Glutamate uptake in cultured astrocytes depends on age: a study about the effect of guanosine and the sensitivity to oxidative stress induced by H(2)O(2)

Relatively few studies have been conducted to investigate the relationship between glutamate and development and/or aging. Rat cortical astrocyte cultures were used as a model to investigate glutamate uptake during development. The immunocontent of the markers glial fibrillary acidic protein (GFAP) and S100B increased, while basal secretion of S100B decreased, in astrocytes from 10 to 40 days in vitro (DIV). Basal glutamate uptake increased with age. Exposure to hydrogen peroxide decreased glutamate uptake more potently at 40 than 10 DIV. Moreover, 40 DIV astrocytes showed earlier loss of integrity (at 6 h) than 10 DIV astrocytes (at 24 h) after H(2)O(2) exposure. Addition of guanosine stimulated glutamate uptake only in 10 DIV astrocytes. The present work shows that mature astrocytes in culture present some neurochemical alterations also observed in astrocytes of aged animals. These results can contribute to the understanding of some consequences of the excitotoxicity and oxidative stress during brain aging.     

Evidence for differential expression of candida albicans virulence genes during oral infection in intact and human immunodeficiency virus type 1-transgenic mice

To comprehensively assess the in vivo expression of Candida albicans hydrolytic enzyme genes during oropharyngeal candidiasis (OPC), a controlled sequential analysis of the temporal expression of individual members of the SAP (secretory aspartyl proteinase) gene family and PLB1 (phospholipase B) in a murine model of OPC was conducted. Acute infections in intact C3H and DBA/2 mice were terminated by clearance of C. albicans within 7 days after oral inoculation, but transgenic (Tg) mice expressing human immunodeficiency virus type 1 were persistently colonized until a final outgrowth before death. In contrast to the sustained expression of other SAP genes and PLB1, SAP7 and SAP8 were conspicuously distinguished by their transient expression in both intact and Tg mice. SAP5 and SAP9 were most strongly expressed throughout the course of infection in the Tg mice. These findings indicate that expression of individual members of the C. albicans SAP gene family is differentially regulated during experimental OPC.     

Breast imaging and biopsy procedures in the diagnosis of breast cancer

THE INTEREST OF IMAGING: Mammography permits diagnosis of infra-clinical breast lesions with a sensitivity of around 80%. Moreover, with the improvement of the apparatuses and films, the latter permit analysis of the breast areas in most cases. Sonography, indisputable support for the study of dense breasts, is a complement to mammography and clinical examination. Magnetic resonance imaging is the most sensitive technique, but cannot be used in routine controls. The principle images are essentially opacities characterised by enhanced density in the glandular parenchyma (circular or round, asymmetrical opacities of architectural density and disorganisation, stellar and epiculated opacities) and micro-calcifications without specific appearance, revealing when isolated in situ intra-ductal or micro-invasive lesions. THE INTEREST OF BIOPSY PROCEDURES: For non-palpable tumours discovered on imaging, stereo or radio-guided cytological aspirations are proposed so long as the image is not too small. In the presence of infra-clinical images inaccessible to guided cytology, stereotaxy micro-biopsies can be performed. The relative insufficiency of results obtained has led to the proposal of needles of larger calibre used in an apparatus called a mammotome or in the ABBI system, the latter permitting radio-guided surgical excision. PRIORITY GIVEN TO CLINICAL CONTROLS: The technical progress must not lead one to neglect the clinical examination, which, in 5 to 30% of cases, reveals a cancer when the mammography or sonography does not.     

Skin disorders

Dermatologic aberrants in the elderly need special attention. The health care provider who is assessing or providing the physical exam must be astute and well-read. Diagnosis should be quick and a treatment plan initiated with the same acumen. Do not linger. The complications of other systemic diseases can change the presentation. The most important fact to remember is to search for an underlying etiology and to work as a team in eliciting all the facts.     

Recurrence of keratoconus characteristics: a clinical and histologic follow-up analysis of donor grafts

PURPOSE: To report on clinical corneal topography, histopathologic analysis, and fine structure findings in failed grafts after penetrating keratoplasty (PK) for keratoconus (KC). DESIGN: Retrospective, consecutive, interventional case series with histologic and clinical correlation. PARTICIPANTS: Twelve corneal buttons were obtained from consecutive patients undergoing repeated PK 10 to 28 years after the initial PK for KC. The indication for regrafting was endothelial deficiency in seven cases, irreversible immune graft rejection in two cases, and corneal ectasia in three cases. METHODS: Removed corneal buttons were examined by light and transmission electron microscopy. A potential correlation between the clinical and videokeratoscopic findings and the microscopic structural observations was analyzed. RESULTS: Preoperative simulated keratometry measured by TMS-1 (Tomey, New York, NY) or EyeSys CAS (EyeSys Technology, Houston, TX) ranged from 49.8 to 66.1 diopters. A pattern compatible with KC characteristics was observed in all cases. Fine structure analysis revealed Bowman's layer disruption or folds and stromal deposits in all corneal buttons. However, central corneal thinning was not present in any of the removed buttons. CONCLUSIONS: Structure changes compatible with the diagnosis of KC were observed in all donor buttons many years after PK on KC recipients. Recurrence of the KC characteristics may result from graft repopulation by recipients' keratocytes, aging of the grafted tissue, or both.     

Strong general health care systems: a prerequisite to reach global tuberculosis control targets

We argue that tuberculosis control cannot reach its proposed global targets without investment in an adequate network of accessible, effective and comprehensive health services. Lessons from the past are reviewed. They underscore that passive case-detection and adequate case management is the central technical strategy for tuberculosis control. There is no compelling evidence to support active case-detection in the general population. We elaborate on why a strong health care system is a prerequisite in the framework of case-detection and treatment. The necessity to improve quality and accessibility of general health services for ensuring early detection and subsequent cure is demonstrated. It is argued why the need for strong public health care system becomes even more eminent in the light of the tuberculosis/HIV dual epidemics and of the rapid growth of unregulated private-for-profit services. We finally examine the financial gaps for tuberculosis control and discuss the need for allocating more resources to the strengthening of general health care systems.     

Resveratrol analog (Z)-3,5,4'-trimethoxystilbene is a potent anti-mitotic drug inhibiting tubulin polymerization

Resveratrol (3,5,4'-trihydroxystilbene) a natural polyphenol present in medicinal plants, grapes and wines, has potent chemopreventive properties on intestinal carcinogenesis. A methylated derivative (Z-3,5,4'-trimethoxystilbene: R3) was synthesized. R3 at 0.3 microM exerted a 80% growth inhibition of human colon cancer Caco-2 cells and arrested growth completely at 0.4 microM (R3 was 100-fold more active than resveratrol). The cis conformation of R3 was also 100-fold more potent than the trans isomer. R3 (0.3 microM) caused cell cycle arrest at the G2/M phase transition. The drug inhibited tubulin polymerization in a dose-dependent manner (IC50=4 microM), and it reduced also by 2-fold ornithine decarboxylase and s-adenosylmethionine decarboxylase activities. This caused the depletion of the polyamines, putrescine and spermidine, which are growth factors for cancer cells. R3 inhibited partially colchicine binding to its binding site on tubulin, indicating that R3 either partially overlaps with colchicine binding or that R3 binds to a specific site of tubulin that is not identical with the colchicine binding site modifying colchicine binding by allosteric influences. The resveratrol derivative (Z)-3,5,4'-trimethoxystilbene (R3) is an interesting anti-mitotic drug that exerts cytotoxic effects by depleting the intracellular pool of polyamines and by altering microtubule polymerization. Such a drug may be useful for the treatment of neoplastic diseases.