Selective cytotoxicity associated with in vitro exposure of fresh rat renal fragments and continuous cell lines to atractyloside

The consumption of plants containing the diterpenoid atractyloside (ATR) causes selective proximal tubule injury, renal failure and death in humans. We have compared the effects of ATR in freshly isolated renal proximal tubules and glomeruli from rat and also in cell lines: NRK, derived from the proximal tubules, and MDBK and MDCK more closely representing the distal nephron. The effects of ATR (10– 500?μM) on proximal tubules and glomeruli were assessed by changes in lipid peroxidation, de novo protein synthesis and the leakage of alkaline phosphatase (ALP), lactate dehydrogenase (LDH), glutamate dehydrogenase (GDH) and N-acetyl-β-D-glucosaminidase (NAG). The susceptibility of NRK, MDBK and MDCK cell lines to ATR was assessed by the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, measuring mitochondrial reduction. Enzyme leakage was the most sensitive of the markers of cell injury in fresh fragments and ranked LDH>GDH>ALP>NAG in proximal tubules. As little as 20?μM ATR caused significant enzyme leakage from proximal tubules, but there were no increases in enzyme leakage from glomeruli at concentrations ?500?μM ATR. De novo protein synthesis was only inhibited 50% at ATR concentration >5?mM in the proximal tubules, but there were no effects in glomeruli. Malondialdehyde production was significantly elevated at 1?mM ATR for proximal tubules, and 500?μM for glomeruli. NRK cells were sensitive to ATR (IC₅₀, 120?μM), but MDBK or MDCK cells were unaffected by?1?mM of this diterpenoid. Both freshly isolated fragments and continuous cell lines representing the proximal tubules are more sensitive to ATR than either glomeruli or cells representing the distal nephron. These data also show that protein synthesis is a less specific and sensitive measure of ATR cytotoxicity than enzyme leakage in fragments. MTT reduction to formazan was the most sensitive in the NRK cell line. The low levels of lipid peroxidation products in proximal tubular fragments or sensitive renal cell lines at toxic levels of ATR suggest that oxidative injury is not a key mechanism.     

Heterotopic microvascular epiphyseal plate transplantation: A new model using the rabbit metatarsal

The purpose of this study is to develop a new vascularized epiphyseal plate model in the New Zealand White rabbit using a metatarsal epiphyseal plate having limited longitudinal growth potential. Such a model could be utilized in various experiments aimed at manipulating epiphyseal plate growth. The viability of the harvested live subject grafts was demonstrated with continued epiphyseal uptake during Tc99-MDP radionuclide bone scanning. The currently described models used in epiphyseal transplant research all involve long bone epiphyseal plates with significantly greater growth potential than the new metatarsal model. This new model therefore fills a void in the field by allowing investigators to transplant a growth plate with limited growth potential into any heterotopic site and study the effects of various hormonal and physical influences upon epiphyseal plate growth performance. © 1995 Wiley-Liss, Inc.     

Changes in depression during and following pregnancy

Summary. .Rates of depression were studied in a sample of over 9000 women who were participants in the Avon Longitudinal Study of Pregnancy and Childhood. Assessments of depression were made at 18 and 32 weeks gestation, and at 8 and 32 weeks postpartum. Changes in depressive status across time were modelled using latent Markov modelling methods. This analysis showed that when classification errors were taken into account there was relatively high stability in diagnostic status during pregnancy and after pregnancy. However, the transition from late pregnancy to the early postnatal period showed evidence of increased instability and remission of depression. The net effects of this were that rates of depression tended to decline following childbirth. The implications of these results for a series of issues including measurement errors in depression reports and the prevalence of depression before and after childbirth are discussed.     

The Development and Teaching of the Ethical Principles and Guidelines for Family Scientists*

This article describes the development of the Ethical Principles and Guidelines for Family Scientists that the National Council on Family Relations Board of Directors unanimously approved. Furthermore, it discusses the importance of ethics education for family professionals and provides suggestions for educators. Finally, the ethical principles and guidelines are delineated. We argue that the development of a scholarship on ethics education is important for current and future family scientists.