Management of gastrointestinal complaints in differentiated thyroid cancer patients treated with 131I: Comparison of the efficacy of pantoprazole, metoclopra-mide, and ondansetron – a randomized clinical trial

Objective: To compare safety and efficacy of pantoprazol, metoclopramide, ondansetron, as compared to placebo, in controlling gastrointestinal (GI) complaints of thyroid cancer patients treated with I-131these patients. Design: Four-armed, parallel group, single blind, randomized controlled clinical trial, setting: A university hospital, registration: database for clinical trials IRCT2013061713705N1. Patients: 85 patients with differentiated thyroid cancer who received131I. Main outcome measures: Post-radioiodine nausea and vomiting within three days of therapy (primary endpoint); occurrence of adverse reaction. Results: The patients' characteristics were similar within the study groups. Among the study variables, age, sex, administered dosage, history of previous GI complaints, and history of hyper -emesis gravidarum in female patients were not statistically different among the groups (p > 0.05). The results revealed that only ond-ansetron shows a therapeutic benefit over the placebo in controlling nausea (p 0.05). The other two drugs, pantoprazole and meto-clopramide, did not control nausea (p > 0.05) or vomiting (p > 0.05). Conclusions: This study may demonstrate that the therapeutic dose of ondansetron could be an effective prophylactic agent in controlling GI complaints in differential thyroid carcinoma (DTC) patients following RAI therapy; however, these pre -liminary findings should be validated in larger studies. © Schattauer 2014

Partial adenosine A1 receptor agonists for cardiovascular therapies

Adenosine, a purine nucleoside, is present in all cells in tightly regulated concentrations. It has many different physiological effects in the whole body and in the heart. Adenosine activates four G protein-coupled receptors A1, A2a, A2b, and A3. Activation of myocardial A1 receptors has been shown to inhibit a variety of myocardial pathologies associated with ischemia and reperfusion injury, including stunning, arrhythmogenesis, coronary and ventricular dysfunction, acute myocardial infarction, apoptosis, and chronic heart failure, implying several options for new cardiovascular therapies for diseases, like angina pectoris, control of cardiac rhythm, ischemic injury during an acute coronary syndrome, or heart failure. However, the main issue of using full A1 receptor agonists in such indications is the broad physiologic spectrum of cardiac and extracardiac effects. Desired A1 receptor-mediated protective and regenerative cardiovascular effects might be counter-regulated by unintended side effects when considering full A1 receptor agonists. These effects can be overcome by partial A1 agonists. Partial A1 agonists can be used to trigger only some of the physiological responses of receptor activation depending on endogenous adenosine levels and on receptor reserve in different tissues. CV-Therapeutics reported the identification of a partial A1 receptor agonist CVT-3619, and recently, another partial A1 receptor agonist VCP28 was published. Both compounds are adenosine derivatives. Adenosine-like A1 receptor agonists often have the drawback of a short half-life and low bioavailability, making them not suitable for chronic oral therapy. We identified the first non-adenosine-like partial A1 receptor agonist(s) with pharmacokinetics optimal for oral once daily treatment and characterized the qualities of the partial character of the A1 receptor agonist(s) in preclinical and clinical studies