Ca pushes and pulls energetics to maintain ATP balance in atrial cells: computational insights.

To maintain atrial function, ATP supply-to-demand matching must be tightly controlled. Ca can modulate both energy consumption and production. In light of evidence suggesting that Ca affects energetics through "push" (activating metabolite flux and enzymes in the Krebs cycle to push the redox flux) and "pull" (acting directly on ATP synthase and driving the redox flux through the electron transport chain and increasing ATP production) pathways, we investigated whether both pathways are necessary to maintain atrial ATP supply-to-demand matching.

cAMP signaling affects age-associated deterioration of pacemaker beating interval dynamics.

Sinoatrial node (SAN) beating interval variability (BIV) and the average beating interval (BI) are regulated by a coupled-clock system, driven by Ca-calmodulin activated adenylyl cyclase, cAMP, and downstream PKA signaling. Reduced responsiveness of the BI and BIV to submaximal, [X], β-adrenergic receptor (β-AR) stimulation, and phosphodiesterase inhibition (PDEI) have been documented in aged SAN tissue, whereas the maximal responses, [X], do not differ by age. To determine whether age-associated dysfunction in cAMP signaling leads to altered responsiveness of BI and BIV, we measured cAMP levels and BI in adult (2-4 months n = 27) and aged (22-26 months n = 25) C57/BL6 mouse SAN tissue in control and in response to β-AR or PDEI at X and [X].

[Long-term sequelae of malignant tumors in childhood: consequences of late side-effects].

110 children with malignant diseases (leukemia excepted) who survived 5-20 years (median 9) post-therapy were followed (1996-1998). Median age during follow-up was 15 years (range 5-23). The most common malignancies were brain tumors, lymphoma, retinoblastoma and Wilm's tumor.