Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 12 de 12
Filter
Add more filters










Publication year range
1.
Nurs Res ; 50(3): 178-83, 2001.
Article in English | MEDLINE | ID: mdl-11393640

ABSTRACT

BACKGROUND: Chronic iron-overload is a major cause of organ failure and mortality worldwide, but its pathogenesis remains to be elucidated. OBJECTIVES: To examine the relationship between various measures of body iron burden, selenium concentrations and glutathione peroxidase (GPx) activity in patients with beta-thalassemia major. METHODS: An age- and gender-matched case control study was conducted to examine the relationship between various measures of body iron burden (serum ferritin, transferrin saturation, total serum iron), plasma concentrations of selenium and glutathione peroxidase (GPx) activity in patients with homozygous beta-thalassemia major (N = 20) and healthy controls (N = 10). Ten patients received the experimental oral chelator L1 and ten received chelation therapy with subcutaneous desferal. RESULTS: Significantly decreased plasma concentrations of selenium (microg/L) were observed in patients chelated with L1 (1.4 +/- 0.2) or desferal (1.4 +/- 0.1), in comparison to healthy controls (1.8 +/- 0.1, p < 0.01). Significantly decreased plasma activity of GPx (microg/L) was observed in patients chelated with L1 (166 +/- 43) or desferal (178 +/- 46), in comparison to healthy controls (296 +/- 22, p < 0.001). Significantly increased concentrations of all measures of body iron burden were observed in beta-thalassemia patients, in comparison to healthy controls (p < 0.001). CONCLUSION: Patients with beta-thalassemia major and chronic iron-overload have decreased concentrations of the essential element selenium and the protective selenium-dependent antioxidant enzyme GPx. Additional research examining the effects of dietary antioxidant supplementation with selenium on these aforementioned parameters in patients with beta-thalassemia major and iron-overload is warranted.


Subject(s)
Glutathione Peroxidase/blood , Selenium/blood , beta-Thalassemia/blood , Adult , Case-Control Studies , Chelating Agents/therapeutic use , Chelation Therapy , Deferoxamine/therapeutic use , Female , Humans , Male , beta-Thalassemia/therapy
3.
West J Nurs Res ; 22(8): 927-35, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11109409

ABSTRACT

Although iron is an essential element for normal cell metabolism, in excess quantities it is highly cytotoxic and lethal. In fact, acute iron poisoning is a leading cause of overdose mortality in young children. Hereditary hemochromatosis, a disorder of iron metabolism, is currently the most prevalent genetic disorder in the world, which results in organ failure and premature mortality. Hence, an enhanced understanding of its pathogenesis is critical for providing safe and effective nursing care to affected individuals and their families. Although the exact mechanism of iron's toxicity is not known, it was hypothesized that chronic iron loading would result in increased tissue (heart, liver, and spleen) concentrations of iron and increased free radical production in a murine model (n = 20). Our results show that chronic iron loading results in highly significant dose-dependent increases in tissue concentrations of iron and systemic free radical generation (p < 0.001).


Subject(s)
Free Radicals/blood , Iron/toxicity , Analysis of Variance , Animals , Dose-Response Relationship, Drug , Iron/metabolism , Male , Mice , Mice, Inbred Strains , Random Allocation
4.
J Trace Elem Med Biol ; 14(1): 14-20, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10836529

ABSTRACT

Although the mechanism of myocardial failure following acute iron poisoning is not known, excess iron-catalyzed free radical generation is conjectured to play a role. The effects of time (0 to 360 minutes) on total iron concentrations, glutathione peroxidase activity, and cytotoxic aldehyde production in heart of mice (B6D2F1, n = 65) were first investigated following acute iron-loading (20 mg iron dextran i.p./mouse). In a subsequent experiment, the effects of dose (0 to 80 mg iron dextran i.p./mouse, n = 75) on the aforementioned parameters were investigated. Our results show that the concentrations of cytotoxic aldehydes: (1) significantly differ over-time, with corresponding increases in total concentrations of iron (r = 0.93, p < 0.001); and (2) increase parallel to the total dose of iron administered (r = 0.95, p < 0.001). Furthermore, dose-and time-dependent alterations to glutathione peroxidase activity are observed, which is most likely due to an acute up-regulation of the enzyme as an endogenous protective response to increased free radical activity in the heart subsequent to iron-loading. While no single mechanism is likely to account for the complex pathophysiology of acute iron-induced heart failure, our results shown that iron-loading can result in significant free radical generation, as quantified by cytotoxic aldehydes, in heart tissue of mice. This is the first report on the effects of time and dose on cytotoxic aldehyde generation and glutathione peroxidase activity in heart of mice following acute iron-loading.


Subject(s)
Aldehydes/metabolism , Iron/administration & dosage , Myocardium/metabolism , Animals , Glutathione Peroxidase/metabolism , Heart/drug effects , Iron/metabolism , Iron/toxicity , Male , Mice , Myocardium/enzymology
5.
Biol Res Nurs ; 2(1): 49-59, 2000 Jul.
Article in English | MEDLINE | ID: mdl-11232511

ABSTRACT

Iron-overload cardiomyopathy is a restrictive cardiomyopathy that manifests itself as systolic or diastolic dysfunction secondary to increased deposition of iron in the heart and occurs with common genetic disorders such as primary hemochromatosis and beta-thalassemia major. Although the exact mechanism of iron-induced heart failure remains to be elucidated, the toxicity of iron in biological systems is believed to be attributed to its ability to catalyze the generation of oxygen-free radicals. In the current investigation, the dose-dependent effects of chronic iron-loading on heart tissue concentrations of iron, glutathione peroxidase (GPx) activity, free-radical production, and cardiac dysfunction were investigated in a murine model of iron-overload cardiomyopathy. It was shown that chronic iron-overload results in dose-dependent (a) increases in myocardial iron burden, (b) decreases in the protective antioxidant enzyme GPx activity, (c) increased free-radical production, and (d) increased mortality. These findings show that the mechanism of iron-induced heart dysfunction involves in part free radical-mediated processes.


Subject(s)
Cardiomyopathy, Restrictive/etiology , Cardiomyopathy, Restrictive/metabolism , Disease Models, Animal , Free Radicals/metabolism , Iron Overload/complications , Iron Overload/metabolism , Animals , Body Burden , Cardiomyopathy, Restrictive/physiopathology , Dose-Response Relationship, Drug , Glutathione Peroxidase/analysis , Hemodynamics , Iron/analysis , Iron Overload/chemically induced , Iron-Dextran Complex , Male , Mice , Mice, Inbred C57BL , Mice, Inbred DBA , Myocardium/chemistry , Random Allocation
6.
Cardiovasc Pathol ; 8(6): 305-14, 1999.
Article in English | MEDLINE | ID: mdl-10615016

ABSTRACT

Acute iron poisoning and chronic iron overload are well-known causes of myocardial failure. Although the exact mechanism is not known, excess iron-catalyzed free radical generation is conjectured to play a role in damaging the myocardium and altering cardiac function. We report here on the effects of acute and chronic iron-loading on the total iron concentration, glutathione peroxidase activity, and cytotoxic aldehyde production in the heart of a murine model (n = 35). Light microscopic examination for the presence of ferrous and ferric iron was undertaken following histochemical staining for these species. In addition, examination of representative samples by transmission electron microscopy was performed. Our findings show that iron-loading can result in significant increases in total iron concentrations, alterations to glutathione peroxidase activity, and increases in cytotoxic aldehyde concentrations in the hearts of mice. Furthermore, we observe that iron-loading can significantly alter and damage various cellular constituents (e.g., mitochondria, lysosomes, sarcoplasmic reticulum) and this may have bearing on the mechanism of iron-induced heart failure.


Subject(s)
Cardiomyopathies/metabolism , Glutathione Peroxidase/metabolism , Iron Overload/metabolism , Iron/metabolism , Myocardium/metabolism , Myocardium/ultrastructure , Animals , Cardiomyopathies/etiology , Cardiomyopathies/pathology , Free Radicals/analysis , Heart/drug effects , Histocytochemistry , Iron/analysis , Iron Overload/complications , Iron-Dextran Complex/toxicity , Male , Mice , Mice, Inbred Strains , Microscopy, Electron , Organelles/drug effects , Organelles/ultrastructure
8.
Cardiovasc Res ; 43(4): 892-900, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10615416

ABSTRACT

OBJECTIVES: To determine the relationship between the total chronic dose of iron administered, ex-vivo cardiac function and the concentrations of cytotoxic aldehydes in heart tissue of a murine model. METHODS: In the first experiment, 34 male B6D2F1 mice were randomized to receive intraperitoneal injections of 5, 10 or 20 mg of iron dextran for three weeks, or a placebo control. The mice were subsequently randomized to undergo ex-vivo assessment of cardiac function. In the second experiment, free radical generation, quantified by the presence of 20 separate cytotoxic aldehydes, was assessed in heart tissue of 40 mice that were randomized to receive chronic treatment with various concentrations of iron dextran (100 mg to 300 mg total chronic dose administered), placebo treatment with saline, or no treatment at all (baseline). RESULTS: Iron-loaded groups displayed dose-dependent depressions of heart rate, systolic pressure, developed pressure, coronary pressure, -dP/dt and +dP/dt, and increases in diastolic pressure. Monotonic dose-dependent increases in total heart aldehydes were observed in the iron-treated groups (r-0.97, p < 0.0001), whereas no significant differences were observed between baseline or time-placebo control groups. CONCLUSIONS: While no single mechanism is likely to account for the complex pathophysiology of iron-induced heart failure, our findings show that chronic iron-loading in a murine model results in dose-dependent alterations to cardiac function; and results in free radical mediated damage to the heart, as measured by excess concentrations of cytotoxic aldehyde-derived peroxidation products. This is the first description of the effects of excess iron on cardiac function assessed by an ex-vivo Langendorff technique in a murine model of chronic iron-overload.


Subject(s)
Aldehydes/metabolism , Heart Rate/drug effects , Iron Overload/physiopathology , Iron/pharmacology , Myocardium/metabolism , Analysis of Variance , Animals , Blood Pressure/drug effects , Disease Models, Animal , Dose-Response Relationship, Drug , Iron Overload/metabolism , Male , Mice , Mice, Inbred Strains , Perfusion , Random Allocation , Ventricular Pressure/drug effects
9.
Can J Cardiol ; 14(7): 937-41, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9706279

ABSTRACT

OBJECTIVES: To determine whether supplementation with vitamin E and selenium can improve myocardial antioxidant defenses in iron-overloaded mouse hearts. INTERVENTIONS: Iron-overload state was created in B6D2F1 mice (n = 20) by daily injection of iron dextran (5 mg intraperitoneally/mouse) for four weeks. The mice were also simultaneously randomly assigned to receive vitamin E (alpha-tocopherol acetate, 40 mg intraperitoneally, n = 5), selenium (sodium selenite, 1 part/million orally, n = 5), both (vitamin E + selenium, n = 5) or iron-only treatment (n = 5). The hearts were harvested for determination of selenium concentration and glutathione peroxidase activity. In a subsequent study, 15 B6D2F1 mice were randomly assigned to receive daily injections of iron (n = 5) or iron and combined antioxidant treatment (vitamin E + selenium, n = 5), or to serve as controls (n = 5) for four weeks. The hearts were harvested for determination of total iron concentrations. MAIN RESULTS: Significantly greater concentrations of heart selenium and glutathione peroxidase activity were observed in groups supplemented with both agents, as opposed to iron-only treated or single supplemented mice. Significantly lower concentrations of iron were found in controls and in those receiving combined iron and antioxidant treatment (vitamin E + selenium) than in iron-only treated mice. CONCLUSIONS: Vitamin E and selenium function synergistically in the myocardium to provide important antioxidant defenses in iron-overload states, including increased concentrations of selenium, increased glutathione peroxidase activity and decreased concentrations of iron.


Subject(s)
Cardiomyopathies/drug therapy , Iron/administration & dosage , Selenium/administration & dosage , Vitamin E/administration & dosage , Animals , Cardiomyopathies/chemically induced , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Overdose , Drug Synergism , Heart/drug effects , Humans , Iron/adverse effects , Mice , Selenium/pharmacology , Vitamin E/pharmacology
10.
Can J Cardiol ; 11(4): 305-10, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7728642

ABSTRACT

OBJECTIVE: To investigate the relationship of serum ferritin with sex and exercise. DESIGN AND SETTING: A cross-sectional design study carried out in Winnipeg, Manitoba. SUBJECTS: Urban Canadians of Icelandic descent, aged 21 to 60 years, took part in this investigation. Subjects were stratified by age, sex and menstrual status. INTERVENTIONS: Venous blood samples from fasting subjects were drawn for serum ferritin, hemoglobin and hematocrit analyses. Various anthropomorphic measurements were taken, and subjects underwent submaximal cycle ergometry testing. A health and lifestyles questionnaire and a four-day prospective food record were administered. MAIN RESULTS: Mean serum ferritin levels obtained were 187.93 and 47.84 micrograms/L for males and females, respectively. Mean serum ferritin levels were 33.06 micrograms/L and 71.14 micrograms/L for premenopausal and postmenopausal females, respectively. The mean weekly consumption of alcohol was 190 mL/week and 80 mL/week for males and females, respectively. The mean dietary intake of iron was 27.3 and 18.9 mg/day for males and females, respectively. Males, but not females, who exercised 45 mins or more per week had significantly lower levels of serum ferritin than their sedentary counterparts. In males, hemoglobin, hematocrit and the consumption of alcohol were positively correlated with serum ferritin, while exercise time was negatively correlated with serum ferritin. A trend towards lower serum ferritin levels at higher workloads was observed in males, but did not reach statistical significance. In females, age and dietary intake of iron were found to be positively correlated with serum ferritin, while history of anemia, menstrual status and workload were negatively correlated with serum ferritin. CONCLUSIONS: These findings suggest that regular aerobic exercise may decrease iron stores in the body. This may be clinically significant since high serum ferritin has been cited as a risk factor for coronary artery disease.


Subject(s)
Coronary Disease/prevention & control , Exercise , Ferritins/blood , Adult , Alcohol Drinking , Canada , Coronary Disease/blood , Cross-Sectional Studies , Female , Health Status , Humans , Iceland/ethnology , Life Style , Male , Middle Aged , Physical Fitness , Sex Factors
12.
West J Nurs Res ; 16(4): 438-46, 1994 Aug.
Article in English | MEDLINE | ID: mdl-7941489

ABSTRACT

Primary prevention and health promotion have become salient topics in Canadian society and in nursing during the past two decades. The noncommunicable chronic diseases, such as heart disease and cancer, have been linked to specific lifestyle behaviors or habits, which often develop early in life. The success of public health efforts to improve the health status of all Canadians depends substantially on the success of educational programs directed toward children. Effective teaching strategies that seek to promote health and wellness in children need to be developed and empirically evaluated. Educational games may provide an efficient vehicle for carrying out developmentally specific nursing interventions in school settings. This article begins with a brief overview of the historical origins of games, along with their advantages and disadvantages as educational strategies. The results of a pretest-posttest control group design study that evaluated the effectiveness of a board game as a primary prevention teaching strategy with 23 sixth grade children in Winnipeg, Manitoba are presented. The experimental group had significant gains in knowledge related to anatomy and physiology, diet, and lifestyle risk factors associated with the development of heart disease and cancer.


Subject(s)
Games, Experimental , Health Education/methods , Health Promotion/methods , School Health Services , Child , Female , Heart Diseases/prevention & control , Humans , Life Style , Male , Neoplasms/prevention & control , Primary Prevention , Teaching/methods
SELECTION OF CITATIONS
SEARCH DETAIL
...