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Biomedical subjects

E Bonetti

Publications and source records attributed to E Bonetti.

At least 19 recordsLinked to original sources
PubMed2004

Target-specific action of organochlorine compounds in reproductive and nonreproductive tissues of estrogen-reporter male mice.

Organochlorines are lipophylic molecules that accumulate in the fat where they remain for years. During weight loss, they are mobilized and their concentration increases in blood. The present work tests, in transgenic estrogen-reporter mice (ERE-tK-LUC), whether this increase is sufficient to modulate the estrogen receptors (ERs) in the whole body. Three weak estrogens were studied: p,p'DDT [1,1,1-trichloro2,2-bis(p-chlorophenyl) ethane], p,p'DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene], and betaBHC [beta-benzene-hexachloride]. Dose-dependent analysis of reporter expression (luciferase) were performed in tissues of acutely treated mice. A body map of ER activation was obtained. All these chemicals modulated the reporter, although with a different efficiency and depending upon the tissue analyzed. Induction was confirmed in the liver by determining the expression of the endogenous progesterone receptor (PR) gene, at the dose and time point at which the luciferase gene was maximally induced. After experimental accumulation in the fat tissue, followed by a 48-h period of fasting, we tested whether these compounds could be mobilized to reach sufficient levels to activate the ERs in selected reproductive and nonreproductive tissues (testicle, prostate, liver, and lung). This experimental setting produced results that were different than those obtained following acute treatments. In loaded mice, fasting induced betaBHC mobilization resulted in strong ER activation in the liver and the lung, which was blocked by ICI-182780. p,p'DDT mobilization had no effect in these tissues, but it acted efficiently in the prostate and testis. betaBHC inhibited the ERE-mediated reporter in the testicle and induced the reporter in the prostate. In this tissue, betaBHC action was not inhibited by the anti-estrogen ICI-182780. During fasting, betaBHC, p,p'DDT, and metabolite p,p'DDE increased in blood concentration, from 2.25 +/- 0.25, 0.51 +/- 0.09, and 0.38 +/- 0.06 microg/ml to 8.24 +/- 0.95, 4.52 +/- 0.68, and 5.06 +/- 0.57 microg/ml, respectively. The effect produced by these organochlorines in the liver correlates with the modulation of the ERalpha protein. We conclude that these organochlorines modulate differently the expression of estrogen-regulated genes in male mice. Their effect is tissue- and compound-specific and is dependent on the energetic balance.

Adipose Tissue↗
PubMed2004

Whole body action of xenoestrogens with different chemical structures in estrogen reporter male mice.

The present work tested the estrogenic activity of three weak environmental estrogens p,p'DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane], p,p'DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] and betaBHC [beta-benzene-hexachloride] in the transgenic estrogen-reporter mouse model (ERE-tK-LUC). By a time dependent analysis of the transgenic reporter expression (luciferase), we showed that all these chemicals modulated the estrogen receptors (ERs) in the whole body, although with a different efficacy and depending upon the tissue analyzed. Peak activity was registered at 16 h of treatment with 5000 microg/kg of each compound. Organochlorines are lipophylic molecules that accumulate in fat. During weight loss they are mobilized and their concentration increases in blood. We tested whether after experimental accumulation in fat tissue, followed by a 48 h period of fasting, these compounds could be modulated to reach sufficient levels to activate the ERs in target tissues. This experimental setting produced results that were different from those obtained following acute treatments. In loaded mice, fasting induced betaBHC mobilization resulted in strong ER activation in the liver, lung, eye, cerebellum, hypothalamus and cortex. p,p'DDT mobilization had no effect in these tissues, but efficiently acted in the testis, where, on the contrary, betaBHC inhibited reporter expression. During fasting, betaBHC, p,p'DDT and the metabolite p,p'DDE increased in blood concentration, from 2.7 +/- 0.36, 0.65 +/- 0.01 and 0.48 +/- 0.06 microg/ml to 9.51 +/- 1.1, 4.98 +/- 0.77 and 6.0 +/- 0.71 microg/ml, respectively. We conclude that these organochlorines modulate differently the expression of estrogen regulated genes in a tissue- and compound-specific manner and that their action is dependent on the energy balance. Moreover, we show that this mouse model is suitable to detect the estrogenic activity of chemicals with variable structures such as alkyl phenols and polychlorobiphenyls.

Animals↗
PubMed1993

[Neurologic evaluation of 118 patients in the first postoperative period of cardiovascular surgery].

118 patients (79 mean and 39 women, mean age of 50.7 years) who underwent cardiovascular surgery and extracorporeal oxygenation were prospectively evaluated for neurologic complication and its correlation with risk factors. 71 were submitted to coronary artery graft by-pass (RM), 18 to valve replacement (TV), 6 to prosthetic valve replacement (RV), 11 to commissurotomy(Co), 5 to thoracic aortic aneurysm correction (An Ao T) and 7 to other surgeries (OT). All of them received extracorporeal oxygenation. No deaths were registered; 14 (11.9%) patients had neurologic abnormalities: delirium in 7 cases, ischemic stroke in 6, epileptic seizure in 3. Patients with systemic arterial hypertension and older patients exhibited a statistically significant (p < 0.05) higher risk of complication. Compared to data of the literature, we had a lower index of morbidity and mortality.

Adolescent↗
PubMed1978

Modeccin, the toxin of Adenia digitata. Purification, toxicity and inhibition of protein synthesis in vitro.

1. Modeccin, the toxin of Adenia digitata (Modecca digitata), was purified from the roots of this plant by affinity chromatography on Sepharose 4B. 2. This toxin is a protein with mol.wt. 57000, which on treatment with 2-mercaptoethanol can be dissociated into two subunits of mol.wts. 25000 and 32000. 3. Modeccin inhibits protein synthesis in vitro in a lysate of rabbit reticulocytes and in Ehrlich ascites cells; the effect on cells is decreased in the presence of lactose. 4. Dissociation of modeccin into subunits decreases the toxicity to animals and the inhibition of protein synthesis in cells, but enhances the inhibition of protein synthesis in the lysate system.

Animals↗
PubMed1976

Toxic effects of ricin: studies on the pathogenesis of liver lesions.

Rats treated with ricin, an inhibitor of protein synthesis, at the dose of 1 mug/100 g body weight, developed within 72 hours a severe liver necrosis. Protein synthesis was practically unchanged. The ultrastructural changes that ricin induces in rat liver were investigated. The earliest changes were observed in sinusoidal cells which were progressively damaged until they became necrotic. Only after the development of these lesions hepatocytes appeared to be damaged. The hypothesis is formulated that hepatocyte necrosis is a consequence of the disappearance of sinusoidal cells. This might explain why protein synthesis was unaffected in liver: since ricin exerted its toxic effect on the sinusoidal cells the inhibition was not detectable, these cells being "diluted" by the mass of parenchymal cells. Ricin at the dose of 10 mug/100 g body weight did not affect protein synthesis in the liver, but exerted a marked and precocious inhibition of protein synthesis in the spleen, which is very rich in reticuloendothelial cells. Moreover, a severe necrosis of the red pulp of the spleen was observed in rats poisoned with this dose of ricin.

Animals↗
PubMed1975

Cycloheximide-induced ultrastructural changes in hepatocyte nuclei in partially hepatectomized rats.

Nearly all the chromatin in regenerating rat hepatocytes appears to decondensed form 24 h after partial hepatectomy. When cycloheximide (CXM) is administered to partially hepatectomized rats, a marked condensation of chromatin occurs; 4 h after administration the quantity of condensed chromatin present is much higher than that found in the hepatocytes of sham-operated, untreated rats. No segregation or fragmentation of the nucleolus were, however, observed; this shows that the condensation of chromatin is not by itself sufficient to induce the segregation and fragmentation of the nucleolus. The mechanism governing CMX-induced chromatin condensation in regenerating hepatocytes is discussed.

Animals↗
PubMed1975

Studies on the formation of lipid peroxides and on some enzymic activities in the liver of vitamin E-deficient rats.

Rats were fed a 5 or 20% casein diet that causes liver necrosis unless supplemented with vitamin E or selenite. The following activities were studied in liver subcellar fractions: enzymic formation of lipid peroxides, NADPH-cytochrome c reductase, oxidative demethylation of aminopyrine, and incorporation of [14C]leucine into protein (with microsomes); xanthine oxidase (with soluble supernatant); and RNA polymerases I and II (with nuclei). Formation of lipid peroxides was higher in rats fed diets without vitamin E and was not reduced significantly by dietary selenite. The activity of xanthine oxidase was higher in animals fed the 20% casein than in those fed the 5% casein diet; however, a higher activity was observed in the rats fed the latter diet without vitamin E or selenite than in those receiving these supplements. The activity of RNA polymerase I was higher in rats fed the low casein diet. Other activities examined were not affected significantly by the level of dietary casein or by vitamin E or selenits.

Aminopyrine N-Demethylase↗