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1.
BMC Oral Health ; 24(1): 645, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824583

RESUMO

OBJECTIVES: This study aimed to evaluate the preventive and therapeutic effects of rebamipide gargle in comparison with benzydamine in head and neck cancer patients undergoing radiotherapy with or without chemotherapy. MATERIALS AND METHODS: Phase III randomized clinical trial was conducted from January 2021 till August 2022 on one hundred patients with head and neck cancer receiving high doses of radiotherapy. These patients were equally allocated into either rebamipide group or benzydamine group, The measured outcomes were the incidence of oral mucositis ≥ grade1, according to the WHO mucositis scale, in addition to the duration, and the onset of oral mucositis. RESULTS: There was no statistically significant difference between the two groups, regarding the incidence of a severe grade of oral mucositis (WHO grades 3), as well as the onset and duration of oral mucositis. Both gargles succeeded to prevent the development of WHO grade 4 oral mucositis. Side effects reported were mainly burning sensation in benzydamine group and nausea in rebamipide group. CONCLUSION: Rebamipide mouthwash was as beneficial as benzydamine mouthwash in minimizing the incidence of severe oral mucositis induced by treatment of head and neck cancer. However, rebamipide gargle proved to be superior to benzydamine in terms of reduction in the severity of the radiation-induced oral mucositis. TRIAL REGISTRATION: The trial was registered in the protocol Registration and Result system of Clinical Trials (Registration ID: NCT04685395)0.28-12-2020.


Assuntos
Alanina , Benzidamina , Neoplasias de Cabeça e Pescoço , Antissépticos Bucais , Quinolonas , Estomatite , Humanos , Estomatite/prevenção & controle , Estomatite/etiologia , Neoplasias de Cabeça e Pescoço/radioterapia , Benzidamina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Feminino , Quinolonas/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Antissépticos Bucais/uso terapêutico , Quimiorradioterapia/efeitos adversos , Lesões por Radiação/prevenção & controle , Idoso , Adulto
2.
PLoS One ; 19(6): e0305320, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38861561

RESUMO

BACKGROUND: Rebamipide has been widely co-prescribed with non-steroidal anti-inflammatory drugs (NSAIDs) in Japan for decades. This study aimed to evaluate the effectiveness of rebamipide in preventing upper gastrointestinal bleeding in new users of NSAIDs without risk factors of NSAID-induced ulcers other than age. METHODS: A nested case-control study was conducted using medical claims data of 1.66 million inhabitants of 17 municipalities participating in Japan's Longevity Improvement & Fair Evidence study. The cohort entry (t0) corresponded to a new user of NSAIDs for osteoarthritis or low back pain. Patients with risk factors of NSAID-induced ulcers other than age were excluded. Cases were defined as patients who underwent gastroscopy for upper gastrointestinal bleeding (occurrence date was defined as index date). A maximum of 10 controls were selected from non-cases at the index date of each case by matching sex, age, follow-up time, and type and dosage of NSAIDs. Exposure to rebamipide was defined as prescription status from t0 to index date: Non-user (rebamipide was not co-prescribed during the follow-up period), Continuous-user (rebamipide was co-prescribed from t0 with the same number of tablets as NSAIDs), and Irregular-user (neither Non-user nor Continuous-user). Conditional logistic regression analysis was conducted to estimate each category's odds ratio compared to non-users. FINDINGS: Of 67,561 individuals who met the inclusion criteria, 215 cases and 1,516 controls were selected. Compared with that of Non-users, the odds ratios and 95% confidence interval were 0.65 (0.44-0.96) for Continuous-users and 2.57 (1.73-3.81) for Irregular-users. CONCLUSIONS: Continuous co-prescription of rebamipide significantly reduced the risk of upper gastrointestinal bleeding in an Asian cohort of new users of NSAIDs with osteoarthritis or low back pain without risk factors other than age.


Assuntos
Alanina , Anti-Inflamatórios não Esteroides , Hemorragia Gastrointestinal , Quinolonas , Humanos , Alanina/análogos & derivados , Alanina/uso terapêutico , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Inflamatórios não Esteroides/administração & dosagem , Masculino , Quinolonas/efeitos adversos , Quinolonas/uso terapêutico , Quinolonas/administração & dosagem , Feminino , Estudos de Casos e Controles , Idoso , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/prevenção & controle , Pessoa de Meia-Idade , Antiulcerosos/uso terapêutico , Antiulcerosos/efeitos adversos , Antiulcerosos/administração & dosagem , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Osteoartrite/tratamento farmacológico , Japão/epidemiologia , Fatores de Risco
3.
Sci Rep ; 14(1): 13306, 2024 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858411

RESUMO

This study aimed to compare the clinical efficacy and investigate patients' preferences for two mucin secretagogues in the treatment of dry eye disease (DED). Thirty patients with DED were randomly treated with either 3% diquafosol or 2% rebamipide ophthalmic solution for 4 weeks, followed by an additional 4-week treatment using the other eye drop after a 2-week washout period. Objective and subjective assessments, including the corneal and conjunctival staining score, tear breakup time (TBUT), Schirmer 1 test, tear osmolarity, tear matrix metalloproteinase-9 (MMP-9), lipid layer thickness (LLT) and ocular surface disease index (OSDI), were performed at baseline, 4 weeks, 6 weeks, and 10 weeks. Patient preferences were assessed based on four categories (comfort, efficacy, convenience, willingness to continue) using a questionnaire and the overall subjective satisfaction score for each drug was obtained at the end of the trial. In total, 28 eyes from 28 patients were included in the analysis. Both diquafosol and rebamipide significantly improved the OSDI (p = 0.033 and 0.034, respectively), TBUT (p < 0.001 and 0.026, respectively), and corneal (p < 0.001 and 0.001, respectively) and conjunctival (p = 0.017 and 0.042, respectively) staining after 4 weeks of treatment. An increase in Schirmer test scores was observed only after rebamipide treatment (p = 0.007). No significant changes were detected in tear osmolarity, MMP-9, and LLT following both treatments. The patients' preference was slightly greater for diquafosol (46.4%) than rebamipide (36.7%), presumably due to rebamipide's bitter taste. The self-efficacy of both drugs and overall satisfaction scores were comparable. These findings indicate that two mucin secretagogues showed comparable effects in ameliorating symptoms and improving signs (TBUT, corneal and conjunctival staining) in patients with DED.


Assuntos
Alanina , Síndromes do Olho Seco , Mucinas , Quinolonas , Nucleotídeos de Uracila , Humanos , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Quinolonas/uso terapêutico , Estudos Prospectivos , Mucinas/metabolismo , Nucleotídeos de Uracila/uso terapêutico , Nucleotídeos de Uracila/administração & dosagem , Alanina/análogos & derivados , Alanina/uso terapêutico , Idoso , Lágrimas/metabolismo , Estudos Cross-Over , Soluções Oftálmicas , Polifosfatos/uso terapêutico , Resultado do Tratamento , Adulto , Metaloproteinase 9 da Matriz/metabolismo
5.
Int J Immunopathol Pharmacol ; 38: 3946320241260262, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38876119

RESUMO

INTRODUCTION: TYK2 inhibitors and traditional natural drugs as promising drugs for psoriasis therapy are receiving increasing attention. They both affect different molecules of JAK/STAT pathway, but it is currently unclear whether their combination will enhance the effect on psoriasis. In this study, we used imiquimod (IMQ)-induced psoriasis mouse model to investigate the therapeutic effects of the combined administration of deucravacitinib (TYK2 inhibitor) and shikonin. METHODS: Aldara cream containing 5% IMQ was used to topically treat the dorsal skin of each mouse for a total of six consecutive days to induce psoriasis. The psoriasis area and severity index (PASI) scores were recorded every day. On the 7th day, skin tissues were taken for histopathological examination and the content of cytokines in skin were evaluated. The frequency of immune cells in peripheral blood, spleen and skin were detected through flow cytometry. RESULTS: Compared to the vehicle control group, the psoriasis symptoms and immune disorder improved significantly in the combination therapy group and deucravacitinib treatment group on the 7th day, and the expressions of p-STAT3 and Ki67 in skin were reduced as well. Moreover, the combined treatment of deucravacitinib and shikonin for psoriasis was superior to the monotherapy group, especially in inhibiting abnormal capillaries proliferation, reducing immune cells infiltration and decreasing the concentration of IL-12p70 in skin. CONCLUSION: The combination of deucravacitinib and shikonin is a promising clinical application.


Assuntos
Quimioterapia Combinada , Imiquimode , Naftoquinonas , Psoríase , Pele , Animais , Psoríase/tratamento farmacológico , Psoríase/induzido quimicamente , Naftoquinonas/farmacologia , Naftoquinonas/uso terapêutico , Camundongos , Pele/efeitos dos fármacos , Pele/patologia , Pele/metabolismo , Modelos Animais de Doenças , Citocinas/metabolismo , Camundongos Endogâmicos BALB C , Masculino , Feminino , Benzimidazóis , Quinolonas
6.
Georgian Med News ; (348): 151-153, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38807409

RESUMO

Rebamipide contributes to the improvement of blood supply of the GI mucosa, activates its barrier function, activates alkaline secretion of the stomach, increases proliferation and metabolism of epithelial cells of the GI tract, cleanses the mucosa from hydroxyl radicals and suppresses superoxides, produced by polymorphonuclear leukocytes and neutrophils in the presence of Helicobacter pylori, protects the GI mucosa from bacterial invasion and the damaging effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the mucosa. Rebamipide, originally developed as a treatment for gastric ulcers, has attracted the attention of researchers as a potential drug for the treatment of UC due to its ability to stimulate mucus production, reduce oxidative stress, and decrease inflammation. Due to the presence of these properties, it is hypothesized that rebamipide may have a protective effect on the intestinal mucosa during prolonged inflammation, making it a promising candidate for inclusion in therapeutic strategies for ulcerative colitis. The results of this study suggest that rebamipide holds potential therapeutic benefits for the treatment of ulcerative colitis.


Assuntos
Alanina , Colite Ulcerativa , Quinolonas , Quinolonas/uso terapêutico , Quinolonas/farmacologia , Alanina/análogos & derivados , Alanina/uso terapêutico , Alanina/farmacologia , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Ratos , Antiulcerosos/uso terapêutico , Antiulcerosos/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismo , Masculino , Progressão da Doença , Modelos Animais de Doenças , Ratos Wistar
7.
Biol Pharm Bull ; 47(5): 1033-1042, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38797668

RESUMO

Eye drops, including solutions and suspensions, are essential dosage forms to treat ophthalmic diseases, with poorly water-soluble drugs typically formulated as ophthalmic suspensions. In addition to low bioavailability, suspensions exhibit limited efficacy, safety, and usability due to the presence of drug particles. Improving bioavailability can reduce the drug concentrations and the risk of problems associated with suspended drug particles. However, practical penetration enhancers capable of improving bioavailability remain elusive. Herein, we focused on penetratin (PNT), a cell-penetrating peptide (CPP) that promotes active cellular transport related to macromolecule uptake, such as micropinocytosis. According to the in vitro corneal uptake study using a reconstructed human corneal epithelial tissue model, LabCyte CORNEA-MODEL24, PNT enhanced the uptake of Fluoresbrite® YG carboxylate polystyrene microspheres without covalent binding. In an ex vivo porcine eye model, the addition of 10 µM PNT to rebamipide ophthalmic suspension markedly improved the corneal uptake of rebamipide; however, the addition of 100 µM PNT was ineffective due to potentially increased particle size by aggregation. This article provides basic information on the application of PNT as a penetration enhancer in ophthalmic suspensions, including the in vitro and ex vivo studies mentioned above, as well as the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay and storage stability at different pH values.


Assuntos
Peptídeos Penetradores de Células , Córnea , Soluções Oftálmicas , Suspensões , Animais , Peptídeos Penetradores de Células/química , Peptídeos Penetradores de Células/administração & dosagem , Soluções Oftálmicas/administração & dosagem , Humanos , Córnea/metabolismo , Córnea/efeitos dos fármacos , Suínos , Quinolonas/administração & dosagem , Quinolonas/farmacocinética , Quinolonas/química , Administração Oftálmica , Disponibilidade Biológica , Epitélio Corneano/efeitos dos fármacos , Epitélio Corneano/metabolismo , Tamanho da Partícula , Alanina/análogos & derivados
8.
J Environ Sci (China) ; 144: 185-198, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38802230

RESUMO

There is a large surface-groundwater exchange downstream of wastewater treatment plants (WWTPs), and antibiotics upstream may influence sites downstream of rivers. Thus, samples from 9 effluent-receiving urban rivers (ERURs) and 12 groundwater sites were collected in Shijiazhuang City in December 2020 and April 2021. For ERURs, 8 out of 13 target quinolone antibiotics (QNs) were detected, and the total concentration of QNs in December and April were 100.6-4,398 ng/L and 8.02-2,476 ng/L, respectively. For groundwater, all target QNs were detected, and the total QNs concentration was 1.09-23.03 ng/L for December and 4.54-170.3 ng/L for April. The distribution of QNs was dissimilar between ERURs and groundwater. Most QN concentrations were weakly correlated with land use types in the system. The results of a positive matrix factorization model (PMF) indicated four potential sources of QNs in both ERURs and groundwater, and WWTP effluents were the main source of QNs. From December to April, the contribution of WWTP effluents and agricultural emissions increased, while livestock activities decreased. Singular value decomposition (SVD) results showed that the spatial variation of most QNs was mainly contributed by sites downstream (7.09%-88.86%) of ERURs. Then, a new method that combined the results of SVD and PMF was developed for a specific-source-site risk quotient (SRQ), and the SRQ for QNs was at high level, especially for the sites downstream of WWTPs. Regarding temporal variation, the SRQ for WWTP effluents, aquaculture, and agricultural emissions increased. Therefore, in order to control the antibiotic pollution, more attention should be paid to WWTP effluents, aquaculture, and agricultural emission sources for the benefit of sites downstream of WWTPs.


Assuntos
Antibacterianos , Monitoramento Ambiental , Água Subterrânea , Quinolonas , Rios , Águas Residuárias , Poluentes Químicos da Água , Água Subterrânea/química , Poluentes Químicos da Água/análise , China , Rios/química , Quinolonas/análise , Antibacterianos/análise , Águas Residuárias/química , Cidades , Eliminação de Resíduos Líquidos/métodos
9.
Front Biosci (Landmark Ed) ; 29(5): 174, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38812296

RESUMO

BACKGROUND: Colorectal cancer (CRC) is a major cause of mortality and morbidity. A study proved that brexpiprazole, as a novel dopamine receptor partial agonist, can also prevent CRC cell proliferation. Therefore, clarifying the molecular mechanism of brexpiprazole is vital to developing a novel therapeutic strategy for CRC. METHODS: The effect of brexpiprazole on human colorectal cancer cell proliferation was measured with Cell Counting Kit-8 (CCK-8) kits. Cell migration capability was measured using wound healing and transwell. Cell apoptosis was evaluated with a flow cytometer. Western blots and immunohistochemical staining were used to evaluate protein expression. The effects observed in vitro were also confirmed in xenograft models. RESULTS: Brexpiprazole remarkably inhibited the proliferation, suppressed the migration ability, and induced apoptosis of colorectal cancer cells. Mechanism study showed that brexpiprazole exerted these effects by inhibiting the EGFR pathway. Brexpiprazole enhanced HCT116 cells' sensitivity to cetuximab, and a combination of brexpiprazole and cetuximab inhibited xenograft tumor growth in vivo. CONCLUSIONS: Our finding suggested that brexpiprazole inhibits proliferation, promotes apoptosis, and enhances CRC cells' sensitivity to cetuximab by regulating the EGFR pathway and it might be an efficacious treatment strategy for CRC.


Assuntos
Apoptose , Movimento Celular , Proliferação de Células , Cetuximab , Neoplasias Colorretais , Receptores ErbB , Camundongos Nus , Quinolonas , Tiofenos , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Tiofenos/farmacologia , Tiofenos/uso terapêutico , Receptores ErbB/metabolismo , Receptores ErbB/antagonistas & inibidores , Animais , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Cetuximab/farmacologia , Quinolonas/farmacologia , Movimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Camundongos , Células HCT116 , Camundongos Endogâmicos BALB C , Progressão da Doença
10.
Respir Med ; 228: 107664, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38759874

RESUMO

BACKGROUND: Impaired glycemic control and the subsequent development of Cystic fibrosis Related Diabetes (CFRD) are prevalent complications, affecting up to 50 % of adults with cystic fibrosis (CF). CFTR modulator (CFTRm) therapies improve pulmonary functions, reduce exacerbation rates, increase survival in people with CF (pwCF) and appear to have a positive effect on extrapulmonary manifestations, such as nutritional state, improvements in upper respiratory symptoms, and quality of life. Initial findings indicate that CFTRm may have a positive impact on short-term glycemic control; however, long-term effects remain uncertain at present. METHODS: In this retrospective study, data were collected and analyzed on 15 pwCF, ages 13-37 years, started on CFTRm therapy. Oral Glucose Tolerance Test (OGTT) results were compared pre- and post-CFTRm therapy. RESULTS: The 120-min OGTT value decreased from 159.7 mg/dL to 130.4 mg/dL post-CFTRm (p = 0.047). The average time elapsed between the two OGTTs was 49.87 months (ranging 9-157 months, median 38 months). Glycemic status improved in six pwCF (two CFRD to normal (NGT)/indeterminate (INDET) glucose tolerance; two impaired glucose tolerance (IGT) to INDET; two INDET to NGT) and worsened in one (IGT to CFRD). Six pwCF and NGT remained stable with no changes in glycemic status throughout the follow-up period. CONCLUSIONS: CFTRm therapy may decelerate the glycemic control deterioration in pwCF over an extended period. These findings indicate the need for periodic OGTTs following the initiation of CFTRm therapy to appropriately adjust insulin requirements and prevent hypoglycemia. Further larger cohorts are required to authenticate and substantiate these findings.


Assuntos
Glicemia , Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Teste de Tolerância a Glucose , Humanos , Fibrose Cística/tratamento farmacológico , Fibrose Cística/fisiopatologia , Fibrose Cística/complicações , Adolescente , Adulto , Estudos Retrospectivos , Masculino , Feminino , Adulto Jovem , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Glicemia/metabolismo , Glicemia/efeitos dos fármacos , Aminofenóis/uso terapêutico , Quinolonas/uso terapêutico , Aminopiridinas/uso terapêutico , Benzodioxóis/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Controle Glicêmico/métodos , Fatores de Tempo , Glucose/metabolismo , Intolerância à Glucose/tratamento farmacológico , Intolerância à Glucose/metabolismo
11.
BMC Pulm Med ; 24(1): 260, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38807122

RESUMO

BACKGROUND: Physical activity is a crucial demand on cystic fibrosis treatment management. The highest value of oxygen uptake (VO2peak) is an appropriate tool to evaluate the physical activity in these patients. However, there are several other valuable CPET parameters describing exercise tolerance (Wpeak, VO2VT1, VO2VT2, VO2/HRpeak, etc.), and helping to better understand the effect of specific treatment (VE, VT, VD/VT etc.). Limited data showed ambiguous results of this improvement after CFTR modulator treatment. Elexacaftor/tezacaftor/ivacaftor medication improves pulmonary function and quality of life, whereas its effect on CPET has yet to be sufficiently demonstrated. METHODS: We performed a single group prospective observational study of 10 adolescent patients with cystic fibrosis who completed two CPET measurements between January 2019 and February 2023. During this period, elexacaftor/tezacaftor/ivacaftor treatment was initiated in all of them. The first CPET at the baseline was followed by controlled CPET at least one year after medication commencement. We focused on interpreting the data on their influence by the novel therapy. We hypothesized improvements in cardiorespiratory fitness following treatment. We applied the Wilcoxon signed-rank test. The data were adjusted for age at the time of CPET to eliminate bias of aging in adolescent patients. RESULTS: We observed significant improvement in peak workload, VO2 peak, VO2VT1, VO2VT2, VE/VCO2 slope, VE, VT, RQ, VO2/HR peak and RR peak. The mean change in VO2 peak was 5.7 mL/kg/min, or 15.9% of the reference value (SD ± 16.6; p= 0.014). VO2VT1 improved by 15% of the reference value (SD ± 0.1; p= 0.014), VO2VT2 improved by 0.5 (SD ± 0.4; p= 0.01). There were no differences in other parameters. CONCLUSION: Exercise tolerance improved after elexacaftor/tezacaftor/ivacaftor treatment initiation. We suggest that the CFTR modulator alone is not enough for recovering physical decondition, but should be supplemented with physical activity and respiratory physiotherapy. Further studies are needed to examine the effect of CFTR modulators and physical therapy on cardiopulmonary exercise tolerance.


Assuntos
Aminofenóis , Benzodioxóis , Fibrose Cística , Combinação de Medicamentos , Indóis , Pirazóis , Piridinas , Quinolonas , Humanos , Fibrose Cística/tratamento farmacológico , Fibrose Cística/fisiopatologia , Adolescente , Masculino , Feminino , Estudos Prospectivos , Projetos Piloto , Indóis/uso terapêutico , Benzodioxóis/uso terapêutico , Quinolonas/uso terapêutico , Aminofenóis/uso terapêutico , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Aptidão Cardiorrespiratória , Teste de Esforço , Pirróis/uso terapêutico , Tolerância ao Exercício/efeitos dos fármacos , Consumo de Oxigênio , Criança , Pirrolidinas
12.
Molecules ; 29(10)2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38792155

RESUMO

With the rising incidence of various diseases in China and the constant development of the pharmaceutical industry, there is a growing demand for floxacin-type antibiotics. Due to the large-scale production and high cost of waste treatment, the parent drug and its metabolites constantly enter the water environment through domestic sewage, production wastewater, and other pathways. In recent years, the pollution of the aquatic environment by floxacin has become increasingly serious, making the technology to degrade floxacin in the aquatic environment a research hotspot in the field of environmental science. Metal-organic frameworks (MOFs), as a new type of porous material, have attracted much attention in recent years. In this paper, four photocatalytic materials, MIL-53(Fe), NH2-MIL-53(Fe), MIL-100(Fe), and g-C3N4, were synthesised and applied to the study of the removal of ofloxacin and enrofloxacin. Among them, the MIL-100(Fe) material exhibited the best photocatalytic effect. The degradation efficiency of ofloxacin reached 95.1% after 3 h under visible light, while enrofloxacin was basically completely degraded. The effects of different materials on the visible photocatalytic degradation of the floxacin were investigated. Furthermore, the photocatalytic mechanism of enrofloxacin and ofloxacin was revealed by the use of three trappers (▪O2-, h+, and ▪OH), demonstrating that the role of ▪O2- promoted the degradation effect of the materials under photocatalysis.


Assuntos
Estruturas Metalorgânicas , Quinolonas , Poluentes Químicos da Água , Estruturas Metalorgânicas/química , Catálise , Quinolonas/química , Poluentes Químicos da Água/química , Fotólise , Luz , Ofloxacino/química , Processos Fotoquímicos , Antibacterianos/química , Enrofloxacina/química
13.
PLoS One ; 19(5): e0304555, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38820269

RESUMO

Inflammation is a key driver in the pathogenesis of cystic fibrosis (CF). We assessed the effectiveness of elexacaftor/tezacaftor/ivacaftor (ETI) therapy on downregulating systemic and immune cell-derived inflammatory cytokines. We also monitored the impact of ETI therapy on clinical outcome. Adults with CF, heterozygous for F508del (n = 19), were assessed at baseline, one month and three months following ETI therapy, and clinical outcomes were measured, including sweat chloride, lung function, weight, neutrophil count and C-reactive protein (CRP). Cytokine quantifications were measured in serum and following stimulation of peripheral blood mononuclear cells (PBMCs) with lipopolysaccharide (LPS) and adenosine triphosphate and analysed using LEGEND plex™ Human Inflammation Panel 1 by flow cytometry (n = 19). ASC specks were measured in serum and caspase-1 activity and mRNA levels determined from stimulated PBMCs were determined. Patients remained stable over the study period. ETI therapy resulted in decreased sweat chloride concentrations (p < 0.0001), CRP (p = 0.0112) and neutrophil count (p = 0.0216) and increased percent predicted forced expiratory volume (ppFEV1) (p = 0.0399) from baseline to three months, alongside a trend increase in weight. Three months of ETI significantly decreased IL-18 (p< 0.0011, p < 0.0001), IL-1ß (p<0.0013, p = 0.0476), IL-6 (p = 0.0109, p = 0.0216) and TNF (p = 0.0028, p = 0.0033) levels in CF serum and following PBMCs stimulation respectively. The corresponding mRNA levels were also found to be reduced in stimulated PBMCs, as well as reduced ASC specks and caspase-1 levels, indicative of NLRP3-mediated production of pro-inflammatory cytokines, IL-1ß and IL-18. While ETI therapy is highly effective at reducing sweat chloride and improving lung function, it also displays potent anti-inflammatory properties, which are likely to contribute to improved long-term clinical outcomes.


Assuntos
Aminofenóis , Anti-Inflamatórios , Benzodioxóis , Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Citocinas , Indóis , Quinolonas , Humanos , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Benzodioxóis/uso terapêutico , Benzodioxóis/farmacologia , Adulto , Aminofenóis/uso terapêutico , Feminino , Indóis/uso terapêutico , Indóis/farmacologia , Masculino , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Quinolonas/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Citocinas/sangue , Pirazóis/uso terapêutico , Pirazóis/farmacologia , Adulto Jovem , Piridinas/uso terapêutico , Piridinas/farmacologia , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Proteína C-Reativa/metabolismo , Pirróis/uso terapêutico , Pirróis/farmacologia , Suor/química , Suor/metabolismo , Pirrolidinas
14.
BMC Microbiol ; 24(1): 175, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773370

RESUMO

BACKGROUND: Data about the prevalence of plasmid-mediated quinolone resistance (PMQR) and extended-spectrum beta-lactamase (ESBL) production in P. aeruginosa compared to the Enterobacteriaceae family is limited. The availability of limited therapeutic options raises alarming concerns about the treatment of multidrug-resistant P. aeruginosa. This study aimed to assess the presence of PMQR and ESBL genes among P. aeruginosa strains. METHODS: Fifty-six P. aeruginosa strains were isolated from 330 patients with different clinical infections. Phenotypically fluoroquinolone-resistant isolates were tested by PCR for the presence of six PMQR genes. Then, blaTEM, blaSHV, and blaCTX-M type ESBL genes were screened to study the co-existence of different resistance determinants. RESULTS: Overall, 22/56 (39.3%) of the studied P. aeruginosa isolates were phenotypically resistant to fluoroquinolones. PMQR-producing P. aeruginosa isolates were identified in 20 isolates (90.9%). The acc(6')-Ib-cr was the most prevalent PMQR gene (77.3%). The qnr genes occurred in 72.7%, with the predominance of the qnrA gene at 54.5%, followed by the qnrS gene at 27.3%, then qnrB and qnrC at 22.7%. The qepA was not detected in any isolate. The acc(6')-Ib-cr was associated with qnr genes in 65% of positive PMQR isolates. Significant differences between the fluoroquinolone-resistant and fluoroquinolone-susceptible isolates in terms of the antibiotic resistance rates of amikacin, imipenem, and cefepime (P value < 0.0001) were found. The ESBL genes were detected in 52% of cephalosporin-resistant P. aeruginosa isolates. The most frequent ESBL gene was blaCTX-M (76.9%), followed by blaTEM (46.2%). No isolates carried the blaSHV gene. The acc(6')-Ib-cr gene showed the highest association with ESBL genes, followed by the qnrA gene. The correlation matrix of the detected PMQR and ESBL genes indicated overall positive correlations. The strongest and most highly significant correlation was between qnrA and acc(6')-Ib-cr (r = 0.602) and between qnrA and blaCTX-M (r = 0.519). CONCLUSION: A high prevalence of PMQR genes among the phenotypic fluoroquinolone-resistant P. aeruginosa isolates was detected, with the co-carriage of different PMQR genes. The most frequent PMQR was the acc(6')-Ib-cr gene. Co-existence between PMQR and ESBL genes was found, with 75% of PMQR-positive isolates carrying at least one ESBL gene. A high and significant correlation between the ESBL and PMQR genes was detected.


Assuntos
Antibacterianos , Testes de Sensibilidade Microbiana , Plasmídeos , Infecções por Pseudomonas , Pseudomonas aeruginosa , Quinolonas , beta-Lactamases , Humanos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Pseudomonas aeruginosa/enzimologia , beta-Lactamases/genética , Egito , Plasmídeos/genética , Antibacterianos/farmacologia , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/epidemiologia , Quinolonas/farmacologia , Farmacorresistência Bacteriana/genética , Farmacorresistência Bacteriana Múltipla/genética , Fluoroquinolonas/farmacologia , Adulto , Feminino , Masculino
15.
Biochemistry ; 63(10): 1278-1286, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38690676

RESUMO

Metallo-ß-lactamases (MBL) deactivate ß-lactam antibiotics through a catalytic reaction caused by two zinc ions at the active center. Since MBLs deteriorate a wide range of antibiotics, they are dangerous factors for bacterial multidrug resistance. In this work, organic synthesis, computational design, and crystal structure analysis were performed to obtain potent MBL inhibitors based on a previously identified hit compound. The hit compound comprised 3,4-dihydro-2(1H)-quinolinone linked with a phenyl-ether-methyl group via a thiazole ring. In the first step, the thiazole ring was replaced with a tertiary amine to avoid the planar structure. In the second step, we virtually modified the compound by keeping the quinolinone backbone. Every modified compound was bound to a kind of MBL, imipenemase-1 (IMP-1), and the binding pose was optimized by a molecular mechanics calculation. The binding scores were evaluated for the respective optimized binding poses. Given the predicted binding poses and calculated binding scores, candidate compounds were determined for organic syntheses. The inhibitory activities of the synthesized compounds were measured by an in vitro assay for two kinds of MBLs, IMP-1 and New Delhi metallo-ß-lactamase (NDM-1). A quinolinone connected with an amine bound with methyl-phenyl-ether-propyl and cyclohexyl-ethyl showed a 50% inhibitory concentration of 4.8 µM. An X-ray crystal analysis clarified the binding structure of a synthesized compound to IMP-1. The δ-lactam ring of quinolinone was hydrolyzed, and the generated carboxyl group was coordinated with zinc ions. The findings on the chemical structure and binding pose are expected to be a base for developing MBL inhibitors.


Assuntos
Inibidores de beta-Lactamases , beta-Lactamases , beta-Lactamases/química , beta-Lactamases/metabolismo , Inibidores de beta-Lactamases/farmacologia , Inibidores de beta-Lactamases/química , Cristalografia por Raios X , Desenho de Fármacos , Simulação de Acoplamento Molecular , Antibacterianos/farmacologia , Antibacterianos/química , Quinolonas/química , Quinolonas/farmacologia , Quinolonas/metabolismo
16.
BMJ Case Rep ; 17(5)2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38719244

RESUMO

Brexpiprazole is a relatively new drug that has no published research or applications within the paediatric population. Brexpiprazole targets multiple receptors and can manifest as multisystem symptoms when ingested in supratherapeutic quantities. In this report, we discuss the case of a child in early childhood who presented with delayed neurological and cardiac symptoms 24 hours after accidental ingestion of brexpiprazole. Due to delayed onset, this case highlights that a high index of suspicion and prolonged observation are necessary to appropriately manage brexpiprazole overdose or accidental ingestion.


Assuntos
Quinolonas , Tiofenos , Humanos , Tiofenos/efeitos adversos , Quinolonas/efeitos adversos , Quinolonas/intoxicação , Masculino , Overdose de Drogas , Pré-Escolar , Antipsicóticos/efeitos adversos , Feminino
17.
Acta Parasitol ; 69(2): 1275-1283, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38753101

RESUMO

PURPOSE: Toxoplasmosis is caused by the parasite Toxoplasma gondii (T. gondii). In immunocompetent individuals, the infection is often asymptomatic; however, in expectant mothers and those with immune system deficiencies, complications may arise. Consequently, there is a need for new drugs that cause minimal damage to host cells. The purpose of this study was to investigate the in vitro antiparasitic efficacy of quinolone-coumarin hybrids QC1-QC12, derived from quinolone antibacterials and novobiocin, against T. gondii. METHODS: The derivatives were compared with novobiocin and ciprofloxacin during testing, with pyrimethamine used as a positive control. We conducted the MTT assay to examine the anti-toxoplasmic effects of the test compounds and novobiocin. Evaluation included the infection and proliferation indices, as well as the size and number of plaques, based on the viability of both healthy and infected cells. RESULTS: The in vitro assays revealed that QC1, QC3, QC6, and novobiocin, with selectivity indices (SIs) of 7.27, 13.43, and 8.23, respectively, had the least toxic effect on healthy cells and the highest effect on infected cells compared to pyrimethamine (SI = 3.05). Compared to pyrimethamine, QC1, QC3, QC6, and novobiocin Without having a significant effect on cell viability, demonstrated a significant effect on reducing in both infection index and proliferation index, in addition to reducing the quantity and dimensions of plaques ( P < 0.05). CONCLUSION: Based on our results, QC1, QC3, QC6, and novobiocin due to their significant therapeutic effects could be considered as potential new leads in the development of novel anti-Toxoplasma agents.


Assuntos
Novobiocina , Quinolonas , Toxoplasma , Toxoplasma/efeitos dos fármacos , Novobiocina/farmacologia , Animais , Quinolonas/farmacologia , Quinolonas/química , Fluoroquinolonas/farmacologia , Cumarínicos/farmacologia , Cumarínicos/química , Antiprotozoários/farmacologia , Humanos , Sobrevivência Celular/efeitos dos fármacos , Testes de Sensibilidade Parasitária
19.
Food Chem ; 454: 139796, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38797102

RESUMO

This study aimed to present a selective and effective method for analyzing quinolones (QNs) in food matrix. Herein, a NiFe2O4-based magnetic sodium disulfonate covalent organic framework (NiFe2O4/COF) was prepared using a simple solvent-free grinding method, and was adopted as a selective adsorbent for magnetic solid phase extraction of QNs. Coupled with UHPLC-Q-Orbitrap HRMS, an efficient method for simultaneous detection of 18 kinds of QNs was established. The method exhibited good linearity (0.01-100 ng g-1), high sensitivity (LODs ranging from 0.0011 to 0.0652 ng g-1) and precision (RSDs below 9.5%). Successful extraction of QNs from liver and kidney samples was achieved with satisfactory recoveries ranging from 82.2% to 108.4%. The abundant sulfonate functional groups on NiFe2O4/COF facilitated strong affinity to QNs through electrostatic and hydrogen bonding interactions. The proposed method provides a new idea for the extraction of contaminants with target selectivity.


Assuntos
Compostos Férricos , Contaminação de Alimentos , Estruturas Metalorgânicas , Quinolonas , Extração em Fase Sólida , Extração em Fase Sólida/métodos , Extração em Fase Sólida/instrumentação , Quinolonas/análise , Quinolonas/isolamento & purificação , Quinolonas/química , Cromatografia Líquida de Alta Pressão , Contaminação de Alimentos/análise , Animais , Estruturas Metalorgânicas/química , Compostos Férricos/química , Níquel/química , Níquel/análise , Níquel/isolamento & purificação , Espectrometria de Massas , Adsorção , Fígado/química
20.
Anal Chim Acta ; 1311: 342714, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38816153

RESUMO

BACKGROUND: Antibiotics residues can accelerate the growth of drug-resistant bacteria and harm the ecological environment. Under the effect of enrichment and biomagnification, the emergence of drug-resistant pathogenic bacteria may eventually lead to humans being ineffective to drugs in the face of bacterial or fungal disease infections in the future. It is urgent to develop an efficient separation medium and analytical method for simultaneous extraction and determination of antibiotics in the water environment. RESULTS: This work doped 2,6-Di-O-methyl-ß-cyclodextrin, randomly methyl-ß-cyclodextrin, 2-hydroxypropyl-ß-cyclodextrin with thymol:fatty acid respectively to construct non-covalent interaction-dominated pH-responsive ternary supramolecular deep eutectic solvents (SUPRADESs), which can undergo a hydrophilic/hydrophobic transition with aqueous phase to achieve an efficient microextraction. Semi-empirical method illustrated that SUPRADESs have a wide range of hydrogen bond receptor sites. We developed a SUPRADES-based analytical method combined with liquid chromatography-triple quadrupole mass spectrometry for the extraction and determination of trace quinolones and sulfonamides in wastewater. The overall limits of detection of the method were 0.0021-0.0334 ng mL-1 and the limits of quantification were 0.0073-0.1114 ng mL-1. The linearity maintained good in the spiked level of 0.01-100 ng mL-1 (R2 > 0.99). The overall enrichment factors of the method were 157-201 with lower standard deviations (≤8.7). SIGNIFICANCE: The method gave an extraction recovery of 70.1-115.3 % for 28 antibiotics in livestock farming wastewater samples from Zhejiang, China, at trace levels (minimum 0.5 ng mL-1). The results demonstrated that inducing the phase transition between SUPRADES and aqueous phase by adjusting pH for extraction is a novel and efficient pretreatment strategy. To our knowledge, this is the first application of cyclodextrin-based ternary SUPRADESs with pH-responsive reversible hydrophobicity-hydrophilicity transition behavior in wastewater analysis.


Assuntos
Ciclodextrinas , Solventes Eutéticos Profundos , Quinolonas , Sulfonamidas , Águas Residuárias , Poluentes Químicos da Água , Águas Residuárias/química , Águas Residuárias/análise , Concentração de Íons de Hidrogênio , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação , Sulfonamidas/química , Sulfonamidas/análise , Sulfonamidas/isolamento & purificação , Quinolonas/química , Quinolonas/isolamento & purificação , Quinolonas/análise , Ciclodextrinas/química , Solventes Eutéticos Profundos/química
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