The prodynorphin system in the rat hippocampus is differentially influenced by kainic acid and pentetrazole.

Administration of kainic acid (15 mg/kg, i.p.) or pentetrazole (75 mg/kg, i.p.) to rats evoked recurrent limbic or tonic-clonic seizures, respectively. Radioimmunoassay showed that the level of alpha-neoendorphin (prodynorphin-derived peptide) in the hippocampus was decreased after 3 h (by c. 60%) and 72 h (by c. 40%), but was not changed after 24 h following kainic acid administration. The basal release of alpha-neoendorphin from hippocampal slices of kainic acid-treated rats was decreased after 3, 24 and 72 h following the drug injection by c. 50%. The K(+)-stimulated release was decreased after 3 and 24 h (by c. 300 and 200%, respectively) and was back to the control level after 72 h. An in situ hybridization study showed that kainic acid strongly enhanced the prodynorphin messenger RNA levels in the dentate gyrus after 3 and 24 h (by c. 200%), whereas after 72 h it tended to decrease. Twenty four hours after pentetrazole injection the hippocampal level of alpha-neoendorphin was elevated (by c. 33%) and remained unchanged after 3 and 72 h. No significant changes in the basal or K(+)-stimulated alpha-neoendorphin release from hippocampal slices of pentetrazole-treated rats were found at any time points measured. Three and 24 h after pentetrazole administration the level of prodynorphin mRNA in the dentate gyrus was slightly decreased (by c. 30%), but was back to the control values after 72 h. Hence seizure-related changes in hippocampal prodynorphin neuron activity seem to depend on the experimental model of epilepsy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of various light sources on visual functions in the age aspect. I. Conscious reaction time and the manual spatial visual localization]

The authors present the results of investigations performed in 28 right-handed, normally seeing persons divided into 2 groups: 15 of them were in productive age and 13 in older age. The authors compared the dynamics of the behaviour of the visual functions in dependence on the age of the subjects and the stay in the glow and sodium light. No adverse influence of the sodium light on the hand localization could be detected, instead it seems that it negatively influenced the selective reaction in older productive persons in the sense of an increased number of faults.     

Pentobarbital in tobacco.

The spectrometric analysis of extracts from tobacco and tobacco smoke revealed the presence of pentobarbital in the analyzed substances. Tobacco samples and tobacco smoke were extracted with chloroform, determinations were performed with the Perkin-Elmer Autosystem XL system, on a Turbo Mass spectrometer. Subject to analysis were 4 cigarette brands manufactured in Poland and raw, unprocessed tobacco. The presence of pentobarbital in the analyzed samples was confirmed by the analysis of the mass spectrum of the substance, as well as by comparison of retention time with standard of pentobarbital. The determined pentobarbital concentrations in tobacco amounted to 3-6 microg/cigarette, and in tobacco smoke they were approximately 45% lower. In case of tobacco extracts it can with high probability be excluded that pentobarbital is synthesized during chromatographical analysis. The presence of pentobarbital in tobacco is thus beyond question.     

Pharmacokinetics of phenazone after bilateral ovariectomy in female rabbits]

The aim of this study was to evaluate the influence of female sex hormones on phenazone pharmacokinetics using as an experimental model female rabbits after a bilateral ovariectomy. Eighteen female rabbits divided into two groups: control animals and experimental rabbits, that underwent ovariectomy, were used in the study. Pharmacokinetic assays were performed in all animals: prior to the study, after 1 month and after 2 months. Blood was sampled within 24 hours after intragastric administration of phenazone at a dose 50 mg/kg b.w. Two compartment open model was used for calculations. Significant increase in AUC and prolongation of phenazone halflife as well as a decrease in the total body clearance were noted. The study demonstrated the possible inhibition of the microsomal mixed-function oxidase system by oestrogens.     

The role of quinone reductase (NQO1) and quinone chemistry in quercetin cytotoxicity.

The effects of quercetin on viability and proliferation of Chinese Hamster Ovary (CHO) cells and CHO cells overexpressing human quinone reductase (CHO+NQO1) were studied to investigate the involvement of the pro-oxidant quinone chemistry of quercetin. The toxicity of menadione was significantly reduced in CHO+NQO1 cells compared to wild-type CHO cells, validating the NQO1-overexpression in the CHO+NQO1 transfectant. Quercetin inhibited the proliferation of wild-type CHO and CHO+NQO1 cells to a similar extent without affecting cell viability, indicating that NQO1 enrichment of CHO cells did not provide increased protection. On the other hand, inhibition of NQO1 in both types of cells by dicoumarol significantly potentiated the inhibitory effect of quercetin on cell proliferation, revealing the role of NQO1 in cellular protection against quercetin. Altogether, these results can be explained by the hypothesis that both wild-type CHO and CHO+NQO1 cells contain sufficient NQO1 activity for optimal protection against the pro-oxidant effect of quercetin on cell proliferation. The results also point at a cellular NQO1 threshold for optimal protection against quercetin. This NQO1 threshold seems to be in the range of NQO1 activities already present in various tissues.     

Brain uptake of radiolabeled N‐oleoyl‐dopamine in the rat

N‐acyl‐dopamines are a novel class of biologically active lipids that have recently been identified in the brain and have the potential to interact with neural signaling pathways. This study seeks to determine the ability of N‐oleoyl‐dopamine, a synthetic amide of oleic acid and dopamine, to cross the blood brain barrier. We determined the tissue content of radioactivity in selected brain regions, in a short‐run study design, following injections of [³H]N‐oleoyl‐dopamine (0.4 µCi) into the internal carotid artery in the rat. These results were compared with intracarotid injections of [³H]dopamine and with intravenous injections of both radiolabeled compounds. The level of radioactivity was determined using liquid scintillation and was expressed as the percentage of its total dose injected per gram of tissue. We found that the 15‐min brain uptake of radioactivity, with no distinct regional variations, amounted to about 6% following the intracarotid [³H]N‐oleoyl‐dopamine, which was a significant 3–4‐fold increase over that following similar administration of [³H]dopamine. Intravenous injections of [³H]N‐oleoyl‐dopamine gave a much smaller yield of radioactivity in brain tissue samples which was still severalfold greater than that for intravenous [³H]dopamine. Qualitative thin‐layered chromatography screening showed the presence of unchanged N‐oleoyl‐dopamine in the brain following injections. We conclude that N‐oleoyl‐dopamine has an appreciable ability to cross the blood‐brain barrier, which contrasts the limited transfer of dopamine alone. N‐oleoyl‐dopamine might exert physiological effects due to its known affinity for the central vanilloid receptors or to better satisfying the brain tissue demand for dopamine. The study suggests a potential pharmacological role for N‐oleoyl‐dopamine delivered exogenously in helping regulate the brain function. Drug Dev. Res. 60:217–224, 2003. © 2003 Wiley‐Liss, Inc.     

Inhibitory effect of tritoqualine on activation of latent polymorphonuclear leukocyte collagenase

Treatment of rats with histamine releaser compound 48/80 caused changes in blood leukocyte populations. An increased number of PMN-leukocytes was observed. Tritoqualine only modestly reduced the number of granulocytes. In animals treated with compound 48/80 an activation of PMN-leukocyte latent collagenase of up to 80% was observed. This activation was partially inhibited (about 40%) in animals pretreated with tritoqualine. The results presented suggest that the beneficial effect of tritoqualine in allergic diseases may be in part connected with an indirect inhibition of collagenase activity.