THE RENIN-ANGIOTENSIN SYSTEM AND HYPERTENSIVE LEFT VENTRICULAR HYPERTROPHY IN THE RAT

The relationship between left ventricle-to-body weight ratio (LV/BW), mean arterial pressure (MAP, the average of 12 h of intra-arterial monitoring in conscious animals) and plasma renin activity (PRA) was assessed at 12 weeks after unilateral clipping or sham operation in twenty-four one-kidney rats and twenty-six two-kidney rats. The degree of hypertension and left ventricular hypertrophy were similar in one-kidney and two-kidney groups. There was a close linear relationship between LV/BW and MAP which was similar in one-kidney and two-kidney rats. PRA was significantly elevated only in two-kidney rats and was not related to the degree of hypertrophy after accounting for the effect of PRA on MAP. These data suggest that activation of the renin-angiotensin system does not contribute directly to myocardial hypertrophy in rats with renal-clip hypertension.     

Inhibition of immune complex-mediated activation of complement

Several known chemical compounds were shown to selectively inhibit the interaction between immune aggregates and Clq, the activation of Clr-Cls complex by immune aggregate-bound C1q, and the esterolytic activity of the activated Cls, . These reactions are relevant to the functions of the first complement component, Cl, and its activation induced by immune complexes. The effects of these inhibitors on tissue injury mediated by immune complex-induced complement activation, such as immune hemolysis, passive cutaneous anaphylaxis, and experimental glomerulonephritis were examined. The results suggest an approximate correlation between the activity shown on the molecular level and that obtained in vivo. One such compound, suramin, was shown to be an effective inhibitor of PCA and the proteinuria manifestation of EGN while not affecting antibody fixation to tissue or histamine-mediated skin reaction. These results suggest that effective suppression of the initial steps of complement activation may be of value in controlling immune complex-mediated tissue injuries in disease.Abbreviation used PCA passiave cutaneous anaphylaxis in guinea pigs - BSA bovine serum albumin - PBS 0.15 M NaCl containing 10 mM sodium phosphate buffer or 10 mM Tris-HCl buffer, pH 7.40 - SDS sodium dodecyl sulfate - PAGE polyacrylamide gel electro Phoresis - EACA epsilon-aminocaproic acid     

Concerted contractions of tumour fragments derived from a pure mucoid carcinoma of the breast in vitro

Summary Organized tissue fragments obtained by dissociation of a pure mucoid carcinoma of the breast were cultured in vitro. The cellular organization of the fragments appcars similar to that observed in vivo, and consist of mucous-filled spherules surrounded by a single layer of tumour cells. Time-lapse video recordings revealed that the cells surrounding these fragments undergo a concerted contraction and relaxation over the time span of several hours. The presence of cytokeratin and oestrogen receptors in the cells suggests an epithelial derivation. Movement of tumour fragments of the type described here could potentially influence the metastatic process of some breast cancers.Supported by a grant from the Medical Research Council of Canada     

Radionuclide determination of right and left ventricular stroke volumes

The relationship between radionuclide and thermodilution measurement of stroke volumes (SV) was investigated in 30 patients without valvular regurgitation or intracardiac shunt (group A) at rest and during exercise. Both attenuated radionuclide right ventricular (RV) and left ventricular (LV) SV measurements correlated well with the SV determined by the thermodilution method (r=0.87 and r=0.93, all P< 0.001). The reliability of the radionuclide method to estimate SV was evaluated prospectively in two additional groups of patients. In 11 patients without valvular regurgitation or intracardiac shunt (group B) the radionuclide RVSV and LVSV closely approximated to thermodilution SV at rest and during exercise. In 15 patients with aortic regurgitation (group C) the radionuclide stroke volume ratio correlated well with the angiographic regurgitant fraction. Thus, both RVSV and LVSV and the severity of aortic regurgitation can be reliably measured with gated radionuclide ventriculography.     

Regulation of insulin and interleukin-1 release after Propionibacterium acnes-induced macrophage activation in mice

The administration of a potent activator of macrophages (M phi), Propionibacterium acnes, in nondiabetic mice was associated with the release of significant amounts of interleukin-1 (IL-1) in the peritoneal cavity and plasma within 4 hours after treatment. Shortly before IL-1 peaks were observed, the levels of pancreatic insulin, [3H]leucine-proinsulin, and insulin/total protein ratio were elevated, and followed by a transient but marked hyperinsulinemia at 4 hours after treatment. A single dose of recombinant murine IL-1 in mice was also associated with a 2- to 9-fold increase in the levels of insulin in the pancreas and plasma at 4 hours after treatment. During the period of observation after the administration of P. acnes, plasma glucose levels in treated mice were significantly less than in parallel controls. Mild hypoglycemia was observed at 7 to 10 days posttreatment. Although circulating IL-1-like activity could not be detected in plasma 1 to 10 days after P. acnes treatment, this activity was measured in activated peritoneal and liver M phi. IL-1-like activity (specific activity: 276 units/mg protein) was detected in plasma, after it was chromatographed on a Sephadex G-150 column to remove proteins with higher molecular weight. Peritoneal and liver M phi from P. acnes mice were also able to elaborate significant amounts of IL-1-like activity in their supernatants with or without Escherichia coli lipopolysaccharide. At the same time, total protein synthesis and insulin content in the pancreas in P. acnes mice were significantly lower than the parallel control (p less than 0.01). These results suggest that P. acnes-induced M phi activation in mice was associated with the modulation of insulin release and glucose homeostasis which may be attributed to the accumulation and release of IL-1 by activated M phi.