We evaluated the AxSYM immunoassay for the quantification of cardiac troponin I (cTnI). Total assay imprecision, expressed as coefficient of variation, ranged between 5.6% and 8.3% for commercial ...control serum samples and between 4.2% and 13.9% for pooled patient samples. Linearity was verified up to 42 micrograms/L. Triglycerides (up to 1,000 mg/dL) did not interfere with the assay, but minor hemolysis and clinically relevant hyperbilirubinemia caused a negative bias. In 186 patient samples, AxSYM cTnI levels correlated significantly with data obtained with the Stratus II cTnI fluorometric enzyme immunoassay but were 3 to 4 times higher on AxSYM than on Stratus II. In 111 healthy blood donors, the reference range for cTnI levels on AxSYM was 0.0 to 0.4 microgram/L. After eccentric isokinetic exercise, healthy volunteers showed a rise in creatine kinase MB mass (AxSYM) but not in cTnI. On AxSYM and Stratus II, cTnI levels increased above the manufacturer's cutoff for acute myocardial infarction in all 17 patients followed up after onset of infarction-related chest pain but in only 1 of 91 control subjects. The AxSYM cTnI assay is a valid alternative for the detection of myocardial injury with diagnostic performance comparable to the established Stratus cTnI assay.
The prevalence of circulating macromolecular creatine kinase type 1 (macro CK type 1 or CK-immunoglobulin complexes) is significantly higher in a patient population selected for CK isoenzyme assay ...than in age- and sex-matched blood donors (n = 1304). In greater than 8000 patients studied, 49 individuals with macro CK type 1 were identified, yielding an overall prevalence of 0.61%. Macro CK type 1 complexes occurred more frequently in women and in patients older than 70 years, and were often associated with complications of cardiovascular disease, life-threatening conditions, and poor outcome. These latter clinical associations could arise, at least partly, from the selection of patients for whom CK isoenzyme analysis was ordered.
With electrolyte reference fluid (ERF)00, results from Kodak Ektachem slides for the direct potentiometric assay of sodium in plasma were significantly correlated with results from flame photometry, ...but also appeared to be systematically higher, especially in hypernatremic patients. Indirect potentiometry with the Technicon RA-1000 yielded intermediate values. In 23 hypernatremic patients with greater than or equal to 6 mmol/L difference in sodium between Ektachem ERF00 and flame photometry, a clinical survey disclosed the frequent association of large between-method differences with renal failure, diabetes mellitus, and gastrointestinal disease. However, there was no correlation between differences in sodium on the one hand and anion gaps or (lipo)protein concentrations on the other, nor did in vitro addition studies implicate metabolites that often accumulate in the above-mentioned disorders. Unlike indirect methods, sodium measurements by direct potentiometry on Ektachem and Corning were influenced by in vitro changes of pH between 7.0 and 7.9. However, in a group of patients that included many acidotic individuals, between-method differences in sodium appeared not significantly correlated with in vivo blood pH. Use of the equitransferant ERF04 on Ektachem strongly diminishes the systematic differences with flame photometry, reduces the pH-dependency of the results to that of the direct Corning method, and brings the mean analytical recovery of sodium to below 95% (instead of 115% previously) without affecting the ability of Ektachem slides to avoid spuriously low results in the presence of increased (monoclonal) protein concentrations.
HIF prolyl hydroxylases (PHD1-3) are oxygen sensors that regulate the stability of the hypoxia-inducible factors (HIFs) in an oxygen-dependent manner. Here, we show that loss of Phd1 lowers oxygen ...consumption in skeletal muscle by reprogramming glucose metabolism from oxidative to more anaerobic ATP production through activation of a Pparalpha pathway. This metabolic adaptation to oxygen conservation impairs oxidative muscle performance in healthy conditions, but it provides acute protection of myofibers against lethal ischemia. Hypoxia tolerance is not due to HIF-dependent angiogenesis, erythropoiesis or vasodilation, but rather to reduced generation of oxidative stress, which allows Phd1-deficient myofibers to preserve mitochondrial respiration. Hypoxia tolerance relies primarily on Hif-2alpha and was not observed in heterozygous Phd2-deficient or homozygous Phd3-deficient mice. Of medical importance, conditional knockdown of Phd1 also rapidly induces hypoxia tolerance. These findings delineate a new role of Phd1 in hypoxia tolerance and offer new treatment perspectives for disorders characterized by oxidative stress.
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Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
To study the association of autoantibodies against a 38-kDa glycated islet cell membrane-associated (GLIMA) protein with (pre)type 1 diabetes, patient characteristics, and other immune and genetic ...markers of the disease and to evaluate the possible added value of GLIMA antibody determinations for disease prediction and classification.
Recent-onset type 1 diabetic patients (n = 100), prediabetic siblings (n = 23), and nondiabetic control subjects (n = 100) were consecutively recruited by the Belgian Diabetes Registry. GLIMA antibodies were determined by immunoprecipitation of radiolabeled islet cell proteins; islet cell antibodies (ICAs) were determined by indirect immunofluorescence; and insulin autoantibodies (IAAs), insulinoma-associated protein-2 antibodies (IA-2As), and GAD antibodies (GADAs) were determined by radioligand assays.
GLIMA antibodies were detected in 38% of type 1 diabetic patients and 35% of prediabetic siblings (during follow-up) vs. 0% in control subjects (P < 0.001). Their prevalence was lower than that of other antibodies and was significantly associated with high levels of IA-2A and ICA (P < 0.0001). In (pre)diabetes, GLIMA antibodies could only be demonstrated in sera positive for > or = 1 other autoantibody.
GLIMA antibodies are strongly associated with type 1 diabetes and antibody markers of rapid progression to clinical onset but have a lower diagnostic sensitivity for the disease than IAA, ICA, IA-2A, or GADA. In its present form, the GLIMA antibody assay does not provide much additional information for prediction or classification of diabetes, compared with that obtained from the measurement of IA-2As alone or in combination with IAAs, ICAs, and GADAs.
Alloxan rapidly binds to or accumulates in pancreatic B-cells as distinct from non-B-cells. The selective uptake of this cytotoxic agent by the insulin-producing B-cells might account for its ...well-known diabetogenic effect.
We analytically and clinically evaluated Abbott's IMx assay for creatine kinase (CK) isoenzyme MB (CK-MB) in serum. Over a 1-year period, the method was more specific but less precise than catalytic ...isoenzyme measurements by electrophoresis or immunoinhibition. Sera from different individuals without electrophoretic evidence of CK-MB but containing macro CK type 1 (n = 20), mitochondrial CK (n = 5), or CK-BB (n = 5) were scored as CK-MB negative by the IMx. Likewise, CK-MB-negative by the sera remained so after addition of purified human CK-MM (< or = 7600 U/L) or CK-BB (< or = 8100 U/L). For 39 patients admitted for suspicion of uncomplicated acute myocardial infarction (precordial pain for < or = 4 h), the diagnostic performance of the IMx CK-MB assay on admission and 4 h later was superior to that of total CK activity and compared well with that of CK-MB activity measured by electrophoresis or immunoinhibition. An admission, myoglobin showed a higher diagnostic sensitivity, specificity, and predictive value than did CK-MB and was the most informative test. Diagnostic performance on admission and 4 h later was further improved by considering positivity for myoglobin and for CK-MB by IMx and for the change in each over the first 4 h of hospitalization as criteria. Twelve hours after admission, diagnostic performance was further improved for all CK and CK-MB methods but began to decline for myoglobin.
An 11-month-old boy with a relapsing dancing eye syndrome associated with elevation of serum alkaline phosphatase, lactate dehydrogenase, and aminotransferase activities is reported. During two ...clinical episodes the serum alkaline phosphatase activity increased up to four times the upper reference limit, remained elevated for a few weeks and normalized gradually in parallel with clinical improvement under steroid therapy. We found no evidence of liver or bone pathology nor of a neural crest tumor. The association between dancing eye syndrome and hyperphosphatasemia has not yet been described. The beneficial effect of the steroid therapy strengthens the hypothesis of an autoimmune origin.
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