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)

In the 6-year period 1984-1989, 101 liver biopsies or 'needle necropsies' from human immunodeficiency virus positive patients were examined histologically. Of these, only nine showed no abnormality whatsoever. The commonest histological findings were either fatty change or changes related to co-existent chronic viral hepatitis. Granulomas were seen in 15 cases, four of which were positive for acid-fast bacilli. A range of organisms were recorded: cytomegalovirus (4); Histoplasma capsulatum (1); Pneumocystis carinii (2); Cryptococcus neoformans (1); and Leishmania donovani (1). There were two cases of non-Hodgkin's lymphoma, but no cases of Kaposi's sarcoma. Marked iron deposition, which correlated with multiple blood transfusions was seen in nine biopsies. We were unable to identify any histological feature in the liver as being specific for HIV infection. The high incidence of liver abnormalities reflects: (i) the coincident exposure to hepatotropic viruses; (ii) the presence of opportunistic infections and neoplasms, usually part of a disseminated multi-organ process arising in the setting of profound immune depression; (iii) iatrogenic causes, in particular iron overload related to multiple blood transfusions received for treatment of zidovudine-induced anaemia; and (iv) non-specific changes associated with chronic debilitating disease.
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PMID:Surgical pathology of the liver in HIV infection. 165 81

An inhibitor of hepatic uroporphyrinogen decarboxylase (EC 4.1.1.37) was demonstrated in heat-treated extracts of livers from C57BL/10ScSn mice with iron overload after a single dose (100 mg/kg; 350 mumol/kg) of hexachlorobenzene (HCB). Inhibition was not due to accumulated uroporphyrin since this could be removed by a SEP-PAK C18 cartridge without affecting inhibitor activity. The presence of the inhibitor could be first demonstrated 2 weeks after mice received HCB and before major elevation of hepatic porphyrin levels. Maximum inhibitory potential was reached at about 8 weeks and was still detected 25 weeks after the chemical, thus paralleling the depression of enzyme activity reported previously [Smith, Francis, Kay, Greig & Stewart (1986) Biochem. J. 238, 871-878]. The inhibitor was not detected following treatment of mice with either iron or HCB alone or after the decarboxylase activity was destroyed in vitro by the combination of uroporphyrin and light. The formation of the inhibitor by inbred mouse strains nominally Ah-responsive (C57BL/6J, C57BL/10ScSn, BALB/c, C3H/HeJ, CBA/J and A/J) and Ah-nonresponsive (SWR, AKR, 129, SJL, LP and DBA/2) did not correlate fully with their reported Ah-phenotype. There was a correlation amongst the Ah-responsive strains only, with hepatic ethoxyphenoxazone de-ethylase activity induced in parallel experiments by treatment with beta-naphthoflavone. De-ethylase activity induced by HCB, however, was considerably less than that with beta-naphthoflavone, which has not been reported as porphyrogenic. Other polyhalogenated chemicals, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,4,2',3',4'-hexachlorobiphenyl and hexabromobenzene, also caused the formation of the inhibitor of uroporphyrinogen decarboxylase.
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PMID:Chemically-induced formation of an inhibitor of hepatic uroporphyrinogen decarboxylase in inbred mice with iron overload. 367 56

Deferoxamine is a chelating agent used for the treatment of chronic iron overload in patients requiring long-term blood transfusions. Audiological testing of patients with B-thalassemia major and steroid-unresponsive Diamond-Blackfan anemia who were on long-term deferoxamine treatment indicated a possible ototoxic side-effect. In the present study we have investigated this potential toxicity to the cochlea of experimental animals by monitoring electrophysiological responses to sound and also by histological evaluation of the cochlea. In animals having chronic deferoxamine treatment, there were no significant changes in cochlear function or morphology. Data from acutely treated animals indicated an elevation of cochlear response thresholds together with morphological changes at the inner hair-cell level. However, these changes were highly correlated with the respiratory depression caused by an acute general toxicity, rather than a direct ototoxic effect of deferoxamine.
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PMID:A study of the ototoxicity of deferoxamine in chinchilla. 369 44

The role of iron and heme was examined in bone marrow cells from iron-deficient and chronically iron-overloaded rats. Erythroid colony cultures (CFU-E) demonstrated that iron-overloaded bone marrow cells were poor hemin (iron carrier) and CFU-E responders in vitro, whereas iron-deficient marrows grew exuberant numbers of CFU-E and responded to hemin. Results support the concept that iron, or associated factors, plays an important role in the manipulation of HO activity which modulates the hemopoietic potential of the organism. Using cultures of erythroid (CFU-E, BFU-E) and myeloid (CFU-GM), results demonstrated that exogenous hemin (iron carrier) has a specific beneficial effect on human bone marrow progenitor cells, which is not seen with iron (10(-4)M) or other metalloporphyrins. Higher concentrations of iron (10(-3)M) and ZnPP were in fact inhibitory to bone marrow growth. This inhibition was not reversed with higher concentrations of Epo or GM-CSF. The beneficial effect of iron may be best realized in the bound form such as heme. In addition, the effect of bound and nonbound iron was tested for its effect on gene transfer. By using a murine adherent cell layer (ACL) in a prestimulation phase, followed by human gene transfer of ADA into mouse bone marrow cells and Southern blot analysis, successful gene transfer was accomplished. ADA integration patterns were detected in CFU-S from stem cells of mice 5-11 months after transfer. When 10 microM ferric chloride was included in the ACL prestimulation phase, there was a marked depression in ADA integration into stem cells as compared to heme or non-heme controls. Furthermore, heme-bound iron had no effect and deferoxamine included with iron was able to reverse the inhibitory effect of iron on the gene transfer process. Thus, iron must be non-bound to exert its suppressive effect, and chelation of excess iron under clinical conditions of iron overload may be essential for successive gene transfer.
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PMID:Differential effects of iron and iron carrier on hematopoietic cells differentiation and human ADA gene transfer. 788 24

In mice, depression of hepatic uroporphyrinogen decarboxylase (UROD) leading to porphyrin accumulation (uroporphyria) occurs with chlorinated ligands of the aryl hydrocarbon (AH) receptor especially after iron overload. However, in the absence of chlorinated ligands, iron itself will eventually cause uroporphyria, but this response is not associated with the Ahr genotype. These effects are potentiated by administration of the haem precursor 5-aminolaevulinate (ALA). The aim of this study was to investigate the effects of ALA alone. Prolonged administration of 2 mg ALA/mL in the drinking water to SWR mice also led to decarboxylase insufficiency (11% of control) and uroporphyria by 8 weeks, whereas DBA/2 mice did not show reduced enzyme activity. Both strains are considered AH nonresponsive and analysis of the Ahr gene using restriction fragment length polymorphism was consistent with SWR, like DBA/2, possessing the Ahrd allele. Exposure of isolated hepatocytes to ALA (150-500 microM) for up to 48 hr showed a significant accumulation of both uroporphyrin and coproporphyrin in the medium, which for uroporphyrin particularly was significantly greater with SWR than with DBA/2 cells. Basal in vivo CYP1A2 activity, measured as microsomal methoxyresorufin dealkylation, was significantly greater in SWR than in DBA/2 mice (1.3-fold), but it was unclear whether this was sufficient to explain the marked difference in sensitivities of the two strains. Despite SWR mice being AH nonresponsive, uroporphyria and decarboxylase depression after an initial iron overload and ALA for 3 weeks were greatly potentiated by a single dose (100 mg/kg) of hexachlorobenzene (a weak AH ligand). The results demonstrate that there is a genetic difference in mice independent of the Ahr genotype and response to iron, which influences the susceptibility to ALA-induced uroporphyria. Thus chemicals, iron and ALA can act independently, but also together, to cause porphyria in susceptible individuals.
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PMID:Uroporphyria induced by 5-aminolaevulinic acid alone in Ahrd SWR mice. 893 51

This study tested the hypothesis that acute iron overload (500 mg/kg) alters Kupffer cell functioning by promoting free radical reactions associated with the respiratory burst of liver macrophages, assessed in the isolated perfused rat liver under conditions of Kupffer cell stimulation by carbon infusion and inactivation by gadolinium chloride pretreatment. Total serum and hepatic iron levels were markedly enhanced compared with control values 2 to 24 hours after iron treatment. Total liver O2 uptake progressively increased by iron overload reaching a maximum at 6 hours after treatment, an effect that was completely blocked by GdCl3. Concomitantly, carbon-induced GdCl3-sensitive liver O2 uptake was either enhanced by 119% at 2 hours after iron overload, diminished compared with control values at 4 hours, or abolished at 6 hours. Iron-overloaded rats showed a marked increase in liver sinusoidal lactate dehydrogenase efflux at 4 and 6 hours after treatment, an effect that is exacerbated by carbon infusion and reduced (69%-89%) by GdCl3 pretreatment. Both basal and carbon-induced lactate dehydrogenase effluxes returned to control values at 24 hours after iron overload concomitantly with depression of the basal O2 uptake, without development of iron-induced GdCl3-sensitive respiration or Kupffer cell activation by carbon infusion. It is concluded that iron overload induces a derangement in the Kupffer cell functional status represented by early increases in macrophage-dependent respiratory activity, which may contribute to the concomitant liver injury that developed and to the impairment of both hepatic respiration and the macrophage response to particle stimulation observed at later times after treatment.
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PMID:Time course study of the influence of acute iron overload on Kupffer cell functioning and hepatotoxicity assessed in the isolated perfused rat liver. 958 85

Braak and co-workers have recently shown that movement disorders such as Parkinson's disease develop progressively over years with early neuronal losses in brainstem regions caudal to the substantia nigra. The relevance of this finding to notions of comorbidity between movement disorders and psychiatric symptoms was recognised at the recent meeting concerning, "Implications of Comorbidity for the Etiology and Treatment of Neuropsychiatric Disorders" held in Oct. 2005 in Mazagon, Spain. The identification of stages in the early development of neurodegenerative disorders appeared to unify multiple, diverse findings. These included: novel therapeutic innovations for Parkinson's disease, Alzheimer's disease and depression in the aged; the neurochemical ontogeny of drug-induced oral dyskinesias; the types of chemical agents abused in neuropsychiatric states; postnatal iron overload effects upon the functional and interactive role of dopaminergic and noradrenergic pathways that contribute to the expression of movement disorders; and the spectrum of motor symptoms expressed in schizophrenia and attention deficit hyperactivity disorder and the eventual treatment of these disorders. A continued focus on a number of neuropsychiatric diseases as progressive disorders may lead to further advances in understanding their etiology and in developing better therapeutics.
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PMID:Movement disorders: neurodevelopment and neurobehavioural expression. 1702 25

ABSTRACT Genetically modified rice that incorporates twofold to threefold increased amounts of iron is being developed. The product could provide improved nutrition to iron-deficient persons but may be a health hazard to large numbers of humans who are prone to iron overload. Clinical disorders such as African siderosis, beta-thalassemia, hemochromatosis, and alcoholic siderosis are of special concern. Conditions associated with iron loading include fatigue and depression; arthritis; endocrine disorders such as stunted growth, impotence, and diabetes; gastrointestinal maladies; infections and malignancies; several neurological diseases; and, not least, cardiovascular system decay. Therefore, it would be prudent to label sacks of iron-enriched rice to indicate that "this product may be dangerous to persons with iron loading conditions".
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PMID:Iron-enriched rice: the case for labeling. 1923 76

Several studies have demonstrated that the outcome of chronic hepatitis C (CHC) infection is profoundly influenced by a variety of comorbidities. Many of these comorbidities have a significant influence on the response to antiviral therapy. These comorbidities negatively affect the course and outcome of liver disease, often reducing the chance of achieving a sustained virological response with PEGylated interferon and ribavirin treatments. Comorbidities affecting response to antiviral therapy reduce compliance and adherence to inadequate doses of therapy. The most important comorbidities affecting the course of CHC include hepatitis B virus coinfection, metabolic syndrome, and intestinal bacterial overgrowth. Comorbidities affecting the course and response to therapy include schistosomiasis, iron overload, alcohol abuse, and excessive smoking. Comorbidities affecting response to antiviral therapy include depression, anemia, cardiovascular disease, and renal failure.
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PMID:Hepatitis C comorbidities affecting the course and response to therapy. 1985 90

A 26-year-old African-American male presented with chest and back pain, fatigue and a history of the following: homozygous sickle cell anemia, pain crises, stroke, hip replacement following avascular necrosis of the femoral head, priapism, chronic transfusions, iron overload, hypertension, migraine headaches, port infections, depression and type II diabetes.
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PMID:Homozygous sickle cell anemia and secondary complications: a case study. 2165 39


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