14 research outputs found
Microvascular Responsiveness to Cardiopulmonary Bypass
Cardiopulmonary bypass can result in multiple organ failure due to mechanisms of ischemia reperfusion injury and the systemic inflammatory response syndrome. The primary objective of this thesis was to investigate and monitor the microvasculature in cardiac surgery patients using multiple methodologies and real-time monitoring techniques. The purpose of our first study was to determine whether pulsatile blood flow during bypass improves microvascular perfusion compared to non-pulsatile flow. We found that changes in sublingual mucosal microcirculation using orthogonal polarization spectral imaging correlate with indices of thenar muscle tissue oxygen saturation and its recovery during a vascular occlusion test using near-infrared spectroscopy in both groups. There were significantly fewer normally perfused vessels, along with impaired microvascular responsiveness and elevated levels of lactate in the non-pulsatile group. Although these technologies help to better understand the pathophysiology of acute circulatory failure, a need exists for improved monitors that can continuously track real-time changes in the microcirculation. Our subsequent studies involved the application of a custom broadband continuous wave near-infrared monitor to determine the feasibility of tracking microvascular hemoglobin content as a surrogate for red blood cell (RBC) flow in skeletal muscle during non-pulsatile bypass. We measure changes in optical density at the isosbestic wavelength as an index of change in hemoglobin over time. The changes in optical density relative to baseline values were continuously monitored throughout the procedure, and showed a positive correlation with various interventions during bypass and with potentially negative outcomes. In our third study we applied continuous wavelet transform analysis to the near-infrared data to reflect the dynamic variability in RBC distribution within the microvasculature as an indicator of autoregulation. We showed signal power composition varied within and between patients at all time points, and shifting of power distribution from high to low frequency ranges, and vice versa, in relation to specific events during the procedure. These studies support the potential for clinical devices that can be easily interpreted by a clinician in real-time to guide therapeutic targets and improve clinical outcomes. Our current research and related future work is an important first step and compelling pre-requisite for such a monitor
Effects of Intensified Vasodilatory Antihypertensive Treatment on Renal Function, Bloodsupply and Oxygenation in Chronic Kidney Disease
Smoking and Second Hand Smoking in Adolescents with Chronic Kidney Disease: A Report from the Chronic Kidney Disease in Children (CKiD) Cohort Study
The goal of this study was to determine the prevalence of smoking and second hand smoking [SHS] in adolescents with CKD and their relationship to baseline parameters at enrollment in the CKiD, observational cohort study of 600 children (aged 1-16 yrs) with Schwartz estimated GFR of 30-90 ml/min/1.73m2. 239 adolescents had self-report survey data on smoking and SHS exposure: 21 [9%] subjects had “ever” smoked a cigarette. Among them, 4 were current and 17 were former smokers. Hypertension was more prevalent in those that had “ever” smoked a cigarette (42%) compared to non-smokers (9%),
Being a Relative to Patients with Chronic Kidney Disease:Experiences of Participation in Care and Treatment
High prevalence of malnutrition and impact symptoms in older patients with cancer:results of a Brazilian multicenter study
Cross cultural adaptation and validation of the 'Pátient-Generated Subjective Global Assessment (PG-SGA) for nutritional status of cancer patients in Iran
Cross cultural adaptation and validation of the 'Pátient-Generated Subjective Global Assessment (PG-SGA) for nutritional status of cancer patients in Iran
Pharmacological Modulation of Cancer Migration and Invasion Through Targeting AQP1 Ion and Water Channel Activity
Cancer invasion and metastasis are the leading causes of cancer-related deaths. Aquaporin-1 is a dual water and ion channel that is upregulated in many aggressive cancers including colon, breast, and brain cancer; aquaporin-1 enhances cell migration, invasion and metastasis in these cancer types. Other aquaporins with water channel function are not able to substitute for aquaporin-1 in facilitating cell migration. There is a gap in knowledge regarding the properties of aquaporin-1 that permit its migration-enhancing effect, but both the ion and water channel activities appear to be involved. Thus, it was hypothesised that aquaporin-1 water and ion channels exhibit a coordinated role in aquaporin-1-facilitated cancer cell motility. The aims of this thesis were to test whether pharmacological block of the aquaporin-1 water and ion channel would impede cell migration and invasion in aquaporin-1-expressing cancer cell lines, and to see if the efficacy of aquaporin-1 inhibitors depended on membrane localisation of the channel. Proposed aquaporin-1 blocker AqB050, AQP1 water channel blocker bacopaside II, and an aquaporin-1 ion channel blocker AqB011 were used. The circular wound closure assay is an innovative alternative approach for measuring cell migration and was introduced and utilised in this thesis. Cell viability and proliferation was quantified using an alamarBlue assay. Cell invasion was measured with the transwell assay. Glioblastoma, colorectal adenocarcinoma, and mammary gland tumour cell lines were used. Results showed that combined pharmacological inhibition of aquaporin-1 water and ion conductance amplified the block of cancer cell migration as compared to block by each inhibitor alone, suggesting a cooperative role of aquaporin-1 water and ion channels in cell migration. Cancer cells that express aquaporin-1 on the membrane were more sensitive to block by aquaporin-1 inhibitors; this could be an important screening tool for identifying cancer subtypes likely to respond to AQP1 inhibitors. AqB011 and AqB050 inhibited glioblastoma, breast and colon cancer invasiveness. A newly generated mixture of compounds (AqB051) containing the proposed AQP1 blocker AqB050 and related derivatives was found to strongly block cancer transwell invasion. The potent biologically active agent (not AqB050) was then narrowed to one fraction (fraction E) from AqB051. AqB051 and fraction E significantly inhibited invasiveness in all glioblastoma cell lines. Work in this thesis paves the way for improving methods utilized for measuring cell migration, investigating the role of AQP1 ion conductance and subcellular localisation in cancer migration and growth, investigating a novel and potent inhibitor for glioblastoma invasion, and testing the effects of AQP1 modulators in treating other non-neoplastic diseases.Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 201