Growth hormone treatment inTurner syndrome: data and reflections

Short stature is the major characteristic of Turner syndrome. The statural appeal is premature and become evident in the puberty. Haploinsuficiency of SHOX gene has been related as main factor on final height of these patients. Despite the majority of the patients are not growth hormone deficient, the GHr therapy improves the final height. Recently, a great number of publications have described the association between GH and cancer. The cancer risk, in these patients, is mainly associated with the presence of Y chromosome sequences that can lead to the gonadoblastoma development. In conclusion, the GHr therapy in ST patients deserves caution. The investigation of Y chromosome sequences should be performed as well as the prophylactic gonadectomy in the positive cases conferring confidence to the treatment.A baixa estatura é a principal característica na síndrome de Turner (ST). O agravo estatural na ST é precoce e torna-se mais evidente na puberdade. A haploinsuficiência do gene SHOX tem sido implicada como principal fator na definição da estatura de mulheres, no entanto, ainda que a maioria das pacientes não tenha deficiência do hormônio de crescimento, a terapia com GHr melhora a altura final. Recentemente, tem-se chamado a atenção para a associação entre GH e câncer. O risco de câncer nessas pacientes está associado à presença de fragmentos do cromossomo Y que pode levar ao desenvolvimento de gonadoblastoma. Dessa forma, a administração de GHr na ST deve ser feita com cautela. A investigação de seqüências do cromossomo Y deve ser realizada, bem como a gonadectomia profilática nos casos positivos, conferindo maior segurança ao tratamento.Universidade Federal de São Paulo (UNIFESP) Departamento de MedicinaUNIFESP Departamento de Morfologia e GenéticaUNIFESP, Depto. de MedicinaUNIFESP, Depto. de Morfologia e GenéticaSciEL

Spin-dependent inertial force and spin current in accelerating systems

The spin-dependent inertial force in an accelerating system under the presence of electromagnetic fields is derived from the generally covariant Dirac equation. Spin currents are evaluated by the force up to the lowest order of the spin-orbit coupling in both ballistic and diffusive regimes. We give an interpretation of the inertial effect of linear acceleration on an electron as an effective electric field and show that mechanical vibration in a high frequency resonator can create a spin current via the spin-orbit interaction augmented by the linear acceleration.Comment: 11 pages,4 figure

Distinction between the Poole-Frenkel and tunneling models of electric field-stimulated carrier emission from deep levels in semiconductors

The enhancement of the emission rate of charge carriers from deep-level defects in electric field is routinely used to determine the charge state of the defects. However, only a limited number of defects can be satisfactorily described by the Poole-Frenkel theory. An electric field dependence different from that expected from the Poole-Frenkel theory has been repeatedly reported in the literature, and no unambiguous identification of the charge state of the defect could be made. In this article, the electric field dependencies of emission of carriers from DX centers in AlxGa1-xAs:Te, Cu pairs in silicon, and Ge:Hg have been studied applying static and terahertz electric fields, and analyzed by using the models of Poole-Frenkel and phonon assisted tunneling. It is shown that phonon assisted tunneling and Poole-Frenkel emission are two competitive mechanisms of enhancement of emission of carriers, and their relative contribution is determined by the charge state of the defect and by the electric-field strength. At high-electric field strengths carrier emission is dominated by tunneling independently of the charge state of the impurity. For neutral impurities, where Poole-Frenkel lowering of the emission barrier does not occur, the phonon assisted tunneling model describes well the experimental data also in the low-field region. For charged impurities the transition from phonon assisted tunneling at high fields to Poole-Frenkel effect at low fields can be traced back. It is suggested that the Poole-Frenkel and tunneling models can be distinguished by plotting logarithm of the emission rate against the square root or against the square of the electric field, respectively. This analysis enables one to unambiguously determine the charge state of a deep-level defect

Hemangiopericytoma in the sacrococcygeal space: a case report

<p>Abstract</p> <p>Introduction</p> <p>A hemangiopericytoma is a rare, soft-tissue tumor of vascular origin derived from a pericyte of Zimmerman, which is a modified smooth muscle cell that surrounds the small blood vessels. Hemangiopericytomas can occur wherever there are vascular capillaries. However, there are no previous reports of a hemangiopericytoma in the sacrococcygeal space.</p> <p>Case presentation</p> <p>We describe the first reported case of a hemangiopericytoma found in the sacrococcygeal space. A 47-year-old Japanese woman presented with a palpable tumor on the left side of her anus. Preoperative imaging indicated that the tumor was in the sacrococcygeal space without invasion of other organs. A complete resection was performed via a parasacral incision. The histological and immunohistochemical staining patterns supported the diagnosis of a hemangiopericytoma.</p> <p>Conclusion</p> <p>A complete resection without piecemeal excision is the best way to treat a hemangiopericytoma. Recognizing the presence of a hemangiopericytoma in the sacrococcygeal space requires appropriate surgery.</p

Human cell dedifferentiation in mesenchymal condensates through controlled autophagy

Tissue and whole organ regeneration is a dramatic biological response to injury that occurs across different plant and animal phyla. It frequently requires the dedifferentiation of mature cells to a condensed mesenchymal blastema, from which replacement tissues develop. Human somatic cells cannot regenerate in this way and differentiation is considered irreversible under normal developmental conditions. Here, we sought to establish in vitro conditions to mimic blastema formation by generating different three-dimensional (3D) condensates of human mesenchymal stromal cells (MSCs). We identified specific 3D growth environments that were sufficient to dedifferentiate aged human MSCs to an early mesendoderm-like state with reversal of age-associated cell hypertrophy and restoration of organized tissue regenerating capacity in vivo. An optimal auophagic response was required to promote cytoplasmic remodeling, mitochondrial regression, and a bioenergetic shift from oxidative phosphorylation to anaerobic metabolism. Our evidence suggests that human cell dedifferentiation can be achieved through autonomously controlled autophagic flux

In vitro epigenetic reprogramming of human cardiac mesenchymal stromal cells into functionally competent cardiovascular precursors

Adult human cardiac mesenchymal-like stromal cells (CStC) represent a relatively accessible cell type useful for therapy. In this light, their conversion into cardiovascular precursors represents a potential successful strategy for cardiac repair. The aim of the present work was to reprogram CStC into functionally competent cardiovascular precursors using epigenetically active small molecules. CStC were exposed to low serum (5% FBS) in the presence of 5 \ub5M all-trans Retinoic Acid (ATRA), 5 \ub5M Phenyl Butyrate (PB), and 200 \ub5M diethylenetriamine/nitric oxide (DETA/NO), to create a novel epigenetically active cocktail (EpiC). Upon treatment the expression of markers typical of cardiac resident stem cells such as c-Kit and MDR-1 were up-regulated, together with the expression of a number of cardiovascular-associated genes including KDR, GATA6, Nkx2.5, GATA4, HCN4, NaV1.5, and \u3b1-MHC. In addition, profiling analysis revealed that a significant number of microRNA involved in cardiomyocyte biology and cell differentiation/proliferation, including miR 133a, 210 and 34a, were up-regulated. Remarkably, almost 45% of EpiC-treated cells exhibited a TTX-sensitive sodium current and, to a lower extent in a few cells, also the pacemaker I(f) current. Mechanistically, the exposure to EpiC treatment introduced global histone modifications, characterized by increased levels of H3K4Me3 and H4K16Ac, as well as reduced H4K20Me3 and H3s10P, a pattern compatible with reduced proliferation and chromatin relaxation. Consistently, ChIP experiments performed with H3K4me3 or H3s10P histone modifications revealed the presence of a specific EpiC-dependent pattern in c-Kit, MDR-1, and Nkx2.5 promoter regions, possibly contributing to their modified expression. Taken together, these data indicate that CStC may be epigenetically reprogrammed to acquire molecular and biological properties associated with competent cardiovascular precursors

Thymosin Beta 4 Prevents Oxidative Stress by Targeting Antioxidant and Anti-Apoptotic Genes in Cardiac Fibroblasts

Thymosin beta-4 (Tβ4) is a ubiquitous protein with diverse functions relating to cell proliferation and differentiation that promotes wound healing and modulates inflammatory responses. The effecter molecules targeted by Tβ4 for cardiac protection remains unknown. The purpose of this study is to determine the molecules targeted by Tβ4 that mediate cardio-protection under oxidative stress.Rat neonatal fibroblasts cells were exposed to hydrogen peroxide (H(2)O(2)) in presence and absence of Tβ4 and expression of antioxidant, apoptotic and pro-fibrotic genes was evaluated by quantitative real-time PCR and western blotting. Reactive oxygen species (ROS) levels were estimated by DCF-DA using fluorescent microscopy and fluorimetry. Selected antioxidant and antiapoptotic genes were silenced by siRNA transfections in cardiac fibroblasts and the effect of Tβ4 on H(2)O(2)-induced profibrotic events was evaluated.Pre-treatment with Tβ4 resulted in reduction of the intracellular ROS levels induced by H(2)O(2) in the cardiac fibroblasts. This was associated with an increased expression of antioxidant enzymes Cu/Zn superoxide dismutase (SOD) and catalase and reduction of Bax/Bcl(2) ratio. Tβ4 treatment reduced the expression of pro-fibrotic genes [connective tissue growth factor (CTGF), collagen type-1 (Col-I) and collagen type-3 (Col-III)] in the cardiac fibroblasts. Silencing of Cu/Zn-SOD and catalase gene triggered apoptotic cell death in the cardiac fibroblasts, which was prevented by treatment with Tβ4.This is the first report that exhibits the targeted molecules modulated by Tβ4 under oxidative stress utilizing the cardiac fibroblasts. Tβ4 treatment prevented the profibrotic gene expression in the in vitro settings. Our findings indicate that Tβ4 selectively targets and upregulates catalase, Cu/Zn-SOD and Bcl(2), thereby, preventing H(2)O(2)-induced profibrotic changes in the myocardium. Further studies are warranted to elucidate the signaling pathways involved in the cardio-protection afforded by Tβ4

Does the disturbance hypothesis explain the biomass increase in basin-wide Amazon forest plot data?

Positive aboveground biomass trends have been reported from old-growth forests across the Amazon basin and hypothesized to reflect a large-scale response to exterior forcing. The result could, however, be an artefact due to a sampling bias induced by the nature of forest growth dynamics. Here, we characterize statistically the disturbance process in Amazon old-growth forests as recorded in 135 forest plots of the RAINFOR network up to 2006, and other independent research programmes, and explore the consequences of sampling artefacts using a data-based stochastic simulator. Over the observed range of annual aboveground biomass losses, standard statistical tests show that the distribution of biomass losses through mortality follow an exponential or near-identical Weibull probability distribution and not a power law as assumed by others. The simulator was parameterized using both an exponential disturbance probability distribution as well as a mixed exponential–power law distribution to account for potential large-scale blowdown events. In both cases, sampling biases turn out to be too small to explain the gains detected by the extended RAINFOR plot network. This result lends further support to the notion that currently observed biomass gains for intact forests across the Amazon are actually occurring over large scales at the current time, presumably as a response to climate change