有症状门诊病人深静脉血栓形成的诊断,临床评价和D-二聚体分析可能减少对影像学诊断的需要

深静脉血栓形成(DVT)的年发病率为48-182／10万,一般估计为1／1000。DVT病死率为1%-5%,发病率和病死率与年龄密切相关。慢性疼痛、肿胀、偶尔腿部皮肤溃疡等血栓后综合征见于1／3发生过DVT的患者。血栓后综合征可出现较早,也可迟至10年才出现,总的发病率为2年23%,5年28%。患者如使用弹力加压袜至少2年以上,腿部病变的发生率可     

Evaluation of the effects of VKORC1 polymorphisms and haplotypes, CYP2C9 genotypes, and clinical factors on warfarin response in Sudanese patients

Objective

African populations, including the Sudanese, are underrepresented in warfarin pharmacogenetic studies. We designed a study to determine the associations between the polymorphisms and haplotype structures of CYP2C9 and VKORC1 and warfarin dose response in Sudanese patients, one of the most genetically diverse populations in Africa.

Material and methods

The effect of the CYP2C9 polymorphisms (*2, *3, *5, *6, *8, *9, and *11), 20 VKORC1 tag SNPs and haplotypes, and clinical covariates were comprehensively assessed in 203 Sudanese warfarin-treated patients.

Results

Patients with the CYP2C9*2,*5,*6, or *11 variant required a daily warfarin dose that was 21% lower than those with CYP2C9*1/*1 (4.7 vs 5.8?mg/day, P?VKORC1 and POL3S genes were divided into two haplotype blocks in Sudanese populations. According to multiple linear regression results, rs8050984, rs7294, and rs7199949 in the VKORC1 and POL3S genes (P?<0.001, <0.001, <0.001, respectively), CYP2C9 genotype (*2, *5, *6, *11; P?P?=?0.04), target INR (P?=?0.007), and concurrent medications (P?=?0.029) could explain about 36.7% of the total warfarin dose variation.

Conclusion

Our data revealed that VKORC1 and CYP2C9 polymorphisms are important factors that influence warfarin dose response in Sudanese patients. Our data suggest that combinations of the SNPs may improve predictions of warfarin dose requirements.     

Attenuating effect of lycopene and ellagic acid on 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced spermiotoxicity and testicular apoptosis

This study was conducted to investigate the prophylactic effects of lycopene (LC) and ellagic acid (EA) on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced testicular and spermatozoal toxicity. These toxicological changes are associated with the oxidative stress and apoptosis in male rats. Forty-eight male rats were allocated to one of six groups of 8 rats each: control, LC, EA, TCDD, TCDD+LC, and TCDD+EA. The control group was treated with 0.5?mL/rat slightly alkaline solution+0.5?mL/rat corn oil every other day. The LC group was treated with 0.5?mL/rat slightly alkaline solution+0.5?mL/rat corn oil containing 10?mg/kg of LC every other day. The EA group received 0.5?mL/rat corn oil+0.5?mL/rat slightly alkaline solution containing 2?mg/kg of EA every other day. The TCDD group received 0.5?mL/rat corn oil containing 100?ng/kg/day of TCDD+0.5?mL/rat slightly alkaline solution. The TCDD+LC group was treated with 0.5?mL/rat TCDD+0.5?mL/rat LC. The TCDD+EA group was treated with 0.5?mL/rat TCDD+0.5?mL/rat EA. All treatments were made by gavage, and the experimental period was maintained during 8 weeks. Sperm motility, concentration, and abnormal sperm rate in epididymal tissue, testicular tissue lipid peroxidation (LPO), antioxidant enzyme activity, histopathological changes, and apoptosis (i.e., Bax and Bcl-2 proteins) were determined. TCDD exposure resulted in significant decreases in sperm motility, concentration, testicular superoxide dismutase activity, germinal cell-layer thickness, Johnsen's testicular score, and significant increases in abnormal sperm rate, testicular malondialdehyde, glutathione levels, Bax-positive staining, and Bax-positive apoptotic cell score, along with some testicular histopathological lesions. TCDD treatment did not affect significantly catalase activity. However, combined treatment with LC or EA, in addition to TCDD, prevented the development of TCDD-induced damages in sperm quality, testicular histology, and LPO. Improvements in testicular apoptosis after the administration of LC and EA to TCDD-treated rats were minimal, but not statistically significant. TCDD-induced lipid peroxidation leads to functional and structural damages, as well as apoptosis, in spermatogenic cells of rats. Both LC and EA protected against the development of these effects.     

The Use of 3,5,4'-Tri-O-acetylresveratrol as a Potential Pro-drug for Resveratrol Protects Mice from γ-Irradiation-Induced Death

Currently, no drugs are available to protect humans from γ-irradiation-induced death. Because reactive oxygen species are produced upon exposure to γ-irradiation and directly responsible for the resulting death, we hypothesized that antioxidants found in foodstuffs may provide a safe and potent means of antioxidant-dependent radioprotection. Here, we describe our studies investigating the radioprotective properties of resveratrol and 3,5,4'-tri-O-acetylresveratrol. Each of these natural antioxidants was found to protect live cells after γ-irradiation. In mice, the use of 3,5,4'-tri-O-acetylresveratrol with Cremophor EL was particularly effective, indicating that this natural antioxidant may be a leading candidate for radioprotective drug development.