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)

Nitrates are frequently found in vegetables and ground water. Nitrate levels in ground water have increased over the past two decades because of the heightened use of nitrogenous fertilizers. Following ingestion, nitrates are converted to nitrites by fecal organisms. Nitrites are absorbed and form methemoglobin, which interferes with the oxygen-carrying capacity of hemoglobin. Infants are particularly susceptible to nitrate poisoning because fetal hemoglobin is more readily oxidized to methemoglobin. In infants, the most common source of nitrate exposure is well water, which is mixed with infant formula. Affected infants may present with asymptomatic cyanosis, which can progress to dyspnea and lethargy or coma. Blood methemoglobin concentrations are elevated. Treatment consists of the administration of oxygen and intravenous and oral methylene blue.
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PMID:Methemoglobinemia: nitrate toxicity in rural America. 162 30

Four aluminum compounds--nitrate, chloride, sulphate and bromide--were administered orally and intraperitoneally to rats and mice. The LD50-values (14 days) were determined. The majority of deaths occurring during the first four days. The clinical and physical signs appearing after intoxication include among other lethargy, decreased locomotor activity, piloerection, weight loss and perorbital bleeding. After 14 days no alterations in liver and renal functions were detected in the animals which received intraperitoneally the LD50-values of aluminum nitrate as a single dose. Aluminum concentrations were highest in liver and spleen. No histopathological lesions could be observed. To compare the efficacies of nine chelating agents on the toxicity of aluminum in mice, the therapeutic index and the therapeutic effectiveness of each chelating agent have been calculated. Malic, succinic, oxalic and malonic acids showed the best results with malic and succinic acids being the most effective. Deferoxamine mesylate (DFOA), sodium salicylate, L-cysteine and citric acid were not so effective as antidotes for acute aluminum toxicity. Aurin tricarboxylic acid (ATCA) should not be used due to its high toxicity.
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PMID:Acute toxicity studies of aluminium compounds: antidotal efficacy of several chelating agents. 358 26

11 adult female dogs were given periodic intravenous injections of uranyl nitrate [UO2(NO3)2 . 6H2O] to create a syndrome of chronic uremia. Initially, dogs usually received 2.0 mg/kg of uranyl nitrate; subsequent doses were generally less. After the initial injection, there was an abrupt fall in creatinine clearance and rise in plasma urea nitrogen. Low and relatively constant creatinine clearances (10.2 +/- SD 2.7 ml/min) were easily maintained with further injections. Dogs developed proteinuria, aminoaciduria, weight loss, and plasma amino acid levels similar to those of chronically uremic humans and rats. With creatinine clearances of 4 ml/min or less, dogs became listless and lethargic, and daily activity and food intake decreased. Repeated injections of uranyl nitrate appear to be an easy and reliable method for creating a model of chronic uremia in dogs.
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PMID:Chronic uremia syndrome in dogs induced with uranyl nitrate. 736 Feb 99

We hypothesized that plasma nitric oxide (NO), generated via inducible NO synthase (iNOS) or endothelial constitutive NO synthase and measured via its by-products NO2- and NO3- (NO2- + NO3- = NOx) would increase and remain elevated during chronic peritoneal sepsis. We further hypothesized that treatment with aminoguanidine (AG; 50 mg/kg), a selective iNOS inhibitor, would decrease NO production and alter blood flow. Sprague Dawley rats were randomized to septic and nonseptic groups. Septic rats received an intraperitoneal cecal slurry (200 mg of cecal material/5 mL 5% dextrose-H2O/kg); control rats received sterile 5% dextrose-H2O (5 mL/kg) only. Plasma NOx and hemodynamics were measured 0, 4, 12, 24, and 48 h after sepsis or sham induction. We also examined the effect of AG, an iNOS inhibitor, on plasma NOx levels and tissue blood flow at 24 h. Septic rats uniformly displayed signs of sepsis, including lethargy, piloerection, and diarrhea. NOx levels were significantly elevated compared with controls at 4, 12, 24, and 48 h (p < or = .05). Septic rats also demonstrated hypotension (t = 12, 24, and 48 h) and tachycardia (t = 4, 12, 24, and 48 h). The infusion of AG (50 mg/kg intravenously for 30 min) at 24 h significantly decreased plasma NOx in septic animals. Plasma NOx concentrations returned to basal levels by 90 min after infusion of AG. In addition, blood flow studies demonstrated that AG treatment in nonseptic rats resulted in a significant decrease in blood flow to the stomach, skin, and adipose tissue, whereas AG infusion did not significantly alter the regional perfusion profile in septic animals. Furthermore, treatment with AG did not significantly alter mean arterial pressure in either group; however, nonseptic animals exhibited a decrease in stroke volume, and septic animals demonstrated an increase in heart rate. In contrast to the rise and fall of NOx levels in endotoxemia, this study demonstrates that the initial rise is sustained during 48 h of peritoneal sepsis. This sustained increase in NOx levels in this model correlated with the observable signs of systemic infection and may relate to enhanced iNOS activity. AG infusion demonstrated variable effects on regional tissue blood flow profiles in septic and nonseptic animals and attenuated the increase in plasma NOx levels in septic animals, an index of iNOS activity.
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PMID:Effect of aminoguanidine on plasma nitric oxide by-products and blood flow during chronic peritoneal sepsis. 956 58

The use of nitrate-contaminated drinking water to prepare infant formula is a well-known risk factor for infant methemoglobinemia. Affected infants develop a peculiar blue-gray skin color and may become irritable or lethargic, depending on the severity of their condition. The condition can progress rapidly to cause coma and death if it is not recognized and treated appropriately. Two cases of blue baby syndrome were recently investigated. Both cases involved infants who became ill after being fed formula that was reconstituted with water from private wells. Water samples collected from these wells during the infants' illnesses contained nitrate-nitrogen concentrations of 22.9 and 27.4 mg/L.
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PMID:Blue babies and nitrate-contaminated well water. 1117 32

Heart failure is associated with an increase in plasma nitrate and nitrite (NOx). To date there is still some controversy regarding the causes of nitrate accumulation during the development of heart failure. The goal of this study was to analyze the underlying mechanisms that cause accumulation of plasma nitrates during the development of heart failure in dogs. Dogs were chronically instrumented for measurement of hemodynamics and renal function. Hearts were paced initially at 210 bpm for 3 weeks and then at 240 until the development of heart failure. Hemodynamics, renal function, renal blood flow, arterial blood gases, hemoglobin, plasma and urine NOx levels, and creatinine levels were measured weekly. Heart failure was assessed by hemodynamic alterations, physical signs such as lethargy, ascites, cachexia, and postmortem evidence of cardiac hypertrophy. LVSP (from 127 +/- 3 to 106 +/- 3 mmHg), LV dP/dt (from 2658 +/- 173 to 1439 +/- 217 mmHg/s), MAP (from 101 +/- 1.9 to 83 +/- 1.8 mmHg) fell, whereas LVEDP tripled (from 6.4 +/- 0.9 to 20 +/- 2.6 mmHg), and heart rate rose (from 101 +/- 4.2 to 117 +/- 6.3 bpm), all changes P < 0.05. RBF (from 146 +/- 10 to 96 +/- 9.9 ml/min), urine output (V) (from 0.26 +/- 0.02 to 0.16 +/- 0.02 ml/min), GFR (from 63 +/- 1.8 to 49 +/- 2 ml/min), and Na excretion (from 45 +/- 4.5 to 14 +/- 4.6 microEq/min) all decreased (P < 0.05), whereas RVR increased (from 0.68 +/- 0.05 to 0.94 +/- 0.1 mmHg/ml/min). These changes took place during a rise in plasma NOx (from 3.7 +/- 0.5 to 16+/-3.3 microM), a decrease in urine NOx (from 33 +/- 9.9 to 8.1 +/- 4.9 microM), and a concurrent increase in NOx reabsorption (from 221 +/- 31 to 818 +/- 166 nmol/min). There was a direct correlation between the increase in plasma NOx levels and an increase in filtered load (r(2) = 0.97, P = 0.02), a negative correlation between NOx levels and NOx excretion (r(2) = 0.65 P < 0.09), and a direct correlation between plasma NOx levels and NOx reabsorption (r(2) = 0.97, P = 0.02). These results indicate that elevated plasma NOx during heart failure are most likely the result of an impairment of the renal function and not increased NOx production. Furthermore, without knowing changes in renal function the measurement of plasma NOx in and of itself is a meaningless index of NO formation.
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PMID:Plasma nitrate accumulation during the development of pacing-induced dilated cardiac myopathy in conscious dogs is due to renal impairment. 1117 32

Accumulation of long-chain 3-hydroxy fatty acids is the biochemical hallmark of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (MTP) deficiencies. These disorders are clinically characterized by neurological symptoms, such as convulsions and lethargy, as well as by cardiomyopathy and muscle weakness. In the present work we investigated the in vitro effect of 3-hydroxydodecanoic (3HDA), 3-hydroxytetradecanoic (3HTA) and 3-hydroxypalmitic (3HPA) acids, which accumulate in these disorders, on important oxidative stress parameters in cerebral cortex of young rats in the hope to clarify the mechanisms leading to the brain damage found in patients affected by these disorders. It was first verified that these compounds significantly induced lipid peroxidation, as determined by increased thiobarbituric acid-reactive substances levels. In addition, carbonyl formation was significantly increased and sulfhydryl content decreased by 3HTA and 3HPA, which indicates that these fatty acids elicit protein oxidative damage. 3HTA and 3HPA also diminished the reduced glutathione (GSH) levels, without affecting nitrate and nitrite production. Finally, we observed that the addition of the antioxidants and free radical scavengers trolox and deferoxamine (DFO) was able to partially prevent lipid oxidative damage, whereas DFO fully prevented the reduction on GSH levels induced by 3HTA. Our present data showing that 3HDA, 3HTA and 3HPA elicit oxidative stress in rat brain indicate that oxidative damage may represent an important pathomechanism involved in the neurologic symptoms manifested by patients affected by LCHAD and MTP deficiencies.
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PMID:Long-chain 3-hydroxy fatty acids accumulating in LCHAD and MTP deficiencies induce oxidative stress in rat brain. 2038 65