[Trauma and resilience among children 3 to 6 years old in three neighborhoods of Port-au-Prince after the 2010 earthquake in Haiti]. / Traumatismes et résiliences chez les enfants de 3 à 6ans dans trois quartiers de Port-au-Prince après le séisme de 2010 en Haïti.

The paper describes an action research for indicative assessment of psychological problems of young children following the 2010 earthquake in Haiti, and the interest of using the Creole version of the questionnaire PSYCa 3-6. The survey took place in Port-au-Prince, and the evaluators were trained to a proper standardized administration of the questionnaire. BACKGROUND: The mental health needs of young children in natural disaster contexts often remain unaddressed. The lack of a rapid and simple tool for screening combined with few mental health professionals available to accurately diagnose and provide appropriate care mean that young children remain without care. Here, we present the results of psychological screening of young children aged 3 to 6 using the questionnaire PSYCa 3-6. METHODS: This study was conducted in Port-au-Prince, Haiti. The scale was translated into Haitian Creole using corroboration of independent translations and submitted twice to the parents at home, at the end of 2011 and again at the beginning of 2013. At the first stage 166 children 3 to 6 years old were included 49 of whom were included at the second stage. The results and diagnostic properties were assessed comparing the PSYCa 3-6 to the Clinical Global Impression Severity Scale as the gold standard. RESULTS: Boys were more prone to psychological disturbances than girls. The size and position among the siblings increased the score of psychological disturbance. The neighborhood and the perception of environmental violence had a significant impact on the score of psychological disturbance. The significant improvement in scores between the two examinations showed moderate resiliency whose main factors seemed to be the social support received by the family, the rapid return to school, faith and religious practice.

Moxisylyte: a review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in impotence.

Moxisylyte is a competitive noradrenaline antagonist, acting preferentially on post-synaptic alpha-1 adrenoceptors. It was introduced more than thirty years ago for the treatment of cerebro-vascular disorders and shown more recently effective in the urological field due to its ability to modulate the urethral pressure. Renewal of interest in this drug has been observed in recent years since the demonstration of the possibilities of vasoactive drugs in evaluation and treatment of erectile dysfunctions. Moxisylyte is a prodrug, rapidly transformed into an active metabolite in plasma (Deacetylmoxisylyte or DAM). Elimination of the active metabolite occurs by N-demethylation, sulpho- and glucuroconjugation. The N-demethylated metabolite is sulphoconjugated only. Urine is the main route of excretion. The metabolites of moxisylyte can be determined in biological fluids by various methods using high-performance liquid chromatography. Their pharmacokinetics is dependent on the route of administration. By the oral route, the concentrations of the active metabolite are low, and the glucuroconide of DAM predominates over the sulphates. After intravenous and intracavernous injection, the active metabolite is proportionally higher, the two sulphates are equivalent and in larger amounts than the glucuronide. In the treatment of impotence, intracavernous injection of moxisylyte at 10, 20 or 30 mg can induce an erection adequate for intercourse in most of the patients. Compared to inducing agents such as papaverine and prostaglandin E1, moxisylyte must be considered as a facilitator of male erection, its interest lying in the low rate of adverse effects, either general or local.

Pharmacokinetics of a prodrug thymoxamine: dose-dependence of the metabolite ratio in healthy subjects.

Thymoxamine, a prodrug, is rapidly deacetylated in the plasma to give two phase I metabolites, DMAT and DAT, which are further sulpho- and glucuro-conjugated and then excreted mainly in the urine. In a cross-over study, the dose-dependence of the metabolite ratio was evaluated in nine healthy volunteers after three doses (120, 240, 480 mg) of thymoxamine-HCl. Regardless of the dose, DMAT and its glucuronide were not detected, while the amount of DMAT-sulphate was found to be proportional to the dose administered. Plasma levels of DAT were measurable in only four of the nine subjects after the 480 mg dose and showed great intersubject variability. The pharmacokinetics of both DAT-sulphate and DAT-glucuronide were dose-dependent. As the dose increased, the proportion of DAT undergoing sulphatation decreased; this saturation was compensated by glucuronidation.

[Effects of an extract of the bark of Pygeum africanum (V.1326) on prostatic secretions in the rat and in man]. / Effets d'un extrait d'écorce de Pygeum africanum (V.1326) sur les sécrétions prostatiques du rat et de l'homme.

Treatment with V.1326 in the rat induces an increase in prostatic secretion. In men with insufficient prostatic secretion, this treatment also induces an increased secretion.

Reasons for defaulting from drug-resistant tuberculosis treatment in Armenia: a quantitative and qualitative study.

SETTING: Armenia, a country with a high prevalence of drug-resistant tuberculosis (DR-TB). OBJECTIVE: To identify factors related to default from DR-TB treatment in Yerevan. DESIGN: Using a retrospective cohort design, we compared defaulters with patients who were cured, completed or failed treatment. Patients who initiated DR-TB treatment from 2005 to 2011 were included in the study. A qualitative survey was conducted including semi-structured interviews with defaulters and focus group discussions with care providers. RESULTS: Of 381 patients, 193 had achieved treatment success, 24 had died, 51 had failed treatment and 97 had defaulted. The number of drugs to which the patient was resistant at admission (aRR 1.16, 95%CI 1.05-1.27), the rate of treatment interruption based on patient's decision (aRR 1.03, 95%CI 1.02-1.05), the rate of side effects (aRR 1.18, 95%CI 1.09-1.27), and absence of culture conversion during the intensive phase (aRR 0.47, 95%CI 0.31-0.71) were independently associated with default from treatment. In the qualitative study, poor treatment tolerance, a perception that treatment was inefficient, lack of information, incorrect perception of being cured, working factors and behavioural problems were factors related to treatment default. CONCLUSION: In addition to economic reasons, poor tolerance of and poor response to treatment were the main factors associated with treatment default.

Isolation and pharmacological characterization of AdTx1, a natural peptide displaying specific insurmountable antagonism of the alpha1A-adrenoceptor.

BACKGROUND AND PURPOSE: Venoms are a rich source of ligands for ion channels, but very little is known about their capacity to modulate G-protein coupled receptor (GPCR) activity. We developed a strategy to identify novel toxins targeting GPCRs. EXPERIMENTAL APPROACH: We studied the interactions of mamba venom fractions with alpha(1)-adrenoceptors in binding experiments with (3)H-prazosin. The active peptide (AdTx1) was sequenced by Edman degradation and mass spectrometry fragmentation. Its synthetic homologue was pharmacologically characterized by binding experiments using cloned receptors and by functional experiments on rabbit isolated prostatic smooth muscle. KEY RESULTS: AdTx1, a 65 amino-acid peptide stabilized by four disulphide bridges, belongs to the three-finger-fold peptide family. It has subnanomolar affinity (K(i)= 0.35 nM) and high specificity for the human alpha(1A)-adrenoceptor subtype. We showed high selectivity and affinity (K(d)= 0.6 nM) of radio-labelled AdTx1 in direct binding experiments and revealed a slow association constant (k(on)= 6 x 10(6).M(-1).min(-1)) with an unusually stable alpha(1A)-adrenoceptor/AdTx1 complex (t(1/2diss)= 3.6 h). AdTx1 displayed potent insurmountable antagonism of phenylephrine's actions in vitro (rabbit isolated prostatic muscle) at concentrations of 10 to 100 nM. CONCLUSIONS AND IMPLICATIONS: AdTx1 is the most specific and selective peptide inhibitor for the alpha(1A)-adrenoceptor identified to date. It displays insurmountable antagonism, acting as a potent relaxant of smooth muscle. Its peptidic nature can be exploited to develop new tools, as a radio-labelled-AdTx1 or a fluoro-labelled-AdTx1. Identification of AdTx1 thus offers new perspectives for developing new drugs for treating benign prostatic hyperplasia.

High-performance liquid chromatographic determination of the conjugate metabolites of moxisylyte in human plasma and urine.

Sensitive and specific high-performance liquid chromatographic methods with fluorescence detection are described for the determination of the metabolites of moxisylyte (4-(2-dimethylaminoethoxy)-5-isopropyl-2-methylphenyl acetate) in human plasma and urine. Deacetylmoxisylyte glucuroconjugate (DAM-G) was hydrolysed enzymatically using 1-glucuronidase and quantified as the difference between the DAM concentrations determined after and before hydrolysis. The two sulphate derivatives (deacetylmoxisylyte sulphoconjugate, DAM-S and monomethyldeacetylmoxisylyte sulphoconjugate, MDAM-S), were analysed without prior hydrolysis. Their extraction from plasma and urine, as well as that of DAM from plasma, involved the use of C18 cartridges adapted on a Benchmate workstation. DAM in urine was quantified after liquid-liquid extraction. The two methods were validated for specificity, linearity, intra- and inter-day precision and accuracy. Precision was generally < or = 15% and accuracy < or = 12%. In plasma, the limits of quantification were 2.5 ng/ml for DAM and 2.8 ng/ml for the two sulphates, in urine, they were 40 ng/ml for DAM and 200 ng/ml for the sulphates. These methods were used for pharmacokinetic studies in healthy subjects.

Pharmacokinetics of moxisylyte in healthy volunteers after intracavernous injection of increasing doses.

OBJECTIVE: The concentration-time profiles of specific metabolites of moxisylyte, an alpha-adrenoceptor blocking agent, in the plasma and urine from 18 healthy volunteers were investigated after intracavernous (IC) administrations at three dose levels (10, 20 and 30 mg). RESULTS: Four metabolites, unconjugated desacetyl-moxisylyte (DAM), DAM glucuronide, and DAM and monodesmethylated DAM (MDAM) sulphates were found in plasma and urine. For all metabolites, t1/2 elimination was independent of the administered dose (1.19 h for unconjugated DAM; 1.51 h for DAM glucuronide; 1.51 h for DAM sulphate; and 2.17 h for MDAM sulphate). Cmax and AUC increased in direct proportion to dose, except for the inactive DAM glucuronide. Any the differences detected were small and equivalence of the three doses can be accepted. CONCLUSION: The pharmacokinetics of moxisylyte in humans following intracavernous administration were linear in the dose range 10 to 30 mg.

Pharmacokinetics of moxisylyte in healthy volunteers after intravenous infusion and intracavernous administration with and without a penile tourniquet.

The concentration-time profiles of metabolites of moxisylyte (or thymoxamine), an alpha-blocking agent, were investigated in 18 healthy volunteers after intravenous (i.v.) and intracavernous (i.c.) administrations with and without a tourniquet. Four metabolites, unconjugated desacetylmoxisylyte (DAM), DAM glucuronide, and DAM and monodesmethylated DAM (MDAM) sulfates, were found in plasma and urine. For all metabolites, tmax was significantly increased after i.c. administrations and Cmax was significantly decreased. Maximum plasma level of unconjugated DAM was lower after i.c. administration with (1.81-fold) and without (1.26-fold) a tourniquet than after i.v. administration (43.6 +/- 19.6 ng/ml). The elimination half-life of each metabolite showed no change between the three treatments. The difference of 19 min between the mean residence times of unconjugated DAM after i.c. administration with and without a tourniquet may be compared with the difference between the mean duration of the intumescence, that is, 19 min (73 and 54 min with and without a tourniquet, respectively). Total percentages of metabolites recovered in urine were 66.2 +/- 20.9, 61.4 +/- 12.2, and 58.7 +/- 9.1% after i.v. and i.c. administrations with and without a tourniquet, respectively. In conclusion, tourniquet placed before i.c. administration increased the mean residence time of unconjugated DAM of approximately 25% and seemed to increase the efficacy of the drug in healthy volunteers.