The effect of mycophenolate mofetil on podocytes in nephrotoxic serum nephritis.

Mycophenolate mofetil (MMF) is applied in proteinuric kidney diseases, but the exact mechanism of its effect on podocytes is still unknown. Our previous in vitro experiments suggested that MMF can ameliorate podocyte damage via restoration of the Ca2+-actin cytoskeleton axis. The goal of this study was to characterize podocyte biology during MMF treatment in nephrotoxic serum (NTS) nephritis (NTN). NTN was induced in three-week old wild-type mice. On day 3, half of the mice were treated with MMF (100 mg/kgBW/d p.o.) for one week. On day 10, we performed proteomic analysis of glomeruli as well as super-resolution imaging of the slit diaphragm. For multiphoton imaging of Ca2+ concentration ([Ca2+]i), the experimental design was repeated in mice expressing podocyte-specific Ca2+ sensor. MMF ameliorated the proteinuria and crescent formation induced by NTS. We identified significant changes in the abundance of proteins involved in Ca2+ signaling and actin cytoskeleton regulation, which was further confirmed by direct [Ca2+]i imaging in podocytes showing decreased Ca2+ levels after MMF treatment. This was associated with a tendency to restoration of podocyte foot process structure. Here, we provide evidence that MPA has a substantial direct effect on podocytes. MMF contributes to improvement of [Ca2+]i and amelioration of the disorganized actin cytoskeleton in podocytes. These data extend the knowledge of direct effects of immunosuppressants on podocytes that may contribute to a more effective treatment of proteinuric glomerulopathies with the least possible side effects.

The influence of beta-cyclodextrin on the solubility of chlorthalidone and its enantiomers.

The solubility of chlorthalidone in 16 solvent systems was determined in the absence and presence of different amounts of beta-cyclodextrin (beta-CD). Chlorthalidone (CT) was shown to be more soluble in hydrophilic organic solvents, with the highest solubility in ethylacetate (EtOAc) saturated with water. The solubility of CT in water, butanol, octanol, and dichloromethane (DCM) was enhanced by the addition of beta-cyclodextrin. The enantioselective partitioning of CT between water and EtOAc, DCM, butan-1-ol, butan-2-ol, and octan-1-ol was determined in the presence of beta-CD at pH 5, 7, and 9. According to the results, both the solubility and partitioning properties of CT are affected by beta-CD in aqueous solution. It was also shown that the solubility of the individual enantiomers differs in the presence of beta-CD.

Sociocultural factors and fertility.

PIP: The author analyzes the relationships among sociocultural factors and fertility levels in South Africa. Attention is given to the transition to low fertility, fertility trends, and fertility differences by region. Race or ethnic group, religion, educational status, and employment are the major factors considered.^ieng

Response stability in social research: lessons from a longitudinal study of the family-building process.

"Responses to questions, phrased to elicit identical answers from the same individuals over time, are compared. The questions were used in a South African longitudinal study on the family-building process. Although consistency for certain questions was high, consistency was particularly low for questions on family-planning methods used and desired number of children at the time of marriage.... The need to evaluate the quality of data obtained in survey research, especially where heavy reliance is placed on memory recall, is stressed." (summary in AFR)