Is meteorin-like (Metrnl) a novel biomarker to distinguish patients with obstructive sleep apnea (OSA) and patients with OSA at vascular risk.

PURPOSE: Metrnl, a newly discovered adipokine with significant expression in white adipose tissue, promotes energy expenditure and contributes to the development of cardiovascular disorders. Endocan is a surrogate marker for endothelial dysfunction and is linked to cardiovascular risk factors. Higher cardiovascular morbidity and mortality have been linked to obstructive sleep apnea (OSA). In this study, we investigated the potential of serum Metrnl and endocan as biomarkers to identify patients with OSA who are at increased cardiovascular risk and differentiate them from healthy controls. METHODS: The study included the evaluation of serum levels of endocan and Metrnl in individuals with OSA and healthy controls. All participants underwent full polysomnography to evaluate their sleep, and carotid intima-media thickness (CIMT) was measured in each of them. RESULTS: Patients with OSA (n = 117) had considerably lower levels of Metrnl and significantly higher levels of endocan than controls (n = 59). Once confounding factors were taken into account, both Metrnl and endocan were effective predictors of OSA. Additionally, the severity of OSA, as determined by the apnea-hypopnea index (AHI), was linked to Metrnl and endocan levels. The study also found a significant and independent inverse association between CIMT and Metrnl, along with a positive association with endocan after making multiple adjustments. Furthermore, there was a significant and independent connection between CIMT and AHI. CONCLUSION: Based on these findings, Metrnl and endocan have the potential to be valuable markers for identifying patients with OSA who are at increased risk of early vascular damage.

Investigation of serum E-Cadherin, VEGF121, Survivin, Tenascin C and Tetraspanin 8 levels in patients with glioblastoma.

OBJECTIVE: The aim of this study is to determine biomarkers, which may be used in order to understand the pathophysiology, the diagnosis, progression surveillance/monitoring, and treatment efficacy of high graded glial tumors. BACKGROUND: Radiological imaging in the diagnosis and relapse surveillance of glial tumors is sometimes insufficient. There is need for additional methods of diagnosis and surveillance in order to rule out contradictory circumstances. METHOD: Using enzyme like immune sorbent assay method, E-Cadherin, Tenascin C, Tetraspanin 8, Survivin and VEGF121 levels were investigated in serum and tumor tissues of 28 patients diagnosed with pathological glioblastoma, and in the serum of 26 healthy individuals. Correlation between tumor tissue values and Ki67 percentage, and P53 mutation, and difference between unhealthy and healthy serum levels were sought. RESULTS: It was found out that E-Cadherin and VEGF 121 levels in the unhealthy serum were high in comparison to the control group (p 0.05). CONCLUSION: EC and VEGF121 are biomarkers, which have the potential to be used in the diagnosis, recurrence and treatment follow-up in high graded glial tumors (Tab. 2, Fig. 1, Ref. 37). Text in PDF www.elis.sk Keywords: E-Cadherin, VEGF, Survivin, Tenascin-C, Tetraspanin, glioblastoma.

Assessment of salusin alpha and salusin beta levels in patients with newly diagnosed dipper and non-dipper hypertension.

OBJECTIVE: The pathophysiology of non-dipper hypertension has not been clarified. The relationship between salusins with atherosclerosis and hypertension has gained attention in recent years. The aim of this paper is to investigate whether salusins are associated with circadian blood pressure, left ventricular mass index, and diastolic functions in newly diagnosed hypertensives. METHODS: The study included 88 newly diagnosed hypertensive individuals. Twenty-four-hour ambulatory blood pressure monitoring and echocardiographic examinations were performed. The patients were assigned to dipper hypertension (n = 41) and non-dipper hypertension (n = 47) groups based on the ambulatory blood pressure monitoring results according to the presence of ≥ a 10% decrease in nighttime blood pressure values or not. Serum salusin α and ß levels were determined by electrochemiluminescence immunological test method. RESULTS: Compared to dipper hypertension, non-dipper hypertension group demonstrated lower salusin α levels (1818.71 ± 221.67 vs 1963 ± 200.75 pg/mL, p = .002), mitral E/A, septal E'/A' and higher salusin ß levels (576.24 ± 68.15 vs 516.13 ± 90.7 pg/ml, p = .001) and left ventricular mass index. Multivariate logistic regression analysis revealed salusin-α (OR 0.474, 95% CI 0.262 to 0.986, p = .001), salusin-ß (OR 2.550, 95% CI 2.123 to 2.991, p = .018), and left ventricular mass index (OR 2.620, 95% CI 2.124 to 2.860, p = .011) as independent predictors of non-dipper hypertension. As candidate markers to predict non-dipper hypertension, decreased salusin α, and increased salusin ß levels may mediate crosstalk between sympathetic and parasympathetic systems and indicate poor cardiovascular prognosis in hypertension.

MicroRNA 21 and microRNA 155 levels in resistant hypertension, and their relationships with aldosterone.

AIM: MicroRNAs (miRNAs) are non-coding RNA molecules that serve as regulators following gene expression transcription. While studies have investigated the role of miRNAs in the pathogenesis of essential hypertension (HT), very few have considered their place in the pathogenesis of resistant hypertension (RH). The purpose of this study was to investigate levels of miRNA 21 and miRNA 155 in RH and their relationships with aldosterone. METHOD: Thirty-two normotensive patients, 30 newly diagnosed HT patients, and 20 RH patients were included in the study. Patients' demographic data were recorded, and office blood pressure measurement and 24-h ambulatory blood pressure monitoring (24-h ABPM) were performed. Blood specimens were collected for miRNA 21, miRNA 155 and aldosterone measurement. MiRNA 21 and miRNA 155 levels in the control and patient groups and their relations with other demographic and biochemical parameters were then subjected to analysis. RESULTS: No difference was determined in miRNA 155 levels between the groups, but miRNA 21 and aldosterone levels were significantly higher in the RH group (p < 0.001 and <0.05, respectively). At correlation analysis, miRNA 21 exhibited positive correlation with aldosterone, age, office SBP, 24-h ABPM all-day SBP. A 9.6 copy/uL level for miRNA 21 predicted presence or absence of RH with 95% sensitivity and 71% specificity (AUC:0.823, 95% CI (0.72-0.92). CONCLUSION: The study results revealed significantly higher miRNA 21 and aldosterone in RH patients than in healthy individuals and newly diagnosed hypertensives.

Tumour necrosis factor like cytokine 1A levels and lesion complexity in non-smoking patients with coronary artery disease.

Background: Tumour necrosis factor like cytokine 1A (TL1A), which is a member of tumour necrosis factor alpha superfamily (TNF-α), is a novel indicator of atherosclerosis.Objective: Smoking is an established stimulant of TNF-α. We aimed to investigate whether TLA1 plays a role in the presence and complexity of coronary artery atherosclerosis, exclusively in non-smoking patients with CAD.Methods: We enrolled 103 participants in the study, who underwent coronary angiography for stable angina pectoris. We divided the study population into 2 groups: The CAD group consisted of 62 patients with CAD and the control group consisted of 41 subjects with non-CAD. SYNTAX and Gensini scores, indicating CAD severity and complexity, were analysed as well as TLA1 levels.Results: TLA1 levels was higher in patients with CAD than those in controls (228[119-824] vs 178[15-418]pg/ml, p < 0.001). Presence of CAD (ß ± SE = 106.29 ± 33.11, p = 0.002), Syntax score (ß ± SE= 6.57 ± 1.75, p = 0.012), and Gensini score (ß ± SE = 2.30 ± 0.65, p = 0.001) were found to be predictors of TL1A levels. Gensini score and Syntax score were positively correlated with TL1A levels (r = 0.420, p < 0.001, and r = 0.402, p < 0.001, respectively).Conclusions: Non-smoker CAD patients have higher TLA1 levels that are promising biomarker for diagnosing CAD and indicating CAD lesion complexity.

Decreased serum orexin A levels in drug-naive children with attention deficit and hyperactivity disorder.

Attention deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders of childhood and characterized by inattention, hyperactivity, and impulsivity. ADHD is a neurodevelopmental disorder, and its etiology has not yet been determined precisely. Orexin A is thought to play an important role in different forms of learning, memory, and attention. Despite its importance in attention and learning, no study has investigated serum orexin levels in patients with ADHD. In the present study, we aimed to compare serum orexigenic neuropeptides such as orexin A and orexin B, neuropeptide Y, and ghrelin between drug naive children with ADHD and healthy children. Fifty-six drug-naive children with ADHD and 40 healthy controls were enrolled in the study. After comparison of serum orexin A and orexin B, neuropeptide Y, and ghrelin, we found that serum orexin A levels were significantly lower in the ADHD group (p = 0.001). Furthermore, serum orexin A levels were compared between ADHD subgroups. Orexin A levels were significantly lower in the inattentive subtype compared with the hyperactive subtype and combined subtype (p = 0.009). Our results indicate that orexin A might be a neurobiological etiological factor in ADHD, particularly associated with attention symptoms. The present study is the first to demonstrate decreased serum orexin A levels in drug-naive children with ADHD. Further studies are needed to confirm our results and to show the effects of treatments involving orexin A in patients with ADHD.

Elevated serum levels of procollagen C-proteinase enhancer-1 in patients with chronic kidney disease is associated with a declining glomerular filtration rate.

BACKGROUND: Procollagen C-proteinase enhancer-1 (PCPE-1) is a 55 kDa glycoprotein, which increases the activity of procollagen C-proteinases that break down C-terminal propeptides. Studies have shown that PCPE-1 is involved in the fibrotic process that occurs in various tissues and organs. Our review of the literature revealed no data concerning the relation between PCPE-1 and chronic kidney disease (CKD). The purpose of this study was to determine PCPE-1 levels in CKD. METHODS: One hundred thirty-one CKD patients and 34 healthy controls were included in our study. Demographic data were recorded, and routine biochemical tests were performed. Blood specimens were collected for PCPE-1 investigation. Demographic data, biochemical test results and PCPE-1 levels were compared between the control and patient groups. Parameters affecting PCPE-1 levels in our patient group were assessed. RESULTS: Procollagen C-proteinase enhancer-1 levels were significantly higher in our patient group compared to the control group. Parameters affecting PCPE-1 elevation in the patient group were identified as systolic blood pressure, blood urea nitrogen, phosphorus, haemoglobin, intact parathormone levels, glomerular filtration rate and body mass index. CONCLUSION: We determined high PCPE-1 levels in CKD patients. PCPE-1 levels being negatively correlated with glomerular filtration rate suggests that PCPE-1 may be associated with progression in CKD patients.

Soluble endothelial protein C is associated with blood pressure variability and salt consumption but not mean blood pressure in patients with newly diagnosed primary hypertension.

BACKGROUND: Hypertension is a widespread disease involving frequent thrombotic complications. Blood pressure variability (BPV) has recently been shown to be associated with end-organ damage and cardiovascular events. However, the pathogenesis of the relation between BPV and cardiovascular events has not yet been explained. Soluble endothelial protein C (sEPCR) exhibits a procoagulant effect by reducing the anticoagulant and anti-inflammatory effects of protein C and activated protein C. The purpose of this study was to evaluate sEPCR levels in hypertensive individuals and the parameters affecting that level, particularly BPV. METHODS: Fifty-one newly diagnosed hypertensive subjects and 31 healthy individuals were included in the study. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) was performed after office control, and simultaneous 24-h urine was collected. BPV was calculated with average real variability (ARV) from ABPM data. Blood specimens were collected under appropriate conditions for sEPCR levels and biochemical tests. sEPCR levels were compared between the patient and healthy groups, after which parameters affecting sEPCR elevation in the hypertensive group were evaluated. RESULTS: sEPCR levels were significantly high in the hypertensive group (p < 0.05). At multivariate regression analysis in the hypertensive group, sEPCR was determined to be independently associated with 24-h systolic ARV (ß = 0.572, p < 0.05) and 24-h urine Na (ß = 0.428, p < 0.05). CONCLUSION: In our study, sEPCR was high in hypertensive individuals, and this elevation was related to ARV and urine Na excretion independently of mean blood pressure.

The role of novel cytokines in inflammation: Defining peripheral artery disease among patients with coronary artery disease.

Coronary artery disease (CAD) patients with concomitant peripheral artery disease (PAD) experience more extensive and calcified atherosclerosis, greater lesion progression and more common coronary events compared to patients with CAD only. To characterize the distinct features of this aggressive atherosclerotic disease, we studied novel cytokines that code different stages of atherogenesis. One hundred and eighty consecutive subjects (60 patients into each group of CAD+PAD, CAD and controls) were recruited among patients with stable angina pectoris scheduled for coronary angiography. An ankle-brachial index (ABI) ≤0.9 was determined as occlusive PAD. Fasting serum tumor necrosis factor (TNF)-like antigen 1A (TL1A) and its receptor death receptor 3 (DR3), NOGO-B (reticulon 4B) and its receptor NUS1, high-sensitivity C-reactive protein (hsCRP), A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 1, 4, 5 and interleukin (IL) 6 levels were determined. Serum hsCRP and DR3/TL1A concentrations were similar and higher than controls in the CAD and CAD+PAD groups. Levels of NOGO-B and its receptor NUS1 were increased and ADAMTS-5 was decreased in patients with CAD+PAD. Independent predictors of ABI in multivariate analysis were smoking (B = -0.13, p = 0.04), NUS1 (B = -0.88, p < 0.001), ADAMTS-5 (B = 0.63, p < 0.001) and SYNTAX score (B = -0.26, p < 0.001). Similarly, smoking (OR = 5.5, p = 0.019), SYNTAX score (OR = 1.2, p < 0.001), NUS1 (OR = 14.4, p < 0.001), ADAMTS-5 (OR = 1.1, p < 0.001) and age (OR = 1.1, p = 0.042) independently predicted the involvement of peripheral vasculature in logistic regression. The diagnostic performance of these cytokines to discriminate CAD+PAD were AUC 0.79 ( p < 0.001) for NUS1 and 0.37 ( p = 0.013) for ADAMTS-5. We report herein that circulating cytokines can give clues to the ongoing atherosclerotic process and the extent of vascular involvement in which distinct features of ADAMTS-5 and NUS1 make them promising cytokines for future research.

Effect of hesperetin on inflammatory and oxidative status in trinitrobenzene sulfonic acid-induced experimental colitis model.

In our study, the effect of hesperetin on inflammatory and oxidative status in trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis model was investigated through different methods. Eighteen Wistar albino male rats were divided in to three groups: Group I (Control, n = 8; 1 ml physiological saline), Group II (Colitis, n = 8; 1 ml TNBS), Group III (Hesperetin, n = 8; 1 ml TNBS and 100 mg/kg hesperetin). Macroscopic and microscopic scores were calculated to determine the damage to the colon at the end of the experiment. Serum tumor necrosis factor-α (TNF-α) and tissue interleukin-6 (IL-6) levels were determined using the ELISA method. Myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) levels were investigated spectrophotometrically. The TUNEL method was used for the detection of apoptotic cells in the colon tissue. Inducible nitric oxide synthase (iNOS) and nuclear factor-kappa-B (NF-ĸß) expression in the colon were determined immunohistochemically. Hesperetin administration has shown to significantly reduce levels of MPO, MDA, and proinflammatory agents (TNF-α, IL-6, and NF-ĸß). It has also been proven to inhibit mucosal apoptosis. This study indicates that hesperetin is protective against TNBS-induced colitis model via antiinflammatory, antioxidant and antiapoptotic effects.

Novel imaging modalities in detection of cardiovascular involvement in ankylosing spondylitis.

OBJECTIVES: The diagnosis of cardiovascular involvement in ankylosing spondylitis (AS) is usually delayed since conventional echocardiography relies mainly on the morphological alterations. The aim of this study was to evaluate the role of echocardiographic methods such as tissue Doppler and strain imaging of left ventricle (LV) and proximal aorta; and concentrations of biomarkers of cardiac fibrosis such as galectin-3 (Gal-3) and soluble suppression-of-tumorogenicity-2 (sST2) in determining early cardiovascular impairment in AS. DESIGN: In this prospective study of 75 AS and 30 healthy subjects (mean age 41.7 ±10.1 years; 37.3% female), we determined layer-specific strain and strain rates in longitudinal, circumferential and radial axes for LV as well as transverse and longitudinal strains of proximal aorta; central pulse wave velocity(cPWV); plasma high sensitivity C-reactive protein(hsCRP), Gal-3 and sST2 levels. RESULTS: Patients with AS had increased levels of hsCRP and sST2 when compared to healthy controls. cPWV, E and e' velocities; longitudinal strain and strain rates at all myocardial layers; and transverse strains of both anterior and posterior aortic walls were reduced in AS patients. Gal-3 levels with strain and strain rates at circumferential and radial axes were similar between the groups. Among all echocardiographic and clinical parameters, AS was independently associated with LV dysfunction (expressed by longitudinal strain of LV) and aortic impairment (expressed by transverse strain of anterior wall). CONCLUSIONS: This study demonstrates that functional impairment in AS occurs early in the disease course and strain imaging is an effective tool in discriminating involvement. sST2 may represent the link between inflammation and fibrosis in AS.

Implications of circulating irisin and Fabp4 levels in patients with polycystic ovary syndrome.

The aim of the study was to evaluate the fatty acid-binding protein-4 (FABP4) and irisin concentrations in women with polycystic ovary syndrome (PCOS). Forty-nine women with PCOS, diagnosed according to Rotterdam criteria and 39 healthy women matched for body mass index (BMI) and age. Serum irisin and plasma FABP4 concentrations were measured in both groups. The association of irisin and FABP4 concentrations with metabolic parameters were also tested. Women with PCOS had significantly lower mean serum irisin concentrations than control subjects (158.5 ± 123.3 versus 222.9 ± 152.2 ng/ml, p < 0.05). Concentrations of FABP4 in PCOS and control groups were not significantly different (10.5 ± 4.4 versus 10.9 ± 4.2 ng/ml, p > 0.05). FABP4 concentrations were correlated with BMI, waist-hip ratio (WHR) and HOMA-IR (r = 0.57, p = 0.001; r = 0.26, p = 0.03; r = 0.26, p = 0.03, respectively). No associations between irisin and all the others parameters except serum levels of LH were found. Serum irisin concentrations of women with PCOS were lower compared to the controls. Moreover, there were no difference in plasma FABP4 concentrations between women with PCOS and controls.

Serum YKL-40: a potential biomarker for psoriasis or endothelial dysfunction in psoriasis?

Psoriasis is a disease that can contribute to a risk of atherosclerosis. In several studies, impaired endothelial dysfunction (ED) is correlated with psoriasis. Serum YKL-40 is a new inflammatory biomarker of vascular damage, like ED and cardiovascular diseases. The aim of the study was to compare relevance of serum YKL-40 levels in psoriasis patients and healthy subjects according to ED diagnosis and identifiable cardiovascular risk factors. Sixty (31 female, 29 male) patients with plaque psoriasis, and 30 (18 female, 12 male) healthy controls were selected according to whether they had at least one or no identifiable risk factors for cardiovascular disease. All subjects were evaluated ultrasonographically for endothelial function and diagnosed as with or without ED and all groups compared for serum YKL-40 levels. YKL-40 levels of psoriatic patients with ED were higher than healthy controls with ED (P = <0.05). There were no statistical differences in between subjects without ED. YKL-40 levels of patients over age of 40 were higher than younger ones (P < 0.05). But in healthy controls, there were no differences. In comparison of cardiovascular risk-positive (RP) patients and RP healthy subjects, YKL-40 levels were higher in RP patients (P = <0.05). The elevation of plasma YKL-40 in psoriasis can be associated not only with inflammation of the disease, but also with ED. YKL-40 can be used as a marker for predicting and preventing cardiovascular diseases in RP psoriatic patients with age above 40.

No relationship between osteoprotegerin concentrations and endothelial dysfunction in non-obese women with and without polycystic ovary syndrome.

PURPOSE: To investigate the relationships of osteoprotegerin (OPG) concentrations to brachial artery flow-mediated vasodilation (FMD) and the carotid artery intima media thickness (CIMT) in polycystic ovary syndrome (PCOS). METHODS: Thirty-seven women with PCOS and 41 controls matched for body mass index (BMI) and age were included in study. The serum OPG concentrations, hormonal and metabolic profiles were measured in women with PCOS and in control group. The CIMT and brachial artery FMD were evaluated in both groups. RESULTS: The mean serum concentrations of all hormones were comparable, except LH, which was higher in women with PCOS. Lipid parameters were similar between groups. There were no differences between groups with respect to fasting glucose, 2-h glucose, fasting insulin, HbA1c and HOMA-IR. The mean osteoprotogerin concentrations were higher in PCOS group (11.39 ± 2.29 vs. 10.22 ± 2.25 pmol/L, P = 0.026). The mean CIMT was higher in PCOS group than control group (0.52 ± 0.058 vs. 0.45 ± 0.059 mm, P < 0.01). The mean brachial artery FMD was lower in PCOS group (0.068 ± 0.022 vs. 0.055 ± 0.029, P = 0.017). CONCLUSIONS: We found high osteoprotogerin concentrations, increased CIMT and decreased FMD, in women with PCOS. However, there was no correlation between osteoprotegerin and cardiovascular risk markers.

Effects of 12-week combined exercise therapy on oxidative stress in female fibromyalgia patients.

The aims of this study were to investigate the effect of exercise therapy on the oxidative stress in fibromyalgia patients and relationship between oxidative stress and fibromyalgia symptoms. Thirty women diagnosed with fibromyalgia according to the American College of Rheumatology preliminary criteria, and 23 healthy women whose age- and weight-matched women were enrolled the study. Pain intensity with visual analog scale (VAS), the number of tender points, the fibromyalgia impact questionnaire (FIQ), the Beck depression inventory (BDI) were evaluated. The oxidative stress parameters thiobarbituric acid reactive substances, protein carbonyls, and nitric oxide, and antioxidant parameters thiols and catalase were investigated in patients and control group. After, combined aerobic and strengthen exercise regimen was given to fibromyalgia group. Exercise therapy consisted of a warming period of 10 min, aerobic exercises period of 20 min, muscle strengthening exercises for 20 min, and 10 min cooling down period. Therapy was lasting 1 h three times per week over a 12-week period. All parameters were reevaluated after the treatment in the patient group. The oxidative stress parameters levels were significantly higher, and antioxidant parameters were significantly lower in patients with fibromyalgia than in the controls. VAS, FIQ, and BDI scores decreased significantly with exercise therapy. The exercise improved all parameters of oxidative stress and antioxidant parameters. Also, all clinical parameters were improved with exercise. We should focus on oxidative stress in the treatment for fibromyalgia with the main objective of reducing oxidative load.

The effects of isotretinoin on the ovarian reserve of females with acne.

There are some side effects of isotretinoin in many organs. However, a study investigating the effects of isotretinoin on the human ovarian reserve has not been reported previously. The study was conducted to investigate possible effects of isotretinoin on ovarian reserve. Serum anti-Müllerian hormone (AMH) levels were measured at the beginning and at the end of isotretinoin treatment in 22 patients with acne and in 22 women without. The mean AMH level before treatment was 5.77 ng/mL in the study group and 3.79 ng/mL in the control group (p = 0.008). Following treatment, the mean AMH level was 4.69 ng/mL in the study group. This mean AMH level after treatment was statistically lower than the AMH level before treatment (p = 0.012). There was no significant difference between the mean AMH level at the end of treatment and that of the control group (p = 0.20). The high level of pre-treatment AMH levels could be an evidence of hyperandrogenism in women with acne, even if they are not identified as having polycystic ovary syndrome (PCOS) or hyperandrogenism. Decrease in AMH levels following exposure to isotretinoin may suggest that it has a detrimental effect on the ovaries.

Decreased ovarian reserve in female Sprague-Dawley rats induced by isotretinoin (retinoic acid) exposure.

Isotretinoin is a retinoid widely used for the treatment of severe nodulocystic acne. Although it has broad side effects, there is no well-designed study about its effects on the ovary. This study investigated possible toxic effects of isotretinoin on female gonads. A total of 30 female rats were randomly divided into three equal groups according to the dose of isotretinoin they were administered: 0 mg/kg/day (group 1), 7.5 mg/kg/day (group 2) or 15 mg/kg/day (group 3). Thirty days after the treatment, the effects of isotretinoin on the ovaries were evaluated with serum anti-Müllerian hormone (AMH) concentrations, apoptosis by TUNEL assay and immunohistochemical observations by proliferating cell nuclear antigen (PCNA). The percentage of atretic follicles was calculated for each stage of folliculogenesis. The serum AMH concentrations were found to be lower in both isotretinoin groups. The percentage of atretic follicles in both isotretinoin groups was higher than the control. The number of PCNA-positive granulosa cells was decreased in the isotretinoin groups. The number of ovarian follicles with apoptotic granulosa cells was increased in the experimental groups. These data are the first to identify that exposure of isotretinoin may be responsible for decreased ovarian reserve and toxic effects on rat ovaries.

Visfatin, Leptin, and TNF-α: Interrelated Adipokines in Insulin-Resistant Clinical and Subclinical Hypothyroidism.

PURPOSE: This study is designed to evaluate the interrelationships among adipokines-visfatin, leptin, and tumor necrosis factor-α (TNF-α)- and insulin resistance (IR) in overt (n = 40) and subclinic hypothyroid (n = 25) patients and compare our findings with sex and body mass index-matched healthy controls (n = 25). METHODS: Serum visfatin, leptin, and TNF-α levels were measured by enzyme-linked immunosorbent assay and C-reactive protein by immunoturbidimetry. Thyroid status (TSH, FT3, FT4) and lipid status (triglyceride, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, total cholesterol) parameters were measured. IR was determined by homeostatic model assessment (HOMA-IR) and McAuley (McA) indices. RESULTS: HOMA-IR (p < 0.05) and McA indices (p < 0.01) revealed the presence of IR in overt hypothyroid patients. C-reactive protein, TNF-α, leptin, and visfatin levels were significantly higher (p < 0.01, p < 0.01, p < 0.001, and p < 0.001) in overt hypothyroid patients than euthyroid control group. Subclinic hypothyroid patients were observed to have significantly higher leptin and visfatin levels (p < 0.05) than euthyroid control group. In overt hypothyroid patients, we found plasma visfatin to be significantly positively correlated with HOMA-IR index (r = 0.336, p < 0.05) and body mass index (r = 0.445, p < 0.01) and negatively correlated with McA index (r = -0.574, p < 0.01). CONCLUSION: This study demonstrates the presence of IR in overt hypothyroid patients by HOMA and McA indices. Increased levels of visfatin, leptin, and TNF-α in overt and subclinic hypothyroid patients and the correlations among these adipokines highlighten their crucial role in the IR-associated disorders.

Cardiovascular disease risk prediction in scleroderma.

OBJECTIVE: Cardiovascular disease risk prediction in scleroderma is important. In this study of scleroderma patients, the aim was to investigate the relationship between cardiac myosin-binding protein-C, sensitive troponin T, and trimethylamine N-oxide and cardiovascular disease risk with the Systematic COronary Risk Evaluation 2 model of the European Society of Cardiology. METHODS: Systematic COronary Risk Evaluation 2 risk groups of 38 healthy controls and 52 women with scleroderma were evaluated. Cardiac myosin-binding protein-C, sensitive troponin T, and trimethylamine N-oxide levels were analyzed with commercial ELISA kits. RESULTS: In scleroderma patients, cardiac myosin-binding protein-C and trimethylamine N-oxide levels were higher than healthy controls but sensitive troponin T was not (p<0.001, p<0.001, and p=0.274, respectively). Out of 52 patients, 36 (69.2%) were at low risk, and the other 16 (30.8%) patients were at high-moderate risk with the Systematic COronary Risk Evaluation 2 model. At the optimal cutoff values, trimethylamine N-oxide could discriminate high-moderate risk with sensitivity 76%, specificity 86% and cardiac myosin-binding protein-C with sensitivity 75%, specificity 83%. Patients with high trimethylamine N-oxide levels (≥10.28 ng/mL) could predict high-moderate- Systematic COronary Risk Evaluation 2 risk 15 times higher than those with low trimethylamine N-oxide (<10.28 ng/mL) levels (odds ratio [OR]: 15.00, 95%CI 3.585-62.765, p<0.001). Similarly, high cardiac myosin-binding protein-C (≥8.29 ng/mL) levels could predict significantly higher Systematic COronary Risk Evaluation 2 risk than low cardiac myosin-binding protein-C (<8.29 ng/mL) levels (OR: 11.00, 95%CI 2.786-43.430). CONCLUSION: Noninvasive cardiovascular disease risk prediction indicators in scleroderma, cardiac myosin-binding protein-C, and trimethylamine N-oxide could be recommended to distinguish between high-moderate risk and low risk with the Systematic COronary Risk Evaluation 2 model.

Prenatal immobility stress: Relationship with oxidative stress, inflammation, apoptosis, and intrauterine growth restriction in rats.

BACKGROUND: Prenatal stress is a significant risk factor affecting pregnant women and fetal health. In the present study, we aimed to investigate the effect of immobility stress at different periods of pregnancy on oxidative stress, inflammation, placental apoptosis and intrauterine growth retardation in rats. METHODS: Fifty adult virgin female Wistar albino rats were used. Pregnant rats were exposed to 6 h/day immobilization stress in a wire cage at different stages of pregnancy. Groups I and II (Day 1-10 stress group) were sacrificed on the 10th day of pregnancy, and Group III, Group IV (10-19th-day stress group), and Group V (1-19th-day stress group) were sacrificed on the 19th day of pregnancy. Inflammatory cytokines, including interleukin-6 (IL-6) and interleukin-10 (IL-10), serum corticotropin-releasing hormone (CRH), and corticosterone levels were measured by enzyme-linked immunosorbent assay. Malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels in the placenta were spectrophotometrically measured. Histopathological analyses of the placenta were evaluated by hematoxylin and eosin staining. Tumor necrosis factor-alpha (TNF-α) and caspase-3 immunoreactivity in placenta tissues were determined by the indirect immunohistochemical method. Placental apoptosis was determined by the TUNEL staining method. RESULTS: We found that the immobility stress during pregnancy significantly increased serum corticosterone levels. Our results showed that the immobility stress diminished the number and weight of fetuses in rats compared to the non-stress group. The immobility stress caused significant histopathological changes in the connection zone and labyrinth zone and increased placental TNF-α and caspase-3 immunoreactivity and placental apoptosis. In addition, immobility stress significantly increased the levels of pro-inflammatory IL-6 and MDA and caused a significant decrease in the levels of antioxidant enzymes such as SOD, CAT, and anti-inflammatory IL-10. CONCLUSIONS: Our data suggest that immobility stress causes intrauterine growth retardation by activating the hypothalamic-pituitary-adrenal axis and deteriorating placental histomorphology and deregulating inflammatory and oxidative processes.