Genes in idiopathic calcium oxalate stone disease

An examination of the urinary excretions of 101 normal subjects indicated that the major genetic influence on calcium excretion is a codominant pair of alleles giving rise to three phenotypes, low, intermediate and high (hypercalciuric) excretors. This inference was based on variance, Hardy-Weinberg and segregation analyses. Similar independent gene pairs also appear to influence oxalate and citrate excretion, A 3-locus Hardy-einberg table using estimates of gene frequencies derived from the study of normals suggests that only 3 or 4 leading genes are involved in oxalate stone disease. Strong candidate genes identified from molecular and physiological studies cannot be proposed at present, but it is assumed that they influence the transport of these ions in either the intestine, kidney or both organs. The identification of the genes involved should be facilitated by the reduction of dietary influences on urinary excretions through the use of formula diets.     

The Risk of Sulfasalazine- and Mesalazine-Associated Blood Disorders

Sulfasalazine (SASP) has often been reported to cause serious blood disorders, particularly agranulocytosis; however, little quantitative information is available to estimate the risk or to identify possible modifiers of the risk. We used comprehensive clinical information recorded on office computers by selected general practitioners in Britain to conduct a follow-up study of some 10,000 users of SASP and some 4000 users of mesalazine to estimate the risk of blood disorders associated with these drugs. Overall, the frequency of blood disorders attributable to SASP was 27/10,332 (2.6/1000 users). The risk for SASP users who were treated for arthritic disorders (6.1/1000 users) was some 10 times higher than that for users who were treated for inflammatory bowel disease (0.6/1000 users). There were no cases of blood disorders in users of mesalazine.     

Depressive symptoms during buprenorphine vs. methadone maintenance: findings from a randomised, controlled trial in opioid dependence

Research suggests that buprenorphine may possess antidepressant activity. The Beck Depression Inventory was completed at baseline and 3 months by heroin dependent subjects receiving either buprenorphine or methadone maintenance as part of a larger, pre-existing, double blind trial conducted by NDARC (Australia). Depressive symptoms improved in all subjects, with no difference between methadone and buprenorphine groups, suggesting no differential benefit on depressive symptoms for buprenorphine compared to methadone.     

Matrix vesicles are enriched in metalloproteinases that degrade proteoglycans

Summary This study examined the presence of extracellular matrix processing enzymes in matrix vesicles produced by rat costochondral resting zone and growth zone chondrocytes in culture. Optimum procedures for the extraction of each enzyme activity were determined. Enzyme activity associated with chondrocyte plasma membrane microsomes was used for comparison. There was a differential distribution of the enzyme activities related to the cartilage zone from which the cells were isolated. Acid and neutral metalloproteinase (TIMP), plasminogen activator, and betaglucuronidase were highest in the growth zone chondrocyte (GC) membrane fractions when compared with matrix vesicles and plasma membranes isolated from resting zone chondrocyte (RC) cultures. There was a threefold enrichment of total and active acid metalloproteinase in GC matrix vesicles, whereas no enrichment in enzyme activity was observed in RC matrix vesicles. Total and active neutral metalloproteinase were similarly enriched twofold in GC matrix vesicles. TIMP, plasminogen activator, and betaglucuronidase activities were highest in the plasma membranes of both cell types. No collagenase, lysozyme, or hyaluronidase activity was found in any of the membrane fractions. The data indicate that matrix vesicles are selectively enriched in enzymes which degrade proteoglycans. The highest concentrations of these enzymes are found in matrix vesicles produced by growth zone chondrocytes, suggesting that this may be a mechanism by which the more differentiated cell modulates the matrix for calcification.