Influence of propranolol, enalaprilat, verapamil, and caffeine on adenosine A2A-receptor–mediated coronary vasodilation

AbstractObjectivesThe study was done to determine the effects of propranolol, enalaprilat, verapamil, and caffeine on the vasodilatory properties of the adenosine A2A-receptor agonist ATL-146e (ATL).BackgroundATL is a new adenosine A2A-receptor agonist proposed as a vasodilator for myocardial stress perfusion imaging. Beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium blockers are commonly used for the treatment of coronary artery disease (CAD), and their effect on ATL-mediated vasodilation is unknown. Dietary intake of caffeine is also common.MethodsIn 19 anesthetized, open-chest dogs, hemodynamic responses to bolus injections of ATL (1.0 μg/kg) and adenosine (60 μg/kg) were recorded before and after administration of propranolol (1.0 mg/kg, ATL only), enalaprilat (0.3 mg/kg, ATL only), caffeine (5.0 mg/kg, ATL only), and verapamil (0.2 mg/kg bolus, ATL and adenosine).ResultsNeither propranolol nor enalaprilat attenuated the ATL-mediated vasodilation (225 ± 86% and 237 ± 67% increase, respectively, p = NS vs. control). Caffeine had an inhibitory effect (97 ± 28% increase, p < 0.05 vs. control). Verapamil blunted both ATL- and adenosine-induced vasodilation (63 ± 20% and 35 ± 7%, respectively, p < 0.05 vs. baseline), and also inhibited the vasodilation induced by the adenosine triphosphate-sensitive potassium (KATP) channel activator pinacidil.ConclusionsBeta-blockers and ACE inhibitors do not reduce the maximal coronary flow response to adenosine A2A-agonists, whereas verapamil attenuated this vasodilation through inhibition of KATPchannels. The inhibitory effect of verapamil and KATPchannel inhibitors like glybenclamide on pharmacologic stress using adenosine or adenosine A2A-receptor agonists should be evaluated in the clinical setting to determine their potential for reducing the sensitivity of CAD detection with perfusion imaging

A longitudinal investigation of psychological morbidity in patients with ovarian cancer

Ovarian cancer patients may experience psychological disorders due to the aggressive nature of the illness and treatment. We investigated the presence of psychological disorders longitudinally in women with a new diagnosis of ovarian cancer and the factors that predicted development and maintenance of these disorders. Patients were assessed in a prospective longitudinal study at the beginning of chemotherapy treatment, mid-treatment, end of treatment and 3 months follow-up for depression, anxiety, perceived social support, neuroticism and cognitive strategies to control unwanted thoughts. A total of 121 patients were recruited and 85 patients were assessed at all four time points. Three different longitudinal profiles of anxiety and depression caseness were found: non-cases (never cases), occasional cases (cases on at least one but not all four occasions) and stable cases (cases on all four occasions). Most of the women were occasional cases of anxiety (52%, 44), whereas for depression, the majority of women were non-cases (55%, 47). A subset of patients were stable cases of anxiety (22%, 19). Neuroticism and marital status were significant independent predictors of anxiety caseness profile. Neuroticism and use of anti-depressants were independent predictors of depression caseness profile. Social support was not related to psychological morbidity

Effects of adenosine A2A receptor activation and alanyl-glutamine in Clostridium difficile toxin-induced ileitis in rabbits and cecitis in mice

<p>Abstract</p> <p>Background</p> <p>Severe <it>Clostridium difficile </it>toxin-induced enteritis is characterized by exuberant intestinal tissue inflammation, epithelial disruption and diarrhea. Adenosine, through its action on the adenosine A_2Areceptor, prevents neutrophillic adhesion and oxidative burst and inhibits inflammatory cytokine production. Alanyl-glutamine enhances intestinal mucosal repair and decreases apoptosis of enterocytes. This study investigates the protection from enteritis by combination therapy with ATL 370, an adenosine A_2Areceptor agonist, and alanyl-glutamine in a rabbit and murine intestinal loop models of <it>C. difficile </it>toxin A-induced epithelial injury.</p> <p>Methods</p> <p>Toxin A with or without alanyl-glutamine was administered intraluminally to rabbit ileal or murine cecal loops. Animals were also given either PBS or ATL 370 parenterally. Ileal tissues were examined for secretion, histopathology, apoptosis, Cxcl1/KC and IL-10.</p> <p>Results</p> <p>ATL 370 decreased ileal secretion and histopathologic changes in loops treated with Toxin A. These effects were reversed by the A_2Areceptor antagonist, SCH 58261, in a dose-dependent manner. The combination of ATL 370 and alanyl-glutamine significantly further decreased ileal secretion, mucosal injury and apoptosis more than loops treated with either drug alone. ATL 370 and alanyl-glutamine also decreased intestinal tissue KC and IL-10.</p> <p>Conclusions</p> <p>Combination therapy with an adenosine A_2Areceptor agonist and alanyl-glutamine is effective in reversing <it>C. difficile </it>toxin A-induced epithelial injury, inflammation, secretion and apoptosis in animals and has therapeutic potential for the management of <it>C. difficile </it>infection.</p