Convulsant and subconvulsant doses of norfloxacin in the presence and absence of biphenylacetic acid alter extracellular hippocampal glutamate but not gamma-aminobutyric acid levels in conscious rats.

Fluoroquinolones are antibiotics with central excitatory side effects. These adverse effects presumably result from inhibition of gamma-aminobutyric acid (GABA) binding to GABA(A) receptors. This GABA antagonistic effect is greatly potentiated by the active metabolite of fenbufen, biphenylacetic acid (BPAA). Nevertheless, it remains questionable whether GABA receptor antagonism alone can explain the convulsant activity potentials of these antimicrobial agents. The present study was undertaken to investigate the possible effects of norfloxacin, both in the absence and in the presence of BPAA, on the extracellular hippocampal levels of GABA and glutamate, the main central inhibitory and excitatory amino acid neurotransmitters, respectively. This in vivo microdialysis approach with conscious rats allows monitoring of behavioral alterations and concomitant transmitter modulation in the hippocampus. Peroral administration of 100 mg of BPAA per kg of body weight had no effect on behavior and did not significantly alter extracellular GABA or glutamate concentrations. Intravenous perfusion of 300 mg of norfloxacin per kg did not change the rat's behavior or the concomitant neurotransmitter levels in about half of the experiments, while the remaining animals exhibited severe seizures. These norfloxacin-induced convulsions did not affect extracellular hippocampal GABA levels but were accompanied by enhanced glutamate concentrations. Half of the rats receiving both 100 mg of BPAA per kg and 50 mg of norfloxacin per kg displayed lethal seizures, while the remaining animals showed no seizure-related behavior. In the latter subgroup, again no significant alterations in extracellular GABA levels were observed, but glutamate overflow remained significantly elevated for at least 3 h. In conclusion, norfloxacin exerts convulsant activity in rats, accompanied by elevations of extracellular hippocampal glutamate levels but not GABA levels, even in the presence of BPAA.

Using the POPULIS framework for interprovincial comparisons of expenditures on health care. Population Health Information System.

OBJECTIVES: Motivated by Manitoba Health's desire to know how health spending in Manitoba compared with other provinces, this study is a descriptive project designed to inform the health policy process by comparing indicators of need and expenditure across Canada. RESEARCH DESIGN: Population characteristics that are known to influence the need for health care constitute the comparative data categories. FINDINGS: In terms of all five health status indicators and five of eight socioeconomic indicators, Manitoba ranked medium (fourth to seventh of 10 provinces) or average. Demographic characteristics placed Manitoba second to Saskatchewan in proportion of both elderly residents and Registered Indians. This is notable, because both groups traditionally have high health needs. With provincial characteristics established, the second part of the study compares provincial per capita health expenditure data with expected need for health care services. RESULTS: Overall, the study finds provincial health expenditures are not related to health care need indicators. Saskatchewan is a case in point; despite having similar population characteristics to Manitoba, Saskatchewan has a population with good health status and lower health care expenditures. This offers a model that invites further exploration. CONCLUSIONS: At the provincial level the amount of health care spending is not positively related to the need for health care.