Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anxiolytic agents disinhibit suppressed behaviors in rodents in preclinical models of anxiety such as the non-conditioned social interaction and elevated plus maze assays and the conditioned conflict Cook and Davidson procedure. The (+) and (-) enantiomers of (+/-)-3-amino-1-hydroxy-2-pyrrolidinone (HA-966) have been resolved and revealed that R-(+)-HA-966 significantly disinhibits both non-conditioned and conditioned suppressed behavior similar to the benzodiazepine diazepam, while the S-(-) enantiomer was devoid of anxiolytic activity and only produced behavioral sedation. Furthermore, R-(+)-HA-966 lacked side-effects in rodents commonly associated with the administration of benzodiazepines such as motor incoordination and ataxia, significant interactions with ethanol, and amnesia. These data suggest that R-(+)-HA-966, an antagonist at the strychnine-insensitive glycine/NMDA receptor site, was anxioselective and lacked some of the side-effects associated with benzodiazepine anxiolytics.
 ...
PMID:Stereoselective R-(+) enantiomer of HA-966 displays anxiolytic effects in rodents. 135 34

The serine/cysteine hydrolase inhibitor phenylmethylsulfonyl fluoride (PMSF) markedly intensifies the clinical expression of organophosphorus-induced delayed neurotoxicity (OPIDN) in adult chickens when administered after organophosphate exposure. In this study, we have examined the ability of PMSF post-treatment to affect sensitivity to OPIDN in developing animals at ages normally showing resistance. Chickens (35, 49 or 70 days of age) were treated with diisopropylphosphorofluoridate (DFP, 2 mg/kg, sc) and then treated four hours later with PMSF (90 mg/kg, sc) or vehicle only and examined for clinical signs of ataxia and incoordination. Chickens treated with DFP alone showed a marked age-related increase in the severity of motor deficits. Birds treated with DFP followed by PMSF showed more extensive clinical deficits relative to those treated with DFP only, but relatively similar degrees of motor dysfunction among the age groups. Cervical spinal cord samples processed by the Fink-Heimer degeneration method indicated that PMSF post-treatment induced more extensive axonal degeneration in all age groups relative to treatment with DFP only. As the DFP treatment alone caused greater than or equal to 90% inhibition of neurotoxic esterase activity (NTE, the putative molecular target site for OPIDN), interaction with NTE by PMSF does not appear to be involved in potentiation. We hypothesize that PMSF potentiates OPIDN through impairment of a physiological process which normally imparts resistance to young animals and which regresses during development.
 ...
PMID:Phenylmethylsulfonyl fluoride alters sensitivity to organophosphorus-induced delayed neurotoxicity in developing animals. 143 55

We investigated motor function and pain sensation in the gracile axonal dystrophy (GAD) mutant mouse, using the tail-flick test and the rotarod test. GAD (gad/gad) and normal sib mice (gad/+ or +/+) were used between 5 and 11 weeks of age, during which time the behavioral signs of GAD mice shifted from sensory ataxia (about 4 to 8 weeks of age) to paresis (after about 9 weeks of age). In the tail-flick test, significant shortening of latency was observed at 6 and 8 weeks of age in female GAD mice, in comparison with normal female mice. This may be related to dysfunction or degeneration of axons in the fasiculus gracilis, whose collaterals are thought to control the transmission of nociceptive information. In the rotarod test, a cumulative chi 2 test showed significant reduction in the performance times of GAD mice beginning at 5 and 6 weeks of age in males and females, respectively, indicating that the rotarod test can detect the development of motor incoordination as early as these ages. The performance times of GAD mice dropped sharply from 9 weeks of age onwards, and this is believed to reflect the progression of paresis. The rotarod test therefore appears to be a good method of quantifying behavioral changes in GAD mice and to be applicable both to objective selection of GAD mice before 8 weeks of age and to evaluation of drugs to treat ataxia or paresis.
 ...
PMID:Behavioral study on the gracile axonal dystrophy (GAD) mutant mouse. 145 62

Involvement of the central nervous system (CNS) is common in patients with advanced disease due to human immunodeficiency virus (HIV). Symptoms range from lethargy and apathy to coma, incoordination and ataxia to hemiparesis, loss of memory to severe dementia, and focal to major motor seizures. Involvement may be closely associated with HIV infection per se, as in the AIDS dementia complex, but is frequently caused by opportunistic pathogens such as Toxoplasma gondii and Cryptococcus neoformans or malignancies such as primary lymphoma of the CNS. The clinical presentations of attendant and direct CNS involvement are remarkably non-specific and overlapping, yet a correct diagnosis is critical to successful intervention. Toxoplasmic encephalitis is one of the most common and most treatable causes of AIDS-associated pathology of the CNS. A great deal has been learned in the last 10 years about its unique presentation in the HIV-infected patient with advanced disease. Drs. Benjamin J. Luft of the State University of New York at Stony Brook and Jack S. Remington of the Stanford University School of Medicine and Palo Alto Medical Foundation's Research Institute have studied T. gondii for many years and are two of the leading experts in the field. This commentary comprises an update of their initial review (J Infect Dis 1988;157:1-6) and a presentation of the current approaches to diagnosing and managing toxoplasmic encephalitis in HIV-infected patients.
 ...
PMID:Toxoplasmic encephalitis in AIDS. 152 Jul 57

The literature contains about 500 cases of equine leucosis, though the reports are deposited in a great number of journals and vary considerably concerning particular topics. During the last years there has been a remarkable increase of publications about this syndrome in the equine. The clinical leucosis key recommended by us has been confirmed in principle considering the latest literature. In about 70 individual symptoms which can be clinically observed in equine with leucosis 11 can be considered as main symptoms because of their frequency; they are again classified in primary (lymph node tumours including splenomegaly--loss of condition, weakness--cachexia, weight loss, periphery oedema), secondary (anorexia, inappetence--fever--paleness of mucous membrane--anaemia--tachycardia) and accessory (incoordination--tachypnoea, dyspnoea--apathy, lethargy) main symptoms. Furthermore in future it will be necessary to take into more consideration the symptoms "recurrent colic" and "hydrothorax" within differential diagnosis. The main symptom "incoordination" (ataxia, asynergy, paresis, paralysis) is used by us more precisely only in case of impairment of nervous system by neoplastic infiltrations and does not signify as possible symptoms of general physical weakness, for example faltering, staggering, tumbling or lameness. The morphological classification follows further on our previous recommendation. There exist generalized forms with tumour infiltrations in abdominal and in thoracic cavity as well as especially in peripheral lymph nodes. On the other hand there are characteristic manifestations in certain regions of the body, which establish distinctly the clinical symptomatology. They are marked as regional multicentric forms with the main localizations "mediastinal", "splenic", "mesenteric" or "intestinal".(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Clinical diagnostic keys and special manifestations in equine leukosis]. 195 30

Three piperidine alkaloid containing plants, Conium maculatum (poison-hemlock), Nicotiana glauca (tree tobacco) and Lupinus formosus (lunara lupine), induced multiple congenital contractures (MCC) and palatoschisis in goat kids when their dams were gavaged with the plant during gestation days 30-60. The skeletal abnormalities included fixed extension or flexure of the carpal, tarsal, and fetlock joints, scoliosis, lordosis, torticollis and rib cage abnormalities. Clinical signs of toxicity included those reported in sheep, cattle and pigs--ataxia, incoordination, muscular weakness, prostration and death. One quinolizidine alkaloid containing plant, Lupinus caudatus (tailcup lupine), on the other hand, which is also known to cause MCC in cows, caused only slight signs of toxicity in pregnant goats and no teratogenic effects in their offspring.
 ...
PMID:Congenital skeletal malformations and cleft palate induced in goats by ingestion of Lupinus, Conium and Nicotiana species. 208 36

The clinical signs and gross lesions caused by Eimeria uzura (10(5) oocysts) in Japanese quail (Coturnix coturnix japonica) exhibited little or no influence in the face of intercurrent dietary aflatoxicosis (1 p.p.m. of aflatoxin B1 from Day 0 to 55). Similarly, no significant differences in the mucosal morphology of the intestine were evident histologically between the two groups of Japanese quail. The nervous signs of ataxia, leg weakness, incoordination of movement, torticollis and terminal opisthotonos were toxin-induced manifestations. In the aflatoxic quail, hypoplastic changes and selective depletion of lymphocytes were more prominent in the bursa of fabricius. Increased relative mean weights of liver, kidney, spleen, crop, proventriculus and gizzard were observed in birds due to aflatoxin sensitivity. The combination of E. uzura infection and aflatoxicosis in Japanese quail may cause significant weight loss, and increased oocyst production and reproductive potential.
 ...
PMID:Interaction between Eimeria uzura infection and aflatoxicosis in Japanese quail (Coturnix coturnix japonica). 211 99

Benzodiazepines are widely prescribed anxiolytics and anticonvulsants which bind with high affinity to sites on the GABAA receptor/Cl- channel complex and potentiate the effect of the neurotransmitter GABA (gamma-aminobutyric acid). The heterogeneity of benzodiazepine recognition sites in the central nervous system was revealed by studies showing different classes of GABAA receptor subunits (classes alpha, beta and gamma) and variant subunits in these classes, particularly in the alpha-class. Expression of recombinant subunits produces functional receptors; when certain alpha-variants are coexpressed with beta- and gamma-subunits the resulting receptors have pharmacological properties characteristic of GABAA-benzodiazepine type I or type II receptors. The alpha-variants are differentially expressed in the central nervous system and can be photoaffinity-labelled with benzodiazepines. Here we report a novel alpha-subunit (alpha 6) of cerebellar granule cells. We show that recombinant receptors composed of alpha 6, beta 2 and gamma 2 subunits bind with high affinity to the GABA agonist [3H]muscimol and the benzodiazepine [3H]Ro15-4513 but not the other benzodiazepines or beta-carboniles. The same distinctive pharmacology is observed with GABAA receptors from rat cerebellum immunoprecipitated by an antiserum specific for the alpha 6 subunit. We conclude that this alpha-subunit is part of a cerebellar receptor subtype, selective for Ro15-4513, an antagonist of alcohol-induced motor incoordination and ataxia.
 ...
PMID:Cerebellar GABAA receptor selective for a behavioural alcohol antagonist. 217 13

The intent of this paper is to review the recent literature on exercise-induced hyperammonemia (EIH) and to compare the current interpretations of ammonia accumulation during exercise with the recognized clinical symptoms of progressive ammonia toxicity. In doing so, we will speculate on possible exercise-induced symptoms of CNS dysfunction which could result from elevated ammonia during intense short-duration or prolonged exercise. Ammonia is a ubiquitous metabolic product producing multiple effects on physiological and biochemical systems. Its concentration in several body compartments is elevated during exercise, predominantly by increased activity of the purine nucleotide cycle (PNC) in skeletal muscle. Depending on the intensity and duration of exercise, muscle ammonia may be elevated to the extent that it leaks (diffuses) from muscle to blood, and thereby can be carried to other organs. The direction of movement of ammonia or the ammonium ion is dependent on concentration and pH gradients between tissues. In this manner, ammonia can also cross the blood-brain barrier (BBB), although the rate of diffusion of ammonia from blood to brain during exercise is unknown. It seems reasonable to assume that exhaustive exercise may induce a state of acute ammonia toxicity which, although transient and reversible relative to disease states, may be severe enough in critical regions of the CNS to affect continuing coordinated activity. Regional differences in brain ammonia content, detoxification capacity, and specific sensitivity may account for the variability of precipitating factors and latency of response in CNS-mediated dysfunction arising from an exercise stimulus, e. g., motor incoordination, ataxia, stupor. There have been numerous suggestions that elevated ammonia is associated with, or perhaps is responsible for, exercise fatigue, although evidence for this relies extensively on temporal relationships. Fatigue may become manifest both as a peripheral organ or central nervous system phenomenon, or combination of both. Thus, we must examine the sequential or concomitant changes in ammonia concentration occurring in the periphery, the central nervous system (CNS), and the cerebrospinal fluid (CSF) induced by any effector, not only exercise, to interpret and rationalize the diverse physical, physiological, biochemical, and clinical symptoms produced by hyperammonemic states. Since more is known about elevated brain ammonia during other diverse conditions such as disease states, chemically induced convulsion, and hyperbaric hyperoxia, some of these relevant data are discussed.
 ...
PMID:Exercise-induced hyperammonemia: peripheral and central effects. 219 91

The powdered bark of Maquira sclerophylla is consumed as snuff in north Brazil. Both the crude and the purified hydrosoluble extract (WP) injected i.p. in the dose range of 0.05-0.5 g/kg induced hyperexcitability, tremors, motor incoordination, ataxia, quietness and muscle relaxation in rats. The effects were progressive, dose-related and reversed after 30 min. Anesthetized rats, guinea-pigs and dogs injected with the purified extract (10-50 mg/kg, i.v.) showed a biphasic change of carotid blood pressure. The early and transient hypotension was blocked by atropine but not by vagotomy: the secondary hypertension was long lasting and sustained for over 30 min. The hypertension was shortened but not blocked after ganglionic blockade or reserpine treatment. Either pithing or alpha receptor blockade with yohimbine reduced both effects of the extract. Guinea-pigs and dogs were more responsive than rats and died by heart arrest. Incubation of WP (20 micrograms/ml) increased both the rate and force of contraction of isolated guinea-pig right atria by 2 and 5 times, respectively. Propranolol (4 micrograms/ml) blocked the chronotropic effect but did not decrease the inotropic effect. In electrically driven guinea-pig left atria, WP (10 micrograms/ml) increased the force of contraction by 80% and the maximum rate of force development by 60%, but did not change the time to peak tension, the time to 50% relaxation, or the rate of relaxation. These cardiovascular effects resemble those of digitalis-like drugs. Cardenolides were detected in WP by phytochemical screening.
 ...
PMID:Pharmacology of an Indian-snuff obtained from Amazonian Maquira sclerophylla. 221 23


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>