3 results for Aitken, JF

  • Quantitative data describing the impact of the flavonol rutin on in-vivo blood-glucose and fluid-intake profiles, and survival of human-amylin transgenic mice

    Aitken, JF; Loomes, Kerry; Riba-Garcia, I; Unwin, RD; Prijic, G; Phillips, AS; Phillips, Anthony; Wu, D; Poppitt, Sally; Ding, K; Barran, PE; Dowsey, AW; Cooper, Garth (2017-02)

    Journal article
    The University of Auckland Library

    Here we provide data describing the time-course of blood-glucose and fluid-intake profiles of diabetic hemizygous human-amylin (hA) transgenic mice orally treated with rutin, and matched control mice treated with water. We employed “parametric change-point regression analysis” for investigation of differences in time-course profiles between the control and rutin-treatment groups to extract, for each animal, baseline levels of blood glucose and fluid-intake, the change-point time at which blood glucose (diabetes-onset) and fluid-intake (polydipsia-onset) accelerated away from baseline, and the rate of this acceleration. The parametric change-point regression approach applied here allowed a much more accurate determination of the exact time of onset of diabetes than do the standard diagnostic criteria. These data are related to the article entitled “Rutin suppresses human-amylin/hIAPP misfolding and oligomer formation in-vitro, and ameliorates diabetes and its impacts in human-amylin/hIAPP transgenic mice” (J.F. Aitken, K.M. Loomes, I. Riba-Garcia, R.D. Unwin, G. Prijic, A.S. Phillips, A.R.J. Phillips, D. Wu, S.D. Poppitt, K. Ding, P.E. Barran, A.W. Dowsey, G.J.S. Cooper. 2016) [1].

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  • Clinical whole-body skin examination reduces the incidence of thick melanomas

    Aitken, JF; Elwood, James; Baade, PD; Youl, P; English, DR (2010)

    Journal article
    The University of Auckland Library

    Survival from melanoma is strongly related to tumour thickness, thus earlier diagnosis has the potential to reduce mortality from this disease. However, in the absence of conclusive evidence that clinical skin examination reduces mortality, evidence-based assessments do not recommend population screening. We aimed to assess whether clinical whole-body skin examination is associated with a reduced incidence of thick melanoma and also whether screening is associated with an increased incidence of thin lesions (possible overdiagnosis). We conducted a population-based case-control study of all Queensland residents aged 20-75 years with a histologically confirmed first primary invasive cutaneous melanoma diagnosed between January 2000 and December 2003. Telephone interviews were completed by 3,762 eligible cases (78.0%) and 3,824 eligible controls (50.4%). Whole-body clinical skin examination in the three years before diagnosis was associated with a 14% lower risk of being diagnosed with a thick melanoma (>0.75 mm) (OR = 0.86, 95% CI = 0.75, 0.98). Risk decreased for melanomas of increasing thickness: the risk of being diagnosed with a melanoma 0.76-1.49 mm was reduced by 7% (OR = 0.93, 95% CI 0.79, 1.10), by 17% for melanomas 1.50-2.99 mm (OR = 0.83, 95% CI = 0.65, 1.05) and by 40% for melanomas > or =3 mm (OR = 0.60, 95% CI = 0.43, 0.83). Screening was associated with a 38% higher risk of being diagnosed with a thin invasive melanoma (< or =0.75 mm) (OR = 1.38, 95% CI = 1.22, 1.56). This is the strongest evidence to date that whole-body clinical skin examination reduces the incidence of thick melanoma. Because survival from melanoma is strongly related to tumour thickness, these results suggest that screening would reduce melanoma mortality.

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  • Rutin suppresses human-amylin/hIAPP misfolding and oligomer formation in-vitro, and ameliorates diabetes and its impacts in human-amylin/hIAPP transgenic mice

    Aitken, JF; Loomes, Kerry; Riba-Garcia, I; Unwin, RD; Prijic, G; Phillips, AS; Phillips, Anthony; Wu, D; Poppitt, Sally; Ding, K; Barran, PE; Dowsey, AW; Cooper, Garth (2017-01-22)

    Journal article
    The University of Auckland Library

    Pancreatic islet β-cells secrete the hormones insulin and amylin, and defective β-cell function plays a central role in the pathogenesis of type-2 diabetes (T2D). Human amylin (hA, also termed hIAPP) misfolds and forms amyloid aggregates whereas orthologous mouse amylin does neither. Furthermore, hA elicits apoptosis in cultured β-cells and β-cell death in ex-vivo islets. In addition, hA-transgenic mice that selectively express hA in their β-cells, manifest β-cell apoptosis and progressive islet damage that leads to diabetes closely resembling that in patients with T2D. Aggregation of hA is thus linked to the causation of diabetes. We employed time-dependent thioflavin-T spectroscopy and ion-mobility mass spectrometry to screen potential suppressors of hA misfolding for anti-diabetic activity. We identified the dietary flavonol rutin as an inhibitor of hA-misfolding and measured its anti-diabetic efficacy in hA-transgenic mice. In vitro, rutin bound hA, suppressed misfolding, disaggregated oligomers and reverted hA-conformation towards the physiological. In hA-transgenic mice, measurements of glucose, fluid-intake, and body-weight showed that rutin-treatment slowed diabetes-progression by lowering of rates of elevation in blood glucose (P = 0.030), retarding deterioration from symptomatic diabetes to death (P = 0.014) and stabilizing body-weight (P < 0.0001). In conclusion, rutin treatment suppressed hA-aggregation in vitro and doubled the lifespan of diabetic mice (P = 0.011) by a median of 69 days compared with vehicle-treated control-diabetic hA-transgenic mice.

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