Effect of Carbohydrate Demand on the Remobilization of Starch in Stolons and Roots of White Clover (Trifolium repens L.) after Defoliation

White clover plants were grown from stolon tips in growth cabinets and then defoliated. Thereafter, changes in the contents of non-structural carbohydrates such as starch, sucrose, glucose, fructose, maltose, and pinitol in stolons and roots were monitored. Initial contents of carbohydrate reserves, photosynthetic supply of new carbohydrates and carbohydrate demand after defoliation were varied by growing the plants at various CO2 partial pressures, by varying the extent of defoliation and by removing either roots or stolon tips at the time of defoliation. Remobilization of carbohydrate reserves in stolons increased proportionally to their initial contents and was greater when plants had been severely defoliated, suggesting that carbohydrates were remobilized according to availability and demand. Starch was the predominant reserve carbohydrate. Starch degradation was associated with decreased contents of sucrose, glucose and fructose in young stolon parts and roots but not in old stolon parts suggesting that starch degradation was not strictly controlled by the contents of these sugars. A decrease in the demand for carbohydrates by removal of roots did not decrease starch degradation but increased the contents of sucrose, glucose, and fructose. Removal of stolon tips decreased starch degradation and contents of sucrose, glucose, and fructose. The results suggest that starch degradation was controlled by a factor other than sucrose, glucose, and fructose which was exported from stolon tips, e.g. gibberelli

Combinations of QT-prolonging drugs: towards disentangling pharmacokinetic and pharmaco-dynamic effects in their potentially additive nature.

Background: Whether arrhythmia risks will increase if drugs with electrocardiographic (ECG) QT-prolonging properties are combined is generally supposed but not well studied. Based on available evidence, the Arizona Center for Education and Research on Therapeutics (AZCERT) classification defines the risk of QT prolongation for exposure to single drugs. We aimed to investigate how combining AZCERT drug categories impacts QT duration and how relative drug exposure affects the extent of pharmacodynamic drug–drug interactions. Methods: In a cohort of 2558 psychiatric inpatients and outpatients, we modeled whether AZCERT class and number of coprescribed QT-prolonging drugs correlates with observed rate-corrected QT duration (QTc) while also considering age, sex, inpatient status, and other QTc-prolonging risk factors. We concurrently considered administered drug doses and pharmacokinetic interactions modulating drug clearance to calculate individual weights of relative exposure with AZCERT drugs. Because QTc duration is concentration-dependent, we estimated individual drug exposure with these drugs and included this information as weights in weighted regression analyses. Results: Drugs attributing a ‘known’ risk for clinical consequences were associated with the largest QTc prolongations. However, the presence of at least two versus one QTc-prolonging drug yielded nonsignificant prolongations [exposure-weighted parameter estimates with 95% confidence intervals for ‘known’ risk drugs + 0.93 ms (–8.88;10.75)]. Estimates for the ‘conditional’ risk class increased upon refinement with relative drug exposure and coadministration of a ‘known’ risk drug as a further risk factor. Conclusions: These observations indicate that indiscriminate combinations of QTc-prolonging drugs do not necessarily result in additive QTc prolongation and suggest that QT prolongation caused by drug combinations strongly depends on the nature of the combination partners and individual drug exposure. Concurrently, it stresses the value of the AZCERT classification also for the risk prediction of combination therapies with QT-prolonging drugs