Progesterone regulates corticosterone elevation and alterations in spatial memory and exploratory behavior induced by stress in Wistar rats

The hippocampus is sensitive to high levels of glucocorticoids during stress responses; it suffers biochemical and cellular changes that affect spatial memory and exploratory behavior, among others. We analyzed the influence of the neurosteroid progesterone (PROG) on stress-induced changes in urinary corticosterone (CORT) levels, spatial memory and exploratory behavior.Castrated adult male rats were implanted with PROG or vehicle (VEHI),and then exposed for ten days to chronic stress created by overcrowding or ultrasonic noise. PROG and CORT levels were assessed in urine using highperformanceliquid chromatography (HPLC). Implanted PROG inhibited the rise of stress-induced CORT, prevented spatial memory impairment in the Morris water maze, and eliminated increased exploratory behavior in the hole-board test. These results suggest a protective role of PROG, possibly mediated by its anxiolytic mechanisms, against corticosteroids elevation and the behavioral deficit generated by stressful situations

Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial

PURPOSE Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease. METHODS This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control. RESULTS Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents. CONCLUSION Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer

Progesterone regulates corticosterone elevation and alterations in spatial memory and exploratory behavior induced by stress in Wistar rats * joaquín GarCía-eStrada

La progesterona regula la elevación de corticosterona y las alteraciones en memoria espacial y conducta exploratoria inducidas por estrés en ratas Wistar Received: february 12th, 2010 Reviewed: august 13th, 2010 Accepted: september 1st, 2010 Yolanda diaz-Burke a B S t r a C t The hippocampus is sensitive to high levels of glucocorticoids during stress responses; it suffers biochemical and cellular changes that affect spatial memory and exploratory behavior, among others. We analyzed the influence of the neurosteroid progesterone (PROG) on stress-induced changes in urinary corticosterone (CORT) levels, spatial memory and exploratory behavior. Castrated adult male rats were implanted with PROG or vehicle (VEHI), and then exposed for ten days to chronic stress created by overcrowding or ultrasonic noise. PROG and CORT levels were assessed in urine using highperformance liquid chromatography (HPLC). Implanted PROG inhibited the rise of stress-induced CORT, prevented spatial memory impairment in the Morris water maze, and eliminated increased exploratory behavior in the hole-board test. These results suggest a protective role of PROG, possibly mediated by its anxiolytic mechanisms, against corticosteroids elevation and the behavioral deficit generated by stressful situations. .5/03/2175 for YDB ** E-mail: [email protected] *** E-mail: [email protected] **** E-mail: [email protected] ***** E-mail: [email protected] ****** E-mail: [email protected] ******* E-mail: [email protected] ******** E-mail: [email protected] ********* E-mail: [email protected] y. diaz, c. gonzalez, c. valencia, m. hUerta, X. trUjillo, l. diaz, j. garcía, s. lUqUín 628 U n i v e r s i ta s P s yc h o l o g i c a v. 9 no . 3 s e P t i e m B r e -d i c i e m B r e 2010 r e S u M e n El hipocampo es sensible a altos niveles de glucocorticoides. Durante la respuesta de estrés, esta estructura sufre cambios bioquímicos y celulares que afectan funciones tales como la memoria espacial y la conducta exploratoria, entre otras. En este estudio analizamos la influencia del neuroesteroide progesterona (PROG) sobre los cambios inducidos por estrés en corticosterona (CORT) urinaria, memoria espacial y conducta exploratoria. Se implantó PROG o vehículo (VEHI) a ratas macho adultas castradas y se les expuso a estrés crónico por hacinamiento o ruido ultrasónico durante 10 días. Se evaluaron niveles de PROG y CORT en orina usando cromatografía líquida de alta resolución (HPLC). Los implantes de PROG inhibieron el incremento de CORT inducido por estrés, previnieron el detrimento de la memoria espacial en el laberinto acuático de Morris y eliminaron el incremento en la actividad exploratoria en la prueba del campo de agujeros. Estos resultados sugieren un efecto protector de la PROG, posiblemente mediado por los mecanismos ansiolíticos de la hormona, contra la elevación de corticoesteroides y el déficit conductual generado por las situaciones estresantes. Keywords author

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes