Evaluation of mucin-1, nuclear factor κB, and hemoglobin A1c levels in obese and non-obese individuals.

OBJECTIVE: Obesity is a chronic multisystem disease associated with increased morbidity and mortality. Obesity, which is a complex, multifactorial, and heterogeneous condition, is thought to result from the interaction of environmental, physiological, and genetic factors. In this study, the relationship between serum levels of hemoglobin A1c, mucin-1, and nuclear factor κB in obese and healthy cohorts was evaluated along with biochemical and gene expressions and with demographic and clinical covariates, and their effects on obesity were evaluated. METHODS: This case-control study included a total of 80 individuals, 40 healthy controls and 40 obesity patients, consisting of female and male aged between 18 and 63 years. Hemoglobin A1c, mucin-1, and nuclear factor κB levels were determined by ELISA in serum samples obtained from patients. In addition, aspartate aminotransferase, alanine transaminase, low density lipoprotein, and glucose values were measured. The gene expressions of the same markers were analyzed by quantitative real-time polymerase chain reaction, and their regulation status was defined. RESULTS: Serum levels of hemoglobin A1c, mucin-1, and nuclear factor κB were found to be high in obese individuals (p<0.05). The gene expression of these serum markers was found to be upregulated. Of the anthropometric measurements, waist circumference and body mass index were correlated with both serum markers and gene expressions (p<0.05). CONCLUSION: In addition to the known association of hemoglobin A1c and nuclear factor κB with obesity, serum levels of mucin-1 as well as upregulation of genes point to its modifier effect on obesity. These parameters can be the powerful markers in the diagnosis of obesity.

Patients' Persistent Symptoms, Clinician Demographics, and Geo-Economic Factors Are Associated with Choice of Therapy for Hypothyroidism by European Thyroid Specialists: The "THESIS" Collaboration.

Background: Hypothyroidism is common, however, aspects of its treatment remain controversial. Our survey aimed at documenting treatment choices of European thyroid specialists and exploring how patients' persistent symptoms, clinician demographics, and geo-economic factors relate to treatment choices. Methods: Seventeen thousand two hundred forty-seven thyroid specialists from 28 countries were invited to participate in an online questionnaire survey. The survey included respondent demographic data and treatment choices for hypothyroid patients with persistent symptoms. Geo-economic data for each country were included in the analyses. Results: The response rate was 32.9% (6058 respondents out of 17,247 invitees). Levothyroxine (LT4) was the initial treatment preferred by the majority (98.3%). Persistent symptoms despite normal serum thyrotropin (TSH) while receiving LT4 treatment were reported to affect up to 10.0% of patients by 75.4% of respondents, while 28.4% reported an increasing such trend in the past 5 years. The principal explanations offered for patients' persistent symptoms were psychosocial factors (77.1%), comorbidities (69.2%), and unrealistic patient expectations (61.0%). Combination treatment with LT4+liothyronine (LT3) was chosen by 40.0% of respondents for patients who complained of persistent symptoms despite a normal TSH. This option was selected more frequently by female thyroid specialists, with high-volume practice, working in countries with high gross national income per capita. Conclusions: The perception of patients' dissatisfaction reported by physicians seems lower than that described by hypothyroid patients in previous surveys. LT4+LT3 treatment is used frequently by thyroid specialists in Europe for persistent hypothyroid-like symptoms even if they generally attribute such symptoms to nonendocrine causes and despite the evidence of nonsuperiority of the combined over the LT4 therapy. Pressure by dissatisfied patients on their physicians for LT3-containing treatments is a likely explanation. The association of the therapeutic choices with the clinician demographic characteristics and geo-economic factors in Europe is a novel information and requires further investigation.

Characteristics of specialists treating hypothyroid patients: the "THESIS" collaborative.

Introduction: Thyroid specialists influence how hypothyroid patients are treated, including patients managed in primary care. Given that physician characteristics influence patient care, this study aimed to explore thyroid specialist profiles and associations with geo-economic factors. Methods: Thyroid specialists from 28 countries were invited to respond to a questionnaire, Treatment of Hypothyroidism in Europe by Specialists: an International Survey (THESIS). Geographic regions were defined according to the United Nations Statistics Division. The national economic status was estimated using World Bank data on the gross national income per capita (GNI per capita). Results: 5,695 valid responses were received (response rate 33·0%). The mean age was 49 years, and 65·0% were female. The proportion of female respondents was lowest in Northern (45·6%) and highest in Eastern Europe (77·2%) (p <0·001). Respondent work volume, university affiliation and private practice differed significantly between countries (p<0·001). Age and GNI per capita were correlated inversely with the proportion of female respondents (p<0·01). GNI per capita was inversely related to the proportion of respondents working exclusively in private practice (p<0·011) and the proportion of respondents who treated >100 patients annually (p<0·01). Discussion: THESIS has demonstrated differences in characteristics of thyroid specialists at national and regional levels, strongly associated with GNI per capita. Hypothyroid patients in middle-income countries are more likely to encounter female thyroid specialists working in private practice, with a high workload, compared to high-income countries. Whether these differences influence the quality of care and patient satisfaction is unknown, but merits further study.

Comparison of 68Ga-FAPI-04 and 18F-FDG PET/CT for diagnosis of metastatic lesions in patients with recurrent papillary thyroid carcinoma.

OBJECTIVE: We aimed to evaluate the gallium-68-labeled fibroblast-activation protein inhibitor (68Ga-FAPI) positron emission tomography/computed tomography (PET/CT) in localizing papillary thyroid carcinoma (PTC) foci in patients with biochemical relapse. Papillary thyroid carcinoma has achieved biochemical recovery after appropriate treatment and had biochemical relapse in the last follow-up were included in this retrospective study. Gallium-68-FAPI and fluorine-18-fluorodeoxyglucose (68F-FDG) PET/CT were performed to detect recurrence foci. SUBJECTS AND METHODS: Biochemically relapsed patients who underwent total thyroidectomy and were diagnosed with pathologically differentiated thyroid cancer were included in our study. Gallium-68-FAPI and 18F-FDG PET/CT imaging methods were used to determine the focus of metastasis or recurrence in all patients. RESULTS: Among 29 patients enrolled to the study, pathological subgroups were papillary (n=26) and poorly differentiated (n=3) PTC. Anti-thyroglobulin (TG) antibody positivity were noted in 5 of the patients, while all 29 of them were TG positive and had been consist of three groups as follows: 2-10ng/mL (n=4), 11-300ng/mL (n=14), 301ng/mL and above (n=11). Recurrence was detected in 72.4% (n=21) and 86% (n=25) of the patients via 18F-FDG and 68Ga-FAPI, respectively. Accuracy of detection noted as 100% (5/5), 75% (3/4), and 92.9% (13/14) in groups with the anti-TG antibody positivity, TG levels of 2-10ng/mL and 11-300ng/mL, respectively, when the two imaging modalities were utilized together. Furthermore, accuracy of 68Ga-FAPI was 100% (11/11) in the group with TG levels of 301ng/mL and above, whereas accuracy of 18F-FDG was 81.8% (9/11). Lastly, median maximum standardized uptake value (SUVmax) of recurrent lesions detected by the 68Ga-FAPI (median SUVmax: 6.0) were statistically higher than the ones detected by the 18F-FDG (median SUVmax: 3.7) (P=0.002). CONCLUSION: In recurrent PTC especially in case of higher TG levels, 68Ga-FAPI can be used in patients with inconclusive 18F-FDG findings.

Effects of antidiabetics and exercise therapy on suppressors of cytokine signaling-1, suppressors of cytokine signaling-3, and insulin receptor substrate-1 molecules in diabetes and obesity.

OBJECTIVE: Pathological destruction of insulin signaling molecules such as insulin receptor substrate, especially due to the increase in suppressors of cytokine signaling molecules, has been demonstrated in experimental diabetes. The contribution of suppressors of cytokine signaling proteins to the development of insulin resistance and the effects of antidiabetic drugs and exercise on suppressors of cytokine signaling proteins are not clearly known. METHODS: A total of 48 Wistar albino adult male rats were divided into six groups: control group, obese group with diabetes, obese diabetic rats treated with metformin, obese diabetic rats treated with pioglitazone, obese diabetic rats treated with exenatide, and obese diabetic rats with applied exercise program. Immunohistochemical staining was performed in both the liver and adipose tissue. RESULTS: There was a statistically significant decrease in suppressors of cytokine signaling-1, a decrease in suppressors of cytokine signaling-3, an increase in insulin receptor substrate-1, and a decrease in immunohistochemical staining in the obese group treated with metformin and exenatide compared to the obese group without treatment in the liver tissue (p<0.05). A statistically significant decrease in immunohistochemical staining of suppressors of cytokine signaling-1 and suppressors of cytokine signaling-3 was found in the obese group receiving exercise therapy compared to the obese group without treatment in visceral adipose tissue (p<0.05). Likewise, no significant immunohistochemistry staining was seen in diabetic obese groups. CONCLUSION: Metformin or exenatide treatment could prevent the degradation of insulin receptor substrate-1 protein by reducing the effect of suppressors of cytokine signaling-1 and suppressors of cytokine signaling-3 proteins, especially in the liver tissue. In addition, exercise can play a role as a complementary therapy by reducing suppressors of cytokine signaling-1 and suppressors of cytokine signaling-3 proteins in visceral adipose tissue.

Effects of antidiabetics and exercise therapy on suppressors of cytokine signaling-1, suppressors of cytokine signaling-3, and insulin receptor substrate-1 molecules in diabetes and obesity

SUMMARY OBJECTIVE: Pathological destruction of insulin signaling molecules such as insulin receptor substrate, especially due to the increase in suppressors of cytokine signaling molecules, has been demonstrated in experimental diabetes. The contribution of suppressors of cytokine signaling proteins to the development of insulin resistance and the effects of antidiabetic drugs and exercise on suppressors of cytokine signaling proteins are not clearly known. METHODS: A total of 48 Wistar albino adult male rats were divided into six groups: control group, obese group with diabetes, obese diabetic rats treated with metformin, obese diabetic rats treated with pioglitazone, obese diabetic rats treated with exenatide, and obese diabetic rats with applied exercise program. Immunohistochemical staining was performed in both the liver and adipose tissue. RESULTS: There was a statistically significant decrease in suppressors of cytokine signaling-1, a decrease in suppressors of cytokine signaling-3, an increase in insulin receptor substrate-1, and a decrease in immunohistochemical staining in the obese group treated with metformin and exenatide compared to the obese group without treatment in the liver tissue (p<0.05). A statistically significant decrease in immunohistochemical staining of suppressors of cytokine signaling-1 and suppressors of cytokine signaling-3 was found in the obese group receiving exercise therapy compared to the obese group without treatment in visceral adipose tissue (p<0.05). Likewise, no significant immunohistochemistry staining was seen in diabetic obese groups. CONCLUSION: Metformin or exenatide treatment could prevent the degradation of insulin receptor substrate-1 protein by reducing the effect of suppressors of cytokine signaling-1 and suppressors of cytokine signaling-3 proteins, especially in the liver tissue. In addition, exercise can play a role as a complementary therapy by reducing suppressors of cytokine signaling-1 and suppressors of cytokine signaling-3 proteins in visceral adipose tissue.

The effects of metformin, pioglitazone, exenatide and exercise on fatty liver in obese diabetic rats: the role of IRS-1 and SOCS-3 molecules.

BACKGROUND: Obesity-induced inflammation mechanism is seen as a mechanism that may be the cause of insulin resistance and non-alcoholic fatty liver disease (NAFLD). Pathological destruction of insulin signaling molecules such as insulin receptor substrate proteins (IRS), especially due to the increase of cytokine signal suppressors (SOCS), has been demonstrated in experimental diabetes. The aim of this study was to determine the effects of metformin, pioglitazone, exenatide and exercise treatments used in type 2 diabetes on fatty liver and the role of Irs-1 and Socs3 molecules in this process in obese diabetic rats. METHODS: The study was conducted on 48 Wistar albino adult male rats weighing 180-220 g and randomly divided into 6 groups. The obese rat model with fatty liver was formed with a 60% fat diet for 4 weeks. Afterwards, drug treatment with metformin (Ob + D + M), pioglitazone (Ob + D + P), exenatide (Ob + D + ExA)) or exercise (Ob + D + ExE) was applied for 4 weeks to these obese groups, in which diabetes was induced by streptozocin (STZ). At the end of the experimental protocol, liver tissue samples were taken from all rat groups and histopathological and genetic analyses were performed. RESULTS: The mean steatosis degrees of the Ob + D + ExA and Ob + D + ExE groups were statistically significantly decreased compared to the obese diabetic group (p < 0.001). The group with the lowest mean steatosis grade was the Ob + D + ExE. Decrease in SOCS-3 expression was significant in Ob + D + M and Ob + D + P groups than other groups (p < 0.05). Mean staining intensities of Ob + D + Ex group, Ob + D + ExE group and Ob + D + P group according to IRS-1 expression statistically significantly increased compared to obese diabetic group (p < 0.05). Average staining intensity of Ob + D + ExE group according to IRS-1 expression was significant than other groups. CONCLUSION: Exercise and exenatide treatments seemed to be the prominent treatment methods by showing a statistically significant effect in decreasing the degree of steatosis, decreasing the Socs3 expression level and increasing the Irs-1 expression level.

Clinical and demographic aspects of Paget disease of bone: A multicentric study from Turkey.

OBJECTIVE: Paget disease of bone (PDB) is a metabolic bone disease that has been rarely reported in the Eastern countries. This study aimed to evaluate the clinical and demographic characteristics of patients with PDB followed up at endocrinology clinics in Turkey. METHODS: An invitation was sent to tertiary endocrinology clinics to complete a survey on the demographic, clinical, radiological, and laboratory parameters, as well as treatment modalities of patients with PDB. This study enrolled clinically and radiologically proven 185 patients with PDB from 18 endocrinology centers based in 10 cities of Turkey. RESULTS: This cohort of PDB had female preponderance (women/men: 105/80) with a mean age, during diagnosis, of 57±10 years. Most of the patients (59.6%) were symptomatic at diagnosis. Bone pain and headache were the predominant clinical symptoms. Polyostotic disease was observed in 67.5% (n=125) of patients. Frequently affected bones were skull (41.6%), pelvis (53.5%), spine (41%), and femur (25.4%). Moreover, 17 patients with skull involvement had hearing loss. Mean serum alkaline phosphatase (ALP) level (552±652 IU/L; range: 280-5762 IU/L) was over the normal reference cutoff with normal serum calcium levels. Intravenous bisphosphonates (zoledronic acid, 5 mg; pamidronate, 60-90 mg) were the most used drugs (75%) for the treatment of PDB. Most of the patients (87.1%) treated with intravenous bisphosphonates responded well, with a decrease in serum ALP level (117±114 IU/L) in the 12th month of therapy. Furthermore, 16 patients relapsed after the second year of therapy; 3 patients did not respond to the initial intravenous bisphosphonate treatment. CONCLUSION: The patients with PDB followed up by endocrinology clinics of Turkey exhibited polyostotic disease with classical clinical, radiological, and biochemical features and women's predominance with good response to intravenous bisphosphonate therapy.

The Relationship Between Dipeptidyl Peptidase-4 Inhibitor Usage and Asymptomatic Amylase Lipase Increment in Type 2 Diabetes Mellitus Patients.

OBJECTIVES: In different studies, it has been shown that the use of dipeptidyl peptidase-4 (DPP-4) inhibitors (DPP-4 inh) does not increase the risk of pancreatitis or pancreatic cancer. Although the number of studies involving clinical pancreatitis clinics is sufficient, the number of studies involving clinical non-pancreatitis hyperamylasemia is rare. The aim of the study was to investigate the relationship between DPP-4 inh usage and amylase and lipase increment without clinical pancreatitis symptoms. MATERIALS AND METHODS: Eighty-seven patients who met the inclusion criteria were enrolled. The patients were divided into 3 groups according to their use of saxagliptin, sitagliptin, or vildagliptin. All patients included in the study were receiving metformin at a dose of 2 g/day. Fasting blood glucose, postprandial blood glucose, HbA1C, serum creatinine, ALT, amylase, and lipase results were recorded at the beginning of treatment and at the end of 3 months. RESULTS: There was an increase in all groups in terms of amylase and lipase values but there was no significant difference between the groups in terms of increase (p>0.05) There was no statistically significant increase in the saxagliptin and vildagliptin groups (p>0.05) when the baseline and 3-month values of lipase and amylase increase were examined. However, there was a statistically significant increase in amylase and lipase in the sitagliptin group (p<0.05). CONCLUSION: The use of DPP-4 inh can increase amylase and lipase levels without clinical findings of acute pancreatitis in the patient. DPP-4 inh should be used with caution in patients at risk for pancreatitis and pancreatic cancer. Patients using DPP-4 inh, especially sitagliptin, should be evaluated carefully for pancreatitis risk factors.

Evaluation of Serum S100A8/S100A9 Levels in Patients with Autoimmune Thyroid Diseases.

BACKGROUND: The correlation of S100A8/S100A9 with various inflammatory conditions, including autoimmune diseases have been reported. There is no study investigating the levels of S100A8/S100A9 in autoimmune thyroid diseases (AITD). AIMS: We aimed to evaluate the level of serum S100A8/S100A9 in AITD. STUDY DESIGN: Case control study. METHODS: Fifty patients with AITD (25 Hashimoto's thyroiditis (HT) and 25 Graves' disease (GD)) were included in the study. Twenty seven healthy subjects participated as a control group. Blood samples were obtained in the 3 months after the initiation of medical treatment. Serum levels of total antioxidant status (TAS), total oxidative status (TOS), total free sulfhydryl (SH), lipid hydroperoxide (LOOH) and S100A8/S100A9 were analyzed. RESULTS: The patients with AITD had significantly higher S100A8/S100A9, OSI, LOOH and TOS levels than the healthy control group. There was no significant difference between GD and HT patients in terms of S100A8/S100A9, TOS and OSI levels. S100A8/S100A9 level was positively correlated with LOOH, TOS and OSI levels but negatively correlated with -SH level in the patients with AITD. CONCLUSION: Serum S100A8/S100A9 levels were increased in patients with AITD and positively correlated with LOOH, TOS and OSI whereas negatively correlated with SH.

Paraoxonase and arylesterase levels in autoimmune thyroid diseases.

OBJECTIVE: The aim of this study was to evaluate serum paraoxonase-1 (PON1) activity and its association with oxidative stress in autoimmune thyroid disease (AITD). METHODS: A total of 50 patients with AITD, including 25 with Hashimoto's thyroiditis and 25 with Graves' disease were enrolled. The control group comprised 27 healthy subjects. Blood samples were obtained in the euthyroid period and 3 months after initiation of medical treatment. Serum samples from patients with AITD and the healthy control group were analyzed for basal PON1, salt-stimulated PON1, and arylesterase (ARE) activities, along with lipid hydroperoxide (LOOH) and total free sulfhydryl (-SH) levels. RESULTS: Serum PON1 activities and -SH levels were significantly lower (P < 0.001, for each), whereas LOOH levels were significantly higher (P < 0.001, for each) in patients with AITD, compared to the control group. We observed no significant differences in ARE levels between the patient and healthy control groups (P > 0.05). PON1 activity was positively correlated with -SH (r = 0.522, P < 0.001) and negatively correlated with LOOH (r = -0.487, P < 0.001). PON1 phenotype distribution of the subjects was not significantly different among the three groups (P = 0.961). CONCLUSIONS: Serum PON1 activity is decreased in patients with AITD, and correlated positively with -SH, a well-known antioxidant, and negatively with LOOH, an index of lipid oxidation.

Is calprotectin a novel biomarker of neuroinflammation in diabetic periferal neuropathy?

BACKGROUND: In the present study, we aimed to investigate serum calprotectin levels in patients with diabetic peripheral neuropathy, and possible role of this molecule in the disease pathogenesis. METHOD: Twenty nine patients with diabetic peripheral neuropathy, 30 type 2 diabetic patients without neuropathy, and 40 healthy controls were enrolled in the study. Fasting plasma glucose (FPG), high-density lipoprotein- cholesterol (HDL-C), low-density lipoprotein- cholesterol (LDL-C), total cholesterol, triglyceride, HbA1c, calprotectin and hsCRP levels were measured in diabetic and healthy control groups. RESULTS: Serum calprotectin and hsCRP levels were significantly higher in patients with and without neuropathy than healthy controls (p < 0.001, p = 0.017, p < 0.001 and p = 0.001, respectively). Serum calprotectin and hsCRP levels were higher in diabetics with neuropathy than the ones without (p = 0.021 and p < 0.001, respectively). The positive correlation was detected between calprotectin levels and hsCRP and HbA1c in Spearman correlation analysis (r = 0.510, p < 0.001; r = 0.437, p < 0.001 respectively). The results of multiple logistic regression analysis demonstrated the important association between neuropathy development and hsCRP and serum calprotectin levels in diabetic individuals. CONCLUSION: Seum calprotectin levels were increased in diabetic peripheral neuropathy. It may have a role in the pathogenesis of the disease.

Liraglutide-related cholelithiasis.

Liraglutide is a glucagon-like peptide-1 analog and recently started to be using as an incretin-based treatment for diabetes mellitus. Liraglutide causes some adverse affects including nausea, vomiting, acute nasopharyngitis and acute pancreatitis. However, development of liraglutide-dependent cholelithiasis has not been reported in the literature. A 75-year-old female patient had been diagnosed with type 2 diabetes mellitus for 10 years and she has been treated by liraglutide for 6 months. The patient was admitted to the emergency service due to sudden onset of abdominal pain. After laboratory and imaging studies, she was diagnosed with acute cholecystitis and cholelithiasis. And then patient's oral intake was stopped, intravenous fluid and ceftriaxone 2 g/day were started. Furthermore, liraglutide treatment discontinued and ursodeoxycholic acid (UDCA) was started to treat cholelithiasis. During follow-up, abdominal pain completely relieved. Hepatobiliary ultrasonography in sixth month follow-up showed entirely regression of cholelithiasis. Any liraglutide-related cholelithiasis case has not been reported in the literature previously. Therefore, our case is the first case. Especially, elderly diabetic patients who are started to liraglutide treatment should be monitored closely for the formation of cholelithiasis. UDCA treatment would be an alternative prior to surgical treatment for liraglutide-related cholelithiasis.

Paraoxonase and arylesterase activities in patients with papillary thyroid cancer.

OBJECTIVE: The aim of this study was to evaluate paraoxonase-1 (PON1) activities and oxidative stress status, and the changes in their levels after total thyroidectomy in patients with papillary thyroid cancer (PTC). MATERIALS AND METHODS: Twenty-five patients with PTC and 27 healthy controls were enrolled in the study. Blood samples were obtained from the PTC patients before and 3 months after the operation. Preoperative and postoperative serum samples from PTC patients and healthy controls were analyzed for paraoxonase (PON), arylesterase (ARE) activities, and lipid hydroperoxide (LOOH) and -SH (total free sulfhydryl) levels. RESULTS: The preoperative PON, ARE and -SH levels of the patients with PTC were significantly lower compared to those of the control group (p = 0.033, p < 0.001, p = 0.002, respectively), while LOOH levels were significantly higher (p < 0.001). The levels of PON and ARE decreased significantly in patients with PTC after the operation (p = 0.038, p = 0.023, respectively), while LOOH and -SH levels remained unchanged (p = 0.117, p = 0.487, respectively). PON and ARE levels showed a positive correlation with -SH (r = 0.211, p = 0.065; r = 0.471, p < 0.001, respectively) and a negative correlation with LOOH (r = - 0.391, p < 0.001, r = - 0.486, p < 0.001, respectively). CONCLUSION: Serum PON1 activity is decreased in patients with PTC, and serum PON1 is positively correlated with -SH, a well-known antioxidant, and negatively correlated with LOOH, an oxidant. PON1 activity is significantly decreased after total thyroidectomy.

Investigation of the role of 8-OHdG and oxidative stress in papillary thyroid carcinoma.

The aim of this study was to determine levels of serum 8-hydroxy-2'-deoxyguanosine (8-OHdG) as an indicator of oxidant-induced DNA damage and oxidant status in patients with papillary thyroid carcinoma before and after surgery. This study included 25 patients with papillary thyroid carcinoma and age-matched 27 healthy controls. Total antioxidant status (TAS), total oxidant status (TOS), lipid hydroperoxide (LOOH), and 8-OHdG levels were measured. 8-OHdG levels were significantly higher in the preoperative papillary thyroid carcinoma (PTC) group compared with the healthy control group (p < 0.001) and were significantly lower after operation in patients with papillary thyroid carcinoma (p = 0.004). Oxidative stress index (OSI) levels were significantly higher in both preoperative and postoperative PTC patients compared with the healthy control group (p < 0.001 and p < 0.001, respectively). TOS levels were higher in the preoperative and postoperative PTC groups compared to the healthy control group (p < 0.001 and p < 0.001, respectively). TAS levels was lower in the preoperative PTC groups compared to the healthy control group (p = 0.011). Serum LOOH levels were higher in both preoperative and postoperative PTC groups compared to the healthy control group (p < 0.001 and p < 0.001, respectively). Correlation analysis yielded that serum 8-OHdG levels were positively correlated with OSI and LOOH levels in patients with PTC before surgery (r = 0.668, p < 0.001; r = 0.446, p = 0.025, respectively) and had a negative correlation with TAS levels (r = -0.616, p = 0.001). We have shown severe oxidative DNA damage and impaired antioxidant status in papillary thyroid carcinoma.

Differential expression of a set of genes in follicular and classic variants of papillary thyroid carcinoma.

Fine-needle aspiration biopsy (FNA) is currently the best initial diagnostic test for evaluation of a thyroid nodule. FNA cytology cannot discriminate between benign and malignant thyroid nodules in up to 30% of thyroid nodules. Therefore, an adjunct to FNA is needed to clarify these lesions as benign or malignant. Using differential display-polymerase chain reaction method, the gene expression differences between follicular and classic variants of papillary thyroid carcinoma (PTC) and benign thyroid nodules were evaluated in a group of 42 patients. Computational gene function analyses via Cytoscape, FuncBASE, and GeneMANIA led us to a functional network of 17 genes in which a core sub-network of five genes coexists. Although the exact mechanisms underlying in thyroid cancer biogenesis are not currently known, our data suggest that the pattern of transformation from healthy cells to cancer cells of PTC is different in follicular variant than in classic variant.

Effects of pulse methylprednisolone and oral methylprednisolone treatments on serum levels of oxidative stress markers in Graves' ophthalmopathy.

BACKGROUND: Recent evidence has shown that oxidative stress may play a role in the pathogenesis of autoimmune diseases, and this is an issue of considerable research interest in the field of infiltrative ophthalmopathy. Therefore, we evaluated both the relationship between Graves' ophthalmopathy (GO) and serum levels of certain indicators of oxidative stress, and the effects of methylprednisolone treatment on serum malondialdehyde (MDA) and glutathione (GSH) levels in patients with euthyroid GO. MATERIALS AND METHODS: We compared GO patients to both Graves' patients without ophthalmopathy and healthy controls. Ultimately, we assessed four subject groups. Graves' patients with ophthalmopathy (GO) were subcategorized into two groups: Group A subjects (n = 18) were given intravenous glucocorticoid and Group B patients (n = 15) were given oral glucocorticoid. Graves' patients without ophthalmopathy comprised Group C (n = 20), and healthy controls comprised Group D (n = 15). Serum levels of MDA and GSH were measured at baseline and after 4 and 24 weeks of observation via spectrophotometric methods. RESULTS: We found that serum MDA levels were significantly higher in the two GO groups (Groups A and B) than in GO patients without ophthalmopathy or healthy controls. Conversely, GSH levels were significantly lower in the two GO groups than in Groups C and D. MDA and GSH levels were not different between the latter two groups. MDA levels were strongly and positively correlated with a clinical activity score (CAS). In Group A, MDA levels and the CAS were significantly lower than in Group B at 4 weeks. After 24 weeks, however, MDA levels and the CAS were similar in these two groups. CONCLUSION: Oxidative stress appears to be involved in the pathophysiology of GO. Relative to oral dosing, the intravenous administration of a glucocorticoid seems to yield more rapid improvement in disease activity. MDA might be useful as an indicator of clinical activity.

The prevalence of non-classic adrenal hyperplasia among Turkish women with hyperandrogenism.

The prevalence of non-classic adrenal hyperplasia (NCAH) among Turkish women with hirsutism has not been established so far. Thus, we aimed to evaluate the prevalence of 21-hydroxylase (21-OH) deficiency by ACTH stimulation test among hirsute women. The study population consisted of 285 premenopousal women, aged 16-46 years (mean: 23.2 ± 0.3). All were hirsute and hyperandrogenic. Androgen secreting tumors of the ovaries and the adrenal glands were excluded as well as thyroid dysfunction and hyperprolactinemia. All the patients were evaluated by 0.25 mg (i.v.) ACTH stimulation test and 17-OHP responses were obtained at 30 and 60 min. The diagnosis of NCAH due to 21-OH deficiency was considered in patients with the poststimulation 17-OHP level exceed 10 ng/ml. Six (2.1%) of the patients had NCAH due to 21-OH deficiency confirmed by genotyping. The rest of the patients were polycystic ovary syndrome (n = 166, 58.2%) and idiopathic hyperandrogenemia (n = 113, 39.7%). There were no patients with idiopathic hirsutism because patients with normal serum androgen levels were excluded. This first and most extensive national study investigating NCAH prevalence among Turkish population showed that NCAH is not prevalent in this population.

Evaluation of urinary oxalate levels in patients receiving gastrointestinal lipase inhibitor.

OBJECTIVE: The purpose of this study was to examine the possible effects of a gastrointestinal lipase inhibitor "Orlistat (Xenical)" on the intestinal absorption of oxalate and thereby on the urinary levels of oxalate excretion in overweight patients. METHODS AND PROCEDURES: Long-term follow-up data of 95 cases (57 men, 38 women; M/W=1.5) were documented. Patients were randomly assigned into two groups. While the patients in group I (n=55) were treated with orlistat (Xenical) for 6 months, patients in group II (n=40) received no specific medication. Calcium, oxalate, and citrate levels were determined in a 24-h urine collection from each patient. To evaluate the significance in the groups as well as the differences between the two groups, ANOVA test was performed and the results were given as mean +/- s.d. RESULTS: Comparative evaluation of urinary oxalate levels during 3-month follow-up clearly showed that urinary oxalate excretion significantly increased in 34/55 patients (61.8%) in the first group (P<0.05). Of these 34 patients, 30 (88.2%) continued to have increased urinary oxalate excretion during 6-month follow-up (P=0.001). However, our data did not show any significant effect of this medication on urinary citrate and calcium levels during 3- and 6-month follow-up evaluation (P=0.05). DISCUSSION: Our results suggest that increased intestinal absorption of dietary oxalate due to this type of medication in obese patients could make a substantial contribution to urinary oxalate excretion and may increase the risk of stone formation.