Deficiency of the Transcription Factor NR4A1 Enhances Bacterial Clearance and Prevents Lung Injury During Escherichia Coli Pneumonia

This study aims to explore the role of NR4A1 in Escherichia coli (E. coli) pneumonia. Methods: Alveolar macrophages (AMs) were isolated from wild-type (WT) and NR4A1 knock out (Nr4a1−/−) mice, and the NR4A1 expression and phagocytic capacity against E. coli were measured in vitro. WT and Nr4a1−/− mice were subjected to E. coli or sham pneumonia. Bacterial load, lung injury severity, inflammatory cell infiltration, and cytokines were assessed at 0, 4, and 18 h after surgery. Survival rates within 48 h were evaluated in WT and Nr4a1−/− mice. In addition, NR4A1 antagonist (DIM-C-pPhCO2Me) was also used to confirm the role of NR4A1 in vivo and ex vivo. Results: NR4A1 was rapidly induced in AMs at 15 min after E. coli stimulation. Compared with untreated WT AMs, NR4A1 deficiency and DIM-C-pPhCO2Me treatment showed an enhanced phagocytic function (47.72 ± 0.74% vs. 62.3 ± 0.9%, P 
Source: Shock - Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research

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Baicalin alleviated APEC-induced acute lung injury in chicken by inhibiting NF-κB pathway activation. Int Immunopharmacol. 2019 Apr 26;72:467-472 Authors: Peng LY, Yuan M, Song K, Yu JL, Li JH, Huang JN, Yi PF, Fu BD, Shen HQ Abstract Bacterial pneumonia is a leading cause of death in the animal husbandry. Acute lung injury (ALI), most often seen as a part of systemic inflammatory process, characterized by progressive hypoxemia, edema, and neutrophil accumulation in the lung. Baicalin has been reported to inhibit inflammatory response, but its role in ALI remains unknown. The purpose of our stud...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research
In conclusion, we demonstrated that the selective boosting of lung innate immunity is a conceptually advantageous approach for improving the effectiveness of antibiotic treatment and fighting antibiotic-resistant bacteria. Introduction Pneumonia constitutes a major cause of death, morbidity and health resource use worldwide. The main causative agents identified in adult patients hospitalized for community-acquired pneumonia (CAP) are viruses (in 27–30% of cases, the most common being rhinovirus, influenza and coronavirus) and bacteria (14–23% of cases, with a marked predominance of Streptococcus pneumonia...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
The objective of these analyses was to provide dose selection support for and demonstrate the appropriateness of ertapenem to empirically treat patients with HABP/VABP when administered with murepavadin, a novel targeted antimicrobial exhibiting a highly specific spectrum of activity against P. aeruginosa A previously-developed population pharmacokinetic model, total-drug epithelial lining fluid to free-drug serum penetration ratio, contemporary in vitro surveillance data for ertapenem against Enterobacteriaceae, and %T>MIC targets associated with efficacy were used to conduct Monte Carlo simulations for five ertapenem ...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
ConclusionsThe potent activity of omadacycline against Gram-positive and Gram-negative bacteria indicates that omadacycline merits further study in serious infections in which multidrug resistance and mixed Gram-positive and Gram-negative infections may be a concern.
Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
ConclusionsDespite the inclusiveness and universality of the Italian healthcare system, children born to immigrant mothers experienced more need of avoidable hospital care than children born to Italian mothers. Access barriers to primary care are plausible causes for the observed disparities.
Source: Indian Journal of Pediatrics - Category: Pediatrics Source Type: research
By  SAURABH JHA After Dr. Hadiza Bawa-Garba was convicted for manslaughter for delayed diagnosis of fatal sepsis in Jack Adcock, a six-year-old boy who presented to Leicester Royal Infirmary with diarrhea and vomiting, she was referred to the Medical Practitioners Tribunal (MPT). The General Medical Council (GMC) is the professional regulatory body for physicians. But the MPT determines whether a physician is fit to practice. Though the tribunal is nested within the GMC and therefore within an earshot of its opinions, it is a decision-making body which is theoretically independent of the GMC. The tribunal met in 2017...
Source: The Health Care Blog - Category: Consumer Health News Authors: Tags: NHS #BawaGarba @roguerad Source Type: blogs
LITFL • Life in the Fast Lane Medical Blog LITFL • Life in the Fast Lane Medical Blog - Emergency medicine and critical care medical education blog aka Tropical Travel Trouble 009 The diagnosis of HIV is no longer fatal and the term AIDS is becoming less frequent. In many countries, people with HIV are living longer than those with diabetes. This post will hopefully teach the basics of a complex disease and demystify some of the potential diseases you need to consider in those who are severely immunosuppressed. While trying to be comprehensive this post can not be exhaustive (as you can imagine any patient with ...
Source: Life in the Fast Lane - Category: Emergency Medicine Authors: Tags: Clinical Cases Tropical Medicine AIDS art cryptococcoma cryptococcus HIV HIV1 HIV2 PEP PrEP TB toxoplasma tuberculoma Source Type: blogs
Authors: Cho JC, Childs-Kean LM, Zmarlicka MT, Crotty MP Abstract Omadacycline is a novel aminomethylcycline antimicrobial agent that is available in both oral and intravenous formulations. The distinguishing structural characteristics of omadacycline from other tetracyclines allow for its continued antimicrobial activity in the presence of traditional tetracycline resistance mechanisms (efflux pumps and ribosomal protection proteins). Omadacycline has been found to have potent activity against antibiotic-resistant pathogens including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, e...
Source: Drugs of Today - Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research
This study provides the first proof of principle that protein polysaccharide conjugate vaccines produced in E. coli can be used to prevent pneumococcal infection. Vaccines produced in this manner may provide a low-cost alternative to the current vaccine production methodology. PMID: 29778517 [PubMed - as supplied by publisher]
Source: Vaccine - Category: Allergy & Immunology Authors: Tags: Vaccine Source Type: research
Discussion Normal kidneys regulate water balance to maintain a plasma osmolality of 275-290 mOsm/kg normally. Thirst and arginine vasopressin or antidiuretic hormone (ADH) are the primary regulators of plasma osmolality. ADH is made in the hypothalamus and released by the posterior pituitary gland. ADH acts on the kidney’s distal collecting duct to increase water reabsorption. ADH is appropriately released in hypovolemic states, such as dehydration caused by gastroenteritis. ADH has an ~10 minute half-life and therefore can respond to rapid changes in volume status. Sodium balance is regulated by aldosterone (as part...
Source: - Category: Pediatrics Authors: Tags: Uncategorized Source Type: news
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