Glucocorticoids and aging

In this review we analyze the morphologic changes, hypothalamic-pituitary-adrenal (HPA) axis functions, glucocorticoid (GC) receptors, and steroidogenic enzyme activities in both animals and humans during aging. In rodent studies, older animals tend to show: 1) hypertrophy of adrenal zona fasciculata (ZF) cells; 2) neuronal loss in the hypothalamic area; 3) loss of GC receptors in the hippocampus; 4) raised circulating adrenocorticotropic hormone (ACTH) and GC levels, and increased release of corticotropin-releasing hormone from the hypothalamus; 5) reduced suppression of endogenous GC secretion after administration of dexamethasone; 6) decreased attenuation of response to chronic stress; and 7) increased activity of P450scc and 21-hydroxylase. According to the GC cascade hypothesis, stress and GCs facilitate the aging process in rats. Stress induces downregulation of GC receptors in the hippocampus, then impairs GC feedback on stress-induced HPA axis activation. Finally, an increase in the basal level of corticosterone and extended GC secretion following stress occurs. Because activation of the hippocampus decreases HPA axis function, the unrestrained elevation of GC concentration and the reduction in the level of GC receptors in the hippocampus may gradually weaken the feedback mechanisms and halt the response to stress. In humans, there are conflicting reports of HPA axis function during aging, so it is difficult to make a final conclusion regarding the relationship between aging and HPA axis function.     

The liberal ophthalmologists of the northern France and management of children with vision deficiencies

PURPOSE: The purpose of this analysis was to appreciate the management of visually handicaped children outside specialized structures. We also assessed relays between primary physicians, hospitals and specialized structures. METHOD: A 12-question survey was sent to 144 liberal ophthalmologists of the North of France. The questionnary included 12 questions. We compared the results to litterature. RESULTS: The response-rate was 59.6%. This study indicated that the observed children by the liberal ophtalmologists had more simple diseases than in specialized structures. In hospitals, it seemed that the ophtalmologists diagnosed more severe diseases. These practitioners diagnosed some of these diseases. However some of diagnosis were to late. This study showed that specialized structures were not enough known by the practitioners who detected this handicap and that the families prefered the taking in charge near their home. CONCLUSION: We demonstrated the necessary organisation of precocious and systematic detection, and the necessary information to all practitioners on specialized structures.     

Autonomic paroxysms: their pathogenesis, diagnosis and treatment

In the article the rules about etiology and pathogenesis of vegetative paroxysms are stated based on careful analysis of the publications of researches as Russian, so foreign authors, and also own experimental and clinical supervision. During experimental and clinical researches the modern methods were used, enabling to estimate from positions of the system analysis different parts of pathogenesis of vegetative paroxysms, and also to offer ways of differential diagnostics of the various forms of disease. The application of some new preparations and direction of therapy of vegetative paroxysms are substantiated, and also the various circuits of treatment of the patients with distinguishing forms of given pathology are motivated.     

Health trajectories: long-term dynamics among black and white adults

Flow cytometry is a unique technology useful in the examination of effects of immunotoxic agents on target cells of the immune system. The purpose of this workshop was to provide an overview of the use of flow cytometry in new and established models of immunotoxicity, with emphasis on the potential applications, assay validation, and potential pitfalls. This overview begins with a discussion of methods useful in the assessment of Ca2+-dependent mechanisms of lymphoid cell activation in surface marker-defined human B cells, T cells, and monocytes. A discussion of the use of flow cytometry in analysis of apoptosis is also presented in this paper. The second paper presents data on the development and use of flow cytometry as an alternative to a Cr51 release assay for an assessment of cytotoxic T cell activation. The use of surface markers for characterizing and distinguishing the effects of chemical irritants from sensitizers is next presented, followed by an overview of the use of fluorescent probes to assess cell thiol status and overall oxidant-induced injury to lymphoid cells. Finally, an interlaboratory study designed to compare and evaluate the use of flow cytometry procedures in rat splenic cell subtyping is presented. Overall, these studies demonstrate the utility of flow cytometry assays in immunotoxicologic research, but further efforts are needed in the validation of many of these assays for routine use in immunotoxicologic testing.     

Experimental peri-implant tissue breakdown around hydroxyapatite-coated implants

Factor V Leiden mutation was initially detected in thrombophilic patients and relatives by PCR RFLP (Restriction Fragment Length Polymorphism) according to Bertina (1). This technique presents some drawbacks and the current trend is to simplify the diagnosis. We describe a technique of Allele Specific Amplification (ASA) which is optimized in terms of reliability: an additional mismatch in antepenultimate position enables to obtain the same specificity as PCR RFLP. Furthermore, coamplification of internal control warrants an optimal sensitivity. All the PCR have been simplified: the DNA extraction improvement allows to analyse the genotype with only a few microliters of whole blood whatever the anticoagulant and the procedure of preservation (freezing, dried blood spots, storage at +4 degrees C for several days). This technique saves time. Moreover, full automation of the ASA technique may be shortened thanks to the lack of extraction and the positive/negative reading of the PCR signal.     

Postoperative radiotherapy with concurrent cisplatin appears to improve locoregional control of advanced, resectable head and neck cancers: RTOG 88-24

PURPOSE: Despite aggressive surgery and postoperative radiation therapy, only 30% of patients who have advanced, potentially resectable carcinomas of the head and neck survive for 5 years. In the hope of improving this situation we studied the effect of postoperative radiotherapy delivered concurrently with cisplatin. METHODS AND MATERIALS: Patients who had Stage IV tumors and/or involved surgical margins received 60 Gy in 30 fractions over 6 weeks plus 100 mg/m2 of cisplatin on radiotherapy days 1, 23 and 43. Fifty-two patients participated in this trial and 51 were evaluated. Forty-three (84%) patients had pathologic T3 or T4 disease, 43 (84%) had Stage IV disease, and 27 (53%) had histologically involved surgical margins. RESULTS: Severe and life-threatening toxicities occurred in 20% and 12% of patients, respectively; the most common drug-related toxicities were leukopenia, anemia, nausea, and vomiting. Seventeen patients (43%) remain alive with no evidence of disease. Four patients (8%) died with no evidence of neoplastic disease, and one patient has died of a second independent malignancy. By actuarial analysis at 3 years, 48% of patients are alive, 81% have locoregional control of disease, and 57% are free of distant metastases. CONCLUSIONS: Based on comparison with similar patients treated in a prior Radiation Therapy Oncology Group/Intergroup trial (RTOG), we conclude that postoperative radiotherapy with concurrent cisplatin may improve locoregional control rates and should be prospectively tested.     

Prostate enlargement in mice due to fetal exposure to low doses of estradiol or diethylstilbestrol and opposite effects at high doses

On the basis of results of studies using high doses of estrogens, exposure to estrogen during fetal life is known to inhibit prostate development. However, it is recognized in endocrinology that low concentrations of a hormone can stimulate a tissue, while high concentrations can have the opposite effect. We report here that a 50% increase in free-serum estradiol in male mouse fetuses (released by a maternal Silastic estradiol implant) induced a 40% increase in the number of developing prostatic glands during fetal life; subsequently, in adulthood, the number of prostatic androgen receptors per cell was permanently increased by 2-fold, and the prostate was enlarged by 30% (due to hyperplasia) relative to untreated males. However, as the free serum estradiol concentration in male fetuses was increased from 2- to 8-fold, adult prostate weight decreased relative to males exposed to the 50% increase in estradiol. As a model for fetal exposure to man-made estrogens, pregnant mice were fed diethylstilbestrol (DES) from gestation days 11 to 17. Relative to controls, DES doses of 0.02, 0.2, and 2.0 ng per g of body weight per day increased adult prostate weight, whereas a 200-ng-per-g dose decreased adult prostate weight in male offspring. Our findings suggest that a small increase in estrogen may modulate the action of androgen in regulating prostate differentiation, resulting in a permanent increase in prostatic androgen receptors and prostate size. For both estradiol and DES, prostate weight first increased then decreased with dose, resulting in an inverted-U dose-response relationship.