RGS2 and RGS4 mRNAs are regulated in the rat striatum by dopaminergic agents. The present study further characterizes this regulation in three experiments. First, dopamine type 1 (receptor) (D1)- and dopamine type 2 (receptor) (D2)-mediated regulator of G-protein signalling (RGS) gene regulation was investigated in animals with deleted ascending dopaminergic pathways. We showed that RGS2 expression is controlled by D1 receptors either by direct action on D1 receptors or indirectly by presynaptic D2 receptors. Conversely, RGS4 gene expression is independent of presynaptic D2 receptors. Second, the study of colocalization between RGS2 or RGS4 and D1 or D2 by double labelling in situ hybridization histochemistry revealed broad expression of RGS2 and RGS4 mRNA in striatal subpopulations with colocalization of RGS2 and RGS4 with both D1 and D2 receptors. Finally, to test how far their gene regulation is temporally concerted, changes in RGS2 and RGS4 mRNA levels were measured in parallel with receptor occupancy by specific dopaminergic drugs at different time-points. RGS2 was rapidly/transiently up-regulated by the D1 agonist SKF82958 and the D2 antagonist haloperidol (peak at 0.5 h) and down-regulated by the D1 antagonist SCH23390 and the D2 agonist quinpirole (trough at 1 and 2 h). RGS4 showed a delayed/transient up-regulation with SCH23390 and quinpirole (peak at 4 and 2 h) and down-regulation with haloperidol (trough at 8 h). Depending on the drug used, the degree of receptor occupancy did (D1 agonist and RGS2) or did not (D2 antagonist and RGS2) run parallel to RGS gene expression changes, indicating that certain drug effects are direct and others indirect. The precise control of RGS2 and RGS4 expression by dopamine receptors pleads in favour of their potential contribution to the fine-tuning of D1 and D2 receptor signalling cascades.

The cerebrospinal fluid (CSF) penetration of ofloxacin given orally or intravenously was studied in cancer patients without meningitis. Each patient was assigned to a different sampling time to assess the relation between time and penetration. Ofloxacin was measured in serum and CSF by high-pressure liquid chromatography and bioassay. In addition, the bactericidal titers were measured in CSF and serum against a set of relevant bacteria. Concentrations measured by high-pressure liquid chromatography and bioassay were well correlated. Peak concentrations in CSF (0.4 to 1 ,ig/ml) were observed 2 to 4 h after infusion or oral administration. Peak concentrations in serum were observed just after infusion (2 to 3.5 pg/ml) or 1 to 2 h after oral administration (1.7 to 4 ,ug/ml). Measured bactericidal titers were well correlated with the titers expected from the MBC and concentration. High CSF bactericidal titers were observed against Neisseria meningitidis, Haemophilus influenzae, and Escherichia coli, whereas low or no bactericidal titers were obtained against Staphylococcus aureus, Listeria monocytogenes, and Streptococcus pneumoniae.

11 patients with a prostatic adenoma received a single oral 200 mg dose of ofloxacin 2 h before transurethral resection of the prostate. During the operation, blood samples and prostatic tissue cuttings were collected simultaneously. Ofloxacin was assayed by an original HPLC method with UV detection. The mean concentration of the unchanged drug was 5.10 mg/kg wet tissue and 1.81 mg/l in prostatic tissue and plasma, respectively. The 3.17 prostate/plasma ratio reflected a good penetration of ofloxacin into the prostatic tissue.