Neurologic Biomarkers, Neuroimaging, and Cognitive Function in Persistent Atrial Fibrillation: A Cross-Sectional Study.

The aim of this study was to evaluate the specific neurologic biomarkers, neuroimaging findings, and cognitive function in patients with persistent atrial fibrillation (AF) undergoing electrical cardioversion, compared to control subjects. This cross-sectional study included 25 patients with persistent AF undergoing electrical cardioversion and 16 age- and sex-matched control subjects. Plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light protein (NFL), and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), as well as parameters of neuroimaging and cognitive function, were compared between the groups. Neuroimaging was performed using the standard magnetic resonance imaging (MRI) protocol. Cognitive function was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive Function Index. Further analysis of neurologic biomarkers was performed based on the subsequent electrical cardioversion. There was no significant difference in GFAP (median of 24.7 vs. 28.7 pg/mL, p = 0.347), UCH-L1 (median of 112.8 vs. 117.7 pg/mL, p = 0.885), and NFL (median of 14.2 vs. 15.4 pg/mL, p = 0.886) levels between AF patients and control subjects. Similarly, neuroimaging showed no between-group difference in large cortical and non-cortical lesions (n = 2, 8.0% vs. n = 0, 0.0%, p = 0.246), small non-cortical lesions (n = 5, 20.0% vs. n = 5, 31.3%, p = 0.413), white matter hyperintensity (n = 23, 92.0% vs. n = 14, 87.5%, p = 0.636), and thromboembolic lesions (n = 0, 0.0% vs. n = 1, 6.3%, p = 0.206). Cognitive assessment did not show any between-group difference in the PROMIS index (52.2 ± 9.6 vs. 51.2 ± 6.2, p = 0.706). Finally, there were no significant dynamics in neurologic biomarkers following electrical cardioversion (p > 0.05). This hypothesis-generating study did not find a significant difference in neurologic biomarkers, neuroimaging findings, or cognitive function between patients with persistent AF and controls. The restoration of sinus rhythm was not significantly associated with a change in neurologic biomarkers. Further powered longitudinal studies are needed to re-assess these findings in an AF population.

Assessment of ovarian reserve after unilateral diathermy with thermal doses adjusted to ovarian volume.

Women with polycystic ovary syndrome seem to have a larger ovarian reserve. However, regardless of a greater reserve, diminished ovarian reserve has been reported after laparoscopic diathermy. The aim of this article was to determine whether the doses adjusted unilateral laparoscopic ovarian drilling with diathermy (ULOD) diminishes ovarian reserve to compare with bilateral laparoscopic ovarian drilling with diathermy (BLOD). Ninety-six women were assigned in two groups. One group underwent ULOD receiving thermal doses (0-840 J per ovary) adjusted to volume one ovary. The other group underwent BLOD receiving fixed doses (600 J per ovary). Ovarian reserve markers [anti-Müllerian hormone (AMH); antral follicle count (AFC) and ovarian volume] were measured before and after surgery (1 and 6 months). Both groups showed a decrease in AMH after surgery, but it was significantly more distinct in the BLOD versus ULOD group (2.0 ng/mL versus 1.3 ng/mL; p = 0.018) in the first follow-up month and remained significantly different through the sixth follow-up month (1.9 ng/mL versus 1.15 ng/mL; p = 0.023). In contrast, in the sixth month, the ULOD versus BLOD showed a significantly greater increase AFC (p < 0.001) and volume (p = 0.013). Our findings evidenced that the dose-adjusted unilateral diathermy (60 J/cm(3)) does not have significant and long-term effects on ovarian reserve.

Effects of Hypoxia and Inflammation on Hepcidin Concentration in Non-Anaemic COVID-19 Patients.

Background/Objectives: This study aimed to explore the influence of hypoxia, inflammation, and erythropoiesis on hepcidin and other iron status parameters in non-anaemic COVID-19 patients admitted to the emergency unit before the introduction of therapeutic interventions. Methods: Ninety-six COVID-19 patients and 47 healthy subjects were recruited. Patients were subdivided into hypoxic or normoxic groups and, after follow-up, into mild and moderate, severe or critical disease severity groups. Iron, unsaturated iron-binding capacity (UIBC), ferritin, C-reactive protein (CRP), and interleukin 6 (IL-6) were measured on automatic analysers. ELISA kits were used for hepcidin and erythropoietin (EPO) determination. We calculated total iron-binding capacity (TIBC) and ratios of hepcidin with parameters of iron metabolism (ferritin/hepcidin, hepcidin/iron), inflammation (hepcidin/CRP, hepcidin/IL-6), and erythropoietic activity (hepcidin/EPO). Results: Hepcidin, ferritin, EPO, CRP, IL-6, ferritin/hepcidin, and hepcidin/iron were increased, while UIBC, TIBC, hepcidin/CRP, and hepcidin/IL-6 were decreased in hypoxic compared to normoxic patients as well as in patients with severe or critical disease compared to those with mild and moderate COVID-19. Regarding predictive parameters of critical COVID-19 occurrence, in multivariable logistic regression analysis, a combination of EPO and ferritin/hepcidin showed very good diagnostic performances and correctly classified 88% of cases, with an AUC of 0.838 (0.749-0.906). Conclusions: The hypoxic signal in our group of patients was not strong enough to overcome the stimulating effect of inflammation on hepcidin expression. EPO and ferritin/hepcidin might help to identify on-admission COVID-19 patients at risk of developing a critical form of the disease.

The Predictors of Early Treatment Effectiveness of Intravitreal Bevacizumab Application in Patients with Diabetic Macular Edema.

The aim of this study was to establish whether multiple blood parameters might predict an early treatment response to intravitreal bevacizumab injections in patients with diabetic macular edema (DME). Seventy-eight patients with non-proliferative diabetic retinopathy (NPDR) and DME were included. The treatment response was evaluated with central macular thickness decrease and best corrected visual acuity increase one month after the last bevacizumab injection. Parameters of interest were the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), vitamin D, and apolipoprotein B to A-I ratio (ApoB/ApoA-I). The NLR (2.03 ± 0.70 vs. 2.80 ± 1.08; p < 0.001), MLR (0.23 ± 0.06 vs. 0.28 ± 0.10; p = 0.011), PLR (107.4 ± 37.3 vs. 135.8 ± 58.0; p = 0.013), and SII (445.3 ± 166.3 vs. 675.3 ± 334.0; p < 0.001) were significantly different between responder and non-responder groups. Receiver operator characteristics analysis showed the NLR (AUC 0.778; 95% CI 0.669-0.864), PLR (AUC 0.628; 95% CI 0.511-0.735), MLR (AUC 0.653; 95% CI 0.536-0.757), and SII (AUC 0.709; 95% CI 0.595-0.806) could be predictors of response to bevacizumab in patients with DME and NPDR. Patients with severe NPDR had a significantly higher ApoB/ApoA-I ratio (0.70 (0.57-0.87) vs. 0.61 (0.49-0.72), p = 0.049) and lower vitamin D (52.45 (43.10-70.60) ng/mL vs. 40.05 (25.95-55.30) ng/mL, p = 0.025). Alterations in the NLR, PLR, MLR, and SII seem to provide prognostic information regarding the response to bevacizumab in patients with DME, whilst vitamin D deficiency and the ApoB/ApoA-I ratio could contribute to better staging.

Relationship between interleukin-6 and cardiac involvement in systemic sclerosis.

OBJECTIVES: To explore the relationship between IL-6 levels and echocardiographic abnormalities, and N-terminal probrain natriuretic peptide (NT-proBNP) levels in SSc patients and to correlate tested parameters with European Scleroderma Activity (EUSTAR) score. METHODS: This case-control study included 31 SSc patients with preserved left ventricular ejection fraction (LVEF) and 32 matched healthy controls. Serum IL-6 and NT-proBNP levels were measured and subjects were evaluated by conventional and pulsed-wave tissue Doppler echocardiography. RESULTS: The level of IL-6 was significantly increased in patients with SSc (3.2 vs 2.2 pg/ml, P < 0.001). SSc patients had significantly lower values of LV systolic (7.7 vs 9.25 cm/s, P < 0.001) and early diastolic (8.7 vs 10.3 cm/s, P = 0.014) myocardial velocities and higher E/e' (9.04 vs 7.37, P = 0.001) ratio, although there was no between-group difference according to LVEF (68% vs 65%, P = 0.248). On evaluating the right ventricle there was no significant between-group difference in systolic tricuspid annular velocity (13 vs 13.9 cm/s, P = 0.105), but the peak early diastolic velocity was significantly lower (11.7 vs 13.6, P = 0.044) and E/e' was significantly higher (4.3 vs 3.38, P = 0.008) in SSc patients. IL-6 level showed correlation with LV mean e' (r = -0.57, P = 0.001), E/e' (r = 0.55, P = 0.001) and NT-proBNP (r = 0.52, P = 0.003). EUSTAR score correlated with LV E/e' (r = 0.48, P = 0.006), mean e' (r = -0.67, P < 0.001), mean s' (r = -0.51, P = 0.004), NT-proBNP (r = 0.60, P < 0.001) and IL-6 (r = 0.79, P < 0.001). CONCLUSION: IL-6 level is increased in patients with SSc and significantly correlates with LV diastolic dysfunction, NT-proBNP and EUSTAR score. These results support the role of IL-6 in the development of cardiac disease in SSc patients.

Serum Catestatin Level as a Stratification Assessment Tool in Non-Critical COVID-19 Patients.

Introduction: Catestatin (CST) is a peptide with immunomodulatory, anti-inflammatory, and anti-microbial activities. There are only a few studies that have investigated plasma CST levels in COVID-19 patients (mostly in ICU patients). In our work, the aim was to demonstrate serum CST levels and their correlation with clinical outcomes in a group of severe COVID-19 patients admitted to the non-ICU department. Methods: The subjects were 32 patients (25 females, 7 males) admitted to the non-ICU unit for COVID-19 patients. Results: CST levels in our cohort were higher (8.91 ± 7.00) than previously reported CST levels in control subjects. We found a significant positive correlation between serum CST levels and C-reactive protein (r = 0.423, p = 0.008), D-dimers (r = 0.395, p = 0.013), hsTNT (high-sensitivity troponin T) (r = 0.603, p < 0.001), proBNP (N-terminal pro-brain natriuretic peptide) (r = 0.569, p < 0.001), and hospitalization days (r = 0.388, p = 0.014). There was a difference between groups of participants with SOFA <3 (n = 18) and SOFA >=3 (n = 14) in catestatin serum levels (7.25 ± 3.66 vs. 11.05 ± 9.52 ng/mL), but the difference was statistically insignificant (p = 0.065). Conclusion: We considered plasma CST level at hospital admission as a possible tool for early risk assessment in non-critical COVID-19 patients. This study is an attempt to clarify the complex pathophysiological mechanisms present in the development of severe forms of SARS-CoV2 infection.

Associations of Serum Calprotectin, Arterial Stiffness and Long COVID Symptoms in Dalmatian Kidney Transplant Recipients.

We aimed to explore long COVID symptoms, serum calprotectin levels, and the parameters of arterial stiffness in Dalmatian kidney transplant recipients (KTRs) and their possible associations. A cross-sectional, single-center case-control study on 98 KTRs who had recovered from COVID-19 was performed. Long COVID symptoms were explored via standardized questionnaires assessing quality of life, and serum calprotectin was also measured. Out of 98 KTRs with a mean age of 62 years, 63 (64.3%) were men. Medical history, clinical and laboratory parameters, and arterial stiffness measurements were obtained for each study participant. Difficulties with mobility were present in 44.3% of the KTRs, while difficulties with self-care were present in 6.2%, difficulties with usual activities were demonstrated by 35.1%, pain in the extremities was present in 52.5%, and anxiety and depression were present in 26.8%. Our results showed significant differences regarding serum calprotectin levels in clinical manifestations of acute COVID-19 and follow-up laboratory parameters. The most significant positive predictors of the serum calprotectin value in the KTRs were respiratory insufficiency, acute kidney failure, the prescription of antihypertensives, leukocyte and neutrophil counts, the neutrophil/lymphocyte ratio and lactate dehydrogenase levels. Negative predictors were the time since COVID-19, high-density lipoprotein levels, kidney function parameters, and the lymphocyte count. To conclude, serum calprotectin has emerged as a possible promising biomarker for subclinical allograft rejection; however, further studies are needed to better understand this subject.

Association of Electrical Cardioversion with Brain Perfusion and Cognitive Function in Patients with Atrial Fibrillation.

BACKGROUND: The association of atrial fibrillation (AF) and brain perfusion (BP) has not been well-defined. This study aimed to determine the association of persistent AF with BP and cognition, in comparison to control subjects and with regards to electrical cardioversion (ECV). METHODS: This study compared 25 patients with persistent AF undergoing elective ECV with 16 age/sex-matched controls. We measured regional BP by using the magnetic resonance (MRI) arterial spin labelling technique. Cognitive function was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) cognitive function index. Measurements were performed at baseline and 6 weeks after ECV. RESULTS: There was no significant difference in BP between AF patients and control subjects (p > 0.05). Following the ECV, there was a significant improvement in BP in 15 patients who maintained sinus rhythm, while there was no significant change in the recurrence group (297 ± 24 before vs. 328 ± 37 after ECV, p = 0.008, and 297 ± 22 before vs. 307 ± 24 after ECV, p = 0.45, respectively). There was no difference in the cognitive assessment between AF patients and control subjects, as well as before and after ECV within the AF group (52.2 ± 9.6 vs. 51.2 ± 6.2, p = 0.71 and 53 ± 10 vs. 54 ± 9, p = 0.46, respectively). CONCLUSIONS: This study did not show difference in BP between persistent AF patients and matched control subjects. Restoration of sinus rhythm was associated with significantly improved BP. There was no association of ECV and changes in cognitive function.

Association of inflammatory biomarkers and disease activity with subclinical myocardial dysfunction in psoriatic arthritis.

We examined the role of adipokines and pro-inflammatory cytokines in psoriatic arthritis-associated subclinical myocardial dysfunction, and the relationship between these variables and psoriatic arthritis (PsA) disease activity. Fifty-five PsA patients without cardiovascular risk factors and 25 controls underwent standard and speckle tracking echocardiography with global longitudinal strain (GLS) calculated. Standard anthropometric data and Disease Activity in Psoriatic arthritis (DAPSA) scores were recorded, with low disease activity defined as DAPSA ≤ 14 and moderate and high disease activity DAPSA > 14. Standard biochemical tests, adiponectin, resistin, leptin, tumor necrosis factor (TNF) alfa, interleukin 17 A (IL-17A), B lymphocyte chemoattractant (BLC), and monokine induced by intereferon gamma (MIG) were analyzed. Median age was 53.0 (46.0-61.0), median PsA duration 6.0 (4.0-13.0) years and median DAPSA score 25.5 (13.0-41.5). Lower GLS, tricuspid annular plane systolic excursion (TAPSE) and left ventricular ejection fraction (LVEF) were found in moderate and high PsA disease activity compared to low PsA disease activity and controls. PsA patients with GLS < 20 had higher body mass index (BMI), DAPSA score and uric acid levels, and lower adiponectin levels. Although patients with GLS < 20 had higher IL-17A levels, it was not statistically significant (P = 0.056). However, when we included healthy controls and analyzed differences based on a GLS cut-off of 20% in the entire population, the difference in IL-17A became statistically significant, 0.17 pg/mL (0.06-0.32) vs. 0.43 pg/mL (0.23-0.65), P = 0.017. The association between DAPSA score and GLS and IL-17 remained significant in multivariate analysis. Moreover, the association between GLS and IL-17 and adiponectin was significant after adjustment for age and BMI. Patients with moderate and high PsA disease activity have reduced myocardial function, lower adiponectin, and higher IL-17A levels.

Association between Salivary Cortisol and α-Amylase with the Psychological Profile of Patients with Oral Lichen Planus and Burning Mouth Syndrome: A Case-Control Study.

The aim of our study was to assess the relationship between the concentration/activity of salivary stress biomarkers (cortisol, α-amylase) and the psychological profile of patients with oral lichen planus (OLP) and primary burning mouth syndrome (BMS). A total of 160 subjects participated in this case-control study: 60 patients with OLP; 60 patients with primary BMS; and 40 control subjects. Unstimulated whole saliva (UWS) was collected between 9 and 10 a.m. Salivary biomarkers were analyzed by enzyme-linked immunosorbent assays (ELISAs). Psychological assessment was evaluated with the Depression, Anxiety, and Stress Scale (DASS-21). The patients with primary BMS had higher salivary cortisol concentrations and α-amylase activity (0.52 vs. 0.44 µg/dL; 160,531 vs. 145,804 U/L; one-way analysis of variance (ANOVA) with post hoc Scheffe test) compared with patients with OLP. The patients with primary BMS had statistically significant higher scores for depression, anxiety, and stress compared with patients with OLP and control subjects (p < 0.001, Kruskal-Wallis test). There was a strong positive correlation between anxiety and depression, stress and depression, and stress and anxiety in patients with OLP and BMS (p < 0.001 and p < 0.001, respectively; Spearman's correlation). There was a good positive correlation between symptom intensity (pain/burning) and psychological profile (depression, anxiety, stress) in patients with primary BMS (r = 0.373, p = 0.003; r = 0.515, p < 0.001; r = 0.365, p = 0.004, respectively; Spearman's correlation). This case-control study is the first to compare the psychoendocrinological profile of patients with two different oral diseases. The patients with BMS showed a higher concentration/activity of salivary stress biomarkers (cortisol, α-amylase) and a stronger association with mental disorders compared with patients with OLP. However, an interdisciplinary psychoneuroimmunological approach is equally important in both patient groups (OLP and BMS), regardless of whether mental disorders are the cause or the consequence.

Laboratory medicine in pandemic of COVID-19.

After the outbreak in China in the year 2019, severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) quickly spread around the world causing a protracted pandemic. Approximately one-third of infections appear to be asymptomatic. Symptomatic disease is characterized primarily by symptoms of respiratory tract infection of varying severity. But Coronavirus Disease 2019 (COVID-19) is much more than an acute respiratory disease because SARS-CoV-2 affects many organs inducing a vast number of symptoms such as cardiovascular, neurological, gastrointestinal, dermatological, with numerous complications. Short and long-term effects of infection, severe ones, and especially mild forms of the disease which affect a huge number of patients need to be further investigated. Laboratory medicine has a crucial role in early diagnosis of the disease, recognition of the patients who need hospital care, and close monitoring of hospitalized patients to timely identify associated clinical complications as well as follow-up of patients with long-term COVID-19.

Effects of Moderate Consumption of Red Wine on Hepcidin Levels in Patients with Type 2 Diabetes Mellitus.

Iron overload is often associated with type 2 diabetes (T2D), indicating that hepcidin, the master regulator of iron homeostasis, might be involved in diabetes pathogenesis. Alcohol consumption may also result in increased body iron stores. However, the moderate consumption of wine with meals might be beneficial in T2D. This effect has been mainly attributed to both the ethanol and the polyphenolic compounds in wine. Therefore, we examined the effects of red wine on hepcidin in T2D patients and non-diabetic controls. The diabetic patients (n = 18) and age- and BMI-matched apparently healthy controls (n = 13) were men, aged 40−65 years, non-smoking, with BMI < 35 kg/m2. Following a 2-week alcohol-free period, both groups consumed 300 mL of red wine for 3 weeks. The blood samples for the iron status analysis were taken at the end of each period. The red wine intake resulted in a decrease in serum hepcidin in both the diabetic subjects (p = 0.045) and controls (p = 0.001). The levels of serum ferritin also decreased after wine in both groups, reaching statistical significance only in the control subjects (p = 0.017). No significant alterations in serum iron, transferrin saturation, or soluble transferrin receptors were found. The suppression of hepcidin, a crucial iron-regulatory hormone and acute-phase protein, in T2D patients and healthy controls, is a novel biological effect of red wine. This may deepen our understanding of the mechanisms of the cardiometabolic effects of wine in T2D.

Haemoglobin A1c-based screening for prediabetes and diabetes mellitus: a multi-center study in Croatian adult population.

INTRODUCTION: Based on the hypothesis that there is a substantial rate of adults with prediabetes and undiagnosed diabetes mellitus (DM), our aim was to perform haemoglobin A1c (HbA1c)-based screening in a cohort of Croatian adults and estimate the prevalence of prediabetes and undiagnosed DM according to American Diabetes Association criteria. MATERIALS AND METHODS: This multi-center, cross-sectional study performed in six Croatian hospitals included 5527 patients aged 40 to 70 years admitted to the Emergency Department or undergoing a primary care check-up. Haemoglobin A1c was measured from leftover whole blood samples using the enzymatic method on either Alinity c or Architect c-series analyser (Abbott Laboratories, Chicago, USA). Haemoglobin A1c between 39-47 mmol/mol was classified as prediabetes, while ≥ 48 mmol/mol as undiagnosed DM. RESULTS: After exclusion of 435 patients with known DM, the final cohort included 5092 patients (median age 57; 56% males). A total of 882 (17.3%) patients had HbA1c values between 39 and 47 mmol/mol. There were 214 (4.2%) patients with HbA1c ≥ 48 mmol/mol. Prediabetes prevalence ranged from 14.2% to 20.5%, while undiagnosed DM from 3.3% to 7.3%, with statistically significant differences among settings (P < 0.001). Age-stratified analysis showed that prediabetes and undiagnosed DM prevalence increase with age (P < 0.001), being 25.4% and 5.8%, respectively, in patients aged 60 to 70 years. CONCLUSION: Underlying impairment of glucose metabolism was identified in about one in five adults, with significant number of patients with already overt DM. These results should serve as a starting point for further steps directed towards promotion of preventive measures for DM in Croatia.

Seasonal variations in nutritional status and oxidative stress in patients on hemodialysis: Are they related?

OBJECTIVE: Seasonal variations in body composition and parameters that reflect nutritional status are well established in patients on hemodialysis (HD). However, to our knowledge, no study has assessed the changes in oxidative stress (OS). The aims of this study were to assess seasonal variations in OS, body composition, and other nutritional parameters. METHODS: Seasonal variations in fat tissue mass (FTM), fat tissue index (FTI), adipose tissue mass (ATM), lean tissue mass (LTM), lean tissue index (LTI), body cell mass (BCM), overhydration (OH) volume, and OS (blood levels of derivatives of reactive oxygen metabolites [d-ROMs], thiobarbituric reactive substances, plasma protein reduced thiol content [THIOLS], and ferric reducing ability of plasma) were assessed in 45 patients on HD, 70 y of age (60.5-76.5 y). RESULTS: FTM (P < 0.001), FTI (P < 0.001), and ATM (P < 0.001) significantly increased, whereas LTI (P < 0.001), LTM (P < 0.001), BCM (P < 0.001), and OH volume (P = 0.004) significantly decreased over the season. Additionally, significant seasonal variations in the levels of d-ROMs (P = 0.02) and THIOLS (P = 0.02) were found. Levels of d-ROMs were found to be a significant predictor of LTM and BCM (ß = -0.57; 95% confidence interval [CI], -1.08 to -0.06; P = 0.03; ß = -0.04; 95% CI, -0.075 to -0.006; P = 0.02). Furthermore, hip circumference was found to be the most significant predictor of the level of d-ROMs (ß = 2.66; 95% CI; 0.28-5.04; P = 0.03) and waist-to-height ratio (ß = 251; 95% CI, 16.6-477.2; P = 0.03) and serum prealbumin levels of THIOLS (ß = 263; 95% CI, 6.8-521.1; P = 0.04). CONCLUSION: These results suggest seasonal variations in OS in patients on HD and a possible interaction between OS and nutritional status in these patients.

Blood markers of endothelial dysfunction and their correlation to cerebrovascular reactivity in patients with chronic hepatitis C infection.

Although liver cirrhosis and hepatocellular carcinoma are major consequences of hepatitis C (HCV), there has been an increasing number of studies examining extrahepatic manifestations, especially those caused by systemic chronic inflammation and metabolic complications that might predispose HCV patients to atherosclerosis and ischemic cerebrovascular disease (CVD). The aim of our study was to assess E-selectin, VCAM-1, ICAM-1 and VEGF-A serum levels in patients with chronic HCV infection and to correlate them with cerebrovascular reactivity. A blood sample was taken from eighteen patients with chronic hepatitis C infection and from the same number of healthy blood donors in the control group. The aim was to analyse markers of endothelial dysfunction and to correlate them with cerebrovascular reactivity expressed as breath-holding index (BHI) determined using transcranial color Doppler. The obtained results revealed significant differences between the groups in all endothelial markers except for the E selectin. While the ICAM-1 and sVCAM-1 were significantly increased in the hepatitis group, VEGF-A was significantly decreased. A significant reduction of 0.5 (95% CI 0.2, 0.8) in the mean BHI was found in the hepatitis group (mean BHI 0.64) compared to controls (mean BHI 1.10). No significant association between the BHI and any of the endothelial markers was found in the control group, while in the hepatitis group, the scatter plot of ICAM-1 vs BHI suggested that the association might be present. In conclusion, the results of this study confirm an association between a chronic HCV infection and altered cerebrovascular reactivity as well as higher levels of markers of endothelial activation (ICAM-1, VCAM-1) as possible indicators of an increased CVD risk.

Association between vitamin D, oestradiol and interferon-gamma in female patients with inactive systemic lupus erythematosus: A cross-sectional study.

Objectives To investigate possible associations between 25-hydroxyvitamin D3 (25(OH)D3), oestradiol (E2) and IFN-gamma (IFNγ) in female patients with inactive systemic lupus erythematosus (SLE). Methods Female patients with inactive SLE and age-matched healthy controls were recruited into this cross-sectional study. Serum concentrations of 25(OH)D3, E2 and IFNγ were measured by radioimmunoassay with gamma-counters and enzyme-linked immunosorbent assay. Results 36 patients and 37 controls were enrolled. In patients with SLE, the concentration of 25(OH)D3 was lower and E2 was higher compared with controls. In vitamin D deficient (i.e., 25(OH)D3≤20 ng/ml) patients, IFNγ was 150% higher compared with patients with 25(OH)D3>20 ng/ml and controls. The concentration of E2 was higher in all patients compared with controls independently of the vitamin D level. A difference was found between patients and controls in the correlation of 25(OH)D3 with E2 and a positive correlation was found between E2 and IFNγ in all participants. Conclusions Our results suggest that E2 may have a strong modulating effect on vitamin D function which is significant only at low concentration of E2.

Systemic inflammation up-regulates serum hepcidin in exacerbations and stabile chronic obstructive pulmonary disease.

OBJECTIVES: Hepcidin is the main regulator of systemic iron homeostasis and its expression is modulated by iron status, hypoxia, erythroid factors and inflammation. The aim of our study was to examine a relationship between level of hepcidin and iron status, erythropoietic activity, hypoxia and inflammation in exacerbations and stable COPD patients. We hypothesized that hepcidin concentration is changed in COPD patients and is substantially influenced by inflammation and/or hypoxia. DESIGN AND METHODS: The study included 40 COPD patients and 30 healthy subjects. We measured haemoglobin, serum level of hepcidin and parameters indicative for inflammation: interleukin-6 (IL-6) and C reactive protein (CRP); hypoxia: partial oxygen pressure and haemoglobin oxygen saturation; iron status: iron, total iron binding capacity (TIBC), transferring saturation and ferritin; and erythropoietic activity: soluble transferrin receptors, reticulocytes, and erythropoietin. RESULTS: Hepcidin was elevated in exacerbations and in a stable phase compared to the control group and we found positive correlations of hepcidin with inflammatory markers IL-6 and CRP. Hepcidin also correlated positively with ferritin and inversely with TIBC. However, in COPD patients reticulocyte count was significantly reduced and negative correlation with hepcidin was established in exacerbation. No correlations were observed with iron, or indices of hypoxia. In the control group, positive associations were observed only with indices of iron status, positive with ferritin and negative one with TIBC. CONCLUSION: Systemic inflammation and elevated values of IL-6 present in exacerbations and stabile COPD might be responsible for the observed increased hepcidin level.

Association of age-related macular degeneration with erythrocyte antioxidant enzymes activity and serum total antioxidant status.

The aim was to estimate association of the oxidative stress with the occurrence of age-related macular degeneration (AMD). The activities of erythrocyte antioxidant enzymes: superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) and additionally serum total antioxidant status (TAS) were used as indicators of the oxidative stress level. 57 AMD patients (32 early and 25 late AMD) and 50 healthy, age and gender matched controls were included. GPx activity (P < 0.001) and serum TAS (P = 0.015) were significantly lower in AMD patients. The difference was not significant for SOD or CAT activities. Significant interaction between GPx and SOD was detected (P = 0.003). At high levels of SOD activity (over 75th percentile), one standard deviation decrease in GPx increases the odds for AMD for six times (OR = 6.22; P < 0.001). ROC analysis revealed that combined values of GPx activity and TAS are significant determinants of AMD status. Accuracy, sensitivity, specificity, and positive and negative predictive values were 75%, 95%, 52%, 69%, and 90%, respectively. The study showed that low GPx activity and TAS are associated with AMD. SOD modulates the association of GPx and AMD. The results suggest that erythrocyte antioxidant enzymes activity and serum TAS could be promising markers for the prediction of AMD.

Iron metabolism: current facts and future directions.

Iron metabolism has been intensively examined over the last decade and there are many new players in this field which are worth to be introduced. Since its discovery many studies confirmed role of liver hormone hepcidin as key regulator of iron metabolism and pointed out liver as the central organ of system iron homeostasis. Liver cells receive multiple signals related to iron balance and respond by transcriptional regulation of hepcidin expression. This liver hormone is negative regulator of iron metabolism that represses iron efflux from macrophages, hepatocytes and enterocytes by its binding to iron export protein ferroportin. Ferroportin degradation leads to cellular iron retention and decreased iron availability. At level of a cell IRE/IRP (iron responsive elements/iron responsive proteins) system allows tight regulation of iron assimilation that prevents an excess of free intracellular iron which could lead to oxidative stress and damage of DNA, proteins and lipid membranes by ROS (reactive oxygen species). At the same time IRE/IRP system provides sufficient iron in order to meet the metabolic needs. Recently a significant progress in understanding of iron metabolism has been made and new molecular participants have been characterized. Article gives an overview of the current understanding of iron metabolism: absorption, distribution, cellular uptake, release, and storage. We also discuss mechanisms underlying systemic and cellular iron regulation with emphasis on central regulatory hormone hepcidin.