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1.
BMJ Case Rep ; 13(7)2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32690571

RESUMO

A 45-year-old man presented with acute sinusitis. He was treated with a 10-day course of trimethoprim/sulfamethoxazole, and a subsequent 14-day course of amoxicillin-clavulanate with no improvement in symptoms. Culture of purulent nasal secretions revealed the rare enterobacter Cedecea lapagei The patient had complete resolution of his symptoms after a 14-day course of gentamicin/dexamethasone nasal rinses. Emerging pathogens have been a timeless concern for physicians, as witnessed by the current SARS-CoV-2 outbreak. C. lapagei has been reported to cause human infection only a dozen times since its discovery, all in severely compromised patients. This is the first documented case of sinusitis reported with C. lapagei and may portend a rising prevalence of disease burden in the general population. This case demonstrates the necessity of obtaining cultures when standard antibiotics result in treatment failure.


Assuntos
Dexametasona/administração & dosagem , Infecções por Enterobacteriaceae/tratamento farmacológico , Gentamicinas/administração & dosagem , Sinusite/tratamento farmacológico , Doença Aguda , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Antibacterianos/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Dexametasona/uso terapêutico , Quimioterapia Combinada/métodos , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/complicações , Gentamicinas/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Sinusite/microbiologia , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
2.
Bone Joint J ; 102-B(6_Supple_A): 151-157, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32475290

RESUMO

AIMS: We propose a state-of-the-art temporary spacer, consisting of a cobalt-chrome (CoCr) femoral component and a gentamicin-eluting ultra-high molecular weight polyethylene (UHMWPE) tibial insert, which can provide therapeutic delivery of gentamicin, while retaining excellent mechanical properties. The proposed implant is designed to replace conventional spacers made from bone cement. METHODS: Gentamicin-loaded UHMWPE was prepared using phase-separated compression moulding, and its drug elution kinetics, antibacterial, mechanical, and wear properties were compared with those of conventional gentamicin-loaded bone cement. RESULTS: Gentamicin-loaded UHMWPE tibial components not only eradicated planktonic Staphylococcus aureus, but also prevented colonization of both femoral and tibial components. The proposed spacer possesses far superior mechanical and wear properties when compared with conventional bone cement spacers. CONCLUSION: The proposed gentamicin-eluting UHMWPE spacer can provide antibacterial efficacy comparable with currently used bone cement spacers, while overcoming their drawbacks. The novel spacer proposed here has the potential to drastically reduce complications associated with currently used bone cement spacers and substantially improve patients' quality of life during the treatment. Cite this article: Bone Joint J 2020;102-B(6 Supple A):151-157.


Assuntos
Antibacterianos/administração & dosagem , Cimentos para Ossos , Portadores de Fármacos , Gentamicinas/administração & dosagem , Prótese do Joelho/efeitos adversos , Polietilenos , Próteses e Implantes , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/etiologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , Humanos , Tíbia
4.
Life Sci ; 254: 117760, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32418889

RESUMO

AIM: The present study focused on the possible underlying protective mechanisms of UDCA against GNT-induced hepatic injury. METHODS: For achieving this goal, adult male rats were allocated into 4 groups: normal control (received vehicle), GNT (100 mg/kg, i.p. for 8 days), UDCA (60 mg/kg, P.O. for 15 days), and GNT + UDCA (received UDCA for 15 days and GNT started from the 7th day and lasted for 8 days). RESULTS: The results revealed that UDCA significantly improved GNT-induced hepatic injury, oxidative stress, apoptosis, and inflammatory response. Interestingly, UDCA inhibited apoptosis by marked down-regulation of the Bax gene, Caspase-3, and cleaved Caspase-3 protein expressions while the level of Bcl-xL gene significantly increased. Moreover, UDCA strongly inhibited the inflammatory response through the down-regulation of both NF-κB-p65 and TNF-α accompanied by IL-10 elevation. Furthermore, the obtained results ended with the restored of mitochondria function that confirmed by electron microscopy. Histological analysis showed that UDCA remarkably ameliorated the histopathological changes induced by GNT. SIGNIFICANCE: UDCA may be a promising agent that can be used to prevent hepatotoxicity observed in GNT treatment. This effect could be attributed to, at least in part, the ability of UDCA to modulate NF-κB-p65/TNF-α, Bax/Bcl-xl/Caspase-3, and eNOS/iNOS signaling pathways.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Gentamicinas/antagonistas & inibidores , Gentamicinas/toxicidade , Hepatócitos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Ácido Ursodesoxicólico/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Interações Medicamentosas , Hepatócitos/metabolismo , Hepatócitos/patologia , Masculino , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Wistar , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteína bcl-X/metabolismo
6.
Life Sci ; 251: 117628, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32247620

RESUMO

AIM: Investigation whether androgen/androgen receptor (AR) might regulate megalin expression and/or functionality and thus affecting Gentamicin-induced nephrotoxicity (GIN). MAIN METHODS: Male Wistar rats were treated with gentamicin with/out AR ligands (testosterone as agonist and flutamide as antagonist). Megalin expression in the kidney tissues was determined by real-time RT-PCR and western blot. Besides, megalin functionality was assessed using immunofluorescence imaging of fluorescein isothiocyanate (FITC) conjugated bovine serum albumin (BSA) (FITC-BSA). The effects of different treatments on the kidney were assessed at the structural level by histopathological evaluation and the biochemical level by colorimetric assay of blood urea nitrogen (BUN), serum creatinine (SCr) and urinary albumin/creatinine (A/C) ratio, besides, kidney expression of neutrophil gelatinase-associated lipocalin (NGAL) by immunoblotting. KEY FINDINGS: Our results revealed that treatment with testosterone either alone or combined with gentamicin increased megalin expression at mRNA and protein levels as well as at the functional level. These effects were paralleled by increased GIN as manifested by increased SCr, BUN, A/C ratio, renal expression of NGAL or histopathological changes. On the other hand, treatment with flutamide ameliorated GIN and megalin expression and functionality. Computational analysis of megalin promotor revealed the presence of multiple response elements that mediate androgen response. SIGNIFICANCE: Androgen/AR regulates megalin expression at the transcriptional level and consequently GIN. This may explain the sexual dimorphism in GIN and might represent a druggable target for treatment or prevention of GIN.


Assuntos
Androgênios/metabolismo , Antibacterianos/toxicidade , Gentamicinas/toxicidade , Nefropatias/induzido quimicamente , Receptores Androgênicos/metabolismo , Animais , Flutamida/farmacologia , Nefropatias/fisiopatologia , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Masculino , Ratos , Ratos Wistar , Testosterona/farmacologia
7.
PLoS One ; 15(4): e0231583, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294120

RESUMO

Infections caused by antibiotic-resistant strains of Staphylococcus aureus have reached epidemic proportions globally. Our previous study showed antimicrobial effects of anandamide (AEA) and arachidonoyl serine (AraS) against methicillin (MET)-resistant S. aureus (MRSA) strains, proposing the therapeutic potential of these endocannabinoid/endocannabinoid-like (EC/EC-like) agents for the treatment of MRSA. Here, we investigated the potential synergism of combinations of AEA and AraS with different types of antibiotics against MRSA grown under planktonic growth or biofilm formation. The most effective combinations under planktonic conditions were mixtures of AEA and ampicillin (AMP), and of AraS and gentamicin (GEN). The combination with the highest synergy in the biofilm formation against all tested bacterial strains was AEA and MET. Moreover, the combination of AraS and MET synergistically caused default of biofilm formation. Slime production of MRSA was also dramatically impaired by AEA or AraS combined with MET. Our data suggest the novel potential activity of combinations of EC/EC-like agents and antibiotics in the prevention of MRSA biofilm formation.


Assuntos
Antibacterianos/farmacologia , Ácidos Araquidônicos/farmacologia , Agonistas de Receptores de Canabinoides/farmacologia , Endocanabinoides/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Alcamidas Poli-Insaturadas/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Ampicilina/farmacologia , Ampicilina/uso terapêutico , Antibacterianos/uso terapêutico , Ácidos Araquidônicos/uso terapêutico , Biofilmes/efeitos dos fármacos , Agonistas de Receptores de Canabinoides/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Endocanabinoides/uso terapêutico , Gentamicinas/farmacologia , Gentamicinas/uso terapêutico , Humanos , Resistência a Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Alcamidas Poli-Insaturadas/uso terapêutico , Serina/análogos & derivados , Serina/farmacologia , Serina/uso terapêutico , Infecções Estafilocócicas/microbiologia
8.
Otolaryngol Head Neck Surg ; 162(2_suppl): S1-S55, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32267799

RESUMO

OBJECTIVE: Ménière's disease (MD) is a clinical condition defined by spontaneous vertigo attacks (each lasting 20 minutes to 12 hours) with documented low- to midfrequency sensorineural hearing loss in the affected ear before, during, or after one of the episodes of vertigo. It also presents with fluctuating aural symptoms (hearing loss, tinnitus, or ear fullness) in the affected ear. The underlying etiology of MD is not completely clear, yet it has been associated with inner ear fluid (endolymph) volume increases, culminating in episodic ear symptoms (vertigo, fluctuating hearing loss, tinnitus, and aural fullness). Physical examination findings are often unremarkable, and audiometric testing may or may not show low- to midfrequency sensorineural hearing loss. Conventional imaging, if performed, is also typically normal. The goals of MD treatment are to prevent or reduce vertigo severity and frequency; relieve or prevent hearing loss, tinnitus, and aural fullness; and improve quality of life. Treatment approaches to MD are many and typically include modifications of lifestyle factors (eg, diet) and medical, surgical, or a combination of therapies. PURPOSE: The primary purpose of this clinical practice guideline is to improve the quality of the diagnostic workup and treatment outcomes of MD. To achieve this purpose, the goals of this guideline are to use the best available published scientific and/or clinical evidence to enhance diagnostic accuracy and appropriate therapeutic interventions (medical and surgical) while reducing unindicated diagnostic testing and/or imaging.


Assuntos
Doença de Meniere/diagnóstico , Doença de Meniere/terapia , Audiometria , Aconselhamento , Diagnóstico Diferencial , Diuréticos/uso terapêutico , Orelha Interna/cirurgia , Gentamicinas/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Doença de Meniere/epidemiologia , Transtornos de Enxaqueca/diagnóstico , Educação de Pacientes como Assunto , Qualidade de Vida , Vertigem/diagnóstico , Doenças Vestibulares/diagnóstico
10.
Epidemiol Mikrobiol Imunol ; 69(1): 3-9, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32326710

RESUMO

AIM: The presented study was to compare in vitro biofilm production by bacterial strains from chronic/recurrent and from acute non-complicated UTIs. The activity of gentamicin and colistin on biofilm form of these strains has also been detected, with goal to predict the gentamicin and colistin therapeutic efficacy in the antimicrobial treatment of patients with a suspected presence of biofilm in urinary tract. MATERIAL AND METHODS: The group of 40 bacterial strains repeatedly isolated from patients with chronic or recurrent UTIs was compared with the group of 40 strains from acute UTIs. Both groups contained comparable number of strains of Escherichia coli, Klebsiella spp., Proteus mirabilis and Pseudomonas aeruginosa. Biofilm production was assessed by method in polystyrene microtiter plate. The MIC and MBC values of gentamicin and colistin were detected by broth microdilution assay. The minimal biofilm inhibitory (MBIC) and biofilm eradication concentrations (MBEC) were tested by microdilution method. Non-inactivated biofilm-associated bacteria were detected after overnight incubation in broth medium free of antimicrobials. The statistical analysis of results was performed by Fisher's exact test and by Student's t-test. RESULTS: Biofilm was produced by 90% strains from chronic UTIs, but only by 52% of strains from acute UTIs (p = 0.0004). In the biofilm producing strains, the MBIC values of gentamicin reached from four to 256 mg/L, the MBIC levels of colistin from two to 64 mg/L. The minimal biofilm eradicating concentrations were even higher: for gentamicin from eight to > 512 mg/L, and for colistin from 32 to > 512 mg/L. The differences between MIC and MBIC/MBEC levels were statistically highly significant (p < 0.0001). Presumably, the therapeutic success of parenterally applied gentamicin or colistin on biofilm-related urinary tract infections would be, without respect to the high concentration of gentamicin or colistin achievable in urine during parenteral application, rather unpredictable. Local intravesical instillation would allow for achieving higher gentamicin and colistin concentrations; however, there is need for interpretation criteria for MBEC values concerning therapy, as well as for clinical studies allowing for application of those values to predict clinical success of therapy. CONCLUSIONS: Laboratory detection of biofilm production and evaluation of the MBIC/MBEC values of antimicrobials for strains producing biofilm might be a valuable complement to the microbiologic diagnostics of chronic and recurrent UTIs. It might provide valuable information for more reliable individualised therapy and so decrease the risk of emergence and selection of multiresistant strains during repeated and non-eradicating therapy of chronic and recurrent UTIs.


Assuntos
Bactérias , Fenômenos Fisiológicos Bacterianos , Biofilmes , Colistina , Infecções Urinárias , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Fenômenos Fisiológicos Bacterianos/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Doença Crônica , Colistina/farmacologia , Gentamicinas/farmacologia , Humanos , Técnicas In Vitro , Testes de Sensibilidade Microbiana , Infecções Urinárias/microbiologia
12.
Environ Sci Pollut Res Int ; 27(14): 16189-16202, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32112355

RESUMO

Polycyclic aromatic hydrocarbons (PAHs)/aryl hydrocarbon receptor (AhR) regulate the expression of target genes, including drug transporter genes which harbor xenobiotic response element (XRE) in their promoter regions. Thus, PAHs/AhR could alter the toxicokinetic profile of many nephrotoxic drugs, including aminoglycosides. In the current study, we investigated the expression and localization of AhR and megalin in rat kidney. Furthermore, we investigated whether AhR and its ligands could modulate the expression of megalin and consequently the gentamicin-induced nephrotoxicity (GN) in rats. Both megalin and AhR receptors are expressed in the proximal tubules of the rat kidney. Treatment with AhR agonist benzo(a)pyrene aggravated GN as indicated by a significant increase in serum creatinine, BUN, KIM1, NAGL, CD-86, and urinary albumin/creatinine ratio. On the other hand, treatment with AhR antagonist resveratrol ameliorated GN as manifested by a pronounced decrease in the aforementioned parameters. The effects of AhR ligands on GN were associated with altered expression of megalin receptor.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Receptores de Hidrocarboneto Arílico , Animais , Benzo(a)pireno , Gentamicinas , Ligantes , Ratos
13.
Pesqui. vet. bras ; 40(2): 129-133, Feb. 2020. tab
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1098445

RESUMO

Enterococcus are recognized worldwide as significant nosocomial agents that have been continuously envolving to adapt to different niches and acquire resistance to several antibiotic classes. Vancomycin and gentamicin-resistant strains of E. faecalis and E. faecium have been associated with nosocomial human infections. Some epidemiological studies suggest the participation of pets as reservoirs of vancomycin and gentamicin-resistant Enterococcus strains. However, the role of companion birds as reservoirs of these strains has been poorly studied. In this study, 126 psittacine birds were evaluated and 26.9% carried Enterococcus spp., including the species E. faecalis, E. faecium, E. hirae, E. phoeniculicola, E. gallinarum and E. casseliflavus. The antibiotic resistance profile showed four high-level gentamicin-resistance (HLGR) strains. In addition, two strains presented intermediate levels of vancomycin resistance. Resistant strains were isolated from fecal and oropharynx samples of sick and clinically healthy birds, suggesting that psittacine birds may act as reservoirs of HLGR Enterococcus spp. However, sick birds appear to be more implicated in the enterococci transmission than healthy birds.(AU)


Enterococcus são reconhecidos mundialmente como significantes agentes nosocomiais, que têm continuamente se adaptado a diferentes nichos e adquirido resistência a várias classes de antibióticos. Cepas de E. faecalis e E. faecium vancomicina e gantamicina-resistentes têm sido associadas a infecções nosocomiais em humanos. Alguns estudos epidemiológicos sugerem a participação de aves como reservatórios de cepas de Enterococcus vancomicina e gentamicina-resistentes. Entretanto, a relação das aves de companhia como reservatórios destas cepas tem sido pouco estudada. Neste estudo, 126 psitacídeos foram avaliados, e 26,9% destes eram portadores de Enterococcus spp., incluindo as espécies E. faecalis, E. faecium, E. hirae, E. phoeniculicola, E. gallinarum e E. casseliflavus. O perfil de resistência antibiótica mostrou quatro cepas com alto nível de resistência a gentamicina (ANRG). Além de duas cepas com nível intermediário de resistência a vancomicina. As cepas resistentes foram isoladas de amostras fecais e de orofaringe de aves doentes e clinicamente saudáveis, sugerindo que psitacídeos podem estar atuando como reservatórios para Enterococcus spp. com ANRG. Contudo, Aves doentes parecem estar mais relacionadas à transmissão de enterococcus, do que aves saudáveis.(AU)


Assuntos
Animais , Papagaios/microbiologia , Reservatórios de Doenças/veterinária , Gentamicinas , Resistência a Vancomicina , Farmacorresistência Bacteriana , Animais de Estimação/microbiologia , Enterococcus/isolamento & purificação
15.
Eur J Vasc Endovasc Surg ; 59(4): 635-641, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32094049

RESUMO

OBJECTIVE: The aim of this study was to assess the effectiveness of gentamicin containing collagen implants in the reduction of surgical site infections (SSIs) in patients undergoing an inguinal incision for vascular surgery. METHODS: Prospective blinded randomised controlled multicentre trial (RCT), performed in four hospitals in The Netherlands and Belgium. This study included 288 patients who underwent an inguinal incision for primary arterial repair (femoral endarterectomy, femorofemoral or femoropopliteal bypass, aortobifemoral bypass, thrombectomy, embolectomy, endovascular aneurysm repair) between October 2012 and December 2015. Patients were randomised to receive a gentamicin implant (study group) or no implant (control group). The calculated sample sizes of 304 patients per group were not reached. Primary outcome was SSI incidence after six weeks. Secondary outcomes were time to onset of infection, length of hospital stay, allergic reactions, treatment with antibiotics, need for re-admission, re-operation and mortality. RESULTS: One hundred fifty-one patients were allocated to the study group (mean age 69 ± 9.2 years) and 137 patients were allocated to the control group (mean age 70 ± 10.4 years). Both groups were homogeneous regarding baseline and intra-operative characteristics. Gentamicin implants did not result in a significant overall reduction of SSIs in the study group (7% vs. 12%, p = .17). In a post hoc analysis comparing two study sites with low (<10%) and two study sites with high (>10%) infection rates in the control group, gentamicin implants significantly reduced SSIs in high risk centres (22% vs. 1%, p < .001), whereas there was no significant effect in low risk centres (13% vs. 7%, p = .30). There were no allergic reactions and all secondary outcomes were comparable between groups. CONCLUSION: Gentamicin implants did not result in a significant overall reduction of SSIs in this RCT. Gentamicin implants did reduce the incidence of SSIs in high risk centres and may be a valuable adjunct to improve outcomes in such vascular centres with a high incidence of wound infections. However, the limitation of not reaching the calculated sample sizes should be considered.


Assuntos
Antibacterianos/farmacologia , Aneurisma da Aorta Abdominal/cirurgia , Gentamicinas/farmacologia , Virilha/cirurgia , Infecção da Ferida Cirúrgica , Idoso , Idoso de 80 Anos ou mais , Antibioticoprofilaxia/métodos , Aneurisma da Aorta Abdominal/tratamento farmacológico , Colágeno/farmacologia , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecção da Ferida Cirúrgica/tratamento farmacológico
16.
Cancer Radiother ; 24(2): 93-98, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32057645

RESUMO

OBJECTIVE: Postradiation nasopharyngeal necrosis (PRNN) is a notorious complication after radiotherapy that affects prognosis in patients with nasopharyngeal carcinoma (NPC). It is important for clinical doctors to realize this problem in order to cope with this severe clinical situation. The aim of our study was to assess the bacteriology of PRNN and to demonstrate the antimicrobial susceptibility pattern that should guide the clinicians towards more appropriate antibiotic use. METHODS: Sixty-nine NPC patients with PRNN in our department between March 2013 and December 2017 were retrospectively enrolled. Pathogenic culture and drug sensitivity test were performed in these 69 NPC patients with PRNN. The infection rate of Pathogens and the sensitivity of the drugs were analyzed based on these results. RESULTS: Sixty-nine NPC patients with PRNN were enrolled in our study. Pathogens were identified in 58 (84%) patients. Of the 58 patients, Staphylococcus aureus was isolated in 34 (58.6%) patients. And the second most common group of bacterial isolates was Pseudomonas aeruginosa. Antibiotic sensitivity showed that Levofloxacin was the highest (88.5%), followed by Ciprofloxacin (85.2%) and Gentamicin (80.3%). The only pathologic fungus was Candidaalbicans, about 6.8%. The positive rates of bacterial and fungal culture in PRNN patients were not significantly different from the patients' gender, age, stage, number of radiotherapy courses (P>0.05), but the cure rate was statistically higher in culture-negative patients in comparison with culture-positive patients (63.6% vs 20.7%, P=0.011). CONCLUSION: Our results provide an overall picture of the microbiology and drug susceptibility patterns for NPC patients with PRNN and could help implement guidelines for more rational treatment and improve therapeutic outcome.


Assuntos
Antibacterianos/uso terapêutico , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Nasofaringe/efeitos da radiação , Lesões por Radiação/microbiologia , Adulto , Idoso , Candida albicans/efeitos dos fármacos , Ciprofloxacino/uso terapêutico , Feminino , Gentamicinas/uso terapêutico , Humanos , Levofloxacino/uso terapêutico , Masculino , Pessoa de Meia-Idade , Nasofaringe/diagnóstico por imagem , Nasofaringe/patologia , Necrose/diagnóstico por imagem , Necrose/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/patologia , Estudos Retrospectivos , Staphylococcus aureus/efeitos dos fármacos , Resultado do Tratamento
17.
Expert Opin Drug Saf ; 19(2): 167-186, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31914328

RESUMO

Introduction: Aminoglycosides have been long used for antibacterial treatment and are still commonly used in clinical practice. Despite their extensive application and positive effects, drug-related toxicity is considered as the main obstacle for aminoglycosides. Aminoglycosides induce nephrotoxicity through the endocytosis and accumulation of the antibiotics in the epithelial cells of proximal tubule. Most importantly, however, a number of pharmacological agents were demonstrated to have protective activities against nephrotoxicity in experimental animals.Areas covered: In the present systematic review, the authors provide and discuss the mechanisms and epidemiological features of aminoglycoside-induced nephrotoxicity, and focus mainly on recent discoveries and key features of pharmacological interventions. In total, 39 articles were included in this review.Expert opinion: The majority of studies investigated gentamicin-induced nephrotoxicity in animal models. Antioxidants, chemicals, synthetic drugs, hormones, vitamins, and minerals showed potential values to prevent gentamicin-induced nephrotoxicity. Indicators used to evaluate the effectiveness of nephroprotection included antioxidative indexes, inflammatory responses, and apoptotic markers. Among the nephroprotective agents studied, herbs and natural antioxidant agents showed excellent potential to provide a protective strategy against gentamicin-induced nephrotoxicity.


Assuntos
Aminoglicosídeos/efeitos adversos , Antibacterianos/efeitos adversos , Nefropatias/prevenção & controle , Substâncias Protetoras/administração & dosagem , Aminoglicosídeos/administração & dosagem , Animais , Antibacterianos/administração & dosagem , Gentamicinas/administração & dosagem , Gentamicinas/efeitos adversos , Humanos , Nefropatias/induzido quimicamente , Substâncias Protetoras/farmacologia
18.
Chem Commun (Camb) ; 56(15): 2316-2319, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31990011

RESUMO

Carbon quantum dots derived from gentamicin sulfate are directly developed by facile calcination at different temperatures. A promising nanomaterial, CQD180, even shows a much superior antibacterial activity compared with the antibiotic counterpart and low drug resistance, by preserving the active structure of the starting materials and providing an additional antibacterial mode arising from the positive charge surface and induced reactive oxygen species simultaneously. Moreover, CQD180 can effectively disrupt mature Staphylococcus aureus biofilm and selectively eliminate bacteria over mammalian cells.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Carbono/farmacologia , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Gentamicinas/farmacologia , Pontos Quânticos/química , Staphylococcus aureus/efeitos dos fármacos , Células 3T3 , Animais , Antibacterianos/química , Carbono/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Gentamicinas/química , Células HEK293 , Humanos , Camundongos , Testes de Sensibilidade Microbiana
19.
Pediatrics ; 145(2)2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31915192

RESUMO

OBJECTIVE: To assess the association between gentamicin exposure in the neonatal period and hearing in school age. METHODS: This study included children exposed to a high-dose (6 mg/kg) gentamicin regimen as neonates (2004-2012), invited for follow-up at school age, and a healthy age-matched control group. We assessed hearing with pure tone audiometry including the extended high-frequency (EHF) range. Outcomes were average hearing thresholds in the midfrequencies (0.5-4 kHz) and the EHFs (9-16 kHz). The measures of gentamicin exposure were cumulative dose and highest trough plasma concentration. We used linear regression models to assess the impact of gentamicin exposure, and other peri- and postnatal morbidities, on hearing thresholds. RESULTS: A total of 219 gentamicin-exposed and 33 healthy-control children were included in the audiological analysis. In the gentamicin cohort, 39 (17%) had a birth weight <1500 g. Median cumulative doses and trough plasma concentrations were 30 (interquartile range 24-42) mg/kg and 1.0 (interquartile range 0.7-1.2) mg/L, respectively. Median hearing thresholds for the midfrequencies and the EHFs were 2.5 (0 to 6.3) dB hearing level and -1.7 (-5.0 to 5.0) dB hearing level, both of which were within the normal range. In an adjusted analysis, increasing hearing thresholds were associated with lower birth weight and postnatal middle-ear disease but not level of gentamicin exposure. After adjusting for birth weight, there was no difference in hearing threshold between the gentamicin-exposed cohort and healthy controls. CONCLUSIONS: Exposure to a high-dose gentamicin regimen in the neonatal period was not associated with an increase in hearing thresholds in schoolchildren being able to complete audiometry.


Assuntos
Antibacterianos/administração & dosagem , Limiar Auditivo/efeitos dos fármacos , Gentamicinas/administração & dosagem , Audição/efeitos dos fármacos , Adolescente , Antibacterianos/efeitos adversos , Antibacterianos/sangue , Audiometria de Tons Puros , Limiar Auditivo/fisiologia , Estudos de Casos e Controles , Criança , Potenciais Evocados Auditivos/fisiologia , Feminino , Gentamicinas/efeitos adversos , Gentamicinas/sangue , Audição/fisiologia , Humanos , Recém-Nascido de Baixo Peso/fisiologia , Recém-Nascido , Modelos Lineares , Masculino , Noruega , Tamanho da Amostra
20.
Chem Biol Interact ; 315: 108863, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31628940

RESUMO

Gentamicin-induced nephrotoxicity has been well documented, although the causing mechanisms and preventative measures need further investigation. The current study aimed to explore the potential protective impacts of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on gentamicin-induced nephrotoxicity and the potential mechanisms in rats. Rats were randomly divided into four groups as follows: group1: normal control, group 2: received gentamicin only (100 mg/kg intraperitoneally), group 3: concurrently received gentamicin and celecoxib (30 mg/kg, orally) and group 4: received celecoxib. Celecoxib administration decreased gentamicin-induced rise in kidney weight, renal somatic index (RSI), blood urea nitrogen (BUN), serum creatinine (Cr), protein in urine, lactate dehydrogenase (LDH), nitric oxide (NOx), meanwhile, it increased serum albumin, urine Cr level and creatinine clearance (CCr), increased the renal endogenous antioxidant status, revealed by decreased malondialdehyde (MDA) and increased superoxide dismutase (SOD) and reduced glutathione (GSH). Gentamicin-induced elevated nuclear factor kappa B-P65 subunit (NFκB-p65), tumor necrosis factor-alpha (TNF-α) and apoptotic markers (tumor suppressor protein (p53) and caspase-3) protein levels were significantly decreased upon celecoxib treatment. Moreover, celecoxib suppressed renal myeloperoxidase (MPO) activity and posed improvement of histological features. In immunohistochemistry, celecoxib-treated rats showed decreased immunoreactivity against COX-2 in tubular cells and a mild positive immunoreactivity against heat shock protein 70 (HSP70) in renal interstitial cells. These findings propose that celecoxib treatment mitigates renal dysfunction via decreasing renal inflammation, oxidative/nitrosative stress, and apoptosis.


Assuntos
Caspase 3/metabolismo , Celecoxib/farmacologia , Nefropatias/tratamento farmacológico , Rim/efeitos dos fármacos , NF-kappa B/metabolismo , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Creatinina/metabolismo , Ciclo-Oxigenase 2/metabolismo , Gentamicinas/farmacologia , Glutationa/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Masculino , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Fator de Transcrição RelA/metabolismo
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