scholarly journals Ablation of the leptin receptor in myeloid cells impairs pulmonary clearance ofStreptococcus pneumoniaeand alveolar macrophage bactericidal function

2018 ◽  
Vol 315 (1) ◽  
pp. L78-L86 ◽  
Author(s):  
Peter Mancuso ◽  
Jeffrey L. Curtis ◽  
Christine M. Freeman ◽  
Marc Peters-Golden ◽  
Jason B. Weinberg ◽  
...  
Keyword(s):  
Pneumococcal Pneumonia ◽  
Respiratory Tract Infections ◽  
Bronchoalveolar Lavage Fluid ◽  
Leptin Receptor ◽  
Lavage Fluid ◽  
Bacterial Killing ◽  
Leptin Deficiency ◽  
Tract Infections ◽  
Bactericidal Function

Leptin is a pleiotropic hormone produced by white adipose tissue that regulates appetite and many physiological functions, including the immune response to infection. Genetic leptin deficiency in humans and mice impairs host defenses against respiratory tract infections. Since leptin deficiency is associated with obesity and other metabolic abnormalities, we generated mice that lack the leptin receptor (LepRb) in cells of the myeloid linage (LysM-LepRb-KO) to evaluate its impact in lean metabolically normal mice in a murine model of pneumococcal pneumonia. We observed higher lung and spleen bacterial burdens in LysM-LepRb-KO mice following an intratracheal challenge with Streptococcus pneumoniae. Although numbers of leukocytes recovered from bronchoalveolar lavage fluid did not differ between groups, we did observe higher levels of pulmonary IL-13 and TNFα in LysM-LepRb-KO mice 48 h post infection. Phagocytosis and killing of ingested S. pneumoniae were also impaired in alveolar macrophages (AMs) from LysM-LepRb-KO mice in vitro and were associated with reduced LTB4and enhanced PGE2synthesis in vitro. Pretreatment of AMs with LTB4and the cyclooxygenase inhibitor, indomethacin, restored phagocytosis but not bacterial killing in vitro. These results confirm our previous observations in leptin-deficient ( ob/ob) and fasted mice and demonstrate that decreased leptin action, as opposed to metabolic irregularities associated with obesity or starvation, is responsible for the defective host defense against pneumococcal pneumonia. They also provide novel targets for therapeutic intervention in humans with bacterial pneumonia.

scholarly journals The Ovine Cathelicidin SMAP29 Kills Ovine Respiratory Pathogens In Vitro and in an Ovine Model of Pulmonary Infection

2001 ◽  
Vol 45 (1) ◽  
pp. 331-334 ◽  
Author(s):  
K. A. Brogden ◽  
V. C. Kalfa ◽  
M. R. Ackermann ◽  
D. E. Palmquist ◽  
P. B. McCray ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Respiratory Tract Infections ◽  
Bronchoalveolar Lavage Fluid ◽  
Pulmonary Infection ◽  
Lavage Fluid ◽  
Respiratory Pathogens ◽  
Broth Microdilution ◽  
Ovine Model ◽  
Tract Infections

ABSTRACT Cathelicidins are antimicrobial peptides from sheep (SMAP29 and SMAP34), rabbits (CAP11 and CAP18), rodents (CRAMP), and humans (FALL39, LL37, and h/CAP18). In a broth microdilution assay against nine ovine pathogens, SMAP29, SMAP34, mouse CRAMP, CAP18, CAP1831, CAP1828, CAP1822, and CAP1821a were the most active, with MICs as low as 0.6 μg/ml. Other cathelicidins were less active. In lambs with pneumonia, 0.5 mg of SMAP29 reduced the concentration of bacteria in both bronchoalveolar lavage fluid and consolidated pulmonary tissues. Hence, the antimicrobial activity of SMAP29 suggests that it has applications in the treatment of respiratory tract infections.

scholarly journals Combined nanopore adaptive sequencing and enzyme-based host depletion efficiently enriched microbial sequences and identified missing respiratory pathogens

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mingyu Gan ◽  
Bingbing Wu ◽  
Gangfeng Yan ◽  
Gang Li ◽  
Li Sun ◽  
...  
Keyword(s):  
Standard Method ◽  
Respiratory Tract Infections ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Interquartile Range ◽  
Clinical Samples ◽  
Respiratory Pathogens ◽  
Combined Method ◽  
Tract Infections ◽  
Enrichment Efficiency

Abstract Background Enzyme-based host depletion significantly improves the sensitivity of clinical metagenomics. Recent studies found that real-time adaptive sequencing of DNA molecules was achieved using a nanopore sequencing machine, which enabled effective enrichment of microbial sequences. However, few studies have compared the enzyme-based host depletion and nanopore adaptive sequencing for microbial enrichment efficiency. Results To compare the host depletion and microbial enrichment efficiency of enzyme-based and adaptive sequencing methods, the present study collected clinical samples from eight children with respiratory tract infections. The same respiratory samples were subjected to standard methods, adaptive sequencing methods, enzyme-based host depletion methods, and the combination of adaptive sequencing and enzyme-based host depletion methods. We compared the host depletion efficiency, microbial enrichment efficiency, and pathogenic microorganisms detected between the four methods. We found that adaptive sequencing, enzyme-based host depletion and the combined methods significantly enriched the microbial sequences and significantly increased the diversity of microorganisms (p value < 0.001 for each method compared to standard). The highest microbial enrichment efficiency was achieved using the combined method. Compared to the standard method, the combined method increased the microbial reads by a median of 113.41-fold (interquartile range 23.32–327.72, maximum 1812), and the number of genera by a median of 70-fold (interquartile range 56.75–86.75, maximum 164). The combined method detected 6 pathogens in 4 samples with a median read of 547, compared to 5 pathogens in 4 samples with a median read of 4 using the standard method. Conclusion The combined method is an effective, easy-to-run method for enriching microbial sequences in clinical metagenomics from sputum and bronchoalveolar lavage fluid samples and may improve the sensitivity of clinical metagenomics for other host-derived clinical samples.

scholarly journals Epidemiology of Human Respiratory Viruses in Children with Acute Respiratory Tract Infections in Jinan, China

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yanqin Lu ◽  
Shifu Wang ◽  
Lehai Zhang ◽  
Chao Xu ◽  
Cuirong Bian ◽  
...  
Keyword(s):  
Respiratory Tract Infections ◽  
Bronchoalveolar Lavage Fluid ◽  
Respiratory Virus ◽  
Lavage Fluid ◽  
Virus Infections ◽  
Rt Pcr ◽  
Viral Pathogens ◽  
Tract Infections ◽  
Respiratory Virus Infections ◽  
Viral Etiologies

The viral etiologies of UTRIs and LTRIs in children in Jinan city were investigated between July 2009 and June 2010. Nasal and throat swabs were collected from 397 children with URTIs and bronchoalveolar lavage fluid specimens were collected from 323 children with LRTIs. RT-PCR/PCR was used to examine all samples for IFV, PIV, RSV, RV, hMPV, HBoV, CoV, ADV, RSV, and EV. Viral pathogens were detected in 47.10% of URTI samples and 66.57% samples, and the incidence of viral coinfection was 5.29% and 21.05%, respectively. IFV was the most common virus in URTIs, with a detection rate of 19.40%, followed by PIV (10.83%), RV (10.58%), and EV (6.30%). For LRTIs, PIV and RV were both detected in 27% of samples, followed by RSV (9.91%), HBoV (8.36%), IFV (5.57%), and hMPV (5.57%). RSV and HBoV were more prevalent in the youngest children of no more than six months. Meanwhile, RV, PIV, and RSV were the most frequent viruses combined with bacterial pathogens in LRTIs. In conclusion, the spectrum of respiratory virus infections in URTIs and LRTIs differed in terms of the most common pathogens, seasonal distribution, and coinfection rate.

scholarly journals Pyopneumothorax from coinfection by Trichomonas tenax and Geotrichum capitatum in a child from China: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuhui Wu ◽  
Yuanzhen Ye ◽  
Yanlan Yang ◽  
Weiguo Yang ◽  
Jiayin Lin ◽  
...  
Keyword(s):  
Pleural Effusion ◽  
Respiratory Tract Infections ◽  
Bronchoalveolar Lavage Fluid ◽  
Clinical Symptoms ◽  
Lavage Fluid ◽  
Lower Respiratory Tract Infections ◽  
Case Presentation ◽  
Geotrichum Capitatum ◽  
Tract Infections ◽  
Generation Sequencing

Abstract Background Trichomonas tenax may appear in the oral cavity of humans due to poor dentition or oral hygiene. Pyopneumothorax is a serious complication of lower respiratory tract infections that very rarely can be caused by a trichomonad species in predisposed individuals. We report a rare case of pleurisy due to T. tenax with coinfection by a fungus. Case presentation We describe a 16-year-old patient with cerebral palsy who presented with severe pyopneumothorax. T. tenax was identified by microscopic examination of the pleural effusion and next-generation sequencing. We also identified Geotrichum capitatum in the pleural effusion and bronchoalveolar lavage fluid cultures. Treatment with voriconazole and metronidazole successfully eliminated these pathogens and relieved the clinical symptoms. A literature review indicated this is the first reported case of pleurisy due to T. tenax with coinfection by a fungus. Conclusion The rarity of pyopneumothorax caused by T. tenax coinfection with a fungus should not be overlooked in the clinic. These patients should be and treated in a timely manner.

Telithromycin: The First of the Ketolides

2002 ◽  
Vol 36 (3) ◽  
pp. 452-464 ◽  
Author(s):  
Christopher S Shain ◽  
Guy W Amsden
Keyword(s):  
Respiratory Tract ◽  
Clinical Efficacy ◽  
Respiratory Tract Infections ◽  
Safety Issue ◽  
Qtc Interval ◽  
Phagocytic Cells ◽  
Medline Search ◽  
Atypical Pathogens ◽  
Tract Infections

OBJECTIVE: To review the chemistry, spectrum of activity, pharmacology, clinical efficacy, and safety of telithromycin. DATA SOURCES: A MEDLINE search from 1966 to December 2000 was performed via OVID and PubMed using the following search terms: HMR 3647, HMR3647, Ketek, RU 66647, and telithromycin. An extensive review of retrieved literature, abstracts from international scientific conferences, and minutes from regulatory authority meetings was also performed. DATA EXTRACTION: Medicinal chemistry, in vitro, animal, and human trials were reviewed for information on the antimicrobial activity, clinical efficacy, pharmacology, and safety of telithromycin. DATA SYNTHESIS: Several chemical modifications to the macrolide structure have led to the development of telithromycin, the first ketolide antimicrobial that demonstrates improved activity against penicillin- and macrolide/azalide-resistant Streptococcus pneumoniae due to its unique binding to the ribosomal target site. Although telithromycin may be useful in the treatment of community-acquired respiratory tract infections due to its activity against common typical and atypical pathogens, questions concerning its reliable activity against Haemophilus influenzae need to be addressed. Telithromycin's pharmacokinetics permit once-daily dosing for abbreviated periods and good distribution into lung tissue and phagocytic cells. Clinical and bacteriologic cure rates have been similar to those of comparator agents in human efficacy trials; however, the incidence of adverse gastrointestinal events were generally higher with telithromycin patients. Like other macrolides and many newer fluoroquinolones, telithromycin's ability to prolong the QTc interval is a potential safety issue, especially in elderly patients with predisposing conditions or those who are concurrently receiving drugs that are substrates for CYP2D6 and 3A4. Liver function test elevations demonstrated during clinical trials, although not overtly severe, may warrant monitoring in some patients taking multiple hepatically metabolized/cleared agents. CONCLUSIONS: Telithromycin offers potential advantages over traditional macrolides/azalides for community-acquired respiratory tract infections caused by macrolide-resistant pathogens. Further studies are needed to elucidate its clinical efficacy against H. influenzae, potential drug interactions, and safety in various subpopulations.

scholarly journals Yupingfeng Pulvis Regulates the Balance of T Cell Subsets in Asthma Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Zhigang Wang ◽  
Xueting Cai ◽  
Zhonghua Pang ◽  
Dawei Wang ◽  
Juan Ye ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Th17 Cells ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Treg Cells ◽  
T Cell Subsets ◽  
Control Group ◽  
Group Model ◽  
Therapy Effect ◽  
Tract Infections

Background. Yupingfeng Pulvis (HFBP) had played an active role in many diseases, especially respiratory tract infections. Exploring the possible prevention mechanism of HFBP may provide new ideas in clinical applications for this well-known herbal formula.Purpose. To study the possible mechanisms of therapy effect of HFBP on asthma mice via regulating the balance of Tregs and Th17 cells.Method. The female BALB/c mice were divided into five groups: control group, model group, prednisone (5.5 mg/kg) group, and 22 g/kg HFBP and 44 g/kg HFBP groups. Ovalbumin was used to make the asthma model of mice; the drug was ig administered daily after atomization for consecutive 15 d. The mice were killed after the last administration. The paraffin-embedded tissue sections of the lungs were stained by H&E. Tregs and Th17 cells in bronchoalveolar lavage fluid were detected by flow cytometry. IL-4, TGF-β, and TNF-αin the serum were detected by ELISA assay.Results. HFBP could alleviate the inflammation in the lung tissue of mice, decrease the proportion of Th17 cells, and increase the proportion of Treg cells in bronchoalveolar lavage fluid. HFBP could decrease IL-4 and TNF-αlevel and increase TGF-βlevel in blood.Conclusion. HFBP could treat the asthma through impacting the balance of Th17 cells and Treg cells as well as the levels of related inflammatory cytokines in asthma mice.

scholarly journals In Vitro Activity of AR-709 against Streptococcus pneumoniae

2008 ◽  
Vol 52 (3) ◽  
pp. 1182-1183 ◽  
Author(s):  
W. T. M. Jansen ◽  
A. Verel ◽  
J. Verhoef ◽  
D. Milatovic
Keyword(s):  
Streptococcus Pneumoniae ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Lower Respiratory Tract Infections ◽  
Excellent Activity ◽  
Tract Infections

ABSTRACT We investigated the in vitro activity of AR-709, a novel diaminopyrimidine antibiotic currently in development for treatment of community-acquired upper and lower respiratory tract infections, against 151 Streptococcus pneumoniae strains from various European countries. AR-709 showed excellent activity against both drug-susceptible and multidrug-resistant pneumococci.

Sign in / Sign up

Export Citation Format

Share Document