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)

Ethylene glycol (EG) is a toxic chemical found in antifreeze and heat exchangers. Standard therapy for EG intoxication in administration of ethanol (ETOH) to inhibit its metabolism by alcohol dehydrogenase (ADH). Studies indicate 1,3-butylene glycol (BG) binds to ADH more efficiently than EG and is orally less toxic than EG or ETOH. Male rats were divided into 5 groups of 6 animals. Groups received by oral intubation a single dose of EG (32 mmole/kg), BG (39 mmole/kg) initially and every 6 h up to 72 h, ETOH (39 mmole/kg) initially and every 6 h up to 72 h, or EG initially and then either BG or ETOH every 6 h up to 72 h. Administration of ETOH produced hepatotoxicity and pulmonary pathology as indicated by changes in clinical chemistry, urinalysis, and histopathology, while BG did not. Neither ETOH nor BG produced any apparent nephrotoxicity. ETOH produced ataxia, lethargy and central nervous system depression while BG did not. BG produced a higher concentration of urinary EG indicating a better inhibition of ADH metabolism of EG. Ethanol produced a higher EG blood concentration than BG. Ethanol's higher EG blood concentration may be partially attributed to dehydration and a decreased urine output as well as inhibition of ADH metabolism. Ethanol produced mortality in all animals prior to 72 h. The EG/ETOH combination produced mortality more quickly due to additive toxicity of the combination. Lack of any significant toxicity produced by BG and the production of significant toxicities by ETOH indicates that BG is potentially a better antidote than ETOH.
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PMID:The toxicokinetics of 1,3-butylene glycol versus ethanol in the treatment of ethylene glycol poisoning. 162 60

Juliflorine (CAS 76202-00-1), an antibacterial and antidermatophytic alkaloid, was studied for its toxicity in mice, rabbits, chicks, chick embryos and vero cell line. In mice LD50 was determined as 17.46 mg/kg; in rabbits 33.11 mg/kg; in chicks 24.104 mg/kg; and in chick embryos 18.284 mg/kg. In rabbits the subsequent injection of non-lethal doses (10 mg/kg) through the same route induced swelling, induration, inflammation and tissue degeneration (around injected area) with sterile abcess. Topically 1% juliflorine in polyethylene glycol-400 was found non-toxic but higher concentrations (less than or equal to 2.5%) produced irritation and inflammation; the severity of reaction was dose dependent. In vero cell-line juliflorine was found toxic at greater than or equal to 5 micrograms/ml. Injected animals showed lethargy, prostration and weakness (dose dependent) but recovered after some days, while newly hatched chicks, from injected eggs with higher dose, did not survive after 48 to 72 h. Internal organs (liver, kidney, brain, etc.) of dead, sick and healthy animals were examined and found normal.
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PMID:Toxicological studies of the antimicrobial alkaloid juliflorine. 204 77

Three patients had neurologic signs due to isopropyl alcohol (IPA) intoxication. Over a several-week period, a known alcoholic developed apathy, confusion, ataxia, and hyperreflexia. During this period, there was no ethanol available to him, and he denied use of other intoxicants. He was found stuporous in the hospital after drinking IPA and admitted to IPA abuse during the preceding weeks. Two other men were admitted in a stupor after large ingestions of IPA. Intoxication with IPA has two different presentations: stupor in a known alcoholic and encephalopathy of unknown cause in individuals who hide their addiction. Ethanol, methanol, IPA, and ethylene glycol intoxications are associated with different clinical and laboratory findings.
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PMID:Isopropyl alcohol intoxication. 198 19

The toxicity of Garlon4, the ethylene glycol butyl ether ester formulation of the herbicide tryclopyr, to juvenile coho salmon (Oncorhynchus kisutch) was investigated at several lethal and sublethal concentrations. Fish behavior, random activity and oxygen uptake were monitored. Coho salmon exhibited three distinct responses related to concentration and duration of exposure: (1) at concentrations greater than 0.56 mg/L fish were initially lethargic, then regressed to a highly distressed condition characterized by elevated oxygen uptake and finally death, (2) at 0.32-0.43 mg/L fish were lethargic throughout the exposure period with reduced oxygen uptake, and (3) at concentrations less than or equal to 0.10 mg/L fish were hypersensitive to stimuli, exhibiting elevated activity and oxygen uptake levels during photoperiod transitions. Whole body residue analysis showed that uptake of the ester and subsequent hydrolysis to the acid form in the fish was rapid, with significant accumulation of the acid in the tissues. This suggests that some threshold tissue concentrations were associated with the observed results. For juvenile coho salmon the 96-hr LC50 of Garlon4 was 0.84 mg/L.
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PMID:Sublethal and acute toxicity of the ethylene glycol butyl ether ester formulation of triclopyr to juvenile coho salmon (Oncorhynchus kisutch). 238 16

Pregnant rats were exposed by inhalation to vapor concentrations of 100, 200, 400 or 800 ppm of ethylene glycol monopropyl ether acetate on days 6 through 15 of gestation. Concentrations of 400 and 800 ppm reduced the feed intake, mean body weight and red blood cell counts. Mean corpuscular volume and mean corpuscular hemoglobin were increased. Clinical signs of toxicity included lethargy and red discolored urine in the dams exposed to 400 or 800 ppm. The incidence of resorptions was significantly increased and the mean fetal body weight was reduced in litters of dams exposed to 800 ppm. Reproductive indices were not affected. Examinations at cesarean section revealed no major external malformations. Internal soft tissue examinations revealed three fetuses with a cardiovascular defect consisting of a right-sided aortic arch. Two of these fetuses were from dams exposed to 800 ppm, while the third was from a control litter. Skeletal examinations revealed no major skeletal malformations, while minor rib anomalies were slightly increased in litters from dams exposed to 400 or 800 ppm of ethylene glycol monopropyl ether acetate. The incidence of common skeletal variants was slightly increased at 200 ppm.
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PMID:Developmental toxicity of ethylene glycol monopropyl ether acetate (EGPEA) in the rat. 649 10

A fatal case of poisoning by a mixture of methanol and ethylene glycol is described. A 72-year-old man was hospitalized when he was found stuporous to semicomatose, and despite massive bicarbonate therapy, died 36 hr after the admission. While the presence of numerous oxalate crystals in urine strongly suggested ethylene glycol intoxication, the GC analysis of the liquid the patient ingested revealed that he presumably drunk about 150 to 200 ml of a mixture of methanol (80%) and ethylene glycol (20%), the amount well over the lowest lethal dose when the additiveness of toxicity was considered. Retrospective evaluation of the signs suggested that while some of them such as oxalate crystalluria, elevated CPK, hypocalcemia, renal failure are attributable to the toxicity of ethylene glycol, others including elevated serum amylase and cyanosis are indicative of methanol poisoning. Disturbed consciousness was considered to be of metabolic origin; the high anion gap observed (38.2 mEq/liter) may be due not only to lactic acidosis but also to acidogenicity of the two chemicals ingested. The importance of gas chromatographic analysis for identification of the causative chemical(s) is stressed.
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PMID:A case of poisoning by a mixture of methanol and ethylene glycol. 667 Jan 3

Alcoholics are predisposed to certain metabolic disorders that cause stupor and coma. These entities include acute ethanol intoxication, ethanol-induced hypoglycemia, alcoholic ketoacidosis, ethylene glycol and methanol intoxications, thiamine deficiency, and hepatic encephalopathy. The recognition and management of these entities and the evaluation of stuporous alcoholics are discussed.
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PMID:Saturday Conference: stuporous alcoholics: metabolic considerations. 704 Dec 82

A 36-year-old man with a history of depression presented to the emergency department after ingesting approximately 3,000 mL of ethylene glycol antifreeze in a suicide attempt. The patient's ethylene glycol concentration, 1,889 mg/dL, was higher than any level previously documented in the medical literature. Although his course was complicated by nausea, emesis, lethargy, metabolic acidosis, and kidney failure, the patient survived without persistent kidney failure or other chronic problems. Sustained hemodialysis and ethanol infusion were instituted in the ED, on the basis of the patient's history, before laboratory confirmation of the ingestion was obtained.
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PMID:Emergency department hemodialysis in a case of severe ethylene glycol poisoning. 986 97

2-Butoxyethanol is a member of a family of ethylene glycol monoalkyl ethers. It is used extensively as a solvent in surface coatings such as lacquers, enamels, varnishes, and latex paint; in paint thinners, paint stripping formulations, and inks; and in degreasers and industrial and household cleaners. 2-Butoxyethanol was nominated for study because of its widespread use in industrial and consumer applications, the potential for exposure to workers and the general population, and the absence of chronic toxicity data. Male and female F344/N rats and B6C3F1 mice were exposed to 2-butoxyethanol (greater than 99% pure) by inhalation (primary route of human exposure) for 14 weeks or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and the bone marrow of male F344/N rats and B6C3F1 mice. 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were exposed to 2-butoxyethanol by inhalation at concentrations of 0, 31, 62.5, 125, 250, or 500 ppm, 6 hours per day, 5 days per week for 14 weeks. One female rat in the 250 ppm group was killed moribund during week 8; four females in the 500 ppm group were killed moribund during week 1 and one during week 5. Final mean body weights of females exposed to 500 ppm were significantly less than those of the chamber controls. Clinical findings included abnormal breathing, pallor, red urine stains, nasal and eye discharge, lethargy, and increased salivation and/or lacrimation. Due to vascular thrombosis and infarction in the tail vertebrae of 500 ppm female rats, the tails became necrotic and either sloughed off or were chewed off. The primary effect on the hematopoietic system was an anemia characterized as macrocytic, normochromic, and regenerative in males exposed to 125 ppm or greater and, to a greater extent, in all exposed groups of females. Compared to the chamber controls, kidney weights of males exposed to 500 ppm and females exposed to 125 ppm or greater and liver weights of males exposed to 250 or 500 ppm and females exposed to 125 ppm or greater were significantly increased, and thymus weights of females exposed to 500 ppm were significantly less. In female rats killed moribund, there was considerable histologic evidence of thrombosis in tissues and organs including the nasal cavity, incisors, liver, lung, and heart. In addition to thrombosis, infarction occurred in the vertebrae of the tail resulting in necrosis and loss of the distal portion of the tail. There were also inflammation, necrosis, and ulceration of the forestomach; necrosis and centrilobular degeneration of the liver; renal tubule degeneration; and atrophy of the spleen and thymus. Exposure-related increases in the incidences of Kupffer cell pigmentation, forestomach inflammation and epithelial hyperplasia, bone marrow hyperplasia, splenic hematopoietic cell proliferation, and renal tubule pigmentation were observed in male and/or female rats surviving to the end of the study. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were exposed to 2-butoxyethanol by inhalation at concentrations of 0, 31, 62.5, 125, 250, or 500 ppm, 6 hours per day, 5 days per week for 14 weeks. Two male and two female mice exposed to 500 ppm died and two males and two females were killed moribund during the first 2 weeks of the study. Final mean body weights of 125, 250, and 500 ppm male mice were significantly less than those of the chamber controls. Clinical findings were observed only in 500 ppm males and females that died or were killed moribund and included abnormal breathing, red urine stains, and lethargy. Hematologic evaluation indicated an anemia that was characterized as normocytic, normochromic, and regenerative in mice exposed to 62.5 ppm or greater; the anemia was more pronounced in females. Liver weights of males exposed to 500 ppm were significantly greater than the chamber controls. In mice either dying early or killed moribund, there were inflammation, necrosis, and ulceration of the forestomach; mediastinal pleura and peritoneal inflammationmmation associated with the forestomach lesions; liver necrosis; renal tubule degeneration; atrophy of the spleen, thymus, and mandibular and mesenteric lymph nodes; and degeneration of the testis. Exposure-related increases in the incidences of hematopoietic cell proliferation and hemosiderin pigmentation of the spleen, Kupffer cell hemosiderin pigmentation of the liver, inflammation and epithelial hyperplasia of the forestomach, and renal tubule hemosiderin pigmentation occurred in male and/or female mice surviving to the end of the study. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were exposed to 2-butoxyethanol by inhalation at concentrations of 0, 31.2, 62.5, or 125 ppm, 6 hours per day, 5 days per week for 104 weeks. For hematology and bone marrow analyses, additional groups of 27 male and 27 female rats were exposed to 0, 62.5, or 125 ppm for evaluation at 3, 6, and 12 months and nine male and nine female rats were exposed to 31.2 ppm for evaluation at 3 (hematology only) and 6 months. Survival and Body Weights: Survival of exposed male and female rats was similar to the chamber control groups. The mean body weights of females exposed to 125 ppm were generally less than the chamber control group. Hematology and Bone Marrow Cellularity: The most consistent exposure-related effect on the hematopoietic system was an exposure concentration-related mild macrocytic, normochromic, regenerative anemia present at 3, 6, and 12 months, with females more affected than males. Significant increases in bone marrow cellularity and decreases in the myeloid/erythroid ratio relative to the chamber controls were observed at all time points in females exposed to 125 ppm, and a decrease in the myeloid/erythroid ratio was observed in males exposed to 125 ppm at 12 months. Pathology Findings: The incidence of benign or malignant pheochromocytoma (combined) of the adrenal medulla in females exposed to 125 ppm was not significantly increased compared to the chamber controls but exceeded the historical control range. Exposure-related increases in the incidences of hyaline degeneration of the olfactory epithelium and Kupffer cell pigmentation of the liver were observed in male and female rats. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were exposed to 2-butoxyethanol by inhalation at concentrations of 0, 62.5, 125, or 250 ppm, 6 hours per day, 5 days per week for 104 weeks. For hematology and bone marrow analyses, additional groups of 30 male and 30 female mice were exposed to 0, 62.5, 125, or 250 ppm for evaluation at 3, 6, and 12 months. Survival and Body Weights: Survival of male mice exposed to 125 or 250 ppm was significantly less than that of the chamber control group. The mean body weights of exposed males were generally less than those of the chamber control group during the last 6 months of the study. The mean body weights of exposed female mice were less than those of the chamber control group; the reductions were greater and occurred earlier than those observed in males. Hematology: The most consistent exposure-related effect on the hematopoietic system was an exposure concentration-related minimal normocytic, normochromic, regenerative anemia present at 3, 6, and 12 months, with females affected slightly more than males. Pathology Findings: In females exposed to 250 ppm, incidences of forestomach squamous cell papilloma and squamous cell papilloma or carcinoma (combined) were significantly increased relative to the chamber controls, and these incidences exceeded the ranges in historical chamber controls. In 2-butoxyethanol exposed males, there were possible exposure-related increases in the incidences of squamous cell papilloma of the forestomach, although the increases were not significant and the incidences were within the historical control range for chamber controls. Accompanying these neoplasms in females and, to a lesser extent, in males were exposure-related increases in the incidences of ulcer and epithelial hyperplasia of the forestomach. In male mice exposed to 250 ppm, the incidence of hemangiosarcoma of the liver was significantly increased relative to chamber controls and exceeded the range in historical controls; in addition, there were possible exposure-related increases in the incidence of hepatocellular carcinoma. Incidences of hemosiderin pigmentation in the Kupffer cells were significantly increased in 125 and 250 ppm males and all exposed groups of females. The incidences of splenic hematopoietic cell proliferation and hemosiderin pigmentation were generally increased in males and females, and the incidences of bone marrow hyperplasia were increased in males. The incidences of hyaline degeneration of the olfactory and respiratory epithelia of the nose were increased in female mice. GENETIC TOXICOLOGY: 2-Butoxyethanol did not induce mutations in any of the S. typhimurium strains tested, with or without induced hamster or rat liver S9. 2-Butoxyethanol induced cycle delay but did not induce either sister chromatid exchanges or chromosomal aberrations in cultured Chinese hamster ovary cells with or without S9. 2-Butoxyethanol did not induce micronuclei in bone marrow cells of male rats or mice administered the chemical by intraperitoneal injection three times at 24-hour intervals. CONCLUSIONS: Under the conditions of these 2-year inhalation studies, there was no evidence of carcinogenic activity of 2-butoxyethanol in male F344/N rats exposed to 31.2, 62.5, or 125 ppm. There was equivocal evidence of carcinogenic activity of 2-butoxyethanol in female F344/N rats based on the increased combined incidences of benign or malignant pheochromocytoma (mainly benign) of the adrenal medulla. There was some evidence of carcinogenic activity of 2-butoxyethanol in male B6C3F1 mice based on increased incidences of hemangiosarcoma of the liver. A marginal increase in the incidences of forestomach squamous cell papilloma and an increase in the incidences of hepatocellular carcinoma may have been exposure related. There was some evidence of carcinogenic activity of 2-butoxyethanol in female B6C3F1 mice based on increased incidences of fore stomach squamous cell papilloma or carcinoma (mainly papilloma). Increased incidences of forestomach neoplasms in male and female mice occurred in groups in which ulceration and hyperplasia were also present. Exposure to 2-butoxyethanol caused a mild regenerative anemia and effects secondary to the anemia. Synonyms: 2-Butoxy-1-ethanol; m-butyl ether; butyl glycol; ethylene glycol monobutyl ether Trade name: Butyl Cellosolve
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PMID:NTP Toxicology and Carcinogenesis Studies 2-Butoxyethanol (CAS NO. 111-76-2) in F344/N Rats and B6C3F1 Mice (Inhalation Studies). 1257 79

We report a case of anaphylactoid shock occurring immediately after the initiation of second intravenous administration of high-dose immunoglobulin (IVIg) in a patient with Crow-Fukase syndrome. The patient was a 57-year-old woman, who was admitted to our hospital because of numbness and muscle weakness in the four extremities, difficulty in walking, and foot edema. On admission, her skin was dry and rough, and also showing scattered pigmentation, small hemangiomas, and hypertrichosis in both legs. She had distal dominant muscle weakness, more prominent in her legs, and was not able to walk. Deep tendon reflexes in her four extremities were markedly diminished or absent. She had a glove and stocking type of paresthesia, severe impairment of vibration, and absence of joint position sensation in her four extremities. On laboratory data, serum vascular endothelial growth factor (VEGF) was markedly elevated to 5,184 pg/ml (normal: below 220 pg/ml). Cerebrospinal fluid examination revealed cell counts of 2/microliter and protein level of 114 mg/dl. Abdominal echo showed marked hepatosplenomegaly. On peripheral nerve conduction study, both motor and sensory conduction velocity were undetectable in her legs. We diagnosed her condition as Crow-Fukase syndrome, and started IVIg of polyethyleneglycol-treated gamma-globulin (PEG-glob) at 400 mg/kg/day for 5 consecutive days for polyneuropathy. Since the first IVIg mildly improved muscle weakness, we tried the second IVIg of PEG-glob. However, immediately after the initiation of second IVIg of PEG-glob, she developed hypotention, dyspnea, cold sweating, cyanosis, and became lethargic. We immediately stopped IVIg and started first-aid treatment with epinephrine and corticosteroid for these symptoms. This treatment was successful and the patient fully recovered without any sequelae. Since serum IgE level remained unchanged and lymphocyte stimulation test (LST) was positive against the same rot number of PEG-glob, we diagnosed these symptoms as anaphylactoid shock. Based on the results of LST, we speculated that PEG-glob was the causative agent of anaphylactoid reaction. Anaphylactic or anaphylactoid reaction as adverse effects of IVIg is very rare, and to our knowledge, there are only 4 previous reports of anaphylactic or anaphylactoid reaction caused by IVIg. Therefore, we speculated that the prominent high level of serum VEGF in the present patient might play a significant contributory role in the development of anaphylactoid shock, since the vascular permeability of VEGF is 50,000 times stronger than that of histamine. We consider that it is necessary to carefully monitor IVIg of PEG-glob administration for polyneuropathy in patients with high level of serum VEGF, like Crow-Fukase syndrome.
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PMID:[A case of anaphylactoid shock occurring immediately after the initiation of second intravenous administration of high-dose immunoglobulin (IVIg) in a patient with Crow-Fukase syndrome]. 1450 55


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