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

Induced abortion and future use of IVF treatment; A nationwide register study

Peer 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

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

Äitiys- ja lastenneuvolatoiminta sekä kouluterveydenhuolto - Valtakunnallinen seuranta 2012

Äitiys- ja lastenneuvolatoiminnan ja kouluterveydenhuollon tilaa selvitettiin osastonhoitajille ja vastuulääkäreille vuoden 2012 lopulla lähetetyllä kyselyllä. Selvityksen tavoitteena oli tutkia, miten toimintoja on kehitetty vastaamaan kuntalaisten tarpeita ja uusia säännöksiä. Kyselyyn vastasi 150 terveyskeskusta 94 prosenttia kyselyn saaneista. Tulosten mukaan neuvolan ja kouluterveydenhuollon palvelut olivat kehittyneet säännösten suuntaisesti. Lähes kaikissa terveyskeskuksissa oli nimetty toimintojen vastuuhenkilö. Laajat terveystarkastukset ja muut määräaikaiset terveystarkastukset järjestettiin lähes kaikissa terveyskeskuksissa säännösten mukaisina ajankohtina. Laajoissa terveystarkastuksissa perheiden hyvinvointia arvioitiin monipuolisesti, vaikka henkilöstö- ja aikaresurssit olivat osin puutteellisia. Henkilöstöresurssit olivat parantuneet kaikilla palvelusektoreilla, mutta jäävät vielä alle suositusten. Myönteisestä kehityksestä huolimatta palveluissa on edelleen eroja alueellisesti ja terveyskeskusten väestöpohjan koon perusteella. Selvityksen tuottamaa tietoa voidaan hyödyntää neuvola- ja kouluterveydenhuoltopalvelujen valvonnassa, seurannassa ja kehittämistyössä kunnissa ja valtakunnallisesti. Raportissa esitetään myös toimenpide-ehdotuksia eri toimijoille

Fear of childbirth after medical versus surgical abortion. Population-based register study from Finland

Introduction To evaluate the effect of method of induced abortion and other abortion-associated variables on the incidence of fear of childbirth in subsequent pregnancy. Material and methods This population-based register study cohort includes all nulliparous women with their first pregnancy ending in an induced abortion in 2000-2015 and subsequent pregnancy with live singleton delivery between 2000 and 2017 (n = 21 479). Data were derived from three national registers maintained by the Finnish Institute for Health and Welfare. We divided the study population in three cohorts: (a) medical and (b) surgical abortion during first trimester ( Results The overall incidence of fear of childbirth was 5.6% (n = 1209). Altogether, 19.2% (n = 4121) of women underwent cesarean delivery. The odds were elevated especially for elective cesarean delivery (odds ratio [OR] 9.30, 95% CI 7.95-10.88, P <.001) in women with fear of childbirth. In multivariable analysis, the odds for fear of childbirth (adjusted OR [aOR] 0.80, 95% CI 0.68-0.94) and cesarean delivery (aOR 0.66, 95% CI 0.84-0.90) were decreased in women with a history of first-trimester medical abortion compared with those with first-trimester surgical abortion. Second-trimester medical abortion had no effect on the odds for fear of childbirth (aOR 1.04, 95% CI 0.71-1.50). Maternal age of 30-39 years and interpregnancy interval over 2 years were additional risk factors for both fear of childbirth and cesarean delivery, but surgical evacuation of uterus after the abortion was not. Conclusions One first- or second-trimester medical abortion does not increase the odds for fear of childbirth, and cesarean delivery related to it in subsequent pregnancy when compared with first-trimester surgical abortion. Older maternal age and longer interpregnancy interval emerged as risk factors for fear of childbirth.Peer reviewe

Polycystic ovary syndrome and risk factors for gestational diabetes

Objective: To study the roles of self-reported symptoms and/or prior diagnosis of polycystic ovary syndrome (PCOS) and other potential risk factors for gestational diabetes mellitus (GDM) and to clarify whether the screening of GDM in early pregnancy is beneficial for all women with PCOS. Design: The FinnGeDi multicentre case-control study including 1146 women with singleton pregnancies diagnosed with GDM and 1066 non-diabetic pregnant women. There were 174 women with PCOS (symptoms and/or diagnosis self-reported by a questionnaire) and 1767 women without PCOS (data missing for 271). Methods: The study population (N=1941) was divided into four subgroups: GDM+ PCOS (N= 105), GDM+ non-PCOS (N =909), non-GDM+PCOS (N=69), and controls (N=858). The participants' characteristics and their parents' medical histories were compared. Results: The prevalence of PCOS was 10.4% among GDM women and 7.4% among non-diabetics (odds ratios (OR) 1.44, 95% CI: 1.05-1.97), but PCOS was not an independent risk for GDM after adjustments for participants' age and pre-pregnancy BMI (OR 1.07, 95% CI: 0.74-1.54). In a multivariate logistic regression analysis, the most significant parameters associated with GDM were overweight, obesity, age >= 35 years, participant's mother's history of GDM, either parent's history of type 2 diabetes (T2D) and participant's own preterm birth. Conclusions: The increased risk of GDM in women with PCOS was related to obesity and increased maternal age rather than to PCOS itself, suggesting that routine early screening of GDM in PCOS women without other risk factors should be reconsidered. Instead, family history of GDM/T2D and own preterm birth were independent risk factors for GDM.Peer reviewe

Elevated One-Hour Post-Load Glucose Is Independently Associated with Albuminuria: A Cross-Sectional Population Study

The purpose of this study was to examine and compare the associations between albuminuria and fasting (FPG), 1 h post-load (1 h PG) and 2 h post-load plasma glucose (2 h PG) in an oral glucose tolerance test (OGTT). A total of 496 people free of known diabetes (mean age 72 years) participated in the examinations including the OGTT with plasma glucose measurements at 0, 1, and 2 h and levels of HbA1c. Albuminuria was determined by the urinary albumin-to-creatinine ratio and was defined as ≥3.0 mg/mmol. Compared with those without albuminuria, participants with albuminuria had significantly higher 1 h PG and 2 h PG levels, but not FPG or HbA1c levels. An elevated 1 h PG increased the estimated odds ratio of albuminuria more than three times in people with prediabetic 1 h PG (8.6–11.5 mmol/L: OR 3.60; 95% CI 1.70–7.64) and diabetic 1 h PG (≥11.6 mmol/L: OR 3.05; 95% CI 1.29–7.23). After adjusting for blood pressure and age, the association of elevated 1 h PG with albuminuria remained significant. Prediabetic or diabetic FPG, 2 h PG, or HbA1c did not have a statistically significant association with albuminuria. These findings suggest that 1 h PG seems to be the best glycemic parameter and is useful in recognizing persons with an elevated risk of early kidney disease due to hyperglycemia