ABSTRACT
BACKGROUND: Enterovirus 71 (EV71) infections are associated with a high prevalence of hand, foot and mouth disease (HFMD) in children and occasionally cause lethal complications. Most infections are self-limiting. However, resulting complications, including aseptic meningitis, encephalitis, poliomyelitis-like acute flaccid paralysis, and neurological pulmonary edema or hemorrhage, are responsible for the lethal symptoms of EV71 infection, the pathogenesis of which remain to be clarified. RESULTS: In the present study, 2-week-old Institute of Cancer Research (ICR) mice were infected with a mouse-adapted EV71 strain. These infected mice demonstrated progressive paralysis and died within 12 days post infection (d.p.i.). EV71, which mainly replicates in skeletal muscle tissues, caused severe necrotizing myositis. Lesions in the central nervous system (CNS) and other tissues were not observed. CONCLUSIONS: Necrotizing myositis of respiratory-related muscles caused severe restrictive hypoventilation and subsequent hypoxia, which could explain the fatality of EV71-infected mice. This finding suggests that, in addition to CNS injury, necrotic myositis may also be responsible for the paralysis and death observed in EV71-infected mice.
Subject(s)
Enterovirus A, Human/physiology , Enterovirus Infections/pathology , Host-Pathogen Interactions , Hypoventilation , Myositis/pathology , Myositis/virology , Animals , Death , Disease Models, Animal , Enterovirus Infections/complications , Enterovirus Infections/virology , Hypoxia , Mice, Inbred ICR , Myositis/complications , ParalysisABSTRACT
A series novel of N-(2-hydroxyethyl)amide derivatives was synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test, and their neurotoxicity was evaluated by the rotarod test (Tox). The maximal electroshock test showed that N-(2-hydroxyethyl)decanamide 1g, N-(2-hydroxyethyl)palmitamide 1l, and N-(2-hydroxyeth-yl)stearamide 1n were found to show a better anticonvulsant activity and also had lower toxicity than the marked anti-epileptic drug valproate. In the anti-MES potency test, these compounds exhibited median effective doses (ED50) of 22.0, 23.3, 20.5 mg/kg, respectively, and median toxicity doses (TD50) of 599.8, >1000, >1000 mg/kg, respectively, resulting in a protective index (PI) of 27.5, >42.9, >48.8, respectively. This is a much better protective index than that of the marked anti-epileptic drug valproate (PI = 1.6). To further investigate the effects of the anticonvulsant activity in several different models, compounds 1g, 1l, and 1n were tested having evoked convulsions with chemical substances, including pentylenetetrazloe, isoniazide, 3-mercaptopropionic acid, bicuculline, thiosemicarbazide, and strychnine.
Subject(s)
Amides/chemical synthesis , Anticonvulsants/chemical synthesis , Amides/pharmacology , Amides/toxicity , Animals , Anticonvulsants/chemistry , Anticonvulsants/pharmacology , Anticonvulsants/toxicity , Disease Models, Animal , Drug Evaluation, Preclinical , Mice , Neurotoxicity Syndromes/etiology , Seizures/drug therapy , Seizures/etiology , Structure-Activity RelationshipABSTRACT
In order to explore the educational model of combined research aidding basic medical education and clinical practice, the educational form of combined research, teaching and clinical practice was adopted and brought into the education of medical genetics for medical students. The consequence of five-year educational practice has revealed that the educational effects and quality have been obviously increased, and the deeply activated studying initiative, self-studying ability, ability of cooperation, discovering and creative ability have been achieved in culturing practical general medical students with in-depth basic knowledge, great ability and high quality.
