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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 -
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 -
Frontiers in Immunology 2021Palearctic vipers are medically significant snakes in the genera , and which occur throughout Europe, Central Asia, Near and Middle East. While the ancestral condition... (Comparative Study)
Comparative Study
Palearctic vipers are medically significant snakes in the genera , and which occur throughout Europe, Central Asia, Near and Middle East. While the ancestral condition is that of a small-bodied, lowland species, extensive diversification has occurred in body size, and niche specialization. Using 27 venom samples and a panel of coagulation assays, we evaluated the relative coagulotoxic potency of Palearctic viper venoms and compared their neutralization by three antivenoms (Insoserp Europe, VIPERFAV and ViperaTAb) and two metalloprotease inhibitors (prinomastat and DMPS). We show that variation in morphology parallels variation in the Factor X activating procoagulant toxicity, with the three convergent evolutions of larger body sizes ( genus, genus, and uniquely within the genus) were each accompanied by a significant increase in procoagulant potency. In contrast, the two convergent evolutions of high altitude specialization (the genus and uniquely within the genus) were each accompanied by a shift away from procoagulant action, with the species being particularly potently anticoagulant. Inoserp Europe and VIPERFAV antivenoms were both effective against a broad range of species, with Inoserp able to neutralize additional species relative to VIPERFAV, reflective of its more complex antivenom immunization mixture. In contrast, ViperaTAb was extremely potent in neutralizing but, reflective of this being a monovalent antivenom, it was not effective against other species. The enzyme inhibitor prinomastat efficiently neutralized the metalloprotease-driven Factor X activation of the procoagulant venoms. In contrast, DMPS (2,3-dimercapto-1-propanesulfonic acid), which as been suggested as another potential treatment option in the absence of antivenom, DMPS failed against all venoms tested. Overall, our results highlight the evolutionary variations within Palearctic vipers and help to inform clinical management of viper envenomation.
Topics: Animals; Antivenins; Blood Coagulation; Blood Coagulation Tests; Evolution, Molecular; Humans; Immunoglobulin Fab Fragments; Matrix Metalloproteinase Inhibitors; Organic Chemicals; Snake Bites; Species Specificity; Time Factors; Unithiol; Viper Venoms; Viperidae
PubMed: 34177943
DOI: 10.3389/fimmu.2021.688802 -
Journal of Medical Toxicology :... Jul 2021
Topics: Antidotes; Brain Diseases; Dimercaprol; Humans; Lead; Pharmaceutical Preparations; United States
PubMed: 33687652
DOI: 10.1007/s13181-021-00830-x -
BMC Pulmonary Medicine Jan 2024Flexible bronchoscopy procedures require detailed anatomical knowledge and advanced technical skills. Simulation-based training offers a patient-safe training...
BACKGROUND
Flexible bronchoscopy procedures require detailed anatomical knowledge and advanced technical skills. Simulation-based training offers a patient-safe training environment that can be more efficient than patient-based training. Physical models are cheaper than virtual reality simulators and allow trainees to be acquainted with the equipment used in the clinic. The choice of a physical model for training depends on the local context. The aim of this study was to compare four different bronchoscopy models for flexible bronchoscopy training.
METHODS
The BronchoBoy manikin, the Koken manikin, a human cadaver, and a preserved porcine lung were included in the study. Seven physicians experienced in bronchoscopy performed a bronchoscopic airway inspection, bronchoalveolar lavage (BAL), and tissue sampling on all four models with performance evaluated by observation and participant evaluation of models by questionnaire.
RESULTS
Nineteen segments were identified in all human anatomy models, and the only significant difference found was that only the Thiel embedded cadaver allowed all participants to enter RB1 with an instrument in the working channel (p = 0.001). The Thiel embedded cadaver and the BronchoBoy manikin had low fluid return on BAL (22 and 52 ml), whereas the Koken manikin and the preserved porcine lung had high return (132 and 134 ml), (p = 0.017). Tissue samplings were only completed in the preserved porcine lung and the Thiel embedded cadaver (p < 0.001).
CONCLUSIONS
An anatomically correct bronchoscopy is best simulated with the Koken manikin or the Thiel embedded cadaver. Bronchoalveolar lavage should be simulated with the Koken manikin or the preserved porcine lung. Tissue sampling procedures are best simulated using the Thiel embedded cadaver or the preserved porcine lung.
Topics: Swine; Animals; Humans; Bronchoscopy; Bronchoalveolar Lavage; Cadaver; Dimercaprol; Manikins
PubMed: 38195463
DOI: 10.1186/s12890-024-02846-9 -
Neurology India 2018
Topics: Adult; Cerebellar Ataxia; Chelating Agents; Dimercaprol; Humans; Male; Medicine, Ayurvedic; Mercury; Mercury Poisoning; Treatment Outcome
PubMed: 30233025
DOI: 10.4103/0028-3886.241403 -
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 -
Journal of Applied Biomaterials &... 2024To evaluate the antitumor and antimicrobial properties of an alginate-based membrane (ABM) loaded with bismuth lipophilic nanoparticles (BisBAL NPs) and cetylpyridinium...
OBJECTIVE
To evaluate the antitumor and antimicrobial properties of an alginate-based membrane (ABM) loaded with bismuth lipophilic nanoparticles (BisBAL NPs) and cetylpyridinium chloride (CPC) on clinically isolated bacteria and a pancreatic cancer cell line.
MATERIAL AND METHODS
The BisBAL NP-CPC ABM was characterized using optical and scanning electron microscopy (SEM). The antimicrobial potential was measured using the disk-diffusion assay, and antibiofilm activity was determined through the live/dead assay and fluorescence microscopy. The antitumor activity was analyzed on the pancreatic cell line (Panc 03.27) using the MTT assay and live/dead assay with fluorescence microscopy.
RESULTS
After a 24-h exposure (37°C, aerobic conditions), 5 µM BisBAL NP reduced the growth of by 77.9%, while 2.5 µM BisBAL NP inhibited the growth of , and by 82.9%, 82.6%, and 78%, respectively (). The BisBAL NPs-CPC ABM (at a ratio of 10:1; 500 and 50 µM, respectively) inhibited the growth of all isolated bacteria, producing inhibition halos of 9.5, 11.2, 7, and 10.3 mm for , and , respectively, in contrast to the 6.5, 9.5, 8.5, and 9.8 mm obtained with 100 µM ceftriaxone (). The BisBAL NPs-CPC ABM also reduced bacterial biofilms, with 81.4%, 74.5%, 97.1%, and 79.5% inhibition for , and , respectively. Furthermore, the BisBAL NPs-CPC ABM decreased Panc 03.27 cell growth by 76%, compared to 18% for drug-free ABM. GEM-ABM reduced tumoral growth by 73%. The live/dead assay confirmed that BisBAL NPs-CPC-ABM and GEM-ABM were cytotoxic for the turmoral Panc 03.27 cells.
CONCLUSION
An alginate-based membrane loaded with BisBAL NP and CPC exhibits dual antimicrobial and antitumoral efficacy. Therefore, it could be applied in cancer treatment and to diminish the occurrence of surgical site infections.
Topics: Bismuth; Cetylpyridinium; Anti-Infective Agents; Alginates; Klebsiella pneumoniae; Dimercaprol; Organometallic Compounds
PubMed: 38444166
DOI: 10.1177/22808000241236590 -
Pediatric Emergency Care Oct 2019Elemental mercury is a toxic liquid element that is used widely in the home, medicine, agriculture, and industry. It is readily vaporized and inhaled at room...
OBJECTIVE
Elemental mercury is a toxic liquid element that is used widely in the home, medicine, agriculture, and industry. It is readily vaporized and inhaled at room temperature. Thereby, inhalation can cause acute or chronic poisoning. Mercury can be found in environmental naturally find but some dangers sources give rise to contaminations. It can be very dangerous to all living organisms, especially children.
METHODS
This study presents the features of mercury poisoning in a group of pediatric cases. Data were obtained for 29 pediatric cases exposed to elemental mercury in a high school chemistry laboratory in Turkey. Patients with a blood mercury level exceeding 10 μg/L or a urine mercury level exceeding 15 μg/L were considered to have mercury poisoning. The patients were treated with 2,3-dimercaptopropane sulfonic acid or D-penicillamine.
RESULTS
Twenty-nine children with mercury poisoning were admitted to the hospital. The median duration of exposure was 58 (range, 15-120) minutes. Ten (29%) children were asymptomatic. Physical and neurological examinations were normal in 19 (65.5%) children. The most common presenting complaint was headache. The most common neurological abnormality, partly dilated/dilated pupils, was present in 9 (31%) children. Mercury levels were measured in blood samples every 5 days, and the median blood mercury level was 51.98 (range, 24.9-86.4) μg/L. There was a positive correlation between the duration of exposure and maximum blood/urine mercury levels (P = 0.001).
CONCLUSIONS
Elemental mercury exposure is potentially toxic; its symptomatology varies, especially in children. Secure storage of mercury and other toxic substances and provision of information about this subject to individuals who might be exposed to mercury and their families might help to prevent mercury poisoning.
Topics: Acute Disease; Adolescent; Chelating Agents; Child; Environmental Exposure; Female; Humans; Male; Mercury; Mercury Poisoning; Pediatric Emergency Medicine; Penicillamine; Schools; Turkey; Unithiol
PubMed: 27977534
DOI: 10.1097/PEC.0000000000001011 -
Toxins Jun 2016Zinc concentrations strongly influence aflatoxin accumulation in laboratory media and in food and feed crops. The presence of zinc stimulates aflatoxin production, and...
Zinc concentrations strongly influence aflatoxin accumulation in laboratory media and in food and feed crops. The presence of zinc stimulates aflatoxin production, and the absence of zinc impedes toxin production. Initial studies that suggested a link between zinc and aflatoxin biosynthesis were presented in the 1970s. In the present study, we utilized two zinc chelators, N,N,N',N'-tetrakis (2-pyridylmethyl) ethane-1,2-diamine (TPEN) and 2,3-dimercapto-1-propanesulfonic acid (DMPS) to explore the effect of zinc limitation on aflatoxin synthesis in Aspergillus parasiticus. TPEN but not DMPS decreased aflatoxin biosynthesis up to six-fold depending on whether A. parasiticus was grown on rich or minimal medium. Although we observed significant inhibition of aflatoxin production by TPEN, no detectable changes were observed in expression levels of the aflatoxin pathway gene ver-1 and the zinc binuclear cluster transcription factor, AflR. Treatment of growing A. parasiticus solid culture with a fluorescent zinc probe demonstrated an increase in intracellular zinc levels assessed by increases in fluorescent intensity of cultures treated with TPEN compared to controls. These data suggest that TPEN binds to cytoplasmic zinc therefore limiting fungal access to zinc. To investigate the efficacy of TPEN on food and feed crops, we found that TPEN effectively decreases aflatoxin accumulation on peanut medium but not in a sunflower seeds-derived medium. From an application perspective, these data provide the basis for biological differences that exist in the efficacy of different zinc chelators in various food and feed crops frequently contaminated by aflatoxin.
Topics: Aflatoxins; Arachis; Aspergillus; Chelating Agents; Ethylenediamines; Seeds; Transcription Factors; Unithiol; Zinc
PubMed: 27271668
DOI: 10.3390/toxins8060171