To refine selection criteria for adult living liver donors and improve donor quality of care, risk factors for poor postdonation health-related quality of life (HRQOL) must be identified. This cross-sectional study examined donors who underwent a right hepatectomy at the University of Toronto between 2000 and 2007 (n = 143), and investigated predictors of (1) physical and mental health postdonation, as well as (2) willingness to participate in the donor process again. Participants completed a standardized HRQOL measure (SF-36) and measures of the pre-and postdonation process. Donor scores on the SF-36 physical and mental health indices were equivalent to, or greater than, population norms. Greater predonation concerns, a psychiatric diagnosis and a graduate degree were associated with lower mental health postdonation whereas older donors reported better mental health. The majority of donors (80%) stated they would donate again but those who perceived that their recipient engaged in risky health behaviors were more hesitant. Prospective donors with risk factors for lower postdonation satisfaction and mental health may require more extensive predonation counseling and postdonation psychosocial follow-up. Risk factors identified in this study should be prospectively evaluated in future research. participate (n = 204). Procedures used by our center to determine donor suitability for right hepatectomy have been reported elsewhere (1). Eleven donors who had been either lost to follow-up (n = 9) or who informed our program that they were doing well and no longer required follow-up (n = 2) were not contacted. Study designThis is a cross-sectional study in which donors who were at least 3 months postdonation were mailed a package of materials that contained a cover letter explaining the study objectives, a consent form and a written questionnaire. Only those measures that were analyzed in this report will be described here. Postdonation questionnaireLiving liver donors completed a one-time comprehensive questionnaire assessing demographics (sex, age, marital status, ethnicity, education, income and employment

Early-life environmental events can induce profound long-lasting changes in several behavioral and neuroendocrine systems. The neonatal handling procedure, which involves repeated brief maternal separations followed by experimental manipulations, reduces stress responses and sexual behavior in adult rats. The purpose of this study was to analyze the effects of neonatal handling on social behaviors of male and female rats in adulthood, as manifest by the results of social memory and social interaction tests. The number of oxytocin (OT) and vasopressin (VP) neurons in the paraventricular (PVN) and supraoptic (SON) nuclei of hypothalamus were also analyzed. The results did not demonstrate impairment of social memory. Notwithstanding, handling did reduce social investigative interaction and increase aggressive behavior in males, but did not do so in females. Furthermore, in both males and females, handling was linked with reduced number of OT-neurons in the parvocellular region of the PVN, while no differences were detected in the magnocellular PVN or the SON. On the other hand, handled males exhibited increased number of VP-neurons in the magnocellular zone of the PVN. We may conclude that the repeated brief maternal separations can reduce affiliative social behavior in adult male rats. Moreover, the disruption of the mother-infant relationship caused by the handling procedure induced long-lasting morphological changes in critical neuroendocrine areas that are involved in social bonding in mammals.

Paulin R, Meloche J, Jacob MH, Bisserier M, Courboulin A, Bonnet S. Dehydroepiandrosterone inhibits the Src/STAT3 constitutive activation in pulmonary arterial hypertension. Am J Physiol Heart Circ Physiol 301: H1798 -H1809, 2011. First published September 2, 2011; doi:10.1152/ajpheart.00654.2011.-Pulmonary arterial hypertension (PAH) is an obstructive vasculopathy characterized by enhanced pulmonary artery smooth muscle cell (PASMC) proliferation and suppressed apoptosis. This phenotype is sustained by the activation of the Src/signal transducer and activator of transcription 3 (STAT3) axis, maintained by a positive feedback loop involving miR-204 and followed by an aberrant expression/activation of its downstream targets such as Pim1 and nuclear factor of activated T-cells (NFATc2). Dehydroepiandrosterone (DHEA) is a steroid hormone shown to reverse vascular remodeling in systemic vessels. Since STAT3 has been described as modulated by DHEA, we hypothesized that DHEA reverses human pulmonary hypertension by inhibiting Src/STAT3 constitutive activation. Using PASMCs isolated from patients with PAH (n ϭ 3), we demonstrated that DHEA decreases both Src and STAT3 activation (Western blot and nuclear translocation assay), resulting in a significant reduction of Pim1, NFATc2 expression/activation (quantitative RT-PCR and Western blot), as well as Survivin and upregulation of bone morphogenetic protein receptor 2 (BMPR2) and miR-204. Src/STAT3 axis inhibition by DHEA is associated with 1) mitochondrial membrane potential (tetramethylrhodamine methyl-ester perchlorate; n ϭ 150; P Ͻ 0.05) depolarization increasing apoptosis by 25% (terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling; n ϭ 150; P Ͻ 0.05); and 2) decreased intracellular Ca 2ϩ concentration (fluo-3 AM; n ϭ 150; P Ͻ 0.05) and proliferation by 30% (PCNA). Finally, in vivo similarly to STAT3 inhibition DHEA improves experimental PAH (monocrotaline rats) by decreasing mean PA pressure and right ventricle hypertrophy. These effects were associated with the inhibition of Src, STAT3, Pim1, NFATc2, and Survivin and the upregulation of BMPR2 and miR-204. We demonstrated that DHEA reverses pulmonary hypertension in part by inhibiting the Src/STAT3.

BackgroundPulmonary arterial hypertension (PAH) is a vascular remodeling disease characterized by enhanced proliferation of pulmonary artery smooth muscle cell (PASMC) and suppressed apoptosis. This phenotype has been associated with the upregulation of the oncoprotein survivin promoting mitochondrial membrane potential hyperpolarization (decreasing apoptosis) and the upregulation of growth factor and cytokines like PDGF, IL-6 and vasoactive agent like endothelin-1 (ET-1) promoting PASMC proliferation. Krüppel-like factor 5 (KLF5), is a zinc-finger-type transcription factor implicated in the regulation of cell differentiation, proliferation, migration and apoptosis. Recent studies have demonstrated the implication of KLF5 in tissue remodeling in cardiovascular diseases, such as atherosclerosis, restenosis, and cardiac hypertrophy. Nonetheless, the implication of KLF5 in pulmonary arterial hypertension (PAH) remains unknown. We hypothesized that KLF5 up-regulation in PAH triggers PASMC proliferation and resistance to apoptosis.Methods and resultsWe showed that KFL5 is upregulated in both human lung biopsies and cultured human PASMC isolated from distal pulmonary arteries from PAH patients compared to controls. Using stimulation experiments, we demonstrated that PDGF, ET-1 and IL-6 trigger KLF-5 activation in control PASMC to a level similar to the one seen in PAH-PASMC. Inhibition of the STAT3 pathway abrogates KLF5 activation in PAH-PASMC. Once activated, KLF5 promotes cyclin B1 upregulation and promotes PASMC proliferation and triggers survivin expression hyperpolarizing mitochondria membrane potential decreasing PASMC ability to undergo apoptosis.ConclusionWe demonstrated for the first time that KLF5 is activated in human PAH and implicated in the pro-proliferative and anti-apoptotic phenotype that characterize PAH-PASMC. We believe that our findings will open new avenues of investigation on the role of KLF5 in PAH and might lead to the identification of new therapeutic targets.

Like cancer, pulmonary arterial hypertension (PAH) is characterised by a proproliferative and anti-apoptotic phenotype. In PAH, pulmonary artery smooth muscle cell (PASMC) proliferation is enhanced and apoptosis suppressed. The sustainability of this phenotype requires the activation of pro-survival transcription factors, such as signal transducer and activator of transcription (STAT)3 and nuclear factor of activated T-cells (NFAT). There are no drugs currently available that are able to efficiently and safely inhibit this axis. We hypothesised that plumbagin (PLB), a natural organic compound known to block STAT3 in cancer cells, would reverse experimental pulmonary hypertension.Using human PAH-PASMC, we demonstrated in vitro that PLB inhibits the activation of the STAT3/NFAT axis, increasing the voltage-gated K + current bone morphogenetic protein receptor type II (BMPR2), and decreasing intracellular Ca 2+ contentration ([Ca 2+ ] i ), rho-associated coiledcoil containing protein kinase (ROCK)1 and interleukin (IL)-6, contributing to the inhibition of PAH-PASMC proliferation and resistance to apoptosis (proliferating cell nuclear antigen (PCNA), TUNEL, Ki67 and anexine V). In vivo, PLB oral administration decreases distal pulmonary artery remodelling, mean pulmonary artery pressure and right ventricular hypertrophy without affecting systemic circulation in both monocrotaline-and sugen/chronic hypoxia-induced PAH in rats.This study demonstrates that the STAT3/NFAT axis can be therapeutically targeted by PLB in human PAH-PASMC and experimental PAH rat models. Thus, PLB could be considered a specific and attractive future therapeutic strategy for PAH.

Objective: to describe sociodemographic and family relationships, health status, depression and degree of functional capacity in institutionalized elderly persons in eleven long-term care facilities for the elderly in the north coastal region of Rio Grande do Sul, Brazil. Methods: a cross-sectional study was carried out of 60 institutionalized elderly persons without cognitive impairment, confirmed by a score greater than 13 in the Mini Mental State Exam. Questionnaires were used to obtain data on sociodemographic conditions, family relationships, and self-perception of health. Functional capacity was evaluated with the Barthel Index and the Geriatric Depression Scale was applied. Results: A predominance of women, widowed and single, with a of low level of education and precarious financial status, most of whom who did not have children, was observed. The elderly persons complained about difficulty walking (38.3%), generalized pain (16.7%) and vision problems (13.3%). The majority (95%) reported suffering from two to three chronic diseases and making daily use of three or more drugs. Although 55% of the participants presented depressive symptoms and morbidity, they reported functional independence and 50% rated their health as good. Conclusions: These data contributed to the knowledge of the health status and functional capacity of these institutionalized elderly persons, aiming to improve the care provided to this public.

Ageing is an inevitable biological process characterized by a general decline in various physiological functions. DHEA and DHEAS levels are maximal between the second and third life decades, then start to decline 2% per year, leaving a residual of 10-20% of the peak production by the eighth decade. Erythrocytes are exposed to frequent oxidative stress due to the oxygen radicals continuously generated by haemoglobin auto-oxidation. We investigated DHEA chronic (10 mg/kg, subcutaneously, for 5 weeks) effects over oxidative stress markers in erythrocytes of male Wistar rats of 3, 13 and 18 month-old. In the 13 month-old group, we found increased lipid peroxidation (LPO), superoxide dismutase (SOD), glutathione-S-transferase and catalase activities when compared to the other age groups. DHEA produced a marked increase in LPO of 13 month-old group when compared to its control. DHEA exerted this pro-oxidant effects in all ages studied, especially in age 13 month-old. It seems that at 13 month-old there would be an important depletion of some specific anti-oxidant in order to determine such susceptibility to DHEA effects. Since this approach allows a minimally invasive assessment, it would be useful as a routine method in human clinical studies investigating DHEA effects during the ageing process.

Low-income pregnant women of Mexican descent were studied to determine whether their food habits could be improved by nutrition education. Biochemical indices of nutritional status were also investigated. Twenty-four-hour dietary recalls were obtained at an initial interview and again at a final interview after a nutrition education program, which was offered to a randomly selected treatment group. At the initial interview, the mean nutrient intakes that were most often below two-thirds of the Recommended Dietary Allowance (RDA) were iron, vitamin A, thiamin, and calcium. The mean energy value of the diets was also frequently below the RDA. At the final intakes, although the mean energy values and the calcium and carbohydrate of both the control and treatment groups increased significantly, the following improvements in dietary intakes were seen only within the treatment group: 1) there were significant increases in the mean intake of protein, ascorbic acid, niacin, riboflavin, and thiamin, 2) there were significant decreases in the percentage of intakes below two-thirds of the RDA for ascorbic acid and riboflavin, and 3) there was a significant decrease in the incidence of multiple low nutrient intakes. These dietary improvements, which occurred only in the treatment group, suggest the effectiveness of the nutrition education program. The most common biochemical deficiencies were of folic acid, thiamin, and riboflavin. Except for an improvement in mean serum folate levels, the biochemical indices for the treatment group did not appear to be influenced by the nutrition education. It is possible that the vitamin and mineral supplements which were taken by 80% of the women could have obscured improvements in biochemical indices which may have been due to the education program.