11 research outputs found
dissectum
No full textLomatium dissectum (Nuttall) Mathias & Constancefern-leaved desert-parsley;fern-leaved biscuitroot;chocolate-tips;coughrootlomatium à feuilles découpéesLomatium dissectumUpper Lee Creek Drainage, east of Watertongrassy stream side ban
Deletion of vitamin D receptor leads to premature emphysema/COPD by increased matrix metalloproteinases and lymphoid aggregates formation
Get PDFDeficiency of vitamin D is associated with accelerated decline in lung function. Vitamin D is a ligand for nuclear hormone vitamin D receptor (VDR), and upon binding it modulates various cellular functions. The level of VDR is reduced in lungs of patients with chronic obstructive pulmonary disease (COPD) which led us to hypothesize that deficiency of VDR leads to significant alterations in lung phenotype that are characteristics of COPD/emphysema associated with increased inflammatory response. We found that VDR knock-out (VDR(-/-)) mice had increased influx of inflammatory cells, phospho-acetylation of nuclear factor-kappaB (NF-κB) associated with increased proinflammatory mediators, and up-regulation of matrix metalloproteinases (MMPs) MMP-2, MMP-9, and MMP-12 in the lung. This was associated with emphysema and decline in lung function associated with lymphoid aggregates formation compared to WT mice. These findings suggest that deficiency of VDR in mouse lung can lead to an early onset of emphysema/COPD because of chronic inflammation, immune dysregulation, and lung destruction
Lichen refugia within sub-boreal spruce forests: The role of riparian alder swales.
Get PDFWetland swales, corridors of willows and alders adjacent to streams and seepage areas, may play a role as refugia for lichen biodiversity because likely escape stand replacement disturbance such as fire more often than adjacent upland forest, especially moist to drier sub-boreal and boreal landscapes, and are also not disturbed by forest harvesting. Macrolichen communities in 75 alder-dominated wetland swales along an east (wet) to west (dry) gradient in the Sub-Boreal Spruce biogeoclimatic zone of central interior British Columbia were examined. Spatial analysis of wetland swales indicated an average size of 20.5 m wide by 854 m long (following patch contours). A total of 43 macrolichen species (and six other macrolichen genera) were found in the alder dominated sites, with a maximum of 30 taxa present in the richest site. The macrolichen diversity of alder swales included the old-growth associated lichens Lobaria scrobiculata, L. retigera, Nephroma isidiosum, and Sticta limbata. Canonical Correspondence Analysis identified mean annual temperature and abundance of large stems (dbh > 10 cm) as significant explanatory variables for chlorolichens and mean annual precipitation and age of adjacent conifer forest as significant explanatory variables for the majority of the cyanolichens. Regional precipitation gradients explained the exclusion of many lichen species from both the most westerly and most easterly swales, with drier summer conditions and heavy winter snowpack, respectively, being major limiting factors. Within sites, lichens preferentially occupied large leaning stems, which provided greater precipitation interception and long-lived substrates for many old-growth associated lichen species. Physiological analyses of six common cyanolichens indicated low contributions of cyanolichens to the nitrogen budgets of alder swales. However, adaptations and niches of each of the cyanolichens were revealed. Nephroma parile was the best adapted to the widest range of conditions, followed by Lobaria pulmonaria. PseudThe original print copy of this thesis may be available here: http://wizard.unbc.ca/record=b162504
Phenotyping airway disease with optical coherence tomography
No full textAirway diseases are amajor concern around the world. However, the pace of new drug and biomarker discovery has lagged behind those of other common disorders such as cardiovascular diseases and diabetes. One major barrier in airway research has been the inability to accurately visualize large or small airway remodelling or dysplastic/neoplastic (either pre or early cancerous) changes using non- or minimally invasive instruments. The advent of optical coherence tomography (OCT) has the potential to revolutionize airway research and management by allowing investigators and clinicians to visualize the airway with resolution approaching histology and without exposing patients to harmful effects of ionizing radiation. Thus, with the aid of OCT,we may be able to accurately determine and quantify the extent of airway remodelling in asthma and chronic obstructive pulmonary disease, detect early pre-cancerous lesions in smokers for chemoprevention, study the upper airway anatomy of patients with obstructive sleep apnea in real time while they are asleep and facilitate optimal selection of stents for those with tracheal obstruction. In this paper, we review the current state of knowledge of OCT and its possible application in airway diseases. © 2010 The Author Journal compilation © 2010 Asian Pacific Society of Respirology
Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease
Get PDFChronic obstructive pulmonary disease (COPD) is a global health problem. The current therapies for COPD are poorly effective and the mainstays of pharmacotherapy are bronchodilators. A better understanding of the pathobiology of COPD is critical for the development of novel therapies. In the present review, we have discussed the roles of oxidative/aldehyde stress, inflammation/immunity, and chromatin remodeling in the pathogenesis of COPD. An imbalance of oxidants/antioxidants caused by cigarette smoke and other pollutants/biomass fuels plays an important role in the pathogenesis of COPD by regulating redox-sensitive transcription factors (e.g., NF-κB), autophagy and unfolded protein response leading to chronic lung inflammatory response. Cigarette smoke also activates canonical/alternative NF-κB pathways and their upstream kinases leading to sustained inflammatory response in lungs. Recently, epigenetic regulation has been shown to be critical for the development of COPD because the expression/activity of enzymes that regulate these epigenetic modifications have been reported to be abnormal in airways of COPD patients. Hence, the significant advances made in understanding the pathophysiology of COPD as described herein will identify novel therapeutic targets for intervention in COPD
Effects of Whey Protein on Skeletal Muscle Microvascular and Mitochondrial Plasticity Following 10-Weeks of Exercise Training in Men with Type-2 Diabetes
Get PDFCopyright remains with the author(s) or their institution(s).Abstract
Skeletal muscle microvascular dysfunction and mitochondrial rarefaction feature in type 2 diabetes mellitus (T2DM) linked to low tissue glucose disposal rate (GDR). Exercise training and milk protein supplementation independently promote microvascular and metabolic plasticity in muscle associated with improved nutrient delivery, but combined effects are unknown. In a randomised-controlled trial, 24 men (55.6 y, SD 5.7) with T2DM ingested whey protein drinks (protein/carbohydrate/fat: 20/10/3 g; WHEY) or placebo (carbohydrate/fat: 30/3 g; CON) before/after 45 mixed-mode intense exercise sessions over 10 weeks, to study effects on insulin-stimulated (hyperinsulinemic clamp) skeletal-muscle microvascular blood flow (mBF) and perfusion (near-infrared spectroscopy), and histological, genetic, and biochemical markers (biopsy) of microvascular and mitochondrial plasticity. WHEY enhanced insulin-stimulated perfusion (WHEY-CON 5.6%; 90% CI −0.1, 11.3), while mBF was not altered (3.5%; −17.5, 24.5); perfusion, but not mBF, associated (regression) with increased GDR. Exercise training increased mitochondrial (range of means: 40%–90%) and lipid density (20%–30%), enzyme activity (20%–70%), capillary:fibre ratio (∼25%), and lowered systolic (∼4%) and diastolic (4%–5%) blood pressure, but without WHEY effects. WHEY dampened PGC1α −2.9% (90% compatibility interval: −5.7, −0.2) and NOS3 −6.4% (−1.4, −0.2) expression, but other messenger RNA (mRNA) were unclear. Skeletal muscle microvascular and mitochondrial exercise adaptations were not accentuated by whey protein ingestion in men with T2DM.
ANZCTR Registration Number: ACTRN12614001197628.
Novelty:
• Chronic whey ingestion in T2DM with exercise altered expression of several mitochondrial and angiogenic mRNA.
• Whey added no additional benefit to muscle microvascular or mitochondrial adaptations to exercise.
• Insulin-stimulated perfusion increased with whey but was without impact on glucose disposal.
Résumé
Le dysfonctionnement microvasculaire du muscle squelettique et la raréfaction mitochondriale caractérisant le diabète de type 2 (« T2DM ») sont liés à un faible taux d’élimination du glucose tissulaire (« GDR »). L’entraînement physique et la supplémentation en protéines du lait favorisent indépendamment la plasticité microvasculaire et métabolique dans le muscle; cette plasticité est associée à une amélioration de l’apport de nutriments, mais les effets combinés sont inconnus. Dans un essai contrôlé randomisé, 24 hommes (55,6 ans, SD 5,7) aux prises avec le T2DM consomment des boissons protéinées de lactosérum (protéines / glucides / lipides: 20/10/3 g; « WHEY ») ou un placebo (glucides / lipides: 30/3 g; « CON ») avant / après 45 séances d’exercice intense en mode mixte sur 10 semaines, et ce, pour examiner les effets sur le flux sanguin microvasculaire (« mBF ») et la perfusion (spectroscopie proche infrarouge) stimulés par l’insuline (clamp hyperinsulinémique), des variables histologiques, génétiques et des marqueurs biochimiques (biopsie) de la plasticité microvasculaire et mitochondriale. WHEY améliore la perfusion stimulée par l’insuline (WHEY-CON 5,6 %; IC 90 % −0,1, 11,3), tandis que le mBF n’est pas modifié (3,5 %; −17,5, 24,5); la perfusion, mais pas le mBF, est associée (régression) à une augmentation du GDR. L’entraînement à l’exercice augmente la densité mitochondriale (gamme de moyennes: 40-90 %) et lipidique (20−30 %), l’activité enzymatique (20−70 %), le ratio capillaire: fibre (∼25 %) et diminue les pressions systolique (∼4 %) et diastolique (4−5 %), mais sans effets de WHEY. WHEY amortit l’expression de PGC1α −2,9 % (intervalle de compatibilité de 90 % : −5,7, −0,2) et NOS3 −6,4 % (−1,4, −0,2), mais les autres ARN messager (ARNm) ne sont pas clairs. Les adaptations microvasculaires et mitochondriales des muscles squelettiques causées par l’entraînement physique ne sont pas accentuées par la consommation de protéines de lactosérum chez les hommes aux prises avec le T2DM.
Numéro d’enregistrement ANXCTR : ACTRN12614001197628. [Traduit par la Rédaction]
Les nouveautés:
• La consommation prolongée de lactosérum en présence de T2DM combinée à l’entraînement physique modifie l’expression de plusieurs ARNm mitochondriaux et angiogéniques.
• Le lactosérum n’ajoute aucun avantage supplémentaire aux adaptations microvasculaires ou mitochondriales musculaires à l’exercice physique.
• La perfusion stimulée par l’insuline augmente avec le lactosérum mais n’a pas d’impact sur l’élimination du glucose.falseGaffney, Kim Lucero, Adam Macartney-Coxson, Donia Clapham, Jane Whitfield, Patricia Palmer, Barry Wakefield, StJohn Faulkner, James Stoner, Lee Rowlands, David Stephen eng Canada Appl Physiol Nutr Metab. 2021 Feb 16. doi: 10.1139/apnm-2020-0943.
Skeletal muscle microvascular dysfunction and mitochondrial rarefaction feature in type-2 diabetes mellitus (T2DM) linked to low tissue glucose disposal rate (GDR). Exercise training and milk protein supplementation independently promote microvascular and metabolic plasticity in muscle associated with improved nutrient delivery, but combined effects are unknown. In a randomised-controlled trial, 24 men (55.6 y, SD5.7) with T2DM ingested whey protein drinks (protein/carbohydrate/fat: 20/10/3 g; WHEY) or placebo (carbohydrate/fat: 30/3 g; CON) before/after 45 mixed-mode intense exercise sessions over 10 weeks, to study effects on insulin-stimulated (hyperinsulinemic clamp) skeletal-muscle microvascular blood flow (mBF) and perfusion (near-infrared spectroscopy), and histological, genetic, and biochemical markers (biopsy) of microvascular and mitochondrial plasticity. WHEY enhanced insulin-stimulated perfusion (WHEY-CON 5.6%; 90%CI -0.1, 11.3), while mBF was not altered (3.5%; -17.5, 24.5); perfusion, but not mBF, associated (regression) with increased GDR. Exercise training increased mitochondrial (range of means: 40-90%) and lipid density (20-30%), enzyme activity (20-70%), capillary:fiber ratio (~25%), and lowered systolic (~4%) and diastolic (4-5%) blood pressure, but without WHEY effects. WHEY dampened PGC1alpha -2.9% (90%CI -5.7, -0.2) and NOS3 -6.4% (-1.4, -0.2) expression, but other mRNA were unclear. Skeletal muscle microvascular and mitochondrial exercise adaptations were not accentuated by whey protein ingestion in men with T2DM. Clinical Trial Registration Number: ACTRN12614001197628 Novelty Bullets: * Chronic whey ingestion in T2DM with exercise altered expression of several mitochondrial and angiogenic mRNA. * Whey added no additional benefit to muscle microvascular or mitochondrial adaptations to exercise. * Insulin-stimulated perfusion increased with whey but was without impact on glucose disposal
Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity
Get PDFRecently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies. Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765. One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking), lung cancer, and chronic obstructive pulmonary disease (COPD). We performed a meta-analysis across 34 datasets of European-ancestry subjects, including 38,617 smokers who were assessed for cigarettes-per-day, 7,700 lung cancer cases and 5,914 lung-cancer-free controls (all smokers), and 2,614 COPD cases and 3,568 COPD-free controls (all smokers). We demonstrate statistically independent associations of rs16969968 and rs588765 with smoking (mutually adjusted p-values < 10(-35) and < 10(-8) respectively). Because the risk alleles at these loci are negatively correlated, their association with smoking is stronger in the joint model than when each SNP is analyzed alone. Rs578776 also demonstrates association with smoking after adjustment for rs16969968 (p < 10(-6)). In models adjusting for cigarettes-per-day, we confirm the association between rs16969968 and lung cancer (p < 10(-20)) and observe a nominally significant association with COPD (p = 0.01); the other loci are not significantly associated with either lung cancer or COPD after adjusting for rs16969968. This study provides strong evidence that multiple statistically distinct loci in this region affect smoking behavior. This study is also the first report of association between rs588765 (and correlates) and smoking that achieves genome-wide significance; these SNPs have previously been associated with mRNA levels of CHRNA5 in brain and lung tissue
VEGFA gene locus (6p12) amplification and colorectal cancer : implications for patients' response to therapy
Get PDFThe aims of this study was to assess the presence of VEGFA genomic alterations in colorectal cancer (CRC) and clarify how these genomic alterations can modulate CRC patients’ response to BV treatment in addition to first line therapy (5fluorouracil, leucovorin, capecitabine, oxaliplatin, mephedrone). Among our goals we aim to find out predictive biomarkers to improve anti-angiogenic therapy efficacy and possibly to develop new therapeutic approaches by setting out new rational drug combinations. Of importance, this study allowed us to contribute to the improving patient’s treatment efficiency as well as reducing the economic cost of ineffective therapy. To conclude, we believe that CRC patients will greatly benefit from our research activities. Altogether, our study helped the setting of personalized therapeutic strategies by: i) identifying those patients who really will profit of BV treatment, ii) sparing unnecessary side effects and costs for the non-responder CRC patients especially and iii) planning future alternative and/or combination treatments for CRC patients based on the functional results
A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13
No full textThe genetic risk factors for chronic obstructive pulmonary disease (COPD) are still largely unknown. To date, genome-wide association studies (GWASs) of limited size have identified several novel risk loci for COPD at CHRNA3/CHRNA5/IREB2, HHIP and FAM13A; additional loci may be identified through larger studies. We performed a GWAS using a total of 3499 cases and 1922 control subjects from four cohorts: the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); the Normative Aging Study (NAS) and National Emphysema Treatment Trial (NETT); Bergen, Norway (GenKOLS); and the COPDGene study. Genotyping was performed on Illumina platforms with additional markers imputed using 1000 Genomes data; results were summarized using fixed-effect meta-analysis. We identified a new genomewide significant locus on chromosome 19q13 (rs7937, OR = 0.74, P = 2.9 × 10 -9). Genotyping this singlenucleotide polymorphism (SNP) and another nearby SNP in linkage disequilibrium (rs2604894) in 2859 subjects from the family-based International COPD Genetics Network study (ICGN) demonstrated supportive evidence for association for COPD (P = 0.28 and 0.11 for rs7937 and rs2604894), pre-bronchodilator FEV 1 (P = 0.08 and 0.04) and severe (GOLD 3&4) COPD (P = 0.09 and 0.017). This region includes RAB4B, EGLN2, MIA and CYP2A6, and has previously been identified in association with cigarette smoking behavior. © The Author 2011. Published by Oxford University Press. All rights reserved
Functional Magnetic Nerve Stimulation: The development of a method of generation of explosive expiratory flows in the intubated patient through abdominal muscle stimulation.
Get PDFFunctional Magnetic Nerve Stimulation: The development of a method of generation of explosive expiratory flows in the intubated patient through abdominal muscle stimulation.
A voluntary cough is an explosive expiratory manoeuvre where the larynx is closed during the early expiratory phase. Subsequent opening of the larynx generates high peak flows to facilitate the removal of mucus and inhaled material from the large airways.
The objective of the thesis was to explore the mechanics of a voluntary cough and develop a surrogate voluntary cough with application to the intubated critical care patient.
The thesis developed an understanding of voluntary cough mechanics through a variety of laboratory and clinical models. A modification of the classic Starling Resistor demonstrated that during a peak expiratory flow (PEF) manoeuvre, the addition of a surrogate larynx produced a significant reduction in the time to develop a peak flow, 0.2 to 0.04 seconds.
In clinical trials of the surrogate larynx, cough mechanics were compared with a PEF. A large rise in esophageal pressure (Pes) (118cmH2O ±14cmH2O) was a signature of a voluntary cough when compared with Pes during a PEF (66cmH2O ±9cmH2O). The addition of a surrogate larynx during a PEF created an elevation in Pes and rapid rise in peak flow, comparable to a voluntary cough. Observation of the transdiaphragmatic pressure (Pdi) suggested that thoracic muscles contribute to the elevation in Pes during a voluntary cough.
Though gastric pressure is applied as a surrogate marker of abdominal pressure, the validity of this was confirmed in a clinical trial when compared with actual abdominal pressure recorded with a laparoscope.
The surrogate cough model considered for application to the critical care subject was the application of functional magnetic nerve stimulation of the abdominal muscles in intubated patients during sedation or anaesthesia. The development of this model needed to consider the deleterious effects on the force of muscle contraction following anaesthesia with Propofol, and the potential for abdominal muscle stimulation to provide the force driving a voluntary cough. A clinical trial observed a reduction in twitch strength of 14% - 28%, following magnetic nerve stimulation of the phrenic nerve with Propofol anaesthesia. The magnitude of the effect of the abdominal muscles upon expulsive manoeuvres was also considered. In a clinical trial, spinal anaesthesia, with the loss of abdominal muscle function, diminished maximum expiratory pressure compared with baseline value (P = 0.003), with no observed reduction in maximum inspiratory pressure.
Cough function in subjects following a laryngectomy observed the changes in Pes during a volitional cough. The objective was to observe if the rise in Pes may or may not be related to laryngeal closure. The observation were that the volitional “cough” generated a large elevation in thoracic pressure with (145cmH2O) that exceeded the maximum abdominal pressure (126cmH2O), but there was no rapid rise in time to peak flow. The latter could be reversed with the addition of a surrogate larynx.
Testing of the surrogate cough model in anaesthetised subjects demonstrated the potential of the model to reproduce some elements of a voluntary cough. However, the expiratory flow generated was limited even in the presence of a surrogate larynx. The surrogate larynx confirmed that it supports the rapid rise in expiratory flow but does not promote a rise in thoracic pressure.
Some elements of the thesis objective were realised. A voluntary cough bears similarities to a forced expiratory flow manoeuvre. Thoracic muscles are actively recruited to support the rise in esophageal pressure characteristic of a voluntary cough. Laryngeal closure does not support the elevation in thoracic pressure but shortens the time to peak flow improving the force generated.
The complex pattern of expiratory muscle recruitment observed during a voluntary cough is not easily reproducible through magnetic nerve stimulation of the abdominal muscles. The mechanics of delivery of a surrogate cough applying magnetic nerve stimulation is perhaps too complex to have practical application to intensive care respiratory physical therapy. The thesis developed a model of pressure and flow generation of a voluntary cough that could have application to the development of alternative physical therapy techniques. In particular a surrogate larynx may find practical applications to subjects following a laryngectomy or in critical care where the normal larynx is bypassed by an endotracheal tube
