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Öğe Adipocyte volumes and levels of adipokines in diabetes and obesity(Elsevier Sci Ltd, 2008) Gokalp, Deniz; Bahceci, Mithat; Ozmen, Sehmus; Arikan, Senay; Tuzcu, Alpaslan; Danis, RamazanAim: Obesity is a major risk factor for insulin resistance, type 2 diabetes, heart disease, and many other chronic diseases. The factors regulating cytokine production seem to have a role on the determination of adipocyte volume. We aimed to investigate the association of plasma adiponectin and resistin concentrations with adipocyte volumes in obese, diabetic, obese-diabetic and control groups. Methods: Plasma adiponectin, resistin and lipid levels and adipocyte volumes were investigated in obese, non-diabetic, non-obese diabetic, obese diabetic and control groups consisting 100 subjects who planned to undergo elective surgery. Differences in clinical or laboratory parameters among groups were compared by using one-way ANOVA test. Chi-square test was used for comparing the frequencies. Results: The lipid values in all three groups were higher than the control group. A negative correlation was found between adiponectine levels and adipocyte volumes. When adipocyte volumes were compared with other groups, adipocyte volumes were significantly higher in the obese diabetic group (p = 0.000). The adipocyte volumes in the obese group were determined to be higher than the control group. Conclusions: Although a positive correlation was found between adipocyte volumes and adiponectin in literature, adiponectin concentrations in our study were lower. These conditions can be explained by the effect of insulin resistance on the adiponectin levels in obese diabetic groups. Moreover, adiponectin levels are mostly associated with subcutaneous adipose tissue which may have been less. Resistin levels may play an important role in the development of obesity, insulin resistance and diabetes. (C) 2008 Diabetes India. Published by Elsevier Ltd. All rights reserved.Öğe Analysis of thrombophilic genetic mutations in patients with Sheehan's syndrome: is thrombophilia responsible for the pathogenesis of Sheehan's syndrome?(Springer, 2011) Gokalp, Deniz; Tuzcu, Alpaslan; Bahceci, Mithat; Ayyildiz, Orhan; Yurt, Murat; Celik, Yusuf; Alpagat, GulistanThe gene mutations of Factor V R506Q (FV-Leiden), prothrombin (FII G20210A), methylene tetrahydrofolate reductase (MTHFR) C677T and A1298C and PAI-1 4G/5G are well-established risk factors for thrombosis. We aimed to investigate the prevalence of these gene mutations and their possible impact on the development of pathogenesis in patients with Sheehan's syndrome (SS). 40 female patients with SS compared to a control group of 45 healthy women. The presence of FV-Leiden, FII G20210A, MTHFR C677T, MTHFR A1298C and PAI-1 4G/5G gene mutations were assessed by polymerase chain reaction analysis with a light cycler analyzer. An odds ratio of greater than one is considered to increase the risk of SS disease as found in Factor V Leiden, FII G20210A, MTHFR C677T, MTHFR A1298C and PAI-1 4G/5G polymorphism, as follows respectively: 1.13, 1.85, 6.00, 8.14 and 1.45. MTHFR C677T and MTHFR A1298C polymorphism were found significantly higher in SS patients than the control group (P < 0.001), however FV-Leiden, FII G20210A and PAI-1 4G/5G polymorphism showed no significant difference (P > 0.05). The level of plasma total homocysteine (tHcy) was significantly higher in patients with SS than in the control group (P < 0.001). We suggest that the genetic mutations of FV-Leiden, FII G20210A, MTHFR C677T, MTHFR A1298C and PAI-1 4G/5G increase the risk of SS. Also, high plasma tHcy levels may be a risk factor for the development of SS.Öğe Assessment of bleeding disorders in Sheehan's syndrome: Are bleeding disorders the underlying cause of Sheehan's syndrome??(Informa Healthcare, 2011) Gokalp, Deniz; Tuzcu, Alpaslan; Bahceci, Mithat; Ayyildiz, Orhan; Erdemoglu, Mahmut; Alpagat, GulistanSheehan's syndrome (SS) is an adenopituitary insufficiency caused by hypovolemia secondary to excessive blood loss during or after childbirth. However, the mechanism of postpartum hemorrhage and ischemia is not clear. We aimed to evaluate the bleeding disorders among patients with SS, in comparison with healthy controls. In addition, we investigated underlying causes in postpartum hemorrhage that begin the event. The present study was conducted at the Dicle University School of Medicine. Forty-eight patients with SS and 50 age-matched female healthy controls were included. Biochemical and hormonal variables were measured, as was platelet function by means of closure times (PFA-100 testing using collagen plus epinephrine and collagen plus ADP), von Willebrand factor (vWF) level, prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR), and coagulation factors. Although PT and INR were significantly higher in patients with SS (both P < 0.01), aPTT and levels of fibrinogen, vWF, and factors II, V, VII, VIII, IX, X, XI, and XII did not differ significantly. Closure times with collagen/epinephrine and collagen/ADP also did not differ significantly between patients with SS and control patients. The nonspecific etiology and presence of excessive postpartum hemorrhage in patients with SS suggest that coagulation disorders may play a role in their predisposition to bleeding. The increased PT and INR noted might implicate bleeding diathesis as the underlying etiology, although no significant decreases were noted in factor levels. Further studies are needed to elucidate this complex mechanism of this disorder.Öğe Audiological Findings in Acromegaly Patients(Mediterranean Soc Otology & Audiology, 2011) Baylan, Muzeyyen Yildirim; Gokalp, Deniz; Celik, Yusuf; Tuzcu, Alpaslan; Meric, Faruk; Topcu, IsmailObjective: The aim of this study was to evaluate otologic problems in patients with acromegaly. Materials and Methods: This retrospective study was performed on 26 patients with acromegaly and 27 age-matched healthy controls. Otoscopic examination, pure tone odiometry, tympanometry, otoacoustic emissions, and stapes reflex were performed in all cases. Hearing thresholds of air and bone conduction (AC and BC), middle ear function, cochlear function, tympanic membrane compliance, gradient, peak pressure, and external ear canal volume were researched in patients with acromegaly. Results: The hearing thresholds for all frequencies except Right-AC 4000 frequencies were found to be significantly higher in patients with acromegaly as compared to the control group (p<0.05). Also significant correlation coefficients were calculated among disease duration, hearing thresholds, and tympanometric variables (p<0.05). There was a significant difference in tympanometry results between the two groups in regard to external ear canal volumes of the right and left ears (p <= 0.05). No differences were observed between the two groups in their type of tympanometry, stapes reflex, and otoacoustic emissions (OAE) (p>0.05). Conclusions: We have determined that patients with acromegaly have lower levels of hearing in both bone and air conduction compared with the normal population. This may be ascribed to deformation of hearing physiology related to hypertrophy in the temporal bone.Öğe A Case with Lipoid Proteinosis Intersected with Diabetes Mellitus(Galenos Yayincilik, 2009) Gokalp, Deniz; Tuzcu, Alpaslan; Bahceci, Mithat; Yildirm, Muzeyyen; Akdeniz, Sedat; Ozekinci, Selver; Urakci, ZuhatLipoid proteinosis (LP) is a rare disorder inherited as an autosomal recessive trait. LP is characterized by deposition of hyaline-like material in the skin, mucous membranes, and other tissues. LP has been mapped to chromosome 1q21, the locus for the extracellular matrix protein 1 (ECM1) gene. In this case report, we aimed to present a case with LP accompanied by diabetes mellitus, and to discuss the possible mechanisms of diabetes in LP. A 16-year-old girl presented to the endocrinology department with hyperglycemia. She reported a history of progressive hoarseness of her voice since she was two years old. Our patient meets the clinical and histopathological criteria for the diagnosis of LP. Her fasting glucose was 310 mg/dl. Plasma insulin and C-peptide levels were 5.1 uU/ml and 1.57 ng/ml, respectively. Hemoglobin A1c was 12.3%. HOMA-IR (Homeostasis Model Assessment-Insulin Resistance) ratio was 3.1 (normal range <3.7). Serum islet cell antibodies, anti-GAD antibodies and anti-insulin antibodies were negative. Diabetes mellitus was diagnosed and insulin treatment was initiated. In conclusion, possible mechanism of diabetes mellitus may be result of the diffuse deposition of amorphous material into the capillary vessels or in pancreas. The other possible mechanism responsible for the association of diabetes mellitus and insulin resistance in LP patients may be sharing a mutation at 1q21 locus. Future studies which aimed screening of insulin resistance and diabetes mellitus in LP patients may be helpful to explain this association.Öğe Ectopic lingual thyroid as a rare cause of primary hypothyroidism - A case report(Lippincott Williams & Wilkins, 2008) Pasa, Semir; Beyaz, Coskun; Arikan, Senay; Altintas, Abdullah; Gokalp, Deniz; Cil, Timucin; Tuzcu, AlparslanEctopic lingual thyroid gland is all uncommon abnormality of migration of the thyroid gland. Although it is uncommon, it is often found in the region of the foramen cecum as a lingual thyroid at the base of the tongue in patients whose gland fails to descend. The true incidence of lingual thyroid is unknown. Treatment depends on the presence of symptoms. In this case report, we described a 17-year-old mail who presented with growth retardation due to severe hypothyroidism associated with a lingual thyroid gland. He did not complain of pressure symptoms. We recommended regular follow-up visits to monitor this state of thyroid function and the size and shape of the gland. We wanted to note that ectopic thyroid tissue should be taken into consideration in the differential diagnosis of all lingual and pharyngeal masses, and in the differential diagnosis of hypothyroidism.Öğe An Embryological Cause of Primer Hypothyroidism, Lingual Thyroid(Galenos Yayincilik, 2006) Arikan, Senay; Gokalp, Deniz; Tuzcu, Alpaslan; Bahceci, Mithat; Bahceci, SelenLingual thyroid is a rare developmental thyroid abnormality usually affecting females. It is often found in the region of the foramen caecum as a lingual thyroid at the base of the tongue in patients whose gland fails to descend. A 16-year-old female patient with severe hypothyroidism applied to our outpateint clinic. She was complaining from growth retardation, primary amenorrhea, weakness, decreases of school performance and short stature. No thyroid tissue was seen at the usual site with ultrasonography. Scintigrapy with 99mTC pertechnetate showed an ectopic functioning thyroid in the lingual area. CT scan showed a mass in the base of lingular region. The thyroid profile implied severe hypothroidism (free T3: 0,142 ng/ dl, free T4: 0,741 ng/dl, and TSH: 100 mu IU/ml). Patient was accepted as primary hypothyrodism due to ectopic thyroid tissue (lingual thyroid) and substitution treatment with L-thyroxine was started at the dose of 2-3 mu gr/kg. Surgical treatment did not consider because of patient was asymptomatic in terms of pressure. As a result we reported a rare cause of primary hypothyroidism due to ectopic thyroid gland (lingual) in a young female patient.Öğe Evaluation of Bone Mineral Density in Terms of Veiling, Socioeconomiical Status and Educatiional Level in Turkish Women Over 40 Years. Veiling May Be A Risk Factor For Osteoporosis(Galenos Yayincilik, 2006) Bahceci, Mithat; Ertem, Meliksah; Saka, Gunay; Gokalp, Deniz; Karacomak, Zuhre; Akdeniz, Nurten; Tuzcu, AlpaslanBackground and aims: Headscarf is a mild kind of veiling, worn for various intentions. We aimed to evaluate effect of veiling, educational status, living area and nutrition on BMD in women over 40 years. Subjects and methods: Four hundred thirty nine moslem women, living in different region (suburb and house provided to workers) of Diyarbakir, aged over 40 years (with mean age 48,9+ 11,3 years) were included to study. The predicted factors influencing BMD were investigated by using a questionnaire. Body weights and heights were measured. BMI was expressed as weight (kilograms) per height (meters) squared. Body fat percent and fat mass were determined by bioelectric impedance. Bone Mineral Density (BMD) was determined with radiographic absorptiometry (RA) in three middle fingers. Results: Living in suburban region (p=0.0001), family history of osteoporosis (p<0.002), low education level (p=0.0001), insufficient calcium intake (p<0.001), parity over 4 (p=0.0001), low body height (p=0.0001), veiling (p=0.0001) and low body weight (p< 0.002) and height (p=0.0001) and duration of menopause (p=0.0001) were the factors with negative effects on BMD. Prevalence of osteoporosis was also higher in illiterate women (p=0.0001), women living in slum (p=0.0001), veiled women (p=0.0001), insufficient nutritional status (p< 0.03) and positive family history for osteoporosis (p< 0.002). Conclusions: In addition to well known factors for osteoporosis such as living in slum, illiteracy, high parity number, insuficient nutrition, and duration of menopause; veiling may also be an important factor for low BMD. Veiled women should be screened for low BMD and osteoporosis regularly.Öğe The evaluation of endothelial function with flow-mediated dilatation and carotid intima media thickness in young nonobese polycystic ovary syndrom patients; existence of insulin resistance alone may not represent an adequate condition for deterioration of endothelial function(Elsevier Science Inc, 2009) Arikan, Senay; Akay, Hatice; Bahceci, Mithat; Tuzcu, Alpaslan; Gokalp, DenizObjective: To evaluate endothelial function with flow-mediated dilatation (FMD) and carotid intima media thickness (IMT) in young nonobese polycystic ovary syndrome (PCOS) patients. Design: Prospective case-control study. Setting: Healthy volunteers and nonobese young PCOS patients in clinical research. Patient(s): Thirty-nine PCOS patients with mean age of 22.82 +/- 5.53 years and 30 body mass index- and age-matched healthy controls were evaluated. Intervention(s): Insulin resistance was calculated with area under the curve, quantitative insulin sensitivity check, and the Matsuda index. Endothelial function was assessed with FMD and carotid IMT by ultrasonography. Main Outcome Measure(s): Antropometric, hormonal, biochemical (insulin and glucose, tumor necrosis factor-alpha, hs-c-reactive protein, and homocysteine levels, and so forth), FMD, and IMT were measured. Result(s): There was a significant insulin resistance in PCOS patients. Serum FSH, total and free testosterone, cortisol, androstenedione, and DHEA-S levels of PCOS patients were also higher than control subjects, but we could not find any significant difference in terms of endothelial function determined with FMD. Conculsion(s): Existence of insulin resistance alone may not bean adequate factor for deterioration of endothelial function and carotid IMT in young, nonobese patients with PCOS. Other factors such as duration of insulin resistance, older age, presence of obesity, and inflammatory markers may play an important role in this process. (Fertil Steril (R) 2009;91:450-5. (C)2009 by American Society for Reproductive Medicine.)Öğe Evaluation of insulin sensitivity in hyperprolactinemic subjects by euglycemic hyperinsulinemic clamp technique(Springer, 2009) Tuzcu, Alpaslan; Yalaki, Serkan; Arikan, Senay; Gokalp, Deniz; Bahcec, Mithat; Tuzcu, SadiyeThe background and aim of the study is to evaluate insulin sensitivity in hyperprolactinemic subjects via euglycemic hyperinsulinemic clamp technique. Sixteen hyperprolactinemic subjects and 12 healthy subjects were included in the study. HOMA-B and HOMA-IR values of groups were calculated. Euglycemic hyperinsulinemic clamp technique was performed in both groups, and the M value of the groups was defined. Mann-Whitney U and chi-square tests were used in statistical analysis. Basal insulin level of hyperprolactinemic patients were higher than the control group (6.85 +/- A 4.68; 3.66 +/- A 0.88 mu U/ml respectively; P < 0.05). Mean HOMA-IR and HOMA-B values of patients were higher than control group (1.49 +/- A 1.30; 0.78 +/- A 0.27 respectively; P = 0.02 and 136.28 +/- A 72.53; 64.77 +/- A 23.31, respectively, P < 0.001). M values of the patients were statistically lower than the control group (5.64 +/- A 2.36; 7.05 +/- A 1.62 kg/mg/min respectively; P < 0.05). (1) Hyperprolactinemic patients were more insulin resistant than control subjects. (2) Insulin resistance in hyperprolactinemic patients is not associated with obesity or anthropometric parameters such as fat content, waist circumference and BMI.Öğe Flow-mediated dilatation in polycystic ovary syndrome women Reply(Elsevier Science Inc, 2009) Arikan, Senay; Akay, Hatice; Bahceci, Mithat; Tuzcu, Alpaslan; Gokalp, Deniz[Abstract Not Available]Öğe Four decades without diagnosis: Sheehan's syndrome, a retrospective analysis(Taylor & Francis Ltd, 2016) Gokalp, Deniz; Alpagat, Gulistan; Tuzcu, Alpaslan; Bahceci, Mithat; Tuzcu, Sadiye; Yakut, Fatime; Yildirim, AzadAim: Sheehan's syndrome (SS) remains a frequent cause of hypopituitarism in undeveloped and developing countries, but due to improvements in obstetric care, it is rare in developed countries. We aimed to share the results of a retrospective study analyzing the demographic, clinical, imaging, and hormonal characteristics of a large group of patients with SS, and also increase awareness of this syndrome especially in developed countries. Methods: The medical records of 124 patients with SS patients who were followed up in the Endocrinology Department of Dicle University between 1995 and 2015 were assessed retrospectively. Results: The mean period of diagnostic delay was 20.37 +/- 8.34 years on average. 5.7% of patients with SS were literate; 62% of patients delivered at home. Anemia was identified in 64.5% of SS patients. Mean blood sodium levels were 129.8 +/- 11.3 mEq/L. The mean urine densities were 1013 +/- 6.5. Osteoporosis and osteopenia were found in 44 (35.4%) and 71 (57.2%) patients, respectively, According to pituitary magnetic resonance imaging (MRI) analyses, 92 (74.2%) patients with SS had completely empty sella, 29 (23.3%) had partially empty sella, and 1 patient had microadenoma, and 2 had normal pituitary MRI results. Conclusions: Improved obstetric care and effective interventions for postpartum hemorrhage have limited the prevalence of SS in developed countries. However, in developing countries like Turkey, SS due to postpartum bleeding remains common. Thus, physician's awareness of the symptoms of SS is urgently required to avoid the associated morbidity and mortality.Öğe Hyperthyroidism may affect serum N-terminal pro-B-type natriuretic peptide levels independently of cardiac dysfunction(Wiley, 2007) Arikan, Senay; Tuzcu, Alpaslan; Gokalp, Deniz; Bahceci, Mithat; Danis, RamazanBackground It is known that NT-proBNP levels increase in cardiac failure. However, NT-proBNP levels in different thyroid states are still unclear. We aimed to evaluate serum NT-proBNP levels in both hyperthyroid and hypothyroid patients without cardiac insufficiency. Subjects and methods Thirty-six patients with hyperthyroidism (42.9 +/- 16.7 years), 25 patients with hypothyroidism (35.4 +/- 13.9 years) and 34 age-matched euthyroid subjects (41.4 +/- 13.8 years) were included in the study. After anthropometric evaluations, body fat analyses were determined by bioelectrical impedance. Electrocardiography and echocardiography were used in cardiac evaluations. Serum NT-proBNP was measured by immunoassay. Results Mean serum NT-proBNP levels in hyperthyroid patients were higher than in both control subjects (13.65 +/- 13.02 vs. 6.50 +/- 4.83 pmol/l, P = 0.002) and hypothyroid patients (13.65 +/- 13.02 vs. 5.98 +/- 5.08 pmol/l, P = 0.003). However, mean serum NT-proBNP levels in hypothyroid patients were not different from those in control subjects. There was a positive correlation between serum NT-proBNP and thyroid hormones (NT-proBNP and FT3: r = 0.324, P = 0.001; NT-proBNP and FT4: r = 0.269, P = 0.009, respectively). Serum NT-proBNP levels were positively correlated with left ventricle end-diastolic diameters (r = 0.232, P = 0.04), interventricular septum thickness (r = 0.315, P = 0.006), and negatively correlated with left ventricular ejection fraction (r = -0.238, P = 0.04). Conclusions Serum NT-proBNP levels may increase in hyperthyroidism independently of cardiac insufficiency. Therefore, hyperthyroidism may lead to cardiac ultrastructural changes undetermined by conventional echocardiography and these changes may be responsible for elevation of NT-proBNP levels. In contrast to decreased thyroid hormones, excess thyroid hormones may have a more pronounced effect on serum NT-proBNP levels.Öğe Increased cortisol level in type 1 diabetic patient may lead decreasing of bone mineral density(Nature Publishing Group, 2007) Tuzcu, Alpaslan; Bayer, Semir; Arikan, Senay; Gokalp, Deniz; Bahceci, Mithat; Canoruc, Naime[Abstract Not Available]Öğe Insulin Resistance in Type 2 Diabetes Mellitus May Be Related to Bone Mineral Density(Elsevier Science Inc, 2012) Arikan, Senay; Tuzcu, Alpaslan; Bahceci, Mithat; Ozmen, Sehmuz; Gokalp, DenizThe mechanism of bone mineral density (BMD) changes in type 2 diabetes mellitus is not clear. We aimed to investigate the effect of insulin resistance in type 2 diabetics on BMD. Insulin resistance was determined using the homeostasis model assessment index (HOMA-IR). Nineteen type 2 diabetic patients with a HOMA-IR < 2.7 (mean age, 51.5 +/- 9.6 yr; body mass index [BMI] 27.3 +/- 5.1 kg/m(2); duration of diabetes, 10.5 +/- 7.3 yr) were included in Group A, and 30 BMI- and age-matched type 2 diabetic patients with a HOMA-IR >= 2.7 were included in Group B. The BMD was measured with dual-energy X-ray absorptiometry. Independent t-test was used for statistical analysis. The Group A values for mean fasting glucose and insulin levels were 160.1 +/- 77.0 mg/dL and 4.79 +/- 2.89 mu U/L, respectively, whereas the Group B values were 195.1 +/- 58.9 mg/dL (p > 0.05) and 19.30 +/- 16.89 mu U/L (p = 0.0001). Significantly higher total lumbar vertebra T-score (p = 0.02) and total lumbar vertebra BMD in Group A were determined than Group B (p = 0.033). The lumbar vertebra total Z-score was significantly lower in Group B (p = 0.042). Marked insulin resistance may have a negative effect on BMD in type 2 diabetics, while the presence of hyperinsulinemia may be associated with the low BMD.Öğe Late Histopathological Features of Testis Tissue in a Patient With Male Pseudohermaphroditism Due to Leydig Cell Aplasia(Galenos Yayincilik, 2006) Bahceci, Selen; Nergiz, Yusuf; Bahceci, Mithat; Tuzcu, Alpaslan; Gokalp, DenizLeydig cell aplasia is a rare form of male pseudohermaphroditism. We determined Leydig cell aplasia in a 39 yr old patient, grown up as a female, with female external genitalia and primary amenorrhea. Gonads were bilaterally palpable in the inguinal regions. Karyotype was 46, XY. Hormonal evaluation revealed markedly elevated gonadotropin levels with a low testosterone, which failed to increase after human chorionic gonadotropin stimulation. In Leydig cell aplasia, classically, testicular histology reveals seminiferous tubules, whereas Leydig cells are not present or appear only as immature forms. In addition to classical features of Leydig cell aplasia, we determined diffuse fibrosis, atrophy, interstitial edema and marked thickness in lamina propria of seminiferous tubules, and although Sertoli cells were seen, no germ cell was present. Very long duration of undescended testes (cryptorchidism) may be responsible for these additional histopathological changes. Becasue of a criptorchid testis is more likley to undergo malignant degeneration than normal testes, many urologists recommend orchiectomy for unilaterally undescended testicle.Öğe Levels of proinflammatory cytokines and hs-CRP in patients with homozygous familial hypercholesterolaemia(Acta Cardiologica, 2009) Gokalp, Deniz; Tuzcu, Alpaslan; Bahceci, Mithat; Arikan, Senay; Pirinccioglu, Ayfer Gozu; Bahceci, SelenObjective - Homozygous familial hypercholesterolemia (FH) is an extremely rare (1/1.000.000) condition characterized by markedly increased LDL cholesterol levels and a significantly increased risk of premature coronary heart disease (CHD). We aimed to evaluate the levels of high-sensitivity C-reactive protein (hs-CRP) and proinflammatory cytokines, which are known to be associated with atherogenesis, in patients with this condition. Method and results - A total of 10 patients with homozygous FH (5 women and 5 men, mean age 17.0 +/- 6.9 years, body mass index (BMI) (18.8 +/- 1.9 kg/m(2)) and 16 healthy controls were included. hs-CRP levels, proinflammatory cytokine levels and lipid parameters were measured and compared between patients and control subjects. Homozygous FH patients had significantly higher total cholesterol, LDL-cholesterol and Lp(a) levels and significantly lower triglycericle and HDL cholesterol levels, compared to controls (P = 0.0001, for all). Serum hs-CRP (3.7 +/- 1.3 mg/L vs. 0.6 +/- 0.6 mg/L) and IL-1 beta, IL-2R, IL-6, IL-8, IL- 10, TNF-alpha levels were all significantly higher in the homozygous FH group, compared to controls (P = 0.0001, for all). Conclusions - Homozygous FH patients have significantly higher levels of hs-CRP and circulating proinflammatory cytokines, which may explain their increased risk of atherosclerotic disease. hs-CRP is an important biomarker that may be helpful in the identification of asymptomatic CHD in FH patients.Öğe Malondialdehyde (MDA) and protein carbonyl (PCO) levels as biomarkers of oxidative stress in subjects with familial hypercholesterolemia(Pergamon-Elsevier Science Ltd, 2010) Pirinccioglu, Ayfer Gozu; Gokalp, Deniz; Pirinccioglu, Mihdiye; Kizil, Goksel; Kizil, MuratObjective: Familial hypercholesterolemia (FH) is clinically characterized by elevated total and low-density lipoprotein (LDL) cholesterol levels in plasma, which has high risk for developing atherosclerosis. Increased oxidative stress (OS) and FH have been related to atherosclerosis. The study aims to evaluate oxidative stress in patients with hypercholesterolemia by measuring lipid peroxidation and protein carbonyl (PCO) levels in these patients. PCO in these patients may provide a new diagnostic biomarker for oxidative damage in atherosclerosis. Design and method: Total cholesterol (Tc), low-density lipoprotein-cholesterol (LDL-c), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-c), lipoprotein(a) (Lp-a) levels and carotid intima-media thickness were measured to evaluate characteristics of patients (11 homozygous and 25 heterozygous) with FH. 25 age-gender-BMI matched healthy control subjects were included in the study for comparison. Results: MDA and PCO levels were significantly higher in homozygous patients compared with those of heterozygous and controls and it was found that they are positively correlated with LDL-c, Tc, Lp-a and IMT while negatively correlated with HDL-c. The heterozygous group also had significantly higher MDA and PCO levels compared with controls. Conclusion: The data obtained could be important for understanding the alterations presented by FH and could be related to their increased risk of developing atherosclerosis. To our knowledge, measurements of PCO in patients with FH are not recorded before and this may be used as a biomarker for protein oxidation, which may play a role in the increased cardiovascular risk of patients with FH. (C) 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.Öğe Massive Metformin Overdose in Two Subjects with Suicidal Behavior: Brief Communication(Ortadogu Ad Pres & Publ Co, 2012) Arikan, Senay; Tuzcu, Alpaslan; Bahceci, Mithat; Kaplan, Mehmet Ali; Gokalp, DenizLactic acidosis is a well-recognized side effect of metformin, especially in patients with renal failure. Only a few cases of deliberate self-poisoning with metformin have been described in the literature. The mechanism of metformin-associated lactic acidosis is complex. In the absence of acute overdose, metformin-associated lactic acidosis rarely develops in patients without comorbidities such as renal or hepatic insufficiency or acute infection. We report two patients who had a large dose of metformin in an attempt to harm themselves and presented with lactic acidosis. In our experience, metformin intoxication may lead a high anion gap metabolic acidosis after a suicide attempt. Sodium bicarbonate infusion is able to correct the acid-base metabolism sufficiently in subjects with normal renal functions.Öğe Mutations in the Amino-Terminal Region of Proopiomelanocortin (POMC) in Patients with Early-Onset Obesity Impair POMC Sorting to the Regulated Secretory Pathway(Endocrine Soc, 2008) Creemers, John W. M.; Lee, Yung Seng; Oliver, Robert L.; Bahceci, Mithat; Tuzcu, Alpaslan; Gokalp, Deniz; Keogh, JuliaContext: Mutations in the proopiomelanocortin (POMC) gene that impair the synthesis or structure of POMC-derived peptides predispose to human obesity. Objective: Our objective was to identify and characterize novel mutations in the POMC gene found in patients with early-onset obesity. Design and Patients: The POMC gene was screened in 500 patients with severe early-onset obesity. The biosynthesis, processing, sorting, and secretion of wild-type POMC and two newly identified POMC mutants was studied using metabolic labeling, Western blotting, and immunoassay analysis of lysates and conditioned media of transiently transfected beta-TC3 cells. Results: Two novel heterozygous missense mutations in POMC (C28F and L37F) were identified in unrelated probands with early-onset obesity and their overweight or obese family members. Both mutations lie in a region of the N terminus of POMC that has been suggested to be involved in its sorting to the regulated secretory pathway. Metabolic labeling studies indicate that whereas the mutations do not reduce intracellular levels of POMC, both mutations (C28F>L37F) impair the ability of POMC to be processed to generate bioactive products. Studies of the secretion of POMC products suggest, particularly with C28F, that the impaired propeptide processing of these mutations results, at least in part, from a mistargeting of mutant POMC to the constitutive rather than the regulated secretory pathway. Conclusion: These mutations in patients with early-onset obesity represent a novel molecular mechanism of human POMC deficiency whereby naturally occurring mutations in its N-terminal sequence impair the ability of POMC to enter the trafficking pathway in which serial propeptide processing normally occurs. (J Clin Endocrinol Metab 93: 4494-4499, 2008)
