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Biomedical subjects

S Garattini

Publications and source records attributed to S Garattini.

At least 343 records · Page 19Linked to original sources
PubMed1976

On thrombocytopenia developing in mice bearing a spontaneously metastasizing tumor.

Thrombocytopenia was observed in mice during development and metastatization of Lewis Lung Carcinoma (3LL). Survival of labelled platelets was not modified throughout the observation period, whereas platelet turn-over was markedly reduced, suggesting a defective platelet production. An increase in the splenic platelet pool could be excluded. Other hematological data indicated that, among blood cells, only platelet production was impaired. The origin of thrombocytopenia occurring during spontaneous metastatization of 3LL seems to be quite different from the mechanism of the decrease in platelet count observed after rapid intravenous injection of the same tumoral cells.

Animals↗
PubMed1976

Uptake of 14C-5-hydroxytryptamine by human and rat platelets and its pharmacological inhibition. A comparative kinetic analysis.

In order to approach the uptake of 14C-5HT by platelets as a first-order process, experimental conditions were selected in which accumulation of the amine either by diffusion or by other passive nonsaturable processes could be excluded. These conditions included an incubation period of 14C-5HT with human or rat platelets of 4 min or 30 s, respectively and the use of substrate concentrations around the calculated apparent Km values (0.25 - 2.0 muM). While the apparent Km values were rather similar for human and rat platelets, Vmax was about 5 times higher in rat than in human platelets. The kinetic model adopted in this study was used to evaluate the relative potency and the type of inhibiton of 14C-5HT uptake exhibited by imipramine, chlorimipramine and (+)-fenfluramine. All 3 compounds inhibited 14C-5HT uptake by platelets. Chlorimipramine was about 10 times more effective than imipramine both in rat and in human platelets. Both drugs were more potent inhibitors on human than on rat platelets. (+)-Fenfluramine was almost as active as imipramine on rat but 30 times less potent than imipramine on human platelets. Both imipramine and chlorimipramine inhibited 14C-5HT uptake by an apparent non-competitive mechanism, whereas (+)-fenfluramine appeared to act as a competitive inhibitor. No differences were found in this respect between human and rat platelets. Pharmacological or therapeutic doses of these drugs usually result in plasma concentrations similar to those found in this study to effectively inhibit platelet 14C-5HT uptake.

Adult↗
PubMed1976

Positive chronotropic effect of dialysable peptides derived from plasmin digestion of bovine fibrinogen preparations.

Low-molecular weight dialysable peptides, obtained by plasmin degradation of purified bovine fibrinogen preparations, have been shown to increase the chronotropic activity of isolated rat atria. This effect was dose dependent and was inhibited by inhibitors of glycolysis (NaF and 2-deoxy-D-glucose), but not by an inhibitor of oxidative phosphorylation (2, 4-dinitrophenol). Propranolol, a beta-blocking agent, was also ineffective. Fibrinogen-derived peptides increased both cAMP levels and phosphorylase alpha activity in stimulated atria. The increase of these parameters was transitory and appeared to precede the occurrence of the positive chronotropic effect. In the test situation used, the biochemical and functional modifications induced by fibrinogen-derived peptides were similar to those induced by glucagon.

Animals↗
PubMed1976

Effect of nomifensine on acetylcholine and choline in the rat striatum and brainstem.

Nomifensine, at a dose of 40 mg/kg, slightly but significantly increased rat striatal acetylcholine 60 min after i.p. administration without affecting choline levels or choline O-acetyltransferase and cholinesterase activities. This drug had no effect on brainstem acetylcholine. In contrast, d-amphetamine and desipramine both produced a small but significant increase in brainstem acetylcholine. It is suggested that nomifensine increased striatal acetylcholine indirectly through blockade of dopamine uptake.

Acetylcholine↗
PubMed1976

Lack of influence of the phase of estrus cycle or treatment with steroid contraceptive drugs on cholinergic parameters in mouse and rat brain.

Acetylcholine and choline levels were found not to fluctuate with the phase of the estrus cycle in the cerebral hemispheres, deincephalon and mesencephalon in the rat and mouse. Choline acetyltransferase activity was not altered in these brain areas in the mouse while in the rat there was a small but significant decrease in the cerebral hemispheres during proestrus (p less than 0.01), and in the mesencephalon during estrus (p less than 0.05), both with respect to diestrus. Chronic 30-day treatment with steroid contraceptive drug combinations (lynestrenol, 5 mg/kg+ mestranol, 0.3 mg/kg; lynestrenol, 2.5 mg/kg+ mestranol, 0.15 mg/kg; norethindrone, 4 mg/kg+ mestranol, 0.2 mg/kg; norethynodrel, 4 mg/kg+ mestranol, 0.06 mg/kg) did not alter cholinergic parameters in the brain areas of these two species except for minor changes in rare instances.

Acetylcholine↗
PubMed1976

Effects of 6-aminochrysene on liver microsomal enzyme activity.

1. No transformation of 6-aminochrysene took place during its incubation with rat liver microsomes under oxygen or anaerobic conditions. 2. 6-Aminochrysene inhibited the hydroxylation of aniline, O-demethylation of p-nitroanisole, and N-demethylation of aminopyrine by rat liver microsomes. 3. Pre-treatment of rats with 6-aminochrysene markedly decreased the N-demethylation in vitro but significantly increased the hydroxylation and the O-demethylation. Similar effects were observed also with microsomal preparations from livers perfused with 6-aminochrysene.

Aminopyrine N-Demethylase↗
PubMed1976

6-Aminochrysene kinetics in isolated perfused liver.

1. New quantitative assays of 6-aminochrysene by spectrophotometric and g.l.c. methods and t.l.c. separation systems are described. 2. The decline in blood levels of the antitumoral agent 6-aminochrysene was due to its distribution rather than to metabolism to polar metabolites, during liver perfusion experiments. 3. No marked changes in kinetics of 6-aminochrysene were observed during perfusion of livers isolated both from normal and from Walker 256 carcinosarcoma-bearing rats.

Animals↗
PubMed1976

Microsomal styrene mono-oxygenase and styrene epoxide hydrase activities in rats.

1. Styrene epoxide formation and styrene epoxide hydration have been studied in liver, lung, kidney, heart, spleen and brain of female and male rats. 2. Styrene epoxide formation is NADPH-dependent although it is enhanced when NADH is added together with NADP. This enzymic activity is inhibited by metyrapone and SKF 525-A but not by the effective inhibitors of epoxide hydrase, 1,2-epoxy-3,3,3-trichloropropene and cyclohexene oxide. 3. Known inducers of liver microsomal mono-oxygenases show a different activity on the two enzymes. Phenobarbital increases both formation and hydration of styrene epoxide; and carbamazepine increase the hydration but not the formation of styrene epoxide; a steroid contraceptive combination (lynestrenol+ mestranol) increases styrene epoxide formation while it inhibits epoxide hydrase; 3-methylcholanthrene does not affect either of the activities.

Animals↗
PubMed1976

Effect of phenobarbital on cyclophosphamide metabolism in rats.

1. The pharmacokinetics of cyclophosphamide and its alkylating metabolites have been studied in rats whose liver microsomal enzymes had been induced by phenobarbital pre-treatment. 2. Serum levels of cyclophosphamide were determined using a new g.l.c. method. The half-life of cyclophosphamide in blood of rats pre-treated with phenobarbital was shorter than in control rats. This change is closely related to higher rates of production of p-nitrobenzylpyridine-positive alkylating metabolites of cyclophosphamide, which in turn is followed by their more rapid disappearance from the circulation. 3. Urinary excretion reflects this situation; lower amounts of cyclophosphamide and higher concentrations of its alkylating metabolites are present in the urine of phenobarbital-treated rats. 4. Perfusion of livers isolated from phenobarbital-pre-treated rats confirmed the results in vivo. With this preparation, too, disappearance of cyclophosphamide was more rapid and formation of its alkylating metabolites was accelerated after phenobarbital treatment.

Alkylating Agents↗
PubMed1976

Relationships between chronotropic effect, 1-3H-noradrenaline uptake and tissue concentrations of desipramine, protripyline and doxepin in rat isolated atria.

The pharmacological effects of three tricyclic antidepressant agents (desipramine, protriptyline and doxepin) are evaluated in rat isolated atria in relation to their accumulation and efflux kinetics. The pharmacological effects studed are: inhibition of 1-3H-noradrenaline uptake, potentiation of 1-noradrenaline chronotropic response, and changes in spontaneous atrial rate. All drugs inhibit noradrenaline uptake and potentiate noradrenaline chronotropic response (desipramine congruent to protriptyline greater than doxepin). Desipramine and protriptyline, at concentrations of 10(-7) -- 10(-6)M stimulate the spontaneous rate; higher concentrations (greater than 10(-6)M) depress it. Doxepin has only a negative chronotropic effect. When the drugs are removed from the incubation medium, the depressing effect starts to disappear immediately for doxepin and desipramine and after 20 min for protriptyline. On the contrary the stimulating effect persists after repeatedly washing the preparations. Desipramine, protriptyline and doxepin extensively accumulate in the myocardial tissue (desipramine larger than or equal to protriptyline greater than doxepin). In the efflux studies doxepin is washed out more rapidly than desipramine and protriptyline. Although the kinetics of uptake and efflux of the three compounds are not sufficient to interpret their different pharmacological activities in isolated atria, they give useful information on the persistance of the sympathomimetic effect and the rapid disappearing of the negative chronotropic effect after washing.

Animals↗
PubMed1976

Carbamazepine pharmacokinetics in young, adult and pregnant rats. Relation to pharmacological effects.

Adult, male, female and pregnant rats were treated with single and repeated doses of carbamazepine (CBZ). The time course of the drug concentrations in plasma and tissues was followed. In all cases, data on plasma levels were subjected to pharmacokinetic analyses. Attempts were made to relate pharmacokinetic properties of carbamazepine to its effect on pentobarbital sleeping time and on protection against electroshock, after acute and repeated administration: --it was found that male rats eliminate carbamazepine faster than females: the total body clearance (TBC) was 16 ml/min/kg and 9.4 ml/min/kg, respectively. Two dose levels (25 and 50 mg/kg) had the same pharmacokinetic properties in young rats. Pregnant rats clear CBZ to a lesser extent than controls. --CBZ was found to accelerate its own elimination after repeated administration in both adult and young rats as revealed by the shortening of its half-life and an increase of 50% in clearance. Moreover, the protection against electroshock was significantly reduced after repeated administration, compared with a single-dose administration. Repeated administration of CBZ in rats shortens pentobarbital sleeping time and decreases the pentobarbital brain level significantly.

Aging↗