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Five adult Saanen goats received a single oral dose of Heterophyllaea pustulata containing 42.25 μg/kg rubiadin (anthraquinone) and 3 adult goats were untreated controls. All goats were exposed to sunlight and sequential ear skin biopsies were collected before treatment and at 32 hours, 3 days, 8 days, and 15 days after treatment. Changes at 32 hours after dosing included epidermal spongiosis, single cell death and acantholysis, an increased BAX/BCL-2 protein ratio, and dermal edema. Lesions at day 3 included epidermal and adnexal necrosis, crust formation, and acanthosis. Acanthosis, hyperkeratosis, and dermal fibrosis and neovascularization were present at day 15. The pro-apoptotic (BAX)/anti-apoptotic (BCL-2) protein ratio increased at 32 hours, whereas epidermal and dermal PCNA immunolabeling increased between days 8 and 15 after treatment. The cutaneous lesions were consistent with sunlight-induced damage, and the occurrence in treated but not control goats indicates photosensitization.

Embryonic death followed by resorption is a conserved process in mammals. Among the polyovular species, Lagostomus maximus (plains viscacha) constitutes a model of early and physiological embryonic death, since out of a total of 10-12 implants, 8-10 are resorbed during early/intermediate gestation, surviving are only the most caudal implantations of each uterine horn. This regular reproductive event is unique to this species, but many characteristics of the implantations during the early gestation of L. maximus, when embryonic death processes begin are unknown. The aim of the present work was to analyze the implantation sites of this species using morphological, morphometric, histochemical, lectinhistochemical, and immunohistochemical techniques to infer the possible causes of this event. Macroscopically, the length and width of the implantation sites significantly increased in a craniocaudal direction. Histochemically, the implantation sites did not differ in the expression of glycoconjugates and glycosidic residues. Furthermore, no variations were observed in cell renewal, hormone receptor expression, and decidualization. Both the glandular and vascular areas of the implantation sites significantly increased in the craniocaudal axis. Some necrotic cells and an inflammatory response with a predominance of lymphocytes and fibrin were observed in the cranial and middle but not in the caudal implantation sites. We conclude that signs of embryonic death and resorption are already observed in the early gestation of L. maximus. Our results reaffirm the hypothesis that postulates the key potential role of uterine glands and blood vessels in the gestation of the species, with emphasis on embryonic death. This pattern of embryonic death in L. maximus makes this species an unconventional mammalian model, which adds to the peculiarities of polyovulation (200-800 oocytes/estrus) and hemochorial placentation.

Several countries have established self-help cryonics groups whose mission is to cryopreserve human bodies or brains after legal death and ship them to cryonics organizations. The objective of this study was to report the first case of human brain cryopreservation in Argentina and complementary experiments in rats. After legal death, the body of a 78-year-old Caucasian woman was transported to a funeral home where her head was submitted to intracarotid perfusion with 5 L cold physiologic saline followed by the same volume of cold saline containing 13% dimethyl sulfoxide and 13% glycerol. The brain was removed, temporarily frozen at -80°C, and shipped to a U.S. cryostasis facility. Three groups of rats were intracardially perfused with fixative but not frozen (Reference group), vitrification solution VM1 (Control group), or the cryoprotection solution used in the patient (Experimental group). Control and Experimental brains were stored at -80°C and subsequently assessed by immunohistochemistry for the adult neuron marker (NeuN), the immature neuron marker doublecortin (DCX), the dopaminergic neuron marker tyrosine hydroxylase, and the presynaptic marker synaptophysin (SYN). The number of NeuN-positive neurons remained unchanged in the experimental brain cortex, whereas the number of immature DCX neurons in the hippocampus fell markedly in the cryoprotected brains. The results were highly variable for hypothalamic dopaminergic neurons. Confocal microscopy for SYN revealed that cryopreservation did not affect the synaptic network in the hippocampus. To our knowledge, this is the first report correlating a human cryoprotection procedure with results in complementary experiments in laboratory animals.

Development of alternative therapies for treating functional deficits after different neurological damages is a challenge in neuroscience. Insulin-like growth factor-1 (IGF-1) is a potent neurotrophic factor exerting neuroprotective actions in brain and spinal cord. It is used to prevent or treat injuries of the central nervous system using different administration routes in different animal models. In this study, we evaluated whether intracisternal (IC) route for IGF-1 gene therapy may abrogate or at least reduce the structural and behavioral damages induced by the intraparenchymal injection of kainic acid (KA) into the rat spinal cord. Experimental (Rad-IGF-1) and control (Rad-DsRed-KA) rats were evaluated using a battery of motor and sensory tests before the injection of the recombinant adenovector (day -3), before KA injection (day 0) and at every post-injection (pi) time point (days 1, 2, 3 and 7 pi). Histopathological changes and neuronal and glial counting were assessed. Pretreatment using IC delivery of RAd-IGF-1 improved animal's general condition and motor and sensory functions as compared to Rad-DsRed-KA-injected rats. Besides, IC Rad-IGF-1 therapy abrogated later spinal cord damage and reduced the glial response induced by KA as observed in Rad-DsRed-KA rats. We conclude that the IC route for delivering RAd-IGF-1 prevents KA-induced excitotoxicity in the spinal cord.

The uterus is an organ with great plasticity due to the morphological and physiological changes it experiences during the estrous cycle and pregnancy. In mammals, pregnancy requires diverse sex hormones, growth factors and cytokines, among others, for promoting uterine remodeling to favor implantation, placentation, and embryo/fetus survival and growth. The hystricognathi rodent Lagostomus maximus (plains viscacha) has a high rate of embryonic resorption. The cranial and middle implants are reabsorbed 25-35 days after intercourse while the caudal embryos continue with their development until two precocial offspring are born. So far, no uterine studies of non-pregnant L. maximus females were performed to determine the possible existence of variations in the organ that could be related to the differential survival of the implants. We used ultrasonography, as well as morphological, morphometric, histochemical, lectinhistochemical, and immunohistochemical methods to study differences in the uterine glands (area), vasculature (area), and musculature (thickness) along the uterine horns in non-pregnant females. Along the uterus, all these structures were in more advanced developmental condition in the caudal region as compared to more anterior positions. These regional variations could be decisive in explaining the reason why only caudal implantations come to term. In contrast, no differences in the in the luminal and glandular epithelial cells, nor in the degree of cell proliferation and apoptosis, and hormonal receptor staining were found. These parameters could be related to implantation along the uterine horns, but not to the differential survival of the implants.

Fil: Delgado Stagnares, Juan J.. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina

Spontaneous embryonic death is a conserved reproductive event in Eutherians. The macro and microscopic characteristics of this type of death are similar between the different taxa. However, in the hystricomorphic rodent plains viscacha (Lagostomus maximus) is exceptional in terms of massiveness (80% embryonic resorption). In this species, of the 10-12 implantation sites (IS) (half in each uterine horn), only the caudal embryos will survive, resorbing the cranial and intermediate IS. We hypothesize that uterine structural variations in L. maximus restrict growth and promote embryo death, with the consequent loss of placental homeostasis in the cranial and middle IS. In this study, different studies (ultrasonography, macroscopy and microscopy) were carried out to analyze different aspects of the intermediate gestation of L. maximus (46 days postcoitus). Ultrasonographic studies revealed that the cranial and middle IS (IS-1, IS-2, and IS-3) had no recognizable embryonic and placental structures as compared to the caudal implantation sites (IS-4). Macroscopically, the areas corresponding to the embryos in the cranial and middle IS were occupied by a necrotic black semi-fluid mass. Moreover, the placenta in these IS was undifferentiated. However, in the caudal IS both the embryo and its placenta were distinguishable. Using histological and immunohistochemical techniques, it was observed that the placentas of IS-1, IS-2 and IS-3 were disorganized and showed hemorrhage, inflammatory infiltration containing neutrophils, macrophages, mast cells and foreign body giant cells, apoptotic trophoblast, and a layer of collagen fibers and fibroblasts that circumscribed each of these IS. In contrast, the placenta of the caudal IS showed an organized maternal-embryonic interface. The characteristics observed in IS in resorption of viscachas in intermediate gestation show that, regardless of gestation time, embryonic death has a similar macro and microscopic morphological pattern among eutherians with invasive placentation. However, the massiveness and sectorization of embryonic death in the plains viscacha make the species a unique model for the study of this reproductive event.

Heart failure is the leading cause of death among diabetic people. Cellular and molecular entities leading to diabetic cardiomyopathy are, however, poorly understood. Coupling of cardiac carbonic anhydrase II (CAII) and Na+/H+ exchanger 1 (NHE1) to form a transport metabolon was analyzed in obese type 2 diabetic mice (ob−/−) and control heterozygous littermates (ob+/−). Echocardiography showed elevated systolic interventricular septum thickness and systolic posterior wall thickness in ob−/− mice at 9 and 16 weeks. ob−/− mice showed increased left ventricular (LV) weight/tibia length ratio and increased cardiomyocyte cross sectional area as compared to controls, indicating cardiac hypertrophy. Immunoblot analysis showed increased CAII expression in LV samples of ob−/− vs. ob+/− mice, and augmented Ser703 phosphorylation on NHE1 in ob−/− hearts. Reciprocal co-immunoprecipitation analysis showed strong association of CAII and NHE1 in LV samples of ob−/− mice. NHE1-dependent rate of intracellular pH (pHi) normalization after transient acid loading of isolated cardiomyocytes was higher in ob−/− mice vs. ob+/−. NHE transport activity was also augmented in cultured H9C2 rat cardiomyoblasts treated with high glucose/high palmitate, and it was normalized after CA inhibition. We conclude that the NHE1/CAII metabolon complex is exacerbated in diabetic cardiomyopathy of ob−/− mice, which may lead to perturbation of pHi and [Na+] and [Ca2+] handling in these diseased hearts.

Prediabetic myocardium, induced by fructose-rich diet (FRD), is prone to increased sarcoplasmic reticulum (SR)-Ca2+ leak and arrhythmias due to increased activity of the Ca2+/ calmodulin protein kinase II (CaMKII). However, little is known about the role of SR-mitochondria microdomains, mitochondrial structure, and mitochondrial metabolisms. To address this knowledge gap we measured SR-mitochondrial proximity, intracellular Ca2+, and mitochondrial metabolism in wild type (WT) and AC3-I transgenic mice, with myocardial-targeted CaMKII inhibition, fed with control diet (CD) or with FRD. Confocal images showed significantly increased spontaneous Ca2+ release events in FRD vs. CD WT cardiomyocytes. [ 3H]-Ryanodine binding assay revealed higher [ 3H]Ry binding in FRD than CD WT hearts. O2 consumption at State 4 and hydrogen peroxide ( H2O2) production rate were increased, while respiratory control rate (RCR) and Ca2+ retention capacity (CRC) were decreased in FRD vs. CD WT isolated mitochondria. Transmission Electron Microscopy (TEM) images showed increased proximity at the SR-mitochondria microdomains, associated with increased tethering proteins, Mfn2, Grp75, and VDAC in FRD vs. CD WT. Mitochondria diameter was decrease and roundness and density were increased in FRD vs. CD WT specimens. The fission protein, Drp1 was significantly increased while the fusion protein, Opa1 was unchanged in FRD vs. CD WT hearts. These differences were prevented in AC3-I mice. We conclude that SR-mitochondria microdomains are subject to CaMKII-dependent remodeling, involving SR-Ca2+ leak and mitochondria fission, in prediabetic mice induced by FRD. We speculate that CaMKII hyperactivity induces SR-Ca2+ leak by RyR2 activation which in turn increases mitochondria Ca2+ content due to the enhanced SR-mitochondria tethering, decreasing CRC., Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Veterinarias

Brain aging is characterized by chronic neuroinflammation caused by activation of glial cells, mainly microglia, leading to alterations in homeostasis of the central nervous system. Microglial cells are constantly surveying their environment to detect and respond to diverse signals. During aging, microglia undergo a process of senescence, characterized by loss of ramifications, spheroid formation, and fragmented processes, among other abnormalities. Therefore, the study of microglia senescence is of great relevance to understand age‐related declines in cognitive and motor function.We have targeted the deleterious effects of aging by implementing gene therapy with IGF-1, employing recombinant adenoviral vectors (RAds) as a delivery system. In this study, we performed intracerebroventricular (ICV) IGF-1 gene therapy on aged female rats and evaluated its effect on Caudate-Putamen unit (CPu) gene expression and inflammatory state. IGF-1 gene therapy modified senescent microglia of the CPu towards an anti-inflammatory state increasing the proportion of Iba1+Arg1+ cells. Moreover, IGF-1 gene therapy was able to regulate the pro-inflammatory environment of CPu in female aged rats by down-regulating the expression of genes typically over-expressed during aging. Our results demonstrate that, ICV IGF-1 gene therapy, is capable to modulate microglia cells and CPu gene expression, leading to an improvement in motor function., Instituto de Investigaciones Bioquímicas de La Plata

En la era de la tecnología, la educación y la enseñanza incursionan cada vez más dentro de las áreas multimediales. Esto se produce ya que es una forma más amena de transmitir conocimientos. La acreditación de los conocimientos tiene como uno de sus objetivos el evaluar los saberes de las personas a acreditar, mediante un proceso continuo de certificación. El presente trabajo muestra un ejemplo de programación basada en bloques, mediante un programa de acceso libre, para la generación de una aplicación para dispositivos móviles, que sirve para ayudar a los estudiantes en el estudio para la acreditación de sus conocimientos. Basados en una experiencia de dos años consecutivos, se concluye que este tipo de aplicaciones produce beneficios en los estudiantes para la fijación de saberes., In the era of technology, education and teaching are increasingly entering the multimedia areas. This occurs because it is a more pleasant way of transmitting knowledge. One goal of the accreditation of knowledge is to evaluate the knowledge of the people to be accredited, through a continuous process of certification. The present work shows an example of blocks-based programming, using a free access program, for generating an application for mobile devices, which will help students in the study for the accreditation of their knowledge. Based on a two years’ experience, it is concluded that this type of applications produces benefits for students to fix knowledge., Secretaría de Ciencia y Técnica

Introduction The thoracic limbs of cats facilitate jumping and represent one of their main ways for pursuing and capturing prey. The main muscles and nerves involved in these activities are present in the region of the forearm and of the hand. The scant anatomical reference availabe on South American cats species justifies the present comparative study. Materials and Methods The forelimbs of wildcat, ocelot and jaguar wild felines were fixed. Images of the dissected limbs were captured using a digital camera. Measurements were made using a caliper. Results The long and short heads of the extensor carpi radialis muscle of the ocelot and of the jaguar showed a great development in comparison with those of the wildcat. The flexor digitorum profundus muscle in the three felines is formed by five heads. In the jaguar, the radial or deep head presented two sesamoid bones. The brachioradialis muscle of the jaguar and of the ocelot is inserted medially at the distal end of the radius and at the proximal row of the carpus by a thick and flattened tendon. The pronator teres muscle of the jaguar extended to the carpal region. In the wildcat and in the ocelot, this muscle was less developed Conclusions The main variations observed between the forearms and the hands of these South American cats were found between the supinator and the pronator muscles, presenting a variation in the size of their bellies and tendons. Our study of the muscular characteristics represents a contribution to the homologies and differences of the forearm and hand muscles of each of these species of felines. Fil: Sánchez, Hilda Liliana. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina Fil: Rafasquino, M. E.. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina Fil: Portiansky, Enrique Leo. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Cátedra de Patología General Veterinaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina

After injury of the nervous system glial cells react according to the stimuli by modifying their morphology and function. Glia activation was reported in different kainic acid (KA)-induced neurodegeneration models. Here, we describe glial morphometric changes occurring in an excitotoxic KA-induced cervical spinal cord injury model. Concomitant degenerative and apoptotic processes are also reported. Male rats injected at the spinal cord C5 segment either with KA or saline were euthanized at post-injection (PI) days 1, 2, 3 or 7. Anti-IBA-1 and anti-GFAP antibodies were used to identify microglia and activated astrocytes, respectively, and to morphometrically characterized them. Fluoro-Jade B staining and TUNEL reaction were used to determine neuronal and glial degeneration and apoptosis. KA-injected group showed a significant increase in microglia number at the ipsilateral side by PI day 3. Different microglia reactive phenotypes were observed. Reactive microglia was still present by PI day 7. Astrocytes in KA-injected group showed a biphasic increase in number at PI days 1 and 3. Degenerative and apoptotic events were only observed in KA-injected animals, increasing mainly by PI day 1. Understanding the compromise of glia in different neurodegenerative processes may help to define possible common or specific therapeutic approaches directed towards neurorestorative strategies. Fil: Zanuzzi, Carolina Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Ciencias Básicas. Cátedra de Histología y Embriología; Argentina Fil: Nishida, Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Ciencias Básicas. Cátedra de Histología y Embriología; Argentina Fil: Sisti, María Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Ciencias Básicas. Cátedra de Histología y Embriología; Argentina Fil: Barbeito, Claudio Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Ciencias Básicas. Cátedra de Histología y Embriología; Argentina Fil: Portiansky, Enrique Leo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Ciencias Básicas. Cátedra de Histología y Embriología; Argentina

Ghrelin is a stomach-derived hormone that regulates rewarding behaviors and reinforcement by acting on the ventral tegmental area (VTA). The VTA is a complex midbrain structure mainly comprised of dopamine (DA) and gamma-aminobutiric acid (GABA) neurons that are distributed in several VTA sub-nuclei. Here, we investigated the neuroanatomical distribution and chemical phenotype of ghrelin-responsive neurons within the VTA. In wild-type mice, we found that: (1) ghrelin binding cells are present in most VTA sub-nuclei but not in its main target, the nucleus accumbens (Acb); (2) systemically injected ghrelin increases food intake but does neither affect locomotor activity nor the levels of the marker of neuronal activation c-Fos in the VTA sub-nuclei; (3) centrally injected ghrelin increases food intake, locomotor activity and c-Fos levels in non-DA neurons of all VTA sub-nuclei; (4) intra-VTA-injected ghrelin increases food intake, locomotor activity and c-Fos levels in non-DA neurons of all VTA sub-nuclei; (5) both centrally and intra-VTA-injected ghrelin increase c-Fos levels in DA neurons of the parabrachial pigmented VTA sub-nucleus. In genetically modified mice in which a subset of GABA neurons expresses the red fluorescent protein tdTomato, we found that centrally injected ghrelin increases c-Fos levels in GABA neurons of the interfascicular VTA sub-nucleus. These results suggest that ghrelin can recruit specific subsets of VTA neurons in order to modulate food intake and locomotor activity. Fil: Cornejo, María Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina Fil: Barrile, Franco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina Fil: de Francesco, Pablo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina Fil: Portiansky, Enrique Leo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina Fil: Reynaldo, Mirta Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina Fil: Perello, Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina

The poisonous eggs of Pomacea canaliculata hardly have any predators. This invasive snail, listed among 100 of the worst invasive species, is a serious crop pest and a vector of human parasitic diseases. Females lay eggs in pink-reddish masses, the colour presumably a warning of their chemical defenses. Egg ingestion alters rodent gastrointestinal tracts and is lethal if injected, but its effect on other taxa is unknown. Here we explored the toxic effects of Pomacea canaliculata eggs on the bullfrog Lithobathes catesbeianus (Anura, Ranidae).Juvenile bullfrogs were gavaged with egg extracts and their digestive tract analyzed after 24 h and 48 h using histological, immunohistochemical and lectin-histochemical techniques. Toxicity was also evaluated by intraperitoneal injection of egg extract.Egg extract ingestion adversely affected the small intestine of the bullfrogs. Short term (24 h) effects included large, reversible changes of the intestinal wall, villi morphology, and changes in the glycosylation patterns of enterocytes. The mucosal area increased and infiltration of inflammatory cells, mainly eosinophils and macrophages, were observed together with a weak hemorrhage. Most of these changes reversed after 48 h. In addition, intraperitoneal injection of egg extract was nontoxic to bullfrog juveniles and no lethality or behavioral changes were observed, a remarkable difference from the effect on rodents.Overall, these results indicate that toxins of apple snail eggs reversibly modify gut morphology, which may alter bullfrog physiology, limiting their ability to absorb egg nutrients. This study extends the known targets of the apple snail egg defenses against predation to amphibians.

Caviomorpha are an exceptional group among rodents due to their extended gestational period and the delivery of precocial offspring. Among them, Lagostomus maximus is characterized by its polyovulation, polyembryony, and the highest embryonic death known in mammals. Its chorioallantoic placenta is hemomonochorial, an ancestral character among rodents. It resembles more the human placenta than the murine models. As in all caviomophs, the chorioallantoic placenta is divided in a main placenta and a subplacenta. The former is organized in labyrinth lobes surrounded by trophospongium, as in most caviomorphs. The giant cells (more numerous than in other caviomorphs) near the decidua could be related to invasiveness. During placentation of L. maximus, uterine natural killer cells are found. These cells have been related to invasiveness and remodeling of blood vessels in Mus musculus and Homo sapiens, although in other caviomorphs are not frequently found. In L. maximus, the placenta develops in all conceptuses (5-6 per uterine horn). Necrosis was observed in each implantation site at day 70 post-coitum, except in that closest to the vagina in each horn. This process of embryo death followed by resorption begins at day 26-30 post-coitum. Recently, we found variations in the percentage of blood vessel and uterine gland areas that could explain the regional differences in embryo survival. The characteristics of the placenta and implantation of L. maximus are important to stablish a unique model for studying placentation as well as early embryonic death, of interest for human and veterinary medicine.

Some years ago, our group reported the presence of the female prostate in all the studied females of the plains viscacha (Lagostomus maximus). The goal of the present study was to characterize and compare the female prostate gland between adult pregnant and non-pregnant plains viscacha using histochemical, lectin-histochemical and immunohistochemical techniques, as well as optic and electron microscopy. Structurally, alveoli are lined by a simple epithelium formed by different cell types: basal cells, secretory cells in different stages of the secretory cycle and cells of clear cytoplasm. Secretory cells are the most abundant cell type, differing between them depending on the quantity and electron-density of their granules. The basal cells are less abundant and are responsible for the renewal of the alveolar epithelium. Likewise, other cells with secretory morphology were found in all the studied females; these have a clear cytoplasm, few granules and mitochondria. It could be considered that they are degranulated secretory cells or that they have partially released their granules. The stroma of the organ is formed by connective tissue and smooth muscle fibers, which are immunohistochemically evidenced against desmin. Histochemical and lectin-histochemical analysis revealed the presence of different glucidic residues in the different cell types. No structural, histochemical, lectin-histochemical, and ultrastructural differences were observed between pregnant and non-pregnant females of plain viscachas, except for the expression of some lectins. The paraurethral gland of Lagostomus maximus can be used as a model for studying the gland in other species since its structural and ultrastructural characteristics do not depend on the hormonal status of the female.

The poisonous eggs ofPomacea canaliculata(Caenogastropoda, Ampullariidae) hardly have any predator. This invasive snail, listed among the 100 worst invasive species, is a serious crop pest and a vector of a human parasitosis. Females lay eggs in pink-reddish masses, presumably as a warning coloration of their chemical defenses. Egg ingestion alters rodents’ gastrointestinal tract and is lethal if injected, but its effect on other taxa is unknown. Here we explored the toxic effects ofPomacea canaliculataeggs on bullfrogLithobathes catesbeianus(Anura, Ranidae).Juvenile bullfrogs were gavaged with egg extracts and their digestive tract analyzed after 24 h and 48 h using histological, immunohistochemical and lectin-histochemical techniques. Toxicity was also evaluated by intraperitoneal injection of eggs extracts.Egg extract ingestion adversely affected small intestine of bullfrogs. Short term (24 h) effects included large, reversible changes of the intestinal wall, villi morphology, and changes in the glycosylation patterns of enterocytes. The mucosal area increased and infiltration of inflammatory cells, mainly eosinophils and macrophages, were observed together with a weak hemorrhage. Most of these changes reversed after 48 h. Besides, intraperitoneal injection of egg extract was nontoxic to bullfrog juveniles and no lethality or behavioral changes were observed, a remarkable difference with egg’ effect on mammals.As a whole, these results indicate that toxins of apple snail eggs reversibly modify gut morphology, which may alter bullfrog physiology limiting their ability to absorb egg nutrients. This study extends the known targets of the apple snail egg defenses against predation to amphibians.

ANALECTA VETERINARIA, órgano oficial de comunicación científica de la Facultad de Ciencias Veterinarias de la Universidad Nacional de La Plata, ya ha cumplido 115 años desde su creación, con el nombre de “Revista de la Facultad de Agronomía y Veterinaria de La Plata”, y 50 años desde la instauración de su actual denominación. Hoy, como antaño, Analecta Veterinaria se compromete con el saber científico en el área de las ciencias veterinarias, sea este correspondiente a conocimientos básicos, como aquellos que se relacionan con las prácticas clínicas, la producción agropecuaria y los alimentos destinados al consumo humano y animal. La pandemia del COVID­19 ha golpeado, en mayor o en menor medida, sobre cada puerta de nuestro planeta y ha cambiado, en poco tiempo, muchos de los aspectos de nuestras vidas. Las prácticas profesionales se han visto reducidas y los laboratorios de investigación prácticamente están cerrados. Ante esta situación, los resultados que se puedan obtener en los próximos meses surgirán, mayoritariamente, del análisis de los datos obtenidos con anterioridad a la declaración de la pandemia o de los que obtengan aquellos grupos beneficiados a través de los subsidios otorgados por organismos gubernamentales o privados para afrontar la situación epidemiológica. A partir de todo evento desafortunado surgen las ideas más brillantes para sobrellevarlo y esta pandemia no está exenta de ese principio. Día a día se leen artículos en revistas científicas que proponen nuevos o antiguos tratamientos para combatir al coronavirus. Con una celeridad nunca antes vista estamos conociendo nuevos aspectos de la enfermedad y diferentes grupos de investigadores de diferentes partes del mundo se aúnan para potenciar sus conocimientos. Sin embargo, es tiempo de ser responsables. Es fundamental que los resultados que se pretendan publicar hayan sido científicamente consolidados bajo las estrictas normas del método científico y los estándares de la ética que la situación requiere. Generar conocimiento científico es un proceso lento y tedioso, el que finalmente requiere del rigor de la aceptación por parte de pares. Desde ANALECTA VETERINARIA instamos a seguir trabajando en beneficio de la ciencia, cada uno en su área específica, dando lo mejor de sí. La pandemia del coronavirus es coyuntural, aún no ha finalizado o su final es incierto, pero nos dejará una enseñanza: debemos estar preparados científicamente para afrontar cualquier situación emergente. Consejo Editorial ANALECTA VETERINARIA

Previously, we have shown that an increased cGMP-activated protein Kinase (PKG) activity after phosphodiesterase 5 (PDE5) inhibition by Sildenafil (SIL), leads to myocardial Na+/H+ exchanger (NHE1) inhibition preserving its basal homeostatic function. Since NHE1 is hyperactive in the hypertrophied myocardium of spontaneous hypertensive rats (SHR), while its inhibition was shown to prevent and revert this pathology, the current study was aimed to evaluate the potential antihypertrophic effect of SIL on adult SHR myocardium. We initially tested the inhibitory capability of SIL on NHE1 in isolated cardiomyocytes of SHR by comparing H+ efflux during the recovery from an acid load. After confirmed that effect, eight-month-old SHR were chronically treated for one month with SIL through drinking water. Compared to their littermate controls, SIL-treated rats presented a decreased NHE1 activity, which correlated with a reduction in its phosphorylation level assigned to activation of a PKG-p38 MAP kinase-PP2A signaling pathway. Moreover, treated animals showed a decreased oxidative stress that appears to be a consequence of a decreased mitochondrial NHE1 phosphorylation. Treated SHR showed a significant reduction in the pro-hypertrophic phosphatase calcineurin, despite slight tendency to decrease hypertrophy was detected. When SIL treatment was prolonged to three months, a significant decrease in myocardial hypertrophy and interstitial fibrosis that correlated with a lower myocardial stiffness was observed. In conclusion, the current study provides evidence concerning the ability of SIL to revert established cardiac hypertrophy in SHR, a clinically relevant animal model that resembles human essential hypertension.

This study reports the histochemistry and the distribution of glycoconjugates (GCs) in the zona pellucida (ZP) of preantral, secondary, tertiary, polyovulatory and atretic follicles of ovaries from non-pregnant (NPr) and pregnant (Pr) females of Lagostomus maximus. GCs were studied using histochemical and lectin histochemical methods. The viscacha ZP was positive to all the histochemical techniques. In addition, it was observed that the intensity of staining of the ZP was constant in the different follicular stages between both female groups. The lectin histochemical study revealed that ZP was positive for certain lectins (WGA, RCA-I and CON-A) and that the labelling did not vary between the different follicular stages, but between the two groups of females. By using both histochemical techniques, it was established that the GCs present in the ZP label the complexity of the area. These results allow us to increase our knowledge on the biology of the viscacha's ovary, particularly contributing to the study of polyovulation. Fil: Acuña, Francisco. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina Fil: Tano de la Hoz, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentina Fil: Díaz, Alcira Ofelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentina Fil: Portiansky, Enrique Leo. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina Fil: Barbeito, Claudio Gustavo. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina Fil: Flamini, Mirta Alicia. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina

Los sarcomas asociados a sitios de inoculación son neoplasias de origen mesenquimático que aparecen en las regiones corporales utilizadas rutinariamente para la aplicación de vacunas u otros inóculos. Con el objetivo de caracterizar estas neoplasias se seleccionaron 117 tumores diagnosticados como sarcomas posinoculación. Se realizaron estudios histopatológicos e inmunohistoquímicos que permitieron reclasificar los diferentes sarcomas hallados y establecer el porcentaje de células proliferantes. Además, se consideraron los datos demográficos y se realizaron encuestas a los médicos veterinarios para conocer la evolución de los pacientes. El diagnóstico más frecuente fue el de fibrosarcoma (87,18%). También, se encontraron, en menor proporción, otros tumores como: sarcomas pleomórficos (HFM), osteosarcomas extraesqueléticos y mixosarcomas. El grado histológico más frecuente fue el II y la mayoría presentó abundante inflamación. El promedio de células proliferantes alcanzó el 50,12%. La edad de los pacientes al momento del diagnóstico fue mayor que la informada por otros autores. Si bien los sarcomas asociados a sitios de inoculación en la República Argentina comparten características histopatológicas y clínicas con aquellos informados en otros países, existen diferencias vinculadas a la edad al momento del diagnóstico, a la presentación de las recidivas y al tiempo de sobrevida, entre otras características., Feline injectionsite sarcomas are neoplasms of mesenchymal origin frequently found in sites of the body routinely used for inoculation of vaccines and other drugs. With the aim of characterizing these neoplasms, 117 postinoculation sarcomas were selected and analyzed. Histopathological and immunohistochemical techniques were performed to reclassify different sarcomas and determine cellular proliferation percentages. In addition, demographic data were considered, and surveys were conducted to obtain information about the clinical followup of patients. Of all tumors analyzed, fibrosarcoma was the most frequently diagnosed (87.18%), followed by pleomorphic sarcomas (HFM), extra skeletal osteosarcomas and mixosarcomas. The most frequent histological grade was type II which was associated with great inflammation. Cell proliferation percentage of these tumors was 50.12%. The average age of diagnosis for these sarcomas was higher than that reported by other authors. Although in Argentina injectionsite sarcomas shared histopathological and clinical characteristics with those reported in other countries, differences such as the age in the moment of diagnosis, recurrence and survival were found., Facultad de Ciencias Veterinarias

Spinal cord injury (SCI) is a common pathological condition that leads to permanent or temporal loss of motor and autonomic functions. Kainic acid (KA), an agonist of kainate receptors, a type of ionotropic glutamate receptor, is widely used to induce experimental neurodegeneration models of CNS. Mesenchymal Stem Cells (MSC) therapy applied at the injured nervous tissue have emerged as a promising therapeutic treatment. Here we used a validated SCI experimental model in which an intraparenchymal injection of KA into the C5 segment of rat spinal cord induced an excitotoxic lesion. Three days later, experimental animals were treated with an intracerebroventricular injection of human umbilical cord (hUC) MSC whereas control group only received saline solution. Sensory and motor skills as well as neuronal and glial reaction of both groups were recorded. Differences in motor behavior, neuronal counting and glial responses were observed between hUC-MSC-treated and untreated rats. According to the obtained results, we suggest that hUC-MSC therapy delivered into the fourth ventricle using the intracerebroventricular via can exert a neuroprotective or neurorestorative effect on KA-injected animals., Facultad de Ciencias Veterinarias

Hypertrophic osteopathy is commonly associated with primary lung neoplasms. It may also be secondary to intrathoracic lesions such as pulmonary metastasis, granulomatous pleurisy and chronic pneumonia, among others. It is characterized by progressive proliferation of sub periosteal bone tissue in limb bones. Clinically, patient usually exhibits lameness. It is a rare disease most frequently observed in dogs among domestic animals. A case of a dog with pulmonary hypertrophic osteopathy associated with pulmonary metastases coming from an appendicular periosteal osteosarcoma is reported., Facultad de Ciencias Veterinarias

Background The impact of cardiac apoptosis in pre-diabetic stages of diabetic cardiomyopathy is unknown. We described that myocytes from fructose-rich diet (FRD) animals exhibit arrhythmias produced by exacerbated Ca2+/calmodulin-protein kinase (CaMKII) activity, ryanodine receptors (RyR2) phosphorylation and sarcoplasmic reticulum (SR) Ca2+ leak. We tested the hypothesis that this mechanism also underlies cardiac apoptosis in pre-diabetes. Methods and Results We generated a pre-diabetic model in mice fed with FRD. FRD-mice showed an increase in oxidative stress, hypertrophy and systolic dysfunction. FRD myocytes exhibited enhanced SR Ca2+ spontaneous events in the absence of SR Ca2+ load alterations vs. control-diet (CD) myocytes. In HEK293 cells, hyperglycemia significantly enhanced [3H]Ryanodine binding and CaMKII phosphorylation of RyR2-S2814 residue vs. normoglycemia. CaMKII-inhibition prevented hyperglycemia-induced alterations. FRD also evoked cardiac apoptosis in WT mice vs. CD-WT mice. Co-treatment with the ROS scavenger Tempol prevented FRD-induced apoptosis in WT-mice. In contrast, FRD enhanced oxidative stress but not apoptosis in FRD-SR-AIP mice, in which a CaMKII inhibitor is targeted to the SR. FRD produced mitochondrial membrane depolarization in WT mice but not in S2814A mice, in which the CaMKII phosphorylation site on RyR2 was ablated. Furthermore, FRD decreased mitochondrial area, mean Feret diameter and mean SR-mitochondrial distance vs. CD-WT hearts. This remodeling was prevented in AC3I mice, with cardiac-targeted CaMKII inhibition. Conclusions CaMKII phosphorylation of RyR2, SR Ca2+ leak and mitochondrial membrane depolarization are critically involved in the apoptotic pathway of pre-diabetic heart. The FRD-induced decrease in SR-mitochondrial distance is likely to additionally favor Ca2+ transit between both organelles. This article is protected by copyright. All rights reserved

Intermediate filaments (IF) can be altered under disorders such as neurodegenerative diseases. Kainic acid (KA) induce behavioral changes and histopathological alterations of the spinal cord of injected rats. Our goal was to evaluate the IF expression in neurons during this injury model. Animals were injected with KA at the C5 segment of the cervical spinal cord and euthanized at 1, 3 and 7 post injection (pi) days. Neuronal cell counting showed a significant loss of neurons at the injection site when compared with those of sham and non-operated animals. Immunohistochemistry for vimentin and neurofilament showed positive labeling of perikarya in sham and KA-injected animals since day 1 pi that lasted for the remaining experimental days. Colocalization analysis between enolase and vimentin or neurofilament confirmed a high index of colocalization in both experimental groups at day 1 pi. This index decreased in sham animals by day 3 pi whereas that of KA-injected animals remained high throughout the experiment. These results may suggest that perikarya initiate an unconventional IF expression, which may respond to the neuronal damage induced by the mechanical injury and the excitotoxic effect of KA. It seems that vimentin and neurofilament expression may be a necessary change to promote recovery of the damaged tissue. Fil: Nishida, Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina Fil: Sisti, María Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina Fil: Zanuzzi, Carolina Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Ciencias Básicas. Cátedra de Histología y Embriología; Argentina Fil: Barbeito, Claudio Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Ciencias Básicas. Cátedra de Histología y Embriología; Argentina Fil: Portiansky, Enrique Leo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina

This study describes the changes observed in the placentas of mice experimentally infected with an abortigenic strain of EHV-1 at mid-pregnancy and euthanized at days 3 and 4 post-infection. We analyzed microscopic vascular alterations, cell proliferation and death by immunohistochemistry, and the expression of IFN-γ, TNF-α and the IL-10 by qPCR and flow cytometry. Infected mice showed slight respiratory signs and ruffled fur during the first two days post-infection. Virus isolation and DNA detection were positive only in the lungs of the infected mice. Vascular congestion, increase in the labyrinth area, and a significant reduction in fetal capillary endothelium surface of infected placentas were found. Cell proliferation was significantly reduced in the infected placentas, whereas the apoptosis was significantly increased. IL10, TNF and IFN-γ showed different expression in the infected placentas and uteri. The effects of EHV-1 during pregnancy depend on different pathogenic mechanisms in which vascular alterations, and cell death and proliferation and local cytokine changes are compromised. Fil: Zanuzzi, Carolina Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Ciencias Básicas. Cátedra de Histología y Embriología; Argentina Fil: Bravi, Maria Emilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Ministerio de Ciencia. Tecnología e Innovación Productiva. Agencia Nacional de Promoción Cientifíca y Tecnológica; Argentina Fil: Scrochi, Mariela Rita. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Ciencias Básicas. Cátedra de Histología y Embriología; Argentina Fil: Nishida, Fabian. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina Fil: Fuentealba, Nadia Analia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina Fil: Diessler, Mónica Elizabeth. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Ciencias Básicas. Cátedra de Histología y Embriología; Argentina Fil: Sguazza, Guillermo Hernán. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina Fil: Muglia, Cecilia Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina Fil: Gimeno, Eduardo Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Portiansky, Enrique Leo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina Fil: Barbeito, Claudio Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Ciencias Básicas. Cátedra de Histología y Embriología; Argentina Fil: Galosi, Cecilia Monica. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina

Herbivores exhibit specializations at the intestinal level that facilitate the bacterial fermentation. The available information on the digestive physiology of Lagostomus maximus makes this rodent an interesting model to evaluate morpho-functional adaptations to herbivory. The general objective of this work was centered on the study of the morphology and histochemistry of the descending colon and rectum of L. maximus. To do so, a comparative analysis of the morphology, ultrastructure and glycosylation pattern of both anatomical regions was carried out. Histochemical results revealed that in both sectors of the large intestine, there are goblet cells with different glycosylation pattern within a morphologically homogeneous cell population. The main difference between both intestinal segments lay in the fact that the most distal region of the large intestine showed a greater proportion of sialomucins, characterized by being slightly O-acetylated. Further specific differences were revealed by lectin histochemistry. These data allowed to perform a functional interpretation of the cell types and secreted substances, thus contributing to a better understanding of the role of mucins in the intestinal tract functioning. Fil: Tano de la Hoz, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentina Fil: Flamini, Mirta Alicia. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina Fil: Portiansky, Enrique Leo. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina Fil: Díaz, Alcira Ofelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina

The plains viscacha is a hystricognathi rodent with special reproductive characteristics. Despite poly-ovulation of 800 oocytes, it generates a high embryonic mortality since from 10 to 12 implantations only one or two offspring are born. The present work analyses the morphological, morphometrical, histochemical and lectinhistochemical characteristics of the uterus and uterine cervix of pregnant and non-pregnant viscacha. Anatomically, the uterus has two horns each one continued with a short cervix devoid of glands. The structure of the uterus is like that of other species; however, the proportion and size of its glands varies according to the physiological state. In viscacha, there is no uterine body and cervices cannot be differentiated externally. The formation of two sack bottoms is determined by the presence of a middle raphe in the cranial portion of the vagina. The so-described anatomy is different from that described in other hystricognathi such as guinea pig and coypu. The cervix presents two microscopically differentiable regions: the endocervix and the ectocervix lined by epithelia with different characteristics. The general characteristics of the uterus of L. maximus do not show specific differences with those of other mammals that might explain its peculiar gestation. Fil: Flamini, Mirta Alicia. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina Fil: Barbeito, Claudio Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina Fil: Portiansky, Enrique Leo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina

Chronic activation of the renin angiotensin system (RAS) favors several cardiac diseases, among which myocardial hypertrophy occupies an outstanding place. In this context, the hyperactivity of the cardiac Na+/H+ (NHE-1) exchanger plays a key role. The pathologic remodeling of the myocardium constitutes an independent risk factor for morbidity and mortality with continuously increasing healthcare cost. Therefore, the development of better therapeutic strategies emerges as highly mandatory. Our goal was to prevent angiotensin II (ANGII)-induced cardiac hypertrophy by NHE-1 gene silencing in Wistar rats. The intramyocardial injection of a lentivirus coding a specific small interference RNA (l-shNHE1) significantly reduced NHE-1 expression exclusively in the heart (~ 50 %) and prevented cardiac remodeling in rats exposed to chronic infusion of ANG II (heart weigh/tibia length: 24,03 ± 0,7915 mg/mm vs 28,45 ± 0,9779 mg/mm and collagen volume fraction 2,526 ± 0,5003 vs 5,982 ± 1,043 in l-shNHE1 + ANGII and ANGII, respectively).Interestingly, this was accompanied by an improvement in cardiac function determined by echocardiography even though blood pressure remained elevated (Fractional shortening 0,5960 ± 0,4228 vs -0,9567± 0,06888 and blood pressure at the end of ANGII treatment 141,2 ± 6,117 mm Hg vs 134,1 ± 6,723 mm Hg ; in l-shNHE1 + ANGII and ANGII, respectively). ANGII infusion increased myocardial NADPH oxidase activity but the l-shNHE1 injection prevented oxidative stressas revealed by the normalization of lipid peroxidation (T-BARS 12,40 ± 2,887.vs 23,05 ± 1,537 in lshNHE1 + ANGII and ANGII, respectively). These results allow as to propose the partial silencing of the cardiac NHE-1 through lentiviralinjection as a promising tool in the prevention of ANGII-induced cardiac hypertrophy. Fil: Medina, Andrés Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina Fil: Pinilla, Oscar Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina Fil: Portiansky, Enrique Leo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina Fil: Caldiz, Claudia Irma. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina Fil: Ennis, Irene Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina

There is currently a crucial need of innovative multifunctional nanoparticles combining, in one formulation, imaging and therapy capacities allowing thus an accurate diagnosis and a therapy monitored by imaging. Multimodal imaging will ensure to speed up diagnosis, and to increase its sensitivity, reliability and specificity for a better management of the disease. Combined with a therapeutic action, it will also enable to treat the disease in a specific personalized manner in feedback mode. The mastered design of such bioprobes as well as the demonstration of their efficiency are still challenges to face in nanomedicine. In this work, novel fluorescent and magnetic core–shell nanocomposites have been designed to ensure, in one nanoformulation, bimodal fluorescence and MRI imaging coupled with therapy by magnetic hyperthermia. They consist in the coating of a magnetic iron oxide (IO) core (ca. 18 nm diameter to ensure magnetic hyperthermia) by an original large pore stellate mesoporous silica (STMS) shell to produce uniform and mono-core magnetic core–shell nanocomposites denoted IO@STMS NPs. To confer fluorescence properties, CdSe/ZnS quantum dots (QDs) NPs were grafted inside the large pores of the IO@STMS nanocomposites. To provide biocompatibility and opsonization-resistance, a tightly-bound human serum albumin (HSA) coating is added around the nanocomposite using an original IBAM-based strategy. Cellular toxicity and non-specific cell–nanomaterial interactions allowed to determine a concentration range for safe application of these NPs. Cellular endosomes containing spontaneously-uptaken NPs displayed strong and photostable QD fluorescence signals while magnetic relaxivity measurements confirm their suitability as contrast agent for MRI. HeLa cell-uptaken NPs exposed to a magnetic field of 100 kHz and 357 Gauss (or 28.5 kA m−1) display an outstanding 65% cell death at a very low iron concentration (1.25 μg Fe mL−1), challenging current magnetic hyperthermia nanosystems. Furthermore, at the particularly demanding conditions of clinical use with low frequency and amplitude field (100 kHz, 117 Gauss or 9.3 kA m−1), magnetic hyperthermia combined with the delivery of a chemotherapeutic drug, doxorubicin, allowed 46% cell death, which neither the drug nor the NPs alone yielded, evidencing thus the synergistic effect of this combined treatment., Facultad de Ciencias Veterinarias, Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas, Instituto de Física La Plata

El análisis de imágenes se define como la ciencia de extracción cuantitativa de datos (numéricos, geométricos, densitométricos y espectrométricos) a partir de las imágenes. Desde el comienzo de los tiempos el hombre ha tratado de clasificar elementos y registrar variaciones para comprender fenómenos físicos, químicos o biológicos. Particularmente, la biología se ha basado en la medición de las formas de los organismos y sus células para comprender los fenómenos evolutivos. Hoy en día, la morfometría permite establecer normas que sirven para comprender los cambios fisiológicos o patológicos observados en estas estructuras. Este libro no pretende ser un compendio de información tecnológica sobre el conocimiento actual del análisis de imágenes. Por el contrario, trata de ser un texto dinámico, dirigido a todas aquellas personas que quieran comenzar a interiorizarse en esta ciencia. En esta segunda edición, corregida y aumentada, el lector encontrará las bases del conocimiento del tema, así como ejemplos de cómo capturar las imágenes, procesarlas, segmentarlas y medirlas, para obtener valores numéricos a ser analizados estadísticamente. En su último capítulo se presentan ejemplos de rutina en el laboratorio que requieren el uso de la morfometría. Estos pueden servir como guía para la iniciación el lector en esta fascinante rama de la ciencia., Facultad de Ciencias Veterinarias

Physical training stimulates the development of physiologic cardiac hypertrophy (CH), being a key event in this process the inhibition of the Na+/H+ exchanger. However, the role of the sodium bicarbonate cotransporter (NBC) has not been explored yet under this circumstance. C57/Bl6 mice were allowed to voluntary exercise (wheel running) for five weeks. Cardiac mass was evaluated by echocardiography and histomorphometry detecting that training promoted the development of physiological CH (heart weight/tibia length ratio, mg/mm: 6.54 ± 0.20 vs 8.81 ± 0.24; interstitial collagen content, %: 3.14 ± 0.63 vs. 1.57 ± 0.27; and cross-sectional area of cardiomyocytes, μm2: 200.6 ± 8.92 vs. 281.9 ± 24.05; sedentary (Sed) and exercised (Ex) mice, respectively). The activity of the electrogenic isoform of the cardiac NBC (NBCe1) was estimated by recording intracellular pH under high potassium concentration and by measuring action potential duration (APD). NBCe1 activity was significantly increased in isolated cardiomyocytes of trained mice. Additionally, the APD was shorter and the alkalization due to high extracellular potassium-induced depolarization was greater in this group, indicating that the NBCe1 was hyperactive. These results are online with the observed myocardial up-regulation of the NBCe1 (Western Blot, %: 100 ± 13.86 vs. 202 ± 29.98; Sed vs. Ex, n = 6 each group). In addition, we detected a reduction in H2O2 production in the myocardium of trained mice. These results support that voluntary training induces the development of physiologic CH with up-regulation of the cardiac NBCe1 in mice. Furthermore, the improvement in the antioxidant capacity contributes to the beneficial cardiovascular consequences of physical training.

Previous work has established that the hormone ghrelin engages the hypothalamic-pituitary-adrenal neuroendocrine axis via activation of corticotropin-releasing factor (CRF) neurons of the hypothalamic paraventricular nucleus (PVN). The neuronal circuitry that mediates this effect of ghrelin is currently unknown. Here, we show that ghrelin-induced activation of PVN CRF neurons involved inhibition of γ-aminobutyric acid (GABA) inputs, likely via ghrelin binding sites that were localized at GABAergic terminals within the PVN. While ghrelin activated PVN CRF neurons in the presence of neuropeptide Y (NPY) receptor antagonists or in arcuate nucleus (ARC)-ablated mice, it failed to do it so in mice with ghrelin receptor expression limited to ARC agouti gene related protein (AgRP)/NPY neurons. These data support the notion that ghrelin activates PVN CRF neurons via inhibition of local GABAergic tone, in an ARC-independent manner. Furthermore, these data suggest that the neuronal circuits mediating ghrelin's orexigenic action vs. its role as a stress signal are anatomically dissociated., Instituto Multidisciplinario de Biología Celular, Laboratorio de Análisis de Imágenes