Association of obesity with cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease: Insights from TECOS.

BACKGROUND: Obesity is a risk factor for type 2 diabetes (T2D) and cardiovascular disease (CVD). Whether obesity affects outcomes among those with T2D and atherosclerotic CVD (ASCVD) remains uncertain. Our objective was to investigate the relationship between body mass index (BMI) and ASCVD outcomes among TECOS participants with T2D and ASCVD. METHODS: BMI categories were defined as underweight/normal weight (BMI <25 kg/m2), overweight (25-29.9 kg/m2), obese class I (30-34.9 kg/m2), obese class II (35-39.9 kg/m2), and obese class III (≥ 40 kg/m2). Asian-specific BMI categories were applied to Asian participants. Kaplan-Meier survival analysis and Cox proportional hazards models were used to examine associations between baseline BMI and a composite CV outcome (CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina). RESULTS: For 14,534 TECOS patients with available BMI, mean age was 65.5 years; 29.3% were female, 32.0% non-White, and 23.1% insulin-treated, with median 3 years' follow-up. At baseline, 11.6% (n = 1686) were underweight/normal weight, 38.1% (n = 5532) overweight, 32.2% (n = 4683) obese class I, 12.4% (n = 1806) obese class II, and 5.7% (n = 827) obese class III. The composite CV outcome occurred in 11.4% (n = 1663) of participants; the outcome risk was lower, compared with under/normal weight, in overweight (HR 0.83, 95% CI 0.71-0.98) and obese class I (HR 0.79, 95% CI 0.67-0.93) individuals. Obesity was not associated with worse glycemic control. CONCLUSIONS: The majority of TECOS participants with ASCVD and T2D were overweight or obese, yet overweight or obese class I individuals had lower CV risk than those who were under/normal weight. These results suggest the presence of an obesity paradox, but this paradox may reflect an epidemiological artifact rather than a true negative association between normal weight and clinical outcomes.

Sitagliptin does not reduce the risk of cardiovascular death or hospitalization for heart failure following myocardial infarction in patients with diabetes: observations from TECOS.

BACKGROUND: To examine the effects of the DPP-4i sitagliptin on CV outcomes during and after incident MI in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). METHODS: TECOS randomized 14,671 participants with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) to sitagliptin or placebo, in addition to usual care. For those who had a within-trial MI, we analyzed case fatality, and for those with a nonfatal MI, we examined a composite cardiovascular (CV) outcome (CV death or hospitalization for heart failure [hHF]) by treatment group, using Cox proportional hazards models left-censored at the time of the first within-trial MI, without and with adjustment for potential confounders, in intention-to-treat analyses. RESULTS: During TECOS, 616 participants had ≥ 1 MI (sitagliptin group 300, placebo group 316, HR 0.95, 95% CI 0.81-1.11, P = 0.49), of which 25 were fatal [11 and 14, respectively]). Of the 591 patients with a nonfatal MI, 87 (15%) died subsequently, with 66 (11%) being CV deaths, and 57 (10%) experiencing hHF. The composite outcome occurred in 58 (20.1%; 13.9 per 100 person-years) sitagliptin group participants and 50 (16.6%; 11.7 per 100 person-years) placebo group participants (HR 1.21, 95% CI 0.83-1.77, P = 0.32, adjusted HR 1.23, 95% CI 0.83-1.82, P = 0.31). On-treatment sensitivity analyses also showed no significant between-group differences in post-MI outcomes. CONCLUSIONS: In patients with type 2 diabetes and ASCVD experiencing an MI, sitagliptin did not reduce subsequent risk of CV death or hHF, contrary to expectations derived from preclinical animal models. Trial registration clinicaltrials.gov no. NCT00790205.

Secondary Prevention of Cardiovascular Disease in Patients With Type 2 Diabetes Mellitus: International Insights From the TECOS Trial (Trial Evaluating Cardiovascular Outcomes With Sitagliptin).

BACKGROUND: Intensive risk factor modification significantly improves outcomes for patients with diabetes mellitus and cardiovascular disease. However, the degree to which secondary prevention treatment goals are achieved in international clinical practice is unknown. METHODS: Attainment of 5 secondary prevention parameters-aspirin use, lipid control (low-density lipoprotein cholesterol <70 mg/dL or statin therapy), blood pressure control (<140 mm Hg systolic, <90 mm Hg diastolic), angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, and nonsmoking status-was evaluated among 13 616 patients from 38 countries with diabetes mellitus and known cardiovascular disease at entry into TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin). Logistic regression was used to evaluate the association between individual and regional factors and secondary prevention achievement at baseline. Cox proportional hazards regression analysis was used to determine the association between baseline secondary prevention achievement and cardiovascular death, myocardial infarction, or stroke. RESULTS: Overall, 29.9% of patients with diabetes mellitus and cardiovascular disease achieved all 5 secondary prevention parameters at baseline, although 71.8% achieved at least 4 parameters. North America had the highest proportion (41.2%), whereas Western Europe, Eastern Europe, and Latin America had proportions of ≈25%. Individually, blood pressure control (57.9%) had the lowest overall attainment, whereas nonsmoking status had the highest (89%). Over a median 3.0 years of follow-up, a higher baseline secondary prevention score was associated with improved outcomes in a step-wise graded relationship (adjusted hazard ratio, 0.60; 95% confidence interval, 0.47-0.77 for those patients achieving all 5 measures versus those achieving ≤2). CONCLUSIONS: In an international trial population, significant opportunities exist to improve the quality of cardiovascular secondary prevention care among patients with diabetes mellitus and cardiovascular disease, which in turn could lead to reduced risk of downstream cardiovascular events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00790205.

Evaluation of biomechanical properties of the cornea in patients with primary hyperparathyroidism.

The purpose of this study is to compare the corneal biomechanical properties in primary hyperparathyroid patients and healthy control subjects. The study consisted of 31 patients with primary hyperparathyroidism (study group) and 31 healthy subjects (control group). Corneal biomechanical properties, including corneal hysteresis (CH), corneal resistance factor (CRF), and intraocular pressure (IOP) were measured with an ocular response analyzer (ORA). IOP was also measured using Goldmann applanation tonometry (GAT), and central corneal thickness (CCT) was measured with an ultrasonic pachymeter. The differences in ORA parameters and CCT between study and control group participants were analyzed. The mean CH in study and control groups was 8.7 ± 1.9 mmHg (5.3-13.7 mmHg) and 9.8 ± 1.5 mmHg (7.7-14.3 mmHg), respectively (p = 0.018). The mean CRF was 9.5 ± 1.8 (5.5-13.7) in the study group compared with 9.8 ± 1.5 (6.2-12.8) in the control group. The difference for CRF was not statistically significant (p = 0.41). In study and control group, corneal-compensated IOP (IOPcc) values were 18.2 ± 4.2 and 16.9 ± 2.7 mmHg, respectively (p = 0.12). Mean IOP measurement values with GAT were 16.3 ± 3.4 mmHg for study group and 16.5 ± 2.7 mmHg for control group (p = 0.71). The mean differences of IOPcc and IOPGAT in the study group eyes were higher than that of control group eyes (1.9 vs. 0.4 mmHg). CCT was 536.5 ± 25.4 µm (490-593 µm) in study group eyes compared with 534.2 ± 31.4 µm (472-602 µm) in control eyes (p = 0.75). Hyperparathyroidism could be associated with a decrease of CH. The differences between IOPcc and IOPGAT in these patients were higher than normal subjects. Underestimation of IOP readings with GAT may be a consequence of the lower CH in patients with hyperparathyroididsm.

The role of BRD7 in embryo development and glucose metabolism.

Bromodomain-containing protein 7 (BRD7) is a member of bromodomain-containing protein family and its function has been implicated in several diseases. We have previously shown that BRD7 plays a role in metabolic processes. However, the effect of BRD7 deficiency in glucose metabolism and its role in in vivo have not been fully revealed. Here, we report the essential role of BRD7 during embryo development. Mice homozygous for BRD7 led to embryonic lethality at mid-gestation. Homozygous BRD7 knockout (KO) mice showed retardation in development, and eventually all BRD7 KO embryos died in utero prior to E16.5. Partial knockdown of Brd7 gene displayed mild changes in glucose metabolism.

Normocalcemic hyperparathyroidism is associated with complications similar to those of hypercalcemic hyperparathyroidism.

Normocalcemic primary hyperparathyroidism (NC-PHPT) is a variant of hyperparathyroidism, characterized by normal serum calcium levels, high parathyroid hormone (PTH) and normal 25-OH vitamin D status. The present study aimed to compare complications related to hyperparathyroidism in patients with NC-PHPT and hypercalcemic PHPT (HC-PHPT). We retrospectively evaluated the records of 307 PHPT patients between January 2010 and March 2013. We excluded patients with impaired renal function and liver failure. All patients underwent a biochemical and hormonal examination including serum glucose, albumin, total calcium, phosphorus, creatinine, lipoproteins, PTH and 25-OH vitamin D. Nephrolithiasis and bone mineral density were documented based on a review of the medical records. The study population consisted of 36 (12 %) males and 271 (88 %) females with a mean age of 53.3 ± 9.5 years (29-70 years). Twenty-three of the patients were diagnosed with NC-PHPT (group 1) and 284 were diagnosed with HC-PHPT (group 2). There were no significant differences in terms of age, gender, prevalence of hypertension, low bone mineral density and kidney stones between the groups. The mean thyroid-stimulating hormone (TSH) and low-density lipoprotein (LDL) levels were significantly higher in group 1 than in group 2. Our study found that patients with NC-PHPT have similar several complications as patients with HC-PHPT. NC-PHPT patients have higher TSH levels despite being within the normal range, and higher LDL-C levels than patients with HC-PHPT. However, this relationship needs to be clarified in future studies with larger cohorts.

Serum vaspin and adiponectin levels in patients with prolactinoma.

BACKGROUND: Studies investigating serum vaspin and adiponectin levels in patients with prolactinoma are inconclusive. The aim of this study was to evaluate serum vaspin and adiponectin levels in patients with prolactinoma and healthy controls. METHODS: A total of 42 prolactinoma patients (Group 1, 21 patients; Group 2, 21 patients) and 30 healthy controls were enrolled in the study. Group 1 consisted of newly diagnosed patients who were never treated or had not received a dopamine agonist (DA) within 6 months prior to screening. Group 2 consisted of prolactinoma patients who were on DA treatment for at least 6 months at the time of screening. The control group (group 3) consisted of healthy controls. RESULTS: Patients with prolactinoma had higher homeostasis model assessment of insulin resistance and lower quantitative insulin sensitivity check index values in comparison to healthy controls (p < 0.001 for both). Serum levels of adiponectin and vaspin were also significantly lower in prolactinoma patients when compared to the control group (p < 0.01 and p < 0.001, respectively). Following adjustment for confounding factors, the respective odds ratios for prolactinoma in patients in the lower subgroup compared with those in the higher subgroup for adiponectin and vaspin were 2.733 (0.621-12.035; p > 0.05) and 5.041 (1.191-21.339; p < 0.05). CONCLUSION: This is the first study to demonstrate the presence of low vaspin levels in patients with prolactinomas. Further studies are needed to help establish the roles of vaspin and adiponectin in prolactinoma patients.

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

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.

Patient characteristics and statin discontinuation-related factors during treatment of hypercholesterolemia: an observational non-interventional study in patients with statin discontinuation (STAY study).

OBJECTIVE: The purpose of this study was to identify patient characteristics and statin discontinuation-related factors in patients with hypercholesterolemia. METHODS: A total of 532 patients (age mean±SD: 57.4±11.5 years; 52.4% women, 47.6% men) with hypercholesterolemia and statin discontinuation were included in this national cross-sectional non-interventional observational study. Data on socio-demographic characteristics of patients, cardiovascular risk factors, past treatment with and discontinuation of statin treatment were collected in one visit. RESULTS: Mean±SD duration of hypercholesterolemia was 4.9±4.2 years at time of discontinuation of statin treatment. Statin treatment was initiated by cardiologists in the majority of cases (55.8%), whereas discontinuation of statin treatment was decided by patients in the majority of cases (73.7%), with patients with higher (at least secondary education, 80.4%) more likely than those with lower (only primary education, 69.7%) to decide to discontinue treatment (p=0.022). Negative information about statin treatment disseminated by TV programs-mostly regarding coverage of hepatic (38.0%), renal (33.8%), and muscular (32.9%) side effects (32.9%)-was the most common reason for treatment discontinuation. CONCLUSION: The decision to discontinue statin treatment was made at the patient's discretion in 74% of cases, with higher likelihood of patients with higher educational status deciding to discontinue treatment and switch to non-drug lipid-lowering alternatives. Cardiologists were the physicians most frequently responsible for the initiation of the statin treatment; coverage of several non-life-threatening statin side effects by TV programs and patients' lack of information regarding high cholesterol and related risks were the leading factors predisposing to treatment discontinuation.

Effect of allogeneic limbal mesenchymal stem cell therapy in corneal healing: role of administration route.

AIMS: To investigate whether allogeneic limbal mesenchymal stem cell (LMSC) therapy affects corneal healing after a severe chemical burn and whether the route of administration of LMSCs differs in its therapeutic effect in this respect. METHODS: A total of 60 Sprague-Dawley rats with clinically proven alkali injury were divided into four equal groups (n = 15) as follows: group 1: 2 × 10(5) cells/drop LMSCs, topically applied 6 times a day for 2 days; group 2: 2.4 × 10(6) cells in 0.5 ml LMSCs, subconjunctivally applied; group 3: 2.4 × 10(6) cells in 1 ml LMSCs, intraperitoneally applied, and group 4: no LMSC treatment. The groups were compared according to grades of corneal opacity (CO), corneal neovascularization (CNV) and corneal fluorescein staining (CFS). The migration of LMSCs into the cornea and the inflammatory characteristics of the groups were evaluated with BrdU (5-bromo-2'-deoxyuridine bromodeoxyuridine) immunostaining and histopathologically in a 4-week follow-up. RESULTS: There were statistically significant differences between the LMSC-treated and control groups in each week regarding mean CO scores and in the 3rd week regarding the mean CNV and CFS scores (p < 0.05). The statistical significance was due to the differences between the topical and the control group and between the subconjunctival and the control group. BrdU+ LMSCs were seen in the corneal epithelium of the all LMSC-administered rats, and fewer inflammatory changes were observed in these rats. CONCLUSION: Allogeneic LMSC treatment, especially topical and subconjunctival administration, seems to be helpful in affecting corneal healing after a severe corneal burn.

Zofenopril attenuates injury induced by ischemia-reperfusion on rat ovary.

AIM: The aim of the study was to investigate the effectiveness of zofenopril in an experimental model of ovarian torsion in rats with histologic and biochemical assessments. MATERIAL AND METHODS: Experimental procedures were performed on 35 female rats (Wistar albino). Rats were randomly divided into five groups as: sham (sham operated, n = 7); vehicle group 1 (torsion-detorsion, n = 7) with 2 h ischemia and 2 h reperfusion; vehicle group 2 (torsion-detorsion, n = 7) with 2 h ischemia and 5 days' reperfusion; zofenopril group 1 (torsion-detorsion, n = 7) with 2 h ischemia, 2 h reperfusion and a signal dose of oral 15 mg/kg zofenopril; and zofenopril group 2 (torsion-detorsion, n = 7) with 2 h ischemia, 5 days' reperfusion and 5 days' oral 15 mg/kg zofenopril. A scoring of histopathologic evaluation was performed on the ovaries according to congestion, bleeding, edema, and cellular degeneration. Biochemical assessments included catalase, tissue malondialdehyde and protein carbonyl. RESULTS: Compared with the vehicle groups, histopathologic scores, tissue malondialdehyde and protein carbonyl levels, which reflect oxidative stress markers, were significantly lower in the zofenopril groups. Furthermore, catalase levels were significantly increased in the zofenopril group. CONCLUSION: Our study results revealed that zofenopril attenuates injury induced by ischemia-reperfusion on rat ovary.

The relationship between cytotoxin-associated gene A positive Helicobacter pylori infection and autoimmune thyroid disease.

OBJECTIVE: The aim of this study was to determine whether there is an association between cagA [cytotoxin-associated gene A] positivity and thyroid autoimmunity and thyroid volume. METHODS: This prospective study included 78 Helicobacter pylori-positive (H. pylori) dyspeptic patients in the study group, and 50 age-, gender-, and body mass index-matched H. pylori-negative dyspeptic patients in the control group. All the controls were evaluated via upper gastrointestinal endoscopic biopsy or breath test, and were found as H. pylori negative. Gastric biopsy specimens were obtained via endoscopy and histological examination was performed for documentation of H. pylori. RESULTS: In all, 55.1% (n = 43) of the H. pylori-positive patients were cagA positive. There was no significant difference in metabolic syndrome parameters or thyroid function test results between the study and control groups. The frequency of anti-TPO and Hashimoto's thyroiditis positivity was significantly higher in the study group than in the control group. Thyroid volume was higher and severe parenchymal heterogeneity was more common in the H. pylori-positive patients. CONCLUSIONS: H. pylori infection might be a risk factor for autoimmune thyroid disease and high thyroid volume in patients diagnosed with histological evaluation. However, cagA positivity has no additional effect on these parameters.

Elastography in the differential diagnosis of thyroid nodules.

Despite the publication of a recent meta-analysis of elastography in thyroid nodules, further work is necessary on this issue in different populations. In this study, we aimed to evaluate the clinical value of elastography on nodular goiters in mild iodine-deficient regions without excluding patients according to nodule characteristics. This prospective study was conducted between April 2010 and December 2011 in Yildirim Beyazit Diskapi Research Hospital Endocrinology outpatient clinic. Five hundred twenty-eight nodular goiter patients who underwent thyroid fine-needle aspiration biopsy were included in our study. Elastography scores and indexes were measured with real-time ultrasound elastography (Hitachi® EUB 7000 HV machine with 13 MHz linear transducer). There were 471 females and 57 males and their ages ranged from 45 years to 78 years. A total of 601 nodules were evaluated in these patients. The area under the curve (AUC) for the elasto score was 0.91 (p < 0.0001) and AUC for the strain index (SI) was 0.96 (p < 0.0001). We suggest that the SI reflects malignancy better than the elasto score. We conclude that elastography scores greater than 3 have 76% sensitivity and 96% specificity for diagnosing malignancy. For SI, we conclude that 3.75 (83% sensitivity and 95% specificity) is the cutoff point. Elasto score and SI measurements of thyroid nodules in our population are efficient and increase the diagnostic performance of the sonography.

Isolated vitamin D deficiency is not associated with nonthyroidal illness syndrome, but with thyroid autoimmunity.

AIM: This study aimed to compare thyroid functions, thyroid autoantibodies, and the existence of nonthyroidal illness syndrome (NTIS) according to vitamin D level. MATERIALS AND METHODS: The study included age- and BMI-matched healthy volunteers with and without vitamin D deficiency. In addition, the nonthyroidal illness syndrome status was evaluated. RESULTS: Anti-TPO positivity was significantly more common in those with severe and moderate vitamin D deficiency, as compared to those with a normal 25(OH)D level. Furthermore, TSH levels were significantly lower in those with severe and moderate vitamin D deficiency than in those with a normal 25(OH)D level. In addition, there was a significant weak inverse correlation between anti-TPO positivity and the 25(OH)D level and a positive correlation between the TSH level and 25(OH)D level. Only 1 thyroid function test result was compatible with NTIS among the participants with moderate vitamin D deficiency; therefore the difference was not significant. CONCLUSIONS: The prevalence of thyroid autoantibody positivity was higher in those with severe and moderate vitamin D deficiency than in those with a normal 25(OH)D level. Additional large-scale studies must be conducted to determine if vitamin D deficiency plays a causal role in the pathogenesis of Hashimoto's thyroiditis and NTIS.

Three noninvasive methods in the evaluation of subclinical cardiovascular disease in patients with acromegaly: epicardial fat thickness, aortic stiffness and serum cell adhesion molecules.

CONTEXT: Several studies have reported increased risk of cardiovascular disease due to early development of endothelial dysfunction and structural vascular changes in patients with acromegaly. OBJECTIVE: The aim of this study was to evaluate subclinical cardiovascular disease with epicardial fat thickness (EFT), aortic stiffness and serum levels of cell adhesion molecules (CAMs) in patients with acromegaly. DESIGN: Cross-sectional study. PATIENTS: Twenty-seven patients with active acromegaly (AA), 13 patients with remission acromegaly (RA) and 37 age- and sex-matched healthy controls were studied. MEASUREMENTS: Epicardial fat thickness was evaluated by transthoracic echocardiography (TTE). Aortic stiffness (ß) index, aortic strain (AoS) and aortic distensibility (AoD) were calculated from the aortic diameters measured by TTE. Serum levels of CAMs such as intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1 and E-selectin were measured. RESULTS: Epicardial fat thickness was significantly increased in patients with RA and AA as compared to controls 9·71 ± 1·54 and 10·08 ± 1·95 mm vs 5·74 ± 0·92 mm, P < 0·001, respectively). A significant positive correlation was found between the EFT and growth hormone (GH) levels (r = 0·365, P = 0·024). ß-index was similarly higher in patients with RA and AA than controls (15·68 ± 7·27 and 11·90 ± 8·24 vs 6·85 ± 2·87, P < 0·001, respectively). AoS and AoD were significantly decreased in patients with RA and AA as compared to the control group (3·81 ± 1·94 and 3·68 ± 1·99 vs 8·19 ± 4·19%, P < 0·001, respectively; and 1·21 ± 0·66 and 1·18 ± 0·63 vs 2·58 ± 1·50, 10(-6) cm(2) /dyn, P < 0·001, respectively). Serum ICAM-1 and VCAM-1 levels were significantly higher in patients as compared to the control group (P < 0·001 vs P = 0·032, respectively). There were no significant differences in EFT, AoD, AoS, ß-index and serum CAMs between two patients groups (AA vs RA, P > 0·05). There was a significant negative correlation between E-selectin and AoD (r = -0·45, P = 0·008). In multiple linear regression analysis, EFT was found to be associated with GH levels (ß-coefficient = 0·575, P = 0·008). CONCLUSION: This study suggests that EFT and risk of subclinical cardiovascular disease are increased in patients with acromegaly. Serum GH level is an independent risk factor for EFT.

Preclinical atherosclerosis in patients with prolactinoma.

OBJECTIVE: The aim of this study was to evaluate the effect of hyperprolactinemia on body fat, insulin sensitivity, inflammatory markers, and cardiovascular risk in patients with prolactinoma. METHODS: The study included 35 untreated hyperprolactinemic patients with pituitary adenomas, and 36 age-, gender-, and body mass index (BMI)-matched healthy controls without any known disease. Serum glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR, lipid profile, high-sensitivity C-reactive protein (hs-CRP), and heart-type fatty acid binding protein (H-FABP) levels were measured. Waist and hip circumference (WC and HC) were measured in all the participants. The body fat percentage was measured, and the visceral fat and abdominal fat percentages were measured via bioelectrical impedance (BIA). In addition, carotid intima media thickness (CIMT) was measured using high-resolution B-mode ultrasound. RESULTS: The serum glucose level, HOMA-IR, triglyceride level, and SC were significantly higher in the patient group than in the control group. The hs-CRP level and CIMT were significantly higher in the hyperprolactinemic patients. Visceral and truncal fat percentages were significantly higher in the patients with prolactinoma. H-FABP levels were similar in the 2 groups, and there was a positive correlation between the prolactin (PRL) and H-FABP protein levels. CONCLUSIONS: Based on the present findings, hyperprolactinemia is associated with preclinical atherosclerosis and metabolic abnormalities. Patients with hyperprolactinemia might experience cardiovascular disease in the long term. Metabolic control should be achieved in addition to the control of hyperprolactinemia in the clinical management of patients diagnosed with prolactinoma.

Protection from cyclophosphamide-induced ovarian damage with bone marrow-derived mesenchymal stem cells during puberty.

OBJECTIVE: In female cancer survivors, the accelerated loss of primordial follicles may lead to premature ovarian failure. We investigated the protective effects of bone marrow derived mesenchymal stem cells (BMMSC) and gonadotropin releasing hormone analogue (GnRHa) against chemotherapeutic-induced ovarian toxicity in a rat model. MATERIAL AND METHODS: Forty-eight Wistar albino female rats were divided into four groups. Group 1 was composed of rats that were given 200 mg/kg cyclophosphamide injection for each cycle (two cycles for each rat). Both cyclophosphamide and 0.4 µg GnRHa were administered to Group 2. Cyclophosphamide and 4 million/kg BMMSC were administered to Group 3. Cyclophosphamide, GnRHa, and BMMSC were administered to Group 4. Germ cell apoptosis, DNA fragmentation and primordial follicular count were investigated with Cleave Caspase-9 and TUNEL analysis. The presence of the SRY gene on the Y chromosome in the ovary of the recipient female rats was checked with PCR. RESULTS: Immunohistochemical staining (IHS) of Caspase-9 and TUNEL was higher in Group 1 than in Group 3 (p < 0.05). Similarly, Group 4 had higher values than Group 3 (p < 0.05). The presence of the SRY gene was detected in Groups 3 and 4 with the PCR analysis. The mean primordal follicle count was lowest in Group 1 and the mean primordial follicle counts were higher in Groups 2 and 3 than in Group 1. The difference between Group 1 and Group 4 was not significant. CONCLUSION: BMMSC therapy was found to be protective from germ cell apoptosis and DNA damage when it was used with chemotherapy regimens including alkylating agents.

M30 does not predict the severity of hepatosteatosis, whereas adiponectin level declined with increase of ALT and the severity of hepatic steatosis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is an emerging problem all over the world. Because NAFLD and polycystic ovary syndrome (PCOS) are both closely related with insulin resistance, it would be necessary to determine the rate of presence of NAFLD in PCOS patients. So, this study aimed to investigate the utility of M30 in PCOS patients for the diagnosis of hepatic injury. METHODS: Eighty patients with PCOS were included in the study. Ultrasonographic examination for the presence of hepatic steatosis, M30 serum level for determining the severity of ongoing apoptotic cell death in liver, and BARD index for defining the hepatic injury were performed during the study. 25-OH vitamin D and adiponectin level in sera were studied using ELISA (Enzyme-Linked ImmunoSorbent Assay). RESULTS: M30 and vitamin D levels did not change significantly with the severity of hepatic steatosis. On the other hand, M30 levels showed a positive correlation with ALT and AST levels, and M30 level suddenly increased with the presence of hepatic steatosis from 159.7 to 170 U/l, however stabilized with the increasing severity of hepatic setatosis. Adiponectin levels decreased with the increasing severity of hepatic steatosis and significantly varied between ALT greater than 40 U/l and less than 40 U/l. CONCLUSIONS: M30 level in serum increased with the appearance of hepatic steatosis and had a positive correlation with a noninvasive hepatic injury test, BARD (BMI, aspartate aminotransferase [AST]/alanine aminotransferase [ALT] ratio [AAR], diabetes mellitus [DM]) index. Adiponectin level decreased with the increasing ALT level and severity of hepatic steatosis.

Permanent central diabetes insipidus as a complication of sphenoid sinus mucocele.

Although mucocele is a benign lesion, its unavoidable expansions may result in irreversible damages in adjacent organs. In spheno-ethmoid mucoceles which are extremely rare, this condition may cause more severe problems. Central diabetes insipidus, developed secondary to sphenoid sinus mucocele, was detected in a 54-year-old male patient, who underwent endoscopic sinus surgery 2 times due to nasal polyposis. Endoscopic sphenoid mucocele marsupialization was performed to the patient, but despite partial regression in the 1-year follow up, complete recovery was not observed.

Hyperprolactinaemia associated with increased thyroid volume and autoimmune thyroiditis in patients with prolactinoma.

OBJECTIVE: The aim of this investigation was to evaluate the effects of hyperprolactinaemia on thyroid function, volume and nodularity in patients with prolactinoma. CONTEXT: Hyperprolactinaemia has been associated with various autoimmune diseases; however, the data on the correlation between the level of prolactin (PRL) and thyroid disorders have not been adequately clarified. DESIGN: Case-control study. PATIENTS: Forty-eight subjects with new diagnosis of hyperprolactinaemia (group 1) and 39 subjects undergoing treatment for prolactinoma (group 2) were recruited from our outpatient clinic. Fifty-two healthy subjects were included as a control group (group 3). MEASUREMENTS: The serum PRL, thyroid-stimulating hormone (TSH), thyroxine (free T4), thyroidal microsome (anti-TPO) and antithyroglobulin antibodies (TgAb) levels were evaluated, and ultrasonographic thyroid volume was calculated. RESULTS: The frequencies of positive anti-TPO and TgAb were significantly higher in group 1 than in groups 2 and 3 (P = 0·008). Also, the percentage of patients with thyroid heterogeneity were significantly higher in groups 1 and 2 than in group 3 (P < 0·05). The percentage of patients with thyroid nodules were higher in group 1 than in groups 2 and 3 (p1-2 = 0·03, p1-3 = 0·05 and p2-3 = 0·637). The mean thyroid volume was significantly higher in group 1 (P = 0·001), and a positive correlation was found between thyroid volume and the level of PRL (r = 0·616; P = 0·0001). Prolactin had a significant effect on the total volume according to stepwise multiple linear regression analysis (adjusted R(2) is 0·268; P < 0·0001). CONCLUSIONS: Patients with hyperprolactinaemia have significantly increased thyroid volume, thyroid autoimmunity and nodule prevalence.