scholarly journals Pharmacological Screening Identifies SHK242 and SHK277 as Novel Arginase Inhibitors with Efficacy against Allergen-Induced Airway Narrowing In Vitro and In Vivo

2020 ◽  
Vol 374 (1) ◽  
pp. 62-73 ◽  
Author(s):  
M.P.M. van den Berg ◽  
S.H. Kurhade ◽  
H. Maarsingh ◽  
S. Erceg ◽  
I.R. Hulsbeek ◽  
...  
Keyword(s):  
Airway Narrowing ◽  
Pharmacological Screening ◽  
Arginase Inhibitors

scholarly journals Evaluation of Plant Phenolic Metabolites as a Source of Alzheimer's Drug Leads

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Yara Hassaan ◽  
Heba Handoussa ◽  
Ahmed H. El-Khatib ◽  
Michael W. Linscheid ◽  
Nesrine El Sayed ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Epidemiological Studies ◽  
Aqueous Alcohol ◽  
Alcohol Extract ◽  
Y Maze ◽  
Pharmacological Screening

Epidemiological studies have proven an association between consumption of polyphenols and prevention of Alzheimer’s disease, the most common form of dementia characterized by extracellular deposition of amyloid beta plaques. The aim of this study is pharmacological screening of the aqueous alcohol extract ofMarkhamia platycalyxleaves,Schotia brachypetalaleaves and stalks, and piceatannol compared to aqueous alcohol extract ofCamellia sinensisleaves as potential Alzheimer’s disease drugs. LC-HRESI(-ve)-MSnwas performed to identify phenolics’ profile ofSchotia brachypetalastalks aqueous alcohol extract and revealed ten phenolic compounds as first report: daidzein, naringin, procyanidin isomers, procyanidin dimer gallate, quercetin 3-O-rhamnoside, quercetin 3-O-glucuronide, quercetin hexose gallic acid, quercetin hexose protocatechuic acid, and ellagic acid. Alzheimer’s disease was induced by a single intraperitoneal injection of LPS. Adult male Swiss albino mice were divided into groups of 8–10 mice each receiving treatment for six days.In vivobehavioral tests (Y maze and object recognition) andin vitroestimation of amyloid beta 42 by ELISA showed significant differences between results of treated and nontreated animals.

scholarly journals Decreased airway narrowing and smooth muscle contraction in hyperresponsive pigs

2002 ◽  
Vol 93 (4) ◽  
pp. 1296-1300 ◽  
Author(s):  
Debra J. Turner ◽  
Peter B. Noble ◽  
Matthew P. Lucas ◽  
Howard W. Mitchell
Keyword(s):  
Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Porcine Model ◽  
Smooth Muscle Contraction ◽  
Airway Wall ◽  
Muscle Contractility ◽  
Smooth Muscle Contractility ◽  
Airway Narrowing

Increased smooth muscle contractility or reduced smooth muscle mechanical loads could account for the excessive airway narrowing and hyperresponsiveness seen in asthma. These mechanisms were investigated by using an allergen-induced porcine model of airway hyperresponsiveness. Airway narrowing to electric field stimulation was measured in isolated bronchial segments, over a range of transmural pressures (0–20 cmH2O). Contractile responses to ACh were measured in bronchial segments and in isolated tracheal smooth muscle strips isolated from control and test (ovalbumin sensitized and challenged) pigs. Test airways narrowed less than controls ( P < 0.0001). Test pigs showed reduced contractility to ACh, both in isolated bronchi ( P < 0.01) and smooth muscle strips ( P < 0.01). Thus isolated airways from pigs exhibiting airway hyperresponsiveness in vivo are hyporesponsive in vitro. The decreased narrowing in bronchi from hyperresponsive pigs may be related to decreased smooth muscle contractility. These data suggest that mechanisms external to the airway wall may be important to the hyperresponsive nature of sensitized lungs.

Adaptation to chronic length change in explanted airway smooth muscle

2003 ◽  
Vol 95 (1) ◽  
pp. 448-453 ◽  
Author(s):  
Jahanbakhsh Naghshin ◽  
Lu Wang ◽  
Peter D. Paré ◽  
Chun Y. Seow
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Culture Media ◽  
Length Change ◽  
Functional Change ◽  
Muscle Stiffness ◽  
Airway Narrowing

It has been shown that airway smooth muscle in vitro is able to maintain active force over a large length range by adaptation in the absence of periodic stimulations at 4°C (Wang L, Paré PD, and Seow CY. J Appl Physiol 90: 734–740, 2001). In this study, we show that such adaptation also takes place at body temperature and that long-term adaptation results in irreversible functional change in the muscle that could lead to airway hyperresponsiveness. Rabbit tracheal muscle explants were passively maintained at shortened and in situ length for 3 and 7–8 days in culture media; the length-tension relationship was then examined. The length associated with maximal force generation decreased by 10.5 ± 3.8% (SE) after 3 days and 37.7 ± 8.5% after 7 or 8 days of passive shortening. At day 3, the left shift in the length-tension curve due to adaptation at short lengths was reversible by readapting the muscle at a longer length. The shift was, however, not completely reversible after 7 days. The results suggest that long-term adaptation of airway smooth muscle could lead to increased muscle stiffness and force-generating ability at short lengths. Under in vivo condition, this could translate into resistance to stretch-induced relaxation and excessive airway narrowing.

A role for transient receptor potential ankyrin 1 cation channel (TRPA1) in airway hyper-responsiveness?

2015 ◽  
Vol 93 (3) ◽  
pp. 171-176 ◽  
Author(s):  
Aruni Jha ◽  
Pawan Sharma ◽  
Vidyanand Anaparti ◽  
Min H. Ryu ◽  
Andrew J. Halayko
Keyword(s):  
Airway Inflammation ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Cation Channel ◽  
Chronic Obstructive ◽  
Airway Narrowing ◽  
Airway Caliber ◽  
Transient Receptor

Airway smooth muscle (ASM) contraction controls the airway caliber. Airway narrowing is exaggerated in obstructive lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD). The mechanism by which ASM tone is dysregulated in disease is not clearly understood. Recent research on ion channels, particularly transient receptor potential cation channel, subfamily A, member 1 (TRPA1), is uncovering new understanding of altered airway function. TRPA1, a member of the TRP channel superfamily, is a chemo-sensitive cation channel that can be activated by a variety of external and internal stimuli, leading to the influx of Ca2+. Functional TRPA1 channels have been identified in neuronal and non-neuronal tissues of the lung, including ASM. In the airways, these channels can regulate the release of mediators that are markers of airway inflammation in asthma and COPD. For, example, TRPA1 controls cigarette-smoke-induced inflammatory mediator release and Ca2+ mobilization in vitro and in vivo, a response tied to disease pathology in COPD. Recent work has revealed that pharmacological or genetic inhibition of TRPA1 inhibits the allergen-induced airway inflammation in vitro and airway hyper-responsiveness (AHR) in vivo. Collectively, it appears that TRPA1 channels may be determinants of ASM contractility and local inflammation control, positioning them as part of novel mechanisms that control (patho)physiological function of airways and ASM.

scholarly journals Design, Synthesis and Characterization of Some Novel benzamide derivatives and it's Pharmacological Screening

2020 ◽  
pp. 68-74 ◽  
Author(s):  
Akshay R. Yadav ◽  
Shrinivas K. Mohite
Keyword(s):  
Chemical Structure ◽  
Design Synthesis ◽  
Different Types ◽  
Anti Inflammatory ◽  
Benzoyl Isothiocyanate ◽  
Pharmacological Screening ◽  
Benzamide Derivatives

The new series of substituted N-(phenylcarbamothioyl)benzamide derivatives (2a-2f) was designed, development and synthesized by using conventional and microwave method. In present work 6 different N-(phenylcarbamothioyl)benzamide were synthesized. Substituted benzoyl chloride is converted into benzoyl isothiocyanate by esterification. Benzoyl isothiocyanate is converted into Substituted (phenylcarbamothioyl)benzamide by treating with different types of substituted aniline. Confirmation of the chemical structure of the synthesized was substantiated by TLC, IR, 1H NMR, MS spectroscopy.Novel synthesized compounds screened for their in vivo and in-vitro anti-inflammatory studies and compound 2f shows promising anti-inflammatory activity.

scholarly journals The synthesis and the antioxidant activity of 1-phenoxymethyl-4-aryl-5,6,7,8-tetrahydro-2a,4a,8a-triazacyclopenta[cd]azulene-3-carboxylic (or carbothionic) acid derivatives

Pharmacia ◽  
2021 ◽  
Vol 68 (1) ◽  
pp. 251-258
Author(s):  
Sergii Demchenko ◽  
Hanna Yeromina ◽  
Yulia Fedchenkova ◽  
Zinaida Ieromina ◽  
Vitaliy Yaremenko ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Ascorbic Acid ◽  
Carboxylic Acid ◽  
In Silico ◽  
Pharmacokinetic Profile ◽  
High Antioxidant Activity ◽  
Pharmacological Screening

New 1-phenoxymethyl-4-aryl-5,6,7,8-tetrahydro-2а,4a,8a-triazacyclopenta[cd]azulene-3-carboxylic (or carbothionic) acid derivatives have been designed, synthesized and evaluated for their in vitro antioxidant activity under conditions of the artificial oxidative stress using ionol, ascorbic acid and α-tocopherol as the reference drugs. It has been found that 1-phenoxymethyl-4-aryl-5,6,7,8-tetrahydro-2а,4a,8a-triazacyclopenta[cd]azulene-3-carbothionic acid derivatives 9b, 9c, 9d, 9e, 9f, 9i and 1-phenoxymethyl-4-(41-chlorophenyl)-5,6,7,8-tetrahydro-2,2a,8-triazacyclopenta[cd]azulene-3-carboxylic acid phenylamide 10 reveal a high antioxidant activity and a good in silico pharmacokinetic profile. The data obtained allowed us to select the most promising objects from the substances synthesized for further pharmacological screening for the presence of the antioxidant activity in vivo.

scholarly journals Airway mechanical compression: its role in asthma pathogenesis and progression

2020 ◽  
Vol 29 (157) ◽  
pp. 190123 ◽  
Author(s):  
Punnam Chander Veerati ◽  
Jennifer A. Mitchel ◽  
Andrew T. Reid ◽  
Darryl A. Knight ◽  
Nathan W. Bartlett ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Experimental Models ◽  
Normal Lung ◽  
Mechanical Forces ◽  
Mechanical Compression ◽  
Cell Hyperplasia ◽  
Airway Narrowing ◽  
The Impact

The lung is a mechanically active organ, but uncontrolled or excessive mechanical forces disrupt normal lung function and can contribute to the development of disease. In asthma, bronchoconstriction leads to airway narrowing and airway wall buckling. A growing body of evidence suggests that pathological mechanical forces induced by airway buckling alone can perpetuate disease processes in asthma. Here, we review the data obtained from a variety of experimental models, including in vitro, ex vivo and in vivo approaches, which have been used to study the impact of mechanical forces in asthma pathogenesis. We review the evidence showing that mechanical compression alters the biological and biophysical properties of the airway epithelium, including activation of the epidermal growth factor receptor pathway, overproduction of asthma-associated mediators, goblet cell hyperplasia, and a phase transition of epithelium from a static jammed phase to a mobile unjammed phase. We also define questions regarding the impact of mechanical forces on the pathology of asthma, with a focus on known triggers of asthma exacerbations such as viral infection.

Airway narrowing and bronchodilation to deep inspiration in bronchial segments from subjects with and without reported asthma

2013 ◽  
Vol 114 (10) ◽  
pp. 1460-1471 ◽  
Author(s):  
Peter B. Noble ◽  
Robyn L. Jones ◽  
Alvenia Cairncross ◽  
John G. Elliot ◽  
Howard W. Mitchell ◽  
...  
Keyword(s):  
Mechanical Stretch ◽  
Control Group ◽  
Deep Inspiration ◽  
Airway Wall ◽  
Normal Response ◽  
Airway Narrowing ◽  
History Of ◽  
Static Conditions

The present study presents preliminary findings on how structural/functional abnormalities of the airway wall relate to excessive airway narrowing and reduced bronchodilatory response to deep inspiration (DI) in subjects with a history of asthma. Bronchial segments were acquired from subjects undergoing surgery, mostly to remove pulmonary neoplasms. Subjects reported prior doctor-diagnosed asthma ( n = 5) or had no history of asthma ( n = 8). In vitro airway narrowing in response to acetylcholine was assessed to determine maximal bronchoconstriction and sensitivity, under static conditions and during simulated tidal and DI maneuvers. Fixed airway segments were sectioned for measurement of airway wall dimensions, particularly the airway smooth muscle (ASM) layer. Airways from subjects with a history of asthma had increased ASM ( P = 0.014), greater maximal airway narrowing under static conditions ( P = 0.003), but no change in sensitivity. Maximal airway narrowing was positively correlated with the area of the ASM layer ( r = 0.58, P = 0.039). In tidally oscillating airways, DI produced bronchodilation in airways from the control group ( P = 0.0001) and the group with a history of asthma ( P = 0.001). While bronchodilation to DI was reduced with increased airway narrowing ( P = 0.02; r = −0.64)), when the level of airway narrowing was matched, there was no difference in magnitude of bronchodilation to DI between groups. Results suggest that greater ASM mass in asthma contributes to exaggerated airway narrowing in vivo. In comparison, the airway wall in asthma may have a normal response to mechanical stretch during DI. We propose that increased maximal airway narrowing and the reduced bronchodilatory response to DI in asthma are independent.

Sign in / Sign up

Export Citation Format

Share Document