Involvement of astrocytes in purine-mediated reparative processes in the brain

Astrocytes are involved in multiple brain functions in physiological conditions, participating in neuronal development, synaptic activity and homeostatic control of the extracellular environment. They also actively participate in the processes triggered by brain injuries, aimed at limiting and repairing brain damages. Purines may play a significant role in the pathophysiology of numerous acute and chronic disorders of the central nervous system (CNS). Astrocytes are the main source of cerebral purines. They release either adenine-based purines, e.g. adenosine and adenosine triphosphate, or guanine-based purines, e.g. guanosine and guanosine triphosphate, in physiological conditions and release even more of these purines in pathological conditions. Astrocytes express several receptor subtypes of P1 and P2 types for adenine-based purines. Receptors for guanine-based purines are being characterised. Specific ecto-enzymes such as nucleotidases, adenosine deaminase and, likely, purine nucleoside phosphorylase, metabolise both adenine- and guanine-based purines after release from astrocytes. This regulates the effects of nucleotides and nucleosides by reducing their interaction with specific membrane binding sites. Adenine-based nucleotides stimulate astrocyte proliferation by a P2-mediated increase in intracellular [Ca2+] and isoprenylated proteins. Adenosine also, via A2 receptors, may stimulate astrocyte proliferation, but mostly, via A1 and/or A3 receptors, inhibits astrocyte proliferation, thus controlling the excessive reactive astrogliosis triggered by P2 receptors. The activation of A1 receptors also stimulates astrocytes to produce trophic factors, such as nerve growth factor, S100beta protein and transforming growth factor beta, which contribute to protect neurons against injuries. Guanosine stimulates the output of adenine-based purines from astrocytes and in addition it directly triggers these cells to proliferate and to produce large amount of neuroprotective factors. These data indicate that adenine- and guanine-based purines released in large amounts from injured or dying cells of CNS may act as signals to initiate brain repair mechanisms widely involving astrocytes.     

An immunopharmacological approach for prevention of retrovirus-associated disease in human pathology

Retroviruses of the HTLV and HIV subfamilies share a number of similar properties in terms of route of transmission and ultimate targeting to CD4+ T-cells, which results in leukaemic transformation in the case of HTLV and in depletion of CD4+ population and failure of T-helper function in HIV-infected individuals. Both diseases gain poor benefit from therapy at the stage of clinical diagnosis as ATL leukaemia or AIDS, respectively. Therefore the best chances to limit the worldwide distribution of these human retroviruses reside in an effective prevention of viral diffusion, possibly by vaccination, and of the onset of disease in virus-positive subjects. The possibility is discussed of defining protocols to prevent the development of clinical disease. These protocols could be based on pharmacological reconstitution of host's immune reactivity, that is altered early after infection with these retroviruses, and on the control of virus replication by antiviral therapy.     

Neuroborreliosis: a Sardinian case with cerebellar symptoms

We report the case of a patient long resident in Sardinia in whom the clinical history, neurological symptoms, serological and neuroradiological investigations pointed to the diagnosis of neuroborreliosis. We emphasize the rarity of cerebellar involvement in this disease.

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Sommario Viene descritto un paziente residente in Sardegna nel quale la storia clinica, la sintomatologia neurologica, le indagini sierologiche e neuroradiologiche e la buona risposta alla terapia specifica, hanno consentito di porre diagnosi di neuroborreliosi. Viene sottolineate la rarità del coinvolgimento cerebellare in tale malattia.

     

Women in Academic Emergency Medicine

OBJECTIVE: To evaluate the achievement of women in academic emergency medicine (EM) relative to men. METHODS: This study was a cross-sectional mail survey of all emergency physicians who were employed at three-fourths full-time equivalent or greater at the 105 EM residency programs in the United States from August 1997 to December 1997. The following information was obtained: demographics, training and practice issues, roles and responsibilities in academic EM, percentage of time spent per week in clinical practice, teaching, administrative and research activities, academic productivity, and funding. RESULTS: Of the 1,575 self-administered questionnaires distributed by the office of the chairs, 1,197 (76%) were returned. Two hundred seventy-four (23%) of the respondents were women, and 923 (77%) were men. There was a significant difference noted between men and women in all demographic categories. The numbers of respondents who were nonwhite were extremely small in the sample and, therefore, the authors are hesitant to draw any conclusions based on race/ethnicity. There was no difference in training in EM between men and women (82% vs 82%, p = 0.288), but a significantly higher proportion of male respondents were board-certified in EM (84% vs 76%, p < 0.002). Women in academic EM were less likely to hold major leadership positions, spent a greater percentage of time in clinical and teaching activities, published less in peer-reviewed journals, and were less likely to achieve senior academic rank in their medical schools. CONCLUSIONS: These findings mirror those of most medical specialties: academic achievement of women in academic EM lags behind that of men. The paucity of minority physicians in academic EM didn't permit analysis of their academic achievements.     

Isoflurane or halothane for cesarean section: comparative maternal and neonatal effects

The maternal and neonatal effects of isoflurane and halothane combined with 50% N2O - 50% O2 were compared in 60 healthy parturients undergoing primary or repeat cesarean section. All patients had rapid sequence induction of anesthesia with sodium thiamylal 4 mg/kg followed by succinylcholine for tracheal intubation. Patients were randomly assigned to one of three groups of 20 each (inspired 0.5% isoflurane, 1% isoflurane or 0.5% halothane), combined with 50% N2O and O2. After delivery, 67% N2O in O2 was used, supplemented by butorphanol. Maternal blood loss did not differ significantly among the three groups and none of the patients developed intraoperative awareness. At the time of delivery, maternal plasma epinephrine levels were significantly above preinduction levels in the 0.5% isoflurane group but unchanged in the other two groups. Neonatal status as ascertained by Apgar scores, cord acid base status and the Neurologic and Adaptive Capacity Scores (NACS) was equally good in the three groups of patients. Serum inorganic fluoride concentrations in the mother after anesthesia were not significantly above preanesthetic levels in any of the groups and there was no biochemical evidence of renal toxicity. In all neonates fluoride ion concentrations in the first voided urine sample were less than 7 mumol/l, a value well below that associated with nephrotoxicity. It is concluded that isoflurane is a safe supplement to N2O - O2 mixture for cesarean section and is a safer alternative to halothane in situations when patients receiving beta-adrenergic therapy require cesarean section since halothane might potentiate arrhythmias caused by beta adrenergic agonists.     

Diminished active T rosette levels and increased spontaneous B lymphocyte blastogenesis in hepatitis B virus positive chronic active hepatitis

The present investigation was designed to detect abnormalities in CMI and the presence of polyclonally activated B cells in patients with HBV positive CAH. We studied the peripheral levels and 3H-thymidine incorporation of three lymphocyte subsets: B lymphocytes, as well as two T cell subsets that are either active or late rosetters with high and low affinity receptors respectively for sheep red blood cells (SRBC). In patients the level of peripheral T active cells was decreased, but they exhibited elevated B cell activation. There was also a significant correlation between the decreased levels of T active cells and increased 3H-thymidine incorporation by B lymphocytes. Taken together, our results are consistent with the hypothesis that patients with HBV positive CAH have a severe impairment of T cell function that may lead to an abnormal B cell activation. The increased B cell activity may account for the presence of circulating immune complexes and the variety of autoantibodies often observed in patients with HBV positive CAH.