Cardiospecificity of the 3rd generation cardiac troponin T assay during and after a 216 km ultra-endurance marathon run in Death Valley.

BACKGROUND: The reasons for the appearance of cardiacspecific troponin (cTnT) after strenuous exercise are unclear. The aim of the present study was to evaluate the cardiospecificity of the 3(rd) generation cardiac cTnT assay during and after an ultra-endurance race of 216 km at extreme environmental conditions in Death Valley. STUDY DESIGN AND METHODS: We measured serially cTnT, creatine kinase (CK), activity and mass of the isoenzyme MB of CK (CK-MB(act) and CK-MB(mass)), and myoglobin in 10 well-trained athletes before, repeatedly during and after the race. RESULTS: Six of 10 participants finished the race within a preset time of 60 hours. Postrace values of biochemical markers CK, CK-MB(act), CKMB(mass), and myoglobin were significantly increased compared to baseline (p<0.05). CK-MB(act) increased from (median (25(th)/ 75(th)percentile) 12 (10/13) U/L to 72 (32/110) U/L, CK-MB(mass) from 3.9 (2.9/5.6) U/L to 65 (18/80) U/L and CK increased from median 136 (98/ 228) U/L to 3,570 (985/6,884) U/L respectively. Pre-race myoglobin was 27 (22/31) microg/l compared to 530 (178/657) microg/l after the run. One runner developed significant exercise-induced rhabdomyolysis with spontaneous recovery. cTnT values remained below the 99(th) percentile reference limit in all athletes including the runner who developed significant rhabdomyolysis (peak CK 27,951 U/L). CONCLUSIONS: Strenuous endurance exercise, even under extreme environmental conditions, does not result in structural myocardial damage in well-trained ultra-endurance athletes. We found no crossreactivity between cTnT and CK, neither in exercise-induced skeletal muscle trauma nor after rhabdomyolysis underscoring the excellent analytical performance of 3(rd) generation cTnT assay.

Activation of the MAP kinase pathway induces chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) expression in human breast cancer cell lines.

Growth factors are essential for cellular growth and differentiation in both normal and malignant human breast epithelial cells. In the present study we investigated the effect of epidermal growth factor (EGF), transforming growth factor alpha (TGFalpha) and phorbol myristate acetate (PMA) on chicken ovalbumin upstream promoter-transcription factor (COUP-TF) expression in human breast cancer cells. The orphan receptors COUP-TFI and COUP-TFII are members of the nuclear receptor superfamily. The high degree of evolutionary conservation of these proteins strongly argues for an important biological function. COUP-TF expression was highest in SK-BR3 cells (approximately 130 amol/ micro g total RNA), while the lowest COUP-TF expression was observed in MCF-7 cells (3.5 amol/ micro g total RNA). While treatment of EGF, TGFalpha and PMA induced expression of COUP-TFII, COUP-TFI did not respond to these agents. Oncostatin M (OSM) is known to exert an antiproliferative effect in breast cancer cells. Treatment of MCF-7 cells with OSM resulted in an approximately 90% reduction of COUP-TFII mRNA expression. In SK-BR3 cells, treatment with the MEK inhibitor UO126 resulted in a profound suppression of endogenous COUP-TFII expression. Furthermore, cotreatment with UO126 prevented induction of COUP-TFII expression by EGF in MCF-7 cells. In conclusion, our data provide evidence, for the first time, that mitogenic substances which activate the MAP kinase pathway, can induce COUP-TFII expression. Our results strongly suggest that an active MAP kinase pathway is essential for COUP-TFII expression in human breast cancer cells.