Smooth Muscle Endothelin B Receptors Regulate Blood Pressure but Not Vascular Function or Neointimal Remodeling

The role of smooth muscle endothelin$_{B}$ (ET$_{B}$) receptors in regulating vascular function, blood pressure (BP), and neointimal remodeling has not been established. Selective knockout mice were generated to address the hypothesis that loss of smooth muscle ET$_{B}$ receptors would reduce BP, alter vascular contractility, and inhibit neointimal remodeling. ET$_{B}$ receptors were selectively deleted from smooth muscle by crossing floxed ET$_{B}$ mice with those expressing cre-recombinase controlled by the transgelin promoter. Functional consequences of ET$_{B}$ deletion were assessed using myography. BP was measured by telemetry, and neointimal lesion formation induced by femoral artery injury. Lesion size and composition (day 28) were analyzed using optical projection tomography, histology, and immunohistochemistry. Selective deletion of ET$_{B}$ was confirmed by genotyping, autoradiography, polymerase chain reaction, and immunohistochemistry. ET$_{B}$-mediated contraction was reduced in trachea, but abolished from mesenteric veins, of knockout mice. Induction of ET$_{B}$-mediated contraction in mesenteric arteries was also abolished in these mice. Femoral artery function was unaltered, and baseline BP modestly elevated in smooth muscle ET$_{B}$ knockout compared with controls (+4.2±0.2 mm Hg; $\textit{P}$<0.0001), but salt-induced and ET$_{B}$ blockade-mediated hypertension were unaltered. Circulating endothelin-1 was not altered in knockout mice. ET$_{B}$-mediated contraction was not induced in femoral arteries by incubation in culture medium or lesion formation, and lesion size was not altered in smooth muscle ET$_{B}$ knockout mice. In the absence of other pathology, ET$_{B}$ receptors in vascular smooth muscle make a small but significant contribution to ET$_{B}$-dependent regulation of BP. These ET$_{B}$ receptors have no effect on vascular contraction or neointimal remodeling.This work was funded by the British Heart Foundation (Project Grant PG/08/068/25461, P.W.F. Hadoke and D.J. Webb; Intermediate Clinical Research Fellowship FS/13/30/29994, N. Dhaun; and Centre of Research Excellence Award) and the Wellcome Trust (107715/Z/15/Z, A.P. Davenport and R.E. Kuc)

Effects of fatigue on trunk stability in elite gymnasts

The aim of the present study was to test the hypothesis that fatigue due to exercises performed in training leads to a decrement of trunk stability in elite, female gymnasts. Nine female gymnasts participated in the study. To fatigue trunk muscles, four series of five dump handstands on the uneven bar were performed. Before and after the fatigue protocol, participants performed three trials of a balancing task while sitting on a seat fixed over a hemisphere to create an unstable surface. A force plate tracked the location of the center of pressure (CoP). In addition, nine trials were performed in which the seat was backward inclined over a set angle and suddenly released after which the subject had to regain balance. Sway amplitude and frequency in unperturbed sitting were determined from the CoP time series and averaged over trials. The maximum displacement and rate of recovery of the CoP location after the sudden release were determined and averaged over trials. After the fatigue protocol, sway amplitude in the fore-aft direction was significantly increased (p = 0.03), while sway frequency was decreased (p = 0.005). In addition, the maximum displacement after the sudden release was increased (p = 0.009), while the rate of recovery after the perturbation was decreased (p = 0.05). Fatigue induced by series of exercises representing a realistic training load caused a measurable decrement in dynamic stability of the trunk in elite gymnasts

Effect of spinal manipulation on sensorimotor functions in back pain patients: study protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Low back pain (LBP) is a recognized public health problem, impacting up to 80% of US adults at some point in their lives. Patients with LBP are utilizing integrative health care such as spinal manipulation (SM). SM is the therapeutic application of a load to specific body tissues or structures and can be divided into two broad categories: SM with a high-velocity low-amplitude load, or an impulse "thrust", (HVLA-SM) and SM with a low-velocity variable-amplitude load (LVVA-SM). There is evidence that sensorimotor function in people with LBP is altered. This study evaluates the sensorimotor function in the lumbopelvic region, as measured by postural sway, response to sudden load and repositioning accuracy, following SM to the lumbar and pelvic region when compared to a sham treatment.</p> <p>Methods/Design</p> <p>A total of 219 participants with acute, subacute or chronic low back pain are being recruited from the Quad Cities area located in Iowa and Illinois. They are allocated through a minimization algorithm in a 1:1:1 ratio to receive either 13 HVLA-SM treatments over 6 weeks, 13 LVVA-SM treatments over 6 weeks or 2 weeks of a sham treatment followed by 4 weeks of full spine "doctor's choice" SM. Sensorimotor function tests are performed before and immediately after treatment at baseline, week 2 and week 6. Self-report outcome assessments are also collected. The primary aims of this study are to 1) determine immediate pre to post changes in sensorimotor function as measured by postural sway following delivery of a single HVLA-SM or LVVA-SM treatment when compared to a sham treatment and 2) to determine changes from baseline to 2 weeks (4 treatments) of HVLA-SM or LVVA-SM compared to a sham treatment. Secondary aims include changes in response to sudden loads and lumbar repositioning accuracy at these endpoints, estimating sensorimotor function in the SM groups after 6 weeks of treatment, and exploring if changes in sensorimotor function are associated with changes in self-report outcome assessments.</p> <p>Discussion</p> <p>This study may provide clues to the sensorimotor mechanisms that explain observed functional deficits associated with LBP, as well as the mechanism of action of SM.</p> <p>Trial registration</p> <p>This trial is registered in ClinicalTrials.gov, with the ID number of <a href="http://www.clinicaltrials.gov/ct2/show/NCT00830596">NCT00830596</a>, registered on January 27, 2009. The first participant was allocated on 30 January 2009 and the final participant was allocated on 17 March 2011.</p

Myocardial ischemia and reperfusion: The role of oxygen radicals in tissue injury

Thrombolytic therapy has gained widespread acceplance as a means of treating coronary artery thrombosis in patients with acute myocardial infarction. Although experimental data have demonstrated that timely reperfusion limits the extent of infarction caused by regional ischemia, there is growing evidence that reperfusion is associated with an inflammatory response to ischemia that exacerbates the tissue injury. Ischemic myocardium releases archidonate and complement-derived chemotactic factors, e.g., leukotriene B 4 and C 5a , which attract and activate neutrophils. Reperfusion of ischemic myocardium accelerates the influx of neutrophils, which release reactive oxygen products, such as superoxide anion and hydrogen peroxide, resulting in the formation of a hydroxyl radical and hypochlorous acid. The latter two species may damage viable endothelial cells and myocytes via the peroxidation of lipids and oxidation of protein sulfhydryl groups, leading to perturbations of membrane permeability and enzyme function. Neutrophil depletion by antiserum and inhibition of neutrophil function by drugs, e.g., ibuprofen, prostaglandins (prostacyclin and PGE 1 ), or a monoclonal antibody, to the adherence-promoting glycoprotein Mo-1 receptor, have been shown to limit the extent of canine myocardial injury due to coronary artery occlusion/reperfusion. Recent studies have challenged the hypothesis that xanthine-oxidase-derived oxygen radicals are a cause of reperfusion injury. Treatment with allopurinol or oxypurinol may exert beneficial effects on ischemic myocardium that are unrelated to the inhibition of xanthine oxidase. Furthermore, the human heart may lack xanthine oxidase activity. Further basic research is needed, therefore, to clarify the importance of xanthine oxidase in the pathophysiology of reperfusion injury. Current data are highly suggestive of a deleterious role of the neutrophil in organ reperfusion and justify consideration of the clinical investigation of neutrophil inhibitors in patients receiving thrombolytic agents during the evolution of an acute myocardial infarction.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44595/1/10557_2004_Article_BF00133206.pd

The 'long' 16th century : a key period of animal husbandry change in England

Although many historians have extensively discussed the agricultural history of England between the Late Middle Ages and the Modern Era, this period of crucial changes has received less attention by archaeologists. In this paper, zooarchaeological evidence dated between the Late Middle Ages and the Early Modern period is analysed to investigate changes in animal husbandry during the ‘long’ sixteenth century. The size and shape of the main domestic animals (cattle, sheep, pig and chicken) is explored through biometrical data and discussed in line with evidence of taxonomic frequencies, ageing and sex ratios. Data from 12 sites with relevant chronologies and located in different areas of the country are considered. The results show that, although a remarkable size increase of animals occurred in England throughout the post-medieval period, much of this improvement occurred as early as the sixteenth century. The nature and causes of such improvement are discussed, with the aim of understanding the development of Early Modern farming and the foundations of the so-called Agricultural Revolution

Teaching with technology in the post-pandemic digital age: Technological normalisation and AI-induced disruptions

This is the author accepted manuscript. The final version is available from SAGE Publications via the DOI in this record Technology has long been a valuable resource for language teachers to use to support their teaching and student learning (Li, 2017). Despite efforts from educators, scholars, and policymakers, however, the full integration of technology into language teaching, or ‘normalisation’ defined by Bax (2003) as “the stage when a technology is invisible, hardly even recognised as a technology, taken for granted in everyday life” (p. 23), had not been evident in language classrooms in many contexts (John, 2018). Following the steps of ‘normalised’ technology integration in other human domains (e.g., banking, travel, medicine, entertainment), this special issue examines how technology might be reimagined in the language teaching context.University Grants Committee, Hong Kong SA