Acute, I day administration had no affect on proliferation. Caffeine administration does not affect the expression of early or late markers of neuronal SN-38 nmr differentiation, or rates of long-term survival. However, neurons induced in response to supraphysiological levels of caffeine have a lower survival

rate than control cells; increased proliferation does not yield an increase in long-term neurogenesis. These results demonstrate that physiologically relevant doses of caffeine can significantly depress adult hippocampal neurogenesis. (C) 2009 Elsevier Ltd. All rights reserved.”
“Background Most malaria deaths occur in rural areas. Rapid progression from illness to death can be interrupted by prompt, effective medication. Antimalarial treatment cannot rescue terminally ill patients but could be effective if given earlier. If patients who cannot be treated orally are several hours from facilities for injections, rectal artesunate can be given before referral and acts rapidly on parasites. We investigated whether this intervention reduced mortality and permanent disability.

Methods A-1155463 in vitro In Bangladesh, Ghana, and Tanzania, patients with suspected severe

malaria who could not be treated orally were allocated randomly to a single artesunate (n=8954) or placebo (n=8872) suppository by taking the next numbered box, then referred to clinics at which injections could

be given. Those with antimalarial injections or negative blood smears before randomisation were excluded, leaving 12068 patients (6072 artesunate, 5996 placebo) for analysis. Primary endpoints were mortality, assessed 7-30 days later, and permanent disability, reassessed periodically. All investigators were masked to group assignment. Analysis was by intention to treat. This study is registered in all three countries, numbers ISRCTN83979018, 46343627, and 76987662.

Results Mortality was 154 of 6072 artesunate versus 177 of 5996 placebo (2.5% vs 3 . 0%, p=0 . 1). Two versus 13 (0 . 03% vs 0 . 22%, p=0 . 0020) were permanently disabled; total dead or disabled: 156 versus 190 (2 . 6% vs 3.2%, p=0 science . 0484). There was no reduction in early mortality (56 vs 51 deaths within 6 h; median 2 h). In patients reaching clinic within 6 h (median 3 h), pre-referral artesunate had no significant effect on death after 6 h or permanent disability (71/4450 [1.6%] vs 82/4426 [1.9%], risk ratio 0.86 [95% Cl 0.63-1.18], p=0.35). In patients still not in clinic after more than 6 h, however, half were still not there after more than 15 h, and pre-referral rectal artesurate significantly reduced death or permanent disability (29/1566 [1.9%] vs 57/1519 [3.8%], risk ratio 0.49 [95% CI 0.32-0.77], p=0 . 0013).