ABSTRACT
The synthesis of a series of d-gluco-like configured 4,5,6-trihydroxyazepanes bearing a triazole, a sulfonamide or a fluorinated acetamide moiety at C-3 is described. These synthetic derivatives have been tested for their ability to selectively inhibit the muropeptide recycling glucosaminidase NagZ and to thereby increase sensitivity of Pseudomonas aeruginosa to ß-lactams, a pathway with substantial therapeutic potential. While introduction of triazole and sulfamide groups failed to lead to glucosaminidase inhibitors, the NHCOCF3 analog proved to be a selective inhibitor of NagZ over other glucosaminidases including human O-GlcNAcase and lysosomal hexosaminidases HexA and B.
Subject(s)
Anti-Bacterial Agents/pharmacology , Azepines/chemistry , Azepines/pharmacology , Glycoside Hydrolases/antagonists & inhibitors , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/enzymology , beta-Lactams/pharmacology , Azepines/chemical synthesis , Azepines/metabolism , Ceftazidime/pharmacology , Drug Synergism , Glycoside Hydrolases/chemistry , Glycoside Hydrolases/metabolism , Hydroxylation , Molecular Docking Simulation , Protein ConformationSubject(s)
Maxillary Diseases/pathology , Maxillary Neoplasms/pathology , Odontogenic Cyst, Calcifying/pathology , Periapical Periodontitis/pathology , Radicular Cyst/pathology , Adult , Chronic Disease , Diagnosis, Differential , Humans , Incisor/pathology , Male , Maxillary Diseases/complications , Maxillary Neoplasms/complications , Odontogenic Cyst, Calcifying/complications , Periapical Periodontitis/complications , Radicular Cyst/complications , Tooth Root/pathologyABSTRACT
The system described here provides a simple method of delivering anesthetic vapor to the fruit-fly Drosophila melanogaster. This system delivers known concentrations of volatile anesthetic vapor obtained from liquid anesthetics in a continuous gas stream of pure humidified air. It controls for evaporation, and absorption of volatile agents, whilst allowing for extracellular electrophysiological recordings. Recordings were made from the fly's escape muscles, the jump tergotrochanter muscle (TTM) and the flight dorsal longitudinal muscle (DLM). The system minimizes the quantity of anesthetic used, making the use of more expensive and more conventional anesthetics cost effective and practicable. It also permits monitoring the fly's movements during anesthesia.
Subject(s)
Anesthesia, General/instrumentation , Anesthetics, General/administration & dosage , Drosophila melanogaster/physiology , Halothane/pharmacology , Absorption , Anesthesia, General/methods , Animals , Electrophysiology/instrumentation , Electrophysiology/methods , Muscles/drug effects , Muscles/physiology , Reaction TimeABSTRACT
A formal course in Human Ecology in the Himalayas proved to be a powerful educational innovation partly because of its international setting. The six students in the medical part of this course experienced a profound affective impact on their career goals, a totally new orientation toward the problems of poverty in the United States, and a changed appreciation of the need for preventive measures and a community approach. The effect was far greater than that usually associated with individualized international experiences because of careful preparatory seminars, group activities which included surveys and research, and abundant opportunity for interpretive discussions as cultural and health care shock was being experienced. Clinical work was kept in perspective and provided opportunities for learning, not only about exotic diseases but also about what could be done under the simplest of conditions.
