Stress-Induced Cardiomyopathy

Stress-induced cardiomyopathy is a relatively uncommon syndrome with difficult definition. Cases with transient and reversible left ventricular dysfunction, precipitated by emotional stress and without coronary artery disease, are called takotsubo syndrome, left ventricular apical ballooning, and broken heart syndrome. Many names used to refer to this syndrome are related to the shape of the left ventricle and/or the precipitating factors, but there is not yet a consensus about the proper name. Situations related to physical stress, such as intracranial bleeding, have similar patterns, including the absence of previous cardiac involvement. The increased blood levels of endogenous catecholamine, and increase of myocardial catecholamine in areas with high density of sympathetic innervations, seem to be the mechanisms for myocardial cell necrosis with eosinophilic transverse bands. The localized spasm of the epicardial coronaries, or diffuse microcirculatory dysfunction, is also one of the proposed mechanisms. There are still some areas of controversy that have no definite answer.Facultad de Ciencias Médica

Prognostic utility of ischemic response in functional imaging tests (SPECT or stress echocardiography) in low-risk unstable angina patients

Background: The aim of this study is to determine the ability of ischemic response in imaging stress tests (single-photon emission computed tomography [SPECT] or stress echocardiography [SE]) to predict events in low-risk unstable angina patients. Methods: Three hundred and fifty-nine patients with unstable angina (< 24 h), asymp­tomatic at admission, without ST-segment elevation or depression, normal troponins, and undergoing SPECT (n = 188) or SE (n = 171) during hospitalization (median = 1 day) were included. A positive imaging test (IMAGING+) was defined as the presence of reversible perfusion defects or wall motion abnormalities in at least 2 contiguous segments. Multivariate models were constructed using these results and clinical variables to predict events at 6 months. Results: Ninety-nine (27%) patients had IMAGING+, 72/188 (38%) in SPECT and 27/17 (16%) in SE (p < 0.0001). Events occurred in 84 (23%) patients: 4 had myocardial infarc­tion, 47 new hospitalizations due to angina and 33 coronary artery revascularizations. Inde-pendent predictors of coronary artery disease were: IMAGING+ (OR: 6.4, 95% CI: 3.4–11.8, p < 0.0001), history of coronary artery disease (OR: 2.5, 95% CI: 1.2–5.2, p < 0.02) and TIMI risk (OR: 1.5, 95% CI: 1.1–2.2, p < 0.03). Conclusions: In low-risk unstable angina patients, an ischemic response in functional stress tests (SPECT or SE) was associated with adverse events and severe coronary artery disease

Neonatal thymulin gene therapy prevents ovarian dysgenesis and attenuates reproductive derangements in nude female mice

Congenitally athymic (nude) female mice show severe ovarian dysgenesis after puberty, which seems to be consequential to a number of neuroendocrine derangements described in these mutants. Thus, considerable evidence suggests that thymulin, a thymic peptide, may be involved in thymus-pituitary communication. In order to clarify the relevance of thymulin for the maturation of the female reproductive system, we assessed at hypothalamic, pituitary, ovarian, and uterine level the preventive action of neonatal thymulin gene therapy (NTGT) on the changes that typically occur after puberty in congenitally athymic female mice. We injected (im) an adenoviral vector harboring a synthetic DNA sequence encoding a biologically active analog of thymulin, methionine-serum thymic factor, in newborn nude mice (which are thymulin deficient) and killed the animals at 70-71 d of age. NTGT in the athymic mice restored the serum thymulin levels. Morphometric analysis revealed that athymic nudes have reduced numbers of brain GnRH neurons and pituitary gonadotropic cells as compared with heterozygous controls. NTGT prevented these changes and also rescued the premature ovarian failure phenotype typically observed in athymic nude mice (marked reduction in the number of antral follicles and corpora lutea, increase in atretic follicles). Serum estrogen, but not progesterone, levels were low in athymic nudes, a reduction that was partially prevented by NTGT. Little to no morphological changes were observed in the endometrium of female nudes. The delay in the age of vaginal opening that occurs in athymic nudes was significantly prevented by NTGT. Our results suggest that thymulin plays a relevant physiologic role in the thymus-hypothalamo-pituitary- gonadal axis.Instituto de Investigaciones Bioquímicas de La Plat

Neonatal thymulin gene therapy prevents ovarian dysgenesis and attenuates reproductive derangements in nude female mice

Congenitally athymic (nude) female mice show severe ovarian dysgenesis after puberty, which seems to be consequential to a number of neuroendocrine derangements described in these mutants. Thus, considerable evidence suggests that thymulin, a thymic peptide, may be involved in thymus-pituitary communication. In order to clarify the relevance of thymulin for the maturation of the female reproductive system, we assessed at hypothalamic, pituitary, ovarian, and uterine level the preventive action of neonatal thymulin gene therapy (NTGT) on the changes that typically occur after puberty in congenitally athymic female mice. We injected (im) an adenoviral vector harboring a synthetic DNA sequence encoding a biologically active analog of thymulin, methionine-serum thymic factor, in newborn nude mice (which are thymulin deficient) and killed the animals at 70-71 d of age. NTGT in the athymic mice restored the serum thymulin levels. Morphometric analysis revealed that athymic nudes have reduced numbers of brain GnRH neurons and pituitary gonadotropic cells as compared with heterozygous controls. NTGT prevented these changes and also rescued the premature ovarian failure phenotype typically observed in athymic nude mice (marked reduction in the number of antral follicles and corpora lutea, increase in atretic follicles). Serum estrogen, but not progesterone, levels were low in athymic nudes, a reduction that was partially prevented by NTGT. Little to no morphological changes were observed in the endometrium of female nudes. The delay in the age of vaginal opening that occurs in athymic nudes was significantly prevented by NTGT. Our results suggest that thymulin plays a relevant physiologic role in the thymus-hypothalamo-pituitary- gonadal axis.Instituto de Investigaciones Bioquímicas de La Plat

Estudios de la transferencia génica en células del tejido nervioso por medio de vectores adenovirales asistidos por fuerzas magnéticas

Estamos interesados en desarrollar herramientas biotecnológicas destinadas a una futura prevención y tratamiento de los cambios degradativos normales o patológicos que ocurren en el cerebro durante el envejecimiento, como la pérdida de neuronas dopaminérgicas y colinérgicas, cuyo reflejo clínico son las enfermedades de Parkinson y Alzheimer. Se desea desarrollar estrategias terapéuticas que mimeticen los mecanismos neuroprotectores fisiológicos. Dichas estrategias se basan en la transferencia en distintas regiones del cerebro de la rata senil de genes para moléculas neurotróficas que participen en dichos mecanismos naturales de neuroprotección.Facultad de Ciencias Médica

Estudios de la transferencia génica en células del tejido nervioso por medio de vectores adenovirales asistidos por fuerzas magnéticas

Estamos interesados en desarrollar herramientas biotecnológicas destinadas a una futura prevención y tratamiento de los cambios degradativos normales o patológicos que ocurren en el cerebro durante el envejecimiento, como la pérdida de neuronas dopaminérgicas y colinérgicas, cuyo reflejo clínico son las enfermedades de Parkinson y Alzheimer. Se desea desarrollar estrategias terapéuticas que mimeticen los mecanismos neuroprotectores fisiológicos. Dichas estrategias se basan en la transferencia en distintas regiones del cerebro de la rata senil de genes para moléculas neurotróficas que participen en dichos mecanismos naturales de neuroprotección.Facultad de Ciencias Médica

Estudios de la transferencia génica en células del tejido nervioso por medio de vectores adenovirales asistidos por fuerzas magnéticas

Estamos interesados en desarrollar herramientas biotecnológicas destinadas a una futura prevención y tratamiento de los cambios degradativos normales o patológicos que ocurren en el cerebro durante el envejecimiento, como la pérdida de neuronas dopaminérgicas y colinérgicas, cuyo reflejo clínico son las enfermedades de Parkinson y Alzheimer. Se desea desarrollar estrategias terapéuticas que mimeticen los mecanismos neuroprotectores fisiológicos. Dichas estrategias se basan en la transferencia en distintas regiones del cerebro de la rata senil de genes para moléculas neurotróficas que participen en dichos mecanismos naturales de neuroprotección.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

Neonatal thymulin gene therapy prevents ovarian dysgenesis and attenuates reproductive derangements in nude female mice

Congenitally athymic (nude) female mice show severe ovarian dysgenesis after puberty, which seems to be consequential to a number of neuroendocrine derangements described in these mutants. Thus, considerable evidence suggests that thymulin, a thymic peptide, may be involved in thymus-pituitary communication. In order to clarify the relevance of thymulin for the maturation of the female reproductive system, we assessed at hypothalamic, pituitary, ovarian, and uterine level the preventive action of neonatal thymulin gene therapy (NTGT) on the changes that typically occur after puberty in congenitally athymic female mice. We injected (im) an adenoviral vector harboring a synthetic DNA sequence encoding a biologically active analog of thymulin, methionine-serum thymic factor, in newborn nude mice (which are thymulin deficient) and killed the animals at 70-71 d of age. NTGT in the athymic mice restored the serum thymulin levels. Morphometric analysis revealed that athymic nudes have reduced numbers of brain GnRH neurons and pituitary gonadotropic cells as compared with heterozygous controls. NTGT prevented these changes and also rescued the premature ovarian failure phenotype typically observed in athymic nude mice (marked reduction in the number of antral follicles and corpora lutea, increase in atretic follicles). Serum estrogen, but not progesterone, levels were low in athymic nudes, a reduction that was partially prevented by NTGT. Little to no morphological changes were observed in the endometrium of female nudes. The delay in the age of vaginal opening that occurs in athymic nudes was significantly prevented by NTGT. Our results suggest that thymulin plays a relevant physiologic role in the thymus-hypothalamo-pituitary- gonadal axis.Instituto de Investigaciones Bioquímicas de La Plat

Efectos de la terapia génica con el gen de la timulina sobre la población tirotropa en ratones atímicos

Objetivo: implementar una terapia génica mediante el vector adenoviral: el Rad-FTS en ratones inmunodeficientes (nude) con el fin de prevenir cambios en la población tirotropa.Facultad de Ciencias Médica