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 present experiment was performed to see the influence of phlebotomy on hematology, serum chemistry, and pathology data in rats. When normal rats received a single phlebotomy of 2 or 3 ml blood, erythrocyte count and hematocrit were slightly reduced along with a persistent depression of the blood pressure. In repeated phlebotomy studies, 0.25 to 2 ml each of blood was removed from each rat every other day for 10 days. Normal rats from which 0.5 ml and more of blood was withdrawn showed decreases in erythrocyte count and serum iron level concomitant with an increase in reticulocyte count. Similar findings were obtained in rats with CCl4 liver damage or gentamicin nephrotoxicity, except that those rats hardly exhibited anemia because of a simultaneous occurrence of hemoconcentration. Histopathological findings of the liver and kidney were not different between animals with and without phlebotomy. In phenylhydrazine-treated rats receiving repeated phlebotomy, one rat in the 1-ml phlebotomy and two rats in the 2-ml phlebotomy died from severe anemia. Surviving rats receiving 2-ml phlebotomy showed higher serum GOT and GPT activities together with fatty deposition and/or focal necrosis of hepatocytes. It is concluded that every-other-day phlebotomy of up to 0.25 ml each does not significantly influence the physiological condition of normal or diseased rats.
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PMID:The influence of single or repeated phlebotomy on the physiological condition of normal and diseased rats. 359 1

Disorders of neurotransmitter balance are observed in Parkinson's disease, pharmacotoxic psychosis and depression. The dopamine-serotonin ratio is reduced to about 20% in Parkinson and pharmacotoxic patients in the caudate nucleus and in the substantia nigra. The serotonin content in these brain areas is lowered only to about 50% in comparison to that of the control, whereas the dopamine level is reduced to 85% in Parkinson patients. This dopamine deficiency has been substituted by exogenous supply of L-dopa in combination with decarboxylase and monoaminooxydase inhibitors. First evidence is presented that L-dopa can be replaced, at least partially, by iron in form of a ferriascorbate complex. This iron compound improves the symptoms of Parkinson's disease to almost the same extent as L-dopa.
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PMID:Dopamine action and disorders of neurotransmitter balance. 365 99

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

Recently many findings about the physiological and biochemical functions of recombinant human tumor necrosis factor (rHu-TNF) have been reported. In the present study, the effect of rHu-TNF on serum iron in C3H/HeN and C57BL/6 mice was determined. Blood samples were obtained before intravenous injection of rHu-TNF, and also at various times after the injection. Results from five experiments showed that the serum iron was depressed between 1/3 to 1/5 of that of untreated mice 4 to 24 h after injection of 5 or 10 micrograms of rHu-TNF. The low level persisted for 33 h, rebounded at 48 to 72 h, and returned to normal by 96 h after the injection. Serum iron was determined by the colorimetric method using the sensitive reagent, ferrozine (3-(2-pyridyl)-5,6-bis(4-sulfophenyl)-1,2,4-triazine. We believe that this is the first report of depression of serum iron in mice by intravenous injection of rHu-TNF. The physiological role of repressed serum iron in the in vivo response to TNF remains to be established.
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PMID:Recombinant human tumor necrosis factor depresses serum iron in mice. 368 44

Interactions of riboflavin and iron deficiencies on utilization and storage of iron in the rat were investigated. Rats were fed diets deficient in iron (ID), riboflavin (RD) or iron and riboflavin (DD) for a period of 7 wk, at which time they were either killed and measurements of hematological indices and tissue iron concentration done or a further group of DD rats was supplemented with either iron, riboflavin or both nutrients for 2 wk. Growth was impaired in all deficient groups but the impairment was greatest in the DD rats. Iron depletion was associated with the greatest reductions in hematological indices and tissue iron concentrations, riboflavin depletion the least, while the combined deficiencies had intermediate effects. Riboflavin deficiency was found to have a "sparing effect" on iron status probably because the lower growth rate associated with riboflavin deficiency reduced iron requirements. Refeeding either iron alone or iron with riboflavin to the DD rats resulted in significant improvement in hematological status, but there was no significant difference in the response to either supplement. Feeding riboflavin alone to DD rats resulted in a further depression of hematological status and tissue iron concentration.
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PMID:Effects of combined riboflavin and iron deficiency on the hematological status and tissue iron concentrations of the rat. 374 63

Myoglobin, an intracellular iron containing protein that binds oxygen reversibly, has been shown in model systems to facilitate the diffusion of oxygen and thereby maintain the mechanical function of exercising canine skeletal muscle and of hypoxic benthic fish hearts. Since no such role has yet been established for mammalian cardiac muscle small diameter (less than or equal to 0.70 mm) isolated kitten papillary muscles were stimulated at 24 X min-1 under isometric conditions in a physiological bath maintained at 30 degrees C with an oxygen tension of approximately equal to 450 mm Hg (59.8 kPa) to obtain a level of oxygenation just adequate to meet the metabolic needs of the muscles, as confirmed experimentally. Myoglobin was inactivated by adding 2 X 10(-3) mol X litre-1 sodium nitrite to the bath to abolish the facilitated diffusion of oxygen in the presence or absence of glycolytic blockade by 10(-4) mol X litre-1 sodium iodoacetate. This resulted in a 22(8)% (with blockade) or 10(3)% (without blockade) decrease (p less than 0.05) in the maximal rate of relaxation (-dT/dtmax) of the papillary muscles. Since the depression in mechanical function was reversible by increasing the bath oxygen tension to approximately equal to 600 mm Hg (79.8 kPa) it is concluded that the myoglobin facilitated diffusion of oxygen plays a role in maintaining the mechanical function of mammalian cardiac muscle under normal conditions. Furthermore, the maximal rate of relaxation of cardiac muscle is a sensitive indicator of the presence of hypoxia.
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PMID:Myoglobin facilitated oxygen diffusion maintains mechanical function of mammalian cardiac muscle. 379 52

The hematologic status of 265 patients with rheumatoid arthritis was assessed. In the group as a whole, a mild depression in the hemoglobin concentration and mean cell volume (MCV) was associated with an increase in the red blood cell distribution width (RDW), erythrocyte sedimentation rate (ESR), and platelet count. Bone marrow trephine biopsies and further measurements of iron status and disease activity were done in [a further] 38 more anemic patients, and the findings in those with absent marrow iron (iron deficiency) were compared with those having stainable stores (anemia of chronic disorders). The RDW was raised in both, and there was no significant difference between the two groups. The concentrations of nonheme iron in the marrow and of serum ferritin were significantly lower in the iron-deficient group, but the geometric mean serum ferritin of 34 micrograms/L was still a good deal higher than that associated with uncomplicated iron deficiency. This was presumably because of the fact that the serum ferritin, which was significantly correlated with the ESR (r 0.55; P less than 0.0004) and C-reactive protein (CRP) r 0.41; P less than 0.01), was also functioning as an acute phase protein. While there was a weak correlation (r 0.37; P less than 0.04) between the marrow nonheme iron and the serum ferritin concentrations, it disappeared when nonactive patients with normal CRP concentrations were excluded. The absence of a correlation is unlike the findings that have previously been noted in other chronic inflammatory conditions and in neoplasia. This raises the possibility that serum ferritin concentrations in rheumatoid arthritis may reflect, in part at least, another store of iron located in affected joints.
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PMID:Hematologic and iron-related measurements in rheumatoid arthritis. 381 50

Tumor-infiltrating lymphocytes (TIL) from human pulmonary tumors have been studied as a model for local depression of cell-mediated immunity at the tumor site. To better characterize these lymphoid infiltrates, a new method of lymphocyte extraction of high yield and purity was developed. The TIL from 11 human lung tumors of varying histologic types were prepared. After mechanical disaggregation to a single cell suspension, the TIL, contaminated with tumor cells and macrophages, were incubated with carbonyl iron to deplete macrophages. Further purification was performed in a unit gravity sedimentation apparatus utilizing a continuous 2-4% Ficoll gradient. Usable TIL recovery was 41.2 +/- 7.7% of input cells and was minimally contaminated by tumor cells and macrophage/monocytes. The high yield and purity of TIL preparations have resulted in a higher proportion of tumors suitable for immunological analysis. An example of the type of experiments possible with such preparations is shown.
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PMID:A method for improved yield and purity in extracting lymphocytes from lung tumors. 396 5

Hexachlorobenzene (HCB) was fed to male and female F344 rats as 0.02% of the diet for 15 weeks. Females developed a massive porphyria, due to depression of uroporphyrinogen decarboxylase activity, whereas males did not. Although hepatic non-haem iron levels in control females were 3-5 times greater than males (iron is implicated in the pathogenesis of this condition) preloading the latter with iron did not increase their susceptibility. After 90 weeks of HCB treatment 100% of surviving females had multiple liver tumours which were strongly gamma-glutamyl transpeptidase (GGT) positive and histologically classified as neoplastic nodules or hepatocellular carcinomas. In contrast, only 16% of males developed tumours which were smaller and fewer in number per liver than those in females. Accumulation of porphyrins was still significantly less in males than females although no uroporphyrinogen decarboxylase activity was detected in treated livers of either sex. No differences in porphyrin levels or enzyme activity were found between tumours and surrounding tissue showing that tumours did not revert to a non-porphyric state. The sex difference in tumour response could not be explained by differences in hepatic HCB concentrations. Non-haem iron concentrations of livers fell after HCB treatment for 90 weeks in both sexes and were even lower in tumours. These studies demonstrate that not only are female rats far more sensitive than males to the porphyrinogenic effects of HCB but also to the hepatocarcinogenic actions, suggesting a link between these two manifestations of toxicity that may also apply to other polyhalogenated aromatics.
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PMID:Hepatocarcinogenicity of hexachlorobenzene in rats and the sex difference in hepatic iron status and development of porphyria. 398 65

Indicators of copper and iron metabolism were studied in pregnant rats and their 90-d-old offspring fed copper-sufficient or copper-deficient diets containing marginal or adequate levels of iron from the beginning of pregnancy until the offspring were 90 d of age. Offspring had more severe signs of copper deficiency (including anemia, hypertrophy of the heart, decreased activity of ferroxidase I and II, depression of growth and death) than the dams. In both dams and offspring, copper deficiency resulted in anemia when dietary iron was marginal but not when it was adequate. Liver iron was elevated in copper-deficient male offspring, but not in female offspring. Anemia and growth retardation were more pronounced in copper-deficient males than in females, despite similarly low levels of ferroxidase I and II. Iron absorption was reduced by copper deficiency only in female offspring. Activity of 59Fe in various tissues 6 or 48 h after gavage did not reveal any other effect of copper deficiency on iron metabolism. Thus age at the time copper-deficient diets were introduced, sex and dietary iron strongly influence the effect of copper deficiency.
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PMID:Determinants of copper-deficiency anemia in rats. 399 65


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