Cambios morfológicos en la población somatotropa inducidos por terapia génica neonatal con el vector RAd-FTS en ratones nude

Se ha detectado un eje bidireccional timo-pituitario, hallándose receptores de GH en las células epiteliales tímicas. La GH estimularía la secreción de timulina, mientras que los niveles bajos de timulina circulante en período prenatal inducirían hipopituitarismo. El presente estudio tiene por objetivo: implementar una terapia génica mediante el vector adenoviral RAd-FTS en ratones inmunodeficientes, con el fin de prevenir cambios en la población somatotropa

Effect of different immunosuppressive therapies on the lipid pattern in kidney-transplanted rats

We analyzed the effect of oral administration of cyclosporine- methylprednisone (CsA-MP) and sirolimus (SRL) on the lipid pattern of kidney-transplanted rats after a 7-day survival. A significant increase in plasma cholesterol in CsA-MP group (control: 26 ± 3 mg/dl vs. 59 ± 8 mg/dl, P < 0.05) and in triglyceride levels in SRL group (control: 53 ± 4 mg/dl vs. 114 ± 3 mg/dl, P < 0.05), was shown. Kidney microsomal membranes from both treated groups showed that cholesterol and triglyceride values and the relative percentage of arachidonic acid in the total amount of n-6 fatty acids decreased. A diminution of linoleic acid occurred in testis (control: 9.4 ± 0.1 mg/dl vs. CsA-MP: 6.0 ± 0.3 mg/dl and vs. SRL: 6.8 ± 0.2 mg/dl, P < 0.05), liver (control: 17.7 ± 0.6 mg/dl vs. CsA-MP: 15.1 ± 0.6 mg/dl and SRL: 13.5 ± 0.8 mg/dl, P < 0.05) and erythrocyte membranes (control:11.7 ± 0.1% vs. CsA-MP: 10.6 ± 0.2% and SRL: 10.0 ± 0.4%, P < 0.01). The immunosuppressive therapies improved the rejection rate of the graft, fact that was remarkable in the SRL-treated group. However, lipid abnormalities still remain in spite of immunosuppressive therapies. (150).Facultad de Ciencias Médica

Effect of different immunosuppressive therapies on the lipid pattern in kidney-transplanted rats

We analyzed the effect of oral administration of cyclosporine- methylprednisone (CsA-MP) and sirolimus (SRL) on the lipid pattern of kidney-transplanted rats after a 7-day survival. A significant increase in plasma cholesterol in CsA-MP group (control: 26 ± 3 mg/dl vs. 59 ± 8 mg/dl, P < 0.05) and in triglyceride levels in SRL group (control: 53 ± 4 mg/dl vs. 114 ± 3 mg/dl, P < 0.05), was shown. Kidney microsomal membranes from both treated groups showed that cholesterol and triglyceride values and the relative percentage of arachidonic acid in the total amount of n-6 fatty acids decreased. A diminution of linoleic acid occurred in testis (control: 9.4 ± 0.1 mg/dl vs. CsA-MP: 6.0 ± 0.3 mg/dl and vs. SRL: 6.8 ± 0.2 mg/dl, P < 0.05), liver (control: 17.7 ± 0.6 mg/dl vs. CsA-MP: 15.1 ± 0.6 mg/dl and SRL: 13.5 ± 0.8 mg/dl, P < 0.05) and erythrocyte membranes (control:11.7 ± 0.1% vs. CsA-MP: 10.6 ± 0.2% and SRL: 10.0 ± 0.4%, P < 0.01). The immunosuppressive therapies improved the rejection rate of the graft, fact that was remarkable in the SRL-treated group. However, lipid abnormalities still remain in spite of immunosuppressive therapies. (150).Facultad de Ciencias Médica

Impact of transient correction of increased adrenocortical activity in hypothalamo-damaged, hyperadipose female rats

Objective: To explore the effects of transient correction of enhanced corticoadrenal activity in monosodium L-glutamate (MSG)-damaged female rats on peripheral insulin sensitivity and in vitro retroperitoneal (RP) adipocyte function. Designs: A dose of 4 mg/g body weight (BW) of MSG or vehicle (CTR) was i.p. injected, once every 2 days, between days 2 and 10 of age, in female rats. Intact and 21 day-operated (sham or adrenal enucleation (AE)) rats from both (CTR and MSG) groups were used for experimentation on day 120 of age. Circulating levels of several hormones, in basal and after i.v. high-glucose load conditions, and RP adiposity morphology and function were then evaluated. Results: MSG rats developed increased adrenocortical function, hyperadiposity, hyperleptinemia, hyperinsulinemia and decreased peripheral insulin sensitivity. These characteristics were fully reversed after transient correction of corticoadrenal hyperactivity induced by AE. In addition, in vitro experimentation with isolated RP adipocytes indicated that cells from intact MSG animals displayed decreased sensitivity to insulin and dexamethasone stimulation of leptin secretion. Interestingly, adipocyte dysfunction in MSG rats was fully abrogated after AE-induced transient correction of insulinemia, leptinemia and adrenocortical activity. Importantly, the reversion of these metabolic abnormalities, induced by AE for 21 days, in MSG animals did occur, despite no significant changes in BW values. Conclusion: Our results support that the changes in adipocyte characteristics and peripheral insulin resistance, developed in this pseudo-obese female rat model, are mainly due to increased glucocorticoid production. Importantly, appropriate correction of the enhanced adrenocortical activity fully reversed these abnormal functions.Instituto Multidisciplinario de Biología CelularFacultad de Ciencias MédicasFacultad de Ciencias Exacta

Mechanisms involved in the β-cell mass increase induced by chronic sucrose feeding to normal rats

The aim of the present study was to clarify the mechanisms by which a sucrose-rich diet (SRD) produces an increase in the pancreatic β-cell mass in the rat. Normal Wistar rats were fed for 30 weeks either an SRD (SRD rats; 63% wt/wt), or the same diet but with starch instead of sucrose in the same proportion (CD rats). We studied body weight, serum glucose and triacylglycerol levels, endocrine tissue and β-cell mass, β-cell replication rate (proliferating cell nuclear antigen; PCNA), islet neogenesis (cytokeratin immunostaining) and β-cell apoptosis (propidium iodide). Body weight (g) recorded in the SRD rats was significantly (P<0.05) larger than that of the CD group (556.0 ± 8.3 vs 470.0 ± 13.1). Both serum glucose and triacylglycerol levels (mmol/l) were also significantly higher (P<0.05) in SRD than in CD rats (serum glucose, 8.11 ± 0.14 vs 6.62 ± 0.17; triacyglycerol, 1.57 ± 0.18 vs 0.47 ± 0.04). The number of pancreatic islets per unit area increased significantly (P<0.05) in SRD rats (3.29 ± 0.1 vs 2.01 ± 0.2). A significant increment (2.6 times) in the mass of endocrine tissue was detected in SRD animals, mainly due to an increase in the β-cell mass (P=0.0025). The islet cell replication rate, measured as the percentage of PCNA-labelled β cells increased 6.8 times in SRD rats (P<0.03). The number of apoptotic cells in the endocrine pancreas decreased significantly (three times) in the SRD animals (P=0.03). The cytokeratin-positive area did not show significant differences between CD and SRD rats. The increase of β-cell mass induced by SRD was accomplished by an enhanced replication of β cells together with a decrease in the rate of β-cell apoptosis, without any evident participation of islet neogenesis. This pancreatic reaction was unable to maintain serum glucose levels of these rats at the level measured in CD animals.Centro de Endocrinología Experimental y AplicadaFacultad de Ciencias Médica

Mechanisms involved in the β-cell mass increase induced by chronic sucrose feeding to normal rats

The aim of the present study was to clarify the mechanisms by which a sucrose-rich diet (SRD) produces an increase in the pancreatic β-cell mass in the rat. Normal Wistar rats were fed for 30 weeks either an SRD (SRD rats; 63% wt/wt), or the same diet but with starch instead of sucrose in the same proportion (CD rats). We studied body weight, serum glucose and triacylglycerol levels, endocrine tissue and β-cell mass, β-cell replication rate (proliferating cell nuclear antigen; PCNA), islet neogenesis (cytokeratin immunostaining) and β-cell apoptosis (propidium iodide). Body weight (g) recorded in the SRD rats was significantly (P<0.05) larger than that of the CD group (556.0 ± 8.3 vs 470.0 ± 13.1). Both serum glucose and triacylglycerol levels (mmol/l) were also significantly higher (P<0.05) in SRD than in CD rats (serum glucose, 8.11 ± 0.14 vs 6.62 ± 0.17; triacyglycerol, 1.57 ± 0.18 vs 0.47 ± 0.04). The number of pancreatic islets per unit area increased significantly (P<0.05) in SRD rats (3.29 ± 0.1 vs 2.01 ± 0.2). A significant increment (2.6 times) in the mass of endocrine tissue was detected in SRD animals, mainly due to an increase in the β-cell mass (P=0.0025). The islet cell replication rate, measured as the percentage of PCNA-labelled β cells increased 6.8 times in SRD rats (P<0.03). The number of apoptotic cells in the endocrine pancreas decreased significantly (three times) in the SRD animals (P=0.03). The cytokeratin-positive area did not show significant differences between CD and SRD rats. The increase of β-cell mass induced by SRD was accomplished by an enhanced replication of β cells together with a decrease in the rate of β-cell apoptosis, without any evident participation of islet neogenesis. This pancreatic reaction was unable to maintain serum glucose levels of these rats at the level measured in CD animals.Centro de Endocrinología Experimental y AplicadaFacultad de Ciencias Médica

Efectos de la terapia génica con timulina sobre las poblaciones adenohipofisarias en ratones nude

Existe una comunicación bidireccional en el eje timo-pituitario y receptores de hormonas pituitarias en las células epiteliales tímicas. Objetivos: Implementar terapia génica neonatal mediante RAd-FTS (timulina) en ratones inmunodeficientes.Facultad de Ciencias Médica

Cambios morfológicos en la población somatotropa inducidos por terapia génica neonatal con el vector RAd-FTS en ratones nude

Se ha detectado un eje bidireccional timo-pituitario, hallándose receptores de GH en las células epiteliales tímicas. La GH estimularía la secreción de timulina, mientras que los niveles bajos de timulina circulante en período prenatal inducirían hipopituitarismo. El presente estudio tiene por objetivo: implementar una terapia génica mediante el vector adenoviral RAd-FTS en ratones inmunodeficientes, con el fin de prevenir cambios en la población somatotropa.Facultad de Ciencias Médica

Morphological changes induced by insulin-like growth factor-I gene therapy in pituitary cell populations in experimental prolactinomas

In previous studies, we assessed the effects of intrapituitary injection of a recombinant adenoviral vector (RAd) harboring the cDNA for rat insulin-like growth factor type I (RAd-IGF-I) on the lactotrope and somatotrope populations in estrogen-induced prolactinomas. In the present study, we aimed to confirm these findings and further analyze the effect of transgenic RAd-IGF-I on the other pituitary cell populations in female rats. All animals except the intact group (no estrogen and no stereotaxic injection) received subcutaneous estrogen for 30 days, and the groups which received RAd-IGF-I or RAd expressing green fluorescent protein (control) were additionally treated with the appropriate vectors on experimental day 0. The RAd-IGF-I group showed a significant decrease in serum growth hormone and prolactin levels and lactotrope and somatotrope cell size induced by estrogen treatment. Cell density was not affected by 7 days of IGF-I gene therapy. Estrogen had an inhibitory effect on thyrotrope cell density, whereas with RAd-IGF-I there was a nonsignificant trend towards restoration of cell density, without changes in cell size. RAd-IGF-I treatment decreased corticotrope cell size without changing cell density. Estrogen decreased gonadotrope cell size and density, which was reversed by RAd-IGF-I. We conclude that in estrogen-induced pituitary tumors, IGF-I gene therapy has inhibitory effects on the lactotrope, somatotrope and corticotrope populations, while reversing the effect of estrogen on gonadotropic cells.Facultad de Ciencias MédicasInstituto de Investigaciones Bioquímicas de La Plat

Cambios morfológicos en la población somatotropa inducidos por terapia génica neonatal con el vector RAd-FTS en ratones nude

Se ha detectado un eje bidireccional timo-pituitario, hallándose receptores de GH en las células epiteliales tímicas. La GH estimularía la secreción de timulina, mientras que los niveles bajos de timulina circulante en período prenatal inducirían hipopituitarismo. El presente estudio tiene por objetivo: implementar una terapia génica mediante el vector adenoviral RAd-FTS en ratones inmunodeficientes, con el fin de prevenir cambios en la población somatotropa.Facultad de Ciencias Médica