Comparative in vitro and in vivo studies between morphine and methionine-enkephalin: genotype dependent response in two different strains of mice.
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Biomedical subjects
Publications and source records attributed to F Bruno.
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A simple procedure for the preparation of beta-N-acetylhexosaminidase (EC 3.2.1.52), free from other glycosidases, from commercial bovine serum albumin is described. It has been fractionated into three peaks on a DEAE-cellulose column. The Km and V values for 4-methylumbelliferyl-beta-D-N-acetylglucosaminide (4MU-gluNAc), 4-methvlumbelliferyl-beta-D-N-acetylgalactosaminide (4MU-galNAc), p-nitrophenyl-beta-D-N-acetylglucosaminide, and p-nitrophenyl-beta-D-N-acetylgalactosaminide for each was established. The inhibition by several structural analogues on 4MU-gluNAc and 4MU-galNAc hydrolysis by the enzyme present in peak 1 was investigated.
alpha-Fetoprotein and the synthesis of heme associated with hemoglobin were measured simultaneously in short-term cultures of human fetal liver cells to correlate the relationship of alpha-fetoprotein to erythroid cell function. Both synthetic processes decreased exponentially during the first 5 days of culture. The use of media supplemented with different batches of fetal calf serum and porcine portal vein serum indicated that the optimal conditions for the production of alpha-fetoprotein were different from those required for the synthesis of heme associated with hemoglobin. Moreover, the alpha-fetoprotein-producing cells could be separated from erythroid cells after velocity sedimentation in Ficoll gradients. Although it is well known that erythropoiesis and alpha-fetoprotein production occur simultaneously during ontogenesis, alpha-fetoprotein itself (0.01-100 micron g/ml) did not stimulate heme synthesis in liver erythroid cells. Erythropoietin did not stimulate alpha-fetoprotein production. It is concluded that there is no cause-effect relationship between alpha-fetoprotein production and erythroid cell fuction in human fetal liver cells and that the two processes occur independently in different cell types.
The effects of testosterone and 17beta-estradiol on the synthesis of fetal and adult hemoglobins have been studied using a short-term primary cell culture system of human fetal liver at midgestation. There was a significant 23% increase in incorporation of 59Fe into adult hemoglobin relative to the total after the addition of 5 X 10(-8)M testosterone. 17beta-Estradiol (10(-6)M) lowered the incorporation of 59Fe by 21%. beta-Globin chain synthesis, measured as 3H- or 14C-leucine incorporation into globin chains, was identical in control and testosterone-treated cells and only slightly lower when 17beta-estradiol was added. For this reason the observed changes in adult hemoglobin resulting from the action of testosterone and 17beta-estradiol are caused by an indirect effect either in the final hemoglobin assembly or by small changes in the gamma/alpha-chain ratio which may be undetected by the methodology used.
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Thanks to the increasing knowledge of the pathogenesis of atherosclerosis, much effort has been made in the last years to develop new drugs aimed at controlling risk factors correlated with the disease as well as to investigate more deeply their mechanism of action. In particular, this brief review will describe some new aspects of the mechanism of action of drugs widely used in the control of risk factors like hyperlipemia, hypertension and blood viscosity. Among drugs active on plasma lipid profile, HMG-CoA reductase inhibitor are, at present, under study for their promising activity in the modulation of the interaction between the cells of the arterial wall and circulating blood elements. Indeed, these compounds have been found to control the proliferation of smooth muscle cells and other events related to the formation of atheroma. As far as antithrombotic drugs are concerned, the efficacy of low doses of aspirin has emerged by recent clinical trials. The successful use of low doses of aspirin has been possible following the comprehension of the mechanism by which this compound inhibits TXA-dependent platelet function, thus allowing a dose-dependent dissociation of the antithrombotic activity from other undesirable effects. Also for calcium antagonist an antiatherogenic effect which deserves further investigations has been recently clarified. Indeed it has been demonstrated that calcium antagonists have a protective effect against vascular lesions because they inhibit smooth muscle cell proliferation, lipid uptake by macrophages and the production of collagen and elastin. Another class of drugs which represents a new approach in the control of some risk factors is represented by n-3 fatty acids. Besides their activity on triglycerides, these compounds exert a positive effect on hemostatic and thromboembolic event, by reducing platelet aggregation and blood viscosity. Also for those molecules which appear to exert promising antiatherosclerotic and antithrombotic action, further studies will define their exact mechanism of action.
OBJECTIVE: To describe the possible clinical and laboratory effects of exogenous surfactant instillation into the tracheal tube of a child with severe acute bronchiolitis undergoing mechanical ventilation. CASE REPORT: a 2-month-old girl with clinical diagnosis of acute viral bronchiolitis underwent mechanical ventilation. She required high positive inspiratory peak pressure (35 to 45 cmH(2)O) and high inspiratory fraction of oxygen (FiO(2) = 0.9), but showed no clinical response or improvement in the arterial blood gas analysis. An exogenous surfactant (Exosurf(R), Glaxo - 50 mg/kg) was used to facilitate the use of a less aggressive ventilatory strategy. RESULTS: Four hours after surfactant administration, it was possible to reduce the positive peak inspiratory pressure (PIP) from 35 to 30 cmH(2)O, and FiO(2) from 0.9 to 0.6; and to increase the positive end-expiratory pressure (PEEP) from 6 to 9 cmH(2)O. During this period the paO(2)/FiO(2) ratio increased from 120 to 266. At the end of 24 hours, FiO(2) could be reduced to 0.4. DISCUSSION: Surfactant inactivation may be a decisive factor in the unfavorable evolution of some severe cases of acute bronchiolitis. The tracheal instillation of exogenous surfactant, in these cases, allows us to adopt less aggressive ventilatory strategies, and promotes rapid clinical responses.