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    Acromegaly is associated with high fibroblast growth factor-21 levels
    (Springer, 2019) Yurekli, B. S.; Kutbay, N. O.; Aksit, M.; Suner, A.; Simsir, I. Y.; Seckiner, S.; Kocabas, G. U.; Bozkaya, G.; Saygili, F.
    PurposeFibroblast growth factor-21 (FGF-21) is a member of fibroblast growth factor family. Both growth hormone (GH) and FGF-21 take place in the regulation of glucose and lipid metabolism. We aimed to investigate FGF-21 levels in acromegaly which is characterized by excess GH levels and is associated with comorbidities and altered body composition.MethodsWe studied 43 subjects (21 females and 22 males, mean age of 50.012.8) with acromegaly. The control group consisted of 40 gender- and age-matched subjects (25 females and 15 males, mean age of 48.88.8). Acromegaly patients were classified into two groups; active acromegaly (AA; n=26) and controlled acromegaly (CA; n=17). Metabolic, anthropometric and laboratory values of subjects were recorded. FGF-21 level was measured by ELISA assay.Results Median FGF-21 levels were significantly higher in acromegaly group compared to control group (85.5 vs. 59.0pg/mL, p=0.02, respectively). In the multiple regression model, FPG, A1c, HOMA-IR, glucose intolerance, BMI, visceral fat, hs-CRP, presence of hypertension, dyslipidemia and acromegaly were included as independent variables to explain variability of plasma FGF-21 levels in whole study group. The presence of acromegaly was the only determinant of increased FGF-21 levels in the whole study group ( coefficient=0.253, p=0.006).Conclusion FGF-21 levels were increased significantly in acromegaly group. Increased FGF-21 levels were significantly and independently associated with the state of acromegaly. Acromegaly may also be a FGF-21 resistance state independent from insulin resistance, glucose intolerance, obesity, hypertension and dyslipidemia.
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    AT-101 acts as anti-proliferative and hormone suppressive agent in mouse pituitary corticotroph tumor cells
    (Springer, 2018) Yurekli, B. S.; Karaca, B.; Kisim, A.; Bozkurt, E.; Atmaca, H.; Cetinkalp, S.; Ozgen, G.; Yilmaz, C.; Uzunoglu, S.; Uslu, R.; Saygili, F.
    Purpose Gossypol, a naturally occurring compound in cottonseeds, has anticancer effects against several tumor cell lines. It has been extensively studied in clinical trials and is well tolerated with a favorable safety profile. AT-101, a derivative of R (-)-gossypol, binds to Bcl-2 family proteins and induces apoptosis in vitro. Although transsphenoidal surgical excision of the pituitary corticotroph adenoma is the gold standard of care, it is not successful all the time. Medical therapy for Cushing's disease still remains a challenge for the clinicians. We aimed to investigate the cytotoxic and apoptotic effects of AT-101 in mouse pituitary corticotroph tumor AtT20 cells. Methods Cytotoxic effect of AT-101 was assessed by XTT cell viability assay. Apoptosis was shown by measuring DNA fragmentation and Caspase-3/7 activity. Changes in mRNA expressions of apoptosis-related genes were investigated by qPCR array after treatment with AT-101. ACTH was measured by ACTH-EIA Kit. Results AT-101 induced cytotoxicity and apoptosis in AtT20 cells. mRNA levels of pro-apoptotic genes such as TNFR-SF-10B, Bid, PYCARD, Caspase-8, Caspase-3, and Caspase-7 were induced by 2.0-, 1.5-, 1.7-, 1.5-, 1.6-, and 2-fold, respectively, in AtT20 cells by AT-101 treatment. Moreover, some of the anti-apoptotic genes such as BCL2L10, NAIP1, and PAK-7 were reduced by 2.1-, 2.3-, 4.0-fold, respectively, in AtT20 cells. AT-101 also decreased ACTH secretion significantly. Conclusion AT-101 induces apoptosis in mouse pituitary corticotroph tumor cells.
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    Epicardial fat, body mass index, and triglyceride are independent contributors of serum fibroblast growth factor 21 level in obese premenopausal women
    (Springer, 2015) Akyildiz, Z. I.; Polat, S.; Yurekli, B. S.; Kocabas, G. U.; Tuluce, K.; Tuluce, S. Y.; Kocabas, U.; Bozkaya, G.; Yuksel, A.; Nazli, C.
    Purpose The hormone fibroblast growth factor 21 (FGF-21) regulates carbohydrate and lipid homeostasis. FGF-21 represents an attractive novel therapy for obesity since administration of FGF-21 has been shown to improve metabolic abnormalities in obese animal models. We investigated FGF-21 and its relationship with epicardial fat thickness (EFT), metabolic parameters, and inflammatory markers in premenopausal obese women compared to controls with similar Systematic Coronary Risk Evaluation (SCORE) project risk profiles. Methods Forty-five obese premenopausal women with body mass index (BMI) >= 30 kg/m(2) and 41 control premenopausal women with BMI <25 kg/m(2) with similar SCORE project risk profiles were included in this case-control study. EFT was evaluated by two-dimensional transthoracic echocardiography. Serum FGF-21 was measured with an ELISA kit. Results FGF-21 and EFT were significantly higher in obese women compared to controls (p < 0.001). Multiple stepwise linear regression analysis showed that EFT, BMI, and triglycerides (TG) independently contributed to FGF-21 (R-2 = 0.757, p < 0.001). However, homeostasis model assessment of insulin resistance (HOMA-IR), visceral ectopic fat, and inflammatory markers were not found as a direct contributor to serum FGF-21 level (p > 0.05). Conclusions EFT, BMI, and TG may play an important role in predicting serum FGF-21 level which may be a potential therapeutic target in cardiometabolic disorders in the future.
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    PSEUDOPSEUDOHYPOPARATHYROIDISM AS A CAUSE OF FAHR SYNDROME: HYPOPARATHYROIDISM NOT THE ONLY ONE
    (Editura Acad Romane, 2020) Ozisik, H.; Yurekli, B. S.; Tuncel, R.; Ozdemir, N.; Baklaci, M.; Ekmekci, O.; Saygili, F.
    Introduction. Fahr's syndrome is an infrequent disorder characterized by bilateral symmetrical calcification of basal ganglia and the cerebral cortex. It can be seen genetic, idiopathic, or secondary to endocrine diseases. This disease is related to different metabolic disorders particularly with diseases of the parathyroid gland. Case 1. A 63-year-old female patient applied to our clinic due to having hypoparathyroidism with bilateral basal ganglia calcification in head computed tomography(CT). She had subtotal thyroidectomy 25 years ago. in the neurological examination, mild symmetrical parkinsonism was determined. in laboratory examination Ca:8 mg/dL (8.6- 10.2), P:5.1 mg/dL (2.3-4.5), PTH:9.53 pg/mL (15-65) were detected. Calcitriol 0.25 mu/day was added to her treatment. Her parkinsonism disappeared after the treatment. Case 2. A 49-year-old male patient was consulted when he was admitted to the department of neurology in our hospital. the physical examination demonstrated the characteristics of Albright's hereditary osteodystrophy. the neurological examination shows bilateral symmetrical bradykinesia, dysphagia, and moderate dysarthria. in the laboratory examination PTH: 46.5 ng/L(15-65), Ca:8.6 mg/dL (8.6-10.2), P:2.7 mg/dL (2.3-4.5) were detected and were all within the normal ranges. Consequently, pseudopseudohypoparathyroidism was decided as a diagnosis. G protein alpha subunit mutation (Gs alpha) was not detected due to technical limitations. Conclusion. When a patient is diagnosed as Fahr's syndrome, we should keep in mind parathyroid disorders. Fahr's syndrome must be evaluated in patients showing intracranial calcification accompanied by parathyroid diseases.