Desferoxamine
desferoxamine
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- Search all fields for: desferoxamine
- Published in 1966 through 1999
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Documents: 1 to 61 of 61
NLM database Documents
Record 1 from database: MEDLINE
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- Title
- Desferoxamine mesylate (Desferal): a contrast-enhancing agent for gallium-37
imaging.
- Author
- Hoffer PB; Samuel A; Bushberg JT; Thakur M
- Address
-
- Source
- Radiology, 1979 Jun, 131:3, 775-9
- Abstract
- Desferal (desferoxamine mesylate) was investigated as a contrast-enhancing
agent for tumor and abscess imaging with 67Ga-citrate. Tumor studies were
performed in mice with Cloudman S-91 melanoma. Abscess studies were performed
with a subcutaneous abscess model in rabbits. When Desferal is administered 16
to 18 hours after injection of 67Ga, rapid blood clearance of 67 Ga occurs with
only slight (tumor) or no (abscess) loss of activity from the lesion. Retention
in other organs is variable. Tumor-to-blood ratios are improved eightfold in
tumor and fourfold in abscess in studies performed with single Desferal
injections of 150 mg/kg. Blood and total body clearance studies in rabbits
reveal that maximum Desferal effect is achieved in the 17 to 50 mg/kg dose range
and that only minimal improvement occurs at higher doses.
- Language of Publication
- English
- Unique Identifier
- 79180979
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- MeSH Heading (Major)
- Abscess|ME/*RI; Deferoxamine|*AA/BL/ME; Gallium Radioisotopes|*DU/ME;
Melanoma|ME/*RI
- MeSH Heading
- Animal; Drug Interactions; Image Enhancement; Mice; Neoplasms,
Experimental|ME/RI; Rabbits; Time Factors; Tissue Distribution
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0033-8419
- Country of Publication
- UNITED STATES
Record 2 from database: MEDLINE
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- Title
- Antineuroblastoma activity of desferoxamine in human cell lines.
- Author
- Blatt J; Stitely S
- Address
-
- Source
- Cancer Res, 1987 Apr, 47:7, 1749-50
- Abstract
- That ferritin, an iron storage protein, can be produced by neuroblastoma
cells raises the possibility that iron may have some role in promoting tumor
cell growth. To explore this possibility, we studied the effects of
desferoxamine, a compound which chelates iron, on viability of CHP 126 and CHP
100, two human neuroblastoma cell lines. Cells (5 X 10(4)) were incubated with
graded amounts of desferoxamine or ferrioxamine, an iron-saturated analogue of
desferoxamine. Within 5 days of exposure to 60 microM desferoxamine,
approximately 90% of cells from each of these cell lines were dead. This effect
was dose dependent, was not seen with ferrioxamine, and could be prevented by
coincubation with greater than stoichiometric amounts of ferric citrate. As
determined by binding of OK-T9, desferoxamine also resulted in increased
expression of receptors for transferrin, an iron transport protein.
Desferoxamine had only minimal effects on viability of several non-neuroblastoma
cell lines. These results suggest that iron is required for growth of
neuroblastoma and that desferoxamine has potent, specific, antineuroblastoma
activity in vitro.
- Language of Publication
- English
- Unique Identifier
- 87130756
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- MeSH Heading (Major)
- Antineoplastic Agents|*; Deferoxamine|*TO; Neuroblastoma|*PA
- MeSH Heading
- Cell Line; Cell Survival|DE; Human; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0008-5472
- Country of Publication
- UNITED STATES
Record 3 from database: MEDLINE
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- Title
- Effect of iron and desferoxamine on cell growth and in vitro ferritin
synthesis in human hepatoma cell lines.
- Author
- Hann HW; Stahlhut MW; Hann CL
- Address
- Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
- Source
- Hepatology, 1990 Apr, 11:4, 566-9
- Abstract
- To investigate the effects of iron supplementation on hepatoma cell growth,
cells from a human hepatoma cell line, PLC/PRF/5, were grown in RPMI 1640
supplemented with 0, 10 and 20 micrograms/ml of FeSO4 and harvested weekly. At
the end of 6 wk culture, cell mass measured 9.6, 14.7 and 13.2 gm, respectively.
Amounts of ferritin from these cell masses were 0 (undetectable), 0.89 and 2.27
micrograms/gm of cells. To study the effects of iron deprivation of hepatoma
cells, three human hepatoma cell lines (PLC/PRF/5, Hep G2 and Hep 3B) were
incubated in tissue culture medium mixed with graded amounts of an
iron-chelating agent, desferoxamine, for 48 to 96 hr at 37 degrees C with 5%
CO2. Over 50% cell death in PLC/PRF/5 cells and 30% to 50% cell death in Hep G2
and Hep 3B cells were observed 48 to 72 hr after exposure to desferoxamine.
Addition of ferric citrate partially reversed the cytotoxic effect of
desferoxamine. On the other hand, viability of control cells, human diploid cell
line (WI 38), was not affected by desferoxamine. Even after 96 hr exposure to
desferoxamine, cell death was only 2% to 4%. These results suggest that (a) iron
enhances tumor cell growth, (b) iron induces increased ferritin synthesis by
tumor cells in vitro and (c) iron depletion causes tumor cell death but has
little effect on normal human diploid cells. These findings should be considered
when designing treatment of patients with hepatoma. Iron oversupply in patients
with cancer might enhance tumor growth and adversely affect cancer therapy. Iron
chelation with desferoxamine might have a place in the treatment of patients
with hepatoma in conjunction with other anticancer agents.
- Language of Publication
- English
- Unique Identifier
- 90228900
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- MeSH Heading (Major)
- Antineoplastic Agents|*; Carcinoma, Hepatocellular|ME/*PA; Deferoxamine|*PD;
Ferritin|*BI; Iron|*PD; Liver Neoplasms|ME/*PA
- MeSH Heading
- Cell Division|DE; Cell Survival|DE; Human; Support, Non-U.S. Gov't; Support,
U.S. Gov't, P.H.S.; Tumor Cells, Cultured|DE/ME/PA
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0270-9139
- Country of Publication
- UNITED STATES
Record 4 from database: MEDLINE
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- Title
- Suppression of delayed type hypersensitivity by desferoxamine.
- Author
- Sahasrabudhe DM; Dusel J; Jedlika S
- Address
- Cancer Center, University of Rochester School of Medicine and Dentistry, New
York.
- Source
- J Immunother, 1991 Apr, 10:2, 112-9
- Abstract
- Desferoxamine, a chelating agent, inhibits proliferation of T cells in
vitro. We reasoned that it may also suppress T-cell-mediated immune responses in
vivo. The effect of desferoxamine on delayed type hypersensitivity reaction to
dinitrofluorobenzene was evaluated in Balb/c mice. We report that desferoxamine
inhibits sensitization and elicitation of skin test reactivity and that the
immunosuppressive effect of desferoxamine is transient. While its mechanism of
action remains to be determined, it may be a potentially useful
immunosuppressive agent.
- Language of Publication
- English
- Unique Identifier
- 91255147
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- MeSH Heading (Major)
- Deferoxamine|AD/*PD; Hypersensitivity, Delayed|*/IM
- MeSH Heading
- Animal; Cell Division|DE; Dinitrofluorobenzene|IM; Ferric Compounds|PD;
Immunosuppression; Mice; Mice, Inbred BALB C; Support, Non-U.S. Gov't; Support,
U.S. Gov't, P.H.S.; T-Lymphocytes|CY/IM
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 1053-8550
- Country of Publication
- UNITED STATES
Record 5 from database: MEDLINE
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- Title
- Determination of desferoxamine and a major metabolite by high-performance
liquid chromatography. Application to the treatment of aluminium-related
disorders.
- Author
- Kruck TP; Kalow W; McLachlan DR
- Address
-
- Source
- J Chromatogr, 1985 May, 341:1, 123-30
- Abstract
- A high-performance liquid chromatography method is described that permits
separation and quantification of desferoxamine, a major metabolite, the
iron(III) and the aluminum(III) chelates of desferoxamine. This method now
facilitates pharmacokinetic studies on desferoxamine and derivatives designed to
study side-effects and metabolite patterns in patients undergoing treatment.
- Language of Publication
- English
- Unique Identifier
- 85261771
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- MeSH Heading (Major)
- Aluminum|BL/*PO; Chelating Agents|BL/*TU; Deferoxamine|*AN/BL/TU/UR
- MeSH Heading
- Alzheimer Disease|BL; Chromatography, High Pressure Liquid; Female; Human;
Kinetics; Middle Age; Spectrophotometry, Ultraviolet; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-9673
- Country of Publication
- NETHERLANDS
Record 6 from database: MEDLINE
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- Title
- Altered biodistribution of gallium-67 in a patient with aluminum toxicity
treated with desferoxamine.
- Author
- Brown SJ; Slizofski WJ; Dadparvar S
- Address
- Department of Radiation Oncology and Nuclear Medicine, Hahnemann University
Hospital, Philadelphia, Pennsylvania 19102.
- Source
- J Nucl Med, 1990 Jan, 31:1, 115-7
- Abstract
- Markedly altered biodistribution of [67Ga]citrate was observed in a
66-yr-old hemodialysis patient imaged at 48 hr postinjection. A review of the
patient's hospital records revealed toxic serum levels of aluminum, treated with
the chelating agent desferoxamine. Based on what is known about the biologic
interactions between gallium, aluminum, transferrin, and desferoxamine, we
believe that both toxic serum aluminum levels and desferoxamine therapy may
cause altered biodistribution on [67Ga]citrate scintigraphy.
- Language of Publication
- English
- Unique Identifier
- 90111855
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- MeSH Heading (Major)
- Aluminum|*AE; Citrates|*DU/PK; Deferoxamine|*TU; Gallium Radioisotopes|*DU
- MeSH Heading
- Aged; Case Report; Drug Interactions; Hemodialysis; Human; Kidney Failure,
Chronic|TH; Male; Tissue Distribution
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0161-5505
- Country of Publication
- UNITED STATES
Record 7 from database: MEDLINE
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- Title
- Synthesis of indium-labeled antibody-chelate conjugates for radioassays.
- Author
- Gokce A; Nakamura RM; Tubis M; Wolf W
- Address
-
- Source
- Int J Nucl Med Biol, 1982, 9:2, 85-95
- Abstract
- A method has been developed to achieve rapid and reproducible complexation
of indium to transferrin at pH 7.4. The system consists of nitrilotriacetic acid
(NTA) as the intermediate carrier ligand, whose function is to allow the 113m In
ion, in a solution in Tris buffer, pH 7.4, to be transferred rapidly to the
specific binding sites on transferrin. Just as in the case of iron, this
complexation requires the presence of a synergistic ion such as bicarbonate. The
present system can be used to allow the binding of 113mIn to transferrin when
coupled to an antibody. This method has been tested by studying the conjugation
of an antibody, the IgG fraction of goat anti-rabbit-IgG, with either
transferrin or desferoxamine, using glutaraldehyde as the coupling agent.
Optimization in terms of total protein concentration and glutaraldehyde levels
lead to products where the specific metal binding capacity of the transferrin
moiety remains unchanged, and where the antibody retains 70% of its antigenic
activity. The present system can be considered an extension of the ELISA
techniques and can be used to determine, by a terminal 113mIn labeling
technique, the level of specific binding of an antibody to its antigen.
- Language of Publication
- English
- Unique Identifier
- 82264575
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- MeSH Heading (Major)
- IgG|*; Indium|*DU; Radioisotopes|*DU; Transferrin|*
- MeSH Heading
- Animal; Binding Sites, Antibody; Deferoxamine; Glutaral; Human; Hydrogen-Ion
Concentration; Isotope Labeling; Nitrilotriacetic Acid; Radioimmunoassay;
Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0047-0740
- Country of Publication
- UNITED STATES
Record 8 from database: MEDLINE
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- Title
- Accidental iron poisoning in childhood. Six cases including one fatality.
- Author
- Greenblatt DJ; Allen MD; Kock Weser J
- Address
-
- Source
- Clin Pediatr (Phila), 1976 Sep, 15:9, 835-8
- Abstract
- Between 1962 and 1973, six children were admitted to the Massachusetts
General Hospital because of accidental iron poisoning. Intoxication was
life-threatening in two children whose serum iron concentrations exceeded their
iron binding capacities. One of these patients died despite intensive supportive
care and desferoxamine therapy. Although iron poisoning appears to be relatively
uncommon, it can produce life-threatening and fatal intoxication in children.
- Language of Publication
- English
- Unique Identifier
- 76256275
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- MeSH Heading (Major)
- Iron|BL/*PO/UR
- MeSH Heading
- Case Report; Child, Preschool; Deferoxamine|TU; Female; Heart Arrest|CO;
Human; Infant; Male; Pulmonary Edema|CO; Support, U.S. Gov't, P.H.S.;
Tracheotomy
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0009-9228
- Country of Publication
- UNITED STATES
Record 9 from database: MEDLINE
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- Title
- Low lung capacity and hypoxemia in children with thalassemia major.
- Author
- Cooper DM; Mansell AL; Weiner MA; Berdon WE; Chetty Baktaviziam A; Reid L;
Mellins RB
- Address
-
- Source
- Am Rev Respir Dis, 1980 Apr, 121:4, 639-46
- Abstract
- We evaluated lung function in 17 children with thalassemia major in stable
condition receiving blood transfusions at regular intervals and subcutaneous
desferoxamine daily. Total lung capacity (TLC) was below 2 SD of normal values
for height in 7 of the 17 children and arterialized capillary PO2 was below the
normal range in 15. We studied lung mechanics in 4 children with reduced TLC and
found static and dynamic compliance below 2 SD of normal values for height in 3,
and lung recoil at TLC above normal values and specific upstream conductance
(Gus/TLC) above 2 SD of normal values in all 4. Although these alterations in
lung function have been described in patients with pulmonary fibrosis, we found
no fibrosis in autopsy specimens of lung from 8 other patients with thalassemia.
The rate constant of carbon monoxide diffusion (kCO) was above the predicted
mean in 14 of 15 children. These findings can be explained by a decrease in the
growth of airspace relative to the vascular bed and major airways during
childhood.
- Language of Publication
- English
- Unique Identifier
- 80218412
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- MeSH Heading (Major)
- Anoxemia|*PP; Lung|PA/*PP; Thalassemia|PA/*PP
- MeSH Heading
- Adolescence; Blood Gas Analysis; Child; Esophagus|PP; Human; Lung Volume
Measurements; Maximal Expiratory Flow Rate; Oxygen|BL; Partial Pressure;
Pulmonary Diffusing Capacity; Support, U.S. Gov't, P.H.S.; Total Lung Capacity
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0003-0805
- Country of Publication
- UNITED STATES
Record 10 from database: MEDLINE
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- Title
- Desferoxamine blocks IL 2 receptor expression on human T lymphocytes.
- Author
- Carotenuto P; Pontesilli O; Cambier JC; Hayward AR
- Address
-
- Source
- J Immunol, 1986 Apr, 136:7, 2342-7
- Abstract
- Thymidine uptake by PHA-stimulated human lymphocytes is reduced in the
presence of 100 microM or greater concentrations of the iron-chelating agent
desferoxamine (DF). We assessed expression of IL 2 receptor, 4F2 and Ia
antigens, IL 2 production, and cell cycle progression by blood mononuclear cells
(MNC) stimulated by PHA in the presence or absence of DF to determine whether
the lack of T cell proliferation was a manifestation of inhibition of an earlier
activation event. Tac antigen expression on PHA-stimulated MNC was inhibited by
DF throughout 8 days of culture, and those cells which were positive had a low
density of Tac antigen as compared with controls without DF. Expression of other
activation antigens, 4F2 and Ia, was not impaired by DF. The supernatants of the
DF-containing and control cultures contained equivalent IL 2 activity, as
measured on the HT-2 cell line. Cell cycle analysis of these cultures shows that
the addition of DF at the beginning of culture blocks most cells from undergoing
G0 to G1 transition, whereas later addition of DF arrests the progression of the
T cell blasts through the cell cycle. Separation of cells cultured with PHA and
DF into Tac and Tac- subsets showed that progression from G0 to G1 was
restricted to the former subset. These results suggest that interference with IL
2 receptor expression might contribute to the block in mitogen-induced
proliferation caused by DF.
- Language of Publication
- English
- Unique Identifier
- 86141831
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- MeSH Heading (Major)
- Deferoxamine|*PD; Interleukin-2|BI/*ME; Receptors, Antigen, T-Cell|*DE;
Receptors, Immunologic|*DE; T-Lymphocytes|CL/CY/IM/*ME
- MeSH Heading
- Antigens, Surface|AN; Cell Cycle|DE; Human; Lymphocyte Transformation|DE;
Phenotype; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Thymidine|ME
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0022-1767
- Country of Publication
- UNITED STATES
Record 11 from database: MEDLINE
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- Title
- Transferrin in FRTL5 cells: regulation of its receptor by mitogenic agents
and its role in growth.
- Author
- Lombardi A; Tramontano D; Braverman LE; Ingbar SH
- Address
- Charles A. Dana Research Institute, Beth Israel Hospital, Boston,
Massachusetts.
- Source
- Endocrinology, 1989 Aug, 125:2, 652-8
- Abstract
- Transferrin, a serum iron-binding protein, delivers iron to the cell after
binding to specific receptors on the cell surface and is an important component
of culture medium for virtually all cell lines, including the FRTL5 line of rat
thyroid follicular cells. Therefore, we undertook studies in FRTL5 cells to
examine the regulation of the transferrin receptor, the effects of transferrin
on growth and differentiated functions, and the interactions of transferrin with
several mitogenic pathways. FRTL5 cells possess one class of saturable
transferrin receptors (Ka, 0.7 x 10(9) M-1). Binding of 125I-labeled transferrin
was highest in actively growing cells and declined progressively, reaching
minimal values when confluence was achieved. Removal of transferrin from culture
medium caused a rapid increase in transferrin binding. TSH, acting within 5 min,
induced a modest increase in transferrin binding, due to a
cycloheximide-resistant increase in binding sites. Binding of transferrin after
a 24-h incubation was also increased by other mitogenic agents, (Bu)2cAMP,
forskolin (FK), insulin, insulin-like growth factor-I (IGF-I), and the phorbol
ester TPA. Transferrin alone stimulated growth only minimally, but enhanced the
mitogenic effect of TSH, (Bu)2cAMP, and FK, all of which act through the cAMP
pathway. In contrast, transferrin did not alter the cAMP-independent mitogenic
effects of insulin and IGF-I. Transferrin did not affect TSH-induced cAMP
generation. Desferoxamine, an iron chelator, inhibited the mitogenic effects of
all of the agents tested. Desferoxamine had no significant effect on TSH-induced
cAMP accumulation. We conclude that FRTL5 cells contain saturable receptors for
transferrin whose abundance varies with the rate of cell replication.
Transferrin down-regulates its own receptors, while stimulation of growth by
various mitogens is accompanied by increased binding of transferrin. Transferrin
enhances the mitogenic effect of the cAMP-dependent mitogens, TSH, (Bu)2cAMP,
and FK, without modifying basal or stimulated cAMP generation. In contrast,
transferrin fails to affect the mitogenic responses to IGF-I and insulin, which
are cAMP independent. Iron is required for the mitogenic response to various
mitogens, especially those that are cAMP dependent.
- Language of Publication
- English
- Unique Identifier
- 89325152
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- MeSH Heading (Major)
- Mitogens|*PD; Receptors, Transferrin|*DE/ME; Transferrin|ME/PD/*PH
- MeSH Heading
- Animal; Bucladesine|PD; Cell Differentiation|DE; Cell Division|DE; Cell
Line; Cells, Cultured; Cyclic AMP|ME; Deferoxamine|PD; Insulin|PD; Insulin-Like
Growth Factor I|PD; Rats; Support, U.S. Gov't, P.H.S.; Tetradecanoylphorbol
Acetate|PD; Thyroid Gland|CY/DE/UL; Thyrotropin|PD
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0013-7227
- Country of Publication
- UNITED STATES
Record 12 from database: MEDLINE
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- Title
- Hepatocyte injury resulting from the inhibition of mitochondrial respiration
at low oxygen concentrations involves reductive stress and oxygen activation.
- Author
- Niknahad H; Khan S; OBrien PJ
- Address
- Faculty of Pharmacy, University of Toronto, Ontario, Canada.
- Source
- Chem Biol Interact, 1995 Oct, 98:1, 27-44
- Abstract
- By correlating lactate/pyruvate ratios and ATP levels, cytotoxicity induced
by the mitochondrial respiratory inhibitors or hypoxia:reoxygenation injury can
be attributed not only to ATP depletion but also to reductive stress and oxygen
activation. Thus hypoxia, cyanide or antimycin markedly increases reductive
stress, non-heme Fe release and H2O2 formation in hepatocytes. Cytotoxicity was
partly prevented with the ferric chelator desferoxamine, the xanthine oxidase
inhibitor oxypurinol and the hydrogen peroxide scavenger glutathione. No lipid
peroxidation could be detected and phenolic anti-oxidants had little effect.
However, polyphenolic antioxidants or the superoxide dismutase mimics TEMPO or
TEMPOL partly prevented cytotoxicity. Furthermore, increasing the hepatocyte
NADH/NAD ratio with NADH generating compounds such as ethanol, glycerol, or
beta-hydroxybutyrate markedly increased cytotoxicity (prevented by
desferoxamine) and further increased the intracellular release of non-heme iron.
Cytotoxicity could be prevented by glycolytic substrates (eg. fructose,
dihydroxyacetone, glyceraldehyde) or the NADH utilising substrates acetoacetate
or acetaldehyde which decreased the reductive stress and prevented intracellular
iron release. These results suggest that liver injury resulting from
insufficient respiration involves reductive stress which releases intracellular
Fe, converts xanthine dehydrogenase to xanthine oxidase and causes mitochondrial
oxygen activation. The cell's antioxidant defences are compromised and ATP
catabolism contributes to oxygen activation.
- Language of Publication
- English
- Unique Identifier
- 96080343
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- MeSH Heading (Major)
- Liver|*CY/ME; Mitochondria, Liver|DE/*ME; Oxygen Consumption|*/DE
- MeSH Heading
- Adenosine Triphosphate|ME; Animal; Antimycin A|AA/PD; Antioxidants|PD; Cell
Death|DE; Cell Hypoxia; Cyanides|PD; Ethanol|PD; Hydrogen Peroxide|ME; Iron|ME;
Lactates|ME; Male; NAD|ME; Oxidation-Reduction; Pyruvates|ME; Rats; Rats,
Sprague-Dawley; Reactive Oxygen Species|ME; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0009-2797
- Country of Publication
- IRELAND
Record 13 from database: MEDLINE
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- Title
- Hepatocyte toxicity of mechlorethamine and other alkylating anticancer
drugs. Role of lipid peroxidation.
- Author
- Khan S; Ramwani JJ; OBrien PJ
- Address
- Faculty of Pharmacy, University of Toronto, Ontario, Canada.
- Source
- Biochem Pharmacol, 1992 May, 43:9, 1963-7
- Abstract
- The alkylating anticancer drugs, mechlorethamine (HN2), chlorambucil,
cyclophosphamide, carmustine and lomustine readily induced cytotoxicity in
isolated rat hepatocytes. Hepatocyte glutathione (GSH) was depleted rapidly
following addition of the drugs. Lipid peroxidation ensued following GSH
depletion and before cytotoxicity occurred. Furthermore, cytotoxicity was
delayed by the antioxidants butylated hydroxyanisole (BHA) and alpha-tocopherol,
the ferric iron chelator desferoxamine or the radical trap
4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) even when added 10 min
later. HN2 was much less toxic to hepatocytes under nitrogen and caused much
less lipid peroxidation than under aerobic conditions. Cytotoxicity induced by
HN2 was also prevented by choline, suggesting that a choline carrier is
responsible for HN2 uptake in the hepatocytes. Various sulfur compounds acted as
antidotes for HN2 cytotoxicity. Thiosulfate was still effective when added 30
min after HN2. Depletion of GSH in the hepatocytes markedly increased their
susceptibility to HN2. However, BHA, desferoxamine or TEMPO protected these
hepatocytes from HN2. This suggests that antioxidants could prove useful in
preventing the increased risk of hepatotoxicity if GSH-depleting agents are used
to overcome tumor resistance to nitrogen mustards.
- Language of Publication
- English
- Unique Identifier
- 92281562
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- MeSH Heading (Major)
- Alkylating Agents|*TO; Lipid Peroxidation|*; Liver|*DE/ME;
Mechlorethamine|AI/*TO
- MeSH Heading
- Animal; Antioxidants|PD; Butylated Hydroxyanisole|PD; Cell Death|DE; Cyclic
N-Oxides|PD; Deferoxamine|PD; Glutathione|ME; Male; Malondialdehyde|AN; Rats;
Rats, Inbred Strains; Vitamin E|PD
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-2952
- Country of Publication
- ENGLAND
Record 14 from database: MEDLINE
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- Title
- Conjugated desferoxamine attenuates hepatic microvascular injury following
ischemia/reperfusion.
- Author
- Drugas GT; Paidas CN; Yahanda AM; Ferguson D; Clemens MG
- Address
- Division of Pediatric Surgery, Johns Hopkins University School of Medicine,
Baltimore, MD 21205.
- Source
- Circ Shock, 1991 Jun, 34:2, 278-83
- Abstract
- Iron-dependent oxy radicals have been implicated in reperfusion injury.
Although the iron chelator desferoxamine (DFO) is beneficial, its hemodynamic
effects and short vascular retention limit its use in vivo. We tested whether
DFO conjugated to a high-molecular-weight starch might ameliorate in vivo
hepatic microvascular injury without adverse side effects following 120 min of
ischemia. Prior to reperfusion, conjugated DFO (100 mg/kg), vehicle (Veh), or
saline (I/R) was administered. After 90 min of reperfusion, blood was collected
for serum transaminase determination (ALT; U/liter), and fluorescein-albumin was
injected to label perfused microvessels, which were quantified in frozen
sections by a point-count technique. Tissue edema was estimated by wet to dry
weight ratios (W/D). Reperfusion results in hepatocyte injury (rise in ALT and
W/D) and a 30% loss of perfused microvessels. Intravenous administration of
conjugated DFO produces no significant change in systemic hemodynamics, whereas
both ALT and tissue edema were decreased by approximately 50%. Moreover,
perfused microvessels were restored virtually to nonischemic control levels.
Enhanced perfusion and attenuated cell injury with DFO suggest that
microvascular failure and resultant cell death are mediated, at least in part,
by iron-dependent mechanisms in reperfusion.
- Language of Publication
- English
- Unique Identifier
- 92035373
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- MeSH Heading (Major)
- Deferoxamine|*PD; Liver Circulation|*DE; Starch|*AA
- MeSH Heading
- Animal; Blood Vessels|PA; Ischemia|PA; Male; Microcirculation|DE; Rats;
Rats, Inbred Strains; Reperfusion; Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0092-6213
- Country of Publication
- UNITED STATES
Record 15 from database: MEDLINE
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- Title
- Free radicals may contribute to oxidative skeletal muscle fatigue.
- Author
- Barclay JK; Hansel M
- Address
- School of Human Biology, University of Guelph, Ont., Canada.
- Source
- Can J Physiol Pharmacol, 1991 Feb, 69:2, 279-84
- Abstract
- We used mouse soleus in vitro (n = 30) and canine gastrocnemius-plantaris
preparations (n = 20) pump-perfused at the animal's blood pressure to establish
if free radicals contribute to fatigue in oxidative skeletal muscle. The soleus
from each leg contracted for 200 ms (70 Hz) once every minute for 60 min in
Hepes buffer gassed with 100% oxygen at 27 degrees C. When contracting in Hepes
alone, both muscles fatigued at 0.9 mN/mm2.min over the 60 min. The addition of
purines to the bath increased the rate to 1.4 mN/mm2.min and the addition of
xanthine oxidase to generate free radicals increased the rate again to 1.9
mN/mm2.min. Thus free radicals appeared to attenuate oxidative skeletal muscle
function. Each canine muscle contracted isometrically at 4 Hz for 30 min and
then rested for 45 min before contracting for a second 30 min at 4 Hz. In each
experiment, we infused saline at 0.76 mL/min into resting muscle and at 1.91
mL/min during the first contraction period. During the remainder of the
experiment, we infused, at the same rates, saline (n = 4), 10 microM dimethyl
sulfoxide (DMSO) (n = 4) to identify the effect of scavenging hydroxyl radicals,
1 mM allopurinol to establish the effect of blocking xanthine oxidase (n = 4),
or 200 microM desferoxamine to determine the effect of chelating iron (n = 4).
With saline, the fatigue rate over the 30 min of contractions increased from 5.0
0.2 to 6.3 0.5 N/kg.min from the first to the second stimulation period. The
fatigue rate was slower in the second period with each of the three experimental
substances (DMSO, 5.9 0.8 to 3.2 0.3; allopurinol, 7.3 1.1 to 4.6 0.6;
desferoxamine, 6.8 0.8 to 4.4 0.8 N/kg.min). The fatigue rate was the same as
control when DMSO was infused only during the second contraction period.
Therefore, free radicals appeared to contribute to fatigue in oxidative skeletal
muscle.
- Language of Publication
- English
- Unique Identifier
- 91275049
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- MeSH Heading (Major)
- Fatigue|*ME; Muscles|BS/EN/*ME
- MeSH Heading
- Animal; Dogs; Free Radical Scavengers; Free Radicals; Hindlimb|PH; In Vitro;
Isometric Contraction|PH; Mice; Muscle Contraction|PH; Oxidation-Reduction;
Oxygen Consumption|PH; Regional Blood Flow|PH; Xanthine Oxidase|ME
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0008-4212
- Country of Publication
- CANADA
Record 16 from database: MEDLINE
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- Title
- Mechanism of hemoglobin-induced protection against endotoxemia in rats: a
ferritin-independent pathway.
- Author
- Otterbein L; Chin BY; Otterbein SL; Lowe VC; Fessler HE; Choi AM
- Address
- Division of Pulmonary and Critical Care, Johns Hopkins University School of
Medicine, Baltimore, Maryland 21205, USA.
- Source
- Am J Physiol, 1997 Feb, 272:2 Pt 1, L268-75
- Abstract
- Hemoglobin (Hb) induces heme oxygenase-1 (HO-1), which catalyzes the
breakdown of heme to bilirubin, and ferritin. Rats pretreated with Hb have been
shown to survive lethal doses of lipopolysaccharide (LPS; see L. Otterbein, S.
L. Sylvester, and A. M. Choi. Am. J. Respir. Cell Mol. Biol. 13: 595-601, 1995).
The physiological basis of this increased survival and the mechanism(s) involved
in the protection against LPS by Hb are unknown. Here we investigated 1) the
effects of Hb on the hemodynamic and biochemical parameters of LPS-induced
tissue injury and 2) the mechanism(s) by which Hb conferred protection against
shock and tissue injury. Hb-treated rats maintained normal mean arterial blood
pressure, whereas control rats experienced cardiovascular collapse after a
lethal dose of LPS. Hepatic and renal functions, peripheral white blood cells,
serum lactate dehydrogenase, and phosphate also remained normal after LPS in
Hb-treated rats. Hb also attenuated LPS-induced neutrophil alveolitis and tumor
necrosis factor-alpha levels. Pretreatment with both desferoxamine, which, like
ferritin, can bind iron, and with exogenous apoferritin failed to protect
against LPS. In contrast, treatment with Hb plus desferoxamine, which induced
HO-1 but not ferritin, did protect against LPS. Treatment with iron-dextran,
which induced ferritin but not HO-1, did not protect against LPS. We conclude
that Hb pretreatment reduces the inflammatory and physiological consequences of
LPS and that the Hb-induced protection against LPS is dependent on HO-1 and not
ferritin induction.
- Language of Publication
- English
- Unique Identifier
- 97216006
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- MeSH Heading (Major)
- Endotoxemia|*PC/PP; Ferritin|GE/*PH; Hemoglobins|*PD
- MeSH Heading
- Animal; Blood Pressure|DE; Enzyme Induction; Heme Oxygenase
(Decyclizing)|GE/ME; Inflammation|PC/PP; Lipopolysaccharides|PD; Male; Rats;
Rats, Sprague-Dawley; Reference Values; RNA, Messenger|ME; Shock, Septic|MO/PC;
Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tumor Necrosis Factor|AN
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0002-9513
- Country of Publication
- UNITED STATES
Record 17 from database: MEDLINE
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- Title
- Preparation of 67Ga-labelled human IgG and its Fab fragments using
desferoxamine as chelating agent.
- Author
- Motta Hennessy C; Eccles SA; Dean C; Coghlan G
- Address
-
- Source
- Eur J Nucl Med, 1985, 11:6-7, 240-5
- Abstract
- Human IgG and its Fab fragments were chosen as a model system for studying
the desferoxamine (DF) coupling reaction using glutaraldehyde or carbodiimide at
various concentrations. The labelling of the IgG-DF conjugates with 67Ga proved
to be highly efficient and reproducible. The labelling efficiency in relation to
storage time of the conjugate was analysed over a 1-month period by
Sephadex-G-50 chromatography. Gel-filtration analysis on Sephacryl S-300 showed
that, following the coupling procedure, a high proportion (more than 80%) of the
conjugate remained monomeric. Immunoelectrophoresis on agar plates demonstrated
that the antibody immunoreactivity was preserved. The biodistribution in mice of
the 67Ga-DF-IgG conjugates was comparable to that of the conventional
radiopharmaceutical, 125I-HSA. Conditions were established for the coupling of
DF to two rat IgG2b monoclonal antibodies M10/76 and 11/160, that are specific
for the Hooded rat sarcomata MC 24 and HSN respectively; the immunoreactivity of
these conjugates was tested by a cell-binding assay. The data indicate that
monoclonal-antibody/DF conjugates prepared with the bifunctional reagent
glutaraldehyde maintain their capacity for binding to their tumour-associated
antigens.
- Language of Publication
- English
- Unique Identifier
- 86081879
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- MeSH Heading (Major)
- Antibodies, Monoclonal|*DU; Deferoxamine|*; Gallium Radioisotopes|*/DU;
IgG|*; Immunoglobulins, Fab|*
- MeSH Heading
- Animal; Chelating Agents; Chromatography, Gel; Human; Immunoelectrophoresis;
Isotope Labeling|MT; Mice; Rats
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0340-6997
- Country of Publication
- GERMANY, WEST
Record 18 from database: MEDLINE
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- Title
- Pulmonary clearance of three aerosolized solutes in oleic acid-induced lung
injury.
- Author
- Huchon GJ; Montgomery AB; Lipavsky A; Hoeffel JM; Murray JF
- Address
- UniversitÆe RenÆe Descartes, Clinique de Pneumophtisiologie, HÈopital
LÂaennec, Paris, France.
- Source
- J Appl Physiol, 1988 Mar, 64:3, 1171-8
- Abstract
- We studied the effects of oleic acid (OA) on pulmonary clearance of three
aerosolized radioactive solutes: 99mTc-diethylenetriamine pentaacetate
(99mTc-DTPA), 67Ga-desferoxamine (67Ga-DFOM), and 111In-transferrin (111In-TF).
Either 0.09 ml/kg OA or an equivalent volume of 0.9% NaCl (controls) was
administered intravenously to 48 anesthetized, paralyzed dogs. Each animal
received one aerosolized solute either 60 min after (protocol A) or 30 min
before (protocol B) the infusion of OA or NaCl. In protocol A clearances of all
three solutes were similar in OA and control animals. In contrast, in protocol B
clearances of all three solutes increased significantly during OA infusion;
during the next 60 min clearances of 99mTc-DTPA and 67Ga-DFOM returned to
control values but 111In-TF remained increased. We conclude that 1) in
OA-induced permeability edema pulmonary clearance of aerosolized solutes is
increased when the aerosol is delivered 30 min before but not 60 min after
injury, and 2) increased clearance persists only for large molecules, presumably
because smaller molecules cross injured epithelium quickly and completely. These
phenomena are best explained by a nonhomogeneous distribution of OA-induced
injury.
- Language of Publication
- English
- Unique Identifier
- 88213228
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- MeSH Heading (Major)
- Lung|DE/*ME/RI; Oleic Acids|*PD; Pulmonary Edema|*ME
- MeSH Heading
- Aerosols; Analysis of Variance; Animal; Capillary Permeability; Comparative
Study; Deferoxamine|DU; Dogs; Extracellular Space|ME; Gallium Radioisotopes|DU;
Indium Radioisotopes|DU; Organometallic Compounds|DU; Oxygen|BL; Pentetic
Acid|DU; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Technetium|DU;
Time Factors; Transferrin|DU
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 8750-7587
- Country of Publication
- UNITED STATES
Record 19 from database: MEDLINE
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- Title
- Oxygen consumption in Plasmodium berghei-infected murine red cells: a direct
spectrophotometric assay in intact erythrocytes.
- Author
- Deslauriers R; Moffatt DJ; Smith IC
- Address
-
- Source
- Biochim Biophys Acta, 1986 May, 886:3, 319-26
- Abstract
- A spectrophotometric assay has been devised to measure oxygen consumption
non-invasively in intact murine red cells parasitized by Plasmodium berghei. The
method uses oxyhemoglobin in the erythrocytes both as a source of oxygen and as
an indicator of oxygen consumption. Spectra of intact cells show broad peaks and
sloping baselines due to light-scattering. In order to ascertain the number of
varying components in the 370-450 nm range, the resolution of the spectra was
enhanced using Fourier transforms of the frequency domain spectra. Calculation
of oxygen consumption was carried out for two-component systems (oxyhemoglobin,
deoxyhemoglobin) using absorbances at 415 and 431 nm. Samples prepared from
highly parasitized mice (greater than 80% parasitemia, 5% hematocrit) showed
oxygen consumption rates of (4-8) X 10(-8) microliter/cell per h. This rate was
not attributable to the presence of white cells or reticulocytes. The rate of
oxygen consumption in the erythrocytes is shown to be modulated by various
agents: the respiratory inhibitors NaN3 and KCN (1 mM) reduced oxygen
consumption 2-3-fold; salicylhydroxamic acid (2.5 mM) caused a 20% reduction in
rate and 10 mM NaN3, completely blocked deoxygenation. Antimalarial drugs and
metal-chelating agents were also tested. Chloroquine, EDTA and desferal
(desferoxamine mesylate) did not decrease the deoxygenation rate of hemoglobin
in parasitized cells. Quinacrine, quinine and primaquine reduced the rate of
formation of deoxyhemoglobin but also produced substantial quantities of
methemoglobin. The lipophilic chelator, 5-hydroxyquinoline, decreased the rate
of deoxygenation one-third. The spectrophotometric assay provides a convenient
means to monitor oxygen consumption in parasitized red cells, to test the
effects of various agents thereon, and potentially to explore possible
mechanisms for oxygen utilization.
- Language of Publication
- English
- Unique Identifier
- 86216302
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- MeSH Heading (Major)
- Malaria|*BL; Plasmodium berghei|*ME
- MeSH Heading
- Animal; Antimalarials|PD; Azides|PD; Chelating Agents|PD; Comparative Study;
Erythrocytes|PS; Male; Mice; Oxygen Consumption|DE; Oxyhemoglobins|AN; Potassium
Cyanide|PD; Rats; Spectrophotometry; Time Factors
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-3002
- Country of Publication
- NETHERLANDS
Record 20 from database: MEDLINE
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- Title
- Gastric injury induced by ethanol and ischemia-reperfusion in the rat.
Differing roles for lipid peroxidation and oxygen radicals.
- Author
- Smith GS; Mercer DW; Cross JM; Barreto JC; Miller TA
- Address
- Department of Surgery, University of Texas Medical School, USA.
- Source
- Dig Dis Sci, 1996 Jun, 41:6, 1157-64
- Abstract
- This study determined the role that oxygen-derived free radicals played in
the production of gastric injury in rats challenged orally with concentrated
ethanol or subjected to vascular compromise. In the ethanol study, rats were
pretreated with a variety of free radical scavengers or enzyme inhibitors prior
to exposing the stomach to 100% ethanol. At sacrifice, the degree of macroscopic
damage to the glandular gastric mucosa was quantified. In separate studies, the
effects of ethanol on gastric mucosal levels of enaldehydes (malondialdehyde and
4-hydroxynonenal) were examined as an index of lipid peroxidation. Superoxide
dismutase and catalase pretreatment were without benefit in reducing injury in
our ethanol model, excluding potential contributory roles for the superoxide
anion or hydrogen peroxide, respectively. Dimethyl sulfoxide and desferoxamine
were likewise without protective capabilities, eliminating a role for the
hydroxyl radical. Allopurinol, a xanthine oxidase inhibitor, provided no
protection under acute conditions, even though partial protection was noted when
administered chronically. Further, enaldehyde levels were not increased over
control levels in alcohol-exposed mucosa, indicating no enhanced lipid peroxide
formation. In contrast, in animals in which ischemia to the stomach was induced
followed by reperfusion, marked gastric injury was observed in combination with
enhanced enaldehyde levels. Prevention of enaldehyde formation by a
21-aminosteroid concomitantly prevented injury induced by ischemia-reperfusion.
These findings support the conclusion that ischemia-reperfusion injury to the
stomach is an oxygen-derived free radical process whereas ethanol-induced injury
clearly involved some other process. Although allopurinal was partially
protective against ethanol damage when administered chronically, observations in
other models of injury suggest that this action is independent of its inhibitory
effect on xanthine oxidase.
- Language of Publication
- English
- Unique Identifier
- 96258871
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- MeSH Heading (Major)
- Ethanol|*TO; Gastric Mucosa|BS/*DE/ME/*PA; Lipid Peroxidation|*; Reperfusion
Injury|ME/*PA
- MeSH Heading
- Allopurinol|PD; Animal; Antioxidants|PD; Catalase|PD; Deferoxamine|PD;
Dimethyl Sulfoxide|PD; Free Radicals|ME; Pregnatrienes|PD; Rats; Rats,
Sprague-Dawley; Superoxide Dismutase|PD
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0163-2116
- Country of Publication
- UNITED STATES
Record 21 from database: MEDLINE
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- Title
- Relationship of bacterial growth phase to killing of Listeria monocytogenes
by oxidative agents generated by neutrophils and enzyme systems.
- Author
- Bortolussi R; Vandenbroucke Grauls CM; van Asbeck BS; Verhoef J
- Address
- Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia,
Canada.
- Source
- Infect Immun, 1987 Dec, 55:12, 3197-203
- Abstract
- Listeria monocytogenes, a gram-positive motile bacterium which can cause
severe bacterial infection in humans, is considered to be pathogenic by virtue
of its ability to resist intracellular killing. Since the mechanism of
intracellular survival is poorly understood, we assessed the sensitivity of L.
monocytogenes to several potent antibacterial products. Phorbol myristate
acetate (PMA)-stimulated polymorphonuclear cells (PMNs) produced extracellular
antibacterial products which were inhibited completely by catalase, suggesting a
role for oxidative agents in this process. L. monocytogenes in logarithmic (log)
growth phase resisted PMA-stimulated PMN extracellular products significantly
more than L. monocytogenes in stationary (stat) growth phase or Escherichia coli
(three strains) in either phase of growth. The role of oxidative agents was
studied further by using xanthine oxidase-xanthine, glucose oxidase-glucose, and
myeloperoxidase enzyme systems to generate hydroxyl radical (.OH), hydrogen
peroxide (H2O2), and hypochlorous acid (OCl-), respectively. L. monocytogenes in
log phase resisted the antibacterial products of these enzyme systems under
conditions which produced superoxide (O2-) and H2O2 at concentrations similar to
those produced extracellularly by PMA-stimulated PMNs, while stat-growth-phase
L. monocytogenes and E. coli in either phase of growth were susceptible.
Antibacterial activity could be blocked or inhibited by exogenous catalase (for
all oxygen radical-generating systems), mannitol, or desferoxamine (for xanthine
oxidase-xanthine) and alanine (for myeloperoxidase), suggesting that .OH and
OCl- were responsible for this activity. Log-phase L. monocytogenes had 2.5-fold
higher bacteria-associated catalase activity, as compared with stat-phase L.
monocytogenes. These experiments, therefore, suggest that log-phase L.
monocytogenes resists oxidative antibacterial agents by producing sufficient
catalase to inactivate these products. This may contribute to the ability of L.
monocytogenes to survive intracellularly.
- Language of Publication
- English
- Unique Identifier
- 88057619
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- MeSH Heading (Major)
- Listeria monocytogenes|DE/*GD/IM; Neutrophils|*IM; Oxygen|*TO
- MeSH Heading
- Blood Bactericidal Activity; Catalase|ME; Extracellular Space; Free
Radicals; Glucose Oxidase|ME; Hydrogen Peroxide|BI; Hydroxides; Monocytes|PH;
Peroxidase|PH; Superoxides|BI; Support, Non-U.S. Gov't; Tetradecanoylphorbol
Acetate|PD; Xanthine Oxidase|PH
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0019-9567
- Country of Publication
- UNITED STATES
Record 22 from database: MEDLINE
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- Title
- Superoxide mediates the toxicity of paraquat for Chinese hamster ovary
cells.
- Author
- Bagley AC; Krall J; Lynch RE
- Address
-
- Source
- Proc Natl Acad Sci U S A, 1986 May, 83:10, 3189-93
- Abstract
- The roles of superoxide and H2O2 in the cytotoxicity of paraquat were
assessed in Chinese hamster ovary cells. Neither catalase nor superoxide
dismutase inhibited the loss of ability to form colonies when added to the
medium. When introduced into the cells, superoxide dismutase but not catalase
inhibited the toxicity of paraquat. That superoxide dismutase acted by its known
catalytic action is shown by the loss of inhibition when the enzyme was
inactivated by H2O2 before being introduced into the cells. The lack of
inhibition by catalase, by dimethyl sulfoxide, and by desferoxamine suggests
that the toxicity is not mediated by a reaction between H2O2 and superoxide to
engender the hydroxyl radical. Exposure of Chinese hamster ovary cells to
paraquat may be a suitable means to determine the effects of superoxide anion in
cultured cells and the ways in which cells can resist this toxic action.
- Language of Publication
- English
- Unique Identifier
- 86205862
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- MeSH Heading (Major)
- Paraquat|*TO; Superoxides|*TO
- MeSH Heading
- Animal; Catalase|AD/ME; Cell Line; Cell Survival|DE; Female; Hamsters;
Ovary; Superoxide Dismutase|AD/ME; Support, Non-U.S. Gov't; Support, U.S. Gov't,
P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0027-8424
- Country of Publication
- UNITED STATES
Record 23 from database: MEDLINE
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- Title
- Lungs in thalassaemia major patients receiving regular transfusion.
- Author
- Tai DY; Wang YT; Lou J; Wang WY; Mak KH; Cheng HK
- Address
- Dept of Respiratory Medicine, Tan Tock Seng Hospital, Singapore.
- Source
- Eur Respir J, 1996 Jul, 9:7, 1389-94
- Abstract
- Progressive tissue iron deposition from multiple blood transfusions is
common in beta-thalassaemia and pulmonary iron deposition may result in
parenchymal damage. The objectives of this study were to: 1) determine the
predominant pulmonary dysfunction in patients with thalassaemia major; and 2)
demonstrate that parenchymal disease, if present, is at the level of the
alveolocapillary membrane. Fourteen thalassaemia major patients (13 nonsmokers)
receiving regular blood transfusion and without any history of chronic
respiratory disease were recruited. Pulmonary function tests and
echocardiography were performed before the scheduled transfusions. Three
patients with the most restricted lung function were selected for high
resolution computerized tomography (CT) of the lungs. One patient had an
obstructive pattern with a forced expiratory volume in one second as percentage
of forced vital capacity (FEV1/FVC) of 71%. Four patients demonstrated a
restrictive pattern, as defined by total lung capacity (TLC) less than 80%
predicted with normal FEV1/FVC%. Twelve patients had pulmonary transfer factors
for carbon monoxide (TL,CO) below 80% pred, even after correction for the
anaemia, indicating parenchymal disease. Eight of these 12 patients had
alveolocapillary membrane defect, as demonstrated by a gas transfer factor of
the pulmonary membrane (Tm) less than 80% pred. Mean resting arterial oxygen
saturation was 95 2 (range 92-98) %. Eleven patients had oxygen desaturation of
5% or more during exercise on a bicycle ergometer, consistent with interstitial
lung disease. There was no clinical or echocardiographic evidence of heart
failure. Percentage predicted TLC was inversely correlated with age (r = -0.547;
p = 0.043). Both percentage predicted TLC and TL,CO were not correlated with
iron burden or desferoxamine ratio. High resolution CT in the three selected
patients showed no evidence of pulmonary fibrosis. We conclude that thalassaemia
major patients have a predominant restrictive lung dysfunction with pulmonary
parenchymal disease and alveolocapillary membrane block. The restrictive and
interstitial lung disease could not be accounted for by iron loading or
pulmonary fibrosis in our patients.
- Language of Publication
- English
- Unique Identifier
- 96433668
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- MeSH Heading (Major)
- beta-Thalassemia|CO/*PP/TH; Blood Transfusion|*AE; Lung Diseases|DI/*ET/PP
- MeSH Heading
- Adolescence; Blood-Air Barrier|PH; Echocardiography; Exercise Test; Female;
Human; Iron Overload|DI; Lung|RA; Male; Respiratory Function Tests; Spirometry
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0903-1936
- Country of Publication
- DENMARK
Record 24 from database: MEDLINE
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- Title
- Involvement of nitric oxide in nitroprusside-induced hepatocyte
cytotoxicity.
- Author
- Niknahad H; OBrien PJ
- Address
- Faculty of Pharmacy, University of Toronto, Ontario, Canada.
- Source
- Biochem Pharmacol, 1996 Apr, 51:8, 1031-9
- Abstract
- Sodium nitroprusside (SNP) cytotoxicity towards rat hepatocytes was
accompanied by peroxynitrite formation, lipid peroxidation, inhibition of
glycolysis, cyanide (CN) release, partial inhibition of hepatocyte respiration,
and ATP depletion. Antioxidants and desferoxamine prevented both cytotoxicity
and lipid peroxidation induced by SNP. The CN antidote thiosulfate or the CN
trapping agents dihydroxyacetone and glyceraldehyde increased SNP metabolism,
SNP-induced peroxynitrite formation, cytotoxicity, and lipid peroxidation. On
the other hand, addition of non-toxic concentrations of CN to hepatocytes
prevented SNP metabolism and SNP-induced lipid peroxidation and cytotoxicity.
SNP depleted hepatocyte GSH immediately upon addition, and GSH-depleted
hepatocytes were more susceptible to SNP. The results of this study suggest that
nitric oxide rather than CN mediates SNP cytotoxicity in isolated cells.
- Language of Publication
- English
- Unique Identifier
- 97020446
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- MeSH Heading (Major)
- Liver|*DE/ME; Nitric Oxide|*ME; Nitroprusside|*PD/TO
- MeSH Heading
- Animal; Cell Survival; Cells, Cultured; Lipid Peroxidation; Male;
Nitrates|ME; Rats; Rats, Sprague-Dawley; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-2952
- Country of Publication
- ENGLAND
Record 25 from database: MEDLINE
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- Title
- Non-proteolytic activation of latent human neutrophil collagenase and its
role in matrix destruction in periodontal diseases.
- Author
- Sorsa T; Saari H; Konttinen YT; Suomalainen K; Lindy S; Uitto VJ
- Address
- Department of Medical Chemistry, University of Helsinki, Finland.
- Source
- Int J Tissue React, 1989, 11:4, 153-9
- Abstract
- Collagenases are known to be associated with tissue destruction in chronic
inflammatory diseases such as periodontal diseases and rheumatoid arthritis.
Collagenases are secreted by circulating inflammatory cells (polymorphonuclear
leukocytes and monocytes), resident mesenchymal cells and epithelial cells in
latent forms, which can be activated by proteases and compounds reacting with
protein thiol groups. We have studied here the effects of oxygen-derived free
radicals (ODFR) on latent human neutrophil collagenase. Also, in order to
elucidate the cellular sources of collagenases, the ability of human gingival
crevicular fluid (GCF) collagenases both from adult periodontitis (AP) and
localized juvenile periodontitis (LJP) patients to degrade soluble interstitial
collagen types I and II was studied. ODFR generated by the xanthine
oxidase/hypoxanthine system in the presence of trace amounts of iron and EDTA
activated latent neutrophil collagenase to an equal extent as the known
activators phenylmercuric chloride and gold thioglucose. ODFR activation was
inhibited by desferoxamine and mannitol as well as by superoxide dismutase and
catalase. Clear differences in the susceptibility of collagen types I and II to
AP and LJP GCF collagenases were observed. AP GCF collagenase degraded type I
and II collagens at equal rates, resembling the substrate-specificity of human
neutrophil collagenase. LJP GCF collagenase degraded type I collagen
considerably faster than type II collagen, which was only negligibly degraded.
This corresponds to the substrate specificity of fibroblast collagenase.
Zymographic evaluation of gelatinolytic proteases showed the presence of 90 and
68 kD gelatinases in both AP and LJP GCF. Non-proteolytic means apparently
provide a potent activation pathway of neutrophil collagenase in vivo and the
hydroxyl radical was identified to be one of the potent activating
oxidants.(ABSTRACT TRUNCATED AT 250 WORDS)
- Language of Publication
- English
- Unique Identifier
- 90236600
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- MeSH Heading (Major)
- Extracellular Matrix|*ME; Microbial Collagenase|*BL/IP/PH; Neutrophils|*EN;
Oxygen|*PD; Periodontal Diseases|*EN/ME
- MeSH Heading
- Body Fluids|EN; Collagen|ME; Electrophoresis, Polyacrylamide Gel; Enzyme
Activation; Free Radicals; Gingiva|EN; Human; Molecular Weight; Support,
Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0250-0868
- Country of Publication
- SWITZERLAND
Record 26 from database: MEDLINE
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- Title
- Elucidation of antioxidant activity of alpha-lipoic acid toward hydroxyl
radical.
- Author
- Matsugo S; Yan LJ; Han D; Trischler HJ; Packer L
- Address
- Department of Molecular and Cell Biology, University of California at
Berkeley 94720-3200.
- Source
- Biochem Biophys Res Commun, 1995 Mar, 208:1, 161-7
- Abstract
- The photosensitive organic hydroperoxide, NP-III, which produces hydroxyl
radicals on illumination by UVA light, was used to examine the antioxidant
activity of alpha-lipoic acid and its derivatives toward hydroxyl radical.
Apolipoprotein (apo-B) of human low density lipoprotein (LDL) and bovine serum
alubumin (BSA) were irradiated with UVA in the presence of NP-III and
alpha-lipoic acid. The oxidation of BSA and the apo-B protein of LDL by NP-III
was completely suppressed by alpha-lipoic acid. ESR studies using
dimethylpyrroline oxide (DMPO) as a spin trapping reagent also revealed that in
the presence of alpha-lipoic acid, the DMPO-OH adduct produced from the
irradiation of NP-III and DMPO completely disappeared. DMPO-OH quenching
experiments were performed in the presence or absence of desferoxamine but no
change in the signal intensity was found. Hence, the quenching activity of
alpha-lipoic acid is not due to its chelating activity toward transition metals
(ferrous ions). The results lead us to conclude that alpha-lipoic acid is an
efficient hydroxyl radical quencher owing to the disulfide bond in the
dithiolane ring.
- Language of Publication
- English
- Unique Identifier
- 95194401
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- MeSH Heading (Major)
- Antioxidants|*/PD; Apolipoproteins B|*DE/RE; Hydroxyl Radical|*; Serum
Albumin, Bovine|*DE/RE; Thioctic Acid|*/PD
- MeSH Heading
- Cyclic N-Oxides; Electron Spin Resonance Spectroscopy; Human; Kinetics;
Naphthalenes; Radiation-Sensitizing Agents; Salicylic Acids; Spin Labels;
Ultraviolet Rays
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-291X
- Country of Publication
- UNITED STATES
Record 27 from database: MEDLINE
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- Title
- Modulating hypoxia-induced hepatocyte injury by affecting intracellular
redox state.
- Author
- Khan S; OBrien PJ
- Address
- Faculty of Pharmacy, University of Toronto, Ont., Canada.
- Source
- Biochim Biophys Acta, 1995 Nov, 1269:2, 153-61
- Abstract
- Hypoxia-induced hepatocyte injury results not only from ATP depletion but
also from reductive stress and oxygen activation. Thus the NADH/NAD ratio was
markedly increased in isolated hepatocytes maintained under 95% N2/5% CO2 in
Krebs-Henseleit buffer well before plasma membrane disruption occurred.
Glycolytic nutrients fructose, dihydroxyacetone or glyceraldehyde prevented
cytotoxicity, restored the NADH/NAD ratio, and prevented complete ATP depletion.
However, the NADH generating nutrients sorbitol, xylitol, glycerol and
beta-hydroxybutyrate enhanced hypoxic cytotoxicity even though ATP depletion was
not affected. On the other hand, NADH oxidising metabolic intermediates
oxaloacetate or acetoacetate prevented hypoxic cytotoxicity but did not affect
ATP depletion. Restoring the cellular NADH/NAD ratio with the artificial
electron acceptors dichlorophenolindophenol and Methylene blue also prevented
hypoxic injury and partly restored ATP levels. Ethanol which further increased
the cellular NADH/NAD ratio increased by hypoxia also markedly increased
toxicity whereas acetaldehyde which restored the normal cellular NADH/NAD ratio,
prevented toxicity even though hypoxia induced ATP depletion was little affected
by ethanol or acetaldehyde. The viability of hypoxic hepatocytes is therefore
more dependent on the maintenance of normal redox homeostasis than ATP levels.
GSH may buffer these redox changes as hypoxia caused cell injury much sooner
with GSH depleted hepatocytes. Hypoxia also caused an intracellular release of
free iron and cytotoxicity was prevented by desferoxamine. Furthermore,
increasing the cellular NADH/NAD ratio markedly increased the intracellular
release of iron. Hypoxia-induced hepatocyte injury was also prevented by
oxypurinol, a xanthine oxidase inhibitor. Polyphenolic antioxidants or the
superoxide dismutase mimic, TEMPO partly prevented cytotoxicity suggesting that
reactive oxygen species contributed to the cytotoxicity. The above results
suggests that hypoxia induced hepatocyte injury results from sustained reductive
stress and oxygen activation.
- Language of Publication
- English
- Unique Identifier
- 96087038
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- MeSH Heading (Major)
- Cell Hypoxia|*PH; Liver|*CY/DE/*ME
- MeSH Heading
- Acetaldehyde|PD; Adenosine Triphosphate|ME; Animal; Antioxidants|PD;
Calcium|PD; Cell Death; Cell Survival; Cells, Cultured; Chelating Agents|PD;
Deferoxamine|PD; Ethanol|PD; Free Radical Scavengers|PD; Lactates|ME; Models,
Biological; NAD|ME; Oxidation-Reduction; Phenols|PD; Polymers|PD; Pyruvates|ME;
Rats; Rats, Sprague-Dawley
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-3002
- Country of Publication
- NETHERLANDS
Record 28 from database: MEDLINE
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- Title
- Scavenging of reactive oxygen species as the mechanism of drug action.
- Author
- Robak J; Marcinkiewicz E
- Address
- Department of Pharmacology, Medical College of Jagiellonian University,
KrakÆow, Poland.
- Source
- Pol J Pharmacol, 1995 Mar, 47:2, 89-98
- Abstract
- Reactive oxygen species (ROS) are generated when oxygen is supplied in
excess and/or its reduction is insufficient. The best explored ROS are
superoxide anions, hydroxyl radicals and hydrogen peroxide. The first two are
free radicals. ROS are harmful for the living cells and are implicated in a
variety of pathological processes and diseases. Drugs used in the treatment of
these states are either stimulators of endogenous defense mechanisms against ROS
or inhibitors of ROS formation. Six groups of anti-ROS substances have been
described in this paper. 1) Antioxidant substances used in substitutive therapy
such as enzymes (e.g. superoxide dismutase), substances containing thiol groups
and vitamins (A, E, P, C). 2) Chelating agents (e.g. desferoxamine), which lower
the level of prooxidative transition metal ions. 3) Inhibitors of superoxide
ions generation by stimulated cells or xanthine oxidase. Such mechanism of
action was described for xanthine oxidase inhibitor-allopurinol. 4) Superoxide
scavengers. Many known drugs were investigated for this activity, but the best
documentation was presented for flavonoids. 5) Substances which eliminate
hydrogen peroxide, mainly glutathione and its precursors. 6) Scavengers of
hydroxyl radicals. Studies of the above activity were conducted mainly using an
unspecific method--estimation of malondialdehyde generated during the action of
hydroxyl radicals on lipids or on desoxyribose. Inhibition of malondialdehyde
formation was described for many drugs of plant and synthetic origin.
- Language of Publication
- English
- Unique Identifier
- 96296419
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- MeSH Heading (Major)
- Free Radical Scavengers|AE/*ME; Reactive Oxygen Species|AE/CL/*ME
- Publication Type
- JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
- ISSN
- 1230-6002
- Country of Publication
- POLAND
Record 29 from database: MEDLINE
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- Title
- The uptake of ascorbic acid into human umbilical vein endothelial cells and
its effect on oxidant insult.
- Author
- Ek A; Ström K; Cotgreave IA
- Address
- Division of Toxicology, Karolinska Institute, Stockholm, Sweden.
- Source
- Biochem Pharmacol, 1995 Oct, 50:9, 1339-46
- Abstract
- Intracellular reduced ascorbate (AA) levels in confluent cultures of human
umbilical vein endothelial (HUVE) cells, grown under conventional conditions,
were shown to be very low, ranging between undetectable, < 0.1 nmol/mg
protein, and 0.3 nmol/mg protein. Reduced ascorbate was accumulated into the
endothelial cells from M199 culture medium in time- and concentration-dependent
manners, and was saturated at medium concentrations related to the normal plasma
concentrations of the antioxidant (i.e. between 50 microM and 100 microM). Cells
derived from different individuals demonstrated considerable inter-individual
variation in these AA uptake parameters. The uptake of AA was sensitive to
temperature and the presence of the structural analogue isoascorbate in the
medium, indicating the involvement of an active transport mechanism. A role for
the glucose transporter is, however, not indicated, as AA uptake was not
sensitive to phloretin, an inhibitor of the cellular glucose transporter, nor
greatly enhanced by depletion of glucose from the medium. Incubation of HUVE
cells with dehydroascorbate (DHAA) caused a dose-dependent, but transient
increase in intracellular AA. This indicates that HUVE cells are both competent
in the uptake and intracellular reduction of oxidised ascorbate, and may
resecrete AA into the medium. Indeed, reduced ascorbate in the medium was shown
to be preferentially maintained in the presence of cells. The uptake of AA was
not sensitive to the presence of DHAA in the medium, perhaps indicating
different transporters for reduced and oxidised forms of ascorbate in these
human cells. Pre-loading HUVE cells with AA was shown to protect control cells
only weakly from the acute, sub-lethal toxicity of H2O2 generated by xanthine
oxidase (1 U/mL or 10 U/mL). Protection was optimal at intracellular levels of
3-4 nmol AA/mg protein, with higher concentrations lacking a protective effect.
Additionally, the presence of the iron chelator, desferoxamine, significantly
protected GSH-depleted HUVE cells only in response to the peroxide, but did not
potentiate the protective action of intracellular AA in either control or GSH-depleted cells. This indicates that ascorbate-driven
redox-cycling of the
Fe2ﱗ does not hamper the intracellular protective function of ascorbate during
hydrogen peroxide-derived oxidative stress. These results are discussed in terms
of the central role of endothelial cells in the distribution of AA to the
tissues of the body, the use of the HUVE cell system for model studies of the
toxicity of oxidants in the human endothelium, and the balance between the
antioxidant and pro-oxidant actions of AA.
- Language of Publication
- English
- Unique Identifier
- 96080268
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- MeSH Heading (Major)
- Ascorbic Acid|*PK; Endothelium, Vascular|*ME; Hydrogen Peroxide|*TO;
Oxidative Stress|*PH
- MeSH Heading
- Cells, Cultured; Culture Media; Dehydroascorbic Acid|ME/PK; Human;
Intracellular Fluid|ME; Iron|ME; Monosaccharide Transport Proteins|ME;
Oxidation-Reduction; Support, Non-U.S. Gov't; Umbilical Veins|ME
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-2952
- Country of Publication
- ENGLAND
Record 30 from database: MEDLINE
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- Title
- Aluminum levels and stores in patients with total hip endoprostheses from
TiAIV or TiAINb alloys.
- Author
- Dittert DD; Warnecke G; Willert HG
- Address
- Abteilung Pathologie I, UniversitÂatsklinik, GÂottingen, Germany.
- Source
- Arch Orthop Trauma Surg, 1995, 114:3, 133-6
- Abstract
- Aluminum ranks as a potentially hazardous agent. Pathologic findings in
different organs show that it can accumulate in brain, muscle, liver and bone.
Therefore, we investigated whether patients with cementless total hip
endoprostheses made out of titanium alloys containing aluminum are at risk. In
order to determine the complete aluminum body loading in patients who have had
their hip replacement for a long period of time (mean 58 months), we mobilized
possible stores of aluminum with desferoxamine (DFO). Electrothermal atomic
absorption spectroscopy was used to quantify the level of aluminum in serum and
urine before and after DFO treatment. A serum aluminum value of 10 micrograms/l
or less is internationally accepted as safe. The average serum aluminum level in
this study was 14.2 micrograms/l, which is slightly above the limit, but clearly
below those levels which can lead to disease (> 50 micrograms/l). No relevant
storage of aluminum was found. This latter finding is more important since
chronically elevated aluminum levels lead to cellular deposits, which affect the
cellular biochemistry. The values before and after DFO mobilization did not
differ substantially, indicating that aluminum in alloys for biomaterials can be
regarded as safe as far as the risk of aluminum release in vivo is concerned.
Histologic studies of bone from the bone-metal interface also showed no deposits
of local aluminum release.
- Language of Publication
- English
- Unique Identifier
- 95344894
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- MeSH Heading (Major)
- Aluminum|BL/*ME/UR; Biocompatible Materials|*ME; Hip Prosthesis|*IS;
Titanium|*ME
- MeSH Heading
- Adult; Aged; Bone and Bones|ME/PA; Deferoxamine|AD/DU; Female; Human; Male;
Middle Age; Prognosis; Prosthesis Design; Spectrophotometry, Atomic Absorption;
Time Factors
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0936-8051
- Country of Publication
- GERMANY
Record 31 from database: MEDLINE
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- Title
- Reactive oxygen species as regulators of human neutrophil and fibroblast
interstitial collagenases.
- Author
- Saari H; Sorsa T; Lindy O; Suomalainen K; Halinen S; Konttinen YT
- Address
- IVth Department of Medicine, Helsinki University Central Hospital, Finland.
- Source
- Int J Tissue React, 1992, 14:3, 113-20
- Abstract
- The effects of various reactive oxygen species on latent human neutrophil
and fibroblast-type interstitial collagenases were studied. Latent human
neutrophil collagenases (proMMP-8) was efficiently activated by hypochlorous
acid and hydrogen peroxide and less efficiently by the serine proteinases
trypsin and chymotrypsin. Human plasmin and plasma kallikrein did not activate
latent human neutrophil collagenase. The activation of latent human neutrophil
collagenase by hypochlorous acid and hydrogen peroxide corresponded to the
activation obtained with the other known non-proteolytic activators
phenylmercuric chloride and gold thioglucose. The activation by hydrogen
peroxide was inhibited by mannitol and desferoxamine, suggesting a localized
Fenton-type reaction to be responsible for the generation of hydroxyl radical
and/or hydroxyl radical-like reactive oxygen pathway of neutrophil
procollagenase does not involve plasmin and plasma kallikrein, which are
efficient proteolytic activators of latent fibroblast-type procollagenase
(proMMP-1). Fibroblast procollagenase was also slightly activated by
hypochlorous acid and gold thioglucose. Thus neutrophil procollagenase seems to
prefer non-proteolytic means of activation and reactive oxygen species can be
regarded as potent activators in vivo. Synovial-fluid neutrophils from
rheumatoid arthritis patients were found to release collagenase in 30% active
form when compared to same patients' peripheral blood neutrophils, which
released collagenase in completely latent form. This may indicate that the
triggering of neutrophil at the site of inflammation in vivo involves initial
oxidative activation of collagenase upon the degranulation process.
- Language of Publication
- English
- Unique Identifier
- 93077254
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- MeSH Heading (Major)
- Collagenases|*ME; Neutrophils|*EN; Reactive Oxygen Species|*ME
- MeSH Heading
- Comparative Study; Fibroblasts|EN; Human; Support, Non-U.S. Gov't; Synovial
Fluid|CY
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0250-0868
- Country of Publication
- SWITZERLAND
Record 32 from database: MEDLINE
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- Title
- The mechanism of cytogenetic genotoxicity of exogenous glutathione in V-79
cells in vitro--implication of hydrogen peroxide and general traits of oxidative
chromosome damage.
- Author
- Thust R
- Address
- Institute of Pathological Anatomy, Medical Academy of Erfurt, German
Democratic Republic.
- Source
- Cell Biol Toxicol, 1988 Jun, 4:2, 241-57
- Abstract
- The mechanism of cytogenetic genotoxicity (clastogenicity, induction, cell
cycle delay) of 10(-3) M glutathione in V79-E cells, as described by Thust and
Bach (1985), was studied in detail by using different treatment conditions. It
was found that 1-cystine is the essential cofactor in the incubation system.
Catalase, but not superoxide dismutase, abolished the genotoxic effect, and the
iron chelator desferoxamine, as well as the hydroxyl radical scavenger mannitol,
diminished the activity. It is suggested that glutathione, in combination with
V79-E cells and cystine, forms a hydrogen peroxide-generating system which
provokes the adverse effects. Glutathione as well as 1-cysteine and
2-mercaptopropionylglycine, which were checked for comparison, show a "paradoxic
genotoxicity," i.e., at 10(-2) M the effects return almost to the level of
controls. Concentration dependence and other criteria of cytogenetic
genotoxicity observed with glutathione show obvious similarities to those of
other oxidatively acting agents and reveal striking differences to the
cytogenetic effects of "typical" genotoxins.
- Language of Publication
- English
- Unique Identifier
- 89167840
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- MeSH Heading (Major)
- Glutathione|*TO
- MeSH Heading
- Animal; Cell Cycle|DE; Cells, Cultured; Chromosome Aberrations|DE;
Dose-Response Relationship, Drug; Guinea Pigs; Mutagenicity Tests; Rats
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0742-2091
- Country of Publication
- UNITED STATES
Record 33 from database: MEDLINE
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- Title
- Are ethane and pentane evolution and thiobarbituric acid reactivity specific
for lipid peroxidation in erythrocyte membranes? [published erratum appears in
Scand J Clin Lab Invest 1993 Apr;53(2):201]
- Author
- Pitkänen OM
- Address
- Children's Hospital, University Central Hospital, Helsinki, Finland.
- Source
- Scand J Clin Lab Invest, 1992 Sep, 52:5, 379-85
- Abstract
- Peroxidation of human erythrocyte membranes was followed in vitro with head
space analysis of ethane and pentane and a thiobarbituric acid assay in a
standardized system liberating free oxygen radicals. Simultaneously, the
decrease of the membrane palmitic, linoleic, arachidonic and docosahexaenoic
acid was monitored. The recoveries of the peroxidation products of the red cell
ghost preparations were compared with those obtained by peroxidation of pure
fatty acids. Experiments using purified fatty acids revealed that ethane was
preferentially produced from docosahexaenoic and linolenic, and pentane from
linoleic and arachidonic acids. Thiobarbituric acid-reactive material (TBAR) was
produced from each unsaturated fatty acid tested, but the amount was dependent
on the number of carbon chain double bonds. During peroxidation of the
erythrocyte ghosts, 72% of ethane and 51% pentane were produced during the first
12 h of incubation, whereas TBAR was produced at a constant rate throughout the
36-h test period. Hydrocarbon and TBAR production were similarly inhibited by
desferoxamine (at p less than 0.005 and p less than 0.0001, respectively). The
total recoveries of ethane, pentane and TBAR exceeded the amount expected by
7.8-, 1.4- and 5.5-fold, respectively. It was concluded that measurement of
pentane is a reliable method to monitor lipid peroxidation during oxidative
damage of the erythrocyte membrane.
- Language of Publication
- English
- Unique Identifier
- 92383503
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- MeSH Heading (Major)
- Erythrocyte Membrane|*ME; Ethane|*BL; Lipid Peroxidation|*; Pentanes|*BL;
Thiobarbiturates|*BL
- MeSH Heading
- Fatty Acids|BL; Free Radicals; Human; Kinetics; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0036-5513
- Country of Publication
- ENGLAND
Record 34 from database: MEDLINE
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- Title
- Detailed characterization of experimental acute alcoholic pancreatitis.
- Author
- Nordback IH; Olson JL; Chacko VP; Cameron JL
- Address
- Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Md
21205-2196.
- Source
- Surgery, 1995 Jan, 117:1, 41-9
- Abstract
- BACKGROUND. With the ex vivo perfused canine pancreas preparation, the
infusion of acetaldehyde, the primary metabolite of ethanol oxidation, plus a
short period of ischemia to convert xanthine dehydrogenase to xanthine oxidase,
results in the physiologic injury response of acute pancreatitis (edema, weight
gain, hyperamylasemia). The free radical scavengers superoxide dismutase and
catalase and a xanthine oxidase inhibitor, allopurinol, ameliorate this injury
response, suggesting that toxic oxygen metabolites generated by xanthine oxidase
play an intermediary role. METHODS. The isolated ex vivo canine pancreas
preparation was perfused for 4 hours, and weight gain of the preparation and
amylase activity in the perfusate were monitored. Changes in pancreatic acinar
cell architecture were characterized by light and electron microscopy, and
intracellular phosphate metabolism was followed by magnetic resonance
spectroscopy in control preparations and in glands simulating alcoholic
pancreatitis. RESULTS. Control preparations and preparations with a 1-hour
period of ischemia before perfusion gained little weight (7 3 gm and 8 1 gm),
amylase activity in the perfusate remained normal (933 513 units/dl and 1537 553
units/dl), and no changes in architecture were observed. Weight gain (5 6 gm)
and amylase activity (1188 173 units/dl) were also normal in the preparations
receiving acetaldehyde without preceding ischemia, but mild vascular and islet
cell injury were observed on electron microscopy. One hour of ischemia followed
by acetaldehyde infusion resulted in edema, increased weight gain (21 12 gm [p
< 0.05]), and amylase activity (2487 1484 units/dl [p < 0.05]). Microscopy
showed mild acinar cell damage and greater injury to the capillaries and the
islets. The capillary and islet cell changes were reduced by superoxide
dismutase and catalase. Intracellular adenosine triphosphate levels remained at
baseline levels in the control preparations. Adenosine triphosphate decreased
during ischemia but quickly recovered during perfusion without a significant
difference whether acetaldehyde was infused after ischemia. An iron chelator
desferoxamine ameliorated the injury response in the preparations simulating
acute pancreatitis (weight gain, 13 6 gm [p = 0.09] and amylase activity, 1198
471 units/dl [p = 0.08]), but a cholecystokinin receptor antagonist L364,718 did
not have an effect. A sulfhydryl group protector, dithiothreitol, decreased
weight gain (10 7 gm [p = 0.06]), and amylase activity was not significantly
increased over that of the control group (1582 641 units/dl), but a serine
protease inhibitor phenylmethylsulphonylfluoride was ineffective. CONCLUSIONS.
In this model simulating acute alcoholic pancreatitis, both the early
physiologic injury response and the early morphologic changes are mediated at
least in part by free radicals, which are generated by xanthine oxidase
converted reversibly from xanthine dehydrogenase. In addition to the superoxide
radical, the hydroxyl radical may also be an important early intermediate step,
but the cholecystokinin receptor is not.
- Language of Publication
- English
- Unique Identifier
- 95108785
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- MeSH Heading (Major)
- Alcoholism|*ET/ME/PA; Pancreatitis|*ET/ME/PA
- MeSH Heading
- Acetaldehyde; Acute Disease; Animal; Disease Models, Animal; Dogs; Free
Radicals|ME; Ischemia|PP; Pancreas|UL; Receptors, Cholecystokinin|ME; Support,
Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Xanthine Oxidase|ME
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0039-6060
- Country of Publication
- UNITED STATES
Record 35 from database: MEDLINE
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- Title
- The role of thiols in mitochondrial susceptibility to iron and tert-butyl
hydroperoxide-mediated toxicity in cultured mouse hepatocytes.
- Author
- Shertzer HG; Bannenberg GL; Zhu H; Liu RM; Moldéus P
- Address
- Department of Environmental Health, University of Cincinnati Medical Center,
Ohio 45267-0056.
- Source
- Chem Res Toxicol, 1994 May, 7:3, 358-66
- Abstract
- Cultured hepatocytes derived from the newborn mutant c14CoS/c14CoS mouse
(14CoS/14CoS cells) have 3-fold higher levels of reduced glutathione (GSH) and
greater resistance to menadione toxicity than hepatocytes derived from the
wild-type cch/cch mouse (ch/ch cells). Therefore, we used these cell lines to
examine mechanisms of oxidative stress produced by iron and tert-butyl
hydroperoxide (TBHP). Both cell types were resistant to 25 microM Fe2 toxicity
in the absence of added TBHP. However, in the presence of Fe2, striking
differences in susceptibility to TBHP toxicity between the cell types were
observed. With 25 microM Fe2, ch/ch cells showed TBHP concentration-dependent
toxicity, with total lethality at 500 microM; in contrast, 14CoS/14CoS cells
were completely resistant to the lethal effects of this concentration of TBHP.
Concentration-dependent TBHP-mediated increases in cytosolic Ca2, pH, and
GSSG/GSH ratios, and decreases in GSH levels, were evident in ch/ch cells.
14CoS/14CoS cells exhibited concentration-dependent TBHP-mediated changes in GSH
and GSSG/GSH ratios, but cytosolic Ca2 and pH remained at control levels.
Mitochondrial GSH pools were also diminished by TBHP, although there was no
selective depletion; mitochondrial GSH remained at about 14% of total cellular
GSH. Both cell types exhibited the same time-dependent decrease in plasma
membrane protein thiols and a time-dependent increase in plasma membrane protein
carbonyls. However, only ch/ch cells displayed a time-dependent depletion of
mitochondrial protein thiols, concomitant with an increase in mitochondrial
protein carbonyls, while 14CoS/14CoS cells were resistant to such changes. All
of the effects produced by TBHP were prevented by desferoxamine.(ABSTRACT
TRUNCATED AT 250 WORDS)
- Language of Publication
- English
- Unique Identifier
- 94355623
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- MeSH Heading (Major)
- Hepatitis, Toxic|*PP; Iron|*TO; Mitochondria, Liver|*DE; Peroxides|*TO;
Reactive Oxygen Species|*TO; Sulfhydryl Compounds|*PD
- MeSH Heading
- Animal; Calcium|ME; Cell Death|DE; Cell Line; Cell Membrane|ME; Cell
Nucleus|DE/ME; DNA|CH; Glutathione|ME; Lipid Peroxidation|DE; Mice; Microscopy,
Fluorescence; Oxidation-Reduction; Spectrometry, Fluorescence; Support, Non-U.S.
Gov't; Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0893-228X
- Country of Publication
- UNITED STATES
Record 36 from database: MEDLINE
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- Title
- Effects of ethanol treatment upon sources of reactive oxygen species in
brain and liver.
- Author
- Bondy SC; Orozco J
- Address
- Department of Community and Environmental Medicine, University of California
at Irvine 92717.
- Source
- Alcohol Alcohol, 1994 Jul, 29:4, 375-83
- Abstract
- Sources of reactive oxygen species (ROS) generation have been compared in
microsomal and mitochondrial fractions of brain and liver from ethanol-treated
and control rats. Rates of ROS generation were quantitated with the fluorescent
probe precursor, 2'7'-dihydrochloroflurescin diacetate, whose validity has been
previously established. The production of active pro-oxidant species was
measured in the presence of various selective inhibitors of enzymes potentially
able to contribute to oxidative events. Several steps in the arachidonic acid
cascade appeared to constitute a large fraction of total ROS generating
capacity. Chelation of intrinsic iron with desferoxamine greatly reduced such
capacity, especially in cerebral tissue. Aldehyde oxidases were active in
generating ROS in both tissues. Inhibition of catalase dramatically enhanced ROS
in liver but not in brain microsomes. While no ethanol-treatment effects were
found in brain, there was evidence that ethanol consumption decreased hepatic
levels of catalase, aldehyde oxidases and cyclooxygenase. However, despite these
reductions, total basal ROS production was elevated in liver but not brain
fractions from treated animals. The addition of an exogenous iron salt enhanced
ROS formation to a lesser extent in ethanol-consuming rats than in controls. The
elevation of basal hepatic ROS levels in ethanol-treated rats may thus be
compatible with the release of cytosolic low molecular weight free iron
compounds into the cytosol.
- Language of Publication
- English
- Unique Identifier
- 95077599
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- MeSH Heading (Major)
- Alcoholism|PA/*RH; Brain|*PA; Liver|*PA; Reactive Oxygen Species|*ME
- MeSH Heading
- Aldehyde Oxidoreductases|PH; Animal; Arachidonic Acid|ME; Catalase|PH;
Ethanol|PK; Free Radicals; Iron|ME; Male; NADP|PH; Prostaglandin-Endoperoxide
Synthase|PH; Rats; Rats, Sprague-Dawley; Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0735-0414
- Country of Publication
- ENGLAND
Record 37 from database: MEDLINE
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- Title
- Drug binding by reservoirs in elastomeric infusion devices.
- Author
- Jenke DR
- Address
- Baxter Healthcare Corporation William B. Graham Science Center Round Lake,
Il 60073.
- Source
- Pharm Res, 1994 Jul, 11:7, 984-9
- Abstract
- Drug binding by an elastomeric infusion device reservoir was assessed by
measuring its ability to bind fifteen model solutes. Octanol/water (o/w) and
hexane/water (h/w) partition coefficients were regressed against the reservoir's
solute equilibrium binding constant to generate a binding model. The reservoir's
drug binding ability was calculated with the model and drug partition
coefficients, which were determined for seventeen commonly infused drugs
including tobramycin, gentamicin, penicillin G, piperacillin, lidocaine,
morphine, ceftriaxone, imipenem-cilastatin, amphotericin B, ticarcillin and
clavulanate, pentamidine, vancomycin, foscarnet, desferoxamine, acyclovir,
fluconazole and vinblastine. Formulations studied included 0.9% Saline and 5%
Dextrose. With the exception of lidocaine, imipenem, vinblastine and
fluconazole, octanol/formulation and hexane/formulation partition coefficients
were too low to be measured for these drugs. Thus, the majority of the drugs,
when reconstituted in 0.9% Saline or 5% Dextrose, will not be bound by the
reservoirs. The magnitude of drug loss for the most highly bound species,
fluconazole, is less than 2%. Therefore the reservoirs used in this study are
essentially inert with respect to binding of the drugs evaluated in this study.
- Language of Publication
- English
- Unique Identifier
- 95023622
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- MeSH Heading (Major)
- Infusion Pumps|*; Pharmaceutical Preparations|*ME; Rubber|*
- MeSH Heading
- Binding Sites; Models, Chemical
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0724-8741
- Country of Publication
- UNITED STATES
Record 38 from database: MEDLINE
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- Title
- Acute systemic vanadate poisoning presenting as cerebrovascular ischemia
with prolonged reversible neurological deficits (PRIND).
- Author
- Schlake HP; Bertram HP; Husstedt IW; Schuierer G
- Address
- Department of Neurosurgery, University of WÂurzburg, Germany.
- Source
- Clin Neurol Neurosurg, 1994 Feb, 96:1, 92-5
- Abstract
- A 22-year-old woman is reported who attempted suicide by oral ingestion of
approximately 10-15 g ammonium metavanadate (NH4VO3). A few hours later she
developed gastrointestinal symptoms followed by a transient right sensomotor
hemiparesis and aphasic disturbances. Brain MRI and SPECT with 99mTc-HMPAO
revealed a lesion in the left parietal cortex. Plasmapheresis, ascorbic acid and
desferoxamine led to a complete clinical recovery within a few days.
- Language of Publication
- English
- Unique Identifier
- 94244172
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- MeSH Heading (Major)
- Cerebral Ischemia, Transient|BL/*CI/DI; Suicide, Attempted|*;
Vanadates|PK/*PO
- MeSH Heading
- Adult; Aphasia|CI; Case Report; Dose-Response Relationship, Drug; Female;
Human; Metabolic Clearance Rate|PH; Neurologic Examination|DE
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0303-8467
- Country of Publication
- NETHERLANDS
Record 39 from database: MEDLINE
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- Title
- Oxidation pathways for the intracellular probe 2',7'-dichlorofluorescein.
- Author
- Zhu H; Bannenberg GL; Moldéus P; Shertzer HG
- Address
- Department of Environmental Health, University of Cincinnati Medical Center,
OH 45267-0056.
- Source
- Arch Toxicol, 1994, 68:9, 582-7
- Abstract
- The oxidation of 2',7'-dichlorofluorescin (DCFH) to a fluorescent product is
currently used to evaluate oxidant stress in cells. However, there is
considerable uncertainty as to the enzymatic and nonenzymatic pathways that may
result in DCFH oxidation. Iron/hydrogen peroxide-induced DCFH oxidation was
inhibited by catalase or by the hydroxyl radical scavenger dimethylsulfoxide;
however, superoxide dismutase (SOD) had no effect on DCFH oxidation. The
formation of hydroxyl radical (indicated by the oxidation of salicylic acid to
2,3-dihydroxybenzoic acid) was proportional to DCFH oxidation, suggesting that
the hydroxyl radical is responsible for the iron/peroxide-mediated oxidation of
DCFH. Utilizing a superoxide generating system consisting of
hypoxanthine/xanthine oxidase, oxidation of DCFH was unaffected by SOD, catalase
or desferoxamine, and stimulated by removing hypoxanthine from the reaction
mixture. In contrast, SOD or elimination of hypoxanthine abolished superoxide
formation. In addition, potassium superoxide did not support the oxidation of
DCFH. Thus, superoxide is not involved in DCFH oxidation. Boiling xanthine
oxidase eliminated its concentration-dependent oxidation of 1 microM DCFH,
indicating that xanthine oxidase can enzymatically utilize DCFH as a high
affinity substrate. Kinetic studies of the oxidation of DCFH by xanthine oxidase
indicated a Km(app) of 0.62 microM. Hypoxanthine competed with DCFH with a
Ki(app) of 1.03 mM. These studies suggest that DCFH oxidation may be a useful
indicator of oxidative stress. However, other types of cellular damage may
produce DCFH oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)
- Language of Publication
- English
- Unique Identifier
- 95091511
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- MeSH Heading (Major)
- Fluoresceins|*ME; Hydrogen Peroxide|*ME; Iron|*ME; Superoxides|*ME
- MeSH Heading
- Hydroxyl Radical|ME; In Vitro; Oxidation-Reduction; Oxidative Stress;
Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Xanthine Oxidase|ME
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0340-5761
- Country of Publication
- GERMANY
Record 40 from database: MEDLINE
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- Title
- Cobalt-mediated generation of reactive oxygen species and its possible
mechanism.
- Author
- Leonard S; Gannett PM; Rojanasakul Y; Schwegler Berry D; Castranova V;
Vallyathan V; Shi X
- Address
- Pathology and Physiology Research Branch, National Institute for
Occupational Safety and Health, Morgantown, WV 26505, USA.
- Source
- J Inorg Biochem, 1998 Jul, 70:3-4, 239-44
- Abstract
- Electron spin resonance spin trapping was utilized to investigate free
radical generation from cobalt (Co) mediated reactions using
5,5-dimethyl-1-pyrroline (DMPO) as a spin trap. A mixture of Co with water in
the presence of DMPO generated 5,5-dimethylpyrroline-(2)-oxy(1) DMPOX,
indicating the production of strong oxidants. Addition of superoxide dismutase
(SOD) to the mixture produced hydroxyl radical (.OH). Catalase eliminated the
generation of this radical and metal chelators, such as desferoxamine,
diethylenetriaminepentaacetic acid or 1,10-phenanthroline, decreased it.
Addition of Fe(II) resulted in a several fold increase in the .OH generation. UV
and O2 consumption measurements showed that the reaction of Co with water
consumed molecular oxygen and generated Co(II). Since reaction of Co(II) with
H2O2 did not generate any significant amount of .OH radicals, a Co(I) mediated
Fenton-like reaction [Co(I) H2O2-->Co(II) .OH OH-] seems responsible for .OH
generation. H2O2 is produced from O2.- via dismutation, O2.- is produced by
one-electron reduction of molecular oxygen catalyzed by Co. Chelation of Co(II)
by biological chelators, such as glutathione or beta-ananyl-3-methyl-L-histidine
alters, its oxidation-reduction potential and makes Co(II) capable of generating
.OH via a Co(II)-mediated Fenton-like reaction [Co(II) H2O2-->Co(III) .OH
OH-]. Thus, the reaction of Co with water, especially in the presence of
biological chelators, glutathione, glycylglycylhistidine and
beta-ananyl-3-methyl-L-histidine, is capable of generating a whole spectrum of
reactive oxygen species, which may be responsible for Co-induced cell injury.
- Language of Publication
- English
- Unique Identifier
- 98386779
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- MeSH Heading (Major)
- Cobalt|*CH/*PD; Reactive Oxygen Species|*
- MeSH Heading
- Catalase|CH; Cyclic N-Oxides|CH; Electron Spin Resonance Spectroscopy;
Microscopy, Electron, Scanning; Oxygen|CH; Spectrophotometry, Ultraviolet;
Superoxide Dismutase|CH
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0162-0134
- Country of Publication
- UNITED STATES
Record 41 from database: MEDLINE
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- Title
- Inhibition of carbon tetrachloride-induced liver injury by liposomes
containing vitamin E.
- Author
- Yao T; Degli Esposti S; Huang L; Arnon R; Spangenberger A; Zern MA
- Address
- Department of Medicine, Jefferson Medical College, Thomas Jefferson
University, Philadelphia 19107.
- Source
- Am J Physiol, 1994 Sep, 267:3 Pt 1, G476-84
- Abstract
- We tested a variety of antioxidants as possible therapeutic agents in an
acute CCl4 mouse model of hepatotoxicity. Liver damage, gauged by the amount of
serum aminotransferase released into the blood, morphological changes, lethal
dose response, and presence of thiobarbituric acid-reactive substances (TBARS),
were significantly inhibited in a dose-dependent manner by liposomes containing
vitamin E (LVE) or by Rocavit E, a water-soluble emulsion of alpha-tocopherol.
Serum aminotransferase levels in LVE- or Rocavit E-treated animals were always
> 10-fold lower than levels in corresponding CCl4 controls. Other
liposome-associated antioxidants, butylated hydroxytoluene, vitamin E succinate,
catalase, desferoxamine, superoxide dismutase, and ascorbic acid 6-palmitate,
were also able to elicit a decrease in damage; however, they were substantially
less effective. Intravenous therapy with LVE decreased mortality by nearly 90%
when a lethal dose of CCl4 was given. When the biodistribution of the liposomes
was examined, it was determined that the vast majority were localized in the
Kupffer cell population. This approach of delivering nontoxic therapeutic agents
selectively to the liver offers a variety of clinical applications in humans.
- Language of Publication
- English
- Unique Identifier
- 95029797
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- MeSH Heading (Major)
- Carbon Tetrachloride|*AE; Liver|*DE/PA; Vitamin E|*AD/PD/PK
- MeSH Heading
- Animal; Antioxidants|PD; Carbocyanines; Dose-Response Relationship, Drug;
Female; Fluorescent Dyes; Injections, Intraperitoneal; Lipid Peroxides|AI;
Liposomes; Mice; Mice, Inbred Strains; Necrosis; Support, U.S. Gov't, P.H.S.;
Survival Analysis; Thiobarbituric Acid Reactive Substances|ME; Tissue
Distribution
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0002-9513
- Country of Publication
- UNITED STATES
Record 42 from database: MEDLINE
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- Title
- Most free-radical injury is iron-related: it is promoted by iron, hemin,
holoferritin and vitamin C, and inhibited by desferoxamine and apoferritin.
- Author
- Herbert V; Shaw S; Jayatilleke E; Stopler Kasdan T
- Address
- Nutrition Center, Mount Sinai, Bronx, New York.
- Source
- Stem Cells (Dayt), 1994 May, 12:3, 289-303
- Abstract
- Iron is a double-edged sword. In moderate quantities and leashed to protein,
it is an essential element in all cell metabolism and growth, but it is toxic
when unleashed. Because of its ability to switch back and forth between ferrous
and ferric oxidation states, iron is both a strong biological oxidant and
reductant. The human diet contains a multitude of natural chemicals which are
carcinogens and anticarcinogens, many of which act by generating oxygen
radicals, which initiate degenerative processes related to cancer, heart disease
and aging (the "oxygen radical hypothesis of aging"). Among these many dietary
chemicals are many redox agents, including vitamin C and beta carotene. Free
radical damage is produced primarily by the hydroxyl radical (.OH). Most of the
.OH generated in vivo comes from iron-dependent reduction of H2O2. Supporting
too much iron as a free radical-generating culprit in the risk of cancer, NHANES
I data indicated that high body iron stores, manifested by increased transferrin
saturation, are associated with an increased cancer risk. Other data shows an
increased heart attack risk.
- Language of Publication
- English
- Unique Identifier
- 94355914
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- MeSH Heading (Major)
- Apoferritin|*PD; Ascorbic Acid|*PD; Deferoxamine|*PD; Diet|*; Ferritin|*PD;
Hemin|*PD; Iron|*TO; Neoplasms|CI/*ET; Superoxides|*
- MeSH Heading
- Animal; Anticarcinogenic Agents; Carcinogens; Free Radicals; Heart
Diseases|ET; Human; Oxidation-Reduction; Support, Non-U.S. Gov't; Support, U.S.
Gov't, Non-P.H.S.
- Publication Type
- JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC
- ISSN
- 1066-5099
- Country of Publication
- UNITED STATES
Record 43 from database: MEDLINE
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- Title
- Production of melanins by ceruloplasmin.
- Author
- Rosei MA; Foppoli C; Wang XT; Coccia R; Mateescu MA
- Address
- Department of Biochemical Sciences, University La Sapienza of Rome, Italy.
rosei@axcasp.caspur.it
- Source
- Pigment Cell Res, 1998 Apr, 11:2, 98-102
- Abstract
- It was shown that ceruloplasmin, apart from the known oxidative conversion
of dopamine into melanin, can also produce (DHI)-melanin from
5,6-dihydroxyindole and THP-melanin from tetrahydropapaveroline. Ceruloplasmin
acts as an oxidase and the kinetic parameters for these oxidative reactions are
reported. Since these ceruloplasmin-catalyzed reactions occur also at pH 7.4,
they could have a significant physiological impact. This ceruloplasmin-oxidasic
activity is enhanced by copper ions and inhibited by chelators, such as
ethylenediaminetetraacetic acid (EDTA) and desferoxamine (DEF). Some possible
implication of melanin production in blood are discussed.
- Language of Publication
- English
- Unique Identifier
- 98244646
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- MeSH Heading (Major)
- Ceruloplasmin|*ME; Melanins|*ME
- MeSH Heading
- Chelating Agents; Copper; Hydrogen-Ion Concentration; Oxidation-Reduction;
Support, Non-U.S. Gov't; Tetrahydropapaveroline|ME
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0893-5785
- Country of Publication
- DENMARK
Record 44 from database: MEDLINE
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- Title
- Evaluation of the role of reactive oxygen species in doxorubicin
hydrochloride nephrosis.
- Author
- Bertolatus JA; Klinzman D; Bronsema DA; Ridnour L; Oberley LW
- Address
- Department of Internal Medicine, University of Iowa College of Medicine,
Iowa City.
- Source
- J Lab Clin Med, 1991 Nov, 118:5, 435-45
- Abstract
- In subcellular systems, doxorubicin hydrochloride (ADR) leads to the
generation of reactive oxygen species such as superoxide anion. Because reactive
oxygen species have been shown to be important mediators of glomerular injury in
several animal models, we sought to determine whether reactive oxygen species
play a significant role in the pathogenesis of ADR-induced nephrotic syndrome in
the rat. Rats pretreated with a variety of free radical scavengers (superoxide
dismutase conjugated to polyethylene glycol [PEGSOD], catalase, catalase plus
PEGSOD, dimethylsulfoxide, desferoxamine, or n-acetyl cysteine) had no
significant reduction in proteinuria at 3 weeks after ADR administration when
compared with rats receiving ADR in the absence of scavengers. No evidence was
seen of increased lipid peroxidation or depletion of reduced glutathione in
renal cortex tissue obtained up to 24 hours after administration of ADR. No
changes were seen in the renal cortical levels of either enzyme activity or
immunoreactive protein for the endogenous antioxidant enzymes superoxide
dismutase (either the Mn or CuZn forms) or catalase after ADR. Total and MnSOD
activities in glomeruli isolated from rats after ADR administration fell
significantly, though CuZnSOD activity was increased. The effect of ADR on
cultured rat mesangial or epithelial cells was also evaluated. ADR inhibited
growth of both cell types at concentrations of approximately 5 to 10 mumol/L, an
order of magnitude below the reported Michaelis-Menten constant for ADR-induced
superoxide production. The growth inhibitory effect could not be prevented in
either cell type by treatment with PEGSOD, catalase, or PEGSOD plus catalase.
This combination of results from in vivo and in vitro studies provides no
evidence for an important role of reactive oxygen species in ADR nephrosis and
suggests that other known mechanisms of ADR cytotoxicity, such as interference
with DNA metabolism, mediate the glomerular injury.
- Language of Publication
- English
- Unique Identifier
- 92044046
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- MeSH Heading (Major)
- Nephrosis|CI/ME/*PP; Oxygen|ME/*PH
- MeSH Heading
- Animal; Catalase|ME/PD; Cells, Cultured; Dimethyl Sulfoxide|ME/PD;
Dose-Response Relationship, Drug; Doxorubicin; Epithelium|DE/ME/PA; Female; Free
Radical Scavengers; Glomerular Mesangium|DE/ME/PA; Glutathione|AN/ME; Kidney
Cortex|CH/ME; Male; Malondialdehyde|AN/ME; Platelet Activation|DE/PH;
Polyethylene Glycols|ME/PD; Proteinuria|ME/PP; Rats; Rats, Inbred Strains;
Superoxide Dismutase|ME/PD; Support, U.S. Gov't, Non-P.H.S.; Support, U.S.
Gov't, P.H.S.; Thrombin|ME/PD
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0022-2143
- Country of Publication
- UNITED STATES
Record 45 from database: MEDLINE
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- Title
- Effects of paraquat on the green alga Dunaliella salina: protection by the
mimic of superoxide dismutase, Desferal-Mn(IV).
- Author
- Rabinowitch HD; Privalle CT; Fridovich I
- Address
- Department of Biochemistry, Duke University Medical Center, Durham, NC
27710.
- Source
- Free Radic Biol Med, 1987, 3:2, 125-31
- Abstract
- Paraquat caused a time-, dose-, and light-dependent bleaching of the
halophilic green alga Dunaliella salina. Sublethal levels of paraquat elicited
increases in cell content of both superoxide dismutase and catalase, with
changes in the pattern of electromorphs of these enzymes. Desferal-Mn(IV), which
catalyzes the dismutation of O2- in vitro, protected against the toxic effect of
paraquat. Desferal (desferoxamine mesylate) alone was toxic to D. salina, and
the salts of Mn(II), Mn(III), and Mn(IV), in the absence of Desferal, did not
protect. Desferal-Mn(IV) is green, but its absorbance was 15% or less than the
peak absorbances due to the chlorophyll in D. salina under the conditions of
exposure; hence, masking of incident light could not have been the basis of the
protective effect of the complex. Incubation of the cells with Desferal-Mn(IV),
for up to 8 h prior to the addition of paraquat, did not increase its protective
action, and brief washing, following 30 min incubation with the complex,
eliminated its protective effect. Neither catalase nor superoxide dismutase,
added to the medium, provided protection against paraquat. These results support
the view that Desferal-Mn(IV) gains entry into D. salina and protects against
the lethal effect of paraquat by there catalyzing the dismutation of O2- into
H2O2 O2.
- Language of Publication
- English
- Unique Identifier
- 88030779
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- MeSH Heading (Major)
- Algae, Green|*DE/ME; Catalase|*ME; Deferoxamine|*PD; Manganese|*PD;
Paraquat|AI/*PD; Superoxide Dismutase|*ME
- MeSH Heading
- Chlorophyll|ME; Kinetics; Support, Non-U.S. Gov't; Support, U.S. Gov't,
Non-P.H.S.; Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0891-5849
- Country of Publication
- UNITED STATES
Record 46 from database: MEDLINE
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- Title
- The role of bone biopsy in the management of patients with renal
osteodystrophy [editorial]
- Author
- Malluche HH; Monier Faugere MC
- Address
-
- Source
- J Am Soc Nephrol, 1994 Mar, 4:9, 1631-42
- Abstract
- Renal osteodystrophy is not a uniform disease. Therefore, knowledge of the
underlying bone abnormalities is essential in deciding specific therapeutic
regimens. To date, however, there is no unequivocal noninvasive means with which
to define bone abnormalities accurately. The best tool remains mineralized bone
histology requiring bone biopsies. Despite recent technical improvements, this
technique is underused because of perceived constraints. This article outlines
the procedures necessary for increasing the value of bone biopsies, such as
tetracycline labeling, and various biopsy techniques and their potential
complications. Bone biopsies provide important information on precisely the type
of renal bone disease affecting patients: (1) predominant hyperparathyroid bone
disease; (2) low-turnover uremic osteodystrophy, encompassing osteomalacic and
adynamic renal bone disease; and (3) mixed uremic osteodystrophy, consisting of
mild to moderate hyperparathyroid bone disease and defective mineralization.
Also, the degree of the severity of the lesions may be assessed. Finally, the
presence and quantity of aluminum deposition in bone can be demonstrated. The
determination of aluminum overload is needed before the initiation of any
therapeutic regimens because it is well known that potentially serious
complications can occur with current treatments such as vitamin D therapies,
desferoxamine administration, or parathyroidectomy.
- Language of Publication
- English
- Unique Identifier
- 94281577
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- MeSH Heading (Major)
- Biopsy|*/AE/IS/MT; Bone and Bones|ME/*PA; Renal Osteodystrophy|DI/*PA/*TH
- MeSH Heading
- Aluminum|ME; Bone Density; Equipment Design; Human; Support, Non-U.S. Gov't
- Publication Type
- EDITORIAL; REVIEW; REVIEW, TUTORIAL
- ISSN
- 1046-6673
- Country of Publication
- UNITED STATES
Record 47 from database: MEDLINE
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- Title
- Pulmonary function in thalassemia major.
- Author
- Fung KP; Chow OK; So SY; Yuen PM
- Address
- Department of Pediatrics, National University of Singapore.
- Source
- J Pediatr, 1987 Oct, 111:4, 534-7
- Abstract
- Pulmonary function tests were evaluated in 28 Chinese patients with
beta-thalassemia major receiving regular transfusions and desferoxamine, and in
34 height-matched normal Chinese children. Comparison of lung function using
analysis of covariance with reference to standing height showed that patients
with thalassemia had a proportional decrease in forced vital capacity and forced
expiratory flow volume in 1 second, whereas their expiratory flow rates,
residual volume, and total lung capacity were comparable to those in normal
children. The single-breath carbon monoxide diffusion capacity was normal. Our
findings suggest that children with thalassemia major have mild restrictive lung
disease. The previous controversy regarding the presence of restrictive or
obstructive lung disease in patients with thalassemia may be related to the use
of inappropriate control values.
- Language of Publication
- English
- Unique Identifier
- 88010352
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- MeSH Heading (Major)
- Respiratory Function Tests|*; Thalassemia|EH/*PP
- MeSH Heading
- Adolescence; Adult; Child; Child, Preschool; China; Female; Forced
Expiratory Flow Rates; Forced Expiratory Volume; Functional Residual Capacity;
Human; Male; Pulmonary Diffusing Capacity; Residual Volume; Total Lung Capacity;
Vital Capacity
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0022-3476
- Country of Publication
- UNITED STATES
Record 48 from database: MEDLINE
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- Title
- Alterations in the course of acid-induced lung injury in rats after general
anesthesia: volatile anesthetics versus ketamine.
- Author
- Nader Djalal N; Knight PR; Bacon MF; Tait AR; Kennedy TP; Johnson KJ
- Address
- Department of Anesthesiology, State University of New York at Buffalo, USA.
nnaderdj@acsu.buffalo.edu
- Source
- Anesth Analg, 1998 Jan, 86:1, 141-6
- Abstract
- Pulmonary aspiration of gastric acid is a complication that occurs during
anesthesia. The effects of the often used anesthetics on the inflammatory
response after aspiration of acid are not known. We examined the effects of
three different inhaled anesthetics--halothane, enflurane, and isoflurane--as
well as parenteral ketamine, on the associated immediate mortality, alveolar
protein leakage, and morphometric changes after intrapulmonary instillation of
acidic solution in rats. Animals in deep state of anesthesia had a higher
mortality after the instillation of acidic solutions than those in lighter
stages (82.5% vs 31.6%). Protein leakage over 5 h was greater in the animals
receiving volatile anesthetics (range 0.9-1.2) compared with those receiving
ketamine (0.6 0.05). Desferoxamine did not decrease protein leakage in
acid-injured animals (1.1 0.06 vs 1.02 0.08). Furthermore, volatile anesthetics
resulted in an increase in the acute inflammatory response and leukocytic
infiltration compared with ketamine in acid-injured lungs. We conclude that the
administration of inhaled anesthetics was associated with exacerbation of an
acute inflammatory response after aspiration of acidic solution. Lung injury was
not increased with ketamine anesthesia. This difference was the result of the
hypotensive effects of inhaled anesthetics. Implications: This study reveals
that the use of inhaled anesthetics aggravates inflammation secondary to gastric
aspiration and should be avoided on diagnosis of the situation.
- Language of Publication
- English
- Unique Identifier
- 98090543
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- MeSH Heading (Major)
- Anesthesia, General|*AE; Anesthetics, Inhalation|*AE; Ketamine|*AE;
Pneumonia, Aspiration|*ET
- MeSH Heading
- Animal; Comparative Study; Male; Rats; Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0003-2999
- Country of Publication
- UNITED STATES
Record 49 from database: MEDLINE
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- Title
- Reactive oxygen species-induced DNA damage and its modification: a chemical
investigation.
- Author
- Yu TW; Anderson D
- Address
- BIBRA International, Carshalton, Surrey, UK.
- Source
- Mutat Res, 1997 Oct, 379:2, 201-10
- Abstract
- The main purpose of this study was to determine whether well-known reactive
oxygen species (ROS)-generating agents can induce DNA damage in a simple
chemical system with or without Fenton reaction components (iron and reducing
agents), and to explore whether antioxidants which normally exist in the
cellular environment can modify such damage, i.e. to determine chemical
reactions of relevance to biological systems. A neutral electrophoresis
technique was used to investigate DNA double stranded breaks (DSBs) caused by
chemical treatments of lambda-DNA in eppendorf tubes by various ROS-generating
compounds and the degree of DNA damage was categorised by analysis of enhanced
digital images. Double strand breaks were induced by hydroquinone (HQ),
benzoquinone (BQ), benzenetriol (BT), hydrogen peroxide (H2O2), bleomycin (BLM)
and sodium ascorbate (Vit C). DNA damage was modulated by various agents
including catalase (CAT), superoxide dismutase (SOD), desferoxamine mesylate
(DFO), ferrous chloride (FeCl2), reduced glutathione (GSH), trolox, silymarin
and myricetin. Individual chemicals (except BLM) at the concentration of 1 mM
did not induce large numbers of DSBs without iron [Fe(II) or Fe(III) at 25
microM]. GSH enhanced the damaging effect of HQ, BT and Vit C, did not alter the
non-damaging effect of H2O2, but had a small protective effect on BLM. When
compared with the non-enzyme protein, bovine serum albumin (BSA), SOD had a
protective effect against BT, H2O2 and BLM; in the presence of GSH, SOD
diminished the effect of HQ, BQ and Vit C but enhanced the effect of BT, H2O2
and BLM. With both GSH and Fe and compared with BSA, SOD enhanced the effect of
HQ, BQ and BLM, ameliorated the effect of H2O2, and did not affect the others.
CAT showed a protective effect for almost all examined compounds, but had little
effect on BLM. With GSH alone, DFO enhanced the effect of HQ, BQ, H2O2 and
ameliorated the effect of BT, BLM and Vit C and trolox was largely protective.
With GSH and Fe, DFO was protective for all compounds except doxorubicin (Dox),
trolox was protective for all compounds except Dox and BLM, silymarin was
protective except that it had little effect on BLM and Dox, but myricetin did
not show any protective effect. In conclusion, the results from the present
study have further highlighted the adverse potential of reducing agents and
redox cycling agents, and also the need for a cautious view of antioxidants.
- Language of Publication
- English
- Unique Identifier
- 98020420
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- MeSH Heading (Major)
- DNA Damage|*; Reactive Oxygen Species|*PH
- MeSH Heading
- Antioxidants|PD; Bacteriophage lambda; DNA, Viral|CH/DE; Electrophoresis,
Agar Gel|MT; Ferrous Compounds|PD; Image Processing, Computer-Assisted;
Oxidation-Reduction; Reducing Agents|PD
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0027-5107
- Country of Publication
- NETHERLANDS
Record 50 from database: MEDLINE
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- Title
- Desferoxamine and iron dextran in acute Salmonella cholerae-suis infection
in pigs.
- Author
- Kramer TT; Saucke L; Griffith RW; Kunesh JP
- Address
-
- Source
- Am J Vet Res, 1986 Jul, 47:7, 1452-7
- Abstract
- Serum iron (SI)-related and hematologic changes were evaluated in a herd of
weaned pigs inoculated with a strain of Salmonella cholerae-suis, causing 83%
mortality within 22 days after inoculation was done. Serum iron concentrations
decreased to 35% of base-line values 2 days after inoculation was done, but
recovered to near base line subsequently. Total SI-binding capacity (TIBC)
decreased gradually for 14 days after inoculation was done. Transferrin (TF)
concentrations decreased to near half the base line throughout the
postinoculation observation period. The calculated SI saturation coefficient
decreased to half the base line, but recovered to or above the base-line value
subsequently. Combined observations of SI, TIBC, TF, and SI saturation
coefficient concentrations indicated that there was higher saturation of host
iron-binding proteins and recruitment of additional iron-binding systems
subsequent to 2 days after inoculation was done. Day 2 after inoculation seemed
to be a critical period for host iron metabolism. Injection of supplemental iron
dextran simultaneously with Salmonella infection resulted in lower mortality of
iron-injected pigs (P less than 0.005). A highly significant negative
correlation was observed between SI concentration and rectal temperatures after
pigs were inoculated with Salmonella (r = -0.54; P less than 0.0001). Hemoglobin
concentrations, mean corpuscular volume, and mean corpuscular hemoglobin were
not significantly affected by Salmonella infection or iron injection concurrent
with Salmonella infection.(ABSTRACT TRUNCATED AT 250 WORDS)
- Language of Publication
- English
- Unique Identifier
- 86293914
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- MeSH Heading (Major)
- Deferoxamine|*TU; Iron-Dextran Complex|*TU; Salmonella Infections,
Animal|BL/*DT/PA; Swine Diseases|BL/*DT/PA
- MeSH Heading
- Acute Disease; Animal; Body Temperature; Comparative Study; Drug Therapy,
Combination; Erythrocyte Count; Iron|BL; Support, U.S. Gov't, Non-P.H.S.; Swine
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0002-9645
- Country of Publication
- UNITED STATES
Record 51 from database: MEDLINE
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- Title
- Hydrogen peroxide induces DNA single strand breaks in respiratory epithelial
cells.
- Author
- McDonald RJ; Pan LC; St George JA; Hyde DM; Ducore JM
- Address
- Department of Pediatrics, University of California, Davis.
- Source
- Inflammation, 1993 Dec, 17:6, 715-22
- Abstract
- The respiratory epithelium is often exposed to oxidant gases, including
ozone from photochemical smog and toxic oxygen metabolites released from
neutrophils recruited in conditions of airway inflammation. We evaluated DNA
single strand break formation by alkaline elution as a measure of
oxidant-induced DNA damage to bronchial epithelial cells. Human
AdenoSV-40-transformed bronchial epithelial cells (BEAS), subclone R1.4 or
nonhuman primate bronchial epithelial cells were cultured in growth factor
supplemented Ham's F12 medium on polycarbonate filters. DNA was labeled by
incubation with [3H]thymidine. Cells were incubated for 1 h in HBSS or HBSS and
increasing concentrations of hydrogen peroxide (H2O2). Cells incubated in H2O2
demonstrated dose-dependent increases in strand break formation, and BEAS cells
were more sensitive to H2O2-induced injury than primary bronchial epithelial
cells. The addition of catalase or preincubation of cells with the iron chelator
desferoxamine prevented H2O2-induced strand breakage. DNA strand break formation
may be an important mechanism of oxidant injury in respiratory epithelial cells.
- Language of Publication
- English
- Unique Identifier
- 94156444
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- MeSH Heading (Major)
- Bronchi|*DE/ME; DNA Damage|*; DNA, Single-Stranded|*DE/ME; Hydrogen
Peroxide|*TO
- MeSH Heading
- Animal; Catalase|PD; Clone Cells|DE/ME; Deferoxamine|PD; Epithelium|DE/ME;
Human; In Vitro; Macaca mulatta; Oxidation-Reduction; Support, Non-U.S. Gov't;
Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0360-3997
- Country of Publication
- UNITED STATES
Record 52 from database: MEDLINE
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- Title
- S-nitrosyl glutathione-mediated hepatocyte cytotoxicity.
- Author
- Meloche BA; OBrien PJ
- Address
- Faculty of Pharmacy, University of Toronto, Ontario, Canada.
- Source
- Xenobiotica, 1993 Aug, 23:8, 863-71
- Abstract
- 1. The addition of n-butyl nitrite (BN) to isolated rat hepatocytes caused
rapid S-nitrosyl glutathione (GSNO) formation, then a concomitant decrease in
protein thiols, followed by a marked ATP depletion. Cytotoxic concentrations of
BN also caused lipid peroxidation after a long lag period but before
cytotoxicity ensued. 2. Prior glutathione (GSH) depletion protected hepatocytes
against the BN-induced decrease in protein thiols, ATP depletion, lipid
peroxidation and cytotoxicity. Thus cytotoxic effects were thought to be
mediated via GSNO formed by reaction of BN with GSH, a reaction catalysed by the
cytosolic fraction. 3. Cytotoxicity and lipid peroxidation, but not depletion of
GSH, protein thiols or ATP, could be averted by the subsequent addition of
antioxidants or the iron chelator, desferoxamine. 4. Addition of the thiol
reductant, dithiothreitol to BN-treated hepatocytes restored GSH and protein
thiols and also prevented cytotoxicity.
- Language of Publication
- English
- Unique Identifier
- 94112860
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- MeSH Heading (Major)
- Glutathione|*AA/ME; Liver|CY/*DE; Nitrites|*TO; Nitroso Compounds|*ME;
Street Drugs|*TO
- MeSH Heading
- Adenosine Triphosphate|ME; Animal; Cell Survival|DE; In Vitro; Lipid
Peroxidation|DE; Male; Membranes|DE; Rats; Rats, Sprague-Dawley
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0049-8254
- Country of Publication
- ENGLAND
Record 53 from database: MEDLINE
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- Title
- Molecular mechanisms of chloroacetaldehyde-induced cytotoxicity in isolated
rat hepatocytes.
- Author
- Sood C; OBrien PJ
- Address
- Faculty of Pharmacy, University of Toronto, Ontario, Canada.
- Source
- Biochem Pharmacol, 1993 Nov, 46:9, 1621-6
- Abstract
- 2-Chloroacetaldehyde (CAA) induced a loss in hepatocyte viability in a
concentration- and time-dependent manner. Three phases before cytotoxicity
ensued could be distinguished. Glutathione (GSH) was depleted immediately upon
addition of CAA but only partial depletion occurred with subtoxic CAA
concentrations. GSH-depleted hepatocytes were much more susceptible to CAA
toxicity, indicating that CAA was detoxified by GSH. The second phase of changes
involved a steady decrease in protein thiol levels, mitochondrial respiration,
transmembrane potential and ATP levels. The third phase involved lipid
peroxidation which commenced at around 60 min with a CAA concentration that
caused 50% cytotoxicity in 120 min. Addition of antioxidants
(diphenylphenylenediamine, butylated hydroxyanisole) and iron chelators
(desferoxamine) at 40 min prevented lipid peroxidation and delayed CAA-induced
cytotoxicity without restoring protein thiols, hepatocyte respiration or
preventing further ATP depletion. Addition of dithiothreitol at 40 min, however,
restored protein thiols and hepatocyte respiration, and prevented further ATP
depletion and cytotoxicity. CAA-induced hepatocyte cytotoxicity therefore
involved reversible thiol protein adduct formation, mitochondrial toxicity and
lipid peroxidation.
- Language of Publication
- English
- Unique Identifier
- 94059179
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- MeSH Heading (Major)
- Acetaldehyde|*AA/PD; Liver|*DE/ME
- MeSH Heading
- Adenosine Triphosphate|DF; Animal; Antioxidants|PD; Calcium|ME; Cell
Survival|DE; Cells, Cultured|DE; Dithiothreitol; Dose-Response Relationship,
Drug; Glutathione|DF; Lipid Peroxidation; Male; Malondialdehyde|AN; Oxygen
Consumption|DE; Rats; Rats, Sprague-Dawley
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-2952
- Country of Publication
- ENGLAND
Record 54 from database: MEDLINE
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- Title
- Scavengers of free radical oxygen affect the generation of low molecular
weight DNA in stimulated lymphocytes from patients with systemic lupus
erythematosus.
- Author
- Benke PJ; Levcovitz H; Paupe J; Tozman E
- Address
- Mailman Center, University of Miami School of Medicine, FL 33101.
- Source
- Metabolism, 1990 Dec, 39:12, 1278-84
- Abstract
- Factors that potentially affect the generation of excess low molecular
weight DNA (LMW-DNA) in cultured phytohemagglutinin (PHA)-stimulated lymphocytes
of patients with systemic lupus erythematosus (SLE) were studied because this
species of DNA is consistently found and this DNA may play a role in the
pathogenesis of the disease. Superoxide dismutase (SOD; 0.05 mg/mL), a scavenger
of free radical oxygen, decrease LMW-DNA formation in lymphocytes by 22%.
Co-cultivation with cysteamine, a second scavenger of free radical oxygen and a
sulfhydryl radioprotective agent, resulted in a 32% decrease in the generation
of excess LMW-DNA at a concentration of 0.5 x 10(-3) mol/L and largely prevented
its formation at 1.0 x 10(-3) mol/L. Other free radical scavengers (catalase,
mannitol, vitamins C and E), cyclooxygenase inhibitors (ibuprofen and aspirin),
a xanthine oxidase inhibitor (allopurinol), and an iron chelator (desferoxamine)
did not affect excess LMW-DNA formation. Glutathione (1 x 10(-3) mol/L) had no
effect and cysteine was toxic. Because scavengers of free radicals might be
useful in the therapy of lupus, a trial of cysteamine (30 to 60 mg/kg/d) was
administered to six acutely ill patients with SLE. A therapeutic benefit was not
demonstrated, and some patients had exacerbation of disease. Lymphocyte cell
growth from control and lupus subjects was stimulated when cysteamine, 1 x
10(-5) to 1 x 10(-4) mol/L was added to the media, but inhibited at
concentrations of 2 x 10(-4) mol/L or greater. These studies suggest that the
autooxidation and toxicity of high-dose cysteamine preclude its therapeutic use
as a free radical scavenger.
- Language of Publication
- English
- Unique Identifier
- 91061614
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- MeSH Heading (Major)
- DNA|*ME; Free Radical Scavengers|*; Lupus Erythematosus, Systemic|BL/*ME;
Lymphocytes|*ME; Oxygen|*ME
- MeSH Heading
- Adult; Cells, Cultured; Centrifugation, Density Gradient; Cysteamine|AE/PD;
Human; Molecular Weight; Phytohemagglutinins|PD; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0026-0495
- Country of Publication
- UNITED STATES
Record 55 from database: MEDLINE
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- Title
- Technical aspects of quantification of aluminum.
- Author
- Chan S; Gerson B
- Address
- Nichols Institute Reference Laboratories, San Juan Capistrano, California.
- Source
- Clin Lab Med, 1990 Jun, 10:2, 423-33
- Abstract
- Aluminum has been implicated as a contributing factor to dialysis
encephalopathy syndrome (DES) and osteomalacic osteodystrophy. Monitoring of its
level together with i-PTH, desferoxamine infusion test, or bone biopsy gives the
degree of intoxication. Specimens for aluminum must be collected in containers
washed in nitric acid or disodium EDTA to avoid contamination. Determination is
made with flameless atomic absorption spectrometry or neutron activation.
Various experimental conditions for the former together with discussion on their
merits and shortcomings are given. Included are protein precipitation, matrix
modification, background correction, and sampling technique.
- Language of Publication
- English
- Unique Identifier
- 90322760
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- MeSH Heading (Major)
- Aluminum|*BL; Brain Diseases|*ET
- MeSH Heading
- Hemodialysis|AE; Human; Spectrophotometry, Atomic Absorption
- Publication Type
- JOURNAL ARTICLE; REVIEW; REVIEW LITERATURE
- ISSN
- 0272-2712
- Country of Publication
- UNITED STATES
Record 56 from database: MEDLINE
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- Title
- Correction of hyperinsulinemia by glyburide treatment in nondiabetic
patients with thalassemia major.
- Author
- Jones TW; Boulware SD; Caprio S; Merkel P; Amiel SA; Pearson HA; Sherwin RS;
Tamborlane WV
- Address
- Department of Pediatrics, Yale University, New Haven, Connecticut 06510.
- Source
- Pediatr Res, 1993 May, 33:5, 497-500
- Abstract
- Hyperinsulinemia and insulin resistance precede the development of diabetes
in patients with thalassemia major on hypertransfusion/desferoxamine therapy. To
examine whether these early metabolic defects could be reversed, seven
nondiabetic patients with thalassemia (17 4 y) were studied for 12 mo before and
during 12 mo of low-dose treatment with glyburide (1.25 to 3.75 mg/d), a
second-generation oral hypoglycemic agent. Plasma glucose responses to oral
glucose (1.75 g/kg body weight) were normal before and after glyburide. Plasma
insulin responses were markedly increased before glyburide therapy (area under
insulin response curve 86 15 and 96 15 versus 40 5 nmol/min/L in normal
controls, p < 0.001). However, insulin responses to glucose fell
significantly after 3 mo of glyburide (to 52 7 nmol/min/L, p < 0.05 versus
pretreatment) and were normalized after 12 mo (42 7 nmol/min/L, p = NS versus
controls). The rate of insulin-stimulated glucose metabolism during euglycemic
insulin clamps (40 mU/m2/min) was low in the patients before treatment (163 10
versus 215 17 mg/m2/min in controls, p < 0.05) and increased to 205 30
mg/m2/min after 3 mo of glyburide. The treatment was well tolerated. In
conclusion, in nondiabetic, hyperinsulinemic, thalassemic patients, chronic
glyburide therapy normalizes insulin responses to oral glucose. To the extent
that insulin hypersecretion contributes to the development of diabetes in
thalassemia, glyburide therapy may provide a means of postponing this
complication of the disease.
- Language of Publication
- English
- Unique Identifier
- 93288524
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- MeSH Heading (Major)
- beta-Thalassemia|*CO/*DT/ME; Glyburide|AE/*TU; Hyperinsulinism|*DT/*ET/ME
- MeSH Heading
- Adolescence; Adult; Child; Diabetes Mellitus|PC; Female; Glucose Tolerance
Test; Human; Insulin|BL; Insulin Resistance; Male; Support, Non-U.S. Gov't;
Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0031-3998
- Country of Publication
- UNITED STATES
Record 57 from database: MEDLINE
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- Title
- Effects of mononuclear cells on pulmonary arteries from rejecting
transplanted lungs.
- Author
- Wiklund L; Miller VM; Tazelaar HD; McGregor CG
- Address
- Department of Physiology, Mayo Clinic and Foundation, Rochester, Minnesota
55905, USA.
- Source
- Am J Physiol, 1997 Mar, 272:3 Pt 1, L379-84
- Abstract
- Experiments were designed to determine responses of pulmonary arteries from
an acutely rejecting, transplanted lung to rejection-activated mononuclear
cells. Pulmonary arteries and macrophage-depleted mononuclear cells were
obtained from unoperated dogs (control) and dogs with rejecting single lung
allotransplants (transplanted, rejecting). In some arteries, the endothelium was
removed deliberately. Pulmonary arteries were suspended for measurement of
isometric force in organ chambers. Contractions to potassium chloride (60 M)
were greater in rings of pulmonary arteries from rejecting compared with control
dogs. Mononuclear cells from both control and transplanted dogs caused cell
number-dependent contractions of autogenous pulmonary arteries. Contractions to
cells were decreased when the endothelium was present only in arteries from
control dogs; these contractions were increased by the L-arginine analog
N(G)-monomethyl-L-arginine (10(-4) M) but not by indomethacin (10(-5) M).
Contractions to mononuclear cells were reduced by superoxide dismutase (150
U/ml) and catalase (1,200 U/ml) in arteries without endothelium from control but
not transplanted dogs. In arteries from transplanted dogs, contractions to
mononuclear cells were reduced by desferoxamine (10(-3) M). Results suggest that
interactions between mononuclear cells and pulmonary arteries are modified
during rejection of lung allografts so that, during rejection, 1)
endothelium-derived nitric oxide no longer antagonizes contractions to
substances produced by the mononuclear cells and 2) contractions of smooth
muscle from rejecting arteries to mononuclear cells may be mediated by radicals
other than superoxide.
- Language of Publication
- English
- Unique Identifier
- 97240641
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- MeSH Heading (Major)
- Graft Rejection|*PP; Leukocytes, Mononuclear|*PH; Lung Transplantation|*IM;
Pulmonary Artery|PA/*PP
- MeSH Heading
- Acute Disease; Animal; Dogs; In Vitro; Male; Microscopy, Electron, Scanning;
Muscle Contraction; Muscle, Smooth, Vascular|PP; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0002-9513
- Country of Publication
- UNITED STATES
Record 58 from database: MEDLINE
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- Title
- Spectrophotometric measurement of plasma 2-thiobarbituric acid-reactive
substances in the presence of hemoglobin and bilirubin interference.
- Author
- Pyles LA; Stejskal EJ; Einzig S
- Address
- Variety Club Research Center, University of Minnesota, Minneapolis.
- Source
- Proc Soc Exp Biol Med, 1993 Apr, 202:4, 407-19
- Abstract
- The 2-thiobarbituric acid reaction with malondialdehyde has been used to
assess lipid peroxidation in a variety of biologic systems. However, in an
attempt to measure plasma thiobarbituric acid-reactive substances (TBARS) during
extracorporeal membrane oxygenation, a form of sustained cardiopulmonary bypass,
it became apparent that the absorbance signal at the 532-nm wavelength was
composed not only of the peak absorbance of TBARS, but also of interfering
substances from heme pigments and bilirubin. A method of subtracting interfering
substances was developed and applied to normal human plasma. The method was
tested by adding varying amounts of red blood cell hemolysate, bilirubin, and
1,1,3,3-tetramethoxypropane (TMP) standard to plasma and determining TBARS in
the resulting mixture. In addition, varying the amount of added desferoxamine
was investigated to determine the effects of iron chelation on the assay. This
was important because the different samples would have varying amounts of free
iron from hemoglobin to catalyze the reaction. It was found that the following
equation could be used in this system to determine that amount of 532-nm
absorption due to TBARS: MDA532 = 1.22[(A532) - (0.56)(A510) (0.44)(A560)].
Regression analysis revealed an 86.6% recovery of the TMP spike. Analysis of
variance showed that the variability in the model could be explained mainly by
the additive increments of TMP spike (94.6%).
- Language of Publication
- English
- Unique Identifier
- 93205705
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- MeSH Heading (Major)
- Bilirubin|*BL; Hemoglobins|*/AN; Thiobarbituric Acid Reactive Substances|*AN
- MeSH Heading
- Deferoxamine|PD; Human; Mathematics; Spectrophotometry|MT; Support, Non-U.S.
Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0037-9727
- Country of Publication
- UNITED STATES
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Record 59 from database: MEDLINE
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- Title
- A moderate transfusion regimen may reduce iron loading in beta-thalassemia
major without producing excessive expansion of erythropoiesis.
- Author
- Cazzola M; Borgna Pignatti C; Locatelli F; Ponchio L; Beguin Y; De Stefano P
- Address
- Department of Internal Medicine, University of Pavia, Italy.
- Source
- Transfusion, 1997 Feb, 37:2, 135-40
- Abstract
- BACKGROUND: Hypertransfusion with a baseline hemoglobin of 10 to 12 g per dL
is still considered by many to be the mainstay of conservative therapy for
beta-thalassemia major. However, this regimen is frequently associated with
manifestations of transfusion iron overload, despite regular chelation therapy
with subcutaneous desferoxamine. STUDY DESIGN AND METHODS: To verify whether a
transfusion regimen with a target pretransfusion hemoglobin level between 9 and
10 g per dL can allow a significant reduction in blood consumption, while still
effectively suppressing erythropoiesis, the records were reviewed of 32
beta-thalassemia major patients, who were maintained at a pretransfusion
hemoglobin of 11.3 0.5 g per dL between 1981 and 1986. These patients were
switched at the beginning of 1987 to a transfusion regimen with pretransfusion
hemoglobin of 9.4 0.4 g per dL. The degree of erythroid marrow activity was
evaluated in these patients and in 32 subjects with beta-thalassemia intermedia
through the simple measurement of serum transferrin receptor. RESULTS: After the
adoption of the moderate transfusion regimen, transfusion requirements decreased
from 137 26 to 104 23 mL per kg per year of red cells (p < 0.0001), and mean
serum ferritin decreased from 2448 1515 to 1187 816 micrograms per L (p <
0.0001), with one-half of patients achieving serum ferritin levels lower than
1000 micrograms per L. The proportion of patients having spontaneous pubertal
development increased significantly (p < 0.01), as a result of less
iron-related gonadotropin insufficiency. At the lower pretransfusion hemoglobin,
erythroid marrow activity did not exceed two to three times normal levels in
most subjects. CONCLUSION: As compared with hypertransfusion, moderate
transfusion may allow more effective prevention of iron loading, with higher
likelihood of spontaneous pubertal development and without producing excessive
expansion of erythropoiesis.
- Language of Publication
- English
- Unique Identifier
- 97203514
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- MeSH Heading (Major)
- beta-Thalassemia|BL/ME/*TH; Blood Transfusion|*/AE; Erythropoiesis|*PH; Iron
Overload|*TH
- MeSH Heading
- Adolescence; Child; Deferoxamine|TU; Growth; Hemoglobins|AN; Human;
Receptors, Transferrin|BL; Siderophores|TU; Support, Non-U.S. Gov't; Ventricular
Dysfunction|ET
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0041-1132
- Country of Publication
- UNITED STATES
Record 60 from database: MEDLINE
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- Title
- Multiple hormone deficiencies in children with hemochromatosis.
- Author
- Oerter KE; Kamp GA; Munson PJ; Nienhuis AW; Cassorla FG; Manasco PK
- Address
- Developmental Endocrinology Branch, National Institute of Child Health and
Human Development, National Institutes of Health, Bethesda, Maryland 20892.
- Source
- J Clin Endocrinol Metab, 1993 Feb, 76:2, 357-61
- Abstract
- Patients with thalassemia major require multiple blood transfusions leading
to hemochromatosis. These patients often have pubertal delay and growth failure,
the etiology of which has not been fully elucidated. We performed an extensive
endocrine evaluation which included measurements of spontaneous and stimulated
levels of gonadotropins, GH, thyroid hormone, and adrenal hormones in 17
patients between the ages of 12 and 18 yr with hemochromatosis receiving
desferoxamine therapy. All of the 17 patients had at least one endocrine
abnormality, and 12 had more than one abnormality. Abnormalities of the
hypothalamic-pituitary-gonadal axis were the most common. Six patients had
clinical evidence of delayed puberty with spontaneous and stimulated
gonadotropin and sex steroid levels appropriate for their delayed pubertal
stage. All 14 children in puberty LH pulsatility index below the mean for
pubertal stage compared to normal children. Six of the 14 had LH pulsatility
index more than 2 SD below the mean for pubertal stage. This may be an indicator
of abnormal pituitary function. Six patients failed either the provocative GH
tests (peak GH < 7 micrograms/L) or had a mean spontaneous GH less than 1
microgram/L. The 4 patients who failed provocative tests had growth velocities
more than 2 SD below the mean for bone age. Three patients had evidence of
primary hypothyroidism. We conclude that all patients with hemochromatosis need
periodic careful endocrine evaluations because the incidence of endocrine
dysfunction is substantial and they may benefit from hormonal therapy.
- Language of Publication
- English
- Unique Identifier
- 93163205
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- MeSH Heading (Major)
- Endocrine Diseases|*ET; Hemochromatosis|*CO/DT/PP
- MeSH Heading
- Adolescence; Child; Deferoxamine|TU; Female; FSH|SE; Growth; Human;
Hypothyroidism|CO; Iron|ME; LH|SE; Male; Periodicity; Pituitary Gland|ME/RA;
Puberty, Delayed|ET; Sex Hormones|BL; Somatotropin|BL; Support, Non-U.S. Gov't;
Testis|ME/RA
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-972X
- Country of Publication
- UNITED STATES
Record 61 from database: MEDLINE
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- Title
- Activation of endothelial cell phospholipase D by hydrogen peroxide and
fatty acid hydroperoxide.
- Author
- Natarajan V; Taher MM; Roehm B; Parinandi NL; Schmid HH; Kiss Z; Garcia JG
- Address
- Department of Medicine, Indiana University School of Medicine, Indianapolis
46202.
- Source
- J Biol Chem, 1993 Jan, 268:2, 930-7
- Abstract
- We have investigated oxidant-mediated stimulation of phospholipase D (PLD)
activity in bovine pulmonary artery endothelial cells (BPAEC), prelabeled with
[32P]orthophosphate or [32P]lysophospholipids. Treatment of cells incubated in
Hanks' balanced salt solution (HBSS) containing 0.5% ethanol with hydrogen
peroxide (H2O2) or linoleic acid hydroperoxide (18:2-OOH) enhanced the formation
of 32P-labeled phosphatidylethanol (PEt) and phosphatidic acid (PA) in a dose-
and time-dependent manner, indicating the activation of PLD. The H2O2- and
18:2-OOH-mediated PLD activation was not associated with cytotoxicity as
determined by [3H]deoxyglucose release. The addition of ferrous chloride (50
microM) augmented H2O2-induced formation of [32P]PEt and [32P]PA about 2-fold,
whereas the addition of the iron chelator desferoxamine blocked the potentiating
effect of ferrous chloride. Replacement of the HBSS medium with Medium 199
containing 20% calf serum also potentiated the effect of H2O2-induced PLD
activation. In addition to phosphatidylcholine (PC), phosphatidylethanolamine
(PE), and phosphatidylinositol (PI) were readily hydrolyzed by PLD in response
to H2O2 and 18:2-OOH treatment. The substrate specificity for oxidant-stimulated
PLD activity differed from that observed in the presence of bradykinin or
exhibited by agonist stimulation with 12-O-tetradecanoylphorbol 13-acetate (TPA)
where PC was the major phospholipid hydrolyzed by PLD. The formation of PEt in
the presence of H2O2 and 18:2-OOH was not abolished by chelation of either
extracellular Ca2 with EGTA (5 mM) or intracellular Ca2 with
1,2-bis-(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid-acetoxymethyl ester
(BAPTA-AM) (25 microM, 30 min). Furthermore, pretreatment of BPAEC with the
protein kinase C (PKC) inhibitor staurosporine and down-regulation of PKC by
chronic TPA treatment (100 nM, 18 hr) had no effect on H2O2-induced PLD
activation, suggesting that PLD activation by H2O2 is independent of PKC
activity. It is possible that H2O2- and 18:2-OOH-induced activation of PLD
represents an important mechanism to produce PA and diacylglycerol in
endothelial cells.
- Language of Publication
- English
- Unique Identifier
- 93123305
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- MeSH Heading (Major)
- Endothelium, Vascular|DE/*EN; Hydrogen Peroxide|*PD; Linoleic Acids|*PD;
Lipid Peroxides|*PD; Phospholipase D|*ME
- MeSH Heading
- Animal; Bradykinin|PD; Cattle; Cells, Cultured; Deferoxamine|PD; Enzyme
Activation; Kinetics; Phosphates|ME; Phosphatidylethanolamines|ME;
Phospholipids|IP/ME; Phosphorus Radioisotopes; Pulmonary Artery; Support,
Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.;
Tetradecanoylphorbol Acetate|PD
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-9258
- Country of Publication
- UNITED STATES
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