Maksa-arvojen viiterajat tarkistettava

Pääkirjoitus-editoria

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

Plasma total calcium concentration is associated with blood pressure and systemic vascular resistance in normotensive and never-treated hypertensive subjects

Purpose: The underlying causes of primary hypertension are not fully understood. Evidence on the relation of plasma calcium concentration with blood pressure (BP) is inconsistent and relies largely on studies utilizing office BP measurements in populations using cardiovascular drugs. In many studies adjustment for confounders was not optimal. In this cross-sectional study we examined the association of plasma total calcium concentration with the haemodynamic determinants of blood pressure. Subjects and methods: Supine haemodynamics were recorded using pulse wave analysis, whole-body impedance cardiography, and heart rate variability analysis in 618 normotensive or never-treated hypertensive subjects (aged 19–72 years) without diabetes, cardiovascular or renal disease, or cardiovascular medications. Linear regression analysis was used to investigate factors associated with haemodynamic variables. Results: Mean age was 45.0 years, body mass index 26.8 kg/m2, seated office BP 141/89 mmHg, and 307 subjects (49.7%) were male. Mean values of routine blood and plasma chemistry analyses were within the reference limits of the tests except for low-density lipoprotein cholesterol (3.05 mmol/l). In the laboratory, mean supine radial BP was 131/75 mmHg, and both systolic and diastolic BP correlated directly with plasma total calcium concentration (r = 0.25 and r = 0.22, respectively, p < 0.001 for both). In regression analysis plasma total calcium concentration was an independent explanatory variable for radial and aortic systolic and diastolic BP, and systemic vascular resistance, but not for cardiac output, pulse wave velocity, or any of the heart rate variability parameters. Conclusion: Plasma total calcium concentration was directly associated with systolic and diastolic BP and systemic vascular resistance in normotensive or never-treated hypertensive subjects without comorbidities and cardiovascular medications. Higher plasma calcium concentration potentially plays a role in primary hypertension via an effect on vascular resistance

Unfavorable Reduction in the Ratio of Endothelin B to A Receptors in Experimental 5/6 Nephrectomy and Adenine Models of Chronic Renal Insufficiency

Chronic renal insufficiency (CRI) is characterized by increased endothelin 1 (ET-1) synthesis. We studied rat kidney endothelin receptor A (ETA) and receptor B (ETB) expressions after 12 and 27 weeks of 5/6 nephrectomy, and after 12 weeks of 0.3% adenine diet, representing proteinuric and interstitial inflammation models of CRI, respectively. Uric acid and calcium-phosphate metabolism were modulated after 5/6 nephrectomy, while ETA blocker and calcimimetic were given with adenine. Endothelin receptor mRNA levels were measured using RT-qPCR and protein levels using autoradiography (5/6 nephrectomy) or ELISA (adenine model). Both 12 and 27 weeks after 5/6 nephrectomy, kidney cortex ETA protein was increased by similar to 60% without changes in ETB protein, and the ETB:ETA ratio was reduced. However, the ETB:ETA mRNA ratio did not change. In the adenine model, kidney ETA protein was reduced by similar to 70%, while ETB protein was suppressed by similar to 95%, and the ETB:ETA ratio was reduced by similar to 85%, both at the protein and mRNA levels. The additional interventions did not influence the observed reductions in the ETB:ETAratio. To conclude, unfavorable reduction in the ETB:ETA protein ratio was observed in two different models of CRI. Therefore, ETA blockade may be beneficial in a range of diseases that cause impaired kidney function.Peer 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

Flash-Like Albuminuria in Acute Kidney Injury Caused by Puumala Hantavirus Infection

Transient proteinuria and acute kidney injury (AKI) are characteristics of Puumala virus (PUUV) infection. Albuminuria peaks around the fifth day and associates with AKI severity. To evaluate albuminuria disappearance rate, we quantified albumin excretion at different time points after the fever onset. The study included 141 consecutive patients hospitalized due to acute PUUV infection in Tampere University Hospital, Finland. Timed overnight albumin excretion (cU-Alb) was measured during the acute phase in 133 patients, once or twice during the convalescent phase within three months in 94 patients, and at six months in 36 patients. During hospitalization, 30% of the patients had moderately increased albuminuria (cU-Alb 20–200 μg/min), while 57% presented with severely increased albuminuria (cU-Alb >200 μg/min). Median cU-Alb was 311 μg/min (range 2.2–6460) ≤7 days after fever onset, 235 μg/min (range 6.8–5479) at 8–13 days and 2.8 μg/min (range 0.5–18.2) at 14–20 days. After that, only one of the measurements showed albuminuria (35.4 μg/min at day 44). At six months, the median cU-Alb was 2.0 μg/min (range 0.6–14.5). Albuminuria makes a flash-like appearance in PUUV infection and returns rapidly to normal levels within 2–3 weeks after fever onset. In the case of AKI, this is a unique phenomenon

Coeliac disease and HLA-conferred susceptibility to autoimmunity are associated with IgE sensitization in young children.

Non peer reviewe

Flash-Like Albuminuria in Acute Kidney Injury Caused by Puumala Hantavirus Infection

Transient proteinuria and acute kidney injury (AKI) are characteristics of Puumala virus (PUUV) infection. Albuminuria peaks around the fifth day and associates with AKI severity. To evaluate albuminuria disappearance rate, we quantified albumin excretion at different time points after the fever onset. The study included 141 consecutive patients hospitalized due to acute PUUV infection in Tampere University Hospital, Finland. Timed overnight albumin excretion (cU-Alb) was measured during the acute phase in 133 patients, once or twice during the convalescent phase within three months in 94 patients, and at six months in 36 patients. During hospitalization, 30% of the patients had moderately increased albuminuria (cU-Alb 20–200 μg/min), while 57% presented with severely increased albuminuria (cU-Alb >200 μg/min). Median cU-Alb was 311 μg/min (range 2.2–6460) ≤7 days after fever onset, 235 μg/min (range 6.8–5479) at 8–13 days and 2.8 μg/min (range 0.5–18.2) at 14–20 days. After that, only one of the measurements showed albuminuria (35.4 μg/min at day 44). At six months, the median cU-Alb was 2.0 μg/min (range 0.6–14.5). Albuminuria makes a flash-like appearance in PUUV infection and returns rapidly to normal levels within 2–3 weeks after fever onset. In the case of AKI, this is a unique phenomenon

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

The prevalence of hemoglobin Tacoma in Finland detected by HbA1c capillary electrophoresis

Previous studies have identified occasional cases of heterozygous Hb Tacoma in areas that have attracted Finnish immigrants, especially in Sweden and North America, but large studies of this slightly unstable beta variant in vitro have not been carried out. Here we determined the prevalence of hemoglobin variants across Finland. A total of 5059 samples from 11 different hospital districts were analyzed using HbA1c capillary electrophoresis and reviewed for atypical profiles (HbA1c, Capillarys 3 Tera, Sebia). 38 heterozygous Hb Tacoma cases were found (0.75%). The prevalence was highest in South Ostrobothnia (2.0%), located in western Finland, and second highest in the neighboring provinces (1.0-1.4%), but only two districts were devoid of variants. Heterozygous Hb Tacoma was confirmed by genetic testing (NM_000518.5(HBB):c.93G > T (p.Arg31Ser)). In addition, five other variants were found, suggestive of HbE, Hb Helsinki (two cases) and an alpha variant, as interpreted from the electropherograms. The fifth variant, belonging to the South Ostrobothnian cohort, remained unknown at the time of the initial analyses, but was later interpreted as homozygous Hb Tacoma and confirmed by hemoglobin fraction analysis (Hemoglobin(E), Capillarys 3 Tera). In a subsequent retrospective study of the electropherograms of routine HbA1c diagnostics, altogether nine homozygous Hb Tacoma cases were identified in South Ostrobothnia. While heterozygous Hb Tacoma is usually an incidental finding, it interferes with several HbA1c assays. The present study is the first demonstration of homozygous Hb Tacoma. The clinical presentations of homozygous Hb Tacoma are not known and need to be addressed in future studies.Peer reviewe