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1.
Adv Healthc Mater ; 13(13): e2303016, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38431929

RESUMO

Curcumin, a natural bioactive polyphenol with diverse molecular targets, is well known for its anti-oxidation and anti-inflammatory potential. However, curcumin exhibits low solubility (<1 µg mL-1), poor tissue-targeting ability, and rapid oxidative degradation, resulting in poor bioavailability and stability for inflammatory therapy. Here, poly(diselenide-oxalate-curcumin) nanoparticle (SeOC-NP) with dual-reactive oxygen species (ROS) sensitive chemical moieties (diselenide and peroxalate ester bonds) is fabricated by a one-step synthetic strategy. The results confirmed that dual-ROS sensitive chemical moieties endowed SeOC-NP with the ability of targeted delivery of curcumin and significantly suppress oxidative degradation of curcumin for high-efficiency inflammatory therapy. In detail, the degradation amount of curcumin for SeOC is about 4-fold lower than that of free curcumin in an oxidative microenvironment. As a result, SeOC-NP significantly enhanced the antioxidant activity and anti-inflammatory efficacy of curcumin in vitro analysis by scavenging intracellular ROS and suppressing the secretion of nitric oxide and pro-inflammatory cytokines. In mouse colitis models, orally administered SeOC-NP can remarkably alleviate the symptoms of IBD and maintain the homeostasis of gut microbiota. This work provided a simple and effective strategy to fabricate ROS-responsive micellar and enhance the oxidation stability of medicine for precise therapeutic inflammation.


Assuntos
Colite , Curcumina , Nanopartículas , Espécies Reativas de Oxigênio , Curcumina/química , Curcumina/farmacologia , Animais , Colite/tratamento farmacológico , Colite/metabolismo , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Nanopartículas/química , Células RAW 264.7 , Oxirredução , Antioxidantes/química , Antioxidantes/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Camundongos Endogâmicos C57BL , Masculino
2.
Sci Adv ; 9(23): eadg4205, 2023 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-37294761

RESUMO

In the face of the alarming rise in global antimicrobial resistance, only a handful of novel antibiotics have been developed in recent decades, necessitating innovations in therapeutic strategies to fill the void of antibiotic discovery. Here, we established a screening platform mimicking the host milieu to select antibiotic adjuvants and found three catechol-type flavonoids-7,8-dihydroxyflavone, myricetin, and luteolin-prominently potentiating the efficacy of colistin. Further mechanistic analysis demonstrated that these flavonoids are able to disrupt bacterial iron homeostasis through converting ferric iron to ferrous form. The excessive intracellular ferrous iron modulated the membrane charge of bacteria via interfering the two-component system pmrA/pmrB, thereby promoting the colistin binding and subsequent membrane damage. The potentiation of these flavonoids was further confirmed in an in vivo infection model. Collectively, the current study provided three flavonoids as colistin adjuvant to replenish our arsenals for combating bacterial infections and shed the light on the bacterial iron signaling as a promising target for antibacterial therapies.


Assuntos
Proteínas de Bactérias , Colistina , Colistina/farmacologia , Proteínas de Bactérias/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Bactérias/metabolismo , Ferro , Homeostase
3.
Int J Mol Sci ; 24(5)2023 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-36902398

RESUMO

Influenza A virus (IAV) infections have been a serious hazard to public health everywhere. With the growing concern of drug-resistant IAV strains, there is an urgent need for novel anti-IAV medications, especially those with alternative mechanisms of action. Hemagglutinin (HA), an IAV glycoprotein, plays critical roles in the early stage of virus infection, including receptor binding and membrane fusion, making it a good target for developing anti-IAV drugs. Panax ginseng is a widely used herb in traditional medicine with extensive biological effects in various disease models, and its extract was reported to show protection in IAV-infected mice. However, the main effective anti-IAV constituents in panax ginseng remain unclear. Here, we report that ginsenoside rk1 (G-rk1) and G-rg5, out of the 23 screened ginsenosides, exhibit significant antiviral effects against 3 different IAV subtypes (H1N1, H5N1, and H3N2) in vitro. Mechanistically, G-rk1 blocked IAV binding to sialic acid in a hemagglutination inhibition (HAI) assay and an indirect ELISA assay; more importantly, we showed that G-rk1 interacted with HA1 in a dose-dependent manner in a surface plasmon resonance (SPR) analysis. Furthermore, G-rk1 treatment by intranasal inoculation effectively reduced the weight loss and mortality of mice challenged with a lethal dose of influenza virus A/Puerto Rico/8/34 (PR8). In conclusion, our findings reveal for the first time that G-rk1 possesses potent anti-IAV effects in vitro and in vivo. We have also identified and characterized with a direct binding assay a novel ginseng-derived IAV HA1 inhibitor for the first time, which could present potential approaches to prevent and treat IAV infections.


Assuntos
Ginsenosídeos , Vírus da Influenza A Subtipo H1N1 , Virus da Influenza A Subtipo H5N1 , Vírus da Influenza A , Influenza Humana , Animais , Camundongos , Humanos , Antivirais/farmacologia , Ginsenosídeos/farmacologia , Hemaglutininas/farmacologia , Vírus da Influenza A Subtipo H3N2 , Ligação Viral , Vírus da Influenza A/fisiologia
4.
J Control Release ; 351: 896-906, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36202152

RESUMO

Targeted antibiotic delivery system would be an ideal solution for the treatment of enteropathogenic infections since it avoids the excessive usage of antibiotics clinically, which may lead to threat on public health and food safety. Salmonella spp. are Enteropathogens, but they are also robust H2S producers in the intestinal tracts of hosts. To this end, the PEGylated poly (α lipoic acid) (PEG-PALA) copolymer nanoparticles with hydrophilic exterior and hydrophobic interior were designated in this study to encapsulate the antibiotics and release them in response to H2S produced by Salmonella spp. The PEG-PALA nanoparticles demonstrated excellent stability in vitro and biocompatibility toward mammalian Caco-2 and 293 T cells. The release of ciprofloxacin from PEG-PALA nanoparticle was only 25.44 ± 0.57% and 26.98 ± 1.93% (w/w) in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) solutions without H2S stimulation. However, the release amounts of ciprofloxacin were up to 73.68 ± 1.63% (w/w) in the presence of 1 mM Na2S as H2S source. In the mouse infection model, PEG-PALA nanoparticles encapsulated with ciprofloxacin (PEG-PALA@CIP) reduced the Salmonella colonization in the heart, liver, spleen, lung, cecum, and faeces, prolonged ciprofloxacin persistence in the intestine while reducing its absorption into the blood. More importantly, these nanoparticles reduced 3.4-fold of Enterobacteriaceae levels and increased 1.5-fold of the Lactobacillaceae levels compared with the drug administered in the free form. Moreover, these nanoparticles resulted in only minimal signs of intestinal tract inflammation. The H2S-responsive antibiotic delivery systems reported in this study demonstrating a variety of advantages including protected the drug from deactivation by gastric and intestinal fluids, maintained a high concentration in the intestinal tract and maximally kept the gut microbiota homeostasis. As such, this targeted antibiotic delivery systems are for the encapsulation of antibiotics to target specific enteropathogens.


Assuntos
Nanopartículas , Ácido Tióctico , Humanos , Camundongos , Animais , Ciprofloxacina/química , Células CACO-2 , Nanopartículas/química , Salmonella , Antibacterianos/química , Polietilenoglicóis/química , Sistemas de Liberação de Medicamentos , Mamíferos
5.
Sci Total Environ ; 758: 143654, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33277010

RESUMO

Vast reservoirs of antibiotic resistance genes (ARG) are discharged into the environment via pig manure. We used metagenomic analysis to follow the distribution and shifts of ARGs and their bacterial hosts along wastewater treatment in three large pig farms. The predominating ARGs potentially encoded resistance to tetracycline (28.13%), aminoglycosides (23.64%), macrolide-lincosamide-streptogramin (MLS) (12.17%), sulfonamides (11.53%), multidrug (8.74%) and chloramphenicol (6.18%). The total relative ARG abundance increased along the treatment pathway prior to anaerobic digestion that had a similar degradative capacity for different ARGs and these ARGs were reduced by about 25% after digestion, but ARGs enriched erratically in manured soils. Distinctive ARG distribution patterns were found according to the three sample locations; feces, soil and wastewater and the differences were primarily due to the tetracycline ARGs (feces > wastewater > soil), sulfonamide ARGs (soil > wastewater > feces) and MLS ARGs (feces > wastewater > soil). Metagenomic assembly-based host analyses indicated the Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes were primary ARG carriers. The Streptococcaceae increased the abundance of multidrug, MLS and aminoglycoside ARGs in feces; Moraxellaceae were the primary contributors to the high abundance of multidrug ARGs in wastewater; the Comamonadaceae led to the higher abundance of bacA in wastewater and soil than feces. We found a high level of heterogeneity for both ARGs and ARG-hosts in the wastewater treatment system and in the agricultural soils for these pig farms.


Assuntos
Esterco , Purificação da Água , Animais , Antibacterianos , Resistência Microbiana a Medicamentos/genética , Fazendas , Genes Bacterianos , Solo , Microbiologia do Solo , Suínos
6.
Medicine (Baltimore) ; 99(26): e20790, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590760

RESUMO

INTRODUCTION: Hypertrophic scars are a common disease in plastic surgery, which is the reaction of skin connective tissue to trauma beyond the normal range. Although scholars around the world have explored the tissue structure and formation mechanism of HS for decades, they are not satisfactory the result of. No effective treatment has been found. Therefore, the search for safe and effective treatments for HS has always been the focus of medical attention and research. Acupuncture therapy has a definite effect on HS and has unique advantages. METHODS/DESIGN: In this study, we will use our own front-to-back clinical research method. We plan to include 120 young and middle-aged female patients who meet the diagnostic criteria for HS. The untreated HS of the enrolled patients will be used as blank controls. The intervention group will be given acupuncture treatment. The assessment of scar area, color, hardness, thickness, itching and pain will be recorded for 30 days of treatment. DISCUSSION: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of Acupuncture for patients with HS. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000032624, Registered on 04 May 2020.


Assuntos
Terapia por Acupuntura/métodos , Cicatriz Hipertrófica , Adulto , Cicatriz Hipertrófica/diagnóstico , Cicatriz Hipertrófica/fisiopatologia , Cicatriz Hipertrófica/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Projetos de Pesquisa , Resultado do Tratamento
7.
Medicine (Baltimore) ; 99(25): e20623, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569192

RESUMO

INTRODUCTION: Pathological scar is the abnormal manifestation of skin fiber hyperplasia caused by the failure of normal healing after skin damage. At present, there are many clinical treatments for pathological scars. However, there is no cure for clinically effective pathological scars with high recurrence rate. In this study, we will use a combination of Chinese and western medicine treatment methods to evaluate the clinical efficacy and related indicators of young and middle-aged female patients who meet pathological scars, looking for an objective and effective treatment method for pathological scars. METHODS/DESIGN: In this study, we will use our own front-to-back clinical research method. We plan to include 120 young and middle-aged female patients who meet the diagnostic criteria for pathological scars. The untreated pathological scars of the enrolled patients will be used as blank controls. The intervention group will be given conventional western medicine treatment and combined Chinese and western medicine treatment. The assessment of scar area, color, hardness, thickness, itching, and pain was recorded for 8 weeks of treatment. DISCUSSION: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of traditional Chinese medicine for patients with pathological scars. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000032187, Registered on April 22, 2020.


Assuntos
Cicatriz/terapia , Medicina Tradicional Chinesa/métodos , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto Jovem
8.
Medicine (Baltimore) ; 99(14): e19673, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32243402

RESUMO

INTRODUCTION: Interstitial cystitis (IC), as a common disease in urology, is prolonged and repeated. IC has caused great harm to the patient's physical and psychological. Traditional Chinese medicine (TCM) is characterized by overall concepts and dialectical treatment. It provides clinicians with safer and more reliable alternatives in terms of clinical prescriptions and prepared medicines, and also improves the quality of life of patients with IC. Therefore, in this study, we will use the research method of randomized controlled trials to explore the effects of TCM combined with western medicine on renal function and urine metabolism on middle-aged women with IC. METHODS/DESIGN: Use randomized controlled trials. According to the proposed diagnostic, inclusion, and exclusion criteria. Sixty patients with interstitial bladder inflammation that met the criteria were randomized into a treatment group and a control group of 30 cases each. The intervention group was treated with integrated traditional Chinese and western medicine. The control group was given conventional Western medicine treatment. The course of treatment is 8 weeks. Interstitial bladder inflammation symptoms score (ICS worker), problem score (worker CPI), pelvic pain and urinary urgency symptoms, and urodynamics were used as the evaluation criteria. DISCUSSION: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of TCM for patients with IC. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000029971, Registered on 17 February 2020.


Assuntos
Cistite Intersticial/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa/métodos , Agentes Urológicos/farmacologia , Cistite Intersticial/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Simples-Cego , Resultado do Tratamento , Urodinâmica/efeitos dos fármacos
9.
J Antimicrob Chemother ; 74(1): 87-95, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30346547

RESUMO

Objectives: The emergence of NDM- and MCR-1-co-producing Escherichia coli has compromised the use of carbapenems and colistin, which are critically important in clinical therapy, and represents a severe threat to public health worldwide. Here, we demonstrate synergism of colistin combined with existing antibiotics as a potential strategy to overcome XDR E. coli co-harbouring NDM and MCR-1 genes. Methods: To comprehensively evaluate their combined activity, antibiotic combinations were tested against 34 different E. coli strains carrying both NDM and MCR-1 genes. Antibiotic resistance profiles and molecular characteristics were investigated by susceptibility testing, PCR, MLST, S1-PFGE and WGS. Antibiotic synergistic efficacy was evaluated through in vitro chequerboard experiments and dose-response assays. A mouse model was used to confirm active combination therapies. Additionally, combinations were tested for their ability to prevent high-level colistin-resistant mutants (HLCRMs). Results: Combinations of colistin with rifampicin, rifabutin and minocycline showed synergistic activity against 34 XDR NDM- and MCR-1-co-producing E. coli strains, restoring, in part, susceptibility to both colistin and the partnering antibiotics. The therapeutic effectiveness of colistin combined with rifampicin or minocycline was demonstrated in a mouse model. Furthermore, colistin plus rifampicin showed significant activity in preventing the occurrence of HLCRMs. Conclusions: The synergism of colistin in combinations with rifampicin, rifabutin or minocycline offers viable therapeutic alternatives against XDR NDM- and MCR-positive E. coli.


Assuntos
Antibacterianos/administração & dosagem , Colistina/administração & dosagem , Farmacorresistência Bacteriana , Infecções por Escherichia coli/tratamento farmacológico , Proteínas de Escherichia coli/metabolismo , Escherichia coli/efeitos dos fármacos , beta-Lactamases/metabolismo , Animais , Antibacterianos/farmacologia , Colistina/farmacologia , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Escherichia coli/enzimologia , Feminino , Técnicas de Genotipagem , Camundongos Endogâmicos ICR , Testes de Sensibilidade Microbiana , Resultado do Tratamento
10.
Viruses ; 10(11)2018 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-30469357

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) is a continuous threat to the pork industry as it continues to cause significant economic loss worldwide. Currently, vaccination strategies provide very limited protection against PRRSV transmission. Consequently, there is an urgent need to develop new antiviral strategies. Platycodin D (PD) is one of the major bioactive triterpenoid saponins derived from Platycodon grandiflorum, a traditional Chinese medicine used as an expectorant for pulmonary diseases and a remedy for respiratory disorders. Here, we demonstrate that PD exhibits potent activity against PRRSV infection in Marc-145 cells and primary porcine alveolar macrophages. PD exhibited broad-spectrum inhibitory activities in vitro against high pathogenic type 2 PRRSV GD-HD strain and GD-XH strain as well as classical CH-1a and VR2332 strains. PD at concentrations ranging 1⁻4 µM significantly inhibited PRRSV RNA synthesis, viral protein expression and progeny virus production in a dose-dependent manner. EC50 values of PD against four tested PRRSV strains infection in Marc-145 cells ranged from 0.74 to 1.76 µM. Mechanistically, PD inhibited PRRSV replication by directly interacting with virions therefore affecting multiple stages of the virus life cycle, including viral entry and progeny virus release. In addition, PD decreased PRRSV- and LPS-induced cytokine (IFN-α, IFN-ß, IL-1α, IL-6, IL-8 and TNF-α) production in PAMs. Altogether, our findings suggested that PD is a potent inhibitor of PPRSV infection in vitro. However, further in vivo studies are necessary to confirm PD as a potential novel and effective PPRSV inhibitor in swine.


Assuntos
Antivirais/farmacologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/efeitos dos fármacos , Vírus da Síndrome Respiratória e Reprodutiva Suína/fisiologia , Saponinas/farmacologia , Triterpenos/farmacologia , Replicação Viral/efeitos dos fármacos , Animais , Células Cultivadas , Testes de Sensibilidade Microbiana , Suínos , Internalização do Vírus/efeitos dos fármacos , Liberação de Vírus/efeitos dos fármacos
11.
J Antimicrob Chemother ; 73(7): 1899-1907, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29897466

RESUMO

Objectives: The chloramphenicol/florfenicol resistance gene cfr, which mediates cross-resistance to linezolid and other classes of antimicrobial agents, represents a global therapeutic challenge due to its dissemination among MDR nosocomial pathogens, including MRSA. This study aimed to compare the efficacy of the linezolid/rifampicin combination in a murine pneumonia model caused by cfr-positive and cfr-negative clinical MRSA strains. Methods: Synergistic activity between linezolid and rifampicin was evaluated by chequerboard and time-kill assays. Pharmacokinetic profiles in plasma and epithelial lining fluid (ELF) as well as the therapeutic efficacy of linezolid alone and in combination with rifampicin were investigated in a murine pneumonia model. The Emax Hill equation was used to model the dose-response relationship. Results: Increased susceptibility of the study MRSA strains to linezolid was observed with the rifampicin combination (MIC decreased 2- to 16-fold versus linezolid alone). The combination had synergistic activity (fractional inhibitory concentration index ≤0.5) against all cfr-positive MRSA isolates. Linezolid demonstrated excellent pulmonary penetration with an ELF/fplasma AUC ratio of 2.68 ±âŸ0.17. The addition of rifampicin significantly improved the efficacy of linezolid in the pneumonia model due to cfr-positive and cfr-negative MRSA strains. The fAUC/MIC targets of linezolid associated with stasis, 1 log10 kill and 2 log10 kill were 15.9, 38.8 and 175 in plasma, and 43.5, 108 and 415 in ELF, respectively. Importantly, the linezolid fAUC/MIC targets in both plasma and ELF were 2.4-6.7 times lower in combined linezolid/rifampicin therapy versus linezolid monotherapy (P < 0.005). Conclusions: Combination of linezolid with rifampicin significantly improved the efficacy of linezolid in the murine pneumonia model caused by MRSA strains in the presence and absence of the cfr gene.


Assuntos
Antibacterianos/uso terapêutico , Linezolida/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pneumonia Bacteriana/tratamento farmacológico , Rifampina/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Animais , Proteínas de Bactérias/genética , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Camundongos , Camundongos Endogâmicos ICR , Testes de Sensibilidade Microbiana , Organismos Livres de Patógenos Específicos
12.
Artigo em Inglês | MEDLINE | ID: mdl-29038275

RESUMO

Antimicrobial resistance among uropathogens has increased the rates of infection-related morbidity and mortality. Antofloxacin is a novel fluoroquinolone with broad-spectrum antibacterial activity against urinary Gram-negative bacilli, such as Escherichia coli This study monitored the in vivo efficacy of antofloxacin using bioluminescent imaging and determined pharmacokinetic (PK)/pharmacodynamic (PD) targets against E. coli isolates in a neutropenic murine thigh infection model. The PK properties were determined after subcutaneous administration of antofloxacin at 2.5, 10, 40, and 160 mg/kg of body weight. Following thigh infection, the mice were treated with 2-fold-increasing doses of antofloxacin from 2.5 to 80 mg/kg administered every 12 h. Efficacy was assessed by quantitative determination of the bacterial burdens in thigh homogenates and was compared with the bioluminescent density. Antofloxacin demonstrated both static and killing endpoints in relation to the initial burden against all study strains. The PK/PD index area under the concentration-time curve (AUC)/MIC correlated well with efficacy (R2 = 0.92), and the dose-response relationship was relatively steep, as observed with escalating doses of antofloxacin. The mean free drug AUC/MIC targets necessary to produce net bacterial stasis and 1-log10 and 2-log10 kill for each isolate were 38.7, 66.1, and 147.0 h, respectively. In vivo bioluminescent imaging showed a rapid decrease in the bioluminescent density at free drug AUC/MIC exposures that exceeded the stasis targets. The integration of these PD targets combined with the results of PK studies with humans will be useful in setting optimal dosing regimens for the treatment of urinary tract infections due to E. coli.


Assuntos
Antibacterianos/farmacologia , Infecções por Escherichia coli/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Neutropenia/microbiologia , Ofloxacino/análogos & derivados , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Feminino , Meia-Vida , Camundongos Endogâmicos ICR , Testes de Sensibilidade Microbiana , Ofloxacino/administração & dosagem , Ofloxacino/farmacocinética , Ofloxacino/farmacologia , Plasmídeos/genética , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções dos Tecidos Moles/microbiologia , Coxa da Perna/microbiologia
13.
Artigo em Inglês | MEDLINE | ID: mdl-28264844

RESUMO

Antofloxacin is a novel broad-spectrum fluoroquinolone under development for the treatment of infections caused by a diverse group of bacterial species. We explored the pharmacodynamic (PD) profile and targets of antofloxacin against seven Klebsiella pneumoniae isolates by using a neutropenic murine lung infection model. Plasma and bronchopulmonary pharmacokinetic (PK) studies were conducted at single subcutaneous doses of 2.5, 10, 40, and 160 mg/kg of body weight. Mice were infected intratracheally with K. pneumoniae and treated using 2-fold-increasing total doses of antofloxacin ranging from 2.5 to 160 mg/kg/24 h administered in 1, 2, 3, or 4 doses. The Emax Hill equation was used to model the dose-response data. Antofloxacin could penetrate the lung epithelial lining fluid (ELF) with pharmacokinetics similar to those in plasma with linear elimination half-lives over the dose range. All study strains showed a 3-log10 or greater reduction in bacterial burden and prolonged postantibiotic effects (PAEs) ranging from 3.2 to 5.3 h. Dose fractionation response curves were steep, and the free-drug area under the concentration-time curve over 24 h (AUC0-24)/MIC ratio was the PD index most closely linked to efficacy (R2 = 0.96). The mean free-drug AUC0-24/MIC ratios required to achieve net bacterial stasis, a 1-log10 kill, and a 2-log10 kill for each isolate were 52.6, 89.9, and 164.9, respectively. When integrated with human PK data, these PD targets could provide a framework for further optimization of dosing regimens. This could make antofloxacin an attractive option for the treatment of respiratory tract infections involving K. pneumoniae.


Assuntos
Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Ofloxacino/análogos & derivados , Infecções Respiratórias/tratamento farmacológico , Animais , Feminino , Humanos , Klebsiella pneumoniae/isolamento & purificação , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos ICR , Testes de Sensibilidade Microbiana , Neutropenia/tratamento farmacológico , Neutropenia/microbiologia , Ofloxacino/farmacocinética , Ofloxacino/uso terapêutico , Infecções Respiratórias/microbiologia
14.
Vet Microbiol ; 192: 1-9, 2016 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-27527758

RESUMO

Horizontal transfer of plasmid-encoded multidrug-resistant determinants is a major health problem and has attracted much public attention. We studied the dissemination of the efflux pump gene oqxAB located on transferable plasmid pHXY0908 between Salmonella Typhimurium and Escherichia coli in the gut of chickens. After an inoculation with Salmonella Typhimurium harboring oqxAB-bearing plasmid pHXY0908, chickens were treated with enrofloxacin and florfenicol. Inoculated, but non-treated chickens were included as a control group. Our results revealed that commensal E. coli isolates from the gut of chickens acquired the oqxAB-bearing plasmid in both treated and non-treated groups. Additionally, in the florfenicol treatment group, the average isolation rate of oqxAB-positive E. coli was significantly higher than that in the non-treated group. PFGE analysis showed that oqxAB-positive E. coli strains belonged to different patterns with one predominating. Moreover, multilocus sequence typing analysis revealed that E. coli ST533 was closely associated with the spread of oqxAB gene. qPCR analysis indicated that antibiotic administration provided selective advantages for sustaining a significantly high level of oqxAB gene from the DNA extracted from the feces. There was also a fluctuation in the intestinal microbiota with antibiotic therapy. In conclusion, the present study indicates that the oqxAB gene could be readily spread within the intestinal microflora. This could be enhanced by administrated with clinical doses of florfenicol and enrofloxacin, resulting in the enlargement of resistance gene reservoirs. In addition, ST533 E. coli isolates were found to contribute to transfer of the oqxAB gene.


Assuntos
Galinhas/microbiologia , Farmacorresistência Bacteriana Múltipla/genética , Escherichia coli/efeitos dos fármacos , Fluoroquinolonas/farmacologia , Salmonella typhimurium/efeitos dos fármacos , Tianfenicol/análogos & derivados , Animais , Antibacterianos/farmacologia , Cloaca/microbiologia , DNA Bacteriano , Enrofloxacina , Escherichia coli/genética , Fezes/microbiologia , Regulação Bacteriana da Expressão Gênica , Transferência Genética Horizontal , Genes Bacterianos , Intestinos/microbiologia , Testes de Sensibilidade Microbiana , Salmonella typhimurium/genética , Tianfenicol/farmacologia
15.
Rev. iberoam. micol ; 33(1): 38-42, ene.-mar. 2016. ilus
Artigo em Inglês | IBECS | ID: ibc-149373

RESUMO

Background. Sporothrix species have proved to show high degrees of endemicity. Sporothrix globosa is the only pathogenic Sporothrix species that has till date been reported from China, where it is endemic in the northeastern provinces. Aims. We report two cases of lymphocutaneous sporotrichosis with diabetes mellitus as underlying disease in patients from the non-endemic area of China. Methods. A 59-year-old farmer and a 60-year-old gardener were admitted in February and June 2014, respectively. Both patients were right-handed men and presented with progressive plaques and nodules, which they had for several years, involving the right upper extremity. Skin biopsy from the granuloma was taken and cultured on Sabouraud medium, and molecular identification based on the calmodulin region was performed. Antifungal susceptibility testing was also performed with the microdilution method. Results. Biopsy of the lesions showed the presence of infectious granuloma. The fungal cultures were identified as Sporothrix globosa by conventional methods, and confirmed by molecular identification. A subsequent course of oral antifungal therapy with low dosage of itraconazole was well tolerated and resolved the infection. Conclusions. Identification of fungal species and antifungal susceptibility testing are mandatory for epidemiological and therapeutic reasons. Early diagnosis of sporotrichosis is essential to prevent those sequelae when the disease progresses and provides highly effective methods for treating this emerging disease. Avoiding the exposure to plant material potentially contaminated with fungal spores should be recommended, especially in immunocompromised patients (AU)


Antecedentes. Las especies de Sporothrix han demostrado un alto nivel de endemicidad. Sporothrix globosa es la única especie patógena descrita hasta la fecha en China, donde es endémica en las provincias del nordeste. Objetivos. Se describen dos casos de esporotricosis linfocutánea con diabetes mellitus como enfermedad de base, en pacientes procedentes de un área no endémica de China. Métodos. Un campesino de 59 años y un jardinero de 60 años de edad fueron atendidos en febrero y junio de 2014, respectivamente. Ambos eran varones, diestros y se presentaron con placas y nódulos de varios años de evolución, que afectaban a la zona superior del brazo derecho. Se tomaron biopsias de los granulomas de la piel, que fueron cultivados en medio de Sabouraud, y se realizó una identificación molecular basada en la región de la calmodulina. Se evaluó la sensibilidad a los antifúngicos mediante el método de microdilución. Resultados. La biopsia de las lesiones mostró la presencia de un granuloma infeccioso. Los hongos aislados en los cultivos fueron identificados como Sporothrix globosa por métodos convencionales, y confirmados mediante identificación molecular. La subsecuente administración de terapia antifúngica oral con bajas dosis de itraconazol fue bien tolerada y resolvió la infección. Conclusiones. La identificación de las especies fúngicas y el análisis de la sensibilidad a los antifúngicos son necesarios por razones epidemiológicas y terapéuticas. El diagnóstico temprano de la esporotricosis es esencial para prevenir las secuelas que genera el progreso de la enfermedad y para ofrecer métodos altamente efectivos para el tratamiento de esta enfermedad emergente. Debe recomendarse evitar la exposición a material vegetal potencialmente contaminado con esporas fúngicas, especialmente en pacientes inmunocomprometidos (AU)


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Esporotricose/diagnóstico , Esporotricose/tratamento farmacológico , Esporotricose/microbiologia , Sporothrix/isolamento & purificação , Granuloma/diagnóstico , Granuloma/tratamento farmacológico , Granuloma/microbiologia , Fungos/isolamento & purificação , Itraconazol/uso terapêutico , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/fisiopatologia , Extremidade Superior/patologia , Calmodulina , Calmodulina/isolamento & purificação , Esporos Fúngicos , Esporos Fúngicos/isolamento & purificação
16.
J Ethnopharmacol ; 148(1): 271-6, 2013 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-23612420

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Scutellaria baicalensis Georgi, also called Huangqin in China, is an herbal-based nutraceutical which is usually used in Chinese medicated diet (CMD). As an abundant ingredient in Huangqin, wogonoside is a flavonoid glycoside. The present work investigated the anti-inflammatory activities of wogonoside in lipopolysaccharides (LPS)-induced RAW264.7 cells. MATERIALS AND METHODS: RAW264.7 cells were used. The inhibition of wogonoside against nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in LPS-induced RAW264.7 cells were measured. Additionally, the effects of wogonoside on mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX2), TNF-α and IL-6 were also investigated. RESULTS AND DISCUSSION: Wogonoside not only dose-dependently decreased the production of inflammatory mediators including NO and PGE2 but also inhibited the release of pro-inflammatory cytokines including TNF-α and IL-6 in LPS-induced RAW264.7 cells. Furthermore, wogonoside possessed significantly in vitro inhibitory effects on the gene expression of iNOS, COX2, TNF-α and IL-6. CONCLUSION: These results suggest that wogonoside may be used as a functional food component for prevention and treatment of inflammation.


Assuntos
Anti-Inflamatórios/farmacologia , Flavanonas/farmacologia , Glucosídeos/farmacologia , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Dinoprostona/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolissacarídeos , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
17.
J AOAC Int ; 88(4): 1104-7, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16152927

RESUMO

Clopidol was extracted from chicken with acetonitrile, and the extract was evaporated to about 5 mL. The concentrated solution was centrifuged and applied to a glass column filled with basic alumina. The column was eluted with methanol and the methanol was evaporated to dryness. The residue was derivatized with Sylon BFT and analyzed by gas chromatography/mass spectrometry (GC/MS). Mass characteristics of trimethylsilyl derivative of clopidol were interpreted manually. The selected-ion monitoring mode was performed at m/z 191, 248, 263, and 265. A sensitive, reproducible GC/MS method was developed for monitoring residues of clopidol in chickens. All recoveries of the drug from chicken muscle fortified at 1, 10, and 100 ng/g were > 65%, and relative standard deviations were < 15%. The detection limit was about 0.5 ng/g, and the quantitation limit was the lower limit of the standard curve, which was about 1 ng/g.


Assuntos
Clopidol/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Músculos/metabolismo , Óxido de Alumínio/análise , Animais , Galinhas , Resíduos de Drogas/análise , Contaminação de Alimentos , Íons , Metanol/análise , Modelos Químicos , Reprodutibilidade dos Testes , Compostos de Trimetilsilil/análise
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