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.     

Are calcium and vitamin D supplements for everyone?: Pro

Calcium and vitamin D are essential for the health of our bones and various scientific societies recommend an intake of 1,000 mg of calcium and 800 IU of vitamin D daily. Most people with osteoporosis do not eat food with this amount of calcium and also have insufficient levels of vitamin D, so supplements are recommended to provide osteoporotic patients with these amounts. Calcium supplements and vitamin D improve the effectiveness of anabolic and anti-catabolic agents and may have a small effect in reducing the number of fractures. Calcium supplements alone have not shown efficacy preventing fractures in patients with osteoporosis and may increase cardiovascular risk in healthy elderly women and is therefore not recommended for widespread use. Vitamin D supplements are recommended in persons with 25-OH vitamin D levels below 30 ng/ml, in particular the elderly and osteoporotic patients, due to its ability to halt the remodeling resulting from secondary hyperparathyroidism and reduce the loss of bone mass. Vitamin D supplements could help reduce falls and fractures in the institutionalized elderly. In addition, supplements of vitamin D may have other beneficial effects due to extra-osseous regulatory functions on the immune response and cell differentiation and proliferation that is associated with vitamin D. Trials begun in recent years clearly indicate a beneficial effect of vitamin D supplements on mortality, cardiovascular risk,development of tumors and prevention of infections.     

Osteoblast-osteoclast interaction mechanisms

Bone tissue is constantly renewed by the coordinated action of osteoclasts and osteoblasts. Osteocytes have a prominent role in the onset of bone remodeling at selected sites of the skeleton. These and other osteoblastic cells produce a variety of mediators that modulate the differentiation of osteoclast precursors, a critical step for bone resorption to occur. Among them, M-CSF and RANKL are especially important.     

Stability of continuous renal replacement therapy solutions after phosphate addition: an experimental study

The incidence of hypophosphatemia is high in critically ill children on continuous renal replacement therapy (CRRT) and the addition of phosphate supplements to the replacement and dialysis fluids reduces the frequency of hypophosphatemia. The objective of this study was to determine the in vitro stability of the CRRT solutions after phosphate addition. Three different concentrations of phosphate, 2.5, 4.6 and 7.7 mg/dL, in the replacement and dialysis fluids were analyzed. The pH, glucose, total calcium, phosphate, and magnesium were determined before adding the phosphate and at 2, 24, and 48 h after its addition. The bags were macroscopically observed for possible precipitation. After addition of the phosphate, its concentration remained stable and there were no significant changes in the concentrations of the other components. There were no visible signs of precipitation up to 48 h. The addition of phosphate to the CRRT fluids at concentrations of up to 7.7 mg/dL does not cause problems with precipitation or instability of the mixture.