Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.1.1.49 (glucose-6-phosphate dehydrogenase)
 7,794 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyanosis in a 36 year old patient which persisted 20 years after a successful surgical closure of her patent foramen ovale has been finally diagnosed as due to congenital methemoglobinemia: a 28% level of methaemoglobin and no activity od NAD-dependent methaemoglobin reductase were found. Erythrocyte antioxidative system was studied i.e. glutathione peroxidase, reductase, transferase, superoxidase dismutase and glucose-6-phosphate dehydrogenase. Increased activity was disclosed of superoxide dismutase and glucose-6-phosphate dehydrogenase in erythrocytes in comparison to normal individuals as well as increased concentration of lipid peroxidation products coexisting with methaemoglobin reductase deficiency.
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PMID:[Congenital methemoglobinemia found in an adult. Case report]. 749 53

1. Endosulfan insecticide is a polychlorinated compound used for controlling a variety of insects; it is practically water-insoluble, but readily adheres to clay particles and persists in soil and water for several years. Its mode of action involves repetitive nerve-discharges positively correlated to increase in temperature. This compound is extremely toxic to most fish and can cause massive mortalities. In fish, it causes marked changes in Na and K concentrations, decrease in blood Ca(2+) and Mg levels and inhibits Na, K and Mg-dependent ATPase (in brain). 2. Bioaccumulation of endosulfan is reported for marine animals; however, freshwater animals (e.g., crayfish) accumulate it to some extent, but they lose the compound rapidly during depuration. Endosulfan is generally less toxic to aquatic invertebrates than fish. However, it causes decreases in adenylate energy charge, oxygen consumption, hemolymph amino acids, succinate dehydrogenase, heart-beat (mussel) and altered osmoregulation. 3. Generally, mammals are less susceptible to endosulfan's toxicity than aquatic animals. The majority of studies conducted on laboratory mammals can be summarized. (a) Neurotoxicity: male rats are more sensitive than females to endosulfan, which decreases brain and plasma acetylcholinesterase activity. Endosulfan I (a metabolite) causes a significant change in norepinephrine, 5-HT and GABA. (b) Renal toxicity: inhibition of MFOs activity was noticed in rats; other effects included changes in proximal convoluted tubules and necrosis of the tubular epithelium. (c) Hepatotoxicity: chemically-induced aminopyrine N-demethylase and aniline hydrolase were found in rat liver, and reduction in the glycogen level occurred. (d) Hematologic toxicity: endosulfan exposure resulted in a significant decrease in the level occurred. (d) Hematologic toxicity: endosulfan exposure resulted in a significant decrease in the erythrocyte glutathione reductase, hemoglobin amount, RBC number and mean corpuscular volume. 4. Respiratory toxicity: involved dyspnea, acute emphysema, cyanosis and hemorrhages in teh interalveolar portions of rat's lungs. 5. Biochemical: in rats, endosulfan caused increased glucose-6-phosphate dehydrogenase activity, blood glucose level, phospholipid contents of the microsomal and surfactant system, and profoundly induced the activity of alcohol dehydrogenase and cytosolic glutathione S-transferases. It also decreased significantly Na+, K+ and Mg(2+) ATPases, plasma calcium level and alkaline phosphatase in the intestinal epithelium. 6. Immunologic toxicity: rat serum antibody titer to tetanus toxin, IgG, IgM and gammaglobulins were significantly reduced. 7. Reproductive toxicity: degenerative changes in the seminiferous epithelium, induction of the rate-limiting enzyme in testosterone production (3beta-hydroxysteroid transferase and 17 beta-hydroxysteroid transferase), histological changes in reproductive organs, testicular atrophy and the occurrence of ovarian cysts were noticed in rat. Reduction in the weight of secondary sex organ was also observed.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Bioaccumulative potential and toxicity of endosulfan insecticide to non-target animals. 790 Sep 59

In normal erythrocytes, small quantities of methaemoglobin are formed constantly and are continuously reduced, almost entirely by the reduced nicotine adenine dinucleotide (NADH) diaphorase system, rather than the reduced nicotine adenine dinucleotide phosphate (NADPH) diaphorase system. Methaemoglobinaemias are usually the result of xenobiotics, either those that may directly oxidise haemoglobin or those that require metabolic activation to an oxidising species. The most clinically relevant direct methaemoglobin formers include local anaesthetics (such as benzocaine and, to a much lesser extent, prilocaine) as well as amyl nitrite and isobutyl nitrite, which have become drugs of abuse. Indirect, or metabolically activated, methaemoglobin formation by dapsone and primaquine may cause adverse reactions. The clinical consequences of methaemoglobinaemia are related to the blood level of methaemoglobin; dyspnoea, nausea and tachycardia occur at methaemoglobin levels of > or = 30%, while lethargy, stupor and deteriorating consciousness occur as methaemoglobin levels approach 55%. Higher levels may cause cardiac arrhythmias, circulatory failure and neurological depression, while levels of 70% are usually fatal. Cyanosis accompanied by a lack of responsiveness to 100% oxygen indicates a diagnosis of methaemoglobinaemia, which should be confirmed using a CO-oximeter. Pulse oximeters do not detect methaemoglobin and may give a misleading impression of patient oxygenation. Methaemoglobinaemia is treated with intravenous methylene blue (methyl-thioninium chloride; ;1 to 2 mg/kg of a 1% solution). If the patient does not respond, perhaps because of glucose-6-phosphate dehydrogenase (G6PD) deficiency or continued presence of toxin, admission to an intensive care unit and exchange transfusion may be required. Dapsone-mediated chronic methaemoglobin formation can be reduced by coadministration of cimetidine to aid patient tolerance. Increasing knowledge and awareness of drug-mediated acute methaemoglobinaemia among physicians should lead to prompt diagnosis and treatment of this potentially life-threatening condition.
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PMID:Drug-induced methaemoglobinaemia. Treatment issues. 882 17

Methaemoglobinemia is a rare condition and can give surprise in emergency setup. We have encountered one such case in emergency recently that presented with both peripheral and central cyanosis without cardio-respiratory compromise. The patient was confirmed to be suffering from methaemoglobinemia due to antimalarials that he had received before coming to the hospital. Cyanosis due to methaemoglobinemia in our patient was precipitated by concomitant glucose 6-phosphate dehydrogenase (G6PD) deficiency. The patient was managed with conservative management and vitamin C administration.
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PMID:Cyanotic child--can it be methaemoglobinemia? 1292 26

Acute ingestion of copper sulfate has been reported to cause gastrointestinal injury, hemolysis, methemoglobinemia, hepatorenal failure, shock; or even death. The toxicity of organocopper compounds, however, remains largely unknown. A 40-y-old man attempted suicide by ingesting some 50 ml of Sesamine fungicide. He immediately developed headache, vomiting and abdominal pain, followed by progressive dyspnea, cyanosis, dark urine and diarrhea. Severe methemoglobinemia and hemolysis were documented, and treatment with ascorbic acid and hydration was commenced. He was referred to our service 3 d later for methylene blue treatment. Despite the above treatment, his symptomatology persisted and it was not until 5 d post-ingestion that the implicated fungicide was identified as copper-8-hydroxyquinolate. BAL therapy and plasma exchange were instituted, which decreased his plasma hemoglobin from 1,300 mg/dL to 29.1 mg/dL, and lowered his methemoglobin level from 20.9% to 1.1%. His serum and urine copper concentration dropped from 238 microg/dL to 96 microg/dL and from 112 microg/dL to 16 microg/dL, respectively. He was discharged uneventfully 18 d post-ingestion. Pre-existing glucose-6-phosphate dehydrogenase (G6PD) deficiency as well as copper-induced inhibition of G6PD activity was documented during hospitalization. Organocopper compounds may cause prolonged hemolysis and methemoglobinemia through oxidative stress, especially among patients with G6PD deficiency. Antidotal therapy with methylene blue is not likely to be effective in this setting: treatment with intensive supportive measures and other therapeutic options, such as plasma exchange, should be sought.
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PMID:Prolonged hemolysis and methemoglobinemia following organic copper fungicide ingestion. 1558 50

Rasburicase is frequently used in tumor lysis syndrome (TLS). Although it is very well tolerated, it can cause severe oxidative hemolytic anemia and methemoglobinemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We report another case of rasburicase-induced methemoglobinemia in a patient with previously unrecognized G6PD deficiency and review the cases of methemoglobinemia and oxidative hemolysis reported in the literature to date. Patients from ethnicities in which G6PD deficiency is prevalent at high risk of TLS should be screened for G6PD deficiency prior to administration of rasburicase where practical. Asymptomatic decrease in oxygen saturation by oximetry and cyanosis are signs of methemoglobinemia; patients recover with conservative measures including supplemental oxygen and packed red cell transfusion.
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PMID:Rasburicase causing severe oxidative hemolysis and methemoglobinemia in a patient with previously unrecognized glucose-6-phosphate dehydrogenase deficiency. 2386 May 72

Rasburicase is indicated for the prevention and treatment of tumor lysis syndrome which can be a potentially life-threatening emergency. The drug has oxidizing potential and as an adverse effect, it can convert the ferrous form of iron in erythrocytes to its ferric form resulting in the formation of methemoglobin which makes the heme component incapable of carrying oxygen. Patients with glucose-6-phosphate dehydrogenase enzyme deficiency are at high risk of methemoglobinemia from oxidizing agents. Symptoms of methemoglobinemia range from none to life-threatening hypoxemia, cyanosis and respiratory compromise. Treatment is indicated at levels above 20% and at lower levels if the patient is significantly anemic. We present a case of a 60-year-old male with diffuse large B cell lymphoma at high risk of tumor lysis syndrome. Rasburicase was administered to prevent renal failure and further rise in uric acid. Twenty-four hours later, a bedside pulse oximetry showed an oxygen saturation ranging from 60 to 65% with minimal cyanosis. Co-oximetry revealed a methemoglobin level of 9.8%. Methylene blue was administered and the methemoglobin level decreased to 2.6%. However, the patient developed hemolysis several hours later, likely secondary to rasburicase and methylene blue, requiring transfusion support. We discuss this potentially fatal and initially asymptomatic adverse effect of rasburicase along with diagnostic and treatment considerations, and review the cases described in the current literature.
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PMID:Rasburicase-induced methemoglobinemia: The eyes do not see what the mind does not know. 2834 92