24 research outputs found

    Biomarkers of Atherosclerosis A study of plasma and solid tissues from animal and human models using nuclear magnetic resonance (NMR) technology

    Get PDF
    Introduction: Current recommendations for surgical management of asymptomatic 50-99% carotid stenosis are guided by two factors, patient’s fitness for surgical intervention and the clinical/imaging features associated with an increased risk of late stroke. Despite the advances in imaging modalities and their ability to detect some features of plaque instability, full understanding the pathophysiology of plaque instability will allow early intervention in patients with high risk of developing stroke from the unstable plaque. To date, no serum or urine marker has been shown to predict plaque instability and the risk of future cerebrovascular events. Aims and methods: The aim of this study was to compare metabolic profiles of plasma and plaques from patients with symptomatic carotid stenosis undergoing endarterectomy, plasma and plaques from patients with symptomatic femoral stenosis, and plasma from patients without carotid or femoral disease (control). We also aim to compare plasma and solid tissues from mammalian model (mice), and further compare them to the human experiment. Nuclear magnetic resonance (NMR) spectroscopy will be used to analyse the metabolic profiles of plasma and plaques, and potentially identify predictive biomarkers of plaque instability. Animal experiment was carried out using 6 apolipoprotein E–deficient versus 6 control mice. For the human experiment, carotid and femoral plaques alongside plasma and urine samples were collected from 84 patients. NMR analysis was performed on all the samples and further analysis was done on the resulting spectra and correlating data. Results: The animal experiment showed weak models with inconclusive outcomes. Plasma human experiment also showed weak models and could not confidently establish certain metabolites as atherosclerotic biomarkers. However, similarities were observed between the animal and human models, and 3 metabolites (2-oxoglutarate, choline and taurine) were identified as potential biomarkers. In contrary, human solid tissue experiments have shown much stronger models and clearer results. Spectra gained from these experiments were the first to be described, with no comparable studies in the literature. The most notable finding is the possible effect of taurine on carotid plaques. Taurine signals have been observed in the animal (plasma and solid) as well as human plasma models in this study. Although, they were merely affecting the control groups. Conclusions: Identifying plaque instability in asymptomatic carotid disease was the centre of this study. Taurine’s strong influence on the metabolic profiling of carotid plaques raises the possibility of a potential biomarker of plaque instability. Further work is required regarding the histological examination of plaque sections. An objective assessment of the plaque instability will improve the study outcome and add a different aspect to the current results

    Attenuation of Skeletal Muscle and Renal Injury to the Lower Limb following Ischemia-Reperfusion Using mPTP Inhibitor NIM-811.

    Get PDF
    INTRODUCTION: Operation on the infrarenal aorta and large arteries of the lower extremities may cause rhabdomyolysis of the skeletal muscle, which in turn may induce remote kidney injury. NIM-811 (N-metyl-4-isoleucine-cyclosporine) is a mitochondria specific drug, which can prevent ischemic-reperfusion (IR) injury, by inhibiting mitochondrial permeability transition pores (mPTP). OBJECTIVES: Our aim was to reduce damages in the skeletal muscle and the kidney after IR of the lower limb with NIM-811. MATERIALS AND METHODS: Wistar rats underwent 180 minutes of bilateral lower limb ischemia and 240 minutes of reperfusion. Four animal groups were formed called Sham (receiving vehicle and sham surgery), NIM-Sham (receiving NIM-811 and sham surgery), IR (receiving vehicle and surgery), and NIM-IR (receiving NIM-811 and surgery). Serum, urine and histological samples were taken at the end of reperfusion. NADH-tetrazolium staining, muscle Wet/Dry (W/D) ratio calculations, laser Doppler-flowmetry (LDF) and mean arterial pressure (MAP) monitoring were performed. Renal peroxynitrite concentration, serum TNF-alpha and IL-6 levels were measured. RESULTS: Less significant histopathological changes were observable in the NIM-IR group as compared with the IR group. Serum K+ and necroenzyme levels were significantly lower in the NIM-IR group than in the IR group (LDH: p<0.001; CK: p<0.001; K+: p = 0.017). Muscle mitochondrial viability proved to be significantly higher (p = 0.001) and renal function parameters were significantly better (creatinine: p = 0.016; FENa: p<0.001) in the NIM-IR group in comparison to the IR group. Serum TNF-alpha and IL-6 levels were significantly lower (TNF-alpha: p = 0.003, IL-6: p = 0.040) as well as W/D ratio and peroxynitrite concentration were significantly lower (p = 0.014; p<0.001) in the NIM-IR group than in the IR group. CONCLUSION: NIM-811 could have the potential of reducing rhabdomyolysis and impairment of the kidney after lower limb IR injury

    Haemodynamics and flow modiïŹcation stents for peripheral arterial disease:a review

    Get PDF
    Endovascular stents are widely used for the treatment of peripheral arterial disease (PAD). However, the development of in-stent restenosis and downstream PAD progression remain a challenge. Stent revascularisation of PAD causes arterial trauma and introduces abnormal haemodynamics, which initiate complicated biological processes detrimental to the arterial wall. The interaction between stent struts and arterial cells in contact, and the blood flow field created in a stented region, are highly affected by stent design. Spiral flow is known as a normal physiologic characteristic of arterial circulation and is believed to prevent the development of flow disturbances. This secondary flow motion is lost in atheromatous disease and its re-introduction after endovascular treatment of PAD has been suggested as a method to induce stabilised and coherent haemodynamics. Stent designs able to generate spiral flow may support endothelial function and therefore increase patency rates. This review is focused on secondary flow phenomena in arteries and the development of flow modification stent technologies for the treatment of PAD

    Angiogenesis and mast cell density as predictors of patient survival in squamous cell carcinoma of lung

    No full text
    Background: Measuring the microvascular and mast cell density in squamous cell carcinoma of lung and correlating them with the patient survival may be helpful to guide the use of cancer chemotherapeutic agents which target molecular mechanisms of tumour angiogenesis and mast cells. Materials and Methods: It was an observational study. It included 39 newly diagnosed, adult patients of pulmonary squamous cell carcinoma. Angiogenesis was determined by Chalkleyâ€Čs method after immunohistochemical staining of micro-vessels with CD34. Mast cells per HPF were counted in Tolouidine blue stained sections. Results: Mean age of the patients was 58.33 ± 9.14 years. Male to female ratio was 9:1. Most (92.3%) patients were current smokers. Majority of tumours (71.8%) were localised to major bronchi and/or near to hilum and many of them (74.4%) were poorly differentiated. Mean micro-vascular density was 11.80 ± 3.66 per HPF which showed strong negative correlation (r = -0.481, p =0.002) between microvascular density (MVD) and tumour grade. Mean mast cell density was 1.60 ± 2.04 which showed strong negative correlation (r=-.683, p =0.0001) with grade. Angiogenesis and mast cell density were found to be positively correlated (r=0.439, p =0.005). High MVD, but not the MCD was associated with poor survival. Conclusion: Angiogenesis and mast cell density are positively correlated with each other however; only high MVD is associated with decreased survival. Thus, the anti-angiogenic agents may be useful in squamous cell carcinoma lung, especially the well differentiated tumours

    Microcytic anemia due to ileocolic anastomotic ulcer

    No full text
    corecore