Positive association between abdominal aortic diameter and serum collagen XVIII levels.

BACKGROUND: The identification of abdominal aortic aneurysm (AAA) biomarker offers a perspective to determine disease progress and rupture risk. The aim of our study was to evaluate the association between selected circulating biomarkers and diameter of abdominal aorta. METHODS: One hundred and two patients (88 men and 14 women) with mean age 70.0±8.7 years were included in a single center cross-sectional study conducted between February 2016 and October, 2018. AAA was defined as subrenal aortic dilatation ≥3 cm. Serum biomarker concentrations (insulin-like growth factor-1, peroxiredoxin-1, collagen IV, collagen XVIII) were measured by an enzyme-linked immunosorbent assay (ELISA). Adjustments including variables with different baseline distribution at univariate level with P<0.1 (age, body mass index, coronary artery disease, fibrinogen) were performed in multivariate models. RESULTS: Higher collagen XVIII was found in AAA patients in comparison with the control group of patients (39.5 vs. 25.0 ng/mL; P=0.002). Diameter of abdominal aorta was positively associated with collagen XVIII levels in univariate (B=0.16; P=0.004), and in multivariate analysis (B=0.14; P=0.027), i.e. increase in collagen XVIII by 1 ng/mL corresponded to an increase in abdominal aortic diameter by 0.14 mm. Patients with serum collagen XVIII levels in the third tertile (˃47 ng/mL) had 4.23 times higher risk of AAA compared to patients with collagen XVIII levels in the first and second tertiles (OR 4.23; 95% CI 1.42-11.6; P=0.020). No association was found between other examined biomarkers and abdominal aortic diameter. CONCLUSIONS: Diameter of abdominal aorta was positively associated with serum collagen XVIII level.

Surgical Anatomy of the Gastrointestinal Tract and Its Vasculature in the Laboratory Rat.

The aim of this study was to describe and illustrate the morphology of the stomach, liver, intestine, and their vasculature to support the planning of surgical therapeutic methods in abdominal cavity. On adult Wistar rats corrosion casts were prepared from the arterial system and Duracryl Dental and PUR SP were used as a casting medium and was performed macroscopic anatomical dissection of the stomach, liver, and intestine was performed. The rat stomach was a large, semilunar shaped sac with composite lining. On the stomach was very marked fundus, which formed a blind sac (saccus cecus). The rat liver was divided into six lobes, but without gall bladder. Intestine of the rat was simple, but cecum had a shape as a stomach. The following variations were observed in the origin of the cranial mesenteric artery. On the corrosion cast specimens we noticed the presence of the anastomosis between middle colic artery (a. colica media) and left colic artery (a. colica sinistra). We investigated the second anastomosis between middle colic artery and left colic artery. The results of this study reveal that the functional anatomical relationship between the rat stomach, liver and intestine is important for the development of surgical research in human and veterinary medicine.

Biomarkers associated with obesity and overweight in the Roma population residing in eastern Slovakia.

BACKGROUND: Obesity and overweight are major contributors to the global burden of chronic diseases and disability in both majority and minority populations. METHODS: Data from the cross-sectional population-based HepaMeta study conducted in Slovakia in 2011 were used. The sample comprised a total of 452 Roma. Measurements of special bioactive mediators were taken in final groups consisting of 63 male Roma respondents (mean age = 32.59; SD = 8.63) and 117 female Roma respondents (mean age = 34.55; SD = 8.35). Respondents were divided into three groups: those with normal weight, those with overweight and obese. Values for anthropometric parameters, lipids parameters, C-reactive protein, TNF-alpha, IL-6, leptin, and adiponectin were determined. RESULTS: 27.6% of examined Roma females and 26.9% of males were overweight. Obesity (BMI > 30.0 kg/m2) appeared in a higher proportion of males (28.8%) compared with female (26.5%). Mean levels of total cholesterol, triacylglycerol and LDL-cholesterol were significantly elevated in the overweight and obese subjects compared to normal-weight Roma respondents. The relation was reversed for HDL-C level, with significantly decreased levels in both male and female obese Roma (p < 0.001). The concentration of adiponectin was significantly lower in obese subjects of both genders versus non-obese (Roma male p < 0.001, Roma female p < 0.05). Plasma levels of leptin, IL-6, hs-CRP as well as TNF-alpha increased in Roma significantly with increasing BMI. CONCLUSION: The study is the first one to provide data about selected biomarkers. Results may be useful in predicting obesity and its related diseases in the Roma population from the eastern part of Slovakia.

Circulatory osteoprotegerin is related to osteoporosis of the hip in patients with COPD.

BACKGROUND: Osteoprotegerin (OPG), a potent inhibitor of osteoclastogenesis, decreases bone resorption and has protective effects on bone mineral density (BMD). Recently we have shown that the adipose-tissue derived OPG relates to BMD in patients with chronic obstructive pulmonary disease (COPD), a condition associated with increased risk of osteoporosis. OBJECTIVE: Here we aimed to investigate the potential of circulatory OPG to reflect hip BMD in patients with COPD. PATIENTS AND METHODS: In 56 subjects with COPD [age, 61.7 ± 6.7 years; forced expiratory volume in 1 s (FEV1), 53.6 ± 19.2% predicted], total femur BMD was assessed by dual energy X-ray absorptiometry, serum OPG and ß-crosslaps, a marker of increased bone resorption, by commercially available assays. RESULTS: From patients with normal hip BMD (n = 32, T-score 0.1 ± 0.8) to those with osteopenia (n = 14, T-score -1.6 ± 0.4) and osteoporosis (n = 10, T-score -3.4 ± 0.7) serum OPG levels significantly increased (6.6 ± 1.8 versus 7.2 ± 2.9 and versus 8.6 ± 1.5 pmol/l, p = 0.036). In addition, hip T-scores were directly related to FEV1, and inversely to ß-crosslaps (R = 0.40, p = 0.002; R = 0.38, p = 0.01, respectively). In multivariate analysis, OPG independently predicted hip T-scores after adjustments for age, gender, FEV1, and ß-crosslaps (p = 0.011, adjusted R(2) = 0.354). Area under receiver operator curve for OPG as a discriminator of osteoporosis was 0.787 (95% CI, 0.653-0.921) (p = 0.005). CONCLUSIONS: Present results suggest that osteoporosis of the hip is associated with increased circulatory levels of OPG in patients with COPD. OPG might serve as a biomarker of this COPD-related comorbidity.

Left ventricular morphology and function in patients with rheumatoid arthritis.

OBJECTIVES: Congestive heart failure (CHF) and inflammation are important contributors to the excess of overall morbidity and mortality in patients with rheumatoid arthritis (RA). CHF rather than ischaemic heart disease (IHD) appears to participate on the mortality in these patients. However, there are controversial results about significance of plasma N-terminal of pro-B type natriuretic peptide (NT-proBNP) and other inflammatory markers investigation for an early detection of heart dysfunction. The aim of this study was to examine the cardiac morphology and function in patients with RA in relation to the plasma NT-proBNP and to inflammatory markers. SUBJECTS AND METHODS: Sixty patients with RA (52 women and 8 men) and 30 gender and age matched controls were included in the study. Blood samples were analyzed for NT-proBNP, tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and C-reactive protein (CRP). Transthoracic echocardiography was performed on the same day in all subjects. RESULTS: RA patients had significantly higher plasma NT-pro BNP as compared with controls (99.39 ± 8.98 vs. 66.90 ± 7.93 pg/ml, p < 0.05) and significantly higher levels of TNF-alpha, IL-6 and CRP (for all p < 0.01). In RA group higher levels of NT-proBNP were detected in rheumatoid factor (RF) posivite patients. Patients with RA had significantly worse left ventriclular (LV) systolic function (LV ejection fraction (LVEF) 64.6 ± 0.8 vs. 70.1 ± 1.3 %, p < 0.01) and diastolic function (E/A 1.11 ± 0.05 vs. 1.32 ± 0.07, p < 0.05). There were no correlations of NT-proBNP with paramaters of systolic and diastolic function, however, a negative correlation of TNF-alpha with these parameters was detected (TNF-alpha vs. LV mass index (LVM-i): r = - 0.34, p < 0.05), TNF-alpha vs. LVEF: r = - 0.30, p < 0.05 and TNF-alpha vs. E/A: r = - 0.30, p < 0.05). CONCLUSION: We conclude that TNF-alpha may be better marker of heart impairment caused by chronic inflammation in RA patients than NT-proBNP.

Acute and long-term effect of infliximab on humoral and echocardiographic parameters in patients with chronic inflammatory diseases.

Tumor necrosis factor alpha (TNF-alpha) plays an important role in the pathogenesis of chronic inflammatory diseases, i.e., rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD), and ulcerative colitis (UC). Anti-TNF-alpha strategies are successfully used in their treatment. However, their effect on heart function is still uncertain. The objectives of the study were to examine the acute and long-term effect of infliximab on the heart morphology and function in patients with chronic inflammatory disorders. Thirty-one patients (21 men and 10 women) were included. Ten percent of them were diagnosed with RA, 22.5 % with AS, 22.5 % with CD, and 45 % with UC, respectively. N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) was measured before and immediately after infliximab administration at the beginning of the study and in the sixth and 12th months. Echocardiography was performed at baseline and in the sixth and 12th months. There was a significant increase in NT-proBNP after the first infliximab infusion (88.40 ± 14.09 vs. 95.24 ± 14.28 pg/ml, p = 0.0046) and similar response was detected after each infusion in the sixth and 12th months. Plasma NT-proBNP slightly but not significantly decreased (88.40 ± 14.09 vs. 81.74 ± 23.14 pg/ml, p = 0.583, and 88.40 ± 14.09 vs. 56.83 ± 17.77 pg/ml, p = 0.0576, in the sixth and 12th months, respectively). There were no significant changes in echocardiographic structural and functional parameters of the left ventricle during follow-up. Plasma NT-proBNP mildly but significantly increases immediately after infliximab infusion. However, long-term infliximab administration does not deteriorate both cardiac morphology and function.

Nutritional status in relation to respiratory impairment and systemic inflammation in patients with acute exacerbations of COPD.

BACKGROUND: Knowledge of the effects of undernourishment on the severity of respiratory impairment, systemic inflammation and oxidative stress during acute exacerbations of COPD (AECOPD) is limited. In patients with AECOPD, we assessed the relationships between BMI, lung function, and markers of systemic inflammation and oxidative stress. MATERIAL/METHODS: We measured pulmonary function, serum C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, malondialdehyde (MDA), erythrocytic glutathione-peroxidase (GPx), superoxiddismutase (SOD), and catalase (CAT) in 113 patients admitted to the hospital due to an AECOPD (80 males, age 66.2+/-11.0 years, FEV1 41.5+/-13.7% predicted). RESULTS: From the low (<21 kg/m2) towards the normal (21-24.9 kg/m2), high (25-29.9 kg/m2) and obese (>30 kg/m2) BMI groups, FEV1, FEV1-to-forced vital capacity (FVC) ratio, inspiratory capacity (IC), and the IC-to-total lung capacity (IC/TLC) ratio increased (p<0.01; p<0.001; p=0.039; p=0.002, respectively), while residual volume (RV), TLC and RV/TLC ratio were reduced (p<0.001; p<0.001; p=0.018, respectively). Patients with low BMI had significantly lower FEV1, FEV1/FVC, IC and IC/TLC, and higher RV and TLC values compared to the high and obese BMI groups. From the low towards the normal, high and obese BMI, reductions in serum CRP, and a trend towards increases in erythrocytic GPx were observed (p=0.023; p=0.056, respectively). No differences were seen in circulating TNF-alpha, IL-6 or IL-8, MDA or erythrocytic CAT and SOD between the groups. CONCLUSIONS: In patients with acute exacerbations of COPD, low BMI is associated with higher degree of bronchial obstruction and pulmonary hyperinflation, in association with higher circulating CRP levels.

Effects of continuous positive airway pressure on cardiovascular risk profile in patients with severe obstructive sleep apnea and metabolic syndrome.

BACKGROUND: The increased risk of atherosclerotic morbidity and mortality in patients with obstructive sleep apnea (OSA) has been linked to arterial hypertension, insulin resistance, systemic inflammation, and oxidative stress. We aimed to determine the effects of 8 weeks of therapy with continuous positive airway pressure (CPAP) on glucose and lipid profile, systemic inflammation, oxidative stress, and global cardiovascular disease (CVD) risk in patients with severe OSA and metabolic syndrome. METHODS: In 32 patients, serum cholesterol, triglycerides, high-density lipoprotein cholesterol, fibrinogen, apolipoprotein A-I, apolipoprotein B (ApoB), high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor (TNF)-alpha, leptin, malondialdehyde (MDA), and erythrocytic glutathione peroxidase (GPx) activity were measured at baseline and after 8 weeks of CPAP. The insulin resistance index (homeostasis model assessment [HOMA-IR]) was based on the homeostasis model assessment method, the CVD risk was calculated using the multivariable risk factor algorithm. RESULTS: In patients who used CPAP for > or = 4 h/night (n = 16), CPAP therapy reduced systolic BP and diastolic BP (p = 0.001 and p = 0.006, respectively), total cholesterol (p = 0.002), ApoB (p = 0.009), HOMA-IR (p = 0.031), MDA (p = 0.004), and TNF-alpha (p = 0.037), and increased erythrocytic GPx activity (p = 0.015), in association with reductions in the global CVD risk (from 18.8 +/- 9.8 to 13.9 +/- 9.7%, p = 0.001). No significant changes were seen in patients who used CPAP for < 4 h/night. Mask leak was the strongest predictor of compliance with CPAP therapy. CONCLUSIONS: In patients with severe OSA and metabolic syndrome, good compliance to CPAP may improve insulin sensitivity, reduce systemic inflammation and oxidative stress, and reduce the global CVD risk.

Oxidative stress in patients with COPD and pulmonary hypertension.

OBJECTIVE: Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Oxidant/antioxidant imbalance has also been reported in various forms of pulmonary hypertension. The present study aimed to assess systemic oxidative stress, as reflected by serum malondialdehyde (MDA) concentrations and activities of antioxidant enzymes in erythrocytes [glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT)] in patients with and without pulmonary hypertension secondary to COPD. PATIENTS AND METHODS: Seventy-five patients (58 male) with COPD (mean age 65.1 +/- 1.2 years; mean smoking history 35.6 +/- 3.8 pack-years) were studied. Twenty-one healthy non-smokers served as a control group. Pulmonary function was evaluated with body plethysmography; mean and systolic pulmonary artery pressures (Ppa) were assessed with Doppler echocardiography. Serum concentrations of MDA and activities of GPX, SOD and CAT in washed red blood cells were measured using spectrophotometry. RESULTS: Pulmonary hypertension was present in 28 patients with COPD (systolic Ppa: 46.4 +/- 2.3 mmHg; mean Ppa: 26.0 +/- 1.9 mmHg) and absent in 47 (systolic Ppa: 22.9 +/- 0.8 mmHg; mean Ppa: 13.4 +/- 0.6 mmHg). Compared with the healthy control group, all the patients (with or without pulmonary hypertension) had higher serum MDA concentrations (1.5 +/- 0.1 versus 2.3 +/- 0.1 versus 2.3 +/- 0.1 nmol/mL, ANOVA, P < 0.001) and lower erythrocyte GPX activity (51.3 +/- 3.2 versus 42.2 +/- 2.0 versus 41.3 +/- 2.5 U/g Hb, P = 0.029), whereas SOD (1121.1 +/- 29.0 versus 1032.6 +/- 21.8 versus 1032.7 +/- 36.2 U/g Hb, P = 0.063) and CAT activities (4.9 +/- 0.2 versus 4.6 +/- 0.1 versus 4.7 +/- 0.2 U/g Hb; P= 0.454) were similar. No differences were observed in serum MDA concentrations or activities of GPX, SOD and CAT in erythrocytes between COPD patients with and without pulmonary hypertension. CONCLUSION: The study demonstrates the presence of oxidative/antioxidative imbalance in the systemic circulation in patients with COPD: compared with healthy subjects, COPD patients had higher serum MDA concentrations and lower GPX activity in erythrocytes. The magnitudes of the increase in MDA and reduction in GPX activity were similar in COPD patients with pulmonary hypertension and in those with normal pulmonary artery pressures.

Systemic inflammation and systemic oxidative stress in patients with acute exacerbations of COPD.

BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD), the inflammatory processes and oxidative stress are closely linked in the lung compartment. However, the relationships between systemic inflammation and parameters of oxidative stress in the systemic circulation during acute exacerbations of COPD remain to be explored. OBJECTIVE: To analyze relationships between erythrocytic glutathione peroxidase (GPx), a marker of systemic oxidative stress, and parameters reflecting systemic inflammation, such as circulating neutrophils, C-reactive protein (CRP), and interleukin (IL)-6, in patients with acute exacerbations of COPD. PATIENTS AND METHODS: We measured erythrocytic GPx activity, circulating neutrophil count, and serum high-sensitivity (hs) CRP and IL-6 in 177 patients admitted to the hospital due to an acute exacerbation of COPD (91 males, mean age 66.8+/-0.9 years, mean FEV1 45.3+/-1.3% predicted). RESULTS: From GOLD Stage II to Stage III and IV, erythrocytic GPx activity significantly decreased [mean+/-SEM: from 44.3+/-1.7 U/g Hb to 40.8+/-1.1 U/g Hb and to 38.4+/-1.5 U/g Hb, p = 0.037], while serum hsCRP increased [median (25th, 75th percentile): from 9.6 (3.0, 23.0) mg/l to 23.3 (6.4, 46.8) mg/l, and to 26.7 (6.5, 117.2) mg/l, p = 0.004]. Erythrocytic GPx activity was significantly inversely related to both, log neutrophil count (r = -0.219, p = 0.003) and log hsCRP (r = -0.199, p = 0.008). CONCLUSIONS: Our study suggests an association between systemic inflammation and systemic oxidative stress reflected by erythrocytic GPx in patients with acute exacerbations of COPD.

Adiponectin as a biomarker of clinical manifestation of metabolic syndrome.

OBJECTIVES: To search whether there are differences in serum levels of adiponectin in subjects with metabolic syndrome (MS) as compared to the healthy controls. METHODS: Serum levels of adiponectin were measured by ELISA in 22 subjects with MS (MS group: 9 males and 13 females, average age +/- SD 43.19 +/- 6.16) and in 17 healthy controls of about the same age (CONT group: 8 males and 9 females, average age +/- SD 45.88 +/- 11.6). All subjects of MS group had BMI >30 and also other criteria of MS (e.g. obesity, insulin resistance, possible disorders of glucose metabolism, dyslipidemia and hypertension) were manifested in all of them. Adiponectin levels in serum were compared between the groups and also within the pooled MS plus CONT group the interrelations between serum levels of adiponectin and BMI, serum fasting insulin (estimated by RIA method) and smoking were examined. For statistical processing one way ANOVA or its non-parametric parallel (Kruskal-Wallis one-way analysis) as well as regression and correlation analysis were used. RESULTS: Subjects with MS syndrome had significantly higher BMI, systolic and diastolic BP, fasting glycemia and insulin level. Significantly higher were also the values of both indexes of insulin resistance such as IR(HOMA) and IR(QUlCKI). In contrast, however, MS group had significantly lower adiponectin level than CONT group. There was no difference between the average age of both groups. In pooled MS plus CONT group inverse correlations were found between serum levels of adiponectin on one side and BMI and fasting insulin level on the other, while the level of adiponectin between smokers (which was declared by 18/39 subjects) and non-smokers did not show any influence on serum levels of adiponectin. CONCLUSIONS: Low level of adiponectin in obese individuals may be considered as a marker predicting a possibility of the development of metabolic syndrome. It is suggested that early regulation of serum adiponectin levels in obese subjects by treatment of obesity, especially in young ones, could result in a lowering the risk of mainly cardiovascular diseases associated with MS.

Systemic inflammation in patients with COPD and pulmonary hypertension.

STUDY OBJECTIVES: COPD is a systemic disorder that is associated with increases of inflammatory proteins in systemic circulation. However, no data on the potential role of systemic inflammation in pulmonary hypertension secondary to COPD are available. Therefore, our aim was to investigate the degree of systemic inflammation reflected by circulatory levels of C-reactive protein (CRP), tumor-necrosis factor (TNF)-alpha, and interleukin (IL)-6 in COPD patients with and without pulmonary hypertension. DESIGN: Cross-sectional study. SETTING: University hospital, tertiary referral setting. PATIENTS AND MEASUREMENTS: In 43 consecutive patients with COPD (mean [+/- SD] age, 65.0 +/- 10.5 years; mean FEV(1), 46.2 +/- 18.1% predicted), lung function was assessed using body plethysmography; pulmonary artery pressure (Ppa) levels were measured by echocardiography. Serum TNF-alpha and IL-6 levels were assessed by enzyme-linked immunosorbent assay, and high-sensitivity serum CRP levels were measured by chemiluminescent immunoassay. RESULTS: Pulmonary hypertension was present in 19 patients and was absent in 24 patients. In patients with pulmonary hypertension, serum CRP and TNF-alpha levels were significantly higher than in those patients without hypertension (median, 3.6 mg/L [25th to 75th percentile, 1.4 to 13.0 mg/L] vs 1.8 mg/L [25th to 75th percentile, 0.8 to 2.8 mg/L; p = 0.034]; and median, 4.2 pg/mL [25th to 75th percentile, 3.4 to 10.9 pg/mL] vs 3.1 pg/mL [25th to 75th percentile, 2.1 to 4.2 pg/mL]; p = 0.042, respectively). No differences were seen in serum IL-6 (median, 10.4 pg/mL [25th to 75th percentile, 8.8 to 12.2 pg/mL] vs 10.5 pg/mL [25th to 75th percentile, 9.4 to 39.1 pg/mL]; p = 0.651) between the groups. In multiple linear regression analysis, the following two variables were independent predictors of systolic Ppa (R(2) = 0.373): Pao(2) (p = 0.011); and log-transformed serum CRP level (p = 0.044). CONCLUSION: We conclude that increases in Ppa in patients with COPD are associated with higher serum levels of CRP and TNF-alpha, raising the possibility of a pathogenetic role for low-grade systemic inflammation in the pathogenesis of pulmonary hypertension in COPD patients.

Nutrition, body weight and deterioration of familial combined hyperlipidemia.

Lipid and apolipoprotein serum levels as a consequence of excessive nutrition in the overweight individuals with familial combined hyperlipidemia (FCHL) in comparison with the obese ones are studied only sporadically. In this study, the effect of overweight and obesity in subjects with FCHL on serum lipids and apolipoproteins was investigated. The participants were 36 overweight and 10 obese men. 17 normolipidemic healthy men served as the control group. The mean age of all subjects included was 49+/-9 years. Lipid and apolipoprotein serum levels were determined by standard methods. The increased body weight in overweight men with FCHL correlates with increased cholesterol and triacylglycerol serum levels (p<0.001), atherogenous ratio values, apolipoprotein serum levels--apo C-III, apo C-II and apo B100oo (p<0.001) as well as decreased HDL cholesterol serum levels (p<0.05). Lipid metabolism in men with FCHL is deteriorated by a high energy intake and its low output. The overweight and not only obesity, in association with FCHL, is an important risk factor for premature development of ischemic events.