The relationship between elevated plasma zonulin levels and Hashimoto's thyroiditis.

BACKGROUND: Hashimoto thyroiditis (HT) is one of the most prevalent autoimmune diseases. The intestine microbiota is strongly associated with autoimmune diseases. Zonulin, a modulator of tight junctions that controls the selective permeability of the intestine can induce an elevation in gut permeability. We aimed to investigate the association of plasma zonulin levels with HT. METHODS: We compared 77 HT patients with 66 age-gender and BMI-matched healthy individuals in the case of plasma zonulin levels. Plasma zonulin levels were measured by ELISA. The statistical analyses were performed using Student's t-test and chi-square tests. The predictive power was investigated using univariate and multivariate logistic regression analysis. RESULTS: We found that the increase in plasma zonulin levels in the HT group was statistically significant compared to the control group (p < 0.001). The regression analysis showed that urea, anti-thyroid peroxidase, aspartate aminotransferase, thyroid-stimulating hormone, free T3, and serum zonulin levels were found to be associated with HT in both univariate and multivariate models (p < 0.05). DISCUSSION: Zonulin is a possible biomarker candidate that may link intestinal permeability with the etiology of autoimmune diseases.

Significance of Cyclooxgenase-2 gene polymorphism and related miRNAs in pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with a poor prognosis. The suppression of cyclooxygenase-2 (COX-2) expression has been known to impair vascular function in endothelial cells; however, the epigenetic factors that cause this are largely obscure. Our aim in this study was to examine the polymorphisms in the gene for COX-2 (PTGS2) and related miRNAs regulating its level in a single-center cohort of patients with PAH. METHOD: In this study, three SNPs and miRNAs (rs5275, rs689470, rs20417, miR-26b-5p, miR-146a-5p, and miR-101-5p) in the PTGS2 were screened in PAH and controls by qPCR. In addition, the COX-2 level was determined by immunoassay to examine the effects of epigenetic factors on its expression levels. RESULTS: The non-dominant genotypes of rs20417 and rs5275 were found to be related to PAH (OR = 8.56, 95% CI = 3.39-21.63, p < 0.0001 and OR = 7.82, 95% CI = 3.30-18.53, p < 0.0001, respectively). We also observed a significant increase in the miR-26b-5p and miR-146a-5p levels in PAH patients (2.18 and 2.35-fold, respectively; for both, p < 0.05). In addition, it was found that SNPs influenced the COX-2, miR-26b-5p, and miR-146a-5p levels in PAH. A negative correlation was also found between COX-2 levels and miR-26b-5p and miR-146a-5p. CONCLUSIONS: As conventional drug therapies may cause lower COX-2 levels, the development of new genetic or epigenetic biomarkers is crucially important for early diagnosis and prognosis. The presence of minor alleles for rs5275 and rs689470 might also be considered as a significant risk factor for developing PAH. Furthermore, locus-specific miRNAs, such as miR-26b-5p and miR-146a-5p, seem to play a critical role in the regulation of PTGS2 expression.

Does Tacrolimus Use Have a Sexual Dysfunctional Effect in Women After Renal Transplant?

BACKGROUND: Tacrolimus, one of the immunosuppressive agents, is used to prevent tissue rejection in renal transplant recipients, but the relationship between the plasma concentrations of tacrolimus and female sexual dysfunction has not yet been elucidated. The aim of this study was to determine the effect of tacrolimus use on sexual dysfunction of women after renal transplant. METHODS: Twenty-one female patients who successfully underwent transplant and were treated with tacrolimus were enrolled as the patient group, while 21 patients presented to the obstetrics and gynecology clinic for different reasons were included in the study as the control group. The Beck Depression Inventory, Beck Anxiety Inventory, and Female Sexual Function Index were applied. Plasma concentrations of tacrolimus were simultaneously measured in transplant recipients. RESULTS: The scores of all scales did not differ among groups in terms of depression, anxiety, and sexual dysfunction. All transplant recipients had a plasma concentration of tacrolimus in the range of 3 to 7 ng/L. When the patients were compared by the scores of depression and anxiety scales, the drug levels showed no effect on the depression, anxiety, and female sexual functions. CONCLUSIONS: Sexual dysfunction appears to be ameliorated in women because of the hormone levels after renal transplant at the end of the dialysis process, hence enhancing the quality of life. Normal plasma levels of tacrolimus, which is known to cause sexual dysfunction, could not change this result.

Angioedema after favipiravir treatment: Two cases.

Drug-induced angioedema often affects elderly patients with chronic drug use. Proper diagnosis and prompt with effective treatment reduce mortality. With the increasing use of favipiravir, many side effects, especially increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels due to liver toxicity, and also skin lesions are reported. First patient oral favipiravir treatment on the second day was admitted to the hospital with rash and swelling on the eyelids. Second patient suffered from significant swelling on the upper lip and displayed angioedema. In this cases, angioedema findings regressed after rapid diagnosis and parenterally administered antihistamine and steroid treatment. Although there is no effective drug therapy in the treatment of COVID-19, favipiravir is also included in the treatment protocols in many countries. Clinicians should be careful about the side effects and possible skin manifestations, especially including angioedema, related to the use of favipiravir.

Treatment methods for vulvovaginal candidiasis in pregnancy.

INTRODUCTION: Vulvovaginal candidiasis (VVC) is one of the three most common vaginal infections of women. Our goal is to check which treatment method (vaginal or vaginal combined with oral) is more effective for each trimester to treat VVC. MATERIALS AND METHOD: A retrospective analysis was performed and vaginal culture results after treatment of 61 pregnant women who were treated with vaginal or vaginal plus oral antifungals, were collected. Women were grouped according to the method were treated and the trimester they were in. Patients who had used vaginal 750 mg metronidazole + 200 mg miconazole nitrate were determined as the vaginal treatment group. Patients who had used vaginal 750 mg metronidazole + 200 mg miconazole nitrate and oral 150 mg fluconazole were determined as the vaginal plus oral treatment group. RESULTS: When the patients were grouped according to treatment method, there were no significant differences in demographic characteristics except previous antibiotic use. Previous antibiotic use was significantly higher in the vaginal treatment group (p<0.05). There were no statistically significant differences between the recurrence of VVC in the vaginal and vaginal plus oral treatment group in the first, second, and third trimesters. DISCUSSION: The results of the study showed that the efficiency of the vaginal treatment was the same as the vaginal plus oral treatment in all three trimesters in the aspect of VVC recurrence. Local treatment of VVC has several advantageous features when compared with oral therapy including a low rate of adverse events, safe utilization during pregnancy, and breastfeeding.

The Anti-Inflammatory Effects of Anacardic Acid on a TNF-α - Induced Human Saphenous Vein Endothelial Cell Culture Model.

BACKGROUND AND OBJECTIVE: Coronary bypass operations are commonly performed for the treatment of ischemic heart diseases. Coronary artery bypass surgery with autologous human saphenous vein maintains its importance as a commonly used therapy for advanced atherosclerosis. Vascular inflammation-related intimal hyperplasia and atherosclerotic progress have major roles in the pathogenesis of saphenous vein graft disease. METHODS: In our study, we investigated the effect of anacardic acid (AA), which is a bioactive phytochemical in the shell of Anacardium occidentale, on atherosclerosis considering its inhibitory effect on NF-κB. We observed relative ICAM-1 and NF-κB mRNA levels by qRT-PCR method in a TNF-α- induced inflammation model of saphenous vein endothelial cell culture after 0.1, 0.5, 1 and 5 µM of AA were applied to the cells. In addition, protein levels of ICAM-1 and NF-κB were evaluated by immunofluorescent staining. The results were compared between different concentrations of AA, and also with the control group. RESULTS: It was found that 5 µM, 1 µM and 0.5 µM of AA had toxic effects, while cytotoxicity decreased when 0.1 µM of AA was applied both alone and with TNF-α. When AA was applied with TNF-α, there was a decrease and suppression in NF-κB expression compared with the TNF-α group. TNF-α-induced ICAM-1 expression was significantly reduced more in the AA-applied group than in the TNF-α group. CONCLUSION: In accordance with our results, it can be said that AA has a protective role in the pathogenesis of atherosclerosis and hence in saphenous vein graft disease.

The Effects of Pitavastatin on Nuclear Factor-Kappa B and ICAM-1 in Human Saphenous Vein Graft Endothelial Culture.

OBJECTIVE: To study pitavastatin's effects on nuclear factor-kappa B (NF-κB ) and adhesion molecules in human saphenous vein graft endothelial culture indicating its pleotropic properties. MATERIALS AND METHOD: Low-dose (0.1 µM/L) and high-dose (1µM/L) pitavastatin calcium were administered as a frontline therapy in human saphenous endothelial cell culture, followed by induction of inflammation by TNF-α and determination of mRNA level alterations of ICAM-1 and NF-κB genes of endothelial cells using the qRT-PCR method. Additionally, immunofluorescence method was used to show the expression of NF-κB and ICAM-1. Finally, LDH levels were determined by the ELISA method to quantify cytotoxicity. RESULTS: ICAM-1 mRNA expression in the low-dose pitavastatin+TNF-α group was significantly higher than that in the TNF-α group and significantly lower than that in the high-dose pitavastatin+TNF-α group (for all comparisons, P = 0.001). The low-dose pitavastatin+TNF-α group had a similar NF-κB mRNA expression with TNF-α and high-dose pitavastatin+TNF-α groups. CONCLUSION: Pitavastatin increases ICAM-1 mRNA expression in saphenous vein endothelial cells. Furthermore, the effect of pitavastatin on adhesion molecules appears independent of NF-κB. Novel studies are needed in this field.

Receptor for advanced glycation end products gene polymorphisms in cardiac syndrome X.

Endothelial and microvascular dysfunction serve important roles in the formation and pathogenesis of cardiac syndrome X (CSX). Expression of receptor for advanced glycation end products (RAGE) is suggested to be increased in several conditions, including diabetes, inflammation and vascular diseases. In the present study, RAGE gene polymorphisms in patients with CSX and healthy controls were investigated. A total of 114 patients, diagnosed with CSX using coronary angiography results following complaints of angina and objective ischemia, and 103 healthy controls participated in the study. Whether there was a difference in genotype distributions of RAGE gene -374T/A, -429T/C and Glys82Ser polymorphisms between patients with CSX and healthy controls was investigated. Following DNA isolation from blood samples of the participants, the polymorphic regions were examined by quantitative polymerase chain reaction, and the genotyping results were statistically analyzed. When the genotypic distributions of -374T/A, -429T/C and Gly82Ser polymorphisms were investigated in patients with CSX and healthy controls, no statistically significant differences were identified between the two groups (P>0.05). Likewise, no statistically significant differences were observed in the allelic distributions of all 3 polymorphic regions (P>0.05). To the best of our knowledge, the present study also investigated the association between CSX and RAGE gene polymorphisms for the first time. No statistically significant differences in RAGE gene polymorphisms between the CSX and control groups were observed. We hypothesized that significant results may be obtained by increasing the numbers of patients and healthy controls in future studies.

Investigation of MTHFR gene C677T polymorphism in cardiac syndrome X patients.

BACKGROUND: Definition of Cardiac Syndrome X (CSX) refers to groups of patients with positive exercise stress test and normal epicardial coronary arteries on coronary angiography accompanied by chest pain. Although the etiology of CSX is not completely understood, there is a common consensus that its pathophysiology may be associated with endothelial dysfunction resulting in impaired coronary flow. Some polymorphisms observed on the MTHFR gene cause inactivation of the MTHFR enzyme, leading to hyperhomocysteinemia and homocysteinuria, which are prominent risk factors of cardiovascular and cerebrovascular diseases. It was aimed to explain the association of the endothelial dysfunction, which is thought to play a role in the pathophysiology of CSX, with C677T polymorphism on MTHFR gene based on genetic basis. METHODS: A total of 176 CSX patients and 196 healthy subjects with similar age and clinical features were compared in terms of C677T polymorphism of the MTHFR gene. RESULTS AND CONCLUSION: There was no significant difference in terms of MTHFR gene C677T polymorphism between CSX patients and controls. When genotypic distribution was compared based on gender in both patients and controls, no significant difference was found between male and female subjects (P>.05). As fasting blood sugar and urea values were significantly higher, alanine aminotransferase and gamma-glutamyl transferase levels were significantly lower in the patients than the controls (P<.05). Described family story of the patients was significantly higher than the controls (P<.05). These suggest that homocysteine metabolism in CSX is not directly related to the endothelial dysfunction and thus the effect on the microvascular circulation.

Plasma Betatrophin Levels of Subjects Classified with Normal, Impaired, and Diabetic Glucose Tolerance, and Subjects with Impaired Fasting Glucose.

This study was aimed to investigate whether betatrophin shows glucose intolerance or not. To access the plasma betatrophin levels after basal and glucose load, groups were classified as normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetic glucose tolerance (DGT) according to WHO 2012 criteria. An oral glucose tolerance test was performed on age-matched subjects (n=220) with a body mass index (BMI)<27 kg/m2. Subjects were categorized as normoglycemic (n=55), IFG (n=50), IGT (n=60), and DM (n=55) according to the WHO criteria. Baseline betatrophin levels in DGT are significantly higher than in NGT (p<0.005), IFG (p<0.004), and IGT (p<0.001). Male subjects have significantly higher betatrophin levels than female subjects (p<0.01). In DGT, betatrophin of male subjects was found to be significantly higher than the betatrophin of male subjects in NGT (p<0.04), IFG (p<0.01), and IGT (p<0.01). Significant relationship between betatrophin and both ages and HbA1c in all groups were observed. When ages were accepted as an independent factor, significant correlation between betatrophin and ages were found. Betatrophin is increased and associated with age and HbA1c in DGT. Males had higher betatrophin levels compared with females in DGT group. As no obvious betatrophin deficiency to substitute in IFG and IGT individuals were observed, betatrophin levels appeared to be related to the pathogenesis of the diabetic stages rather than prediabetic stages.

Vitamin D deficiency might pose a greater risk for ApoEɛ4 non-carrier Alzheimer's disease patients.

Vitamin D is a secosteroid hormone that shares a synthetic pathway with cholesterol. ApoE, which is involved in the transport of cholesterol, is the most significant genetic risk factor for sporadic Alzheimer's disease (AD). Surprisingly, recent studies have indicated the presence of an evolutionary juncture between these two molecules. To demonstrate this possible relationship, we investigated serum levels of 25-hydroxyvitamin-D3 (25OHD) in patients with early onset-AD (EOAD; n:22), late onset-AD (LOAD; n:72), mild cognitive impairment (MCI; n:32) and in healthy subjects (n:70). We then analyzed the correlation between 25OHD and cytokines, BDNF and Hsp90 with respect to ApoE alleles, as these molecules were investigated in our previous studies. The LOAD patients had low levels of 25OHD, but these low levels originated only from ApoEɛ4 non-carrier patients. Negative correlations were observed between serum 25OHD and TNFα, IL-1ß or IL-6 levels in healthy subjects or MCI patients, but these same correlations were positive in LOAD patients. ApoE alleles indicated that these positive correlations exist only in ɛ4 carrier LOAD patients. Consequently, our results indicate that vitamin D deficiency presents a greater risk for ApoEɛ4 non-carrier AD patients than for ɛ4 carriers. Therefore, it might be beneficial to monitor the vitamin D status of ApoEɛ4 allele non-carrier AD patients.

Does Inflammation Have a Role in the Pathogenesis of Cardiac Syndrome X? A Genetic-Based Clinical Study With Assessment of Multiple Cytokine Levels.

We compared Turkish patients with cardiac syndrome X (CSX) and controls with respect to serum pro- and anti-inflammatory cytokine levels, as well as the single-nucleotide polymorphisms located in the promoter regions of their related genes. This study included 111 consecutive patients angiographically diagnosed with CSX and 111 healthy controls with similar demographic characteristics. Serum interleukin (IL) 6, tumor necrosis factor α (TNF-α), and IL-10 levels were measured, and the genotypes of the patients and controls were determined using standard methods. Serum IL-6 and IL-10 levels were significantly higher in the CSX group than in the control group (P < .01, respectively). Serum TNF-α level was lower in the CSX group than in the control group (P < .001). On the other hand, participants with CSX and healthy controls were not significantly different with respect to the genotype distributions of IL-6, TNF-α, and IL-10 genes. As a result of our study, both pro-inflammatory and anti-inflammatory cytokines may play a role in the pathogenesis of CSX. In contrast, the studied gene polymorphisms did not influence CSX pathogenesis.

Cathelicidin as a link between sarcoidosis and tuberculosis.

SETTING: Sarcoidosis and tuberculosis share notable clinical, radiological, histological, and immunological similarities. The importance of vitamin D has long been investigated in these two granulomatous lung diseases. Cathelicidin is an antimicrobial peptide of the innate immune system, directly induced by vitD3. OBJECTIVE: To evaluate the role of cathelicidin in sarcoidosis and tuberculosis development. DESIGN: The study included 30 consecutive patients with active lung tuberculosis, 30 patients with sarcoidosis, and 20 healthy controls. 25-hydroxyvitamin D [25(OH)D] and cathelicidin levels were measured in blood samples. RESULTS: Vitamin D levels were significantly higher (p<0.001) in tuberculosis patients (22.5 ± 9.96 ng/ml) than in sarcoidosis patients (11.75 ± 8.92 ng/ml). Severe vitamin D deficiency was as frequent as 47% in sarcoidosis patients compared to only 3% in tuberculosis patients. Cathelicidin levels were significantly higher in the control group (120.37 ± 41.03 pg/ml) than in sarcoidosis (67.68 ± 38.03 pg/ml) and tuberculosis (68.74 ± 39.44 pg/ml) patients (p<0.001). However, no significant difference in cathelicidin levels was observed between tuberculosis and sarcoidosis patients (p=0.966). The optimum cathelicidin cut-off value to distinguish sarcoidosis patients from healthy controls was 107.14 pg/ml (sensitivity 81.5%, specificity 71.2%). CONCLUSION: Cathelicidin appears to play different roles in the development of granulomatous lung disease.

The interleukin 1 alpha, interleukin 1 beta, interleukin 6 and alpha-2-macroglobulin serum levels in patients with early or late onset Alzheimer's disease, mild cognitive impairment or Parkinson's disease.

Alzheimer's disease (EOAD, LOAD), mild cognitive impairment (MCI), Parkinson's disease (PD) and healthy controls were included to determine the serum interleukin-1s (IL-1α, IL-1ß), IL-6 and alpha-2-macroglobulin (α2M) levels using ELISA. IL-6 might be a significant contributor to the inflammatory response in LOAD. The MCI data indicate that IL-1s, α2M and BDNF are somehow related, and this relationship might allow MCI patients to be more similar to the healthy controls. A correlation analysis of multiple biomarkers in different neurodegenerative disorders might be more useful than determining the levels of a single cytokine in a single disorder.

Lectin-like oxidised LDL receptor-1 as a marker of endothelial dysfunction in Behçet's disease.

OBJECTIVES: The aim of this study was to examine the distribution of lectin-like oxidised LDL receptor-1 (LOX-1) levels in patients with active BD, possible association of LOX-1 with the oxidised LDL (oxLDL), endothelial nitric oxide synthase (eNOS), nitric oxide (NO), endothelin-1 (ET-1) levels, and to characterise the differences between patients with active BD and those with systemic lupus erythematosus( SLE) in terms of these parameters compared with healthy controls. METHODS: A total of 30 patients with active BD, 22 patients with SLE as patients controls, and 30 healthy subjects were enrolled in this study. RESULTS: Significantly lower eNOS ve NO levels were observed in patients with BD and SLE compared with healthy controls. oxLDL, LOX-1 ve ET-1 levels were significantly increased in active periods of patients with BD and SLE compared with healthy control. There was no significant difference in oxLDL levels between subjects with BD and SLE. LOX-1 levels were significantly higher in active periods of patients with BD than in SLE , ET-1 levels were significantly lower. CONCLUSIONS: Endothelial dysfunction parameters are elevated in patients with BD having active disease. The necessary measures should be considered in terms of risk of atherosclerosis in BD, especially for the early identification of endothelial damage by looking at LOX-1 levels.

BDNF, TNFα, HSP90, CFH, and IL-10 serum levels in patients with early or late onset Alzheimer's disease or mild cognitive impairment.

Identifying early-detection biomarkers have become an increasingly important approach in the treatment and prevention of Alzheimer's disease (AD). In this study, we investigated the potential of brain-derived neurotrophic factor (BDNF), complement factor H (CFH), tumor necrosis factor-α (TNFα), interleukin 10 (IL-10), and heat shock protein 90 (Hsp90) as serum biomarkers for AD in a cohort of the Turkish population because they have been suggested to be associated with AD. Serum BDNF, CFH, TNFα, IL-10, and Hsp90 levels in three groups of patients, early-onset AD (EOAD; age of onset < 65; n = 22), late-onset AD (LOAD; age of onset > 65; n = 54), and mild cognitive impairment (MCI) (n = 30), were compared with age-matched healthy controls (age < 65, n = 18 and age > 65; n = 32) using ELISA. The serum BDNF levels significantly decreased and TNFα levels significantly increased in the EOAD and LOAD groups compared to the age-matched healthy controls. There was a correlation between serum TNFα and IL-10 levels in the LOAD and healthy control groups. Serum CFH levels in the LOAD and MCI patients were significantly decreased compared with controls. Serum Hsp90 levels in the EOAD, LOAD, and MCI patients were significantly decreased compared with controls. The protein misfolding, the inflammatory response, and decreased neurotrophic factor synthesis are all suggested to be related to AD type brain pathology, and our results indicate these alterations might be traced from serum samples. For accurate early diagnosis of AD, it is important to determine a profile of alterations in multiple biomarkers in large-scale population studies.