Lactobacillus GG is associated with mucin genes expressions in type 2 diabetes mellitus: a randomized, placebo-controlled trial.

PURPOSE: Recent studies indicate that dysbiosis of gut microbiota and low-grade inflammation are important pathogenic determinants of type two diabetes mellitus (T2DM). The aim of this study is to investigate the effects of Lactobacillus GG on glycemic control, lipid profile, inflammatory parameters, and some gene expression levels in individuals with T2DM. METHODS: In a randomized, placebo-controlled trial, 34 women, aged 30-60 years with T2DM consumed daily probiotics or placebo for 8 weeks. The probiotic group consumed 10 × 109 Cfu/day Lactobacillus rhamnosus GG ATCC 53,103 (LGG), approved by the TR Ministry of Food, Agriculture, and Livestock. Anthropometric measurements, food diary, fasting blood, and fecal samples were taken at baseline and post-treatment. RESULTS: Fasting blood glucose was significantly decreased in probiotic (p = 0.049) and placebo (p = 0.028), but there was no difference between the groups. In the probiotic group, no significant difference was observed in HbA1c, fructosamine, lipid profile, and inflammatory variables compared to baseline. In this group, with LGG supplementation, mucin 2 and 3A (MUC2 and MUC3A) gene expressions increased more than ninefolds (p = 0.046 and p = 0.008, respectively) at post-treatment. Meanwhile, there was no significant change in any of the gene expressions in the placebo group. There was no significant difference in energy, protein, dietary fiber, and cholesterol intakes between placebo and probiotic groups during the study. However, daily fat intake (p = 0.003), body weight (p = 0.014), and body fat (p = 0.015) in the probiotic group were significantly decreased. CONCLUSION: In this study, the effects of a single probiotic strain were investigated for 8 weeks. At the end of the study, although there was no finding that clearly reflected on the glycemic parameters of T2DM, its beneficial effects on the expression of mucin genes, which are responsible for weight loss and protection of intestinal barrier functions, cannot be denied. Further studies are needed to reveal the importance of these findings. CLINICAL TRIAL REGISTRATION: ID: NCT05066152, October 4, 2021 retrospectively registered in ClinicalTrials.gov PRS web site.

Firmicutes/Bacteroidetes Ratio in the Gut Microbiota and IL-1ß, IL-6, IL-8, TLR2, TLR4, TLR5 Gene Expressions in Type 2 Diabetes.

BACKGROUND: The aim of this study was to determine the Firmicutes/Bacteroidetes ratio in the gut microbiota and IL-1ß, IL-6, IL-8, TLR2, TLR4 and TLR5 gene expression levels in the blood of adult type 2 diabetes (T2D) patients and compare it with that of adult nondiabetic healthy controls (HC). METHODS: Between May 2016 and April 2017, 99 T2D patients and 99 HCs were enrolled in the study. Bacteroidetes and Firmicutes levels were assessed from stool sample DNA and IL-1ß, IL-6, IL-8, TLR2, TLR4, and TLR5 gene expression levels assesed from blood sample RNA via qPCR from both T2D patients and healthy controls. RESULTS: The Firmicutes/Bacteroidetes ratio detected in the stool of type 2 diabetes patients was found to be higher with a statistically significant difference (p < 0.0001). Gene expression levels of IL-1ß, IL-6, IL-8, TLR2, TLR4, and TLR5 were found to be upregulated. CONCLUSIONS: The highest upregulation was detected in IL-6 with 11 fold in T2D patients comparing with HCs. F/B ratio and gene expression levels were elevated in T2D patients. Firmicutes were positively correlated with studied gene expressions. A better understanding of the complex interaction between gut microbiota, environment, and diabetes will allow for more effective prevention and treatment strategies for T2D.

Investigation of DPYD, MTHFR and TYMS polymorphisms on 5-fluorouracil related toxicities in colorectal cancer.

Aim: To investigate the association of DPYD, MTHFR and TYMS polymorphisms on 5-fluorouracil (5-FU) related toxicities and patient survival. Materials & methods: A total of 103 colorectal cancer patients prescribed 5-FU were included in the study. Genotyping was conducted for several DPYD, MTHFR and TYMS polymorphisms using a microarray analyzer. Results: DPYD 496A>G polymorphism was found to be significantly associated with 5-FU related grade 0-2, but not severe toxicities (p = 0.02). Furthermore, patients with DPYD 85TC and CC genotypes had longer progression and overall survival times compared to TT genotypes in our study group (log rank = 6.60; p = 0.01 and log rank = 4.40; p = 0.04, respectively). Conclusion: According to our results, DPYD 496AG and GG genotypes might be protective against severe adverse events compared to the AA genotype. Another DPYD polymorphism, 85T>C, may be useful in colorectal cancer prognosis. Further studies for both polymorphisms should be conducted in larger populations to achieve accurate results.

5-fluorouracil (5-FU) is a widely used drug for chemotherapy in colorectal cancer. In this study, we investigated the relationship between the severity of 5-FU induced adverse events and several variations in DPYD, MTHFR and TYMS genes, which encode the enzymes involved in 5-FU metabolism in a total of 103 colorectal patients. We also examined the relationship between the polymorphisms and progression-free and overall survival times of the patients in our study group. Among the variations, DPDY 496A>G polymorphism was found to be associated with 5-FU induced adverse events. Also, the DPYD 85T>C polymorphism was detected to be associated with longer progression-free and overall survival times.

The effects of glipizide on DNA damage and nuclear transport in differentiated 3T3-L1 adipocytes.

BACKGROUND: Despite commonly use for treatment of type II diabetes, possible effects of glipizide on nuclear transport and DNA damage in cells are unknown. Since clinical response of glipizide may change with aging, the aim of the study was to investigate the effect of glipizide by comparing mature and senescent adipocytes. METHODS AND RESULTS: The effects of glipizide were investigated in 3T3-L1 adipocytes. Effective and lethal doses were determined by real-time monitoring iCELLigence system. Comet assay was performed to determine DNA damage and quantitative PCR was conducted to detect gene expression levels. RAN expressions were found to be up regulated in mature 180 µM glipizide treated adipocytes compared to control group (p < 0.05); whereas down regulated in senescent 180 µM glipizide treated adipocytes compared to their control adipocytes (p < 0.05). Olive Tail Moment values were significantly higher in mature 180 µM glipizide treated adipocytes (MTG) and senescent 180 µM glipizide treated adipocytes (STG) comparing their untreated controls (p < 0.001 and p < 0.001 respectively). Also class 5 comets that shows severe DNA damage were found to be higher in both MTG and STG groups than their controls (p < 0.001 and p < 0.001, respectively). OTM values were higher in STG than MTG (p < 0.001). CONCLUSIONS: This is the first study that reports glipizide caused DNA damage increasing with senescence in adipocytes. As a response to glipizide treatment Ran gene expression increased in mature; and decreased in senescent adipocytes. Further studies are needed to reveal the effect of glipizide on DNA and nuclear interactions in molecular level.

DNA Damage in AML-12 Hepatocytes and 3T3-L1 Adipocytes Treated with Clopidogrel.

BACKGROUND: Clopidogrel has been commonly prescribed as a selective P2Y12 receptor antagonist to reduce heart attack and stroke risk. Nearly 10% of absorbed clopidogrel is metabolized to active forms by cytochrome P450 (CYP) enzymes in the liver and 90% to inactive clopidogrel carboxylate by esterases. OBJECTIVE: Since different forms of clopidogrel have cytotoxic potential, our aim was to determine the effect of 7.5, 40, and 75µM clopidogrel over DNA damage in adipocytes and hepatocytes. METHODS: In the present study, DNA damage was investigated by Comet analysis using 3T3-L1 adipocytes and Alpha Mouse 12 (AML-12) hepatocytes. RESULTS: DNA fragmentation was found to be increased as a response to 7.5 µM, 40 µM, and 75 µM clopidogrel treatment compared to non-treated control groups in AML-12 hepatocytes (p<0.01, p<0.001, p<0.01 respectively) and 3T3-L1 adipocytes (p<0.001, p<0.001 and p<0.001respectively). DNA damage levels as a response to clopidogrel treatment were found to be higher in 3T3-L1 adipocytes than AML-12 hepatocytes. Also, DNA damage levels in adipocytes and hepatocytes were found to increase dose-dependently for 7.5 and 40 µM clopidogrel, whereas decreased as a response to 75 µM. CONCLUSION: According to our results, clopidogrel results in more DNA damage in adipocytes than in hepatocytes. The molecular mechanism of clopidogrel genotoxicity needs to be further investigated especially in adipose tissue.

The effects of CYP2C9 and VKORC1 gene polymorphisms on warfarin maintenance dose in Turkish cardiac patients.

Aim: Our aim was to examine the effect of CYP2C9 and VKORC1 polymorphisms on warfarin dose requirements in Turkish patients. Materials & methods: 24 warfarin prescribed patients were included and analyzed for eight VKORC1 and 6 CYP2C9 polymorphisms in the study. Results: Patients with CYP2C9 *1/*1 and VKORC1 -1639 GG and GA genotypes required higher warfarin doses in comparison to wild type VKORC1 genotype. Patients with CYP2C9 *1/*3 and VKORC1 -1639 GG genotypes simultaneously, required the lowest dose of warfarin (4.64 mg/day). Patients with CYP2C9 *1/*1 and VKORC1 9041 AA genotype were found to require higher warfarin doses. Conclusion: Our results provide additional evidence to support the hypothesis that CYP2C9 *2, *3, VKORC1 9041 G > A polymorphisms explain considerable proportion of inter-individual variability in warfarin dose requirement.

Evaluation of Cytotoxicity and Mutagenicity of Wastewater from Istanbul: Data from Hospitals and Advanced Wastewater Treatment Plant.

Wastewater (WW) carry considerable amount of chemicals that could have mutagenic or cytotoxic effect from hospital discharges to aquatic environment. Our objective was to determinate the possible mutagenic and toxic effects of hospital originated WWs and effectiveness of the wastewater treatment plants (WTP) functions. In the study the mutagenic and cytotoxic potential of three hospitals and influent/effluent of a treatment plant WW collected in Istanbul and was examined using AMES, XTT, and lactate dehydrogenase (LDH) assays. Mutagenic effects were detected at both hospital discharges and advanced biological wastewater plant. We observed no cytotoxic effect in fibroblasts for LDH and XTT assays whereas high cytotoxicity for all samples was found in hepatocytes by XTT assay. According to the results even if advanced technology is used for treatment of WW, mutagenic and cytotoxic effects still remain, and the present technologies need to be further improved.

Bacteroidetes and Firmicutes levels in gut microbiota and effects of hosts TLR2/TLR4 gene expression levels in adult type 1 diabetes patients in Istanbul, Turkey.

AIM: The aim of this study was to determine and compare the levels of both Bacteroidetes and Firmicutes in the gut microbiota and TLR2/TLR4 gene expression in the blood of patients with type 1 diabetes mellitus (T1DM) and healthy individuals. These results may serve as a preliminary assessment to guide future research. METHOD: Between January and October 2014, stool and blood samples were collected from 53 adult T1DM patients and 53 age- and gender-matched healthy individuals. Bacteroidetes and Firmicutes levels were assessed from stool sample DNA and TLR2 and TLR4 expression levels were analyzed via qPCR using RNA from EDTA blood samples from both patients and healthy controls. RESULTS: The amounts of Bacteroidetes and Firmicutes were statistically significantly higher and lower, respectively, in the T1DM group than in the healthy control group (p < 0.001 and p < 0.001, respectively). In addition, the Firmicutes/Bacteroidetes ratios in patients with T1DM were significantly lower than in healthy controls. The TLR4 and TLR2 gene expression levels in T1DM patients were significantly upregulated and downregulated, respectively, compared to those in the control group. CONCLUSION: Our data are the first to show a relationship between T1DM and gut microbiota in our country. In addition, our results provide information about the connections between T1DM, gut microbiota, and TLR2 and TLR4 expression. We believe that Bacteroidetes and Firmicutes in the gut microbiota may play a role in the autoimmune process of T1DM and that these findings should be further investigated in the future.

Comparison of arterial and venous blood gases in patients with obesity hypoventilation syndrome and neuromuscular disease.

OBJECTIVES: Obesity hypoventilation syndrome (OHS) and some neuromuscular diseases (NMD) present with hypercapnic respiratory failure. Arterial blood gas (ABG) analysis is important in the diagnosis, follow-up, and treatment response of these diseases. However, ABG sampling is difficult in these patients because of excessive subcutaneous fat tissue, muscle atrophy, or contracture. The aim of this study is to investigate the value of venous blood gas (VBG), which is an easier and less complicated method, among stable patients with OHS and NMD. METHODS: The study included stable OHS and NMD patients who had been previously diagnosed and followed up between March 2017 and May 2017 in the outpatient clinic. ABG was taken from all patients in room air, and peripheral VBG was taken within 5 min after ABG sampling. RESULTS: Thirty-six patients with OHS and 46 patients with NMD were included in the study. There was a moderate positive correlation between arterial and venous pH values for all patients (r s = 0.590, P < 0.001). There were a strong and very strong positive correlations between arterial and venous pCO2 and HCO3 values (r s = 0.725 and r s = 0.934, respectively) (P < 0.001). There was no correlation between arterial and venous pO2 and saturation values. There was an agreement in Bland-Altman method for the values of ABG and VBG (pH, pCO2, and HCO3). CONCLUSIONS: There was a correlation between ABG and VBG values (pH, pCO2, and HCO3). VBG parameters (pH, pCO2, and HCO3) can be used safely instead of ABG parameters which have many risks, during treatment and follow-up of patients with OHS and NMD.

Follow-up of 1887 patients receiving tumor necrosis-alpha antagonists: Tuberculin skin test conversion and tuberculosis risk.

OBJECTIVES: To evaluate the characteristics of patients who developed tuberculosis while receiving tumor necrosis factor-alpha (TNF-α) antagonists and the related factors with tuberculosis. METHODS: Patient's demographics, tuberculin skin test (TST), isoniazid prophylaxis and type of TNF-α antagonist were recorded. TST conversion (≥5 mm increase) was evaluated for patients who had baseline and 1-year TST. RESULTS: Files of 1887 patients who were receiving TNF-α antagonists between August 2005 and June 2015 were evaluated. TST significantly increased at the end of 1 year (n = 748 baseline:7.36 ± 7.2 mm vs. 1 year:9.52 ± 7.5 mm, P < 0.001). One-third of patients (31.2%) who had negative TST at baseline had positive TST at 1 year. Tuberculosis developed in 22 patients (1.16%). The annual incidence of tuberculosis was 423/100 000 patient-year. TNF-α antagonist indications were ankylosing spondylitis (n = 8), inflammatory bovel diseases (n = 7) and rheumatoid arthritis (n = 4). Ten (45.5%) patients received infliximab, six (27.3%) patients received etanercept and six (27.3%) patients received adalimumab. Nineteen (86.4%) patients were under isoniazid prophylaxis. Twelve patients had extrapulmonary tuberculosis (54.5%; four lymph node, three pleura, two periton, one pericarditis, one intestinal, one joint). Atypical mycobacterium was detected in one patient. Adalimumab treatment (9.5× increase), male sex (15.6× increase) and previous tuberculosis disease history (11.5× increase) were risk factors for active tuberculosis. Conversion of TST was not found related with tuberculosis. CONCLUSIONS: Despite the high proportion of isoniazid prophylaxis, the incidence of tuberculosis in our patients receiving TNF-α antagonist was higher than the literature. Adalimumab treatment, male sex and previous tuberculosis disease history were found as risk factors for tuberculosis.

Evaluation of Adenovirus-36 (Ad-36) antibody seropositivity and adipokine levels in obese children.

Adenovirus 36 (Ad-36) has recently been suggested as a possible contributor to the current obesity epidemic. The aim of this study was to investigate the prevalence of Ad-36 antibodies in obese children, as well as investigate the role of serum leptin and lipid levels in Ad-36-obesity. Seventy-one obese children and 62 non-obese children were included as the patient group (PG), including the healthy control group (HCG), respectively. Simultaneously, Ad-36 antibodies and adipokine levels were assessed with serum neutralization assays (SNA) and ELISA. Ad-36 antibody was detected in 9 patients (12.7%) and 1 patient (1.6%) in both the PG and HCG, respectively, while a significant difference was detected between groups (p < 0.05). Although serum LDL, total cholesterol, triglycerides and leptin levels were detected significantly higher, adiponectin level was detected paradoxically lower in the PG. However, a significant difference was not detected for lipids and leptin levels; adiponectin levels were found to be significantly lower in Ad-36 antibody-positive PG (p < 0.05). In conclusion, we suggest there is an association between Ad-36 and obesity in children, including IL-6 levels increasing in obese children with Ad-36 seropositivity. Conversely, adiponectin levels in obese children with Ad-36 seropositivity were higher. As such, there is a need for studies to understand the mechanisms underlying this observation.

Association of sweet taste receptor gene polymorphisms with dental caries experience in school children.

Sweet taste is a powerful factor influencing food acceptance. The peripheral taste response to sugar is mediated by the TAS1R2/TAS1R3 taste receptors. The aim of the study was to determine the relationship between TAS1R2 (rs35874116 or rs9701796) and/or TAS1R3 (rs307355) single nucleotide polymorphisms with dental caries experience in schoolchildren. A total of 184 schoolchildren aged between 7 and 12 years (101 girls, 83 boys) were included in the study. Genomic DNA was extracted from saliva samples and the genotypes were identified by qPCR. The genotype frequencies were as follows: 6.6% for homozygous wild type, 41.8% for heterozygous and 51.6% for homozygous polymorphic genotype carriers of TAS1R2 gene rs35874116; 27.8% for heterozygous and 72.2% for homozygous polymorphic genotype carriers of TAS1R2 gene rs9701796, and 83.1% for homozygous wild type and 16.9% for heterozygous genotype carriers of TAS1R3 gene rs307355 polymorphism. A significant association was observed between total caries experience (dft + DMFT - decayed filled primary teeth + decayed, missing and filled permanent teeth) and TAS1R2 rs35874116 (p = 0.008) and TAS1R3 rs307355 (p = 0.04) gene polymorphisms but not for TAS1R2 gene rs9701796 polymorphism. TAS1R3 gene rs307355 polymorphism has been found to be an independent risk factor for dental caries experience by logistic regression analysis and to have increased the risk of caries. Moderate caries experience (4-7 caries) was found to be associated with TAS1R3 rs307355 heterozygous genotype, whereas high-risk caries experience (>8 caries) was found to be associated with TAS1R2 rs35874116 homozygous polymorphic genotype.

Clinical predictors of obesity hypoventilation syndrome in obese subjects with obstructive sleep apnea.

BACKGROUND: Arterial blood gas (ABG) analysis is not a routine test in sleep laboratories due to its invasive nature. Therefore, the diagnosis of obesity hypoventilation syndrome (OHS) is underestimated. We aimed to evaluate the differences in subjects with OHS and pure obstructive sleep apnea (OSA) and to determine clinical predictors of OHS in obese subjects. METHODS: Demographics, body mass index (BMI), Epworth Sleepiness Scale score, polysomnographic data, ABG, spirometric measurements, and serum bicarbonate levels were recorded. RESULTS: Of 152 obese subjects with OSA (79 females/73 males, mean age of 50.3 ± 10.6 y, BMI of 40.1 ± 5.6 kg/m(2), 51.9% with severe OSA), 42.1% (n = 64) had OHS. Subjects with OHS had higher BMI (P = .02), neck circumference (P < .001), waist circumference (P < .001), waist/hip ratio (P = .02), Epworth Sleepiness Scale scores (P = .036), ABG and serum bicarbonate levels (P < .001), apnea-hypopnea index (P = .01), oxygen desaturation index (P < .001), and total sleep time with S(pO2) < 90% (P < .001) compared with subjects with pure OSA (n = 88). They also had lower daytime PaO2 (P < .001), sleep efficiency (P = .032), mean S(pO2) (P < .001), and nadir S(pO2) (P < .001). Serum bicarbonate levels and nadir S(pO2) were the only independent predictive factors for OHS. A serum bicarbonate level of ≥ 27 mmol/L as the cutoff gives a satisfactory discrimination for the diagnosis of OHS (sensitivity of 76.6%, specificity of 74.6%, positive predictive value of 54.5%, negative predictive value of 88.9%). A nadir S(pO2) of < 80% as the cutoff gives a satisfactory discrimination for the diagnosis of OHS (sensitivity of 82.8%, specificity of 54.5%, positive predictive value of 56.9%, negative predictive value of 81.4%). When we used a serum bicarbonate level of ≥ 27 mmol/L and/or a nadir S(pO2) of < 80% as a screening measure, only 3 of 64 subjects with OHS were missed. CONCLUSIONS: Serum bicarbonate level and nadir saturation were independent predictive factors for the diagnosis of OHS.

Does the 6-minute walk test predict nocturnal oxygen desaturation in patients with moderate to severe COPD?

Patients with chronic obstructive pulmonary disease (COPD) who have nocturnal oxygen desaturation (NOD) can be treated with nocturnal oxygen therapy (NOT) to avoid possible morbidity and mortality. Although there is no definite data recommending NOT alone, our aim is to evaluate the relationship between desaturation during the six-minute walk test (6MWT) and NOD in COPD. Fifty-five stable patients with COPD were enrolled in this study. The 6MWT and nocturnal oximetry were performed. Patients with comorbid diseases and respiratory failure were excluded. In total, 55 patients (49 males and 6 females, mean age: 65.8 ± 8.4 years) were analysed. Twenty-seven of the patients had moderate COPD and the remainder (n = 28) had severe COPD. Three patients (11%) with moderate COPD and 12 patients (42.9%) with severe COPD desaturated during 6MWT (p = 0.003). NOD was observed in five patients with severe COPD (17.9%). There were no patients with NOD in the moderate COPD group. Three (25%) of patients with severe COPD who desaturated during the 6MWT also had NOD. NOD was more common in patients with severe COPD and the patients with higher carbon dioxide levels (p = 0.02 and p = 0.001). Three patients (11%) with moderate COPD desaturated during the 6MWT; however they did not have NOD. Although the sample size in this study was too small to be conclusive, NOD was more common in desaturators during the 6MWT particularly in patients with severe COPD.

The relationship of Bradykinin B2 receptor gene variation with obesity, hypertension and lipid variables in obese patients.

OBJECTIVE: This study examined the association of C-58T genotypes with obesity/hypertension related parameters and serum lipids in obese (n=108) and non-obese (n=80) patients. MATERIALS AND METHODS: Bradykinin receptor (B2R) C-58T genotypes were determined by PCR-RFLP. RESULTS: B2R gene C-58T frequencies for T/T (homozygous wild type), T/C (heterozygous) and C/C (homozygous polymorphic) genotypes for obese and non-obese patients were respectively: 36.1%, 37.5%; 45.4%, 52.5% and 18.5%, 10%. Obese patients using diuretic medication had lower C/C genotype frequency compared to T/T and T/C genotypes. Total cholesterol (T-Chol) (p=0.035) levels were found to be associated with B2R C-58T polymorphism, where the T/T genotype had higher total cholesterol levels compared to the T/C genotype in obese patients. Non-obese patients using oral antidiabetic medication had higher C/C genotype frequency than that of T/T and T/C genotypes. Waist circumference (p=0.016) and diastolic blood pressure (p=0.01) levels were elevated in the non-obese subjects with the C/C genotype compared to T/C and T/T. CONCLUSION: Although B2R C-58T gene polymorphism was not found to be effective on obesity with logistic regression analysis in the whole study population in obese subjects, the T-Chol decreasing effect of the B2R gene C allele and the higher waist circumference measurements in the non-obese subjects may indicate there may be a link between B2R gene C-58T polymorphism and obesity in study populations of higher numbers.

Interaction between caspofungin or voriconazole and cefoperazone-sulbactam or piperacillin-tazobactam by in vitro and in vivo methods.

Immunosuppressive patients are at risk of fungal and bacterial infections. Therefore, these patients receive prophylactic, preemptive, empirical or target antifungal and concomitant antibiotic therapy. To this end, caspofungin (CAS) or voriconazole (VRC) antifungals and cefoperazone-sulbactam (CPZ/SAM) or piperacillin-tazobactam (PIP/TAZ) antibiotics may be used. Here, we aimed to investigate the interaction between these antifungals and antibiotics by in vitro and in vivo methods. The interaction was tested by chequerboard analysis and fractional inhibitory concentration index (FICI). It was also tested in a neutropenic mice-invasive candidiasis model and evaluated by fungal burden in kidney tissue of infected animals from the first day to the fifth day of treatment with 24 h intervals. A synergism was detected between CAS and CPZ/SAM (FICI = 0.1) and PIP/TAZ (FICI = 0.3). Fungal burden in tissues of drug-treated mice was reduced compared with controls in a time-dependent manner. In comparison with CAS-alone treated group, there were 1.32 log10 reductions of fungal burden in CAS + CPZ/SAM (p = 0.002) and in CAS + PIP/TAZ group (p = 0.14). The same interactions were not found with VRC and antibiotics. CPZ/SAM had stronger synergistic interaction with CAS than PIP/TAZ. The mechanism of synergism is not well understood. This is most likely due to an increase in the anticandidal effect of CAS plus antibiotics.

Prevalence of endothelial nitric oxide synthase E298D polymorphism in Turkish patients with essential hypertension.

AIMS: Our aim was to evaluate the effects of endothelial nitric oxide synthase (eNOS) E298D polymorphism in obesity variables and essential hypertension (eHT) development risk. The genotype frequencies of E298D polymorphism in eHT patients and non-hypertensive (non-HT) controls (proven to have normal coronaries angiographically) were analyzed for their association with demographic and obesity related data of the eHT patients and controls. MATERIALS AND METHODS: eNOS gene E298D genotypes were determined with qPCR. RESULTS: The eNOS E298D polymorphism frequencies for 298E/E, 298E/D and 298D/D genotypes were respectively as 41.1%, 44.6%, 14.3% in subjects eHT and 52.8%, 38.9%, 8.3% in the non-HT groups. The combined E298D homozygous polymorphic and heterozygous genotypes were found to have a decreasing effect on serum total-cholesterol levels in comparison to wild-type genotypes in eHT patients but not controls. CONCLUSIONS: Our results support the idea that, the eNOS E298D polymorphism, which is not associated with hypertension, may increase the risk of hypertension when associated with high serum total-cholesterol levels.

Evaluation of depression, quality of life and body image in patients with Cushing's disease.

The aim of this study was to evaluate patients with Cushing's disease (CD) who had undergone transsphenoidal surgery in terms of depression, quality of life (QoL), and perception of body image in comparison to healthy controls. Forty patients with CD and 40 healthy controls matched for demographic characteristics were included in the study. The subjects were evaluated with the Beck depression inventory (BDI), the health survey-short form (SF-36) and the multidimensional body-self relations questionnaire (MBSRQ). Subgroups of the patients with CD were formed on the basis of remission status and BDI scores. In this study, QoL in the general health category and body image were lower in the patients with CD than in the healthy subjects. However, no differences in depression scores were found between the two groups. When the CD group was evaluated according to remission rate, the mean BDI score was significantly higher in the CD patients without remission than in both the CD patients with remission and the healthy subjects (p = 0.04). However, the physical functioning, bodily pain and general health scores of the CD patients without remission on the SF-36 questionnaire were lower than in the CD patients in remission and the healthy subjects (p = 0.002, p = 0.04, p = 0.002, respectively). Fitness evaluation, health evaluation and body areas satisfaction scores of the MBSRQ were significantly different in the three groups (p = 0.003, p = 0.009 and p = 0.001, respectively). In this study, patients with CD were found to have lower QoL, lower body image perception and higher levels of depression compared to healthy controls, particularly if the disease is persistant despite surgery.

Relationship of RIC-3 gene rs1528133 polymorphism with varying degrees of body weight and eating behavior.

AIMS: The aim of this study was to determine the allele frequencies of resistance to inhibitors of cholinesterase 3 homologue (RIC-3) gene rs1528133 polymorphism in overweight+obese+morbid obese and non-obese (non-OB) subjects. The effects of rs1528133 genotypes on anthropometric, diabetes and obesity related parameters, self-reported macronutrient intake and drugs were also evaluated. The study was performed on overweight+obese+morbid obese and non-obese subjects. METHODS: RIC-3 gene rs1528133 genotypes were determined with qPCR. RESULTS: The RIC-3 rs1528133 genotype frequencies were respectively as 89.4% for homozygous wild type (A/A), 10.6% for heterozygous (A/C) genotypes in overweight+obese+morbid obese patients and 92.7% for A/A, 7.3% for A/C genotypes in non-OB subjects. The homozygous mutant genotype (C/C) was not detected in our study population. Genotype frequencies were not significantly different among study groups. Heterozygous genotype carriers for the rs1528133 polymorphism were found to prefer higher glycemic load, fat and protein diet content compared to homozygous wild type genotype carriers (p=0.0001). The frequency of rs1528133 heterozygous individuals (16.7%) using antihypertensive drugs was lower (p=0.045) in comparison to wild type genotype carriers (46.9%) in the whole study population. CONCLUSIONS: RIC-3 gene rs1528133 variation was not found to be effective over any analyzed obesity related parameter, but associated with higher glycemic load, protein and fat eating behavior and antihypertensive drug use.

Relationship of transcription factor 7 like 2 gene rs7903146 variation with type 2 diabetes and obesity related parameters.

AIMS: The allele frequencies of transcription factor 7 like 2 (TCF7L2) gene rs7903146 polymorphism in type 2 diabetes mellitus (T2DM) and non-T2DM controls were determined. METHODS: TCF7L2 rs7903146 genotypes were determined with qPCR. RESULTS: The TCF7L2 gene rs7903146 genotype frequencies for homozygous wild type (C/C), heterozygous (C/T) and homozygous polymorphic (T/T) for T2DM patients were determined, respectively, as 71.4%, 14.3%, 14.3% and 72.5%, 11.8%, 15.7% for controls. The weight, length and lean body mass were higher in C/T+T/T compared to C/C carriers. Glucose, insulin, insulin resistance and homeostatic model assessment (HOMA) were nonsignificantly higher in rs7903146C/T+T/T in comparison to C/C. TCF7L2 gene rs7903146 genotypes were not found to interact with drugs. The absence of any difference between genotype frequencies among study groups indicates that no association persists with TCF7L2 gene rs7903146 polymorphism and T2DM. CONCLUSIONS: The effects of rs7903146 variation over some obesity variables suggest that this variation may effect T2DM development via obesity.