Early alterations in vascular contractility associated to changes in fatty acid composition and oxidative stress markers in perivascular adipose tissue

<p>Abstract</p> <p>Aim</p> <p>To test the early effect of fructose-induced changes in fatty acid composition and oxidative stress markers in perivascular adipose tissue (PVAT) upon vascular contractility.</p> <p>Methods</p> <p>Adult male Wistar rats were fed a commercial diet without (CD) or with 10% fructose (FRD) in the drinking water for 3 weeks. We measured plasma metabolic parameters, lipid composition and oxidative stress markers in aortic PVAT. Vascular contractility was measured in aortic rings sequentially, stimulated with serotonin (5-HT) and high K⁺-induced depolarization using intact and thereafter PVAT-deprived rings.</p> <p>Results</p> <p>Comparable body weights were recorded in both groups. FRD rats had increased plasma triglyceride and fructosamine levels. Their PVAT had an increased saturated to mono- or poly-unsaturated fatty acid ratio, a significant decrease in total superoxide dismutase and glutathione peroxidase activities and in the total content of glutathione. Conversely, lipid peroxidation (TBARS), nitric oxide content, and gluthathione reductase activity were significantly higher, indicating an increase in oxidative stress. In aortic rings, removal of PVAT increased serotonin-induced contractions, but the effect was significantly lower in rings from FRD rats. This effect was no longer observed when the two contractions were performed in PVAT-deprived rings. PVAT did not affect the contractions triggered by high K⁺-induced depolarization either in CD or FRD rats.</p> <p>Conclusions</p> <p>FRD induces multiple metabolic and endocrine systemic alterations which also alter PVAT and the vascular relaxant properties of this tissue. The changes in PVAT would affect its paracrine modulation of vascular function.</p

Valor del índice de resistencia arterial medido por Doppler en la función del injerto renal a mediano y largo plazos

Objective: To evaluate the association between the value of the arterial resistance index (RI) measured by Doppler at the month after transplantation, and the loss of graft. Secondary outcomes of loss greater than or equal to 50% of renal function, eath with functioning graft, biopsy findings (inflammation, hyalinosis, rejection, interstitial fibrosis - tubular atrophy, IFTA) are reported. Methods: A cohort study of 66 patients, who underwent renal transplantation at San José Hospital of Bogotá between October 2007 and April 2011. The RI of the hilar artery was measured by Doppler ultrasound at the month post-transplant. Most patients had follow-up until the second year. We describe the cumulative incidence of renal graft loss, loss greater than or equal to 50% of the glomerular filtration rate. At the second year after transplantation, rejection, IFTA, hyalinosis and documented inflammation were reported in protocol biopsies. Association analysis was performed on the histological outcomes. Results: only 2 cases of renal graft loss were reported, belonging to the group with normal RI (3.8%). At 3 years of follow-up, 5 patients had lost more than 50% of GFR compared to baseline, 4 occurred in patients with RI &lt;0.8, 2 of them (3.7%) ocurred in the first year and only one patient with RI&gt; 0.8 ocurred at 3 years. The median GFR at 3 years of follow-up in both groups is greater than 60 ml / min. In the first year of follow-up 22 (47%) patients with normal RI had IFTA, and 7 (54%) with RI&gt; 0.8 had IFTA. Hyalinosis was reported for 23% with RI&gt; 0.8 and 25.5% with RI &lt;0.8. Conclusion: the outcome of the grafts depends not only on RI, but also on factors such as cold ischemia, induction and maintenance immunosuppressive treatment, degree of incompatibility between donor and recipient. Histopathological changes such as IFTA, inflammation, hyalinosis, were observed in both groups, suggesting that there are other factors stronger than the RI, which correlates with the occurrence of these findings.Objetivo: evaluar la asociación entre el valor del índice de resistencia arterial (IR) medido por doppler al&nbsp;mes postrasplante y la pérdida de injerto. Se reportan los desenlaces secundarios de pérdida mayor o igual&nbsp;al 50% de la función renal, muerte con injerto funcionante, hallazgos de la biopsia (inflamación, hialinosis,&nbsp;rechazo, fibrosis intersticial - atrofia tubular, IFTA, por sus siglas en inglés). Métodos: se realizó un estudio de cohorte de 66 pacientes, que recibieron trasplante renal, del Hospital San José de Bogotá, entre octubre de 2007 y abril de 2011; se midió el IR de la arteria hilar por ecografía doppler al mes postrasplante. La mayoría de los pacientes fueron seguidos hasta el segundo año. Se describe la incidencia acumulada de pérdida del injerto renal, pérdida mayor o igual al 50% de la tasa filtración glomerular; al segundo año postrasplante se reporta el rechazo, IFTA, hialinosis e inflamación documentada en las biopsias de protocolo. Se realizó análisis de asociación en los desenlaces histológicos. Resultados: solo se reportaron 2 casos de pérdida del injerto renal, pertenecientes al grupo con IR normal (3.8%). A los 3 años de seguimiento 5 pacientes habían perdido más del 50% de la TFG respecto a la basal, 4 ocurrieron en los pacientes con IR &lt;0.8, 2 de ellos (3.7%) fueron al primer año y solo un paciente con IR &gt;0.8 a los 3 años. La mediana de la TFG a los 3 años de seguimiento en ambos grupos es mayor de 60 ml/ min. En el primer año de seguimiento 22 (47%) pacientes con IR normal presentaron IFTA y 7 (54%) con IR &gt;0.8 presentaron IFTA; la hialinosis con un 23% para IR &gt;0.8 y 25.5% para IR &lt;0.8. Conclusión: los desenlaces de los injertos no solo dependen del IR, hay otros factores que pueden influir como es el tiempo de isquemia fría, esquema de tratamiento inmunosupresor de inducción y mantenimiento, grado de incompatibilidades entre donante, receptor. Cambios histopatológicos como IFTA, inflamación, hialinosis, se observaron en cualquiera de los 2 grupos, lo que sugiere que hay otros factores más fuertes que el IR, que se correlaciona con la aparición de estos hallazgos

Intracellular amyloid formation in muscle cells of Aβ-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification

Background: The amyloid β-peptide is a ubiquitous peptide, which is prone to aggregate forming soluble toxic oligomers and insoluble less-toxic aggregates. The intrinsic and external/environmental factors that determine Aβ aggregation in vivo are poorly understood, as well as the cellular meaning of this process itself. Genetic data as well as cell biological and biochemical evidence strongly support the hypothesis that Aβ is a major player in the onset and development of Alzheimer's disease. In addition, it is also known that Aβ is involved in Inclusion Body Myositis, a common myopathy of the elderly in which the peptide accumulates intracellularly. Results: In the present work, we found that intracellular Aβ aggregation in muscle cells of Caenorhabditis elegans overexpressing Aβ peptide is affected by two single amino acid substitutions, E22G (Arctic) and V18A (NIC). Both variations show decrease intracellular amyloidogenesis compared to wild type Aβ. We show that intracellular amyloid aggregation of wild type Aβ is accelerated by Cu2+ and diminished by copper chelators. Moreover, we demonstrate through toxicity and behavioral assays that Aβ-transgenic worms display a higher tolerance to Cu2+ toxic effects and that this resistance may be linked to the formation of amyloid aggregates. Conclusion: Our data show that intracellular Aβ amyloid aggregates may trap excess of free Cu2+ buffering its cytotoxic effects and that accelerated intracellular Aβ aggregation may be part of a cell protective mechanism

Resultados clínicos en receptores de trasplante renal posterior a la conversión a ImTOR

Introducción: los ImTOR, sirolimus y everolimus son una alternativa de inmunosupresión en personas que han recibido transplantes rena-les. En este artículo, se describe la experiencia de pacientes que han experimentado una conversión a ImTOR, y a los que se les ha hecho un seguimiento por más de cinco años.Materiales y métodos: se incluyeron pacientes con transplantes renales desde 1995 hasta 2013, quienes tuvieron indicación de suspensión del inhibidor de calcineurina (ICN) después del tercer mes posterior al trasplante. Todos los pacientes fueron sometidos a biopsia renal antes de la administración de ImTOR. Ningún paciente tuvo diagnóstico de nefropatía crónica, IFTA >40 % o proteinuria >350 mg/24h. Se elaboró un análisis descriptivo para todas las variables. Para estudiar la supervivencia del paciente y del injerto, y la incidencia de rechazo agudo, se usó el método de Kaplan-Meier.Resultados: de 1273 trasplantes renales, la conversión de ICN a ImTOR se realizó en 166 casos (13 %). Al 78 % (n=129) se le administró sirolimus. El 13 % de los pacientes perdió la función del injerto y 7 pacientes (4,2 %) fallecieron. En el 37 % de los casos, se retiró el ImTOR. La principal causa de retiro fue el hallazgo de proteinuria patológica. La incidencia de rechazo agudo después del cambio a ImTOR fue de 9,6 %. La supervivencia del injerto tras uno y cinco años fue de 96,6 % y 83,5 %, respectivamente; y la supervivencia del paciente a uno y cinco años fue de 98 % y 97 %, respectivamente.Conclusiones: el uso de inhibidores ImTOR parece ser seguro en este grupo de pacientes trasplantados, pues hubo una baja tasa de rechazo y buena supervivencia del injert

Enforcing market -based environmental policies

The market-based approach to controlling industrial pollution is a major innovation in environmental policy, and is rapidly gaining support among policy makers. It is likely that environmental quality standards can be achieved at much lower cost with market-based policies than with traditional command-and-control regulations because they provide sources of pollution more flexibility and greater incentives to find and implement cost-effective ways to control their emissions. However, a key component of market-based systems has not been adequately addressed; namely, how they should be enforced to achieve acceptable levels of compliance. This dissertation extends the theoretical analysis of compliance and enforcement in market-based environmental policies, focusing primarily on developing practical guidelines for the design of appropriate enforcement strategies. After a description of the structural design and enforcement strategies being pursued in two major U.S. market-based systems, three theoretical models are developed. Each of the models assumes that the enforcement objective is to achieve complete compliance to a transferable emissions permit system (each firm holds enough permits to cover its emissions) in a cost-effective manner. In addition, each of the models assumes that firms in a market-based control system are required to provide reports of their emissions to an enforcement authority. The first model of this dissertation assumes that regulated sources of pollution operate under a perfectly competitive transferable permit system. The model allows the development of a number of practical guidelines for enforcing competitive market-based policies that are focused primarily on the use and value of self-reporting, the value of firm-specific information to an enforcer, the desirability of targeted monitoring, and guidelines for setting penalties. The second and third models of this dissertation reconsider the design of effective enforcement strategies when certain market imperfections exist. Specifically, the second model considers the consequences of transaction costs on enforcing transferable emissions permit system. Finally, the third model considers enforcement design when a firm can exercise price-setting power in a market-based system