Testosterone modulates the expression of molecules linked to insulin action and glucose uptake in endometrial cells.

Polycystic ovary syndrome (PCOS) is a common hyperandrogenic disorder associated with insulin resistance. Insulin exerts its metabolic function by activating the PI3K/Akt pathway and favoring glucose uptake. Caveolin-1 is a scaffolding protein which increases insulin receptor (IR) stability. Alternatively, activation of IR increases caveolin-1 phosphorylation on tyrosine-14. Furthermore, endometrial tissue from PCOS patients is proposed to be insulin resistant; however, the particular role of testosterone in modulating the metabolic effects of insulin remains unexplored in endometrial stromal cells. To evaluate whether androgens modulate the response to insulin, T-HESCs cells were stimulated with 100 nM testosterone for 24 h and changes in the protein levels of caveolin-1, IR, and Akt were determined by Western blotting (WB). After testosterone treatment, the consequences of acute insulin stimulation were evaluated by WB analysis of phospho-S473Akt and phospho-Y14Caveolin-1, as well as by measuring glucose incorporation analyzing 2-deoxyglucose (2-DOG) uptake. For cells pretreated with testosterone, higher IR, IRS-1, and caveolin-1 protein levels compared with control conditions were detected. However, in testosterone treated cells acute insulin stimulation did not increase phospho-S473Akt and phospho-Y14caveolin-1 levels and reduced 2-DOG uptake was observed compared to control cells. Our results suggest that testosterone may have a detrimental role on the metabolic effects of insulin in endometrial stromal cell cultures. Thus, the high androgen levels in patients with PCOS may favor insulin resistance observed in endometria from these women.

Decreased phosphorylation of Y¹4caveolin-1 in endometrial tissue of polycystic ovary syndrome patients may be related with an insulin resistant state in this tissue.

Endometrial tissue of patients with polycystic ovary syndrome (PCOS) shows an impaired expression of insulin signaling molecules. Tyrosine phosphorylation of the insulin receptor (IR) by insulin promotes glucose uptake by activating the PI3K/Akt pathway. IR stability and function depend on the presence of the protein caveolin-1. Activation of IR increases phosphorylation of Y¹4caveolin-1. Since the endometrium of PCOS patients is proposed to be insulin resistant, we evaluated the phosphorylation of IR and caveolin-1 in endometria of patients with insulin resistance (PCOSE-IR) compared to controls (CE). To explore the mechanism associated with this condition, cultured endometrial cells (T-HESC) were exposed to high glucose (25 mM, 24 h), an experimental condition that leads to insulin resistance in other cell types. Endometrial protein levels of phospho-Y97²IR, phospho-Y¹4caveolin-1 and caveolin-1 were determined by Western blotting. In cultured cells, protein levels of caveolin-1, IR, and Akt were evaluated by Western blotting. After acute insulin stimulation, phospho-S47³Akt, phospho-Y¹4caveolin-1, and 2-deoxyglucose (2-DOG) uptake were determined. PCOSE-IR samples showed high protein levels of caveolin-1, but reduced phospho-Y¹4caveolin-1 compared to CE. No differences were observed for phospho-Y97²IR between both groups. Cells pretreated with glucose showed a reduction in protein levels of IR and caveolin-1 and were unable to increase 2-DOG uptake, phospho-S47³Akt and phospho-Y¹4caveolin-1 after insulin stimulation. In conclusion, in PCOSE-IR the impaired phosphorylation of IR downstream molecules such as phospho-Y¹4caveolin-1 suggests a diminished insulin sensitivity in endometria, condition that could be supported in vitro by the ability of T-HESCs to become insulin resistant when they are exposed to high glucose.

Cirugía de la fisura anal crónica: resultados a largo plazo / Surgical treatment of chronic anal fissure: long-term results

Introducción. La esfinterotomía lateral interna es el procedimiento de elección para tratar la fisura anal crónica. Sin embargo, no está exenta de complicaciones, especialmente alteraciones de la continencia. El objetivo de este trabajo ha sido conocer los resultados obtenidos con el tratamiento quirúrgico de esta molesta afección. Pacientes y métodos. Se han revisado 170 expedientes clínicos correspondientes a los pacientes intervenidos de fisura anal crónica entre enero de 1992 y diciembre de 1996. Elaboramos un cuestionario, contactando por teléfono o en consultas externas para conocer el grado de satisfacción, aparición de cualquier forma de incontinencia o recidiva de la fisura. Resultados. Logramos interrogar a un 95,29 por ciento de los pacientes, con un tiempo de seguimiento medio de 39,9 meses. Se realizaron un 85,9 por ciento de esfinterotomías laterales internas cerradas. Se produjo sangrado en 7 pacientes (4,3 por ciento), precisando dos de ellos revisión y hemostasia. Hubo 5 recidivas (3 por ciento), 7 casos de incontinencia a gases (4,3 por ciento), tres de soiling (1,8 por ciento) y dos de incontinencia a heces (1,23 por ciento). Se consiguió la curación sin secuelas y con un grado alto de satisfacción en un 88 por ciento de los casos. Conclusiones. Los resultados obtenidos se sitúan entre los mejores de las series publicadas. A partir de estos datos, el interés se centra en estudiar de forma prospectiva las diferentes formas de tratamiento, incluyendo las conservadoras, a fin de conseguir las tasas más altas de curación con las mínimas secuelas posibles (AU)

Swallowing of hydrochloric acid: study of 25 cases.

INTRODUCTION: Ingestion of hydrochloric acid solutions (Salfumant/Salfuman) constitute a relatively frequent emergency in our environment. It is a strong acid, highly corrosive, the swallowing of which causes a very serious necrosis of the gastrointestinal tract. AIM: We review our experience on emergency treatment of inpatients after the swallowing of watery hydrochloric acid solutions, in order to identify the most important prognosis factor. PATIENTS AND METHODS: During the last thirteen years, 25 patients have been attended in our center with the diagnosis of hydrochloric acid swallowing. The clinical and therapeutical characteristics are respectively analyzed, as well as the high morbi-mortality of these kind of emergencies. RESULTS: Global mortality of the series has been 48% (12 patients). The common characteristic of these 12 patients was the esophagogastric massive necrosis, and the duodenopancreatic frame necrosis. Ten patients who did not present duodenal necrosis or were operated on of later complications, survived. Three patients could be managed with medical conservative treatment. CONCLUSIONS: Hydrochloric acid swallowing constitutes an extraordinary severe emergency, with a high mortality, mainly related to necrosis extension to the duodenopancreatic frame.