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Biomedical subjects

S Garattini

Publications and source records attributed to S Garattini.

At least 307 records · Page 17Linked to original sources
PubMed1978

Distribution and localization of p-hydroxy-d-amphetamine in rat brain.

p-Hydroxy-d-amphetamine (p-OHdA) penetrates the blood--brain barrier poorly, when given acutely or by repeated systemic treatments, or when formed by biotransformation from administered d-amphetamine. However its distribution is relatively selective as it accumulates in the striatum more than in the brainstem. The rate of disappearance also differs in the two areas, being slower in the striatum than in the brainstem. These findings suggest that p-OHdA might be stored in different compartments. To check whether p-OHdA specificially accumulated in nerve terminals, catecholaminergic nerve endings were destroyed with 6-hydroxydopamine (6-OHDA). It has been shown that p-HOdA accumulates much less in the striatum of 6-OHDA-treated rats than of controls. This effect was not present in the brainstem. Accumulation of p-OHdA was similar after repeated d-amphetamine administration. The results are interpreted as showing that p-OHdA tends to accumulate in dopaminergic structures.

Amphetamines↗
PubMed1978

The absorption by human volunteers of glutamic acid from monosodium glutamate and from a partial enzymic hydrolysate of casein.

Peripheral plasma concentrations of glutamic and aspartic acids and alanine were measured after ingestion of monosodium glutamate or a pancreatic hydrolysate of casein by human volunteers. The doses of each material were such that they contained similar amounts of glutamic acid. Plasma glutamic acid concentrations rose promptly after the monosodium glutamate but mean peak concentrations were well below those likely to cause neurological damage. Plasma aspartic acid concentrations also rose after the monosodium glutamate but the behaviour of plasma alanine concentrations suggested that intestinal transamination of glutamic acid was insufficient to cause an appreciable rise in alanine concentration in the peripheral plasma. Significant increments in plasma glutamic acid concentrations did not occur after the pancreatic hydrolysate of casein and it is probable that competition for absorptive mechanisms by other amino acids, both free and peptide-bound, causes absorption of glutamic acid to be slower from mixtures of peptides and amino acids than from monosodium glutamate itself.

Absorption↗
PubMed1978

Biochemical and pharmacological properties of oxazepam.

Oxazepam is the final metabolic product in vitro and in vivo of a large number of pharmacologically active benzodiazepines. Oxazepam shows antimetrazol activity varying in intensity and duration according to the animal species considered. This difference is in part related to different "sensitivity" and in part due to different disposition of oxazepam. Particularly relevant is the difference in biliary excretion by various animal species. Oxazepam is currently available as a racemate but two optical isomers can be separated as succinate half esters. The (+) form appears to be more active than the (-) form, probably because more oxazepam is released from the (+) than the (-) isomer in vivo. In vitro studies confirm that the liver hydrolyzes the (+) oxazepam succinate half ester more than the (-) form. Other work has aimed at analyzing the effects of oxazepam on brain chemical mediators, with particular reference to the cholinergic system. Finally it is shown that oxazepam, similarly to other benzodiazepines, increased aggressiveness in male mice during chronic treatment.

Acetylcholine↗
PubMed1978

Some examples of interactions between drugs in cancer chemotherapy.

Drug combinations in cancer treatment are widely utilized because they frequently result in better therapeutic activity than the single treatments. The mechanism(s) by which this can be achieved may reside in an enhanced chemotherapeutic effect or in reduced toxicity, it being difficult to dissociate the two aspects. To underline this difficulty, experimental studies will be reported. A first example illustrates the interaction between phenobarbital and cyclophosphamide. Depending on the schedule of administration, different effects can be obtained. These effects cannot always be explained by pharmacokinetic data. A second example deals with the combination of anthracycline antibiotics (daunomycin and adriamycin) with immunostimulant treatment (C. parvum). Both in vitro and in vivo adriamycin was less toxic than daunomycin for macrophages. As predicted on the basis of this finding, adriamycin resulted in a synergistic antitumoral effect when combined with macrophage activators.

Animals↗
PubMed1978

Variable oral absorption of hexamethylmelamine in man.

Plasma levels of hexamethylmelamine were measured by a sensitive and specific gas chromatographic assay in 11 patients after they received oral doses ranging from 120 to 300 mg/m2. Peak levels were reached in 0.5--3 hours and ranged from 0.2 to 20.8 micrograms/ml. The area under the curve ranged from 70.2 to 3606.6 micrograms/ml x minute. The half-life of the beta-phase of elimination also showed considerable variability, ranging between 4.66 and 10.2 hours. These parameters were not related to the dose administered. No plasma accumulation of the drug was observed after daily treatment with hexamethylmelamine for 14--21 days.

Absorption↗
PubMed1978

Distribution of fenfluramine in normal and obese mice.

Concentrations of fenfluramine and its metabolite, norfenfluramine, were measured in blood, brain and parametrial adipose tissues 15, 30, 60 and 120 min after intraperitoneal (i.p.) administration of fenfluramine hydrochloride (10 mg/kg) to normal and gold-thioglucose obese mice. Concentrations of fenfluramine were higher in the brain of obese mice than in normal mice, while there was no difference in norfenfluramine levels in the two groups. This difference may be related to higher blood levels of fenfluramine but not of norfenfluramine in obese animals. The drug was presented in about the same concentrations in the adipose tissue of the two groups. These results may explain previous findings that fenfluramine was more effective as an anorectic agent in obese than in lean mice.

Adipose Tissue↗
PubMed1978

Distribution and antitumor activity of adriamycin given in a high-dose and a repeated low-dose schedule to mice.

Experimental studies on the distribution of adriamycin (AM) under different treatment conditions and possible correlations between tissue and plasma levels and chemotherapeutic activity are discussed. C57BL/6J mice bearing im Lewis lung carcinoma and (C3H x O2O)F1 mice bearing mammary carcinoma were injected iv with AM at a single dose of 15 mg/kg or with the same total amount of drug administered in spaced doses of 3.75 mg/kg for 4 consecutive days. In the two experimental systems studied, the drug reached approximately the same value in the tumor and spleen with both types of treatment, but with the 3.75-mg/kg x 4 schedule much lower AM concentrations were observed in the heart than with the single high-dose treatment. The therapeutic activity of the two treatments also differed: the antitumor and antimetastatic effect was the same in the two tumor systems, but with the 3.75-mg/kg x 4 schedule, increased survival and somewhat lower toxicity were observed. Daunorubicin, tested in the mammary carcinoma system with the two schedules of treatment, behaves very similarly to AM in terms of both distribution and chemotherapeutic effect.

Animals↗