Comparative bioavailability between two Tramadol once-daily oral formulations.

The aim of this study was to compare the pharmacokinetic profile and oral bioavailability of Tramadol Contramid once-daily (o.d.) 200 mg tablets (Labopharm, Canada) with that of Zytram 200 mg tablets (Zambon, Spain), following single-dose administration in 26 healthy volunteers. The study had an open, randomized, crossover design with a 7-day wash-out. Data from 24 subjects were used for the pharmacokinetic (PK) analysis. Racemic tramadol and racemic O-demethyltramadol (M1) were assayed in plasma using a liquid chromatography/tandem mass spectrometry method. Primary PK parameters estimated were AUC(0-t), AUC(0-infinity), C(max), C(24 h), and T(max). Results were compared using an ANOVA, and the residual variability thereby obtained was used to construct the classical 90% confidence intervals. The parametric Schuirmann's test was also performed. T(max) was analyzed by a nonparametric approach. For both racemic tramadol and racemic O-demethyltramadol, the ANOVA showed a statistically significant formulation effect. Significantly higher values were obtained for Tramadol Contramid o.d. for all PK parameters, except for T(1/2). For Tramadol Contramid o.d., mean tramadol plasma levels were maintained at a plateau level above 200 ng/ml from 4 to 16 h after dose, while for the reference formulation, that level was sustained from 4 to only 6 h. Consistent results for both formulations were obtained for the metabolite. At the end of the dosing interval, plasma tramadol and O-demethyltramadol concentrations were 39% and 49% higher, respectively, for Tramadol Contramid o.d. than those for Zytram (p < 0.0001). Tramadol Contramid o.d. could be considered suprabioavailable to Zytram o.d.

Aplicación del método de hanlon en la priorización de riesgos y daños para la salud / Application of the hanlon method while priorizing health risks and damages

En la Jurisdicción Sanitaria Ecatepec, se realizó un taller de Riesgos y Daños para la salud con el propósito de priorizar el daño a la salud susceptible a ser intervenido a través de la aplicación del método de Hanlón, por los estudiantes de posgrado de Enfermería en salud pública y el equipo multidisciplinario de la jurisdicción. Participaron 48 personas con cargos normativos y operativos de los Centros Municipales de Salud (COMUSA), DIF, CONALEP, y Salud Municipal a quienes se les capacitó sobre la utilidad y aplicación del Método de Hanlón, proporcionándoles la información estadística para hacer los cálculos respectivos. Los resultados de la priorización de mayor a menor puntuación fueron: Diabetes Mellitus tipo 2, Neumonía e Influenza, Enfermedades del corazón, Tumores malignos, Accidentes, agresiones y suicidios, Enfermedades del hígado, SIDA, e insuficiencia renal. Tomando en cuenta que en las primeras cuatro causas ya han sido trabajadas por generaciones previas de estudiantes de la Especialidad, se determinó que la causa a ser intervenida es: accidente, agresiones y suicidios.

In the Health Jurisdiction Ecatepec, a risk and darrage workshop health was carried out which used the Hanlon method in order to prioritize the possible damage and give the attention through the multidisciplinary staff and the Public Health Nursing speciality students. The number of participants in the workshop were 48 from health Municipality Centers, DIF, CONALEP, whom were trained about the features and how to use Hanlon method. The statistical information was given to do the respective calculation. The results of prioritize were ordered from the highest to the lowest score: diabetes mellitus type 2, Pneumania and influenza, heart illness, malign tumors, accidents, agrressions and suicides, liver sickeness, AIDS, renal insufficiency. Because the first 4 causes had been studied before, it was determined that the causes to be intervened will be accidents, agrressions and suicides.

Proteínas Hedgehog: expresión y función en el timo / Hedgehog proteins: expression and function in the thymus

Evidencias crecientes demuestran que los morfógenos clásicos, altamente conservados durante la evolución y tradicionalmente implicados en el desarrollo embrionario, donde determinan diferenciación celular y patrones de desarrollo, son expresados en tejidos adultos, como son la médula ósea y el sistema inmunitario. Estas moléculas podrían ser piezas importantes del rompecabezas que orquesta la diferenciación y la homeostasis del sistema inmune, aunque sea sólo recientemente cuando estamos comenzando a entender donde encajan en el entramado del sistema inmune. En esta revisión, describimos la ruta de señalización de las proteínas Hedgehog (Hh) centrándonos en su implicación en la diferenciación de las células T y su posible conexión con otros morfógenos, como son las proteínas morfogénicas del hueso (Bone Morphogenetic Proteins, BMPs) (AU)

Acute effects of 3,4-methylenedioxymethamphetamine alone and in combination with ethanol on the immune system in humans.

Cell-mediated immune response and release of cytokines after the administration of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") alone and in combination with ethanol were assessed in a double blind, randomized, crossover, controlled clinical trial. Six healthy male recreational users of MDMA participated in four different experimental sessions, with a washout interval between sessions of 1 week, in which single oral doses of MDMA (100 mg), ethanol (0.8 g/kg), the combination of both drugs, and placebo were tested. Acute MDMA administration produced a time-dependent immune dysfunction in association with serum concentrations of the drug as well as cortisol stimulation kinetics. Although total leukocyte count remained unchanged, there was a decrease in the CD4 T/CD8 T-cell ratio due to a decrease in both the percentage and absolute number of CD4 T-helper cells and simultaneous increase in natural killer (NK) cells. Ethanol consumption produced a decrease in T-helper cells and B lymphocytes. The combination of MDMA and ethanol caused the highest suppressive effect on CD4 T cells and increasing effect in NK cells. Drugs treatment produced a high increase of immunosuppressive cytokines (transforming growth factor-beta and interleukin-10) and a switch from Th1-type cytokines (interleukin-2 and interferon-gamma) to Th2-type cytokines (interleukin-4 and interleukin-10). Disregulation in the production of pro- and anti-inflammatory cytokines with an unbalance toward anti-inflammatory response was also observed. The immune function shows a trend toward baseline levels at 24 h after MDMA kinetics. This transient defect in immunological homeostasis, if temporarily repeated, might alter the immune response with a risk for the general health status.

[Immunomodulator properties of ecstasy (MDMA)]. / Proprietà immunomodulanti dell'ecstasy (MDMA).

In vitro exposure to ecstasy (3,4-methylenedioxymethamphetamine, MDMA) alters some immune parameters such as T-cell regulatory function, cytotoxic T-lymphocyte activity, natural killer cell activity and macrophage function. Administration of MDMA in rats produces a suppression of lympho-proliferation response and a decrease in circulating lymphocytes, accompanied by an increase in plasma corticosterone. It was postulated a direct action of MDMA on lymphocytes or rather an indirect action mediated by the hypothalamic pituitary adrenal axis (HPA-AXIS) and/or the sympathetic nervous system (SNS). Acute MDMA treatment effected on healthy-volunteers produces an immune dysfunction associated with pharmaceutical characteristics and so with MDMA plasma concentrations. There is a decrease in CD4+ T-cells and functional responsiveness of lymphocytes, while percentage of natural killer cells increases. A contemporary rise of cortisol plasma concentrations supports the hypothesis of MDMA-induced release of corticotrophin-releasing factor from the hypothalamus and subsequent HPA-axis and SNS activation.

[Ultrastructural morphometric study of the prostate of the rat after microsurgical denervation]. / Estudio morfométrico ultraestructural de la próstata de la rata tras la denervación microquirúrgica.

OBJECTIVE: To analyze the effects of rat prostate denervation on the ultrastructure of this gland. MATERIAL AND METHODS: Eighty Sprague-Dawley rats (300-350 g. weight) were studied. Forty-two were anesthetized and right major pelvic ganglion (MPG) excised. After 28-30 days, same size prostatic ventral lobe (VL) was obtained for transmission electron microscopy (TEM) study and computerized image analysis. These results were compared with those from 38 right VLs of same aged, non-operated rats. RESULTS: A significant decrease of supranuclear and cell heights was observed as well as of the area of epithelial cells after denervation (change in cell polarity). A reduction of Golgi apparatus and endoplasmic reticulum areas, and of secretory granules and apical microvilli count (p < 0.001) was also demonstrated in the denervated rats. These findings are consistent with a change of these cells towards a less active phenotype. Stromal smooth muscle cells, on the other hand, showed only an increase of cytoplasmic ribosomal aggregates area. CONCLUSIONS: The present study showed an epithelial atrophy of rat prostate after denervation. Ultrastructural findings also suggest an overall decrease of epithelial cell's secretory activity. Nevertheless, the increase of ribosomal area in stromal smooth muscle cells could reflect their activation after denervation.