Search

This article addresses an apparent paradox found in Pali Buddhist literature: while the "uncompounded" (asaṅkhata) is valued over and above what is "compounded" (saṅkhata), the texts also encourage careful attention to relative (or, physical) health. The mind is the laboratory and the object of a thorough work meant to lead to final liberation from mental affliction and from the cycle of existence, whereas the body is perceived as impure, limited, and intrinsically unsatisfactory. Nonetheless, a disciple of the Buddha is supposed to take care of his/her own and others' physical wellbeing, and monastic equipment includes a set of medicines. "Ultimate health" is the final goal, but conventional healthcare supports the path to nibbāna and represents a value per se. The present article will explore the intricate connection between these two dimensions.

Adenosine represents a powerful modulating factor, which has been shown to orchestrate the scope, duration, and remission of the inflammatory response through the activation of four specific receptors, classified as A 1 , A 2A , A 2B , and A 3 , all being widely expressed in a variety of immune cells. Several selective A 2A receptor agonists have displayed anti-inflammatory effects, through the suppression of IL-12, TNF, and IFN-γ production by monocytes and lymphocytes, in the setting of chronic intestinal inflammation. However, the therapeutic application of A 2A receptor agonists remains hindered by the risk of serious cardiovascular adverse effects arising from the wide systemic distribution of A 2A receptors. The present study focused on evaluating the anti-inflammatory effects of the novel poorly absorbed A 2A receptor agonist PSB-0777 in a rat model of oxazolone-induced colitis as well as to evaluate its cardiovascular adverse effects, paying particular attention to the onset of hypotension, one of the main adverse effects associated with the systemic pharmacological activation of A 2A receptors. Colitis was associated with decreased body weight, an enhanced microscopic damage score and increased levels of colonic myeloperoxidase (MPO). PSB-0777, but not dexamethasone, improved body weight. PSB-0777 and dexamethasone ameliorated microscopic indexes of inflammation and reduced MPO levels. The beneficial effects of PSB-0777 on inflammatory parameters were prevented by the pharmacological blockade of A 2A receptors. No adverse cardiovascular events were observed upon PSB-0777 administration. The novel A 2A receptor agonist PSB-0777 could represent the base for the development of innovative pharmacological entities able to act in an event-specific and site-specific manner.

The pharmacokinetics of Factor VIII was evaluated by mathematical modeling in a large-scale study in 62 haemophilia-A subjects, in whom 137 plasma Factor VIII-time curves were measured during single dose (n = 87) and repeated-dose (n = 47) treatments for prophylaxis or minor bleeding episodes. The pharmacokinetic parameters [mean (SD)] estimated from single-dose curves were: clearance 3.85 ml.h-1.kg-1, volume of distribution 58.2 ml.kg-1, mean residence time 15.9 h. Parameters calculated from repeated-dose curves were: clearance 3.93 ml.h-1.kg-1, volume of distribution 61.8 ml.kg-1, and half-life 12.2 h. In patients with mild haemophilia, pharmaco-statistical analysis revealed that the endogenous synthesis of Factor VIII was constant and was not influenced by the administration of exogenous Factor VIII. The coefficient of variation for intra-individual variability of Factor VIII kinetics (estimated according to the Standard Two-Stage method) was 20.7% in single-dose curves and 23.2% in repeated-dose curves.