Species differences in the effect of isoproterenol and pindolol on renin release in vitro.

The effects of selective beta adrenergic receptor stimulation with isoproterenol (3 X 10(-8) M) and of beta adrenergic blockade with pindolol (3 X 10(-5) M) on the renin release in vitro were investigated in incubated canine and rat kidney slices. Bioassay was used to measure the renin content of the tissue samples and incubation media; renin content in the canine incubation medium was measured also by radioimmunoassay. Isoproterenol in a concentration of 3 X 10(-8) M brought about a significant increase in the renin content of the incubation media as well as the tissue slices obtained from canine kidney, however, there was no change in these parameters under similar conditions if rat kidneys were incubated. Pindolol, on the other hand, in a concentration of 3 X 10(-5) M caused a significant decrease in the renin release from as well as in the renin content of the rat kidney slices, while canine kidney slices failed to respond to the same dose of the drug. The differences between the two species is suggested to be due to the differences in basal renin levels.     

Priming of the fluid pump by osmotic gradients across rabbit corneal endothelium

The present study shows that the inclusion of 5% Dextran (average mol. wt. 40 000) in solutions to preserve in vitro rabbit corneal endothelium induces a sizable osmotic flow across the preparation which is superimposed on the existing fluid transport. Furthermore, even after fluid transport ceases due to in vitro deterioration, the Dextran-induced flow remains for some addition time. The osmotic permeability was 162 +/- 17 micrometer/s in the presence of glucose and 451 +/- 84 micrometer/s in its absence. The latter, comparatively high value suggests that such osmotic flow traverses the intracellular junctions. In addition, temporary (10--15 min) imposition of an osmotic gradient has a separate stimulatory 'priming' effect on the rate of fluid transport. Thus, the rate of fluid pumping increased by about 40% after challenge with Dextran. It was further noted that, after addition of Dextran, preparations in the absence of glucose escape gross deterioration for a time longer than those in the presence of glucose. On the other hand, mere addition of Dextran to a glucose-containing solution does not appear to prolong the estimated 'survival time' of the pumping mechanism. The sizable osmotic flows and the priming effect described here may provide a physiological context with which previously described Dextran effects on cornea preservation can now be compared.     

Interference of Mycotoxins with Prenatal Development of the Mouse

The prenatal effects of mycotoxins were investigated in GBA mice given by stomach tube a single dose of either aflatoxin B1 (4 mg/kg), ochratoxin A (8 mg/kg) or zearalenone (20 mg/kg) on pregnancy day 8 or 9. Aflatoxin caused foetal anomalies (exencephaly, open eyes, and protrusion of intestines) after exposure on gestation day 8 but not on day 9. The effects (increased prenatal mortality, reduced foetal growth, and a wide variety of malformations) caused by ochratoxin were much more severe and occurred after treatment on either of the 2 days of gestation. Among the spectrum of malformations, predominantly involving the craniofacial complex and the axial skeleton, the most striking was the total aplasia/dysplasia of the upper facial structures. These defects were always accompanied by exencephaly and anophthalmia. Zearalenone caused no effects. It is concluded that of the 3 mycotoxins screened with the technique used, ochratoxin is the most potent teratogen in mice.     

SYNTHESIS AND METABOLISM OF l-KYNURENINE IN RAT BRAIN

Abstract— A method for the quantitative analysis of femtomole amounts of kynurenine (along with tryptophan, 3-hydroxykynurenine and kynuramine) in rat brain using high pressure liquid chroma-tography and electron-capture GLC is described. Endogenous concentrations of these substances in rat brain regions were measured, and their formation after the injection of radioactive tryptophan or kynurenine was determined. Kynurenine was formed from tryptophan in brain and was also taken up from the periphery. Extracerebral kynurenine was calculated to account for 60% of the cerebral pool of kynurenine. The cerebral rates of synthesis of kynurenine and 3-hydroxykynurenine were 0.29 and 0.17nmol/g/h. The turnover rate of kynurenine in the brain was 1.02 nmol/g/h measured from [¹⁴C]tryptophan or 1.14 nmol/g/h from [³H]kynurenine injected intraperitoneally. Kynuramine levels in different areas of the brain were similar to those of tryptamine. Following intraperitoneal injection of [¹⁴C]tryptophan, the presence of anthranilic, 3-hydroxyanthranilic, xanthurenic, kynurenic and quinaldic acids was demonstrated in the brain.     

The role of glucagon in the regulation of blood glucose: Model studies

Mathematical models afford a procedure of unifying concepts and hypotheses by expressing quantitative relationships between observables. The model presented indicates the roles of both insulin and glucagon as regulators of blood glucose, albeit in different ranges of the blood glucose concentrations. Insulin secretion is induced during hyperglycemia, while glucagon secretion results during hypoglycemia. These are demonstrated by simulations of a mathematical model conformed to data from the oral glucose tolerance test and the insulin infusion test in normal control subjects and stable and unstable diabetic patients. The model studies suggest the parameters could prove of value in quantifying the diabetic condition by indicating the degree of instability. Presented at the Society for Mathematical Biology Meeting, University of Pennsylvania, Philadelphia, August 19–21, 1976.     

Cytomegalovirus-induced membrane antigens in productively infected cells.

Adsorbed but not penetrated virus can be removed from the CMV-infected cell membrane by digestion with cystine-activated papain. Membrane antigens appear on 80-90% of the infected cells 14-20 hr after infection as a result of de novo protein synthesis. Antigen synthesis can be blocked with inhibitors of protein synthesis, but not with DNA inhibitors. In the early stage of infection, pooled human convalescent serum reacted well with the membrane antigen, whereas pooled antiserum of rabbits immunized with CMV virion suspension gave a positive reaction with a small proportion of the cells. After the 48th hr, both the human and the rabbit serum pool reacted with the membrane of the infected cells. Absorption with cell cultured for 24 hr after CMV infection reduced the neutralization titres of the antisera only slightly but the titre reduction was considerable when absorption was performed with cells cultured for more than 48 hr after infection. It is concluded that on the membrane of cells productively infected by CMV at least two membrane antigens are present, one coded for by the DNA of the parent virus and another which is the product of the DNA of the virus progeny. The two antigens can be differentiated serologically.