Association of variable number of tandem repeats in endothelial nitric oxide synthase gene with coronary artery disease

Endo-derived nitric oxide (NO) is synthesized from L-arginine by endothelium nitric oxide synthase (eNOS). Since reduced NO synthesis has been implicated in the development of coronary atherosclerosis; we hypothesized that polymorphisms of NOS gene might be associated with increased susceptibility to this disorder and coronary artery disease (CAD). We studied the 27 base pair tandem repeat polymorphism in intron4 of the endothelial nitric oxide synthase (eNOS) gene in 141 unrelated CAD patients with positive coronary angiograms in Shahid Rajaee Heart Hospital and 159 age matched control subjects without a history of symptomatic CAD. The study protocol was approved by the Iran University of Medical Sciences Ethics Committee. The eNOS gene intron4a/b VNTR polymorphism was analyzed by polymerase chain reaction. The plasma lipids levels and other risk factors were also determined. The genotype frequencies for eNOS4b/b, eNOS4a/b and eNOS4a/a were 68.8, 29.1 and 2.1 in CAD subjects, and 81, 18.4 and 0.6 in control subjects, respectively. The genotype frequencies differed significantly between the two groups (�2= 6.38 P= 0.041). The frequency of the allele was 16.7 in CAD subjects and 9.8 in control subjects and was significantly higher in the patients (�2= 6.18 P= 0.013, odds ratio=1.84). Plasma lipids, except HDL-C were also remarkablely increased in CAD group

A review of the most important native medicinal plants of Iran effective on leishmaniasis according to Iranian ethnobotanical references

The World Health Organization has declared that leishmaniasis is one of the six leading infectious diseases of tropical regions. The disease is transmitted to humans by the bite of sandflies from the genus Phlebotomus and develops cutaneous, mucosal or visceral clinical forms. Although cutaneous leishmaniasis is not a main health issue in terms of mortality, it causes numerous problems due to long period of the wound, tremendous healthcare costs, remaining scar, the likelihood of developing secondary infections or associated complications and sometimes malignancies in the scar site, and complications due to available pharmacotherapies. Studies are being conducted on medicinal plants to identify a suitable drug against Leishmania to treat leishmaniasis. We sought to identify medicinal plants that are used to treat cutaneous leishmaniasis according to references of Iranian traditional medicine. To conduct this review, Leishmania, leishmaniasis, ethnobotany, Iran, and medicinal plants were used to retrieve relevant publications indexed in databases including Scopus, Islamic World Science Citation Center, Scientific Information Database, and Magiran. According to the findings of this review, nine medicinal plants native to Iran are used to treat leishmaniasis. Medicinal plants Calotropis procera, Morus alba, Nerium oleander, Emex spinose, Artemisia absinthium, Artemisia absinthium, and etc are used to treat the wound according to herbal and traditional references. According to phytochemical analysis of these plants, gutaprecha, prenylated flavonoid, scopolin, reseosaid, skimmin, mulberroside A, astroglide, artemisinin, quercetin, and lawson are the most important active anti-leishmaniasis compounds with pharmaceutical potential as well as antiparasitic and disinfectant properties. These compounds can also be used to treat leishmaniasis wound

Hypozincemia in bipolar i disorder (BID) patients

One-third of the world's population is at risk of zinc deficiency. It has been hypothesized that low serum/plasma zinc may contribute to alteration of brain Zn homeostasis and thus had to various psychological disorders. This study was designed to evaluate serum zinc (Zn) as well as copper (Cu) concentrations in patients with Bipolar I Disorder (BID) in our community to support the findings on the possible association of Zn in neuropsychological functions. Participants included 30 BID patients with different phases of mania and depression and 30 healthy controls. Results indicated the mean serum Zn level of the BID group was significantly lower than that of controls (P< 0.0001). Similar results were obtained for Cu. These findings suggest a possible association of Zn levels on neuropsychological dysfunction. Copyright © 2007 by New Century Health Publishers, LLC. All rights of reproduction in any form reserved

Endothelial nitric oxide synthase gene intron4 VNTR polymorphism in patients with coronary artery disease in Iran

Background & objectives: Endo-derived nitric oxide (NO) is synthesized from L-arginine by endothelium nitric oxide synthase (eNOS) encoded by the NOS3 gene on chromosome7. Since reduced No synthesis has been implicated in the development of coronary atherosclerosis; polymorphisms of NOS gene might be associated with increased susceptibility to this disorder and coronary artery disease (CAD). We therefore undertook this study to determine the association between the occurrence of CAD and eNOS4 b/a polymorphism in Iranian patients. Methods: We studied the 27 base pair tandem repeat polymorphism in intron4 of the endothelial nitric oxide synthase (eNOS) gene in 141 unrelated CAD patients with positive coronary angiograms and 159 age matched control subjects without a history of symptomatic CAD. The eNOS gene intron4a/b VNTR polymorphism was analyzed by polymerase chain reaction. The plasma lipids levels and other risk factors were also determined. Results: The genotype frequencies for eNOS4b/b, eNOS4a/b and eNOS4a/a were 68.8, 29.1 and 2.1 per cent in CAD subjects, and 81, 18.4 and 0.6 per cent in control subjects, respectively. The genotype frequencies differed significantly (P<0.05) between the two groups. The frequency of the a allele was 16.7 per cent in CAD subjects and 9.8 per cent in control subjects and was significantly higher in the patients (P<0.05, Odds ratio=1.84). Plasma lipids, except HDL-C were also significantly increased in CAD group. Interpretation & conclusion: Though the genotype frequencies for eNOS4b/ b, eNOS4a/b and eNOS4a/a, also 'a' allele frequency differed significantly between the CAD patients and controls, this polymorphism was not an independent risk factor for the development of CAD in Iranian patients. Further studies with larger samples need to be done to confirm these findings

Association of IL-10 & IL-10RA polymorphisms with lymphatic filariasis in South Indian population

Aim: The filariasis infection is initiated by mosquito derived third stage larva (L3), which establishes itself in different immunocompetent niches by adopting different evasion and immunomodulatory mechanisms. Immunological and clinical outcomes can vary considerably at the individual and population levels during lymphatic filariasis infection. The protein product coded by the interleukin-10 (IL-10) gene has broad immunomodulatory function in filarial load and patency of the disease. The potential influence of altered IL-10 expression encoded by IL-10 promoter single nucleotide polymorphisms (SNPs) and IL-10RA signaling pathway, in pathogenesis and clinical outcome of filarial infection was established in the present study Study Design: Genetic association based on case-control study. Place and Duration of Study: Lymphatic filariasis cases referred to National Filariasis Control Program (NFCP), Siddipet, Medak, Andhra Pradesh, India between Feb 2006 to Dec 2009. Methodology: A total of 100 non-endemic, 50 endemic and 118 lymphatic filariasis patients were included in the present study based on clinical and diagnostic criteria. Genetic polymorphisms in the IL-10 promoter region (-1082G/A, -819C/T and -592 A/C) and IL-10 RA coding region S138G were screened following PCR-RFLP and ARMS-PCR technique respectively. Results: Patients with familial aggregation of lymphedema exhibited significant association with IL-10 -1082 ‘A’ allele (A vs G OR 2.68, CI - 1.12-6.37, P=0.02) coding for lower IL-10 levels. Similarly the G variant of IL-10RA S138G SNP revealed a significant association with lymphatic filariasis in the endemic population studied (GG vs AA OR 2.50 CI-1.22-5.13, P= 0.021). The Haplotype analysis also revealed the low signaling ATA is significantly associated with the disease in this cohort (P=0.03). The Multifactor Dimensionality Reduction Analysis (MDR) for IL-10 and IL-10RA SNPs interaction revealed the three locus model as the best model wherein the epistatic interactions of variant G allele of IL-10RA S138G, the A allele of the -1082G/A and the T allele of the - 819C/T SNPs in IL-10 were found to be a possible risk genotype for filarial infection. (TA = 0.5230, CV-10/10, P=0.001). Conclusion: IL-10 promoter haplotypes and IL-10 RA S138G polymorphisms are the possible genetic determinants of susceptibility to lymphatic filariasis. Further functional studies are warranted to validate these results.Yasmeen Sheik, Sameera Fatima Qureshi, Ananthapur Venkateshwari, Saeed Nourmohammadi, Basheeruddin Mohammad and Pratibha Nallar

Divalent cations regulate the ion conductance properties of diverse classes of aquaporins

Aquaporins (AQPs) are known to facilitate water and solute fluxes across barrier membranes. An increasing number of AQPs are being found to serve as ion channels. Ion and water permeability of selected plant and animal AQPs (plant Arabidopsis thaliana AtPIP2;1, AtPIP2;2, AtPIP2;7, human Homo sapiens HsAQP1, rat Rattus norvegicus RnAQP4, RnAQP5, and fly Drosophila melanogaster DmBIB) were expressed in Xenopus oocytes and examined in chelator-buffered salines to evaluate the effects of divalent cations (Ca2+, Mg2+, Ba2+ and Cd2+) on ionic conductances. AtPIP2;1, AtPIP2;2, HsAQP1 and DmBIB expressing oocytes had ionic conductances, and showed differential sensitivity to block by external Ca2+. The order of potency of inhibition by Ca2+ was AtPIP2;2 > AtPIP2;1 > DmBIB > HsAQP1. Blockage of the AQP cation channels by Ba2+ and Cd2+ caused voltage-sensitive outward rectification. The channels with the highest sensitivity to Ca2+ (AtPIP2;1 and AtPIP2;2) showed a distinctive relief of the Ca2+ block by co-application of excess Ba2+, suggesting that divalent ions act at the same site. Recognizing the regulatory role of divalent cations may enable the discovery of other classes of AQP ion channels, and facilitate the development of tools for modulating AQP ion channels. Modulators of AQPs have potential value for diverse applications including improving salinity tolerance in plants, controlling vector-borne diseases, and intervening in serious clinical conditions involving AQPs, such as cancer metastasis, cardiovascular or renal dysfunction.Mohamad Kourghi, Saeed Nourmohammadi, Jinxin V. Pei, Jiaen Qiu, Samantha McGaughey, Stephen D. Tyerman, Caitlin S. Byrt and Andrea J. Yoo

Fundamental structural and functional properties of Aquaporin ion channels found across the kingdoms of life

Aquaporin (AQP) channels in the Major Intrinsic Protein (MIP) family are known to facilitate transmembrane water fluxes in prokaryotes and eukaryotes. Some classes of AQPs also conduct ions, glycerol, urea, CO₂ , nitric oxide, and other small solutes. Ion channel activity has been demonstrated for mammalian AQPs 0, 1, 6, Drosophila big brain (BIB), soybean nodulin 26, and rockcress AtPIP2;1. More classes are likely to be discovered. Newly identified blockers are providing essential tools for establishing physiological roles of some of the AQP dual water and ion channels. For example, the arylsulfonamide AqB011 which selectively blocks the central ion pore of mammalian AQP1 has been shown to impair migration of HT29 colon cancer cells. Traditional herbal medicines are sources of selective AQP1 inhibitors that also slow cancer cell migration. The finding that plant AtPIP2;1 expressed in root epidermal cells mediates an ion conductance regulated by calcium and protons provided insight into molecular mechanisms of environmental stress responses. Expression of lens MIP (AQP0) is essential for maintaining the structure, integrity and transparency of the lens, and Drosophila BIB contributes to neurogenic signalling pathways to control the developmental fate of fly neuroblast cells; however, the ion channel roles remain to be defined for MIP and BIB. A broader portfolio of pharmacological agents is needed to investigate diverse AQP ion channel functions in situ. Understanding the dual water and ion channel roles of AQPs could inform the development of novel agents for rational interventions in diverse challenges from agriculture to human health. This article is protected by copyright. All rights reserved.Mohamad Kourghi, Jinxin V. Pei, Michael L. De Ieso, Saeed Nourmohammadi, Pak Hin Chow, Andrea J. Yoo