Calpain inhibition attenuates angiotensin II-induced abdominal aortic aneurysms and atherosclerosis in low-density lipoprotein receptor-deficient mice

Chronic infusion of angiotensin II (AngII) augments atherosclerosis and abdominal aortic aneurysm (AAA) formation in hypercholesterolemic mice. AngII-induced AAAs are associated with medial macrophage accumulation and matrix metalloproteinase (MMP) activation. Inhibition of calpain, a calcium-activated neutral cysteine protease, by overexpression of its endogenous inhibitor, calpastatin, attenuates AngII-induced leukocyte infiltration, perivascular inflammation, and MMP activation in mice. The purpose of this study was to define whether pharmacological inhibition of calpain influences AngII-induced AAAs in hypercholesterolemic mice. Male low-density lipoprotein receptor-/- mice were fed a fat-enriched diet and administered with either vehicle or a calpain-specific inhibitor, BDA-410 (30 mg/kg per day) for 5 weeks. After 1 week of feeding, mice were infused with AngII (1000 ng/kg per minute) for 4 weeks. AngII-infusion profoundly increased aortic calpain protein and activity. BDA-410 administration had no effect on plasma cholesterol concentrations or AngII-increased systolic blood pressure. Calpain inhibition significantly attenuated AngII-induced AAA formation and atherosclerosis development. BDA-410 administration attenuated activation of MMP12, proinflammatory cytokines (IL-6, monocyte chemoattractant protein-1), and macrophage infiltration into the aorta. BDA-410 administration significantly attenuated thioglycolate-elicited macrophage accumulation in the peritoneal cavity. We conclude that calpain inhibition using BDA-410 attenuated AngII-induced AAA formation and atherosclerosis development in low-density lipoprotein receptor-/- mice.     

药用植物抗肝毒性的最新研究进展

肝脏损害是由于微循环障碍、肝细胞变性坏死而引起的肝功能异常,它影响到几乎每个年龄段人群肝脏细胞的重要生物活性,而常规用药来抑制肝脏损害是远远不够的。而且,由于对抗疗法所用药物往往具有肝毒性,反而加剧了肝脏功能的紊乱。为了寻找安全有效的替代药物,人们逐渐把目光转向了具有保肝作用的药用植物,并对其进行系统性的方法学研究和药用原理评估。药用植物治疗肝病具有悠久的历史,最早可追溯到公元前2100年的中国夏朝和古印度吠陀时期,但是能证明那个时期药用植物有效治疗肝病的证据却很难寻觅。本文旨在系统性地概述现今在临床治疗和实验研究中最常用以及最有效的保肝类药用植物。     

Strategies to reduce attrition in weight loss interventions: A systematic review and meta‐analysis

The primary objective of the study was to identify the effect of intervention strategies on attrition within a weight loss programme among adults aged 18 to 65 years. The secondary objective of the study was to assess the impact of such intervention strategies among female‐only weight loss programmes. The literature search was performed in Ovid (CINAHL Plus, MEDLINE, EMBASE, Cochrane [Cochrane Database of Reviews, Cochrane Central Register of Controlled Trials, and Cochrane Methodology Register], and PsycINFO). Studies must have identified weight loss as the main aim and compared the primary weight loss programme alone (control) with the primary weight loss programme coupled with an additional intervention strategy (intervention). Papers must have had a mean participant age between 18 and 65 years and available in English. Fifty‐seven trials met the inclusion criteria and were included in the meta‐analysis. Strategies that successfully reduced attrition included the incorporation of financial incentives (n = 8), a multicomponent approach (n = 13), and use of self‐monitoring technology (n = 4). The majority of studies were of low to moderate methodological quality because of insufficient reporting. A limited number of female‐only trials were found (n = 13). Implementation of financial incentives, multicomponent interventions, and self‐monitoring technology help reduce attrition among adult weight loss programmes. Further studies are required to identify the impact of intervention strategies on attrition in women.     

Clinical and biochemical characteristics and the association of angiotensin type 1 receptor with normoalbuminuric chronic kidney disease among South Indian type 2 diabetes population

International Journal of Diabetes in Developing Countries - The aim of the study was to determine the clinical and biochemical characteristics especially cystatin C and the association of...     

Adrenocortical carcinoma: the range of appearances on CT and MRI

OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare, aggressive tumor arising from the adrenal cortex that typically presents late with a large mass. The increased use of cross-sectional imaging for unrelated reasons has led to a greater number of ACCs being detected incidentally at an earlier stage. Recognition of the typical clinical, biochemical, and imaging findings is imperative for rapid diagnosis, prompt intervention, and early use of the appropriate therapy. CONCLUSION: Cross-sectional imaging with CT and MRI is essential for determining the extent of local and distant tumor spread. Complete surgical resection is currently the only potentially curative treatment of ACC, and the information attained from CT and MRI is important to guide surgery and further patient management.     

Adenosine receptor subtype expression and activation influence the differentiation of mesenchymal stem cells to osteoblasts and adipocytes

Osteoblasts and adipocytes differentiate from a common precursor cell, the mesenchymal stem cell (MSC). Adenosine is known to signal via four adenosine receptor subtypes, and significantly, recent findings indicate that these may play a role in MSC differentiation. We therefore investigated adenosine receptor expression and activation during the differentiation of MSCs to osteoblasts and adipocytes. The A_2BR was dominant in MSCs, and its expression and activity were transiently upregulated at early stages of osteoblastic differentiation. Both activation and overexpression of A_2BR induced the expression of osteoblast‐related genes [Runx2 and alkaline phosphatase (ALP)], as well as ALP activity, and stimulation increased osteoblast mineralization. The expression of A_2AR was upregulated during later stages of osteoblastic differentiation, when its activation stimulated ALP activity. Differentiation of MSCs to adipocytes was accompanied by significant increases in A₁R and A_2AR expression, and their activation was associated with increased adipogenesis. Enhanced A_2AR expression was sufficient to promote expression of adipocyte‐related genes (PPARγ and C/EBPα), and its activation resulted in increased adipocytic differentiation and lipid accumulation. In contrast, the A₁R was involved mainly in lipogenic activity of adipocytes rather than in their differentiation. These results show that adenosine receptors are differentially expressed and involved in lineage‐specific differentiation of MSCs. We conclude, therefore, that fruitful strategies for treating diseases associated with an imbalance in the differentiation and function of these lineages should include targeting adenosine receptor signal pathways. Specifically, these research avenues will be useful in preventing or treating conditions with insufficient bone or excessive adipocyte formation. © 2011 American Society for Bone and Mineral Research