The little we know about the pharmacokinetics and pharmacodynamics of praziquantel (racemate and R-enantiomer).

Praziquantel has been the mainstay of schistosomiasis control since 1984 and widely distributed since 2006 through 'preventive chemotherapy' programmes to school-aged children or at-risk populations. In addition, preschool-aged children are now recognized as a vulnerable population and a group for targeted treatment, but they may be difficult to dose correctly with the available product--a racemate, based on the biologically active enantiomer (R-praziquantel) and the inactive distomer (S-praziquantel), which contributes the bitter taste and doubles the size of the tablets. Hence, a paediatric formulation is required, possibly enantiomerically pure. Developing such a product and extending its use to younger children should be pharmacologically guided, but limited data exist on pharmacokinetics and pharmacokinetic/pharmacodynamic correlations for praziquantel. This article presents available data on the chemistry, pharmacokinetics and pharmacodynamics of praziquantel, as well as R-praziquantel, and points to gaps in our knowledge.

Corte epidemiológico del consumo de drogas de personas atendidas en emergencias de hospitales del Estado Carabobo - Venezuela / Epidemiological profile of drug consumption in persons treated at emergency rooms in hospitals in the state of Carabobo, Venezuela

Estudio con diseño no experimental y transversal tiene como finalidad relacionar los ingresos por accidentes, hechos violentos e intoxicaciones con el consumo de drogas en las salas de emergencia de los hospitales públicos establecidos en el estado Carabobo. Muestra: 1595 pacientes entre 14 y 65 años de edad que ingresaron a los hospitales seleccionados. Resultados:Perfil sociodemográfico con predominio del sexo masculino, menores de 30 años, con mayor consumo de alcohol, marihuana y cocaína, sin Pareja, con asociación significativa entre marihuana y situación de pareja con p=0,000. Mayor consumo de drogas en fines de semana. Asociación entre Motivo de ingreso y consumo de drogas: alcohol, cocaína y marihuana, con valores de p=0,000 para las tres drogas mencionadas. Además, 5,4% ha recibido tratamiento para el consumo de drogas. Estos resultados muestran elementos que permitirán profundizar sobre el impacto del consumo de drogas en la población con mayor cantidad de incidentes violentos

Cross sectional non-experimental study aiming at relating drug abuse to admissions to emergency rooms in public hospitals situated in the state of Carabobo due to accidents, violence and drug poisoning. Sample: 1595 patients between 14 and 65 years old who were admitted to the selected hospitals. Results: socio-demographic profile predominantly male, under 30 years old, with increased use of alcohol, marijuana and cocaine, single without partner, with significant association between marijuana and marital status with p=0.000. Increased drug use at weekends. Association between reason of admission and drug consumption: alcohol, cocaine and marijuana, with values of p=0.000 for the three drugs mentioned. In addition, 5.4% have received treatment for drug abuse. These results show elements that will allow a deeper study of the impact of drug abuse in the population with the highest number of violent incidents

Corte epidemiológico del consumo de drogas de personas atendidas en emergencias de hospitales del Estado Carabobo - Venezuela / Epidemiological profile of drug consumption in persons treated at emergency rooms in hospitals in the state of Carabobo, Venezuela

Estudio con diseño no experimental y transversal tiene como finalidad relacionar los ingresos por accidentes, hechos violentos e intoxicaciones con el consumo de drogas en las salas de emergencia de los hospitales públicos establecidos en el estado Carabobo. Muestra: 1595 pacientes entre 14 y 65 años de edad que ingresaron a los hospitales seleccionados. Resultados:Perfil sociodemográfico con predominio del sexo masculino, menores de 30 años, con mayor consumo de alcohol, marihuana y cocaína, sin Pareja, con asociación significativa entre marihuana y situación de pareja con p=0,000. Mayor consumo de drogas en fines de semana. Asociación entre Motivo de ingreso y consumo de drogas: alcohol, cocaína y marihuana, con valores de p=0,000 para las tres drogas mencionadas. Además, 5,4% ha recibido tratamiento para el consumo de drogas. Estos resultados muestran elementos que permitirán profundizar sobre el impacto del consumo de drogas en la población con mayor cantidad de incidentes violentos(AU)

Cross sectional non-experimental study aiming at relating drug abuse to admissions to emergency rooms in public hospitals situated in the state of Carabobo due to accidents, violence and drug poisoning. Sample: 1595 patients between 14 and 65 years old who were admitted to the selected hospitals. Results: socio-demographic profile predominantly male, under 30 years old, with increased use of alcohol, marijuana and cocaine, single without partner, with significant association between marijuana and marital status with p=0.000. Increased drug use at weekends. Association between reason of admission and drug consumption: alcohol, cocaine and marijuana, with values of p=0.000 for the three drugs mentioned. In addition, 5.4% have received treatment for drug abuse. These results show elements that will allow a deeper study of the impact of drug abuse in the population with the highest number of violent incidents(AU)

Pubertal impairment in Nhlh2 null mice is associated with hypothalamic and pituitary deficiencies.

Pubertal development is impaired in mice lacking the basic helix-loop-helix transcription factor Nhlh2. The mechanisms underlying changes in reproduction in Nhlh2-deficient mice (Nhlh2(-/-)) are unclear. Here we show that hypothalamic GnRH-1 content is reduced in adult Nhlh2(-/-) mice as is the number of GnRH-1 neurons localized to mid- and caudal hypothalamic regions. This reduction was detected postnatally after normal migration of GnRH-1 neurons within nasal regions had occurred. Phenotype rescue experiments showed that female Nhlh2(-/-) mice were responsive to estrogen treatment. In contrast, puberty could not be primed in female Nhlh2(-/-) mice with a GnRH-1 regimen. The adenohypophysis of Nhlh2(-/-) mice was hypoplastic although it contained a full complement of the five anterior pituitary cell types. GnRH-1 receptors (GnRHRs) were reduced in Nhlh2(-/-) pituitary gonadotropes as compared with wild type. In vitro assays indicated that Nhlh2 expression is regulated in parallel with GnRHR expression. However, direct transcriptional activity of Nhlh2 on the GnRHR promoter was not found. These results indicate that Nhlh2 plays a role in the development and functional maintenance of the hypothalamic-pituitary-gonadal axis at least at two levels: 1) in the hypothalamus by regulating the number and distribution of GnRH-1 neurons and, 2) in the developing and mature adenohypophysis.

Análisis del gen HOX11 en un paciente con asplenia / Analysis of HOX11 gene in a patient with asplenia

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Predisposition to arrhythmia and autonomic dysfunction in Nhlh1-deficient mice.

Nhlh1 is a basic helix-loop-helix transcription factor whose expression is restricted to the nervous system and which may play a role in neuronal differentiation. To directly study Nhlh1 function, we generated null mice. Homozygous mutant mice were predisposed to premature, adult-onset, unexpected death. Electrocardiograms revealed decreased total heart rate variability, stress-induced arrhythmia, and impaired baroreceptor sensitivity. This predisposition to arrhythmia is a likely cause of the observed death in the mutant mice. Heterozygosity for the closely related transcription factor Nhlh2 increased the severity of the Nhlh1-null phenotype. No signs of primary cardiac structural or conduction abnormalities could be detected upon necropsy of the null mice. The pattern of altered heart rhythm observed in basal and experimental conditions (stress and pharmacologically induced) suggests that a deficient parasympathetic tone may contribute to the arrhythmia in the Nhlh1-null mouse. The expression of Nhlh1 in the developing brain stem and in the vagal nuclei in the wild-type mouse further supports this hypothesis. The Nhlh1 mutant mouse may thus provide a model to investigate the contribution of the autonomic nervous system to arrhythmogenesis.