Association between NOS 2 gene polymorphisms and susceptibility of anti-tuberculous drug induced liver injury / 中华传染病杂志

Objective Inducible isoform of NO synthase(iNOS),coded by NOS2,is one of the antioxidant enzymes. The aim of this study is to explore the association between NOS2 gene polymorphisms and susceptibility of anti-tuberculous drug induced liver injury(ATDILI).Methods Sixteen tagSNP of NOS2 gene were selected using systematic bioinformatic analysis(HWE-P> 0.001, MAF>0.1,r2>0.8).A population based case-control study was performed to genotype 16 tagSNP of NOS2 gene in 461 ATDILI patients and 466 non-ATDILI patients using SNPscanTMtechnology.The genotype and haplotype frequencies were compared between case and control groups.Three genetic models including dominant,recessive and additive models were used to analyze the association between all the selected SNP polymorphisms and susceptibility of ATDILI.Results All the alleles frequencies of these SNP were in Hardy-Weinberg equilibrium.NOS2 rs9906835 G/A genotype,rs944725 T/C genotype, rs3794763 G/A genotype,rs3794764 G/A and A/A genotype,rs6505469 T/A genotype were associated with increased risk for developing ATDILI(all P< 0.05).NOS2 rs9906835,rs944725,rs3794763, rs3794764 and rs6505469 were associated with susceptibility of ATDILI in dominant model(all P<0.05).NOS2 rs944725,rs3794763 and rs3794764 were associated with increased risk for developing ATDILI in recessive model(all P< 0.05).In addition,CGCATT,AC and AAA haplotypes of NOS2 gene were found to have association with susceptibility of ATDILI(all P<0.05).Conclusion Our study showed that NOS2 gene is a susceptible gene of ATDILI.

The methyl ester of rosuvastatin elicited an endothelium-independent and 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent relaxant effect in rat aorta

The relaxant effect of the methyl ester of rosuvastatin was evaluated on aortic rings from male Wistar rats (250-300 g, 6 rats for each experimental group) with and without endothelium precontracted with 1.0 µM phenylephrine. The methyl ester presented a slightly greater potency than rosuvastatin in relaxing aortic rings, with log IC50 values of -6.88 and -6.07 M, respectively. Unlike rosuvastatin, the effect of its methyl ester was endothelium-independent. Pretreatment with 10 µM indomethacin did not inhibit, and pretreatment with 1 mM mevalonate only modestly inhibited the relaxant effect of the methyl ester. Nω-nitro-L-arginine methyl ester (L-NAME, 10 µM), the selective nitric oxide-2 (NO-2) inhibitor 1400 W (10 µM), tetraethylammonium (TEA, 10 mM), and cycloheximide (10 µM) partially inhibited the relaxant effect of the methyl ester on endothelium-denuded aortic rings. However, the combination of TEA plus either L-NAME or cycloheximide completely inhibited the relaxant effect. Inducible NO synthase (NOS-2) was only present in endothelium-denuded aortic rings, as demonstrated by immunoblot with methyl ester-treated rings. In conclusion, whereas rosuvastatin was associated with a relaxant effect dependent on endothelium and hydroxymethylglutaryl coenzyme A reductase in rat aorta, the methyl ester of rosuvastatin exhibited an endothelium-independent and only slightly hydroxymethylglutaryl coenzyme A reductase-dependent relaxant effect. Both NO produced by NOS-2 and K+ channels are involved in the relaxant effect of the methyl ester of rosuvastatin.

Genotyping analysis of a polymorphic G-954C of NOS2A in diabetic retinopathy with cystoid macular edema / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the genotype of the allele distribution of a polymorphic G-954C within the 5 upstream promoter region of the nitric oxide synthetase 2A gene (NOS2A) in samples of diabetic retinopathy in patients with cystoid macular edema in the mainland of China.METHODS: Eighty-nine patients with diabetic retinopathy and cystoid macular edema and 90 healthy controls were enrolled in this study. Nest polymerase chain reaction (PCR)was performed, and restriction endonudease digestion and gene fragments sequence were examined to detect the genotype of NOS24 G-954C.RESULTS: The genotypes of the sample population of 89 cases and 90 healthy controls were all detected as GG.CONCLUSION: The distribution of G-954C of NOS2A polymorphism are at a lower frequency in China, with little relevancy to the frequency of diabetic retinopathy combined with cystoid macular edema.

Expression Pattern of Nitric Oxide Synthases in Rat Skeletal Muscle after Cyclic Episodes of Short Ischemia and Reperfusion / 체질인류학회지

The ischemic preconditioning was initially identified as a protective maneuver induced by brief periods of ischemia followed by reperfusion. Although ischemic preconditioning can reduce ischemic injury of heart, skeletal muscle and neuronal tissue, it's protective mechanism remains elusive. Recently, several investigations suggest the associations of nitric oxide with protection from ischemic injury. Nitric oxide synthesized by a member of nitric oxide synthase (NOS) family has been known to increase or decrease the ischemic injury. The purpose of this study was to observe the expression patterns of NOS 1, NOS 2 and NOS 3 in the rat skeletal muscle after cyclic episodes of short ischemia and reperfusion. Nine and thirty-five weeks-old male Sprague-Dawley rats were divided into control and cyclic short ischemia and reperfusion groups. The experimental group was further divided into 3 groups based on cycles of short ischemia and reperfusion. For cyclic short ischemia and reperfusion, left commom iliac artery was occluded 3, 6 and 10 times for 5 minutes ischemia followed by 5 minutes reperfusion using rodent vascular clamps. The animals were sacrificed at hours 0, 3, 6, 24 and 72 after reperfusion and the left rectus femoris muscles were removed. The expression profiles and distribution of NOS 1, NOS 2 and NOS 3 were examined with immunohistochemical staining. The results were as follows; In the cyclic of short ischemia and reperfusion groups, the mortality was increased with increasing of cyclic episodes at 72 hours after reperfusion, and aging. In the control group, NOS 1, NOS 2 and NOS 3 immunoreactivities showed no differenes with aging. In the 9 weeks-old rats, NOS 1 immunoreactivities were observed moderate at 24 hours after 6 times of short ischemia and reperfusion, and moderate and strong at 24 hours after 10 times of short ischemia and reperfusion. In the 35 weeks-old rats, NOS 1 immunoreactivities were observed trace or mild at 24 hours after 6 and 10 times of short ischemia and reperfusion. At 3 hours after 3 times of short ischemia and reperfusion, NOS 2 immunoreactivities were observed moderate or strong, and trace in the 9 and 35 weeks-old rats, respectively. At 3 hours after 10 times of short ischemia and reperfusion, NOS 3 immunoreactivities were observed mild or moderate, and trace or negative in the 9 and 35 weeks-old rats, respectively. In summary, the expression profile of NOS 1, NOS 2 and NOS 3 were observed differently with increasing episodes of short ischemia and reperfusion. The alteration was the most prominent in NOS 3 than in NOS 1 and NOS 2. These results suggest that the alteration of NOS 3 known to protect tissue against ischemic injury may be associated with increasing mortality after multiple episodes of short ischemia and reperfusion.

Expressions of NOS2 and NOS3 in human non-small cell lung cancer and the relationship with tumor angiogenesis and lymph node metastasis / 医学研究生学报

Objective: To investigate the expression and distribution of NOS2 and NOS3 in human non-small cell lung cancer (NSCLC),and to evaluate the relationship between their expression and tumor angiogenesis and lymph node metastasis. Methods: the expression of NOS2, NOS3 and IMVD in 95 patients with NSCLC were examined using immunohistochemical methods (S-P), and the relationship between them and many clinicopathological parameters was analyzed. Results: The positive expression of NOS3 was associated with histological subtype, IMVD and lymph node metastases of NSCLC(P

Expressions of VEGF, b-FGF,NOS_2 and NOS_3 in human non-small cell lung cancer and the relationship between them and tumor angiogenesis and lymph node metastasis / 中国癌症杂志

Purpose:To investigate the expression and distribution of VEGF, b FGF, NOS 2 and NOS 3 in human non small cell lung cancer (NSCLC),and to evaluate the relationship between their expression and tumor angiogenesis and lymph node metastasis.Methods:The expression of VEGF, b FGF, NOS 2, NOS 3 and IMVD in 95 patients with NSCLC were examined using immunohistochemical methods (SP), and the relationship between them and many clinicopathological parameters was analyzed.Results:The positive expression of VEGF and b FGF was associated with intratumor microvessel density(IMVD), TNM stage and lymph node metastases of NSCLC, respectively( P

Radiation Effect on NO, NOS and TGF-beta Expressions In Rat Lung / 대한방사선종양학회지

PURPOSE: NOS2 induce NO production and NO activate TGF-beta. The TGF-beta is a inhibitor of NOS2. If this negative feedback mechanism operating in radiation pneumonitis model, NOS2 inhibitor may play a role in TGF-beta suppression. We planned this study to evaluate the expression patterns of NO, NOS2 and TGF-beta in vivo radiation pneumonitis model. MATERIALS AND METHODS: Sixty sprague-Dawley rat were irradiated 5 Gy or 20 Gy. They were sacrificed 3, 7, 14, 28 and 56 days after irradiation. During sacrifice, we performed broncho-alveolar lavage (BAL). The BAL fluids were centrifuged and supernatents were used for measure NO and TGF-beta, and the cells were used for RT-PCR. RESULTS: After 5 Gy of radiation, NO in BAL fluid increased at 28 days in both lung and TGF-beta in left lung at 56 days. NO increased in BAL fluid at 28 days in both lung after irradiation and TGF-beta in right lung at 28-56 days after 20 Gy of radiation. After 5 Gy of radiation, NOS2 expression was increased in right lung at 14 days, in both lung at 28 days and in left lung at 56 days. TGF-beta expression was reduced in both lung at 28 days and increased in left lung at 56 days. CONCLUSIONS: The proposed feedback mechanism of NO, NOS2 and TGF-beta was operated in vivo radiation pneumonitis model. At 56 days, however, NOS2 and TGF-beta expressed concurrently in left lung after 5 Gy and in both lung after 20 Gy of radiation.