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https://www.readbyqxmd.com/read/28920154/pharmacokinetics-of-doripenem-in-plasma-and-epithelial-lining-fluid-elf-comparison-of-two-dosage-regimens
#1
Zoe Oesterreicher, Iris Minichmayr, Robert Sauermann, Daniela Marhofer, Edith Lackner, Walter Jäger, Alexandra Maier-Salamon, Richard Schwameis, Charlotte Kloft, Markus Zeitlinger
PURPOSE: In 2014, FDA released a warning for prescription of doripenem for ventilator-associated bacterial pneumonia due to unsatisfactory clinical cure rates. The present study explores if the observed lack of efficacy might be explained by insufficient target site pharmacokinetics in intensive care patients after two different infusion schemes. METHODS: Plasma and bronchoalveolar lavage sampling was performed in 16 intubated patients with pneumonia receiving doripenem either as 1-h or as 4-h infusion...
September 17, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28890202/dexamethasone-palmitate-large-porous-particles-a-controlled-release-formulation-for-lung-delivery-of-corticosteroids
#2
Alain N'Guessan, Elias Fattal, David Chapron, Claire Gueutin, Armand Koffi, Nicolas Tsapis
We have optimized a formulation of a prodrug of dexamethasone (DXM), dexamethasone palmitate (DXP) for pulmonary delivery as a dry powder. Formulations were prepared by spray drying DXP with 1,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine (DPPC) and Hyaluronic Acid (HA) as excipients. Large porous particles around 13 μm were produced with a tap density of 0.05g/cm(3) and a Fine particle fraction around 40%. The palmitate moiety favors DXP insertion into DPPC bilayers therefore limiting its in vitro release as shown by differential scanning calorimetry...
September 7, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28855579/expression-of-il-33-in-ocular-surface-epithelium-induces-atopic-keratoconjunctivitis-with-activation-of-group-2-innate-lymphoid-cells-in-mice
#3
Yasutomo Imai, Yuka Hosotani, Hiroto Ishikawa, Koubun Yasuda, Makoto Nagai, Orie Jitsukawa, Fumi Gomi, Kenji Nakanishi, Tomohiro Yoshimoto, Takahiro Nakamura, Kiyofumi Yamanishi
In a transgenic mouse line hK14mIL33tg, with the expression of interleukin-33 (IL-33) driven by a keratin 14 promoter, keratoconjunctivitis developed spontaneously between 18 and 22 weeks of age under specific-pathogen-free conditions. These mice showed blepharitis and corneal impairments, and the histology revealed epithelial thickening in the conjunctiva and the cornea with infiltration of eosinophils, mast cells and basophils. IL-5, IL-13 and CCL11 were abundant in lacrimal fluid in the mice, and the gene expressions of IL-4, IL-5, IL-13, IL-33, Prg2 and Mmcp8 were significantly increased in the cornea...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28855375/shear-stress-induces-non-canonical-autophagic-flux-in-intestinal-epithelial-monolayers
#4
Sun Wook Kim, Jonathan Ehrman, Mok-Ryeon Ahn, Jumpei Kondo, Andrea A Mancheno Lopez, Yun Sik Oh, Hanjune X Kim, Scott W Crawley, James R Goldenring, Matthew J Tyska, Erin C Rericha, Ken S Lau
Flow of fluids through the gut, such as milk from a neonatal diet, generates a shear stress on the unilaminar epithelium lining the lumen.  We report that exposure to physiological levels of fluid shear stress leads to the formation of large vacuoles, containing extracellular content, within polarizing intestinal epithelial cell monolayers.  These observations lead to two questions: how can cells lacking primary cilia transduce shear stress, and what molecular pathways support the formation of vacuoles that can exceed 80% of the cell volume...
August 30, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28853638/self-assembled-nanoparticles-made-from-a-new-pegylated-poly-aspartic-acid-graft-copolymer-for-intravaginal-delivery-of-poorly-water-soluble-drugs
#5
Seungil Kim, Yannick Leandre Traore, Jae Sang Lee, Ji-Heung Kim, Emmanuel A Ho, Song Liu
New amphiphilic PEGylated poly(aspartic acid) graft copolymer (PASP-PEG-Ph) was synthesized as a nanocarrier for intravaginal drug delivery of poorly water-soluble drugs. PASP-PEG-Ph self-assembled in pH 4.5 and pH 7.0 vaginal fluid simulants (VFSs) to negatively-charged spherically-shaped nanoparticles with a diameter of approximately 200 nm as evidenced by Zeta-potentiometer, scanning electron microscope (SEM), dynamic light scattering (DLS) analysis. A significant number of stable NPs could be maintained at pH 4...
August 30, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28839105/alcohol-abuse-is-associated-with-enhanced-pulmonary-and-systemic-xanthine-oxidoreductase-activity
#6
Mehdi A Fini, Jeanette Gaydos, Alicia McNally, Vijaya Karoor, Ellen L Burnham
The acute respiratory distress syndrome (ARDS) is a common and devastating disorder. Alcohol use disorders (AUDs) increase ARDS risk, and worsen outcomes, through mechanisms that may include enhancing pulmonary oxidative stress. Alcohol consumption increases activity of the enzyme xanthine oxidoreductase (XOR) that contributes to production of both reactive oxygen species (ROS) and uric acid, a damage-associated molecular pattern. These by-products have the potential to modulate pro-inflammatory pathways such as those involving cyclooxygenase (COX)-2, and to activate the nucleotide-binding domain, leucine-rich-containing family, pyrin-domain containing-3 (NLRP3) inflammasome...
August 24, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28814497/extracellular-acid-base-balance-and-ion-transport-between-body-fluid-compartments
#7
REVIEW
Julian L Seifter, Hsin-Yun Chang
Clinical assessment of acid-base disorders depends on measurements made in the blood, part of the extracellular compartment. Yet much of the metabolic importance of these disorders concerns intracellular events. Intracellular and interstitial compartment acid-base balance is complex and heterogeneous. This review considers the determinants of the extracellular fluid pH related to the ion transport processes at the interface of cells and the interstitial fluid, and between epithelial cells lining the transcellular contents of the gastrointestinal and urinary tracts that open to the external environment...
September 2017: Physiology
https://www.readbyqxmd.com/read/28807905/pulmonary-pharmacokinetics-of-colistin-following-administration-of-dry-powder-aerosols-in-rats
#8
Yu-Wei Lin, Qi Tony Zhou, Yang Hu, Nikolas J Onufrak, Siping Sun, Jiping Wang, Alan Forrest, Hak-Kim Chan, Jian Li
Colistin has been administered via nebulization for the treatment of respiratory tract infections. Recently, dry powder inhalation (DPI) has attracted increasing attention. The current study aimed to investigate the pharmacokinetics (PK) of colistin in epithelial lining fluid (ELF) and plasma following DPI and intravenous (IV) administration in healthy Sprague-Dawley rats. Rats were given colistin as DPI intratracheally (0.66 and 1.32 mg base/kg) or IV injection (0.66 mg base/kg). Histopathological examination of lung tissue was performed at 24 h...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28775098/influenza-virus-infection-alters-ion-channel-function-of-airway-and-alveolar-cells-mechanisms-and-physiological-sequelae
#9
James D Londino, Ahmed Lazrak, James F Collawn, Zsuzsanna Bebok, Kevin S Harrod, Sadis Matalon
The cystic fibrosis transmembrane conductance regulator (CFTR) and the amiloride-sensitive epithelial sodium channels (ENaC) are located in the apical membranes of airway and alveolar epithelial cells. These transporters play an important role in the regulation of lung fluid balance across airway and alveolar epithelia by being the conduits for chloride (Cl(-)) and bicarbonate (HCO3(-)) secretion and sodium (Na(+)) ion absorption, respectively. The functional role of these channels in the respiratory tract is to maintain the optimum volume and ionic composition of the bronchial pericilary fluid (PCL) and alveolar lining fluid (ALF) layers...
August 3, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28759204/variation-in-extracellular-detoxification-is-a-link-to-different-carcinogenicity-among-chromates-in-rodent-and-human-lungs
#10
Casey Krawic, Michal W Luczak, Anatoly Zhitkovich
Inhalation of soluble chromium(VI) is firmly linked with higher risks of lung cancer in humans. However, comparative studies in rats have found a high lung tumorigenicity for moderately soluble chromates but no tumors for highly soluble chromates. These major species differences remain unexplained. We investigated the impact of extracellular reducers on responses of human and rat lung epithelial cells to different Cr(VI) forms. Extracellular reduction of Cr(VI) is a detoxification process, and rat and human lung lining fluids contain different concentrations of ascorbate and glutathione...
September 18, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28758820/antibacterial-activity-of-human-simulated-epithelial-lining-fluid-concentrations-of-amikacin-inhale-alone-and-in-combination-with-meropenem-against-acinetobacter-baumannii
#11
Islam M Ghazi, Mordechai Grupper, David P Nicolau
BACKGROUND: Acinetobacter baumannii(ACBN) is a MDR organism causing pneumonia in ventilated patients. High MICs often result in insufficient lung exposures, thus poor outcomes have been observed with parenteral antimicrobials. Amikacin Inhale(AMK-I), is a drug-device combination of amikacin and a Pulmonary Drug Delivery System device. We aimed to describe the pharmacodynamic profile of human simulated epithelial lining fluid(ELF) exposures of AMK-I and intravenous meropenem alone and in combination against ACBN with variable susceptibility profiles...
July 31, 2017: Infectious Diseases
https://www.readbyqxmd.com/read/28753407/il-29-enhances-cxcl10-production-in-tnf-%C3%AE-stimulated-human-oral-epithelial-cells
#12
Yoshitaka Hosokawa, Ikuko Hosokawa, Satoru Shindo, Kazumi Ozaki, Takashi Matsuo
Interleukin-29 (IL-29) is a cytokine belonging to the Type III interferon family. It was recently detected in the gingival crevicular fluid of periodontitis patients. However, the role of IL-29 in the pathogenesis of periodontal disease remains unknown. The aim of this study was to examine the effects of IL-29 on C-X-C motif chemokine ligand 10 (CXCL10) production in human oral epithelial cells. We measured CXCL10 production in TR146 cells, which is a human oral epithelial cell line, using an enzyme-linked immunosorbent assay...
August 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28743822/bronchial-microdialysis-monitoring-of-inflammatory-response-in-open-abdominal-aortic-aneurysm-repair-an-observational-study
#13
Stig S Tyvold, Torbjørn Dahl, Stein Dragsund, Sigurd Gunnes, Oddveig Lyng, Jan K Damås, Petter Aadahl, Erik Solligård
Aortic surgery results in ischemia-reperfusion injury that induces an inflammatory response and frequent complications. The magnitude of the inflammatory response in blood and bronchi may be associated with the risk of immediate complications. The purpose of the study was to evaluate bronchial microdialysis as a continuous monitoring of cytokines in bronchial epithelial lining fluid (ELF) and to determine whether bronchial ELF cytokine levels reflect the ischemia-reperfusion injury and risk for complications during open abdominal aortic aneurysm (AAA) repair...
July 2017: Physiological Reports
https://www.readbyqxmd.com/read/28735671/choroid-plexus-cyst-in-a-neonatal-burmeister-s-porpoise-phocoena-spinipinnis
#14
J Díaz-Delgado, K R Groch, M W Wiegand, E R Secchi, R Réssio, F C C Natália, J L Catão-Dias
Neuroectodermal developmental anomalies are reported rarely in cetaceans and central nervous system cysts are not described. We describe the gross, microscopical, histochemical and immunohistochemical features of a neuraxial myelencephalic cyst in a stranded neonatal Burmeister's porpoise (Phocoena spinipinnis). Grossly, a subdural, extra-axial, well-demarcated, yellow fluid-filled cystic structure (1.9 × 1.6 × 1 cm) expanded the left foramen of Luschka, the left caudolateral cerebellar recess and the left cranioventral myelencephalon...
July 2017: Journal of Comparative Pathology
https://www.readbyqxmd.com/read/28732179/kgf-enhances-oral-epithelial-adhesion-and-rete-peg-elongation-via-integrins
#15
G L Sa, X P Xiong, J G Ren, J Y Wang, H F Xia, Z K Liu, S G He, Y F Zhao
Oral epithelial adhesion to the lamina propria underlies the physiologic function of the oral mucosa and contributes to resisting bacterial invasion, preventing body fluid loss, and maintaining routine chewing; thus, understanding the factors that positively influence oral epithelial adhesion is a research topic of great interest. Rete pegs contribute to oral epithelial adhesion by enlarging the contact areas, whereas integrins are the major molecules that mediate epithelial cell adhesion to the basement membrane...
July 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28729052/tedizolid-inhibits-muc5ac-production-induced-by-methicillin-resistant-staphylococcus-aureus-in-human-airway-epithelial-cells
#16
Kazuaki Takeda, Norihito Kaku, Yoshitomo Morinaga, Kosuke Kosai, Naoki Uno, Yoshifumi Imamura, Hiroo Hasegawa, Taiga Miyazaki, Koichi Izumikawa, Hiroshi Mukae, Katsunori Yanagihara
The innate immune system plays an important role in early immunity against respiratory tract infection. Although airway epithelial cells produce mucus to eliminate pathogens and irritants, hypersecretion of mucus is harmful for the host as it may cause airway obstruction and inhibit influx of antimicrobial agents. It has been reported that several antimicrobial agents have an immunomodulatory effect in vitro and in vivo, but little is known about whether tedizolid, a novel oxazolidinone, can modulate immune responses...
September 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28724639/production-of-reactive-persulfide-species-in-chronic-obstructive-pulmonary-disease
#17
Tadahisa Numakura, Hisatoshi Sugiura, Takaaki Akaike, Tomoaki Ida, Shigemoto Fujii, Akira Koarai, Mitsuhiro Yamada, Katsuhiro Onodera, Yuichiro Hashimoto, Rie Tanaka, Kei Sato, Yutaka Shishikura, Taizou Hirano, Satoru Yanagisawa, Naoya Fujino, Tatsuma Okazaki, Tsutomu Tamada, Yasushi Hoshikawa, Yoshinori Okada, Masakazu Ichinose
BACKGROUND: Oxidative stress is a major aetiological factor driving chronic obstructive pulmonary disease (COPD). Recently recognised as potent antioxidants, reactive persulfide and polysulfide species are biosynthesised by cystathionine β-synthase and cystathionine γ-lyase. The production of reactive persulfide and polysulfide species in the lungs of patients with COPD remain unknown. OBJECTIVES: The aim of this study was to examine the production of reactive persulfides and polysulfides, such as glutathione persulfide (GSSH), cysteine persulfide (CysSSH) and glutathione trisulfide (GSSSH), in lung-resident cells and epithelial lining fluid (ELF) obtained from patients with mild to moderate COPD...
July 19, 2017: Thorax
https://www.readbyqxmd.com/read/28716705/pathobiology-of-biliary-epithelia
#18
REVIEW
Angela C Cheung, Maria J Lorenzo Pisarello, Nicholas F LaRusso
Cholangiocytes are epithelial cells that line the intra- and extrahepatic biliary tree. They serve predominantly to mediate the content of luminal biliary fluid, which is controlled via numerous signaling pathways influenced by endogenous (e.g., bile acids, nucleotides, hormones, neurotransmitters) and exogenous (e.g., microbes/microbial products, drugs etc.) molecules. When injured, cholangiocytes undergo apoptosis/lysis, repair and proliferation. They also become senescent, a form of cell cycle arrest, which may prevent propagation of injury and/or malignant transformation...
July 15, 2017: Biochimica et Biophysica Acta
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
#19
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/28708417/association-of-antibiotics-airway-microbiome-and-inflammation-in-infants-with-cystic-fibrosis
#20
Jessica E Pittman, Kristine M Wylie, Kathryn Akers, Gregory A Storch, Joseph Hatch, Jane Quante, Katherine B Frayman, Nadeene Clarke, Miriam Davis, Stephen M Stick, Graham L Hall, Gregory Montgomery, Sarath Ranganathan, Stephanie D Davis, Thomas W Ferkol
RATIONALE: The underlying defect in the cystic fibrosis (CF) airway leads to defective mucociliary clearance and impaired bacterial killing, resulting in endobronchial infection and inflammation that contributes to progressive lung disease. Little is known about the respiratory microbiota in the early CF airway and its relationship to inflammation. OBJECTIVES: To examine the bacterial microbiota and inflammatory profiles in bronchoalveolar lavage fluid and oropharyngeal secretions in infants with CF...
July 14, 2017: Annals of the American Thoracic Society
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