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1.
The continuous use of synthetic hormones as contraceptive pill or hormonal replacement therapy among women is increasing day by day. The widespread use of different formulations as oral contraceptives by women throughout their reproductive cycle has given rise to a serious concern for studying the effects of oral contraceptives on enzymatic profile and DNA damage in peripheral blood lymphocytes among users. The present study was carried out on women taking oral contraceptives. The study was based on the questionnaire having the information of reproductive history, fasting, age, health, nature of menstrual cycle, bleeding and other disease. The profile of the blood serum enzymes i.e. alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), aminotransferases (SGOT and SGPT), serum proteins (albumin and globulin) and DNA damage in lymphocytes was studied among users and non-users. The results of the present study suggest that OCs not only effects enzymatic activity but also results in DNA damage that may vary with the duration of using oral contraceptives. A significant increase in LDH, GGT, SGPT, SGOT, globulin and decrease in ALP as well as albumin was found among users as compared to non-users. The observed DNA damage was more in users as compared to non-users. Hormonal contraceptives seem to exert DNA damage and also have significant effects on blood serum enzymes.  相似文献   

2.
Hepatitis B virus (HBV) infection is a worldwide health concern which is associated with significant morbidity and mortality. Both viral and host factors have a significant effect on infection, replication and pathogenesis of HBV. The aim of this study was to investigate the effect of CYP2E1 and CYP1A1 genetic variants on susceptibility to HBV. 143 individuals including 54 chronic HBV patients and 89 healthy controls were enrolled in the genotyping procedure. rs2031920 and rs3813867 at CYP2E1 as well as rs4646421 and rs2198843 at CYP1A1 loci were studied in all subjects using PCR–RFLP (restriction fragment length polymorphism) analysis. Both variants at CYP2E1 locus were monomorphic in all studied subjects. Genotype frequency of rs4646421 was significantly different between chronic HBV patients and healthy blood donors (P = 0.04, OR 4.31; 95% CI 1.04–17.7). Furthermore, individuals carrying at least one C allele (CC or CT genotypes) for rs4646421 seemed to have a decrease risk of hepatitis in comparison with TT genotype (P = 0.039). Our results showed a relationship between rs4646421 TT genotype (rare genotype) and the risk for developing chronic HBV infection (four times higher). Further studies are needed to examine the role of CYP1A1 polymorphism in susceptibility to chronic HBV infection.  相似文献   

3.
Coumarinic oral-anticoagulants (COAs) are commonly used for treatment of thromboembolic events. However, these medications have a narrow therapeutic range and there are large inter-individual variations in drug response. This is especially important in the initial phases of oral-anticoagulant therapy. Recent advancements in pharmacogenetics have established that clinical outcomes in oral-anticoagulant therapy are affected by genetic factors. The allelic variants of genes like cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) are closely associated with maintenance dose of oral anti-coagulants. In addition, GGCX (Gamma-glutamyl carboxylase) polymorphism at position 12970 (rs11676382), CYP4F2 (rs2108622; V433M; 1347 C > T) and Apolipoprotein E (APOE) variants have been shown to explain a small but significant influence on dose requirements. There are large differences in the frequencies of these polymorphisms between different world populations which are also related to the requirements of oral anticoagulants. However, the final drug dosage in an individual is determined by complex sets of genetic and environmental factors and several dosing algorithms which combine clinical and genetic parameters to predict therapeutic COA doses have also been developed. The algorithm based dose prediction shows the importance of pharmacogenetic testing in patients undergoing oral anticoagulant therapies.  相似文献   

4.
Cripto-1 (CR-1) is an oncofetal protein with its role as a key factor in early process of carcinoma has been evaluated in cases of various cancers. However, very few studies have reported its role in oral cancer, which is the sixth most common cancer around the world, particularly with high prevalence in developing countries. Oral squamous cell carcinoma (OSCC) is the most predominant (90%) of all the histological types of oral cancer. Late detection, associated with increased morbidity and mortality, is mainly attributed to non-availability of a suitable biomarker for the disease. In the present pilot study, we have evaluated the role of soluble CR-1, in serum as a potential tumor marker for OSCC. CR-1 was estimated using sandwich ELISA in serum samples of 50 biopsy proven OSCC patients (pre and post treatment) along with age and gender matched healthy controls. Immunohistochemistry was also done in corresponding tumor tissue sections to check the expression of CR-1. Pre-treatment CR-1 was found to be 2.25-fold higher in serum of OSCC patients as compared to control (p < 0.0001***), which was reduced to 1.6 folds post treatment (p = 0.0006***). CR-1 levels were comparatively higher in early stage of disease. Upon IHC 80% of the cases were found to be positive for CR-1. This study provides evidence that serum levels of CR-1 are elevated in patients of Oral Squamous Cell Carcinoma, which decrease post treatment. Also, the association of expression of protein with tumor progression predicts CR-1 as a molecule that can be further evaluated as a potential tumor maker in OSCC.  相似文献   

5.
Type 2 diabetes mellitus (T2DM) is a worldwide epidemic with considerable health and economic consequences. T2DM patients are often treated with more than one drug, including oral antidiabetic drugs (OAD) and drugs used to treat diabetic complications, such as dyslipidemia and hypertension. If genetic testing could be employed to predict treatment outcome, appropriate measures could be taken to treat T2DM more efficiently. Here we provide a review of pharmacogenetic studies focused on OAD and a role of common drug-metabolizing enzymes (DME) and drug-transporters (DT) variants in therapy outcomes. For example, genetic variations of several membrane transporters, including SLC22A1/2 and SLC47A1/2 genes, are implicated in the highly variable glycemic response to metformin, a first-line drug used to treat newly diagnosed T2DM. Furthermore, cytochrome P450 (CYP) enzymes are implicated in variation of sulphonylurea and meglitinide metabolism. Additional variants related to drug target and diabetes risk genes have been also linked to interindividual differences in the efficacy and toxicity of OAD. Thus, in addition to promoting safe and cost-effective individualized diabetes treatment, pharmacogenomics has a great potential to complement current efforts to optimize treatment of diabetes and lead towards its effective and personalized care.  相似文献   

6.
Polycyclic aromatic hydrocarbons (PAHs) are among the most prevalent environmental pollutants and result from the incomplete combustion of hydrocarbons (coal and gasoline, fossil fuel combustion, byproducts of industrial processing, natural emission, cigarette smoking, etc.). The first phase of xenobiotic biotransformation in the PAH metabolism includes activities of cytochrome P450 from the CYP1 family and microsomal epoxide hydrolase. The products of this biotransformation are reactive oxygen species that are transformed in the second phase through the formation of conjugates with glutathione, glucuronate or sulphates. PAH exposure may lead to PAH-DNA adduct formation or induce an inflammatory atherosclerotic plaque phenotype. Several genetic polymorphisms of genes encoded for enzymes involved in PAH biotransformation have been proven to lead to the development of diseases. Enzyme CYP P450 1A1, which is encoded by the CYP1A1 gene, is vital in the monooxygenation of lipofilic substrates, while GSTM1 and GSTT1 are the most abundant isophorms that conjugate and neutralize oxygen products. Some single nucleotide polymorphisms of the CYP1A1 gene as well as the deletion polymorphisms of GSTT1 and GSTM1 may alter the final specific cellular inflammatory respond. Occupational exposure or conditions from the living environment can contribute to the production of PAH metabolites with adverse effects on human health. The aim of this study was to obtain data on biotransformation and atherosclerosis, as well as data on the gene polymorphisms involved in biotransformation, in order to better study gene expression and further elucidate the interaction between genes and the environment.  相似文献   

7.
Single nucleotide polymorphisms in CYP3A5 (A6986G) and MDR-1 (C3435T) genes have been shown to be associated with the pharmacokinetics of tacrolimus in case of renal transplant recipients. Knowing these genotypes of the recipients before undergoing transplantation, is therefore essential for physicians to adjust the starting dose of tacrolimus in order to avoid drug induced nephrotoxicity. We have designed an allele specific PCR method for easier and rapid detection of these polymorphisms. 20 Indian renal transplant recipients on tacrolimus who developed nephrotoxicity within 1 month of transplantation and 58 Indian non-transplant subjects having the risk factors for kidney disease i.e. hypertension or diabetes or the family history of these, have been studied for these SNPs by allele specific PCR method. The data suggest that the heterozygosity of CYP3A5 and mutant allele frequency of MDR-1 SNP is higher in transplant patients as well as in general population.  相似文献   

8.
The case control study was conducted to quantify the amount of the carcinogenic tobacco specific nitrosamine in smokeless tobacco users and smokers in patients with oral leukoplakia and also to emphasize the role of tobacco-specific nitrosamine in the incidence of oral leukoplakia. The study was conducted on 30 patients. The urine samples were obtained from smokeless tobacco users with oral leukoplakia, smokers with oral leukoplakia and non-tobacco users (i.e. people who do not use tobacco in any form). The collected samples were processed by gas chromatography-mass spectrometry. A highly significant difference of NNAL[4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol] in smokeless tobacco users than tobacco smokers P = 0.0002 (Table 1) was obtained. This significant difference shows smokeless tobacco is more carcinogenic than smoked tobacco. This study confirmed that NNAL is a potent biomarker for calculating the risk of occurrence of carcinoma in smokeless tobacco users and smokers, and that smokeless tobacco is more harmful than smoked tobacco.  相似文献   

9.
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10.
Oral squamous cell carcinoma is one of the most common malignancies recognized. Biomarkers which can predict presence of cancer and its progression can help in better management of these disorders. Over production of lipid peroxidation byproducts and disturbances in antioxidant defense system have been implicated in the pathogenesis of several diseases including oral cancer. Studies have shown a correlation of butyrylcholinesterase (BChE), with tumourigenesis, cell proliferation and cell differentiation. Earlier we have observed a significant elevation in plasma BChE and protein thiols in oral cancer patients which correlated well with stages of cancer. As it was not clear whether the above markers will be altered in saliva of oral cancer patients this study was undertaken. Institutional Ethics Committee gave permission to carry out this study. Total of 55 subjects comprising healthy controls (n = 30) and biopsy proven oral cancer patients (n = 25) consented to participate in this study. Salivary samples from cases were taken before any definitive treatment. Protein thiols and BChE were estimated in salivary samples using validated assay methods. Oral cancer patients had a significant increase in pre-treatment salivary BChE levels (p ≤ 0.001) and a significant decrease (p ≤ 0.001) in salivary thiols as compared to respective values in controls. Salivary protein thiols and BChE may have a role in pathophysiology of oral cancer. Saliva can be used as a potential non-invasive screening tool in oral cancer patients.  相似文献   

11.
Bisphenol-A (BPA) is a ubiquitous environmental chemical that produces adverse effect on reproduction system due to its potent estrogenic endocrine disruptive activity. The present study was aimed to investigate the monotonic dose effect of BPA on estrogen synthesis in female Sprague-Dawley rats. For this purpose, we administered three different doses of BPA (10, 50, 100 µg/kg bw/day) into rats and analyzed various biochemical, hormonal, molecular and histological parameters. 10 µg BPA treated rats showed significantly decreased levels of phase I detoxification agents (CYP450, Cyt-b5). Overexpression of eNOS with decreased expression of StAR and steroidogenic enzymes (CYP11A1, aromatase) indicate decreased production of estrogen. Increased levels of serum gonadotropins (FSH, LH) and decreased levels of estradiol suggest mimetic action of BPA and its feedback inhibition. Increased body weight, lipid profile status of 10 µg BPA treated rats and histological analysis of ovary and mammary tissue support the study. Overall, our results suggest that BPA exerts its estrogen mimetic effects in a monotonic manner.  相似文献   

12.
To analyse the association of high sensitivity C-reactive (hsCRP) protein levels and −717A/G single nucleotide polymorphism of CRP with acute myocardial infarction (AMI) in the Indian population. Study population included 100 MI cases wherein 32 patients had experienced previous MI (MI-Group-1), 68 MI cases were recruited at presentation (MI-Group-2) and equal number of age and gender matched healthy individuals. hsCRP levels were determined by ELISA and genotyping of −717A/G was carried out by polymerase chain reaction-based restriction digestion method. The −717A/G genotypes did not influence hsCRP level and their distribution did not differ between groups. However, in the present study hsCRP demonstrated significant correlation with BMI in controls of both the genders and with triglycerides in females of AMI at presentation who otherwise are with low risk profile. Identifying traditional risk factors associated with inflammation may help in controlling the acute event.  相似文献   

13.
The paraoxonase gene family in humans includes three members: PON1, PON2 and PON3. The products of those three genes are the following enzymes: paraoxonase 1 (PON1), paraoxonase 2 (PON2) and paraoxonase 3 (PON3). PON1 is mainly associated with a high density lipoprotein (HDL). A small amount of this enzyme is also bound to very low-density lipoprotein (VLDL) and postprandial chylomicrons. PON1 possess organophosphatase, arylesterase and lactonase activity and it hydrolyzes many different substrates. It is also known that PON1 may have antiatherogenic function. Compared to the PON1, PON2 and PON3 are much less studied and described. PON2 is ubiquitously expressed intracellular protein, while PON3 is bound to HDL, like PON1. The both enzymes possess antioxidant properties.  相似文献   

14.
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15.
Homocysteine (Hcy) is a non-protein forming amino-acid, whose metabolism is at the intersection of two metabolic pathways: remethylation and transsulfuration which are dependent on the vitamins folic acid, B12 and B6, and the enzymes methylenetetrahydrofolate reductase and cystathionine-β-synthetase. A deficiency of any of these vitamins or enzymes results in hyperhomocysteinemia. This causes oxidative and other damage to blood vessels, thus affecting various organ systems of the body. As part of our ongoing research on cardiovascular risk factors, we have studied the Hcy levels in the plasma of normal controls and those suffering from vascular diseases. It was observed that Hcy is significantly higher in patients of vascular diseases (21.59±1.28 μmol/L, mean±SEM), as compared to normal controls (11.33±0.18 μmol/L). This significance, was more pronounced in cases of venous thrombosis (26.77±2.43 μmol/L) as opposed to cases of arterial block (17.27±0.84 μmol/L). This signifies that Hcy estimation would be beneficial in obtaining a differential diagnosis in addition to being a modifiable vascular risk factor.  相似文献   

16.
Cytochrome P450 2C9 (CYP2C9) is involved in metabolism of many important drugs and its genotype variations is thought to affect drug efficacy and the treatment process. The aim of this study was to assess the distribution of CYP2C9 allele and genotypic variants in Sistani ethnic group, living in Gorgan, South East of Caspian Sea and North East of Iran. This study included 140 Sistani, referred to the health center of Gorgan. CYP2C9 genotyping was carried out by polymerase chain reaction–restriction fragment length polymorphism technique. The allele frequency of CYP2C9*1, CYP2C9*2 and CYP2C9*3 was 76.1, 16.1 and 7.8%, respectively. The frequency of CYP2C9*1/*1, CYP2C9*1/*2, CYP2C9*1/*3, CYP2C9*2/*2, CYP2C9*2/*3 and CYP2C9*3/*3 genotypes was 53.9, 22.1, 11.4, 2.9, 4.3% and nil, respectively. In this study the genotypic variations of the CYP2C9 allele among the Sistani ethnic group was investigated and great differences were observed in comparison to other populations. Our findings suggest that different genotypes of CYP2C9 may influence the pharmacokinetics of some drugs. More studies on the pharmacokinetic effects of CYP2C9 genotypes may help physicians choose optimal dosage of some drugs for treatment and prevention of their side effects. Since different ethnic groups from all over the world use medications, it suggests to investigate the pharmacokinetic effects of CYP2C9 genotypes in different populations.  相似文献   

17.
Although HbA1C is widely accepted as a useful index of mean blood glucose in type 2 diabetic patients its usefulness as screening test for diabetes has been controversial. The present study was undertaken to determine whether the level of HbA1C predicted diabetes in a prediabetic group of subjects. Plasma lipids, oral glucose tolerance, HbA1C was determined in 90 normal control subjects, 57 offspring of one type 2 diabetes mellitus parent and 11 diagnosed type 2 diabetes mellitus individuals. The mean age of participants was 44.5 yrs (not significantly different amongst the three groups) and the mean body mass index was 26.8 (not significantly different amongst the three groups). Two hours after a 75 g glucose challenge, the offspring had a significantly higher plasma glucose level (mean = 7.1 mmol/L, p value = 0.002) than the normals. Similarly the HbA1C values were higher in the offspring than in the normals (mean = 5.78%, p value = 0.016). Besides the significantly higher values for oral glucose tolerance test and HbA1C, the diabetics also were significantly higher for triglycerides (mean = 2.25mmol/L), total cholesterol (mean = 6.24mmol/L) and systolic blood pressure (mean = 138.45mm Hg) than the offspring (P value = 0.031, 0.006, 0.010) and the normals (P value = 0.026, 0.018, 0.002) respectively. The mean values of diastolic blood pressure, LDL cholesterol and HDL cholesterol were not significantly different amongst the three groups.  相似文献   

18.
This study was carried out to see the effect of the aqueous extract ofOcitum sanctum Linn (Tulsi) with Vitamin E on biochemical parameters and retinopathy in the streptozotocin-induced diabetic albino male rats. Adult albino male rats weighing 150–200 gm were made diabetic by intraperitoneal injection of streptozotocin in the dose 60 mg/kg in citrate buffer (pH 6.3). The diabetic animals were left for one month to develop retinopathy. Biochemical parameters like plasma glucose, oral glucose tolerance and glycosylated hemoglobin HbA1c, were measured along with lipid profile, and enzymes like glutathione peroxidase (GPX), lipid peroxidase (LPO), superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) in normal, untreated diabetic rats and diabetic rats treated withOcimum sanctum L extracts and vitamin E. Fluorescein angiography test was done for assessing retinopathy. Results on biochemical parameters were analyzed statistically by using ANOVA followed by Dunnet's ‘t’-test. A p-value of <0.05 was considered as significant. Evaluation of biochemical profile in treated groups showed statistically significant reduction in plasma levels of glucose, HbA1c, lipid profile and LPO, and elevation of GPX, SOD, CAT and GST. Treatment of the diabetic animals withOcimum sanctum and Vitamin E, alone and in combination for 16 weeks showed reversal of most of the parameters studied including plasma glucose levels. Angiography showed improvement in retinal changes following combined antidiabetic treatment.  相似文献   

19.
The main adverse consequences of excess bodyweight are cardiovascular disease, type II diabetes, and several cancers, IL-1Ra serum concentration has been reported earlier to increase in human obesity and it is therefore assumed that the polymorphism of IL-1Ra may influence cytokine production. We designed this study to investigate whether the IL-1Ra polymorphism was associated with obesity. A total number of 103 individuals; 19 lean (BMI<25 Kg/m2), 51 overweight (BMI 25–29.9 Kg/m2) and 33 obese (BMI≥30.0 Kg/m2) were enrolled in this study. Genotyping was performed using a polymerase chain reaction PCR amplification of the intron-2 fragment harboring a variable number of tandem repeat (VNTR) nucleotide sequences 86 pb of tandem repeat. The PCR products were separated on 2% agarose gel. Statistical analysis was performed using SPSS software (version 11.5). We found no significant difference in genotype and allele frequencies between the three groups; lean vs. overweight and lean vs. obese (p=0.323; 0.202; 0.123 and 0.068 resp). However, an increased risk for obesity had a propensity to be higher in those having genotype II/II. This genotype has been reported to be a ‘high producer’ of IL-1Ra. Although no statistically significant relationship between IL-1Ra polymorphism and BMI was observed, however, a trend towards an increase of allele*II in overweight and obese group was observed. This may suggest that IL-1Ra appears to be induced by inflammatory stimuli as well as obesity-associated factors. This is relatively a pilot study: but nevertheless, may assist in identifying the pathophysiological cause for obesity.  相似文献   

20.
基于国产GF-1遥感影像的山区细小水体提取方法研究   总被引：5，自引：0，他引：5  
以国产"高分一号"16m遥感图像为数据源,在特克斯县选取两个研究区域,针对山区细小线状河流提取难度较大的问题,使用基于规则的面向对象的方法实现了对山区细小水体的精确化提取。首先,在总结前人选择最优分割尺度的基础上,考虑了各层权重信息,针对某一特定地物,提出了指示最优分割尺度的指标——改进的与邻域绝对均值差分方差比(MRMAS),并由此获取了影像上细小水体的最优分割尺度。其次,为区分水体和山体阴影,构建阴影水体指数SWI=B1+B2-B4,成功剔除了绝大部分阴影信息。最后,利用形态学膨胀滤波及Pavlidis异步细化算法对提取的细小水体进行后处理,最终得到细小河流的矢量化水系图。实验结果表明,该方法可以完整、快速地提取出山区细小线状河流信息,总体精度在90%以上,Kappa系数在85%以上,有效排除阴影等暗色地物的干扰,基本消除椒盐噪声。该研究成果或对国产高分影像处理系统的研发与应用提供一定的科学参考。  相似文献   

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