Regression of morphological alterations and oxidative stress-related parameters after acute lindane-induced hepatotoxicity in rats

Changes in rat liver oxidative stress-related parameters, morphological alterations, as well as circulating and tissue levels of lindane were studied 1-7 days after the administration of a single dose of 60 mg of lindane/kg. One day after lindane treatment, a significant enhancement in the oxidative stress status of the liver was observed, characterized by an increase in thiobarbituric acid reactants production and in the microsomal generation of superoxide radical (O.-2) coupled to cytochrome P450 induction, and a decrement in the activity of superoxide dismutase (SOD) and catalase. Consequently, the O.-2 production/SOD activity ratio was enhanced two-fold. In this condition, light microscopy studies revealed the incidence of liver lesions in periportal areas, together with significant changes at the mitochondrial level observed by electron microscopy, which coincide with the maximal levels of lindane in the liver, adipose tissue, plasma and whole blood. Changes in oxidative stress-related parameters observed after 1 day of lindane treatment regressed to normal from the third day and thereafter, together with the decrement in circulating and tissue levels of the insecticide. It is concluded that morphological and oxidative stress-related changes induced in the liver by acute lindane intoxication are readily reversible, depend on the hepatic content of the insecticide, and seem to be conditioned by the changes in O.-2 generation.     

Electron spectroscopic imaging analyses of the distribution of phosphorus in Balbiani ring granules and in the surrounding nucleoplasm

When they were introduced to the world market in the 1980s, levonorgestrel subdermal implants offered the promise of an exciting alternative to traditional hormonal contraception. They provide highly effective, long-acting protection from pregnancy, without the need for user compliance. Broad acceptability of the drug has been reported throughout the world. Recently, however, the implants have met with opposition. The drug is associated with a variety of adverse effects, and removal of implants can be problematic. Serious events have been reported in women using levonorgestrel subdermal implants, although causal relationships have not been demonstrated. Additionally, concerns have been raised over the potential for coercive use of the drug. Numerous law suits have been filed alleging serious problems with implants. As a result, the drug has received considerable negative media attention. Before the controversy over levonorgestrel subdermal implants erupted, contraceptive development had declined, resulting from limitations to profits and funding, legal threats, and changes in the insurance industry. The levonorgestrel subdermal implant experience may serve to accelerate this trend. While the introduction of levonorgestrel subdermal implants offered an alternative to the current array of medical contraception, its experience may serve to dampen future contraceptive development efforts. Costly litigation and much controversy involving the implants have acted to create disincentives to further research and development of new methods of medical contraception.     

Mechanisms of action for an androgen-mediated autoregulatory process in rat thecal-interstitial cells

In rat thecal-interstitial cells (TIC), treatment with the synthetic androgen mibolerone has led to the documentation of an autoregulatory process for androgen production. In the present study, accumulated evidence has provided insight into the mechanisms of mibolerone action that control this process. Investigations using the nonsteroidal antiandrogen hydroxyflutamide were conducted to characterize mibolerone's mode of action. Hydroxyflutamide had differential effects on hCG action, the 1-microM dose stimulating hCG-induced androsterone synthesis by 27% and the 10-microM concentration decreasing the androgen levels by 84%. In addition, treatment with 1 microM hydroxyflutamide was effective in partially reversing the inhibitory action of mibolerone on hCG-stimulated androsterone production. Thus, the data indicated that mibolerone's mode of action may be mediated, at least in part, via the androgen receptor. The possibility that mibolerone had multiple sites of action prompted studies on the effectiveness of this androgen to alter various signaling pathways. Treatment with increasing concentrations (0.01-100 nM) of the phorbol ester 12-0-tetradecanoylphorbol 13-acetate (TPA), which activates protein kinase C, resulted in a 75% decrease in hCG-stimulated androgen production at a dose of 100 nM TPA. Treatment with mibolerone (100 nM) was unable to alter the action of TPA on androgen synthesis when doses of 1 and 10 nM TPA were employed. It was also found that Ca2+ can serve as a mediator of mibolerone action. Treatment with a 0.01-microM dose of A23187, a Ca2+ ionophore known to increase intracellular Ca2+, was ineffective in altering hCG-stimulated androsterone synthesis. The concurrent treatment of mibolerone (100 nM) and A23187 (0.01 microM) resulted in the potentiation of mibolerone's inhibitory effects on hCG-stimulated androgen production, thereby suggesting that mibolerone can stimulate Ca2+ influx. Additional studies revealed that the administration of a 1-microM dose of the L-type Ca2+ channel blocker verapamil to TIC cultures was able to partially block the inhibitory effect of mibolerone on androgen synthesis. Evidence for an additional site of mibolerone action was revealed through an analysis of the mRNA levels of P450scc and P450(17) alpha enzymes. Although hCG and insulin-like growth factor I treatment resulted in 20- and 32-fold increases in the amount of P450scc and P450(17) alpha mRNA, respectively, the addition of mibolerone (100 nM) reduced only P450(17) alpha mRNA levels by 91%. Overall, the evidence indicates that mibolerone has multiple sites of action in exerting its regulatory effect on androgen synthesis.     

Gliding motility: an efficient mechanism for cell penetration

An important group of animal and human pathogens, belonging to the phylum Apicomplexa, employs a novel form of motility, known as gliding, to move on solid substrates and to enter host cells. Gliding is dependent on the parasite cytoskeleton and involves a conserved family of secretory adhesins.     

Reduced engraftment and wound closure of cryopreserved cultured skin substitutes grafted to athymic mice

A simulation model was developed to test the accuracy of indirect estimates of maternal mortality (the sisterhood method). The model generated a first generation of grandmothers, a second generation of mothers (with brothers and sisters), and a third generation of children (births). In the second generation, maternal mortality was introduced. Empirical values for the parameters of fertility and mortality were taken from a prospective survey in Senegal (Niakhar). Results based on 100 simulations of the same situation revealed several limitations of the sisterhood method: The indirect estimates could fall as far as 33 percent from the true values on individual cases; the indirect estimates tended to be systematically higher than the direct estimates; their range was wider, as were their confidence intervals; and biases were particularly strong for the younger age groups of respondents. Reasons for these biases are explored.     

In support of a gerontological nursing program: a resource exchange model

Master's programs in gerontological nursing have not proven to be popular over the years, and that is still true today despite the increasing numbers of older adults with multiple health care needs. In an effort to market a new gerontological nursing masters' project successfully, a resource exchange network was developed to build a support system rather than a traditional advisory group. This article describes the Gerontological Nursing Network (GNN), provides examples of how resource exchange between GNN members and the project have been beneficial to each, and discusses pluses and problems in using such a model.