Päivikki Kangastupa

Comparison of ethyl glucuronide and carbohydrate-deficient transferrin in different body fluids for post-mortem identification of alcohol use.

AIMS Alcohol abuse is a major risk factor for premature death. Confirming the role of alcohol consumption in cause-of-death investigations has, however, remained difficult, due to lack of reliable biomarkers. METHODS We compared ethyl glucuronide (EtG) and carbohydrate-deficient transferrin (CDT) assays from serum, urine, cerebrospinal fluid and vitreous humor in a forensic autopsy population with either a positive (n = 38) or negative (n = 22) history of alcohol abuse based on detailed medical and police records and forensic toxicological investigations. RESULTS A positive blood alcohol concentration (median 1.15‰, range 0-3.3‰) was found in 26/38 (68%) of the cases with a documented history of alcohol abuse. EtG concentrations (mean ± SD) in urine (339 ± 389 mg/l, P < 0.001), vitreous humor (4.2 ± 4.8 mg/l, P < 0.001), serum (6.9 ± 8.9 mg/l, P < 0.01) and cerebrospinal fluid (1.7 ± 2.7 mg/l, P < 0.01) were significantly higher among the cases with a positive history of alcohol use than those in the alcohol-history negative group, whereas in corresponding comparisons CDT was significantly different only in cerebrospinal fluid (4.3 ± 2.1 vs. 2.3 ± 0.6%, P < 0.05). The highest sensitivities (92%) in detecting ante-mortem alcohol use were obtained for urine and vitreous humor EtG assays. CONCLUSION Our data indicate that measurements of EtG in urine or vitreous humor show the highest diagnostic accuracies in post-mortem investigations of excessive alcohol consumption and can be recommended for routine applications.

Dose- and Gender-dependent Interactions between Coffee Consumption and Serum GGT Activity in Alcohol Consumers

AIMS Coffee consumption has been recently linked with decreased blood gamma-glutamyltransferase (GGT) activities and protection from alcoholic liver disease. To explore the relationship and dose response, we assessed the impacts of coffee and alcohol intake on serum GGT activity in apparently healthy men and women with varying levels of coffee and alcohol consumption. METHODS Data on coffee, alcohol consumption and serum GGT activities were collected from 18,899 individuals (8807 men and 10,092 women), mean age 48 years, range 25-74 years, who participated in a large national cross-sectional health survey. Body mass index, smoking index and age were used as covariates in all analyses. RESULTS Among the study population, 89.8% reported varying levels of coffee consumption; 6.9% were abstainers from alcohol, 86.1% moderate drinkers, 3.7% heavy drinkers and 3.3% former drinkers. In men, the elevation of GGT induced by heavy drinking (>280 g/week) was found to be significantly reduced by coffee consumption exceeding 4 cups per day. A similar trend was also observed among women, which however, did not reach statistical significance. CONCLUSION Coffee modulates the effect of ethanol on serum GGT activities in a dose- and gender-dependent manner. These observations should be implicated in studies on the possible hepatoprotective effects of coffee in alcohol consumers.

Immunoassay for ethyl glucuronide in vitreous humor: A new tool for postmortem diagnostics of alcohol use

Although excessive alcohol consumption plays a major role in fatal events, the role of alcohol use as a possible contributing factor at the time of death is not easy to establish due to lack of suitable biomarkers for postmortem analyses. We used an immunological approach to measure ethyl glucuronide (EtG) concentrations from vitreous humor (VH) and serum from 58 individuals representing a forensic autopsy population of cases with either a well-documented history of excessive alcohol use (n=37) or cases without such history (n=21), according to medical and police records and blood alcohol determinations (BAC). The immunoassay was based on the Microgenics DRI-EtG EIA reagents applied on an automated Abbott Architect c8000 clinical chemistry analyzer. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) determination of EtG and ethyl sulfate (EtS) was used as a reference method. At a cut-off of 0.3mg/l for VH-EtG, the immunoassay correctly identified 92% of the cases with a history of excessive alcohol use, whereas the BAC was positive (cut-off 10mg/dl) in 68% of the cases. A significant correlation emerged between VH-EtG and serum EtG (r=0.77, p<0.001) and between VH-EtG and BAC (r=0.62, p<0.001), although VH-EtG was frequently elevated also in cases with no detectable BAC. The EtG immunoassay showed a strong correlation with the LC-MS/MS reference method (r=0.94, p<0.001) and there was 100% agreement in the frequency of marker positive and negative findings between the immunoassay EtG results and the LC-MS/MS analysis of EtG and EtS. The present data indicate that the immunoassay for VH-EtG is a useful forensic tool for screening of antemortem alcohol use.

Impacts of common factors of life style on serum liver enzymes

AIM To investigate the impacts of gender, age and factors of life style (alcohol, overweight, coffee and smoking) on serum liver enzymes. METHODS Serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) were measured from 6269 apparently healthy individuals (2851 men, 3418 women, mean age 45 ± 12 years, range 25-74 years) in a national cross-sectional health survey. All subjects underwent detailed clinical examinations and interviews including the amount and pattern of alcohol use, coffee consumption and smoking habits. RESULTS In this population with a mean ± SD alcohol consumption of 65 ± 105 g/wk and body mass index (BMI) of 26.1 ± 4.3 kg/m(2), both ALT and GGT were significantly influenced by alcohol use (P < 0.001) and BMI (P < 0.001), whereas smoking increased only GGT (P < 0.001). A significant effect of age on ALT was seen in men (P < 0.001) whereas not in women. Significant two-factor interactions of alcohol use in men were observed with age (ALT: P < 0.01; GGT: P < 0.001) and BMI (GGT: P < 0.05). For ALT, a significant interaction also occurred between BMI and age (P < 0.005). In contrast, women showed significant interactions of alcohol use with BMI (GGT: P < 0.05), smoking (GGT: P < 0.001), and coffee consumption (GGT: P < 0.001). CONCLUSION Life-style associated changes in liver enzymes may reflect health risks, which should be considered in the definition of normal limits for liver enzymes.

Individual responses in biomarkers of health after marathon and half-marathon running: is age a factor in troponin changes?

Abstract Although strenuous physical activity is known to cause notable perturbations in blood chemistries, only few studies exist observing exercise-induced simultaneous changes in biomarkers of health status. We compared markers of muscle, cardiovascular, renal, hepatic and inflammatory status at baseline and at 3-h and at 48-h postrace in recreational runners who successfully completed either a marathon (mean age 27 ± 13 years, finishing time 199 ± 8 min, n = 4) or half-marathon (mean age 38 ± 13 years, finishing time 131 ± 6 min, n = 6) race. Significant postrace changes occurred in myoglobin (p < .001), creatinine kinase (p < .01), CK-MB-mass (p < .01), high sensitivity troponin I (p < .05), high sensitivity troponin T (p < .05), brain natriuretic peptide (p < .001), creatinine (p < .01), aminotransferase enzymes (p < .001 for AST and p < .01 for ALT), uric acid (p < .001) cortisol (p < .01), C-reactive protein (p < .05), leukocytes (p < .001), haematocrit (p < .05) and mean corpuscular volume (p < .01). In comparison between the two types of exercise, marathon running lead to more pronounced responses in myoglobin, CK-MB-mass, ALT, AST, lactate and phosphate. Notable elevations in troponin levels were observed only in young participants (<30 years), most strikingly in those ≤20 years of age. The data indicates that prolonged running leads to distinct biomarker alterations, which should be considered in the assessment of health status after recent acute bouts of strenuous exercise. The observations suggesting more pronounced cardiac troponin responses in young individuals warrant further studies in larger populations.