Subject(s)
Anti-HIV Agents/chemical synthesis , Drug Design , Foscarnet/analogs & derivatives , Foscarnet/chemistry , Prodrugs/chemical synthesis , Acquired Immunodeficiency Syndrome/drug therapy , Anti-HIV Agents/chemistry , Anti-HIV Agents/therapeutic use , Cytomegalovirus Infections/drug therapy , Humans , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Conformation , Prodrugs/chemistry , Prodrugs/therapeutic useABSTRACT
[formula: see text] Aminocyclodextrins (ACDs), perfunctionalized at the 6-position with amino groups, bind phosphonoformate (PFA) diesters and accelerate acyl transfer reactions with high efficiency at neutral pH. Aminolysis and esterolysis are accelerated and hydrolysis of PFA diesters is catalyzed by ACDs. PFA diesters have significant antiviral activity. The rapid reactions observed with ACDs show that biological nucleophiles may undergo facile covalent modification by PFA esters at physiological pH, which has significant implications for prodrug and drug design strategies.
Subject(s)
Cyclodextrins/metabolism , Drug Design , Catalysis , Cyclodextrins/chemistry , Esters , Foscarnet/chemistry , Kinetics , Models, Chemical , Molecular MimicrySubject(s)
Ethics, Medical , Legislation, Hospital , Australia , Canada , Humans , Medical Laboratory Science , Professional Staff Committees , United StatesABSTRACT
Orthopaedic specialists and family physicians practicing in skiing communities are faced with unavoidable, stringent, and expanding legal responsibilities to properly manage ski trauma. Their legal obligations apply to each component of clinical case management: (1) diagnosis; (2) treatment; and (3) rehabilitation. Neither medically nor legally is any one aspect less critical than another. Concomitant with accelerating rates of participation in sports. It is clear that the law is demanding more from specialists and also primary care physicians whose practice is increasingly involving musculoskeletal athletic injuries. The legal responsibilities and liabilities of both generalists and specialists are extensively reviewed in this report. The principles apply to the management of all athletic trauma by physicians.
