Modulation of Rat Skeletal Muscle Branched-Chain α-Keto Acid Dehydrogenase In Vivo Effects of Dietary Protein and Meal Consumption

The effects of dietary protein on the activity of skeletal muscle branched-chain a-keto acid dehydrogenase (BCKAD) were investigated. BCKAD is rate-limiting for branched-chain amino acid (BCAA) catabolism by muscle; its activity is modulated by phosphorylation-dephosphorylation. In rats fed an adequate protein (25% casein) diet, BCKAD was - 2% active postabsorptively and increased to 10% or 16% active after a 25% or 50% protein meal, respectively. Prolonged feeding of a 50% protein diet increased postabsorptive BCKAD activity to 7% with further increases to 40% active postprandially. On a low protein (9% casein) diet BCKAD remained - 2% active regardless of meal-feeding. Dose-dependent activation of BCKAD by intravenous leucine in postabsorptive rats was blunted by a low protein diet. We conclude that excesses of dietary protein enhance the capacity of skeletal muscle to oxidize BCAA, muscle conserves BCAA when protein intake is inadequate, and skeletal muscle may play an important role in whole-body BCAA homeostasis

Novel aspects of the pathogenesis of aneurysms of the abdominal aorta in humans

Aneurysm of the abdominal aorta (AAA) is a particular, specifically localized form of atherothrombosis, providing a unique human model of this disease. The pathogenesis of AAA is characterized by a breakdown of the extracellular matrix due to an excessive proteolytic activity, leading to potential arterial wall rupture. The roles of matrix metalloproteinases and plasmin generation in progression of AAA have been demonstrated both in animal models and in clinical studies. In the present review, we highlight recent studies addressing the role of the haemoglobin-rich, intraluminal thrombus and the adventitial response in the development of human AAA. The intraluminal thrombus exerts its pathogenic effect through platelet activation, fibrin formation, binding of plasminogen and its activators, and trapping of erythrocytes and neutrophils, leading to oxidative and proteolytic injury of the arterial wall. These events occur mainly at the intraluminal thrombus–circulating blood interface, and pathological mediators are conveyed outwards, where they promote matrix degradation of the arterial wall. In response, neo-angiogenesis, phagocytosis by mononuclear cells, and a shift from innate to adaptive immunity in the adventitia are observed. Abdominal aortic aneurysm thus represents an accessible spatiotemporal model of human atherothrombotic progression towards clinical events, the study of which should allow further understanding of its pathogenesis and the translation of pathogenic biological activities into diagnostic and therapeutic applications

Modulation of rat skeletal muscle branched-chain alpha-keto acid dehydrogenase in vivo. Effects of dietary protein and meal consumption.

The effects of dietary protein on the activity of skeletal muscle branched-chain alpha-keto acid dehydrogenase (BCKAD) were investigated. BCKAD is rate-limiting for branched-chain amino acid (BCAA) catabolism by muscle; its activity is modulated by phosphorylation-dephosphorylation. In rats fed an adequate protein (25% casein) diet, BCKAD was approximately 2% active postabsorptively and increased to 10% or 16% active after a 25% or 50% protein meal, respectively. Prolonged feeding of a 50% protein diet increased postabsorptive BCKAD activity to 7% with further increases to 40% active postprandially. On a low protein (9% casein) diet BCKAD remained approximately 2% active regardless of meal-feeding. Dose-dependent activation of BCKAD by intravenous leucine in postabsorptive rats was blunted by a low protein diet. We conclude that excesses of dietary protein enhance the capacity of skeletal muscle to oxidize BCAA, muscle conserves BCAA when protein intake is inadequate, and skeletal muscle may play an important role in whole-body BCAA homeostasis

Does CTAP prior to hepatic resection improve patient survival rates?

The purpose of our study was to compare survival rates of colon carcinoma patients who had undergone attempted curative hepatic resection based on liver staging by computed tomographic angiography (CTA) or portography (CTAP) with previously reported survival rates of patients who underwent similar surgery without preoperative CTAP evaluations. A total of 404 CTAP studies performed at three institutions were reviewed. Of this group, 197 had colon carcinoma. Sixty-nine of the colon patients went to surgery. Actuarial adjusted yearly survival rates were calculated for the prior CTAP colon group and compared to historical controls. The control survival data were taken from reports published prior to the CTAP era. Our study demonstrated no difference in the 1-year survival data between the groups. However, the CTAP patients had greater survival in years 2-4. This greater survival may be multifactorial but in part due to better surgical selection caused by CTAP