Modulation of quinolinic acid-induced depletion of striatal NADPH diaphorase and enkephalinergic neurons by inhibition of nitric oxide synthase

The present study was designed to examine the role of nitric oxide (NO) in quinolinic acid (QUIN)-induced depletion of rat striatal nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase and enkephalinergic neurons. Intrastriatal injection of QUIN produced a dose-dependent decrease in NADPH diaphorase and enkephalin positive cells, with cell loss being evident following the injection of 6 and 18 nmol QUIN, respectively. To evaluate the role of NO in QUIN-induced toxicity, animals were pretreated with the non-specific nitric oxide synthase (NOS) inhibitor, Nomega-nitro-l-arginine (l-NAME) or the selective neuronal NOS inhibitor, 7-nitro indazole (7-NI). l-NAME (2x250 mg/kg, i.p. 8 h apart) maximally inhibited striatal NOS activity by 85%, while 7-NI (50 mg/kg, i.p.) maximally inhibited striatal NOS activity by 60%. Pretreatment with l-NAME or 7-NI potentiated the loss of NADPH diaphorase neurons resulting from intrastriatal injection of low doses of QUIN (18 nmol). Neither NOS inhibitor had any effect on the loss of striatal NADPH diaphorase neurons induced by a higher dose of QUIN (24 nmol). In contrast, 7-NI partially prevented the QUIN (18 and 24 nmol)-induced loss of enkephalinergic neurons, while l-NAME had no effect. These results indicate that NO formation may play a role in QUIN-induced loss of enkephalinergic neurons, but not in the loss of NADPH diaphorase neurons.     

Management of rhesus isoimmunization by preimplantation genetic diagnosis

Intracranial osteolipomas are rare lesions which occur in the region of the tuber cinereum. All cases reported to date have been incidental autopsy findings. We describe a patient who presented with a variety of neurological symptoms and had a typical osteolipoma surgically removed.     

Stereoselective epoxidation of arachidonic acid by cytochrome P-450s 2CAA and 2C2

In the present study, we determined the stereoselective epoxidation of arachidonic acid by cytochrome P-450 (P-450) 2CAA and P-450 2C2, two arachidonic acid epoxygenases found in rabbit renal cortex, by chiral normal-phase high-performance liquid chromatography (HPLC)-analysis. Purified P-450 2CAA reconstituted with P-450 oxidoreductase, lipid and cytochrome b5 or microsomes isolated from COS-1 cells expressing P-450 2C2 were incubated in the presence of [1-14C]arachidonic acid. The epoxide metabolites 14,15- and 11,12-epoxyeicosatrienoic acids (EETs) were purified by reverse-phase HPLC and derivatized to methyl (14,15-EET) and pentafluorobenzyl (11,12-EET) esters. Enantiomers of 14,15-EET-methyl ester and 11,12-EET-pentafluorobenzyl ester were resolved on Chiralcel OB and OD columns, respectively, with a mobile phase of 0.15% 2-propanol in n-hexane. P-450 2CAA and P-450 2C2 produce 11,12- and 14,15-EETs in distinct ratios but are equally stereoselective at the 11,12-position. P-450 2CAA produced 11(S), 12(R)-EET with 63% stereoselectivity, and P-450 2C2 produced the same enantiomer with 61% stereoselectivity. Both enzymes are also stereoselective at the 14,15- position, preferentially producing the 14(R), 15(S)-EET. P-450 2CAA produces this enantiomer with 72% selectivity, and P-450 2C2 produces it with 62% selectivity. The results of this study indicate that P-450 2CAA and P-450 2C2 are not only regioselective but also exhibit a high degree of stereoselectivity.     

Thymoma in dogs: 23 cases (1980-1991)

OBJECTIVE: To assess the efficacy of misoprostol for the treatment of chronic erosive gastritis and associated symptoms. METHODS: We performed a double-blind controlled trial, administering 200-micrograms misoprostol tablets or placebo twice daily for 2 months to 48 patients with symptomatic chronic erosive gastritis. Symptomatology was assessed by means of a standard questionnaire at the beginning and at the end of the study, as well as endoscopic and histologic changes of the gastric mucosa. RESULTS: At the end of the treatment period, a significant reduction in symptom score was observed in misoprostol-treated (from 86.6 +/- 66.2 to 17.6 +/- 18.2, p < 0.001) but not in placebo-treated patients. Endoscopic score was significantly reduced at the end of the treatment period in the misoprostol group, compared with that of the placebo group (p < 0.05). A significant reduction in the activity of histologic gastritis was observed only in patients on misoprostol. The prevalence of gastric colonization by Helicobacter pylori was rather low (30%), and no effect of treatment was observed. CONCLUSIONS: Patients with symptomatic chronic erosive gastritis seem to profit from treatment with misoprostol: the treatment with misoprostol, but not with placebo, was effective in significantly reducing the extent of symptoms. Such an improvement was associated with a substantial improvement in the endoscopic and histologic appearance of the gastric mucosa.     

Taste receptor response to sodium chloride and natriuresis in the workers and employees of an industrial enterprise

Studied in the course of one-stage epidemiologic survey of 1191 individuals were the threshold of gustatory sensitivity to table salt and nycterine natriuresis, relation of these indices to dietary habits, some risk factors for cardiovascular disorders and clinical parameters. Differing relations were established between gustatory sensitivity to table salt and natriuresis and age and gender of the examinees, the level of blood pressure, aggravated heredity in respect of arterial hypertension, smoking and alcohol abuse, this enabling one to embark upon a differential approach to dietetic correction of salt consumption.     

3-Alkanoyl-5-hydroxymethyl tetronic acid homologues and resistomycin: new inhibitors of HIV-1 protease. I. Fermentation, isolation and biological activity

In the course of a screening program for HIV-1 protease inhibiting activity, six new homologues of 3-alkanoyl-5-hydroxymethyl tetronic acids (1 approximately 6) and the known natural product resistomycin (7) were isolated from cultures of the Actinomycete strain DSM 7357. The substituted tetronic acids belong to a recently described structural class of secondary metabolites. The HIV-1 activity of resistomycin (7) has not been reported before.