IMBICE

URI permanente para esta comunidad

https://digital.cic.gba.gob.ar/handle/11746/114
El Instituto Multidisciplinario de Biología Celular aborda la investigación científica de temas de importancia regional y/o nacional en áreas de Medicina Humana, Bioquímica, Genética Humana y Animal y Neurociencias, y forma recursos humanos con un adecuado nivel de conocimientos teóricos y prácticos. En sus instalaciones se esarrollan programas que comprenden distintos proyectos de investigación subsidiados con fondos de Agencias nacionales y del exterior.
Dentro de los programas de investigación se incluye la formación de recursos humanos, el desarrolo temas de Tesis Doctorales y Tesinas a cargo de Becarios del Instituto o Concurrentes a tal fin. En otros casos los trabajos de Tesis constituyen temas independientes que pueden ser dirigidos por Científicos del IMBICE y codirigidos por Profesionales de otros Centros de Investigación, de la Universidad, o de empresas privadas.
Entre los servicios ofrecidos se encuentran el análisis microscópico y de imágenes, cultivos celulares y bancos de células STAN CONICET, servicios técnicos asistenciales a los diferentes Laboratorios de Investigación del IMBICE e investigadores del país que lo requieran, como así también el mantenimiento, preservación y establecimiento de líneas celulares "in vitro" de diferentes tejidos y especies. Estos objetivos derivaron hoy en que sea la colección de líneas celulares establecidas más numerosa del país.

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  • Artículo
    Acceso Abierto
    Actividad antimicrobiana de germicidas halogenados frente a aislamientos hospitalarios
    (2001) Magariños, María del Carmen; Penacca, Alejandra C.; Castelo, Sandra M.; Martínez, Anabela M.; Demartini, Eduardo A.; Landriel, Lorena; Reynaldo, Mirta Beatriz
    Antiseptics and disinfectants are extensively used in hospitals and health care settings for a variety of topical and hard-surface applications. In particular, they are essential part of infection control practices and in the prevention of nosocomial infections. Despite this, few is known about the mode of action of these biocides with respect to antibiotics. In general, the antimicrobial activity can be influenced by many factors such as formulation effects, presence of organic matter, synergy, temperature, dilution and test method. The widespread use of antiseptics and disinfectant products has prompted some speculation on the development of microbial resistance, in particular cross-resistance to antibiotics. The aim of this study was to evaluate microbiological resistance to halogenated compounds by studying the behaviour of the grampositive and gramnegative clinical isolates against halogenated biocides usually applied, with and without organic substance and applying distilled water, potable water and water of 300 ppm hardness as dilution means. The results indicate that the hospital microorganisms show a higher resistance to the biocides than the strain Staphylococcus aureus ATCC 6538, although the effective concentration in clean conditions was lesser than the recommended ones, for all the dilution means. In presence of organic matter the antimicrobial activity was reduced in accordance with the bactericidal concentration of each microorganisrn, due to the oxidant action of these disinfectants
  • Artículo
    Acceso Abierto
    Adolescentes bonaerenses institucionalizados por delitos
    (2016) Wiese, Renata; Catanesi, Cecilia Inés; Folino, Jorge Oscar; Calcena, Eugenio
    Publicaciones de la última década pusieron de manifiesto la escasez de investigación en la provincia de Buenos Aires sobre los adolescentes y sus conductas antisociales . Asimismo, destacaron la necesidad de disponer de instrumentos que permitan evaluar las vulnerabilidades y características sobre las que se pueda intervenir a los efectos de prevenir la persistencia en trayectorias delictuales. Con la meta de contribuir a completar esa información faltante se diseñó una amplia sistemática de evaluación con obtención de información sistematizada de las dimensiones biológica, psicológica y social. En este informe se describen aspectos de las dimensiones psicológica y social.
  • Artículo
    Acceso Abierto
    Alteraciones inducidas por administración neonatal de monosodio L-glutamato (MSG) y su remisión mediante la administración de N-acetil cisteína
    (2016) Villagarcía, Hernán Gonzalo; Castro, María Cecilia; Gonzáles Arbelaez, Luisa; Schinella, Guillermo Raúl; Castrogiovanni, Daniel; Massa, María Laura; Spinedi, Eduardo; Francini, Flavio
    La administración neonatal de monosodio L-glutamato (MSG) a ratas genera daño a nivel de neuronas del núcleo arcuato hipotalámico, lo cual determina en la adultez anormalidades morfológicas, neuroendocrinas y del comportamiento, similares a las observadas en el Síndrome Metabólico (SM) humano. Por otro lado, se reconoce un rol patogénico clave del estrés oxidativo en numerosas enfermedades, incluido el mencionado SM. En consecuencia, el objetivo del presente trabajo fue evaluar los efectos de la administración de N-acetil cisteína (NAC), un reconocido antioxidante, que además promueve el incremento en la síntesis de GSH, sobre las alteraciones ocasionadas por el tratamiento neonatal con MSG.
  • Artículo
    Acceso Abierto
    Asociación entre polimorfismos del gen NAT2 y fisura labiopalatina no sindrómica en Argentina
    (2015) Santos, María Rita; Ramallo, Virginia; Muzzio, Marina; López Camelo, Jorge Santiago; Bailliet, Graciela
    Background: NAT genes are considered candidate genes for the genetic predisposition to non-syndromic Cleft lip with or without cleft palate (NSCLP), since they codify for N-acetyltransferases, enzymes responsible for the biotransformation of arylamines, hydrazine drugs, and a great number of toxins and carcinogens present in diet, cigarette smoke, and environment. Aim: To determine the association between alleles determining slow acetylator phenotype and the risk of NSCLP. Material and methods: We analyzed *5 (481C>T), *6 (590G>A) and *7 (857G>A) alleles which determine the slow acetylator phenotype and *4 (wild type) allele by polymerase chain reaction/restriction fragment length polymorphism in 97 progenitor-case trios of NSCLP in Argentinian Obstetric Wards. We evaluated the transmission disequilibrium (TDT). Results: TDT showed a positive association between allele *5 and NSCLP (odds ratio=1.6; p=0.03). Conclusions: The presence of *5 allele is significantly higher in cases with congenital NSCLP.
  • Artículo
    Acceso Abierto
    Association between a Maternal History of Miscarriages and Birth Defects
    (John Wiley & Sons, 2017) Campaña, Hebe Edith; Rittler, Mónica; Gili, Juan A.; Poletta, Fernando A.; Pawluk, Mariela S.; Giménez, Lucas G.; Cosentino, Viviana R.; Castilla, Eduardo E.; López Camelo, Jorge Santiago
    Some studies, mainly in the older literature, observed a significant association between miscarriages and birth defects (BDs) occurring in the same sibship. However, few studies examined the BD/miscarriage relationship in depth. In addition nothing has been added to the underlying mechanisms possibly linking both events. The purpose of this work was to identify specific BDs associated with maternal miscarriages. In particular it examined whether the risk depended on the number of losses, and it did suggest the existence of specific factors for each BD/miscarriage association observed. Methods: The study relied on the Latin American Collaborative Study on Congenital Malformations (ECLAMC) database registries including 26,906 live and stillborn infants with one out of 19 selected isolated BDs and 93,853 normal controls. Infants born to primigravid mothers were excluded from the present study. Demographic and reproductive variables were compared between control mothers With and Without previous miscarriages. The number, frequency, and distribution of miscarriages were observed for each BD and controls. A conditional logistic regression was computed to evaluate the miscarriage risk for each BD. Results: Control mothers with previous miscarriages were older, had had more pregnancies, and were less educated. Three risk patterns of miscarriages were observed: a very high risk of miscarriages associated with gastroschisis, omphalocele, and talipes; only one miscarriage associated with spina bifida, and two or more miscarriages associated with hypospadias. Conclusion: These three patterns suggest that different factors underly each BD/miscarriage association: infertility for hypospadias, vascular disruption for gastroschisis and talipes, while for spina bifida, the much debated trophoblastic cell residue theory could not be discarded.
  • Artículo
    Acceso Abierto
    Association between PER3 length polymorphism and onco-hematological diseases and its influence on patients functionality
    (PiscoMed Publishing, 2015) Cerliani, María Belén; Gili, Juan Antonio; Pavicic, Walter Hernán; Klein, Graciela; Saba, Silvia; Richard, Silvina Mariel
    Circadian clock gene PER3 and its length polymorphism may have a role in oncogenesis as clock genes act as key regulators of cell cycle and DNA repair pathways. The polymorphism may affect the condition of patients who show disrupted circadian rhythm due to tumor development. The aim was to assess the association between PER3 polymorphism and onco-hematological diseases, and analyze whether this variant has an impact on patient’s functionality. We conducted a case-control study on 125 patients with onco-hematological diseases and 310 control patients. PER3 allelic variants were detected by using polymerase chain reaction. Sociodemographic data and information on patient’s habits and functionality were obtained through questionnaire. Genotypes 4/5 + 5/5 showed an odd ratio (OR) = 1.39, with no statistical significance. However, those genotypes were associated with a two-fold increase in the risk of acute/chronic lymphoblastic/myeloblastic leukemia, taken all together. The occurrence of “changes in humor during last two months” was significantly associated with onco-hematological diseases. “Fatigue on awakening” and “self-reported snore” were associated with cases carrying the 4/5 or 5/5 genotypes. The results suggested that PER3 polymorphism may have a role in the risk of leukemia, and might be a possible marker for individual differences in susceptibility to sleep disruption. This work provides insights for the identification of individuals at high risk of cancer, and those who are more susceptible to circadian disruption, which may decrease the physiological defenses against the tumor.
  • Artículo
    Acceso Abierto
    Brain circuits mediating the orexigenic action of peripheral ghrelin: narrow gates for a vast kingdom
    (2015) Cabral, Agustina; De Francesco, Pablo; Perelló, Mario
    The nervous and endocrine systems act together to regulate all physiological processes essential for the body homeostasis control. Given the strict communication restrictions that the brain–blood barrier (BBB) imposes, the interplay between these two systems requires a variety of delicate anatomical interfaces and physiological mechanisms that guarantee the precise function of the neuroendocrine system as a whole. The study of the mechanisms by which hormones act in the brain in order to regulate specific neuronal populations is a research topic rather neglected. Our group studies the neuronal circuitries and molecular mechanisms by which the stomach-produced hormone ghrelin regulates appetite and other physiological functions. A clear notion of the brain targets of peripheral ghrelin is essential for the comprehensive understanding of the physiological role of this hormone. Ghrelin is called “the hunger hormone” since it is the only known orexigenic peptide hormone. The target for ghrelin orexigenic actions is the brain, which contains a variety of ghrelin-responsive nuclei; however, several evidences suggest that the accessibility of peripheral ghrelin to the brain is strikingly low. Here, we briefly summarize the current knowledge in this topic and discuss this intriguing neuroendocrinological issue.
  • Artículo
    Acceso Abierto
    Characterization and expression analysis of KIT and MITF-M genes in llamas and their relation to white coat color
    (2019) Anello, Melina; Daverio, Maria Silvana; Silbestro, Miguel Osvaldo; Vidal Rioja, Lidia Beatriz; Di Rocco, Florencia
    The llama (Lama glama) is a fiber-producing species that presents a wide range of coat colors, among which white is one of the most important for the textile industry. However, there is little information about the molecular mechanisms that control the white phenotype in this species. In domestic mammals, a white coat is usually produced by mutations in the KIT proto-oncogene receptor tyrosine kinase (KIT) and microphthalmia-associated transcription factor (MITF) genes. In this work we have sequenced and described the coding regions of KIT and MITF-M, the melanocyte-specific isoform, and the two transcriptional variants MITF-M( ) and MITF-M(+). Moreover, we studied the expression of these genes in the skin of white and colored llamas. Although no variants were revealed to be associated with white coat color, significant differences between phenotypes were observed in the expression levels of KIT and MITF-M. Interestingly, white llamas expressed less MITF-M(+) than did colored ones, which is consistent with a consequent reduction in the synthesis of melanin. Even though our results indicate that downregulation of KIT and MITF-M expression is involved in white phenotype production in llamas, the causative gene of white coat color remains unknown.
  • Artículo
    Acceso Abierto
    Characterization of smart auto-degradative hydrogel matrix containing alginate lyase to enhance levofloxacin delivery against bacterial biofilms
    (2015) Islan, G.; Dini, C.; Bartel, L.; Bolzan, Agustín Eduardo; Castro, G.
    The aim of the present work is the characterization of smart auto-degradable microspheres composed of calcium alginate/high methoxylated pectin containing an alginate lyase (AL) fromSphingobacterium multivorumand levofloxacin. Microspheres were prepared by ionotropic gelation containing AL in its inactive form at pH 4.0. Incubation of microspheres in Tris–HCl and PBS buffers at pH 7.40 allowed to establish the effect of ion-chelating phosphate on matrix erodability and suggested an intrinsically activation of AL by turning the pH close to neutrality. Scanning electron and optical microscopies revealed the presence of holes and surface changes in AL containing microspheres. Furthermore, texturometric parameters, DSC profiles and swelling properties were showing strong changes in microspheres properties. Encapsulation of levofloxacin into microspheres containing AL showed 70% efficiency and 35% enhancement of antimicrobial activity againstPseudomonas aeruginosabiofilm. Levofloxacin release from microspheres was not changed at acidic pH, but was modified at neutral pH in presence of AL. Advantageously, only gel matrix debris were detectable after overnight incubation, indicating an autodegradative gel process activated by the pH. Absence of matrix cytotoxicity and a reduction of the levofloxacin toxicity after encapsulation were observed in mammalian CHO-K1 cell cultures. These properties make the system a potent and versatile tool for antibiotic oral delivery targeted to intestine, enhancing the drug bioavailability to eradicate bacterial biofilm and avoiding possible intestinal obstructions.
  • Artículo
    Acceso Abierto
    Chronic Glucocorticoid-Rich Milieu and Liver Dysfunction
    (2016) Villagarcía, Hernán Gonzalo; Sabugo, Vanesa; Castro, María Cecilia; Schinella, Guillermo Raúl; Castrogiovanni, Daniel; Spinedi, Eduardo; Massa, María Laura; Francini, Flavio
    We investigated the impact of chronic hypercorticosteronemia (due to neonatal monosodium L-glutamate, MSG, and treatment) on liver oxidative stress (OS), inflammation, and carbohydrate/lipid metabolism in adult male rats. We evaluated the peripheral concentrations of several metabolic and OS markers and insulin resistance indexes. In liver we assessed (a) OS (GSH and protein carbonyl groups) and inflammatory (IL-1b, TNFa, and PAI-1) biomarkers and (b) carbohydrate and lipid metabolisms. MSG rats displayed degenerated optic nerves, hypophagia, low body and liver weights, and enlarged adipose tissue mass; higher peripheral levels of glucose, triglycerides, insulin, uric acid, leptin, corticosterone, transaminases and TBARS, and peripheral and liver insulin resistance; elevated liver OS, inflammation markers, and glucokinase (mRNA/activity) and fructokinase (mRNA). Additionally, MSG liver phosphofructokinase-2, glucose-6-phosphatase (mRNA and activity) and glucose-6-phosphate dehydrogenase, Chrebp, Srebp1c, fatty acid synthase, and glycerol-3-phosphate (mRNAs)were increased. In conclusion adultMSGrats developed an insulinresistant state and increased OS and serious hepatic dysfunction characterized by inflammation and metabolic signs suggesting increased lipogenesis.These features, shared by both metabolic and Cushing’s syndrome human phenotypes, support that a chronic glucocorticoid-rich endogenous environment mainly impacts on hepatic glucose cycle, displacing local metabolism to lipogenesis. Whether correcting the glucocorticoid-rich environment ameliorates such dysfunctions requires further investigation.
  • Artículo
    Embargado
    Circulating Ghrelin Acts on GABA Neurons of the Area Postrema and Mediates Gastric Emptying in Male Mice
    (2017) Cabral, Agustina; Cornejo, María P.; Fernandez, Gimena; De Francesco, Pablo; Garcia-Romero, Guadalupe; Uriarte, Maia; Zigman, Jeffrey M.; Portiansky, Enrique Leo; Reynaldo, Mirta Beatriz; Perelló, Mario
    Ghrelin is known to act on the area postrema (AP), a sensory circumventricular organ located in the medulla oblongata that regulates a variety of important physiological functions. However, the neuronal targets of ghrelin in the AP and their potential role are currently unknown. In this study, we used wild-type and genetically modified mice to gain insights into the neurons of the AP expressing the ghrelin receptor [growth hormone secretagogue receptor (GHSR)] and their role. We show that circulating ghrelin mainly accesses the AP but not to the adjacent nucleus of the solitary tract. Also, we show that both peripheral administration of ghrelin and fasting induce an increase of c-Fos, a marker of neuronal activation, in GHSR-expressing neurons of the AP, and that GHSR expression is necessary for the fasting-induced activation of AP neurons. Additionally, we show that ghrelin-sensitive neurons of the AP are mainly g-aminobutyric acid (GABA)ergic, and that an intact AP is required for ghrelin-induced gastric emptying. Overall, we show that the capacity of circulating ghrelin to acutely induce gastric emptying in mice requires the integrity of the AP, which contains a population of GABA neurons that are a target of plasma ghrelin.
  • Artículo
    Acceso Abierto
    Constitutive and ghrelin-dependent GHSR1a activation impairs CaV2.1 and CaV2.2 currents in hypothalamic neurons
    (Rockefeller University Press, 2015) López Soto, Eduardo Javier; Agosti, Francina; Cabral, Agustina; Mustafa, Emilio Román; Martínez Damonte, Valentina; Gandini, María Alejandra; Rodriguez, Silvia Susana; Castrogiovanni, Daniel; Felix, Ricardo; Perelló, Mario; Raingo, Jesica
    The growth hormone secretagogue receptor type 1a (GHSR1a) has the highest constitutive activity of any G protein coupled receptor (GPCR). GHSR1a mediates the action of the hormone ghrelin and, its activation increases transcriptional and electrical activity in hypothalamic neurons. It is known that GHSR1a is present at some specific GABAergic presynaptic terminals; however, its impact on neurotransmitter release remains elusive. The voltage gated calcium channels, CaV2.1 and CaV2.2, control neurotransmitter release at presynaptic terminals and their activities are modulated by many GPCRs. Here we show that constitutive as well as agonist-dependent GHSR1a activation trigger a strong impairment of both CaV2.1 and CaV2.2 currents in rat and mouse neurons and in a heterologous expression system. Constitutive GHSR1a activity reduces CaV2 currents by a Gi/o-dependent mechanism that involves persistent reduction in channel density at plasma membrane, whereas, ghrelin-dependent GHSR1a inhibition is reversible and involves altered CaV2 current gating via a Gq-dependent pathway. Thus, we show that GHSR1a differentially inhibits CaV2 channels by Gi/o- or Gq-protein pathways depending on its activation mode. Moreover, we present evidence suggesting that GHSR1a-mediated inhibition of CaV2 impairs GABA release in hypothalamic neurons, a mechanism that could contribute to neuronal activation by the disinhibition of postsynaptic neurons.
  • Artículo
    Acceso Abierto
    Corrosión localizada del acero inoxidable austenítico en medio de cultivo celular y evaluación de la citotoxicidad de los iones liberados
    (2021) Parisi, Julieta Marcia; Castrogiovanni, Daniel; Grau, Jorge Enrique; Gregorutti, Ricardo Walter; Elsner, Cecilia Inés
    El acero inoxidable austenítico ASTM F745 ha sido sometido a corrosión localizada en medio de cultivo celular y solución acuosa de NaCl, cuyas concentraciones de cloruro fueron 4413,2 mg L-1 y 5423,1 mg L-1, respectivamente. Se ha observado que la susceptibilidad a la corrosión localizada fue menor en el medio de cultivo debido a su menor contenido de cloruros. El Fe fue el metal más liberado en ambos medios durante el proceso de corrosión. Las concentraciones fueron 0,570 mg L-1 en la solución acuosa de NaCl y 0,480 mg L-1 en el medio de cultivo. Las concentraciones de Cr y Mo fueron similares en ambos medios, habiendo sido 0,040 mg L-1 y 0,010 mg L-1, respectivamente, mientras que Ni solo se detectó en la solución acuosa de NaCl, 0,100 mg L-1. Estas concentraciones de iones liberados no provocaron efectos citotóxicos en células similares a osteoblastos.
  • Artículo
    Acceso Abierto
    Deleterious Metabolic Effects of High Fructose Intake: The Preventive Effect of Lactobacillus kefiri Administration
    (MDPI (Multidisciplinary Digital Publishing Institute), 2017) Zubiría, Guillermina; Gambaro, Sabrina Eliana; Rey, María Amanda; Carasi, Paula; Serradell, María de los Ángeles; Giovambattista, Andrés
    Modern lifestyle and diets have been associated with metabolic disorders and an imbalance in the normal gut microbiota. Probiotics are widely known for their health beneficial properties targeting the gut microbial ecosystem. The aim of our study was to evaluate the preventive effect of Lactobacillus kefiri (L. kefiri) administration in a fructose-rich diet (FRD) mice model. Mice were provided with tap water or fructose-added (20% w/v) drinking water supplemented or not with L. kefiri. Results showed that probiotic administration prevented weight gain and epidydimal adipose tissue (EAT) expansion, with partial reversion of the adipocyte hypertrophy developed by FRD. Moreover, the probiotic prevented the increase of plasma triglycerides and leptin, together with the liver triglyceride content. Leptin adipocyte secretion was also improved by L. kefiri, being able to respond to an insulin stimulus. Glucose intolerance was partially prevented by L. kefiri treatment (GTT) and local inflammation (TNFα; IL1β; IL6 and INFγ) was completely inhibited in EAT. L. kefiri supplementation generated an impact on gut microbiota composition, changing Bacteroidetes and Firmicutes profiles. Overall, our results indicate that the administration of probiotics prevents the deleterious effects of FRD intake and should therefore be promoted to improve metabolic disorders.
  • Documento de conferencia
    Acceso Abierto
    Desnaturalización de alta resolución para estudio de marcadores moleculares asociados a obesidad
    (2017) Sala, Camila; Alzamendi, Ana; Santos, María Rita; Quintana, Silvina; Bravi, Claudio M.; Bailliet, Graciela
    El objetivo del presente trabajo fue determinar la utilidad de la técnica de “High Resolution Melting” (HRM) como método para identificar variantes en genes asociados al desarrollo de obesidad en niños.
  • Artículo
    Acceso Abierto
    Determinantes sociales adversos y riesgo para anomalías congénitas seleccionadas
    (Sociedad Argentina de Pediatría (SAP), 2014) Pawluk, Mariela S.; Campaña, Hebe Edith; Gili, Juan; Comas, Belén; Giménez, Lucas; Villalba, María I.; Scala, Sandra C.; Poletta, Fernando A.; López Camelo, Jorge Santiago
    Introducción. Diferentes trabajos han relacionando condiciones sociales adversas a nivel familiar y regional con resultados perinatales (mortalidad neonatal, bajo peso y prematuridad); sin embargo, pocos estudiaron el efecto de la pobreza sobre anomalías congénitas. Objetivo. Evaluar el riesgo de ocurrencia de 25 anomalías congénitas y determinantes sociales adversos según el nivel socioeconómico de la familia y de la región. Población y métodos. Estudio caso-control exploratorio, en el que se utilizaron datos del Estudio Colaborativo Latinoamericano de Malformaciones Congénitas (ECLAMC). La muestra consistió en 3786 recién nacidos vivos con una única malformación y 13 344 controles, seleccionados entre 546 129 nacimientos, ocurridos en 39 hospitales de Argentina durante el período 1992-2001. Se estimaron los riesgos (OR) directos, indirectos (a través de la región de residencia) y la interacción entre el nivel socioeconómico individual y residencial para cada uno de los 25 defectos congénitos. Resultados. Los defectos labio leporino con/sin paladar hendido (OR= 1,43) y comunicación interventricular (OR= 1,38) mostraron un riesgo significativamente mayor en el nivel socioeconómico más bajo. Los niveles socioeconómicos bajos se asociaron de manera significativa con una mayor frecuencia de consanguinidad parental, ancestros nativos, edad materna menor de 19 años, más de 4 embarazos, bajo número de visitas prenatales y residencia en regiones desfavorables. Conclusión. La fisura labial con o sin paladar hendido y los defectos del tabique interventricular estuvieron asociados significativamente con un nivel socioeconómico más bajo. La falta de planificación familiar, de control prenatal y la exposición a agentes ambientales o teratógenos pueden explicar estos hallazgos.
  • Artículo
    Acceso Abierto
    Effect of Pioglitazone on the Fructose-Induced Abdominal Adipose Tissue Dysfunction
    (Hindawi Publishing Corporation, 2012) Alzamendi, Ana; Giovambattista, Andrés; Garcia, María Elisa; Rebolledo, Oscar R.; Gagliardino, Juan José; Spinedi, Eduardo
    Aim. To test the potential role of PPARγ in the endocrine abdominal tissue dysfunction induced by feeding normal rats with a fructose rich diet (FRD) during three weeks. Methodology. Adult normal male rats received a standard commercial diet (CD) or FRD, (10% in drinking water) without or with pioglitazone (PIO) (i.p. 0.25mg/Kg BW/day; CD-PIO and FRD-PIO). Thereafter, we measured circulating metabolic, endocrine, and oxidative stress (OS) markers, abdominal adipose tissue (AAT) mass, leptin (LEP) and plasminogen activator inhibitor-1 (PAI-1) tissue content/expression, and leptin release by isolated adipocytes incubated with different concentrations of insulin. Results. Plasma glucose, insulin, triglyceride, TBARS, LEP, and PAI-1 levels were higher in FRD rats; PIO coadministration fully prevented all these increments. AAT adipocytes from FRD rats were larger, secreted a higher amount of LEP, and displayed decreased sensitivity to insulin stimulation; these effects were significantly ameliorated by PIO. Whereas AAT LEP and PAI-1 (mRNA) concentrations increased significantly in FRD rats, those of insulin-receptor-substrate- (IRS-) 1 and IRS-2 were reduced. PIO coadministration prevented FRD effects on LEP, PAI-1, and IRS-2 (fully) and IRS-1 (partially) mRNAs in AAT. Conclusion. PPARγ would play a relevant role in the development of the FRD-induced metabolicendocrine dysfunction.
  • Artículo
    Acceso Abierto
    Escalation in high fat intake in a binge eating model differentially engages dopamine neurons of the ventral tegmental area and requires ghrelin signaling
    (2015) Valdivia Torres, Lesly Spring; Cornejo, María P.; Reynaldo, Mirta Beatriz; De Francesco, Pablo; Perelló, Mario
    Binge eating is a behavior observed in a variety of human eating disorders. Ad libitum fed rodents daily and time-limited exposed to a high-fat diet (HFD) display robust binge eating events that gradually escalate over the initial accesses. Intake escalation is proposed to be part of the transition from a controlled to a compulsive or loss of control behavior. Here, we used a combination of behavioral and neuroanatomical studies in mice daily and time-limited exposed to HFD to determine the neuronal brain targets that are activated – as indicated by the marker of cellular activation c-Fos – under these circumstances. Also, we used pharmacologically or genetically manipulated mice to study the role of orexin or ghrelin signaling, respectively, in the modulation of this behavior. We found that four daily and time-limited accesses to HFD induce: (i) a robust hyperphagia with an escalating profile, (ii) an activation of different sub-populations of the ventral tegmental area dopamine neurons and accumbens neurons that is, in general, more pronounced than the activation observed after a single HFD consumption event, and (iii) an activation of the hypothalamic orexin neurons, although orexin signaling blockage fails to affect escalation of HFD intake. In addition, we found that ghrelin receptor-deficient mice fail to both escalate the HFD consumption over the successive days of exposure and fully induce activation of the mesolimbic pathway in response to HFD consumption. Current data suggest that the escalation in high fat intake during repeated accesses differentially engages dopamine neurons of the ventral tegmental area and requires ghrelin signaling.
  • Tesis de doctorado
    Acceso Abierto
    Estudio de los circuitos neuronales involucrados y del rol modulador de ghrelina en los aspectos hedónicos del apetito
    (2015) Valdivia Torres, Lesly Spring
    La ingesta de alimento es una función vital para el reino animal ya que proporciona las necesidades nutricionales y energéticas. Existen, al menos, dos circuitos neuronales complementarios que la regulan: un circuito relacionado a los aspectos homeostáticos, dependiente de las reservas energéticas; y otro que regula aspectos hedónicos, relacionado con la recompensa que generan alimentos específicos.\nLa ingesta de alimento, además, está fuertemente regulada por señales periféricas, como metabolitos y hormonas, que contribuyen a la regulación precisa de los circuitos neuronales que controlan el apetito. Entre las hormonas que regulan el apetito se destaca la ghrelina, la cual se produce en el tracto digestivo y es la única hormona peptídica conocida capaz de estimular la ingesta de alimento, lo cual ocurriría mediante su acción sobre ambos tipos de mecanismos de regulación. El control de la ingesta de alimento puede sufrir alteraciones que derivan en diversas situaciones patológicas. Una de ellas es el llamado atracón alimentario (binge eating), el cual se observa con alta frecuencia y se define como un evento de hiperfagia en el que se consume una gran cantidad de alimento, en un período corto de tiempo y con la sensación de una pérdida de control de lo que se está consumiendo. Episodios de atracón alimentario se pueden observar en una gran variedad de situaciones patológicas como la bulimia, los desórdenes asociados al atracón alimentario (binge eating disorders) y algunas variantes de anorexia nerviosa, así como también pueden ocurrir en personas con sobrepeso u obesidad, e incluso en la población general. La etiología de los episodios de atracón es actualmente desconocida y, lamentablemente, no existe ningún tratamiento farmacológico para mitigarlos.Por lo tanto, el objetivo general de este trabajo de Tesis Doctoral fue estudiar en modelos murinos los circuitos neuronales activados por uno o varios eventos de ingesta de dieta rica en grasa y evaluar el potencial rol modulador de ghrelina sobre ellos.
  • Documento de conferencia
    Acceso Abierto
    Estudio multidisciplinario de enfermedades crónicas relacionadas a desarreglos en el peso corporal de origen multi factorial y de relevancia regional y nacional
    (2017) Instituto Multidisciplinario de Biología Celular
    La obesidad es un trastorno multifactorial que incluye predisposición genética y la exposición a un ambiente obesogénico. La obesidad infantil ha aumentado drásticamente en los últimos años, lo que representa un problema para la salud pública. El desconocimiento de factores genéticos predictivos sobre la susceptibilidad individual y la falta de biomarcadores para objetivar el estado nutricional de los pacientes dificultan el abordaje médico de esta problemática. A través del proyecto de Fortalecimiento de Centros CIC, se propone hallar biomarcadores hormonales y genéticos que puedan brindar utilidad clínica en pacientes infanto-juveniles con desórdenes del peso corporal. Aún no hemos estudiado muestras de los pacientes ya que aguardamos la aprobación del Comité Institucional de Revisión de Protocolos de Investigación del Hospital de Niños. Entretanto, hemos usado la técnica de High Resolution Melting para analizar en muestras de la Argentina algunas variantes de marcadores genéticos conocidos que han sido previamente asociados a la obesidad en otras poblaciones. Gracias a este estudio ya contamos con las muestras controles a través de las cuales se podrán identificar los genotipos de los pacientes participantes del proyecto. Por otro lado, actualmente estamos trabajando en el desarrollo de métodos de la valoración hormonal y en la caracterización de nuevos marcadores circulantes.