Possible involvement of phosphatidylinositol 3-kinase in regulated exocytosis: studies in chromaffin cells with inhibitor LY294002

Several lines of evidence suggest that phosphorylated products of phosphatidylinositol play critical functions in the regulation of membrane trafficking along the secretory pathway. To probe the possible involvement of phosphatidylinositol 3-kinase (PI 3-kinase) in regulated exocytosis, we have examined its subcellular distribution in cultured chromaffin cells by immunoreplica analysis and confocal immunofluorescence. We found that the PI 3-kinase heterodimer consisting of the regulatory and catalytic subunits was associated essentially with the subplasmalemmal cytoskeleton in both resting and nicotine-stimulated chromaffin cells. Attempts to immunoprecipitate PI 3-kinase with anti-phosphotyrosine antibodies failed, suggesting that the activity of PI 3-kinase was not modulated by tyrosine phosphorylation and/or physical interaction with SH2-containing proteins in stimulated chromaffin cells. LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one], a potent inhibitor of PI 3-kinase, produced a dose-dependent inhibition of catecholamine secretion evoked by various secretagogues. Furthermore, cytochemical experiments with rhodamine-labeled phalloidin revealed that LY294002 blocked the disassembly of cortical actin in chromaffin cells stimulated by a depolarizing concentration of potassium. Our results suggest that PI 3-kinase may be one of the important regulatory exocytotic components involved in the signaling cascade controlling actin rearrangements required for catecholamine secretion.     

Determining the core of journals of a research centre: The example of researchers from the Department of Rural Economy and Sociology of the Institut National de la Recherche Agronomique,France

This paper analyses the determination of visibility of journals in which researchers of INRA (National Institute for Agricultural Research) publish. The corpus is comprised of 671 articles published over a period of four years in 258 journals. The advantage of the method applied for determining the visibility of journals is that it combines two approaches: a) bibliometric indicators (coverage by the ISI-publications and by two specific French databases) and b) experts' opinions (10 economists and sociologists). The main results are: a) There is a convergence between the opinion of the experts and «visibility» in the databases, b) The impact factor confirms the main opinions of the experts. The first journals ranked by the experts and JCR Social Sciences are the same but represent only 40 per cent of the total journals analysed. The other journals were revealed by the experts and French databases.«Whoever seeks to pass a balanced but lucid judgement on the general trends of the activity carried out by the profession to which he belongs, is liable to say either banalities or to hurt his colleagues»The notion which we retain of core is that which is successively and conjointly validated by the experts and by the major databases representative of the field.This study was financed by the Department of Rural Economy and Sociology of INRA.     

MRI of intramedullary sarcoidosis: follow-up of a case

Significative enhancement of free radical formation (FRO) in vivo is an important feature of hypertensive disorders of pregnancy (HDP), namely preeclampsia (PIH). The latest investigations about the pathology of HDP, showed the contribution of placental circulation to the development and evolution of such disease. The placental bed can be a potential source of FRO or activation of cells that can produce FRO. Glutathione, is an important molecule for cellular protection against damage, is a cofactor of many enzymes, in particular, for the glutathione peroxidase of the placental tissue; this enzyme in the placenta bed prevent the production of thromboxan and lipoperoxides; the latter are potentially damaging to the endothelium cells and can cause vasoconstriction, the most important feature of PIH. The activity of that enzyme is deficient in PIH. We studied, by fluorometric assay, the concentrations of the two states of glutathione in placental homogenates (PLH) from pregnant women without pathology (PWN) and from pregnant women with PIH (PWPIH). The data showed significant low concentrations in the PLH of the two states of glutathione in the PWN against high concentrations of this molecule in the PLH from PWPIH. This feature can result from a deficient user of the glutathione by the cellular mechanism for prevention against oxidative factors. In addition, our study shows a biochemical marker that is suggestive that the placental bed is a potential source of FRO production in PIH.     

Non-amphetaminic mechanism of stimulant locomotor effect of modafinil in mice

Previously established dose-response curves indicated that modafinil 20-40 mg/kg i.p. elicited in mice an obvious stimulation of locomotor activity roughly similar to that induced by (+)amphetamine 2-4 mg/kg. The effects of various agents modifying dopamine transmission were compared on the locomotor response to both drugs. The preferential D2 dopamine receptor antagonist haloperidol 37.5-150 micrograms/kg i.p. suppressed the stimulant effect of (+)amphetamine in a dose dependent manner, but not that of modafinil. The D1 dopamine receptor antagonist SCH 23390 (7.5-30 micrograms/kg s.c.) reversed the (+)amphetamine but not the modafinil induced hyperactivity. The tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (200 mg/kg) suppressed the hyperactivity induced by 4 mg/kg dexamphetamine but not that induced by 20 mg/kg modafinil. Associating L-DOPA 150 mg/kg and benserazide 37.5 mg/kg with (+)amphetamine 2 mg/kg resulted in stereotyped climbing behavior, that was not observed with modafinil 10-80 mg/kg. The profound akinesia induced by reserpine (4 mg/kg s.c.; 5 h before testing) was reversed by (+)amphetamine 2 mg/kg but not by modafinil 40 mg/kg. Finally, on synaptosomes prepared from mouse striata preloaded with [3H]dopamine, modafinil 10(-5) M did not increase the spontaneous [3H]dopamine release whereas (+)amphetamine, at the same concentration, doubled it. From all these differences between the two drugs, it is concluded that the mechanism underlying the modafinil induced stimulant locomotor effect differs completely from that of (+)amphetamine.     

Average intake of anti-oxidant (pro)vitamins and subsequent cancer mortality in the 16 cohorts of the Seven Countries Study

This ecologic study aimed to investigate whether differences in population mortality from lung, stomach and colorectal cancer among the 16 cohorts of the Seven Countries Study could be explained by differences in the average intake of anti-oxidant (pro)vitamins. In the 1960s, detailed dietary information was collected in small sub-samples of the cohorts by the dietary record method. In 1987, food-equivalent composites representing the average food intake of each cohort at baseline were collected locally and analyzed in a central laboratory. The vital status of all participants was verified after 25 years of follow-up. The average intake of vitamin C was strongly inversely related to the 25-year stomach-cancer mortality (r = -0.66, p = 0.01), also after adjustment for smoking and intake of salt or nitrate. The average intake of alpha-carotene, beta-carotene, and alpha-tocopherol were not independently related to mortality from lung, stomach or colorectal cancer, nor was vitamin C related to lung and colorectal cancer.     

Helicobacter pylori at Hospital Santo Tomás

We studied the incidence of infection with Helicobacter pylori in Panamanians with chronic dyspepsia, gastric or duodenal ulcer, gastritis or gastric cancer. The histopathology was positive in 54 (81%) of 66 patients; the urea test was positive in 52 (82.5%) of 63 cases; the impromptu was positive in 51 (79.6) of 64 patients; the endoscopic examination was positive in 64 (82.9%) of 77 examinations.