Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this investigation was to characterize the acute and short- and long-term toxic potency of orally administered 1,2-dichloropropane (DCP). In the acute and short-term studies, male rats of 250-300 g were gavaged with 0, 100, 250, 500, or 1000 mg DCP/kg in corn oil once daily for up to 10 consecutive days. Although ingestion of DCP caused body weight loss and CNS depression, few other toxic effects were manifest 24 hr after a single dose of the chemical. Morphological changes were limited to liver centrilobular cells in 500 and 1000 mg/kg rats. Similarly, elevated activity of some serum enzymes occurred only at these two highest dose levels. Hepatic nonprotein sulfhydryl (NPS) levels were decreased and renal NPS levels increased at 24 hr. In the short-term study resistance developed to DCP hepatotoxicity over the 10 consecutive days of exposure, as reflected by progressively lower serum enzyme levels and by decreases in the severity and incidence of toxic hepatitis and periportal vacuolization. Nucleolar enlargement in hepatocytes, however, was observed at all dosage levels at 5 and 10 days. There were a number of manifestations of hemolytic anemia, including erythrophagocytosis in the liver, splenic hemosiderosis and hyperplasia of erythropoietic elements of the red pulp, renal tubular cell hemosiderosis, and hyperbilirubinemia. Urinalyses and histopathology revealed no evidence of nephrotoxicity. In the long-term study, male rats initially weighing 180-200 g were gavaged five times weekly for up to 13 weeks with 0, 100, 250, 500, or 750 mg DCP/kg. As over one-half the 750 mg/kg group died within 10 days, the survivors were sacrificed. Histopathological changes in the 750 mg/kg animals included mild hepatitis and splenic hemosiderosis, as well as adrenal medullary vacuolization and cortical lipidosis, testicular degeneration and a reduction in sperm, and increased number of degenerate spermatogonia in the epididymis in some members of the group. Similar testicular and epididymal degenerative change also were observed in some 500 mg/kg animals after 13 weeks of dosing. There was a progressive increase in the number of deaths in the 500 mg/kg group, such that more than 50% were dead by 13 weeks. No deaths occurred in the 100 or 250 mg/kg groups. The DCP dosage regimen also produced a dose-dependent decrease in body weight gain. DCP exhibited very limited hepatotoxic potential and no apparent nephrotoxic potential in the long-term study. Slight elevations in serum ornithine-carbamyltransferase activity, periportal vacuolization, and active fibroplasia in the liver were seen in the 500 mg/kg animals.
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PMID:Oral toxicity of 1,2-dichloropropane: acute, short-term, and long-term studies in rats. 274 74

The structure and function of heart muscle were studied in rats with chronic hemolytic anemia induced by phenylhydrazine. Contractural lesions, myocytolysis, fatty dystrophy, and small-focal necrosis were found in the myocardium along with hypertrophy. The disturbances were accompanied by a compensatory increase in the coronary flow by 2.5-fold during myocardial contractions. When the coronary flow of isolated hearts was experimentally decreased to the control level, a great depression of the contractile function developed. Administration of the antioxidant ionol, an inhibitor of lipid peroxidation, simultaneously with phenylhydrazine did not prevent the development of the hemolytic anemia, but decreased by 2 times the degree of hypertrophy and the amount of the lesion foci in the heart muscle. It also significantly inhibited the compensatory increase of coronary flow and completely eliminated depression of the heart contractile function during the normalization of coronary flow. The data allow a suggestion that hemolytic anemia is accompanied by activated lipid peroxidation, this process playing a role in the myocardial damage of anemia. Antioxidants can prevent such damage.
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PMID:Disturbances of the heart structure and function in chronic hemolytic anemia, their compensation with increased coronary flow, and their prevention with ionol, an inhibitor of lipid peroxidation. 396 13

The mechanism underlying the reversible depression of erythropoiesis by chloramphenicol has been investigated in rabbits in which hemolytic anemia had been induced by phenylhydrazine so that the compensatory erythroid hyperplasia would provide a situation where abnormalities in the bone marrow cells reflected predominantly those of erythroid precursors. Maintenance of chloramphenicol in the serum of these animals at concentrations in the order of 15 mug/ml resulted in erythropoietic depression after several days. The onset of this depression corresponded to the development of a cellular respiratory defect in the erythroid precursors which was associated with an abnormality in the composition of the mitochondrial respiratory pathway. The abnormality took the form of a selective depletion of cytochromes a + a(3) and b which can be explained by an inhibitory effect of the antibiotic on their formation by the mitochondrial protein-synthesizing system. The relationship between the mitochondrial lesion and the depression of proliferative activity was further indicated by the correlation between the restoration of the cytochrome deficit and the recovery of erythropoiesis after chloramphenicol administration was ceased. The features of the reversible depression of erythropoiesis corresponded closely to those in man, so that a specific action of chloramphenicol on mitochondrial formation provides a reasonable explanation for this important manifestation of chloramphenicol toxicity.
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PMID:Mitochondrial lesions in reversible erythropoietic depression due to chloramphenicol. 434 Oct 13

Ninety adult Indian typhoid and paratyphoid fever (enteric fever, EF) patients and 91 controls were tested for glucose-6-phosphate dehydrogenase (G6PD) deficiency using the fluorescent spot test (FST) and the quantitative methaemoglobin reduction test ( QMRT ). There was a threefold higher incidence of G6PD deficiency in North Indian EF patients (10.6%) than in controls (3.6%) (P = 0.15) which may be attributable to the greater morbidity of the G6PD-deficient EF patients; six of nine had haemolytic anaemia. A transient depression of mean erythrocyte G6PD activity was observed in a subgroup of 49 non-deficient EF patients in whom the spectrophotometric G6PD assay was done. It did not appear to be related to reticulocyte count, chloramphenicol therapy, or differences in leucocyte contamination of the haemolysate used for the G6PD assay. If this depression of G6PD activity occurs in deficient patients as well, it may help to explain the haemolysis seen in them during EF. Of the three tests used, the QMRT and the spectrophotometric assay clearly identified G6PD deficiency in males during haemolysis, whereas the FST was unreliable in this situation.
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PMID:Depression of erythrocyte glucose-6-phosphate dehydrogenase (G6PD) activity in enteric fever. 643 56

Strychnine toxicosis is characterized by inducible tetanic seizures and metaldehyde poisoning by fine fasciculations progressing to generalized tremors and seizures. Intoxication with 1080 causes seizures, random running movements, vomiting, defecation, urination, acidosis and hyperglycemia. Intoxication with rodenticides causing coagulopathy is characterized by hemorrhage into body cavities but not necessarily external hemorrhage. Anticholinesterase insecticides cause salivation, urination and defecation, while chlorinated hydrocarbon insecticides cause CNS disturbances. Ethylene glycol intoxication results in ataxia, depression, coma, vomiting and tachypnea, followed by acute renal failure. Urea poisoning causes bloat and CNS signs in cattle. Monensin intoxication in horses lasts several days and causes stiffness, colic, uneasiness and recumbency. Salt poisoning results in depression, seizures and hypernatremia. Lead poisoning is associated with central and peripheral nervous system signs, as well as increased numbers of nucleated RBC and basophilic stippling of RBC. Arsenic poisoning results in GI pain, diarrhea, weakness and death. Copper toxicosis in sheep is manifested by hemolytic anemia, hemoglobinemia and hemoglobinuria. Plants that may intoxicate domestic animals include sorghum, greasewood, halogeton, water hemlock, Japanese yew, larkspur, lupine, milk-weed, philodendron, oleander, castor bean and precatory bean.
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PMID:Practical toxicologic diagnosis. 649 3

A 77-year-old man received cefoxitin for the treatment of peritonitis. He developed hemolytic anemia and became clinically jaundiced. The patient was switched from cefoxitin to doxycycline. His total bilirubin decreased and his hematocrit increased. Several weeks later he developed septicemia. For an infiltration in the left lower lobe, he was treated with cefoxitin and gentamicin. The patient proceeded to develop a mild granulocytopenia and thrombocytopenia. Anemia was not seen because the patient was transfused several times. Bone marrow aspiration showed a mildly hypocellular marrow with a depression of all cell series, suggesting drug-induced bone marrow toxicity. Nine days after discontinuing cefoxitin, his blood elements had gone back to normal. This is the fourth case on file at Merck Sharp & Dohme of hemolytic anemia induced by cefoxitin. There have been several reports of hemolytic anemia or pancytopenia caused by cephalothin, but few, if any, citing the other cephalosporins, particularly cefoxitin. Clinicians should be made aware of the possibility of hematologic toxicities occurring with cefoxitin therapy. Patients should have their erythrocytes, leukocytes, and platelets monitored while on this drug.
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PMID:Hemolytic anemia and pancytopenia induced by cefoxitin. 664 4

Review of the available literature obtained from both acute and chronic experiments utilizing rats, mice and chickens treated with ClO2, ClO2- and ClO3-in drinking water has demonstrated alterations in hematologic parameters in all species tested. The effects were usually dose related and marked changes occurred only at the higher dosages (up to 1000 mg/l.). In chronic studies, rats have been given ClO2 at doses of up to 1000 mg/l., and NaClO2 or NaClO3 at up to 100 mg/l., in their drinking water for one year. Treatment groups receiving ClO2, ClO2- or ClO3- showed alterations in erythrocyte morphology and osmotic fragility; at higher dosages mild hemolytic anemia occurred. An examination of blood glutathione content and RBC enzymes involving glutathione formation showed a dose-related diminution of glutathione in chlorine compound treated groups. The higher oxidative capacity of the chlorine compounds resulting in the decreased erythrocytic glutathione might well be the principal biochemical event leading to the other hematological alterations. More recent data show that ClO2, ClO2- and ClO3- alter the incorporation of 3H-thymidine into the nuclei of various organs of the rat. These data suggest the possibility of increased turnover cells of the gastrointestinal mucosa and inhibited DNA synthesis in several organs. In the latter category, most concern revolves around whether or not the apparent depression of DNA synthesis in the testes is associated with depressed spermatogenesis and reproductive toxicity in the male rat.
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PMID:Toxicological effects of chlorine dioxide, chlorite and chlorate. 675 7

We describe a case of 'warm' antibody-induced haemolytic anaemia (WAIHA) in which marked depression of red cell Rh antigen expression resulted in the patient presenting with severe anaemia but a negative direct antiglobulin test (DAT). The serum contained potent IgG Rh antibodies. Unlike two previously reported cases (Koscielak, 1980; Veer et al. 1981) in which the diagnosis of WAIHA was established before the DAT became negative, this patient presented with negative serological findings during his first episode of anaemia. As a result, the serum antibodies appeared to be allo- not autoimmune in nature and to be unrelated to the patient's anaemia. Confirmation of the autoimmune nature of the Rh antibodies was not possible until nearly 2 years after the first episode of anaemia.
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PMID:Atypical presentation of acute phase, antibody-induced haemolytic anaemia in an infant. 681 75

Structural and functional disorders of the heart muscle were studied in rats with phenylhydrazine-induced chronic hemolytic anemia, as was the possibility of their prevention with anti-oxidant Ionol, a lipid peroxidation inhibitor. Hemolytic anemia was shown to produce myocardial contractural damage, myocytolysis, fatty infiltration, small-focal necrosis, the so-called central lumpy decay phenomenon. These lesions are accompanied with depressed cardiac contractility. Although anti-oxidant Ionol, a lipid peroxidation inhibitor, administered to animals simultaneously with phenylhydrazine, does not prevent hemolytic anemia, it reduces twofold the number of lesion foci in the heart muscle and limits significantly the depression of cardiac contractility.
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PMID:[Prevention of myocardial damage during hemolytic anemia by antioxidants]. 688 90

The erythroid status and levels of splenic plaque-forming cells (PFC) to sheep red blood cells (SRBC) were monitored in mice subsequent to acute phenylhydrazine (PHZ)-induced hemolytic anemia. From ferrokinetic measurements, we noted a shift in erythropoiesis from bone marrow to spleen. The levels of splenic PFC were significantly depressed following PHZ-induced erythroid differentiation. Although this immune depression may reflect competition at the stem cell levels, whereby pluripotent stem cells (CFU-s) are preferentially differentiated into the erythroid line at the expense of lymphopoietic pathways, other possibilities cannot be excluded. In this regard, we have shown that loading of the mononuclear phagocyte system (MPS) by PHZ-damaged erythrocytes effected profound depressions in splenic PFC numbers. Lastly, in addition to the well-documented increases in CFU-s migration from marrow to spleen during enhanced erythropoiesis, we noted increased migration of B lymphocytes (as assessed by PFC) in marrow-shielded lethally-irradiated mice given PHZ. We also provide data which show that PHZ-damaged RBC evoke increased migration of CFU-s in normal mice, indicating a possible involvement of the MPS in stem cell migration.
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PMID:Splenic plaque-forming cells (PFC) and stem cells (CFU-s) during acute phenylhydrazine-induced enhanced erythropoiesis. 700 67


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