Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tetrahydrobiopterin (BH4) is synthesized from guanosine triphosphate (GTP) by GTP cyclohydrolase I (GCH), 6-pyruvoyltetrahydropterin synthase (PTS), and sepiapterin reductase (SPD). GCH is the rate-limiting enzyme. BH4 is a cofactor for three pteridine-requiring monooxygenases that hydroxylate aromatic L-amino acids, i.e., tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH), and phenylalanine hydroxylase (PAH), as well as for nitric oxide synthase (NOS). The intracellular concentrations of BH4, which are mainly determined by GCH activity, may regulate the activity of TH (an enzyme-synthesizing catecholamines from tyrosine), TPH (an enzyme-synthesizing serotonin and melatonin from tryptophan), PAH (an enzyme required for complete degradation of phenylalanine to tyrosine, finally to CO2 + H2O), and also the activity of NOS (an enzyme forming NO from arginine), Dominantly inherited hereditary progressive dystonia (HPD), also termed DOPA-responsive dystonia (DRD) or Segawa's disease, is a dopamine deficiency in the nigrostriatal dopamine neurons, and is caused by mutations of one allele of the GCH gene. GCH activity and BH4 concentrations in HPD/DRD are estimated to be 2-20% of the normal value. By contrast, recessively inherited GCH deficiency is caused by mutations of both alleles of the GCH gene, and the GCH activity and BH4 concentrations are undetectable. The phenotypes of recessive GCH deficiency are severe and complex, such as hyperphenylalaninemia, muscle hypotonia, epilepsy, and fever episode, and may be caused by deficiencies of various neurotransmitters, including dopamine, norepinephrine, serotonin, and NO. The biosynthesis of dopamine, norepinephrine, epinephrine, serotonin, melatonin, and probably NO by individual pteridine-requiring enzymes may be differentially regulated by the intracellular concentration of BH4, which is mainly determined by GCH activity. Dopamine biosynthesis in different groups of dopamine neurons may be differentially regulated by TH activity, depending on intracellular BH4 concentrations and GCH activity. The nigrostriatal dopamine neurons may be most susceptible to a partial decrease in BH4, causing dopamine deficiency in the striatum and the HPD/DRD phenotype.
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PMID:Regulation of pteridine-requiring enzymes by the cofactor tetrahydrobiopterin. 1032 73

In order to evaluate learning and memory deficits separately from and simultaneously with motivational, motor and sensory impairments in identical animals, we developed the allocentric place discrimination task test using a water maze in rats. For this assessment task, two similar, visible platforms, one was fixed and the other was floating, were simultaneously present in a pool, and the working memory of the allocentric place discrimination task was evaluated. After training, the task accuracy was high about 85% correct and animals were used repeatedly. The accuracy decreased significantly when the pool was surrounded with a black curtain. Muscarinic receptor antagonist scopolamine 0.5 mg/kg selectively impaired the accuracy. Muscle relaxant dantrolene 10 mg/kg selectively decreased swimming speed. Under low motivational condition (warm water), still time increased and swimming speed decreased, but the accuracy was not affected. Similar to warm water, opioid receptor agonist morphine 15 mg/kg increased still time and decreased swimming speed. These results suggest that the allocentric place discrimination task is useful in evaluating spatial working memory ability independently of and concurrently with also visual, motor ability and motivation in identical animals.
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PMID:Simultaneous evaluation of spatial working memory and motivation by the allocentric place discrimination task in the water maze in rats. 1042 91

Hot water epilepsy is a reflex epilepsy. Seizures are provoked by hot water, and result from the association of both cutaneous and heat stimuli. Described mainly in India and Japan, the condition seems to be rare in Europe, where it occurs in young children. We report five infants aged from 6 months to 2 years. They had brief seizures during bathing with activity arrest, hypotonia, and vasoactive modification; clonic movements were observed. A simple treatment-decreasing the bath temperature-can be sufficient. Sometimes an antiepileptic drug is required. Seizure course and psychomotor development are favorable. Hot water epilepsy is a benign form of epilepsy. Its incidence could be underestimated because of confusion with febrile convulsions, vagal fits, or aquagenic urticaria.
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PMID:Hot water epilepsy: a benign and unrecognized form. 1069 97

A review was published (1991) of 19 retrospective case-control studies that had investigated the relationship between prone sleeping position (on the stomach) and the sudden infant death syndrome (SIDS). These studies, which had been conducted between 1965 and 1990 in New Zealand, Australia, England, France and the Netherlands, showed an overall higher rate of SIDS in infants who usually slept prone. In those countries, vigorous community intervention to change babies' sleep position away from the prone has resulted in marked declines of 50 per cent or more in the rate of SIDS. Such encouraging reports from many countries prompted the American Academy of Pediatrics to recommend that infants be placed to sleep on their backs to reduce the risk of SIDS. This was followed by a successful campaign in the United States between mid-1994 and 1998. Despite the decreased incidence, SIDS remains the leading cause of death in infants 1 month to 1 year of age of industrialized nations of the world. Studies have been conducted in human infants, mechanical models and animal models to learn the role of risk factors in prone sleeping infants. Soft bedding, thermal stress and biologic risk factors such as impaired ventilatory and arousal responsiveness are among many factors that have been investigated. Hunt states that there is not a single unifying factor that explains increased SIDS in prone sleeping infants. Two major studies conducted in the 1970s showed: (1) muscle weakness in the upper half of the body in infants who subsequently died of SIDS, and (2) shoulder hypotonia in near-miss for SIDS infants. An infant sleeping face-down in the prone position could be jeopardized if he lacked the muscle strength to shift his position or turn his head to rescue himself from a life-threatening situation. In contrast, recent studies in neonates sleeping in the prone position report that normal infants can spontaneously arouse and turn their heads. Some data support the hypothesis that magnesium deficiency contributes to SIDS. Muscle strength is seriously impaired in the young magnesium deficient subject, while magnesium rapidly reverses muscle weakness. In rats, marginal deprivation in dietary magnesium reduces exercise capacity, an early effect of magnesium deficiency which is preventable by consuming magnesium-enriched mineral water. It is concluded that magnesium deficiency is at least one major unifying factor that explains increased SIDS in prone sleeping infants.
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PMID:Magnesium deficiency promotes muscle weakness, contributing to the risk of sudden infant death (SIDS) in infants sleeping prone. 1130 Jun 21

The antihemolytic activity of Rooibos and black tea on Japanese quail erythrocytes was studied. Peroxide and hypotonic hemolysis of the red blood cells of quails, either fed with Rooibos tea supplemented food or fed without tea, was performed. Long-term consumption of Rooibos tea did not change the erythrocyte fragility to either peroxide or hypotonia induced hemolysis. However, Rooibos and black teas decreased peroxide induced hemolysis of erythrocytes incubated with each of them, but not hemolysis induced by hypotonic NaCl solution. Stronger inhibition of hemolysis has been obtained when a boiled water extract of Rooibos tea was used for the inhibition. The degree of inhibition was comparable with the effect of ascorbic acid.
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PMID:Antihemolytic effect of Rooibos tea (Aspalathus linearis) on red blood cells of Japanese quails. 1140 39

The diagnosis of outlet dysfunction constipation in patients with idiopathic constipation that responds poorly or not at all to conservative measures, such as fiber supplements, fluids, and stimulant laxatives, is based upon diagnostic testing. These tests include colonic transit of radio-opaque markers, anorectal manometry or electromyography, barium defecography, and expulsion of a water-filled balloon. The literature suggests that conditions such as pelvic floor dyssynergia exist but may be over-diagnosed as a laboratory artifact. In our laboratory, we screen patients with balloon expulsion studies, and then test for dyssynergia only if the result of the balloon expulsion test is abnormal. In my opinion, anal sphincter electromyogram and manometry are equivalent in establishing the diagnosis. Barium defecography is helpful in making a diagnosis of a rectocele, but I prefer to document that vaginal pressure on the rectocele significantly improves rectal evacuation. Manometry also helps to establish the presence of megarectum, hypotonia, and weak expulsion efforts. Conceptually, biofeedback training, which incorporates simulated defecation, is the most logical approach to pelvic floor dyssynergia. It incurs no risk and benefits 60% to 80% of patients. The drawbacks are the time-intensive nature of the therapy and the short-term costs, which are offset if there is sustained benefit. There is no evidence that biofeedback is helpful in children with constipation. Habit training has established benefits, but recurrences are frequent and long-term reinforcement is helpful to maintain success. Laxatives and enemas are adjunctive therapies in both habit training and biofeedback. Surgery is effective in those uncommon patients with physiologically significant rectoceles, but surgical division of the puborectalis muscle is risky and unproven. Likewise, botulinum toxin injection into the puborectalis is unproven, but the effects are rarely permanent should incontinence occur. Diagnostic measures and therapeutic success are enhanced when patients are seen in centers experienced with the evaluation of these disorders.
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PMID:Outlet Dysfunction Constipation. 1146 87

Down's syndrome (DS) is a major cause of mental retardation, hypotonia and delayed development. Murine models of DS carrying large murine or human genomic fragments show motor alterations and memory deficits. The specific genes responsible for these phenotypic alterations have not yet been defined. DYRK1A, the human homolog of the Drosophila minibrain gene, maps to the DS critical region of human chromosome 21 and is overexpressed in DS fetal brain. DYRK1A encodes a serine-threonine kinase, probably involved in neuroblast proliferation. Mutant Drosophila minibrain flies have a reduction in both optic lobes and central brain, showing learning deficits and hypoactivity. We have generated transgenic mice (TgDyrk1A) overexpressing the full-length cDNA of Dyrk1A. TgDyrk1A mice exhibit delayed cranio-caudal maturation with functional consequences in neuromotor development. TgDyrk1A mice also show altered motor skill acquisition and hyperactivity, which is maintained to adulthood. In the Morris water maze, TgDyrk1A mice show a significant impairment in spatial learning and cognitive flexibility, indicative of hippocampal and prefrontal cortex dysfunction. In the more complex repeated reversal learning paradigm, this defect turned out to be specifically related to reference memory, whereas working memory was almost unimpaired. These alterations are comparable with those found in the partial trisomy chromosome 16 murine models of DS and suggest a causative role of DYRK1A in mental retardation and in motor anomalies of DS.
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PMID:Neurodevelopmental delay, motor abnormalities and cognitive deficits in transgenic mice overexpressing Dyrk1A (minibrain), a murine model of Down's syndrome. 1155 28

Muscle relaxant effect of Elaeagnus angustifolia L. (Elaeagnaceae) fruit seeds was studied in mice using traction test. The aqueous and ethanolic extracts (i.p) induced a muscle relaxant effect in a dose dependent manner as effective as diazepam (1 mg/kg). The aqueous extract was partitioned with methanol-chloroform (MeCh) and n-butanol (Bu.) saturated with water. The MeCh and Bu. fractions did not show activity. Preliminary phytochemical tests showed that the extract contains flavonoid. The results suggested that E. angustifolia fruit seeds exerted muscle relaxant activity via flavonoid component(s).
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PMID:Muscle relaxant activity of Elaeagnus angustifolia L. fruit seeds in mice. 1264 26

An evaluation of potential adverse human health effects of disinfection byproducts requires study of both cancer and noncancer endpoints; however, no studies have evaluated the neurotoxic potential of a common haloacetic acid, dibromoacetic acid (DBA). This study characterized the neurotoxicity of DBA during 6-month exposure in the drinking water of rats. Adolescent male and female Fischer 344 rats were administered DBA at 0, 0.2, 0.6, and 1.5 g/l. On a mg/kg/day basis, the consumed dosages decreased greatly over the exposure period, with average intakes of 0, 20, 72, and 161 mg/kg/day. Weight gain was depressed in the high-concentration group, and concentration-related diarrhea and hair loss were observed early in exposure. Testing with a functional observational battery and motor activity took place before dosing and at 1, 2, 4, and 6 months. DBA produced concentration-related neuromuscular toxicity (mid and high concentrations) characterized by limb weakness, mild gait abnormalities, and hypotonia, as well as sensorimotor depression (all concentrations), with decreased responses to a tail-pinch and click. Other signs of toxicity at the highest concentration included decreased activity and chest clasping. Neurotoxicity was evident as early as one month, but did not progress with continued exposure. The major neuropathological finding was degeneration of spinal cord nerve fibers (mid and high concentrations). Cellular vacuolization in spinal cord gray matter (mostly) and in white matter (occasionally) tracts was also observed. No treatment-related changes were seen in brain, eyes, peripheral nerves, or peripheral ganglia. The lowest-observable effect level for neurobehavioral changes was 20 mg/kg/day (produced by 0.2 g/l, lowest concentration tested), whereas this dosage was a no-effect level for neuropathological changes. These studies suggest that neurotoxicity should be considered in the overall hazard evaluation of haloacetic acids.
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PMID:Neurotoxicity produced by dibromoacetic acid in drinking water of rats. 1497 49

This report describes a male baby with primary hyperoxaluria type-1, presenting at 5 hours of age with cyanotic episodes, hypotonia, unexplained techypnea and tachycardia. This infant also had renal calcinosis, and middle cerebral arterial infarct with unilateral enlargement of ventricle and left porencephalic cyst on CT scan. The infant improved with diuretics, water supplementation, pyridoxine, and Albright solution.
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PMID:Primary hyperoxaluria type-1: an unprecedented presentation at birth. 1576 15


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