Viliam Lustig

Is a Pattern of Increasing Biomarker Concentrations Important for Long-Term Risk Stratification in Acute Coronary Syndrome Patients Presenting Early after the Onset of Symptoms?

BACKGROUND Guidelines for treatment of acute coronary syndrome (ACS) recommend observing a rise or fall in cardiac troponin (cTn) concentrations for assessing acute injury. It is unknown whether a rising pattern presages a more adverse long-term prognosis than elevations that do not change. The present study assessed whether a rising pattern of cardiac biomarkers was more prognostic than simple elevations. METHODS We measured N-terminal pro-brain natriuretic peptide (NT-proBNP) (Roche), cTnT (Roche) and cTnI (Beckman Coulter) in 212 ACS patients. These biomarkers were measured in coincident EDTA and heparin plasma samples available from at least 2 different time points, an early first specimen obtained a median of 2 hours after onset of symptoms, interquartile range (IQR) 2-4 hours, and a later second specimen obtained at 9 hours, IQR 9-9 hours. The cTn concentration in the second specimen was used to classify myocardial necrosis (cTnI >0.04 ug/L; cTnT >0.01 ug/L). Outcomes [death, myocardial infarction (MI), heart failure (HF)] were obtained >8 years after the initial presentation. For patients with myocardial necrosis and a cTn concentration ratio (second/first measured concentrations) > or =1.00, the concentration ratios and the absolute concentrations in the second specimen were used to assess prognosis after 4 years. RESULTS In myocardial necrosis, the relative change (cTn2/cTn1) was greater for cTnI than for cTnT (P <0.01), whereas the relative change in NT-proBNP was the same regardless of which troponin was used to classify necrosis (P = 0.71). The concentration ratio for cTnI, cTnT, and NT-proBNP was not useful for risk stratification (i.e., death/MI/HF; P > or =0.15). CONCLUSIONS A rise in cardiac troponin or NT-proBNP concentration in ACS patients presenting early after onset of pain is not helpful for long-term prognosis.

Vascular versus myocardial dysfunction in acute coronary syndrome: Are the adhesion molecules as powerful as NT-proBNP for long-term risk stratification?

OBJECTIVES To determine if elevations of adhesion molecules in acute coronary syndrome (ACS) are useful for risk stratification. DESIGN AND METHODS A cell adhesion array (Randox Ltd.) and NT-proBNP were measured in 216 ACS patients. RESULTS Kaplan-Meier and Cox models indicate early elevations of NT-proBNP but not the adhesion molecules are predictive of future death/myocardial infarction. DISCUSSION Elevations of adhesion molecules early after pain onset in ACS are not useful for long-term risk stratification.

Evaluation of commercially formulated aspartate aminotransferase and alanine aminotransferase activity determinations by the scandinavian committee on enzymes and IFCC methods as modified for use with automated enzyme analysers

The performance characteristics of the Scandinavian Committee on Enzymes (SCE) methods for the assay of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined using six automated enzyme analysers. The reagent formulation did not include pyridoxal phosphate (PLP). An optimal operating mode was defined for each instrument and precision was assessed in greater detail on four instruments. A points rating system was devised to place the instruments in the following order of proficiency: IL Multistat III, LKB-8600, Gilford 3500, ABA 100. In contrast to AST, the ALT activity of patient samples was unstable at -20 degrees C over periods as short as seven days. The performance characteristics of the IFCC methods for assay of AST and ALT activities were determined by using three automated enzyme analyzers in order to assess the effect of PLP upon precision and activity of four quality control sera, and to compare the SCE and IFCC methods. Precision of AST assays did not alter on omission of PLP from the IFCC formulation, while that of ALT assays showed slight deterioration. The decrease in activity on omitting PLP was variable with each instrument. A points-rating system was devised to place the methods in the following order of precision: AST: IFCC (-PLP) 118, IFCC 109, SCE 61; ALT: IFCC 125, IFCC (-PLP) 97, SCE 66. The IFCC methods offer better precision, and the overall change on omitting PLP is minimal.

Species, organ and subcellular specificity of alkaline phosphatases as determined by amino acid inhibition studies☆

Abstract 1. 1. Alkaline phosphatase activity was present in all tissues from all species examined. 2. 2. The tissue specific enzyme activities in organs from different species are within a comparable range when expressed in milliunits/mg protein. 3. 3. The enzymes from different species and organs have a definite and reproducible pattern of amino acid inhibition. The use of five amino acids ( l -phe, l -arg, l -homoarg, l -met and l -val) enable us to establish this pattern in vitro and to identify in some cases the organ source. 4. 4. Results obtained from amino acid inhibition studies with alkaline phosphatases from one organ or species are valid only for that very organ in that very species.

Temperature optimum of alkaline phosphatases in some homeothermic and poikilothermic species

Abstract 1. 1. Alkaline phosphatases, determined in biological material from different species in vitro, show specific differences in thermostability (after exposure to 56°C), while having a uniform temperature optimum of 37°C. 2. 2. Attempting the valid determination of an enzyme activity in vitro usually assumes an approach derived from inorganic catalysis; rather, it should be considered along with all the complexities of the physiological systems in living organisms. Thus, it is advisable to use caution in drawing conclusions about metabolism and enzyme activity in vivo from routine laboratory methods.

Fructose 1,6-diphosphate activity in rat mammary glands☆

Abstract 1. 1. The presence of FDP-ase activity in mammary glands of virgin and pregnant rats was established. 2. 2. Some of the fundamental properties of the enzyme, such as apparent K m , pH activity curve, substrate dependency, metal ion dependency, heat stability and the effect of 5′AMP were investigated. 3. 3. Possible physiological roles for the enzyme are discussed.

Glucose formation by the R3230AC rat mammary adenocarcinoma

Abstract 1. 1. The presence of d -fructose-1,6-diphosphate 1-phosphohydrolase (E.C.3.1.3.11) activity has been established in the mammary glands of late pregnant Fisher 344 rats and in the R3230AC rat mammary adenocarcinoma. 2. 2. Homogenates of the R3230AC tumour are capable of synthesizing glucose from fructose-1,6-diphosphate a and other gluconeogenic precursors. The rate of glucose synthesis from fructose-1,6-diphosphate is decreased by high substrate concentrations, estrogen administration to the tumour bearing rats and by the addition of 5′AMP or ATP to the incubation mixture. 3. 3. Starvation increases glucose formation from fructose-1,6-diphosphate in the estrogen-treated rats but has no effect in the non-treated animals. 4. 4. Tumour homogenates produced α-glycerophosphate from glucose and other glycolytic precursors. The latter finding points to the presence of the α-glycerophosphate shunt in the R3230AC adenocarcinoma.