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- Gonzalez, Manuel Cruz, 1969-, et al.
(författare)
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Hyperleptinemia is associated with altered endothelial function
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Introduction The adipocyte-derived hormone leptin has been associated with increased risk of cardiovascular disease but the underlying mechanisms are unclear. Leptin effects on vascular endothelium may be a key mediator although contradictory results have been presented. We aimed to explore the effects of leptin on endothelial vasomotor and fibrinolytic function in healthy volunteers and patients with coronary heart disease.Methods and Results The vascular effects of leptin were assessed using venous occlusion plethysmography in healthy volunteers (n=17) and in patients with stable coronary heart disease (CHD) (n=83). In healthy male volunteers, intra-arterial infusion of recombinant human leptin (80, 800 and 8,000 ng/min; n=10) did not affect forearm blood flow or plasma tissue plasminogen activator (tPA) or plasminogen activator inhibitor type 1 (PAI-1) concentrations (all P>0.05). However, during concomitant co-infusion with leptin (800 ng/min; n=10), induced vasodilatation was reduced (P=0.001), and tPA activity increased (P=0.002). In line with this, patients with coronary heart disease included in the highest tertile of plasma leptin concentrations had reduced substance P-induced vasodilatation (P<0.001), and increased tPA antigen and activity release (p<0.001 and p=0.03 respectively) compared to those in the lowest tertile.Conclusions Although leptin does not directly affect basal vascular function, acute local and chronic systemic hyperleptinemia are associated with altered endothelial function in healthy volunteers and patients with coronary heart disease respectively. These results support hyperleptinemia as a link between obesity and cardiovascular disease.
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- Jakobsson, Johan, et al.
(författare)
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Effects and mechanisms of supramaximal High-Intensity Interval Training on extrapulmonary manifestations in people with and without Chronic Obstructive Pulmonary Disease (COPD-HIIT) : study protocol for a multi-centre, randomized controlled trial
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Beyond being a pulmonary disease, chronic obstructive pulmonary disease (COPD) presents with extrapulmonary manifestations including reduced cognitive, cardiovascular, and muscle function. While exercise training is the cornerstone in the non-pharmacological treatment of COPD, there is a need for new exercise training methods due to suboptimal adaptations when following traditional exercise guidelines, often applying moderate-intensity continuous training (MICT). In people with COPD, short-duration high-intensity interval training (HIIT) holds the potential to induce a more optimal stimulus for training adaptations while circumventing the ventilatory burden often associated with MICT in people with COPD. We aim to determine the effects of supramaximal HIIT and MICT on extrapulmonary manifestations in people with COPD compared to matched healthy controls.Methods: COPD-HIIT is a prospective, multi-centre, randomised, controlled trial with blinded assessors and data analysts, employing a parallel-group trial. In Phase 1, we will investigate the effects and mechanisms of a 12-week intervention of supramaximal HIIT compared to MICT in people with COPD (n = 92) and matched healthy controls (n = 70). Participants will perform watt-based cycling 2–3 times weekly. In Phase 2, we will determine how exercise training and inflammation impact the trajectories of neurodegeneration, in people with COPD, over 24 months. In addition to the 92 participants with COPD performing HIIT or MICT, a usual care group (n = 46) is included in phase 2. In both phases, the primary outcomes are change from baseline in cognitive function, cardiorespiratory fitness, and muscle power. Key secondary outcomes include change from baseline exercise tolerance, brain structure and function measured by MRI, neuroinflammation measured by PET/CT, systemic inflammation, and intramuscular adaptations. Feasibility of the interventions will be comprehensively investigated.Discussion: The COPD-HIIT trial will determine the effects of supramaximal HIIT compared to MICT in people with COPD and healthy controls. We will provide evidence for a novel exercise modality that might overcome the barriers associated with MICT in people with COPD. We will also shed light on the impact of exercise at different intensities to reduce neurodegeneration. The goal of the COPD-HIIT trial is to improve the treatment of extrapulmonary manifestations of the disease.Trial registration: Clinicaltrials.gov: NCT06068322. Prospectively registered on 2023-09-28.
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- Muala, Ala, et al.
(författare)
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Bronchial mucosal inflammation in healthy subjects after exposure to wood smoke from incomplete combustion
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Indoor smoke from combustion of solid biomass fuel is a major risk factor for respiratory disease worldwide. The mechanisms by which wood smoke exhibits its effects on human health are not well understood. The aim of this study was to determine whether exposure to wood smoke produced from incomplete combustion would elicit an airway inflammatory response.Methods Fourteen healthy subjects underwent controlled chamber exposure on two occasions to filtered air and to sooty wood smoke (PM1 ~ 314 μg/m3), generated by a common Nordic wood stove firing birch logs. The study was performed with a double-blind randomized cross-over design and the subjects alternated between exercise (VE=20 L/min/m2) and rest at 15-minute intervals for 3 hours. Bronchoscopies were performed 24 hours after each exposure where bronchial wash (BW), bronchoalveolar lavage (BAL) and endobronchial biopsies were taken. Differential cell counts and soluble components were analyzed in BW and BAL. Bronchial mucosal biopsies were analyzed using immunohistochemistry. Blood tests for inflammatory markers were sampled pre-exposure as well as at 24 and 44-hour time points post-exposure. Spirometry and Fraction of exhaled nitric oxide (FENO) were performed before, immediately after and 24 hours after each exposure.Results There was a significant increase in submucosal and epithelial CD3+ lymphocytes (p<0.01 and <0.05 respectively), together with CD8+ cells in the epithelium (p<0.05) after exposure to wood smoke compared to filtered air. Mast cells were also significantly increased in the submucosa (p<0.01) after wood smoke exposure.There were significant reductions in macrophages, neutrophils and lymphocytes in BW after exposure to wood smoke compared to filtered air, accompanied by decreased levels of soluble Intercellular Adhesion Molecule-1 (sICAM-1), myeloperoxidase (MPO) and matrix metalloproteinase-9 (MMP-9). No significant effects on cell numbers or acute inflammatory markers were demonstrated in BAL fluid or peripheral blood. Lung function and FENO were not affected by exposure to wood smoke.Conclusions Wood smoke exposure caused a significant increase in bronchial epithelial and submucosal CD3+ lymphocytes together with an increase in mucosal mast cells. Further examination revealed a significant increase in CD8+ lymphocytes within the epithelium. Unexpectedly there were no indications of any neutrophilic airway response or recruitment of alveolar macrophages. BW cell numbers, MPO and MMP-9 levels were also significantly reduced after wood smoke exposure. Further research is needed to determine the precise role of these events in relationship to the adverse health effects attributed to wood smoke exposure.
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- Nyström, Robin, 1985-, et al.
(författare)
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Effects of dilution conditions on particle formation and size distribution in engine exhaust emissions when introducing biodiesel in comparison to standard petro diesel
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Air pollution, in particular ambient particulate matter (PM), can be linked to a variety of different health effects, and a major contributor to the PM pollution is exhaust from diesel engines and other vehicles. In the global drive towards finding sustainable and clean bio-based alternative fuels for the transport sector, biodiesel is one of the most established alternative. However, there is considerable variation in emission data for biodiesel, preferably explained by influences of engine technology and operating conditions as well as dilution sampling strategy. In this study the focus was therefore to study the effects of dilution conditions on the particle formation and size distribution in the exhaust emissions from an off road engine, when introducing RME biodiesel in comparison to standard petro diesel. Particle size distribution and number concentration were measured on-line with the use of a fast mobility spectrometer, during a transient operation and without engine modification. Differences in particle characteristics were elucidated in the raw exhaust versus diluted exhaust at two subsequent sampling points with different dilution ratios. In addition, the influences on the exhaust particle properties of changing the lubrication oil was investigated. It was found that biodiesel in general generated more nucleation mode particles then petro diesel, and after the oil exchange the total particle number concentration was increased even more. It was also seen that the custom-built dilution setup favors generation of nucleation mode particles, which is in line with real life conditions in chase and road side experiments. However, when using heated primary dilution and a heated line in the raw exhaust the formation of nucleation mode particles was suppressed. Overall, it was concluded that the introduction of the biodiesel, and potentially other renewable fuels, can in a considerable way change the exhaust particle emission and characteristics. This could have implications for the assessment of exhaust from engines running on biodiesel fuels, especially when introducing biodiesel in existing and older engines.
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