Effect of alpha-alpha diaspirin crosslinked hemoglobin (DCLHb) on the potency of sodium nitroprusside and nitroglycerine to decrease blood pressure in rats: a dose-response study.

The nitrovasodilators, sodium nitroprusside and nitroglycerine, effect a dose-dependent decrease in mean arterial blood pressure (MABP) by liberating nitric oxide. Alpha-alpha diaspirin crosslinked hemoglobin (DCLHb) is known to bind nitric oxide. We studied the effect of DCLHb on the potency of sodium nitroprusside (n=36) and nitroglycerine (n=36) to decrease MABP in rats which received 1, 10, 100, 1,000, or 10,000 mg/kg of the DCLHb, or normal saline as the Control. Six doses of sodium nitroprusside or nitroglycerine were given to each rat in a systematically varied sequence. For both drugs, in rats given 1, 10, or 100 mg/kg of DCLHb there were no between groups differences in the change in MABP compared to the Control group. For rats that received 1,000 or 10,000 mg/kg of DCLHb, the potency of nitroglycerine and sodium nitroprusside to decrease MABP was less (p<0.05) than the other groups. These data support the hypothesis that small doses of DCLHb effect a minimal change in the potency of nitrovasodilators to reduce blood pressure. However, they suggest that clinically relevant doses of DCLHb attenuate the vasodilatory ability of sodium nitroprusside and nitroglycerine.

Efficacy of lithium vs. valproate in the treatment of mania in the elderly: a retrospective study.

BACKGROUND: This retrospective study was conducted to assess the efficacy of lithium and valproate and associated serum levels in the treatment of mania in elderly patients. METHOD: Records of 59 patients aged 55 years and older with minimal or no neurologic impairment, hospitalized for mania, and discharged on lithium (N = 30) or valproate (N = 29) therapy were reviewed. Data on mood stabilizer choice, serum levels, and type of mania were recorded. A clinician blinded to medications rated improvement in each case with Clinical Global Impressions (CGI) scores based on abstracted notes. RESULTS: Overall, the percentage of patients improved was significantly greater in the lithium group than in the valproate group (67% vs. 38%, chi2 = 4.88, p = .027). Patients taking lithium with serum levels > or =0.8 mmol/L were more improved at discharge than those outside this range (> or =0.8, CGI 2.0+/-0.6 vs. <0.8, CGI 2.6+/-0.8, t = 2.15, p = .043). Patients taking valproate with serum levels between 65-90 microg/mL were more improved at discharge than those outside this range (65-90, CGI 2.1+/-0.6 vs. <65, >90, CGI 3.3+/-0.8, t = 3.73, p = .002). When response rates among only patients with these "therapeutic" levels were assessed, they were similar for lithium (82%) and valproate (75%). The difference in efficacy between drugs was maintained in classic mania, but the 2 drug groups were similar when only mixed mania was analyzed (lithium 63% vs. valproate 67% improved). CONCLUSION: Results suggest that lithium may be more efficacious than valproate overall, but response rates for the 2 drugs were similar when "therapeutic" serum levels were achieved. For lithium, levels similar to those reported for younger adults were associated with response. For valproate, a "therapeutic window" different from that in younger adults was found. While the retrospective and naturalistic design of this study has limitations, these data may help direct further studies and treatment of mania in the elderly.

Novel antipsychotics and new onset diabetes.

BACKGROUND: The new antipsychotics induce minimal extrapyramidal side effects, probably due to their relatively greater affinity for certain nondopaminergic receptors than their older, conventional counterparts; however, this polyreceptor affinity may be responsible for the development of other adverse effects. One serious adverse effect that may be linked to these effects is non-insulin-dependent diabetes mellitus. METHODS: We summarize 6 new cases of clozapine- and olanzapine-associated diabetes that we have documented in our clinic. We compare our cases to previous reports and tabulate the pertinent similarities among cases. RESULTS: Two of the cases were olanzapine-associated and 4 were clozapine-associated diabetes. Five of our 6 patients had risk factors for diabetes, as have 7 of the 9 previously reported in the literature. Four of our 6 patients, and 2 of the 4 prior cases in which such data were reported, experienced substantial weight gain after starting their antipsychotics. CONCLUSIONS: Novel antipsychotics should be administered with great care to patients with risk factors for diabetes. Although the precise mechanism of the novel antipsychotic-associated diabetes is unclear, we hypothesize that histaminic and possibly serotonergic antagonism induces weight gain, which in turn leads to changes in glucose homeostasis. Additionally, serotonin1A antagonism might decrease pancreatic beta-cell responsiveness, resulting in inappropriately low insulin and hyperglycemia.