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Biomedical subjects

S Garattini

Publications and source records attributed to S Garattini.

At least 253 records · Page 14Linked to original sources
PubMed1981

Plasma kinetics and urinary elimination of saccharin in man.

The plasma kinetics and urinary elimination of saccharin were studied in 3 groups each of 5 healthy male volunteers given the sweetener as three different single oral doses (50, 150 and 333 mg/60 kg body weight). Saccharin concentrations were determined by gas liquid chromatography-stable isotope dilution mass fragmentography. The compound was rapidly absorbed through the gastrointestinal tract, reaching plasma peak concentrations between 30 and 60 min after intake. Plasma saccharin elimination was also fast, with a monoexponential pattern of decay. At the 3 doses studied saccharin was excreted in urine within a few hours, about 60% of the dose being excreted unchanged at 6 h and 76% at 24 h.

Humans↗
PubMed1981

Urinary excretion of an uracilic metabolite from caffeine by rat, monkey and man.

Caffeine (C) metabolism has been studied in rat, monkey (Macaca cynomolgus) and man after oral administration of the compound. Eleven metabolites were quantified in urine; particular attention has been drawn to 4-amino [5-formyl methylamino]1,3-dimethyl uracil (ADMU) because of its structural analogies with 5-fluorouracil. The rat has been found to produce a much larger fraction of ADMU (about 30%) in respect to monkey an man (1-2%). The potential toxicological implications of this findings are discussed.

Adult↗
PubMed1981

Effects of saccharin on primary humoral antibody production in rats.

Rats for 25 to 54 days with diets containing high concentrations (1;2.5; 5%) of saccharin showed marked, dose-dependent suppression of primary humoral antibody production against heterologous erythrocytes. Phytohemagglutinin (PHA)-induced blastogenesis was not consistently affected by these saccharin-containing diets.

Animals↗
PubMed1981

Neurochemical correlates of muricidal behavior in rats.

Surgical, pharmacological or environmental manipulation are widely employed to induce muricidal behavior in naive laboratory male rats. The genetic predisposition of an animal strain to kill mice remains, however, an important factor to obtain the muricidal reaction. Data from the pertinent literature suggest that muricidal behavior may possibly be sustained by increased dopaminergic or catecholaminergic activity in the presence of reduced serotoninergic activity. The results here presented indicate, instead, that complete abolition of brain serotoninergic control, i.e., maximal depletion of brain serotonin, is just enough per se to induce muricidal activity. Further, this chemically-induced muricidal activity goes well beyond any pre-existing strain predisposition to kill mice or not.

Aggression↗
PubMed1981

p-Chlorophenylalanine-induced muricidal aggression in male and female laboratory rats.

p-Chlorophenylalanine (pCPA), a potent inhibitor of serotonin synthesis, specifically depletes brain serotonin in a dose-dependent manner. The resulting impairment of serotonergic inhibitory control of the brain is considered responsible for the consequent muricidal aggression that arises in pCPA-treated rats independent of their strain-dependent genetic predisposition and sex propensity to display this behavior. Judging from the data obtained, the minimal impairment of serotonergic inhibitory control required to induce consistent muricidal aggression in rats of both sexes of the strains considered, corresponds to a brain serotonin depletion of about 55-60%.

Aggression↗
PubMed1981

Studies on some pharmacological activities of 7-nitro-2-amino-5-phenyl-3H-1,5-benzodiazepine (CP 1414 S) in the rat. A comparison with diazepam.

Brain distribution and various pharmacological effects of 7-nitro-2-amino-5-phenyl-1,5-benzodiazepine (CP 1414 S) and diazepam were studied in rats. Injected at 10 mg/kg i.p., the compounds reached brain peak concentrations 15 min after administration and showed an apparent half-life of about 50 min. CP 1414 S was about ten times less potent than diazepam in protecting rats from pentetrazole convulsions, increasing punished responses in a "conflict" test and disrupting rotarod performance. At the lowest doses effective in these tests diazepam, but not CP 1414 S, caused significant reduction of spontaneous locomotor activity in rats. On the basis of the test selected, it is concluded that CP 1414 S causes effects similar to those shown by diazepam in the same conditions, although with less potency. It causes less depression of motor behaviour than diazepam, at least at the lowest doses and in rats.

Animals↗
PubMed1981

Animal models for the study of cancer-induced anorexia.

Walker carcinoma 256/B transplanted sc in CD-COBS rats induce a decrease of food intake when the tumor size is less than 5% of the body weight. This anorexia is accompanied by a decrease of the adipose tissue and, to a lesser extent, of muscular tissue. The mechanism involved in cancer-induced anorexia seems to be different from that of classic centrally acting anorectic agents. Among the drugs tested to counteract this anorexia only cyproheptadine shows a modest effect. Cyclophosphamide reduces tumor growth and prevents decrease in food intake. It is suggested that Walker carcinoma 256/B may be a useful animal model to study problems related to cancer-induced anorexia and cachexia.

Animals↗
PubMed1981

Antileptazol activity and kinetics of clobazam and N-desmethyl-clobazam in the guinea-pig.

The kinetic profiles and antileptazol activity of clobazam and its main metabolite were compared to assess the metabolite's contribution to the anticonvulsant activity of clobazam in the guinea-pig. The metabolite was less effective than the parent compound in terms of doses and active brain levels. However, the metabolite formed after clobazam administration accounted for the persistence of antileptazol activity in this animal species.

Animals↗
PubMed1980

Divergent effects of macrophage toxins on growth of primary tumors and lung metastases in mice.

The effects of silica and carrageenan on primary tumor growth and metastases were evaluated in c57bl/6 and BALB/c mice transplanted with the poorly immunogenic Lewis lung (3ll) carcinoma, mFS6 sarcoma and Madison 109 carcinoma spontaneously metastasizing to the lungs. Silica and carrageenan significantly enhanced lung metastases and decreased primary tumor weight in all three experimental models. A similar augmentation of lung secondaries was found after i.v. inoculation of 3LL tumor cells. The effects of carrageenan on primary 3LL tumor growth and metastases were observed also in thymus-deprived animals. The effect of macrophage toxins was studied also in C57BL/6 mice transplanted with the M5076/73A ovarian carcinoma. This tumor spontaneously metastasizes to various abdominal organs, but not to the lung. After treatment with carrageenan, lung metastases were observed, but no effect on secondaries at other anatomical sites or on the primary tumor was detectable. It is suggested that host defense mechanisms impaired by silica and carrageenan may have divergent effects in the regulation of growth of some primary tumors and spontaneous lung metastases.

Animals↗
PubMed1980

The effect of acute administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on humoral antibody production and cell-mediated activities in mice.

The effect of single doses of TCDD (1.2, 6 or 30 gamma/kg) on several immune parameters has been investigated in young adult C57B1/6 mice. TCDD profoundly suppressed the primary and secondary humoral response to T-dependent (sheep erythrocytes, SRBC) and T-independent (Type III pneumococcal polysaccharide, S III) antigens. In vitro lymphoproliferative responses to Concanavallin A (Con A) and bacterial lypopolysaccharide (LPS), and macrophage and natural killer (NK) cell-mediated cytotoxicity were not significantly affected per unit number of lymphoid cells. Moreover, the ability of splenocytes from TCDD treated animals to mediate a graft versus host (GVH) reaction was not impaired.

Animals↗
PubMed1980

Limits of animal models in cancer chemotherapy.

In animals models used in cancer chemotherapy, there is a low variability in terms of sensitivity of cancer cells in vitro, plasma levels of anticancer drugs, and interhost immune responses. In contrast, human tumors (e.g., ovarian carcinoma) show much greater variability. It is suggested that greater attention should be given to the study of the variables which distinguish the clinical setting from the animal models.

Animals↗