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Biomedical subjects

O Tofanetti

Publications and source records attributed to O Tofanetti.

At least 37 records · Page 2Linked to original sources
PubMed1985

Prevention of cyclophosphamide-induced urotoxicity by reduced glutathione and its effect on acute toxicity and antitumor activity of the alkylating agent.

The effect of reduced glutathione on acute lethal toxicity and urotoxicity induced by cyclophosphamide was studied on both mice and rats. The results of this investigation indicate that reduced glutathione is an effective protective agent against bladder damage from treatment with the alkylating agent. The timing of glutathione administration (IV) with respect to cyclophosphamide treatment influenced the uroprotective efficacy of the thiol compound. A schedule-dependent protective effect of glutathione against acute lethal toxicity of the antitumor drug was also observed. This partial protection was accompanied by a reduction in body weight loss following cyclophosphamide treatment. The therapeutic activity of cyclophosphamide on two experimental tumor systems (L1210 and Gross leukemia) was not impaired by combined treatment with glutathione, even at a relatively high dose of glutathione compared with cyclophosphamide.

Animals↗
PubMed1985

Opiate receptors and beta-endorphin levels in brain areas of dogs with portal-systemic encephalopathy.

Clinical observation has indicated a supersensitivity to morphine in patients with hepatic encephalopathy. With the aim of clarifying the issue, radioreceptor binding studies of opiate receptors were performed in frontal cortex and hypothalamus of 6 dogs with mild portal-systemic encephalopathy induced by chronic treatment with dimethylnitrosamine followed by porto-caval shunt end-to-side. beta-Endorphin assays were performed in the same areas with radioimmunoassay. Opiate receptors labeled with [3H]naloxone in both areas showed a significant increase in the receptor densities (Bmax) without changes in the dissociation constant (KD). In parallel beta-endorphin levels showed a decline during the development of encephalopathy in both areas. The increased densities of opiate receptors in the mild stage of encephalopathy may explain the supersensitivity to morphine in patients with liver diseases.

Animals↗
PubMed1984

Experimental convulsions in rats induced by intraventricular administration of kynurenine and structurally related compounds.

Administration of L-kynurenine and some analogous molecules into the right lateral ventricle caused convulsive attacks in rats. These convulsions are tonic-clonic. Various modifications of the structure of L-kynurenine affected the production of convulsions. In particular, methylation of the carboxyl group increased the potency. Methylation of the carboxyl function and hydroxylation of the benzene ring greatly increased the latency and the duration of the convulsions. Removal of the carboxyl function or its reduction resulted in the loss of the epileptogenic effect. Masking of the amino function with formyl or acetyl residues also produced inactive compounds. The results of structural modification of the kynurenine carbon skeleton clearly show that the structure essential for stimulation of convulsive activity includes a free amino group and a free or masked carboxyl function. The molecular structure able to induce convulsive effects appears to be the laevo -isomer of kynurenine, since the dextro-form has been proved to be inactive. The convulsant activity, evaluated as the ED50, for L-kynurenine, is between that of bicuculline and pentamethylenetetrazole . The convulsant mechanism of kynurenine is unknown, but might very possibly involve interference with the activity of certain inhibitory neurotransmitters.

Animals↗
PubMed1984

Inhibitory effects of 2-guanidinebenzimidazole and 1-phenylbiguanide on gastric acid secretion in rats.

In this study 2-guanidinebenzimidazole (GBI) and 1-phenylbiguanide (PBG) appear to be capable of decreasing gastric acid secretion, while the compounds dimethylbiguanide and cyanoguanidine do not. Thus, the antisecretory effect is present when the biguanide groups are associated with lipophilic molecules. GBI and PBG depress gastric acid secretion, even when it has been stimulated by carbamoylcholine (carbachol) or betazole. The antihistamine effects of GBI and PBG on betazole-stimulated gastric acid secretion were confirmed by the inhibitory activity of these compounds on the isolated guinea pig auricle stimulated by histamine. The antimuscarine activity of GBI and PBG on carbachol-stimulated gastric acid secretion in rats is also supported by the way in which these same drugs depress the motility of the duodenum and colon of the anaesthetized cat stimulated by prostigmine. The above mentioned effects of these compounds are also associated with myolytic activity, since they decrease the spontaneous and histamine-stimulated motility of the duodenum and colon. GBI and PBG probably depress gastric acid secretion by interfering with both histamine and acetylcholine receptors and with other sites involved in the secretory process.

Animals↗
PubMed1983

Protective effect of reduced glutathione against cis-dichlorodiammine platinum (II)-induced nephrotoxicity and lethal toxicity.

Pretreatment of Swiss mice and Sprague-Dawley rats with glutathione (GSH) reduced the acute lethal toxicity of cis-dichlorodiammine platinum (II) (cis-DDP) in a dose-dependent manner. The protection was accompanied by reduction of both body weight loss and by reduction of nephrotoxicity, as measured by a rise in serum blood urea nitrogen (BUN), creatinine levels and by histopathologic changes, which occurred 4 days following cis-DDP treatment. The antitumor effects of cis-DDP on experimental tumor models (P388 and Gross leukemia) were not significantly altered by GSH treatment. It is suggested that the partial protection by GSH from acute toxicity of the antitumor drug is directly related to protection of renal function.

Animals↗
PubMed1979

Gas chromatographic determination of glibenclamide in plasma.

A gas-chromatographic method for glibenclamide determination in plasma is described. It involves derivatization of the drug with dinitrofluorobenzene and the use of an electron-capture detector. The quantitative evaluation is performed using tolbutamide as internal standard. Characteristics and specificity of the method for the principal metabolite of glibenclamide are examined.

Administration, Oral↗
PubMed1977

Enhancement of propoxyphene-induced analgesia by doxepin.

The activity of the centrally acting analgesic, propoxyphene, either alone or combined with the tricyclic antidepressant, doxepin, has been studied. Doses of doxepin, in themselves lacking any analgesic effect, remarkably enhanced the analgesic activity of propoxyphene, either by the oral or intraperitoneal route. On the other hand, oral toxicity data prove that doxepin does not alter significantly propoxyphene acute toxicity.

Analgesia↗
PubMedDate not supplied

Participation of lipid peroxidation in the loss of hepatic drug-metabolizing activities in experimental fascioliasis in the rat.

Fascioliasis causes a dramatic decrease in drug-metabolizing ability of the hepatic monooxygenase (MFO) and glucuronosyltransferase (GT) enzyme systems in the rat. The present study was undertaken to determine whether lipid peroxidation is involved in the enzymatic loss. Peroxidative damage of membrane lipids (as assessed by the tissue content of malonic dialdehyde, MDA, and the diene conjugation absorption in microsomal membranes) was found to occur over the entire course of the liver infection (concomitant to a decrease in glutathione levels), and to different degrees in relation to the various steps of the parasite cycle. The onset (MDA six times the controls; delta E 1% = 1.55 at the 20th day) coincides with the beginning of the loss of MFO (-30%) and GT (-20% at the 20th day), and peaks between the 30th and 40th day (MDA eight times the controls; delta E 1% = 1.96), when the loss in the enzyme activities is maximal (MFO - 60/70%; GT - 65/95%). There was a strict correlation at all the observation times between the extent of lipid peroxidation and the decrease in drug metabolizing ability: this supports the view that lipid peroxidation is the major agent in the impairment of MFO and GT enzyme activities, and very likely in the initiation of the pathological degeneration of the liver tissue. As evidenced by histological examination, the phagocytic response of the liver tissue to the parasite invasion and growth leads to oxidative stress, which is the causative agent in the initiation and development of lipid peroxidation.

Alanine Transaminase↗