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Gobernador Ingeniero Valentín Virasoro, Argentina

Houssay B.A.,Institute Biologia y Medicina Experimental
Revista Argentina de Endocrinologia y Metabolismo | Year: 2015

The production of diabetes after total pancreatectomy in the dog by von Mering and Minkowski was one of the greatest advances of the experimental medicine, that demostrated the internal secretion of the pancreas and led to the discovery of insulin. Diabetes was an unexpected finding in the course of experiments planned for the study of the intestinal absorption of fats. The hazard favored men well prepared, that were active in diabetic research. The real history of the events was unknown until recently and a lot of fantastic stories were widespread. The present publication of a personal letter of Minkowski, in German, accompanied by the Spanish translation (the English translation appeared in Diabetes, 1952, 1, 112-116, but not the german text), explains clearly the truth abouth these facts. Copyright ® 2015 por la Sociedad Argentina de Endocrinología y Metabolismo. Source

Ricci A.G.,CONICET | Ricci A.G.,Institute Biologia y Medicina Experimental | Olivares C.N.,CONICET | Bilotas M.A.,CONICET | And 2 more authors.
Reproductive Sciences | Year: 2011

The main factor involved in neovascularization of ectopic endometrial tissue in endometriosis is the vascular endothelial growth factor (VEGF), which is produced both by the endometrial implant and by peritoneal macrophages. On the other hand, bevacizumab is an antiangiogenic agent used in the treatment of different tumors, like colorectal, pulmonary, and recently mammary. We evaluated the effect of the inhibition of VEGF activity with bevacizumab (Avastin) on ectopic endometrial growth in a murine model of endometriosis. Two months old female BALB/c mice had surgery performed to induce endometriotic-like lesions. Treatment with bevacizumab started on post-surgery day 15 and continued during 2 weeks. Then, animals were sacrificed, peritoneal fluid was collected, and endometriotic-like lesions were counted, measured, and removed. Cell proliferation, vascular density, and apoptosis were assessed by immunohistochemistry for proliferating cell nuclear antigen (PCNA), immunohistochemistry for CD34, and Terminal Deoxynucleotidil Transferase-Mediated dUTP Nick End Labeling (TUNEL), respectively. Vascular endothelial growth factor levels were evaluated in the peritoneal fluid by enzyme-linked immunoassay (ELISA). Treatment with bevacizumab significantly inhibited endometriotic lesion development (P <.05). Consistently, bevacizumab significantly inhibited cell proliferation in lesions (P <.01), reduced vascular density (P <.001), as well as increased the apoptotic cell percentage (P <.001). In addition, bevacizumab reduced VEGF levels in peritoneal fluid of endometriosis-induced animals (P <.05). In conclusion, this study suggests a direct effect of bevacizumab on the reduction of endometrial implant growth and supports further research on VEGF inhibition as a novel therapeutic modality in endometriosis. © The Author(s) 2011. Source

Buffone M.G.,University of Pennsylvania | Ijiri T.W.,University of Pennsylvania | Cao W.,University of Pennsylvania | Merdiushev T.,University of Pennsylvania | And 3 more authors.
Molecular Reproduction and Development | Year: 2012

Sperm structure has evolved to be very compact and compartmentalized to enable the motor (the flagellum) to transport the nuclear cargo (the head) to the egg. Furthermore, sperm do not exhibit progressive motility and are not capable of undergoing acrosomal exocytosis immediately following their release into the lumen of the seminiferous tubules, the site of spermatogenesis in the testis. These cells require maturation in the epididymis and female reproductive tract before they become competent for fertilization. Here we review aspects of the structural and molecular mechanisms that promote forward motility, hyperactivated motility, and acrosomal exocytosis. As a result, we favor a model articulated by others that the flagellum senses external signals and communicates with the head by second messengers to affect sperm functions such as acrosomal exocytosis. We hope this conceptual framework will serve to stimulate thinking and experimental investigations concerning the various steps of activating a sperm from a quiescent state to a gamete that is fully competent and committed to fertilization. The three themes of compartmentalization, competence, and commitment are key to an understanding of the molecular mechanisms of sperm activation. Comprehending these processes will have a considerable impact on the management of fertility problems, the development of contraceptive methods, and, potentially, elucidation of analogous processes in other cell systems. © 2011 Wiley Periodicals, Inc. Source

Braun-Menendez E.,Institute Biologia y Medicina Experimental
Revista Argentina de Endocrinologia y Metabolismo | Year: 2015

Different aspects of the relations between endocrine glands and the kidney are revised, among them the renotrophic action of these glands, their influence upon global kidney function, upon water and electrolite excretion and upon kidney metabolism and enzymes. In spite of the numerous papers written on that subject it has not yet been possible to conclude whether the endocrine glands exercise a direct influence on the kidney or whether the changes that can be detected in its morphology, excretion, and enzymatic activity are a direct consecuence of hormonal excess or defficiences, or secondary to more general metabolic changes. It has been fairly proved that the antidiuretic principle of posterior pitiuitary and the mineralcorticoid hormones act directly upon the kidney. The former increases the maximal capacity of renal tubules to reabsorb water and the latter increases the maximal ability of sodium reabsorption of the same. It is also probable that hormones act directly upon certain renal enzimes. The influence of endocrine glands upon the trophism and speciphic functions of the kidney are indirect owing to the profound influences of the pituitary, the thyroid and the sex male hormones in exerted through modifications in protein metabolism due to the either and excess or a defficiency of those hormones. The administration of protein rich diets has a great a renotrophic action as that of pituitary and thyroid hormones and the administration of protein poor diets produces hypotrophy and hypofunction of the kidney similar to those that follow hypophysectomy or thyroidectomy. These and other reasons have led the authors to the hypothesis that the renal mass and functions are controlled by a hypophetic substance-renotrophin-the blood level of which depends on the intensity of protein metabolism. The renotrophin (or renotrophins) might be a product of the intermediate metabolism of proteins. Copyright ® 2015 por la Sociedad Argentina de Endocrinología y Metabolismo. Source

Maymo J.L.,University of Buenos Aires | Perez A.P.,University of Seville | Duenas J.L.,Hospital Universitario Virgen Macarena | Calvo J.C.,University of Buenos Aires | And 3 more authors.
Endocrinology | Year: 2010

Leptin, a 16-kDa protein mainly produced by adipose tissue, has been involved in the control of energy balance through its hypothalamic receptor. However, pleiotropic effects of leptin have been identified in reproduction and pregnancy, particularly in placenta, where it was found to be expressed. In the current study, we examined the effect of cAMP in the regulation of leptin expression in trophoblastic cells. We found that dibutyryl cAMP [(Bu) 2cAMP], a cAMP analog, showed an inducing effect on endogenous leptin expression in BeWo and JEG-3 cell lines when analyzed by Western blot analysis and quantitative RT-PCR. Maximal effect was achieved at 100 μM. Leptin promoter activity was also stimulated, evaluated by transient transfection with a reporter plasmid construction. Similar results were obtained with human term placental explants, thus indicating physiological relevance. Because cAMP usually exerts its actions through activation of protein kinase A (PKA) signaling, this pathway was analyzed. We found that cAMP response element-binding protein (CREB) phosphorylation was significantly increased with (Bu)2cAMP treatment. Furthermore, cotransfection with the catalytic subunit of PKA and/or the transcription factor CREB caused a significant stimulation on leptin promoter activity. On the other hand, the cotransfection with a dominant negative mutant of the regulatory subunit of PKA inhibited leptin promoter activity. We determined that cAMP effect could be blocked by pharmacologic inhibition of PKA or adenylyl ciclase in BeWo cells and in human placental explants. Thereafter, we decided to investigate the involvement of the MAPK/ERK signaling pathway in the cAMP effect on leptin induction. We found that 50 μM PD98059, a MAPK kinase inhibitor, partially blocked leptin induction by cAMP, measured both by Western blot analysis and reporter transient transfection assay. Moreover, ERK 1/2 phosphorylation was significantly increased with (Bu)2cAMP treatment, and this effect was dose dependent. Finally, we observed that 50 μM PD98059 inhibited cAMP-dependent phosphorylation of CREB in placental explants. In summary, we provide some evidence suggesting that cAMP induces leptin expression in placental cells and that this effect seems to be mediated by a cross talk between PKA and MAPK signaling pathways. Copyright © 2010 by The Endocrine Society. Source

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