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)

In contrast to its lethargy at physiological pH, horse heart cytochrome c can be oxidized at room temperature by the axial inner sphere oxidant bromomalononitrile (BMN) at higher acidities. The following stoichiometry obtains: 2Fe11 c + BrCH(CN2) + H+ leads to 2FeIII c + CH2(CN)2 + Br-, and the rate law is given by: rate = k2(FeIIc)(BMN). At an ionic strength of 1.0 (KCl), second-order rate constants vary from 300 l. per mol per sec (pH 2-3) to 0(pH 9). Below pH 6 there is a noticeable increase in rate with ionic strength while there is no specific salt effect for the process. At pH 7.4 there is no influence of added salt (0.01-1.0 M) upon the slow rate of reaction. The vast changes in rate occur over a pH region (3-6) in which only very minor changes in the visible spectrum of the cytochrome are manifest. The results are interpreted in terms of a conformational isomerism of cytochrome c in which the effective redox geometry alters from a predominantly "short C" form (in which an axial position is available for substitution) at lower pH's to a predominantly "C" form (axial positions encumbered) in the physiological region. At 5 degrees, pH 7.4, both hemes of beef heart cytochrome oxidase are oxidized by the addition of BMN (k2 = 29 plus or minus 3 l. per mol per sec). However, the reaction is inhibited by potassium cyanide and the protein containing iron(II) cyt alpha along with the cyano adduct of iron(II) or iron(III) cyt alpha3 is inert. The results demonstrate cytochrome alpha3 as the site of reaction and that alpha reduces alpha3 in the process. Cytochrome oxidase does catalyze the oxidation of cytochrome c with BMN as substrate. Taken together the results provide additional support for a recent theory and they demonstrate BMN to be an efficient probe for the effective redox geometry of a hemoprotein in solution.
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PMID:Conformational isomerism and effective redox geometry in the oxidation of heme proteins by alkyl halides, cytochrome c, and cytochrome oxidase. 23 44

Chronic renal failure is almost invariably accompanied by symptomatic anemia. It has been demonstrated that the primary cause of this anemia is inadequate production of erythropoietin by the diseased kidneys. The isolation of erythropoietin, followed by the cloning and expression of the human erythropoietin gene, made possible clinical trials of rHuEPO in uremic patients. rHuEPO produced dramatic increases in the hematocrit in almost all patients treated and also ameliorated many symptoms, such as lethargy, dizziness, and poor appetite, that had long been attributed to the effect of uremic toxins. Adverse effects of treatment with rHuEPO noted in the early clinical trials included hypertension, seizures, arteriovenous fistula or shunt thrombosis, and hyperkalemia. Further study of rHuEPO has shown that many of these side effects may be no more frequent in patients receiving rHuEPO than in other uremic patients not receiving rHuEPO. Reduction of the rHuEPO dosage and subcutaneous administration produce less rapid increases in the hematocrit and may lessen the incidence and severity of these side effects. rHuEPO therapy places great demands on both the body's iron stores and the capacity to rapidly transfer iron from storage sites to the erythroid progenitor cells. Thus, almost all patients treated with rHuEPO become iron deficient and require oral or parenteral iron replacement. Response to rHuEPO in uremic patients is diminished if the anemia is complicated by iron deficiency, inflammatory disorders, aluminum overload, or deficiency of folate or vitamin B12. rHuEPO therapy is safe and effective in the treatment of the anemia of chronic renal failure. The use of rHuEPO leads to enhanced quality of life and eliminates the need for red cell transfusions. In addition to hemodialysis patients, predialysis patients and those on CAPD benefit from and are candidates for rHuEPO therapy.
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PMID:Anemia of renal failure. Use of erythropoietin. 157 66

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

Pneumatosis intestinalis (PI) is a well-recognized manifestation of necrotizing enterocolitis (NEC) in the newborn--a condition that often requires surgical intervention for infarcted bowel. However, little information is available concerning PI in older children or its management. Sixteen older infants and children (greater than 2 months) had x-ray findings of PI (intramural air). There were eight girls and eight boys ranging in age from 2 months to 8 years. Associated conditions included short bowel syndrome (SBS) (8), congenital heart disease (2), iron ingestion (1), nesidioblastosis (1), hemolytic anemia (1), rheumatoid arthritis (1), bronchopulmonary dysplasia (BPD) (1), and malrotation (1). Clinical presentation included abdominal distension (13), bloody diarrhea (12), bilious emesis (5), and lethargy (5). Two patients on steroids had unsuspected PI identified as an incidental operative finding during pancreatectomy for nesidioblastosis (1) and splenectomy for hemolytic anemia (1), respectively. Only four other children (iron toxicity, postcardiac catheterization, rheumatoid arthritis, and BPD required surgical intervention. Each manifested peritioneal irritation, acidosis, and hypotension or had pneumoperitoneum on abdominal x-ray. In ten of 14 patients, PI was managed nonoperatively with nasogastric suction, fluid resuscitation, intravenous (IV) antibiotics (seven to ten days), and repeated abdominal x-ray and physical examinations. Children with SBS comprised 50% of the total number of patients and eight of ten treated by observation. All had associated viral syndromes (rotavirus) or rhotozyme-positive stools and developed bloody diarrhea. There were two deaths (12.5%) in patients with iron toxicity and congenital heart disease who required resection of gangrenous bowel. All of the other patients survived.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pneumatosis intestinalis in children beyond the neonatal period. 267 35

Previous studies have shown that manganese (Mn) deficiency in rats results in reduced activity of manganese superoxide dismutase (MnSOD) and increased levels of mitochondrial lipid peroxidation. These findings suggested to us that the Mn-deficient rat may be especially susceptible to the toxic effects of ethanol, as the metabolism of this compound results in production of superoxide anion. Offspring from Mn-sufficient and Mn-deficient adult rats were given either 20% (wt/vol) ethanol or distilled-deionized water as their drinking fluid for 14 d. Response to ethanol feeding was different between Mn-sufficient and deficient rats as evidenced by severe reductions in caloric intake and body weight observed in the Mn-deficient rats. Furthermore, after 14 d of ethanol feeding, these rats were extremely lethargic and in poor physical condition. Although Mn-sufficient rats responded similarly to the deficient rats during the first 6 d of ethanol feeding, they increased their caloric intake and body weight during the remainder of the experimental period. MnSOD activity in the ethanol-fed Mn-sufficient and Mn-deficient rats was similar, thus the alcohol-induced toxicity observed in the deficient rats was not due to reduced MnSOD activity. Iron-induced lipid peroxidation may be one of the mechanisms leading to the toxicity observed, as ethanol feeding resulted in liver Fe levels that were 30% higher than those in Mn-deficient rats that were not fed ethanol.
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PMID:Manganese deficiency: effects on susceptibility to ethanol toxicity in rats. 398 Dec 64

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

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

Dietary cells and the vitamins B12 and folate are necessary for the production of the red blood cells (erythrocytes), which carry oxygen from the lungs to the tissues and carbon dioxide from tissues to lungs. Deficiency of either one results in anaemia, which is characterised by low haemoglobin concentration. Symptoms result from reduced tissue oxygenation and include weakness, lethargy, palpitation, headache and shortness of breath. The first-time laboratory test of all patients suspected of being anaemic is the full blood count. Results of a full blood count may suggest the anaemia is caused by a nutritional deficiency of B12 folate or iron. Laboratory measurement of the concentration in blood of iron and vitamin B12 and folate, along with several other tests described here, are useful in the differential diagnosis of the anaemic patients.
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PMID:Deficiency testing for iron, vitamin B12 and folate. 760 52

A 3.5-year-old male Golden Retriever with lethargy, generalized lymphadenopathy, and hepatosplenomegaly was determined to have malignant histiocytosis, based on the morphologic appearance of neoplastic cells by light and electron microscopic examination, evidence of erythrophagocytosis, the presence of diffuse nonspecific esterase activity, and immunohistochemical demonstration of vimentin intermediate filaments. Because of the appearance of abundant iron stores in the bone marrow, serum was obtained for determination of iron, total iron binding capacity, and ferritin values. Serum ferritin concentrations were markedly increased. Measurement of serum ferritin concentrations may be useful in supporting a diagnosis of malignant histiocytosis, and the monitoring of serum ferritin concentrations may be useful for assessing treatment and regression of the disease.
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PMID:Hyperferritinemia associated with malignant histiocytosis in a dog. 782 79

Haemochromatosis is one of the most common inborn errors of metabolism. In prospective epidemiological studies the frequency of haemochromatosis is 0.0037 (76/20333 subjects) for homozygotes which corresponds to a gene frequency of 0.061 and a frequency of heterozygotes of 0.115. Abnormality in liver function tests, weakness and lethargy, skin hyperpigmentation, diabetes mellitus, arthralgia, impotence and ECG abnormalities are the most frequent findings and symptoms at diagnosis. In recent years about 50% of patients were detected without having liver cirrhosis and 20% of patients did not have any symptoms and pathology except iron overload. Survival analyses in long-term studies showed that in the absence of cirrhosis and diabetes, iron removal by phlebotomy therapy prevents further tissue damage and guarantees a normal life expectancy. Patients with massive and long-lasting iron overload had a worse prognosis than those with less severe iron excess. Iron removal in general ameliorated liver disease, weakness and cardiac abnormalities, and also prevented the progression of endocrine alterations. Therapy, however, did not influence insulin-dependent diabetes. Most deaths in patients with hereditary haemochromatosis were caused by liver cancers which often occurred many years after complete iron removal. In patients with haemochromatosis, liver cirrhosis, cardiomyopathy, and diabetes mellitus are also significantly more frequent causes of deaths when compared with the general population. Further strategies have to evaluate the design of screening programmes in order to diagnose more patients in the precirrhotic and asymptomatic stage.
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PMID:Clinical spectrum and management of haemochromatosis. 788 Nov 58


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