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1.
J Colloid Interface Sci ; 607(Pt 1): 347-356, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34509109

RESUMO

Although silicates are the most common anions in aquatic systems, little is known on the roles they play on the transport of emerging contaminants, such as antibiotics. Using dynamic column experiments, we revealed the controls of Si loadings on goethite (α-FeOOH) coated sands on the transport of a widely used quinolone antibiotic, here focusing on Nalidixic Acid (NA). We find that dynamic flow-through conditions (Darcy velocities of 2.98 cm/h and 14.92 cm/h) sustain monomeric Si species with loadings of up to ~ 0.8 Si/nm2 but that oligomeric species can form at the goethite surfaces under static (batch, no-flow conditions). While these monomeric species occupy no more than ~ 22% of the reactive OH groups on goethite, they can effectively suppress NA binding, and therefore enhance NA mobility in dynamic conditions. NA can also bind on goethite when it is simultaneously injected with high concentrations of Si (2000 µM), yet it becomes progressively replaced by Si over time. Combining kinetics and surface complexation modeling, we present a new transport model to account for the stepwise polymerization of Si on goethite and NA transport. Our findings show that dissolved Si, common to natural surface waters, can play a determining role on the surface speciation and transport of antibiotics in the environment.


Assuntos
Compostos de Ferro , Quinolonas , Adsorção , Cinética , Minerais , Porosidade , Silicatos
2.
Arch Razi Inst ; 76(3): 561-573, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34824749

RESUMO

Quinolone antimicrobials are widely used in clinical medicine due to their wide spectrum with high tissue penetration and ease of use; but increasing resistance with clinical use appears to be common in some bacterial pathogens, including Escherichia coli (E.coli). The aim of this study was to investigate plasmid-mediated quinolone resistance determinants (PMQR) including, qnrA, qnrB, and qnrS as the emerging mechanisms of quinolone resistance of E.coli isolates from different clinical sites in Karbala province, Iraq. A total of 200 clinical samples were collected from patients suffering from infections such as UTI, gastro enteritis (diarrhea), vaginitis, and wound infections; 30 samples were diagnosed as E.coli clinical strain from both sexes and different ages after identification by biochemical test, VITEK-2 compact system, and by molecular method using 16Sr DNA marker. Antimicrobial susceptibility and minimal inhibition concentration (MIC) testing for nalidixic acid, norfloxacin, ciprofloxacin, levofloxacin, and gatifloxacin was performed using the broth microdilution method. All strains were screened for PMQR genes qnrA, qnrB, and qnrS by the PCR method after DNA extraction from tested clinical isolates of E.coli. The results showed that E. coli is largely isolated from vaginal (40%) and urine (32%) samples, followed by wound infections (24%) and stools (21%).The high occurrence rate of E. coli(33.33%) isolates was observed in participants aged 31-45 years, while a lower occurrence (10%)was recorded in a group of ˃ 60-year-old female participants. Females have a notably increased frequency of E.coli compared to males, with the female to male ratio being 87%: 13%. Molecular investigation showed the total percentage of E.coli isolates harboring qnr genes to be 21/30 (70%); this figure is composed of 14/30 isolates harboring qnr in combined or mixed form (46.66%) and 7/30 (23.33%) isolates harboring qnr in single form (3 isolates harboring qnrA alone, 1 isolate harboring qnrB alone, 3 isolates harboring qnrS alone).The prevalence rates of qnrA, qnrB, and qnrS were 40%, 43.33%, and 53.33%, respectively. The results also showed that among E.coli isolates encoding qnr genes A, B, and S, 24%, 12%, and 36% were resistant to nalidixic acid, respectively. Among those isolates carrying qnrA, qnrB, and qnrS genes, 15.8%, 5.3%, and 26.3%, respectively, were resistant to ciprofloxacin. Moreover, Norfloxacin resistance was seen in 20.0%, 5.0%, and 30.0% of E.coli isolates harboring qnr A, B, and S genes, respectively. Levofloxacin resistance was seen in 37.5%, 75.0%, and 37.5% of the isolates carrying the qnrA, qnrB, and qnrS genes, respectively. The lowest resistance rates of qnrA, B, and S-positive E.coli strains were against gatifloxacin (0,0, and 25%, respectively).A high prevalence of qnr genes enhances the increasing resistance rate of E.coli against the quinolone antibiotic under study.


Assuntos
Escherichia coli , Quinolonas , Animais , Farmacorresistência Bacteriana/genética , Escherichia coli/genética , Feminino , Masculino , Testes de Sensibilidade Microbiana/veterinária , Plasmídeos/genética , Quinolonas/farmacologia
3.
Zhonghua Jie He He Hu Xi Za Zhi ; 44(11): 947-952, 2021 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-34758520

RESUMO

Objective: To evaluate the in vitro antibacterial activity of nemonoxacin against clinical isolates of Mycobacterium abscessus (M. abscessus). Methods: A total of 194 clinical strains of M. abscessus were collected from 2014 to 2017 in Shanghai Pulmonary Hospital. The minimum inhibitory concentrations (MICs) of nemonoxacin and other quinolones commonly used (moxifloxacin, levofloxacin and ciprofloxacin) against M. abscessus in clinic was determined by the micro-broth dilution method. Synergy between nemonoxacin and frequently used anti-M. abscessus drugs (clarithromycin, amikacin, imipenem, cefoxitin, tigecycline and linezolid) was assessed in vitro. Results: The MIC range of nemonoxacin to M. abscessus was 0.25-64.00 mg/L. The MIC50 and MIC90 were 4 and 16 mg/L, respectively. Most M. abscessus isolates demonstrated an MIC of ≤ 4 mg/L against nemonoxacin, with a percentage of 68.0% (132/194), which was significantly higher than that against moxifloxacin (51.0%, 99/194; χ2 = 11.651, P<0.01), ciprofloxacin (46.4%, 90/194; χ2 = 18.572, P<0.01) and levofloxacin (25.8%, 50/194; χ2 = 69.586, P<0.01), respectively. Nemonoxacin showed no antagonistic effect with commonly used anti-M. abscessus drugs, except imipenem. Conclusions: Nemonoxacin showed moderate in vitro antibacterial activity against M. abscessus, which was better than that of other fluoroquinolones commonly used in clinic at present. Therefore, nemonoxacin may be one of the options for combined treatment of M. abscessus infection.


Assuntos
Mycobacterium abscessus , Quinolonas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , China , Quinolonas/farmacologia
4.
Br J Hosp Med (Lond) ; 82(11): 1-6, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34817261

RESUMO

Cystic fibrosis is a life-limiting, inherited, multi-organ disease which affects many systems of the body. Until recently, treatments were only able to ameliorate symptoms, but the introduction of precision medications which modulate the underlying defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene has changed this. Notably improvements in nutrition and lung function, reduced use of antibiotics and reduced occupation rates for hospital beds have been seen. This article summarises the discussion of a group of healthcare professionals from different specialties and an expert patient, representing their personal views and experience of treating patients who are using CFTR modulators. The discussion was sponsored by an unrestricted grant from Chiesi Limited (Manchester, UK).


Assuntos
Fibrose Cística , Quinolonas , Aminofenóis , Fibrose Cística/tratamento farmacológico , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Humanos , Mutação , Qualidade de Vida
5.
Shokuhin Eiseigaku Zasshi ; 62(5): 168-174, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34732644

RESUMO

In this study, we developed an analytical method for simultaneous determination of 14 quinolones and 4 tetracyclines in livestock and fishery products using LC-MS/MS. The analytes were extracted from food samples with citrate buffer (containing EDTA)-methanol-acetonitrile (3 : 1 : 1, v/v/v) in the presence of n-hexane, and the extract was purified with an Oasis PRiME HLB cartridge column. It was suggested that this analytical method can also extract analytes from solid samples containing fat by using n-hexane. In addition, using methanol-acetonitrile (3 : 7, v/v) containing 0.1 vol% formic acid as an eluent from the cartridge column, the purification effect could be improved, while minimizing the impairment of the recovery rate. As a result of the validation using six types of food samples, trueness (accuracy) was 70.6%-113.8%, the RSD of repeatability was 9.0% or less, and the RSD of within-laboratory reproducibility was 15.5% or less. Using this approach, the standard values mentioned in the Japanese guideline were successfully met.


Assuntos
Quinolonas , Tetraciclinas , Animais , Cromatografia Líquida , Pesqueiros , Gado , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem
6.
PLoS One ; 16(10): e0258533, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34644336

RESUMO

OBJECTIVE: To investigate the durability of the first integrase inhibitor-based regimen in a HIV geriatric multicentric prospective cohort and to explore the reasons of regimen discontinuation. DESIGN: This is an analysis conducted on the Geriatric Patients Living with HIV/AIDS (GEPPO) cohort, an Italian prospective observational multicentre cohort of people living with HIV with 65 years of age or more. METHODS: The analysis was performed using R (version 4.0.2). The tests performed were two sided assuming a 5% significance level (Kruskal-Wallis test, Chi-squared test, log-rank test and a Cox Proportional Hazard model). The proportion of participants discontinuing the three regimens was displayed using cumulative curves. RESULTS: Among 1531 patients enrolled between 2017 and 2019 in the GEPPO cohort, we included 822 participants in this analysis. At baseline, median age was 69.8, the immunovirological profile good, multimorbidity was present in 42.3% of participants, while 27.4% were on polypharmacy. Overall, 483, 243 and 96 participants received DTG, RAL and EVG/c respectively as first InSTI. At the end of the follow up 6.4%, 21.1% and 22.9% participants discontinued DTG, RAL and EVG/c respectively. Using a log-rank test, EVG showed a significantly lower durability than DTG (p<0.001) or RAL (p 0.05) or both, DTG and RAL (p<0.001). Among participants who discontinued their regimen we found 0 virological failure and 56.7% simplification/deprescription. CONCLUSIONS: The three integrase inhibitors considered showed a good durability and no virological failures in geriatric patients such as those enrolled in the GEPPO cohort when used in a two or three drug regimen.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , Idoso , Amidas/uso terapêutico , Antirretrovirais/uso terapêutico , Quimioterapia Combinada , Feminino , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Estudos Longitudinais , Masculino , Adesão à Medicação , Oxazinas/uso terapêutico , Piperazinas/uso terapêutico , Polimedicação , Modelos de Riscos Proporcionais , Estudos Prospectivos , Piridonas/uso terapêutico , Quinolonas/uso terapêutico , Raltegravir Potássico/uso terapêutico , Resultado do Tratamento
7.
Rev Med Liege ; 76(10): 768-772, 2021 Oct.
Artigo em Francês | MEDLINE | ID: mdl-34632748

RESUMO

Here we present pharmacological and clinical properties of a new fixed triple inhaled combination including an inhaled corticoid, a long acting ?2 agonist and a long acting anticholinergic for the treatment of severe asthma. Enerzair® is the name of this triple combination which contains 160 µg mometasone, 150 µg indacaterol and 50 µg glycopyrronium administered by a Breezhaler®. As compared to an ICS/LABA combination Enerzair® improves expiratory flow rates and reduces exacerbation rate. The Breezhaler® device may be coupled to a sensor (Propeller Health) that, through a bluetooth system, allows to control patient adherence and provides recall to the patient to take his aerosol.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Asma/tratamento farmacológico , Glicopirrolato , Humanos , Indanos , Furoato de Mometasona/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinolonas
8.
Tuberk Toraks ; 69(3): 399-402, 2021 Sep.
Artigo em Turco | MEDLINE | ID: mdl-34581162

RESUMO

Antibiotic hypersensitivity reactions can lead to marked morbidity, mortality and inadequate treatment options. Mycobacterium abscessus infection is a difficult management system for clinicians since it most commonly involves the lungs, progresses if untreated, and the organism is resistant to many antibiotics, as well as the agents used in treatment can cause undesirable side effects. Although macrolides are one of the most reliable antibiotic groups in terms of allergic reactions, early type hypersensitivity reactions against macrolides, one of the main antibiotics used in the treatment of Mycobacterium abscessus lung disease, may make the treatment management of the disease difficult. Due to the rapid increase in the use of quinolone in recent years, the frequency of developing allergic reactions with these agents also increases. In cases where antibiotic hypersensitivity is detected, the use of the responsible agent should be avoided, but desensitization may be necessary in cases without different treatment options. In this study, it was aimed to present a case of successful desensitization with clarithromycin and moxifloxacin in a patient who was diagnosed with Mycobacterium abscessus lung disease and developed anaphylaxis with clarithromycin and moxifloxacin after treatment was initiated.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Quinolonas , Antibacterianos/efeitos adversos , Humanos , Macrolídeos , Testes de Sensibilidade Microbiana , Infecções por Mycobacterium não Tuberculosas/induzido quimicamente , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Quinolonas/efeitos adversos
9.
Int J Mol Sci ; 22(18)2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34576160

RESUMO

Collagen XV (Col XV), a basement membrane (BM) component, is highly expressed in adipose tissue, and studies have found that Col XV is related to extracellular matrix (ECM) remodeling involving in adipose tissue fibrosis and inflammation. Furthermore, the ECM is essential for maintaining normal development and tissue function. In this study, we found that Col XV is related to the endoplasmic reticulum stress (ERS) and inflammation of adipose tissue. Moreover, we found that overexpression of Col XV in mice could cause macrophages to infiltrate white adipose tissue (iWAT). At the same time, the expression of the ERS sensor IRE1α (Inositol-Requiring Enzyme-1α) was significantly up-regulated, which intensified the inflammation of adipose tissue and the polarization of M1 macrophages after the overexpression of Col XV in mice. In addition, after overexpression of Col XV, the intracellular Ca2+ concentration was significantly increased. Using focal adhesion kinase (FAK) inhibitor PF573228, we found that PF-573228 inhibited the phosphorylation of FAK and reversed the upward trend of Col XV-induced protein expression levels of IRE1α, C/EBP-homologous protein (CHOP), and 78 kDa glucose-regulated protein (GRP78). After treatment with IRE1α inhibitor STF-083010, the results showed that the expression of adipocyte inflammation-related genes interleukin 6 (IL-6) and tumor necrosis factor α (TNFα) significantly were decreased. Our results demonstrate that Col XV induces ER-stress in adipocytes by activating the Integrinß1/FAK pathway and disrupting the intracellular Ca2+ balance. At the same time, Col XV regulates the inflammation induced by ER stress in adipocytes by promoting IRE1α/XBP1 (X-Box binding protein 1) signaling. Our study provides new ideas for solving the problems of adipose tissue metabolism disorders caused by abnormal accumulation of ECM.


Assuntos
Tecido Adiposo/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Inflamação/metabolismo , Células 3T3-L1 , Animais , Cálcio/metabolismo , Estresse do Retículo Endoplasmático/genética , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Imuno-Histoquímica , Inflamação/genética , Integrina beta1/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Quinolonas/farmacologia , RNA-Seq , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Sulfonas/farmacologia
10.
Int J Mol Sci ; 22(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34576206

RESUMO

Actinobacillus pleuropneumoniae is a pathogen that infects pigs and poses a serious threat to the pig industry. The emergence of quinolone-resistant strains of A.pleuropneumoniae further limits the choice of treatment. However, the mechanisms behind quinolone resistance in A.pleuropneumoniae remain unclear. The genomes of a ciprofloxacin-resistant strain, A. pleuropneumoniae SC1810 and its isogenic drug-sensitive counterpart were sequenced and analyzed using various bioinformatics tools, revealing 559 differentially expressed genes. The biological membrane, plasmid-mediated quinolone resistance genes and quinolone resistance-determining region were detected. Upregulated expression of efflux pump genes led to ciprofloxacin resistance. The expression of two porins, OmpP2B and LamB, was significantly downregulated in the mutant. Three nonsynonymous mutations in the mutant strain disrupted the water-metal ion bridge, subsequently reducing the affinity of the quinolone-enzyme complex for metal ions and leading to cross-resistance to multiple quinolones. The mechanism of quinolone resistance in A. pleuropneumoniae may involve inhibition of expression of the outer membrane protein genes ompP2B and lamB to decrease drug influx, overexpression of AcrB in the efflux pump to enhance its drug-pumping ability, and mutation in the quinolone resistance-determining region to weaken the binding of the remaining drugs. These findings will provide new potential targets for treatment.


Assuntos
Quinolonas/farmacologia , Actinobacillus pleuropneumoniae/efeitos dos fármacos , Actinobacillus pleuropneumoniae/genética , Biofilmes/efeitos dos fármacos , Porinas/metabolismo , Transcriptoma/genética
11.
PLoS Pathog ; 17(8): e1009425, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34460871

RESUMO

Extracellular DNA (eDNA) is a major constituent of the extracellular matrix of Pseudomonas aeruginosa biofilms and its release is regulated via pseudomonas quinolone signal (PQS) dependent quorum sensing (QS). By screening a P. aeruginosa transposon library to identify factors required for DNA release, mutants with insertions in the twin-arginine translocation (Tat) pathway were identified as exhibiting reduced eDNA release, and defective biofilm architecture with enhanced susceptibility to tobramycin. P. aeruginosa tat mutants showed substantial reductions in pyocyanin, rhamnolipid and membrane vesicle (MV) production consistent with perturbation of PQS-dependent QS as demonstrated by changes in pqsA expression and 2-alkyl-4-quinolone (AQ) production. Provision of exogenous PQS to the tat mutants did not return pqsA, rhlA or phzA1 expression or pyocyanin production to wild type levels. However, transformation of the tat mutants with the AQ-independent pqs effector pqsE restored phzA1 expression and pyocyanin production. Since mutation or inhibition of Tat prevented PQS-driven auto-induction, we sought to identify the Tat substrate(s) responsible. A pqsA::lux fusion was introduced into each of 34 validated P. aeruginosa Tat substrate deletion mutants. Analysis of each mutant for reduced bioluminescence revealed that the primary signalling defect was associated with the Rieske iron-sulfur subunit of the cytochrome bc1 complex. In common with the parent strain, a Rieske mutant exhibited defective PQS signalling, AQ production, rhlA expression and eDNA release that could be restored by genetic complementation. This defect was also phenocopied by deletion of cytB or cytC1. Thus, either lack of the Rieske sub-unit or mutation of cytochrome bc1 genes results in the perturbation of PQS-dependent autoinduction resulting in eDNA deficient biofilms, reduced antibiotic tolerance and compromised virulence factor production.


Assuntos
Biofilmes/crescimento & desenvolvimento , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Vesículas Extracelulares/genética , Pseudomonas aeruginosa/crescimento & desenvolvimento , Quinolonas/metabolismo , Percepção de Quorum , Sistema de Translocação de Argininas Geminadas/metabolismo , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes/efeitos dos fármacos , DNA Bacteriano/genética , Complexo III da Cadeia de Transporte de Elétrons/genética , Regulação Bacteriana da Expressão Gênica , Glicolipídeos/metabolismo , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/metabolismo , Piocianina/metabolismo , Sistema de Translocação de Argininas Geminadas/genética , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
12.
BMJ Open Respir Res ; 8(1)2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34452934

RESUMO

BACKGROUND: Despite currently available standard-of-care inhaled corticosteroid (ICS)/long-acting ß2-agonist therapies, a substantial proportion of patients with asthma remain inadequately controlled. This pooled analysis evaluated efficacy and safety of mometasone furoate/indacaterol acetate (MF/IND) versus fluticasone propionate/salmeterol xinafoate (FLU/SAL) in patients with inadequately controlled asthma. METHODS: This analysis included patients from PALLADIUM (NCT02554786) and IRIDIUM (NCT02571777) studies who received high-dose MF/IND (320/150 µg) or medium-dose MF/IND (160/150 µg) one time a day or high-dose FLU/SAL (500/50 µg) two times a day for 52 weeks. Reduction in asthma exacerbations, improvement in lung function, asthma control, and safety were evaluated for 52 weeks. RESULTS: In total, 3154 patients (high-dose MF/IND, n=1054; medium-dose MF/IND, n=1044; high-dose FLU/SAL, n=1056) were included. High-dose MF/IND showed 26%, 22% and 19% reductions in rate of severe, moderate or severe, and all (mild, moderate and severe) exacerbations versus high-dose FLU/SAL, respectively, over 52 weeks (all, p<0.05). High-dose MF/IND improved trough FEV1 versus high-dose FLU/SAL at weeks 26 (Δ, 43 mL, p=0.001) and 52 (Δ, 51 mL, p<0.001). Reductions in asthma exacerbation rate and improvement in trough FEV1 with medium-dose MF/IND were comparable with high-dose FLU/SAL over 52 weeks. All treatments improved Asthma Control Questionnaire-7 score from baseline to 52 weeks with no difference between treatments. Safety was comparable between high-dose MF/IND and high-dose FLU/SAL. CONCLUSIONS: One time a day, single-inhaler, high-dose MF/IND reduced asthma exacerbations and improved lung function versus two times a day, high-dose FLU/SAL in patients with inadequately controlled asthma. Similarly, improved outcomes were seen with one time a day, medium-dose MF/IND and two times a day, high-dose FLU/SAL, but at a lower ICS dose.


Assuntos
Asma , Paládio , Asma/tratamento farmacológico , Combinação de Medicamentos , Combinação Fluticasona-Salmeterol , Humanos , Indanos , Irídio , Furoato de Mometasona , Quinolonas
13.
Respir Investig ; 59(6): 871-875, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34433521

RESUMO

Spirometry is a crucial test used in the diagnosis and monitoring of patients with chronic obstructive pulmonary disease (COPD). Severe acute respiratory syndrome coronavirus 2 pandemic has posed numerous challenges in performing spirometry. Dynamic-ventilatory digital radiography (DR) provides sequential chest radiography images during respiration with lower doses of radiation than conventional X-ray fluoroscopy and computed tomography. Recent studies revealed that parameters obtained from dynamic DR are promising for evaluating pulmonary function of COPD patients. We report two cases of COPD evaluated by dynamic-ventilatory DR for pulmonary function and treatment efficacy and discuss the potential of dynamic DR for evaluating COPD therapy.


Assuntos
Pulmão/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Intensificação de Imagem Radiográfica/métodos , Radiografia Torácica/métodos , Idoso , Asma/diagnóstico , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Combinação de Medicamentos , Fluticasona/uso terapêutico , Fumarato de Formoterol/uso terapêutico , Glicopirrolato/análogos & derivados , Glicopirrolato/uso terapêutico , Humanos , Indanos/uso terapêutico , Pulmão/fisiologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinolonas/uso terapêutico , Espirometria , Brometo de Tiotrópio/uso terapêutico , Resultado do Tratamento
14.
Clin Lab ; 67(8)2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34383410

RESUMO

BACKGROUND: To investigate the epidemics of plasmid-mediated quinolone resistance (PMQR) gene in carbapenem-resistant Enterobacteriaceae (CRE) and the resistance mechanism. METHODS: We collected CRE bacteria isolated clinically between December 2017 and December 2018 for identification and drug sensitivity testing using a VITEK2 Compact Analyzer. Furthermore, genes, including qnrA, qnrB, qnrS, qepA, and acc (6') Ib-cr, were determined through the polymerase chain reaction and sequencing. The hori-zontal transfer of PMQR gene was validated through the plasmid conjugational test. RESULTS: Drug resistance rate of carbapenem-resistant Escherichia coli against quinolones was 100%, while the rate of carbapenem-resistant Klebsiella pneumoniae ranged from 15.56% to 33.33%. The detection rate of acc (6') Ib-cr was the highest (87.72%), followed by qnrB (77.19%) and qnrS (17.54%). Additionally, there were two bacteria carrying the qnrA gene (3.51%), but qepA gene was not isolated from the samples. In total, 84.21% of these bacteria carried 2 or 3 kinds of PMQR genes. Among 8 bacteria with successful plasmid conjugation, PMQR gene transfer was detected in all of them, but with no significant change in the minimum inhibitory concentration of quinolones. CONCLUSIONS: CRE remain sensitive to quinolones in spite of the high detection rate of PMQR gene in this hospital.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Enterobacteriaceae , Quinolonas , Antibacterianos/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Farmacorresistência Bacteriana/genética , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/tratamento farmacológico , Humanos , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Quinolonas/farmacologia
15.
Artigo em Inglês | MEDLINE | ID: mdl-34444027

RESUMO

We conducted environmental surveillance of antimicrobial resistance (AMR) bacteria in the Msimbazi river basin in Tanzania to determine the occurrence of extended-spectrum ß-lactamase (ESBL)-producing, carbapenem resistant Enterobacteriaceae (CRE) and quinolone resistant Escherichia coli and Klebsiella spp. A total of 213 Enterobacteriaceae isolates were recovered from 219 samples. Out of the recovered isolates, 45.5% (n = 97) were Klebsiella pneumoniae and 29.6% (n = 63) were Escherichia coli. K. pneumoniae isolates were more resistant in effluent (27.9%) compared to the E. coli (26.6%). The E. coli had a higher resistance in river water, sediment and crop soil than the K. pneumoniae (35 versus 25%), respectively. Higher resistance in K. pneumoniae was found in nalidixic acid (54.6%) and ciprofloxacin (33.3%) while the E. coli isolates were highly resistant to ciprofloxacin (39.7%) and trimethoprim/sulfamethoxazole (38%). Resistance increased from 28.3% in Kisarawe, where the river originates, to 59.9% in Jangwani (the middle section) and 66.7% in Upanga West, where the river enters the Indian Ocean. Out of 160 E. coli and K. pneumoniae isolates, 53.2% (n = 85) were resistant to more than three classes of the antibiotic tested, occurrence being higher among ESBL producers, quinolone resistant and carbapenem resistant strains. There is an urgent need to curb environmental contamination with antimicrobial agents in the Msimbazi Basin.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Quinolonas , Antibacterianos/farmacologia , Ecossistema , Escherichia coli , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Rios , Tanzânia , beta-Lactamases
16.
J Enzyme Inhib Med Chem ; 36(1): 1916-1921, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34461785

RESUMO

An earlier described three-component variant of the Castagnoli-Cushman reaction employing homophthalic anhydrides, carbonyl compound and ammonium acetate was applied towards the preparation of 1-oxo-3,4-dihydroisoquinoline-4-carboxamides with variable substituent in position 3. These compounds displayed inhibitory activity towards poly(ADP-ribose) polymerase (PARP), a clinically validated cancer target. The most potent compound (PARP1/2 IC50 = 22/4.0 nM) displayed the highest selectivity towards PARP2 in the series (selectivity index = 5.5), more advantageous ADME prameters compared to the clinically used PARP inhibitor Olaparib.


Assuntos
Acetatos/química , Antineoplásicos/química , Inibidores de Poli(ADP-Ribose) Polimerases/química , Poli(ADP-Ribose) Polimerases/metabolismo , Quinolonas/química , Acetatos/farmacologia , Sequência de Aminoácidos , Antineoplásicos/farmacologia , Sítios de Ligação , Dano ao DNA/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , NAD/metabolismo , Ftalazinas/farmacologia , Piperazinas/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Ligação Proteica , Conformação Proteica , Relação Estrutura-Atividade
17.
J Laryngol Otol ; 135(10): 911-917, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34399860

RESUMO

OBJECTIVE: This study aimed to identify pathogens isolated in acute external otitis cases and determine their distribution according to ages and seasons as well as investigate the susceptibility or resistance to the aminoglycoside and quinolone group antibiotics of which topical forms are available. METHOD: A total of 168 patients diagnosed with acute external otitis were evaluated retrospectively. Growing bacteria were identified according to the species by conventional methods. Antibiotic susceptibility status was determined for the growing bacteria. RESULTS: The most common bacteria detected were pseudomonas group bacteria (38.7 per cent). Resistance to the amikacin group of antibiotics was found to be the lowest and resistance to the ciprofloxacin group of antibiotics was the highest. CONCLUSION: External auditory canal cultures should be taken simultaneously with empirical treatment. Seasonal effect and age group should be taken into consideration in the choice of treatment and after questioning about chronic exposure to water. Empirical treatment should then be started.


Assuntos
Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Otite Externa/tratamento farmacológico , Otite Externa/microbiologia , Doença Aguda , Administração Tópica , Adulto , Fatores Etários , Amicacina/administração & dosagem , Amicacina/uso terapêutico , Aminoglicosídeos/administração & dosagem , Aminoglicosídeos/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Bactérias/crescimento & desenvolvimento , Ciprofloxacina/administração & dosagem , Ciprofloxacina/uso terapêutico , Resistência Microbiana a Medicamentos/fisiologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana/estatística & dados numéricos , Pessoa de Meia-Idade , Otite Externa/diagnóstico , Pseudomonas/isolamento & purificação , Quinolonas/administração & dosagem , Quinolonas/uso terapêutico , Estudos Retrospectivos , Estações do Ano
18.
Molecules ; 26(16)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34443308

RESUMO

A new series of hybrid molecules containing cinnamic acid and 2-quinolinone derivatives were designed and synthesized. Their structures were confirmed by 1H-NMR, 13C-NMR and mass analyses. All the synthesized hybrid molecules were assessed for their in vitro antiproliferative activity against more than one cancer cell lines. Compound 3-(3,5-dibromo-7,8-dihydroxy-4-methyl-2-oxoquinolin-1(2H)-ylamino)-3-phenylacrylic acid (5a) with IC50 = 1.89 µM against HCT-116 was proved to the most potent compound in this study, as compared to standard drug staurosporin. DNA flow cytometry assay of compound 5a revealed G2/M phase arrest and pre-G1 apoptosis. Annexin V-FITC showed that the percentage of early and late apoptosis was increased. The results of topoisomerase enzyme inhibition activity showed that the hybrid molecule 5a displays potent inhibitory activity compared with control.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Cinamatos/síntese química , Cinamatos/farmacologia , Desenho de Fármacos , Quinolonas/síntese química , Quinolonas/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cinamatos/química , DNA Topoisomerases Tipo II/metabolismo , Humanos , Concentração Inibidora 50 , Simulação de Acoplamento Molecular , Quinolonas/química , Inibidores da Topoisomerase/farmacologia
19.
Clin Drug Investig ; 41(9): 785-794, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34333742

RESUMO

BACKGROUND AND OBJECTIVE: In asthma, symptom control is a primary goal that is not consistently met with available treatment options. The first commercially available fixed-dose combination in a single inhaler of a long-acting beta-agonist (indacaterol, IND), an inhaled corticosteroid (mometasone furoate, MF) and a long-acting muscarinic antagonist (glycopyrronium, GLY) has shown promising clinical results in phase III trials. The aim of the present study is to evaluate the cost-utility of IND/GLY/MF fixed-dose combination relative to a combination of salmeterol/fluticasone and tiotropium or salmeterol/fluticasone or IND/MF in adult patients with asthma, from the Italian Health Service (NHS) perspective. METHODS: A two-state and 4-week cycle Markov model was used to estimate lifetime clinical outcomes and costs. Patients entered the model in stable disease and could experience a non-fatal exacerbation event. The exacerbation rate is dependent upon the therapy a patient is receiving, as per the IND/GLY/MF clinical trials. The impact of each type of exacerbation is accounted by applying a utility decrement, obtained from the literature, and a treatment cost. Utility values were obtained from the EQ-5D questionnaires in the IND/GLY/MF clinical trials. Lifetime costs considered in the analysis were drugs and exacerbation management. Probabilistic sensitivity analyses were carried out, with the aim of evaluating the impact of uncertainty on input parameters. RESULTS: IND/GLY/MF is associated with a higher quality of life [+ 0.25 quality-adjusted life-year (QALY)] than salmeterol/fluticasone plus tiotropium, with an incremental cost of -€3213.90. The incremental cost-utility ratio indicates dominance. At a threshold of €5000 per QALY, IND/GLY/MF has nearly a 100% probability of being cost effective. IND/GLY/MF is associated with a higher quality of life (+ 0.21 QALY) than salmeterol/fluticasone, with an incremental cost of €2547.76. Incremental cost-utility ratio results in €11,897 per QALY. At a threshold of €20,000 per QALY, IND/GLY/MF has nearly a 100% probability of being cost effective. IND/GLY/MF is associated with a higher quality of life (+ 0.34 QALY) than IND/MF, with an incremental cost of €4745.91. Incremental cost-utility ratio results in €14,088 per QALY. At a threshold of €20,000 per QALY, IND/GLY/MF has nearly a 100% probability of being cost effective. CONCLUSION: The results indicate that IND/GLY/MF is cost effective against the considered comparators in a cohort representative of adult patients with asthma in Italy.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Acetatos/uso terapêutico , Corticosteroides/uso terapêutico , Adulto , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Análise Custo-Benefício , Combinação de Medicamentos , Glicopirrolato , Humanos , Indanos , Furoato de Mometasona/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Qualidade de Vida , Quinolonas , Resultado do Tratamento
20.
Sci Rep ; 11(1): 16856, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34413359

RESUMO

P-gp-associated multidrug resistance is a major impediment to the success of chemotherapy. With the aim of finding non-toxic and effective P-gp inhibitors, we investigated a panel of quinolin-2-one-pyrimidine hybrids. Among the active compounds, two of them significantly increased intracellular doxorubicin and rhodamine 123 accumulation by inhibiting the efflux mediated by P-gp and restored doxorubicin toxicity at nanomolar range. Structure-activity relationships showed that the number of methoxy groups, an optimal length of the molecule in its extended conformation, and at least one flexible methylene group bridging the quinolinone to the moiety bearing the pyrimidine favored the inhibitory potency of P-gp. The best compounds showed a similar binding pattern and interactions to those of doxorubicin and tariquidar, as revealed by MD and hybrid QM/MM simulations performed with the recent experimental structure of P-gp co-crystallized with paclitaxel. Analysis of the molecular interactions stabilizing the different molecular complexes determined by MD and QTAIM showed that binding to key residues from TMH 4-7 and 12 is required for inhibition.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Pirimidinas/farmacologia , Quinolonas/farmacologia , Morte Celular/efeitos dos fármacos , Humanos , Células K562 , Simulação de Dinâmica Molecular , Transporte Proteico/efeitos dos fármacos , Pirimidinas/química , Pirimidinas/toxicidade , Quinolonas/química , Quinolonas/toxicidade , Rodamina 123/metabolismo , Relação Estrutura-Atividade , Termodinâmica
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