Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
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In northern Sweden, 23 heifers out of 98 cattle died of acute vanadium toxicity in a 10-day period. Eight months earlier a pasture had been fertilized with basic slag, containing 3% vanadium. The fertilizer was laid on the surface without being ploughed in. Mainly heifers, and some cows, were fed with basic slag-contaminated fresh hay. The first signs of illness appeared 11 days later, and the first case of death appeared 14 days after the initial clinical signs. The signs were diffuse and difficult to interpret. Inappetence, black diarrhea, lethargy, dehydration and spontaneous abortions occurred. Further, pulmonary lesions, conjunctivitis, neurological disturbances such as depression, leg incoordination, and paralysis of the hind limbs and face were also noted. Although feeding with the contaminated hay was stopped at the outbreak of the toxicity, the 23 animals died or had to be slaughtered, and at necropsy of another heifer 4 weeks later, large amounts of basic slag were still found in the alimentary tract. High vanadium concentrations were found in the liver, kidneys, spleen and urine, 5.9, 5.5, 1.9 and 4.8 mg/kg w.w., respectively. In bone tissue (coccygeal vertebrae), the highest value in an acutely poisoned heifer was 0.680 mg/kd d.w., in the same range as that of an experimentally poisoned sheep. Surviving heifers were more affected than cows; the state of health of these heifers gradually deteriorated and, therefore, a few were slaughtered 3 months later. Because of residual neurological disturbances and decreased milk production, the rest of the herd was slaughtered 5 months after the outbreak, and samples were collected and analyzed. Elevated vanadium concentrations were found in the organs, especially in the spleen, where values of 1.40 and 1.42 mg/kg w.w. were found in 2 heifers at 3 months. The values in heifers (n = 6) were decreased 5 months after the outbreak. The median concentrations were somewhat higher in the liver than in the spleen, and lowest in the kidney (0.244, 0.213 and 0.058 mg/kg w.w., respectively). In the organs of the cows (n = 24), which were less exposed, the corresponding values were 0.012, 0.095 and 0.013 mg/kg w.w., respectively. Vanadium concentrations were also determined in livers of cows and calves at regular slaughter in four geographic regions of Sweden. In one of the regions, where basic slag (with 3% vanadium) had been used for many years, the values were significantly higher than those in the other regions. In a material of 293 specimens, an upper reference limit of 0.012 mg/kg liver w.w., with a 90% confidence interval of 0.011-0.019 mg/kg w.w., was found to be normal for cattle in Sweden. Concentrations above the Highest Swedish Reference Value, 0.019 mg/kg liver can be considered elevated. Vanadium-containing basic slag used as fertilizer caused poisoning in a herd of cattle and its regional use was detectable in livers from cattle at regular slaughter. Such fertilizer must be applied in a proper way. It should be ploughed in and any direct contact of grazing animals with the hazardous fertilizer should be prevented.
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PMID:Vanadium poisoning of cattle with basic slag. Concentrations in tissues from poisoned animals and from a reference, slaughterhouse material. 881 37

Trifluoroiodomethane (CF3I) is being considered as a replacement compound for halon fire suppressants. Its structure is similar to that of Halon 1301 (CF3Br), but it has very low ozone depletion potential compared to CF3Br. As part of the process of developing environmental and health effects criteria, acute, 2-week, and 13-week nose-only inhalation toxicity studies were conducted in Fischer 344 rats. In the acute study, three groups of 30 male rats each were exposed to 0 (control), 0.5, or 1.0% (v/v) CF3I for 4 hr and euthanized immediately following exposure, 3 days postexposure, or 14 days postexposure. There were no deaths and no clinical signs of toxicity throughout the study. Histopathologic examination of select tissues showed no lesions of pathologic significance. In the 2-week study, four groups of 5 male rats each were exposed for 2 hr/day, 5 days/week to 0, 3, 6, or 12% CF3I. No deaths were observed, though lethargy and slight incoordination were noted in rats of the 6 and 12% groups at the conclusion of each daily exposure. Mean body weight gains were depressed in rats of the 6 and 12% groups. Serum thyroglobulin and reverse T3 (rT3) values were increased at all exposure levels. At necropsy, no gross lesions or differences in absolute or relative organ weights were noted. Histopathologic examination of the thyroid and parathyroid glands indicated no morphological abnormalities in the CF3I-exposed rats. In the 13-week study, four groups of 15 male and 15 female rats were exposed to 0, 2, 4, or 8% CF3I 2 hr/day, 5 days/week for 13 weeks. Rats exposed to 4 or 8% CF3I had lower mean body weights than the controls. Deaths observed in the 2 and 8% groups were attributed to accidents resulting from the restraint system employed. Hematologic alterations were minimal and considered insignificant. Increases in the frequency of micronucleated bone marrow polychromatic erythrocytes were observed in rats of all three CF3I groups. Serum chemistry alterations observed in rats of all CF3I exposure groups included decreases in T3 and increases in thyroglobulin, rT3, T4, and TSH. Relative organ weight increases (8% CF3I group) occurred in the brain, liver, and thyroid glands; decreases were observed in the thymus and testes. A decrease in relative thymus weights and an increase in relative thyroid weights were observed also in rats of the 2 and 4% groups. Histopathological findings included a mild inflammation in the nasal turbinates of rats exposed to 4 or 8% CF3I, mild atrophy and degeneration of the testes (4 and 8% CF3I groups), and a mild increase in thyroid follicular colloid content in rats of all CF3I exposure groups. Though NOAELs were observed for select target organs (e.g., nasal turbinates, testes), NOAELs were not apparent in all target organs examined (e.g., thyroid glands, bone marrow).
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PMID:Acute and subchronic inhalation studies on trifluoroiodomethane vapor in Fischer 344 rats. 902 74

Fischer 344 rats (250-300 g) were exposed to the resulting aerosols from the pyrolysis of Spectrex Fire Extinguishant (SFE) Formulation A, a pyrotechnically generated aerosol fire suppressant, at a loading equivalent of 50 or 80 g m(-3) air for 15 or 60 min. Exposures were conducted in a 700-1 whole-body inhalation chamber under static conditions. The chamber atmosphere was analyzed for mass aerosol concentration and size distribution. Clinical observations were taken throughout the exposure. Animals were euthanized at 1 h, 6 h, 24 h, 7 days or 14 days post-exposure and underwent histopathological examination, enzyme analyses and wet/dry lung weight determination. No deaths occurred during the study. Animals exhibited signs of dyspnea, coughing, lack of coordination and lethargy during each exposure. These signs became more pronounced as the load and exposure length increased. No lesions were noted in the trachea, lung, heart or abdominal organs upon gross examination. A reversible pulmonary edema and olfactory necrosis were observed only in those animals exposed to an SFE loading equivalent to 80 g m(-3) for 60 min. Protein concentrations increased in the bronchoalveolar lavage but no changes in enzyme levels were observed. There was no significant difference between the control groups and the exposure groups for wet/dry lung weight determination.
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PMID:Evaluation of the respiratory tract after acute exposure to a pyrotechnically generated aerosol fire suppressant. 918 52

Sea-run Baltic salmon (Salmo salar) populations are suffering from the M74 syndrome, a reproduction disorder affecting both broodfish and their progeny. The syndrome is usually manifested during the middle part of the yolk-sac fry stage and has been shown to be associated with a thiamine (vitamin B(1)) deficiency. Development of the disease is reversible by thiamine treatments of broodfish or progeny. This study aimed at investigating the ability of the thiamine antagonist pyrithiamine, administered by microinjections 3 days after hatch, to cause M74-like signs i.e. typical clinical symptoms, high mortality rates and histopathological changes. Furthermore, the effects of pyrithiamine on hepatic activities of the thiamine-dependent enzyme transketolase (TK), the glucose-6-phosphate dehydrogenase (G6PDH) and the cytochrome P4501A (CYP1A) were evaluated. Six family groups with differing thiamine status were sampled on three occasions during the yolk-sac fry stage. All pyrithiamine exposed groups, with the exception of the one with the highest thiamine concentration, showed M74-like symptoms and suffered from high mortality. Enzyme activities were not different in pyrithiamine groups as compared with controls. However, the TK-activities were strongly associated with the thiamine concentrations. The G6PDH-activity demonstrated small variations with the highest activities in the M74-groups. The [TK]/[G6PDH]-ratios were considerably lower in the M74-groups than in the healthy controls, indicating an imbalance between the oxidative and the non-oxidative part of the pentose-phosphate shunt due to a deficit in thiamine. The pyrithiamine-injections induced several M74-like symptoms including incoordination, lethargy, whitened liver and yolk-sac precipitates. They also caused high mortality rates, in addition to lowered glycogen levels and increased prevalence of necrotic brain cells. Moreover, the study demonstrates that the TK, G6PDH and CYP1A-activities are associated with the thiamine content.
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PMID:Physiological, biochemical and morphological studies of Baltic salmon yolk-sac fry with an experimental thiamine deficiency: relations to the M74 syndrome. 1229 68

Fifteen cats from Italy with Ehrlichia-like inclusion bodies in their neutrophils were studied. They were diagnosed with Anaplasma (Ehrlichia) phagocytophilum infection on the basis of cytological observation of morulae within 1 to 21 per cent of their neutrophils, clinical signs characteristic of ehrlichiosis and their response to doxycycline. The predominant signs of disease were anorexia, lethargy, hyperaesthesia, muscle and joint pain, lameness, neck rigidity, lymphadenomegaly, gingivitis/periodontitis, conjunctivitis, weight loss, incoordination, pale mucous membranes and hyperglobulinaemia. The cat with inclusions in 21 per cent of its neutrophils had suffered arthralgia, tachypnoea, neck rigidity, vomiting and thrombocytopenia for four months, but recovered promptly after treatment with doxycycline.
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PMID:Microscopic and clinical evidence for Anaplasma (Ehrlichia) phagocytophilum infection in Italian cats. 1595

In this article, we provide information on patient-reported side effects from a cross-section of real-world patients. Specifically, data on side effects were tabulated for patients taking at least one of the following atypical antipsychotic medications: aripiprazole, olanzapine, paliperidone, quetiapine, risperidone, or ziprasidone. Approximately 54 percent of the 353 respondents reported having experienced a side effect as a result of taking an atypical antipsychotic medication. Most common side effects mentioned included the following: weight gain/hunger, tiredness/lethargy, and lack of coordination/muscle problems, such as tenderness, twitches, and tremors. Of those experiencing a side effect, less than 25 percent reported this side effect to their physician.
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PMID:Real-world Data on Atypical Antipsychotic Medication Side Effects. 2080 13

Eighteen-day-old domestic geese (Anser anser f. domestica) and 3-week-old Canada geese (Branta canadensis) were experimentally infected with 10(6) EID50/bird of H5N1 high pathogenicity avian influenza (HPAI) virus isolates belonging to clades 1 and 2.2. Clinical signs were observed in all of the groups and included listlessness, inappetence, marked incoordination, torticollis, paralysis and lethargy. Mortality reached 100% (Canada geese) and 40-50% (domestic geese). During necropsy, congestion and hemorrhagic lesions were most often observed. Histopathological lesions were located in multiple organs and included inflammatory and hemorrhagic changes and, in later stages, occurrences of necrosis. All of the tested organ samples collected between 3 and 8 days PI were found positive in rRT-PCR, but the highest concentration of RNA was found in the brain. The observed delayed onset of mortality and prolonged duration of the disease in young domestic geese may be related to numerous host and virus factors.
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PMID:Experimental infection of juvenile domestic and Canada geese with two different clades of H5N1 high pathogenicity avian influenza virus. 2346 70

This article reviews case reports for 58 suspected impaired driving cases that were positive for the synthetic cannabinoids AB-CHMINACA or AB-PINACA. All cases were submitted to the Washington State Patrol Toxicology Laboratory in 2014 from either Washington State or State of Alaska law enforcement agencies. The population of drivers was predominantly male (95%), with a mean age of 28 years (range, 18-61 years). The range of blood concentrations was 0.6->10 ng/mL for AB-CHMINACA (N = 33) and 0.6-41.3 ng/mL for AB-PINACA (N = 25). Drug Recognition Expert exams were performed in 10 cases for each AB-CHMINACA and AB-PINACA. Horizontal gaze nystagmus was observed in 50 and 60% of the cases, respectively. Overall, several physiological indicators varied from those typically observed with marijuana use. The majority of these cases had very poor driving; subjects were involved in an accident, found passed out in a vehicle or were called in as a suspected impaired driver. Slurred speech, confusion, lack of coordination/dexterity and lethargy were commonly observed.
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PMID:Concentrations of AB-CHMINACA and AB-PINACA and Driving Behavior in Suspected Impaired Driving Cases. 2637 39

The blood protozoan Trypanosoma evansi, which is transmitted by biting flies, is frequently neglected due to subclinical infections. This report describes a case of trypanosomiasis due to T. evansi in a 9-yr-old male puma (Felis concolor) housed at the Lahore Zoo in Pakistan. Early in January 2015, this male puma presented with chronic lethargy, weight loss, incoordination, hyperthermia, anorexia, sunken eyes, and unthriftiness. Microscopic examination of Giemsa-stained blood smears showed numerous Trypanosoma parasites. The puma was treated with diminazene aceturate subcutaneously twice. A few days later, a blood smear examination showed absence of trypanosomes. Five months later the cat presented with acute epistaxis and died. Postmortem examination showed emaciation, pale liver and kidneys, and hemorrhages on the spleen. Examination of a blood smear taken at the time of death showed numerous Trypanosoma parasites. PCR testing confirmed the presence of Trypanosoma DNA. DNA sequencing of two amplicons confirmed the presence of Trypanosoma in the blood smears with a 98-99% identity with the previously identified GenBank sequences. A phylogenetic tree was then constructed. Further studies are needed to improve our knowledge about the epidemiology and pathogenesis of T. evansi infection in wild animal species.
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PMID:FIRST REPORT OF TRYPANOSOMA EVANSI INFECTION (SURRA) IN A PUMA (FELIS CONCOLOR) OF LAHORE ZOO, PAKISTAN. 2892 Jul 78


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