ABSTRACT
A number of guidelines and directives have reinforced the need for a more formalised approach to Independent Ethic Committees (IECs) and support the need to audit IECs. The key elements of an audit of an IEC are reviewed within the context of the European Guidelines for Auditing Independent Ethics Committees published by the European Forum for Good Clinical Practice (EFGCP). Auditing requirements in these recent guidelines and the EU Clinical Trial Directive are discussed as well as the methodology and type of documentation and SOPs that should be present at an audit. It is argued that both inspectorates and independent auditors need to conduct such audits to improve the overall global standard.
Subject(s)
Benchmarking , Ethics Committees, Research/standards , Guidelines as Topic , Management Audit , Clinical Trials as Topic/standards , Documentation , European Union , HumansABSTRACT
The preparation of indium-111 tropolonate-radiolabeled guinea pig peripheral mixed white cells (greater than 80% neutrophils) is described. Autologous rather than homologous cells are required to provide a population of labeled, functional cells on reintroduction to the animals. Surgery has been shown to result in a profound neutropenia from which the animals must recover before removal of blood for cell preparation. The response of radiolabeled cells parallels that of the unlabeled cell population to a chemotaxin, leukotriene B4. This material causes a profound neutropenia of rapid onset accompanied by a parallel fall in blood radioactivity. The fall in circulating radiolabel is accompanied by an increase in radioactivity in the thoracic region. These changes have been monitored externally using an automated isotope monitoring system.
Subject(s)
Indium Radioisotopes , Leukocytes/drug effects , Leukotriene B4/pharmacology , Animals , Cell Separation , Dose-Response Relationship, Drug , Guinea Pigs , Leukocyte Count , Male , Surgical Procedures, Operative , Thorax/cytology , TropoloneABSTRACT
The synthesis and biological properties of 85 benzophenones and related compounds are described. The majority of the compounds inhibit the release of leukotrienes (LT) C4 and D4 in vitro from sensitized guinea pig chopped lung. In addition, some of the compounds inhibited the release of LTs from passively sensitized human chopped lung and protected guinea pigs from the effects of anaphylaxis in a modified Herxheimer test.
Subject(s)
Anaphylaxis/prevention & control , Benzophenones/pharmacology , Anaphylaxis/metabolism , Animals , Benzophenones/chemical synthesis , Benzophenones/therapeutic use , Chemical Phenomena , Chemistry , Guinea Pigs , Humans , Lung/drug effects , Lung/metabolism , Male , SRS-A/metabolism , Structure-Activity RelationshipSubject(s)
Muscle Contraction/drug effects , Muscle, Smooth/physiology , SRS-A/pharmacology , Animals , Arachidonic Acids/pharmacology , Dose-Response Relationship, Drug , Guinea Pigs , Ileum/physiology , Isomerism , Leukotriene B4 , Muscle, Smooth/drug effects , SRS-A/chemical synthesis , Structure-Activity Relationship , Trachea/physiologyABSTRACT
Benoxaprofen [2-(4-chlorophenyl)-alpha-methyl-5-benzoxazole acetic acid], a novel anti-inflammatory compound, is also an orally-active anti-allergic compound in animals. It reduced the anaphylactic release of mediators, particularly slow-reacting substance of anaphylaxis (SRS-A), from both in vitro and in vivo animal models. Benoxaprofen marginally antagonized the activity of histamine on the guinea pig ileum, but not of SRS-A, at concentrations which inhibited the release of SRS-A.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Benzoxazoles/pharmacology , Lipoxygenase Inhibitors , Propionates/pharmacology , Anaphylaxis/immunology , Anaphylaxis/metabolism , Animals , Anti-Inflammatory Agents/therapeutic use , Benzoxazoles/therapeutic use , Bronchial Spasm/drug therapy , Dose-Response Relationship, Immunologic , Guinea Pigs , Histamine Antagonists/pharmacology , Histamine Release/drug effects , Humans , Lung/metabolism , Phosphodiesterase Inhibitors/pharmacology , Propionates/therapeutic use , Rats , Rats, Inbred Strains , SRS-A/antagonists & inhibitors , SRS-A/metabolismABSTRACT
1. Isamoxole [2-methyl-N-butyl-N(4-methyloxazol-2-yl) propanamide] is an effective orally active anti-allergic compound in animals. 2. Isamoxole inhibits the immunological release of mediators, notably slow-reacting substance of anaphylaxis (SRS-A) from sensitized human and guinea-pig chopped lung in vitro. 3. In vivo, allergic responses were inhibited in guinea-pigs and rats by doses as low as 25 mg/kg given orally 180 and 30 min before challenge. The effect of Isamoxole was still present 4 h after a single dose of 100 mg/kg orally in the guinea-pig and 3 h in the rat. 4. Isamoxole is a moderately potent, selective inhibitor of SRS-A activity on the guinea-pig ileum in vitro, at concentrations that do not antagonize histamine, 5-hydroxytryptamine, or bradykinin. 5. Isamoxole causes human bronchial muscle to relax and antagonizes the bronchoconstriction induced by SRS-A.
Subject(s)
Hypersensitivity/drug therapy , Oxazoles/pharmacology , Animals , Bronchial Spasm/prevention & control , Bronchodilator Agents , Cyclooxygenase Inhibitors , Guinea Pigs , Humans , In Vitro Techniques , Lung/metabolism , Male , Passive Cutaneous Anaphylaxis/drug effects , Phosphodiesterase Inhibitors , Rats , SRS-A/metabolismABSTRACT
The synthesis and biological properties of 35 2-(acylamino)oxazoles are described. The majority of the compounds inhibit the release of slow-reacting substance of anaphylaxis (SRS-A) in vitro from sensitized guinea pig chopped lung. In addition, several of the compounds inhibited the release of SRS-A from passively sensitized human chopped lung and protected guinea pigs from the effects of anaphylaxis in a modified Herxheimer test.
