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Lung microdialysis

Wenjing Zhang, Sihui Wan, Lizhi Chen, Xuebing Wang, Zhuo Wang, Yi Huang
A new method for the analysis of cycloserine (4-amino-3-isoxazolidinone, CYC) in rat microdialysis samples has been developed. This method consists of derivatizing the CYC with benzoyl chloride, which transforms primary amines into highly stable derivatives. An attractive feature of this method was that the derivatization reaction is straightforward and can be completed within 10 min. The formed derivative, in contrast to the non-derivatized analyte, exhibited increased chromatographic retention and decreased matrix effects resulting from the co-elution of other components using reversed-phase liquid chromatography and on-line switching...
January 4, 2018: Biomedical Chromatography: BMC
M Tobias Heinrichs, Sergo Vashakidze, Ketino Nikolaishvili, Irina Sabulua, Nestani Tukvadze, Nino Bablishvili, Shota Gogishvili, Brent P Little, Adam Bernheim, Jeannette Guarner, Charles A Peloquin, Henry M Blumberg, Hartmut Derendorf, Russell R Kempker
Background: Moxifloxacin is a second-line anti-TB drug that is useful in the treatment of drug-resistant TB. However, little is known about its target site pharmacokinetics. Lower drug concentrations at the infection site (i.e. in severe lung lesions including cavitary lesions) may lead to development and amplification of drug resistance. Improved knowledge regarding tissue penetration of anti-TB drugs will help guide drug development and optimize drug dosing. Methods: Patients with culture-confirmed drug-resistant pulmonary TB scheduled to undergo adjunctive surgical lung resection were enrolled in Tbilisi, Georgia...
February 1, 2018: Journal of Antimicrobial Chemotherapy
Keith A Rodvold, William W Hope, Sara E Boyd
Bronchoalveolar lavage (BAL) and microdialysis have become the most reliable and relevant methods for measuring lung concentrations of antibiotics, with the majority of BAL studies involving either healthy adult subjects or patients undergoing diagnostic bronchoscopy. Emphasis on the amount of drug that reaches the site of infection is increasingly recognized as necessary to determine whether a dose selection will translate to good clinical outcomes in the treatment of patients with pneumonia. Observed concentrations and/or parameters of exposure (e...
October 2017: Current Opinion in Pharmacology
Bruna G S Torres, Victória E Helfer, Priscila M Bernardes, Alexandre José Macedo, Elisabet I Nielsen, Lena E Friberg, Teresa Dalla Costa
Biofilm formation plays an important role in the persistence of pulmonary infections, for example, in cystic fibrosis patients. So far, little is known about the antimicrobial lung disposition in biofilm-associated pneumonia. This study aimed to evaluate, by microdialysis, ciprofloxacin (CIP) penetration into the lungs of healthy and Pseudomonas aeruginosa biofilm-infected rats and to develop a comprehensive model to describe the CIP disposition under both conditions. P. aeruginosa was immobilized into alginate beads and intratracheally inoculated 14 days before CIP administration (20 mg/kg of body weight)...
July 2017: Antimicrobial Agents and Chemotherapy
Russell R Kempker, M Tobias Heinrichs, Ketino Nikolaishvili, Irina Sabulua, Nino Bablishvili, Shota Gogishvili, Zaza Avaliani, Nestani Tukvadze, Brent Little, Adam Bernheim, Timothy D Read, Jeannette Guarner, Hartmut Derendorf, Charles A Peloquin, Henry M Blumberg, Sergo Vashakidze
Improved knowledge regarding the tissue penetration of antituberculosis drugs may help optimize drug management. Patients with drug-resistant pulmonary tuberculosis undergoing adjunctive surgery were enrolled. Serial serum samples were collected, and microdialysis was performed using ex vivo lung tissue to measure pyrazinamide concentrations. Among 10 patients, the median pyrazinamide dose was 24.7 mg/kg of body weight. Imaging revealed predominant lung lesions as cavitary (n = 6 patients), mass-like (n = 3 patients), or consolidative (n = 1 patient)...
June 2017: Antimicrobial Agents and Chemotherapy
B Yang, J D Gao, X Y Cao, Q Y Wang, G Z Sun, J J Yang
For most bacterial lung infections, the concentration of unbound antimicrobial agent in lung interstitial fluid has been considered as the gold standard for estimating the antibacterial efficacy. In this study, the pharmacokinetics of florfenicol (FF) in porcine lung interstitial fluid was investigated after single intramuscular administration at two different doses (20 and 50 mg/kg). Twelve pigs underwent thoracotomy under general anesthesia. Then, the CMA/30 probe was implanted into the lung and perfused at 1 μL/min...
January 19, 2017: Journal of Veterinary Pharmacology and Therapeutics
Paulo Kofuji, Ludovic S Mure, Logan J Massman, Nicole Purrier, Satchidananda Panda, William C Engeland
Light is a powerful entrainer of circadian clocks in almost all eukaryotic organisms promoting synchronization of internal circadian rhythms with external environmental light-dark (LD) cycles. In mammals, the circadian system is organized in a hierarchical manner, in which a central pacemaker in the suprachiasmatic nucleus (SCN) synchronizes oscillators in peripheral tissues. Recent evidence demonstrates that photoentrainment of the SCN proceeds via signaling from a subpopulation of retinal ganglion cells (RGCs) which are melanopsin-expressing and intrinsically photosensitive (ipRGCs)...
2016: PloS One
P M Bernardi, F Barreto, T Dalla Costa
A bioanalytical LC-MS/MS method was developed and validated to determine tobramycin in plasma and lung microdialysate samples. Tobramycin was separated using a C18 column and a mobile phase consisting of water and acetonitrile, both with 10mM of heptafluorobutyric acid, eluted as gradient. Apramycin was used as internal standard (IS) for plasma samples. Drugs were monitored using electrospray ionization operating on positive mode (ESI+) monitoring the transitions 468.2>163.3 m/z for tobramycin and 540.3>217...
February 5, 2017: Journal of Pharmaceutical and Biomedical Analysis
Estevan Sonego Zimmermann, João Victor Laureano, Camila Neris Dos Santos, Stephan Schmidt, Chakradhar V Lagishetty, Whocely Victor de Castro, Teresa Dalla Costa
Levofloxacin (LEV) is a broad-spectrum fluoroquinolone used to treat pneumonia, urinary tract infections, chronic bacterial bronchitis, and prostatitis. Efflux transporters, primarily P-glycoprotein (P-gp), are involved in LEV's tissue penetration. In the present work, LEV free lung and prostate interstitial space fluid (ISF) concentrations were evaluated by microdialysis in Wistar rats after intravenous (i.v.) and intratracheal (i.t.) administration (7 mg/kg of body weight) with and without coadministration of the P-gp inhibitor tariquidar (TAR; 15 mg/kg administered i...
February 2016: Antimicrobial Agents and Chemotherapy
Stephen W Davies, Kenji L Leonard, Randall K Falls, Ronald P Mageau, Jimmy T Efird, Joseph P Hollowell, Wayne E Trainor, Hilal A Kanaan, Robert C Hickner, Robert G Sawyer, Nathaniel R Poulin, Brett H Waibel, Eric A Toschlog
BACKGROUND: Concomitant lung/brain traumatic injury results in significant morbidity and mortality. Lung protective ventilation (Acute Respiratory Distress Syndrome Network [ARDSNet]) has become the standard for managing adult respiratory distress syndrome; however, the resulting permissive hypercapnea may compound traumatic brain injury. Airway pressure release ventilation (APRV) offers an alternative strategy for the management of this patient population. APRV was hypothesized to retard the progression of acute lung/brain injury to a degree greater than ARDSNet in a swine model...
February 2015: Journal of Trauma and Acute Care Surgery
Rong Li, Meiping Ren, Ni Chen, Mao Luo, Xin Deng, Jiyi Xia, Guang Yu, Jinbo Liu, Bing He, Xu Zhang, Zhuo Zhang, Xiao Zhang, Bing Ran, Jianbo Wu
BACKGROUND: Platelets play a fundamental role in maintaining hemostasis and have been shown to participate in hematogenous dissemination of tumor cells. Abundant platelets were detected in the tumor microenvironment outside of the blood vessel, thus, platelet -tumor cell interaction outside of the bloodstream may play a role in regulating primary tumor growth and metastasis initiation. However, it is unclear that platelet depletion affects tumor vessel structure and dynamics. METHODS: Using thrombocytopenia induction in two different tumor-bearing mouse models, tumor tissues were performed by Westernblotting and immunohistochemical staining...
March 10, 2014: BMC Cancer
Yan Zhou, Huimin Wang, Hua Zhong
BACKGROUND AND OBJECTIVE: The survival rate of lung cancer is low, thus new methods for treating this form of cancer must be explored. This study applies immune therapy with metronomic chemotherapy to observe the effect of combined therapy on suppressing tumor. METHODS: Mice were inoculated with Lewis lung carcinoma cells. Different treatments, namely, saline, metronomic chemotherapy, dendritic cell (DC) vaccine, and metronomic chemotherapy with DC vaccine were administered to corresponding mice groups...
September 2013: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
D Hutschala, K Skhirtladze, C Kinstner, M Zeitlinger, W Wisser, W Jaeger, M Hoeferl, M Müller, E Tschernko
The use of cardiopulmonary bypass (CPB) during cardiac surgery causes regional ventilation-perfusion mismatch, contributing to regional disturbances in antibiotic penetration into lung tissue. Ventilation-perfusion mismatch is associated with postoperative pneumonia, a frequent and devastating complication after cardiac surgery. In this prospective clinical animal study, we performed in vivo microdialysis to determine the effect of CPB on regional penetration of levofloxacin (LVX) into lung tissue. Six pigs underwent surgery with CPB (CPB group), and another six pigs underwent surgery without CPB (off-pump coronary artery bypass grafting; OPCAB group)...
July 2013: Antimicrobial Agents and Chemotherapy
Claire Dahyot-Fizelier, Denis Frasca, Nicolas Grégoire, Christophe Adier, Olivier Mimoz, Bertrand Debaene, William Couet, Sandrine Marchand
Central nervous system (CNS) antibiotic distribution was described mainly from cerebrospinal fluid data, and only few data exist on brain extracellular fluid concentrations. The aim of this study was to describe brain distribution of cefotaxime (2 g/8 h) by microdialysis in patients with acute brain injury who were treated for a lung infection. Microdialysis probes were inserted into healthy brain tissue of five critical care patients. Plasma and unbound brain concentrations were determined at steady state by high-performance liquid chromatography...
June 2013: Antimicrobial Agents and Chemotherapy
Bibiana Verlindo de Araújo, João Victor Laureano, Lauren Dockhorn Grünspan, Teresa Dalla Costa, Leandro Tasso
A liquid chromatography method has been established for the reliable determination of unbound gemifloxacin concentrations in kidney, lung and liver microdialysates of rats. Microdialysis probes were inserted into tissues of rats, and then dialysates were collected at regular time intervals after intravenous administration of gemifloxacin (40 mg kg(-1)). A pilot study was performed to assess gemifloxacin penetration in lung, kidney and liver of rats. Gemifloxacin was separated on a C(18) column eluted using triethylamine solution (0...
March 1, 2013: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Xiaoying Cao, Jianning Geng, Suwen Su, Linan Zhang, Qian Xu, Li Zhang, Yinghua Xie, Shaomei Wu, Yongjun Sun, Zibin Gao
A novel drug delivery system of doxorubicin (DOX)-loaded Zein in situ gel for interstitial chemotherapy was investigated in this study. The possible mechanisms of drug release were described according to morphological analysis by optical microscopy and scanning electronic microscope (SEM). In vitro and in vivo anti-tumor activity studies showed that DOX-loaded Zein in situ gel was superior to DOX solution. Local pharmacokinetics in tumor tissue was studied by quantitative analysis with confocal laser scanning microscopy (CLSM) combined with microdialysis technology...
2012: Chemical & Pharmaceutical Bulletin
Wen-shiann Wu, Ming-ting Chou, Chien-ming Chao, Chen-kuei Chang, Mao-tsun Lin, Ching-ping Chang
AIM: To assess the therapeutic effect of melatonin on heat-induced acute lung inflammation and injury in rats. METHODS: Heatstroke was induced by exposing anesthetized rats to heat stress (36 °C, 100 min). Rats were treated with vehicle or melatonin (0.2, 1, 5 mg/kg) by intravenous administration 100 min after the initiatioin of heatstroke and were allowed to recover at room temperature (26 °C). The acute lung injury was quantified by morphological examination and by determination of the volume of pleural exudates, the number of polymorphonuclear (PMN) cells, and the myeloperoxidase (MPO) activity...
June 2012: Acta Pharmacologica Sinica
E Rostami, M Bondi
PURPOSE: The aim of this study is to investigate the effect of local activation of β-adrenoreceptor by Isoprenaline on metabolism in brain, fat and lung measured by microdialysis. METHODS: We used 8 healthy pigs under general anaesthesia and placed microdialysis catheters in brain, fat, lung and artery. We performed a direct measurement of glucose, lactate, pyruvate and glycerol. The stimulation was performed by one-hour infusion of Isoprenaline, a β-adrenoreceptor agonist...
June 1, 2012: Advances in Medical Sciences
Mao Horio, Mami Kohno, Yuko Fujita, Tamaki Ishima, Ran Inoue, Hisashi Mori, Kenji Hashimoto
D-Serine, an endogenous co-agonist of the N-methyl-D-aspartate (NMDA) receptor, plays an important role in mammalian brain neurotransmission, via the NMDA receptor. D-Serine is synthesized from L-serine by the pyridoxal-5' phosphate-dependent enzyme serine racemase (SRR), and D-serine is metabolized by D-amino acid oxidase (DAAO). In this study, we measured levels of the neurotransmission related amino acids, d-serine, L-serine, glycine, glutamine and glutamate in the frontal cortex, hippocampus, striatum and cerebellum as well as in peripheral tissues of blood, heart, pancreas, spleen, liver, kidney, testis, epididymis, heart, lung, muscle and eyeball, in wild-type (WT) and Srr-knockout (Srr-KO) mice...
November 2011: Neurochemistry International
Oliver Mauric, Christiane Thallinger, Sylvia A Kugler, Samir M Joukhadar, Florian M Kovar, Karl H Konz, Wolfgang Graninger, Christian Joukhadar
BACKGROUND/AIMS: We measured the extracellular concentrations of fluconazole in lung tissue of septic and healthy rats. METHODS: A single intravenous dose of 6 mg/kg total body weight of fluconazole was administered intravenously to rats following insertion of microdialysis probes into lung tissue. Another probe was inserted into skeletal muscle and served as control. RESULTS: The mean peak concentration (C(max)), time to C(max), area under the concentration-versus-time curve from 0 to 6 h (fAUC(0-6)) and area under the concentration-versus-time curve from 0 to ∞ of unbound fluconazole for healthy lung were 11...
2011: Pharmacology
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