Extracellular Elastolytic Activity in Human Lung Lavage: A Comparative study between Smokers and Non-Smokers

1985 ◽  
Vol 69 (1) ◽  
pp. 17-27 ◽  
Author(s):  
S. F. Smith ◽  
A. Guz ◽  
N. T. Cooke ◽  
G. H. Burton ◽  
T. D. Tetley
Keyword(s):  
Proteinase Inhibitor ◽  
Protease Activity ◽  
Human Lung ◽  
Lung Lavage ◽  
Low Molecular Weight ◽  
Elastase Activity ◽  
Significant Difference ◽  
Elastolytic Activity ◽  
Bronchial Mucus ◽  
Extracellular Protease Activity

1. Unrestrained proteolysis in the lung is believed to initiate emphysema, a disease common among tobacco smokers. However, few studies have found extracellular protease activity in human lung lavage. 2. In this investigation, elastase and serine protease activities were measured in broncho-alveolar lavage supernatants (BAL) from patients undergoing routine investigations. Significantly more elastolytic activity (against insoluble [3H]-elastin) was recovered in the lavage of smokers than that of non-smokers. However, no significant difference was found when the levels of serine proteolytic activity (against N-succinyl-L-trialanyl-p-nitroanilide) were compared. 3. The elastolytic component of the protease activity rose from 5% in non-smokers’ BAL to over 30% in that of smokers, suggesting that elastase activity is selectively enhanced by smoking. In lavages from most smokers, 80% or more of the elastase activity was serine-dependent, whereas lavages from non-smokers contained variable proportions of serine elastase. 4. Both α1-proteinase inhibitor (α1-PI) and a low molecular weight antiprotease, bronchial mucus proteinase inhibitor (BMPI) were detectable in the lavage samples, the latter contributing up to 76% of the total antiprotease quantified in the lavage. Functional antiprotease was detected in 85% of the lavages. 5. Since there were no differences in either antiprotease levels or functional inhibitory capacities between lavages from smokers and controls, it is concluded that the imbalance in the protease/antiprotease profile of the smokers’ lung results from an enhancement of proteases, specifically of elastolytic activity, rather than a reduction in inhibitory capacity.

Profile of Elastase Activity Released by Human Lung Lavage Cells in Culture

1987 ◽  
Vol 72 (s16) ◽  
pp. 84P-84P
Author(s):  
S.F. Smith ◽  
A. Guz ◽  
T.D. Tetley
Keyword(s):  
Human Lung ◽  
Lung Lavage ◽  
Elastase Activity ◽  
Cells In Culture

Molecular Docking, Synthesis and anti-HIV-1 Protease Activity of Novel Chalcones

2020 ◽  
Vol 26 (8) ◽  
pp. 802-814 ◽  
Author(s):  
Nemanja Turkovic ◽  
Branka Ivkovic ◽  
Jelena Kotur-Stevuljevic ◽  
Milica Tasic ◽  
Bojan Marković ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Molecular Docking ◽  
Chemical Synthesis ◽  
Protease Activity ◽  
Molecular Mechanisms ◽  
Replication Cycle ◽  
Low Molecular Weight ◽  
Chalcone Derivatives ◽  
Anti Hiv ◽  
Hiv 1

Background: Since the beginning of the HIV/AIDS epidemic, 75 million people have been infected with the HIV and about 32 million people have died of AIDS. Investigation of the molecular mechanisms critical to the HIV replication cycle led to the identification of potential drug targets for AIDS therapy. One of the most important discoveries is HIV-1 protease, an enzyme that plays an essential role in the replication cycle of HIV. Objective: The aim of the present study is to synthesize and investigate anti-HIV-1 protease activity of some chalcone derivatives with the hope of discovering new lead structure devoid drug resistance. Methods: 20 structurally similar chalcone derivatives were synthesized and their physico-chemical characterization was performed. Binding of chalcones to HIV-1 protease was investigated by fluorimetric assay. Molecular docking studies were conducted to understand the interactions. Results: The obtained results revealed that all compounds showed anti-HIV-1 protease activity. Compound C1 showed the highest inhibitory activity with an IC50 value of 0.001 μM, which is comparable with commercial product Darunavir. Conclusion: It is difficult to provide general principles of inhibitor design. Structural properties of the compounds are not the only consideration; ease of chemical synthesis, low molecular weight, bioavailability, and stability are also of crucial importance. Compared to commercial products the main advantage of compound C1 is the ease of chemical synthesis and low molecular weight. Furthermore, compound C1 has a structure that is different to peptidomimetics, which could contribute to its stability and bioavailability.

scholarly journals Safety and efficacy of direct oral anticoagulants (DOACs) vs low molecular weight heparin (LMWH) in malignancy induced venous thromboembolism-a systematic review and meta analysis

2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
A Abdul Razzack ◽  
N Hussain ◽  
S Adeel Hassan ◽  
S Mandava ◽  
F Yasmin ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Low Molecular Weight ◽  
Efficacy And Safety ◽  
Dichotomous Data ◽  
Significant Difference

Abstract Funding Acknowledgements Type of funding sources: None. Background- Low molecular weight heparin (LMWH) and direct oral anticoagulants (DOACs) have been proven to be more effective in the management of venous thromboembolism (MVTE). The efficacy and safety of LMWH or DOACs in treatment of recurrent or malignancy induced VTE is not studied in literature. Objective To compare the efficacy and safety of LMWH and  DOACs in the management of malignancy induced  VTE Methods- Electronic databases ( PubMed, Embase, Scopus, Cochrane) were searched from inception to November  28th, 2020. Dichotomous data was extracted for prevention of VTE and risk of major bleeding in patients taking either LMWH or DOACs. Unadjusted odds ratios (OR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance to be considered if the confidence interval excludes 1 and p < 0.05.  Results- Three studies with 2607 patients (DOACs n = 1301 ; LMWH n = 1306) were included in analysis. All the study population had active cancer of any kind diagnosed within the past 6 months. Average follow-up period for each trial was 6 months. Patients receiving DOACs have a lower odds of recurrence of MVTE as compared to LMWH( OR 1.56; 95% CI 1.17-2.09; P = 0.003, I2 = 0). There was no significant difference in major bleeding among patients receiving LMWH or DOACs  (OR-0.71, 95%CI 0.46-1.10, P = 0.13, I2 = 22%) (Figure 1). We had no publication bias in our results (Egger’s regression p > 0.05). Conclusion- DOACs are superior to LMWH in prevention of MVTE and have similar major bleeding risk as that of LMWH. Abstract Figure. A)VTE Recurrence B)Major Bleeding events

Comparison of elastolytic activity in lung lavage from current, ex- and non-smokers

Life Sciences ◽  
1988 ◽  
Vol 43 (5) ◽  
pp. 459-464 ◽  
Author(s):  
S.F. Smith ◽  
A. Guz ◽  
G.H. Burton ◽  
N.T. Cooke ◽  
T.D. Tetley
Keyword(s):  
Lung Lavage ◽  
Elastolytic Activity

scholarly journals Antimigratory Effects of the Methanol Extract fromMomordica charantiaon Human Lung Adenocarcinoma CL1 Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Hsue-Yin Hsu ◽  
Jung-Hsuan Lin ◽  
Chia-Jung Li ◽  
Shih-Fang Tsang ◽  
Chun-Hao Tsai ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Leaf Extract ◽  
Methanol Extract ◽  
Human Lung ◽  
Human Cancer ◽  
Momordica Charantia ◽  
Invasive Ability ◽  
Human Cancer Cells ◽  
Human Lung Adenocarcinoma ◽  
Significant Difference

Momordica charantiahas been found to exhibit anticancer activity, in addition to its well-known therapeutic functions. We have demonstrated that the leaf extract ofMomordica charantia(MCME) induces apoptosis in several human cancer cells through caspase- and mitochondria-dependent pathways. In this study, a different susceptibility to MCME was found in human lung adenocarcinoma CL1 cells with different metastatic ability, leading to the significant difference of cell viability and invasiveness between MCME-treated CL1-0 and CL1-5 cells. MCME was found to upregulate the expression of Wnt-2 and affect the migratory and invasive ability of CL1 cells through suppressed MMP-2 and MMP-9 enzymatic activities. We proposed that MCME mediates inhibition against migration of CL1 cells by reducing the expression and activation of Src and FAK to decrease the expression of downstream Akt,β-catenin, and MMPs.

scholarly journals Comparative Toxic Effects of Manufactured Nanoparticles and Atmospheric Particulate Matter in Human Lung Epithelial Cells

2020 ◽  
Vol 18 (1) ◽  
pp. 22
Author(s):  
Yun Wu ◽  
Mei Wang ◽  
Shaojuan Luo ◽  
Yunfeng Gu ◽  
Dongyang Nie ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Human Lung ◽  
A549 Cells ◽  
Lung Epithelial Cells ◽  
Atmospheric Particulate Matter ◽  
Toxic Effects ◽  
Ros Generation ◽  
Atmospheric Particulate ◽  
Significant Difference ◽  
Lung Epithelial

Although nanoparticles (NPs) have been used as simplified atmospheric particulate matter (PM) models, little experimental evidence is available to support such simulations. In this study, we comparatively assessed the toxic effects of PM and typical NPs (four carbonaceous NPs with different morphologies, metal NPs of Fe, Al, and Ti, as well as SiO2 NPs) on human lung epithelial A549 cells. The EC50 value of PM evaluated by cell viability assay was 148.7 μg/mL, closest to that of SiO2 NPs, between the values of carbonaceous NPs and metal NPs. All particles caused varying degrees of reactive oxygen species (ROS) generation and adenosine triphosphate (ATP) suppression. TiO2 NPs showed similar performance with PM in inducing ROS production (p < 0.05). Small variations between two carbonaceous NPs (graphene oxides and graphenes) and PM were also observed at 50 μg/mL. Similarly, there was no significant difference in ATP inhibition between carbonaceous NPs and PM, while markedly different effects were caused by SiO2 NP and TiO2 NP exposure. Our results indicated that carbonaceous NPs could be served as potential surrogates for urban PM. The identification of PM model may help us further explore the specific roles and mechanisms of various components in PM.

scholarly journals Effect of ageing on plasma lipoprotein(a) levels

2002 ◽  
Vol 39 (3) ◽  
pp. 237-240 ◽  
Author(s):  
Harukuni Akita ◽  
Miyao Matsubara ◽  
Hitoshi Shibuya ◽  
Hirotoshi Fuda ◽  
Hitoshi Chiba
Keyword(s):  
Molecular Weight ◽  
Coronary Heart Disease ◽  
Risk Factor ◽  
Heart Disease ◽  
The Elderly ◽  
Low Molecular Weight ◽  
Lipoprotein A ◽  
Significant Difference ◽  
The Mean ◽  
Japanese Subjects

Background Lipoprotein(a) [Lp(a)] is a risk factor for atherosclerosis and increases with age. The purpose of this study was to determine the effect of ageing on Lp(a) for three different apo(a) phenotypes. Methods We measured plasma Lp(a) concentrations in 551 unrelated Japanese subjects (20-88 years of age). We performed statistical analyses separately for three apo(a) phenotypes: the low-molecular-weight (LMW) phenotype with the F, B or S1 isoform, the intermediate-molecular-weight (IMW) phenotype with the S2 isoform and the high-molecular-weight (HMW) phenotype with the S3 or S4 isoform. Results For each phenotype, the mean plasma Lp(a) concentration and the frequency of Lp(a) concentrations ≥ 250 mg/L increased with age. Further, a statistically significant difference was always found between the younger subjects (20-39 years of age) and the elderly (over 60 years). The frequency of coronary heart disease increased with age, particularly for the LMW and IMW phenotypes. Conclusions We conclude that ageing elevates plasma Lp(a) concentrations, which may have a role in the prevalence of coronary heart disease in the elderly, especially those with the LMW or IMW phenotypes.

Cigarette smoking, emphysema, and damage to alpha 1-proteinase inhibitor

1994 ◽  
Vol 266 (6) ◽  
pp. L593-L611 ◽  
Author(s):  
M. D. Evans ◽  
W. A. Pryor
Keyword(s):  
Cigarette Smoke ◽  
Proteinase Inhibitor ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Tissue Destruction ◽  
Phagocytic Cells ◽  
Lung Fluid

The proteinase-antiproteinase theory for the pathogenesis of emphysema proposes that the connective tissue destruction associated with emphysema arises from excessive proteinase activity in the lower respiratory tract. For this reason, the relative activities of neutrophil elastase and alpha 1-proteinase inhibitor (alpha 1-PI) are considered important. Most emphysema is observed in smokers; therefore, alpha 1-PI has been studied as a target for smoke-induced damage. Damage to alpha 1-PI in lung fluid could occur by several mechanisms involving species delivered to the lung by cigarette smoke and/or stimulated inflammatory cells. Oxidative damage to alpha 1-PI has received particular attention, since both cigarette smoke and inflammatory cells are rich sources of oxidants. In this article we review almost two decades of research on mechanistic studies of damage to alpha 1-PI by cigarette smoke and phagocytic cells in vitro, studies emphasizing the importance of elastinolytic activity in the pathogenesis of emphysema in vivo and studies of human lung lavage fluid to detect defects in alpha 1-PI at the molecular and functional levels.

scholarly journals Inhibition of Plasmin Generation in Plasma By Heparin, Low Molecular Weight Heparin and a Covalent Antithrombin-Heparin Complex (ATH)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4217-4217
Author(s):  
Gabriela Chang ◽  
Helen M. Atkinson ◽  
Leslie R. Berry ◽  
Anthony K.C. Chan
Keyword(s):  
Molecular Weight ◽  
Plasminogen Activator ◽  
Low Molecular Weight Heparin ◽  
Conflicts Of Interest ◽  
Area Under The Curve ◽  
Low Molecular Weight ◽  
Plasminogen Activator Inhibitor 1 ◽  
Significant Difference

Abstract Introduction: Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are widely used anticoagulants for thrombosis treatment. However, these anticoagulants have limitations such as increased bleeding, variable dose response, required frequent monitoring, and, in the case of LMWH, inability to inhibit thrombin. This has led to the development of a covalent complex of antithrombin and heparin (ATH), which has been shown to overcome many of these shortcomings. ATH has faster rates of inhibition of many coagulation factors, is able to inhibit clot-bound thrombin, and is a more effective inhibitor of both venous and arterial thrombosis in animal models. Moreover, in a rabbit thrombosis model, ATH has been shown to decrease clot mass and fibrin accretion, while the contrary was observed for UFH. From these observations, it was suggested that ATH may enhance fibrin breakdown and thus led to investigations into the effects of UFH and ATH on fibrinolysis. In vitro studies have shown that UFH enhances antithrombin inhibition of plasmin. In addition, ATH displays a slightly greater inhibition of plasmin generation and activity. Such studies were conducted in purified systems, in the absence of other plasmin inhibitors naturally present in plasma. Therefore, the aim of the present study was to compare the effects of UFH, LMWH, and ATH on plasmin generation in plasma. Methods: At 37°C tissue plasminogen activator (tPA) and soluble fibrin fragments (fib) were added to normal adult pooled platelet poor plasma supplemented with 0.35, 0.7, 1.4, or 2.1 U anti-Xa/ml UFH, LMWH, or ATH, to initiate plasmin generation (8.93nM tPA and 300µg/ml fib). At various time points, subsamples were mixed with excess plasminogen activator inhibitor 1 (PAI-1) (55.12nM) to stop further plasmin generation. The plasmin concentration at each time point was determined using a plasmin-specific chromogenic substrate and a standard curve produced from purified plasmin. Results: Comparisons of mean area under the curve (AUC) for plasmin generation displayed a significant decrease in plasmin generation in the presence of all three anticoagulants at all doses tested (p<0.05). Comparing the anticoagulants at similar doses, plasmin generation was significantly decreased in the presence of ATH (15384.66±1930.23nM/min) compared to LMWH (23892.28±3090.54nM/min) at 0.7 U/ml (p<0.05). At a dose of 1.4 U/ml, there was significantly less plasmin generated, over time, in the presence of UFH (20089.49±3022.1623nM/min) and ATH (19273.86±1805.7323nM/min) when compared to LMWH (24743.18±1265.1023nM/min) (p<0.05). There was no significant difference in plasmin inhibition between UFH and ATH at any of the doses tested. Conclusion: The present study supports previous findings that UFH and ATH can facilitate antithrombin inhibition of plasmin. It is also observed that LMWH catalyzes the inhibition of plasmin by antithrombin but possibly to a lesser extent. These findings suggest that ATH has a similar inhibitory effect on plasmin generation and activity in plasma compared to UFH, despite its overall superior anticoagulant properties. Therefore, previous in vivo observations displaying decrease in clot mass with administration of ATH was due to its enhanced anticoagulant abilities and not fibrinolysis enhancement. These findings add to our understanding of ATH mechanisms of action and aid in its development for clinical use. Disclosures No relevant conflicts of interest to declare.

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