These data suggest that hysteroscopic polypectomy before IUI is an effective measure.

Abstract-The renin-angiotensin system plays an important role in renal development. However, it is unknown whether reduction in angiotensin II effects during the nephrogenic period leads to different renal alterations in males and females during the adult age. The aim of this study was to evaluate whether the role of angiotensin II on renal development is sex dependent and whether there are sex differences in blood pressure, renal hemodynamics, and severity of renal damage during adult life when nephrogenesis is altered by blocking angiotensin II effects. Newborn Sprague-Dawley rats were treated with an angiotensin II type 1 receptor antagonist (L-158.809; 7 mg/kg per day) during the first 2 weeks of life. At 3 months of age, changes in blood pressure, albuminuria, and renal hemodynamics were assessed, and stereological and histopathologic studies were performed. Blood pressure increased (127Ϯ0.5 versus 115Ϯ0.7 mm Hg in control rats; PϽ0.05) and nephron number decreased (37%; PϽ0.05) similarly in treated males and females. However, only males had an elevation in albuminuria (5.92Ϯ1.65 versus 0.33Ϯ0.09 mg per day in control rats; PϽ0.05), a fall in glomerular filtration rate (12.6%; PϽ0.05), and a significant decrease in papillary volume (42%; PϽ0.05). Mean glomerular volume, glomerulosclerosis, arteriolar hypertrophy, and tubulointerstitial damage in cortex and medulla were also higher (PϽ0.05) in angiotensin II type 1 receptor antagonist-treated males than in treated females. The results of this study suggest that females seem to be more protected than males to the renal consequences of reducing angiotensin II effects during renal development.

Cyclooxygenase-2 (COX-2) has been identified in renal tissues under normal conditions, with its expression enhanced during sodium restriction. To evaluate the role of COX-2-derived metabolites in the regulation of renal function, we infused a selective inhibitor (nimesulide) in anesthetized dogs with normal or low sodium intake. The renal effects elicited by nimesulide and a non-isozyme-specific inhibitor (meclofenamate) were compared during normal sodium intake. In ex vivo assays, meclofenamate, but not nimesulide, prevented the platelet aggregation elicited by arachidonic acid. During normal sodium intake, nimesulide infusion (n=6) had no effects on arterial pressure or renal hemodynamics but did reduce urinary sodium excretion, urine flow rate, and fractional lithium excretion. In contrast, nimesulide administration increased arterial pressure and decreased renal blood flow, urine flow rate, and fractional lithium excretion during low sodium intake (n=6). COX-2 inhibition reduced urinary prostaglandin E(2) excretion in both groups but did not modify plasma renin activity in dogs with low (8.1+/-1.1 ng angiotensin I. mL(-1). h(-1)) or normal (1.8+/-0.4 ng angiotensin I. mL(-1). h(-1)) sodium intake. Meclofenamate infusion in dogs with normal sodium intake (n=8) induced a greater renal hemodynamic effect than nimesulide infusion. These results suggest that COX-2-derived metabolites (1) are involved in the regulation of sodium excretion in dogs with normal sodium intake, (2) play an important role in the regulation of renal hemodynamic and excretory function in dogs with low sodium intake, and (3) are not involved in the maintenance of the high renin levels during a long-term decrease in sodium intake.

Abstract-We have demonstrated that the reduction of angiotensin II effects during the nephrogenic period reduces the nephron number and induces the development of hypertension. The hypotheses examined are that this reduction of angiotensin effects leads to the development of an age-dependent sodium sensitive hypertension and that the hypertension is angiotensin II dependent. Newborn rats were treated with an angiotensin II type 1 receptor antagonist during the first 2 weeks of age. At 3 to 4 and 11 to 12 months of age, changes in systolic blood pressure, proteinuria, and renal function in response to a prolonged high sodium intake were examined. The basal blood pressure response to the administration of the angiotensin II receptor antagonist was also evaluated at both ages. Basal blood pressure was similarly elevated (PϽ0.05) in male and female treated rats, and the increment was age dependent. High sodium intake only elicited a blood pressure elevation (136Ϯ1 to 154Ϯ3 mm Hg; PϽ0.05) and a decrease in glomerular filtration rate (28%; PϽ0.05) at 11 to 12 months in treated rats. Blockade of angiotensin II receptors during renal development induced an increase (PϽ0.05) in proteinuria that was age and sex dependent, but high sodium intake only induced an elevation in proteinuria in the younger rats (50%; PϽ0.05). Hypertension was maintained by angiotensin II at both ages because blood pressure decreased to normal levels after treatment with an angiotensin II type 1 receptor antagonist. This study shows that the reduction of angiotensin II effects during the nephrogenic period modifies renal function and induces the development of an angiotensin II-dependent hypertension that becomes sodium sensitive during aging. T he importance of nephron number in the development of hypertension and renal dysfunction is supported by experimental and clinical studies [1][2][3][4][5][6][7][8][9] demonstrating that the alteration of nephrogenesis regulation leads to significant changes in arterial pressure and renal function during the adulthood. These effects of the reduction in nephron number during renal development seem to be more significant than those elicited by a decrease in nephron number later in life. 2 One mechanism that is involved in the regulation of nephrogenesis is the renin-angiotensin system (RAS). The role of RAS has been confirmed in previous studies of our group demonstrating that the blockade of the angiotensin II (Ang II) type 1 (AT 1 ) receptors during the late nephrogenic period reduces nephron number by 37%, induces the development of hypertension, and elicits important renal changes that are greater in male than in female rats. 7,8 An age-and sexdependent increment in proteinuria is observed in rats when the effects of Ang II via the AT 1 receptor are reduced during the nephrogenic period. 7,8 These rats also have a decrease in renal functional reserve, because the response to an increment in plasma amino acid levels is deteriorated, and their renal excretory ability to eliminate an acute sodium load is im...

Human metapneumovirus (hMPV) is a leading cause of acute respiratory tract infections in children and the elderly. The mechanism by which this virus triggers an inflammatory response still remains unknown. Here, we evaluated whether the thymic stromal lymphopoietin (TSLP) pathway contributes to lung inflammation upon hMPV infection. We found that hMPV infection promotes TSLP expression both in human airway epithelial cells and in the mouse lung. hMPV infection induced lung infiltration of OX40L + CD11b + DCs. Mice lacking the TSLP receptor deficient mice (tslpr −/− ) showed reduced lung inflammation and hMPV replication. These mice displayed a decreased number of neutrophils as well a reduction in levels of thymus and activation-regulated chemokine/CCL17, IL-5, IL-13, and TNF-α in the airways upon hMPV infection. Furthermore, a higher frequency of CD4 + and CD8 + T cells was found in tslpr −/− mice compared to WT mice, which could contribute to controlling viral spread. Depletion of neutrophils in WT and tslpr −/− mice decreased inflammation and hMPV replication. Remarkably, blockage of TSLP or OX40L with specific Abs reduced lung inflammation and viral replication following hMPV challenge in mice. Altogether, these results suggest that activation of the TSLP pathway is pivotal in the development of pulmonary pathology and pulmonary hMPV replication.Keywords: Dendritic cells r hMPV r Inflammation r Neutrophils r OX40L r TSLP r Viral replication Additional supporting information may be found in the online version of this article at the publisher's web-site Correspondence: Dr. Alexis M. Kalergis e-mail: akalergis@bio.puc.cl * These authors contributed equally to this work.C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2015. 45: 1680-1695 Immunity to infection 1681 IntroductionHuman metapneumovirus (hMPV) is an enveloped virus that belongs to the Paramyxoviridae family, Pneumovirinae subfamily, and the Metapneumovirus genus. The hMPV genome consists of a 13.3-kb single-stranded, negative-sense RNA encoding eight messenger RNAs, which are transcribed directly from the viral genome and translated into nine different polypeptides [1,2]. hMPV was described for the first time in 2001 as a pathogen responsible for acute respiratory tract infections in children [3]. Today, hMPV is considered the second most relevant etiological agent of acute upper and lower respiratory tract infections in children, the elderly, and immunocompromised adults [4]. Furthermore, in young children, hMPV is the second most reported cause of bronchiolitis and pneumonia after human respiratory syncytial virus (hRSV), accounting for ß10% of pediatric hospitalizations related to acute respiratory tract infection [5][6][7]. In addition, hMPV is the cause of outbreaks of acute respiratory tract infections with more than 10% mortality in elderly patients [8,9]. Currently, neither safe-effective vaccines nor specific antiviral therapies are available for hMPV, although promising candidate vaccines have recently be...