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

Oceanic distribution of inorganic germanium relative to silicon: Germanium discrimination by diatoms

Seventeen inorganic germanium and silicon concentration profiles collected from the Atlantic, southwest Pacific, and Southern oceans are presented. A plot of germanium concentration versus silicon concentration produced a near-linear line with a slope of 0.760 × 10−6 (±0.004) and an intercept of 1.27 (±0.24) pmol L−1 (r2 = 0.993, p < 0.001). When the germanium-to-silicon ratios (Ge/Si) were plotted versus depth and/or silicon concentrations, higher values are observed in surface waters (low in silicon) and decreased with depth (high in silicon). Germanium-to-silicon ratios in diatoms (0.608–1.03 × 10−6) and coupled seawater samples (0.471–7.46 × 10−6) collected from the Southern Ocean are also presented and show clear evidence for Ge/Si fractionation between the water and opal phases. Using a 10 box model (based on PANDORA), Ge/Si fractionation was modeled using three assumptions: (1) no fractionation, (2) fractionation using a constant distribution coefficient (KD) between the water and solid phase, and (3) fractionation simulated using Michaelis-Menten uptake kinetics for germanium and silicon via the silicon uptake system. Model runs indicated that only Ge/Si fractionation based on differences in the Michaelis-Menten uptake kinetics for germanium and silicon can adequately describe the data. The model output using this fractionation process produced a near linear line with a slope of 0.76 × 10−6 and an intercept of 0.92 (±0.28) pmol L−1, thus reflecting the oceanic data set. This result indicates that Ge/Si fractionation in the global ocean occurs as a result of subtle differences in the uptake of germanium and silicon via diatoms in surface waters

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