ABSTRACT
The onset of diabetic neuropathy, a complication of diabetes mellitus, has been linked to poor glycemic control. We tested the hypothesis that the mitogen-activated protein kinases (MAPK) form transducers for the damaging effects of high glucose. In cultures of adult rat sensory neurons, high glucose activated JNK and p38 MAPK but did not result in cell damage. However, oxidative stress activated ERK and p38 MAPKs and resulted in cellular damage. In the dorsal root ganglia of streptozotocin-induced diabetic rats (a model of type I diabetes), ERK and p38 were activated at 8 wk duration, followed by activation of JNK at 12 wk duration. We report activation of JNK and increases in total levels of p38 and JNK in sural nerve of type I and II diabetic patients. These data implicate MAPKs in the etiology of diabetic neuropathy both via direct effects of glucose and via glucose-induced oxidative stress.
Subject(s)
Diabetic Neuropathies/etiology , JNK Mitogen-Activated Protein Kinases , Mitogen-Activated Protein Kinases/physiology , Animals , Butadienes/pharmacology , Cell Survival/drug effects , Cells, Cultured , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Type 1/enzymology , Diabetes Mellitus, Type 2/enzymology , Diabetic Neuropathies/enzymology , Dose-Response Relationship, Drug , Enzyme Activation/drug effects , Enzyme Inhibitors/pharmacology , Ganglia, Spinal/cytology , Ganglia, Spinal/drug effects , Ganglia, Spinal/enzymology , Glucose/pharmacology , Humans , Hydrogen Peroxide/pharmacology , Imidazoles/pharmacology , MAP Kinase Kinase 4 , Male , Mitogen-Activated Protein Kinase Kinases/metabolism , Mitogen-Activated Protein Kinases/antagonists & inhibitors , Mitogen-Activated Protein Kinases/metabolism , Neurons, Afferent/drug effects , Neurons, Afferent/enzymology , Nitriles/pharmacology , Pyridines/pharmacology , Rats , Rats, Wistar , Sural Nerve/enzymology , p38 Mitogen-Activated Protein KinasesABSTRACT
The essential oil from the leaves and stems of Tetradenia riparia was analysed by GC and GC/MS and 35 components were identified. The main constituents were alpha-terpineol (22.6%), fenchone (13.6%), beta-fenchyl alcohol (10.7%), beta-caryophyllene (7.9%), and perillyl alcohol (6.0%). Moderate antimalarial activities were recorded against two strains of Plasmodium falciparum.
Subject(s)
Antimalarials/chemistry , Antimalarials/toxicity , Oils, Volatile/chemistry , Oils, Volatile/toxicity , Plants, Medicinal , Animals , Chloroquine/toxicity , Gas Chromatography-Mass Spectrometry , Plant Leaves , Plant Stems , Plasmodium falciparum/drug effects , South AfricaABSTRACT
The Care Windows development project demonstrated the feasibility of an approach designed to add the benefits of an event-driven, graphically-oriented user interface to an existing Medical Information Management System (MIMS) without overstepping economic and logistic constraints. The design solution selected for the Care Windows project incorporates three important design features: (1) the effective de-coupling of severs from requesters, permitting the use of an extensive pre-existing library of MIMS servers, (2) the off-loading of program control functions of the requesters to the workstation processor, reducing the load per transaction on central resources and permitting the use of object-oriented development environments available for microcomputers, (3) the selection of a low end, GUI-capable workstation consisting of a PC-compatible personal computer running Microsoft Windows 3.0, and (4) the development of a highly layered, modular workstation application, permitting the development of interchangeable modules to insure portability and adaptability.
Subject(s)
Management Information Systems , User-Computer Interface , Academic Medical Centers , Computer Systems , Medical Records Systems, Computerized , Michigan , Microcomputers , Software DesignABSTRACT
The demonstration of MIMS/CareWindows will include: (1) a review of the application environment and development history, (2) a demonstration of a very large, comprehensive clinical information system with a cost effective graphic user server and communications interface.