Organophosphate induced delayed polyneuropathy

Organophosphate induced delayed polyneuropathy (OPIDP) is a rare sensory-motor distal axonopathy, which usually occur after ingestion of large doses of certain organophosphate insecticide. The clinical picture is characterized by the distal paresis in lower limb associated with sensory symptoms. Electrodiagnostic studies show a motor axonal neuropathy. This case occurred in a 14 years old girl who developed cramping pain in both calves associated with lower limbs paresis 6 weeks after accidental organophosphate poisoning. After another week, she also developed weakness in both hands. Electrophysiological study was characterized by an axonal polyneuropathy pattern. Patient improved upon oral multivitamin therapy and physiotherapy.     

Analysis of the novel factor X gene mutation Glu51Lys in two families with factor X-Riyadh anomaly

Two families with 'factor X(FX)-Riyadh' have been identified (one of them related to the originally reported family). Affected members of both families exhibit prolongation in prothrombin time (PT) with normal partial thromboplastin time (PTT) and low assay levels of FX, when measured by PT-based assay. They do not have clinical bleeding diathesis, regardless of the PT prolongation. FX genes of the affected family members were analyzed by sequence analysis. A novel missense mutation in exon 4 of the FX gene, which causes the Glu51Lys substitution in the first epidermal growth factor-like domain of FX was found. The Glu51Lys mutation represents a type II mutation with low FX coagulant activity in the extrinsic pathway and normal FX antigen levels. This mutation may result in disruption of the predicted H-bonding between residue Glu51 of FX and the Asn199 residue of the tissue factor (TF) in the FX/TF/factor VIIa ternary complex, producing the phenotype 'FX deficiency Riyadh', with prolonged PT and normal PTT.     

The role of nitric oxide within the nucleus accumbens on the acquisition and expression of morphine-induced place preference in morphine sensitized rats

In the present study, the effects of intra-accumbal administration of L-arginine, a nitric oxide precursor, and N(G)-nitro-L-arginine methyl-ester (L-NAME), a nitric oxide synthase inhibitor, on the acquisition and expression of morphine-induced place conditioning in morphine-sensitized rats were studied. Subcutaneous (s.c.) administration of morphine (2.5, 5 and 7.5 mg/kg) induced conditioned place preference. Repeated pretreatment of morphine (5 mg/kg, i.p.) followed by 5 days without drug treatment, increased conditioning response induced by morphine (0.25, 0.5 and 0.75 mg/kg). Intra-accumbal (intra-nucleus accumbens; 1 microg/rat) administration of L-arginine (0.3, 1 and 3 microg/rat) significantly increased or reduced the acquisition of morphine place conditioning in non-sensitized and sensitized rats respectively. However, the drug reduced expression of place conditioning by morphine in sensitized animals. Intra-nucleus accumbens injections of L-NAME (0.3, 1 and 3 microg/rat) reduced the acquisition and expression of morphine place conditioning in the sensitized animals. The results indicate that nitric oxide (NO) within the nucleus accumbens is involved in the acquisition and expression of morphine place conditioning in morphine-sensitized rats.     

Cytotoxicity of chloroquine in isolated rat hepatocytes

Chloroquine is a synthetic quinoline being used as an antimalaria and antirheumatoid agent. Several cases of hepatotoxicity have been reported with the use of chloroquine. However, the mechanism(s) of its hepatotoxic effect is unknown. The purpose of this study was to investigate the cytotoxic mechanism of chloroquine. Cytotoxicity was studied using freshly isolated rat hepatocytes incubated in Krebs-Henseleit buffer under a flow of 95% O(2) and 5% CO(2). Chloroquine was toxic towards hepatocytes and caused cell death with an ED(50) of about 100 mm in 2 h. The events before cell death were rapid GSH depletion and lipid peroxidation. Cytochrome P-450 inhibitors, troleandromycine, cimetidine and quinidine increased the cytotoxicity of chloroquine. Antioxidants significantly prevented the cytotoxicity of chloroquine. Depleting the hepatocyte GSH beforehand increased the chloroquine cytotoxicity. Preventing chloroquine metabolism by specific P-450 inhibitors increased its toxicity, suggesting that a major part of its toxicity is mediated by chloroquine and not by its metabolites. A depletion of the antioxidant defense system is involved in the mechanism of cytotoxicity.