Internal Medicine

We present a case of an intermediate coronary artery stenosis with concomitant severe mitral regurgitation, in which hyperemic efficacy of intravenous (IV) infusion of adenosine was initially blunted and was completely restored by surgical correction of the diseased valve. As the half-life of adenosine is extremely short, any conditions resulting in a low cardiac output state may hinder the accumulation of serum adenosine given intravenously enough to induce maximal hyperemia. In this situation, alternative methods to increase IV infusion rate or switch to intracoronary injection may be advisable.

Background Improving the quality of life of patients is a key concern in public health. In the context of improving therapeutic compliance, quality of life of patients undergoing anti-tuberculosis treatment, and prevention of antibiotic resistance, we conducted this systematic review to support risk minimization actions. Methods A literature review of risk management strategies targeting adverse drug reactions to anti-tuberculosis drugs was conducted, including published observational studies. Two independent reviewers identified studies through Medline, Scopus, and Web of Science. The methodological quality of the included studies was assessed using criteria defined by the Newcastle Ottawa Scale. Results Seven studies were included in this review, which identified four risk management strategies (psychological intervention, reduction of drug dose with or without prescription of adjunctive medications, change of medication, permanent or temporary discontinuation of medication). The ...

Introduction Schizophrenia is a psychiatric condition in which patient adherence is a key issue in its management. Objectives To estimate the prevalence and determine the factors associated with medication adherence in patients with schizophrenia. Methods This was a cross-sectional study conducted at the psychiatry department of the CHU IBN Rochd of Casablanca among schizophrenic patients followed from May 2019 to January 2020. The sample size was calculated apriori and the measurement of therapeutic compliance and Insight (patients' perception of the disorders related to their pathology) was made thanks to the Medication Adherence Rating Scale (MARS) and the Birchwood insight scale (BIS) respectively. Socio-demographic data and data on the management of schizophrenia were also collected. Statistical analyses were performed with RStudio software and the multivariate analysis method of logistic regression was used. The threshold of significance was set at 5%. Results A total of 3...

Background: Pediatric epilepsy comprises of a chronic neurological disorders characterized by recurrent seizure attack. Sodium valproate is one of the common anti-epileptic drugs used in the treatment. Glucuronide conjugation is the major metabolic pathway of sodium valproate, carried out by the enzyme Uridine 5’-diphospho (UDP) glucuronosyl transferase (UGT) whose genetic polymorphisms may alter clinical outcome. Aim: To find the association between UGT2B7 genetic polymorphism and clinical outcome in terms of efficacy and tolerability in pediatric epileptic patients on sodium valproate monotherapy. Methods and Materials: In this cohort study, 75 pediatric epileptic patients aged 2-18 years receiving sodium valproate monotherapy for past one month were included from Justice K S Hegde Charitable Hospital, Mangalore, India after obtaining informed consent. Genetic polymorphism patterns of UGT2B7 (C161T, A268G, G211T) was evaluated by PCR-RFLP. Clinical outcome was measured in terms of...

Controversy exists regarding the propensity of hypogonadism and metabolic disorders to promote the development of high-risk prostate cancer (PCa). Our aim was to prospectively test whether preoperative circulating testosterone levels, obesity, and metabolic syndrome (MetS) were correlated with aggressive pathological features after radical prostatectomy (RP). Overall, 354 patients undergoing robot-assisted RP at our academic institution, between 2010 and 2013, to treat clinically localized PCa were included in this prospective study. Pelvic lymphadenectomy was performed in 116 (32.8%) patients and confirmed the absence of nodal metastases in all of them. Cardiovascular risk factors and body-mass index (BMI) were used to define MetS and obesity, respectively. Total testosterone (TT) levels were assessed using an immunoassay method, whereas bioavailable testosterone (BT) and free testosterone (FT) levels were estimated using Vermeulen׳s formula. Multivariate logistic regression analys...

BACKGROUNDWe evaluated the predictive ability of cystatin C and creatinine-based estimations of glomerular filtration rate (eGFR), including the Chronic Kidney Disease–Epidemiology (CKD-EPI) equation, in acute coronary syndrome (ACS) patients with (STE-ACS) or without (NSTE-ACS) ST elevation in a large contemporary ACS population.METHODSConcentrations of cystatin C and creatinine, as well as eGFR at randomization, were measured in 16 401 patients in the Platelet Inhibition and Patient Outcomes (PLATO) study and evaluated as predictors of the composite end point of cardiovascular death or myocardial infarction within 1 year. Two Cox proportional hazards models were used, the first adjusting for clinical characteristics and the second for clinical characteristics plus the biomarkers N-terminal pro–B-type natriuretic peptide, troponin I, and C-reactive protein.RESULTSThe median cystatin C value was 0.83 mg/L. Increasing quartiles of cystatin C were strongly associated with poor outcome...

Background— Reduced renal function is associated with a poorer prognosis and increased bleeding risk in patients with acute coronary syndromes and may therefore alter the risk-benefit ratio with antiplatelet therapies. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor compared with clopidogrel reduced the primary composite end point of cardiovascular death, myocardial infarction, and stroke at 12 months but with similar major bleeding rates. Methods and Results— Central laboratory serum creatinine levels were available in 15 202 (81.9%) acute coronary syndrome patients at baseline, and creatinine clearance, estimated by the Cockcroft Gault equation, was calculated. In patients with chronic kidney disease (creatinine clearance <60 mL/min; n=3237), ticagrelor versus clopidogrel significantly reduced the primary end point to 17.3% from 22.0% (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.65 to 0.90) with an absolute risk reduction greater than that...

Background: Cystatin C levels reflects glomerular filtration rate and predict cardiovascular mortality and morbidity in coronary artery disease. Our aim was to determine the predictive power of cystatin C in patients with STEMI as well as in NSTE-ACS. Methods: Cystatin C measured at randomization in 16402 (of 18624 included) patients in the PLATO study (6638 STEMI and 9764 suspected NSTE-ACS) was evaluated as a predictor of the composite endpoint of cardiovascular death or myocardial infarction (MI) within one year. Cystatin C was evaluated as a continuous variable (logarithmized), as quartiles and dichotomized at optimal cutoff using the Integrated Discrimination Improvement (IDI) measure. Two Cox proportional hazards models were used: 1/ established traditional risk factors (e.g. age, gender, heart failure, diabetes, BMI, randomized treatment) and 2/ above mentioned and the addition of further risk markers e.g. NT-proBNP and CRP. The median cystatin C value was 0.77 mg/L in the STEMI group and 0.86 mg/L in the NSTE-ACS group. The hazard ratios for the continuous models were derived per standard deviation 0.35 log(mg/L). The optimal cutoff was 1.09 mg/L. There was no significant cystatin C by type of ACS interaction (STEMI or NSTE-ACS).

Pancreatic cancer (PC) has the highest frequency of developing cancer cachexia (CC)–sarcopenia (SC) syndrome, which negatively influences patients’ outcome, quality of life, and tolerance/response to treatments. However, the clinical impacts of CC, SC, and their associated factors on outcomes for advanced PC has yet to be fully investigated. A total of 232 patients were enrolled in this study for the retrospective review of their clinical information and the measurement of skeletal muscle areas at the third lumber vertebra by computed tomography scan to identify CC or SC. The association and concurrent occurrence of clinicopathological features in each patient, prevalence rates, and prognosis with the CC or SC were calculated. CC and SC were observed in 83.6% (n = 194) and 49.1% (n = 114) of PC patients, respectively. Low hemoglobin levels more often occurred in CC patients than in non-CC patients (p = 0.014). Older age (p = 0.000), female gender (p = 0.024), low body mass index (BM...

Stroke and brain cancer are two distinct diseases. However, the relationship between both diseases has rarely been examined. This study investigated the longitudinal risk for developing brain cancer in stroke patients. To study this, we first reviewed the malignant gliomas previously with or without stroke using brain magnetic resonance imaging (MRI) images and the past histories. Two ischemic stroke patients before the malignant glioma were identified and belonged to the glioblastoma mutiforme (GBM). Particularly, both GBM specimens displayed strong hypoxia-inducible factor 1α (HIF-1α) expression in immunohistochemical (IHC) staining. To elucidate the significance of this relationship, we then used a nationwide population-based cohort in Taiwan to investigate the risk for the incidence of brain cancer in patients previously with or without stroke. The incidence of all tumors in the stroke group was lower than that in the control group with an adjusted hazard ratio (HR) of 0.79 (95% confidence interval [CI]: 0.74-0.84) in both gender and age older than 60 years. But the stroke patients had higher risk of developing only brain cancer with an adjusted HR of 3.09 (95% CI: 1.80-5.30), and otherwise had lower risk of developing head and neck, digestive, respiratory, bone and skin, as well as other tumors, all with p<0.05. After stratification by gender and age, the female and aged 40-60 year old stroke patients had higher risk of developing brain cancer with an adjusted HR of 7.41 (95% CI: 3.30-16.64) and 16.34 (95% CI: 4.45-62.13), www.impactjournals.com/oncotarget/

Interleukin (IL)-20, a proinflammatory cytokine of the IL-10 family, is involved in acute and chronic renal failure. The aim of this study was to elucidate the role of IL-20 during diabetic nephropathy development. We found that IL-20 and its receptor IL-20R1 were upregulated in the kidneys of mice and rats with STZ-induced diabetes. In vitro, IL-20 induced MMP-9, MCP-1, TGF-β1 and VEGF expression in podocytes. IL-20 was upregulated by hydrogen peroxide, high-dose glucose and TGF-β1. In addition, IL-20 induced apoptosis in podocytes by activating caspase-8. In STZ-induced early diabetic nephropathy, IL-20R1-deficient mice had lower blood glucose and serum BUN levels and a smaller glomerular area than did wild-type controls. Anti-IL-20 monoclonal antibody (7E) treatment reduced blood glucose and the glomerular area and improved renal functions in mice in the early stage of STZ-induced diabetic nephropathy. ELISA showed that the serum IL-20 level was higher in patients with diabetes m...

This study aims to assess the effects of smoking on pre-bronchodilator and post-bronchodilator lung function measures that reflect both larger and smaller airways in adults with newly onset asthma. ► Among adults with newly onset asthma, lung function measures (FEV 1 , FEF 25-75% ) were significantly reduced in current regular smokers and in recent former smokers (ie, quit less than a year ago) when compared with never smokers; furthermore, doseresponse patterns were found between daily smoking rate or life-time cumulative smoking and lung function measures. ► This study is the first to clarify the effects of smoking on smaller airways lung function, measured as forced expiratory flows, in a larger sample of patients with adult-onset asthma, and to provide effect estimates for lung function parameters measured both prior to and after the bronchodilation test.

Objective To test the a priori hypothesis that the association between cold spells and ischaemic sudden cardiac death (SCD) is modified by the severity of coronary stenosis. Methods The home coordinates of 2572 autopsy-verified cases of ischaemic SCD aged ≥35 in the Province of Oulu, Finland, were linked to 51 years of weather data. Cold spell was statistically defined for each home address as unusually cold weather pertinent to the location and time of year. We estimated the occurrence of cold spells during the hazard period (7 days preceding death) and reference periods (the same calendar days over 51 years) in a casecrossover setting applying conditional logistic regression, controlling for temporal trends and stratifying by severity of coronary stenosis. results The association between cold spells and ischaemic SCD was stronger among patients with 75%-95% stenosis (OR 2.03; 95% CI 1.31 to 3.17), and weaker to non-existent among patients with <75% stenosis (OR 0.97; 95% CI 0.37 to 2.55) or coronary total occlusion (100% stenosis) (OR 1.01; 95% CI 0.52 to 1.96). Lack of calcium-channel blockers and statin therapy seemed to accentuate the role of stenosis during cold spells. Conclusions We provide evidence that the association between cold spells and ischaemic SCD is modified by the severity of coronary stenosis. The findings suggest that disturbances in coronary circulation play part in the pathogenesis of SCD during cold weather.

Phthalate exposure was shown to alter thyroid function, however it is unclear, whether oxidative and nitrosative stress explains the intermediate biological mechanism. This study aimed to investigate the associations between phthalate exposure, oxidative/nitrosative stress, and thyroid function in adults, and to examine the mediating role of oxidative/nitrosative stress in the associations between phthalate exposure and thyroid function. Levels of eleven urinary phthalate metabolites, three urinary biomarkers of oxidative/nitrosative stress (malondialdehyde [MDA], 8-OHdG, and 8-NO 2 Gua) and five serum thyroid hormones (thyroxine [T 4 ], free T 4 , triiodothyronine, thyroid-stimulating hormone, and thyroxine-binding globulin) were measured in 266 Taiwanese adults. Cross-sectional associations between phthalate metabolites, biomarkers of oxidative/ nitrosative stress and thyroid hormones were analyzed using multivariate regression models. Mediation analysis was conducted to assess the role of oxidative/nitrosative stress in the associations between phthalate metabolites and thyroid hormone levels. Sum of di-(2-ethylhexyl) phthalate (DEHP) metabolites was positively associated with MDA (β T1-T2 = 0.253, 95%CI [0.060, 0.447]; β ≧ T2 = 0.317, 95% CI [0.098, 0.536]; P trend = 0.005) and 8-NO 2 Gua (β T1-T2 = -0.010, 95%CI [-0.138, 0.118]; β ≧ T2 = 0.144, 95% CI [-0.001, 0.289]; P trend = 0.045). Mono-n-butyl phthalate (MnBP) was positively associated with 8-NO 2 Gua (β T1-T2 = 0.201, 95% CI [0.078, -0.324]; β ≧ T2 = 0.161, 95% CI [0.031, -0.292]; P trend = 0.018). T 4 was negatively associated with MDA (β T1-T2 = -0.027, 95% CI [-0.088, 0.0034]; β ≧T2 = -0.094, 95% CI [-0.161, -0.028]; P trend = 0.005) and 8-NO 2 Gua (β T1-T2 = -0.068, 95% CI [-0.127, -0.010]; β ≧T2 = -0.125, 95% CI [-0.184, -0.066]; P trend < 0.001). Free T 4 was positively associated with MDA (P trend = 0.047) and with 8-NO 2 Gua (P trend < 0.001). 8-NO 2 Gua mediated 11% of the association between the sum of DEHP metabolites and T 4 , and 17% of the association between MnBP and free T 4 . These results suggest that phthalate exposure may influence thyroid hormone levels through induced oxidative/nitrosative stress.

BACKGROUND The homeostasis model assessment of insulin resistance (HOMA-IR) is a useful model for application at large epidemiologic studies. The aim of this study was to determine the HOMA cut off values to identify insulin resistance (IR) and metabolic syndrome (MS) in Qazvin, central Iran. METHODS Overall, 480 men and 502 women aged 20-72 yr attended in this cross sectional study from September 2010 to April 2011. The diagnostic criteria proposed by national cholesterol education program third adult treatment panel (ATPIII), International Diabetes Federation (IDF) and new Joint Interim Societies (JIS); were applied to define MS. Lower limit of the top quintile of HOMA values in normal subjects was considered as the threshold of IR. The receiver operating characteristic (ROC) curves of HOMA for MS diagnosis were depicted. The optimal cut point to determine MS was assessed by maximum Youden index and the shortest distance from the point (0, 1) on the ROC curve. RESULTS The threshol...

Background: Prediabetes is a condition that occurs when blood glucose levels are higher than normal, but not high enough to be classified as diabetes. Prediabetic people have an increased risk of developing type 2 diabetes and cardiovascular disease. Moreover Hyperglycemia has multiple effects on the hematological parameters. Objective: To examine the association between hematological indices and anthropometric measurement, with prediabetes. Methods: This cross-sectional study was conducted on 125 diabetics and 259 prediabetics in the 20-70 age range. They were selected by a convenience sampling method at the Taban Diabetes Center in 2015. An oral glucose tolerance test was performed for each participant who had never been diagnosed with diabetes. Participants were characterized as having prediabetes or diabetes according to American Diabetes Association criteria. The hematologic parameters were measured by using Sysmex-KX 21N analyzers. Data were analyzed by IBM-SPSS version 22 using independent-samples t-test, Mann-Whitney U test, and Pearson's correlation coefficient at p<0.05. Results: There was significant difference in mean corpuscular hemoglobin concentration (MCVH) (33.81±0.92 g/dL vs. 34.06±1.05 g/dL) between prediabetes patients and diabetes. There was not a statistically significant difference in the prediabetics' hematological parameters, compared with the diabetics. In the prediabetic group, only the mean corpuscular hemoglobin concentration was found to be negatively correlated with diastolic blood pressure (p=0.013) and FBS (p=0.026). Conclusion: Hematological indices are important markers for the assessment of variations in size, number, and maturity of different blood cells. Hematological indices could be utile indicators of vascular complication and glycemic control in type 2 DM patients. Thus, they are important for the evaluation and early management of patients with per diabetes.

to compare the effectiveness of metformin and pioglitazone in ameliorating insulin resistance and cardiovascular risk factors in women with polycystic ovary syndrome (PCOS). this study was a randomized clinical trial to compare treatment with metformin and pioglitozone. Fifty two women with PCOS aged 20-45 years were randomly allocated to one of the two treatment groups. All patients underwent clinical and biochemical evaluation and analyses involving these measures which consisted of repeated measures MANOVA using the pre- and post-intervention fasting blood sugar (FBS), lipid profiles, body mass index (BMI), serum insulin in two groups. weight and BMI were significantly decreased in metformin group but not in case of pioglitazone. FBS, serum triglycerides, total cholesterol were all reduced significantly by both metfomin and pioglitazone. Insulin resistance measured by homeostasis model assessment (HOMA) method was significantly decreased in both treatment groups (P&lt;0.05). Ther...

The prevalence of Metabolic Syndrome (MS) has been increasing worldwide. Although Uric Acid (UA) Levels are often increased in subjects with MS, it is still unclear whether uric acid plays a causal role for MS or is a marker. The purpose of this study was to examine the association between UA and the MS in Qazvin, Iran. Methods: 529 men and 578 women aged 20 -78 years attended in cross sectional study from September 2010 to April 2011 in Qazvin, Iran. The criteria proposed by new joint Interim societies (JIS) were applied for diagnosis of MS. Hyperuricemia was defined as UA ≥ 7 mg/dL in men and UA ≥ 6 mg/dL in women. Logistic regression analysis was performed to evaluate the relationship between UA quartiles and MS. The prevalence of MS was found to be 39.3%. Prevalence of hyperuricemia was 8.4% in males and 4.1% in females (P=0.004). Mean UA level was higher in males than in females (P<0.001). UA levels increased significantly with an increasing number of MS components in both genders. Prevalence of MS increased across UA quartiles in females; however the increasing trend began from second quartile in males. Using the lowest quartile of UA level as a reference, there were no significant association between UA quartile groups and MS. This study showed that UA levels are not an appropriate predictor of MS in Iranian population. More longitudinal studies are necessary to confirm the role of UA in MS occurrence.

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To determine the level of Lipoprotein (a) in diabetic patients comparing to control group. MATERIALS AND METHODS: This cross-sectional study was conducted on the patients referred to Endocrinology Clinic of Bu Ali-Sina Hospital in 2009. 180 subjects including 90 diabetic and 90 healthy subjects as control group enrolled in this study. All diabetic patients had glycemic control. We measured serum FBS, TG, cholesterol, LDL, HDL and serum Lp (a) in both groups. Data were analyzed by T-test and chi-square. RESULTS: BMI, sex and age were similar in two groups. Lp (a) level was significantly higher in diabetic ones compared with control group (35.27 ± 28.6 vs. 20.22 ± 10.3 mg/dl, P < 0.001). Serum TG, Cholesterol, LDL were also significantly higher in diabetics (P < 0.001) while HDL was lower. HDL-Cholesterol level was significantly higher in diabetic men than women [OR = 0.18 CI 95% (0.06-0.56)], and there was positive correlation between FBS level and lipid profile. CONCLUSION: Lp (a) as an independent risk factor for atherosclerosis has elevated level in diabetic patients. So lowering its concentration would help prevention of CAD, a known cause of death in diabetic patients.

Background: High-sensitivityC-reactive protein (hs-CRP) hasbeenshown predictcardiovascular disease (CVD) andisassociatedwithCVDriskfactors(i.e. central obesity) andthemetabolic syndrome.The aim of this study was to determine the association ofcentral obesity and hs-CRP in Qazvin, Iran Methods:This cross-sectional study was conducted in 1071 people (aged 20-78 years old) who were randomly selected using multistage random sampling method between September 2010 and April 2011 in Qazvin, Iran. Waist circumference (WC) and hs-CRP level weremeasured. Central obesity was defined as WC≥95 cm.According to the risk categories recommended by the American Heart Association and Center for Disease Control, hs-CRP was classified as low risk (3mg/L). A logistic regression analysis was used to examine the association of central obesity and hs-CRP. Results:Of 1107,527 were male.Mean age was 40.08±10.33 years. Mean hs-CRP level was 2.04±4.22. 26.5% and 19.4% of the study subjects had moderate risk and high risk hs-CRP, respectively. Three hundred and seventy (33.5%) subjectshad central obesity. The mean hs-CRP level was 3±4.42inthesubjectswithout central obesity and 2.85±3.70 ,inthesubjectswith central obesity and thedifferencewas significant (P <0.001).WC was associated with moderate risk hs-CRP (OR: 1.05, 95%CI: 1.03 -1.07; P<0.001) and high risk hs-CRP (OR: 1.096, 95%CI: 1.07 -1.11; P<0.001). Conclusion:With regards to the results, hs-CRPisassociatedwithcentral obesityamong adults in Qazvin. Morelongitudinalstudiesareneededtoevaluatethe association between hs-CRP and WC.

Incidence of the esophagus adenocarcinoma has been dramatically increasing in Western countries since the last decade. Gastroesophageal reflux disease and Barrett's esophagus are risk factors for adenocarcinoma. Methylenetetrahydrofolate reductase (MTHFR) genes play a key role not only in folate metabolism but also in esophagus, stomach, pancreatic carcinoma, and acute leukemias. Studies have suggested that genetic polymorphisms of MTHFR (C677T) may clarify the causes and events involved in esophageal carcinogenesis. In this study, we evaluated MTHFR C677T and A1298C polymorphisms, and vitamin B12, folate, and plasma homocystein levels in patients with esophageal adenocarcinoma (EAC), Barrett's esophagus (BE), chronic esophagitis, and healthy controls (n = 26, n = 14, n = 30, and n = 30, respectively). The mean age of patients in the EAC and BE groups was significantly higher compared with the control group (P < 0.001, P = 0.003, respectively). In all patient groups, serum folate levels were significantly lower than that of the control group (P < 0.01, P < 0.05, and P < 0.01, respectively). There was no statistically significant association between folate levels and MTHFR gene polymorphisms. No differences were found in terms of MTHFR gene polymorphisms, homocystein, and B12 levels among the groups. MTHFR gene polymorphisms and folate deficiency are not predictors of early esophageal carcinoma. However, further studies using larger series of patients are needed to evaluate the effect of genetic polymorphisms in the folate metabolic pathway and to clarify the role of folate deficiency and folate metabolism in the development of esophagus adenocarcinoma.

Objective: We examined the endothelial nitric oxide (eNOS) gene Glu298Asp polymorphism to assess its possible association with the extent of coronary collaterals. Methods: A total of 473 consecutive patients who had high grade coronary stenosis or occlusion were evaluated for the extent of coronary collaterals by using Rentrop classification. Patients with grade 0 or 1 collaterals were identified as having poor collaterals. The relation between collateral status and eNOS Glu298Asp polymorphism was studied by multivariate logistic regression analysis. Results: Subjects with poor collaterals were more likely to have diabetes mellitus (p < 0.001) and unstable angina pectoris as clinical presentation (p = 0.014) and more likely to carry Asp298 variant (p = 0.02) but they were less likely to have received statins (p = 0.031). Multivariate analysis demonstrated that Asp298 allele carriers were 1.7 times more likely to have poor collaterals than patients with GluGlu genotype (95% CI: 1.09-2.69, p = 0.024). There was a significant interaction between diabetes mellitus and eNOS Glu298Asp polymorphism in the analysis of collateral development. Among 145 diabetic patients Asp298 allele was the only predictor of poor collateral development with OR of 5.38 (95% CI: 2.41-11.98, p < 0.001). Once diabetic patients were excluded from the analysis Asp298 allele was no longer a significant correlate of poor collateral formation. Conclusions: The present study suggests that the Asp298 allele of the eNOS gene is significantly associated with impaired collateral development, especially in patients with diabetes mellitus. Treatment strategies that modulate eNOS activity and/or NO production may improve coronary collateral development.

Amaç: Bu çalışmada endoteliyal nitrik oksit sentaz (eNOS) geni polimorfizmleri ile Behçet hastalığına yatkınlık arasındaki ilişki araştırıldı. Hastalar ve yöntemler: Akrabalık ilişkisi olmayan 155 hasta (69 erkek, 86 kadın; ort. yaş 40.5 yıl; dağılım 14-66 yıl) ve 98 sağlıklı kontrolde (43 erkek, 55 kadın; ort. yaş 34.2 yıl; dağılım 17-78 yıl) eNOS geni Glu298Asp, -786T>C ve intron 4 a/b polimorfizmleri incelendi. Bulgular: Glu298Asp polimorfizminde GG genotipinin, hasta grubunda anlamlı ölçüde yüksek olduğu saptandı (p= 0.02). -789T>C polimorfizminde ise TT genotipi kontrol grubunda daha yaygın olarak bulundu (p<0.001). İntron 4 a/b polimorfizminin dağılımı ve alel frekansları açısından iki grup arasında anlamlı fark bulunmadı. Sonuç: Çalışmamızda, aile öyküsü, hastalığın başlangıç yaşı veya klinik bulgulardan bağımsız olarak, -786T>C polimorfizminin Behçet hastalığı ile ilişkili olduğu gösterilmiştir. C aleli Behçet hastalığı olanlarda daha yaygın olarak bulundu. Intron 4 a/b ve Glu298Asp polimorfizmleri hastalıkla doğrudan ilişkili bulunmadı. Anahtar sözcükler: Behçet hastalığı/tanı/etyoloji/genetik; nitrik oksit sentaz; polimorfizmler. Objectives: In this study, we investigated the relationship between endothelial nitric oxide synthase (eNOS) gene polymorphisms and predisposition to Behçet's disease. Patients and methods: One hundred and fifty-five unrelated patients (69 males, 86 females; mean age 40.5 years; range 14 to 66 years) and 98 healthy controls (43 males, 55 females; mean age 34.2 years; range 17 to 78 years) were examined for eNOS gene Glu298Asp, -786T>C and intron 4 a/b polymorphisms. The GG genotype in the Glu298Asp polymorphism was found to be significantly higher in the patient group (p=0.02). The TT genotype in the -789T>C polymorphism was found to be more prevalent in the control group (p<0.001). The distribution of the intron 4 a/b polymorphism and allele frequencies did not differ significantly between the two groups. In our study, the -786T>C polymorphism was found to be correlated with Behçet's disease, irrespective of family history, age at onset of the disease, or clinical findings. The C allele was found to be more prevalent in patients with Behçet's disease. The intron 4 a/b and Glu298Asp polymorphisms were not found to be directly related to the disease.

Introduction: Hypertrophic cardiomyopathy (HCM) is characterized by disorganized myocardial architecture, and may cause ventricular arrhythmias and sudden death. The angiotensin-converting enzyme (ACE) with two deletion alleles (DD genotype) has been proposed to be associated with increased myocardial collagen content. We evaluated QT dispersion (QTd), which reflects regional differences in ventricular repolarization, in HCM patient and controls among the three different ACE genotypes. Materials and methods: Sixty-three patients with HCM and 20 healthy subjects were included in the study. QT parameters were measured from 12 lead electrocardiograms. ACE genotypes were determined from the DNA extracted from peripheral blood by a polymerase chain reaction (PCR) method. QT parameters were compared among the three ACE genotypes both in HCM patients and controls. Results: Median ages were similar in HCM and control groups. QTd and corrected QTd (QTcd) were significantly greater in the HCM group compared with the controls. The frequencies of each genotype were similar in both groups. Although QTd and QTcd did not differ among the three genotypes in the control subjects, they were significantly greater in patients with DD genotype compared with other genotypes in the HCM group. Conclusion: QTd and QTcd are increased in patients with HCM, especially in those with the DD genotype.

OBJECTIVE: This study aims to ev aluate the association between preeclampsia and plasma homocysteine, serum folic acid, v itamin B12 concentrations and MTHFR C677T polymorphism. STUDY DESIGN: This study was a case-control study including 20 pregnant females with preeclampsia and 30 healthy normotensive pregnant (ages 18-40) females. Plasma homocysteine, serum folic acid and vitamin B12 concentrations were measured in all patients in the third trimester of pregnancy and MTHFR C677T polymorphism was also analyzed. RESULTS: The risk of preeclampsia in patients with homocysteine concentrations &gt;8.65 μmol/L increased 8-f old as compared to homocysteine concentrations &lt;6.19 μmol/L. While the mean plasma homocysteine concentration (8.65±2.05 μmol/L vs. 6.19±1.52 μmol/L, p&lt;0.001), was high in the preeclampsia group as compared to controls, the mean serum folic acid concentration was signif icantly low (11.49±8.96 ng/ml vs. 15.15±6.7 ng/ml, p= 0.020). No significant difference was n...

Objective: Glucocorticoids (GCs) are the key drugs for the treatment of pediatric acute lymphoblastic leukemia (ALL). Herein, investigation of the relationship between the N363S and BclI polymorphisms of the GC receptor gene (NR3C1) and the side effects of GCs during pediatric ALL therapy was aimed. Materials and Methods: N363S and BclI polymorphisms were analyzed in 49 patients with ALL treated between 2000 and 2012. The control group consisted of 46 patients with benign disorders. The side effects of GCs noted during the induction and reinduction periods were evaluated retrospectively according to the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0. The BclI allele and genotype frequencies were found similar in the two groups. No N363S polymorphism was detected in either of the groups. During induction, dyspepsia was found more frequently in the CG than in the CC (wild-type) genotype (36.4% vs. 5.3%, p=0.018) and depression symptoms more frequent in patients with the G allele (CG+GG) than the CC genotype (39.3% vs. 10.5%, p=0.031). During reinduction, Cushingoid changes, dyspepsia, and depression symptoms were more frequent in patients with the G allele (CG+GG) than in patients with the CC genotype (48.1% vs. 17.6%, p=0.041; 29.6% vs. 0.0%, p=0.016; 40.7% vs. 11.8%, p=0.040, respectively). In our study, patients with the BclI polymorphism were found to have developed more frequent side effects. We think that the BclI polymorphism should be considered while designing individualized therapies in childhood ALL.

Background: The vitamin B12 and folate status in nonanaemic healthy older persons needs attention the more so as decrease in levels may be anticipated from reduced haematinic provision and/or impaired intestinal uptake. Methods: A total of 1143 subjectively healthy Swiss midlands participants (637 females and 506 males), ≥60 years of age were included in this study. Levels of vitamin B12, holotranscobalamin (holoTC), methylmalonic acid (MMA), homocysteine (Hcy), serum folate, red blood cell (RBC) folate were measured. Further, Fedosov's wellness score was determined. Associations of age, gender, and cystatin C/creatinine-based estimated kidney function, with the investigated parameters were assessed. Reference intervals were calculated. Further, ROC analysis was done to assess accuracy of the individual parameters in recognizing a deficient vitamin B12 status. Finally, decision limits for sensitive, specific and optimal recognition of vitamin B12 status with individual parameters were derived. Results: Three age groups: 60-69, 70-79 and ≥ 80 had median B12 (pmol/L) levels of 237, 228 and 231 respectively (p = 0.22), holoTC (pmol/L) of 52, 546 and 52 (p = 0.60) but Hcy (μmol/L) 12, 15 and 16 (p < 0.001), MMA (nmol/L) 207, 221 and 244 (p < 0.001). Hcy and MMA (both p < 0.001), but not holoTC (p = 0.12) and vitamin B12 (p = 0.44) were found to be affected by kidney function. In a linear regression model Fedosov's wellness score was independently associated with kidney function (p < 0.001) but not with age. Total serum folate and red blood cell (RBC) folate drift apart with increasing age: whereas the former decreases (p = 0.01) RBC folate remains in the same bandwidth across all age groups (p = 0.12) A common reference interval combining age and gender strata can be obtained for vitamin B12 and holoTC, whereas a more differentiated approach seems warranted for serum folate and RBC folate. Conclusion: Whereas the vitamin B12 and holoTC levels remain steady after 60 years of age, we observed a significant increment in MMA levels accompanied by increments in Hcy; this is better explained by age-related reduced kidney function than by vitamin B12 insufficiency. Total serum folate levels but not RBC folate levels decreased with progressing age.

Complex interplay of environmental and genetic factors has been known to contribute to CAD pathophysiology. Variations in several genes have been found to be associated with risk for developing CAD in different populations. Glutathione S-transferases (GSTs) play a primer role in cellular defense against electrophilic chemical species and radical oxygen species. This study was designed to assess the GSTM1 gene variant in 120 patients with coronary artery disease (CAD) as compared to equal number of controls. DNA was isolated from the blood samples collected and subjected to PCR with specific GSTM1 specific primers. The frequency of GSTM 1 gene was in 73.3% of cases or patients with CAD and 61.6% in control subjects and the frequency of null genotype was 26.6% in CAD cases and 38.3% in control group. There was no significant association of GSTM1 gene (null) polymorphism ( ² = 3.72, P = 0.053, OR = 1.17, 95% CI = 0.95 -3.07) with CAD in our study. However, diabetes and smoking were significantly associated with CAD (p < 0.001).

Published by Madridge Publishers Abstract Background: Diabetic Nephropathy (DN) is one of the complications in patients with prolonged diabetes. Among the genetic risk factors for DN, TNF-α, an anti-inflammatory cytokine is proposed to act in a paracrine/autocrine manner and is hypothesized to be associated with insulin resistance. In the current study, the relationship of the G ↆC variant of the TNF-α gene in patients, associated with other biochemical parameters with DN was investigated.

INTRODUCTION Two common polymorphisms in cytochrome P450; family 1, subfamily A, polypeptide 1 (CYP1A1); have been implicated as a risk factor of prostate cancer, but individual studies have been inconclusive or controversial. We reviewed studies on CYP1A1 polymorphisms in patients with prostate cancer. MATERIALS AND METHODS The strategy searching in the PubMed was based on combinations of prostate cancer, CYP1A1, CYP1A1 gene polymorphism, and genetic susceptibility. The last search update was May 2008. The retrieved articles and their bibliographies of were evaluated and reviewed independently by 2 experts. We shortlisted 19 studies, of which 14 on sporadic prostate cancer were analyzed. Overall, 2573 patients with prostate cancer and 2576 controls were analyzed. RESULTS The random effects odds ratio was 1.350 (95% confidence interval, 1.110 to 1.641; P = .003) for T/C polymorphism and 1.085 (95% confidence interval, 0.863 to 1.364; P = .49) for A/G polymorphism. The A/G polymorphi...

Diabetes has emerged as a major threat to human life globally. Genomic studies have found a significant link between the Pro12Ala polymorphism of the PPAR-c2 gene with incidence as well as occurrence of the risk of metabolic syndrome. The present study was aimed at assessing the PPAR-c2 variant in an Asian Indian cohort of type 2 diabetes patients and its correlation with metabolic parameters. The present case-control study involved 100 type 2 diabetic patients and 100 asymptomatic healthy volunteers enrolled in random. Assessment of demographic factors and biochemical parameters were done for all enrolled. In addition, genotyping for the Pro12Ala (CCA to GCA) polymorphism was done by polymerase chain reaction -restriction fragment length polymorphism (PCR-RFLP) technology. The genotyping study detected the frequency of the CC genotype (Pro12Pro) to be higher in frequency in comparison to the heterozygous CG genotype in both, cases and controls. The homozygous GG genotype (Ala12Ala) was not detected in any of the cases or controls assessed. Biochemical analysis of the levels of malondialdehyde (MDA) detected a significant increase (p < 0.0001). Additionally, increase in levels of fasting and postprandial glucose, total cholesterol, triglycerides, and parameters of the liver and renal function tests were detected. This study detected the PPAR-c2 to be a significant biomarker for type 2 diabetes mellitus.

Endothelium-derived nitric oxide (NO) is synthesized from l-arginine by endothelial 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 coronary artery disease (CAD). We therefore undertook this study to determine the association between the occurrence of CAD and eNOS4 b/a polymorphism in South Indian patients. We investigated the polymorphisms in the 27 base-pair tandem repeats in intron4 of the eNOS gene in 100 unrelated CAD patients with positive coronary angiograms and 100 age and sex matched control subjects without any history of symptomatic CAD. The eNOS gene intron4 b/a 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 63, 26 and 11 per cent ...

Within the mammalian reproductive system sirtuin 1 and 6 (SIRT1, SIRT6) are considered to contribute to steroid hormone signaling and control of reproductive physiology. Therefore, the specific question is whether and how a commonly used dicarboximide fungicide with antiandrogenic activity, vinclozolin (Vnz) alters SIRT1 and SIRT6 expression and whether both investigated sirtuins positively affect survival of the follicles after vinclozolin exposure. Immunocytochemistry and immunohistochemistry were performed to localize SIRT1 and SIRT6 expression in cultured granulosa cells (GCs; 48 hours) and whole ovarian follicles (24 hours) after treatment with two androgens, testosterone (T; 10-7 M) and dihydrotestosterone (DHT; 10-7 M), and an antiandrogen, Vnz (1.4 x 10-5 M), separately and in combinations. Granulosal and follicular mRNA and protein expression of both sirtuins was also investigated by real-time PCR and Western blot. In addition, their concentration and activity was studied b...

The immunohistochemical expression of the androgen receptor (AR) was investigated in the ovarian atretic follicles and corpora lutea (CL) of pregnant pigs and rats, as well as in porcine uteri and fetuses. Follicular atresia involved either abnormal persistence or depletion of AR in various follicular compartments. Porcine and rat CL expressed nuclear AR. However, in the porcine CL, starting from day 70 of pregnancy, mainly cytoplasmic staining was observed, with exclusively cytoplasmic expression found on day 90. In the CL of pregnant rats, differences in AR distribution within the same CL were observed and decreasing AR expression during luteal regression was found. AR mRNA and protein expression in the porcine uterus depended on the uterine compartment and the day of pregnancy. AR-positive were also testes, ovaries, uteri, kidneys and lungs of fetuses.

Localization of androgen receptor (AR) was investigated in ovarian follicles developing and undergoing atresia during pregnancy in the pig. Immunohistochemical staining was conducted on ovarian antral follicles isolated on different days of gestation: 10, 18, 32, 50, 70, and 90. Paraffin sections were also subjected to in situ DNA labeling. TUNEL staining revealed the presence of positive follicles on all days of pregnancy but the amount of atretic follicles increased with time. However, even on day 90 of gestation many follicles were normal, with no signs of atresia. In atretic follicles, apoptotic cells were localized predominantly in the granulosa while theca was much less affected. Atretic follicles with many apoptotic cells were negative for AR. Nuclear immunostaining for AR was positive in follicles with limited amount of apoptotic cells. The same relationship was observed in ovarian follicles isolated at various days of pregnancy.

Damaraland mole rats (Fukomys damarensis) are cooperatively breeding, subterranean mammals, which exhibit high reproductive skew. Reproduction is monopolized by the dominant female of the group while subordinates are physiologically suppressed to the extent that they are anovulatory. It is thought that in these latter animals normal GnRH secretion from the hypothalamus is disrupted. The RFamide peptides kisspeptin (Kiss1) and RFamidrelated peptide-3 (RFRP-3) are considered potent regulators of gonadotropin release. To assess whether these neuropeptides are involved in the mechanism of reproductive suppression we investigated the distribution and gene expression of Kiss1 and Rfrp by means of in situ hybridisation in wild-caught female Damaraland mole-rats with different reproductive status. In both reproductive phenotypes, substantial Kiss1 expression was found in the arcuate nucleus and only few Kiss1-expressing cells were detected in the AVPV, potentially due to low circulating estradiol concentrations in breeding and non-breeding females. Rfrp gene expression occurred in the dorsomedial nucleus, the paraventricular nucleus and the periventricular nucleus. While in female breeders and non-breeders plasma oestradiol levels were low and not significantly different, quantification of the hybridisation signal for both genes revealed significant differences in relation to reproductive status. Reproductively active females had more Kiss1-expressing cells and a higher number of silver grains per cell in the arcuate nucleus when compared to non-reproductive females. This difference was most pronounced in the caudal part of the nucleus. No such differences were found in the AVPV. Furthermore, breeding status was associated with a reduced number of Rfrp-expressing cells in the anterior hypothalamus. This reproductive status-dependent expression pattern of Kiss1 and Rfrp suggests that both neuropeptides play a role in the regulation of reproduction in Damaraland mole-rats. Enhanced long-term negative feedback effects of oestradiol could be responsible for the lower Kiss1 expression in the arcuate nucleus of reproductively suppressed females.

Western blotting was performed to verify the knockdown efficiency, to estimate the effect on cell differentiation (FOXA2) and the activation of the hypoxia pathway (VEGF). I) HIF1A and PHD3 mRNA expression was evaluated by RT-PCR in H358 cells transfected with control or siRNAs targeting EZH2. J-K) H358 cells were transfected with pooled siRNAs for EZH2 and/or PHD3. Knockdown efficiency was evaluated by western blotting, and changes in HIF1α and FOXA2 expression was evaluated by western blotting. HIF1α levels were quantified by ImageJ (K). L-M) Western blots were performed in H358 cells transfected with siRNAs (L) or expression vectors (M) for EZH2 and PHD3. . *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001; n.s.: not significant.

Pharmacokinetic parameters were studied after i.v. infusion of erythromycin (500 mg) in five patients with alcoholic cirrhosis and six normal subjects. Serum AAG levels were 4.7 +/− 2.4 mumol l‐1 in cirrhotics and 10.3 +/− 2.1 +/− mumol l‐1 in normals. The unbound fraction (fu) of erythromycin was significantly higher in cirrhotic patients (58.3 +/− 17.7%) than in normal subjects (30.5 +/− 2.8%, P less than 0.01), and a negative correlation was found between fu values and serum AAG (r = −0.867, P less than 0.01). Due to increase in fu, volume of distribution (Vss) was significantly augmented in cirrhotics (85.5 +/− 23.8 l vs 57.6 +/− 14.8 l, P less than 0.05). Serum clearance of unbound erythromycin (CLu) was significantly reduced in cirrhotic patients (42.2 +/− 10.1 l h‐1 vs 113.2 +/− 44.2 l h‐1 in normal subjects, P less than 0.01). This led to marked elevation of serum concentrations of unbound drug and was entirely explained by the decrease of non renal (i.e. hepatic intrinsic) ...