No abstract is provided for this article.
P. J. Barnes, J. D. Baty, R. F. Bilton and A. N. Mason, J. Chem. Soc., Chem. Commun., 1974, 115 DOI: 10.1039/C39740000115
A new non‐peptide tachykinin antagonist, CP‐96,345, inhibited airway plasma exudation induced in guinea‐pigs by i.v. substance P in a dose‐dependent manner with dose‐ratios in the main bronchi of 5 at 1 nmol kg −1 and 19 at 100 nmol kg −1 . At 100 nmol kg −1 , CP‐96,345 completely inhibited plasma exudation induced by either electrical stimulation of the cervical vagus nerves or i.v. capsaicin, indicating inhibition of the effects of endogenous tachykinins, but did not inhibit the bronchoconstrictor response to neurokinin A, suggesting selectivity for NK 1 receptors. CP‐96,345 may be useful in examining the role of endogenous tachykinins in vivo .
Wire arc additive manufacturing (WAAM) is a method of metal three-dimensional (3D) printing that has the potential for a significant impact on the construction industry due to its ability to produce large parts with reasonable printing times and costs. However, there is currently a lack of fundamental data on the performance of structural elements produced using this method of manufacturing. Seeking to bridge this gap, the compressive behavior and resistance of WAAM square hollow sections (SHS) are investigated in this paper. In a previous study by the authors, testing reported of sheet material produced in the same manner as the studied SHS is first summarized. The production, measurement, and testing of a series of stainless steel SHS stub columns are then described. Regular cross-section profiles were chosen to isolate the influence of 3D printing and enable direct comparisons to be made against equivalent sections produced using traditional methods of manufacturing. A range of cross-section sizes and thicknesses were considered to achieve variations in the local cross-sectional slenderness of the tested specimens, allowing the influence of local buckling to be assessed. Repeat tests enabled the variability in response between specimens to be evaluated; a total of 14 SHS stub columns of seven different local slendernesses was tested, covering all cross-section classes of AISC 370 and Eurocode 3. Advanced noncontact measurement techniques were employed to determine the as-built geometric properties, while digital image correlation measurements were used to provide detailed insight into the deformation characteristics of the test specimens. Owing to the higher geometric variability of WAAM relative to conventional forming processes, the tested 3D printed stub columns were found to exhibit more variable capacities between repeat specimens than is generally displayed by stainless steel SHS. Comparisons of the stub column test results with existing structural design rules highlight the need to allow for the weakening effect of the geometric undulations that are inherent to the WAAM process in order to achieve safe-sided strength predictions.
Several new drugs are now under development for the treatment of asthma, either as improvements to existing classes of therapy or as novel agents. Amongst bronchodilators, long-acting inhaled beta 2-agonists (salmeterol and formoterol) look very promising and there is also interest in selective phosphodiesterase inhibitors, K+ channel-openers and nitrodilators. There are several new inhaled corticosteroids under development and more selective agents include leukotriene antagonists, 5-lipoxygenase inhibitors, bradykinin and tachykinin antagonists and immunomodulators. In the future, adhesion molecule inhibitors and cytokine inhibitors may be developed.
Abstract An experimental investigation into the structural behaviour of steel frames made up of hybrid steel welded I‐section members is presented in this paper. The tested hybrid steel welded I‐section profile had quenched and tempered S690 steel flanges and an S355 steel web. The experimental programme comprised four two‐dimensional, single storey, single bay frames subjected to different combinations of horizontal and vertical loading, thus enabling different beam, sway as well as combined beam and sway plastic collapse mechanisms to be examined. The frames were fully laterally restrained using a bespoke lateral bracing system to ensure that no out‐of‐plane instability phenomena were experienced during testing. The experimental setup, loading schemes, instrumentation and key experimental results are reported. The experimental results are fundamental to developing an understanding of the behaviour of hybrid steel welded I‐sections at the structural system level. Further research is underway to underpin the development of suitable design rules for steel frames made of such hybrid steel welded I‐section members.
We have investigated whether prejunctional inhibitory muscarinic receptors ("autoreceptors") exist on cholinergic nerves in human airways in vitro and whether guinea pig trachea provides a good model for further pharmacological characterization of these receptors. Pilocarpine was used as a selective agonist and gallamine as a selective antagonist of these autoreceptors. Acetylcholine (ACh) release from postganglionic cholinergic nerves was elicited by electrical field stimulation (EFS) (40 V, 0.5 ms, 32 Hz). In human bronchi, pilocarpine inhibited the contractile response to EFS in a dose-related fashion; the dose inhibiting 50% of the control contraction was 2.2 +/- 0.4 x 10(-7) (SE) M (n = 22), and the inhibition was 96% at 3 x 10(-5) M. The inhibitory effects of pilocarpine were antagonized by gallamine in a dose-related fashion. The results were qualitatively the same in the guinea pig. Gallamine significantly enhanced the contractile response to EFS in the guinea pig, whereas pirenzepine failed to do so, which suggests that M2-receptors are involved. We conclude that prejunctional muscarinic receptors that inhibit ACh release are present on cholinergic nerves in human airways and that guinea pig trachea is a good model for further pharmacological characterization of these receptors, which appear to belong to the M2-subtype.
Nonalcoholic fatty liver disease (NAFLD) is a metabolic disorder characterized by excessive fat accumulation in the liver not associated with infection, medication, or an autoimmune process. The majority of individuals with NAFLD are asymptomatic and are found to have elevated hepatic transaminases on blood work that has been drawn for screening purposes or as part of an entirely different evaluation. NAFLD is a spectrum of disease ranging from relatively benign nonalcoholic fatty liver (NAFL) to an inflammatory process affecting the hepatocytes called nonalcoholic steatohepatitis (NASH) that can ultimately lead to fibrosis, cirrhosis, and increased risk of hepatocellular carcinoma.1–3 Currently, the only way to differentiate between NAFL and NASH is by determining the histopathology on liver biopsy. NAFLD is a common condition, affecting approximately 20% of Americans overall,4,5 and an estimated 3% to 17% of children.6,7 An obesity-associated condition, nearly 75% of overweight/obese adults5 and 38% of overweight/obese children have NAFLD.6 The prevalence of NASH is also rising as it affects approximately 1.1% to 14% of Americans,8,9 including 19% of individuals who are obese, and 50% of individuals who are morbidly obese.10 These numbers may ultimately lead to a rise in progressive liver scarring or NAFLD-associated cirrhosis and hepatocellular carcinoma.11 In addition to adiposity, NAFLD is associated with the metabolic syndrome (MetS), a cluster of risk factors associated with cardiovascular disease and “type 2” diabetes mellitus (T2DM).6,7,12 NAFLD’s associations with cardiovascular disease, type 2 diabetes mellitus, cirrhosis, and hepatocellular carcinoma make NAFLD a serious public health concern. In this review, we will discuss emerging data regarding etiology and clinical features of NAFLD in childhood, particularly as they relate to the need for screening among children with obesity and increased metabolic risk.
