Muammer Karadeniz

Oxidative Stress Markers in Young Patients with Polycystic Ovary Syndrome, The Relationship between Insulin Resistances

OBJECTIVE Polycystic ovary syndrome is a syndrome of ovarian dysfunction. Oxidative stress, inflammation and endothelial cell activation are thought to play concomitant roles in the pathogenesis of the above diseases particularly in the development of atherosclerotic lesions. RESEARCH DESIGN AND METHODS We studied 58 polycystic ovary syndrome patients and age-matched 25 healthy controls consisting of women that have regular, ovulatory cycles and normal androgen levels. Homeostasis Model Assessment-Insulin Resistance for this study was taken as 1.75 that is the upper level of confidence interval of %95 of the mean of the healthy group. PCOS patients were divided into two groups as for below the cut-off level (<1.75) and above the cut-off level (> or =1.75). hs-CRP, fibrinogen, malondialdehyde, nitric oxide and disulfide level results were compared both in PCOS and control groups. RESULTS In this study, sensitive CRP was found to be statical significantly higher in polycystic ovary syndrome groups whose Homeostasis Model Assessment-Insulin Resistance were > or =1.75 and <1.75 when compared to the control group. But, no significantly correlation was determined between malondialdehyde, nitric oxide and disulfide levels and CRP elevation. CONCLUSIONS In our study, because those participants were young and non- obese patients with PCOS, malondialdehyde, nitric oxide and disulfide levels and Carotid Artery Intima-Media Thickness measurements as a pre-indicator of cardiovascular disease were not found to be different from those of the controls.

Association of the angiotensinogen M235T and angiotensin-converting enzyme insertion/deletion gene polymorphisms in Turkish type 2 diabetic patients with and without nephropathy

OBJECTIVE Recent studies have suggested an association between a deletion variant of the angiotensin-converting enzyme (ACE) gene and diabetic nephropathy. However, this finding has not been confirmed by all investigators. Furthermore, an M235T variant of the angiotensinogen (AGT) gene has been associated with hypertension, an important risk factor for the development and progression of diabetic nephropathy. RESEARCH DESIGN AND METHODS We investigated the relationship of the ACE insertion/deletion (I/D) and AGT M235T gene polymorphisms in Turkish patients with type 2 diabetes mellitus (DM) with and without diabetic nephropathy. A total of 102 individuals were screened for the presence of the ACE I/D and AGT M235T polymorphism: 46 individuals who had type 2 DM with diabetic nephropathy and, as controls, 56 individuals who had type 2 DM without diabetic nephropathy. Gene polymorphisms were determined by the specific melting temperature (T(m)) values of the resulting amplicons after real-time online polymerase chain reaction and melting curve analysis. RESULTS The frequencies of the ACE DD, ID, and II genotypes were 34.8%, 37.0%, and 28.3%, respectively, among type 2 diabetic patients with nephropathy, and 33.9%, 42.9%, 23.2%, respectively (P=.788), in the control subjects without diabetic nephropathy. On the other hand, the frequencies of the AGT MM, MT, and TT genotypes among the same groups were 26.1%, 52.2%, 21.7% and 26.8%, 57.1%, 16.1%, respectively (P=.758). CONCLUSIONS There were no differences in the frequencies of the AGT M235T and ACE I/D genotypes between Turkish patients with type 2 DM with and without nephropathy.

The relationship of the interleukin-6 -174 G>C gene polymorphism with oxidative stress markers in Turkish polycystic ovary syndrome patients.

Objective: Interleukin-6 (IL-6) is a key pro-inflammatory and immune-modulatory cytokine of relevance for cardiovascular (CD) diseases. Cardiovascular risk factors that have been reported include oxydative stress markers [nitric oxide (NO), malondialdehyde (MDA), disulphite (SH)]. We aimed to evaluate the relation between the IL-6 G/C gene polymorphism and oxidative stress markers in polycystic ovary syndrome (PCOS) patients. Design and patients: We studied 85 PCOS patients and 115 healthy controls. PCOS was defined by the Rotterdam PCOS consensus criteria. Results: The genotype IL-6 distribution did differ between the control group (CC 9.6%, GC 63.4%, GG 27.0%) and the PCOS patients (CC 4.7%, GC 29.4%, GG 65.9%) (p<0.001). The frequency of the polymorphic G allele was also not similar for the group with PCOS as for the control group with 80.6% and 58.7%, respectively (p<0.001). No statistically significant difference was determined for MDA and NO levels in PCOS patients and control group (p>0.05). Only SH levels were found to be high in favor of patient group (p<0.05). No statistically significant difference was determined between IL-6 G/C gene polymorphism and oxidative stress markers in PCOS patients and in the control group. Conclusion: Gene polymorphism of IL-6 −174 G>C is a risk factor for PCOS in Turkish patients. IL-6 gene polymorphisms are not related to NO, MDA, and SH levels in PCOS. Our negative results in risks factors of CV disorders can probably be explained by the fact that metabolic parameters and endothelial systems of patients may not yet be affected in this short period of time.

Interleukin-10 gene polymorphism in patients with papillary thyroid cancer in Turkish population

Objective: Interleukin-10 (IL-10) is a major anti-inflammatory cytokine that plays a crucial role in the regulation of the immune system. Chronic inflammation has been reported to be a risk factor for thyroid neoplasia. The propensity to mount an inflammatory response is modified by germ line variation in cytokine and other inflammation-related genes. We hypothesized that a proinflammatory genotype would be positively associated with thyroid cancer. We aimed to evaluate the relation between the genotypic and allelic frequencies of the IL-10(-1082 G/A), IL-10(-592 A/C), and IL-10(-819 C/T) polymorphisms, and their association with the risk of developing papillary thyroid cancer (PTC) in the Turkish population. Research design and methods: Forty-two patients with PTC and 113 healthy controls were included in this study. The diagnosis of PTC was confirmed by histopathologic examination after surgery. The evaluation of genotype for IL-10 gene polymorphism was performed using PCR-restriction fragment length polymorphism method. Results: Statistically significant difference IL-10(-1082 G/A) gene polymorphism was determined between 2 (PTC and control) groups. No difference was determined with respect to IL-10(-592 A/C) and IL-10(-819 C/T) gene polymorphisms, and IL-10(-1082 G/A), IL-10(-592 A/C), and IL-10(-819 C/T) allele frequencies of participating between the control group and the patients with PTC (p>0.05). Conclusions: The polymorphism of IL-10(-1082 G/A) gene was significantly associated with the occurrence of PTC. Such studies will contribute significantly to our understanding of the biological role of IL-10(-1082 G/A) gene polymorphism in PTC development. In conclusion, IL-10(-1082 G/A) gene polymorphism may affect the survival of papillary thyroid carcinoma.

Demographic and clinical features of patients with subacute thyroiditis: Results of 169 patients from a single University Center in Turkey

Background: Turkey is an endemic area for thyroid diseases. The Aegean region is well documented for increased prevalence of thyroid disorders. In this study we investigated the demographic and clinical features of subacute thyroiditis (SAT) patients who had been diagnosed and treated in Ege University. Methods: The hospital files of patients admitted to the endocrinology clinic of Ege University between January 1987 and December 2001 were retrospectively evaluated. Patients who had been diagnosed as having any thyroid disorder were determined. Results: 176 fulfilled diagnostic criteria for SAT. The majority of patients with SAT were diagnosed as having subacute granulomatous thyroiditis (169/176) (134 females, 35 males, mean age 34.0±17.8 yr); 69% of the patients were between 30–50 yr of age. Thyroid pain was present in 97.1% of female patients, and in 100% of male patients. High fever was evident in 78 patients (46.2%). Mean erythrocyte sedimentation rate (ESR) was 43.42±39.68 mm/h. Anti-thyroglobulin antibody was positive in 20%, and anti-thyroid peroxydase antibody was positive in 4% of patients. Among patients who were treated with non-steroidal anti-inflammatory drugs (NSAD) 10 female patients (10.6%), and 3 male patients (12%) developed recurrence of the disease. Among patients who were treated with prednisolone 7 female patients (17.5%), and one male patient (10%) developed recurrence. There was no significant difference regarding the recurrence rates between patients who were treated with NSAD and patients who were treated with prednisolone. Conclusion: With the exception of ESR, demographic, clinical, laboratory, and imaging findings and prognoses of our patients were comparable to the previous reports.

The relationship of the methylenetetrahydrofolate reductase C677T gene polymorphism in Turkish type 2 diabetic patients with and without nephropathy

Poor glycaemic control, hypertension and duration of diabetes are risk factors for the development of diabetic nephropathy, but there may be genetic factors. Recently, a common C to T mutation at nucleotide position 677 of the MTHFR gene (MTHFR677C > T) has been reported to be correlated with hyperhomocysteinemia and the severity of coronary artery disease as macroangiopathy. We aim to investigate Turkish type 2 diabetic patients with/without diabetic nephropathy and healthy group and examine the contribution of the MTHFR gene polymorphism to the development of diabetic nephropathy.

Thyrotoxic autoimmune encephalopathy in a female patient: Only partial response to typical immunosuppressant treatment and remission after thyroidectomy

Hashimotos encephalopathy (HE) is a rare immune-mediated encephalopathy developing in patients with high serum concentrations of anti-thyroid antibodies usually in an euthyroid or hypothyroid state. We report a 31-year-old female patient with thyrotoxic HE whose daughter has been followed up with the same diagnosis. Suboptimal response was observed with intravenous methylprednisolone (IVMP), intravenous immunoglobulin (IVIG) and plasmapheresis. Reduction of the anti-thyroid auto-antibody concentrations marked the patients improvement in each episode. She relapsed under oral immunosuppressive therapy. After removing the thyroid tissue, full recovery has been achieved for the last 18 months. These data may contribute to clarification of the pathogenetic role of anti-thyroid antibodies in HE. Thyroidectomy can be considered as one of the treatment options especially in thyrotoxic HE patients with uncontrolled relapses. Our patient is the first reported HE case with a family history. Genetic background can underlie the etiopathogenesis of HE as is the case in other autoimmune disorders.

Increased oxidative DNA damage in lean normoglycemic offspring of type 2 diabetic patients.

OBJECTIVE Several studies have shown increased oxidative stress in patients with pre-diabetes and newly diagnosed Type 2 diabetes mellitus (T2DM). It has been proposed that oxidative stress initiates insulin resistance in genetically predisposed individuals. The aim of this study was to evaluate the markers of oxidative stress in the offspring of patients with T2DM. MATERIAL AND METHODS We examined 60 lean normoglycemic offspring of Type 2 diabetics, and 52 age, sex and body mass index matched subjects without family history of T2DM as controls. Anthropometric, biochemical and carotid intima media thickness (IMT) measurements and oral glucose tolerance test (OGTT) were performed. Erythrocyte superoxide dismutase and glutathione peroxidase activities, serum nitric oxide, plasma total sulfhydryl (tSH) groups, plasma total antioxidant status, plasma malondialdehyde and serum 8-hydroxydeoxy-guanosine (8-OHdG) levels were compared between 2 groups. RESULTS 2 groups were similar for the measurements of anthropometric, blood pressure, lipids, fasting glucose, HOMA-IR and carotid IMT. Glucose levels during OGTT were significantly higher in the offspring of Type 2 diabetics than controls (p=0.035). The offspring of Type 2 diabetics showed a significant increase in serum 8-OHdG level (p=0.005) and plasma tSH groups (p=0.032) when compared to the controls. Significant differences were not obtained in other oxidative stress marker levels between 2 groups. CONCLUSION Main finding of our study was the presence of increased oxidative DNA damage in lean normoglycemic offspring of Type 2 diabetic patients. There is a need for further clinical studies in order to explain whether oxidative stress is present in genetically predisposed subjects and induces the insulin resistance.

Fas/Fas ligand gene polymorphism in patients with papillary thyroid cancer in the Turkish population.

Objective: Fas ligand (FasL) is an apoptotic agent and a member of tumor necrosis factor (TNF) family. FasL exists in cytotoxic T lymphocyte (CTL) and natural killer (NK) cells, and it is increased in tumor cell membrane. On the contrary, CTL and NK are bound to Fas on the surfaces of cell membrane; this triggers apoptosis in cytotoxic cells and leads to their death. This system plays an important role in eliminating viral infections and cancer cells. Malfunction of this system results in the development and spread of the malignancy. This study aims at evaluating the influence of Fas and FasL gene polymorphism in papillary thyroid cancer (PTC) in the Turkish population. Research design and methods: Forty-five patients with PTC and 100 healthy controls were included in this study. The diagnosis of PTC was confirmed by histopathologic examination after surgery. The evaluation of genotype for Fas 670 A/G and FasL 843 C/T gene polymorphism was performed using the PCR-restriction fragment length polymorphism (RFLP) method. Results: The evaluation of Fas/FasL genotype and gene allele frequency did not show statistically significant differences between the patient and control group (p>0.05). In addition, the univariate analysis did not reveal a statistically significant relationship between the size of the nodule and the Fas/FasL gene polymorphism in patients with PTC. Conclusions: As in other types of malignancy, genetic factors in the pathogenesis of PTC may also show changes in different populations. Fas/FasL gene polymorphysms are possible that different mechanisms function in apoptosis balance in PTC development.

Increasing severity of cardiac autonomic neuropathy is associated with increasing prevalence of nephropathy, retinopathy, and peripheral neuropathy in Turkish type 2 diabetics.

BACKGROUND Cardiac autonomic neuropathy (CAN) is the most frequent and clinically important form of diabetic autonomic neuropathy. CAN is associated with increased frequency of other microvascular complications of diabetes mellitus (DM). In this study, we evaluated the prevalence diabetic nephropathy, retinopathy, and peripheral neuropathy, and measured gastric emptying time and bladder emptying time in type 2 diabetic patients with varying degrees of CAN. PATIENTS AND METHODS Fifty-three patients with DM complicated by CAN (30 women and 23 men; mean age, 58.8+/-9.15 years; duration of diabetes, 13.9+/-7.7 years) were included in this study. The patients were grouped according to the degree of CAN as early, definite, and severe CAN. RESULTS There were significant differences regarding the prevalence of nephropathy, retinopathy, and peripheral neuropathy diagnosed by EMG among those groups (P<.05). However, there was no significant difference regarding the prevalence of peripheral neuropathy diagnosed by neurological examination (P>.05), and scintigraphic measurements of gastric and bladder emptying time were comparable among the groups (P>.05). CONCLUSION The prevalence of other diabetic microvascular complications increase as the severity of CAN increases in patients with type 2 DM. This study emphasizes the need for an early screening for peripheral neuropathy, retinopathy, and nephropathy in type 2 diabetic patients with CAN, especially with severe involvement.