Epilepsy and pregnancy.
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Biomedical subjects
Publications and source records attributed to S Ratti.
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Previous studies showed that chromogranin A (CgA), a glycoprotein stored and co-released with various hormones by neuroendocrine cells and neurons, can modulate cell adhesion. We have investigated the structure-activity relationships of CgA using fibroblasts and coronary artery smooth muscle cells in adhesion assays. A recombinant CgA fragment 1-78 and a peptide 7-57 containing reduced and alkylated cysteines (Cys(17) and Cys(38)) induced cell adhesion after adsorption onto solid phases at 50-100 nm. Peptides lacking the disulfide loop region, including residues 47-68, 39-59, and 39-68, induced cell adhesion, either bound to solid phases at 200-400 nm or added to the liquid phase at 5-10 microm, whereas peptide 60-68 was inactive, suggesting that residues 47-57 are important for activity. The effect of CgA-(1-78) was blocked by anti-CgA antibodies against epitopes including residues Arg(53), His(54), and Leu(57). Substitutions of residues His(54), Gln(55), and Asn(56) with alanine decreased the cell adhesion activity of peptide 47-68. These results suggest that the region 47-57 (RILSILRHQNL) contains a cell adhesion site and that the disulfide bridge is not necessary for the proadhesive activity. The ability of soluble peptides to elicit proadhesive effects suggests an indirect mechanism. The high sequence conservation and accessibility to antibodies suggest that this region is important for the physiological role of CgA.
Picotamide is an antiplatelet drug with a peculiar dual mechanism of action: it inhibits thromboxane A2 synthase and antagonizes the pharmacological responses mediated by thromboxane A2 receptor. We investigated the in vitro effect of picotamide on smooth muscle cell migration and proliferation. Picotamide (1-500 microM) decreased human and rat smooth muscle cell proliferation, evaluated as cell number, in a concentration-dependent and reversible manner. Picotamide inhibited DNA synthesis induced by fetal calf serum (10%), platelet-derived growth factor (PDGF-BB (20 ng/ml)), epidermal growth factor (EGF (1 nM)) and (15S)-hydroxy-11,9-(epoxymethano)prosta-5Z,13E-dienoic acid (U46619 (10 microM, thromboxane A2 receptor agonist)). Co-incubation of U46619 together with EGF or PDGF-BB resulted in a marked amplification of [3H]thymidine incorporation that was completely reversed by picotamide. The drug also inhibited smooth muscle cell migration induced by fibrinogen (600 microg/ml) or PDGF-BB (20 ng/ml) in a concentration-dependent manner. The ability of picotamide to interfere with myocyte migration and proliferation confers, at least in vitro, a pharmacological interest on the compound in atherogenesis.
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Preliminary results of a new study on TCDD environmental persistence at Seveso (Milan, Italy) are presented. For this study, the most contaminated territory, Zone A, was divided into areas to fractionate the available TCDD levels in soil into data sets with reduced value spreads. In addition, various time subsets were defined for each area. Selected data were fitted with the exponential model y = y0.e-k.1. It was estimated that at least 1.2 kg TCDD was present in Zone A shortly after the accident. On average, a considerable portion (23%) of this amount lay on vegetation; TCDD which was not photodegraded or volatilized before the heavy rains of fall 1976, was later washed off and transferred to ground by water action. From this study, mean analytical underestimations affecting January 1977 and March 1978 contamination map data were on the order of 30 and 24%. All the above figures are considered optimistic. A few years after the accident, mean TCDD half-life in soil appeared to be 9.1y (t1/2-95% CLs, 6.2-17y).
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Growth conditions for Azospirillum brasilense Sp6 were devised for maximal expression of glutamate synthase. The enzyme levels were largely affected by the type and concentration of the nitrogen source. A 10-fold increase in the synthesis of the enzyme was observed at a limiting concentration of ammonia. The enzyme was purified to homogeneity by a procedure which was fairly rapid and allowed a good recovery of enzyme (30%). Azospirillum glutamate synthase is a complex iron-sulfur flavoprotein with a stoichiometry of 1 flavin adenine dinucleotide:1 flavin mononucleotide:8 Fe:8 S per protomer with a molecular weight of 185,000. The protomer is composed of two dissimilar subunits with molecular weights of 135,000 and 50,000. Kinetic parameters were determined. Km values for NADPH, 2-oxoglutarate, and L-glutamine were 6.25, 29, and 450 microM, respectively. The optimum pH was about 7.5. Complete reduction of the enzyme under anaerobic conditions was obtained either by NADPH (in the presence of a regenerating system) or dithionite or by photochemical reduction (in the presence of EDTA and 5-deazariboflavin). No stable long-wavelength intermediates were observed.
With the purpose of detecting spontaneous variation of systolic time intervals (STI), 20 normal subjects have been examined and the STI has been recorded for 5 consecutive days at the beginning of the test and 20, 40 and 60 min afterwards. Significant differences were found for PEP, LVET and the PEP/LVET ratio between observations (p less than 0.05) and between days (p less than 0.01). All the values of the STI at the fifth day are rather near the values recorded at the last observation of the first day. This may be related to the presence of some factor (catecholamine release induced by emotional stress?) resulting in physiological changes which are reduced by repetition of the test. This hypothesis was confirmed in a second series of normal volunteers where the STI were recorded simultaneously with sampling of blood for assessing circulating CA levels. A highly significant correlation (p less than 0.001) was recorded between PEP, PEP/LVET and plasma CA making it evident that increase of PEPI and PEP/LVET is directly correlated with the reduction of plasma CA level.
A double blind cross-over trial has been carried out on the effects of a nicotinic acid compound on 27 patients affected by hyperlipidemia. The subjects have been treated over one year according the following plan: two peroids of 90 days each with the drug and two with placebo. The statistical analysis showed a significant reduction of serum cholesterol triglycerides, phospholipids and total lipids. In 4 patients out of 27, the treatment has not been completed because of drug intollerance.
Twenty-two cases of Coxsackie virus heart disease diagnosed from November, 1969, to December, 1971, were re-examined after a period of 42 to 68 months from the acute illness. The patients with hypertension, diabetes, chronic alcohol intake, or aged over 35 were eliminated from the trial. With the purpose of assessing myocardial function, the systolic time intervals were recorded by a noninvasive standard technique. The differences in systolic time intervals between the group of patients with previous viral myocarditis and a group of normal control subjects were not statistically significant. However, the pre-ejection period was clearly prolonged in three patients out of 10, a modification consistent with a depressed myocardial function, as in patients with cardiomyopathy.
Left ventricular function of a sample of subjects with chronic alcohol intake, in the form of wine, and without clinical or electrocardiographic signs of heart disease was compared with that of a sample of normal control subjects using non-invasive polygraphic recordings. The statistical analysis has shown significant prolongation of PEP, PEPI, an increase in PEP/LVET, and a shortening of LVET and LVETI in the alcoholic subjects compared with the controls. All these abnormalities may be ascribed to left ventricular malfunction.
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