Impact of Forced Swimming Stress on Serum Adiponectin and Endothelin-1 Levels in Wistar Rats: Comparative Analysis of Dietary Effects.

Aim This study aimed to assess the impact of forced repeated swimming stress on serum adiponectin and endothelin-1 levels in Wistar rats, comparing the effects between those fed a standard diet and those on a high-fat diet. Methods Twenty adult male Wistar rats were divided into two dietary groups: a standard food diet group (NFD, n=10) and a high-fat diet group (HFD, n=10). Both groups underwent daily forced swimming stress for six days, with durations increasing from 5 to 30 minutes. The protocol finished in an acute bout of swimming exercise on the seventh day with a duration of 40 minutes. Adherence to ethical guidelines was strictly maintained, and serum adiponectin and endothelin-1 levels were measured pre- and post-exercise using the ELISA method. Results Before swimming, the mean adiponectin levels were 4.30±1.50 ng/mL in the NFD group and 3.53±0.70 ng/mL in the HFD group. Post-exercise, these levels significantly decreased to 2.4±0.84 ng/mL (p=0.003) and 1.58±0.23 ng/mL (p=0.001), respectively. Endothelin-1 levels also showed significant decreases from 0.86 pg/mL (0.74-0.87) to 0.49 pg/mL (0.43-0.62) (p=0.003) in the NFD group, and from 0.89 pg/mL (0.86-0.93) to 0.69 pg/mL (0.60-0.75) (p=0.027) in the HFD group after swimming. Conclusion The study highlighted the significant effects of forced swimming stress on lowering serum adiponectin and endothelin-1 levels in Wistar rats, with more pronounced decreases observed in rats on a high-fat diet. The results of the study suggest the potential of exercise as a crucial component of strategies aimed at managing obesity and improving cardiovascular health, emphasizing the interaction between physical stress and dietary factors on metabolic and cardiovascular biomarkers.

Difference in the Standard and Novel Lipid Profile Parameters Between Patients With Alzheimer's Disease and Vascular Dementia Stratified by the Degree of Cognitive Impairment.

Background: Lipids and lipoproteins are significantly involved in maintaining structural and functional components of the human brain and neurons, but their role in the development of Alzheimer's disease (AD) and vascular dementia (VD) remains unclear. Objective: The aim of the present study was to explore the differences in the standard and novel lipid profile parameters in patients with AD and VD, stratified by the degree of cognitive impairment (CI). Methods: Present study included 66 patients with AD, 50 patients with VD, and 60 control subjects. For an evaluation of the global cognitive function the Montreal Cognitive Assessment (MoCA) test was used. In order to distinguish patients with VD from those with AD the Hachinski ischemic score was used. Plasma total cholesterol (TC), high-density lipoprotein -cholesterol (HDL-C), and triglycerides (TG) levels were determined using standard enzymatic colorimetric techniques, whereas the Friedewald formula was used to calculate low-density lipoprotein-cholesterol (LDL-C) levels. The non-traditional lipid indices such as TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C ratio were separately calculated. The differences between the groups were analyzed with the Kruskal Wallis test followed by the Mann-Whitney test or with ANOVA followed by the Tuckey posthoc test. Results: Results of the conducted study have found that the patients in AD group with moderate CI and patients in AD group with severe CI exhibited significantly lower levels of serum TC, TG, LDL-C, VLDL-C, Non- HDL-C, atherogenic index, TG/HDL-C, TC/HDL-C and LDL-C/HDL-C compared to cognitively normal control subjects. Moreover, patients in VD group with severe and moderate CI had significantly lower level of TG compared to control group of subjects. Our results have also shown that patients in AD group with moderate CI had significantly lower level of TC, TG, LDL-C, Non-HDL-C, atherogenic index, TG/HDL-C, TC/HDL-C compared to VD patients with moderate CI. In addition, patients in AD group with severe CI had significantly lower level of TC, LDL-C, Non-HDL-C and TC/HDL-C compared to VD patients with severe CI. Conclusion: The results of this study have shown dysregulation of lipid metabolism in AD and VD patients with different degree of CI. In both moderate and in severe CI, patients with AD had lower levels of majority of standard and novel lipid parameters compared to patients with VD. Further larger prospective studies are required to elucidate the accuracy of standard and novel lipid parameters in the assessment of different degree of CI in AD and VD.

The impact of type 2 diabetes duration on serum asymmetric dimethylarginine and C-reactive protein concentration in Bosnian patients.

Objective. The present study assessed the impact of type 2 diabetes mellitus (T2DM) duration on the serum asymmetric dimethylarginine (ADMA) and C-reactive protein (CRP) concentration in Bosnian patients. Methods. Participants for this cross-sectional study were randomly selected from the Family Medicine Clinic (Sarajevo, Bosnia and Herzegovina). Serum ADMA concentration was determined by ELISA. Serum high-sensitivity (hs-CRP) was determined by particle-enhanced immunonephelometry. ANOVA test followed by Scheffe post-hoc test or Kruskal-Wallis test followed by Man-Whitney test were used for statistical analysis. Results. The study included 38 patients in up to 10 years diabetes duration (≤10 years T2DM) group, 22 patients in greater than 10 years diabetes duration (>10 years T2DM) group, and 60 controls. Serum ADMA concentration in the >10 years T2DM group (1.81±0.15 µmol/L) was significantly higher compared to serum ADMA concentration in the ≤10 years T2DM group (1.38±0.41 µmol/L; p<0.001) and in controls (0.62±0.15 µmol/L; p<0.001). A significant difference in serum ADMA concentration was found between the <10 years T2DM group and the controls (p<0.001). The serum CRP concentration in the >10 years T2DM group [5.95 (4.20-9.12) mg/L] was significantly higher compared to serum CRP concentration in the <10 years T2DM group [2.35 (1.40-4.30) mg/L; p<0.001] and controls [0.85 (0.50-1.30) mg/L; p<0.001]. Significant difference in serum CRP concentration was observed between the <10 years T2DM group and controls (p<0.001). Conclusions. The present study showed an increase in the serum ADMA and CRP concentrations with the advancement of T2DM. These results suggest that ADMA and CRP may serve as indicators of endothelial dysfunction and chronic low-grade inflammation progression in patients with T2DM. Larger prospective studies are required to confirm the observed findings.

Traditional and Non-traditional Lipid Profiles in Bosnian Patients with Probable Alzheimer's Disease and Vascular Dementia.

Background: Conflicting data exist on traditional lipid profiles in patients with Alzheimer's disease (AD) and vascular dementia (VD), whereas scarce number of studies evaluated non-traditional lipid profiles in patients with AD and VD. Studies have shown that ethnic background may affect lipid profile. Objective: The aim of the present study was to conduct comparative assessment of traditional and non-traditional lipid profiles in Bosnian patients with AD and VD. Methods: A controlled, cross-sectional study was performed with 66 patients with AD, 50 patients with VD, and 60 control subjects. The Montreal Cognitive Assessment (MoCA) test was used for an evaluation of the global cognitive function. The Hachinski ischemic score was used to distinguish patients with VD from those with AD. Plasma total cholesterol (TC), high-density lipoprotein -cholesterol (HDL-C), and triglycerides (TG) levels were determined using standard enzymatic colorimetric techniques, whereas the Friedewald formula was used to calculate low-density lipoprotein-cholesterol (LDL-C) levels. The non-traditional lipid indices such as TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C ratio were separately calculated. The differences between the groups were analyzed with ANOVA followed by the Tuckey posthoc test or with the Kruskal Wallis test followed by the Mann-Whitney test. Results: Results of the present study have shown that patients in AD group had significantly lower level of TC, TG, LDL-C, VLDL-C, Non-HDL-C and significantly lower atherogenic index compared to the control group (CG) and compared to the VD patients. Significant difference in values of TG and VLDL-C was observed between VD and the CG, whereas no significant difference in values of TC, LDL-C, atherogenic index and Non-HDL-C was observed between these two groups. Our results have also shown that TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C ratios were significantly lower in AD patients compared to the VD and CG. Moreover, TG/HDL-C ratio was significantly lower in VD compared to the CG. However, a significant difference in TC/HDL-C and LDL-C/HDL-C was not observed between VD and the CG. Conclusion: Based on the results of the present study it can be deduced that there is a difference in traditional and non-traditional lipid profiles between AD and VD patients of Bosnian descent. Obtained results suggest that lipids are decreased in AD and in VD to a certain extent. However, since there is an inconsistence in literature whether there is an association between cholesterol and cognition, large prospective studies are required to elucidate this controversy.

Could the neutrophil-to-lymphocyte ratio serve as a marker in the diagnosis and prediction of acute appendicitis complications in children?

INTRODUCTION: Acute appendicitis (AA) is the most common surgical condition of the abdomen in children. The aim of this study was to analyse the possible use of the neutrophil-to-lymphocyte ratio (NLR) in the diagnosis and prediction of AA complications in children. MATERIAL AND METHODS: We included 170 AA patients under 15 years of age, who were divided into the following groups: Group 1 - non-operated patients with AA, and Group 2 - patients who underwent appendectomy. Based on pathologic grades of AA, Group 2 was subdivided into: Group A - phlegmonous, Group B - gangrenous, and Group C - perforated AA. NLR was calculated as the absolute neutrophil count divided by the absolute lymphocyte count. RESULTS: In Group 2 NLR was significantly higher than in Group 1 (5.5 (1.9-9.9) vs. 2.3 (1.2-3.7); p < 0.001). A significant difference in NLR was found between Group C and Group A (p < 0.001), and as well as between Group B and Group A (p = 0.001). The determined optimal cut-off value of NLR in differentiating Group 1 vs. Group 2 was ≥ 3.48 (p < 0.001). In differentiating Group A from Group C the optimal cut-off value of NLR was ≥ 5.61 (p < 0.001). Furthermore, optimal cut-off value of NLR in differentiating Group A from Group B was ≥ 5.45 (p = 0.001). CONCLUSIONS: The obtained results suggest that NLR could be used as a simple and reliable test in the diagnosis and prediction of AA complications in children. However, to draw definite conclusions on the predictive power of NLR as a marker of AA large multicentric studies are required.

Vitamin D3 attenuates oxidative stress and regulates glucose level and leukocyte count in a semi-chronic streptozotocin-induced diabetes model.

PURPOSE: Vitamin D3 (vit-D3) is a potent immunomodulator with anti-inflammatory and antioxidative properties. We used streptozotocin (STZ)-induced rat model of diabetes (DM) to evaluate the effects of vit-D3. We measured serum biochemical parameters, interleukin-17 (IL-17), osteocalcin (OC), malondialdehyde (MDA), and immune cell count on the 21st day of experiment. METHOD: A total of 24 Wistar rats were randomly divided into three groups. Each group had eight rats. During the 1st day of the experiment, the control group was injected intraperitoneally with citrate buffer, while STZ group and STZ + vit-D3 group were injected by a single i.p. dose (35 mg/kg) of STZ dissolved in citrate buffer (pH 4,5; 0,1 M). Vitamin D3 was applied via oral gavage once daily to the STZ + vit-D3 group for a total period of 14 days, starting from the 7th day of the experiment. RESULTS: STZ rats showed a significant reduction in OC and an increase in MDA and IL-17 serum concentrations compared to the control rats. We also observed a significant STZ-associated decrease in the number of lymphocytes and a significant increase in monocyte and eosinophil number. Oral treatment with vit-D3 to STZ-induced diabetic rats significantly increased OC and decreased MDA serum levels. Furthermore, vit-D3 treatment resulted in a good regulation of hematopoiesis such as increase in the number of segmented granulocytes and lymphocytes and a reduction in the number of monocytes and eosinophils. CONCLUSION: Vit-D3 treatment has important therapeutic effects; among many others it can attenuate oxidative stress and ameliorate the hyperglycemic state in the STZ-induced rat diabetic model, which is promising for further clinical trials.

Red blood cell distribution width-to-platelet ratio inversely correlates with indicators of disease activity status in rheumatoid arthritis patients.

Introduction. Present study was performed to verify red blood cell distribution width-to-platelet ratio (RPR) level in rheumatoid arthritis (RA) patients and to examine its correlation with clinical and biochemical indicators of disease activity status.Methods. In this cross-sectional analytical study, 67 patients with RA and 34 age- and gender-matched healthy control subjects were enrolled. Based on the disease activity score 28-ESR (DAS28-ESR), RA patients were divided into subgroups: low disease activity (n = 20), moderate disease activity (n = 22) and high disease activity (n = 25). Laboratory tests included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) concentration, platelet count (PLT), red blood cells count (RBC), red blood cells distribution width (RDW) and fibrinogen concentration. Statistical analyses were carried out using SPSS 13 software. Statistical significance was set at a p-value less than 0.05.Results. There was statistically significant difference (p = 0.006) between RPR in RA patients with different stages of disease activity, with higher values in patients with low disease activity. The RPR showed statistically significant negative correlations with ESR (rho = -0.309; p = 0.012), CRP (rho = -0.421; p = 0.001), swollen joint count - SJC (rho = -0.368; p = 0.002) and tender joint count - TJC (rho = -0.355; p = 0.003), DAS28-ESR (rho = -0.409; p = 0.001), DAS28-CRP (rho = -0.422; p < 0.0005) and Visual analogue scale - VAS (rho = -0.260; p = 0.033) in RA patients.Conclusion. The present study provided evidence that the lower RPR values in RA patients are significantly associated with the disease activity indicators.

Peripheral 8-iso-PGF2α as a Biomarker in Bosnian Patients with Alzheimer's Disease and Vascular Dementia.

BACKGROUND: Cerebrospinal levels of isoprostanes (IsoPs) have been established as biomarkers of oxidative stress in Alzheimer's disease (AD) and vascular dementia (VD). The value of peripheral levels in the diagnostics of these diseases is less conclusive. The aim of this study was to determine serum 8-iso-prostaglandin-F2alpha (8-iso-PGF2α) levels in Bosnian AD and VD patients and to establish whether there is an association between 8-iso-PGF2α serum concentration and cognitive impairment (CI) in patients with dementia. SUBJECTS AND METHODS: Serum levels of 8-iso-PGF2α were measured by enzyme immunoassay method in AD (n=30) and VD patients (n=30) and control subjects (CG, n=30). The AD and VD group were further stratified according to the level of CI. RESULTS: The serum 8-iso-PGF2α levels were significantly higher in the AD (74.00 pg/mL) and VD groups (38.00 pg/mL) compared to the CG (17.50 pg/mL). A significant difference in serum 8-iso-PGF2α levels between patients with moderate and severe CI was not established in either AD or VD. CONCLUSION: Serum 8-iso-PGF2α proved to be a good biomarker in AD and VD, however it cannot be recommended for the differentiation of moderate and severe CI.

The Triglyceride/HDL Ratio and Triglyceride Glucose Index as Predictors of Glycemic Control in Patients with Diabetes Mellitus Type 2.

INTRODUCTION: Poor glycemic control, assessed by higher glycated hemoglobin (HbA1c) levels, is associated with greater risk of diabetic complications. AIM: The aim of this study was to assess the association of triglyceride - to - HDL cholesterol (TG/HDL-C) ratio and triglyceride glucose (TyG) index with HbA1c and to evaluate their potential role as predictors of glycemic control in patients with diabetes mellitus type 2 (DM2). PATIENTS AND METHODS: This cross-sectional study was conducted in Health Center Banovici and included a total of 113 patients with DM2 classified according to their HbA1c values in two groups: DM2 HbA1c <7% - DM2 patients with good glycemic control (n=39) and DM2 HbA1c ≥7% - DM2 patients with poor glycemic control (n=74). Anthropometric, biochemical parameters and blood pressure values were measured, while TG/HDL-C ratio and TyG index were calculated. RESULTS: TG/HDL-C ratio and TyG index were significantly higher in DM2 HbA1c≥7% compared to DM2 HbA1c<7% group (p=0.003 and p<0.001; respectively). Both TG/HDL-C ratio and TyG index were positively associated with HbA1c levels (Rho=0.29; p=0.002; Rho=0.37; p<0.001; respectively). In linear regression analysis TG/HDL-C ratio and BMI, and also TyG index and BMI were significantly independently associated with HbA1c even after controlling for age, gender, diabetes duration and smoking. When we stratified patients according to BMI values, independent association between TG/HDL-C ratio and HbA1c remained significant only in normal weight subjects (OR 0.21; 95%CI: 0.05-0.37; ß=0.65; p=0.017), while independent association between TyG index and HbA1c remained significant only in overweight and obese subjects (OR 0.063; 95%CI: 0.01- 0.12; ß=0.24; p =0.027). CONCLUSION: TG/HDL-C ratio might be a useful predictor of glycemic control in normal weight, and TyG index in overweight and obese patients with DM2.

Relationship between the Neck Circumference, Standard Anthropometric Measures, and Blood Pressure in Bosnian Young Adults.

OBJECTIVE: The association between the neck circumference (NC) and components of metabolic syndrome in different countries and ethnic groups has been insufficiently investigated. The aim of the present study was to assess the impact of gender on NC values and to determine whether NC correlates with standard anthropometric measures and blood pressure values in Bosnian young adults. MATERIALS AND METHODS: Study participants were recruited by the snowball method. The NC, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured by trained personnel. Differences between the means were assessed by a Student's t-test. Coefficients of correlation were determined by Pearson's test. RESULTS: In young men (n=49), the value of NC was 37.71±1.79 cm, while in young women, (n=62) the value of NC was 32.23±1.83 cm (p<0.001). A significant positive correlation in both genders between the NC and BMI (r=0.70, p<0.001 in men; r=0.53,p<0.001 in women), and between the NC and WC (r=0.48, p<0.001 in men; r=0.38, p=0.01 in women), was found. A significant correlation between the NC and SBP (r=0.08, p=0.57), and DBP (r=0.20, p=0.17), in young men was not determined. Likewise, in young women, a significant correlation between the NC and SBP (r=0.08, p=0.54), and DBP (r=0.09, p=0.49), was not observed. CONCLUSION: Our results suggest that the NC measurement can be used as a valid method in obesity assessment in young adults. A lack of association between the NC and blood pressure requires additional investigation.

Leptin is associated with disease activity but not with anthropometric indices in rheumatoid arthritis patients.

INTRODUCTION: Leptin is a cytokine-like hormone which has a complex role in inflammation. However, the importance of leptin in the pathogenesis of rheumatoid arthritis (RA) is far from being fully elucidated. The aim of the study was to determine serum leptin levels in RA patients and to evaluate whether there is an association between disease activity, anthropometric indices and leptin levels. MATERIAL AND METHODS: This hypothesis-generating study included 55 RA patients and 25 matched healthy subjects. The serum leptin concentration was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Median serum leptin level in RA patients of 27.4 ng/ml (14.5-54.9 ng/ml) was statistically significantly higher (p = 0.03) compared with the median leptin value of 16.3 ng/ml (9.6-38.8 ng/ml) determined in healthy controls. The serum leptin level in the high disease activity group was significantly higher (p < 0.0005) than that in the low disease activity group and in healthy controls. A significant difference (p = 0.001) in serum leptin level was also found when the high disease activity group was compared with the moderate disease activity group. In the RA group a statistically significant positive correlation (rho = 0.390; p = 0.003) was observed between serum leptin level and disease activity score (DAS28). CONCLUSIONS: The present results show that serum leptin levels are increased and significantly associated with disease activity in patients with RA and may have a valuable role in the inflammatory reactions and pathogenesis of RA.

Neck Circumference as an Indicator of Central Obesity in Healthy Young Bosnian Adults: Cross-sectional Study.

BACKGROUND: Neck circumference (NC) is an index of subcutaneous adipose tissue distribution in an area of the upper part of the body. The aim of this study was to assess whether NC can be used as an indicator of central obesity and to determine the prevalence of central obesity in apparently healthy Bosnian young adults. METHODS: Participants for this cross-sectional study were recruited using the snowball method. NC was measured in horizontal straight position by placing the top edge of a plastic tape only below the laryngeal prominence and perpendicular to the longitudinal axis of the neck, with the head positioned in the Frankfort horizontal plane. Body mass index, waist circumference (WC), and waist-to-hip ratio were taken following the WHO guidelines. RESULTS: The study included 111 second year University of Sarajevo Dentistry students (49 students of male gender and 62 students of the female gender). Determined the optimal cutoff value of NC in the detection of central obesity based on WC values in healthy young participants of male gender was ≥37.45 cm (P < 0.001), while in healthy young participants of the female gender, it was ≥32.75 cm (P < 0.001). Based on the WHO guidelines for WC, central obesity was determined in 24.49% (n = 12) of male patients, and in 29.03% (n = 18) of female participants included in our investigation (P < 0.05). CONCLUSIONS: The results of the present study indicate that NC may be used as a screening tool for central obesity in healthy young adults. Prevalence of central obesity observed among student population suggests that there is a justified need for an implementation of healthy lifestyle programs in this population that would have preventive purposes.

Electrocardiographic abnormalities in Chagas disease in the general population: A systematic review and meta-analysis.

BACKGROUND: Chagas disease (CD) is a major public health concern in Latin America and a potentially serious emerging threat in non-endemic countries. Although the association between CD and cardiac abnormalities is widely reported, study design diversity, sample size and quality challenge the information, calling for its update and synthesis, which would be very useful and relevant for physicians in non-endemic countries where health care implications of CD are real and neglected. We performed to systematically review and meta-analyze population-based studies that compared prevalence of overall and specific ECG abnormalities between CD and non-CD participants in the general population. METHODS: Six databases (EMBASE, Ovid Medline, Web of Science, Cochrane Central, Google Scholar and Lilacs) were searched systematically. Observational studies were included. Odds ratios (OR) were computed using random-effects model. RESULTS: Forty-nine studies were selected, including 34,023(12,276 CD and 21,747 non-CD). Prevalence of overall ECG abnormalities was higher in participants with CD (40.1%; 95%CIs=39.2-41.0) compared to non-CD (24.1%; 95%CIs=23.5-24.7) (OR=2.78; 95%CIs=2.37-3.26). Among specific ECG abnormalities, prevalence of complete right bundle branch block (RBBB) (OR=4.60; 95%CIs=2.97-7.11), left anterior fascicular block (LAFB) (OR=1.60; 95%CIs=1.21-2.13), combination of complete RBBB/LAFB (OR=3.34; 95%CIs=1.76-6.35), first-degree atrioventricular block (A-V B) (OR=1.71; 95%CIs=1.25-2.33), atrial fibrillation (AF) or flutter (OR=2.11; 95%CIs=1.40-3.19) and ventricular extrasystoles (VE) (OR=1.62; 95%CIs=1.14-2.30) was higher in CD compared to non-CD participants. CONCLUSIONS: This systematic review and meta-analysis provides an update and synthesis in this field. This research of observational studies indicates a significant excess in prevalence of ECG abnormalities (40.1%) related to T. cruzi infection in the general population from Chagas endemic regions, being the most common ventricular (RBBB and LAFB), and A-V B (first-degree) node conduction abnormalities as well as arrhythmias (AF or flutter and VE). Also, prevalence of ECG alterations in children was similar to that in adults and suggests earlier onset of cardiac disease.

Elevated Serum C-Reactive Protein Level Is not Associated with Serum Nitric Oxide in Patients with Posttraumatic Stress Disorder.

BACKGROUND: The aim of the present study was to evaluate serum nitric oxide (NO) and C reactive protein (CRP) concentration in veterans with and without PTSD. Furthermore, we aimed to assess whether there is a correlation between serum NO and CRP concentrations in tested groups. SUBJECTS AND METHODS: Cross-sectional study included 90 male individuals, with and without experience of direct war combat, divided into three equal groups (n=30): group 1- included war veterans with PTSD, group 2 - included war veterans without PTSD, and control group - 30 apparently healthy volunteers, without experience of direct war combat. The diagnosis of PTSD was assessed according to the guidelines in the 10th revision of the International Classification of Diseases (ICD-10). High-sensitivity CRP was determined by immunonephelometry. The serum NO level was determined by classic colorimetrical Griess reaction. RESULTS: Serum CRP concentration in veterans with (3.54±1.19 mg/L) and without PTSD (3.24±2.04 mg/L), was significantly higher (p<0.05) compared to control group (1.26±1.06 mg/L). Serum NO concentration in veterans with (7.64±4.43 µmol/L) and without PTSD (7.12±2.60 µmol/L) was significantly lower (p<0.05) compared to control group (11.26±7.01 µmol/L). Statistically significant correlation between serum NO and CRP concentration was determined in veterans without PTSD (r=-0.473; p<0.01). No correlation was observed between serum NO and CRP concentration in veterans with PTSD (r=0.118; p=0.534) and in control group (r=-0.067; p=0.727). CONCLUSION: The present study has showed significant increase of serum CRP and significant decrease of serum NO concentrations in veterans with and without PTSD. Furthermore, statistically significant negative correlation between serum NO and CRP concentration was determined only in veterans without PTSD. Obtained results indicate that the complex mechanism of the pathogenesis of PTSD requires further research.

Serum homocysteine levels in patients with probable vascular dementia.

Aim To investigate total homocysteine (tHcy) serum concentration in patients with probable vascular dementia (VD) and in agematched controls, as well as to determine an association between tHcy serum concentration and cognitive impairment in patients with probable VD. Methods Serum concentration of tHcy was determined by the Fluorescence Polarization Immunoassay on the AxSYM System. Cognitive impairment was tested by the Mini Mental Status Examination (MMSE) score. Body mass index (BMI) was calculated for each subject included in the study. Results Age, systolic, diastolic blood pressure and BMI did not differ significantly between the two groups. Mean serum tHcy concentration in the control group of subjects was 13.35 µmol/L, while in patients with probable VD it was significantly higher, 19.45 µmol/L (p=0.002). A negative but insignificant association between serum tHcy concentration and cognitive impairment in patients with probable VD was found. Conclusion Increased tHcy concentration in patients with probable VD suggests the possible independent role of Hcy in the pathogenesis of VD.

Relation of antioxidant capacity of diet and markers of oxidative status with C-reactive protein and adipocytokines: a prospective study.

BACKGROUND: The role of dietary antioxidants and plasma oxidant-antioxidant status in low-grade chronic inflammation and adipocytokine levels is not established yet. OBJECTIVES: We aimed to evaluate whether total dietary antioxidant capacity (assessed by dietary ferric reducing antioxidant potential (FRAP)), serum uric acid (UA) and gamma glutamyltransferase (GGT) were associated with low-grade chronic inflammation and circulating adipocytokines. METHODS: Data of 4506 participants aged ≥55years from the Rotterdam Study were analyzed. Baseline (1990-1993) FRAP score was assessed by a food frequency questionnaire. Baseline UA and GGT levels were assessed in non-fasting serum samples. Serum high sensitivity C-reactive protein (hs-CRP) was measured at baseline and 10years later. Plasma leptin, adiponectin, plasminogen activator inhibitor-1 (PAI-1) and resistin levels were assessed 10years later. RESULTS: A high FRAP score was associated with lower levels of UA and GGT. Overall, no association was found between FRAP and hs-CRP levels. FRAP score was associated with lower levels of leptin and PAI-1, higher levels of adiponectin, and no difference in resistin levels. Increased levels of UA were associated with higher levels of hs-CRP, PAI-1 and leptin; lower levels of adiponectin and no difference in resistin levels. Similarly, GGT was associated with higher levels of hs-CRP whereas no association was observed between GGT and adipocytokines. CONCLUSION: These findings suggest that overall antioxidant capacity of diet and low levels of UA are associated with circulating adipocytokines whereas no consistent association was found with hs-CRP.

The Role of DNA Methylation and Histone Modifications in Neurodegenerative Diseases: A Systematic Review.

IMPORTANCE: Epigenetic modifications of the genome, such as DNA methylation and histone modifications, have been reported to play a role in neurodegenerative diseases (ND) such as Alzheimer's disease (AD) and Parkinson's disease (PD). OBJECTIVE: To systematically review studies investigating epigenetic marks in AD or PD. METHODS: Eleven bibliographic databases (Embase.com, Medline (Ovid), Web-of-Science, Scopus, PubMed, Cinahl (EBSCOhost), Cochrane Central, ProQuest, Lilacs, Scielo and Google Scholar) were searched until July 11th 2016 to identify relevant articles. We included all randomized controlled trials, cohort, case-control and cross-sectional studies in humans that examined associations between epigenetic marks and ND. Two independent reviewers, with a third reviewer available for disagreements, performed the abstract and full text selection. Data was extracted using a pre-designed data collection form. RESULTS: Of 6,927 searched references, 73 unique case-control studies met our inclusion criteria. Overall, 11,453 individuals were included in this systematic review (2,640 AD and 2,368 PD outcomes). There was no consistent association between global DNA methylation pattern and any ND. Studies reported epigenetic regulation of 31 genes (including cell communication, apoptosis, and neurogenesis genes in blood and brain tissue) in relation to AD and PD. Methylation at the BDNF, SORBS3 and APP genes in AD were the most consistently reported associations. Methylation of α-synuclein gene (SNCA) was also found to be associated with PD. Seven studies reported histone protein alterations in AD and PD. CONCLUSION: Many studies have investigated epigenetics and ND. Further research should include larger cohort or longitudinal studies, in order to identify clinically significant epigenetic changes. Identifying relevant epigenetic changes could lead to interventional strategies in ND.

The functions of estrogen receptor beta in the female brain: A systematic review.

Females have unique and additional risk factors for neurological disorders. Among classical estrogen receptors, estrogen receptor beta (ERß) has been suggested as a therapeutic target. However, little is known about the role of ERß in the female brain. Six electronic databases were searched for articles evaluating the role of ERß in the female brain and the influence of age and menopause on ERß function. After screening 3186 titles and abstracts, 49 articles were included in the review, all of which were animal studies. Of these, 19 focused on cellular signaling, 7 on neuroendocrine pathways, 8 on neurological disorders, 4 on neuroprotection and 19 on psychological and psychiatric outcomes (6 studies evaluated two or more outcomes). Our findings showed that ERß phosphorylated and activated intracellular second messenger proteins and regulated protein expression of genes involved in neurological functions. It also promoted neurogenesis, modulated the neuroendocrine regulation of stress response, conferred neuroprotection against ischemia and inflammation, and reduced anxiety- and depression-like behaviors. Targeting ERß may constitute a novel treatment for menopausal symptoms, including anxiety, depression, and neurological diseases. However, to establish potential therapeutic and preventive strategies targeting ERß, future studies should be conducted in humans to further our understanding of the importance of ERß in women's mental and cognitive health.

Estrogen receptor ß actions in the female cardiovascular system: A systematic review of animal and human studies.

Five medical databases were searched for studies that assessed the role of ERß in the female cardiovascular system and the influence of age and menopause on ERß functioning. Of 9472 references, 88 studies met our inclusion criteria (71 animal model experimental studies, 15 human model experimental studies and 2 population based studies). ERß signaling was shown to possess vasodilator and antiangiogenic properties by regulating the activity of nitric oxide, altering membrane ionic permeability in vascular smooth muscle cells, inhibiting vascular smooth muscle cell migration and proliferation and by regulating adrenergic control of the arteries. Also, a possible protective effect of ERß signaling against left ventricular hypertrophy and ischemia/reperfusion injury via genomic and non-genomic pathways was suggested in 27 studies. Moreover, 5 studies reported that the vascular effects of ERß may be vessel specific and may differ by age and menopause status. ERß seems to possess multiple functions in the female cardiovascular system. Further studies are needed to evaluate whether isoform-selective ERß-ligands might contribute to cardiovascular disease prevention.

Elevated Serum Leptin Level Is Associated with Body Mass Index But Not with Serum C-reactive Protein and Erythrocyte Sedimentation Rate Values in Hemodialysis Patients.

OBJECTIVES: Aim of the present study was to investigate serum concentration of leptin and its association with values of body mass index (BMI), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) in hemodialysis (HD) patients. METHODS: This cross-sectional study included 60 HD patients (34 male, 26 female) and 30 age- and sex-matched (4 males, 26 females) apparently healthy subjects. Serum leptin concentration was determined by an enzyme-linked immunosorbent assay (ELISA). Serum CRP concentration was measured by means of particle-enhanced immunonephelometry. ESR value was determined by Western Green method. BMI was calculated as weight (kg) divided by height squared (m(2)). RESULTS: Results have shown that median serum leptin concentration (30.65 ng/mL; 12.48-86.40 ng/mL) was statistically significantly higher in HD patients compared to median serum leptin concentration (15.75 ng/mL; 9.15-30.65 ng/mL) in the control group of healthy subjects (p<0.05). Likewise, median serum CRP concentration (5.5 mg/L; 1.93-8.9 mg/L) and median ESR value (57.5 mm/h; 40.5-77.0 mm/h) were significantly higher in HD patients compared to median serum CRP concentration (0.8 mg/L; 0.38-1.43 mg/L) (p<0.001) and median ESR value (10.0 mm/h; 6.5-14.0 mm/h) (p<0.001) determined in the control group. Statistically significant positive correlation was found between BMI values and serum leptin concentration in HD patients (rho=0.434; p<0.001). Positive, although not significant, correlation was observed between serum CRP and leptin levels in HD patients (rho=0.171; p>0.05). Negative correlation between ESR values and serum leptin concentrations in HD patients was determined but it was not statistically significant (rho= -0.029; p>0.05). CONCLUSIONS: Increased serum concentration of leptin as pro-inflammatory cytokine as well as elevated serum values of CRP and ESR indicate presence of systemic micro inflammation in HD patients. Results of the present study point to possible use of serum leptin concentration as an indicator of nutritional status in HD patients based on observed significant positive correlation between serum leptin concentrations and BMI values. However, absence of significant association between serum leptin and CRP levels as well as between serum leptin concentrations and ESR values in HD patients requires further investigation and clarification.