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https://www.readbyqxmd.com/read/28734581/discovery-of-r-5-benzo-d-1-3-dioxol-5-yl-7-1-vinylsulfonyl-pyrrolidin-2-yl-methyl-7h-pyrrolo-2-3-d-pyrimidin-4-amine-b6-as-a-potent-bmx-inhibitor-for-the-treatment-of-nsclc
#1
Linhong He, Da Li, Chufeng Zhang, Peng Bai, Lijuan Chen
Described as a Btk inhibitor, ibrutinib also potently inhibits Bmx and EGFR, two good targets for lung cancer. Owing to its high CLogP (4.07) and low aqueous solubility (<0.01mg/ml), resulting in unfavorable bioavailability, ibrutinib requires high dosages to achieve good clinical response in the treatment of non-small cell lung cancer (NSCLC). In our effort to improve the CLogP of ibrutinib by structural optimization led to the discovery of a potent anti-cancer agent B6, with beneficial physicochemical parameters (CLogP=2...
July 4, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28732229/a-novel-approach-to-fabricate-dye-encapsulated-polymeric-micro-and-nanoparticles-by-thin-film-dewetting-technique
#2
Manosree Chatterjee, Abhiram Hens, Kuldeep Mahato, Namita Jaiswal, Nivedita Mahato, Nagahanumaiah, Nripen Chanda
A new method is reported for fabrication of polymeric micro- and nanoparticles from an intermediate patterned surface originated by dewetting of a polymeric thin film. Poly (d, l-lactide-co-glycolide) or PLGA, a biocompatible polymer is used to develop a thin film over a clean glass substrate which dewets spontaneously in the micro-/nano-patterned surface of size range 50nm to 3.5µm. Since another water-soluble polymer, poly vinyl alcohol (PVA) is coated on the same glass substrate before PLGA thin film formation, developed micro-/nano-patterns are easily extracted in water in the form of micro- and nanoparticle mixture of size range 50nm to 3...
July 8, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28730738/the-effects-of-aspirated-thickened-water-on-survival-and-pulmonary-injury-in-a-rabbit-model
#3
Nogah Nativ-Zeltzer, Maggie A Kuhn, Denise M Imai, Ryan P Traslavina, Amanda S Domer, Juliana K Litts, Brett Adams, Peter C Belafsky
OBJECTIVES/HYPOTHESIS: Liquid thickeners are one of the most frequently utilized treatment strategies for persons with oropharyngeal swallowing dysfunction. The effect of commercially available thickeners on lung injury is uncertain. The purpose of this study was to compare the effects of aspiration of water alone, xanthan gum (XG)-thickened water, and cornstarch (CS)-thickened water on survival and lung morphology in a rabbit model. STUDY DESIGN: Animal model. Prospective small animal clinical trial...
July 21, 2017: Laryngoscope
https://www.readbyqxmd.com/read/28724041/effect-of-rhubarb-on-extravascular-lung-water-in-patients-with-acute-respiratory-distress-syndrome
#4
Jianxin He, Xiaoshui Si, Mingxia Ji, Jing Huang, Wenjuan Zheng, Jiao Wang, Junfeng Wang, Lijun Zhu
Objective: The aim of this study was to evaluate the effect of rhubarb on extravascular lung water (EVLW) in patients with acute respiratory distress syndrome (ARDS). Method: A total of 80 patients with ARDS were randomly divided into a treatment group (40 cases) and control group (40 cases). Patients in the treatment group received rhubarb (30.0 g/d) and patients in the control group received conventional therapy for seven consecutive days. Extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) were determined using pulse contour cardiac output (PiCCO) technology, and the oxygenation index was measured by blood gas analysis at baseline and on days 3, 5 and 7 after treatment...
May 2017: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/28723410/innovative-pmdi-formulations-of-spray-dried-nanoparticles-for-efficient-pulmonary-drug-delivery
#5
Hao-Ying Li, En-Yu Xu
For drug delivery to the lungs, the aerodynamic size of drug particles plays a predominant role in determining the sites of deposition in the airway, and the particles with the size less than 2 microns are highly expected as they will be preferably delivered to the ideal site of alveolar regions. In this paper, a novel platform technology has been developed, where the water (containing pharmaceutically active agents)-in-oil (w/o) microemulsions were spray-dried to generate nanosized drug particles that were able to be homogeneously dispersed in the propellant to form an exceptionally stable suspensions with no precipitates or flocculates during a long time storage...
July 16, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28722353/auramine-o-an-incense-smoke-ingredient-promotes-lung-cancer-malignancy
#6
Jia-Chen Tung, Wei-Chien Huang, Juan-Cheng Yang, Guan-Yu Chen, Chi-Chen Fan, Yu-Chuan Chien, Pei-Shan Lin, Shih-Chun Candice Lung, Wei-Chao Chang
Burning incense to worship deities is a popular religious ritual in large parts of Asia, and is a popular custom affecting more than 1.5 billion adherents. Due to incomplete combustion, burning incense has been well recognized to generate airborne hazards to human health. However, the correlation between burning incense and lung cancer in epidemiological studies remains controversy. Therefore, we speculated that some unknown materials in incense smoke are involved in the initiation or progression of lung cancer...
July 19, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28716688/influence-of-thoracic-fluid-compartments-on-pulmonary-congestion-in-chronic-heart-failure
#7
Steven C Chase, Bryan J Taylor, Troy J Cross, Kirsten E Coffman, Lyle J Olson, Bruce D Johnson
INTRODUCTION: Pulmonary congestion is a common finding of heart failure (HF), but it remains unclear how pulmonary and heart blood volumes (Vp and Vh) and extravascular lung water (EVLW) change in stable HF and impact lung function. METHODS: Fourteen patients with HF (age: 68±11 y; LVEF: 33±8%) and 12 controls (age: 65±9 y) were recruited. A pulmonary function test, thoracic CT scan, and contrast perfusion scan were performed. From the thoracic scan, a histogram of CT attenuation of lung tissue was generated and skew, kurtosis, and full-width half-max were calculated as surrogates of EVLW...
July 14, 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/28715175/airborne-nanoparticle-release-and-toxicological-risk-from-metal-oxide-coated-textiles-toward-a-multi-scale-safe-by-design-approach
#8
Paride Mantecca, Kaja Kasemets, Archana Deokar, Ilana Perelshtein, Aharon Gedanken, Yeon Kyoung Bahk, Baharh Kianfar, Jing Wang
Nano metal oxides have been proposed as alternatives to Silver (Ag) nanoparticles (NPs) for antibacterial coatings. Here cotton and polyester-cotton fabrics were sonochemically coated with Zinc oxide (ZnO) ZnO and Copper oxide (CuO) CuO NPs. By varying the reaction solvent (water or ethanol), NPs with different sizes and shapes were synthesized. The cytotoxic and pro-inflammatory effects of studied NPs were investigated in vitro in human alveolar epithelial A549 and macrophage-like THP1 cells. To understand the potential respiratory impact of the NPs, the coated textiles were subjected to the abrasion tests and the released airborne particles were measured...
July 17, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28713784/identification-of-novel-and-efficacious-chemical-compounds-that-disturb-influenza-a-virus-entry-in-vitro
#9
Hany Khalil, Tamer El Malah, Ahmed I Abd El Maksoud, Ibrahim El Halfawy, Ahmed A El Rashedy, Mahmoud El Hefnawy
Influenza A virus is a negative RNA stranded virus of the family Orthomyxoviridae, and represents a major public health threat, compounding existing disease conditions. Influenza A virus replicates rapidly within its host and the segmented nature of its genome facilitates re-assortment, whereby whole genes are exchanged between influenza virus subtypes during replication. Antiviral medications are important pharmacological tools in influenza virus prophylaxis and therapy. However, the use of currently available antiviral is impeded by sometimes high levels of resistance in circulating virus strains...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28711016/therapeutic-supermolecular-micelles-of-vitamin-e-succinate-grafted-%C3%AE%C2%B5-polylysine-as-potential-carriers-for-curcumin-enhancing-tumour-penetration-and-improving-therapeutic-effect-on-glioma
#10
He-Lin Xu, Zi-Liang Fan, De-Li ZhuGe, Bi-Xin Shen, Bing-Hui Jin, Jian Xiao, Cui-Tao Lu, Ying-Zheng Zhao
Severe toxicity and poor tumour penetration are two intrinsic limited factors to hinder the broad clinical application for most of first-line chemotherapeutics. In this study, a novel vitamin E succinate-grafted ε-polylysine (VES-g-PLL) polymer was synthesized by using ε-polylysine as backbone. By adjusting VES graft ratio, VES-g-PLL (50) with a theoretic VES graft ratio of 50% could self-assemble into a supermolecular micelle with a hydrodynamic diameter (Dh) of ca.20nm, and Zeta potential of 19.6mV. VES-g-PLL micelles themselves displayed a strong anti-tumour effect on glioma...
July 12, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28710963/2-substituted-3-7-8-trimethylnaphtho-1-2-b-furan-4-5-diones-as-specific-l-shaped-nqo1-mediated-redox-modulators-for-the-treatment-of-non-small-cell-lung-cancer
#11
Xiaojin Zhang, Jinlei Bian, Xiang Li, Xingsen Wu, Yanan Dong, Qidong You
Based on the scaffold of 3,7,8-trimethylnaphtho[1,2-b]furan-4,5-dione, a series of L-shaped derivatives with substituted side chains at the position of C2 were designed by analyzing the binding mode with NQO1. The drug-like compound 6q (named as DDO-7178) emerged as the most specific substrate of the two-electron oxidoreductase NQO1 and could hardly be reduced by one-electron oxidoreductases CPR (NQO1/CPR = 20.8). In addition, compound 6q showed much improved physicochemical properties such as water solubility than the control β-lap...
June 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28710351/combination-therapy-for-tuberculosis-treatment-pulmonary-administration-of-ethionamide-and-booster-co-loaded-nanoparticles
#12
Joana Costa-Gouveia, Elisabetta Pancani, Samuel Jouny, Arnaud Machelart, Vincent Delorme, Giuseppina Salzano, Raffaella Iantomasi, Catherine Piveteau, Christophe J Queval, Ok-Ryul Song, Marion Flipo, Benoit Deprez, Jean-Paul Saint-André, José Hureaux, Laleh Majlessi, Nicolas Willand, Alain Baulard, Priscille Brodin, Ruxandra Gref
Tuberculosis (TB) is a leading infectious cause of death worldwide. The use of ethionamide (ETH), a main second line anti-TB drug, is hampered by its severe side effects. Recently discovered "booster" molecules strongly increase the ETH efficacy, opening new perspectives to improve the current clinical outcome of drug-resistant TB. To investigate the simultaneous delivery of ETH and its booster BDM41906 in the lungs, we co-encapsulated these compounds in biodegradable polymeric nanoparticles (NPs), overcoming the bottlenecks inherent to the strong tendency of ETH to crystallize and the limited water solubility of this Booster...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28708889/a-new-index-for-characterizing-micro-bead-motion-in-a-flow-induced-by-ciliary-beating-part-i-experimental-analysis
#13
Mathieu Bottier, Sylvain Blanchon, Gabriel Pelle, Emilie Bequignon, Daniel Isabey, André Coste, Estelle Escudier, James B Grotberg, Jean-François Papon, Marcel Filoche, Bruno Louis
Mucociliary clearance is one of the major lines of defense of the respiratory system. The mucus layer coating the pulmonary airways is moved along and out of the lung by the activity of motile cilia, thus expelling the particles trapped in it. Here we compare ex vivo measurements of a Newtonian flow induced by cilia beating (using micro-beads as tracers) and a mathematical model of this fluid flow, presented in greater detail in a second companion article. Samples of nasal epithelial cells placed in water are recorded by high-speed video-microscopy and ciliary beat pattern is inferred...
July 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28704725/simultaneous-estimation-of-lisofylline-and-pentoxifylline-in-rat-plasma-by-high-performance-liquid-chromatography-photodiode-array-detector-and-its-application-to-pharmacokinetics-in-rat
#14
Kishan S Italiya, Saurabh Sharma, Ishit Kothari, Deepak Chitkara, Anupama Mittal
Lisofylline (LSF) is an anti-inflammatory and immunomodulatory agent with proven activity in serious infections associated with cancer chemotherapy, hyperoxia-induced acute lung injury, autoimmune disorders including type-1 diabetes (T1DM) and islet rejection after islet transplantation. It is also an active metabolite of another anti-inflammatory agent, Pentoxifylline (PTX). LSF bears immense therapeutic potential in multiple pharmacological activities and hence appropriate and accurate quantification of LSF is very important...
June 29, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28701059/brucea-javanica-oil-emulsion-alleviates-cachexia-induced-by-lewis-lung-cancer-cells-in-mice
#15
Chao Chen, Binbin Wang
This study was conducted to evaluate the efficacy and possible mechanism of Brucea javanica oil emulsion (BJOE) on cachexia, by observing changes in related indexes in mice with cachexia and identifying the genes responsible based on gene chip analysis. In the BJOE treatment group, body weight loss, tumor growth and metastasis were found obviously inhibited, food and water intake had markedly increased, and survival time was significantly prolonged, as compared to the control group. Moreover, the BJOE witnessed improvement in body weight, prevention of tumor metastasis and overall increase in survival time, as compared to Indometacin (IND, the positive control medicine)...
July 13, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28696235/evaluation-of-combination-drug-therapy-for-treatment-of-antibiotic-resistant-inhalation-anthrax-in-a-murine-model
#16
H S Heine, S V Shadomy, A E Boyer, L Chuvala, R Riggins, A Kesterson, J Myrick, J Craig, M G Candela, J R Barr, K Hendricks, W A Bower, H Walke, G L Drusano
Bacillus anthracis is considered a likely agent to be used as a bioweapon and use of a strain resistance to the first-line antimicrobial treatments is a concern. We determined treatment efficacy against a ciprofloxacin-resistant (C(r)) strain of B. anthracis (C(r) Ames) in a murine inhalational anthrax model. Ten groups of 46 BALB/c mice were exposed by inhalation to 7-35 LD50 of B. anthracis C(r) Ames spores. Commencing at 36 hours (h) post-exposure, groups were administered intraperitoneal doses of sterile water for injections (SWI) and ciprofloxacinalone (control groups), or ciprofloxacin combined with two antimicrobials including meropenem/linezolid, meropenem/clindamycin, meropenem/rifampin, meropenem/doxycycline, penicillin/linezolid, penicillin/doxycycline, rifampin/linezolid, or rifampin/clindamycin at appropriate dosing intervals(6 or 12 hours) for the respective antibiotics...
July 10, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28694749/variability-of-antioxidant-and-biological-activities-of-rhus-tripartitum-related-to-phenolic-compounds
#17
Hanène Ben Miled, Mariem Saada, Ines Jallali, Zaineb Ben Barka, Mounira Tlili, Hichem Alimi, Mohsen Sakly, Khémais Ben Rhouma, Manef Abderrabba, Hafedh Abdelmelek, Olfa Tebourbi, Riadh Ksouri
Rhus species are known in traditional medicine for their therapeutic virtue and their extracts showed numerous important properties including antimalarial, antimicrobial, antiviral, and hypoglycemic and anticonvulsant activities. Rhus tripartitum (Ucria) is a medicinal plant widely used in Tunisia folk medicine against chronic diarrhea and gastric ulcer. This study was designed to examine in vitro and ex vivo antioxidant, anti-inflammatory and anticancer activities of four extracts of Rhus tripartitum root cortex with increasing solvent polarity (hexane, dichloromethane, methanol and water)...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28694251/advances-in-the-causes-and-management-of-community-acquired-pneumonia-in-adults
#18
REVIEW
Richard G Wunderink, Grant Waterer
Community acquired pneumonia remains a common cause of morbidity and mortality. Usually, the causal organism is not identified and treatment remains empiric. Recent computed tomography and magnetic resonance imaging studies have challenged the accuracy of the clinical diagnosis of pneumonia, and epidemiologic studies are changing our perspective of what causes community acquired pneumonia, especially the role of viral pathogens and the frequent finding of multiple pathogens. The past decade has seen increasing overuse of empiric coverage of meticillin resistant Staphylococcus aureus and antibiotic resistant Gram negative pathogens owing to inappropriate application of guidelines for healthcare associated pneumonia...
July 10, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28690287/stroke-volume-variation-svv-and-pulse-pressure-variation-ppv-as-indicators-of-fluid-responsiveness-in-sevoflurane-anesthetized-mechanically-ventilated-euvolemic-dogs
#19
Yusuke Endo, Jun Tamura, Tomohito Ishizuka, Takaharu Itami, Kiwamu Hanazono, Kenjiro Miyoshi, Tadashi Sano, Kazuto Yamashita, William W Muir
Changes in stroke volume variation (SVV) and pulse pressure variation (PPV) in response to fluid infusion were experimentally evaluated during vecuronium infusion and sevoflurane anesthesia in 5 adult, mechanically ventilated, euvolemic, beagle dogs. Sequential increases in central venous pressure (CVP; 3-7[baseline], 8-12, 13-17, 18-22 and 23-27 mmHg) were produced by infusing lactated Ringer's solution and 6% hydroxyethyl starch solution. Heart rate (beats/min), right atrial pressure (RAP, mmHg), pulmonary arterial pressure (PAP, mmHg), pulmonary capillary wedge pressure (PCWP, mmHg), transpulmonary thermodilution cardiac output (TPTDCO, L/min), stroke volume (SV, ml/beat), arterial blood pressure (ABP, mmHg), extravascular lung water (EVLW, ml), pulmonary vascular permeability index (PVPI, calculated), SVV (%), PPV (%) and systemic vascular resistance (SVR, dynes/sec/cm(5)) were determined at each predetermined CVP range...
July 10, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28687744/ccm111-the-water-extract-of-antrodia-cinnamomea-regulates-immune-related-activity-through-stat3-and-nf-%C3%AE%C2%BAb-pathways
#20
In-Yu Lin, Min-Hsiung Pan, Ching-Shu Lai, Ting-Ting Lin, Chiung-Tong Chen, Tao-Sheng Chung, Chien-Lung Chen, Chen-Huan Lin, Wu-Chang Chuang, Ming-Chung Lee, Ching-Che Lin, Nianhan Ma
Antrodia cinnamomea (AC) exhibits many bioactivities, including anti-inflammatory, anti-cancer, and hepatoprotection activities. Many researchers have studied the functions of the components or fractions of AC, but the functions of the original extractions of AC have not been studied. In addition, the detailed relationship between AC and immune-related signaling pathways is unclear. In this study, we screened the effects of CCM111, which is the extract of AC, on seven immune-related signaling pathways and further investigated whether CCM111 can influence inflammation...
July 7, 2017: Scientific Reports
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