thiourea and Nervous-System-Diseases

P2X receptors are potential therapeutic targets for the treatment of various neurodegenerative disorders, pain, inflammation, hypertension, and cancer. Adamantane ring has been reported to exhibit significant inhibitory potential towards P2X receptors, especially for P2X7R. We have utilized uniqueness of adamantane moiety in our synthesized compounds and introduced various substitutions that enhanced the potency as well as selectivity for P2XR subtypes. Among synthesized derivatives, 4n and 5b were found to be most potent and selective inhibitors for h-P2X4R and h-P2X7R, respectively. 4n was found to be highly selective for h-P2X4R with IC

Topics: Adamantane; Humans; Inflammation; Nervous System Diseases; Purinergic P2X Receptor Antagonists; Receptors, Purinergic P2X7; Thiourea

It has been well established that 2,4-dithiobiuret (DTB) intoxication in rats produces a rapidly progressive hindlimb paralysis within days. The cause of this has, until recently, been explained on the basis of a physiological abnormality that involves a prejunctional impairment in the neuromuscular transmission alone. The morphological correlate of the electrophysiological abnormalities has now been provided. This study describes the sequential morphological alterations resulting from a chronic long-term DTB intoxication (1 mg/kg per day, IP) in the rat nervous system up to 48 days. The findings indicate that DTB neurotoxicity evolves as a central peripheral distal axonopathy initially affecting the motor nerve terminals which show accumulation of interconnecting branched tubulovesicular profiles. With continued exposure, nerve terminal swelling and degeneration took place. Similar pathological changes in distal axons were observed progressively involving the small intramuscular nerve bundles close to the nerve terminals. Central nervous system axons in the long descending tracts of spinal cord and the cerebellar vermis showed similar changes but to a lesser extent in later stage of intoxication.

Topics: Animals; Axons; Male; Motor Neurons; Muscles; Nerve Degeneration; Nerve Endings; Nervous System Diseases; Peroneal Nerve; Rats; Rats, Inbred Strains; Sciatic Nerve; Thiourea

The contribution of toxic O2 metabolites to cerebral ischemia reperfusion injury has not been determined. We found that gerbils subjected to temporary unilateral carotid artery occlusion (ischemia) consistently developed neurologic deficits during ischemia with severities that correlated with increasing degrees of brain edema and brain H2O2 levels after reperfusion. In contrast, gerbils treated just before reperfusion (after ischemia) with dimethylthiourea (DMTU), but not urea, had decreased brain edema and brain H2O2 levels. In addition, gerbils fed a tungsten-rich diet for 4, 5, or 6 wk developed progressive decreases in brain xanthine oxidase (XO) and brain XO + xanthine dehydrogenase (XD) activities, brain edema, and brain H2O2 levels after temporary unilateral carotid artery occlusion and reperfusion. In contrast to tungsten-treated gerbils, allopurinol-treated gerbils did not have statistically significant decreases in brain XO or XO + XD levels, and reduced brain edema and brain H2O2 levels occurred only in gerbils developing mild but not severe neurologic deficits during ischemia. Finally, gerbils treated with DMTU or tungsten all survived, while greater than 60% of gerbils treated with urea, allopurinol, or saline died by 48 h after temporary unilateral carotid artery occlusion and reperfusion. Our findings indicate that H2O2 from XO contributes to reperfusion-induced edema in brains subjected to temporary ischemia.

Topics: Allopurinol; Animals; Brain; Brain Chemistry; Brain Edema; Brain Ischemia; Female; Gerbillinae; Hydrogen Peroxide; Male; Nervous System Diseases; Thiourea; Tungsten; Urea; Xanthine Oxidase

Topics: Adolescent; Adult; Antithyroid Agents; Blood Cell Count; Diagnosis, Differential; Diagnostic Errors; Female; Goiter; Heart Auscultation; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methylthiouracil; Myxedema; Nervous System Diseases; Neurotic Disorders; Propylthiouracil; Radioisotope Dilution Technique; Thiazoles; Thiouracil; Thiourea; Thyrotropin