[Biomarkers of alcohol consumption, an update]. / Biomarkers voor alcoholgebruik.

Alcohol disorder is a growing public health concern, both national and globally. Accurate assessment using standardized questionnaires is an important step towards effective management of the patient suffering from alcohol disorder. The use of biochemical laboratory measures often helps in obtaining independent estimations of alcohol use. Because of (very) low specificity and sensitivity, the use of traditional biomarkers ASAT, ALAT, ASAT-ALAT ratio and MCV is not recommended anymore in the Netherlands. Use of BAC is recommended to detect recent drinking as is CDT measurement in blood, possibly together with gGT, for the diagnosis of chronic excessive alcohol use. EtG in urine can be used for short term monitoring a patient in an abstinence traject. PEth in blood is a very promising biomarker in detecting recent and chronic alcohol consumption as well as monitoring abstinence. The availability of a fast and cheap method for detecting PEth with a well-defined and accepted cut off, are essential study objectives.

The cholesterol content of the erythrocyte membrane is an important determinant of phosphatidylserine exposure.

Maintenance of the asymmetric distribution of phospholipids across the plasma membrane is a prerequisite for the survival of erythrocytes. Various stimuli have been shown to induce scrambling of phospholipids and thereby exposure of phosphatidylserine (PS). In two types of patients, both with aberrant plasma cholesterol levels, we observed an aberrant PS exposure in erythrocytes upon stimulation. We investigated the effect of high and low levels of cholesterol on the ATP-dependent flippase, which maintains phospholipid asymmetry, and the ATP-independent scrambling activity, which breaks down phospholipid asymmetry. We analyzed erythrocytes of a patient with spur cell anemia, characterized by elevated plasma cholesterol, and the erythrocytes of Tangier disease patients with very low levels of plasma cholesterol. In normal erythrocytes, loaded with cholesterol or depleted of cholesterol in vitro, the same analyses were performed. Changes in the cholesterol/phospholipid ratio of erythrocytes had marked effects on PS exposure upon cell activation. Excess cholesterol profoundly inhibited PS exposure, whereas cholesterol depletion led to increased PS exposure. The activity of the ATP-dependent flippase was not changed, suggesting a major influence of cholesterol on the outward translocation of PS. The effects of cholesterol were not accompanied by eminent changes in cytoskeletal and membrane proteins. These findings emphasize the importance of cholesterol exchange between circulating plasma and the erythrocyte membrane as determinant for phosphatidylserine exposure in erythrocytes.

Diagnostic value of zinc protoporphyrin in a screening strategy for alpha-thalassemia.

The definitive diagnosis of alpha-thalassemia involves detection of a deletion of one or more alpha-globin that encode the alpha-chains of Hb (hemoglobin). To determine whether DNA analysis is indicated, screening tests such as mean corpuscular volume (MCV) and Hb typing are employed. alpha-Thalassemia often correlates with normal or low HbA2 values. Zinc protoporphyrin (ZPP) is usually high in ferropenic anemia or lead-poisoning and is normal or slightly raised in beta-thalassemia. Therefore, ZPP is currently used as a marker to discriminate between ferropenic anemia and beta-thalassemia. We investigated the diagnostic potential of ZPP < 150 micromol/mol heme in a screening strategy for alpha-thalassemia. We measured ZPP and performed DNA analysis for detecting the seven most prevalent alpha-thalassemia deletions, namely, alpha3.7, SEA, alpha20.5, alpha4.2, MED, FIL, and THAI, in the blood samples of 200 patients with MCV < 70 fL and HbA2 < or = 3.5%. Deletions were detected in 9% subjects in the ZPP > or = 150 group (n = 175) and 56% subjects in the ZPP < 150 group (n = 29); this difference was statistically significant (chi-square test, P < 0.001). We conclude that ZPP < 150 micromol/mol heme can be used in a new screening strategy for alpha-thalassemia.

Laboratory evaluation of a novel capillary blood sampling device for measuring eight clinical chemistry parameters and HbA1c.

BACKGROUND: The Demecal set enables medically unskilled persons to produce diluted plasma from a single drop of capillary blood at any time and place. The sample is mailed to a certified laboratory for analysis. A marker compound in the dilution buffer enables to correct for individual blood sampling variation. A test dependent factor corrects for recovery of analytes. METHODS: Glucose, cholesterol, triglycerides, HDL and LDL cholesterol, creatinine, BUN, uric acid and HbA1c were evaluated. We studied the correction procedure for sampling variation by the marker compound, the precision of the analyzer in the low range, the influence of characteristics of the set on analyte recovery, and the stability of the samples at different temperatures. RESULTS: Using the marker compound in the buffer, variation in sampling could be corrected accurately. For dilutions up to 15 times, the precision of the analyzer was sufficient. Application of test specific recovery factors gave a good correlation with results of venous blood samples. Samples were stable for 4 days at 4 degrees C, 2-3 days at room temperature and 1 day at 37 degrees C. CONCLUSIONS: The Demecal set can be considered an alternative for venous blood sampling for the tested parameters, enabling patient friendly management of chronic disease.