University of Medicine and Dentistry of New Jersey

About: University of Medicine and Dentistry of New Jersey is a based out in . It is known for research contribution in the topics: Population & Poison control. The organization has 14634 authors who have published 19610 publications receiving 1041794 citations.

Inhibition of endogenous thioredoxin in the heart increases oxidative stress and cardiac hypertrophy

Abstract: Thioredoxin 1 (Trx1) has redox-sensitive cysteine residues and acts as an antioxidant in cells. However, the extent of Trx1 contribution to overall antioxidant mechanisms is unknown in any organs. We generated transgenic mice with cardiac-specific overexpression of a dominant negative (DN) mutant (C32S/C35S) of Trx1 (Tg-DN-Trx1 mice), in which the activity of endogenous Trx was diminished. Markers of oxidative stress were significantly increased in hearts from Tg-DN-Trx1 mice compared with those from nontransgenic (NTg) mice. Tg-DN-Trx1 mice exhibited cardiac hypertrophy with maintained cardiac function at baseline. Intraperitoneal injection of N-2-mercaptopropionyl glycine, an antioxidant, normalized cardiac hypertrophy in Tg-DN-Trx1 mice. Thoracic aortic banding caused greater increases in myocardial oxidative stress and enhanced hypertrophy in Tg-DN-Trx1 compared with NTg mice. In contrast, transgenic mice with cardiac-specific overexpression of wild-type Trx1 did not show cardiac hypertrophy at baseline but exhibited reduced levels of hypertrophy and oxidative stress in response to pressure overload. These results demonstrate that endogenous Trx1 is an essential component of the cellular antioxidant mechanisms and plays a critical role in regulating oxidative stress in the heart in vivo. Furthermore, inhibition of endogenous Trx1 in the heart primarily stimulates hypertrophy, both under basal conditions and in response to pressure overload through redox-sensitive mechanisms.

Summary of the National Demonstration Project and Recommendations for the Patient-Centered Medical Home

Abstract: This article summarizes findings from the National Demonstration Project (NDP) and makes recommendations for policy makers and those implementing patient-centered medical homes (PCMHs) based on these findings and an understanding of diverse efforts to transform primary care. The NDP was launched in June 2006 as the first national test of a particular PCMH model in a diverse sample of 36 family practices, randomized to facilitated or self-directed groups. An independent evaluation team used a multimethod evaluation strategy, analyzing data from direct observation, depth interviews, e-mail streams, medical record audits, and patient and clinical staff surveys. Peer-reviewed manuscripts from the NDP provide answers to 4 key questions: (1) Can the NDP model be built? (2) What does it take to build the NDP model? (3) Does the NDP model make a difference in quality of care? and (4) Can the NDP model be widely disseminated? We find that although it is feasible to transform independent practices into the NDP conceptualization of a PCMH, this transformation requires tremendous effort and motivation, and benefits from external support. Most practices will need additional resources for this magnitude of transformation. Recommendations focus on the need for the PCMH model to continue to evolve, for delivery system reform, and for sufficient resources for implementing personal and practice development plans. In the meantime, we find that much can be done before larger health system reform.

Enhanced autophagy ameliorates cardiac proteinopathy.

Abstract: Basal autophagy is a crucial mechanism in cellular homeostasis, underlying both normal cellular recycling and the clearance of damaged or misfolded proteins, organelles and aggregates. We showed here that enhanced levels of autophagy induced by either autophagic gene overexpression or voluntary exercise ameliorated desmin-related cardiomyopathy (DRC). To increase levels of basal autophagy, we generated an inducible Tg mouse expressing autophagy-related 7 (Atg7), a critical and rate-limiting autophagy protein. Hearts from these mice had enhanced autophagy, but normal morphology and function. We crossed these mice with CryABR120G mice, a model of DRC in which autophagy is significantly attenuated in the heart, to test the functional significance of autophagy activation in a proteotoxic model of heart failure. Sustained Atg7-induced autophagy in the CryABR120G hearts decreased interstitial fibrosis, ameliorated ventricular dysfunction, decreased cardiac hypertrophy, reduced intracellular aggregates and prolonged survival. To determine whether different methods of autophagy upregulation have additive or even synergistic benefits, we subjected the autophagy-deficient CryABR120G mice and the Atg7-crossed CryABR120G mice to voluntary exercise, which also upregulates autophagy. The entire exercised Atg7-crossed CryABR120G cohort survived to 7 months. These findings suggest that activating autophagy may be a viable therapeutic strategy for improving cardiac performance under proteotoxic conditions.