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PubMed1975

The effect of potassium chloride on the Bohr effect of human hemoglobin.

The normal and differential titration curves of liganded and unliganded hemoglobin were measured at various KCl concentrations (0.1 to 2.0 M). In this range of KCl concentrations, the curves for deoxyhemoglobin showed no salt-induced pK changes of titratable groups. In the same salt concentration range oxyhemoglobin showed a marked change in titration behavior which could only be accounted for by a salt-induced increase in pK of some titratable groups. These results show that the suppression of the alkaline Bohr effect by high concentrations of neutral univalent salt is not caused by a weakening of the salt bridges in deoxyhemoglobin but is due to an interaction of chloride ions with oxyhemoglobin. Measurements of the Bohr effect at various KCl concentrations showed that at low chloride ion concentration (5 times 10-3 M) the alkaline Bohr effect is smaller than at a concentration of 0.1 M. This observation indicates that at a chloride ion concentration of 0.1 M, part of the alkaline Bohr effect is due to an interaction of chloride ions with hemoglobin. Furthermore, at low concentrations of chloride ions the acid Bohr effect has almost vanished. This result suggests that part of the acid Bohr effect arises from an interaction of chloride ions with oxyhemoglobin. The dependence of the Bohr effect upon the chloride ion concentration can be explained by assuming specific binding of chloride ions to both oxy- and deoxyhemoglobin, with deoxyhemoglobin having the highest affinity.

Binding Sites↗
PubMed1975

Rate-dependent Effects of drugs. II. effects of some major tranquilizers on multiple fixed-ratio, fixed-interval schedule performance.

The effects of promazine, chlorpromazine, triflupromazine, prochlorperazine, trifluoperazine, perphenazine, fluphenazine, haloperidol, benzquinamide, tetrabenazine and chlorprothixene were determined on the rate of conditioned key pecking of pigeons under a multiple fixed-ratio 30, fixed-interval 5-minute schedule of food presentation. Chlorpromazine, prochlorperazine, perphenazine, chlorprothixene and tetrabenazine decreased responding relatively more within the fixed-interval component than within the fixed-ratio component and also produced rate-dependent effects within the fixed interval component, increasing the low rates of responding early in the fixed-interval but decreasing the high rates of responding in the terminal parts of the fixed interval. Triflupromazine, trifluoperazine, fluphenazine and haloperidol also decreased responding relatively more within the fixed-interval component than within the fixed-ratio component, but did not produce rate-dependent effects within the fixed-interval component. Both low and high rates of responding within the fixed interval were decreased only by these four drugs and they produced small and inconsistent decreases in the quarter-life values. Promazine and benzquinamide decreased responding relatively more within the fixed-ratio component than within the fixed-interval component and also produced rate-dependent effects within the fixed-interval component. There was a structure-activity relationship between the chemical group on the benzene ring of the phenothiazine nucleus and the rate-dependent effect on responding within the fixed-interval component. Phenothiazines with a hydrogen or chlorine group on the benzene ring produced a rate-dependent effect on responding within the fixed interval, while phenothiazines with a trifluoromethyl group on the benzene ring did not produce a rate-dependent effect on responding within the fixed interval.

Animals↗
PubMed1977

Fitness effects of EMS-induced mutations on the X chromosome of Drosophila melanogaster. II. Hemizygous fitness effects.

X chromosomes mutagenized with EMS were tested for their effects on the fitness of hemizygous carriers. The tests were carried out in populations in which treated and untreated X chromosomes segregated from matings between males and attached-X females; the populations were maintained for several generations, during which time changes in the frequencies of the treated and untreated chromosomes were observed. From the rates at which the frequencies changed, the fitness effects of the treated chromosomes were determined. It was found that flies hemizygous for a mutagenized chromosome were 1.7% less fit per mM EMS treatment than those hemizygous for an untreated chromosome. Since the same flies were only 0.5% per mM less viable than their untreated counterparts, the total fitness effect of an X chromosome carrying EMS-induced mutants is three to four times greater than its viability effect. By comparing the heterozygous effect of a mutagenized X chromosome on fitness with the corresponding hemizygous effect, the dominance value for the chromosome is estimated to be about 0.25.

Animals↗
PubMed1979

The long-term hypotensive effect of timolol maleate compared with the effect of pilocarpine in simple and capsular glaucoma.

The long-term intraocular pressure (IOP) lowering effect of a beta-adrenergic blocking agent, timolol maleate, in topical administration was compared with the effect of pilocarpine on simple and capsular glaucoma by means of diurnal pressure curves during a six-month follow-up. In simple glaucoma timolol was more effective than pilocarpine in lowering IOP. In the follow-up a significant but not marked increase of the IOP was observed. In capsular glaucoma timolol was not effective enough, but when it was co-administered with miotics the IOP lowering effect was better than with either substance alone. Timolol induced no accomodative myopia, miosis, reduction of tear flow or other side effects. It increased the outflow facility in simple glaucoma but not in capsular glaucoma. During the trial, the anterior chamber depth increased while the corneal thickness remained unchanged. Four out of the six eyes included in a previous report of secondary glaucoma due to chronic uveitis are still, after one year of therapy, controlled with timolol.

Adrenergic beta-Antagonists↗
PubMed1975

Antimicrobial effect of simple lipids and the effect of pH and positive ions.

Various branched fatty acids, particularly those of iso-configuration, have been shown to possess fungistatic and bacteriostatic properties. On the basis of their swelling effect on hyphae of Fusarium roseum it was suggested that this is due to an increase in the permeability of the plasma membrane. The solubilization of fatty acids in membranes should be expected to be influenced by the degree of dissociation and the presence of counter ions. Therefore, the effects of pH and K(+), Na(+), and Ca(2+) ions were studied. It is demonstrated that the presence of the univalent ions, Na(+) and K(+), markedly enhances the fungistatic effect of iso-tetradecanoic acid, whereas the opposite effect is noted for the divalent ion, Ca(2+). The effects are particularly pronounced at high pH. Furthermore, the antimicrobial effect obtained from the combination of fatty acid and tetramethylthiuramdisulfide is significantly enhanced in the presence of 0.1 and 0.2% KCl.

Anti-Infective Agents↗
PubMed1975

Effect of drugs on effective vascular compliance in acute heart failure.

Effective vascular compliance determined by the delta V/delta P relationship was measured repeatedly in anesthetized open-chest dogs without circulatory arrest utilizing a closed circuit venous bypass system with a constant cardiac output. Production of acute heart failure by gradual aortic constriction was associated with a significant decrease in total effective vascular compliance. The effect of loading and 20-min maintenance doses of different drugs on vascular compliance of animals in acute heart failure was studied. Phenoxybenzamine (total dose 2 mg/kg) produced a rapid and sustained increase in effective vascular compliance and theophylline (12 mg/kg) produced an increase which was more gradual in development than with phenoxybenzamine. Morphine (1 mg/kg) produced a rapid but transient increase in compliance. In contrast, ethacrynic acid (100 mg) or nitroglycerin (0.6 or 1.2 mg) did not alter vascular compliance significantly. These agents differ markedly in the magnitude and time-course of effect on effective vascular compliance.

Acute Disease↗
PubMed1978

Electrophysiologic effects of partial coronary flow reduction in the exposed canine heart. Effects of ischemia and ischemic-induced regional hypothermia on refractoriness and conduction delay.

In the open-chested dog, coronary flow reduction results in a decrese of regional myocardial temperature (T). We assessed the contribution of T decrease to changes in refractoriness and conduction delay attributed to ischemia. The independent effect of regional hypothermia on effective refractory period (ERP) was a linear function of the temperature (ERP = -b T +a) with a -r = 0.97 0.02 in 11 dogs. The effect on conduction time of a ventricular premature beat was a linear function of the dog T at both endocardium (-r = 0.95 +/- 0.02) and epicardium (-r = 0.96 +/- 0.01). A 75% reduction in coronary flow resulted in a mean T decrease of 1.0 +/- 0.3 degrees C. The T decrease was sufficient to mask the effects of ischemia on shortening of the ERP. Furthermore, the conduction delay of ventricular premature beats during 75% coronary flow reduction could be accounted for by the decrease in T alone in five of seven dogs. We conclude that changes in refractoriness and conduction during acute coronary flow reduction in the open-chested dog are due to the composite effects of ischemia and the decrease in regional temperature. The open-chested model may have important limitations in understanding the electrophysiologic effects of acute coronary insufficiency. However, it may have important applications in defining the electrophysiologic environment at the time of coronary artery surgery.

Animals↗
PubMed1978

Anti-convulsant effect of phthalazino-2,3b-phthalazine-5(14H),12(7h)-dione (L-5418). I. Behavioral effect.

Since it had been demonstrated that L5418 has an anti-convulsant effect with no relation to its anti-inflammatory properties, comparative studies were carried out with the use of currently available anti-convulsant agents as controls. L-5418 inhibited tonic convulsions induced by maximal electroshock and strychinine in mice and prevented animals from the death sequence. L-5418 had an inhibitory effect on tonic convulsions induced by pentetrazol and N-sulfamoyl-hexahydroazepine (SaH 41-178), but not on clonic convulsions by those compounds at even a high dosage or on clonic convulsions induced by picrotoxin and bemegride. Trimethadione produced an inhibitory effect on both tonic and clonic convulsions. The hypnotic agents, phenobarbital and glutethimide inhibited both convulsions, but a higher dose was required in the case of clonic convulsions. Anti-convulsant agents are classified into three different groups according to their mode of action. L-5418 had the same mode of action as seen with diphenylhydantoin and carbamazepine. As L-5418 did not inhibit tremor induced by tremorine, an anti-Parkinson effect was ruled out. When L-5418 was administered alone, the animals did not lose the righting reflex nor show muscle relaxation observed in inclined screen and rotarod tests. Moreover, the compound had no influence on the aggressive behavior induced by electrical stimulation or olfactory bulb ablation. L-5418 possesses a selective anti-convulsant effect, yet has no sedative, tranquilizing or disturbing effects on movement such as equilibrium disturbance or muscle relaxation. L-5418 may prove useful for grand mal epilepsy as it is less toxic than diphenylhydantoin and carbamazepine.

Aggression↗
PubMed1979

Environmental effects of increased coal utilization: ecological effects of gaseous emissions from coal combustion.

This report is limited to an evaluation of the ecological and environmental effects of gaseous emissions and aerosols of various types which result from coal combustion. It deals with NOx, SOx, fine particulate, photochemical oxidant and acid precipitation as these pollutants affect natural and managed resources and ecosystems. Also, synergistic effects involving two or more pollutants are evaluated as well as ecosystem level effects of gaseous pollutants. There is a brief summary of the effects on materials and atmospheric visibility of increased coal combustion. The economic implications of ecological effects are identified to the extent they can be determined within acceptable limits. Aquatic and terrestrial effects are distinguished where the pollutants in question are clearly problems in both media. At present, acid precipitation is most abundant in the north central and northeastern states. Total SOx and NOx emissions are projected to remain high in these regions while increasing relatively more in the western than in the eastern regions of the country. A variety of ecological processes are affected and altered by air pollution. Such processes include community succession and retrogression, nutrient biogeochemical cycling, photosynthetic activity, primary and secondary productivity, species diversity and community stability. Estimates of the non health-related cost of air pollutants range from several hundred million dollars to $1.7 billion dollars per year. In general, these estimates include only those relatively easily measured considerations such as the known losses to cultivate crops from acute air pollution episodes or the cost of frequent repainting required as a result of air pollution. No substantial nationwide estimates of losses to forest productivity, natural ecosystem productivity which is tapped by domestic grazing animals and wildlife, and other significant dollar losses are available.

Air Pollution↗
PubMed1979

Effects of glucocorticosteroids on cultured human skin fibroblasts. V. Influence of anabolic steroids on the inhibitory effects of clobetasol-17-propionate on cell proliferation and collagen synthesis.

As previously found, the glucocorticosteroid clobetasol-17-propionate inhibits cell proliferation during the early growth stage of normal baby foreskin fibroblasts and collagen synthesis in confluent cultures of these cells. The degree of inhibition of cell proliferation decreases with increasing cell density and, moreover, is transient. The anabolic steroids nandrolone and nandrolone-phenyl-propionate have similar effects on these cells. Likewise the magnitude of the inhibition is dose-dependent. When present together the two types of drug do not act in an additive manner. Even at low concentrations the anabolic steroids abolish the inhibitory effect of the glucocorticosteroid on cell proliferation. Furthermore, in this case only the inhibitory effect of the glucocorticosteroid on collagen synthesis is found and there is no further increase in this effect due to the presence of the anabolic steroids. Our results imply that the use of low concentrations of anabolic steroids combined with glucocorticosteroids in topical application to the skin may abolish some of the undesirable side effects of the glucocorticosteroids.

Betamethasone↗
PubMed1976

Dual effect of 2,3-diphosphoglycerate on the Bohr effects of human blood.

The influence of the red cell concentration of 2,3-diphosphoglycerate (2,3-DPG, 0.5-26 mumoles/g erythrocytes) on the "CO2-Bohr effect" (pH varied by CO2 at constant base excess) and the "fixed acid-Bohr effect" (pH varied by fixed acid or base at constant PCO2) was studied in human blood at plasma pH values ranging between pH 7.2 and pH 7.6. Elevation of red cell 2,3-DPG concentration leads to a numerical decrease of the "CO2-Bohr coefficient" referring to plasma pH. The "fixed acid-Bohr coefficients" are numerically smaller than the corresponding "CO2-Bohr coefficients" and exhibit a maximum at normal red cell 2,3-DPG concentrations. The Bohr coefficients referring to red cell pH are distinctly higher than those referring to plasma pH, especially at high 2,3-DPG levels. This is due on the one hand to the physico-chemical properties of the intact red cell membrane, and on the other hand to a 2,3-DPG-induced decrease in the ratio deltapHcell/deltapHplasma. From the results it is concluded that 2,3-DPG exerts a dual effect on the Bohr coefficients of whole blood which is mediated 1. by the direct effect of 2,3-DPG on the allosteric properties of hemoglobin (as reflected by changes of the Bohr coefficients referring to red cell pH), and 2. by the effect of 2,3-DPG on deltapHcell/deltapHplasma.

Carbon Dioxide↗
PubMed1978

Absorption, effectiveness and side effects of highly purified porcine NPH-insulin preparations (Leo).

The clinical characteristics of highly purified porcine NPH-insulin (Insulin Retard RI) were investigated, including absorption from the subcutaneous tissue, blood glucose-lowering effect, stability of mixtures of NPH and regular insulin and measurement of circulating porcine proinsulin and insulin antibodies in diabetes. The absorption of NPH-insulin followed first order kinetics. The half time was 6.9 +/- 2.6h, with an intraindividual coefficient of variation of 26% and an interindividual coefficient of variation of 55%. After 24 h 90% of the injected insulin had disappeared from the subcutaneous tissue. The plasma insulin concentration was maximal 4-5 h after the injection and 24 h after the injection it was not significantly higher than before the injection. The blood glucose-lowering effect was significant 2.5 h after subcutaneous injection of NPH-insulin and was maximal after 5.5 h. The blood glucose-lowering effect of a pre-prepared mixture of 70% NPH and 30% regular insulin was not significantly different from the effect of 70% NPH and 30% regular insulin injected separately, which indicates the stability of mixtures of NPH and Regular insulin. Porcine proinsulin disappeared from the serum of patients switched to treatment with highly purified porcine NPH insulin and the insulin antibody titer fell. It was concluded that insulin Retard RI has a well-defined, reproducible effect with a clinically useful time course.

Absorption↗
PubMed1979

Disrupting the conditioned stimulus preexposure effect in flavor-aversion learning: effects of interoceptive distractor manipulations.

Rats exposed to a flavor prior to a conditioning trial involving that stimulus learn a significantly diminished flavor aversion relative to nonpreexposed control animals. A series of four experiments investigated the ability of the conditioned stimulus (CS) preexposure effect to be disrupted by the introduction of a distractor flavor stimulus between the preexposure and conditioning episodes. Experiment 1 demonstrated that the preexposure effect could be reduced by a distractor presented immediately following the preexposure. In Experiment 2, it was discovered that a novel distractor was more effective than a familiar distractor, even though both stimuli were sensorily equivalent. Experiment 3 further analyzed the distractor effect and demonstrated that the magnitude of disruption was more pronounced with immediate than with delayed (3 hr) distractor manipulations. Finally, Experiment 4 assessed the effects of the distractor in the absence of CS preexposure. The relation of the results from these experiments to general information theory is discussed.

Animals↗
PubMed1978

Sympathomimetic effects of pancuronium bromide on the cardiovascular system of the pithed rat: a comparison with the effects of drugs blocking the neuronal uptake of noradrenaline.

1. The effects of pancuronium bromide on the cardiovascular system of the pithed rat were examined. Pancuronium had two effects, a short-lasting cardiovascular stimulation following injection and a longer-lasting potentiation of responses to sympathetic nerve stimulation. 2 The initial effect of pancuronium was compared with that of tyramine. The cardioaccelerator but not the pressor responses to both pancuronium and tyramine were significantly reduced following sympathectomy with 6-hydroxydopamine (6-OHDA). 3 The action of pancuronium in potentiating sympathetic nerve responses was compared with that of known blockers of the neuronal uptake of noradrenaline (NA). Pancuronium (1 mg/kg) and cocaine (0.5 mg/kg) potentiated cardioaccelerator and pressor responses to sympathetic stimulation. These effects of pancuronium could be obtained following adrenalectomy and during neuromuscular blockade with gallamine. Pancuronium and uptake blockers potentiated the cardioaccelerator response to NA, reduced the response to tyramine, but did not affect the response to isoprenaline. Pancuronium and uptake blockers potentiated the pressor response to NA, but did not affect the response to tyramine or clonidine. 4 Following sympathectomy with 6-OHDA, pancuronium failed to potentiate cardioaccelerator and pressor responses to NA. 5 These results are discussed in relation to two main cardiovascular effects of pancuronium; an indirect sympathomimetic action and blockade of the neuronal uptake of NA.

Adrenalectomy↗
PubMed1976

Effect of 1,10-phenanthroline on bacterial conjugation in Escherichia coli K-12: inhibition of maturation from preliminary mates into effective mates.

The addition of 1 mM orthophenanthroline (OP) into a mating mixture drastically reduced the production of recombinants. Examination of the effect of OP on each step of conjugation showed that the effect on the following steps could not account for the up to 500-fold reduction of recombinant formation: (i) preliminary mate formation and (ii) deoxyribonucleic acid transfer and integration. Taking these results and additional experiments together, we conclude that OP inhibits the maturation of preliminary mates into effective mates. Kinetic experiments showed that there were two phases in the maturation of preliminary (OP-sensitive) mates into effective (OP-resistant) mates. The half-time (the time required to reach 50% OP-resistant mates) was 2.5 min for the first phase and 4 min for the second phase, with an overall half-time of 7.5 min. In contrast, only 3 min was required to reach 50% Zn2+-resistant mates. The difference in half-time suggests that there is an intermediate step involved to form an effective mate from a preliminary mate.

Cations, Divalent↗
PubMed1978

The effect of dehydration on the side effects of metrizamide myelography.

The effect of dehydration on the incidence of side effects from metrizamide myelography was studied. One hundred consecutive patients scheduled for myelography fasted overnight and were then randomly divided into two groups. Group I received 2 liters of fluid intravenously just prior to myelography; Group II did not. Both groups were studied in the standard manner, using 170 mg l/ml of metrizamide. Side effects were recorded 24 and 48 hours after the procedure. Headaches, vomiting, and some other side effects were less common and less severe in the hydrated group. Clear liquids given orally or intravenous fluids are recommended prior to myelography to minimize side effects.

Adolescent↗
PubMed1977

The difference in effect of predosing with antiallergic compounds between the rat PCA model and the monkey asthma model. Comparison of the effects of PRD-92-Ea and disodium cromoglycate.

DSCG and PRD-92-Ea showed tachyphylaxis in the rat PCA test when a large intravenous dose (40 mg/kg of DSCG and 20 mg/kg of PRD-92-Ea) was given 30 min before administering intravenously the expected effective doses at the time of antigen challenge. This predosing led to a marked loss of effectiveness. Cross-reacting tachyphylaxis was also demonstrated in this model. Predosing rats with DSCG led to a great loss of effectiveness of a subsequent expected active dose of PRD-92-Ea and predosing with PRD-92-Ea had the same effect in preventing the antiallergic action of a subsequent dose of DSCG. The Rhesus monkey (Macaca mulatta) did not exhibit this phenomenon of tachyphylaxis. PRD-92-Ea and DSCG were given intravenously 30 min before and the same dose of 20 mg/kg repeated just before Ascaris suum challenge in the Rhesus monkey asthma model with no loss of their expected effectiveness.

Administration, Oral↗