Ahmet Yesilyurt

Combined genetic mutations have remarkable effect on deep venous thrombosis and/or pulmonary embolism occurence

PURPOSE Although deep vein thrombosis and thromboembolic diseases differ among various races, they are still important in our day. The difficulties in treatment and following-up of these diseases are caused by secret genetic mutations rather than predisposing factors. METHODS Between January 2011 and May 2013, patients who were traced for deep vein thrombosis and/or pulmonary embolism were evaluated retrospectively. 84 patients (53.6% males and 46.4% females) were included in the study. Their family histories, predisposing factors and treatments were researched. Factor V Leiden (G 1691A), Factor II G20210A, Plasminogen Activator Inhibitor-Type 1 (4G/5G), and Methylene Tetrahydrofolate Reductase (C677T, A1298C) mutations were investigated from peripheral venous blood. RESULTS Among the genetic mutations we searched, the incidence of single mutation rate was observed at 11.9%, double mutation collocation at 44%, triple mutation collocation at 29.8%, quadruple mutation collocation at 13.1%, and finally, quintuplet mutation collocation at 1.2%. Our approximate mutation number was found as 2.47 ± 0.91. CONCLUSION We observed that multiple mutations were high in number compared to single genetic mutations. The patients who have multiple mutations should be more in the front line considering their diagnosis, treatment and following up, and also in terms of decreasing mortality, morbidity and recurrence.

The effects of oral carvacrol treatment against H2O2 induced injury on isolated pancreas islet cells of rats

Pancreatic islet transplantation is an alternative treatment of insulin replacement therapy in diabetes mellitus, but the islets are exposed to many chemical, mechanical damages, and oxidative stress before transplantation. Carvacrol is a well-known essential oil for its antioxidant, antimicrobial, antifungal and antiinflammatory properties. The aim of this study was to investigate the possible protective effects of carvacrol against H2O2 induced cellular injury on isolated pancreas islets. After carvacrol (20, 40 and 80 mg/kg/day) treatment, the pancreas islets were isolated by enzyme digestion. The isolated islets were incubated within 0, 150 and 300 µM H2O2 containing medium at +4°C for 15 min. Then, the islets were examined with fluorescein diacetate and propidium iodide mixture stains for viability. A number of islets were stored for lipid peroxidation, protein oxidation and DNA fragmentation analysis. The cell viability ratio of Carvacrol 20 mg/kg/day group was increased in comparison to control and vehicle (DMSO) groups. Additionally, carvacrol application protected the cells from lipid peroxidation and protein oxidation induced by H2O2. H2O2 caused tissue injury and DNA fragmentation. There was only one DNA fragmentation band from islet cells of 20 mg/kg/day carvacrol treated group, however there were more than one bands from control and DMSO groups. In conclusion, carvacrol treatment ameliorates islet cell injury induced by H2O2. However, the dose of carvacrol is important and our results suggest that 20 mg/kg/day dose is more effective than doses of 40 or 80 mg/kg/day.

BRAFV600E Mutation, RET/PTC1 and PAX8-PPAR Gamma Rearrangements in Follicular Epithelium Derived Thyroid Lesions - Institutional Experience and Literature Review

BACKGROUND Thyroid cancers are the most frequently occurring endocrine malignancy worldwide. In Turkey, thyroid cancers are ranked 2(nd) on the incidence list in women, with a rate of 16.2%, but they are not included among the top 10 cancer types in men. AIMS To identify the contribution of the BRAF(V600E) mutation, and the RET/PTC1 and PAX8-PPARγ rearrangements in the diagnosis and differential diagnosis of follicular epithelial-derived thyroid lesions. STUDY DESIGN Retrospective clinical and molecular genetic study. METHODS A total of 86 thyroid cases diagnosed between 2001 and 2012 at the Department of Pathology were included in the retrospective study group. Samples best representing the lesion and comprising capsules were chosen in the selection of paraffin blocks pertaining to the cases. The BRAF(V600E) mutation, and the RET/PTC1 and PAX8-PPARγ rearrangements were investigated in all cases. RESULTS The BRAF(V600E) mutation was observed in 12 out of 37 papillary carcinoma cases (32.4%), in 1 out of 15 follicular carcinoma cases (6.6%), and in 1 out of 7 undifferentiated carcinoma cases (14.3%). No mutation was detected in benign lesions. The RET/PTC1 rearrangement was detected in 2 out of 7 undifferentiated carcinoma cases (28.6%), and in 1 out of 15 follicular carcinoma cases (6.6%). No gene rearrangement was detected in benign lesions. The PAX8-PPARγ rearrangement was detected in 5 out of 15 follicular thyroid carcinoma cases (33.3%) and in 1 out of 15 follicular adenoma cases (6.6%). CONCLUSION The BRAF(V600E) mutation and RET/PTC1 rearrangement were effective in distinguishing the follicular epithelium-derived benign and malignant lesions of the thyroid in the resection materials. The BRAF(V600E) mutation was rather specific to papillary carcinoma in the thyroid, and in cases where the BRAF(V600E) mutation was detected, multi-centricity, lymph node metastasis and capsular invasion findings were observed more frequently compared to cases in which no mutation was observed. The PAX8-PPARγ rearrangement was observed to be more effective in the differentiation of adenomas and carcinomas in follicular neoplasms of the thyroid, whereas the RET/PTC1 analysis contributed to the differential diagnosis of papillary carcinoma histogenesis at a frequency of 29% in undifferentiated thyroid carcinomas.

The effects of commonly used intravitreal steroids on proliferation index of ciliary body-derived mesenchymal stem cells: an in vitro study

Abstract Aim: To investigate the effects of commonly used intravitreal steroids on survival and proliferation (namely, proliferation index) of ciliary body-derived mesenchymal stem cells (CB-MSC). Methods: CB-MSCs were isolated from newborn rats’ eye, and they were expanded in the medium. Commonly used intravitreal steroids such as dexamethasone (Dex) and triamcinolone acetonide (TA) were added into the medium at commonly used concentration in clinical practice (0.1 mg/mL) and at lower concentration (0.01 mg/mL). Proliferation indexes of CB-MSCs were analyzed with the xCELLigence system at nine consecutive times (at 3rd, 6th, 21th, 30th, 45th, 60th, 75th, 90th and 100th h). Results: Both TA and Dex at both 0.01 mg/mL and 0.1 mg/mL concentrations had negative effect on proliferation indexes of CB-MSC. Although negative effect of TA on proliferation index of CB-MSC at both concentrations was not statistically significant, statistically significant negative effect of Dex at 0.01 mg/mL concentration started 60th h (p = 0.017) and 0.1 mg/mL concentration started 30th h (p = 0.014). Discussion: Even therapeutic doses of intravitreal corticosteroid agents might have negative effects on limited numbers of stem cells. Especially, Dex caused statistically significant toxic effects on CB-MSCs even at lower concentrations of those used clinically. These novel findings deserve further in vivo investigations.

Thyroid hormone resistance in two patients with papillary thyroid microcarcinoma and their BRAFV600E mutation status

Resistance to thyroid hormone (RTH) is a rare autosomal dominant hereditary disorder. Here in, we report two patients with RTH in whom differentiated thyroid cancer was diagnosed. Two patients were admitted to our clinic and their laboratory results were elevated thyroid hormone levels with unsuppressed TSH. We considered this situation thyroid hormone resistance in the light of laboratory and clinical datas. Thyroid nodule was palpated on physical examination. Thyroid ultrasonography showed multiple nodules in both lobes. Total thyroidectomy was performed. The pathological findings were consistent with papillary thyroid microcarcinoma. BRAFV600E mutation analysis results were negative. RTH is very rare and might be overlooked. There is no consensus on how to overcome the persistently high TSH in patients with RTH and differentiated thyroid cancer (DTC). Further studies are needed to explain the relationship between RTH and DTC which might be helpful for the treatment of these patients.

Vitamin D status, serum lipid concentrations, and vitamin D receptor (VDR) gene polymorphisms in Familial Mediterranean fever

Vitamin D (VitD) is critical for the regulation of inflammatory processes, and VitD deficiency has been linked to several chronic inflammatory disorders. We aimed to investigate the concentrations of serum 25(OH)D3, lipid parameters, and three known VDR polymorphisms (BsmI, FokI, and TaqI) in patients with Familial Mediterranean fever (FMF), an autosomal recessive autoinflammatory disease. The study included 123 FMF patients and 105 controls. Seventy patients had no attack (group 1), 30 had 1-2 attacks (group 2), and 23 had 3 or more attacks (group 3) within last three months. Serum 25(OH)D3 concentrations were determined using liquid chromatography-tandem mass spectrometry. BsmI, FokI, and TaqI polymorphisms were analyzed by a competitive allele specific polymerase chain reaction assay (KASPar). Serum lipid parameters were measured with enzymatic colorimetric methods. 25(OH)D3 concentrations were lower in FMF patients compared to controls (p < 0.001). No difference was observed in 25(OH)D3 concentration between groups 1, 2, and 3. The distributions of FokI and TaqI genotypes were not significantly different between FMF patients and controls. There was a significant difference in the distribution of AA BsmI genotype between male FMF patients and male controls. Increased concentrations of triglycerides (p = 0.012) and decreased concentrations of high-density lipoprotein cholesterol [HDL-C] (p = 0.006) were found in FMF patients compared to controls. Although lower 25(OH)D3 concentrations were observed in FMF patients versus controls, no association was determined between FMF attack frequency and 25(OH)D3 concentrations. We showed that the AA genotype of BsmI polymorphism is associated with FMF in males but not in females. The effects of decreased HDL-C and increased triglyceride concentrations on cardiovascular events in FMF patients should be further investigated.

Nonclassical Congenital Adrenal Hyperplasia and Pregnancy

Objective. The most common form of congenital adrenal hyperplasia (CAH) is 21-hydroxylase (21-OH) deficiency due to mutation of the CYP21A2 gene. Patients with nonclassical CAH (NC-CAH) are usually asymptomatic at birth and typically present in late childhood, adolescence, or adulthood with symptoms of excessive androgen secretion. Subfertility is relative in NC-CAH, but the incidence of spontaneous miscarriage is higher. Here, we report a previously undiagnosed female who gave birth to a normal male child and is planning to become pregnant again. Case Report. A 32-year-old female was referred to our clinic for obesity. Her medical history revealed that she had had three pregnancies. She was planning to become pregnant again. Her laboratory results revealed that she had NC-CAH. Since her husband is the son of her aunt and she had miscarriages and intrauterin exitus in her history, their genetic analyses were performed. Conclusion. Since most patients with NC-CAH have a severe mutation, these patients may give birth to a child with the classical CAH (C-CAH) if their partner is also carrying a severe mutation. Females with NC-CAH who desire pregnancy must be aware of the risk of having an infant with C-CAH.