Prakash Chandra Ray

Antihypertensive and Antioxidant Action of Amlodipine and Vitamin C in Patients of Essential Hypertension

The etiology of essential hypertension includes increased oxidative stress. The role of antihypertensive drug amlodipine as an antioxidant and the benefit of addition of vitamin C, an antioxidant to antihypertensive therapy were studied. Forty male patients of essential hypertension were randomly divided into two groups and treated with 5 mg amlodipine. In addition one group also received 1000 mg vitamin C (as two 500 mg tablets) once daily for three months. Although blood pressure decreased in both groups, the systolic blood pressure in patients given vitamin C was less (126.4 ± 7.47) compared to the other group (130.9 ± 7.27). A decrease in malondialdehyde, an increase in erythrocyte sodium-potassium adenosine triphosphatase (Na+ K+ ATPase) and an increase in the superoxide dismutase levels were observed in both groups. The increase in SOD was statistically more in the patients given vitamin C in addition to amlodipine (0.1717 ± 0.0150 compared to 0.152 ± 0.0219 units/100 ml assay). In spite of the known antihypertensive, antioxidant activity, similarity in correcting endothelial dysfunction independently, giving the two drugs together and early introduction of vitamin C perhaps decreases oxidative stress and augments the antioxidant status. This may prevent further vascular damage due to oxidative stress, leading to a better prognosis in essential hypertension patients.

Effect of psychological stress on fertility hormones and seminal quality in male partners of infertile couples.

The present study evaluated the effect of psychological stress on male fertility hormones and seminal quality in male partner of infertile couples. Seventy male partners of infertile couples were evaluated for level of psychological stress using Hospital Anxiety and Depression Score (HADS) questionnaire, serum total testosterone, luteinising hormone (LH) and follicle‐stimulating hormone (FSH) by electrochemiluminescence assay and serum GnRH by ELISA. Seminal analysis was performed as per WHO guideline. Nineteen (27%) of them had HADS anxiety and depression score ≥8 (abnormal HADS score). The persons having abnormal HADS had lower serum total testosterone, higher serum FSH and LH than those of persons having normal HADS. Serum total testosterone correlated negatively with HADS, but LH and FSH correlated positively. There was no change in GnRH with the change in stress or testosterone levels. Sperm count, motility and morphologically normal spermatozoa were lower in persons having abnormal HADS. Sperm count correlated positively with total testosterone and negatively with FSH and LH. Abnormal sperm motility and morphology were related to lower testosterone and higher LH and FSH levels. Psychological stress primarily lowers serum total testosterone level with secondary rise in serum LH and FSH levels altering seminal quality. Stress management is warranted for male infertility cases.

Vitamin D and VDR gene polymorphism ( FokI ) in epithelial ovarian cancer in Indian population

IntroductionVitamin D deficiency and vitamin D receptor (VDR) gene polymorphism, FokI, is reported to increase the risk of many cancers. Role of vitamin D and its receptor polymorphisms in ovarian cancer has not been clearly defined.ObjectiveTo study the levels of serum vitamin D and occurrence of vitamin D receptor gene polymorphism (FokI) in cases of ovarian cancer.Material and methodsFokI genotyping was done by PCR-RFLP technique and vitamin D levels were estimated by chemiluminescence immunoassay.ResultsSerum vitamin D levels were significantly (p < 0.03) lower in ovarian cancer cases as compared to controls. The homozygous (TT) and heterozygous (CT) genotype predispose to the development of ovarian cancer in Indian population (OR: 2.37, 95% CI: 1.04-5.44) as compared to the homozygous (CC) genotype. Vitamin D deficiency and VDR gene polymorphism (FokI) act non-synergistically (p value < 0.4).ConclusionLow blood levels of vitamin D and VDR receptor polymorphism (FokI) might be a risk factor for the development of ovarian cancer. Other novel ligands of vitamin D receptor might be responsible for the non-synergistic effect.

Utility of Serum miR-125b as a Diagnostic and Prognostic Indicator and Its Alliance with a Panel of Tumor Suppressor Genes in Epithelial Ovarian Cancer

MicroRNAs (miRNAs) have been found to be dysregulated in epithelial ovarian cancer (EOC) and may function as either tumor suppressor genes (TSGs) or as oncogenes. Hypermethylation of miRNA silences the tumour suppressive function of a miRNA or hypermethylation of a TSG regulating that miRNA (or vice versa) leads to its loss of function. The present study aims to evaluate the impact of aberrant microRNA-125b (miR-125b) expression on various clinicopathological features in epithelial ovarian cancer and its association with anomalous methylation of several TSGs. We enrolled 70 newly diagnosed cases of epithelial ovarian cancer, recorded their clinical history and 70 healthy female volunteers. Serum miR-125b levels were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and the methylation status of various TSGs was investigated by methylation specific PCR. ROC curves were constructed to estimate the diagnostic and prognostic usefulness of miR-125b. The Kaplan—Meier method was applied to compare survival curves. Expression of miR-125b was found to be significantly upregulated (p<0.0001) in comparison with healthy controls. The expression level of miR-125b was found to be significantly associated with FIGO stage, lymph node and distant metastasis. ROC curve for diagnostic potential yielded significant AUC with an equitable sensitivity and specificity. ROC curves for prognosis yielded significant AUCs for histological grade, distal metastasis, lymph node status and survival. The expression of miR-125b also correlated significantly with the hypermethylation of TSGs. Our results indicate that DNA hypermethylation may be involved in the inactivation of miR-125b and miR-125b may function as a potential independent biomarker for clinical outcome in EOC.

Prevalence of risk factors for chronic non-communicable diseases using who steps approach in an adult population in Delhi

Objective: The burden of non-communicable diseases (NCDs) is increasing worldwide largely due to prevalence of various risk factors, which can be controlled. Therefore, the present study was undertaken to measure the prevalence of major preventable risk factors for chronic non-communicable diseases in an urban resettlement colony of Delhi, using STEPS approach. Materials and Methods: A cross-sectional study, that included a random sample of 200 adults, was conducted. A study tool based on the WHO STEPS questionnaire for assessing non-communicable diseases and their risk factors was used. Fasting venous blood sample was collected to assess the lipid profile and fasting blood sugar. Anthropometric measurements of the participants were also taken. Data was analyzed using SPSS version 17. Results: Out of the 200 participants, 26% (n = 52) were consuming alcohol and 17% (n = 34) were smoking. Majority (77.5%) had a raised waist circumference, and more than two-thirds were either overweight or obese. Fasting blood sugar levels were found to be raised in 18% of the study population. More than third participants had raised systolic and diastolic blood pressures and abnormal lipid profiles. More males were found to be overweight in comparison to females (P < 0.01), but in contrast, obesity (P < 0.05) and raised waist circumference (P < 0.001) were more common in females. Tobacco use was more common in lower class (P < 0.05), whereas obesity was commoner in the upper socio-economic class (P < 0.05). Conclusions: Study showed a high burden of risk factors for NCDs in the study population, pointing towards changing disease epidemiology of non-communicable diseases in India.

Effect of CYP1A1 gene polymorphism and psychological distress on seminal analysis parameters

BackgroundPsychological factor alters fertility hormones and contributes to male infertility. Anxiety and depression are common manifestations of psychological distress. Cytochrome P-4501A1 (CYP1A1) metabolizes xenobiotics and fertility hormones that influence male fertility. The effect of CYP1A1 polymorphism on male fertility has remained controversial.The present study was designed to assess the effect of psychological distress and CYP1A1 polymorphisms and their interactions on parameters of seminal analysis.MethodsEighty male partners of infertile couples were evaluated for level of distress using Hospital anxiety and depression score (HADS) questionnaire. As per WHO guidelines (2010), sperm count, motility and morphology were assessed and subjects were classified as (a) subjects having normal sperm characteristics and (b) subjects having abnormal sperm characteristics. CYP1A1 polymorphisms were detected by ASO-PCR.ResultsThe significant odd’s ratio indicates that psychological distress (OR:10.54; CI:3.72–29.84; P < 0.001), CYP1A1*4(OR:10.31; CI:3.01–35.24; P < 0.001) and CYP1A1*2C (OR:7.01; CI:1.78–27.56; P = 0.002) polymorphisms are risk factors for the development of abnormal sperm characteristics in male subjects. Data analysis with two way ANOVA shows that psychological distress, CYP1A1*4 and CYP1A1*2C polymorphisms significantly affect but do not interact among them to influence sperm parameters.ConclusionsIt is concluded that CYP1A1 gene polymorphisms and psychological distress act independently but do not interact with each other in pathogenesis of male infertility.

Determination of Prevalence of Type 2 Diabetes Mellitus by Screening Tests using a Mathematical Formula in Place of Invasive Blood Tests.

INTRODUCTION True prevalence rate of diabetes mellitus in a population can be obtained by using invasive tests but it is practically difficult on large scale. AIM To find out the feasibility of mass non-invasive screening test to detect the prevalence of diabetes mellitus in rural population of India with the help of a mathematical formula. MATERIALS AND METHODS From population of 18800 residing in two adjacent rural areas of Delhi, a systematic random sample of 1005 adult subjects was screened for diabetes by using urine benedicts test, Canrisk questionnaire, Madras Diabetes Research Foundation-Indian Diabetic Risk Score (MDRF-IDRS) and determined prevalence of diabetes (pA) gauzed by each of these screening tests. Simultaneously, each subjects glycaemic status was confirmed by standard fasting Plasma glucose (FPG) and postprandial plasma glucose (PPPG) levels. The blood test was also used to determine true prevalence which was cross-checked with the prevalence estimated (Pe) by the above stated screening tests using a mathematical formula. RESULTS The true prevalence of T2DM in more than 18 years of population by Fasting Plasma Sugar (FPS) was 4.5% while that by using mathematical formulae that estimated by urine test, Canrisk test and MDRF-IDRS was 4.4%, 4.4 and 4.3% respectively. When more than 35 years age-group was selected, true prevalence was 7.4% and estimated prevalence by Canrisk test was 7.1% (as against gold standard of Fasting) and 6.9% (as against PP). By fasting urine test it came out to be 7.2% and by PP urine test it was 7.4%. In population l8-35 years, the prevalence of diabetes was 1.1% by plasma glucose test. By using Canrisk, it came out to be 1.04%. CONCLUSION Individual screening tests such as urine, Canrisk and MDRF-IDRS can be used to estimate prevalence rates of diabetes in rural areas by means of mathematical formula which would be close to true estimates.

The C609T (Pro187Ser) Null Polymorphism of the NQO1 Gene Contributes Significantly to Breast Cancer Susceptibility in North Indian Populations: a Case Control Study

BACKGROUND Worldwide, breast cancer is the most common cancer among women and is a leading cause of cancer death. In the present study, we investigated the NQO1 C609T genotypic and allelic distribution in north Indian breast cancer patients. MATERIALS AND METHODS The genotypic distribution of the NQ01 C609T polymorphism was assessed in 100 invasive ductal carcinoma (IDC) breast cancer patients and 100 healthy controls using allele specific PCR (AS-PCR). RESULTS A lower frequency of the CC genotype was found in breast cancer patients (24%) than in the controls. On the other hand, TT genotype frequency was also found to be higher in female healthy controls (32%) than the female breast cancer patients (20%). The frequencies of all three genotypes CC, CT, TT in patients were 24%, 56% and 20% and in healthy controls 50%, 22% and 32% respectively. We did not find any significant correlation between the NQO1 C609T polymorphism and age group, grading, menopausal status and distant metastasis. A less significant association was found between the NQ01 C609T polymorphism and the stage of breast cancer (X2=5.931, P=0.05). CONCLUSIONS The present study shows a strong association between NQO1 C609T polymorphism with the breast cancer risk in the north Indian breast cancer patients so that possible use as a risk factor should be further explored.

Initial psychological reaction and social support in patients of type 2 diabetes mellitus in Delhi

Introduction: Diabetes Mellitus Type 2 (DM) is a progressive chronic disease which places a significant burden of self-management on the individuals and their families. Negative attitude and lack of social support, particularly from friends and family, are considered the barriers to adherence and self-care. Objective: To assess the initial psychological reaction, attitude and social support in patients of Diabetes Mellitus Type 2. Materials and Methods: A community based prospective follow up study was conducted in rural and urban areas of Delhi. A total of 98 patients, either known diabetics or those after testing positive with blood-test during screening for diabetes, were selected after systematic random sampling and interviewed using pretested pre-designed questionnaire after 4 months of initial screening survey for diabetes. Data was analysed using SPSS software (version 16). Chi-square and fishers exact tests were used and accepted statistically significant if P value was less than 0.05. Results: It was found that more rural patients (56, 88.9%) felt disappointed compared to those residing in urban areas (13, 61.9%), when their families denied them from eating prohibited diet (χ 2 =13.82, P =0.001). Rural families were reported to be more supportive for food and exercise issue (χ 2 =12.51, P =0.001). A higher proportion of patients in urban area (13, 41.9%) compared to rural patients (3, 4.5%) perceived that disease would affect their married life (χ 2 =22.15, P =0.001). However, no significant difference in negative attitude and social support was found during the gender, occupation and education status assessment. Conclusion: Psycho-social management of diabetes need to be targeted and addressed. Diabetes management programs should find ways to build and improvise social support for patients.

Prognostic and diagnostic significance of epigenetic alterations of p16 and DAPK1 promoter sequences in patients with epithelial ovarian carcinoma (EOC).

62 Background: Novel strategies for early detection of EOC, the most common and second most lethal cancer in Indian women, are urgently needed. Silencing tumor suppressor genes via DNA methylation has established hypermethylation as one of the most frequent molecular alterations that may initiate and drive many types of human neoplasia including EOC. To determine the alterations of tumor suppressor gene DAPK1 and p16INK4A in EOC patients to explore the possibilities of identifying potential minimally invasive markers in blood of the patients, which could help in the clinical practice as a diagnostic and prognostic marker. METHODS Fifty EOC patients with primary epithelial ovarian cancer were selected for the study; these patients were followed for a median of 20 months. Genomic DNA extracted from fresh peripheral blood and serum followed by sodium bisulfate modification. The DAPK1 and p16 methylation was detected using methylation-specific PCR (MSP). The DAPK1 and p16 methylation status was correlated with age, stage,menopause, Ca125.5 and clinic pathological features. RESULTS The frequencies of DAPK1 and p16 methylation in EOC patients was found to be 68% and 84% respectively . Aberrant methylation of DAPK1 and p16 was associated with age at diagnosis (p = 0.043) .The significant association was seen with age,menopause. Patients with high methylation indices had poor prognosis (p<0.001, Hazards ratio=14.58) with age (p = 0.043), and tumor stage (p = 0.033). Aberrant methylation of DAPK1 and p16 was strongly associated with EOC patients (p = 0.037 respectively). CONCLUSIONS our results that the methylated loci of TSGs (DAPK1 and p16) may be employed as clinically useful biomarkers for prognosis and diagnosis of EOC noninvasively using readily available body fluid by MS-PCR and proved to be efficient and cost-effective method.