62 research outputs found

    A comparison of responses to raised extracellular potassium and endothelium-derived hyperpolarizing factor (EDHF) in rat pressurised mesenteric arteries

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    The present study examined the hypothesis that potassium ions act as an endothelium-derived hyperpolarizing factor (EDHF) released in response to ACh in small mesenteric arteries displaying myogenic tone. Small mesenteric arteries isolated from rats were set up in a pressure myograph at either 60 or 90 mmHg. After developing myogenic tone, responses to raising extracellular potassium were compared to those obtained with ACh (in the presence of nitric oxide synthase and cyclo- oxygenase inhibitors). The effects of barium and ouabain, or capsaicin, on responses to raised extracellular potassium or ACh were also determined. The effects of raised extracellular potassium levels and ACh on membrane potential, were measured using sharp microelectrodes in pressurised arteries. Rat small mesenteric arteries developed myogenic tone when pressurised. On the background of vascular tone set by a physiological stimulus (i.e pressure), ACh fully dilated the small arteries in a concentration-dependent manner. This response was relatively insensitive to the combination of barium and ouabain, and insensitive to capsaicin. Raising extracellular potassium produced a more inconsistent and modest vasodilator response in pressurised small mesenteric arteries. Responses to raising extracellular potassium were sensitive to capsaicin, and the combination of barium and ouabain. ACh caused a substantial hyperpolarisation in pressurized arteries, while raising extracellular potassium did not. These data indicate that K+ is not the EDHF released in response to ACh in myogenically active rat mesenteric small arteries. Since the hyperpolarization produced by ACh was sensitive to carbenoxolone, gap junctions are the likely mediator of EDH responses under physiological conditions

    Angiogenesis in a human neuroblastoma xenograft model: mechanisms and inhibition by tumour-derived interferon-γ

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    Tumour progression in neuroblastoma (NB) patients correlates with high vascular index. We have previously shown that the ACN NB cell line is tumorigenic and angiogenic in immunodeficient mice, and that interferon-γ (IFN-γ) gene transfer dampens ACN tumorigenicity. As IFN-γ represses lymphocyte-induced tumour angiogenesis in various murine models and inhibits proliferation and migration of human endothelial cells, we have investigated the antiangiogenic activity of tumour-derived IFN-γ and the underlying mechanism(s). In addition, we characterised the tumour vasculature of the ACN xenografts, using the chick embryo chorioallantoic membrane assay. We show that the ACN/IFN-γ xenografts had a lower microvessel density and less in vivo angiogenic potential than the vector-transfected ACN/neo. The vascular channels of both xenografts were formed by a mixed endothelial cell population of murine and human origin, as assessed by the FICTION (fluorescence immunophenotyping and interphase cytogenetics) technique. With respect to ACN/neo, the ACN/IFN-γ xenografts showed more terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling-positive human and murine endothelial cells, suggesting that inhibition of angiogenesis by IFN-γ was dependent on the induction of apoptosis, likely mediated by nitric oxide. Once the dual origin of tumour vasculature is confirmed in NB patients, the xenograft model described here will prove useful in testing the efficacy of different antiangiogenic compounds

    Cognitive training improves ratio processing and decision making in patients with mild cognitive impairment

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    Background: Patients with mild cognitive impairment (MCI) show lower decision making and ratio processing abilities as compared to healthy peers. Objective: To evaluate whether cognitive training on number processing and/or executive functions improves performance on ratio processing and decision making under risk. Methods: In a controlled cross-over study, patients with MCI (n = 23; mean MMSE 26.48, SD 2.43) underwent a week of numerical training followed by a week of executive-functions training (subgroup A), or vice versa (subgroup B). Before training (T1), patients performed experimental tasks of decision making (Game of Dice Task, GDT; Probability-Associated Gambling task, PAG-60 task) and of ratio processing as well as a neuropsychological background assessment. Experimental tasks were also administered after the first (T2) and the second (T3) training week. Results: The numerical training and the training of executive functions had a differential effect on experimental tasks of ratio processing. Only the numerical training proved to be effective. The effects of the two training types on decision making under risk were less clear-cut. While no changes over time were observed in the GDT, performance on the PAG-60 task improved in both training subgroups. These improvements were apparent in one subgroup after a period of executive-functions training, in the other subgroup after both training weeks. That means, improvements are not attributable to one specific training type. Conclusion: Patients with MCI can profit from a cognitive training on number processing and executive functions. Improvements are reflected in higher ratio processing abilities and more advantageous decisions after training. These results are consistent with assumptions of current cognitive models
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