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)

Although consequences of zinc deficiency have been recognized for many years, it is only recently that attention has been directed to the potential consequences of excessive zinc intake. This is a review of the literature on manifestations of toxicity at several levels of zinc intake. Zinc is considered to be relatively nontoxic, particularly if taken orally. However, manifestations of overt toxicity symptoms (nausea, vomiting, epigastric pain, lethargy, and fatigue) will occur with extremely high zinc intakes. At low intakes, but at amounts well in excess of the Recommended Dietary Allowance (RDA) (100-300 mg Zn/d vs an RDA of 15 mg Zn/d), evidence of induced copper deficiency with attendant symptoms of anemia and neutropenia, as well as impaired immune function and adverse effects on the ratio of low-density-lipoprotein to high-density-lipoprotein (LDL/HDL) cholesterol have been reported. Even lower levels of zinc supplementation, closer in amount to the RDA, have been suggested to interfere with the utilization of copper and iron and to adversely affect HDL cholesterol concentrations. Individuals using zinc supplements should be aware of the possible complications attendant to their use.
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PMID:Zinc toxicity. 240 97

Copper poisoning developed in 1 adult and 3 juvenile llamas after excessive dietary intake of copper resulted in an incorrect copper:molybdenum ratio. Total dietary copper was determined to be 36 mg/kg of feed, with a copper:molybdenum ratio of 16.6:1. Clinical signs associated with the toxicosis included acute onset of anorexia and lethargy. Liver enzyme activities (aspartate amino transaminase, lactate dehydrogenase, gamma-glutamyl transferase) and serum copper concentration were high in specimens obtained within 48 hours before death. Gross necropsy findings were limited to mild hepatomegaly. Histologically, hepatic lesions included acute massive necrosis of hepatocytes with and without bile duct proliferation, double hepatic plates with loss of orientation, anisocytosis, anisokaryosis, and an intralobular mosaic pattern of necrosis involving half of the hepatocytes. Analysis of hepatic copper concentrations suggested that juvenile llamas develop signs of poisoning at lower hepatic copper concentrations, compared with adults.
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PMID:Copper poisoning in four llamas. 279 84

Zinc is essential for many metabolic and enzymatic functions in man. Deficiency of zinc in man has now been recognized to occur not only as a result of nutritional factors, but also in various disease states, including malabsorption syndromes, acrodermatitis enteropathica, Crohn's disease, alcoholism and cirrhosis of the liver. The deficiency state in human subjects exists as a spectrum extending from mild to severe degree. The clinical manifestations of mild zinc deficiency include oligospermia, weight loss and hyperammonaemia. Moderate zinc deficiency is characterized clinically by growth retardation, hypogonadism in males, skin changes, poor appetite, mental lethargy, delayed wound healing, taste abnormalities and abnormal dark adaptation. In severe zinc deficiency states, bullous-pustular dermatitis, alopecia, diarrhoea, emotional disorders, weight loss, intercurrent infections, hypogonadism in males and, if unrecognized, death have been observed. Zinc is needed for the functions of over 100 enzymes. It is essential for DNA, RNA and protein synthesis and, as such, is important for cell division. Zinc is an inducer of mRNA of metallothionein, a protein which may have an important role in the regulation of intestinal zinc absorption. Zinc has a specific effect on testes in animals and man. Recent reports indicate that in human subjects thymopoietin may be zinc dependent and in animal studies somatomedin may be affected adversely due to dietary zinc restriction. Zinc plays an important role in the protection of cell membrane integrity and may be protective against free radical injury. Zinc is known to compete with cadmium, lead, copper, iron and calcium for similar binding sites. In the future, a potential use of zinc may be to alleviate toxic effects of cadmium and lead in human subjects. Recent evidence suggests that thymic-dependent lymphocytes (T cells are zinc dependent. T-helper and suppressor cells, T-effector cells and T-natural killer cells appear to be zinc dependent. Zinc is also essential for some of the neutrophil functions. Thus, it appears that zinc may play an important role in immunity. One may suggest that some of the clinical features of cirrhosis of the liver, such as testicular atrophy, loss of body hair, night blindness, poor wound healing, poor appetite, susceptibility to infections and enhanced sensitivity to drugs, may be related to conditioned deficiency of zinc, future studies are required to determine whether or not zinc supplementation is beneficial to these patients.
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PMID:The role of zinc in gastrointestinal and liver disease. 661 39

Bile duct obstruction was induced in 6 cats by surgical ligation and transection of the common bile duct. Clinical and laboratory changes were monitored weekly for 25 to 54 days. Clinical signs of obstruction were similar in all cats and included anorexia, pyrexia, lethargy, intermittent vomiting, weight loss, palpable gallbladder, hepatomegaly, and bleeding tendencies. Tissue jaundice and acholic feces were evident grossly as early as postsurgical day (PSD) 4 with a mean onset of jaundice at PSD 5.3 +/- 0.4. Hematologic changes were initially characterized by a mild neutrophilic leukocytosis that increased with the chronicity of bile duct obstruction. Regenerative anemia developed in 4 cats associated with gastrointestinal blood loss. Acute serum biochemical changes were characterized by a marked increase in the mean values of aspartate aminotransferase, alanine aminotransferase, total cholesterol, and copper. Comparatively, only moderate increases in mean serum alkaline phosphatase activity were observed. Mean total bilirubin values increased remarkably at postsurgical week (PSW) 1, reaching a maximal value of 23.1 +/- 4.4 mg/dl at PSW 3 with 71.6 +/- 2.7% direct bilirubin. With chronicity of bile duct obstruction ranging from PSW 3 to PSW 7, the mean serum values of aspartate aminotransferase, alanine aminotransferase, total cholesterol, serum alkaline phosphatase, and total and direct bilirubin stabilized and then declined, whereas the increased mean serum copper values persisted. At PSD 25 to 54, hepatic copper values and serum bile acids were markedly increased. Seemingly, clinicopathologic changes of induced cholestatic hepatic injury depended largely on the duration of biliary obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hematologic and biochemical abnormalities associated with induced extrahepatic bile duct obstruction in the cat. 663 41

The total content of zinc in the adult human body averages almost 2 g. This is approximately half the total iron content and 10 to 15 times the total body copper. In the brain, zinc is with iron, the most concentrated metal. The highest levels of zinc are found in the hippocampus in synaptic vesicles, boutons, and mossy fibers. Zinc is also found in large concentrations in the choroid layer of the retina which is an extension of the brain. Zinc plays an important role in axonal and synaptic transmission and is necessary for nucleic acid metabolism and brain tubulin growth and phosphorylation. Lack of zinc has been implicated in impaired DNA, RNA, and protein synthesis during brain development. For these reasons, deficiency of zinc during pregnancy and lactation has been shown to be related to many congenital abnormalities of the nervous system in offspring. Furthermore, in children insufficient levels of zinc have been associated with lowered learning ability, apathy, lethargy, and mental retardation. Hyperactive children may be deficient in zinc and vitamin B-6 and have an excess of lead and copper. Alcoholism, schizophrenia, Wilson's disease, and Pick's disease are brain disorders dynamically related to zinc levels. Zinc has been employed with success to treat Wilson's disease, achrodermatitis enteropathica, and specific types of schizophrenia.
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PMID:Zinc, the brain and behavior. 708 16

We studied the clinical histories of four white American siblings who died at 41/2 to six years of age of an unknown form of cirrhosis, in an effort to identify the etiologic factors in this familial syndrome. The family history disclosed no Indian heritage or parental consanguinity. The children were born and raised in New Jersey. Each had been well until progressive lethargy, abdominal swelling, jaundice, and fever developed four to seven months before death. The liver histopathology in each case closely resembled that of Indian childhood cirrhosis and included severe panlobular liver-cell swelling with Mallory body formation, prominent pericellular fibrosis, "micro-micronodular" cirrhosis, and marked deposits of copper and copper-binding protein. Hepatic copper levels were as high as 2083 microgram per gram of tissue (normal, less than 50 microgram). A number of features distinguish this syndrome from Wilson's disease and familial cholestatic disorders of childhood. A genetically determined disturbance in copper metabolism appears to be the most likely cause.
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PMID:Hepatic copper overload and features of Indian childhood cirrhosis in an American sibship. 708 87

Copper deficiency was produced in weanling C57BL/6J and Hap:(ICR) mice that were fed a milk-sucrose based diet supplemented with appropriate vitamins, minerals, and amino acids. Growth retardation, decreased hematocrit, lethargy, dyspnea, achromotrichia, and high mortality (in ICR mice) were apparent in copper-deficient mice. Cardiac enlargement, hemopericardium, hemothorax, and pleural effusion were observed at necropsy. Thrombosis of the atria, myocardial degeneration and necrosis, and sites of myocardial rupture were observed at histopathologic examination.
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PMID:Experimental copper deficiency in laboratory mice. 714 21

A case history is reported of a 29-year old patient who presented with a chronic illness characterized by lethargy, back pain, fever, and anemia. Evaluation disclosed the presence of a large pelvic mass which was confirmed as a tubo-ovarian abscess at surgery. Histological evaluation demonstrated involvement by Actinomyces species. The patient's illness is discussed as a complication of chronic IUD usage with reference to specific management for this emerging problem. Data from the National Fertility Study conducted in 1973 revealed that nearly 2 million married women in the US, ages 15-44, were using IUDs. Scott noted the serious potentially fatal complications associated with IUD use, including pelvic inflammatory disease (PID), uterine perforation, ectopic pregnancy, and spontaneous or septic abortion. The relative risk of PID among IUD users has been reported to be increased 2-12 fold over controls. The risk of infection appears to increase as the period of IUD use lengthens, but the risk associated with the use of copper IUDs may be slightly less than with plastic IUDs. Actinomycosis has traditionally been described in 3 anatomical regions, the cervicofacial, thoracic, and abdominal areas, but pelvic and genital disease has been recognized with increasing frequency over the past decade. The common denominator associated with the latter syndrome appears to be the concurrent presence of an IUD. The Actinomyces are gram positive, nonacid fast, anaerobic, obligate parasites which are classified somewhere between the true bacteria and the complete fungi. Actinomyces species are not generally considered part of the normal vaginal flora but rather are associated with the presence of a foreign body, most often an IUD. It is thought that the IUD causes the initial tissue injury which permits subsequent colonization by these organisms. It is not known whether orogenital contact is a means of transmission of Actinomyces to the lower genital tract of sexual partners. One might estimate that the overall rate of cytological detection of A. israelii in cervical smears of IUD users at about 10%. This incidence increases sharply in patients being evaluated for symptomatic pelvic infection. Conversely, in women with IUDs in place and Actinomyces demonstrable in cervical smears, PID is up to 4 times as common as in those who have negative smears. Antibiotic treatment should probably be dictated by the clinical setting. As a general guide, the threshold for treatment should be low, since the therapy is relatively benign and the extent to which colonization and tissue invasion may have occurred is unknown.
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PMID:Pelvic actinomycosis and usage of intrauterine contraceptive devices. 718 22

Thirty-four adult ponies were used to determine the effects of single oral doses of copper (Cu) supplements (0, 20, and 40 mg of Cu/kg of body weight) on the toxicity of oral doses of selenium (Se) supplements (0, 2, 4, 6, and 8 mg of Se/kg of body weight) administered 24 hours after the copper was given. Signs of Se toxicosis-sweating, diarrhea, tachycardia, tachypnea, mild pyrexia, lethargy, and colic-developed in ponies given 6 and 8 mg of Se/kg of body weight without Cu pretreatment. Two of 4 ponies given 6 mg of Se/kg and both ponies given 8 mg of Se/kg without Cu pretreatment died within 36 hours after being given the Se. All ponies given either 20 or 40 mg of Cu/kg were unaffected by the subsequent Se supplement, regardless of dosage. The Cu pretreatment did not seem to inhibit absorption of Se, based on serum Se concentrations, but hastened the disappearance of the Se from the serum.
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PMID:Effects of copper pretreatment upon toxicity of selenium in ponies. 721 26

Two sexually intact female silver-shaded domestic ferret siblings from different litters were examined because of CNS depression and lethargy. Ferret 1 was dehydrated and hypothermic, whereas ferret 2 was icteric and febrile and had serum bilirubin concentration > 12.0 mg/dl and BUN of 59 mg/dl. Despite supportive treatment, the ferrets died within days of evaluation. On necropsy, ferret 1 had chronic hepatopathy, with diffuse vacuolation of hepatocytes. In ferret 2, the liver had centrilobular degeneration and necrosis, and hemoglobinuric nephrosis was evident, with hemoglobin in the renal tubules. In both ferrets, Kupffer's cells and macrophages contained eosinophilic material in the cytoplasm. Special staining revealed copper pigment in hepatocytes and phagocytic cells in both livers. Analysis of liver specimens revealed 850 and 700 ppm of copper in ferrets 1 and 2, respectively. Copper values > 200 ppm in liver are considered evidence of toxicosis in most animal species. Copper toxicosis was diagnosed on the basis of the findings from histologic examination of the liver and high hepatic copper values. Lack of related illness in 11 other ferrets in the same environment and fed the same diet, plus sibling relationship and same phenotypic coat color in the affected ferrets, suggested that these ferrets had an inherited defect in their ability to metabolize normal amounts of ingested copper.
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PMID:Copper toxicosis in sibling ferrets. 789 May 74


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