as alternate inspirates upon the time course of the carotid arterial pH, and by inference, the P(CO2).2. This method of administration of CO(2) and air resulted in a lowering of the recorded pH with the production of oscillations of twice the duration seen on air alone. These larger oscillations had a period of two respiratory cycles and their amplitude was approximately twice that of normal oscillations.3. The respiratory response consisted in all cases of an increase in mean tidal volume and ventilation, and in 50-60% of recorded runs, of a highly specific sequence of tidal volume changes. The specific sequence was composed of alternately larger and smaller breaths which persisted while the larger oscillations continued.4. The use of the in vivo pH electrode made it possible to determine whether or not the tidal volume alternation was a result of sensitivity to carotid arterial P(CO2) oscillations. By diverting the carotid arterial blood through a mixing chamber the amplitude of the double (respiratory) period oscillations was, in some cases, reduced but not eliminated. In these cases the specific pattern of tidal volume changes was still present in 60% of trials. In the cases where the pH fluctuations were completely eliminated the specific respiratory pattern was never present.5. Average breath to breath differences in tidal volume seen during control runs with large oscillations present ranged in size from 3.6 to 8.6% of the mean tidal volume. When the oscillations were completely eliminated by means of the mixing chamber the breath by breath differences only ranged from 0.2 to 2.7% of mean tidal volume. The change was highly significant.6. Mean tidal volume and ventilation were not altered by eliminating the large (double period) oscillations.7. It has been shown that the tidal volume is made to change from breath to breath in a persistent manner when there are recurrent changes in carotid arterial blood chemistry. The effects on respiration involve vascular receptors above the mid carotid arterial region. It is argued that the effects involve the sensitivity of the carotid bodies to rapid (within breath) changes in P(a, CO2). There appears to be no significant effect on mean ventilation of the dynamic component of the arterial P(CO2) changes produced in these experiments. | [
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|
PMID:17745 | Further observations on an ether-O-oxidase, formerly called alkyl etherase, from liver tissue. | 1. The microsomal enzyme from liver previously called an "etherase" is now described more accurately as an ether-O-oxidase. It has been investigated further to free it from the membranes in aqueous solution and to try to define its physiological substrate. 2. After a variety of attempts with detergents, etc., the enzyme was obtained in impure solution from precipitation with 35-45% (NH4)2SO4 solution after a short digestion at room temperature. 3. When a suitably reinforced the enzyme in solution forms citrate from added ethyl ether, as it does in membranous form. This indicates the intermediary formation of acetyl CoA. 4. The enzyme in solution is unstable, though some activity remains after standing at 0degrees C for 2-3 days. Activity is lost rapidly by deep freezing, exposure to 2M-NaCl and at a pH more acid than pH 5-0. 5. The enzyme does not appear to be a known oxidase obtainable from liver microsomes; it is not for instance part of the inducible mixed oxygenase system, nor a peroxidase or catalase. 6. Since there were some similarities in stability with enzymes dealing with protozoal plasmalogens, or with lanosterol or cholesterol, we were led to explore these substrates in detail, with negative results. But a specimen of cholesterol oxidase from the branching bacterium Nocardia gave O-oxidation with diethylether. 7. The enzyme is present in the livers of all four animals examined, namely the rat, pig, guinea-pig and pigeon, but not in kidney or brain. 8. The enzyme takes up O2 with some compounds containing O-me groups. 9. The hypothesis is advanced that this normal oxidase in liver membranes exists to deal with some substances from plant sources which might prove toxic upon entering the circulation. | Further observations on an ether-O-oxidase, formerly called alkyl etherase, from liver tissue. 1. The microsomal enzyme from liver previously called an "etherase" is now described more accurately as an ether-O-oxidase. It has been investigated further to free it from the membranes in aqueous solution and to try to define its physiological substrate. 2. After a variety of attempts with detergents, etc., the enzyme was obtained in impure solution from precipitation with 35-45% (NH4)2SO4 solution after a short digestion at room temperature. 3. When a suitably reinforced the enzyme in solution forms citrate from added ethyl ether, as it does in membranous form. This indicates the intermediary formation of acetyl CoA. 4. The enzyme in solution is unstable, though some activity remains after standing at 0degrees C for 2-3 days. Activity is lost rapidly by deep freezing, exposure to 2M-NaCl and at a pH more acid than pH 5-0. 5. The enzyme does not appear to be a known oxidase obtainable from liver microsomes; it is not for instance part of the inducible mixed oxygenase system, nor a peroxidase or catalase. 6. Since there were some similarities in stability with enzymes dealing with protozoal plasmalogens, or with lanosterol or cholesterol, we were led to explore these substrates in detail, with negative results. But a specimen of cholesterol oxidase from the branching bacterium Nocardia gave O-oxidation with diethylether. 7. The enzyme is present in the livers of all four animals examined, namely the rat, pig, guinea-pig and pigeon, but not in kidney or brain. 8. The enzyme takes up O2 with some compounds containing O-me groups. 9. The hypothesis is advanced that this normal oxidase in liver membranes exists to deal with some substances from plant sources which might prove toxic upon entering the circulation. | [
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|
PMID:17746 | 5-Aryl-1,5-dihydro-2H-1,4-benzodiazepin-2-one derivatives as antianxiety agents. | A new series of 7-chloro- and 7-nitro-5-methoxy-5-phenyl-1,5-dihydro-2H-1,4-benzodiazepin-2-ones (7a, c--e) was synthesized and found to have potent antipentylenetetrazole activity. These compounds were also employed as intermediates in the synthesis of 3-substituted 1,3-dihydro-1,4-benzodiazepin-2-ones (8f--v). | 5-Aryl-1,5-dihydro-2H-1,4-benzodiazepin-2-one derivatives as antianxiety agents. A new series of 7-chloro- and 7-nitro-5-methoxy-5-phenyl-1,5-dihydro-2H-1,4-benzodiazepin-2-ones (7a, c--e) was synthesized and found to have potent antipentylenetetrazole activity. These compounds were also employed as intermediates in the synthesis of 3-substituted 1,3-dihydro-1,4-benzodiazepin-2-ones (8f--v). | [
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|
PMID:17747 | 3,4-Methylenedioxyphenyl-, isopropylidenedioxyphenyl-, and benzyl-substituted chiral 2-aminosuccinimides and 3-aminopyrrolidines. Stereoselective investigations of potential anti-parkinsonian, antipsychotic, and anticonvulsant activities. | The chiral title compounds 2--11 were assessed for their potential anti-Parkinsonian, antipsychotic, and anticonvulsant properties. The most striking differences in the biological activity of enantiomeric pairs were noted for D-(R)-2-amino-N-(3,4-methylenedioxyphenyl)succinimide hydrochloride (2) vs. L-(S)-3 and D-(R)-2-amino-N-(3,4-isopropylidenedioxyphenyl)succinimide (4) vs. L-(S)-5. D-(R)-2-partially attenuated amphetamine-induced stereotyped behavior, whereas D-(R)-4 antagonized oxotremorine-induced tremors. Their respective enantiomorphs were inactive in these tests. No differences in anticonvulsant potency of enantiomeric pairs were observed. The stereoselective actions of D-(R)-2 and 4 were rationalized on the basis of the presence or absence of gem-dimethyl functions in isopropylidenedioxy vs. methylenedioxy groups; the data seem to indicate that these methyl groups influence selective receptor site interaction in the D-(R) series. | 3,4-Methylenedioxyphenyl-, isopropylidenedioxyphenyl-, and benzyl-substituted chiral 2-aminosuccinimides and 3-aminopyrrolidines. Stereoselective investigations of potential anti-parkinsonian, antipsychotic, and anticonvulsant activities. The chiral title compounds 2--11 were assessed for their potential anti-Parkinsonian, antipsychotic, and anticonvulsant properties. The most striking differences in the biological activity of enantiomeric pairs were noted for D-(R)-2-amino-N-(3,4-methylenedioxyphenyl)succinimide hydrochloride (2) vs. L-(S)-3 and D-(R)-2-amino-N-(3,4-isopropylidenedioxyphenyl)succinimide (4) vs. L-(S)-5. D-(R)-2-partially attenuated amphetamine-induced stereotyped behavior, whereas D-(R)-4 antagonized oxotremorine-induced tremors. Their respective enantiomorphs were inactive in these tests. No differences in anticonvulsant potency of enantiomeric pairs were observed. The stereoselective actions of D-(R)-2 and 4 were rationalized on the basis of the presence or absence of gem-dimethyl functions in isopropylidenedioxy vs. methylenedioxy groups; the data seem to indicate that these methyl groups influence selective receptor site interaction in the D-(R) series. | [
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|
PMID:17748 | A comparison of the antiserotonin, antihistamine, and anticholinergic activity of cyproheptadine with analogues having furan nuclei fused to the 10,11-vinylene bridge. | A series of cyproheptadine derivatives having furan nuclei fused to the 10,11-vinylene bridge has been prepared. None of the compounds retain the potent antiserotonin and antihistaminic actions of cyproheptadine. 1-methyl-4-(1-methyl-8H-dibenzo[a,e]furo[3,4-c]cyclohepten-8-ylidene)piperidine (7), 1-methyl-4-(1,3-dihydro-1-oxo-8H-[3,4:6,7]cycloheptal[1,2-c]furan-8-ylidene)piperidine (10), and its reduction product 11 retained the peripheral anticholinergic activity of cyproheptadine. | A comparison of the antiserotonin, antihistamine, and anticholinergic activity of cyproheptadine with analogues having furan nuclei fused to the 10,11-vinylene bridge. A series of cyproheptadine derivatives having furan nuclei fused to the 10,11-vinylene bridge has been prepared. None of the compounds retain the potent antiserotonin and antihistaminic actions of cyproheptadine. 1-methyl-4-(1-methyl-8H-dibenzo[a,e]furo[3,4-c]cyclohepten-8-ylidene)piperidine (7), 1-methyl-4-(1,3-dihydro-1-oxo-8H-[3,4:6,7]cycloheptal[1,2-c]furan-8-ylidene)piperidine (10), and its reduction product 11 retained the peripheral anticholinergic activity of cyproheptadine. | [
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|
PMID:17749 | Absolute configuration of glycerol derivatives. 4. Synthesis and pharmacological activity of chiral 2-alkylaminomethylbenzodioxans, competitive alpha-adrenergic antagonists. | The optical isomers of alpha-adrenergic receptor antagonists prosympal (2), piperoxan (3), and dibozane (4) were prepared by methods establishing the absolute configuration of each. (2S)-3(2'-Hydroxyphenoxy)-1,2-propanediol ditosylate (10) was prepared from (2R)-3-tosyloxy-1,2-propanediol acetonide (6). Intramolecular displacement afforded (2S)-tosyloxymethylbenzodioxan [(2R)-11]. Reaction of (2R)-11 with the appropriate amine (diethylamine, piperidine, or piperazine) afforded the 2S isomers of 2, 3, and 12, respectively. Reaction of (2S)-12 with (2R)-11 afforded the SS isomer of 4. Reaction of (2S)-3-benzyloxy-1,2-propanediol ditosylate (14) with catechol (NaOMe) afforded (2R)-benzyloxymethylbenzodioxan (15). Subjecting 15 to hydrogenolysis, tosylation, and displacement with the appropriate amine afforded 2R isomers of 2, 3, and 12. Reaction of (2R)-12 with (2S)-11 afforded (RR)-4. Reaction of (2R)-12 with (2R)-11 afforded meso-4. The S isomers were more effective antagonists to the alpha-adrenergic response of methoxamine-induced contraction of rabbit aortic strips by twofold in 2 and 18-19-fold in 3 and 4. meso-4 was as effective as the SS isomer of 4. The results are interpreted in terms of a similar conformational distribution of aminoalkyl, oxygen, and aromatic functional groups of the (S)-benzodioxans and (R)-epinephrine. | Absolute configuration of glycerol derivatives. 4. Synthesis and pharmacological activity of chiral 2-alkylaminomethylbenzodioxans, competitive alpha-adrenergic antagonists. The optical isomers of alpha-adrenergic receptor antagonists prosympal (2), piperoxan (3), and dibozane (4) were prepared by methods establishing the absolute configuration of each. (2S)-3(2'-Hydroxyphenoxy)-1,2-propanediol ditosylate (10) was prepared from (2R)-3-tosyloxy-1,2-propanediol acetonide (6). Intramolecular displacement afforded (2S)-tosyloxymethylbenzodioxan [(2R)-11]. Reaction of (2R)-11 with the appropriate amine (diethylamine, piperidine, or piperazine) afforded the 2S isomers of 2, 3, and 12, respectively. Reaction of (2S)-12 with (2R)-11 afforded the SS isomer of 4. Reaction of (2S)-3-benzyloxy-1,2-propanediol ditosylate (14) with catechol (NaOMe) afforded (2R)-benzyloxymethylbenzodioxan (15). Subjecting 15 to hydrogenolysis, tosylation, and displacement with the appropriate amine afforded 2R isomers of 2, 3, and 12. Reaction of (2R)-12 with (2S)-11 afforded (RR)-4. Reaction of (2R)-12 with (2R)-11 afforded meso-4. The S isomers were more effective antagonists to the alpha-adrenergic response of methoxamine-induced contraction of rabbit aortic strips by twofold in 2 and 18-19-fold in 3 and 4. meso-4 was as effective as the SS isomer of 4. The results are interpreted in terms of a similar conformational distribution of aminoalkyl, oxygen, and aromatic functional groups of the (S)-benzodioxans and (R)-epinephrine. | [
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|
PMID:17750 | Synthesis and biological evaluation of a tetrahydroisoquinoline derivative possessing selective beta2-adrenergic agonist activity. | This paper reports the synthesis of 4-(3,4,5-trimethoxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (2) and 2-(3,4-dihydroxyphenyl)-3-(3,4,5-trimethoxyphenyl)propylamine (3). The biological activity of these agents relative to that of trimetoquinol (1) in guinea pig atria and guinea pig trachea is reported. The relative activities in relaxation of guinea pig trachea is 1 greater than 2 greater than 3 while in the chronotropic response in guinea pig atria the relative order of activity is 1 greater than 3 greater than 2. | Synthesis and biological evaluation of a tetrahydroisoquinoline derivative possessing selective beta2-adrenergic agonist activity. This paper reports the synthesis of 4-(3,4,5-trimethoxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (2) and 2-(3,4-dihydroxyphenyl)-3-(3,4,5-trimethoxyphenyl)propylamine (3). The biological activity of these agents relative to that of trimetoquinol (1) in guinea pig atria and guinea pig trachea is reported. The relative activities in relaxation of guinea pig trachea is 1 greater than 2 greater than 3 while in the chronotropic response in guinea pig atria the relative order of activity is 1 greater than 3 greater than 2. | [
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|
PMID:17751 | Cyanoguanidine-thiourea equivalence in the development of the histamine H2-receptor antagonist, cimetidine. | In the histamine H2-receptor antagonist metiamide (2a) isosteric replacement of thione sulfur (=S) by carbonyl oxygen (=O) or imino nitrogen (=NH) affords the urea 2c and guanidine 2d which are antagonists of decreased potency. The guanidine is very basic and at physiological pH is completely protonated. However, introduction of strongly electronegative substituents into the guanidine group reduces basicity and gives potent H2-receptor antagonists, viz. the cyanoguanidine 2b (cimetidine, "Tagamet") and nitroguanidine 2e. A correspondence between the activity of thioureas and cyanoguanidines is demonstrated for a series of structures 1-4. The close correspondence between cyanoguanidine and thiourea in many physicochemical properties and the pharmacological equivalence of these groups in H2-receptor antagonists leads to the description of cyanoguanidine and thiourea as bioisosteres. Acid hydrolysis of the cyanoguanidine 2b yields the carbamoylguanidine 2f at ambient temperatures and the guanidine 2d at elevated temperatures. Cimetidine is slightly more active than metiamide in vivo as an inhibitor of histamine-stimulated gastric acid secretion and has clinical use in the treatment of peptic ulcer and associated gastrointestinal disorders. | Cyanoguanidine-thiourea equivalence in the development of the histamine H2-receptor antagonist, cimetidine. In the histamine H2-receptor antagonist metiamide (2a) isosteric replacement of thione sulfur (=S) by carbonyl oxygen (=O) or imino nitrogen (=NH) affords the urea 2c and guanidine 2d which are antagonists of decreased potency. The guanidine is very basic and at physiological pH is completely protonated. However, introduction of strongly electronegative substituents into the guanidine group reduces basicity and gives potent H2-receptor antagonists, viz. the cyanoguanidine 2b (cimetidine, "Tagamet") and nitroguanidine 2e. A correspondence between the activity of thioureas and cyanoguanidines is demonstrated for a series of structures 1-4. The close correspondence between cyanoguanidine and thiourea in many physicochemical properties and the pharmacological equivalence of these groups in H2-receptor antagonists leads to the description of cyanoguanidine and thiourea as bioisosteres. Acid hydrolysis of the cyanoguanidine 2b yields the carbamoylguanidine 2f at ambient temperatures and the guanidine 2d at elevated temperatures. Cimetidine is slightly more active than metiamide in vivo as an inhibitor of histamine-stimulated gastric acid secretion and has clinical use in the treatment of peptic ulcer and associated gastrointestinal disorders. | [
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|
PMID:17752 | beta-Adrenoceptor blocking activity of halogenated thienylethanolamine derivatives. | The synthesis of a number of ring-halogenated N-isopropyl- and N-tert-butyl-2-amino-1-(2-thienyl)ethanols has been carried out in order to ascertain the influence of chloro or bromo substitution at the thiophene moiety on their blocking beta-adrenoceptor activity. It was found that chloro- and bromo-substituted compounds exhibited a similar activity. Monohalo substitution at positions C4 or C5 of the thiophene ring resulted in comparable blocking potency, whereas C3 halo-substituted compounds were practically devoid of activity. The highest activity in these series was observed with compounds dihalogenated at C4 and C5, their effect on myocardial beta-receptors being comparable to that of propranolol. | beta-Adrenoceptor blocking activity of halogenated thienylethanolamine derivatives. The synthesis of a number of ring-halogenated N-isopropyl- and N-tert-butyl-2-amino-1-(2-thienyl)ethanols has been carried out in order to ascertain the influence of chloro or bromo substitution at the thiophene moiety on their blocking beta-adrenoceptor activity. It was found that chloro- and bromo-substituted compounds exhibited a similar activity. Monohalo substitution at positions C4 or C5 of the thiophene ring resulted in comparable blocking potency, whereas C3 halo-substituted compounds were practically devoid of activity. The highest activity in these series was observed with compounds dihalogenated at C4 and C5, their effect on myocardial beta-receptors being comparable to that of propranolol. | [
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|
PMID:17753 | B/C-cis- and -trans-1,3,4,9,10,10a-Hexahydro-2H-10,4a-methanoiminoethanophenanthrene (homo- and homoisomorphinan) derivatives as analgesics. | N-Alkyl derivatives of B/C-cis- and B/C-trans-6-hydroxy-1,3,4,9,10,10a-hexahydro-2H-10,4a-methanoimino-ethanophenanthrene have been prepared. The analgesic potency and physical dependence capacity of these compounds were determined. The N-methyl derivatives were analgesically equipotent with morphine. None of these compounds except the N-methyl-B/C-trans isomer 2b suppressed or precipitated the abstinence syndrome. Compound 2b was a narcotic agonist. The N-methyl-B/C-cis compound 2a appears to warrant further examination for its potential as a potent analgesic having no physical dependence liability. | B/C-cis- and -trans-1,3,4,9,10,10a-Hexahydro-2H-10,4a-methanoiminoethanophenanthrene (homo- and homoisomorphinan) derivatives as analgesics. N-Alkyl derivatives of B/C-cis- and B/C-trans-6-hydroxy-1,3,4,9,10,10a-hexahydro-2H-10,4a-methanoimino-ethanophenanthrene have been prepared. The analgesic potency and physical dependence capacity of these compounds were determined. The N-methyl derivatives were analgesically equipotent with morphine. None of these compounds except the N-methyl-B/C-trans isomer 2b suppressed or precipitated the abstinence syndrome. Compound 2b was a narcotic agonist. The N-methyl-B/C-cis compound 2a appears to warrant further examination for its potential as a potent analgesic having no physical dependence liability. | [
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|
PMID:17756 | Retro-umbilical ectopic testicle: report of a case. | A case of a retro-umbilical ectopic testicle in a 13-year-old cryptorchid boy is reported. To our knowledge this has not been reported previously. There is no definite explanation for this highly aberrant ectopia. During the neonatal period the boy had an umbilical suppuration that required drainage. This may offer a possible explanation since the consequent healing process could have pulled the peritoneum upwards, dragging the testicle with it. Despite the high position of this testicle (and previous operation on the other side) it was easy to cross over both testes successfully to the heterolateral scrotum. | Retro-umbilical ectopic testicle: report of a case. A case of a retro-umbilical ectopic testicle in a 13-year-old cryptorchid boy is reported. To our knowledge this has not been reported previously. There is no definite explanation for this highly aberrant ectopia. During the neonatal period the boy had an umbilical suppuration that required drainage. This may offer a possible explanation since the consequent healing process could have pulled the peritoneum upwards, dragging the testicle with it. Despite the high position of this testicle (and previous operation on the other side) it was easy to cross over both testes successfully to the heterolateral scrotum. | [
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|
PMID:17757 | Complications of autonomic dysreflexia. | Autonomic dysreflexia can be a life-threatening problem if not promptly recognized and treated. Since the most common cause is bladder distension it is essential that the urologist be familiar with this syndrome. Several patients with serious complications owing to autonomic dysreflexia, including 1 mortality, are presented. The complications of autonomic dysreflexia result from a sudden marked rise in blood pressure, which may be severe enough to rupture single or multiple cerebral blood vessels or lead to a considerable increase in intracranial pressure. The neurophysiology, clinical features and therapeutic measures are discussed. | Complications of autonomic dysreflexia. Autonomic dysreflexia can be a life-threatening problem if not promptly recognized and treated. Since the most common cause is bladder distension it is essential that the urologist be familiar with this syndrome. Several patients with serious complications owing to autonomic dysreflexia, including 1 mortality, are presented. The complications of autonomic dysreflexia result from a sudden marked rise in blood pressure, which may be severe enough to rupture single or multiple cerebral blood vessels or lead to a considerable increase in intracranial pressure. The neurophysiology, clinical features and therapeutic measures are discussed. | [
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|
PMID:17760 | High-flow total body perfusion with severe hemodilution and normothermia in infants weighing less than 10 kg--safe limits of hemodilution in cardiopulmonary bypass in infants. | Cardiopulmonary bypass with 17 to 57 per cent dilution of hemoglobin for repair of ventricular septal defect (VSD) was applied to 26 infants weighing less than 10 kg at normal temperature. The higher flow rate was required to compensate the reduced oxygen carrying capacity and to maintain an adequate arterial pressure in proportion to a decrease of hemoglobin value. Perfusion index resulted in 3.0 to 6.5 L/m2/min in this series. When the dilution ratio of hemoglobin became more than 50 per cent and high flow rate was required, however, oxygen transfer ratio decreased remarkably on account of inadequate oxygen delivery and imparied venous return. In these cases, it was difficult to remove the diluent immediately after the operation in spite of powerful diuretic therapy. The results of the present study indicate that the safe limits of hemodilution is 50 per cent in cardiopulmonary bypass at normal temperature in infants. | High-flow total body perfusion with severe hemodilution and normothermia in infants weighing less than 10 kg--safe limits of hemodilution in cardiopulmonary bypass in infants. Cardiopulmonary bypass with 17 to 57 per cent dilution of hemoglobin for repair of ventricular septal defect (VSD) was applied to 26 infants weighing less than 10 kg at normal temperature. The higher flow rate was required to compensate the reduced oxygen carrying capacity and to maintain an adequate arterial pressure in proportion to a decrease of hemoglobin value. Perfusion index resulted in 3.0 to 6.5 L/m2/min in this series. When the dilution ratio of hemoglobin became more than 50 per cent and high flow rate was required, however, oxygen transfer ratio decreased remarkably on account of inadequate oxygen delivery and imparied venous return. In these cases, it was difficult to remove the diluent immediately after the operation in spite of powerful diuretic therapy. The results of the present study indicate that the safe limits of hemodilution is 50 per cent in cardiopulmonary bypass at normal temperature in infants. | [
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|
PMID:17762 | Potassium and intracellular pH. | Recent work has clarified some of the complex interrelationships between cell pH and potassium. These studies have been limited by the techniques available for accurately measuring cell pH. At present it is obvious that intracellular pH is a major regulator of the cellular potassium concentration, but the precise relationship between these two is still uncertain. It has become increasingly clear, however, that no simple relationship exists between the intracellular to extracellular hydrogen ion and potassium ion ratios. Many experiments do demonstrate that the extracellular metabolic alkalosis of potassium depletion is accompanied by a decrease in skeletal muscle pH in rat, rabbit, and probably dog. The response of cardiac and renal tubular cell pH to potassium depletion is less clear, although most evidence indicates that there is also a reduction in the pH of these tissues. This effect on cell pH appears to be independent of chloride. By contrast, hyperkalemia seems to raise muscle cell pH at the same time it induces an extracellular metabolic acidosis. The metabolic and physiologic consequences of potassium-induced alterations in cell pH have yet to be fully elucidated. | Potassium and intracellular pH. Recent work has clarified some of the complex interrelationships between cell pH and potassium. These studies have been limited by the techniques available for accurately measuring cell pH. At present it is obvious that intracellular pH is a major regulator of the cellular potassium concentration, but the precise relationship between these two is still uncertain. It has become increasingly clear, however, that no simple relationship exists between the intracellular to extracellular hydrogen ion and potassium ion ratios. Many experiments do demonstrate that the extracellular metabolic alkalosis of potassium depletion is accompanied by a decrease in skeletal muscle pH in rat, rabbit, and probably dog. The response of cardiac and renal tubular cell pH to potassium depletion is less clear, although most evidence indicates that there is also a reduction in the pH of these tissues. This effect on cell pH appears to be independent of chloride. By contrast, hyperkalemia seems to raise muscle cell pH at the same time it induces an extracellular metabolic acidosis. The metabolic and physiologic consequences of potassium-induced alterations in cell pH have yet to be fully elucidated. | [
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|
PMID:17763 | Relationship of renal ammonia production and potassium homeostasis. | Renal ammonia production appears to be intimately related to potassium homeostasis, and the two may comprise the components of a closed loop regulatory system. Studies with both intact organisms and in vitro systems indicate that potassium depletion stimulates and chronic potassium-loading suppresses renal ammonia production. An increase in ammoniagenesis has been shown to decrease potassium excretion. These observations suggest that changes in potassium modulate ammonia production, which in turn maintains hydrogen ion homeostasis and influences potassium excretion. Potassium depletion increases rat renal cortical ammonia production by altering metabolism in fashion identical to metabolic acidosis, but there is no convincing evidence that both processes are mediated by similar changes in either cellular hydrogen ion or potassium concentration. By contrast, potassium-loading, which depresses ammonia production, appears to affect primarily the outer medulla, a region that is not influenced by potassium depletion. Thus, potassium-loading apparently affects different portions of the renal tubule than depletion does, but the specific mechanism and physiologic significance of the different sites of action is unknown. | Relationship of renal ammonia production and potassium homeostasis. Renal ammonia production appears to be intimately related to potassium homeostasis, and the two may comprise the components of a closed loop regulatory system. Studies with both intact organisms and in vitro systems indicate that potassium depletion stimulates and chronic potassium-loading suppresses renal ammonia production. An increase in ammoniagenesis has been shown to decrease potassium excretion. These observations suggest that changes in potassium modulate ammonia production, which in turn maintains hydrogen ion homeostasis and influences potassium excretion. Potassium depletion increases rat renal cortical ammonia production by altering metabolism in fashion identical to metabolic acidosis, but there is no convincing evidence that both processes are mediated by similar changes in either cellular hydrogen ion or potassium concentration. By contrast, potassium-loading, which depresses ammonia production, appears to affect primarily the outer medulla, a region that is not influenced by potassium depletion. Thus, potassium-loading apparently affects different portions of the renal tubule than depletion does, but the specific mechanism and physiologic significance of the different sites of action is unknown. | [
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|
PMID:17766 | Side effects and contraindications of beta-receptor blocking agents. | Unwanted effects of beta-receptor blocking agents can be divided into three categories: 1. Those arising specifically from the pharmacologic, i.e., beta-blocking action. 2. Side effects not directly (or not with certainty) related to beta-blockade. 3. Adverse and potentially specific reactions to individual beta-blocking agents. Category 1 covers the majority of adverse effects (heart failure, severe bradycardia and hypotension, arterial insufficiency, increased airways resistance, gastrointestinal symptoms, hypoglycemia). These can largely be avoided by proper selection and preparation of patients. Category 2 covers cutaneous reactions (rashes, alopecia, pruritus), purpura (thrombocytopenic and nonthrombocytopenic) etc. as well as side effects attributable to the central nervous system (antianxiety effects, nightmares etc.). In the third category the "oculo-cutaneous syndrome" associated with practolol is discussed. | Side effects and contraindications of beta-receptor blocking agents. Unwanted effects of beta-receptor blocking agents can be divided into three categories: 1. Those arising specifically from the pharmacologic, i.e., beta-blocking action. 2. Side effects not directly (or not with certainty) related to beta-blockade. 3. Adverse and potentially specific reactions to individual beta-blocking agents. Category 1 covers the majority of adverse effects (heart failure, severe bradycardia and hypotension, arterial insufficiency, increased airways resistance, gastrointestinal symptoms, hypoglycemia). These can largely be avoided by proper selection and preparation of patients. Category 2 covers cutaneous reactions (rashes, alopecia, pruritus), purpura (thrombocytopenic and nonthrombocytopenic) etc. as well as side effects attributable to the central nervous system (antianxiety effects, nightmares etc.). In the third category the "oculo-cutaneous syndrome" associated with practolol is discussed. | [
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|
PMID:17770 | [Psychopharmacology in aviation and astronautics]. | Flights aboard modern vehicles are associated with high nervous-emotional and physical stresses. This may induce depletion of reserve capabilities, development of fatigue and, consequently, reduction of work capacity of crewmembers. The paper discusses approaches and results of the use of drugs by pilots and cosmonauts in order to alleviate their fatigue and emotional stress. It gives indications and contraindications for the adminstration of stimulants and tranquilizers. On the basis of a comprehensive analysis of the literature data and their own findings, the authors draw the conclusion that the use of stimulants and anxiolytics may increase the level of reliability and performance of air- and spacecraft pilots during programmed and, particularly, contigent situations of the flight. | [Psychopharmacology in aviation and astronautics]. Flights aboard modern vehicles are associated with high nervous-emotional and physical stresses. This may induce depletion of reserve capabilities, development of fatigue and, consequently, reduction of work capacity of crewmembers. The paper discusses approaches and results of the use of drugs by pilots and cosmonauts in order to alleviate their fatigue and emotional stress. It gives indications and contraindications for the adminstration of stimulants and tranquilizers. On the basis of a comprehensive analysis of the literature data and their own findings, the authors draw the conclusion that the use of stimulants and anxiolytics may increase the level of reliability and performance of air- and spacecraft pilots during programmed and, particularly, contigent situations of the flight. | [
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|
PMID:17771 | [Psychoneurological requirements in evaluating the functional state of cosmonauts in flight]. | Selection and training of experts-psychoneurologists to be included into a team of operational medical monitoring are described. In regards to the capacity for synonymic paraphrasing, the conditions required for stability of individual opinions and their coincidence in different people are discussed. The capacity refers to the choice of the most suitable word among a number of synonyms. On this basis it is recommended to use similarity problems in appraising the function of an expert who involves verbal description of various events. | [Psychoneurological requirements in evaluating the functional state of cosmonauts in flight]. Selection and training of experts-psychoneurologists to be included into a team of operational medical monitoring are described. In regards to the capacity for synonymic paraphrasing, the conditions required for stability of individual opinions and their coincidence in different people are discussed. The capacity refers to the choice of the most suitable word among a number of synonyms. On this basis it is recommended to use similarity problems in appraising the function of an expert who involves verbal description of various events. | [
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|
PMID:17772 | [Dynamic control of the atmospheric parameters of spacecraft]. | On the basis of experimental data a mathematical model of relationships between physiological parameters, oxygen content in the atmosphere and exercises has been developed. Using the model, it has been demonstrated that circulation and respiration reactions to exercises can be optimized by increasing the partial pressure of oxygen as related to the exercise level. A probable law of the dynamic and physiologically optimal control of the oxygen content in the space cabin atmosphere has been advanced. In cases of an uncontrolled decrease of PO2 the oxygen supply of crewmembers can be optimized by the dynamic control of the ambient CO2 content. | [Dynamic control of the atmospheric parameters of spacecraft]. On the basis of experimental data a mathematical model of relationships between physiological parameters, oxygen content in the atmosphere and exercises has been developed. Using the model, it has been demonstrated that circulation and respiration reactions to exercises can be optimized by increasing the partial pressure of oxygen as related to the exercise level. A probable law of the dynamic and physiologically optimal control of the oxygen content in the space cabin atmosphere has been advanced. In cases of an uncontrolled decrease of PO2 the oxygen supply of crewmembers can be optimized by the dynamic control of the ambient CO2 content. | [
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|
PMID:17773 | [Electrolyte content in the blood of animals and potassium ion transport in the erythrocytes under the action of a constant magnetic field]. | The content of potassium and sodium ions in the blood and plasma of rats exposed to constant magnetic fileds (CMF) of 1000 and 4500 oersted for varying time was studied. The transport of potassium ions through membranes of red blood cells was examined in in bitro experiments using a CMF of 4500 oersted. An exposure of animals to a CMF of 1000 oersted for 1 and 24 hours did not produce significant changes in the potassium and sodium content in blood. An exposure of animals to a CMF of 4500 oersted induced certain changes in the electrolyte composition of the blood. During an hour exposure the most distinct changes were an increase in the potassium concentration in plasma and its decrease in blood. During a 3-hour exposure the most marked change was a decrease in the sodium content in blood. Repeated and prolonged chronic exposure did not bring about summation of the effects. The exposure did not influence the transport of potassium ions. The exposure did not affect the pH and hematokrit values of the blood. | [Electrolyte content in the blood of animals and potassium ion transport in the erythrocytes under the action of a constant magnetic field]. The content of potassium and sodium ions in the blood and plasma of rats exposed to constant magnetic fileds (CMF) of 1000 and 4500 oersted for varying time was studied. The transport of potassium ions through membranes of red blood cells was examined in in bitro experiments using a CMF of 4500 oersted. An exposure of animals to a CMF of 1000 oersted for 1 and 24 hours did not produce significant changes in the potassium and sodium content in blood. An exposure of animals to a CMF of 4500 oersted induced certain changes in the electrolyte composition of the blood. During an hour exposure the most distinct changes were an increase in the potassium concentration in plasma and its decrease in blood. During a 3-hour exposure the most marked change was a decrease in the sodium content in blood. Repeated and prolonged chronic exposure did not bring about summation of the effects. The exposure did not influence the transport of potassium ions. The exposure did not affect the pH and hematokrit values of the blood. | [
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|
PMID:17774 | [Study of the nature of the associated microflora in the prolonged substrateless cultivation of beet plants]. | The purpose of the present investigation was to study variations in the population density of microorganisms, their qualitative and quantitative composition during substrate-free cultivation of beats. The results obtained show that the microbial number in the nutrient solution increased by the time of intensive growth of beats and decreased by the time of harvesting. The number of root microorganisms was much greater than the total number of microorganisms in the nutrient solution. Oligonitrophils and nitrogen fixing bacteria were found in the solution. This may be associated with a transient decrease of nitrogen in the solution. The number of ammonifiers and denitrifiers in the solution increased significantly by the end of plant vegetation; the amount of denitrifiers inhabiting the roots decreased during vegetation and that of ammonifiers increased. In the middle of vegetation cellulose decomposing aerobes appeared; this might occur since root hairs began to die off. By the end of vegetation an insignificant amount of fungi was also found. Nitrifying and spore-forming microorganisms were not detected. The identification of predominant microbial species showed them to be bacteria of the genera Pseudomonas and Mycobacterium. Besides, microorganisms of the genera Bacterium, Micrococcus, Mycococcus, Chromobacterium and Pseudobacterium also occurred. | [Study of the nature of the associated microflora in the prolonged substrateless cultivation of beet plants]. The purpose of the present investigation was to study variations in the population density of microorganisms, their qualitative and quantitative composition during substrate-free cultivation of beats. The results obtained show that the microbial number in the nutrient solution increased by the time of intensive growth of beats and decreased by the time of harvesting. The number of root microorganisms was much greater than the total number of microorganisms in the nutrient solution. Oligonitrophils and nitrogen fixing bacteria were found in the solution. This may be associated with a transient decrease of nitrogen in the solution. The number of ammonifiers and denitrifiers in the solution increased significantly by the end of plant vegetation; the amount of denitrifiers inhabiting the roots decreased during vegetation and that of ammonifiers increased. In the middle of vegetation cellulose decomposing aerobes appeared; this might occur since root hairs began to die off. By the end of vegetation an insignificant amount of fungi was also found. Nitrifying and spore-forming microorganisms were not detected. The identification of predominant microbial species showed them to be bacteria of the genera Pseudomonas and Mycobacterium. Besides, microorganisms of the genera Bacterium, Micrococcus, Mycococcus, Chromobacterium and Pseudobacterium also occurred. | [
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PMID:17779 | [The use of Goetze cerclage in the treatment of tibial fractures]. | On the basis of the authors' experiences and the data of the available literature Goetze's cerclage in the treatment of tibia fractures is discussed--as far as the authors know, this is the first report of this method in the Hungarian literature. On the basis of the authors' material, the method is very useful for the treatment of the long, spiral and oblique fractures of the leg. | [The use of Goetze cerclage in the treatment of tibial fractures]. On the basis of the authors' experiences and the data of the available literature Goetze's cerclage in the treatment of tibia fractures is discussed--as far as the authors know, this is the first report of this method in the Hungarian literature. On the basis of the authors' material, the method is very useful for the treatment of the long, spiral and oblique fractures of the leg. | [
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|
PMID:17781 | [Diabetic osteoarthropathy of rare localization]. | The typical location of diabetic osteoarthropathy is the foot. Involvement of other joints is rare. In the case treated by the author, the osteoarthropathy of the ankle and knee joints presented at the same time. The process healed in the ankle joint by grave deformity and arthrosis deformans resulted in the knee joint. If arthrosis appears in an unusual location, it is worth while to look for diabetes. | [Diabetic osteoarthropathy of rare localization]. The typical location of diabetic osteoarthropathy is the foot. Involvement of other joints is rare. In the case treated by the author, the osteoarthropathy of the ankle and knee joints presented at the same time. The process healed in the ankle joint by grave deformity and arthrosis deformans resulted in the knee joint. If arthrosis appears in an unusual location, it is worth while to look for diabetes. | [
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|
PMID:17782 | [Thoracic injury and fat embolism]. | The authors state that fat embolism occurs rather frequently following thoracic injuries. It is difficult to make a diagnosis because of the complexity of the symptoms. The correct evaluation of the characteristic clinical and laboratory signs arising after a period free of symptoms is essential. The authors outline the brief case history of a successfully treated patient, who recovered, owing to the use of the respirator in the intensive care unit. | [Thoracic injury and fat embolism]. The authors state that fat embolism occurs rather frequently following thoracic injuries. It is difficult to make a diagnosis because of the complexity of the symptoms. The correct evaluation of the characteristic clinical and laboratory signs arising after a period free of symptoms is essential. The authors outline the brief case history of a successfully treated patient, who recovered, owing to the use of the respirator in the intensive care unit. | [
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|
PMID:17783 | [Vascular injury associated with shoulder luxation]. | The author reports on the rupture of subscapular artery that followed the reduction of an anterior dislocation of the shoulder joint. On this occasion, vascular injuries associated with shoulder joint dislocation, their diagnosis and treatment is discussed in the article. The aim of the author was to remind the reader to a complication of our everyday activity. He wants to call attention to the importance of gentle manipulation and the careful observation of the circulation after reduction. | [Vascular injury associated with shoulder luxation]. The author reports on the rupture of subscapular artery that followed the reduction of an anterior dislocation of the shoulder joint. On this occasion, vascular injuries associated with shoulder joint dislocation, their diagnosis and treatment is discussed in the article. The aim of the author was to remind the reader to a complication of our everyday activity. He wants to call attention to the importance of gentle manipulation and the careful observation of the circulation after reduction. | [
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|
PMID:17784 | [15 years of anesthesia in hand surgery]. | The authors give an account on their experiences in the anaesthesy on the hand area. Methods used during a 15 year period are reported, different sorts of narcosis and the intravenous regional anaesthesy is discussed. Advantages and disadvantages of the particular methods are outlined. | [15 years of anesthesia in hand surgery]. The authors give an account on their experiences in the anaesthesy on the hand area. Methods used during a 15 year period are reported, different sorts of narcosis and the intravenous regional anaesthesy is discussed. Advantages and disadvantages of the particular methods are outlined. | [
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|
PMID:17787 | [Early surgery of the soft tissues in congenital clubfoot]. | The role and position of early complete operative procedures on the soft tissues in the treatment of the congenital club foot is discussed in the article. The authors report on the operative indications in principles and in their own practice. Closed and operative treatment are not contradictory but complementary terms. The aim of the operative treatment is to bring all residual contractures following conservative treatment to an end. It must be done by relatively minimal intervention on the soft tissues and as early as possible. Thus the proper development of the foot and the prevention of bone deformation can be attained. | [Early surgery of the soft tissues in congenital clubfoot]. The role and position of early complete operative procedures on the soft tissues in the treatment of the congenital club foot is discussed in the article. The authors report on the operative indications in principles and in their own practice. Closed and operative treatment are not contradictory but complementary terms. The aim of the operative treatment is to bring all residual contractures following conservative treatment to an end. It must be done by relatively minimal intervention on the soft tissues and as early as possible. Thus the proper development of the foot and the prevention of bone deformation can be attained. | [
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|
PMID:17788 | [Management of mass injuries in railway accidents]. | Authors write up the experiences they gained at repeated train accidents on the same section of railway line. The circumstances of the two accidents are evaluated and analysed. The experiences they obtained at the first accident were put to use the second time. The authors stress that the growing number of mass accidents makes it necessary to prepare an alarm and provision plan for every institution. | [Management of mass injuries in railway accidents]. Authors write up the experiences they gained at repeated train accidents on the same section of railway line. The circumstances of the two accidents are evaluated and analysed. The experiences they obtained at the first accident were put to use the second time. The authors stress that the growing number of mass accidents makes it necessary to prepare an alarm and provision plan for every institution. | [
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|
PMID:17790 | [Surgical management of thoracic and thoraco-abdominal injuries]. | From 1970 to 1974 407 patients with thoracic injuries have been treated by the authors in the 2nd Surgical and Thoracic Surgical Department of the "János" Hospital, Budapest--out of them 190 patients were classified as severely injured. The material and the operative technique in isolated thoracal and combined thoracal-abdominal injuries are discussed. The importance of the operative stabilization of the thoracic wall is emphasized and fixation of the thoracic wall by means of pericostal sutures is advocated, if because of the intrathoracal injury--just the same--thoracotomy is to be performed. On the basis of their experiences and because of the risk of late complications and of residues impairing the function in certain types of the thoracal injuries surgical treatment is advocated by the authors. | [Surgical management of thoracic and thoraco-abdominal injuries]. From 1970 to 1974 407 patients with thoracic injuries have been treated by the authors in the 2nd Surgical and Thoracic Surgical Department of the "János" Hospital, Budapest--out of them 190 patients were classified as severely injured. The material and the operative technique in isolated thoracal and combined thoracal-abdominal injuries are discussed. The importance of the operative stabilization of the thoracic wall is emphasized and fixation of the thoracic wall by means of pericostal sutures is advocated, if because of the intrathoracal injury--just the same--thoracotomy is to be performed. On the basis of their experiences and because of the risk of late complications and of residues impairing the function in certain types of the thoracal injuries surgical treatment is advocated by the authors. | [
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|
PMID:17791 | [Fracture-dislocation of the hip joint. II. Central luxation]. | 64 cases of central luxation are analysed by the authors. 4--10 years after the injury 31 patients appeared at the check-inspection. It has been stated by the authors that because of the severity of the injury and the age of the injured patients surgical intervention may be performed even in case of greater dislocation but rarely. The result of the conservative treatment is in the case of congruency of the loading surface satisfactory, but it is even in the case of incongruency generally better than it may be supposed on the basis of the roentgenogram. For the prevention of later occurring severe arthrosis the importance of the rehabilitation is emphasized by the authors. | [Fracture-dislocation of the hip joint. II. Central luxation]. 64 cases of central luxation are analysed by the authors. 4--10 years after the injury 31 patients appeared at the check-inspection. It has been stated by the authors that because of the severity of the injury and the age of the injured patients surgical intervention may be performed even in case of greater dislocation but rarely. The result of the conservative treatment is in the case of congruency of the loading surface satisfactory, but it is even in the case of incongruency generally better than it may be supposed on the basis of the roentgenogram. For the prevention of later occurring severe arthrosis the importance of the rehabilitation is emphasized by the authors. | [
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|
PMID:17792 | [Pathological sagittal shifting of vertebral bodies]. | The results of the lumbar spine examinations performed in one year and a half are evaluated by the authors. The types of the sagittal positional changes of the vertebral bodies are discussed in detail. The importance of the functionally centrated and lateral telephotographs in the diagnosis of the antepositional olisthesis and the retropositional retrolisthesis is pointed out, and the indication and the differential diagnostical value of the oblique roentgenograms are dealt with. | [Pathological sagittal shifting of vertebral bodies]. The results of the lumbar spine examinations performed in one year and a half are evaluated by the authors. The types of the sagittal positional changes of the vertebral bodies are discussed in detail. The importance of the functionally centrated and lateral telephotographs in the diagnosis of the antepositional olisthesis and the retropositional retrolisthesis is pointed out, and the indication and the differential diagnostical value of the oblique roentgenograms are dealt with. | [
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|
PMID:17794 | Drug utilization review in an HMO. I. Introduction and examples of methodology. | An experimental drug utilization review program was developed for a health maintenance organization (HMO). The objectives of the program were to develop and implement an ongoing mechanism for reviewing drug use using criteria based on the scientific literature, and to evaluate the effect of the drug use review program on physician precribing patterns. Seven therapeutic categories of drugs, accounting for over 65 per cent of prescribing, were selected and criteria developed for their use. The drug use review prcedure is described briefly. The evaluation of the drug use review program is based on a comparison of rates of prescription use for specific therapeutic categories before and after the criteria were ceveloped and approved. As an example, data for the antihistamine therapeutic category are presented. Criteria for prescribing antihistamines suggested restricting use of combination cold preparations and refraiming from antihistamine use in viral upper respiratory tract infections. After the criteria were adopted, prescribing of antihistamines for viral URIs declined, particularly in pediatrics. In general, prescribing of combination antihistamine preparations did not change; where one combination preparation was deleted from the formulary, prescribers appeared to substitute another combination preparation. | Drug utilization review in an HMO. I. Introduction and examples of methodology. An experimental drug utilization review program was developed for a health maintenance organization (HMO). The objectives of the program were to develop and implement an ongoing mechanism for reviewing drug use using criteria based on the scientific literature, and to evaluate the effect of the drug use review program on physician precribing patterns. Seven therapeutic categories of drugs, accounting for over 65 per cent of prescribing, were selected and criteria developed for their use. The drug use review prcedure is described briefly. The evaluation of the drug use review program is based on a comparison of rates of prescription use for specific therapeutic categories before and after the criteria were ceveloped and approved. As an example, data for the antihistamine therapeutic category are presented. Criteria for prescribing antihistamines suggested restricting use of combination cold preparations and refraiming from antihistamine use in viral upper respiratory tract infections. After the criteria were adopted, prescribing of antihistamines for viral URIs declined, particularly in pediatrics. In general, prescribing of combination antihistamine preparations did not change; where one combination preparation was deleted from the formulary, prescribers appeared to substitute another combination preparation. | [
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|
PMID:17795 | [Effects and side effects of oral drugs used in common cold (author's transl)]. | A report about effects and side effects of common cold remedies that are taken orally is presented. There are advantages and disadvantages in the use of either locally administered nose drops or orally taken cold remedies, which are compared to each other from the pharmacological point of view. Based on the experience of a great toxicological center and a pediatric clinic, the clinical symptoms of poisoning as a result of accidental ingestion are described and contraindications are pointed out. It is concluded that, especially in children, the dosage of both oral and local drugs should not exceed the recommended amount. | [Effects and side effects of oral drugs used in common cold (author's transl)]. A report about effects and side effects of common cold remedies that are taken orally is presented. There are advantages and disadvantages in the use of either locally administered nose drops or orally taken cold remedies, which are compared to each other from the pharmacological point of view. Based on the experience of a great toxicological center and a pediatric clinic, the clinical symptoms of poisoning as a result of accidental ingestion are described and contraindications are pointed out. It is concluded that, especially in children, the dosage of both oral and local drugs should not exceed the recommended amount. | [
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|
PMID:17808 | Alkaline ribonuclease inhibitor in human thyroid. | Thyroids of goitrogen-treated rats contain increased amounts of a protein inhibitor of ribonuclease activity at pH greater than 7 (alkaline ribonuclease inhibitor, ARI). We report here that thyroids from hyperthyroid patients contain more ARI than normal human thyroids. This increase parallels RNA concentration. The inhibitor is heat labile, inactivated by sulfhydryl blocking agents, and has a molecular weight near 50, 000 daltons. ARI is quantitated by its activity against bovine pancreatic RNase, but it also inhibits human thyroid RNase. Analyses of a solitary toxic nodule and its surrounding suppressed tissue confirm in tissues from a single patient our results in tissue from numbers of thyrotoxic and euthyroid individuals and decrease the likelihood that changes are induced by antithyroid medication. A possible regulatory role for ARI is suggested. | Alkaline ribonuclease inhibitor in human thyroid. Thyroids of goitrogen-treated rats contain increased amounts of a protein inhibitor of ribonuclease activity at pH greater than 7 (alkaline ribonuclease inhibitor, ARI). We report here that thyroids from hyperthyroid patients contain more ARI than normal human thyroids. This increase parallels RNA concentration. The inhibitor is heat labile, inactivated by sulfhydryl blocking agents, and has a molecular weight near 50, 000 daltons. ARI is quantitated by its activity against bovine pancreatic RNase, but it also inhibits human thyroid RNase. Analyses of a solitary toxic nodule and its surrounding suppressed tissue confirm in tissues from a single patient our results in tissue from numbers of thyrotoxic and euthyroid individuals and decrease the likelihood that changes are induced by antithyroid medication. A possible regulatory role for ARI is suggested. | [
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|
PMID:17809 | Alcohol: its effect on the kidney. | The effect of ethanol feeding on renal function, gross and microscopic morphology, and constituent content was determined in alcohol-fed rats and compared to similar studies in isocalorically fed animals ingesting the same diet except that dextrimaltose was isocalorically substituted for ethanol. Alcohol-fed animals have significantly reduced renal function and interstitial edema compared to their isocaloric controls. When renal mass and renal constituent analysis were normalized for body weight, alcohol-fed animals were found to have renal hypertrophy characterized by significantly increased absolute amounts of protein (p less than 0.01), fat (p less than 0.01), and water (p less than 0.01). All of these constituents increased in proportion to their percentage of total renal mass in control animals. In contrast, DNA content per kidney was similar for alcohol and isocalorically fed animals. | Alcohol: its effect on the kidney. The effect of ethanol feeding on renal function, gross and microscopic morphology, and constituent content was determined in alcohol-fed rats and compared to similar studies in isocalorically fed animals ingesting the same diet except that dextrimaltose was isocalorically substituted for ethanol. Alcohol-fed animals have significantly reduced renal function and interstitial edema compared to their isocaloric controls. When renal mass and renal constituent analysis were normalized for body weight, alcohol-fed animals were found to have renal hypertrophy characterized by significantly increased absolute amounts of protein (p less than 0.01), fat (p less than 0.01), and water (p less than 0.01). All of these constituents increased in proportion to their percentage of total renal mass in control animals. In contrast, DNA content per kidney was similar for alcohol and isocalorically fed animals. | [
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PMID:17805 | Lophyrotomin, a new toxic octapeptide from the larvae of sawfly, Lophyrotoma interrupta. | Lophyrotomin, a new toxic octapeptide, has been isolated from sawfly (Lophyrotoma interrupta) larvae using solvent extraction, dialysis, adsorption on polyamide, ion exchange chromatography on DEAE cellulose and silica gel G chromatography. On the basis of evidence from chemical methods, pmr and mass spectrometry, a partial structure is proposed. Lophyrotomin has an approximate intraperitoneal LD50 of 2 mg/kg for mice. | Lophyrotomin, a new toxic octapeptide from the larvae of sawfly, Lophyrotoma interrupta. Lophyrotomin, a new toxic octapeptide, has been isolated from sawfly (Lophyrotoma interrupta) larvae using solvent extraction, dialysis, adsorption on polyamide, ion exchange chromatography on DEAE cellulose and silica gel G chromatography. On the basis of evidence from chemical methods, pmr and mass spectrometry, a partial structure is proposed. Lophyrotomin has an approximate intraperitoneal LD50 of 2 mg/kg for mice. | [
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PMID:17815 | Heterogeneity of staphylococcal enterotoxin A on isoelectric focusing and disc electrophoresis. | Heterogeneity of purified staphylococcal enterotoxin A, obtained from a culture supernatant of Staphylococcus aureus, strain 13N-2909, was demonstrated by isoelectric focusing. The toxin was composed of three immunologically identical fractions with isoelectric points of 6.5, 7.0 and approximately 8.0. Heterogeneity of the toxin was also shown by disc electrophoresis. At pH 8.0 and 9.4 two major bands and a faint minor band were observed, while at pH 4.3 only one band was observed. The faster-moving band for the anode in disc electrophoresis at pH 9.4 was found to correspond with the pI 6.5 component from isoelectric focusing, while the slower-moving band corresponded with the pI 7.0 component. From the results of the electrophoretic migration tests of the toxin, the components corresponding to the two major bands found in disc electrophoresis at pH 9.4 were considered to be charge isomers. | Heterogeneity of staphylococcal enterotoxin A on isoelectric focusing and disc electrophoresis. Heterogeneity of purified staphylococcal enterotoxin A, obtained from a culture supernatant of Staphylococcus aureus, strain 13N-2909, was demonstrated by isoelectric focusing. The toxin was composed of three immunologically identical fractions with isoelectric points of 6.5, 7.0 and approximately 8.0. Heterogeneity of the toxin was also shown by disc electrophoresis. At pH 8.0 and 9.4 two major bands and a faint minor band were observed, while at pH 4.3 only one band was observed. The faster-moving band for the anode in disc electrophoresis at pH 9.4 was found to correspond with the pI 6.5 component from isoelectric focusing, while the slower-moving band corresponded with the pI 7.0 component. From the results of the electrophoretic migration tests of the toxin, the components corresponding to the two major bands found in disc electrophoresis at pH 9.4 were considered to be charge isomers. | [
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PMID:17816 | An analysis of factors influencing the isolation rate of herpes simplex virus. | Attempts were made to improve the rate of isolation of herpes simplex virus (HSV) from clinical specimens by minimizing loss of virus infectivity during transportation and employing the most sensitive cells for isolation. Basical analyses using standard strains of type 1 and type 2 HSV indicated that virus titer decrease was marked even at low temperatures in environments free of proteinous stabilizer such as normal serum or tissue extract, negating the generally held concept that HSV is stable in distilled water. YLE (Earle-lactalbumin HYDROLYSATE-YEAST EXTRACT) medium containing 20% inactivated calf serum was determined to be a transport medium of choice, because degradation of suspended virus during storage and freeze-thawing was negligible and loss of virus during Millipore filtration was minimal. Special coating of the membrane could also be obviated by the use of this solution. In a cell susceptibility test using clinical specimens, secondary rabbit kidney (SRK) cells were the most sensitive, showing a quick development of cytopathic effect. Vero and RK-13 cells were the second best, whereas monkey kidney, HeLa and L cells were far less sensitive. A total of 136 specimens from suspected cases, sent by dermatologists, were tested using SRK cells, and 99 strains of type 1 and 15 strains of type 2 HSV were isolated. Excluding one case from which vaccinia virus was isolated, the isolation rate of HSV was 84.4%. | An analysis of factors influencing the isolation rate of herpes simplex virus. Attempts were made to improve the rate of isolation of herpes simplex virus (HSV) from clinical specimens by minimizing loss of virus infectivity during transportation and employing the most sensitive cells for isolation. Basical analyses using standard strains of type 1 and type 2 HSV indicated that virus titer decrease was marked even at low temperatures in environments free of proteinous stabilizer such as normal serum or tissue extract, negating the generally held concept that HSV is stable in distilled water. YLE (Earle-lactalbumin HYDROLYSATE-YEAST EXTRACT) medium containing 20% inactivated calf serum was determined to be a transport medium of choice, because degradation of suspended virus during storage and freeze-thawing was negligible and loss of virus during Millipore filtration was minimal. Special coating of the membrane could also be obviated by the use of this solution. In a cell susceptibility test using clinical specimens, secondary rabbit kidney (SRK) cells were the most sensitive, showing a quick development of cytopathic effect. Vero and RK-13 cells were the second best, whereas monkey kidney, HeLa and L cells were far less sensitive. A total of 136 specimens from suspected cases, sent by dermatologists, were tested using SRK cells, and 99 strains of type 1 and 15 strains of type 2 HSV were isolated. Excluding one case from which vaccinia virus was isolated, the isolation rate of HSV was 84.4%. | [
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PMID:17817 | Human infection caused by penicillin-insensitive pneumococci. | Three cases of infection, including two fatal ones, caused by pneumococci relatively resistant to penicillin are reported. The patients were a 19-year-old New Guinean with fatal multisegmental pneumonia, a 10-week-old Caucasian infant who died suddenly from purulent meningitis, and an Australian Aboriginal child aged two years with bronchiectasis complicated by pneumococcal bacteraemia. The pneumococci isolated (serotypes 6, 16 and 19) showed minimal inhibitory concentrations of penicillin G ranging from 0-1 microgram/ml to 1-0 microgram/ml (resistance ratios five to 50) and were also relatively resistant to penicillin V, methicillin, cloxacillin and cephalosporins. | Human infection caused by penicillin-insensitive pneumococci. Three cases of infection, including two fatal ones, caused by pneumococci relatively resistant to penicillin are reported. The patients were a 19-year-old New Guinean with fatal multisegmental pneumonia, a 10-week-old Caucasian infant who died suddenly from purulent meningitis, and an Australian Aboriginal child aged two years with bronchiectasis complicated by pneumococcal bacteraemia. The pneumococci isolated (serotypes 6, 16 and 19) showed minimal inhibitory concentrations of penicillin G ranging from 0-1 microgram/ml to 1-0 microgram/ml (resistance ratios five to 50) and were also relatively resistant to penicillin V, methicillin, cloxacillin and cephalosporins. | [
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|
PMID:17818 | [Bromureide intoxication with acute renal failure and bilateral deep vein thrombosis (author's transl)]. | A case of bromureide intoxication with 8 gm. of carbromal is described, in which an acute renal failure and bilateral deep vein thromboses occurred. After treatment with heparin and peritoneal dialysis the symptoms regressed completely. | [Bromureide intoxication with acute renal failure and bilateral deep vein thrombosis (author's transl)]. A case of bromureide intoxication with 8 gm. of carbromal is described, in which an acute renal failure and bilateral deep vein thromboses occurred. After treatment with heparin and peritoneal dialysis the symptoms regressed completely. | [
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|
PMID:17826 | In vivo and in vitro studies of nitrate reductase regulation in Asperillus nidulans. | Induced wildtype cells of A. nidulans rapidly lost NADPH--linked nitrate reductase activity when subjected to carbon and or nitrogen starvation. A constitutive mutant at the regulatory gene for nitrate reductase, nir Ac 1, rapidly lost nitrate reductase activity upon carbon starvation. This loss of activity is thought to be due to a decrease in the NADPH concentration in the cells. Cell free extracts from wildtype cells grown in the presence of nitrate, rapidly lost their nitrate reductase activity when incubated at 25 degrees C. NADPH prevented this loss of activity. Wildtype cells grown in the presence of nitrate and urea have a higher initial NADPH:NADP+ ratio and cell free extracts from such cells lost their nitrate reductase activity slower than extracts of cells grown with nitrate alone. The Pentose Phosphate Pathway mutant, pppB-1, had a lower NADPH concentration compared with the wildtype grown under the same conditions and cell free extracts lost their nitrate reductase activity more rapidly than the wildtype. Cell free extracts of nirAc-1 and a non-inducible mutant for nitrate reductase, nirA- -14, upon incubation lost little of their nitrate reductase activity. | In vivo and in vitro studies of nitrate reductase regulation in Asperillus nidulans. Induced wildtype cells of A. nidulans rapidly lost NADPH--linked nitrate reductase activity when subjected to carbon and or nitrogen starvation. A constitutive mutant at the regulatory gene for nitrate reductase, nir Ac 1, rapidly lost nitrate reductase activity upon carbon starvation. This loss of activity is thought to be due to a decrease in the NADPH concentration in the cells. Cell free extracts from wildtype cells grown in the presence of nitrate, rapidly lost their nitrate reductase activity when incubated at 25 degrees C. NADPH prevented this loss of activity. Wildtype cells grown in the presence of nitrate and urea have a higher initial NADPH:NADP+ ratio and cell free extracts from such cells lost their nitrate reductase activity slower than extracts of cells grown with nitrate alone. The Pentose Phosphate Pathway mutant, pppB-1, had a lower NADPH concentration compared with the wildtype grown under the same conditions and cell free extracts lost their nitrate reductase activity more rapidly than the wildtype. Cell free extracts of nirAc-1 and a non-inducible mutant for nitrate reductase, nirA- -14, upon incubation lost little of their nitrate reductase activity. | [
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PMID:17832 | Mutagenicity of 22 N-nitrosamides and related compounds for Salmonella typhimurium TA1535. | Twenty-two N-nitrosamides and related compounds, including 14 nitrosoureas, 5 nitrosocarbamates, and one nitrosocyanamide, were tested at various concentrations for mutagenic activity towards Salmonella typhimurium TA1535 without the use of microsomes. The ether-water partition coefficient, solubility in water, and half-life in aqueous solution were also measured. Twenty compounds were mutagenic, with "standard mutagenic concentrations" (i.e. those producing 100 mutants/dish) of 0.0024--6500 micron. Standard mutagenic concentration was negatively correlated with the partition coefficient. Three compounds (ethyl 2-acetoxyethylnitrosocarbamate, nitrosocarbaryl, and methylnitrosobenzamide) were more active than the classic mutagen methylnitrosonitroguanidine. Nitrosocarbamates were at least 50 times more mutagenic than the corresponding nitrosoureas. Nitrosodihydrouracil and propylene-nitrosourea were more active than related compounds. Ethylnitrosocyanamide was 730 times more mutagenic than ethylnitrosourea. Fifteen of the test compounds (of which 14 were mutagenic) had previously been assayed in rats for carcinogenicity, all with positive results. | Mutagenicity of 22 N-nitrosamides and related compounds for Salmonella typhimurium TA1535. Twenty-two N-nitrosamides and related compounds, including 14 nitrosoureas, 5 nitrosocarbamates, and one nitrosocyanamide, were tested at various concentrations for mutagenic activity towards Salmonella typhimurium TA1535 without the use of microsomes. The ether-water partition coefficient, solubility in water, and half-life in aqueous solution were also measured. Twenty compounds were mutagenic, with "standard mutagenic concentrations" (i.e. those producing 100 mutants/dish) of 0.0024--6500 micron. Standard mutagenic concentration was negatively correlated with the partition coefficient. Three compounds (ethyl 2-acetoxyethylnitrosocarbamate, nitrosocarbaryl, and methylnitrosobenzamide) were more active than the classic mutagen methylnitrosonitroguanidine. Nitrosocarbamates were at least 50 times more mutagenic than the corresponding nitrosoureas. Nitrosodihydrouracil and propylene-nitrosourea were more active than related compounds. Ethylnitrosocyanamide was 730 times more mutagenic than ethylnitrosourea. Fifteen of the test compounds (of which 14 were mutagenic) had previously been assayed in rats for carcinogenicity, all with positive results. | [
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|
PMID:17833 | Nitrosation in vitro and in vivo by sodium nitrite, and mutagenicity of nitrogenous pesticides. | 37 nitrogenous pesticides, belonging to the chemical groups of amides, carbamates and ureas, were nitrosated with sodium nitrite in vitro. The nitrosated compounds were tested for mutagenic activity in the bacterial spot test with Salmonella typhimurium his G 46. Those pesticides reacting positively in this test after nitrosation were then fed to mice in combination with sodium nitrite in order to assess the formation and mutagenicity of these nitroso compounds in vivo. With the already known exception of ethylenethiourea (ETU), no pesticide produced enhanced numbers of micronuclei in mouse bone-marrow erythrocytes when fed together with nitrite. Dose-response experiments with intraperitoneal injection of N-nitroso-ETU revealed an apparent no-effect level of about 15--18 mg/kg. The findings are correlated with the pesticide residues actually present in the environment. | Nitrosation in vitro and in vivo by sodium nitrite, and mutagenicity of nitrogenous pesticides. 37 nitrogenous pesticides, belonging to the chemical groups of amides, carbamates and ureas, were nitrosated with sodium nitrite in vitro. The nitrosated compounds were tested for mutagenic activity in the bacterial spot test with Salmonella typhimurium his G 46. Those pesticides reacting positively in this test after nitrosation were then fed to mice in combination with sodium nitrite in order to assess the formation and mutagenicity of these nitroso compounds in vivo. With the already known exception of ethylenethiourea (ETU), no pesticide produced enhanced numbers of micronuclei in mouse bone-marrow erythrocytes when fed together with nitrite. Dose-response experiments with intraperitoneal injection of N-nitroso-ETU revealed an apparent no-effect level of about 15--18 mg/kg. The findings are correlated with the pesticide residues actually present in the environment. | [
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|
PMID:17845 | Detection of gastroesophageal reflux in the pediatric-age patient by esophageal intraluminal pH probe measurement (Tuttle test). | The esophageal intraluminal pH probe test (Tuttle test) was used in 24 pediatric-age patients who had symptoms of gastroesophageal (GE) reflux to determine its sensitivity in detecting gastric acid reflux and to document its usefulness as a prognostic indicator. Eight children had a positive Tuttle test. Six of these patients failed a trial of medical management and required surgery to control their symptoms. None of these patients had GE reflux on esophagrams. Only one of 16 children with a negative test required surgery. This patient also did not have GE reflux on esophagram. The Tuttle test should be included in the diagnostic evaluation of pediatric patients with the clinical presentation of GE reflux. | Detection of gastroesophageal reflux in the pediatric-age patient by esophageal intraluminal pH probe measurement (Tuttle test). The esophageal intraluminal pH probe test (Tuttle test) was used in 24 pediatric-age patients who had symptoms of gastroesophageal (GE) reflux to determine its sensitivity in detecting gastric acid reflux and to document its usefulness as a prognostic indicator. Eight children had a positive Tuttle test. Six of these patients failed a trial of medical management and required surgery to control their symptoms. None of these patients had GE reflux on esophagrams. Only one of 16 children with a negative test required surgery. This patient also did not have GE reflux on esophagram. The Tuttle test should be included in the diagnostic evaluation of pediatric patients with the clinical presentation of GE reflux. | [
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|
PMID:17844 | alpha-L-fucosidase in cultured skin fibroblasts from normal subjects and fucosidosis patients. | alpha-L-Fucosidase (EC 3.2.1.51) activity was studied in cultured skin fibroblasts obtained from 23 members of a family in which two cases of fucosidosis type 2 had occurred and in the fibroblasts of a patient with fucosidosis type 1. Both the 4-methylumbelliferyl glycoside and the p-nitrophenyl derivative were used as substrates. pH activity profiles showed two major peaks of activity. With the fluorogenic substrate pH optimum was at 4.5, whereas with the colorigenic substrate maximum activity was at pH 5.7. No activity was found in the fibroblasts of the three patients with the colorimetric assay. With the fluorometric assay the mean activity in the two patients with fucosidosis type 2 was 4.1 and 2.8 (range 1.3-9.9); activity in the patient with fucosidosis type 1 was 4.6 nmol 4-methylumbelliferone/mg protein/hr (range 1.0-8.6). The specific activity in the lysates of the patients' fibroblasts decreased as the amount of cellular protein used per assay increased. Fucosidosis fibroblasts cultured for 3 and 5 days in medium without fetal calf serum showed almost the same levels of apparent residual activity as fibroblasts cultured in medium containing fetal calf serum. Maximum activity in the deficient fibroblasts was at pH 4.5-4.75. Mixing experiments between lysates of both of fucosidosis and a normal fibroblast strain showed the expected enzymatic activities. The mean alpha-fucosidase activity in four heterozygotes for fucosidosis was 37.6 (range 24.1-48.7) and 30.3 (range 19.0-44.1) nmol final product split/mg protein/hr with the fluorogenic and the colorigenic substrate, respectively. In 12 normal fibroblast strains the mean activity +/- SD was 85.3 +/- 24.4 (range 50.8-129.3) and 67.6 +/- 21.1 (range 31.1-118.3). However, in four family members in which the alpha-L-fucosidase phenotype (by isoelectric focusing) was type 2-1, and who should therefore be carrying two normal alleles, the activity was within the heterozygote range. This indicates that occasional overlap between normal subjects and carriers may be present in cultured skin fibroblasts. Increased specific activity of alpha-L-fucosidase at pH 3.2-4.0 was observed after incubation of cell lysates with neuraminidase. The alpha-L-fucosidase activity did not show any increase after fusion between fucosidosis fibroblasts type 1 and 2. | alpha-L-fucosidase in cultured skin fibroblasts from normal subjects and fucosidosis patients. alpha-L-Fucosidase (EC 3.2.1.51) activity was studied in cultured skin fibroblasts obtained from 23 members of a family in which two cases of fucosidosis type 2 had occurred and in the fibroblasts of a patient with fucosidosis type 1. Both the 4-methylumbelliferyl glycoside and the p-nitrophenyl derivative were used as substrates. pH activity profiles showed two major peaks of activity. With the fluorogenic substrate pH optimum was at 4.5, whereas with the colorigenic substrate maximum activity was at pH 5.7. No activity was found in the fibroblasts of the three patients with the colorimetric assay. With the fluorometric assay the mean activity in the two patients with fucosidosis type 2 was 4.1 and 2.8 (range 1.3-9.9); activity in the patient with fucosidosis type 1 was 4.6 nmol 4-methylumbelliferone/mg protein/hr (range 1.0-8.6). The specific activity in the lysates of the patients' fibroblasts decreased as the amount of cellular protein used per assay increased. Fucosidosis fibroblasts cultured for 3 and 5 days in medium without fetal calf serum showed almost the same levels of apparent residual activity as fibroblasts cultured in medium containing fetal calf serum. Maximum activity in the deficient fibroblasts was at pH 4.5-4.75. Mixing experiments between lysates of both of fucosidosis and a normal fibroblast strain showed the expected enzymatic activities. The mean alpha-fucosidase activity in four heterozygotes for fucosidosis was 37.6 (range 24.1-48.7) and 30.3 (range 19.0-44.1) nmol final product split/mg protein/hr with the fluorogenic and the colorigenic substrate, respectively. In 12 normal fibroblast strains the mean activity +/- SD was 85.3 +/- 24.4 (range 50.8-129.3) and 67.6 +/- 21.1 (range 31.1-118.3). However, in four family members in which the alpha-L-fucosidase phenotype (by isoelectric focusing) was type 2-1, and who should therefore be carrying two normal alleles, the activity was within the heterozygote range. This indicates that occasional overlap between normal subjects and carriers may be present in cultured skin fibroblasts. Increased specific activity of alpha-L-fucosidase at pH 3.2-4.0 was observed after incubation of cell lysates with neuraminidase. The alpha-L-fucosidase activity did not show any increase after fusion between fucosidosis fibroblasts type 1 and 2. | [
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|
PMID:17848 | [The detection of soluble bacterial antigens studied in various pathological substances using counterimmunoelectrophoresis. Contribution to diagnosis(151 cases)]. | Examinations for soluble bacterial antigens using counter-immunoelectrophoresis (C.I.E.) was carried out in 151 patients suspected of suffering from various infectious syndrome were successful for S. pneumoniae, H. influenzae b, N. meningitis, sero-group B and D streptococcus. Thus meningitis and pneumonia represent those areas in which the technique is particularly useful. Apart from its rapidity--result in a hour--C.I.E., in association with bacteriology, makes possible an increase in aetiological diagnosis of 27% with H. influenzae b, 24% with S. pneumoniae and 6% with N. meningitidis (lower result by virtue of technical difficulties with sero-group B). Thus using this technique we were able to reach an aetiological diagnosis in 10 (23.8%) out of 42 cases of purulent meningitis where blind antibiotic therapy had already been given. These two advantages--rapidity and increase in aetiological diagnosis--justify the introduction of this simple technique in every medical microbiology laboratory. | [The detection of soluble bacterial antigens studied in various pathological substances using counterimmunoelectrophoresis. Contribution to diagnosis(151 cases)]. Examinations for soluble bacterial antigens using counter-immunoelectrophoresis (C.I.E.) was carried out in 151 patients suspected of suffering from various infectious syndrome were successful for S. pneumoniae, H. influenzae b, N. meningitis, sero-group B and D streptococcus. Thus meningitis and pneumonia represent those areas in which the technique is particularly useful. Apart from its rapidity--result in a hour--C.I.E., in association with bacteriology, makes possible an increase in aetiological diagnosis of 27% with H. influenzae b, 24% with S. pneumoniae and 6% with N. meningitidis (lower result by virtue of technical difficulties with sero-group B). Thus using this technique we were able to reach an aetiological diagnosis in 10 (23.8%) out of 42 cases of purulent meningitis where blind antibiotic therapy had already been given. These two advantages--rapidity and increase in aetiological diagnosis--justify the introduction of this simple technique in every medical microbiology laboratory. | [
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|
PMID:17853 | An investigation of renal function in chronic bronchitis. | An investigation has been made into various parameters of renal function in patients with chronic bronchitis and in a group of hypoxic controls. Abnormalities of glomerular filtration rate and of water handling have been demostrated in chronic bronchitic patients but not in hypoxic controls. The abnormalities are related to the arterial Pco2. A hypothesis is presented as to the role of CO2 in causing abnormalities of renal function in chronic bronchitis. | An investigation of renal function in chronic bronchitis. An investigation has been made into various parameters of renal function in patients with chronic bronchitis and in a group of hypoxic controls. Abnormalities of glomerular filtration rate and of water handling have been demostrated in chronic bronchitic patients but not in hypoxic controls. The abnormalities are related to the arterial Pco2. A hypothesis is presented as to the role of CO2 in causing abnormalities of renal function in chronic bronchitis. | [
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PMID:17854 | Polyarteritis nodosa of the liver: a report of two cases. | Two patients with liver disease due to polyarteritis nodosa are described. They presented in a similar manner, with a swinging fever, a polymorphonuclear leucocytosis and high alkaline phosphatase levels, but the natural history of the illness was different, with revocery in one and death in the other. | Polyarteritis nodosa of the liver: a report of two cases. Two patients with liver disease due to polyarteritis nodosa are described. They presented in a similar manner, with a swinging fever, a polymorphonuclear leucocytosis and high alkaline phosphatase levels, but the natural history of the illness was different, with revocery in one and death in the other. | [
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|
PMID:17858 | [Assessment of the mental load of flight managers and of perforating machine operators by means of measuring the residual mental capacity via the subsidiary task method]. | The purpose of the study is to evaluate mental loading due to working activities in two occupational groups--flight managers and punching machine operators. Changes in residual mental capacity are studied in relation to character of the specific work performed and working conditions. Residual capacity changes, measured with the method of double task assignment, disclose an essential difference in the nature of labour inherent of the two professions under study. The increased quantity of tasks performed under normal conditions of work exerts less influence on the level of residual mental capacity than work assignments fulfilled under complicated situations (such as bad weather conditions and the like). The level of residual mental capacity is likewise altered under the effect of fatigue in the course of the working day. | [Assessment of the mental load of flight managers and of perforating machine operators by means of measuring the residual mental capacity via the subsidiary task method]. The purpose of the study is to evaluate mental loading due to working activities in two occupational groups--flight managers and punching machine operators. Changes in residual mental capacity are studied in relation to character of the specific work performed and working conditions. Residual capacity changes, measured with the method of double task assignment, disclose an essential difference in the nature of labour inherent of the two professions under study. The increased quantity of tasks performed under normal conditions of work exerts less influence on the level of residual mental capacity than work assignments fulfilled under complicated situations (such as bad weather conditions and the like). The level of residual mental capacity is likewise altered under the effect of fatigue in the course of the working day. | [
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|
PMID:17872 | Non-equilibrium freezing behaviour of aqueous systems. | The tendencies to non-equilibrium freezing behaviour commonly noted in representative aqueous systems derive from bulk and surface properties according to the circumstances. Supercooling and supersaturation are limited by heterogeneous nucleation in the presence of solid impurities. Homogeneous nucleation has been observed in aqueous systems freed from interfering solids. Once initiated, crystal growth is ofter slowed and, very frequently, terminated with increasing viscosity. Nor does ice first formed always succeed in assuming its most stable crystalline form. Many of the more significant measurements on a given systeatter permitting the simultaneous representation of thermodynamic and non-equilibrium properties. The diagram incorporated equilibrium melting points, heterogeneous nucleation temperatures, homogeneous nucleation temperatures, glass transition and devitrification temperatures, recrystallization temperatures, and, where appropriate, solute solubilities and eutectic temperatures. Taken together, the findings on modle systems aid the identification of the kinetic and thermodynamic factors responsible for the freezing-thawing survival of living cells. | Non-equilibrium freezing behaviour of aqueous systems. The tendencies to non-equilibrium freezing behaviour commonly noted in representative aqueous systems derive from bulk and surface properties according to the circumstances. Supercooling and supersaturation are limited by heterogeneous nucleation in the presence of solid impurities. Homogeneous nucleation has been observed in aqueous systems freed from interfering solids. Once initiated, crystal growth is ofter slowed and, very frequently, terminated with increasing viscosity. Nor does ice first formed always succeed in assuming its most stable crystalline form. Many of the more significant measurements on a given systeatter permitting the simultaneous representation of thermodynamic and non-equilibrium properties. The diagram incorporated equilibrium melting points, heterogeneous nucleation temperatures, homogeneous nucleation temperatures, glass transition and devitrification temperatures, recrystallization temperatures, and, where appropriate, solute solubilities and eutectic temperatures. Taken together, the findings on modle systems aid the identification of the kinetic and thermodynamic factors responsible for the freezing-thawing survival of living cells. | [
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PMID:17873 | Water transport and cell survival in cryobiological procedures. | Living cells may be cooled to 77 K (liquid nitrogen) either to destroy them selectively or to store them for long periods. Water transport across the cell membranes during freezing and thawing is a primary factor determining whether the cells survive. These water movements are controlled by phase changes both intracellular and extracellular and by other factors such as the nature of any cryoprotective agent present, and the rates of cooling and thawing. The relation between cooling procedure, water transport and cell survival is discussed. In particular, the crucial rôle of dilution shock is emphasized: this is the damage to cells induced during the dilution that occurs both as ice melts during rewarming and when any cryoprotective additives are removed after thawing. Apart from the usefulness of understanding these processes for maximizing preservation or controlling selective destruction, the diverse responses of cells to different combinations of water transport and temperature changes appear likely to provide basic information on the properties of cell membranes. | Water transport and cell survival in cryobiological procedures. Living cells may be cooled to 77 K (liquid nitrogen) either to destroy them selectively or to store them for long periods. Water transport across the cell membranes during freezing and thawing is a primary factor determining whether the cells survive. These water movements are controlled by phase changes both intracellular and extracellular and by other factors such as the nature of any cryoprotective agent present, and the rates of cooling and thawing. The relation between cooling procedure, water transport and cell survival is discussed. In particular, the crucial rôle of dilution shock is emphasized: this is the damage to cells induced during the dilution that occurs both as ice melts during rewarming and when any cryoprotective additives are removed after thawing. Apart from the usefulness of understanding these processes for maximizing preservation or controlling selective destruction, the diverse responses of cells to different combinations of water transport and temperature changes appear likely to provide basic information on the properties of cell membranes. | [
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|
PMID:17874 | The organization and function of water in protein crystals. | Dry proteins are dead, or at best asleep. Substitution of D2O can drastically alter biological activity. Water is thus essential in maintaining the structural integrity of biologically active macromolecules, and is implicated in their functioning. Such water may occupy a range of dynamical states, from being strongly bound and localized, to more labile and 'liquid-like'. Spatially ordering the macromolecules aids the search for the more localized water molecules. For example, diffraction experiments on singly crystals can resolve 'bound' water molecules within a protein molecule--ofter at active sites, coordinated to metals or ions. Less precise information is obtained on the partially occupied external water sites, which are of importance to the folding and dynamics of the biomolecule. Orientation of fibrous molecules increases the information obtainable from n.m.r. experiments. Combination of other experimental results on disordered aggregates (e.g. in solution) with chemical and structural data on the macromolecule and water itself yields useful, if circumstantial, information. Statistical and computer techniques may help to elucidate the complex nature of water-protein interactions, and to interpret the results of more complex experiments. | The organization and function of water in protein crystals. Dry proteins are dead, or at best asleep. Substitution of D2O can drastically alter biological activity. Water is thus essential in maintaining the structural integrity of biologically active macromolecules, and is implicated in their functioning. Such water may occupy a range of dynamical states, from being strongly bound and localized, to more labile and 'liquid-like'. Spatially ordering the macromolecules aids the search for the more localized water molecules. For example, diffraction experiments on singly crystals can resolve 'bound' water molecules within a protein molecule--ofter at active sites, coordinated to metals or ions. Less precise information is obtained on the partially occupied external water sites, which are of importance to the folding and dynamics of the biomolecule. Orientation of fibrous molecules increases the information obtainable from n.m.r. experiments. Combination of other experimental results on disordered aggregates (e.g. in solution) with chemical and structural data on the macromolecule and water itself yields useful, if circumstantial, information. Statistical and computer techniques may help to elucidate the complex nature of water-protein interactions, and to interpret the results of more complex experiments. | [
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|
PMID:17878 | Theoretical approaches to the intermolecular nature of water. | A brief review is presented of recent advances in theoretical understanding of liquid water. These advances include detailed quantitative specification of water-molecule interaction potentials, and development of several techniques in statistical mechanics for predicting molecular order in the liquid. Specifically, computer simulation now plays a particularly important rôle. A labile, defective, random network picture for the liquid is the only consistently supported possibility. Implications of this picture for an explanation of hydrophobic solvation and bonding are mentioned. Furthermore, the apparent cooperative restructuring of the random network near the supercolling limit suggests that a dielectric anomaly might exist in this régime. Several areas for future development of water theory are suggested, bearing specifically on phenomena of biological interest. | Theoretical approaches to the intermolecular nature of water. A brief review is presented of recent advances in theoretical understanding of liquid water. These advances include detailed quantitative specification of water-molecule interaction potentials, and development of several techniques in statistical mechanics for predicting molecular order in the liquid. Specifically, computer simulation now plays a particularly important rôle. A labile, defective, random network picture for the liquid is the only consistently supported possibility. Implications of this picture for an explanation of hydrophobic solvation and bonding are mentioned. Furthermore, the apparent cooperative restructuring of the random network near the supercolling limit suggests that a dielectric anomaly might exist in this régime. Several areas for future development of water theory are suggested, bearing specifically on phenomena of biological interest. | [
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PMID:17881 | Stress-induced alterations of cyclic nucleotide levels in brain: effects of centrally acting drugs. | Acute stressing procedures cause a shortlasting increase in the levels of guanosie 3',5'-monophosphate (cGMP) in mouse brain without significantly influencing the concentrations of adenosine 3'-5'-monophosphate (cAMP). Animals were pretreated with various centrally acting drugs before being stressed in order to study the involvement of specific neurotransmitters in the stress-induced rise of cGMP levels. Centrally depressant drugs affecting different synaptic mechanisms, such as chlorpromazine, reserpine, haloperidol, diazepam, and pentobarbital, inhibited the cCMP increase elicited by stress. Pretreatment with atropine, diphenhydramine, antazoline, cyproheptadine, phentolamine, bunitrolol, and indomethacin had no significant effect. Clonidine and both the (-)- and (+)-isomers of propranolol inhibited the stress-induced cGMP increase in a dose-related manner. Our results suggest that norepinephrine, serotonin, acetylcholine, or prostaglandins are not involved in the elevation of cGMP levels elicited by acute stress. Participation of other neurotransmitter(s), such as dopamine or GABA, cannot be excluded. | Stress-induced alterations of cyclic nucleotide levels in brain: effects of centrally acting drugs. Acute stressing procedures cause a shortlasting increase in the levels of guanosie 3',5'-monophosphate (cGMP) in mouse brain without significantly influencing the concentrations of adenosine 3'-5'-monophosphate (cAMP). Animals were pretreated with various centrally acting drugs before being stressed in order to study the involvement of specific neurotransmitters in the stress-induced rise of cGMP levels. Centrally depressant drugs affecting different synaptic mechanisms, such as chlorpromazine, reserpine, haloperidol, diazepam, and pentobarbital, inhibited the cCMP increase elicited by stress. Pretreatment with atropine, diphenhydramine, antazoline, cyproheptadine, phentolamine, bunitrolol, and indomethacin had no significant effect. Clonidine and both the (-)- and (+)-isomers of propranolol inhibited the stress-induced cGMP increase in a dose-related manner. Our results suggest that norepinephrine, serotonin, acetylcholine, or prostaglandins are not involved in the elevation of cGMP levels elicited by acute stress. Participation of other neurotransmitter(s), such as dopamine or GABA, cannot be excluded. | [
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PMID:17891 | Physiological role of yeasts NAD(P)+ and NADP+-linked aldehyde dehydrogenases. | The activity of NAD+ and NADP+-linked aldehyde dehydrogenases has been investigated in yeast cells grown under different conditions. As occurs in other dehydrogenase reactions the NAD(P)+-linked enzyme was strongly repressed in all hypoxic conditions; nervetheless, the NADP+-linked enzyme was active. The results suggest that the NAD(P)+ aldehyde dehydrogenase is involved in the oxidation of ethanol to acetyl-CoA, and that when the pyruvate dehydrogenase complex is repressed the NADP+-linked aldehyde dehydrogenase is operative as an alternative pathway from pyruvate to acetyl-CoA: pyruvate leads to acetaldehyde leads to acetate leads to acetyl-Coa. In these conditions the supply of NADPH is advantageous to the cellular economy for biosynthetic purposes. Short term adaptation experiments suggest that the regulation of the levels of the aldehyde dehydrogenase-NAD(P)+ takes place by the de novo synthesis of the enzyme. | Physiological role of yeasts NAD(P)+ and NADP+-linked aldehyde dehydrogenases. The activity of NAD+ and NADP+-linked aldehyde dehydrogenases has been investigated in yeast cells grown under different conditions. As occurs in other dehydrogenase reactions the NAD(P)+-linked enzyme was strongly repressed in all hypoxic conditions; nervetheless, the NADP+-linked enzyme was active. The results suggest that the NAD(P)+ aldehyde dehydrogenase is involved in the oxidation of ethanol to acetyl-CoA, and that when the pyruvate dehydrogenase complex is repressed the NADP+-linked aldehyde dehydrogenase is operative as an alternative pathway from pyruvate to acetyl-CoA: pyruvate leads to acetaldehyde leads to acetate leads to acetyl-Coa. In these conditions the supply of NADPH is advantageous to the cellular economy for biosynthetic purposes. Short term adaptation experiments suggest that the regulation of the levels of the aldehyde dehydrogenase-NAD(P)+ takes place by the de novo synthesis of the enzyme. | [
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PMID:17892 | Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors. | Adrenergic blockers for beta-receptors were studied for inhibition of mitochrondrial CoQ10-enzymes. These enzymes are indispensable for the bioenegetics of the myocardium. Propranolol is frequently used to treat hypertension; in some patients, it depresses myocardial function as an adverse reaction. This side effect may be related to the inhibition by propranolol of CoQ10-enzymes of the myocardium. Timolol showed negligible inhibition of the CoQ10-enzyme, NADH-oxidase. Metoprolol was less inhibitory than propranolol. Five alprenolols showed inhibition which approached that of propranolol. The 1-isomer of alprenolol showed weak inhibition of another CoQ10-enzyme, succinoxidase, but the other beta-blockers were essentially non-inhibitory to this enzyme. The drug of choice is timolol, based on negligible inhibition of these bioenergetic enzymes of the heart, which correlates with its pharmacologically low cardiac depressant effects. | Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors. Adrenergic blockers for beta-receptors were studied for inhibition of mitochrondrial CoQ10-enzymes. These enzymes are indispensable for the bioenegetics of the myocardium. Propranolol is frequently used to treat hypertension; in some patients, it depresses myocardial function as an adverse reaction. This side effect may be related to the inhibition by propranolol of CoQ10-enzymes of the myocardium. Timolol showed negligible inhibition of the CoQ10-enzyme, NADH-oxidase. Metoprolol was less inhibitory than propranolol. Five alprenolols showed inhibition which approached that of propranolol. The 1-isomer of alprenolol showed weak inhibition of another CoQ10-enzyme, succinoxidase, but the other beta-blockers were essentially non-inhibitory to this enzyme. The drug of choice is timolol, based on negligible inhibition of these bioenergetic enzymes of the heart, which correlates with its pharmacologically low cardiac depressant effects. | [
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PMID:17894 | Ethanol-induced inhibition of guanylate cyclase in liver, pancreas, stomach and intestine. | Ethanol decreases hepatic protein and albumin synthesis, and inhibits pancreatic water, bicarbonate, and protein secretion. Since these actions of ethanol are opposite to those reported for secretin, cholecystokinin-pancreozymin, and pentagastrin which may be mediated through increases in cyclic GMP, it appeared possible that the inhibitory actions of ethanol might be mediated through inhibition of guanylate cyclase, the enzyme that catalyzes the production of cyclic GMP. Ethanol inhibited soluble preparations of guanylate cyclase from rat liver, pancreas, stomach, and ileum. Maximal inhibition was observed at 5.0 and 2.5 percent ethanol. The inhibitory effects of ethanol on the guanylate cyclase-cyclic GMP system of these tissues provide a possible explanation for some of the diverse effects of ethanol on these tissues. | Ethanol-induced inhibition of guanylate cyclase in liver, pancreas, stomach and intestine. Ethanol decreases hepatic protein and albumin synthesis, and inhibits pancreatic water, bicarbonate, and protein secretion. Since these actions of ethanol are opposite to those reported for secretin, cholecystokinin-pancreozymin, and pentagastrin which may be mediated through increases in cyclic GMP, it appeared possible that the inhibitory actions of ethanol might be mediated through inhibition of guanylate cyclase, the enzyme that catalyzes the production of cyclic GMP. Ethanol inhibited soluble preparations of guanylate cyclase from rat liver, pancreas, stomach, and ileum. Maximal inhibition was observed at 5.0 and 2.5 percent ethanol. The inhibitory effects of ethanol on the guanylate cyclase-cyclic GMP system of these tissues provide a possible explanation for some of the diverse effects of ethanol on these tissues. | [
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|
PMID:17895 | Procainamide pharmacokinetics in beagles: urinary pH dependency and comparison with n-acetylprocainamide. | Male and female beagles received intravenous (i.v.) bolus injections of procainamide (PA) to study its pharmacokinetic behavior and to determine the effect of urinary pH upon renal excretion. Urinary alkalinization caused an increase in plasma disappearance half-life (t1/2) and decreases in renal clearance (ClR) and total body clearance (ClB), while the apparent volume of distribution remained unchanged. Acid hydrolysis of the urine collected caused a 17% increase in the amount of PA measured. This hydrolyzable substance was found not to be the N-acetylated metabolite of PA. When i.v. N-acetylprocainamide (NAPA) was administered in crossover fashion to some of the above animals, it exhibited a longer t1/2 than PA. Mean ClR and mean ClB values were smaller with NAPA while both compounds showed similar dependence upon renal and non-renal clearance mechanisms. | Procainamide pharmacokinetics in beagles: urinary pH dependency and comparison with n-acetylprocainamide. Male and female beagles received intravenous (i.v.) bolus injections of procainamide (PA) to study its pharmacokinetic behavior and to determine the effect of urinary pH upon renal excretion. Urinary alkalinization caused an increase in plasma disappearance half-life (t1/2) and decreases in renal clearance (ClR) and total body clearance (ClB), while the apparent volume of distribution remained unchanged. Acid hydrolysis of the urine collected caused a 17% increase in the amount of PA measured. This hydrolyzable substance was found not to be the N-acetylated metabolite of PA. When i.v. N-acetylprocainamide (NAPA) was administered in crossover fashion to some of the above animals, it exhibited a longer t1/2 than PA. Mean ClR and mean ClB values were smaller with NAPA while both compounds showed similar dependence upon renal and non-renal clearance mechanisms. | [
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|
PMID:17896 | Brain gamma-glutamyl transpeptidase levels in mice genetically selected for sensitivity to ethanol. | The present study describes the regional distribution of the enzyme gamma-glutamyl transpeptidase for two lines of mice (long-sleep and short-sleep) selectively bred for differences in sleep-time after the administration of ethanol. The long-sleep animals exhibited higher levels of the enzyme in all areas of brain. | Brain gamma-glutamyl transpeptidase levels in mice genetically selected for sensitivity to ethanol. The present study describes the regional distribution of the enzyme gamma-glutamyl transpeptidase for two lines of mice (long-sleep and short-sleep) selectively bred for differences in sleep-time after the administration of ethanol. The long-sleep animals exhibited higher levels of the enzyme in all areas of brain. | [
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|
PMID:17898 | Blood-gas properties and function in the fossorial mole rat under normal and hypoxic-hypercapnic atmospheric conditions. | Blood and tissue gas exchange properties of mole rats in normoxic and hypoxic-hypercapnic conditions were compared to the common mammalian pattern. RBC count was 14.0 +/- 1.2-10(6)/microliter. Hb concentration was 15.0 +/- 0.4g/100 ml. P50 (at pH 7.4 and 37 degrees C) was 29.5 +/- 0.5 mm Hg. Oxygen capacity averaged 20.2 +/- 0.4 vol% and the Hill coefficient was 2.9 +/- 0.1. The Bohr effect was -0.53 +/- 0.02 (deltalog P/deltapH). The temperature coefficient was 0.0152 +/- 0.0014 (deltalog P/delta degrees C). The Haldane effect was 4.8 +/- 0.5 (deltaCCO2 vol%)at PCO2 =40 mm Hg. Steady-state partial pressures in gas pockets were PO2 = 15.1 +/- 1.4 mm Hg and PCO2 = 85.8 +/- 3.9 mm Hg in normoxia, and 11.5 +/- 3.0 and 101.8 +/- 3.5 repectively in hypoxia-hypercapnia (PIO2 congruent to 85 mm Hg). Under the same conditions 2,3-DPG dropped from 0.87 and 0.88 to 0.62 and 0.65 (mol/mol Hb) in the rat and in the white rat, respectively. Heart muscle myoglobin concentration of the mole rat (1.44 mg/g) did not differ significantly from that of the white rat (1.96 mg/g), whereas masseter myoglobin was 4.0 mg/g--significantly different from the rat (1.21 mg/g). Results indicate that the strategy used by the mole rat to maintain a normal metabolic rate under variable atmospheric conditions, besides having high oxygen affinity, is to expand the physiological range of the oxygen dissociation curve to very low oxygen tensions, at the expense of its acid-base regulation. The regulation of the shape of the oxygen dissociation curve is discussed. | Blood-gas properties and function in the fossorial mole rat under normal and hypoxic-hypercapnic atmospheric conditions. Blood and tissue gas exchange properties of mole rats in normoxic and hypoxic-hypercapnic conditions were compared to the common mammalian pattern. RBC count was 14.0 +/- 1.2-10(6)/microliter. Hb concentration was 15.0 +/- 0.4g/100 ml. P50 (at pH 7.4 and 37 degrees C) was 29.5 +/- 0.5 mm Hg. Oxygen capacity averaged 20.2 +/- 0.4 vol% and the Hill coefficient was 2.9 +/- 0.1. The Bohr effect was -0.53 +/- 0.02 (deltalog P/deltapH). The temperature coefficient was 0.0152 +/- 0.0014 (deltalog P/delta degrees C). The Haldane effect was 4.8 +/- 0.5 (deltaCCO2 vol%)at PCO2 =40 mm Hg. Steady-state partial pressures in gas pockets were PO2 = 15.1 +/- 1.4 mm Hg and PCO2 = 85.8 +/- 3.9 mm Hg in normoxia, and 11.5 +/- 3.0 and 101.8 +/- 3.5 repectively in hypoxia-hypercapnia (PIO2 congruent to 85 mm Hg). Under the same conditions 2,3-DPG dropped from 0.87 and 0.88 to 0.62 and 0.65 (mol/mol Hb) in the rat and in the white rat, respectively. Heart muscle myoglobin concentration of the mole rat (1.44 mg/g) did not differ significantly from that of the white rat (1.96 mg/g), whereas masseter myoglobin was 4.0 mg/g--significantly different from the rat (1.21 mg/g). Results indicate that the strategy used by the mole rat to maintain a normal metabolic rate under variable atmospheric conditions, besides having high oxygen affinity, is to expand the physiological range of the oxygen dissociation curve to very low oxygen tensions, at the expense of its acid-base regulation. The regulation of the shape of the oxygen dissociation curve is discussed. | [
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|
PMID:17899 | Crayfish respiration as a function of water oxygenation. | Crayfish, Astacus leptodactylus, for several hours breathed water equilibrated either with a hypoxic gas mixture, or air, or oxygen. The hydrostatic pressure in the right epibranchial cavity was recorded and the left epibranchial water sempled from time to time. The higher the water oxygenation, the less the duration of ventilation, the frequency of the scaphognathite beats which ensure water convection, the negative of the water hydrostatic pressure relative to ambient water pressure, and the respired water flow. The water convection per unit quantity of oxygen consumed decreased by a factor of about 20 when the animal passed from hypoxic water at PO2 of 72 torr to hyperoxic water at PO2 of 697 torr. Prolonged hyperoxia, up to 100 days, results in a hypercapnic acidosis of the prebranchial blood. pH decreased about 0.2 unit, PCO2 increased from 2.5 torr to a value of 6 torr, and [HCO-3] from 6 to a value of 9 meq-L-1. This hypercapnic acidosis remained uncompensated during several weeks exposure to hyperoxia. Observations on the fresh water crayfish, a marine crab, and several species of fish, suggest that in aquatic animals (1) the ventilatory activity depends greatly on the degree of water oxygenation: the higher the water oxygenation, the lower the ventilation; (2) the change of ventilation may be accompanied by a new equilibrium of the blood acid-base status, quite different from that observed in normoxia. | Crayfish respiration as a function of water oxygenation. Crayfish, Astacus leptodactylus, for several hours breathed water equilibrated either with a hypoxic gas mixture, or air, or oxygen. The hydrostatic pressure in the right epibranchial cavity was recorded and the left epibranchial water sempled from time to time. The higher the water oxygenation, the less the duration of ventilation, the frequency of the scaphognathite beats which ensure water convection, the negative of the water hydrostatic pressure relative to ambient water pressure, and the respired water flow. The water convection per unit quantity of oxygen consumed decreased by a factor of about 20 when the animal passed from hypoxic water at PO2 of 72 torr to hyperoxic water at PO2 of 697 torr. Prolonged hyperoxia, up to 100 days, results in a hypercapnic acidosis of the prebranchial blood. pH decreased about 0.2 unit, PCO2 increased from 2.5 torr to a value of 6 torr, and [HCO-3] from 6 to a value of 9 meq-L-1. This hypercapnic acidosis remained uncompensated during several weeks exposure to hyperoxia. Observations on the fresh water crayfish, a marine crab, and several species of fish, suggest that in aquatic animals (1) the ventilatory activity depends greatly on the degree of water oxygenation: the higher the water oxygenation, the lower the ventilation; (2) the change of ventilation may be accompanied by a new equilibrium of the blood acid-base status, quite different from that observed in normoxia. | [
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PMID:17916 | Pineal vasotocin: release into cat cerebrospinal fluid by melanocyte-stimulating hormone release-inhibiting factor. | The intracarotid injection of both synthetic melanocyte-stimulating hormone release-inhibiting factor (MIF) and purified MIF prepared from bovine hypothalami induces arginine vasotocin release into cerebrospinal fluid of cats and significantly decreases the pineal arginine vasotocin content at 5 minutes after the injection. The present results demonstrate an extrapituitary endocrine effect of synthetic and purified bovine MIF. | Pineal vasotocin: release into cat cerebrospinal fluid by melanocyte-stimulating hormone release-inhibiting factor. The intracarotid injection of both synthetic melanocyte-stimulating hormone release-inhibiting factor (MIF) and purified MIF prepared from bovine hypothalami induces arginine vasotocin release into cerebrospinal fluid of cats and significantly decreases the pineal arginine vasotocin content at 5 minutes after the injection. The present results demonstrate an extrapituitary endocrine effect of synthetic and purified bovine MIF. | [
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|
PMID:17917 | Haloperidol: effect of long-term treatment on rat striatal dopamine synthesis and turnover. | The short- and long-term effects of neuroleptic drugs differ both clinically and biochemically. Short-term treatment with such a drug causes a kinetic activation of striatal tyrosine hydroxylase. Long-term treatment causes a prompt activation of the enzyme which is followed by a delayed, compensatory deactivation below control levels. Tolerance also develops to the stimulating effect of haloperidol on striatal dopamine turnover. | Haloperidol: effect of long-term treatment on rat striatal dopamine synthesis and turnover. The short- and long-term effects of neuroleptic drugs differ both clinically and biochemically. Short-term treatment with such a drug causes a kinetic activation of striatal tyrosine hydroxylase. Long-term treatment causes a prompt activation of the enzyme which is followed by a delayed, compensatory deactivation below control levels. Tolerance also develops to the stimulating effect of haloperidol on striatal dopamine turnover. | [
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|
PMID:17918 | Electrically coupled, photosensitive neurons control swimming in a jellyfish. | Central neurons in Polyorchis (Hydromedusae) were impaled with microelectrodes, and conventional resting potentials were obtained. The waveform of action potentials recorded concurrently with swimming events shows evidence of electrotonic coupling between these neurons, which are also directly photosensitive and receive excitatory synaptic input from other conduction systems. | Electrically coupled, photosensitive neurons control swimming in a jellyfish. Central neurons in Polyorchis (Hydromedusae) were impaled with microelectrodes, and conventional resting potentials were obtained. The waveform of action potentials recorded concurrently with swimming events shows evidence of electrotonic coupling between these neurons, which are also directly photosensitive and receive excitatory synaptic input from other conduction systems. | [
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|
PMID:17914 | [Polyneuropathy due to "allergic vasculitis" possibly related to australia antigen. (author's transl)]. | The authors describe a case of flaccid tetraplegia due to a polyneuropathy in a man aged 50 years, progressing rapidly to death from mesenteric infarction. As significant abnormalities, the hematologic examinations revealed a very high erythrocyte sedimentation rate, a marked leukocytosis and a positive Australia antigen in repeated controls. In spite of the clinical picture being that of a symmetrical polyneuropathy rather than that of mononeuritis multiplex, the diagnose of a collagenosis was suspected. Nevertheless steroid treatment was not given because the patient had a peptic ulcer. On histological investigation many focal infarctions were found in several internal organs but the brain was pratically normal. Instead the nerve trunks examined (the sciatic nerve and the lumbo-sacral plexus) showed gross changes in the vasa nervorum represented by abundant perivascular cuffing and marked evidence of axonal degeneration secondary to an ischaemic damage. In the kidneys there were definite signs of membranous glomerulitis. The pathological findings in this fatal case of diffuse peripheral involvement were not those of classical periarteritis nodosa, but showed the picture of so-called "allergic vasculitis". This type of blood vessels inflammation is now assumed to be part of an immune-complex disease, in which the Australia antigen could be one of the causative agents. | [Polyneuropathy due to "allergic vasculitis" possibly related to australia antigen. (author's transl)]. The authors describe a case of flaccid tetraplegia due to a polyneuropathy in a man aged 50 years, progressing rapidly to death from mesenteric infarction. As significant abnormalities, the hematologic examinations revealed a very high erythrocyte sedimentation rate, a marked leukocytosis and a positive Australia antigen in repeated controls. In spite of the clinical picture being that of a symmetrical polyneuropathy rather than that of mononeuritis multiplex, the diagnose of a collagenosis was suspected. Nevertheless steroid treatment was not given because the patient had a peptic ulcer. On histological investigation many focal infarctions were found in several internal organs but the brain was pratically normal. Instead the nerve trunks examined (the sciatic nerve and the lumbo-sacral plexus) showed gross changes in the vasa nervorum represented by abundant perivascular cuffing and marked evidence of axonal degeneration secondary to an ischaemic damage. In the kidneys there were definite signs of membranous glomerulitis. The pathological findings in this fatal case of diffuse peripheral involvement were not those of classical periarteritis nodosa, but showed the picture of so-called "allergic vasculitis". This type of blood vessels inflammation is now assumed to be part of an immune-complex disease, in which the Australia antigen could be one of the causative agents. | [
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|
PMID:17919 | Stimulation of in vitro translation of messenger RNA by actinomycin D and cordycepin. | Actinomycin D and cordycepin were tested for their effect on translation in the wheat germ embryo extract and reticulocyte lysate assays for in vitro protein synthesis. Both drugs were found to stimulate the incorporation of 35S-labeled methionine into protein up to threefold as compared to control assays. This was true for synthesis directed by murine myeloma polyadenylate-containing RNA, tobacco mosaic virus RNA, and endogenous reticulocyte messenger RNA. | Stimulation of in vitro translation of messenger RNA by actinomycin D and cordycepin. Actinomycin D and cordycepin were tested for their effect on translation in the wheat germ embryo extract and reticulocyte lysate assays for in vitro protein synthesis. Both drugs were found to stimulate the incorporation of 35S-labeled methionine into protein up to threefold as compared to control assays. This was true for synthesis directed by murine myeloma polyadenylate-containing RNA, tobacco mosaic virus RNA, and endogenous reticulocyte messenger RNA. | [
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|
PMID:17920 | Dihydrofolate reductase: x-ray structure of the binary complex with methotrexate. | A central eight-stranded beta-pleated sheet is the main feature of the polypeptide backbone folding in dihydrofolate reductase. The innermost four strands and two bridging helices are geometrically similar to but are connected in a different way from those in the dinucleotide binding domains found in nicotinamide-adenine dinucleotide-linked dehydrogenases. Methotrexate is bound in a 15-angstrom-deep cavity with the pteridine ring buried in a primarily hydrophobic pocket, although a strong interaction occurs between the side chain of aspartic acid 27 and N(1), N(8), and the 2-amino group of methotrexate. | Dihydrofolate reductase: x-ray structure of the binary complex with methotrexate. A central eight-stranded beta-pleated sheet is the main feature of the polypeptide backbone folding in dihydrofolate reductase. The innermost four strands and two bridging helices are geometrically similar to but are connected in a different way from those in the dinucleotide binding domains found in nicotinamide-adenine dinucleotide-linked dehydrogenases. Methotrexate is bound in a 15-angstrom-deep cavity with the pteridine ring buried in a primarily hydrophobic pocket, although a strong interaction occurs between the side chain of aspartic acid 27 and N(1), N(8), and the 2-amino group of methotrexate. | [
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|
PMID:17921 | Calcium-dependent depression of a late outward current in snail neurons. | Neuron cell bodies of Helix pomatia were voltage-clamped with a 300-millisecond depolarizing test pulse (pulse II) delivered I second after a depolarizing conditioning pulse (pulse I). The outward current, measured 200 milliseconds after the onset of pulse. II, exhibited a strong depression that was dependent on the presence of pulse. I. The maximum depression of the pulse II outward current occurred when pulse I voltages lay in the range over which calcium influx is inferred to be greatest; depression of the pulse II current subsided as pulse I potentials approached the putative calcium equilibrium potential. In the presence of extracellular [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA) or D600, the intensity of the pulse II current became largely independent of pulse I, approaching the values of maximal depression seen in normal Ringer solution. On the other hand, lowering the intracellular pH with extracellular carbon dioxide-carbonate buffer had no measurable effect on the outward currents. Other experiments showed that it is primarily the calcium-dependent, outward-current hump of the N-shaped late current-voltage curve that is depressed by presentation of the conditioning pulse. It was concluded that distinct from an early potassium-activating role, calcium entering during a depolarization leads, during a subsequent depolarization, to a depression of the calcium-activated potassium system that persists for many seconds. | Calcium-dependent depression of a late outward current in snail neurons. Neuron cell bodies of Helix pomatia were voltage-clamped with a 300-millisecond depolarizing test pulse (pulse II) delivered I second after a depolarizing conditioning pulse (pulse I). The outward current, measured 200 milliseconds after the onset of pulse. II, exhibited a strong depression that was dependent on the presence of pulse. I. The maximum depression of the pulse II outward current occurred when pulse I voltages lay in the range over which calcium influx is inferred to be greatest; depression of the pulse II current subsided as pulse I potentials approached the putative calcium equilibrium potential. In the presence of extracellular [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA) or D600, the intensity of the pulse II current became largely independent of pulse I, approaching the values of maximal depression seen in normal Ringer solution. On the other hand, lowering the intracellular pH with extracellular carbon dioxide-carbonate buffer had no measurable effect on the outward currents. Other experiments showed that it is primarily the calcium-dependent, outward-current hump of the N-shaped late current-voltage curve that is depressed by presentation of the conditioning pulse. It was concluded that distinct from an early potassium-activating role, calcium entering during a depolarization leads, during a subsequent depolarization, to a depression of the calcium-activated potassium system that persists for many seconds. | [
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|
PMID:17922 | Appetitive and replacement naps: EEG and behavior. | Consistent subjective, behavioral, and electroencephalographic sleep-stage differences were found between afternoon naps of 11 habitual appetitive nappers (who nap lightly for psychological reasons apparently unrelated to reported sleep needs) and 10 replacement nappers (who apparently nap regularly in response to temporary sleep deficits). Both types of naps were compared with naps of 12 confirmed non-nappers. | Appetitive and replacement naps: EEG and behavior. Consistent subjective, behavioral, and electroencephalographic sleep-stage differences were found between afternoon naps of 11 habitual appetitive nappers (who nap lightly for psychological reasons apparently unrelated to reported sleep needs) and 10 replacement nappers (who apparently nap regularly in response to temporary sleep deficits). Both types of naps were compared with naps of 12 confirmed non-nappers. | [
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|
PMID:17927 | The use of counter-immuno-electrophoresis to identify causative organisms in bacterial meningitis: experience in Cape Town. | Crebrospinal fluid (CSF) from 142 patients was tested for the presence of Haemophilus influenzae, pneumococcal and meningococcal antigens by counter-immuno-electrophoresis with commercial antisera. Group- or type-specific antigen was detected in the CSF of 67% of 64 patients with meningitis proved by culture to be due to these organisms, and in 10 of 25 patients with purulent meningitis but negative cultures. No false positive results were obtained in 24 normal CSF specimens, or in the CSF of 29 patients with meningitis caused by other organisms. The diagnostic usefulness of this specific, relatively simple and rapid procedure is confirmed. | The use of counter-immuno-electrophoresis to identify causative organisms in bacterial meningitis: experience in Cape Town. Crebrospinal fluid (CSF) from 142 patients was tested for the presence of Haemophilus influenzae, pneumococcal and meningococcal antigens by counter-immuno-electrophoresis with commercial antisera. Group- or type-specific antigen was detected in the CSF of 67% of 64 patients with meningitis proved by culture to be due to these organisms, and in 10 of 25 patients with purulent meningitis but negative cultures. No false positive results were obtained in 24 normal CSF specimens, or in the CSF of 29 patients with meningitis caused by other organisms. The diagnostic usefulness of this specific, relatively simple and rapid procedure is confirmed. | [
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|
PMID:17928 | Studies on myocardial reperfusion injury. I. Favorable modification by adjusting reperfusate pH. | This study tests the hypothesis that postischemic myocardial depression can be reduced by providing an initial reperfusate pH which is appropriate for myocardial temperature (i.e., metabolic systems function optimally when pH is kept slightly alkaline to the neutral point, which changes with temperature in concordance with the pK of water). Ten dogs underwent 1 hour of ischemic arrest with topical hypothermia (intramyocardial temperature 16+/-2 degrees C). The initial reperfusate (500 cc of blood from the extracorporeal circuit) was infused (100 cc/minute) into the proximal aorta just before removing the cross-clamp. Reperfusate pH was kept at 7.4 in five dogs (control) and raised to 7.8 with THAM [tris (hydroxymethyl) aminomethane] in five dogs. Measurements 30 minutes after reperfusion showed that raising reperfusate pH to 7.8 resulted in (1) higher subendocardial blood flows (109+/-20 vs 61 cc+/-8 cc/100 gm/minute), (2) redistribution of postischemic blood flow toward the subendocardium (endocardial/epicardial flow 1.25+/-0.1 vs 1.0+/-0.03), (3) higher left ventricular oxygen uptakes (0.046 vs 0.033 cc/100 gm/beat), (4) better postischemic left ventricular compliance (56+/-3% more compliant), and (5) improved left ventricular performance (88+/-7% recovery vs only 57+/-3% recovery at pH 7.4). Postischemic edema (2% water gain) was unchanged by pH modification. We conclude that initial reperfusion with the appropriate pH provides an optimal milieu for restoration of cellular metabolism, counteracts the acidosis of ischemia, and improves postischemic left ventricular blood flow, distribution, oxygen uptake, compliance, and performance. | Studies on myocardial reperfusion injury. I. Favorable modification by adjusting reperfusate pH. This study tests the hypothesis that postischemic myocardial depression can be reduced by providing an initial reperfusate pH which is appropriate for myocardial temperature (i.e., metabolic systems function optimally when pH is kept slightly alkaline to the neutral point, which changes with temperature in concordance with the pK of water). Ten dogs underwent 1 hour of ischemic arrest with topical hypothermia (intramyocardial temperature 16+/-2 degrees C). The initial reperfusate (500 cc of blood from the extracorporeal circuit) was infused (100 cc/minute) into the proximal aorta just before removing the cross-clamp. Reperfusate pH was kept at 7.4 in five dogs (control) and raised to 7.8 with THAM [tris (hydroxymethyl) aminomethane] in five dogs. Measurements 30 minutes after reperfusion showed that raising reperfusate pH to 7.8 resulted in (1) higher subendocardial blood flows (109+/-20 vs 61 cc+/-8 cc/100 gm/minute), (2) redistribution of postischemic blood flow toward the subendocardium (endocardial/epicardial flow 1.25+/-0.1 vs 1.0+/-0.03), (3) higher left ventricular oxygen uptakes (0.046 vs 0.033 cc/100 gm/beat), (4) better postischemic left ventricular compliance (56+/-3% more compliant), and (5) improved left ventricular performance (88+/-7% recovery vs only 57+/-3% recovery at pH 7.4). Postischemic edema (2% water gain) was unchanged by pH modification. We conclude that initial reperfusion with the appropriate pH provides an optimal milieu for restoration of cellular metabolism, counteracts the acidosis of ischemia, and improves postischemic left ventricular blood flow, distribution, oxygen uptake, compliance, and performance. | [
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|
PMID:17929 | Endogenous serotonin in the control of gastric acid secretion. | In three dogs with Heidenhain pouches (HP), gastric fistulas (GF), and duodenal cannulas, acidification of the duodenum with 0.1N HC1 (5 ml/minute) resulted in significant inhibition of GF output (preacidification, 8.66+/-0.58 mEq/30 minutes; postacidification, 5.47+/-0.66 mEq/30 minutes) and elevated peripheral venous blood levels of serotonin (basal, 226+/-64 ng/ml; peak, 521+/-168 ng/ml). Infusion of exogenous serotonin to comparable blood levels (basal, 208+/-38 ng/ml; mean postacidification, 571+/-153 ng/ml) resulted in similar GF inhibition (preacidification, 9.17+/-0.92 mEq/30 minutes; postacidification, 6.49+/-0.56 mEq/30 minutes). Per increment in peripheral blood serotonin of 1 ng/ml, endogenous serotonin inhibited 54.59+/-12.99 muEq/hour and exogenous serotonin inhibited 46.54+/-10.39 muEq/hour, p greater than 0.05. Neither endogenously released nor exogenous serotonin inhibited HP acid output. Using mesenteric venous infusions of serotonin, significant amounts of immunoreactive serotonin were found to escape hepatic inactivation; basal peripheral venous levels of serotonin, 233+/-103 ng/ml, increased to 455+/-127 ng/ml at 10 minutes. During release of endogenous serotonin, 92+/-21% of portal venous serotonin was bound to platelets; in contrast, during intraportal serotonin infusion, only 59+/-18% of serotonin was platelet bound. | Endogenous serotonin in the control of gastric acid secretion. In three dogs with Heidenhain pouches (HP), gastric fistulas (GF), and duodenal cannulas, acidification of the duodenum with 0.1N HC1 (5 ml/minute) resulted in significant inhibition of GF output (preacidification, 8.66+/-0.58 mEq/30 minutes; postacidification, 5.47+/-0.66 mEq/30 minutes) and elevated peripheral venous blood levels of serotonin (basal, 226+/-64 ng/ml; peak, 521+/-168 ng/ml). Infusion of exogenous serotonin to comparable blood levels (basal, 208+/-38 ng/ml; mean postacidification, 571+/-153 ng/ml) resulted in similar GF inhibition (preacidification, 9.17+/-0.92 mEq/30 minutes; postacidification, 6.49+/-0.56 mEq/30 minutes). Per increment in peripheral blood serotonin of 1 ng/ml, endogenous serotonin inhibited 54.59+/-12.99 muEq/hour and exogenous serotonin inhibited 46.54+/-10.39 muEq/hour, p greater than 0.05. Neither endogenously released nor exogenous serotonin inhibited HP acid output. Using mesenteric venous infusions of serotonin, significant amounts of immunoreactive serotonin were found to escape hepatic inactivation; basal peripheral venous levels of serotonin, 233+/-103 ng/ml, increased to 455+/-127 ng/ml at 10 minutes. During release of endogenous serotonin, 92+/-21% of portal venous serotonin was bound to platelets; in contrast, during intraportal serotonin infusion, only 59+/-18% of serotonin was platelet bound. | [
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|
PMID:17932 | Sensitization against non-HLA antigens following bone marrow graft rejection. | A patient with severe aplastic anemia rejected consecutive bone marrow transplants from two HLA-identical sibling donors. Following rejection, the patient developed antibodies that reacted strongly against donor lymphocytes in the complement-dependent cytotoxicity assay. Whereas the reactivity was initially directed specifically against the first marrow donor, cells of both donors and most unrelated individuals were killed by sera obtained after the second injection. These sera were also cytotoxic to the patient's own pre-transplant cells but not to her autologous post-transplant lymphocytes. | Sensitization against non-HLA antigens following bone marrow graft rejection. A patient with severe aplastic anemia rejected consecutive bone marrow transplants from two HLA-identical sibling donors. Following rejection, the patient developed antibodies that reacted strongly against donor lymphocytes in the complement-dependent cytotoxicity assay. Whereas the reactivity was initially directed specifically against the first marrow donor, cells of both donors and most unrelated individuals were killed by sera obtained after the second injection. These sera were also cytotoxic to the patient's own pre-transplant cells but not to her autologous post-transplant lymphocytes. | [
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|
PMID:17934 | Enhanced solubility of 2,8 dihydroxyadenine (DOA) in human urine. | Water solubility of the adenine catabolite 2,8 dihydroxyadenine (DOA) frequently forms the basis for predicting potential DOA crystal formation in human urine following infusion of adenine-fortified blood. Measurements relevant to solubility, ionic dissociation, and supersaturability of DOA in aqueous buffers and human urine at 37 C establish striking quantitative differences in the physico-chemical behavior of DOA in the two media. The basal solubility of DOA is 1.53 +/- 0.04 mg/1 (approximately 9 X 10(-6) M) in water (pH 6.5). DOA is an ampholyte characterized by aqueous thermodynamic macrodissociation constants of pKa1 = 2.6, pKa2 = 8.1, and pKa3 = 11.52. This compound displays pH-dependent solubility, although significant solubility increases beyond basal values do not occur within the physiologic pH range for human urine. Supersaturated aqueous solutions (three to sixteen times basal solubility) can be achieved but are unstable. In contrast, human urine at 37 C exhibits enhanced capacity for solubilizing DOA. In vitro basal solubility is 2.68 +/- 0.84 mg/1 at pH 5.0 and 4.97 +/- 1.49 mg/1 at pH 7.8. The apparent pK 2for DOA in urine of 7.9 to 8.1 is dependent upon urine osmolality. Urine can be supersaturated with Doa in vitro to approximately ten times its basal solubility by adding DOA solubilized in weak base, or by evaporation of a urine-DOA mixture. DOA remains supersaturated in urine for at least 16 hours despite gentle agitation. Little variation in in vitro DOA apparent supersaturation was found among urine samples from four normal individuals (40.38 +/- 3.33 mg/1). A patient receiving oral adenine exhibited urinary DOA solubility in considerable excess (96.0 mg/1) of that predicted from water and from in vitro urine solubility studies. Thus, water solubility of DOA is poorly predictive of in vitro and in vivo DOA solubility in human urine. On the basis of these data, estimates of the load of adenine-fortified blood expected to result in urinary DOA crystal formation may be revised upward. | Enhanced solubility of 2,8 dihydroxyadenine (DOA) in human urine. Water solubility of the adenine catabolite 2,8 dihydroxyadenine (DOA) frequently forms the basis for predicting potential DOA crystal formation in human urine following infusion of adenine-fortified blood. Measurements relevant to solubility, ionic dissociation, and supersaturability of DOA in aqueous buffers and human urine at 37 C establish striking quantitative differences in the physico-chemical behavior of DOA in the two media. The basal solubility of DOA is 1.53 +/- 0.04 mg/1 (approximately 9 X 10(-6) M) in water (pH 6.5). DOA is an ampholyte characterized by aqueous thermodynamic macrodissociation constants of pKa1 = 2.6, pKa2 = 8.1, and pKa3 = 11.52. This compound displays pH-dependent solubility, although significant solubility increases beyond basal values do not occur within the physiologic pH range for human urine. Supersaturated aqueous solutions (three to sixteen times basal solubility) can be achieved but are unstable. In contrast, human urine at 37 C exhibits enhanced capacity for solubilizing DOA. In vitro basal solubility is 2.68 +/- 0.84 mg/1 at pH 5.0 and 4.97 +/- 1.49 mg/1 at pH 7.8. The apparent pK 2for DOA in urine of 7.9 to 8.1 is dependent upon urine osmolality. Urine can be supersaturated with Doa in vitro to approximately ten times its basal solubility by adding DOA solubilized in weak base, or by evaporation of a urine-DOA mixture. DOA remains supersaturated in urine for at least 16 hours despite gentle agitation. Little variation in in vitro DOA apparent supersaturation was found among urine samples from four normal individuals (40.38 +/- 3.33 mg/1). A patient receiving oral adenine exhibited urinary DOA solubility in considerable excess (96.0 mg/1) of that predicted from water and from in vitro urine solubility studies. Thus, water solubility of DOA is poorly predictive of in vitro and in vivo DOA solubility in human urine. On the basis of these data, estimates of the load of adenine-fortified blood expected to result in urinary DOA crystal formation may be revised upward. | [
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|
PMID:17940 | Uropharmacology: v. choline esters and other parasympathomimetic drugs. | Various parasympathomimetic drugs are discussed, including the choline esters, bethanechol, carbachol, methacholine chloride, and furtrethonium. Other cholinomimetic agents include muscarine, muscarone, arecholine, and pilocarpine. Anticholinesterase agents inhibit or inactivate acetylcholinesterase enzyme and thus result in a prolonged stimulation of cholinergic receptors by endogenous ACh. Bethanechol is the most widely used parasympathomimetic drug in the United States. Its action is mainly muscarinic with activity largely confined to the urinary bladder and to a lesser degree the gastrointestinal tract. It can be administered only subcutaneously or orally, and adequate dosage is necessary for a successful response. | Uropharmacology: v. choline esters and other parasympathomimetic drugs. Various parasympathomimetic drugs are discussed, including the choline esters, bethanechol, carbachol, methacholine chloride, and furtrethonium. Other cholinomimetic agents include muscarine, muscarone, arecholine, and pilocarpine. Anticholinesterase agents inhibit or inactivate acetylcholinesterase enzyme and thus result in a prolonged stimulation of cholinergic receptors by endogenous ACh. Bethanechol is the most widely used parasympathomimetic drug in the United States. Its action is mainly muscarinic with activity largely confined to the urinary bladder and to a lesser degree the gastrointestinal tract. It can be administered only subcutaneously or orally, and adequate dosage is necessary for a successful response. | [
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|
PMID:17942 | The outbreak of equine influenza in England: January 1976. | Equine influenza type 2 infections occurred in the Newmarket areas in January 1976. The disease did not spread to any extent and while this may have been due to recent vaccination it was found that not all vaccinated horses were fully protected. The virus involved showed some antigenic drift from the prototype strain A/equine/Miami/1/63 (Heq 2 Neq 2). | The outbreak of equine influenza in England: January 1976. Equine influenza type 2 infections occurred in the Newmarket areas in January 1976. The disease did not spread to any extent and while this may have been due to recent vaccination it was found that not all vaccinated horses were fully protected. The virus involved showed some antigenic drift from the prototype strain A/equine/Miami/1/63 (Heq 2 Neq 2). | [
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|
PMID:17944 | Aneurysms of the coronary arteries in infants and children. A review, and report of six cases. | In recent years large numbers of the so-called "mucocutaneous lymph node syndrome" or "Kawasaki's disease" have been described by Japanese workers, but instances of this disorder are only now being reported as isolated cases by European or North American physicians. The disease has, therefore, been considered to be a new entity. One of its most striking features is the development of aneurysms of the coronary arteries in infants or children, which may lead to sudden death. Aneurysms of the coronary arteries in childhood are rare, and hence it was considered relevant to report six such cases, and to examine their possible relationship to Kawasaki's disease. The pathological changes underlying the latter disorder are not well known; they are considered to be indistinguishable from infantile polyarteritis nodosa. A diagnosis of polyarteritis nodosa was also thought to be most likely to apply in the cases presented here, particularly in view of the frequency with which aneurysms of the coronary arteries have been found in this disorder. In the absence of valid pathological distinctions between Kawasaki's disease and infantile polyarteritis nodosa, the question arises whether these entities are, in fact, different, and whether Kawasaki's disease is the new entity it is assumed to be. | Aneurysms of the coronary arteries in infants and children. A review, and report of six cases. In recent years large numbers of the so-called "mucocutaneous lymph node syndrome" or "Kawasaki's disease" have been described by Japanese workers, but instances of this disorder are only now being reported as isolated cases by European or North American physicians. The disease has, therefore, been considered to be a new entity. One of its most striking features is the development of aneurysms of the coronary arteries in infants or children, which may lead to sudden death. Aneurysms of the coronary arteries in childhood are rare, and hence it was considered relevant to report six such cases, and to examine their possible relationship to Kawasaki's disease. The pathological changes underlying the latter disorder are not well known; they are considered to be indistinguishable from infantile polyarteritis nodosa. A diagnosis of polyarteritis nodosa was also thought to be most likely to apply in the cases presented here, particularly in view of the frequency with which aneurysms of the coronary arteries have been found in this disorder. In the absence of valid pathological distinctions between Kawasaki's disease and infantile polyarteritis nodosa, the question arises whether these entities are, in fact, different, and whether Kawasaki's disease is the new entity it is assumed to be. | [
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|
PMID:17945 | [Cardiac output, blood gas analysis and the acid-base state of the blood in chronic cor pulmonale]. | In 61 patients with chronic cor pulmonale with compensation and decompensation of circulation, the stroke and minute heart volume were studied as well as the indices, characterizing the blood-gas contents and acid-base blood state. The minute heart volume in the patients examined proved to be with normal values. Stroke heart volume is decreased in all patients examined with chronic cor pulmonale. The acceleration of heart activity enables the maintenance of normal minute volume. Hypoxemia has a cardiac depressive effect as regards minute volume and heart rate. The moderate hypercapnia has a certain stimulating effect on heart. A direct proportional correlation exists between the hypercapnia degree and the tendency of minute volume increase and especially of heart rate. The campaign against hypoxemia is an essential element in the prophylaxis and early treatment of chronic cor pulmonale. | [Cardiac output, blood gas analysis and the acid-base state of the blood in chronic cor pulmonale]. In 61 patients with chronic cor pulmonale with compensation and decompensation of circulation, the stroke and minute heart volume were studied as well as the indices, characterizing the blood-gas contents and acid-base blood state. The minute heart volume in the patients examined proved to be with normal values. Stroke heart volume is decreased in all patients examined with chronic cor pulmonale. The acceleration of heart activity enables the maintenance of normal minute volume. Hypoxemia has a cardiac depressive effect as regards minute volume and heart rate. The moderate hypercapnia has a certain stimulating effect on heart. A direct proportional correlation exists between the hypercapnia degree and the tendency of minute volume increase and especially of heart rate. The campaign against hypoxemia is an essential element in the prophylaxis and early treatment of chronic cor pulmonale. | [
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|
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