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

General pharmacological effects of [Ethyl p-(6-guanidinohexanoyloxy)benzoate] methanesulfonate (FOY), a new antiproteolytic agent, were studied and the following results were obtained. Acute administration of large doses of FOY in conscious dogs and rabbits caused a decrease in spontaneous motility, ataxia, cyanosis, collapse, mydriasis, and respiratory paralysis. The agent had no effect on the central nervous system and exhibited hypotensive effects in dogs in doses of more than 1 mg/kg. Hypotensive responses were not inhibited by treatment with atropine or hexamethonium. FOY had no effects on ECG in the rabbit at doses of less than 30 mg/kg and at doses from 10(-6) to 10(-4)g/ml, distinctly reduced the amplitude of the spontaneous and rhythmic contractions of the isolated rabbit ileum, guinea-pig ileum and rat uterus preparation. The contractile response to nerve stimulation, noradrenaline and barium was suppressed in isolated guinea-pig vas deferens. FOY had no effects on the twitch response of gastrocnemius muscle to sciatic nerve stimulation in rats. The drug caused local irritant effects in rabbits and rats.
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PMID:[Pharmacological action of [ethyl p(6-guanidinohexanoyloxy)benzoate] methanesulfonate (FOY)]. 23 87

A 14-year-old girl, whose birth and developmental history were normal till the age of 7, was admitted to our hospital because of slowly progressive difficulties in walking, speaking and hearing. She also complained of absence of menstruation. She showed poor school records since the age of 7. On neurological examination, she showed limb and truncal ataxia. There was no nystagmus but slurred speech was found. Muscular power was good and her sensory system was normal. Tendon reflexes were equally present, and plantar reflexes were flexor. Bilateral moderate nerve deafness was also present. Mental deficiency was diagnosed on an intelligence test. Brain CT and MRI showed cerebellar atrophy. Gynecological examination revealed scanty pubic hair and small uterus. Karyotype was 46XX. Endocrinological studies demonstrated high level of FSH, low level of E2, and the normal response to pituitary stimulation with LHRH, indicating the existence of primary hypogonadism. Although the etiology of this multisystem disorder is unknown, it is possible that both nervous and endocrine disorders were genetically determined.
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PMID:[A case of early onset cerebellar ataxia with hearing loss, mental disturbance and primary hypogonadism]. 130 Feb 61

A female showed primary amenorrhea and slowly progressive ataxia of limbs and gait, that had started when she was 18 years old. Endocrine data were consistent with hypogonadotropic hypogonadism. She died at 35 years of age. Post mortem examination showed mucinous carcinoma of the lung, hypoplastic uterus, atrophic ovaries. The cerebellum was small, with the atrophy most marked in the vermis, and the pons was shrinked. There was almost complete Purkinje cell disappearance and neuronal loss in the granular layer and the inferior olives.
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PMID:Cerebellar ataxia and hypogonadism. A clinicopathological report. 215 58

We report a case of primary position downbeating nystagmus due to an occult breast carcinoma in a 57-year-old woman with progressive oscillopsia and truncal ataxia. Acute nausea and vomiting precipitated hospitalization. Magnetic resonance imaging of the brain was normal, though a sterile mononuclear cerebrospinal fluid pleocytosis was present. Search for an occult malignancy disclosed an adenocarcinoma of the breast. Radical mastectomy and oral corticosteroid therapy did not alter the clinical course of the paraneoplastic syndrome in our patient. Primary position downbeating nystagmus is an uncommon manifestation of an occult malignancy. Our report and review of the literature suggests that investigations necessary for the diagnosis of occult malignancies of the lung, breast, uterus, and ovary be included in the search for cryptic causes of downbeating nystagmus.
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PMID:Paraneoplastic downbeating nystagmus. A sign of occult malignancy. 285 13

The present study was designed to evaluate the influence of acrylamide (ACR) on male and female reproductive function. Male rats received ACR in drinking water (50, 100, or 200 ppm) for up to 10 wk. Copulatory behavior, semen, and (for controls and 100 ppm only) fertility and fetal outcomes were evaluated. Females received ACR (25, 50, 100 ppm) for 2 wk prior to initiation of breeding and then throughout gestation and lactation. Hindlimb splaying was apparent in the 200-ppm males by wk 4; less severe splaying appeared in the 100-ppm group at wk 8. Disruptions in copulatory behavior preceded the appearance of this ataxia. These disruptions in mating performance interfered with ejaculatory processes and subsequent transport of sperm, since semen was found in the uterus of only 1 of the 15 females mated with the 100-ppm males at wk 9. Moreover, only 33% of the females mated (wk 10) to the 100-ppm males were pregnant. Postimplantation loss was also significantly increased in this group. Hindlimb splaying appeared in the females receiving 100 ppm ACR during wk 1-2 of pregnancy. Body weight and fluid intake were also depressed. Dams in the 50-ppm group showed depression in these parameters during the last 2 wk of lactation. ACR did not significantly affect mating performance of the females, pregnancy rates, litter size, or survival. However, ACR did significantly depress pup body weight at birth (100-ppm group) and weight gain during lactation through post-weaning, d 42 (50- and 100-ppm groups). Vaginal patency was delayed in the 100-ppm group only.
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PMID:Reproductive toxicity associated with acrylamide treatment in male and female rats. 395 25

Polyoxyethylene (20) sorbitan monooleate (polysorbate 80, Tween 80), a surfactant, has been widely used as a solvent for pharmacological experiments. In the present study, polysorbate 80 was found to have toxicity of a low order in both the mice and rats when given by i.p. and p.o. routes. It produced mild to moderate depression of the central nervous system with a marked reduction in locomotor activity and rectal temperature, exhibited ataxia and paralytic activity and potentiated the pentobarbital sleeping time. On intravenous administration in dogs, it had a dose-dependent hypotensive effect. Polysorbate 80 did not have a direct stimulant or relaxant effect on either guinea pig ileum or rat uterus, however, it antagonised the contractions induced by acetylcholine, histamine, barium, 5-hydroxytryptamine and carbachol in a dose-dependent manner. A direct relaxant effect was observed on rabbit jejunum. A dose-dependent myocardial depressant effect was observed on guinea pig and rabbit paired atrial preparations. On the electrically-driven guinea pig left atrial preparation, polysorbate 80 exhibited a dose-dependent negative inotropic action. Polysorbate 80 did not induce diuresis in rats upto a dose of 2.5 ml/kg. The results of the present study indicate that polysorbate 80 can neither be used as a solvent for isolated tissue experiments nor when considered for intravenous administration. However, polysorbate 80 can be employed safely as a vehicle for neuropsychopharmacological experiments in doses not exceeding 1 ml/kg.
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PMID:Polysorbate 80: a pharmacological study. 402 3

The general pharmacological properties of a novel cognition-enhancing agent, nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide, DM-9384, CAS 77191-36-7) were investigated, and the following results were obtained. 1. Central nervous system: Nefiracetam showed depressant activities (such as ataxia) on general behavior (mice), and inhibited spontaneous locomotor activity, rota-rod and traction performances (mice) and polysynaptic potential of the spinal reflex (rats), and potentiated pentobarbital anesthesia (mice). The drug inhibited electroshock-induced seizure at relatively low doses, but did not affect chemoshock-induced seizure (mice). Nefiracetam failed to show analgesic activity in the tail pinch test, but inhibited the acetic acid-induced writhing syndrome (mice). An inhibitory pattern in the electroencephalogram was observed (cats). Nefiracetam had little or no effect on body temperature (rats). 2. Respiratory and cardiovascular systems: Nefiracetam induced transient decreases in blood pressure, left ventricular pressure and LV dp/dt max at higher doses (dogs). 3. Autonomic nervous system: Nefiracetam had no influence on pupil size (rabbits). The drug induced no significant effect on the pressor response to norepinephrine or depressor response to acetylcholine, but inhibited the contractile response of the nictitating membrane to preganglionic cervical sympathetic nerve stimulation at the highest dose (dogs). 4. Gastrointestinal system: Nefiracetam inhibited gastrointestinal propulsion (mice), gastric emptying rate and gastric secretion (rats) at higher doses. Nefiracetam produced no apparent damage in the gastric mucosa, and had no effect on bile secretion (rats). 5. Isolated smooth muscle: Nefiracetam had no effect on the resting tonus of isolated ileum, whereas it inhibited the contractile response to acetylcholine, histamine, serotonin, nicotine and BaCl2 at higher concentrations (guinea pigs). Nefiracetam had no effect on the resting tonus or the serotonin-induced contraction of stomach fundus (rats). The drug had no effect on the resting tonus or the norepinephrine-induced contraction of vas deferens, but tended to inhibit the contraction induced by nerve stimulation (guinea pigs). Nefiracetam had little or no effect on the resting tonus or oxytocin-induced contraction of virgin uterus, or on spontaneous contraction of pregnant uterus (rats). Nefiracetam did not affect the resting tonus of trachea, whereas it inhibited isoproterenol-induced relaxation at the highest concentration (guinea pigs). Nefiracetam had no chronotropic effect in isolated atria, but showed a slight negative inotropic effect at the highest concentration (guinea pigs). 6. Miscellaneous: Nefiracetam slightly decreased urinary volume, whereas it did not affect urinary electrolyte excretion (rats).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:General pharmacological profile of the new cognition-enhancing agent nefiracetam. 801 90

The purpose of this study was to determine whether intravaginal prostaglandin F2 alpha (PGF2 alpha) would be effective for the treatment of metritis or pyometra in the bitch. Seventeen bitches with metritis or pyometra were treated with PGF2 alpha. Prostaglandin F2 alpha (150 micrograms/kg body weight) was administered once or twice daily by infusing 0.3 ml per 10 kg body wt into the vaginal lumen. Bitches were also treated with amoxicillin (15 mg/kg body wt/48 h) and/or gentamicin (4 mg/kg body wt/day) administered as intramuscular (i.m.) injections. Fifteen bitches were treated successfully with intravaginally administered PGF2 alpha for 3 to 12 days and with intramuscularly administered antibiotics for 4 to 12 days. Success of treatment was judged by cessation of vaginal discharge, the absence of fluid in the uterus as determined by ultrasonography, and the overall health status of the animal. As two bitches with pyometra showed clinical deterioration in spite of medical treatment, ovariohysterectomy was performed after the first and the second treatment, respectively. No side effects (salivation, vomiting, diarrhoea, hyperpnoea, ataxia, urination, anxiety, pupillary dilatation followed by contraction) were observed after PGF2 alpha treatment. The disease did not recur during the subsequent oestrous cycles within 12 months after the initial treatment. The results demonstrate that intravaginal administration of PGF2 alpha was effective in 13 dogs (86.6%) with metritis or pyometra, and caused no side effects. Although the study was based on a relatively small number of cases, it is concluded that prostaglandin F2 alpha can be a useful means of treating bitches with metritis or pyometra. However, in severe cases of pyometra ovariohysterectomy is needed.
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PMID:Intravaginal prostaglandin F2 alpha for the treatment of metritis and pyometra in the bitch. 1021 34

Alpha-tocopherol transfer protein (alpha-TTP), a cytosolic protein that specifically binds alpha-tocopherol, is known as a product of the causative gene in patients with ataxia that is associated with vitamin E deficiency. Targeted disruption of the alpha-TTP gene revealed that alpha-tocopherol concentration in the circulation was regulated by alpha-TTP expression levels. Male alpha-TTP(-/-) mice were fertile; however, placentas of pregnant alpha-TTP(-/-) females were severely impaired with marked reduction of labyrinthine trophoblasts, and the embryos died at mid-gestation even when fertilized eggs of alpha-TTP(+/+) mice were transferred into alpha-TTP(-/-) recipients. The use of excess alpha-tocopherol or a synthetic antioxidant (BO-653) dietary supplement by alpha-TTP(-/-) females prevented placental failure and allowed full-term pregnancies. In alpha-TTP(+/+) animals, alpha-TTP gene expression was observed in the uterus, and its level transiently increased after implantation (4.5 days postcoitum). Our results suggest that oxidative stress in the labyrinth region of the placenta is protected by vitamin E during development and that in addition to the hepatic alpha-TTP, which governs plasma alpha-tocopherol level, the uterine alpha-TTP may also play an important role in supplying this vitamin.
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PMID:Alpha-tocopherol transfer protein is important for the normal development of placental labyrinthine trophoblasts in mice. 1107 32

Twenty-three susceptible newborn kittens were inoculated with feline panleukopenia virus on the day of birth and were sacrificed from 18 hr to 43 days postinoculation (DPI). Macroscopic lesions included thymic atrophy in animals examined at 4 to 14 DPI and cerebellar hypoplasia and degeneration in animals examined at 22 to 43 DPI. Clinical signs of ataxia were not observed in the four kittens with cerebellar lesions sacrificed at 22 to 43 days of age. Intranuclear inclusions were present in a variety of cell types in the organs examined from kittens that died or were sacrificed at 4 to 14 DPI. The most severely infected and depleted tissues were the thymus, spleen, mesenteric lymph nodes, and the cerebellum, whereas the bladder, testes, ovaries, and uterus were the least susceptible to panleukopenia virus infection. Specific fluorescence was demonstrated with panleukopenia antiglobulin conjugate in various cell types in tissues from 2 to 22 DPI and only in cerebellar Purkinje cells of kittens sacrificed at 29, 36, and 43 DPI. The virus replicated in the cells of all layers of blood vessels (endothelial, muscular, and connective tissue cells), suggesting that this is the route of dissemination of the agent throughout the body.
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PMID:Pathogenesis of Feline Panleukopenia Virus in Susceptible Newborn Kittens II. Pathology and Immunofluorescence. 1655 64


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