Serotonin transporter gene polymorphism as a predictor of short-term risk of suicide reattempts.

OBJECTIVE: The serotonin-transporter-linked polymorphic region (5-HTTLPR) polymorphisms are associated with suicidal behavior; however, prospective studies are scarce. Herein we aim to determine if 5-HTTLPR polymorphisms predict risk of short-term suicide reattempt in a high-risk suicidal sample. We also explore possible mediators or moderators of this relationship. METHODS: A multicenter prospective cohort study was designed to compare data obtained form 136 patients admitted to the emergency department for current suicidal ideation or a recent suicide attempt. Subjects were clinically evaluated, genotyped, and monitored for a new suicide attempt for 6 months. RESULTS: At 6 months of follow up, 21% of the subjects had a new suicide attempt. The frequency of L-allele and L-carrier was higher in reattempters when compared with non-reattempters (55.8% vs. 35.4%, p =  0.01 and 76.9% vs. 54.2%, p = 0.04, respectively). Reattempters also differ from non-reattempters patients with respect to age, history of previous suicide attempts, and age of onset of suicidal behavior. The logistic regression model showed that L-carriers had an odds ratio of 2.8 (95% CI: 1.0-7.6) for reattempts when compared to SS genotype. The adjusted model indicates that this association is not mediated or moderated by impulsivity. CONCLUSION: The 5-HTTLPR polymorphisms predicted short-term risk of suicidal reattempt independently of age and sex. L-carriers have almost three times more risk of relapse when compared with SS carriers.

Clozapine Rechallenge After Neutropenia or Leucopenia.

To rechallenge with clozapine for a patient who previously has experienced neutropenia or leucopenia or during clozapine treatment is a difficult clinical decision. Herein, we analyzed the results of such a rechallenge in 19 patients. We analyzed all the reports, from the database of the pharmacovigilance department of the Argentine National Administration of Drugs, Foods, and Medical Devices, of patients who were rechallenged with clozapine after a leucopenia or a neutropenia. Nineteen cases of rechallenge after leucopenia or neutropenia were reported between 1996 and 2014. One third of the patients re-exposed to clozapine developed a new hematologic adverse reaction. The second blood dyscrasia was less severe in 83% of the cases and had a shorter median latency as compared with the first (8 weeks vs 182 weeks, P = 0.0045). There were no significant differences for demographic and clinical characteristics of patients who developed a second dyscrasia as compared with those who did not. The present study shows that almost 70% of the patients rechallenged with clozapine after a leucopenia or a neutropenia did not develop a new hematological adverse effect, whereas the remaining 30% had a faster but less serious neutropenia.

EV-077 in vitro inhibits platelet aggregation in type-2 diabetics on aspirin.

INTRODUCTION: This study aimed to characterize the in vitro effect of EV-077, a compound that antagonises the binding of prostanoids and isoprostanes to the thromboxane receptor (TP) and inhibits the thromboxane synthase (TS), on platelet aggregation of patients with type-2 diabetes and coronary artery disease (CAD) on chronic aspirin treatment. The effect of EV-077 on 8-iso-PGE(2)-mediated TP receptor contraction of human arteries was also investigated. MATERIALS AND METHODS: Fifty-two type-2 diabetics with CAD on chronic aspirin (100 mg) treatment were studied. Arachidonic acid-induced platelet aggregation was measured by impedance aggregometry in platelet-rich plasma (PRP) and whole blood anticoagulated with hirudin, and by light transmission aggregometry in citrate-anticoagulated PRP following 10-min in vitro exposure to EV-077 (100 nmol/l) or control. The effect of EV-077 was measured on isometric contraction of 24 human umbilical arteries induced by isoprostane 8-iso-PGE(2). RESULTS: Arachidonic acid (1 mmol/l) induced substantial aggregation in hirudin-anticoagulated whole blood (63 ± 4 AU), which was significantly reduced by in vitro exposure to EV-077 (38 ± 3 AU, P<0.001). Virtually no arachidonic acid-induced aggregation in citrate-anticoagulated or hirudin-anticoagulated PRP was observed. EV-077 potently, competitively and reversibly inhibited TP mediated contraction of umbilical arteries by 8-iso-PGE(2) (P<0.01). CONCLUSIONS: Aspirin did not completely inhibit arachidonic acid-induced platelet aggregation in whole blood from type-2 diabetics with CAD. This aggregation is likely induced by prostanoids and/or isoprostanes produced by leukocytes, because it was significantly reduced by EV-077. The TP receptor-mediated contraction of human arteries induced by isoprostane 8-iso-PGE(2) was effectively inhibited by EV-077.

Phytomonas: transport of amino acids, hexoses and polyamines.

Phytomonas cells (Phytomonas Jma) isolated from the latex of Jatropha macrantha were assayed for amino acid, hexose and polyamine transport. Results showed high transport rates for glucose and fructose (193 and 128 pmol min(-1) 10(-7) cells, respectively) and lower, but significant rates, for proline, arginine, cysteine and glutamate (between 1.7 and 5.8 pmol min(-1) 10(-7) cells). Minor transport activities were observed for serine, glycine and aspartate (<1 pmol min(-1) 10(-7) cells). Amino acid transport processes do not seem to be regulated by starvation or during the growth phases. Polyamine transport was also evaluated showing a clear preference for spermidine over putrescine (3.4 and 0.4 pmol min(-1) 10(-7) cells, respectively). This work represents the first report on metabolite transport in phytomonads.