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Titanium-based implants have long been studied and used for applications in bone tissue engineering, thanks to their outstanding mechanical properties and appropriate biocompatibility. However, many implants struggle with osseointegration and attachment and can be vulnerable to the development of infections. In this work, we have developed a composite coating via electrophoretic deposition, which is both bioactive and antibacterial. Mesoporous bioactive glass particles with gentamicin were electrophoretically deposited onto a titanium substrate. In order to validate the hypothesis that the quantity of particles in the coatings is sufficiently high and uniform in each deposition process, an easy-to-use image processing algorithm was designed to minimize human dependence and ensure reproducible results. The addition of loaded mesoporous particles did not affect the good adhesion of the coating to the substrate although roughness was clearly enhanced. After 7 days of immersion, the composite coatings were almost dissolved and released, but phosphate-related compounds started to nucleate at the surface. With a simple and low-cost technique like electrophoretic deposition, and optimized stir and suspension times, we were able to synthesize a hemocompatible coating that significantly improves the antibacterial activity when compared to the bare substrate for both Gram-positive and Gram-negative bacteria.
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Antibacterianos , Quitosana , Eletroforese , Gentamicinas , Vidro , Teste de Materiais , Nanopartículas , Tamanho da Partícula , Propriedades de Superfície , Titânio , Gentamicinas/farmacologia , Gentamicinas/química , Titânio/química , Titânio/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Vidro/química , Nanopartículas/química , Quitosana/química , Quitosana/farmacologia , Porosidade , Testes de Sensibilidade Microbiana , Humanos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Próteses e Implantes , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologiaRESUMO
The pork production chain is an important reservoir of antimicrobial resistant bacteria. This study identified and characterized integrons in Salmonella isolates from a Brazilian pork production chain and associate them with their antibiotic resistance pattern. A total of 41 whole-genome sequencing data of nontyphoidal Salmonella were analyzed using PlasmidSPAdes and IntegronFinder software. Nine isolates (21.9%) had some integrons identified (complete and/or incomplete). Six complete class 1 integrons were found, with streptomycin resistance genes (aadA1, aadA2) alone or downstream of a trimethoprim resistance gene (dfrA1, dfrA12), and some also containing resistance genes for sulfonamides (sul1, sul3) and chloramphenicol (cmlA1). Class 2 integron was detected in only one isolate, containing dfrA1-sat2-aadA1 gene cassettes. Five isolates harbored CALINs-clusters attC but lacking integrases-with antimicrobial resistance genes typically found in integron structures. In all, integrons were observed among four serotypes: Derby, Bredeney, Panama, and monophasic var. Typhimurium I 4,[5],12:i:-. The association of integrons with antibiotic resistance phenotype showed that these elements were predominantly identified in multidrug resistance isolates, and six of the seven gentamicin-resistant isolates had integrons. So, surveillance of integrons in Salmonella should be performed to identify the potential for the spread of antimicrobial resistance genes among bacteria.
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Antibacterianos , Farmacorresistência Bacteriana Múltipla , Integrons , Salmonella , Integrons/genética , Brasil , Animais , Suínos , Salmonella/genética , Salmonella/isolamento & purificação , Salmonella/efeitos dos fármacos , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Testes de Sensibilidade Microbiana , Fenótipo , Microbiologia de Alimentos , Sequenciamento Completo do Genoma , Simulação por Computador , Carne de Porco/microbiologiaRESUMO
Gentamicin (GEN), a widely used broad-spectrum antibiotic, faces challenges amid the global emergency of antimicrobial resistance. This study aimed to explore the synergistic effects of zinc oxide nanoparticles (ZnO NPs) in combination with GEN on the bactericidal activity against various bacterial strains. Results showed ZnO NPs with MICs ranging from 0.002 to 1.5 µg/mL, while the precursor salt displayed a MIC range of 48.75-1560 µg/mL. Chitosan (CS)-capped ZnO NPs exhibited even lower MICs than their uncapped counterparts, with the CS-capped synthesized ZnO NPs demonstrating the lowest values. Minimal bactericidal concentrations (MBC) aligned with MIC trends. Combinations of CS-capped synthesized ZnO NPs and GEN proved highly effective, inhibiting bacterial growth at significantly lower concentrations than GEN or ZnO NPs alone. This phenomenon may be attributed to the conformation of CS on the ZnO NPs' surface, enhancing the positive particle surface charge. This possibly facilitates a more effective interaction between ZnO NPs and microorganisms, leading to increased accumulation of zinc and GEN within bacterial cells and an overproduction of reactive oxygen species (ROS). It's crucial to note that, while this study did not specifically involve resistant strains, its primary focus remains on enhancing the overall antimicrobial activity of gentamicin. The research aims to contribute to addressing the global challenge of antimicrobial resistance, recognizing the urgent need for effective strategies to combat this critical issue. The findings, particularly the observed synergy between ZnO NPs and GEN, hold significant implications for repositioning the first-line antibiotic GEN.
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INTRODUCTION: Aminoglycosides are vital antibiotics for treating Brucella infections, because they interfere with bacterial protein production and are often combined with other antibiotics. They are cost-effective, have fewer side effects, and can penetrate biofilms. The prevalence of brucellosis has increased in recent years, increasing the need for effective treatments. In addition, the emergence of multidrug-resistant Brucella strains has highlighted the need for an updated and comprehensive understanding of aminoglycoside resistance. This systematic review aimed to provide a comprehensive overview of the global prevalence of aminoglycoside resistance in B. melitensis and B. abortus. METHODS: A systematic search of online databases was conducted and eligible studies met certain criteria and were published in English. Quality assessment was performed using the JBI Checklist. A random-effects model was fitted to the data, and meta-regression, subgroup, and outlier/influential analyses were performed. The analysis was performed using R and the metafor package. RESULTS: The results of this systematic review and meta-analysis suggested that the average prevalence rates of streptomycin, gentamicin, and amikacin resistance were 0.027 (95% confidence interval [CI], 0.015-0.049), 0.023 (95% CI, 0.017-0.032), and 0.008 (95% CI, 0.002-0.039), respectively. The prevalence of streptomycin resistance was higher in the unidentified Brucella group than in the B. abortus and B. melitensis groups (0.234, 0.046, and 0.017, respectively; p < 0.02). The prevalence of gentamicin resistance increased over time (r = 0.064; 95% CI, 0.018 to 0.111; p = 0.007). The prevalence of resistance did not correlate with the quality score for any antibiotic. Funnel plots showed a potential asymmetry for streptomycin and gentamicin. These results suggest a low prevalence of antibiotic resistance in the studied populations. CONCLUSION: The prevalence of aminoglycoside resistance in B. melitensis and B. abortus was low. However, gentamicin resistance has increased in recent years. This review provides a comprehensive and updated understanding of aminoglycoside resistance in B. melitensis and B. abortus.
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Aminoglicosídeos , Antibacterianos , Brucella abortus , Brucella melitensis , Brucelose , Aminoglicosídeos/farmacologia , Brucella abortus/efeitos dos fármacos , Brucella abortus/genética , Brucella abortus/isolamento & purificação , Antibacterianos/farmacologia , Brucelose/microbiologia , Brucelose/epidemiologia , Brucella melitensis/efeitos dos fármacos , Brucella melitensis/isolamento & purificação , Brucella melitensis/genética , Humanos , Prevalência , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , AnimaisRESUMO
The exposure of bacteria to sub-inhibitory concentrations of antibiotics is of biological significance since it can occur in vivo under many circumstances, including low-dose treatment, poor adherence to a regimen, poor drug penetration, drug-drug interactions, and antibiotic resistance of the pathogen. In this study, we investigated the effects of subinhibitory concentrations of four antibiotics: ampicillin, ceftriaxone, gentamicin, and norfloxacin, which are commonly used in clinical settings and on cell morphology and biofilm formation in Staphylococcus aureus as one of the leading causes of nosocomial and biofilm-associated infections. Nine clinical S. aureus biofilm-producing isolates and two known biofilm-producing reference strains, S. aureus ATCC 29213 and S. aureus ATCC 6538, were used in this study. Sub-MICs of beta-lactam antibiotics (ampicillin and ceftriaxone) significantly induced biofilm formation in S. aureus ATCC 29213 and S. aureus ATCC 6538 and in six clinical isolates out of the nine selected isolates when compared with the antibiotic-free control group (P < 0.05), with an approximately 2- to 2.5-fold increase. Gentamicin and norfloxacin induced biofilms in S. aureus ATCC 29213 and S. aureus ATCC 6538, while gentamicin and norfloxacin induced biofilms only in three and two of the nine tested isolates, respectively (P < 0.05). The chemical nature of the biofilm matrix produced by half the MIC of ceftriaxone in the six isolates that showed increased biofilm was all non-polysaccharide in composition (PIA-independent). Gene expression of biofilm-encoding genes atl and sarA in biofilms of the two tested strains (S. aureus ATCC 6538) and clinical strain (S. aureus 16) showed a significant upregulation after exposure to half MIC of ceftriaxone. Additionally, the bacterial cell morphological changes in planktonic cells caused by half MIC of ceftriaxone were evaluated by scanning electron microscopy, which demonstrated a significant cell enlargement when compared with the antibiotic-free control (P < 0.05), and some deformed cells were also noticed. In S. aureus clinical isolates, sub-MICs of ampicillin, ceftriaxone, gentamicin, and norfloxacin may stimulate substantial production of biofilm, which could have important clinical significance and make infection treatment challenges. Further, in vivo research is needed to fully comprehend how sub-MIC of antibiotics can affect biofilm formation in clinical settings. Additionally, more research is required to reveal the clinical implications of the morphological alterations in S. aureus brought on by exposure to ceftriaxone at concentrations below its MIC.
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Infecções Estafilocócicas , Staphylococcus aureus , Humanos , Ceftriaxona/farmacologia , Norfloxacino/farmacologia , Antibacterianos/farmacologia , Infecções Estafilocócicas/microbiologia , Ampicilina/farmacologia , Gentamicinas/farmacologia , Biofilmes , Testes de Sensibilidade MicrobianaRESUMO
FTIR (Fourier transform infrared spectroscopy) is one analytical technique of the absorption of infrared radiation. FTIR can also be used as a tool to characterize profiles of biomolecules in bacterial cells, which can be useful in differentiating different bacteria. Considering that different bacterial species have different molecular compositions, it will then result in unique FTIR spectra for each species and even bacterial strains. Having this important tool, here, we have developed a methodology aimed at refining the analysis and classification of the FTIR absorption spectra obtained from samples of Staphylococcus aureus, with the implementation of machine learning algorithms. In the first stage, the system conforming to four specified species groups, Control, Amoxicillin induced (AMO), Gentamicin induced (GEN), and Erythromycin induced (ERY), was analyzed. Then, in the second stage, five hidden samples were identified and correctly classified as with/without resistance to induced antibiotics. The total analyses were performed in three windows, Carbohydrates, Fatty Acids, and Proteins, of five hundred spectra. The protocol for acquiring the spectral data from the antibiotic-resistant bacteria via FTIR spectroscopy developed by Soares et al. was implemented here due to demonstrating high accuracy and sensitivity. The present study focuses on the prediction of antibiotic-induced samples through the implementation of the hierarchical cluster analysis (HCA), principal component analysis (PCA) algorithm, and calculation of confusion matrices (CMs) applied to the FTIR absorption spectra data. The data analysis process developed here has the main objective of obtaining knowledge about the intrinsic behavior of S. aureus samples within the analysis regions of the FTIR absorption spectra. The results yielded values with 0.7 to 1 accuracy and high values of sensitivity and specificity for the species identification in the CM calculations. Such results provide important information on antibiotic resistance in samples of S. aureus bacteria for potential application in the detection of antibiotic resistance in clinical use.
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The skin is the largest organ and one of the most important in the human body, and is constantly exposed to pathogenic microorganisms that cause infections; then, pharmacological administration is required. One of the basic medical methods for treating chronic wounds is to use topical dressings with characteristics that promote wound healing. Fiber-based dressings mimic the local dermal extracellular matrix (ECM), maintaining an ideal wound-healing climate. This work proposes electrospun PHB/PEG polymeric microfibers as dressings for administering the antibiotic gentamicin directed at skin infections. PHB-PEG/gentamicin fibers were characterized before and after plasma treatment by Raman spectroscopy, FTIR, and XRD. SEM was used to evaluate fiber morphology and yarn size. The plasma treatment improved the hydrophilicity of the PHB/PEG/gentamicin fibers. The release of gentamicin in the plasma-treated fibers was more sustained over time than in the untreated ones.
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Dowling Degos disease (DDD) is a rare autosomal dominant genodermatosis characterized by acquired, slowly progressive reticulated pigmented lesions primarily involving flexural skin areas. Mutations in KRT5, POGLUT-1 and POFUT-1 genes have been associated with DDD, and loss-of-function mutations in PSENEN, a subunit of the gamma-secretase complex, were found in patients presenting with DDD or DDD comorbid with hidradenitis suppurativa (HS). A nonsense mutation in NCSTN, another subunit of the gamma-secretase, was already described in a patient suffering from HS and DDD but whether NCSTN could be considered a novel gene for DDD is still debated. Here, we enrolled a four-generation family with HS and DDD. Through Whole Exome Sequencing (WES) we identified a novel nonsense mutation in the NCSTN gene in all the affected family members. To study the impact of this variant, we isolated outer root sheath cells from patients' hair follicles. We showed that this variant leads to a premature stop codon, activates a nonsense-mediated mRNA decay, and causes NCSTN haploinsufficiency in affected individuals. In fact, cells treated with gentamicin, a readthrough agent, had the NCSTN levels corrected. Moreover, we observed that this haploinsufficiency also affects other subunits of the gamma-secretase complex, possibly causing DDD. Our findings clearly support NCSTN as a novel DDD gene and suggest carefully investigating this co-occurrence in HS patients carrying a mutation in the NCSTN gene.
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Hidradenite Supurativa , Papulose Atrófica Maligna , Humanos , Secretases da Proteína Precursora do Amiloide/genética , Códon sem Sentido , Hidradenite Supurativa/complicações , Hidradenite Supurativa/genética , Proteínas de Membrana/genética , Mutação , Fatores de Transcrição/genéticaRESUMO
There are conflicting reports on the antibacterial activity of ascorbate; all at concentrations much higher than the typical in human plasma, but that can be reached in urine. The effect of 10 mM ascorbate (in itself not inhibitory) along with antibiotics, was tested both in Mueller-Hinton broth (MHb) and in synthetic human urine (SHU), against resistant isolates of Escherichia coli from lower urinary infections. The activity of nitrofurantoin and sulfamethoxazole was higher in SHU than in MHb; minimal inhibitory concentrations (MICs) in SHU with ascorbate were below typical urinary concentrations. For other antibiotics, MICs were the same in MHb vs. SHU, with no effect of ascorbate in MHb; but in SHU with ascorbate, MICs of ciprofloxacin and gentamicin also went below reported urinary concentrations, with a lesser effect with norfloxacin and trimethoprim, and none with ampicillin. The effect of ascorbate was independent of oxygen and not related to the susceptibility of each strain to oxidative stress. Ascorbate oxidizes during incubation in SHU, and bacterial growth partially prevented oxidation. These results suggest that 10 mM ascorbate can enhance the inhibitory activity of antibiotics upon resistant strains in urine. Clinical experimentation with ascorbate-antibiotic combinations against urinary infections caused by resistant bacteria is warranted.
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BACKGROUND: Bacterial multi-resistance is a serious global problem that continues to worsen over time due to multiple factors. Among these factors, it is important to highlight the clinical misuse of antibiotics and the mechanisms that microorganisms have developed to protect themselves from these drugs. In this sense, Staphylococcus aureus (S. aureus) is a pathogen that has found a way to resist many of the drugs currently in use, so infections by this bacterium represent a serious clinical problem. OBJECTIVES: The purpose of this study was to determine the type of interaction between ciprofloxacin and gentamicin against beta-lactamase-producing S. aureus using isobolographic analysis. METHODS: Ciprofloxacin (0.5-0.05 mg/mL) and gentamicin (10-1 mg/mL) were used to make concentration-dependent curves for each individual drug. Thereafter, the 50 inhibitory concentration (IC50 ) of each drug was obtained, and different proportions of the ciprofloxacin-gentamicin combination-0.5:0.5, 0.8:0.2, 0.2:0.8, 0.9:0.1, 0.1:0.9, 0.95:0.05, and 0.05:0.95-were evaluated. The isobolographic analysis and the interaction index were used to analyze the data. RESULTS: The isobolographic evaluation of the combination showed that the ratios 0.5:0.5, 0.8:0.2, 0.2:0.8, and 0.9:0.1 produced a synergistic anti-staphylococcal effect, and the 0.95:0.05 ratio induced an additive antibacterial effect. Finally, the 0.1:0.9 and 0.05:0.95 ratios of the combination presented antagonistic effects against S. aureus. On the other hand, the interaction index showed similar results to the isobolographic analysis. CONCLUSION: The isobolographic results of this in vitro assay show that the ciprofloxacin-gentamicin combination induces synergistic, additive, and antagonistic antimicrobial effects against S. aureus.
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Ciprofloxacina , Infecções Estafilocócicas , Humanos , Ciprofloxacina/farmacologia , Staphylococcus aureus , Gentamicinas/farmacologia , beta-Lactamases/farmacologia , Sinergismo Farmacológico , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologiaRESUMO
AIMS: Sulforaphane (SFN), a naturally occurring isothiocyanate found in cruciferous vegetables, has received extensive attention as a natural activator of the Nrf2/Keap1 cytoprotective pathway. In this review, a meta-analysis and systematic review of the renoprotective effects of SFN were performed in various preclinical models of kidney diseases. MAIN METHODS: The primary outcome was the impact of SFN on renal function biomarkers (uremia, creatininemia, proteinuria or creatinine clearance) and secondary outcomes were kidney lesion histological indices/kidney injury molecular biomarkers. The effects of SFN were evaluated according to the standardized mean differences (SMDs). A random-effects model was applied to estimate the overall summary effect. KEY FINDINGS: Twenty-five articles (out of 209 studies) were selected from the literature. SFN administration significantly increased creatinine clearance (SMD +1.88 95 % CI: [1.09; 2.68], P < 0.0001, I2 = 0 %) and decreased the plasma creatinine (SMD -1.24, [-1.59; -0.88], P < 0.0001, I2 = 36.0 %) and urea (SMD -3.22 [-4.42, -2.01], P < 0.0001, I2 = 72.4 %) levels. SFN administration (median dose: 2.5 mg/kg, median duration: 3 weeks) significantly decreased urinary protein excretion (SMD -2.20 [-2.68; -1.73], P < 0.0001, I2 = 34.1 %). It further improved two kidney lesion histological indices namely kidney fibrosis (SMD -3.08 [-4.53; -1.63], P < 0.0001, I2 = 73.7 %) and glomerulosclerosis (SMD -2.24 [-2.96; -1.53], P < 0.0001, I2 = 9.7 %) and decreased kidney injury molecular biomarkers (SMD -1.51 [-2.00; -1.02], P < 0.0001, I2 = 0 %). SIGNIFICANCE: These findings provide new insights concerning preclinical strategies for treating kidney disease or kidney failure with SFN supplements and should stimulate interest in clinical evaluations of SFN in patients with kidney disease.
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Nefropatias , Fator 2 Relacionado a NF-E2 , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Creatinina , Fator 2 Relacionado a NF-E2/metabolismo , Nefropatias/tratamento farmacológico , Isotiocianatos/farmacologia , Isotiocianatos/uso terapêutico , Biomarcadores/metabolismoRESUMO
Background and Objectives: Gentamicin (GM) is a nephrotoxic aminoglycoside. Neutral electrolyzed saline (SES) is a compound with anti-inflammatory, antioxidant, and immunomodulatory properties. The objective of the present study was to evaluate whether kidney damage by GM can be prevented and/or reversed through the administration of SES. Materials and Methods: The study was carried out as a prospective, single-blind, five-arm, parallel-group, randomized, preclinical trial. The nephrotoxicity model was established in male BALB/c mice by administering GM at a dose of 100 mg/kg/day intraperitoneally for 30 days, concomitantly administering (+) SES or placebo (physiologic saline solution), and then administering SES for another 30 days after the initial 30 days of GM plus SES or placebo. At the end of the test, the mice were euthanized, and renal tissues were evaluated histopathologically. Results: The GM + placebo group showed significant tubular injury, interstitial fibrosis, and increased interstitial infiltrate of inflammatory cells compared with the group without GM. Tubular injury and interstitial fibrosis were lower in the groups that received concomitant GM + SES compared with the GM + placebo group. SES administration for 30 days after the GM administration periods (GM + placebo and GM + SES for 30 days) did not reduce nephrotoxicity. Conclusions: Intraperitoneal administration of SES prevents gentamicin-induced histologic nephrotoxicity when administered concomitantly, but it cannot reverse the damage when administered later.
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Gentamicinas , Rim , Animais , Masculino , Camundongos , Ratos , Modelos Animais de Doenças , Fibrose , Gentamicinas/metabolismo , Gentamicinas/farmacologia , Rim/patologia , Estresse Oxidativo , Estudos Prospectivos , Ratos Wistar , Solução Salina/farmacologia , Método Simples-CegoRESUMO
Infectious diseases account for nine percent of annual human deaths, and the widespread emergence of antimicrobial resistances threatens to significantly increase this number in the coming decades. The prospect of antimicrobial peptides (AMPs) derived from venomous animals presents an interesting alternative for developing novel active pharmaceutical ingredients (APIs). Small, cationic and amphiphilic peptides were predicted from the venom gland transcriptome of Pamphobeteus verdolaga using a custom database of the arthropod's AMPs. Ninety-four candidates were chemically synthesized and screened against ATCC® strains of Escherichia coli and Staphylococcus aureus. Among them, one AMP, named PvAMP66, showed broad-spectrum antimicrobial properties with selectivity towards Gram-negative bacteria. It also exhibited activity against Pseudomonas aeruginosa, as well as both an ATCC® and a clinically isolated multidrug-resistant (MDR) strain of K. pneumoniae. The scanning electron microscopy analysis revealed that PvAMP66 induced morphological changes of the MDR K. pneumoniae strain suggesting a potential "carpet model" mechanism of action. The isobologram analysis showed an additive interaction between PvAMP66 and gentamicin in inhibiting the growth of MDR K. pneumoniae, leading to a ten-fold reduction in gentamicin's effective concentration. A cytotoxicity against erythrocytes or peripheral blood mononuclear cells was observed at concentrations three to thirteen-fold higher than those exhibited against the evaluated bacterial strains. This evidence suggests that PvAMP66 can serve as a template for the development of AMPs with enhanced activity and deserves further pre-clinical studies as an API in combination therapy.
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BACKGROUND: This study aimed to evaluate different concentrations of vancomycin and/or gentamicin loaded polymethylmethacrylate (PMMA) against biofilm formation of Staphylococcus aureus. METHODS: Biofilm production of S. aureus in PMMA loaded with different concentrations of vancomycin and gentamicin were evaluated by quantitative analysis of biofilm cells, scanning electronic microscopy, viability assay, Fourier transform infrared spectroscopy, and checkerboard. Statistical analysis was performed by Mann Whitney test. The difference in colony forming units per mL was significant when p < 0.05. RESULTS: All loaded PMMA presented a reduction in the number of colony forming units per mL (p < 0.05). The gentamicin-loaded PMMA could inhibits the grown of sessile cells (p < 0.05), where the group vancomycin 4 g + gentamicin 500 mg presented a better result. The Fourier transform infrared spectra showed no significant differences, and checkerboard of vancomycin and gentamicin showed synergism. CONCLUSION: Effects against adherence and bacterial development in PMMA loaded with antibiotics were mainly seen in the group vancomycin 4 g + gentamicin 500 mg, and synergic effect can be applied in antibiotic-loaded cement.
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Biofilm formation is a key factor in the pathogenesis of enterococcal infections. Thus, the biofilm-forming ability and frequency of biofilm-related genes in penicillin-resistant, ampicillin-susceptible Enterococcus faecalis (PRASEF) compared to penicillin- and ampicillin-susceptible E. faecalis (PSASEF) were assessed in the present study. In addition, the effect of sub-inhibitory concentrations (sub-MICs) of antibiotics on biofilm formation and expression of virulence genes was evaluated. Twenty PRASEF and 21 PSASEF clinical isolates were used to determine the effect of sub-MICs of antibiotics (ampicillin, penicillin, and gentamicin) on biofilm formation, and ten selected isolates were subjected to RT-qPCR to detect the transcript levels of virulence genes (efaA, asa1, esp, and ace). Antibiotic susceptibility was evaluated by the microdilution broth method. Biofilm formation assay was performed using the microtiter plate method. All PSASEF and PRASEF isolates produced biofilms in vitro. Most isolates had three or four virulence genes. Sub-MICs of ampicillin significantly decreased biofilm production and expression of ace and asa1 genes, although the transcript levels were significantly lower (-350% and -606.2%, respectively) among the PSASEF isolates only. Sub-MICs of gentamicin did not have any significant effect on biofilm formation, but slightly increased the transcript levels of efaA. In conclusion, this study showed that the biofilm-forming ability and frequency of the evaluated virulence genes were similar among the PRASEF and PSASEF isolates. Further, in vitro antibiotic sub-MICs were confirmed to interfere with the expression pattern of virulence genes and biofilm formation by E. faecalis. However, further studies are required to clarify the role of sublethal doses of antibiotics on enterococcal biofilms.
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INTRODUCTION: Ménière's disease is a multifactorial disorder affecting the inner ear, characterized by episodes of spontaneous and recurrent vertigo, fluctuating hearing loss and tinnitus. Intratympanic gentamicin therapy has been used to reduce the intensity and frequency of attacks in intractable Ménière's disease, but it is associated with hearing loss. There is controversy regarding its efficacy and safety. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified 13 systematic reviews that included 80 primary studies overall, of which three correspond to randomized trials. We concluded that intratympanic gentamicin may improve the control of vertigo, and result in little or no difference to tinnitus, but the certainty of the evidence is low. Furthermore, we are uncertain whether intratympanic gentamicin reduces hearing or the frequency of vertigo attacks as the certainty of the evidence has been assessed as very low.
INTRODUCCION: La enfermedad de Ménière es una anomalía del oído interno de etiología multifactorial, caracterizada por episodios de vértigo espontáneo y recurrente, hipoacusia fluctuante y tinnitus. La terapia con gentamicina intratimpánica para la enfermedad de Ménière ha sido utilizada buscando reducir la intensidad y frecuencia de las crisis, pero se ha asociado a pérdida auditiva, por lo que existe controversia respecto a su eficacia y seguridad. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos 13 revisiones sistemáticas que en conjunto incluyeron 80 estudios primarios, de los cuales tres corresponden a ensayos aleatorizados. Concluimos que la gentamicina intratimpánica podría reducir el control del vértigo y resultar en poca o nula diferencia sobre el tinnitus, pero la certeza de evidencia es baja. Además, no es posible establecer con claridad si el uso de gentamicina intratimpánica disminuye la audición o la frecuencia de los ataques de vértigo porque la certeza de la evidencia existente ha sido evaluada como muy baja.
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Doença de Meniere , Zumbido , Gentamicinas/uso terapêutico , Humanos , Doença de Meniere/tratamento farmacológico , Revisões Sistemáticas como Assunto , Zumbido/tratamento farmacológico , Zumbido/etiologia , Vertigem/tratamento farmacológico , Vertigem/etiologiaRESUMO
Gentamicin induced acute nephrotoxicity (GIAN) is considered as one of the important causes of acute renal failure. In recent years' great effort has been focused on the introduction of herbal medicine as a novel therapeutic agent for prevention of GIAN. Hence, the current study was designed to investigate the effect of green coffee bean extract (GCBE) on GIAN in rats. Results of the present study showed that rat groups that received oral GCBE for 7 days after induction of GIAN(by a daily intraperitoneal injection of gentamicin for 7days), reported a significant improvement in renal functions tests when compared to the GIAN model groups. Moreover, there was significant amelioration in renal oxidative stress markers (renal malondialdehyde, renal superoxide dismutase) and renal histopathological changes in the GCBE-treated groups when compared to GIAN model group. These results indicate that GCBE has a potential role in ameliorating renal damage involved in GIAN.
La nefrotoxicidad aguda inducida por gentamicina (GIAN) se considera una de las causas importantes de insuficiencia renal aguda. En los últimos años, el gran esfuerzo se ha centrado en la introducción de la medicina herbal como un nuevo agente terapéutico para la prevención de GIAN. Por lo tanto, el estudio actual fue diseñado para investigar el efecto del extracto de grano de café verde (GCBE) sobre la GIAN en ratas. Los resultados del presente estudio mostraron que los grupos de ratas que recibieron GCBE oral durante 7 días después de la inducción de GIAN (mediante una inyección intraperitoneal diaria de gentamicina durante 7 días), informaron una mejora significativa en las pruebas de función renal en comparación con los grupos del modelo GIAN. Además, hubo una mejora significativa en los marcadores de estrés oxidativo renal (malondialdehído renal, superóxido dismutasa renal) y cambios histopatológicos renales en los grupos tratados con GCBE en comparación con el grupo del modelo GIAN. Estos resultados indican que GCBE tiene un papel potencial en la mejora del daño renal involucrado en GIAN.
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Animais , Masculino , Ratos , Extratos Vegetais/administração & dosagem , Gentamicinas/toxicidade , Coffea/química , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/prevenção & controle , Antioxidantes/administração & dosagem , Superóxido Dismutase/análise , Extratos Vegetais/farmacologia , Ratos Wistar , Café , Estresse Oxidativo/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/patologia , Testes de Função Renal , Malondialdeído/análise , Antioxidantes/farmacologiaRESUMO
INTRODUCCION La enfermedad de Ménière es una anomalía del oído interno de etiología multifactorial, caracterizada por episodios de vértigo espontáneo y recurrente, hipoacusia fluctuante y tinnitus. La terapia con gentamicina intratimpánica para la enfermedad de Ménière ha sido utilizada buscando reducir la intensidad y frecuencia de las crisis, pero se ha asociado a pérdida auditiva, por lo que existe controversia respecto a su eficacia y seguridad. MÉTODOS Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES Identificamos 13 revisiones sistemáticas que en conjunto incluyeron 80 estudios primarios, de los cuales tres corresponden a ensayos aleatorizados. Concluimos que la gentamicina intratimpánica podría reducir el control del vértigo y resultar en poca o nula diferencia sobre el tinnitus, pero la certeza de evidencia es baja. Además, no es posible establecer con claridad si el uso de gentamicina intratimpánica disminuye la audición o la frecuencia de los ataques de vértigo porque la certeza de la evidencia existente ha sido evaluada como muy baja.
INTRODUCTION Ménière's disease is a multifactorial disorder affecting the inner ear, characterized by episodes of spontaneous and recurrent vertigo, fluctuating hearing loss and tinnitus. Intratympanic gentamicin therapy has been used to reduce the intensity and frequency of attacks in intractable Ménière's disease, but it is associated with hearing loss. There is controversy regarding its efficacy and safety. METHODS We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS We identified 13 systematic reviews that included 80 primary studies overall, of which three correspond to randomized trials. We concluded that intratympanic gentamicin may improve the control of vertigo, and result in little or no difference to tinnitus, but the certainty of the evidence is low. Furthermore, we are uncertain whether intratympanic gentamicin reduces hearing or the frequency of vertigo attacks as the certainty of the evidence has been assessed as very low.
Assuntos
Humanos , Zumbido/etiologia , Zumbido/tratamento farmacológico , Doença de Meniere/tratamento farmacológico , Gentamicinas/uso terapêutico , Vertigem/etiologia , Vertigem/tratamento farmacológico , Revisões Sistemáticas como AssuntoRESUMO
Abstract Introduction Aminoglycoside, as an antimicrobial medication, also has side-effects on the inner ears, bringing about hearing disorders. Curcumin has been proven to be a strong scavenger against various reactive oxygen species (ROS), and the increase in ROS production is considered to play an important role in the process of hearing disorder. Objective To prove that curcumin is an effective antioxidant to prevent cochlear damage based on malondialdehyde (MDA) expression. Methods The present research used 32 Rattus norvegicus, of the Wistar lineage, randomly divided into 8 groups: negative control, ototoxic control (a single dose of 40 mg/ml of gentamicin via intratympanic injection), 2 groups submitted to ototoxic control + curcumin treatment (100 mg/kg, 200 mg/kg), 2 groups who iunderwent ototoxic control + curcumin treatment for 7 days, and two groups submitted to curcumin treatment as prevention for 3 days + ototoxic induction. Results The results showed that the lowest dosage of curcumin (100 mg/kg) could decrease MDA expression on the cochlear fibroblastic wall of the ototoxic model; however using greater doses of curcumin (200 mg/kg) for 7 days would provide a better effect. Curcumin could also significantly decrease MDA expression when it was administered during the preototoxic exposure. Conclusion Curcumin can be used as a therapy for ototoxic prevention based on the decrease in MDA expression.
RESUMO
As preconized by the One Health concept, the intimate relationship between pets and owners is a common source for the trade of microorganisms with zoonotic potential, and with them, antimicrobial resistance genes. In this work, we evaluated the presence of antimicrobial resistance genes, that are usually within mobile genetic elements, in a laboratory collection of 79 canine Staphylococcus strains, mostly Staphylococcus pseudintermedius and Staphylococcus coagulans. Resistance to tetracycline was observed in 34% of the strains, followed by resistance to erythromycin (21%) and gentamicin (19%). These phenotypes were partially correlated with the presence of the tetracycline resistance genes tet(M) and tet(K) in 64% and 44% of all strains, respectively; erythromycin resistance genes erm(A) and erm(C) in 53% and 23%; and gentamicin resistance gene aac(6')-aph(2â³) in 26% of the strains. At least 45% of the strains harbored high- and/or low-molecular weight plasmids, whose transfer may be facilitated by their widespread biofilm-forming capacity, and absence of restrictive CRISPR systems. We selected eight plasmid-bearing and multidrug resistant strains, which were submitted to plasmid curing by stress with SDS. No strain lost resistance during stressing cultivation but, by conjugation experiments, the S. pseudintermedius strain 27 transferred its plasmid-borne resistance to gentamicin, conferred by the aac(6')-aph(2â³) gene, to Staphylococcus aureus. The frequent empirical use of gentamicin to treat skin and ear infections in domestic dogs is likely to select resistant strains. Also, as demonstrated by our study, these strains can serve as gene reservoirs for human pathogens, such as S. aureus.