Endogenous opioid peptides: do they mediate the acute antihypertensive action of clonidine in humans?

The involvement of endogenous opioid peptides in the antihypertensive action of acutely administered clonidine, a centrally acting adrenergic agonist, was studied in humans. Eight hypertensive subjects received clonidine 0.2 mg orally, naloxone 8 mg i.v. followed by a 0.13 mg/min infusion, and both drugs together on separate days. Clonidine resulted in a significant decrease in mean blood pressure, which was not affected by concomitant treatment with naloxone. Naloxone alone or with clonidine caused significant elevations in plasma aldosterone, not mediated by increased plasma renin activity. Plasma beta-endorphin was not increased after clonidine administration. In humans, the antihypertensive effects of acute clonidine administration do not appear to be mediated by the release or action of endogenous opioids.     

Changes in the concentration of metalloproteins in the blood plasma in hypoxia and hyperbaric oxygenation

Dynamics of hemoglobin, ceruloplasmin concentration, the changes of chemiluminescence in blood plasma and kinetics of rat erythrocyte heat denaturation during consequent exposition of high altitude hypoxia and hyperbaric oxygenation have been studied. Severe hypoxia causes the decrease of extraerythrocyte hemoglobin and oxidase activity of ceruloplasmin. Reoxygenation results in significant increase of blood plasma chemiluminescence with simultaneous increase of extraerythrocyte hemoglobin level and with modification of surface structure of the erythrocyte membranes. Possible pathways of activation of oxygen-dependent of free-radical processes during reoxygenation are discussed.     

A simple model for the optical properties of chiral amides

The intramolecular charge-transfer model for the electronic structure of amides has been extended to include the effects of torsion about the peptide bond (Δω = ω – 180) and pyramidalization at the peptide nitrogen (θ_N). The model is used to calculate the absorption and CD spectra of nonplanar amides as a function of the angles Δω and θ_N. For cis-amides, the rotational strengths of the nπ* and ππ* transitions are much more sensitive to θ_N for a given value of Δω than is the case for trans-amides. The results from the model are compared with available experimental and previous theoretical treatments of such systems. The contributions of nonplanarity in amides to the CD of various polypeptide conformations is discussed. The effects should be negligible for α-helixes but may be quite significant in β-sheets and β-turns. The CD spectrum of unordered peptides would be readily explained if there were a significant bias toward negative Δω values in polypeptides of L-amino acids. However, the evidence currently available does not indicate such a bias.     

Lack of endotoxin in Borrelia hispanica and Treponema pallidum

Borrelia hispanica from infected guinea pigs and Treponema pallidum from testicular syphilomas of rabbits were assayed for the presence of endotoxin with the Limulus lysate test. A suspension of Borrelia, containing 1.3 X 10(8) spirochetes/ml, was nonreactive both when it was tested as intact organisms, and when tested after disruption of the spirochetes by sonication. Eight different suspensions of treponemes, ranging from 0.6 X 10(9) to 3 X 10(9) treponemes/ml, were negative at a 1:10 dilution and were no more active than control suspensions of normal rabbit testes. Therefore, it was concluded that T. pallidum, as well as the Borrelia, possessed no endotoxin.     

Clinical trial of chromium and yeast supplements on carbohydrate and lipid metabolism in diabetic men

Chromium (Cr) deficiency in experimental animals and in humans sustained by prolonged total parenteral nutrition has been shown to cause diabetes mellitus. Prior trials in humans indicated that Cr supplements, in either inorganic or organic form, may improve carbohydrate utilization. We report here a clinical double-blind, random cross-over trial of inorganic chromium trichloride, a brewer’s yeast that contained Cr as glucose-tolerance-factor (GTF), a brewer’s yeast extract without GTF, and a placebo. Forty-three outpatient diabetic men received three of these supplements for 4 months each. Subgroups included 21 ketosis-prone, 7 ketosis-resistant non-obese, and 15 ketosis-resistant obese men. Cr levels were followed pre- and post-treatment in hair, red blood cells, plasma, and urine. Response of carbohydrate metabolism to treatment was assessed in terms of change in insulin requirements, fasting plasma glucose, plasma cholesterol, and triglycerides, as well as the change in plasma glucose, glucagon, and insulin or C-peptide levels in response to a standard meal. In some men, these parameters were also measured after iv tolbutamide. Both the inorganic and organic oral Cr supplements increased measurable body pools of Cr in hair and red blood cells by about 25%. However, fasting plasma glucose and lipids and the glucose response to either the standard meal or to tolbutamide were not significantly altered by any of the treatments.     

Maternal smoking and trisomy among spontaneously aborted conceptions

In a study of spontaneous abortions, we found an apparently robust association of trisomy with smoking that varies with maternal age. Among women under age 30, smoking either before or at the time of conception is less common in women aborting trisomic conceptions than in controls delivering at 28 weeks or later. Among older women, smoking is more common in women aborting trisomic conceptions than in controls. Our results point to an effect of smoking on the frequency of trisomic abortions that varies with age, and they suggest that the causes of recognized trisomic abortions differ in younger and older women.     

Lactic acid translocation: terminal step in glycolysis by Streptococcus faecalis

Streptococcus faecalis obtains metabolic energy chiefly from the conversion of glucose to lactic acid; the present experiments deal with the mechanism of lactic acid translocation across the cytoplasmic membrane. Efflux of [(14)C]lactate from preloaded cells was accelerated by raising the external pH, and also by the ionophores nigericin and valinomycin. These results suggest that lactate leaves the cell by an electroneutral process, presumably as lactic acid. Further evidence was obtained by studying the entry of [(14)C]lactate into nonmetabolizing cells. It appears that the membrane is essentially impermeable to the lactate anion, but allows passage of lactic acid. The most persuasive evidence is that, upon establishment of a pH gradient such that the cytoplasm was alkaline, l-[(14)C]lactate accumulated in the cells against the concentration gradient. Accumulation was transient, and dissipated in parallel with the collapse of the pH gradient. The concentration gradient attained at the peak was a function of the pH difference. Ionophores which are known to collapse a pH gradient, such as nigericin and valinomycin, abolished accumulation of l-lactate. We infer that lactic acid translocation, whether into the cells or outward, is an electroneutral process and for that reason the distribution of lactic acid across the membrane is a function of the pH of cytoplasm and medium. The specificity of translocation and its kinetic parameters suggest that it is mediated by a carrier of low specificity.     

Streptomycin resistance in Rhizobium japonicum

Mutants resistant to varying concentrations of streptomycin were recovered from two streptomycin-sensitive, effective nitrogen-fixing strains of Rhizobium japonicum. To determine if there were an upper limit of resistible antibiotic concentration, 3 mutants which were resistant to 10000 μg/ml were challenged by higher concentrations of streptomycin. Only one grew well at 25000 μg/ml, and none grew at 50000 μg/ml. All mutants maintained a smooth colonial morphology, and none exhibited streptomycin-dependence. Streptomycin-resistant mutants of both strains were examined for properties of infectivity and effectiveness. All mutants tested retained the symbiotic properties of the parental strains. The retention of these parental properties by the streptomycin-resistant mutants of R. japonicum is different from the properties described for phenotypically similar mutants in certain other rhizobial species.