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Biomedical subjects

S Garattini

Publications and source records attributed to S Garattini.

At least 271 records · Page 15Linked to original sources

2,3,7,8-Tetrachlorodibenzo-p-dioxin toxic effects and tissue levels in animals from the contaminated area of Seveso, Italy.

After the environmental contamination by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the area of Seveso, Italy, thousands of small domestic animals (mainly rabbits and poultry) died within a few weeks. Autopsies on dead animals showed various pathological signs, such as hepatic lesions and haemorrhage. TCDD was monitored in animal tissues by gas chromatography-mass fragmentography; rabbit liver levels corresponded fairly well to soil contamination, which indicated that this species can be used as a tool for tracking the presence of TCDD in the environment.

Accidents, Occupational↗

Effect of acute exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on humoral antibody production in mice.

The effect of single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 1.2, 6 or 30 micrograms/kg i.p.) on primary humoral antibody production was studied in young adult C57 BL/6J mice. TCDD profoundly suppressed the primary response to thymus-dependent (sheep erythrocytes) and independent (type III pneumococcal polysaccharide) antigens. The inhibitory effect of TCDD was still detectable 42 days after treatment. In contrast, under these experimental conditions, in vitro lymphoproliferative responses to Concanavalin A (Con A) and bacterial lypopolysaccharides and the ability to mediate graft versus host reaction were not significantly affected per unit number of lymphoid cells.

Animals↗

Monosodium glutamate kinetic studies in human volunteers.

(a) A kinetic study of plasma glutamic acid (GA) was made after monosodium glutamate (MSG) administration to human volunteers. MSG was given at doses of 30,60 and 120 mg/kg in a bouillon and of 60 mg/kg in tomato juice. In another experiment a normal meal was consumed without added MSG. (2) Plasma area under the curve (AUC) was found to be lower in females than in males. (3) Plasma AUC was lower when MSG was taken in tomato juice than when consumed in bouillon. (4) Consumption of the normal meal did not result in any significant increase in plasma GA.

Adult↗

Effect of oral monosodium glutamate on glutamic acid levels in the nucleus arcuatus of the hypothalamus and on serum osmolality of adult and infant mice.

Monosodium glutamate (MSG) given by gavage to 7-day-old mice at 2 g/kg body weight (b.wt.) as a 20% solution w/v resulted in a 27% increase in the glutamic acid (GA) content in the nucleus arcuatus of the hypothalamus (NAH). When MSG was administered by gavage to adult mice at 4 g/kg b.wt. as a 20% solution w/v, GA levels in NAH remained unchanged. Serum osmolality, measured after oral MSG, was elevated in infant mice but was unaffected in adults.

Animals↗

Plasma glutamic acid levels in premature newborn.

24 premature, newborn infants were investigated for plasma glutamic acid (GA) levels before and after a normal milk feed, to ascertain if the ingestion of GA present in the milk could result in an increase of its plasma level. No increases were detected in plasma between 5 and 90 min after the feed. These results may be important in respect to the problem of the possible toxicity of monosodium glutamate (MSG) added to baby foods.

Animals↗

Accumulation and metabolism of uneven fatty acids present in single cell protein.

Liquipron and Toprina, obtained by growing yeasts (Candida maltosa and Candida lipolytica) on n-hydrocarbons, were investigated to ascertain the biological significance and possible toxicological implications of their high content of uneven fatty acids (UFA). It was confirmed that the extent to which UFA accumulate in adipose tissue of rats fed the 2 products reflects only partially their UFA contents. The presence of UFA in rat tissues does not appear to alter intermediate metabolism. The capacity of liver mitochondria ot oxidize palmitic acid was similar in control and in Liquipron-treated rats. Palmitic acid and heptadecanoic acid did not compete for oxidation when mixed at concentrations which reflect their presence in the tissues of animals fed high levels of Liquipron.

Adipose Tissue↗

In vitro effects of saccharin on cell-mediated host defence mechanisms.

In vitro exposure to saccharin (0.1-2 mg/ml) did not affect the tumoricidal activity of macrophages and natural killer (NK) cells from mice and rats. In contrast saccharin at doses of 0.5-2 mg/ml significantly and consistently depressed the blastogenic response of rat lymph node cells to phytohemagglutinin (PHA). Similarly mouse splenocytes showed impaired responsiveness to PHA and bacterial lipopolysaccharides n the presence of 2 mg/ml saccharin. Compared with murine lymphoid cells, human peripheral blood lymphocytes were relatively resistant to the immunodepressive activity of saccharin, a low but significant, depression (21%) of the response to PHA being observed only at the highest concentration (2 mg/ml) in 1 of 3 normal healthy donors tested.

Animals↗

Time dependence of the in vitro cytotoxicity of hexamethylmelamine and its metabolites.

The cytotoxicity of hexamethylmelamine (HMM) and its metabolites pentamethylmelamine (PMM), N,2,2,4,6-tetramethylmelamine (TMM) and hydroxymethylpentamethylmelamine (HMPMM) and of the alkylating agent triethylenemelamine (TEM) were studied on a cell line derived from a human ovarian cancer, by measuring [3H]TdR uptake. After 24 h of incubation all the tested compounds inhibited [3H]TdR uptake, but only at a concentration of 100 micrograms/ml. However, after 120 h incubation, concentrations of 0.1--10 micrograms/ml resulted in highly significant cytotoxicity. HMPMM and TEM were the most active and their effect was not reversed 72 h after their removal. In our in vitro system no metabolism of HMM was observed.

Altretamine↗

Metastasizing capacity of tumour cells from spontaneous metastases of transplanted murine tumours.

We investigated the metastasizing capacity of spontaneous lung metastases from the MN/MCA1 and mFS6 sarcoma, the B16 melanoma and colon 26 carcinoma. Spontaneous metastases at other visceral organs (liver, spleen, kidney, ovary, uterus) from the M5076/73A (M5) ovarian carcinoma and colon 26 carcinoma were also studied. Tumour cells from individual spontaneous metastases were used immediately after isolation from the normal parenchyma (mFS6, M5 and colon 26) and/or after 1 s.c. passage in syngeneic mice (MN/MCA1, mFS6, B16 and M5). Spontaneous metastases were examined for all tumours and their secondaries after i.m. or s.c. inoculation of tumour cells; artificial lung colonies were measured after i.v. injection only of cells from the primary mFS6 and MN/MCA1 and B16 or their spontaneous metastases. Individual spontaneous metastases were to some extent heterogeneous in their metastatic potential, a minority of the secondaries having greater or lesser metastatic capacity than the appropriate primary. Overall, tumour cells from spontaneous metastases did not show greater metastasizing capacity than primary neoplasms, nor was there evidence that metastases from specific organs (e.g. spleen and kidney) tended to home to the specific anatomical sites from which they were originally isolated. These observations in a series of murine tumours of different histology, transplantation history and pattern of metastasis, do not support the hypothesis that metastases are the ultimate expression of strong selection of variant cells with greater intrinsic metastatic potential, pre-existing within the primary tumour.

Animals↗

Species differences in clobazam metabolism and antileptazol effect.

The antileptazol effect of clobazam lasts longer in the mouse than in the rat. After intraperitoneal injection of clobazam (10 mg kg-1) plasma and brain concentrations of the drug and its rate of disappearance were similar in both species, whereas the metabolite N-demethylclobazam was present at higher concentrations and for longer in the mouse than in the rat. Although the exact contribution of the N-desmethylclobazam to the anticonvulsant effect of clobazam cannot be assessed, the longer duration in mice than in rats seems to be associated with different brain accumulations of the metabolite.

Animals↗

Comparison of the effects of the stereoisomers of fenfluramine on the acetylcholine content of rat striatum, hippocampus and nucleus accumbens.

The (+)- and (-)- isomeric forms of fenfluramine were compared for their effects on rat brain area acetylcholine (ACh) content. The drugs showed similar patterns in increasing ACh content in the accumbens and hippocampus and in being ineffective in the brainstem. The actions differed in the striatum where the (+)-form markedly increased ACh content while the (-)-form produced no change. Both isomer-induced increases in ACh in the accumbens were prevented when 5-HT synthesis was blocked by p-chlorophenylalanine, thus denoting 5-hydroxytryptaminergic mediation of these effects. In striatum, the increase in ACh induced by (+)-fenfluramine was summated with the increase in ACh induced by dopamine receptor stimulation with apomorphine and was not prevented by dopamine receptor blockade with pimozide. On the other hand, apomorphine's effect was blocked by (-)-fenfluramine while pimozide pretreatment unmasked an increase in ACh induced by (-)-fenfluramine. The results favour the notion that there is a population of cholinergic neurons intrinsic to the striatum which is under inhibitory 5-HT regulation and independent of inhibitory dopamine regulation.

Acetylcholine↗