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Serotonergic dysfunction is implicated in depression, psychiatric disorders and suicidal behaviors. The first and rate-limiting step in the synthesis of serotonin is catalyzed by tryptophan hydroxylase (TPH) which is encoded by TPH1 and THP2 genes. Genetic association studies have revealed contradictory results about the effect of the TPH1 A218C (rs1800532) polymorphism on suicidal behavior in different populations.', "In this study, we investigated A218C polymorphism in 109 suicide attempters and 98 healthy controls. Socio-demographic characteristics of participants were obtained through questionnaire. DNA was extracted from peripheral blood and genotyping was performed by Real Time PCR. Fisher's exact test was used to evaluate the significance of the difference among the independent variables. Hardy-Weinberg equilibrium was tested using Pearson's goodness-of-fit chi-squared test.", 'The frequency of A allele was significantly higher in suicide attempters than controls (46.33% vs. 35.71%, p=0.0357). However, there were no differences in genotype frequencies of this locus between participants having attempted suicide and controls (p>0.05). Among males, frequencies of CC genotype and C allele were found to be significantly higher in controls (p=0.0125, p=0.0298). With regard to the female subjects and female controls, no significant association was detected between suicidal behavior and genotype/allele frequencies (p>0.05).
Is tPH1 A218 allele associated with suicidal behavior in Turkish population?

The 6-min walk test (6MWT) has prognostic value in various pulmonary disorders including idiopathic pulmonary fibrosis (IPF). We determined the individual prognostic accuracy of distance walked and oxygen saturation during the 6MWT in patients with IPF. We defined a new composite index, the distance-saturation product (DSP), which is the product of distance walked and lowest oxygen saturation during the 6-min walk test. We compared the performance of the DSP to the individual 6MWT parameters in predicting mortality.', 'We evaluated pulmonary function tests, 6-min walk parameters and the DSP between survivors and non-survivors. The ability of each measure to discriminate outcomes was determined by receiver operator curves.', '81 patients (48 survivors, 33 non-survivors) were included. Pulmonary function tests were similar and did not correlate with survival. Desaturation was greater (89.4% versus 83.7%, P<0.001) and distance walked was lower (406.9 versus 181.3m, P = 0.005) in non-survivors. The DSP was significantly lower among non-survivors (364.8 versus 153.5m%, P < 0.001) and predicted mortality more accurately than either individual 6MWT component (P = 0.035 versus desaturation, P=0.040 versus distance). A DSP <200 m% was associated with a seven-fold greater risk of 12-month mortality and an 18.0% shorter median survival compared with a DSP > 200 m% (P < 0.001).
Does the distance-saturation product predict mortality in idiopathic pulmonary fibrosis?

Accumulation of acetylcholine in the central nervous system is believed to account for the rapid lethality of organophosphate pesticides and chemical nerve agents. Diazepam is known to supplement atropine therapy, but its specific mechanism of action is uncertain.', 'To test four centrally acting agents for early antidotal efficacy in severe dichlorvos poisoning in the murine model.', 'The up-and-down method was used to dose four candidate antidotes: diazepam, xylazine, morphine, and ketamine. Antidotes were administered subcutaneously to unsedated adult Sprague-Dawley rats who were pretreated with 3 mg/kg intraperitoneal glycopyrrolate. All animals received 20 mg/kg of dichlorvos subcutaneously 5 minutes later. A blinded observer adjudicated the outcomes of 10-minute mortality and survival time.', 'All animals pretreated with either no antidote (8/8 deaths) or glycopyrrolate alone (8/8) died within 10 minutes of dichlorvos injection. Pretreatment with diazepam (3/9 deaths), or xylazine (3/9), decreased lethality substantially (Fisher p = 0.007; median effective doses, 0.12 mg/kg and 3.0 mg/kg, respectively). Intermediate doses of morphine (3.1 to 5.5 mg/kg) resulted in survival, but higher doses did not, presumably because of excessive respiratory depression (7/11 deaths; p = 0.09). Ketamine (7/8 deaths) was ineffective as an antidote. Survival times also were prolonged in the diazepam and xylazine groups (log-rank p < 0.001) and, to a lesser degree, the morphine group (p = 0.07).

Do multiple centrally acting antidotes protect against severe organophosphate toxicity?