Browsing by Author "Kelly-Laubscher, Roisin"

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    The effects of ethanolamine and magnesium on cardiac and neurological function in isoprenaline-induced myocardial infarction and cardiac hypertrophy models in adult Wistar rats Christie Nicole Garson.
    (2012) Garson,Christie Nicole; Kelly-Laubscher, Roisin
    Myocardial infarction (MI) is a principal cause of cardiovascular morbidity and mortality that is associated with other systemic complications. In the heart, MI can result in pump dysfunction, inducing cardiac hypertrophy which may become maladaptive leading to heart failure (HF). In the brain, MI is associated with psychological disorders such as anxiety and depression. Many pharmacological agents have been identified to modulate MI and hypertrophy development.
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    The effects of magnesium treatment on short-term changes in heart rate variability, ventricular function and lipid profile in streptozotocin-induced diabetic rats
    (2017) Amoni, Matthew; Gwanyanya, Asfree; Kelly-Laubscher, Roisin
    INTRODUCTION: Diabetes mellitus is a major and rapidly growing worldwide health problem, causing mortality largely in developing countries such as South Africa. Diabetes induces life threatening cardiovascular complications including cardiac autonomic neuropathy, ventricular dysfunction and dyslipidaemia, which are dependent on the duration and severity of the diabetes. Most complications are identified at a late, irreversible stage following long-standing diabetes; therefore, early detection and treatment of cardiovascular complications may reverse impairments and improve outcomes. The early treatment of diabetic complications remains ineffective, as the associated underlying features, such as electrolyte disturbances, are poorly understood. A key electrolyte disturbance in diabetes is hypomagnesaemia, which is also an independent cardiovascular risk factor. However, the effects of magnesium (Mg²⁺) supplementation are unclear. Therefore, this study investigated the effects of Mg²⁺ treatment on the early manifestations of streptozotocin (STZ)-induced diabetic cardiac complications. METHODS: Adult male Wistar rats were treated once with STZ (50 mg/kg, i.p.) or vehicle (citrate), and daily for seven days with MgSO4 (270 mg/kg, i.p.) or saline. Blood glucose and body weight were monitored daily. On the eighth day, in vivo tail-pulse plethysmography was recorded for analysis of heart rate variability (HRV), a marker of cardiac autonomic function. Ex vivo, Langendorff-based left ventricular (LV) pressure-volume parameters were measured using an intraventricular balloon. Other hearts were stained with Masson's trichrome and haematoxylin and eosin for histological analysis. Cardiac tissue Mg²⁺ concentration as well as plasma lipid- and Mg²⁺ levels were measured by colorimetric assays. RESULTS: Diabetes reduced heart rate and increased the low-frequency (LF)/high-frequency (HF) power ratio. Mg²⁺ treatment prevented theses diabetes-induced changes in heart rate and in the low-frequency (LF)/high-frequency (HF) power ratio (p < 0.05, n = 9/group). In addition, Mg²⁺ restored orthostatic stress induced changes in heart rate, and LF/HF ratio in diabetic rats (p < 0.05, n = 9/group). In isolated hearts, Mg²⁺ reversed the diabetes-induced decrease in LV end-diastolic elastance (p < 0.05, n = 6/group) and the right shift of end diastolic equilibrium volume intercept from 49 ± 6 μ L to 25 ± 5 μL (p < 0.05, n = 6/group), without altering LV developed pressure or end systolic elastance. Diabetes significantly increased plasma triglyceride, total cholesterol and blood glucose (p < 0.05, n = 7/group), and significantly decreased body weight (p < 0.05, n ≥ 16/group) compared to control, but these changes were not prevented by Mg²⁺ treatment. Neither diabetes nor Mg²⁺ treatment altered plasma- and tissue Mg²⁺ levels. Histologically, diabetes and Mg²⁺ treatment also did not alter cardiomyocyte size or the amount of interstitial collagen in myocardial tissue. CONCLUSION: These results show that Mg²⁺ treatment attenuates diabetes-induced autonomic dysfunction and improves LV diastolic distensibility in short-term diabetes. However, the diabetic metabolic disturbances of hyperglycaemia and dyslipidaemia, the changes in cardiac microstructure or the plasma- and cardiac tissue Mg²⁺ levels were uninfluenced by Mg²⁺ treatment. This suggests that Mg²⁺ exerted its beneficial effects independent of these factors, highlighting the underling mechanisms remain to be clarified. The Mg²⁺ levels not measured in this study by which changes could have been mediated was intracellularly; an aspect that should be further explored in future studies. Furthermore, whether these effects would be translatable to chronic diabetes is an important next question. Thus, the results of this study suggest that Mg²⁺ may have a modulatory role in treating early diabetic cardiovascular complications, but future studies will need to clarify the underlying mechanisms.
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    Effects of Mg²⁺ pretreatment and the modulation of Mg²⁺-sensitive cardiac ion channels on Ca²⁺ paradox phenomenon in the heart
    (2016) Alatrag, Fatma; Gwanyanya, Asfree; Kelly-Laubscher, Roisin
    The aim of this study was to investigate the effects of Mg²⁺ pretreatment and of pharmacological inhibitors of TRPM7 channels on CP-induced cardiac injury in the isolated rat heart.
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    Lower limb anatomy wiki
    (2014-09-17) Kelly-Laubscher, Roisin
    The Lower Limb Wiki was created in 2011 as part of an Anatomy & Physiology class project for 1st year Physiotherapy and Occupational Therapy students at the University of Cape Town. Each student wrote a Wiki page. The Lower Limb Wiki was created in 2011 as part of an Anatomy & Physiology class project for 1st year Physiotherapy and Occupational Therapy students at the University of Cape Town. Each student wrote a wiki age. This site is now open to the public and as with any Wiki can be edited by non-members and members.
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    Oleanolic acid: a novel cardioprotective agent that blunts hyperglycemia-induced contractile dysfunction
    (Public Library of Science, 2012) Mapanga, Rudo F; Rajamani, Uthra; Dlamini, Nonkululeko; Zungu-Edmondson, Makhosazane; Kelly-Laubscher, Roisin; Shafiullah, Mohammed; Wahab, Athiq; Hasan, Mohamed Y; Fahim, Mohamed A; Rondeau, Philippe
    Diabetes constitutes a major health challenge. Since cardiovascular complications are common in diabetic patients this will further increase the overall burden of disease. Furthermore, stress-induced hyperglycemia in non-diabetic patients with acute myocardial infarction is associated with higher in-hospital mortality. Previous studies implicate oxidative stress, excessive flux through the hexosamine biosynthetic pathway (HBP) and a dysfunctional ubiquitin-proteasome system (UPS) as potential mediators of this process. Since oleanolic acid (OA; a clove extract) possesses antioxidant properties, we hypothesized that it attenuates acute and chronic hyperglycemia-mediated pathophysiologic molecular events (oxidative stress, apoptosis, HBP, UPS) and thereby improves contractile function in response to ischemia-reperfusion. We employed several experimental systems: 1) H9c2 cardiac myoblasts were exposed to 33 mM glucose for 48 hr vs. controls (5 mM glucose); and subsequently treated with two OA doses (20 and 50 µM) for 6 and 24 hr, respectively; 2) Isolated rat hearts were perfused ex vivo with Krebs-Henseleit buffer containing 33 mM glucose vs. controls (11 mM glucose) for 60 min, followed by 20 min global ischemia and 60 min reperfusion ± OA treatment; 3) In vivo coronary ligations were performed on streptozotocin treated rats ± OA administration during reperfusion; and 4) Effects of long-term OA treatment (2 weeks) on heart function was assessed in streptozotocin-treated rats. Our data demonstrate that OA treatment blunted high glucose-induced oxidative stress and apoptosis in heart cells. OA therapy also resulted in cardioprotection, i.e. for ex vivo and in vivo rat hearts exposed to ischemia-reperfusion under hyperglycemic conditions. In parallel, we found decreased oxidative stress, apoptosis, HBP flux and proteasomal activity following ischemia-reperfusion. Long-term OA treatment also improved heart function in streptozotocin-diabetic rats. These findings are promising since it may eventually result in novel therapeutic interventions to treat acute hyperglycemia (in non-diabetic patients) and diabetic patients with associated cardiovascular complications.
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    The role of the arterial glycocalyx in sphingosine-1- phosphate induced cardioprotection in the isolated heart of the Wistar rat
    (2018) Araibi, Hala; Kelly-Laubscher, Roisin; Gwanyanya, Asfree; Van der Merwe, Elizabeth Lael
    Background: Ischemic heart diseases (IHD) are a leading cause of death among cardiovascular diseases. Unfortunately, the myocardial damage due to ischemia in IHD may be worsened by reperfusion therapy, a phenomenon called ischemic-reperfusion (I/R) injury. Coronary vascular damage is a key feature of I/R injury. Among the coronary vascular structures, the endothelial glycocalyx is a delicate polysaccharide and protein-rich layer that plays an important role in the regulation of vascular permeability, and is easily damaged during I/R. Sphingosine-1-phosphate (S1P) is a membrane phospholipid metabolite that has been shown to protect the heart against I/R. It has also been shown to regulate the synthesis of glycocalyx, but its effects on coronary endothelial glycocalyx damage and possible mechanism during I/R are unknown. Therefore, we hypothesized that S1P-induced cardioprotection is mediated by modulation of the glycocalyx during I/R in the isolated rat heart. Methods: Isolated male Wistar hearts were perfused on a Langendorff system with Krebs-Henseleit buffer via retrograde perfusion at constant temperature and pressure. The hearts were stabilized and pre-treated with S1P (10 nM for 7 minutes) before inducing 20 minutes of global ischemia, followed by 60 minutes reperfusion. Functional parameters were recorded throughout the protocol, including left ventricular developed pressure (LVDP), left ventricular end diastolic pressure (LVEDP), heart rate (HR) and coronary flow (CF). Ventricular infarct size was measured by using triphenyltetrazolium chloride stain. Coronary net filtration rate (NFR) was calculated as a ratio of the amount of transudate to CF. Cardiac edema was assessed by calculating the heart wet/dry weight ratio and histologically quantifying size of the interstitial compartment. The shedding of the glycocalyx was estimated by measuring the release of the glycocalyx component syndecan-1 in the coronary effluent using enzyme-linked immunosorbent assay (ELISA) and determining relative syndecan-1 staining intensity between groups in immuno-stained wax sections of perfusion-fixed hearts. In addition, the histo-morphology of the myocardium was assessed using hematoxylin and eosin staining. Results: The cardiac performance was depressed after I/R, as was reflected by decreased LVDP (P=0.02 vs. control), and an increased LVEDP (P<0.0001 vs. control). I/R also significantly increased infarct size (P=0.04 vs. control). Treatment with S1P before I/R significantly decreased infarct size (P=0.01 vs. I/R), but did not improve the post-ischemic decrease in LVDP or stabilize the LVEDP, and had no effect on CF. I/R significantly increased release of syndecan-1 in the coronary effluent (P=0.0002 vs. control). Immunohistochemically-stained imaging also revealed syndecan-1 staining intensity was significantly decreased or absent in ischemic hearts (P≤0.001 vs. control). Pretreatment with S1P had neither effect on syndecan-1 level in the coronary effluent nor on the intensity of syndecan-1 signal in immuno-stained sections (P=n.s vs. I/R). Histological analysis of cardiac edema revealed an increase in the extracellular area in ischemic hearts compared to the control hearts (P≤0.001 vs. control), and S1P treatment decreased the extracellular area (P≤0.01 I/R+S1P vs. I/R). The NFR, and heart wet/dry ratio were not significantly different post-reperfusion between the groups and S1P had no effect on these parameters. Conclusion: This study showed that pretreatment with S1P protects the heart against I/R injury, as was indicated by the decreased infarct size, and decreased extracellular cardiac edema. S1P had no effect on hemodynamic performance or the shedding of syndecan-1. These results suggest that S1P-induced cardioprotection is not mediated by protection of the glycocalyx via stabilization of syndecan-1. However, it is possible that S1P may stabilize other minor glycocalyx components which were not measured in this study, such as heparan sulphate and hyaluronic acid. This is the first study that evaluated syndecan-1 in the cardiac effluent of the isolated heart of rats with global ischemia, and the study opens up prospects for further investigation of the role of the glycocalyx in other models of I/R injury, such as the more clinically-relevant regional ischemia disease model.
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    The upper limb anatomy wiki
    (2014-09-22) Kelly-Laubscher, Roisin
    The Upper Limb Wiki was created in 2010 as part of an Anatomy & Physiology class project for 1st year Physiotherapy and Occupational Therapy students at the University of Cape Town. It is a comprehensive resource looking at the anatomy of the upper limb in human physiology. Each student involved in the course wrote a wiki page and two Physiotherapy students worked over their vacations to improve the Wiki.