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Biomedical subjects

S Garattini

Publications and source records attributed to S Garattini.

At least 289 records · Page 16Linked to original sources
PubMed1980

Pharmacokinetic approach to in vitro testing of ovarian cancer cell sensitivity.

Cell populations obtained from ovarian cancer specimens were seeded in primary culture and morphologically identified as cancer cells. Methotrexate, cytosine arabinoside, 5-fluorouracil, antinomycin D, melphalan, and adriamycin were added to the culture medium at different concentrations and for various periods of time. The results are discussed in relation to the pharmacokinetic availability of drugs in the plasma compartment of patients treated by different therapuetic regimens. Totally inactive drugs can be identified by comparing plasma levels with active concentrations while for drugs active in vitro at concentrations in the range of pharmacokinetic levels, the percentage of responders among patients might be explained by the intrinsic variability of cancer cells.

Antineoplastic Agents↗
PubMed1980

Pharmacological activities of clobazam and diazepam in the rat: relation to drug brain levels.

Brain distribution and various pharmacological effects of clobazam and diazepam were studied in rats. When given at 10 mg/kg i.p. the compounds reached peak brain levels 15 min after injection, and showed similar half lives. At peak time brain levels were proportional to the dose administered. Very little of the N-desmethylmetabolite of each compound was found in the brain. Clobazam was less effective than diazepam in protecting rats from pentetrazol convulsions. Disrupting rota-rod performance and increasing punished responses in a "conflict" test, the relative potencies ranging from 4 to 8 in the various tests. The results are discussed in relation to the importance of animal species selection for predicting favourable therapeutic effects in humans.

Animals↗
PubMed1980

Carnitine balance in hemodialyzed patients.

1-Carnitine was assayed before and after dialysis in plasma, dialyzate and muscle of four patients undergoing hemodialysis. The findings suggest that plasma carnitine losses occurring during hemodialysis may be at the expense of the carnitine present in extracellular fluid. Carnitine concentrations in muscle of hemodialyzed patients and controls did not differ significantly. Chronic carnitine administration did prevent plasma carnitine from falling below base levels, but did not affect muscle concentration.

Adult↗
PubMed1980

Plasma levels of cyclophosphamide in patients under polychemotherapeutic regimens.

Plasma levels of non metabolized CPA were measured in two groups of lung cancer patients receiving polychemotherapy. There was extreme variability in the data obtained during the first hour after CPA administration. After this period of time a wide range of T 1/2 was found particularly in one of the two groups of patients. "Border-line" patients (with T 1/2 at the upper or lower limits of the range found) are discussed as regards the possible influence of ancillary treatment.

Adult↗
PubMed1980

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on macrophage and natural killer cell-mediated cytotoxicity in mice.

C57Bl/6 J mice (6-8 weeks old) were given single i. p. doses (1, 2, 6 and 30 micrograms/kg) of 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) and macrophage-mediated and natural killer (NK) cell-mediated cytotoxicity was evaluated at different times after treatment. Peritoneal macrophage cytolytic activity was measured as 3H-thymidine release from prelabelled mKSATU5 target cells in a 48 hours assay; macrophage-mediated cytostasis was assessed in terms of inhibitions of 3H-thymidine uptake by SL2 lymphoma cells. Spleen NK activity was measured using 51Cr-labelled YAC-1 lymphoma cells as targets. TCDD did not modify spontaneous macrophage-mediated and NK cell-mediated cytotoxicity per unit number of effector cells nor did it affect the macrophages' capacity to express increased cytolytic and cytostatic activity in the presence of endotoxin. Lower numbers of peritoneal macrophages and splenocytes were recovered from TCDD treated mice. Thus the total numbers of lytic units recovered from animals exposed to TCDD were lower than controls. Impairment of these cellular effector mechanisms, due to cell loss rather than inhibition of function, might play a role in the lowered resistance to bacterial infection of mice given TCDD and in the carcinogenic and cocarcinogenic activity of this chemical.

Animals↗
PubMed1979

Quantitative thin-layer chromatographic measurement of n-trifluoroacetyladriamycin-14-valerate (AD 32) and trifluoroacetyladriamycin (AD 41) in blood and tissues.

A thin-layer chromatographic method has been developed for the detection and measurement of N-trifluoroacetyladriamycin-14-valerate (AD 32) and its major metabolite trifluoroacetyladriamycin (AD 41). The procedure gives satisfactory linearity over a large range of concentrations. The coefficient of variability is about 10% over the entire range of usable concentrations, giving good reproducibility; sensitivity is 25 ng for both AD 32 and AD 41. Analysis is specific for AD 32 and AD 41 since adriamycin or more polar metabolites can be differentiated. Recovery is high (85-90%) and the method is simple and economical to use. Pharmacokinetics of AD 32 and AD 41 are reported in blood and some tissues of mice bearing Lewis Lung carcinoma.

Animals↗
PubMed1979

Chlorophenylpiperazine: a central serotonin agonist causing powerful anorexia in rats.

Meta-chlorophenylpiperazine inhibited serotonin and noradrenaline uptake by synaptosomes to the same extent with IC50 of 1.3 x 10(-6) M and 5.8 x 10(-6) M respectively. Dopamine uptake was less affected by meta-chlorophenylpiperazine (IC50 of 2.2 x 10(-5) M). Unlike d-amphetamine and d-fenfluramine, the drug did not significantly increase monoamine release in synaptosomal preparations. On the other hand, metachlorophenylpiperazine showed an IC50 of 620 nM in displacing 3H-5HT binding to brain membranes. Meta-chlorophenylpiperazine produced a dose-dependent reduction of food intake and this effect was prevented by a pretreatment with methergoline, a serotonin antagonist. The effect of metachlorophenylpiperazine was not modified by an intraventricular injection of 6-hydroxydopamine, electrolytic lesions of nucleus medianus raphe or ventral noradrenergic bundle, nor by a pretreatment with penfluridol, propranolol or phentolamine. The data suggest that the decrease of food intake induced by metachlorophenylpiperazine depends on its ability to act as a serotonin agonist is the brain. The specificity of the effects on serotonin suggests that this compound could prove an important tool for studies aimed at elucidating the functional role of serotonin in the central nervous system.

Animals↗
PubMed1979

Esterase activity of rat muscle.

The esterasic capacity of a series of skeletal muscles in response to three hemisuccinate ester drugs was investigated in rats and compared to that on alpha-naphthylacetate as a reference esterase substrate. Marked variations between different muscles and between given muscles of animals of different sex were observed, indicative of a complex heterogeneity in muscular expression of esterase activity.

Animals↗