St Boniface Hospital Research

Winnipeg, Canada

St Boniface Hospital Research

Winnipeg, Canada

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Xu Y.-J.,University of Manitoba | Tappia P.S.,St Boniface Hospital Research | Neki N.S.,University of Manitoba | Dhalla N.S.,University of Manitoba
Heart Failure Reviews | Year: 2014

Oxidative stress is considered to play an important role in the pathogenesis of diabetes-induced cardiovascular disease (CVD), which is invariably associated with abnormal blood lipid profile, insulin resistance and metabolic syndrome. Stress, smoking, high saturated fat intake as well as low fruit and vegetable intakes have been shown to increase oxidative stress and hyperlipidemia, which increase the predisposition of diabetic subjects to atherosclerosis, stroke and coronary heart disease. The oxidation of low-density lipoprotein by oxidative stress is essential for the development of atherosclerosis, and the reduction in oxidative stress as well as blood glucose and cholesterol is considered critical for the prevention of diabetes-induced CVD. Although epidemiological studies have demonstrated that vitamin C and vitamin E decrease the incidence of coronary heart disease, different clinical trials have failed to support the beneficial effect of these antioxidants. Nonetheless, it has been suggested that natural forms of these vitamins may be more efficacious than synthetic vitamins, and this may explain the inconsistencies in results. Antioxidants, N-acetyl-L-cysteine and resveratrol, have also been shown to attenuate the diabetes-induced cardiovascular complications. It has been indicated that the antioxidant therapy may be effective in a prevention strategy rather than as a treatment for CVD. The evidence presented here supports the view that cardiovascular complications in diabetes may be induced by oxidative stress and appropriate antioxidant therapy may be promising for attenuating the progression of diabetes-induced CVD. © Springer Science+Business Media New York 2013.

Omar S.I.,University of Manitoba | Albensi B.C.,University of Manitoba | Albensi B.C.,St Boniface Hospital Research | Gough K.M.,University of Manitoba
Current Alzheimer Research | Year: 2016

Calcium homeostasis is an essential physiological process requiring tight control in the normal cell. The dysregulation of calcium homeostasis may play a key role in the onset of Alzheimer’s disease (AD) and other disorders, whether through the loss of calcium binding or calcium sensing capacity. Calbindin D28k(CB-D28k), a calcium binding protein composed of six EF-hands, four of which can bind Ca2+, has been implicated in AD-related calcium dysregulation. In this study, docking and molecular dynamics calculations were employed to refine the protein data base model in order to understand the underlying structural variations between functional and non-functional EF-hands. Molecular modeling calculations improved the modelled protein structure: helix-loop-helix sequences were formed in all hands and most canonical interactions were formed in the four functional hands. The protein can also bind Zn2+, potentially altering the Ca2+ binding capability. Analysis of calculated structures of Zn2+ bound protein showed that only half of the correct EF-hand canonical interactions of Ca2+ were formed with loop residues. These results have important implications for the understanding of calcium dysregulation as well as for the development of novel therapeutic strategies in AD and other central nervous system disease processes, or in conditions of brain injury where calcium homeostasis is compromised. © 2016 Bentham Science Publishers.

Tappia P.S.,St Boniface Hospital Research | Xu Y.-J.,University of Manitoba | Rodriguez-Leyva D.,University of Manitoba | Aroutiounova N.,University of Manitoba | Dhalla N.S.,University of Manitoba
Physiological Research | Year: 2013

This study was undertaken to examine the effects of dietary supplementation of cysteine and taurine in rats with diabetes induced with streptozotocin (STZ, 65 mg/kg body weight). Experimental animals were treated orally (by gavage) with cysteine (200 mg/kg) and taurine (400 mg/kg), alone or in combination, daily for 8 weeks. In one group, rats were also pretreated 3 weeks before the induction of diabetes (prevention arm) whereas in the other, the treatment was started 3 days after the induction of diabetes (reversal arm). Diabetes increased heart weight/body weight (HW/BW) ratio, plasma glucose, triglyceride and cholesterol levels as well as depressed heart rate (HR), blood pressure, left ventricular systolic pressure (LVSP), rate of contraction (+dP/dt), rate of relaxation (-dP/dt), fractional shortening (FS) and cardiac output (CO). The left ventricular internal diameter in systole (LViDs) was increased whereas that in diastole (LViDd) was decreased. In the prevention arm, treatment of the diabetic animals with cysteine or taurine decreased HW/BW ratio and improved HR, FS, +dP/dt and -dP/dt, as well as normalized LViDs, without altering the increase in glucose level. Cysteine decreased plasma triglyceride and cholesterol levels and improved LVSP whereas CO was improved by taurine. In the reversal arm, cysteine alone or with taurine did not correct the changes in hemodynamic parameters, FS and plasma triglycerides. Diabetes-induced cardiac dysfunction and increases in plasma triglycerides can be prevented, but not reversed, by dietary cysteine alone or in combination with taurine. © 2013 Institute of Physiology v.v.i., Academy of Sciences of the Czech Republic, Prague, Czech Republic.

Dent M.R.,St Boniface Hospital Research | Tappia P.S.,University of Manitoba | Dhalla N.S.,St Boniface Hospital Research
Journal of Cellular Physiology | Year: 2011

This study was undertaken to determine alterations in the β-adrenoceptor (β-AR) signaling system in male and female rats at 4 weeks after the induction of arteriovenous (AV) fistula or shunt. AV shunt produced a greater degree of cardiac hypertrophy and larger increase in cardiac output in male than in female animals. Increases in plasma levels of norepinephrine and epinephrine (EPI) due to AV shunt were also higher in male than females. While no difference in the β1-AR affinity was seen in males and females, AV shunt induced increase in β1-AR density in female rats was higher than that in males. Furthermore, no changes in basal adenylyl cyclase (AC) V/VI mRNA levels were seen; however, the increase in EPI-stimulated AC activities was greater in AV shunt females than in males. AV shunt decreased myocardial β1-AR mRNA level in male rats and increased β2-AR mRNA level in female hearts; an increase in Gi-protein mRNA was detected only in male hearts. Although GRK2 gene expression was increased in both sexes, an increase in GRK3 mRNA was seen only in AV shunt female rats. β-arrestin1 mRNA was elevated in females whereas β-arrestin 2 gene expression was increased in both male and female AV shunt rats. While these data demonstrate gender associated differences in various components of the β-AR system in cardiac hypertrophy due to AV shunt, only higher levels of plasma catecholamines may account for the greater increase in cardiac output and higher degree of cardiac hypertrophy in males. © 2010 Wiley-Liss, Inc.

Arneja A.S.,University of Manitoba | Tamiji J.,University of Manitoba | Hiebert B.M.,St Boniface Hospital Research | Tappia P.S.,St Boniface Hospital Research | Galimova L.,University of Manitoba
American Journal of Physical Medicine and Rehabilitation | Year: 2015

Objective: The aim of this study was to compare the rehabilitation length of stay and functional outcome of patients with amputation on chronic dialysis with a similar group of patients not on dialysis. Design: This was a retrospective cohort study. Twenty-five patients with amputations on chronic dialysis and 25 nonrenal controls with amputation were included in the two groups. Primary outcome measures were Functional Independence Measure scores through discharge and follow-up, the percentage of patients fitted with a prosthesis, the number of patients able to ambulate independently indoors or outdoors or operate a wheelchair, and acute and rehabilitation length of stay for inpatients. Comorbidities and complications in end-stage renal disease (ESRD) patients with amputation on chronic dialysis vs. those without renal disease were also evaluated. Results: Eleven women and 14 men were included in each group. The study group patients were younger than non-ESRD controls (54 ± 12 and 61 ± 11 yrs, respectively; P = 0.05). No significant differences were found between the groups in sex, race, amputation etiology, or comorbidities, except minor amputations of toes and fingers, which were performed more often in the ESRD group compared with the non-ESRD group (14 and 2, respectively; P = 0.0003). Functional Independence Measure score was higher in the non-ESRD group on discharge (112.1 ± 7.6 vs. 107.5 ± 7.7; P = 0.04) and follow-up (111.3 ± 10.7 vs. 104.4 ± 8.7; P = 0.02). The number of patients able to ambulate indoors and outdoors or operate wheelchair independently on discharge was not statistically different between the groups. Length of stay was higher in the ESRD group (153 ± 67 vs. 105 ± 42 days; P = 0.04). Conclusions: Patients with limb amputations on chronic dialysis had significantly longer length of stay and lower Functional Independence Measure scores compared with the non-ESRD group. It is suggested that current practices may need to be adjusted to accommodate the complex rehabilitation needs of the ESRD patient population. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Babick A.,St Boniface Hospital Research | Chapman D.,St Boniface Hospital Research | Zieroth S.,University of Manitoba | Elimban V.,St Boniface Hospital Research | Dhalla N.S.,St Boniface Hospital Research
Journal of Cellular and Molecular Medicine | Year: 2012

This study tested the reversal of subcellular remodelling in heart failure due to myocardial infarction (MI) upon treatment with losartan, an angiotensin II receptor antagonist. Twelve weeks after inducing MI, rats were treated with or without losartan (20 mg/kg; daily) for 8 weeks and assessed for cardiac function, cardiac remodelling, subcellular alterations and plasma catecholamines. Cardiac hypertrophy and lung congestion in 20 weeks MI-induced heart failure were associated with increases in plasma catecholamine levels. Haemodynamic examination revealed depressed cardiac function, whereas echocardiographic analysis showed impaired cardiac performance and marked increases in left ventricle wall thickness and chamber dilatation at 20 weeks of inducing MI. These changes in cardiac function, cardiac remodelling and plasma dopamine levels in heart failure were partially or fully reversed by losartan. Sarcoplasmic reticular (SR) Ca2+-pump activity and protein expression, protein and gene expression for phospholamban, as well as myofibrillar (MF) Ca2+-stimulated ATPase activity and α-myosin heavy chain mRNA levels were depressed, whereas β-myosin heavy chain expression was increased in failing hearts; these alterations were partially reversed by losartan. Although SR Ca2+-release activity and mRNA levels for SR Ca2+-pump were decreased in failing heart, these changes were not reversed upon losartan treatment; no changes in mRNA levels for SR Ca2+-release channels were observed in untreated or treated heart failure. These results suggest that the partial improvement of cardiac performance in heart failure due to MI by losartan treatment is associated with partial reversal of cardiac remodelling as well as partial recovery of SR and MF functions. © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Rodriguez-Leyva D.,University of Manitoba | Malik A.,University of Manitoba | Tappia P.S.,St Boniface Hospital Research
Clinical Lipidology | Year: 2011

There is now overwhelming evidence that nutritional genomics has the potential to change dietary guidelines and personal dietary recommendations. While the field of nutrigenomics determines the impact of nutrients on the genome, proteome and metabolome, nutrigenetics, involves understanding the role of genetic variation in the interaction between diet and disease. It is evident that nutrigenetics has the potential to provide the basis for personalized dietary recommendations based on the individuals genetic makeup. Although men and women share in common most of their genetic information, significant differences in susceptibilities to complex diseases such as atherosclerosis and cardiovascular disease exist. Accordingly, this review discusses the modulation of gene expression by dietary fatty acids in a gender-specific manner, which may open new approaches in dietary intervention of atherosclerosis and cardiovascular disease that are linked to sex. © 2011 Future Medicine Ltd.

Adlimoghaddam A.,St Boniface Hospital Research | Sabbir M.G.,St Boniface Hospital Research | Albensi B.C.,St Boniface Hospital Research | Albensi B.C.,University of Manitoba
Frontiers in Molecular Neuroscience | Year: 2016

Ammonia is known to be a potent neurotoxin that causes severe negative effects on the central nervous system. Excessive ammonia levels have been detected in the brain of patients with neurological disorders such as Alzheimer disease (AD). Therefore, ammonia could be a factor contributing to the progression of AD. In this review, we provide an introduction to the toxicity of ammonia and putative ammonia transport proteins.We also hypothesize how ammonia may be linked to AD. Additionally, we discuss the evidence that support the hypothesis that ammonia is a key factor contributing to AD progression. Lastly, we summarize the old and new experimental evidence that focuses on energy metabolism, mitochondrial function, inflammatory responses, excitatory glutamatergic, and GABAergic neurotransmission, and memory in support of our ammonia-related hypotheses of AD. © 2016 Adlimoghaddam, Sabbir and Albensi.

Tappia P.S.,St Boniface Hospital Research | Xu Y.-J.,St Boniface Hospital Research | Dhalla N.S.,St Boniface Hospital Research
Clinical Lipidology | Year: 2013

Although synthetic chemicals and pharmacological agents are being used for the treatment of cardiovascular disease in the western world, there now appears to be a cultural and philosophical shift toward Eastern Medicine and many patients are increasingly using alternative approaches for prevention and therapeutic purposes. This brief review summarizes the experimental and clinical evidence of some functional foods, herbal products and medicinal plants for improving plasma HDL cholesterol, LDL cholesterol, triglycerides and glucose levels, as well as reducing oxidative stress. In addition, the potential of acupuncture and Yogic meditation are discussed as emerging approaches for reducing cardiovascular disease risk factors. The available evidence indicates that several functional foods, herbal products and medicinal plants exert lipid-lowering and hypoglycemic actions, as well as exhibit antioxidant properties; however, a great deal of research work and extensive clinical trials are needed to establish their use in medical practice. © 2013 Future Medicine Ltd.

Tappia P.S.,St Boniface Hospital Research | Dhalla N.S.,St Boniface Hospital Research
Clinical Lipidology | Year: 2012

Clinicians and health professionals are increasingly becoming aware of different health needs of men and women. Differences in gender and corresponding sex hormones result in disparities in risk and protection of cardiovascular disease as men develop cardiovascular disease at an earlier age while women are affected at older ages. Myocardial adaptation and lipid metabolism, including plasma levels of cholesterol and triglycerides, are different in men and women. Gender differences in optimal treatment and secondary prevention measures in patients with coronary heart disease are also evident. This report addresses some of the issues relating to gender differences in the risk, clinical manifestation and management of as well as response to therapy, with particular attention given to changes in plasma HDL-cholesterol, LDL-cholesterol and triglyceride levels. Understanding these differences in lipid control will help to improve the diagnosis of cardiovascular disease and provide information for therapeutic or preventive strategies that may be specifically designed for men and women. © 2012 Future Medicine Ltd.

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