Allopurinol Reduces the Lethality Associated with Acute Renal Failure Induced by Crotalus durissus terrificus Snake Venom: Comparison with Probenecid

In Brazil, among registered snake bites, those by the genus Crotalus originate the highest mortality rate. The rattlesnake Crotalus durissus terrificus is the most frequently implicated in these accidents. The kidney is a particularly vulnerable organ to the venom of this rattlesnake. In fact, the most serious complication of Crotalus snake bite is the renal dysfunction, and among the fatal cases of Crotalus bites in Brazil 5% are patients treated with antivenom. The hyperuricemia has been observed in human accidents with snake venoms, but this parameter has not received any special attention as a relevant factor in the etiology of renal dysfunction caused by these venoms. This study examined the effects of treatments with low-cost and low-risk uricostatic (allopurinol) and uricosuric (probenecid) drugs on the envenomation by C. d. terrificus, showing that allopurinol and probenecid mitigated certain nephrotoxic effects, as well as the survival of envenomed mice was improved through the effects of allopurinol on reduction of oxidative stress and intracellular formation of uric acid. This new knowledge provides consistent evidences linking uric acid with the renal dysfunction induced by rattlesnake bites and that the allopurinol deserves to be clinically evaluated as an approach complementary to anti-snake venom serotherapy

Osteoprotegerin (OPG) produced by bone marrow stromal cells protects breast cancer cells from TRAIL-induced apoptosis

Advanced breast cancer is often associated with metastatic bone disease, causing a number of serious complications for the patients such as hypercalceamia, pain, nerve compression and fractures. The formation of bone metastases depends on complex interactions between tumour cells and the cells of the bone microenvironment, but the precise molecular mechanisms involved in the development of tumour-induced bone disease have not been identified. We have investigated the ability of bone marrow stromal cells (BMSC) isolated from breast cancer patients to generate osteoprotegerin (OPG), a molecule involved both in bone turnover and cell survival. The potential survival effects of OPG are mediated through binding to a member of the TNF super family, TNF-related Apoptosis Inducing Ligand (TRAIL), preventing association between TRAIL and its death-inducing receptors present on a number of tumour cell types. In the present report we show that bone marrow stromal cells isolated from breast cancer patients produce OPG when grown in culture. The levels of OPG present in BMSC conditioned medium is sufficient to protect breast cancer cells from undergoing TRAIL induced apoptosis. Our data suggest that bone-derived OPG may increase survival of breast cancer cells that reach the bone microenvironment as part of the metastatic process

Low serum osteoprotegerin levels in normoalbuminuric type 1 diabetes mellitus

“The original publication is available at www.springerlink.com”. Copyright Springer [Full text of this article is not available in the UHRA]The aim of this study is to establish whether abnormal mineral metabolism is present in patients with type 1 DM with normal renal function and in the absence of microalbuminuria. Serum levels of 1,25-dihydroxyvitamin D, osteoprotegerin (OPG) and receptor activator for nuclear factor kappa β ligand (RANKL) and other determinants of bone metabolism were measured in 35 patients with type 1 DM and in 25 age-, sex- and ethnicity-matched healthy controls. Serum OPG (1.98 vs. 2.98 pmol/l: P = 0.001), 1,25-dihydroxyvitamin D (41.1 vs. 48.2 pmol/l: P = 0.035) and magnesium (0.84 vs. 0.89 mmol/l P = 0.029) levels were significantly lower in patients with type 1 DM compared to normal controls. RANKL levels were similar in both groups. The groups did not differ with respect to calcium, phosphate, PTH, 25-hydroxyvitamin D, tubular reabsorption of phosphate and cross-linked N-telopeptides of type 1-collagen levels. Abnormalities of mineral metabolism including low serum OPG and 1,25-dihydroxyvitamin D levels occur in patients with type 1 DM with normal renal function and in the absence of microalbuminuria. These abnormalities may promote altered bone metabolism and vascular pathology.Peer reviewe