Chronotropic Responses to GLP-1 Receptor Agonists and Sitagliptin in Atria From Diabetic Rats.

ABSTRACT: Type 2 diabetes mellitus increases the risk of cardiovascular diseases. Therefore, elucidation of the cardiovascular effects of antidiabetics is crucial. Incretin-based therapies are increasingly used for type 2 diabetes mellitus treatment as monotherapy and in combination. We aimed to study the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sitagliptin on beating rates in isolated atria from diabetic rats. The chronotropic responses to GLP-1 RAs and sitagliptin as monotherapy and in combinations with metformin, pioglitazone, and glimepiride in isolated atria from control and diabetic rats were determined. GLP-1 (7-36), GLP-1 (9-36), and exendin-4 (1-39) produced increases in beating rates in both control and diabetic rat atria. However, sitagliptin increased the beating frequency only in the diabetic group. Exendin (9-39), nitro- l -arginine methyl ester hydrochloride, and indomethacin blocked responses to GLP-1 RAs but not the response to sitagliptin. Glibenclamide, 4-aminopyridine, apamin, charybdotoxin, superoxide dismutase, and catalase incubations did not change responses to GLP-1 RAs and sitagliptin. GLP-1 RAs increase beating rates in isolated rat atrium through GLP-1 receptor, nitric oxide, and cyclooxygenase pathways but not potassium channels and reactive oxygen radicals.

Can lipid mediators and free fatty acids guide acute coronary syndrome diagnosis and treatment?

OBJECTIVE: The aim of this study was to investigate fatty acids, lipid mediator levels, and the desaturase index rates on different acute coronary syndrome types and their possible relationship with routine lipid parameters. METHODS: The study included 81 patients with myocardial infarction (MI), 20 patients with unstable angina pectoris, and 31 healthy people. Fatty acids, CD59, lipoxin A4, 8-isoprostane, serum lipids, albumin, C-reactive protein (CRP), and high sensitive troponin levels were measured in all participants. RESULTS: When the fatty acid groups were evaluated as a ratio of albumin, MUFA/albumin and SFA/albumin ratios were significantly higher in the MI group compared to the control group. Although CD59 and lipoxin A4 levels were higher in the control group, there was no significant differences between the groups. When lipoxin A4/CRP and CD59/CRP ratios were evaluated, the results were significantly lower than those in the control group. CONCLUSION: Lipid mediators may be useful in treating atherosclerosis by contributing to the resolution of inflammation.

Diagnostic value of thyroglobulin washout in fine-needle aspiration samples for diagnosis and follow-up of differentiated thyroid cancer.

Our goal was to assess the effectiveness of fine-needle aspiration thyroglobulin (FNA-Tg) in detecting malignant lymph nodes (LNs) in patients with differentiated thyroid cancer (DTC). We also aimed to determine the factors that affect the accuracy of FNA-Tg. We conducted a retrospective cohort study using the laboratory, ultrasonographic, histopathological, FNA cytology (FNA-C), and FNA-Tg results of 176 DTC patients. We used receiver operating characteristic analysis to identify the cutoff value of FNA-Tg, and binary regression analysis to compare FNA-Tg with other diagnostic parameters. Spearman correlation was utilized to identify factors that influence FNA-Tg. Our study revealed that a cutoff value of 3.14 ng/mL for FNA-Tg had a sensitivity of 91.8% and a specificity of 96.6% in detecting malignant LNs in the entire group. In the subgroup with thyroid tissue, the optimal cutoff value for FNA-Tg was determined to be 15.5 ng/mL. Additionally, FNA-C had a sensitivity of 82.4% and a specificity of 99.4% for the entire group. The combined use of FNA-Tg and FNA-C yielded a sensitivity of 100% and a specificity of 96%, which was found to be more effective than using either test alone. Serum Tg positivity and serum thyroid-stimulating hormone were positively correlated with FNA-Tg levels in detecting malignant LNs. Our study demonstrated that FNA-Tg is a reliable method for detecting LN metastases in DTC patients, with a 3.14 ng/mL cutoff value. However, each center should take into account factors such as serum thyroid-stimulating hormone, serum Tg, and the presence of thyroid tissue when interpreting FNA-Tg results and determining the appropriate cutoff level.

Anti-mutated citrulline vimentin antibodies may be higher in Ankylosing spondylitis, but may not have a role in diagnosing disease and may not be associated with disease severity.

OBJECTIVE: Ankylosing spondylitis (AS) is a rheumatologic disease with severe morbidity and mortality. Many studies in the literature showing that serum antibodies against anti-mutated citrullinated vimentin (anti-MCV ab) can be elevated in rheumatoid arthritis (RA) patients. However, there is little data in the literature about the levels of anti-MCV antibodies in AS patients. We designed the study to evaluate the role of anti-MCV antibody in the diagnosis of AS and to investigate whether it is associated with disease activity parameters. METHODS: There were three separate groups in our study. The number of participants in these groups is 60 patients in the AS group, 60 patients in the RA group, and 50 healthy participants in the control group. The anti-MCV ab levels of the participants were measured by enzyme-like immune assay method. We compared anti-MCV levels between groups. We then evaluated its role in the diagnosis of AS and evaluated its relationship with disease activity parameters. RESULTS: The anti-MCV antibody levels of both AS (p=0.006) and RA (p>0.001) patients were found to be significantly higher than controls. Anti-MCV antibody was higher than predefined threshold level (20 IU/mL) in 4 of 60 (6.7%) AS patients. Anti-MCV levels are similar in patients with or without a -acceptable symptom state (PASS). There is also no appropriate anti-MCV cutoff level with respect to PASS and a highly sensitive and specific level for diagnosis of AS. CONCLUSION: Although AS patients has higher anti-MCV levels than controls, it may have a limited ability to AS diagnosis and to predict severity of the disease.

C allele in transforming growth factor-ß1 rs1800471 gene polymorphisms might indicate a protective feature in encapsulating peritoneal sclerosis development.

INTRODUCTION: Peritoneal fibrosis may progress in peritoneal dialysis (PD) patients to a fatal clinical condition called encapsulating peritoneal sclerosis (EPS). Transforming growth factor (TGF)-ß plays a pivotal role in the pathogenesis of peritoneal fibrosis. We aimed to investigate the association among polymorphisms in the gene encoding TGF-ß1, which were -509C/T (rs1800469), +869T/C (rs1982073), and +915G/C (rs1800471) in EPS patients. METHODS: A total of 16 PD patients who were clinically and radiologically diagnosed with EPS were enrolled and 22 age- and gender-matched PD patients were selected as the non-EPS group. RESULTS: G allele frequency at the rs1800471 gene polymorphism was significantly higher in the EPS group than non-EPS group (p = 0.005). Interestingly, the non-EPS group patients had CC or CG polymorphisms. CONCLUSION: C allele in TGF-ß1 rs1800471 gene polymorphisms might indicate a protective feature in EPS development. Knowing the presence of polymorphism may be effective in selecting renal replacement therapy in patients.

Does proton pump inhibitor reduce the antiaggregant efficacy of aspirin in ischemic stroke?

OBJECTIVE: To evaluate the effect of using acetylsalicylic acid (aspirin) together with lansoprazole in the secondary prevention of ischemic stroke. MATERIALS AND METHODS: 199 patients with a diagnosis of ischemic stroke and transient ischemic attack (TIA) using 100 mg aspirin regularly were included in the study. All patients were evaluated for the presence of aspirin resistance before starting the study. 57 patients with aspirin resistance were excluded from the study. The remaining 142 patients were divided into two groups: the 1st group consisted of those with stomach discomfort and the 2nd group consisted of those without stomach discomfort. Patients in group 1 were given 30 mg of lansoprazole taken before breakfast in addition to aspirin therapy. All patients were re-evaluated for the presence of aspirin resistance at a one-month follow-up. The antiaggregant activity was evaluated by the impedance aggregometry method in both groups. RESULTS: Of 142 patients, 75 were in group 1, and 67 were in group 2. There was no difference between the two groups in terms of age and gender distribution of vascular risk factors. There was no statistically significant difference between the two groups in terms of aspirin efficacy. The dose of aspirin was increased in patients with aspirin resistance (AR). CONCLUSION: The combination of 30 mg lansoprazole and 100 mg aspirin does not cause a decrease in antiaggregant activity in the early period, but chronic use was not evaluated in this study. Patients with AR may benefit from an increase in the dose of aspirin.

Effect of different storage solutions on oxidative stress in human saphenous vein grafts.

BACKGROUND: Ischemia-reperfusion injury of saphenous vein grafts (SVG) during coronary artery bypass grafting surgery negatively impacts endothelial integrity and functionality and is associated with vein graft failure. The aim of this study was to evaluate the level of oxidative stress in human SVG segments following ischemic storage in three intraoperative graft storage solutions: saline (S), autologous heparinized blood (HB) and DuraGraft (DG). METHODS: 3 mm tissue rings derived from surplus SVG segments from 50 patients were stored at room temperature for 30 min in DG, S or HB. Total oxidative status (TOS) and total antioxidant status (TAS) levels were determined from which the oxidative stress index (OSI: TOS/TAS ratio) was calculated. A p-value < 0.017 was considered significant implementing a Bonferroni correction. RESULTS: TOS values were significantly lower for DG stored samples in comparison to both S and HB; there was no difference between S and HB (DG: 32.6 ± 1.8, S: 39.6 ± 2.8 and HB: 40.6 ± 2.4 µmol H2O2 eqv.; DG vs. S and DG vs. HB p < 0.0001, S vs. HB p = 0.047). TAS was higher for both DG and HB in comparison to S (DG: 8.9 ± 0.9, S: 6.9 ± 1.0 and HB: 8.6 ± 0.9 mmol Trolox eqv.; DG vs S p < 0.0001, DG vs. HB p = 0.263, S vs. HB p < 0.0001). OSI differed between all groups with the lowest value for DG (DG: 3.7 ± 0.2, S: 5.8 ± 0.4 and HB: 4.7 ± 0.2 µmol H2O2 eqv./mmol Trolox eqv.; all p < 0.0001). CONCLUSIONS: Saphenous veins grafts stored in DuraGraft had a lower oxidative level, higher antioxidant level and a lower oxidative stress index in comparison to saphenous vein grafts stored in saline or heparinized blood. ClinicalTrials.gov Identifier NCT02922088.

Investigation of asymptomatic intestinal inflammation in ankylosing spondylitis by fecal calprotectin.

BACKGROUND AND STUDY AIMS: This study aimed to investigate the prevalence of intestinal inflammation in patients with ankylosing spondylitis (AS) by assessing fecal calprotectin (FC) levels and comparing them with those in patients with rheumatoid arthritis (RA) and non-inflammatory rheumatic diseases. Our secondary aim was to correlate FC levels with antirheumatic treatment, nonsteroidal anti-inflammatory drug (NSAID) usage, and disease activity measures. PATIENTS AND METHODS: This cross-sectional study included 97 patients with AS fulfilling the modified New York criteria, 48 patients with RA fulfilling the American College of Rheumatology criteria, and 49 patients with non-inflammatory rheumatic diseases. All patients were questioned about intestinal complaints, and symptomatic patients were excluded. Disease activity was measured in the AS and RA patient groups. RESULTS: The AS group had a significantly higher FC test positivity rate than the RA group (p = 0.016). Furthermore, the AS group had FC levels that were negatively correlated with disease duration (p = 0.04). FC levels were not correlated with any disease activity index, erythrocyte sedimentation rate, C-reactive protein, uveitis, or peripheral arthritis. Patients with AS who used NSAIDs had significantly higher FC levels than nonusers (p = 0.001). CONCLUSIONS: This study revealed that 11% of patients with AS without intestinal complaints had elevated FC levels. FC levels were not correlated with disease activity in AS. Subclinical intestinal inflammation was higher in the early stages of AS. The AS group had a significantly higher FC test positivity than the RA group. In the AS group, NSAID users had significantly higher FC levels than nonusers; thus, no statistically significant difference was observed between biological agent users and nonusers.

Serial measurement of soluble endoglin for risk assessment at the diagnosis of fetal growth restriction.

AIM: In this study, we aimed to investigate the soluble endoglin (sEng) levels in pregnant women with fetal growth restriction (FGR) and to examine the possible relation of the sEng levels with the time remaining to delivery and maternal and fetal complications. METHODS: A total of 42 pregnant women diagnosed with FGR were retrospectively reviewed. Using the maternal blood samples it is at the collected 24-37 gestational weeks, the sEng levels were measured. Fetal biometry measurements, umbilical artery, uterine artery, middle cerebral artery Doppler indices were documented. RESULTS: Of all patients, 17 (40%) were diagnosed with early-onset FGR, while 25 (60%) were diagnosed with late-onset FGR. Abnormal Doppler findings were present in 25 (60%) patients. Of 42 newborns, 18 (42%) were hospitalised in the neonatal unit. The mean sEng level calculated by taking the average of the first and second blood samples was 63.24 ± 49.83 ng/mL. There was no statistically significant difference in the mean sEng levels between those who gave birth within four, three, and two weeks after the diagnosis of FGR and those who did not. There was a positive significant correlation between the mean sEng levels and systolic blood pressure (r = 0.319, P = .04). CONCLUSIONS: We did not find a statistically significant relationship between the sEng level and the time remaining to the time of delivery in pregnant women with FGR. We found no statistically significant difference in sEng level between the groups in pregnant women with fetuses with FGR with or without maternal and fetal complications.

Functional effects of visfatin in isolated rat mesenteric small resistance arteries.

A new adipocytokine, visfatin is expressed in perivascular adipose tissue (PVAT) and exerts effects on vascular system in addition to its relationship with various pathological conditions. The present study aimed to investigate the functional effects of visfatin and the possible underlying mechanism(s) of the effects of visfatin in isolated rat mesenteric small resistance arteries. The study was conducted in small resistance arterial rings isolated from rat mesenteric vascular beds. While visfatin incubation did not produce significant alterations in contractile responses of mesenteric arterial rings to noradrenaline, relaxation responses to acetylcholine but not to sodium nitroprusside (SNP) were significantly reduced in endothelium-intact rings. The inhibitory effect of visfatin on responses to acetylcholine was not observed in endothelium-denuded preparations. Incubation of tissues with nicotinamide phosphoribosyl transferase (NAMPT) inhibitor FK866 or superoxide dismutase (SOD) reversed the inhibitory effects of visfatin on relaxation responses to acetylcholine. Co-incubation of visfatin with Nω-nitro-L-arginine methylester (L-NAME) did not produce a significant alteration in vascular responses to acetylcholine compared to L-NAME incubation alone. Mesenteric PVAT visfatin levels were significantly higher than and correlated positively with plasma visfatin levels. The results of our study indicated that visfatin-induced reductions in endothelium-dependent relaxations of rat isolated small resistance arteries are mediated by oxygen free radicals and a reduction in nitric oxide (NO) bioavailability. It was suggested that increment in systemic and/or local visfatin levels due to various pathologies including obesity and excessive weight gain may play a substantial role in initiation and/or propagation of vascular dysfunctions.

Comparison of Serum Free and Bioavailable 25-Hydroxyvitamin D Levels in Alzheimer's Disease and Healthy Control Patients.

OBJECTIVE: Many studies have investigated lower 25-hydroxyvitamin D (25[OH]D) levels in patients with Alzheimer's disease (AD) compared with those in control patients. In the present study, we aimed to evaluate serum free and bioavailable 25(OH)D levels in patients with AD and in healthy control patients. METHODS: The AD group consisted of 85 patients aged >60 years who were diagnosed with possible AD according to National Institute on Aging-Alzheimer's Association criteria and 85 healthy control patients. Serum levels of total 1,25-dihydroxyvitamin D, total 25(OH)D, vitamin D binding protein (VDBP), parathormone, calcium, phosphorus and albumin, free 25(OH)D, bioavailable 25(OH)D, and the bioavailable 25(OH)D/total 25(OH)D ratio were compared in both groups. RESULTS: Total 25(OH)D, free 25(OH)D, bioavailable 25(OH)D, and the bioavailable 25(OH)D/total 25(OH)D ratio were significantly lower (P <.001, P <.001, P <.001, P <.05, respectively) in the AD group, whereas the VDBP level was significantly higher (P <.05) in the AD than in the control group. CONCLUSION: Free and bioavailable 25(OH)D detected at lower levels in patients with AD limit the target central effects of 25(OH)D; this result suggests that reduced levels of the active free form of vitamin D may be a risk factor for AD and dementia.

Lymphocyte and monocyte vitamin D receptor expression during paricalcitol or calcitriol treatments in patients with stage 5 chronic kidney disease.

PURPOSE: In this study, we aimed to investigate the effect of paricalcitol and calcitriol usage on vitamin D receptor (VDR) contents of CD8+ , CD4+ lymphocytes and monocytes in stage 5d chronic kidney disease (CKD) patients. METHODS: Thirty-six hemodialysis patients older than 18 years of age and 19 healthy controls (group HC) without any known acute or chronic diseases were included in the study. The group of patients undergoing scheduled hemodialysis comprised three subgroups: group CL: patients on calcitriol (n: 10), group PC: patients on paricalcitol (n: 13), and group NT: patients not taking any vitamin D or VDR activating medications (n: 13). CD8+/VDR, CD4+/VDR and MONO/VDR values were representing the ratio of VDR representing cells among related cell group. On the other hand, values of CD8+/MFI, CD4+/MFI and MONO/MFI have shown the total amount of cellular VDR content per cell which has been given as of mean fluorescence intensity in the flow cytometric process. Main CKD mineral bone disorder parameters such as a hemogram, serum BUN, creatinine, albumin, Ca, iP, iPTH, 25(OH)D3 levels were also measured. RESULTS: Average VDR contents in CD8+, CD4+ and monocytes were not different among three patient groups on hemodialysis. But in all hemodialysis subgroups, CD8+/VDR, CD4+/VDR, MONO/VDR, CD8+/MFI, CD4+/MFI and MONO/MFI levels were found to be higher compared with the healthy control subjects (p < 0.001). Among hemodialysis groups, no significant CD8+/VDR, CD4+/VDR, and MONO/VDR content differences were found with regard to the type of VDR activator agent used. There was no difference in serum levels of 25(OH)D3 and CRP among groups participating in the study. CONCLUSION: There was no difference between CD8+/VDR, CD4+/VDR, and MONO/VDR levels in hemodialysis patients using calcitriol or paricalcitol, suggesting that both treatment agents may have a similar effect on VDR contents in lymphocytes and monocytes in that patient population. But in all hemodialysis subgroups, CD8+/VDR, CD4+/VDR, and MONO/VDR levels were found to be higher compared with the healthy control subjects, suggesting an overexpression of VDR through a non CRP and/or 25(OH)D3 dependent mechanism.

Effects of Different Immunosuppressive Drugs on Incretins in Renal Transplant Patients.

BACKGROUND: Immunosuppressive drugs used in transplantation patients, may contribute to the development of post-transplant diabetes mellitus through their possible adverse effects on incretins. We aimed to compare the effects of different immunosuppressive drugs used in renal transplantation patients on glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) levels. PATIENTS AND METHODS: Forty five subjects were enrolled in the study (cyclosporine-treated 15 and tacrolimus-treated renal transplant patients 15, and healthy volunteers as a control group 15). Oral glucose tolerance test with 75 gr glucose was performed. GLP-1 and GIP levels were measured at 0 (baseline), 30, 60, 90, 120 min using ELISA method. RESULTS: A statistically significant level of difference was detected in GLP-1 levels at the baseline, 30th and 120th minutes among all three groups (p < 0,001, p = 0,026 and p = 0,022, respectively). Baseline GLP-1 levels in cyclosporine-treated renal transplant patients were higher than in both tacrolimus-treated renal transplant patients (p = 0,016) and control groups (p < 0,001). GLP-1 levels at the 30th minute were higher in tacrolimus-treated renal transplant patients when compared to the cyclosporine-treated renal transplant patients (p = 0,024). GLP-1 levels at the 120th minute were higher in tacrolimus-treated renal transplant patients than the control group (p = 0,024). The areas under the curve of GLP-1 was higher in tacrolimus-treated renal transplant patients when compared to the control group (p = 0,018). GIP levels at 120th was lower in cyclosporine-treated renal transplant patients when compared to control group (p = 0,003). CONCLUSION: These findings showed a temporally affected incretin hormones in renal transplant patients, a preserved GLP-1 response to an oral glucose load in renal transplant patients on cyclosporine and increased GLP -1 response to an oral glucose load in those on tacrolimus.

The Results of 16 Years of Iodization: Assessment of Iodine Deficiency Among School-age Children in Antalya, Turkey

Objective: Iodine deficiency (ID) continues to be a problem around the world. This study investigated the prevalence of ID and goiter among school-age children in the city center of Antalya, Turkey. The aim was to investigate the effect of an iodization program, which had been running for sixteen years, on nutritional iodine status in this population. Methods: A total of 1,594 school children, aged 6-14 years, were included in this cross-sectional study. ID was evaluated based on median [interquartile range (IQR)] urine iodine/creatine (UI/Cr) (µg/g) ratio and median (IQR) UI concentrations (UIC) (µg/L). UICs were measured using the Sandell-Kolthoff method. Goiter was determined by palpation and staged according to World Health Organization classification. Results: Median (IQR) UIC was found to be 174.69 (119.17-242.83) µg/L, and UIC was found to be lower than 50 µg/L in 6.5% of the population. The median UI/Cr ratio increased from 62.3 to 163.3 µg/g and goiter rates had decreased from 34% to 0.3% over the 16 years of the program. However, 19% were still classified as ID (mild, moderate or severe) and, furthermore, 11.5% were classified as excessive iodine intake. Conclusion: Comparison of two cross-sectional studies, carried out 16-years apart, showed that Antalya is no longer an ID region. However, surveillance should be continued and the percentage of ID and iodine excess individuals in the population should be monitored to avoid emerging problems.

Reference intervals for serum 17α-hydroxyprogesterone and ultrasonographic adrenal gland sizes in healthy newborns.

Background and objectives: Serum 17α- hydroxyprogesterone (17OHP) and bilateral adrenal sizes are pivotal for clinical practice in both diagnosis and treatment of congenital adrenal disorders during the first month of life. Our aims were to determine the reference ranges for serum 17OHP and bilateral adrenal gland sizes according to sex and age groups in healthy term newborns.Materials and methods: A total of 156 healthy newborns, aged 4-7 days (Group 1) or 26-30 days old (Group 2) were included in the study. Serum 17OHP concentration was measured in the morning by radioimmunoassay. The right and left adrenal glands' width, length, and depth were measured with ultrasonography by the same radiologist and the volumes were calculated.Results: The clinical characteristics and serum 17OHP concentrations were similar in male and female newborns. Percentiles for serum 17OHP concentration and the volume of adrenal glands according to age groups and sexes were obtained. Mean 17OHP concentration was 4.67 ± 2.6 ng/ml and 4.49 ± 2.7 ng/ml at the first and fourth week of life, respectively (p > .05). There was a significant decrease in adrenal sizes during the fourth week of life. There was no significant correlation between serum 17OHP concentration and adrenal gland sizes.Conclusions: We have determined reference intervals for serum 17OHP concentration and bilateral adrenal gland sizes for healthy newborns. Although serum concentrations of 17OHP did not change significantly through the first month of life, our reference intervals for serum 17OHP concentration and adrenal sizes may improve clinical approach toward newborns who are suspected of adrenal disorder. We conclude that our reference intervals can guide for congenital adrenal screening regarding serum 17OHP concentration besides diagnosis of adrenal hypoplasia or hyperplasia with ultrasonographic adrenal gland sizes.

Serum concentrations of HE4 and Ca125 in uncomplicated pregnancies: a longitudinal study.

In this study, we aimed to evaluate the effects of pregnancy on the serum level of HE4. Forty-six singleton pregnant women in the study group and 40 premenopausal women in the control group were included. HE4 and Ca125 levels were measured longitudinally at each trimester of pregnancy in the study group and once in the control group at the recruitment. In total 46, 38 and 33 pregnant patients blood samples were analysed in the first, second and third trimester of pregnancy, respectively. The analysis was performed in 31 of the pregnant patients (31/46, 67.4%) in each trimester of pregnancy. A comparison of the median HE4 levels of control and study group revealed that the first and second trimester levels were significantly lower than the control group (p < .001 and p = .015, respectively). There was no difference between the control group and third trimester median HE4 levels (p = .55). Impact StatementWhat is already known on this subject? HE4 is a novel tumour marker approved for the detection of ovarian cancer and monitoring the recurrence or disease progression in conjunction with Ca125. However, we do not know much about physiological changes of HE4 level during pregnancy.What the results of this study add? The current study showed HE4 decreases during first and second trimesters of pregnancy and does not change during third trimester of pregnancy according to healthy premenopausal women.What the implications are of these findings for clinical practice and/or further research? HE4 has a potential to be used in pregnancy but a lower cut off value should be considered in the pregnant population during the first and second trimesters of pregnancy.

Role of Soluble Adiponectin Receptor 2 in Non-Alcoholic Fatty Liver Disease in Children.

PURPOSE: The incidence of non-alcoholic fatty liver disease (NAFLD) in children is gradually increasing. The aim of this study was to investigate the use of serum adiponectin and soluble adiponectin receptor 2 (soluble Adipo R2) levels for the diagnosis of fatty liver disease in obese and overweight children. METHODS: The study included 51 obese and overweight children between the ages of 6 and 18 years diagnosed with NAFLD using ultrasonography and 20 children without fatty liver disease. Patients whose alanine transaminase level was two times higher than normal (≥80 U/L) were included in the non-alcoholic steatohepatitis (NASH) group. RESULTS: NASH was observed in 11 (21.6%) of the patients with NAFLD. The incidence of obesity was higher in patients with NASH (80% and 45%, p=0.021). While the adiponectin levels were similar in patients with NAFLD and those without, they were below the normal level in the whole study group. Adiponectin and soluble Adipo R2 levels of patients with NASH were lower than those in patients without NASH; however, this difference was not statistically significant (p=0.064 and p=0.463). Soluble Adipo R2 levels in obese patients with NAFLD were higher than those in obese children without NAFLD (p<0.001). CONCLUSION: Soluble adiponectin receptor 2 level is a noninvasive marker that can be used for the diagnosis of NAFLD in obese children.

Diagnostic value of the late-night salivary cortisol in the diagnosis of clinical and subclinical Cushing's syndrome: results of a single-center 7-year experience.

Late-night salivary cortisol (LNSaC) is an easy-to-use test reflecting the free cortisol level in the serum and does not require hospitalization. Controlled studies reported that LNSaC has a high sensitivity and specificity, but have not set a clearly defined cut-off value to be used in the diagnosis of Cushing's syndrome. In this study, we aimed to evaluate the diagnostic performance of LNSaC in patients with clinical Cushing's syndrome (CCS) and subclinical Cushing's syndrome (SCS). The data of 543 patients, whose LNSaC levels were assessed using electrochemiluminescence immunoassay method, were retrospectively evaluated. The study included a total of 324 patients: 58 patients with CCS, 53 patients with SCS, and 213 patients without Cushing's syndrome (NoCS). The cause of the Cushing's syndrome was hypophyseal in 26 patients (45%), adrenal in 24 patients (41%), and ectopic in 8 patients (14%) in the CCS group. Median LNSaC levels were 0.724 (0.107-33) µg/dL in CCS group, 0.398 (0.16-1.02) µg/dL in SCS group, and 0.18 (0.043-0.481) µg/dL in NoCS group (p=0.001). Accordingly, LNSaC had 89.6% sensitivity and 81.6% specificity at a cut-off value of 0.288 µg/dL in the diagnosis of CCS; and had 80.7% sensitivity and 85.1% specificity at a cut-off value of 0.273 µg/dL in the diagnosis of SCS. In the present study, a lower sensitivity and specificity than previously reported was found for LNSaC in the diagnosis of CCS. Moreover, the diagnostic performance of LNSaC in patients with SCS was close to its diagnostic performance in patients with CCS. Each center should determine its own cut-off value based on the method adopted for LNSaC measurement, and apply that cut-off value in the diagnosis of Cushing's syndrome.

Protective effect of exendin-4 treatment on erectile dysfunction induced by chronic methylglyoxal administration in rats.

OBJECTIVE: The aim of this study was to investigate the effect of chronic exendin-4 (Ex-4) treatment on corpus cavernosum (CC) dysfunction in methylglyoxal (MGO) administered rats. METHODS: Male rats were divided into four groups as control, MGO (75 mg/kg/day in drinking water for 12 weeks), MGO + low-dose Ex-4 (0.1 µg/kg twice daily subcutaneously for 12 weeks concomitant with MGO), and MGO + high-dose Ex-4 (1 µg/kg twice daily subcutaneously for 12 weeks concomitant with MGO). Nitric oxide (NO)-mediated endothelium-dependent and neurogenic CC relaxations were evaluated by acetylcholine (ACh) and electrical field stimulation (EFS), respectively. Apoptosis was determined by TUNEL. Endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS), NADPH oxidase subunit gp91phox (NOX2), and Rho kinase (ROCK2) expressions in CC were investigated by immunohistochemistry. Levels of the malondialdehyde (MDA) and advanced oxidation protein products (AOPP) were also measured. RESULTS: In MGO administered rats, both endothelium-dependent and neurogenic CC relaxations were significantly impaired as compared to controls. Apoptotic cell death and levels of MDA and AOPP increased significantly in MGO administered rats. eNOS and p-eNOS expressions decreased significantly in MGO group, while gp91phox expressions increased significantly. The diminished relaxation in response to ACh or EFS as well as the changes in expression of proteins in MGO groups were significantly improved by exendin-4 treatment. TUNEL-positive cells, and levels of MDA and AOPP in MGO group rats were also significantly reduced by exendin-4. CONCLUSION: Exendin-4 treatment improves NO-mediated CC relaxations in MGO administered rats probably by inhibiting NADPH oxidase.

Evaluation of left ventricular functions with two-dimensional speckle-tracking echocardiography (2D-STE) and N-terminal ProBNP in diabetic children.

Simsek A, Turan Ö, Çiftel M, Kardelen F, Durmaz E, Özdem S, Akçurin G, Ertug H. Evaluation of left ventricular functions with twodimensional speckle-tracking echocardiography (2D-STE) and N-terminal ProBNP in diabetic children. Turk J Pediatr 2018; 60: 633-641. The purpose of this study was to examine the existence of subclinical left ventricular dysfunction by using 2D-STE and NT-ProBNP levels in children and adolescent patients with type 1 diabetes mellitus. Furthermore, it was also aimed to investigate the effects of the diabetes duration and the metabolic control of the disease on cardiac functions. The patient group was composed of 63 children who were being followed up for the type 1 diabetes mellitus. The control group was composed of 36 healthy children who were of the similar age. Patients with type 1 diabetes mellitus were divided into groups; according to the duration of the disease; group 1: 3-5 years, group 2: 6-10 years of follow-up. The conventional echocardiography and 2D-STE were applied to all of the patients and control individuals. NT-Pro BNP level was measured in the diabetes group. In the conventional echocardiographic examination; there was no difference between the patient and control groups in terms of left ventricular systolic functions, left ventricular diastolic functions; late-diastolic flow velocity in mitral valve (A) values increased and E-wave/A-wave ratio (E/A ) values decreased in diabetes mellitus patients. According to the 2D-STE results; global longitudinal strain, (-17.28±2.24 vs. -19.49±2.22; p < 0.05) and circumferential strain (-12.86±3.19 vs. -17.71±4.62; p < 0.05) were lower in diabetic patients compared to the parameters of control group individuals. There was no difference between levels of NT-ProBNP of the group 1 and group 2 diabetes mellitus patients. Our study showed that there was a dysfunction on the left ventricular systolic functions of the patients with type 1 diabetes mellitus. NT-Pro BNP levels were not considered as a distinguishing factor for the early stages of diabetes mellitus.