131 research outputs found
A Novel Morphine Drinking Model of Opioid Dependence in Rats
No full textThe technical assistance of Camila Ezquer, Jorge Ruiz, and Catalina Vallejos is greatly appreciated., This work was supported by FONDECYT 1200287 and ANID ACT210012 to Fernando Ezquer and FONDECYT 3210276 to Pablo Berrios-Carcamo.Se agradece mucho la asistencia técnica de Camila Ezquer, Jorge Ruiz y Catalina Vallejos., Este trabajo fue apoyado por FONDECYT 1200287 y ANID ACT210012 a Fernando Ezquer y FONDECYT 3210276 a Pablo Berrios-Carcamo.The technical assistance of Camila Ezquer, Jorge Ruiz, and Catalina Vallejos is greatly appreciated.; This work was supported by FONDECYT 1200287 and ANID ACT210012 to Fernando Ezquer and FONDECYT 3210276 to Pablo Berrios-Carcamo.Se agradece mucho la asistencia técnica de Camila Ezquer, Jorge Ruiz y Catalina Vallejos.; Este trabajo fue apoyado por FONDECYT 1200287 y ANID ACT210012 a Fernando Ezquer y FONDECYT 3210276 a Pablo Berrios-Carcamo
Diabetic nephropathy, autophagy and proximal tubule protein endocytic transport: A potentially harmful relationship
No full textDiabetic nephropathy (DN) is the most frequent cause of chronic renal failure. Until now, the pathophysiological mechanisms that determine its development and progression have not yet been elucidated. In the present study, we evaluate the role of autophagy at early stages of DN, induced in type 2 diabetes mellitus (T2DM) mouse, and its association with proximal tubule membrane endocytic receptors, megalin and cubilin. In T2DM animals we observed a tubule-interstitial injury with significantly increased levels of urinary GGT and ALP, but an absence of tubulointerstitial fibrosis. Kidney proximal tubule cells of T2DM animals showed autophagic vesicles larger than those observed in the control group, and an increase in the number of these vesicles marked with LBPA by immunofluorescence. Furthermore, a significant decrease in the ratio of LC3II/LC3I isoforms and in p62 protein expression in DN affected animals is shown. Finally, we observed a marked increase in urinary albumin and vitamin D binding-protein levels in T2DM animals as well as a significant decrease in expression of megalin in the renal cortex. These results indicate an alteration of the tubular endocytic transporters in DN, which could be related to autophagic dysfunction, which would in turn result in impaired organelle recycling, thus contributing to the progression of this disease.Fil: Giraud Billoud, Maximiliano German. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Fader Kaiser, Claudio Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Agüero, Rocio. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Ezquer, Fernando. Universidad del Desarrollo; ChileFil: Ezquer, Marcelo. Universidad del Desarrollo; Chil
Tubulointerstitial injury and proximal tubule albumin transport in early diabetic nephropathy induced by type 1 diabetes mellitus
No full textA decrease in the tubular expression of albumin endocytic transporters megalin and cubilin has been associated with diabetic nephropathy (DN), but there are no comprehensive studies to date relating early tubulointerstitial injury and the effect of the disease on both transporters in type 1 diabetes mellitus (T1DM). We used eight-week-old male C57BL/6 mice divided into two groups; one of them received the vehicle (control group), while the other received the vehicle + 200 mg/kg streptozotocin (T1DM). Ten weeks after the injection, we evaluated plasma insulin, enzymuria, urinary vitamin D-binding protein (VDBP), tubulointerstitial fibrosis and proximal tubule histology, markers of autophagy, and megalin and cubilin levels. We found a reduction in tubular protein reabsorption (albumin and VDBP as specific substances carried by both transporters) with increased tubulointerstitial injury, development of fibrosis, thickening of tubular basement membrane, and an increase in tubular cell metalloproteases. This was associated with a decrease in the renal expression of megalin and cubilin. We also observed an increase in the amount of cellular vesicles of the phagocytic system in the tubules, which could be linked to an alteration of normal intracellular trafficking of both receptors, thus affecting the normal function of transporters in early stages of DN. In diabetic animals, the added effects of tubulointerstitial injury, the decreases in megalin and cubilin expression, and an altered intracellular trafficking of these receptors, seriously affect protein reabsorptionFil: Giraud Billoud, Maximiliano German. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Ezquer, Fernando. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; ChileFil: Bahamonde, Javiera. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; ChileFil: Ezquer, Marcelo. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; Chil
Mesenchymal Stem Cell Therapy in Type 1 Diabetes Mellitus and Its Main Complications: From Experimental Findings to Clinical Practice
No full textType 1 diabetes mellitus (T1DM) is a complex multifactorial disorder which involves a loss of self-tolerance leading to the autoimmune destruction of pancreatic β−cells. Exogenous insulin administration cannot mimic precise pancreatic β-cell regulation of glucose homeostasis, thereby leading to severe long-term complications. Pancreas or islet transplant only provides partial exogenous insulin independence and induces several adverse effects, including increased morbidity and mortality. The scientific community and diabetic patients are thus, still waiting for an effective therapy which could preserve the remaining β-cells, replenish islet mass and protect newly-generated β-cells from autoimmune destruction. Mesenchymal stem cells (MSCs) have been envisioned as a promising tool for T1DM treatment over the past few years, since they could differentiate into glucose-responsive insulin-producing cells. Their immunomodulatory and proangiogenic roles can be used to help arrest β-cell destruction, preserve residual β-cell mass, facilitate endogenous β-cell regeneration and prevent disease recurrence, thereby making them ideal candidates for the comprehensive treatment of diabetic patients. This review focuses on recent pre-clinical data supporting MSC use in regenerating β-cell mass and also in treating several T1DM-associated complications. Clinical trial results and the ongoing obstacles which must be addressed regarding the widespread use of such therapy are also discussed.Fil: Ezquer, Marcelo. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; ChileFil: Arango Rodriguez, Martha. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; ChileFil: Giraud Billoud, Maximiliano German. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Ezquer, Fernando. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; Chil
Changes of myoid and endothelial cells in the peritubular wall during contraction of the seminiferous tubule
No full textThe wall of the seminiferous tubule in rodents consists of an inner layer of myoid cells covered by an outer layer of endothelial cells. Myoid cells are a type of smooth muscle cell containing α-actin filaments arranged in two independent layers that contract when stimulated by endothelin-1. The irregular surface relief of the tubular wall is often considered a hallmark of contraction induced by a variety of stimuli. We examine morphological changes of the rat seminiferous tubule wall during contraction by a combination of light, confocal, transmission and scanning electron microscopy. During ET-1-induced contraction, myoid cells changed from a flat to a conical shape, but their actin filaments remained in independent layers. As a consequence of myoid cell contraction, the basement membrane became wavy, orientation of collagen fibers in the extracellular matrix was altered and the endothelial cell layer became folded. To observe the basement of the myoid cell cone, the endothelial cell monolayer was removed by collagenase digestion prior to SEM study. In contracted tubules, it is possible to distinguish cell relief: myoid cells have large folds on the external surface oriented parallel to the tubular axis, whereas endothelial cells have numerous cytoplasmic projections facing the interstitium. The myoid cell cytoskeleton is unusual in that the actin filaments are arranged in two orthogonal layers, which adopt differing shapes during contraction with myoid cells becoming cone-shaped. This arrangement impacts on other components of the seminiferous tubule wall and affects the propulsion of the tubular contents to the rete testis.Fil: Losinno, Antonella Denise. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Sorrivas, Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; ArgentinaFil: Ezquer, Eduardo Marcelo. Universidad del Desarrollo; ChileFil: Ezquer, Fernando. Universidad del Desarrollo; ChileFil: Lopez, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Morales, Alfonsina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin
Acquisition, Maintenance and Relapse-Like Alcohol Drinking: Lessons from the UChB Rat Line
No full text© 2017 Israel, Karahanian, Ezquer, Morales, Ezquer, Rivera-Meza, Herrera-Marschitz and Quintanilla. This review article addresses the biological factors that influence: (i) the acquisition of alcohol intake; (ii) the maintenance of chronic alcohol intake; and (iii) alcohol relapse-like drinking behavior in animals bred for their high-ethanol intake. Data from several rat strains/lines strongly suggest that catalase-mediated brain oxidation of ethanol into acetaldehyde is an absolute requirement (up 80%–95%) for rats to display ethanol’s reinforcing effects and to initiate chronic ethanol intake. Acetaldehyde binds non-enzymatically to dopamine forming salsolinol, a compound that is selfadministered. In UChB rats, salsolinol: (a) generates marked sensitization to the motivational effects of ethanol; and (b) strongly promotes binge-like drinking. The specificity of salsolinol actions is shown by the finding that only the R-salsolinol enantiomer but not S-salsolinol accounted for the lat
Proregenerative microenvironment triggered by donor mesenchymal stem cells preserves renal function and structure in mice with severe diabetes mellitus
No full textIndexación: ScopusThe aim of our work was to evaluate, in an animal model of severe diabetes mellitus, the effect of mesenchymal stem cells (MSCs) administration on diabetic nephropathy (DN) progression. After diabetes induction, one group of mice received the vehicle (DM) and other group received a single dose of MSCs (DM + MSCs). DM + MSCs mice showed a significant improvement in functional parameters of the kidney compared with untreated mice. While DM mice presented marked histopathological changes characteristics of advanced stages of DN (fibrosis, glomerulosclerosis, glomerular basement membrane thickening, capillary occlusion, decreased podocyte density, and effacement of foot processes), DM + MSCs mice showed only slight tubular dilatation. The renoprotection was not associated with an improvement in diabetic condition and very low number of donor cells was found in the kidney of DM + MSCs mice, suggesting that renoprotection could be mediated by paracrine effects. Indeed, DM + MSC mice presented increased renal proliferation index, decreased renal apoptotic index and the restoration of proregenerative factors, and anti-inflammatory cytokines levels. Moreover, macrophage infiltration and oxidative stress damage were also reduced in DM + MSCs mice. Our data demonstrate that MSC administration triggers a proregenerative microenvironment in DN kidney, which allows the preservation of the renal function even if diabetes was uncorrected. © 2015 Fernando Ezquer et al.https://www.hindawi.com/journals/bmri/2015/164703
Mesenchymal stem cell therapy for doxorubicin cardiomyopathy : Hopes and fears
No full textFunding Information: This work was supported by a FONDECYT 1130470 grant to FE. Publisher Copyright: © 2015 Ezquer et al.Chemotherapy has made an essential contribution to cancer treatment in recent decades despite its adverse effects. As cancer survivors have increased, concern about ex-patient lifespan has become more important too. Doxorubicin is an effective anti-neoplastic drug that produces a cardiotoxic effect. Cancer survivors who received doxorubicin became more vulnerable to cardiac disease than the normal population did. Many efforts have been made to prevent cardiac toxicity in patients with cancer. However, current therapies cannot guarantee permanent cardiac protection. One of their main limitations is that they do not promote myocardium regeneration. In this review, we summarize and discuss the promising use of mesenchymal stem cells for cardio-protection or cardio-regeneration therapies and consider their regenerative potential without leaving aside their controversial effects on tumor progression
Effect of Thyromimetic GC-1 Selective Signaling on Reproductive and Lactational Performance in the Hypothyroid Rat
No full textIntroduction: The potential of the thyroid hormone receptor β (TRβ1) selective analog GC-1 has been widely proven in animal models and humans. However, its effect on the reproductive stage of the female rat has not been evaluated. Methods: The effect of the administration of GC-1 or equimolar doses of triiodothyronine (T3) was evaluated on the reproductive performance of the hypothyroid female rat and the indirect effect on pup thyroid status, weight, and survival. Results: Hypothyroidism reduced the number of embryos implanted in the uterus, whereas T3 and GC-1 treatment in hypothyroid females reestablished the number of implanted embryos to normal. Initiation of labor was delayed by hypothyroidism, and T3 replacement treatment reinstated the normal timing of parturition. The administration of GC-1 alone to the lactating mother did not affect pup survival, weight, or thyroidal status. Conclusions: Our findings show the differential effect of thyroid hormone selective signaling during gestation and the indirect exposure of the pups; we also emphasize the plausible use of GC-1 for treatment of hypothyroid mothers during the lactation period.Fil: Rinaldini, Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Campo Verde Arbocco, Fiorella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Ezquer, Eduardo Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; ChileFil: Gamarra Luques, Carlos Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Hapon, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin
Pituitary changes involved in prolactin secretion induced by mifepristone and naloxone during late pregnancy
No full textThe antiprogesterone mifepristone facilitates prolactin release, an effect enhanced by administration of the opioid antagonist naloxone. The present study explores ultrastructural changes in lactotropes after mifepristone and naloxone administration, correlating them with the expression of pituitary prolactin. Methods/Results: Rats were sacrificed at 18:00 h on day 19 of pregnancy. Prolactin immunoelectron microscopy of lactotropes from control rats showed characteristics of quiescent cells with numerous small and spherical secretory granules. Naloxone administration did not modify lactotrope morphology or prolactin expression in terms of mRNA or protein abundances. Mifepristone treatment induced lactotrope activation with development of the rough endoplasmic reticulum and Golgi complex with prolactin immunoreactive small newly formed and large mature secretory granules. Mifepristone increased prolactin mRNA and protein expression. Naloxone administration to mifepristone-treated rats potentiated lactotrope activation compared with mifepristone alone showing exocytotic images of prolactin granules and some cells with evident signs of involution. Conclusions: (1) Blockade of progesterone action by mifepristone activated the lactotrope, increased significantly prolactin mRNA and protein expression and prepared the pituitary for naloxone action. (2) The high serum prolactin levels induced by mifepristone and naloxone may regulate negatively lactotrope activity as suggested by the presence of regressing cells neighboring the actively secreting cells.Fil: Villegas Gabutti, Carlos Mauricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Ezquer, Eduardo Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Deis, Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Maldonado, Cristina Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Soaje, Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin
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