Idiosyncratic NSAID drug induced oxidative stress

Many idiosyncratic non-steroidal anti-inflammatory drugs (NSAIDs) cause GI, liver and bone marrow toxicity in some patients which results in GI bleeding/ulceration/fulminant hepatic failure/hepatitis or agranulocytosis/aplastic anemia. The toxic mechanisms proposed have been reviewed. Evidence is presented showing that idiosyncratic NSAID drugs form prooxidant radicals when metabolised by peroxidases known to be present in these tissues. Thus GSH, NADH and/or ascorbate were cooxidised by catalytic amounts of NSAIDs and hydrogen peroxide in the presence of peroxidase. During GSH and NADH cooxidation, oxygen uptake and activation occurred. Furthermore the formation of NSAID oxidation products was prevented during the cooxidation indicating that the cooxidation involved redox cycling of the first formed NSAID radical product. The order of prooxidant catalytic effectiveness of fenamate and arylacetic acid NSAIDs was mefenamic acid>tolfenamic acid>flufenamic acid, meclofenamic acid or diclofenac. Diphenylamine, a common moiety to all of these NSAIDs was a more active prooxidant for NADH and ascorbate cooxidation than these NSAIDs which suggests that oxidation of the NSAID diphenylamine moiety to a cation and/or nitroxide radical was responsible for the NSAID prooxidant activity. The order of catalytic effectiveness found for sulfonamide derivatives was sulfaphenazole>sulfisoxazolez.Gt;dapsone>sulfanilic acid>procainamide>sulfamethoxazole>sulfadiazine>sulfadimethoxine whereas sulfanilamide, sulfapyridine or nimesulide had no prooxidant activity. Although indomethacin had little prooxidant activity, its major in vivo metabolite, N-deschlorobenzoyl indomethacin had significant prooxidant activity. Aminoantipyrine the major in vivo metabolite of aminopyrine or dipyrone was also more prooxidant than the parent drugs. It is hypothesized that the NSAID radicals and/or the resulting oxidative stress initiates the cytotoxic processes leading to idiosyncratic toxicity.     

Spontaneous insertion and partitioning of alkaline phosphatase into model lipid rafts

Several cell surface eukaryotic proteins have a glycosylphosphatidylinositol (GPI) modification at the C-terminal end that serves as an anchor to the plasma membrane and could be responsible for the presence of GPI proteins in rafts, a type of functionally important membrane microdomain enriched in sphingolipids and cholesterol. In order to understand better how GPI proteins partition into rafts, the insertion of the GPI-anchored alkaline phosphatase (AP) was studied in real-time using atomic force microscopy. Supported phospholipid bilayers made of a mixture of sphingomyelin–dioleoylphosphatidylcholine containing cholesterol (Chl+) or not (Chl–) were used to mimic the fluid-ordered lipid phase separation in biological membranes. Spontaneous insertion of AP through its GPI anchor was observed inside both Chl+ and Chl– lipid ordered domains, but AP insertion was markedly increased by the presence of cholesterol.     

Incremental genetic K-means algorithm and its application in gene expression data analysis

Background  

In recent years, clustering algorithms have been effectively applied in molecular biology for gene expression data analysis. With the help of clustering algorithms such as K-means, hierarchical clustering, SOM, etc, genes are partitioned into groups based on the similarity between their expression profiles. In this way, functionally related genes are identified. As the amount of laboratory data in molecular biology grows exponentially each year due to advanced technologies such as Microarray, new efficient and effective methods for clustering must be developed to process this growing amount of biological data.     

Cyclic thioether peptide mimetics as VCAM-VLA-4 antagonists

Selective substitution of a sulfur atom by carbon in a highly potent 13-membered cyclic disulfide was accomplished by intramolecular displacement of a bromide. The potency of the resulting thioethers in the VCAM/VLA-4 assay was dependent on ring size and the position of the sulfur atom.     

Mobile blood collection sites and their roles in providing safe and adequate supply: A six-year experience

Background

The determination of the role of mobile sites, as compared with fixed sites, in providing safe blood supply will help with the planning of future programs.

Materials and Methods

This retrospective study was carried out at the Khuzestan Blood Transfusion Organization from 2007 to 2012. Samples of the blood collected at mobile sites and fixed sites were compared. Comparisons took into consideration noticeable trends as well as the prevalence of major TTIs including HIV, HBV and HCV.

Results

The total number of blood donations from 2007 to 2012 was 621117 out of which 89590 (14.43%) were collected from mobile sites. The overall blood donation index was estimated at 23.8 per 1000 population. The prevalence of HIV, HBV and HCV in mobile site donations was 5.31, 320.34 and 117.4, and in fixed sites was 5.31, 214.72 and 104.83 per 100000 donations respectively. HBV prevalence in mobile sites was significantly higher than in fixed sites (p = 0.014).

Conclusion

The blood donation index in Khuzestan province is much better when compared with areas of similar socioeconomic status as well as neighboring countries. The allotment of blood units collected by mobile teams is lower than that of national reports. In addition, the prevalence of TTIs in mobile site blood donations was higher than at fixed sites.

     

Molecular confirmation of the occurrence of Elysia cf. tomentosa (Mollusca: Heterobranchia) in the Persian Gulf

The molluscan fauna of the Persian Gulf has recently been relatively well documented, yet there are few records of heterobranch sea slugs (opisthobranchs) from the Arabian parts and no report from the Iranian waters. Here we report for the first time the occurrence of one of these molluscs in the northern Persian Gulf (Bandar Abbas, Iran). Sacoglossan specimens were collected in association with the seaweed, Caulerpa sertularioides. Since morphological attributes were not adequately reliable for species identification, molecular approaches were carried out. Maximum-likelihood and Bayesian Inference analysis of partial DNA sequences of the mitochondrial cytochrome c oxidase subunit I (COI) locus were used for DNA barcoding of large-bodied specimens of Elysia. All Persian Gulf specimens were genetically confirmed as Elysia cf. tomentosa sp. 5, one of at least five morphologically similar but genetically distinct species in the taxonomically challenging and unresolved E. tomentosa complex. This species has previously been recorded only from Australia and Thailand and our finding adds another distant point to the geographic distribution of this species.     

Bioassay evaluation of the entomopathogenic fungus,Lecanicillium longisporum (Petch) Zare & Gams against egg and nymphs of Trialeurodes vaporariorum Westwood in laboratory conditions

Abstract

This study was carried out to determine the lethality of the entomopathogenic fungus, Lecanicillium longisporum on eggs, young and old nymphs of the greenhouse whitefly, Trialeurodes vaporariorum. Mortality percentage was significantly differed based on stage of T. vaporariorum and conidial concentrations of L. longisporum. Average of the infection level to insect was very low particularly in egg with only 9.81%, even with higher conidial concentrations (1×10⁷ conidia mL^-1). Whereas, it was higher in 1^st and 2^nd instar (46.56%) and 3^rd and 4^th instars (37.21%). Three parameters were assessed with T. vaporariorum eggs, namely; egg infection, egg hatchability and crawlers emergence. Egg mortality percentages averaged 3.56, 7.14, 9.64, 16.42 and 20.35% with fungal concentrations of 1×10³, 1×10⁴, 1×10⁵, 1×10⁶ and 1×10⁷ conidia mL^-1, respectively. Daily infection percentages were varied depend upon the conidia concentration where the highest infection rate of eggs was occurred with 1×10⁷. Egg hatch was very high and the mortality among the emerged crawlers was neglectable compared with the control. Efficiency of L. longisporum on whitefly nymphs also was varied based on the insect instar and fungal concentration. Mortality percentages were obviously higher in young nymphs (1^st and 2^nd instars) than in older ones (3^rd and 4^th instars). The results indicated that nymphs were highly susceptible to fungal treatment compared with eggs.