Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum alpha-mannosidase activity and swainsonine concentration were determined in 4 cattle and 15 sheep (3 groups of 5 each) that were administered ground locoweed (Oxytropis sericea or Astragalus lentiginosus) containing swainsonine at dosages of approximately 0.8 mg/kg of body weight/d (cows, 30 days each) and 0, 1.0, and 1.5 mg/kg/d (sheep, 11 days each). The cattle developed mild clinical signs of locoism, including signs of depression, lethargy, and slight intention tremors. Clinical signs of toxicosis were not observed in the sheep. Within 24 hours of initial treatment, serum alpha-mannosidase activity in cows and sheep, measured by the release of 4-methylumbelliferone from an artificial substrate, was markedly decreased to 28 and 40 mumol of 4-methylumbelliferone/L, respectively. Mean serum alpha-mannosidase activity of control cows and sheep was 400 +/- 94 and 422 +/- 42 (mean +/- SD), respectively. In the treated animals, decreased serum alpha-mannosidase activities returned to normal or higher activities within 6 days after treatment was discontinued. Using a jack bean alpha-mannosidase assay, increased swainsonine activity (153, 209, and 381 ng/ml, respectively) was detected in the serum of cattle and of sheep in the high- and low-dose groups within 24 hours after treatment with locoweed. Swainsonine concentration remained high, with mean concentrations of 204, 432, and 395 ng/ml (cows and 2 sheep groups, respectively) during the treatment period. After treatment, swainsonine was rapidly cleared, with estimated serum half-life of 16.4, 17.6, and 20.3 hours (cows, and high- and low-dose sheep groups, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum swainsonine concentration and alpha-mannosidase activity in cattle and sheep ingesting Oxytropis sericea and Astragalus lentiginosus (locoweeds). 771 75

Locoweed poisoning is seen throughout the world and annually costs the livestock industry millions of dollars. Swainsonine inhibits lysosomal alpha-mannosidase and Golgi mannosidase II. Poisoned animals are lethargic, anorexic, emaciated, and have neurologic signs that range from subtle apprehension to seizures. Swainsonine is water-soluble, rapidly absorbed, and likely to be widely distributed in the tissues of poisoned animals. The purpose of this study was to quantify swainsonine in tissues of locoweed-poisoned sheep and determine the rate of swainsonine clearance from animal tissues. Twenty-four crossbred wethers were gavaged with ground Oxytropis sericea to obtain swainsonine doses of 1 mg swainsonine x kg(-1) BW x d(-1) for 30 d. After dosing, the sheep were killed on d 0, 1, 2, 3, 4, 6, 14, 30, 60, and 160. Animal weights and feed consumption were monitored. Serum was collected during dosing and withdrawal periods, and tissues were collected at necropsy. Serum swainsonine concentrations were determined using an alpha-mannosidase inhibition assay. Swainsonine concentrations in skeletal muscle, heart, brain, and serum were similar at approximately 250 ng/g. Clearance from these tissues was also similar, with half-lives (T(1/2)) of less than 20 h. Swainsonine at more than 2,000 ng/g, was detected in the liver, spleen, kidney, and pancreas. Clearance from liver, kidney, and pancreas was about T(1/2) 60 h. These findings imply that poisoned sheep have significant tissue swainsonine concentrations and animals exposed to locoweed should be withheld from slaughter for at least 25 d (10 T(1/2)) to ensure that the locoweed toxin has cleared from animal tissues and products.
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PMID:Tissue swainsonine clearance in sheep chronically poisoned with locoweed (Oxytropis sericea). 958 38

Ipomoea carnea is a toxic plant that affects goats, with symptoms being characterised by nervous disorders and death. Swainsonine and calystegines are the principal toxic components isolated from I. carnea, which also yields lysergic acid derivatives. The aim of this study was to improve the clinical characterisation of experimental intoxication by I. carnea in guinea pigs through the evaluation of behavioural changes and to perform a thorough histopathological analysis of the affected CNS. Leaves of I. carnea were administered to guinea pigs. Open-field gait analysis and monoamine levels were measured. The poisoned animals exhibited increased vocalisation, lethargy, and a reduction in the locomotion frequency after the fourth week of intoxication, as demonstrated in the open-field test. Significant differences were observed in hind-limb gait width by the last week of intoxication. After 65 days, the guinea pigs were euthanised, necropsied, and examined using light and electron microscopy. At the end of the experiment, plasma serotonin decreased. In contrast, dopamine decreased, and noradrenaline increased in urine. Brain sections were evaluated with conventional histological methods and immunohistochemistry (IHC), as well as by transmission electron microscopy (TEM). Vacuoles were observed throughout the brain, but they were particularly prominent in the brainstem. In addition, there were PAS-negative regions, and the Nissl substance was dispersed or absent, which was confirmed with the Kluver-Barreda stain. Moderate microgliosis was observed by immunohistochemistry. In the medulla oblongata, numerous ubiquitin-positive spheroids together with neuronal degeneration were observed in the nucleus gracilis/cuneatus. Furthermore, vacuoles were observed in astrocytes, oligodendrocytes, and endothelial cells by TEM. Our results showed that the behavioural effects may have been caused by alterations in the brain in conjunction with changes in monoamine levels. This research confirms the utility of this model for studying the pathogenesis of plant-induced lysosomal storage diseases.
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PMID:Experimental intoxication of guinea pigs with Ipomoea carnea: behavioural and neuropathological alterations. 2399 28