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Biomedical subjects

A J Monserrat

Publications and source records attributed to A J Monserrat.

At least 19 recordsLinked to original sources
PubMed1989

Effects of lovastatin and leupeptin on ceroidogenesis of vitamin E-deficient and -supplemented young rats.

Previous studies in young normal rats have shown that intracerebral administration of the proteinase inhibitor, leupeptin, caused a rapid accumulation of lipofuscin-like pigment in lysosomes of brain cells (Ivy et al., 1984a). On the other hand, we have recently found that the administration of lovastatin, an inhibitor of HMG-CoA reductase, reduced the ceroid-like pigment and dolichol contents in the crushed epididymal fat pad of rats (Porta et al., 1988). In order to study now the possible modulating effects of these enzyme inhibitors on ceroidogenesis associated with vitamin E deficiency, two main groups of weanling Wistar female rats were respectively fed ad libitum a vitamin E-deficient basal diet, or the same diet supplemented with 16 mg% of dl-alpha-tocopherol acetate. The vitamin E-deficient and -supplemented rats were further subdivided and received for 8 weeks their diets alone or with 2, 1, or 0.5 g of lovastatin/kg of diet. Other subgroups were treated with constant peritoneal infusion of 0.5 mg/day of leupeptin by means of osmotic minipumps (Alzet 2002) consecutively implanted at days 15, 30, and 45. Lovastatin treatment to vitamin E-deficient rats was associated with dose-dependent toxicity, resulting in 100%, 75%, and 50% mortality at concentrations of 2, 1, and 0.5 g/kg diet, respectively. This mortality was mainly due to extensive hepatic necrosis. Food intake and growth rates were reduced, while the relative weights of liver, kidneys, spleen, heart and brain, as well as the serum levels of GPT and GOT were significantly increased over the values of the untreated vitamin E-deficient control rats. The volumetric densities of ceroid pigment and the dolichol contents in liver and kidneys were not significantly modified. Lovastatin toxicity was partially prevented by vitamin E supplementation. However, in these supplemented rats, lovastatin treatment did not modify the volumetric densities of hepatic and renal ceroid, although the contents of hepatic and renal dolichol were significantly increased. No correlations could be found between levels of hepatic or renal ceroid and total dolichol content in vitamin E-deficient and supplemented rats. Leupeptin treatment to vitamin E-deficient rats only slightly reduced food intake and growth rates, and did not significantly modify the relative organ weights or the serum levels of cholesterol, GOT and GPT. Although in both vitamin E-deficient and -supplemented rats the leupeptin treatment consistently showed a tendency to increase the volumetric densities of hepatic and renal ceroid pigment, the differences with the control untreated rats were not statistically significant.(ABSTRACT TRUNCATED AT 400 WORDS)

Alanine Transaminase↗
PubMed1988

Effect of chemical modification with p-bromophenacyl bromide on the enzymatic and lethal properties of phospholipase A2 from Bothrops alternatus (Víbora de la Cruz) venom.

The effects on lethal potency and enzymatic activity were determined following alkylation, with p-bromophenacyl bromide, of the acidic toxic phospholipase A2 from Bothrops alternatus. The modified B. alternatus enzyme, which lost its enzymatic activity, retained considerable toxicity. Histopathologic studies on mice have demonstrated features similar to those of the native enzyme. However, the distribution of the damage was different and the survival time was longer. It is concluded that the enzyme activity is not important for the lethal action of the enzyme although it influences the distribution of the damage and survival time.

Acetophenones↗
PubMed1988

Effects of unilateral ureteric occlusion on renal necrosis occurring in rats fed a methyl-deficient diet.

Wistar male rats were fed from weaning a methyl-deficient diet (groups I and II) or a standard commercial diet (groups III and IV). At the day 3 the left ureter was tied and divided in animals of groups I and III, while those in groups II and IV were sham operated. Rats of all groups were killed on days 8 and 10 to evaluate the incidence and extent of tubular necrosis (day 8) and tubular and cortical necrosis (day 10). The results of this study show that unilateral ureteric obstruction diminishes the incidence, severity and extent of necrosis in the same kidney.

Acute Kidney Injury↗
PubMed1986

Contribution of phospholipase A2 to the lethal potency of Bothrops alternatus (víbora de la cruz) venom.

Purified phospholipase A2 from Bothrops alternatus venom is one single protein species with a molecular weight of 15,000 and isoelectric point 5.08. When injected i.p. or i.v. at a dose of 0.7 microgram/g body weight it is lethal to mice, eliciting a typical syndrome of dyspnea, tachycardia, arrhythmia and irreversible shock. Post mortem and histopathologic studies have demonstrated that the lungs (massive pulmonary hemorrhage), heart (foci of myocardial and endocardial necrosis with interfibrillar hemorrhage), liver (congestion, hepatocytic microvacuolization with zones of massive necrosis) and kidneys (foci of tubular and glomerular necrosis) were severely injured. Except for the less extensive hemorrhages and the significantly longer survival time, the observed lesions are similar to those observed after the injection of lethal doses of whole venom. The lethal potency of the purified enzyme (LD50 i.p. 0.14 microgram/g body weight) is 46-fold greater than that of the whole venom (LD50 i.p. 6.4 micrograms/g body weight). The contribution of phospholipase A2 to the overall lethal effect of B. alternatus venom is suggested by the decreased lethal potency of a venom sample in which a significant amount of phospholipase A2 has been removed and the full restoration of the lethal potency upon supplementation of the depleted sample with purified enzyme. It is concluded that phospholipase A2 is a major component responsible for lethality of the whole B. alternatus venom, while the contribution of other venom components appears to be significant mainly in reducing the time of survival.

Animals↗
PubMed1985

A catabolin-like factor from porcine kidney.

Explants of pig kidney cortex and medulla release a catabolin-like factor (CLF). The CLF of both kidney cortex and medulla can be precipitated with ammonium sulphate, mainly in the 60-95 per cent fraction. By gel chromatography the kidney CLF showed a major active fraction at a molecular weight of around 22 500. Whole glomeruli and dissociated glomerular cells in culture also released into the medium a CLF that could be bioassayed in live cartilage but displayed no effect on dead cartilage. The possible role of such a local hormone is discussed.

Animals↗
PubMed1981

Consumption coagulopathy in acute renal failure induced by hypolipotropic diets.

Weanling male rats fed on a hypolipotropic diet develop acute renal failure whose morphological features vary from focal tubular necrosis to cortical necrosis. We have sequentially studied the hemostatic mechanism in correlation with the morphology of various tissues, mainly renal and hepatic, in choline-deficient rats as well as in three control groups. No important changes were observed in the hemostatic mechanisms before the development of tubular necrosis. Along with tubular necrosis a consumption coagulopathy was found, evidenced mainly by a decrease in the activity of factors V and VIII as well as a prolongation in PTTK and Quick's time and a decrease in platelets. Fibrin degradation products were found in serum and urine and soluble fibrin monomer complexes in the former. Following tubular necrosis thrombi were found in the renal microvasculature. It is possible to speculate that the tubular necrosis induced by choline deficiency could produce an activation of the coagulation system which in turn would lead to thrombosis of the renal microcirculation and cortical necrosis.

Acute Kidney Injury↗
PubMed1975

Effects of repeated injections of sucrose on the kidney. Histologic, cytochemical and functional studies in an animal model.

In previous experiments (Monserrat, Gotelle, and Garay, 1969) we have found that the administration to rats of a single injection of 1.12 M sucrose induces a hydropic reversible vacuolation of the proximal convoluted tubules of the kidney. Along with the vacuolation the PAS and acid phosphatase positive, as well as autofluorescent granules (lysosomes) disappear and vice versa. We now report the effects of multiple intraperitoneal injections of 1.12 M sucrose. The aim of the study was to determine whether the renal cells are able to adapt to this situation or the modifications are permanent. Wistar male rats were allotted to 4 different groups (A : experimental, B, C, and D, controls) and placed in metabolic cages. Animals from group A were injected with 3.0 ml/100 gm body weight of 1.12 M sucrose at 0, 24, 48, 72, and 96 hours after the beginning of the experiment; rats of groups B and C were injected respectively at 0 and 96 hours, and finally, rats of group D were used as normal controls. All rats were killed at 120 hours. The results showed a striking vacuolation in the proximal convoluted tubules of the rats of group C, and complete regression of vacuolar changes in those of group B. Rats of group A, although they maintained the osmotic diuresis, showed mild vacuolation with persistence of acid phosphatase and PAS positive granules, as well as autofluorescent droplets (lysosomes). We postulate that these results are indicative of adaptive changes, whose mechanisms are at present being studied.

Acid Phosphatase↗
PubMed1972

Lysosomes in the pathogenesis of the renal necrosis of choline-deficient rats.

Previously published data from our laboratories led us to postulate that alterations in lysosomes may play a cardinal pathogenic role in the fatal renal necrosis of choline-deficient weanling rats. To explore this hypothesis further a series of five different experiments were carried out. In the first two experiments the effect of a "stabilizer" of the lysosomes, hydrocortisone, was studied; conversely, in the third and fourth experiments, the effect of a "labilizer," vitamin A, was studied. Finally, in the fifth experiment, the renal levels of a lysosomal enzyme, acid phosphatase, were evaluated biochemically. Results of the first two experiments revealed a protective effect of hydrocortisone while those of the third and fourth an aggravating effect of vitamin A. Results of the fifth experiment indicated lysosomal changes in the prenecrotic and early necrotic stages. These results along with those from our previous studies, support the concept that lysosomal alterations play an important pathogenic role in renal changes of choline-deficient weanling rats.

Acid Phosphatase↗