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.     

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.     

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.     

Passive immunotherapy of melanoma

The protocols of tumor immunotherapy have been largely developed in the past ten years due to the identification of many tumor antigens recognized specifically by CD8 and CD4 T lymphocytes. Among the various immunotherapies currently tested, passive immunotherapy (i.e injection of T lymphocytes generated and selected ex-vivo from blood or from the tumor), seems to be particularly promising. Indeed, three recent studies evidence the efficacy of such therapy in melanoma treatment. For the first time, a precise immunological follow-up was carried out, thus showing the correlation between the therapeutic benefit and the injection of tumor antigen specific T lymphocytes, and the survival and the preferential migration of these lymphocytes to the tumor sites. Although all the questions about optimal methods for this mode of therapy are not solved, these recent results constitute a major breakthrough in the field of the tumor immunotherapy.     

Chronomics: circadian and circaseptan timing of radiotherapy, drugs, calories, perhaps nutriceuticals and beyond

We suggest a putative benefit from timing nutriceuticals (substances that are both nutrients and pharmaceuticals) such as antioxidants for preventive or curative health care, based on the proven merits of timing nutrients, drugs, and other treatments, as documented, i.a., in India. The necessity of timing melatonin, a major antioxidant, is noted. A protocol to extend the scope of chronoradiotherapy awaits testing. Imaging in time by mapping rhythms and broader time structures, chronomes, for earliest diagnoses, for example detection of vascular disease risk, is recommended. The study of rhythms and broader chronomes leads to a dynamic functional genomics, guided by imaging in time of free radicals and antioxidants, amongst many other variables.     

Brain activations during motor imagery of locomotor-related tasks: a PET study

Positron emission tomography (PET) was used to study the involvement of supraspinal structures in human locomotion. Six right-handed adults were scanned in four conditions while imagining locomotor-related tasks in the first person perspective: Standing (S), Initiating gait (IG), Walking (W) and Walking with obstacles (WO). When these conditions were compared to a rest (control) condition to identify the neural structures involved in the imagination of locomotor-related tasks, the results revealed a common pattern of activations, which included the dorsal premotor cortex and precuneus bilaterally, the left dorsolateral prefrontal cortex, the left inferior parietal lobule, and the right posterior cingulate cortex. Additional areas involving the pre-supplementary motor area (pre-SMA), the precentral gyrus, were activated during conditions that required the imagery of locomotor movements. Further subtractions between the different locomotor conditions were then carried out to determine the cerebral regions associated with the simulation of increasingly complex locomotor functions. These analyses revealed increases in rCBF activity in the left cuneus and left caudate when the W condition was compared to the IG condition, suggesting that the basal ganglia plays a role in locomotor movements that are automatic in nature. Finally, subtraction of the W from the WO condition yielded increases in activity in the precuneus bilaterally, the left SMA, the right parietal inferior cortex and the left parahippocampal gyrus. Altogether, the present findings suggest that higher brain centers become progressively engaged when demands of locomotor tasks require increasing cognitive and sensory information processing.