Early effects of estrogen on the rat ventral prostate

Complex interactions between androgen and estrogen (E2) regulate prostatic development and physiology. We analyzed the early effects of a high single dose of E2 (25 mg/kg body weight) and castration (separately or combined) on the adult 90-day-old male Wistar rat ventral prostate. Androgen levels, prostate weight, and the variation in the relative and absolute volume of tissue compartments and apoptotic indices were determined for 7 days. Castration and exogenous E2 markedly reduced ventral prostate weight (about 50% of the control), with a significant reduction in the epithelial compartment and increased stroma. The final volume of the epithelium was identical at day 7 for all treatments (58.5% of the control). However, E2 had an immediate effect, causing a reduction in epithelial volume as early as day 1. An increase in smooth muscle cell volume resulted from the concentration of these cells around the regressing epithelium. The treatments resulted in differential kinetics in epithelial cell apoptosis. Castration led to a peak in apoptosis at day 3, with 5% of the epithelial cells presenting signs of apoptosis, whereas E2 caused an immediate increase (observed on day 1) and a sustained (up to day 7) effect. E2 administration to castrated rats significantly increased the level of apoptosis by day 3, reaching 9% of the epithelial cells. The divergent kinetics between treatments resulted in the same levels of epithelial regression after 7 days (~30% of control). These results show that E2 has an immediate and possibly direct effect on the prostate, and anticipates epithelial cell death before reducing testosterone to levels as low as those of castrated rats. In addition, E2 and androgen deprivation apparently cause epithelial cell death by distinct and independent pathways.48749

Early Effects Of Estrogen On The Rat Ventral Prostate.

Complex interactions between androgen and estrogen (E2) regulate prostatic development and physiology. We analyzed the early effects of a high single dose of E2 (25 mg/kg body weight) and castration (separately or combined) on the adult 90-day-old male Wistar rat ventral prostate. Androgen levels, prostate weight, and the variation in the relative and absolute volume of tissue compartments and apoptotic indices were determined for 7 days. Castration and exogenous E2 markedly reduced ventral prostate weight (about 50% of the control), with a significant reduction in the epithelial compartment and increased stroma. The final volume of the epithelium was identical at day 7 for all treatments (58.5% of the control). However, E2 had an immediate effect, causing a reduction in epithelial volume as early as day 1. An increase in smooth muscle cell volume resulted from the concentration of these cells around the regressing epithelium. The treatments resulted in differential kinetics in epithelial cell apoptosis. Castration led to a peak in apoptosis at day 3, with 5% of the epithelial cells presenting signs of apoptosis, whereas E2 caused an immediate increase (observed on day 1) and a sustained (up to day 7) effect. E2 administration to castrated rats significantly increased the level of apoptosis by day 3, reaching 9% of the epithelial cells. The divergent kinetics between treatments resulted in the same levels of epithelial regression after 7 days (approximately 30% of control). These results show that E2 has an immediate and possibly direct effect on the prostate, and anticipates epithelial cell death before reducing testosterone to levels as low as those of castrated rats. In addition, E2 and androgen deprivation apparently cause epithelial cell death by distinct and independent pathways.38487-9

Referencias anatómicas para la tenolisis percutánea de los flexores de la mano

Producción CientíficaResumen: Objetivos: La tenosinovitis estenosante de los flexores de la mano es una patología muy frecuente en el ámbito laboral. Se han descrito distintos tratamientos de tipo conservador, aunque el tratamiento definitivo de los casos que no responden a otros tratamientos es quirúrgico, siendo la técnica abierta y la liberación percutánea las dos técnicas de elección. Esta última ha obtenido resultados superiores de satisfacción aunque la ausencia de visualización incrementa las lesiones neurovasculares y el riesgo de apertura incompleta de la polea, por ello es necesario establecer puntos de referencia anatómicos para realizar una correcta liberación. Material y método: Se realizó un estudio experimental en cinco manos de cadáver en el Departamento de Anatomía de la Universidad de Valladolid. Se realizaron mediciones de las longitudes de los dedos y de la polea. Se registró la posición de la aguja y de cada uno de los dedos al realizar la polectomía percutánea y se comprobó si la sección de la polea A1 fue completa, si existió alguna laceración de los tendones o si se produjo una lesión iatrógena del paquete neurovascular o de la polea A2. Resultados: Para establecer el punto de entrada de la aguja intramuscular se tomó como referencia la intersección entre el eje del dedo y el surco dígito-palmar. En el caso del tercer y cuarto dedo la entrada fue en el punto de la intersección, mientras que en el resto se desplazó 1-1,5 mm en dirección medial. El ángulo de entrada de la aguja intramuscular en el plano anterior osciló entre 0-30 grados en función del dígito, mientras que en el plano lateral fue siempre 0 excepto en el cuarto dedo que corresponde a un valor de -60 grados respecto al eje palmar. No se observó ninguna lesión iatrógena de los tendones flexores, del paquete neurovascular o de la polea A2. La apertura fue completa en todos los dedos salvo en un caso del segundo dedo. Conclusión: La tenolisis percutánea de la polea A1 es una alternativa a la liberación abierta tradicional, aunque existe controversia debido a la relación riesgo-beneficio. El conocimiento de las referencias anatómicas así como la posición exacta del dígito y de los instrumentos utilizados ayudan a evitar la liberación incompleta de la polea, los problemas neurovasculares y la lesión de estructuras adyacente. En el presente estudio anatómico se ha comprobado que es una técnica segura ya que no ha ocurrido ninguna lesión iatrógena y fiable, que se ha conseguido una liberación completa en todos los casos salvo uno

A simple dilute-and-shoot approach for the determination of ultra-trace levels of arsenic in biological fluids via ICP-MS using CH3F/He as a reaction gas

The performance of a mixture of CH3F/He (1/9) as a reaction gas for the determination of As in biological fluids using a quadrupole ICP-MS instrument has been explored. A simple (dilute-and-shoot) interference-free method has been developed to quantify As concentrations at trace and ultra-trace levels in matrices with a high Cl content. As+ reacts with CH3F (through CH3F addition, followed by HF elimination) with high efficiency forming AsCH2 + as the primary reaction product, which can be monitored at a mass-to-charge ratio of 89, free from the Cl-based interferents (e.g., 40Ar35Cl+ and 40Ca35Cl+) that hamper the monitoring of 75As+. Matrix effects are overcome by the use of Te as an internal standard and the addition of 3% v/v ethanol to all samples and calibration standard solutions. The method presented was validated by analysing a set of reference materials (blood, serum and urine) and by assessing As recovery from a set of real blood samples. With this method, the limit of detection was calculated to be 0.8 ng L-1 As, favourably comparable to the vast majority of values reported in the literature, even with those obtained using more sophisticated sector-field instrumentation

Aplicación clínica de la técnica percutánea en la tenosinovitis estenosante de los flexores de la mano

Producción CientíficaLa tenosinovitis estenosante de los flexores de la mano es una patología que conduce al bloqueo de la polea de flexión proximal del dedo. Aunque el tratamiento inicial es conservador, si éste no es efectivo, está indicado el tratamiento quirúrgico mediante liberación abierta o percutánea. Material y método: Estudio descriptivo retrospectivo de 116 pacientes intervenidos de dedo en resorte en el HCUV (enero 2005- diciembre 2007), seguimiento medio 36 meses. Análisis de datos con el 91% de los pacientes (105 pacientes) con un total de 182 dedos afectos realizando comparación de ambas técnicas. Resultados: Edad media varones 53.70 años y la de las mujeres 53.95. El 34% de las manos intervenidas no presentan otras patologías asociadas. Primer dedo más afectado, seguido del tercero y cuarto. Se realizó técnica percutánea en el 42% de los pacientes, abierta en el 53% y ambas en el 5% del total. Destacan los problemas con la cicatriz en la tenolisis abierta. Técnica percutánea permite reincorporación a la vida laboral 8 días antes. Discusión: La liberación percutánea de la polea A1 es una alternativa a la liberación abierta por su bajo coste y por permitir una rápida reincorporación del paciente a su vida laboral. Gracias a estudios experimentales en cadáver, se obtienen referencias topográficas que aportan mayor seguridad, permitiendo ampliar el uso de esta técnica que ha demostrado grandes ventajas en el ámbito socio-económico y labora

Los fosfopétidos de caseína aumentan drásticamente la secreción de proteínas extracelulares en Aspergillus awamori.Estudios de Proteómica revelan cambios en la vía secretora

Comunicaciones a congreso

Genetic and functional analysis of biogenic amine production capacity among starter and non-starter lactic acid bacteria isolated from artisanal cheeses

© 2015, Springer-Verlag Berlin Heidelberg. This work reports the capacity of 137 strains of starter and non-starter LAB belonging to nine species of the genera Lactobacillus, Lactococcus, Streptococcus and Leuconostoc (all isolated from artisanal cheeses) to produce histamine, tyramine, putrescine and β-phenylethylamine, the biogenic amines (BA) most commonly found in dairy products. Production assays were performed in liquid media supplemented with the appropriate precursor amino acid; culture supernatants were then tested for BA by (U)HPLC. In addition, the presence of key genes involved in the biosynthetic pathways of the target BA, including the production of putrescine via the agmatine deiminase pathway, was assessed by PCR. Twenty strains were shown to have genes involved in the synthesis of BA; these belonged to the species Lactobacillus brevis (4), Lactobacillus curvatus (3), Lactococcus lactis (11) and Streptococcus thermophilus (2). With the exception of the two S. thermophilus strains, all those possessing genes involved in BA production synthesized the corresponding compound. Remarkably, all the putrescine-producing strains used the agmatine deiminase pathway. Four L. brevis and two L. curvatus strains were found able to produce both tyramine and putrescine. There is increasing interest in the use of autochthonous LAB strains in starter and adjunct cultures for producing dairy products with ‘particular geographic indication’ status. Such strains should not produce BA; the present results show that BA production capacity should be checked by (U)HPLC and PCR.This work was funded by the Ministry of Economy and Competitiveness, Spain (AGL2013-45431-R), the Fundación para el Fomento en Asturias de la Investigación Científica Aplicada y la Tecnología (FICYT), cofunded by FEDER (GRUPIN14-137) and the INIA (RM2011-00005-00-00).Peer Reviewe

The Role of SeDeM Characterizing the Active Substance and Polyvynilpyrrolidone Eliminating Metastable Forms in an Oral Lyophilizate - A Preformulation Study.

A preformulation study of an oral lyophilisate with cetirizine dihydrochloride (CTZ) as active ingredient, mannitol and PVP K30 as bulking agents is presented. CTZ shown a humidity content of 0.150% and a spontaneous hygroscopicity of 0.200% (both determined by SeDeM diagram), demonstrating an adequate stability behavior in solid form. A design of experiments (DoE) performed with both mannitol and PVP K30, followed by a simple factorial design (32) has determined the optimum combination of excipients and CTZ, and showed that a higher proportion of PVP K30 was able to prevent metastable forms generated by mannitol

Determination of stress-induced degradation products of cetirizine dihydrochloride by a stability-indicating RP-HPLC method

A new, simple and accurate stability-indicating reverse phase high performance liquid chromatography method was developed and validated during the early stage of drug development of an oral lyophilizate dosage form of cetirizine dihydrochloride. For RP-HPLC analysis it was used an Eclipse XDB C8 column 150 mm × 4.6 mm, 5 μm (Agilent columns, Barcelona, Spain) as the stationary phase with a mobile phase consisted of a mixture of 0.2 M K2HPO4 pH 7.00 and acetonitrile (65:35, v/v) at a flow rate of 1 mL min −1. Detection was performed at 230 nm using diode array detector. The method was validated in accordance with ICH guidelines with respect to linearity, accuracy, precision, specificity, limit of detection and quantification. The method results in excellent separation between the drug substance and its stress-induced degradation products. The peak purity factor is >950 for the drug substance after all types of stress, which confirms the complete separation of the drug substance peak from its stress induced degradation products. Regression analysis showed r2 > 0.999 for cetirizine dihydrochloride in the concentration range of 650 μg mL −1 to 350 μg mL−1 for drug substance assay and a r2 > 0.999 in the concentration range of 0.25 μg mL−1 to 5 μg mL−1 for degradation products. The method presents a limit of detection of 0.056 μg mL −1 and a limit of quantification of 0.25 μg mL−1. The obtained results for precision and accuracy for drug substance and degradation products are within the specifications established for the validation of the method. The proposed stability-indicating method developed in the early phase of drug development proved to be a simple, sensitive, accurate, precise, reproducible and therefore useful for the following stages of the cetirizine dihydrochloride oral lyophilizate dosage form development