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Low levels of thrombin activatable fibrinolysis inhibitor (TAFI) in patients with chronic liver disease.

Thrombin Activatable Fibrinolysis Inhibitor (TAFI) is a 60 kappaD glycoprotein present in plasma that regulates fibrinolysis by limiting the amount of fibrin available for fibrinolysis by tissue plasminogen activator (t-PA). Chronic liver disease is well-known to be associated with a low-grade fibrinolytic syndrome that under the appropriate stimulus proceeds to an overt disseminated intravascular coagulopathy (DIC) with demonstrable bleeding. In the present study, TAFI activity was measured in the plasma of 74 patients with advanced liver disease, and the levels of TAFI were related to those of other important coagulation and fibrinolytic factors. TAFI levels were very low and essentially undetectable in the plasma of patients with advanced hepatocellular liver disease. No relationship with the degradation products of fibrin was evident.

Adult↗

[Diagnostic significance of isoenzymes and isoforms of alkaline phosphatase in blood serum of patients with multiple sclerosis on the clinical form of the illness].

In multiple sclerosis there takes place a gradual destruction of most organs and tissues of the sick organism. With progression of the illness changes are noticeable in their functional development. A biochemical mode of assessment of functioning of organs and tissues is analysis of alkaline phosphatase, which is performed with high dilution. Activity of alkaline phosphatase was measured together with its isoenzymes and isoforms in blood serum of 101 patient with disseminated sclerosis depending on the clinical form of the illness. Measurement of blood serum alkaline phosphatase isoenzymes and isoforms can be a marker of the demyelinating process in multiple sclerosis.

Alkaline Phosphatase↗

[Aldolase].

Aldolase (EC 4.1.2.13) plays an important role in glucose metabolism. Aldolase has a molecular weight of 160 kDa and has three isozymes, namely aldolase A, B and C. The enzyme is probably present in all cells; it occurs in particularly large quantities in the muscles, liver and brain. An increase in serum aldolase is found in myotonic muscular disease, such as progressive muscular dystrophy and polymyositis. The enzyme rises in myocardial infarction, reaches a maximum within 24-48 hours and returns to normal in the course of five days. In these muscular diseases, aldolase A isozyme is elevated. Aldolase activity, especially B isozyme, in serum rises to very high levels in acute hepatitis, but is slightly elevated in cirrhosis, chronic hepatitis and obstructive jaundice. Aldolase becomes elevated in serum with malignant tumors, and isozyme A is predominant in serum. Erythrocytes are also rich in aldolase, and the enzyme rises in hemolytic anemia.

Acute Disease↗

[Clinical significance and interpretation of red cell enzyme analyses].

Red cells have a life span of approximately 120 days and disturbances at biochemical pathways such as glycolysis, pentose phosphate shunt, nucleotide metabolism or glutathione synthesis/reduction systems lead to premature cell death, i.e. hemolysis. Red cell enzyme analysis is useful for screening for an enzyme defect which is responsible for hereditary nonspherocytic hemolytic anemia (HNSHA). Further clinical significance of red cell enzyme assay includes the diagnosis of paroxysmal nocturnal hemoglobinuria, methemoglobinemia, Diamond-Blackfan anemia, severe combined immune deficiency, glycogen storage disease, etc. Since several age-dependent enzymes are known, careful evaluation of enzyme activities is required if reticulocyte counts are elevated. It should be noted that deficiency of an isozyme may be masked by activity derived from another isozyme. Recent progress in the molecular genetics of red cell enzymopathies and protein structure-function mechanisms enable us to diagnose "enzyme deficiency" at DNA level.

Anemia, Diamond-Blackfan↗

[Improvement of inter-laboratory imprecision in enzyme measurements].

The traceability chains of the enzyme measurement system were established based on technological advances in instrumentation and reagent systems. The values assigned in reference materials (Japan Certified Enzyme Reference Materials; JCERM) were transferred to daily laboratory analysis via enzyme calibrators included in industrial reagent kits. The imprecision between laboratories was then minimized to within 4 percent in six enzymes, AST, ALT, LD, ALP, CK and gamma-GT.

Biomarkers↗

[Amylase].

alpha-Amylase in human serum consists of at least two isozymes originating from either the pancreas or salivary glands. These isozymes can be determined by three methods, electrophoresis, inhibitor method and antibody method. The committee on enzymes of the International Federation of Clinical Chemistry recommended the approved method for the catalytic concentration of alpha-amylase using 4,6-ethylidene-4-nitrophenyl-alpha-1,4-D-maltoheptaoside as a substrate. However, the assay method using 2-chloro-4-nitrophenyl-alpha-1,4-D-maltotorioside as a substrate is the IFCC method. On the other hand, the committee on enzymes of the Japan Society of Clinical Chemistry recommends an other method using maltoheptaose as a substrate. Various other methods are used as the routine method in clinical laboratories.

Amylases↗

[Abnormal isoenzymes].

Enzyme linked immunoglobulins, tumor production enzymes, alloenzymes (LD, CK, Cholinesterase) were explained by the genetic variants for their characterization and clinical significance. A recent interesting report on enzyme linked immunoglobulins, stated that there is a beta-sheet structural anomaly in Bence Jones protein which combines with LD and that macrolipase results from the combination of lipase and alpha 2-macroglobulin in hyperlipasemia.

Biomarkers↗

[Aspartate aminotransferase (glutamic oxalacetic transaminase) and alanine aminotransferase (glutamic pyruvic transaminase)].

With regard to adding Pyridoxal Phosphate (PALP), which combines with the active sites of AST and ALT, JSCC recommends measuring holoenzymes without adding PALP, reflecting the biological reaction. On the other hand, IFCC recommends the measurement of both holoenzymes and apoenzymes when PALP is added, reflecting the total diverted from the internal organs. It is important which recommendation to follow from a clinical point of view and from the viewpoint of reducing gaps in clinical facilities. Further, it is necessary to consider each isozyme as well as the time difference between apoenzyme and holoenzyme diversion from blood to accurately grasp the pathology and understand the measurement.

Alanine Transaminase↗

[Discrepancies in the measurement of serum pancreatic lipase activities by non-enzymatic and enzymatic assays, and relationships to pseudohyperlipasemia].

I have observed discrepancies in the measurement of serum pancreatic lipase(LIP, Triacylglycerol acylhydrolase, EC 3.1.1.3) activities by non-enzymatic and enzymatic methods using diglyceride(1,2-dilinoleoyl-2-palmitoyl-glycerol, DLPG) as a substrate. The greatest discrepancies were seen in the post-heparin sera of patients with acute coronary syndrome(ACS). It is well-known that serum levels of lipoprotein lipase(LPL, EC 3.1.1.34) and hepatic triglyceride lipase(HTL, EC 3.1.1.3) show a significant increase after the administration of heparin in hemodialysis patients, and even larger quantities of heparin are administered before cardioangiography for ACS. Moreover, inhibitors of LPL and HTL induce almost complete reduction of increased LIP activity in post-heparin serum as measured by enzymatic assays. Pseudohyperlipasemia and positive interference from post-heparin serum LIP activity in enzymatic assays are considered to largely reflect LPL and HTL activities. Therefore, enzymatic reagent kits need improvement.

Acute Disease↗

PSA testing.

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Aged↗

[Biomarkers for toxicity and metabolic abnormalities of the main severe poisonings. Clinical and toxicologic symptoms. Conservative determination].

The members of the joint group "Toxicology and Clinical Biology" of the French Society of Clinical Biology (SFBC), the French Society of Analytical Toxicology (SFTA), and the Society of Clinical Toxicology (STC), suggest guidelines to meet the requirements of clinical biologists who are not specialized in toxicology. Based on good laboratory practice they propose a number of guidelines. Three synthetic tables have been established. They are not only toxicity biomarkers and metabolic disorders associated with the main severe intoxications, but also clinical signs that are observed during these intoxications, finally biological sampling as a precautionary measure. The table also takes into account approximately fifty xenobiotics: main clinical signs emergency, identification or quantification of the suspected product, useful biological markers, therapeutic, quantitations necessary to take into consideration patient care, and poison antidotes, are described. Recommendations regarding medical and forensic techniques are also proposed by the group. It is also necessary to collect and store biological samples when the individual patients are in charge. These samples will be analyzed or not depending on the individual case history.

Biomarkers↗

Fibre diffraction from a single hair can provide an early non-invasive test for colon cancer.

BACKGROUND: Molecular structural changes in hair, skin and breast associated with breast cancer have been observed using synchrotron fibre diffraction. These results raised the possibility that such hair studies might be used as a non-invasive diagnostic marker for breast cancer. A series of double-blinded studies was undertaken to establish the specificity of such a tool. Hair samples from controls, patients with cancers of the breast and other sites including the colon were studied. An associated study of collagenous colon tissue was also undertaken. MATERIAL/METHODS: Single hairs were used for the fibre diffraction study. Collagenous colon samples were dissected near the tumour and from the ends of the colon section. The protocols followed exactly the associated breast cancer studies. RESULTS: A ring of radius 4.53+/- 0.03 nm, superimposed on the patterns obtained for the controls, was observed in the diffraction patterns for the hair of all colon cancer patients. This radius is different from that observed for breast cancer. In the collagen tissue study, two discrete sets of additional rings are superimposed on the normal collagenous colon pattern, one for samples adjacent to the tumour and one for samples distal from the tumour. The latter revealed that tissue at the point of dissection was not always normal. CONCLUSIONS: Here we show that, since the sensitivity and specificity for the difference observed in the diffraction patterns of hair in colon cancer are both 100%, a fibre diffraction analysis could be a simple, non-invasive screening test for colon cancer.

Biomarkers, Tumor↗

Serum osteocalcin as a marker for vitamin K-status in pregnant women and their newborn babies.

Osteocalcin (bone Gla-protein) is a vitamin K-dependent protein synthesized by osteoblasts. Its hydroxylapatite binding capacity (HBC) is generally used to estimate the Gla-content of circulating osteocalcin. Here we have used the HBC of serum osteocalcin as a marker for the vitamin K-status in pregnant women and their offspring. For all cases investigated the HBC values in the cord samples were substantially lower than in the corresponding maternal ones. Babies from mothers who had been treated with vitamin K during the last 6 weeks prior to delivery, had significantly higher HBC values than those from a placebo group. The results presented in this paper are indicative for a generally occurring vitamin K deficiency in newborns. At delivery the HBC in untreated women was low as well. In both the placebo- and the vitamin K-group a good correlation was found between the HBC values in paired samples from mother and child. Whether the maternal HBC value may be used as a prenatal marker for estimating the fetal vitamin K-status remains to be seen.

Adsorption↗