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Physiological Reports Sep 2023The circadian rhythm system regulates lung function as well as local and systemic inflammations. The alteration of this rhythm might be induced by a change in the eating...
The circadian rhythm system regulates lung function as well as local and systemic inflammations. The alteration of this rhythm might be induced by a change in the eating rhythm. Peroxisome proliferator-activated receptor gamma (PPARG) is a key molecule involved in circadian rhythm regulation, lung functions, and metabolic processes. We described the effect of the PPARG agonist pioglitazone (PZ) on the diurnal mRNA expression profile of core circadian clock genes (Arntl, Clock, Nr1d1, Cry1, Cry2, Per1, and Per2) and metabolism- and inflammation-related genes (Nfe2l2, Pparg, Rela, and Cxcl5) in the male murine lung disrupted by reversed feeding (RF). In mice, RF disrupted the diurnal expression pattern of core clock genes. It decreased Nfe2l2 and Pparg and increased Rela and Cxcl5 expression in lung tissue. There were elevated levels of IL-6, TNF-alpha, total cells, macrophages, and lymphocyte counts in bronchoalveolar lavage (BAL) with a significant increase in vascular congestion and cellular infiltrates in male mouse lung tissue. Administration of PZ regained the diurnal clock gene expression, increased Nfe2l2 and Pparg expression, and reduced Rela, Cxcl5 expression and IL-6, TNF-alpha, and cellularity in BAL. PZ administration at 7 p.m. was more efficient than at 7 a.m.
Topics: Animals; Male; Mice; Dimercaprol; Inflammation; Interleukin-6; Lung; Pioglitazone; PPAR gamma; RNA, Messenger; Tumor Necrosis Factor-alpha
PubMed: 37704580
DOI: 10.14814/phy2.15823 -
Immunity, Inflammation and Disease Aug 2023A systemic and local inflammatory immune imbalance is thought to be the cause of traumatic tracheal stenosis (TS). However, with CD4 T lymphocytes being the predominant...
A systemic and local inflammatory immune imbalance is thought to be the cause of traumatic tracheal stenosis (TS). However, with CD4 T lymphocytes being the predominant immune cells in TS, the mechanism of action and recruitment has not been described. In our research, using flow cytometry, ELISA, immunofluorescence, and Transwell chamber assays, the expression, distribution, and potential chemotactic function of CD4 T cells in TS patients were examined before and after treatment. The results showed that the untreated group had significantly more CD4 T cells and their secreted TGF-β1 than the treated group. Additionally, the untreated group's CD4 T cells showed a significant rise in CCL22 and CCL1, as well as a larger proportion of CCR4 and CCR8. CD4 T cells and CD68 macrophages located in TS also expressed CCL1 and CCL22. In vitro, anti-CCL1 and anti-CCL22 can partially block the chemoattractant effect of TS bronchoalveolar lavage (BAL) on purified CD4 T cells. The findings of this study indicated that TS contained unbalanced CD4 immune cells that were actively recruited locally by CCR4/CCL22 and CCR8/CCL1. As a result, it is anticipated that CD4 immune rebalancing can serve as a novel treatment for TS.
Topics: Humans; Tracheal Stenosis; Biological Assay; CD4-Positive T-Lymphocytes; Dimercaprol; Enzyme-Linked Immunosorbent Assay
PubMed: 37647429
DOI: 10.1002/iid3.916 -
The Journal of Infectious Diseases Jan 2024The impact of metagenomic next-generation sequencing (mNGS) on antimicrobial stewardship in patients with lower respiratory tract infections (LRTIs) is still unknown.
Impact of Metagenomic Next-Generation Sequencing of Bronchoalveolar Lavage Fluid on Antimicrobial Stewardship in Patients With Lower Respiratory Tract Infections: A Retrospective Cohort Study.
BACKGROUND
The impact of metagenomic next-generation sequencing (mNGS) on antimicrobial stewardship in patients with lower respiratory tract infections (LRTIs) is still unknown.
METHODS
This retrospective cohort study included patients who had LRTIs diagnosed and underwent bronchoalveolar lavage between September 2019 and December 2020. Patients who underwent both mNGS and conventional microbiologic tests were classified as the mNGS group, while those with conventional tests only were included as a control group. A 1:1 propensity score match for baseline variables was conducted, after which changes in antimicrobial stewardship between the 2 groups were assessed.
RESULTS
A total of 681 patients who had an initial diagnosis of LRTIs and underwent bronchoalveolar lavage were evaluated; 306 patients were finally included, with 153 in each group. mNGS was associated with lower rates of antibiotic escalation than in the control group (adjusted odds ratio, 0.466 [95% confidence interval, .237-.919]; P = .02), but there was no association with antibiotic de-escalation. Compared with the control group, more patients discontinued the use of antivirals in the mNGS group.
CONCLUSIONS
The use of mNGS was associated with lower rates of antibiotic escalation and may facilitate the cessation of antivirals, but not contribute to antibiotic de-escalation in patients with LRTIs.
Topics: Humans; Bronchoalveolar Lavage Fluid; Antimicrobial Stewardship; Retrospective Studies; High-Throughput Nucleotide Sequencing; Respiratory Tract Infections; Anti-Bacterial Agents; Dimercaprol; Metagenomics; Antiviral Agents; Sensitivity and Specificity
PubMed: 37506257
DOI: 10.1093/infdis/jiad296 -
The American Journal of Case Reports Jul 2023BACKGROUND ThinPrep Cytolyt is a methanol-based cell preservation solution frequently used to fix tissue samples immediately following endobronchial ultrasound-guided...
BACKGROUND ThinPrep Cytolyt is a methanol-based cell preservation solution frequently used to fix tissue samples immediately following endobronchial ultrasound-guided fine-needle aspiration. Currently, no published reports describe an iatrogenic exposure to Cytolyt. We report the only known case of an accidental intraoperative administration of a methanol solution, with corresponding plasma concentrations, and successful treatment with fomepizole. CASE REPORT A 70-year-old woman with a history of stage IIIA rectal adenocarcinoma was referred for evaluation of a newly identified lung mass. During the procedure, a bronchoalveolar lavage (BAL) of the right upper lobe was performed. After BAL, the proceduralist was informed that the syringe used to instill fluid for the BAL contained Cytolyt rather than saline. The Department of Medical Toxicology was contacted immediately, and the patient received a 15 mg/kg dose of fomepizole. The first plasma methanol level, before fomepizole administration, was elevated to 21 mg/dL. The methanol level was 13 mg/dL 3 h after fomepizole treatment and even lower thereafter; therefore, no additional fomepizole was required. The patient did not develop signs of systemic toxicity and was discharged on hospital day 3. CONCLUSIONS Following methanol exposures, patients can exhibit metabolic acidosis, with potential for blindness, hemodynamic instability, and possibly death if untreated. Fomepizole (4-methylpyrazole) inhibits alcohol dehydrogenase and is a mainstay of treatment. Preventing medical errors is key in ensuring optimal patient care and decreasing adverse events. Providers using CytoLyt and any similar products should be aware of this potential error and approach the possibility of methanol toxicity as they would other routes of methanol exposure.
Topics: Female; Humans; Aged; Fomepizole; Methanol; Antidotes; Pyrazoles; Dimercaprol; Iatrogenic Disease
PubMed: 37461205
DOI: 10.12659/AJCR.937247 -
Environmental Research Jul 2023Propyl-propane-thiosulfonate (PTSO) is an organosulfur compound found inAllium spp. Due to its antioxidant and antimicrobial activities, PTSO has been proposed for...
Propyl-propane-thiosulfonate (PTSO) is an organosulfur compound found inAllium spp. Due to its antioxidant and antimicrobial activities, PTSO has been proposed for applications in the agri-food sector, such as feed additive. However, its use with commercial purposes depends on its toxicity evaluation. The present work aimed to perform a pilot-study of toxicokinetic profile of PTSO combining in silico and in vitro techniques, important steps in the risk assessment process. In silico ecotoxicity studies were also performed considering the importance of the environmental impact of the compound before its commercial use. First, an analytical method has been developed and validated to determine the original compound and its metabolites by ultra-performance liquid chromatography-tandem mass spectrometry. The phase I and II metabolism of PTSO was predicted using Meta-Pred Web Server. For the phase I metabolism, rat (male and female) and human liver microsomes were incubated with PTSO and NADPH regeneration system. Furthermore, in the phase II, microsomes were incubated with PTSO and glutathione or uridine 5'- diphosphoglucuronic acid. The analysis revealed the presence of propylpropane thiosulfinate (PTS) originated by redox reaction in phase I, and two conjugates from the phase II: S-propylmercaptoglutathione (GSSP) and S-propylmercaptocysteine (CSSP). Additionally, considering the environmental fate of PTSO and its metabolites, the ADME parameters and the potential ecotoxicity were also predicted using in silico softwares. The results of the ecotoxicity in silico study evidenced that the metabolism induced the formation of detoxified metabolites from the parent compound, except for dimercaprol and 3-mercaptopropane1,2-diol. Further in vivo assays are needed to confirm this prediction.
Topics: Male; Rats; Humans; Female; Animals; Allium; Pilot Projects; Antioxidants; Microsomes, Liver; Chromatography, High Pressure Liquid
PubMed: 37116679
DOI: 10.1016/j.envres.2023.116001