Serum Calprotectin, a Marker of Neutrophil Activation, and Other Mediators of Inflammation in Response to Various Types of Extreme Physical Exertion in Healthy Volunteers

Purpose: While extreme physical exertion is known to induce changes in the status of inflammation comparisons of the responses for various mediators of inflammation after acute bouts of high-intensity exercise have been limited. Subjects and Methods: We examined the responses in serum levels of novel inflammatory proteins, calprotectin, suPAR, CD163, and pro- and anti-inflammatory cytokines in 12 physically active volunteers (10 men, 2 women, mean age 37 +/- 14 years) before and after completing various types of extreme physical exertion (marathon run, half-marathon run or 24-h cross-country skiing). For comparisons, the levels of the biomarkers were also measured at rest in 30 healthy controls (25 men, 5 women, mean age 42 +/- 12 years) with low or sedentary activity. Results: Extreme physical exertion induced significant increases in serum calprotectin (p <0.0005), suPAR (p <0.01), CD163 (p <0.05), IL-6 (p <0.0005), IL-8 (p <0.01) and IL-10 (p <0.0005) (pre- vs 3h-post-exercise). These responses were found to normalize within 48 hours. While the increases in blood leukocytes were of similar magnitude following the different types of exercise, markedly more pronounced responses occurred in serum TNF-alpha (p <0.01), IL-8 (p <0.01) and CD163 (p <0.05) in those with more intense activity. In 3-h post-exercise samples significant correlations were observed between serum calprotectin and IL-6 (r(s) = 0.720, p <0.01), IL-10 (r(s) = 0.615, p <0.05), TNF-alpha (r(s) = 0.594, p <0.05), suPAR (r(s) = 0.587, p <0.05) and blood leukocytes (r(s) = 0.762, p <0.01). Conclusion: The present results suggest distinct exercise-intensity dependent changes in mediators of inflammation (including calprotectin, suPAR and CD163) following extreme physical exertion. Our findings indicate that there is a major reversible impact of high-intensity physical exertion on the status of inflammation.Peer reviewe

Patterns of IgA Autoantibody Generation, Inflammatory Responses and Extracellular Matrix Metabolism in Patients with Alcohol Use Disorder

Recent data have emphasized the role of inflammation and intestinal immunoglobulin A (IgA) responses in the pathogenesis of alcoholic liver disease (ALD). In order to further explore such associations, we compared IgA titers against antigens targeted to ethanol metabolites and tissue transglutaminase with pro- and anti-inflammatory mediators of inflammation, markers of liver status, transferrin protein desialylation and extracellular matrix metabolism in alcohol-dependent patients with or without liver disease and in healthy controls. Serum IgAs against protein adducts with acetaldehyde (HbAch-IgA), the first metabolite of ethanol, and tissue transglutaminase (tTG-IgA), desialylated transferrin (CDT), pro- and anti-inflammatory cytokines, markers of liver status (GT, ALP) and extracellular matrix metabolism (PIIINP, PINP, hyaluronic acid, ICTP and CTx) were measured in alcohol-dependent patients with (n = 83) or without (n = 105) liver disease and 88 healthy controls representing either moderate drinkers or abstainers. In ALD patients, both tTG-IgA and HbAch-IgA titers were significantly higher than those in the alcoholics without liver disease (p < 0.0005 for tTG-IgA, p = 0.006 for Hb-Ach-IgA) or in healthy controls (p < 0.0005 for both comparisons). The HbAch-IgA levels in the alcoholics without liver disease also exceeded those found in healthy controls (p = 0.0008). In ROC analyses, anti-tTG-antibodies showed an excellent discriminative value in differentiating between ALD patients and healthy controls (AUC = 0.95, p < 0.0005). Significant correlations emerged between tTG-IgAs and HbAch-IgAs (rs = 0.462, p < 0.0005), CDT (rs = 0.413, p < 0.0001), GT (rs = 0.487, p < 0.0001), alkaline phosphatase (rs = 0.466, p < 0.0001), serum markers of fibrogenesis: PIIINP (rs = 0.634, p < 0.0001), hyaluronic acid (rs = 0.575, p < 0.0001), ICTP (rs = 0.482, p < 0.0001), pro-inflammatory cytokines IL-6 (rs = 0.581, p < 0.0001), IL-8 (rs = 0.535, p < 0.0001) and TNF-α (rs = 0.591, p < 0.0001), whereas significant inverse correlations were observed with serum TGF-β (rs = −0.366, p < 0.0001) and CTx, a marker of collagen degradation (rs = −0.495, p < 0.0001). The data indicate that the induction of IgA immune responses toward ethanol metabolites and tissue transglutaminaseis a characteristic feature of patients with AUD and coincides with the activation of inflammation, extracellular matrix remodeling and the generation of aberrantly glycosylated proteins. These processes appear to work in concert in the sequence of events leading from heavy drinking to ALD.Peer reviewe

Alcohol Drinking Patterns and Laboratory Indices of Health : Does Type of Alcohol Preferred Make a Difference?

Although excessive alcohol consumption is a highly prevalent public health problem the data on the associations between alcohol consumption and health outcomes in individuals preferring different types of alcoholic beverages has remained unclear. We examined the relationships between the amounts and patterns of drinking with the data on laboratory indices of liver function, lipid status and inflammation in a national population-based health survey (FINRISK). Data on health status, alcohol drinking, types of alcoholic beverages preferred, body weight, smoking, coffee consumption and physical activity were recorded from 22,432 subjects (10,626 men, 11,806 women), age range 25–74 years. The participants were divided to subgroups based on the amounts of regular alcohol intake (abstainers, moderate and heavy drinkers), patterns of drinking (binge or regular) and the type of alcoholic beverage preferred (wine, beer, cider or long drink, hard liquor or mixed). Regular drinking was found to be more typical in wine drinkers whereas the subjects preferring beer or hard liquor were more often binge-type drinkers and cigarette smokers. Alcohol use in all forms was associated with increased frequencies of abnormalities in the markers of liver function, lipid status and inflammation even at rather low levels of consumption. The highest rates of abnormalities occurred, however, in the subgroups of binge-type drinkers preferring beer or hard liquor. These results demonstrate that adverse consequences of alcohol occur even at moderate average drinking levels especially in individuals who engage in binge drinking and in those preferring beer or hard liquor. Further emphasis should be placed on such patterns of drinking in policies aimed at preventing alcohol-induced adverse health outcomes.publishedVersionPeer reviewe

Blood Cell Responses Following Heavy Alcohol Consumption Coincide with Changes in Acute Phase Reactants of Inflammation, Indices of Hemolysis and Immune Responses to Ethanol Metabolites

Aberrations in blood cells are common among heavy alcohol drinkers. In order to shed further light on such responses, we compared blood cell status with markers of hemolysis, mediators of inflammation and immune responses to ethanol metabolites in alcohol-dependent patients at the time of admission for detoxification and after abstinence. Blood cell counts, indices of hemolysis (LDH, haptoglobin, bilirubin), calprotectin (a marker of neutrophil activation), suPAR, CD163, pro- and anti-inflammatory cytokines and autoantibodies against protein adducts with acetaldehyde, the first metabolite of ethanol, were measured from alcohol-dependent patients (73 men, 26 women, mean age 43.8 ± 10.4 years) at baseline and after 8 ± 1 days of abstinence. The assessments also included information on the quantities of alcohol drinking and assays for biomarkers of alcohol consumption (CDT), liver function (AST, ALT, ALP, GGT) and acute phase reactants of inflammation. At baseline, the patients showed elevated values of CDT and biomarkers of liver status, which decreased significantly during abstinence. A significant decrease also occurred in LDH, bilirubin, CD163 and IgA and IgM antibodies against acetaldehyde adducts, whereas a significant increase was noted in blood leukocytes, platelets, MCV and suPAR levels. The changes in blood leukocytes correlated with those in serum calprotectin (p < 0.001), haptoglobin (p < 0.001), IL-6 (p < 0.02) and suPAR (p < 0.02). The changes in MCV correlated with those in LDH (p < 0.02), MCH (p < 0.01), bilirubin (p < 0.001) and anti-adduct IgG (p < 0.01). The data indicates that ethanol-induced changes in blood leukocytes are related with acute phase reactants of inflammation and release of neutrophil calprotectin. The studies also highlight the role of hemolysis and immune responses to ethanol metabolites underlying erythrocyte abnormalities in alcohol abusers.publishedVersionPeer reviewe

Long-term observational follow-up study of breast cancer diagnosed in women ≤40 years old

The prognosis of young breast cancer patients has been considered to be much poorer than in older patients. Two hundred and sixty-eight premenopausal women with a median follow-up time of 74.0 months were included in the study. 33.5% had oestrogen receptor-negative and 34.6% progesterone receptor-negative tumours. 15.2% of the tumours were HER2-positive. Five-year breast cancer-specific survival (BCSS) was 81.1% and the corresponding 10-year figure was 72.3%. 91.8% of all relapses occurred within seven years of surgery. Among the ≤35-year-old women, only 2 of 38 (5.3%) relapsed beyond seven years of follow-up. Lymph node ratio was the most significant independent prognostic factor of poor disease-free survival and BCSS. This study revealed a high relapse rate in the youngest women as early as during the first few years after diagnosis, although their prognosis as a whole was surprisingly good. © 2010 Elsevier Ltd.publishedVersionPeer reviewe

Impact of Physical Activity on the Characteristics and Metabolic Consequences of Alcohol Consumption : A Cross-Sectional Population-Based Study

Sedentary lifestyle and excessive alcohol drinking are major modifiable risk factors of health. In order to shed further light on the relationships between physical activity and health consequences of alcohol intake, we measured biomarkers of liver function, inflammation, lipid status and fatty liver index tests in a large population-based sample of individuals with different levels of physical activity, alcohol drinking and other lifestyle risk factors. The study included 21,050 adult participants (9940 men, 11,110 women) (mean age 48.2 ± 13.3 years) of the National FINRISK Study. Data on physical activity, alcohol drinking, smoking and body weight were recorded. The participants were classified to subgroups according to gender, levels of physical activity (sedentary, low, moderate, vigorous, extreme), alcohol drinking levels (abstainers, moderate drinkers, heavy drinkers) and patterns (regular or binge, types of beverages preferred in consumption). Serum liver enzymes (GGT, ALT), C-reactive protein (CRP) and lipid profiles were measured using standard laboratory techniques. Physical activity was linearly and inversely related with the amount of alcohol consumption, with the lowest alcohol drinking levels being observed in those with vigorous or extreme activity (p < 0.0005). Physically active individuals were less frequently binge-type drinkers, cigarette smokers or heavy coffee drinkers than those with sedentary activity (p < 0.0005 for linear trend in all comparisons). In the General Linear Model to assess the main and interaction effects of physical activity and alcohol consumption on biomarker status, as adjusted for anthropometric measures, smoking and coffee consumption, increasing levels of physical activity were found to be associated with more favorable findings on serum GGT (p < 0.0005), ALT (p < 0.0005 for men), cholesterol (p = 0.025 for men; p < 0.0005 for women), HDL-cholesterol (p < 0.0005 for men, p = 0.001 for women), LDL-cholesterol (p < 0.03 for men), triglycerides (p < 0.0005 for men, p < 0.03 for women), CRP (p < 0.0005 for men, p = 0.006 for women) and fatty liver index (p < 0.0005). The data support the view that regular moderate to vigorous physical activity may counteract adverse metabolic consequences of alcohol consumption on liver function, inflammation and lipid status. The role of physical activity should be further emphasized in interventions aimed at reducing health problems related to unfavorable risk factors of lifestyle.publishedVersionPeer reviewe

Evaluation of Heart Rate Variation Analysis during Rest and Tilting in Patients with Temporal Lobe Epilepsy

Objective. To evaluate spectral heart rate (HR) variation using short-term ECG recordings at rest and during the tilt table test. Methods. The values of spectral components of total power (TP), high-frequency power (HF), low-frequency power (LF) and LF: HF ratio were measured at rest and during the head-up tilt in patients with temporal lobe epilepsy (TLE) and their control subjects. Results. Compared to the control subjects, patients with TLE had lower HF (P < 0.05) and LF : HF ratio (P < 0.05) at rest and lower TP (P < 0.001), HF (P < 0.05), and LF (P < 0.05) during the head-up tilt. Upon changing from supine to standing position TP (P < 0.05) and LF (P < 0.05) were attenuated in patients with TLE compared to the control subjects. Conclusion. These results suggest that spectral analysis of HR variation from ECG recordings of short duration may add value to assessment of autonomic nervous system function using autonomic cardiac tests in patients with TLE

Oral and Vaginal Hormonal Contraceptives Induce Similar Unfavorable Metabolic Effects in Women with PCOS: A Randomized Controlled Trial

This clinical trial aims to compare hormonal and metabolic changes after a 9-week continuous use of oral or vaginal combined hormonal contraceptives (CHCs) in women with polycystic ovary syndrome (PCOS). We recruited 24 women with PCOS and randomized them to use either combined oral (COC, n = 13) or vaginal (CVC, n = 11) contraception. At baseline and 9 weeks, blood samples were collected and a 2 h glucose tolerance test (OGTT) was performed to evaluate hormonal and metabolic outcomes. After treatment, serum sex hormone binding globulin (SHBG) levels increased (p < 0.001 for both groups) and the free androgen index (FAI) decreased in both study groups (COC p < 0.001; CVC p = 0.007). OGTT glucose levels at 60 min (p = 0.011) and AUCglucose (p = 0.018) increased in the CVC group. Fasting insulin levels (p = 0.037) increased in the COC group, and insulin levels at 120 min increased in both groups (COC p = 0.004; CVC p = 0.042). There was a significant increase in triglyceride (p < 0.001) and hs-CRP (p = 0.032) levels in the CVC group. Both oral and vaginal CHCs decreased androgenicity and tended to promote insulin resistance in PCOS women. Larger and longer studies are needed to compare the metabolic effects of different administration routes of CHCs on women with PCOS

When does the Autism Spectrum Screening Questionnaire (ASSQ) predict autism spectrum disorders in primary school-aged children?

The aims of this study were, firstly, to study the association between parents’ and teachers’ ratings for the Finnish version of the Autism Spectrum Screening Questionnaire (ASSQ), secondly, to find out whether the original cut-off scores of the ASSQ identify primary school-aged children with Asperger syndrome (AS) or autism by using the Finnish ASSQ, and thirdly, to evaluate the validity of the ASSQ. Parents and/or teachers of higher-functioning (full-scale intelligence quotient ≥ 50) 8-year-old total population school children (n = 4,408) and 7–12-year-old outpatients with AS/autism (n = 47) completed the Finnish version of the ASSQ. Agreement between informants was slight. In the whole total population, low positive correlation was found between parents’ and teachers’ ratings, while in the sample of high-scoring children the correlation turned out to be negative. A cut-off of 30 for parents’ and teacher's summed score and 22 for teachers’ single score is recommended. A valid cut-off for parents’ single score could not been estimated. The clinicians are reminded that the ASSQ is a screening instrument, not a diagnosing instrument. The importance of using both parents’ and teachers’ ratings for screening in clinical settings is underlined