Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030552 (paresis)
 5,831 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Excitotoxicity resulting from the dysfunction of glutamate receptors has been attributed to neurodegeneration seen in many brain disorders. In our laboratory, the spastic Han Wistar mutant is currently utilized as a potential model of excitotoxicity. The mutant is characterized by progressive neuronal degeneration, hindlimb paresis and ataxia which culminates in the animal's death at approximately 65 days of age. In this study, neuroprotection derived from acute administration of the non-NMDA antagonist GYKI 52466, and chronic administration of the non-NMDA antagonist CNQX was examined in order to determine the potential roles of non-NMDA receptors in the observed neurodegeneration. Mutants injected with GYKI 52466 (15 mg/kg), twice a week for 3 weeks, exhibited increased life spans (14%) and extended motor activity than their vehicle-treated mutant siblings. In a separate group of mutants, CNQX (either 50 or 500 microM) was infused directly into the third ventricle of the mutant's brain utilizing osmotic pumps. A statistically significant increase in motor activity (22%) was detected for mutants treated with a dose of 50 microM CNQX compared to their vehicle-treated siblings. Finally, cerebellar histological evaluations of mutants treated with both 50 and 500 microM CNQX showed dose-dependent higher cerebellar Purkinje cell counts. These findings suggest that non-NMDA receptors play a significant role in neurodegeneration in this animal.
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PMID:The neuroprotective effects of non-NMDA antagonists in the cerebellum of the spastic Han Wistar mutant. 1007 5

Using a novel in vivo model for cerebral ischemia produced by short-lasting compression of a well-defined brain area of sensorimotor cortex we studied neuroprotective effects of the NMDA NR2B subunit selective antagonist, CP-101,606, in Sprague-Dawley rats. Cortical compression for 30 min produced a consistent and highly reproducible functional impairment, that is paresis of contralateral hind and fore limbs. The neurological deficit was accompanied by marked brain damage in cerebral cortex, hippocampus and thalamus as identified by Fluoro-Jade, a marker of general neuronal cell death. Using a daily performed beam walking test it was shown that untreated animals recovered from their functional impairment within 5-7 days following surgery. Intravenous administration of increasing doses (1, 5, 10, 20 mg/kg) of the NMDA NR2B subunit receptor specific antagonist, CP-101,606, dose-dependently improved the rate of functional recovery and protected against the ischemic brain damage in cerebral cortex, hippocampus, and thalamus as identified 2 days after the ischemic insult. Based upon these results, we conclude that NMDA NR2B receptor subunits represent potential targets to reduce not only the functional deficits, but also neuronal death in cortex and several midbrain regions produced by moderate, transient, cerebral ischemia.
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PMID:The NMDA NR2B subunit-selective receptor antagonist, CP-101,606, enhances the functional recovery the NMDA NR2B subunit-selective receptor and reduces brain damage after cortical compression-induced brain ischemia. 1498 68

Herpes zoster (HZ) results from recrudescence of varicella zoster virus latent since primary infection (varicella). The overall incidence of HZ is approximately 3/1000 of the population per year rising to 10/1000 per year by 80 years of age. Approximately 50% of individuals reaching 90 years of age will have had HZ. In approximately 6%, a second attack may occur (usually several decades after the first). Patients with HZ can transmit the virus to a non-immune individual causing varicella. HZ is not contracted from individuals with varicella or HZ. Reduced cell-mediated immunity to HZ occurs with ageing, explaining the increased incidence in the elderly and from other causes such as tumours, HIV and immunosuppressant drugs. Diagnosis is usually clinical from typical unilateral dermatomal pain and rash. Prodromal symptoms, pain, itching and malaise, are common. The most common complication of HZ is postherpetic neuralgia (PHN), defined as significant pain or dysaesthesia present >or= 3 months after HZ. PHN results from damage and secondary changes within components of the nervous system subserving pain. Some motor deficit is common; severe and long-lasting paresis may rarely accompany HZ. More than 5% of elderly patients have PHN at 1 year after acute HZ. Predictors of PHN are, greater age, acute pain and rash severity, prodromal pain, the presence of virus in peripheral blood as well as adverse psychosocial factors. Therapy for acute HZ is intended to reduce acute pain, hasten rash healing and reduce the risk of PHN and other complications. Antiviral drugs are close to achieving these aims but do not entirely remove risk of PHN. Oral steroids show no protective effect against PHN. Adequate analgesia during the acute phase may require strong opioid drugs. Nerve blocks and tricyclic antidepressants (TCAs) may reduce the risk of PHN although firm evidence is lacking. PHN requires thorough evaluation and development of a management strategy for each individual patient. Initial therapy is with TCAs (e.g., nortriptyline) or the anticonvulsant gabapentin. Topical lidocaine patches frequently reduce allodynia. Strong opioids are sometimes required. Topical capsaicin cream is beneficial for a small proportion of patients but is poorly tolerated. NMDA antagonists have not proved beneficial with the exception of ketamine. Transcutaneous Electrical Nerve Stimulation (TENS) may be effective in some cases. HZ is a common condition. Severe complications such as stroke, encephalitis and myelitis are relatively rare whereas sight threatening complications of ophthalmic HZ are more common. PHN is common, distressing and often intractable. Good management improves outcome.
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PMID:Management of herpes zoster (shingles) and postherpetic neuralgia. 1501 24