Wally J. Bartfay

Cardiac function and cytotoxic aldehyde production in a murine model of chronic iron-overload

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.

A Biochemical, Histochemical, and Electron Microscopic Study on the Effects of Iron-Loading on the Hearts of Mice

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.

Promoting Health in Schools through a Board Game

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 educationalprograms directedtowardchildren. 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 ofa 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 riskfactors associated with the development of heart disease and cancer.

Selenium and glutathione peroxidase with beta-thalassemia major.

BackgroundChronic iron-overload is a major cause of organ failure and mortality worldwide, but its pathogenesis remains to be elucidated. ObjectivesTo examine the relationship between various measures of body iron burden, selenium concentrations and glutathione peroxidase (GPx) activity in patients with beta-thalassemia major. MethodsAn 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. ResultsSignificantly decreased plasma concentrations of selenium (μg/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 (μg/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). ConclusionPatients 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.

Comparison of Cytotoxic Aldehyde Generation in Beta-Thalassemia Patients Chelated with Deferoxamine or Deferiprone (L1) Versus NO Chelation

The mechanism of iron-induced organ failure in iron overload disorders is not known, but it is conjectured that excess iron-catalyzed free radical generation contributes to organ damage. We hypothesized that free radical generation, quantified by the presence of 20 separate cytotoxic aldehydes in plasma, would be significantly increased in non-chelated beta-thalassemia major patients, in comparison to those chelated with either deferiprone (L1) or deferoxamine (desferal). We also report on red cell glutathione peroxidase activity in these patient groups, an enzyme involved in averting the damaging effects of free radicals. Ten patients were chelated with nightly subcutaneous infusions of desferal and 10 received the experimental oral chelator L1. Body iron burden was assessed by serum ferritin and hepatic iron concentrations. In comparison to non-chelated controls, significant decreases of 62% and 64% in total cytotoxic aldehyde concentrations were observed in patients chelated with desferal and L1, respectively (p < 0.001). Significantly lower red cell glutathione peroxidase activity was also observed in non-chelated controls, in comparison to those chelated with either desferal or L1 (p < 0.001). This is the first report on the concentrations of cytotoxic aldehydes in non-chelated beta-thalassemia major patients, and the first to report on the effects of L1 against cytotoxic aldehyde formation in plasma of patients with iron-overload.

Systemic Oxygen-Free Radical Production in Iron-Loaded Mice

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).

Impact of the Global Economic Crisis on the Health of Unemployed Autoworkers

A phenomenological investigation was undertaken to examine the effects of the 2008-09 global economic recession on the health of unemployed blue-collar autoworkers in the Canadian province of Ontario between September and November 2009. A total of 22 men and 12 women took part. Participants completed a quantitative demographic and financial questionnaire. The qualitative aspect of the study consisted of a phenomenological component comprising semi-structured focus group sessions lasting 2 to 2.5 hours. The number of years employed ranged from 2 to 31.7 with a mean of 15 +/- 8. Participants reported high levels of stress, anxiety, and depression; increased physical pain and discomfort; changes in weight and sexual function; and financial hardships, including inability to purchase prescribed medications. The authors conclude that unemployment associated with the global recession has negative health effects on autoworkers in Ontario.

The Effects of Adult Day Programs on the Quality of Life of Individuals with Alzheimer's Disease: A Pilot Study

Little research has been conducted on examining the relationship between caring interventions such as adult day programs (ADPs) and the quality of life (QOL) of individuals with Alzheimer’s disease. Our study objective was to investigate the merits of attending ADPs on the QOL of these individuals. We hypothesized that individuals with Alzheimer’s disease who attended ADP had higher QOL than those who did not. We also hypothesized that individuals with Alzheimer’s disease who attended ADP enjoyed comparable QOL as their non-diseased counterparts. To explore these issues, we piloted a cross-sectional study in Durham, Ontario, Canada. We recruited 130 participants at five ADPs and at six caregiver support groups in the region. Among them, there were 73 disease-free ADP clients, 28 ADP clients with Alzheimer’s disease and 29 individuals with Alzheimer’s disease who did not attend ADPs. Study procedures involved primary data collection using assisted self-report questionnaires and a 13-item quality-of-life scale. This current paper provided a detailed description of the study process. We also provided results that showed overall QOL scores for individuals with Alzheimer’s disease who attended ADP were comparable to those without the disease (2.7 vs. 2.9, p=0.1), whereas the scores were much lower for individuals with Alzheimer’s disease who did not attend ADP than those who attended ADP (1.9 vs. 2.7, p=0.0001). Individuals who attended ADP consistently provided higher ratings than those who did not attend ADP. Based on our findings, we concluded that attending ADPs may be partially responsible for the observed differences in QOL.

Cardioprotective effects of selenium and morin hydrate in a murine model of chronic iron overload

Iron overload cardiomyopathy is the most prevalent cause of death due to heart failure in young patients in their second and third decades of life. Although the exact mechanism for heart failure is not known, it is hypothesized that a disordered redox balance, such as in selenium deficiency, ultimately leads to free radical mediated damage in a variety of disorders including hemochromatosis. We report here on the effects of selenium and morin hydrate on heart tissue concentrations of iron, glutathione peroxidase activity, and the production of 20 separate aldehyde-derived peroxidation products, in a murine model of chronic iron overload. Sixty B6D2F1 mice were randomized to one of the following four treatment groups for a total period of 4 weeks: (1) control (normal saline, 0.5 ml i.p./ mouse / day); (2) iron-only (iron-dextran, 10 mg i.p. / mouse / day); (3) selenium (sodium selenite, 0.5 ppm orally) and iron, and (4) morin hydrate (0.15 mg i.p./ mouse / day) and iron. Our findings show that supplementation with selenium (sodium selenite) or morin hydrate can decrease, in comparison to iron-only treated groups, both the concentrations of total iron and cytotoxic aldehydes in heart tissue, despite concurrent chronic iron loading in a murine model. Iron and selenium supplemented mice also had significant increases in heart glutathione peroxidase activity, in comparison to iron-only treated mice. This is the first description on the effects of selenium and morin hydrate on the concentrations of iron and cytotoxic aldehydes in heart tissue of a murine model of chronic iron overload. J. Trace Elem. Exp. Med. 13:285–297, 2000.