The cystine‐glutamate exchanger (xCT,Slc7a11) is expressed in significant concentrations in a subpopulation of astrocytes in the mouse brain

The cystine‐glutamate exchanger (xCT) promotes glutathione synthesis by catalyzing cystine uptake and glutamate release. The released glutamate may modulate normal neural signaling and contribute to excitotoxicity in pathological situations. Uncertainty, however, remains as neither the expression levels nor the distribution of xCT have been unambiguously determined. In fact, xCT has been reported in astrocytes, neurons, oligodendrocytes and microglia, but most of the information derives from cell cultures. Here, we show by immunohistochemistry and by Western blotting that xCT is widely expressed in the central nervous system of both sexes. The labeling specificity was validated using tissue from xCT knockout mice as controls. Astrocytes were selectively labeled, but showed greatly varying labeling intensities. This astroglial heterogeneity resulted in an astrocyte domain‐like labeling pattern. Strong xCT labeling was also found in the leptomeninges, along some blood vessels, in selected circumventricular organs and in a subpopulation of tanycytes residing the lateral walls of the ventral third ventricle. Neurons, oligodendrocytes and resting microglia, as well as reactive microglia induced by glutamine synthetase deficiency, were unlabeled. The concentration of xCT protein in hippocampus was compared with that of the EAAT3 glutamate transporter by immunoblotting using a chimeric xCT‐EAAT3 protein to normalize xCT and EAAT3 labeling intensities. The immunoblots suggested an xCT/EAAT3 ratio close to one (0.75 ± 0.07; average ± SEM; n = 4) in adult C57BL6 mice. Conclusions: xCT is present in select blood/brain/CSF interface areas and in an astrocyte subpopulation, in sufficient quantities to support the notion that system provides physiologically relevant transport activity.     

A quantitative assessment of glutamate uptake into hippocampal synaptic terminals and astrocytes: new insights into a neuronal role for excitatory amino acid transporter 2 (EAAT2)

The relative distribution of the excitatory amino acid transporter 2 (EAAT2) between synaptic terminals and astroglia, and the importance of EAAT2 for the uptake into terminals is still unresolved. Here we have used antibodies to glutaraldehyde-fixed d-aspartate to identify electron microscopically the sites of d-aspartate accumulation in hippocampal slices. About 3/4 of all terminals in the stratum radiatum CA1 accumulated d-aspartate-immunoreactivity by an active dihydrokainate-sensitive mechanism which was absent in EAAT2 glutamate transporter knockout mice. These terminals were responsible for more than half of all d-aspartate uptake of external substrate in the slices. This is unexpected as EAAT2-immunoreactivity observed in intact brain tissue is mainly associated with astroglia. However, when examining synaptosomes and slice preparations where the extracellular space is larger than in perfusion fixed tissue, it was confirmed that most EAAT2 is in astroglia (about 80%). Neither d-aspartate uptake nor EAAT2 protein was detected in dendritic spines. About 6% of the EAAT2-immunoreactivity was detected in the plasma membrane of synaptic terminals (both within and outside of the synaptic cleft). Most of the remaining immunoreactivity (8%) was found in axons where it was distributed in a plasma membrane surface area several times larger than that of astroglia. This explains why the densities of neuronal EAAT2 are low despite high levels of mRNA in CA3 pyramidal cell bodies, but not why EAAT2 in terminals account for more than half of the uptake of exogenous substrate by hippocampal slice preparations. This and the relative amount of terminal versus glial uptake in the intact brain remain to be discovered.     

Temporal trends in breast cancer presentation in the third world

Background

Third world breast cancer is characterized by late presentation, occurrence at relatively young ages and dismal mortality. This poor outcome has encouraged patients to patronize quacks and alternative healers. Public control measures have targeted mainly public education and provision of screening facilities. Recent reports from the developed world indicate a high association with obesity, tobacco and alcohol, habits which though not currently very popular in the third world are nevertheless increasingly accepted.

Methods

A prospective study initiated in 1985 for all breast cancer patients attending 4 hospitals located in the Eastern Nigeria heartland where the author practiced. On attendance to hospital detailed epidemiological data including social habits were collected from patients.

Results

Reports from our first series [1987–97] showed some improvement in terms of earlier presentation compared to a historical control of earlier reports from the sub-region. Reports from the present study showed that this improvement has not been maintained probably as a result of diversion of public health campaign finances to HIV/AIDS. However there is an increasing mean age of presentation due to a higher representation of above 70 years age group and a significant reduction in parity. Alcohol intake and smoking have remained at low levels among the patients.

Conclusion

There is need to take another look at cancer public health campaign mechanisms in the face of competing demands from HIV. Public control measures should include among others teaching of Breast Self Examination [BSE] to patients, Clinical Breast Examination [CBE] to health workers and opportunistic CBE to all patients. Strenuous efforts should be made to break the vicious cycle of late presentation, poor treatment outcome and reluctance of patients to present to health facilities because of poor outcome.     

Myocardial uptake and clearance of T1-201 in healthy subjects: comparison of adenosine-induced hyperemia and exercise stress

Pharmacologic stress testing with dipyridamole is useful in patients undergoing thallium-201 myocardial perfusion scintigraphy who cannot adequately exercise. Because dipyridamole increases coronary blood flow by reducing the metabolism of adenosine, the authors compared the uptake and clearance of T1-201 following exercise stress testing (EST) and resting intravenous infusion of adenosine (AI) in crossover fashion in 20 healthy men. No perfusion defects or areas of redistribution were noted in any of the scans. Mean absolute myocardial T1-201 uptake was 1.3 times greater with AI than with EST. Mean absolute extracardiac uptake was 2.0 times greater with AI. Mean T1-201 myocardial clearance was virtually the same in all AI and EST views. During AI, 70% of the subjects experienced subjective side effects, mean arterial blood pressure decreased by 15%, and heart rate increased by 48%. The effects of adenosine on T1-201 kinetics in the myocardium are similar to those of EST. Adenosine may be useful as a pharmacologic stress agent in patients undergoing T1-201 myocardial perfusion scintigraphy.     

Ankylosing spondylitis in a Malawian

I report a case of ankylosing spondylitis in a Malawian patient. I believe this is the first reported case of ankylosing spondylitis in a Malawian. Ankylosing spondylitis is rare in black Africans when compared with the Caucasian population. The clinical features of this disease are also different in these different racial groups. I will present a brief clinical history and a review of ankylosing spondylitis with special reference to the black African.     

Knowledge,attitude, and skills regarding sports medicine among football players and team doctors in the football super league in Malawi

A study was conducted among football players and team doctors in the football super league in Malawi to determine the level of knowledge, skills and attitude in sports medicine. One hundred football players and thirteen team doctors were involved in the study. Standardised questionnaires were used to collect data in an interview format. Among the players 37% had completed tertiary education and 60% had finished secondary school education. Most players had poor knowledge on prevention of injuries; had poor advice on diet; used illicit drugs or knew of fellow players using illicit drugs and believed in the role of magic in sports. All 13 team ‘doctors’ worked full-time in paramedical fields: 3 were orthopaedic clinical officers, 2 were physiotherapists and the rest were in various fields, such as dental technician, pharmacy assistant, medical assistant and dermatology technician, where trauma is not part of their basic training. Most team “doctors” were aware of the impact of HIV/AIDS on sports but few had good knowledge of the role of nutrition in sports and the effect of performance enhancing drugs in sports. Most believed in the role of magic in sports. Recommendations are made on the basis of these findings.