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1.
Medicine (Baltimore) ; 99(16): e19603, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32311928

RESUMO

Hepatic encephalopathy (HE) is a complication occurring in patients with cirrhosis and is associated with neuropsychiatric and motor abnormalities. Symptomatic HE episodes almost always require hospitalization and the frequent recurrence of episodes is associated with poor prognosis and increased medical costs. The utilization of existing therapies for management of HE and adherence to them has yet to be evaluated using real-world claims data.The aim of this study was to evaluate HE drug regimens and adherence and their association with hospital readmissions in Medicare Advantage plan patients.This was a retrospective cohort study of patients discharged from a HE-related hospitalization or emergency room visit. Based on subsequent enrollment in the plan they were categorized into cohorts of 1 month, 3, and 6 months follow-up, and medication regimen was evaluated within the first month. The drugs evaluated included lactulose, rifaximin, and neomycin. Multivariable logistic regression was conducted to evaluate the association of drug regimen and medication adherence measured as proportion of days covered with HE readmissions.There were 347 patients hospitalized for HE with 184 patients having 30-day enrollment and either a drug refill or an outpatient visit in this duration. Medications were not refilled by 67 (36.4%) patients. Various drug regimens had different adherence with mean (standard deviation) proportion of days covered ranging from 0.56 (0.29) to 0.82 (0.16) at 3 months and 0.48 (0.3) to 0.77 (0.15) at 6 months. The results of logistic regression at 3 and 6 months did not show a significant association of medication use or medication adherence with hospital readmissions.Despite availability of therapy, medication utilization was alarmingly low after discharge of patients from HE-related hospitalization. Medication adherence was also low, which may affect the rate of recurrence and costs associated with readmissions. Efforts are needed in both care coordination of these patients to ensure they are prescribed appropriate medications and to enhance adherence to them.


Assuntos
Prescrições de Medicamentos/estatística & dados numéricos , Encefalopatia Hepática/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Demandas Administrativas em Assistência à Saúde , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial/estatística & dados numéricos , Antibacterianos/uso terapêutico , Quimioterapia Combinada , Feminino , Seguimentos , Fármacos Gastrointestinais/uso terapêutico , Humanos , Lactulose/uso terapêutico , Masculino , Medicare Part C , Pessoa de Meia-Idade , Neomicina/uso terapêutico , Recidiva , Estudos Retrospectivos , Rifaximina/uso terapêutico , Estados Unidos
2.
N Z Vet J ; 68(2): 126-133, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31608795

RESUMO

Case history: Gradual onset of ocular opacity was observed in three gold-striped geckos (Woodworthia chrysosiretica), and five Pacific geckos (Dactylocnemis pacificus) held in two adjacent terrariums in a zoological institution located in the North Island of New Zealand. Ultraviolet light and heat had been provided for the previous 3-4 years by a fluorescent bulb, but in the last 4 weeks of winter a ceramic heat bulb had been added, situated 10 cm above the upper mesh of the cageClinical findings: All eight geckos presented with mostly bilateral lesions of varying severity confined to the central or upper quadrant of the spectacles. These lesions ranged from variable areas of opacity within the stroma of the spectacle to similarly distributed ulcers of the surface epithelium of both spectacles. The spectacle lesions in the Pacific geckos responded well to treatment with topical combined antimicrobial therapy, within 18-29 days. The gold-striped geckos suffered complications including dysecdysis, severe spectacle ulceration and perforation, mycotic spectaculitis, and widespread mycotic dermatitis resulting in death or leading to euthanasia.Pathological findings: In the three gold-striped geckos, there were extensive areas of deep ulceration and replacement of the spectacle with a thick serocellular crust containing large numbers of fungal elements. The affected areas of the stroma were expanded by large deposits of proteinaceous and mucinous material, pyknotic cellular debris and moderate numbers of heterophils and macrophages as well as infiltrating fungal hyphae.Diagnosis: Mycotic spectaculitis with ulceration and perforation, and disseminated mycotic dermatitis likely secondary to thermal burns.Clinical relevance: This is the first report of thermal burns of the spectacle in any reptile. There was species variation in the burn severity with gold-striped geckos showing more severe lesions, possibly due to a mix of behavioural and anatomical factors. The thermal burns to the spectacles in three cases were complicated by delayed healing, perforation, dysecdysis and severe mycotic infection.


Assuntos
Queimaduras/veterinária , Oftalmopatias/veterinária , Calefação/instrumentação , Abrigo para Animais , Lagartos , Animais , Animais de Zoológico , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Bacitracina/administração & dosagem , Bacitracina/uso terapêutico , Queimaduras/etiologia , Combinação de Medicamentos , Oftalmopatias/etiologia , Oftalmopatias/patologia , Meloxicam/uso terapêutico , Neomicina/administração & dosagem , Neomicina/uso terapêutico , Polimixina B/administração & dosagem , Polimixina B/uso terapêutico , Raios Ultravioleta
3.
Nat Commun ; 10(1): 4968, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672965

RESUMO

Selectable markers are widely used in transgenesis and genome editing for selecting engineered cells with a desired genotype but the variety of markers is limited. Here we present split selectable markers that each allow for selection of multiple "unlinked" transgenes in the context of lentivirus-mediated transgenesis as well as CRISPR-Cas-mediated knock-ins. Split marker gene segments fused to protein splicing elements called "inteins" can be separately co-segregated with different transgenic vectors, and rejoin via protein trans-splicing to reconstitute a full-length marker protein in host cells receiving all intended vectors. Using a lentiviral system, we create and validate 2-split Hygromycin, Puromycin, Neomycin and Blasticidin resistance genes as well as mScarlet fluorescent proteins. By combining split points, we create 3- and 6-split Hygromycin resistance genes, demonstrating that higher-degree split markers can be generated by a "chaining" design. We adapt the split marker system for selecting biallelically engineered cells after CRISPR gene editing. Future engineering of split markers may allow selection of a higher number of genetic modifications in target cells.


Assuntos
Farmacorresistência Bacteriana/genética , Técnicas de Transferência de Genes , Engenharia Genética/métodos , Inteínas , Proteínas Luminescentes/genética , Processamento de Proteína , Sistemas CRISPR-Cas , Linhagem Celular Tumoral , Cinamatos , Edição de Genes , Vetores Genéticos , Células HEK293 , Células HeLa , Humanos , Higromicina B/análogos & derivados , Células-Tronco Pluripotentes Induzidas , Lentivirus , Neomicina , Nucleosídeos , Puromicina , Trans-Splicing , Transgenes/genética
4.
Am J Physiol Endocrinol Metab ; 317(6): E1121-E1130, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31573841

RESUMO

Metformin beneficially impacts several aspects of metabolic syndrome including dysglycemia, obesity, and liver dysfunction, thus making it a widely used frontline treatment for early-stage type 2 diabetes, which is associated with these disorders. Several mechanisms of action for metformin have been proposed, including that it acts as an anti-inflammatory agent, possibly as a result of its impact on intestinal microbiota. In accord with this possibility, we observed herein that, in mice with diet-induced metabolic syndrome, metformin impacts the gut microbiota by preventing its encroachment upon the host, a feature of metabolic syndrome in mice and humans. However, the ability of metformin to beneficially impact metabolic syndrome in mice was not markedly altered by reduction or elimination of gut microbiota, achieved by the use of antibiotics or germfree mice. Although reducing or eliminating microbiota by itself suppressed diet-induced dysglycemia, other features of metabolic syndrome including obesity, hepatic steatosis, and low-grade inflammation remained suppressed by metformin in the presence or absence of gut microbiota. These results support a role for anti-inflammatory activity of metformin, irrespective of gut microbiota, in driving some of the beneficial impacts of this drug on metabolic syndrome.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Inflamação/metabolismo , Fígado/efeitos dos fármacos , Síndrome Metabólica/metabolismo , Metformina/farmacologia , Ampicilina/farmacologia , Animais , Antibacterianos/farmacologia , Dieta Hiperlipídica , Fígado Gorduroso/metabolismo , Fígado Gorduroso/microbiologia , Microbioma Gastrointestinal/fisiologia , Vida Livre de Germes , Hiperglicemia/metabolismo , Hiperglicemia/microbiologia , Inflamação/microbiologia , Fígado/metabolismo , Síndrome Metabólica/microbiologia , Camundongos , Neomicina/farmacologia , Obesidade/metabolismo , Obesidade/microbiologia
5.
Colloids Surf B Biointerfaces ; 183: 110371, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31408783

RESUMO

The abuse of antibiotics has led to widespread antimicrobial resistance (AMR) and environmental pollution. In order to solve these problems, a lot of studies have been carried out mainly focusing on the modification and recombination of organic reagents, but bacteria are still easy to adapt to it, so they cannot be thoroughly solved. Here, we present an integrated pollution-free synergistic antibacterial nanotechnology using inorganic nano-Cu2O, which could not only enhance the efficacy of aminoglycoside antibiotics, but also eliminate their environmental pollution by photocatalytic degradation. It was found that Cu2O showed significantly synergistic antibacterial effect (1+1>2) when combined with aminoglycoside antibiotics against Escherichia coli. The inhibition zone area increased by 59.0% when Cu2O combined with neomycin. This reduces dosage and the risk of AMR, and does not pollute the environment after degradation. Next, to explore the synergistic mechanisms, we have studied the interaction of antibiotics with nanoparticles, as well as the interaction of antibacterial agents with bacteria. At last, we believe that the destruction of cell walls by Cu2O facilitates the entry of antibiotics into cells is the reason for their synergy.


Assuntos
Antibacterianos/farmacologia , Cobre/farmacologia , Escherichia coli/efeitos dos fármacos , Nanopartículas/química , Neomicina/farmacologia , Antibacterianos/química , Antibacterianos/efeitos da radiação , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Parede Celular/ultraestrutura , Cobre/química , Cobre/efeitos da radiação , Combinação de Medicamentos , Farmacorresistência Bacteriana/efeitos dos fármacos , Sinergismo Farmacológico , Escherichia coli/metabolismo , Escherichia coli/ultraestrutura , Luz , Testes de Sensibilidade Microbiana , Nanopartículas/efeitos da radiação , Nanopartículas/ultraestrutura , Nanotecnologia/métodos , Neomicina/química , Neomicina/efeitos da radiação , Fotólise
6.
BMC Res Notes ; 12(1): 369, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31262338

RESUMO

OBJECTIVES: Consumption of fish/seafood is clearly linked to higher mercury levels in human tissue samples. However, correlations between methylmercury (MeHg) intakes calculated from dietary surveys and mercury body burdens are usually weak and can vary across populations. Different factors may affect MeHg absorption, distribution, metabolism and excretion, including co-exposures to phytochemicals and antibiotics, which were shown to affect mercury body burdens in rodents. Based on the observation that rat pups developmentally exposed to MeHg and a Rhododendron tomentosum extract (Labrador Tea) presented significantly higher blood mercury levels at weaning compared to pups exposed to MeHg alone, the modulation of MeHg toxicokinetics by Labrador Tea was further investigated in adult rats. RESULTS: Total mercury levels were quantified in the blood, liver, kidney and feces of adult male rats exposed to MeHg (1.2 mg/kg bodyweight/day, for 3 weeks) administered either alone or in combination with Labrador Tea (100 mg/kg bodyweight/day) or with an antibiotics cocktail (to inhibit MeHg demethylation by gut bacteria). While the reduced fecal excretion and higher blood mercury levels expected from antibiotics-treated rats were observed, mercury levels in samples from Labrador Tea-treated rats were not significantly different from those measured in samples from rats exposed to MeHg alone.


Assuntos
Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Compostos de Metilmercúrio/farmacocinética , Extratos Vegetais/farmacocinética , Rhododendron/química , Animais , Antibacterianos/administração & dosagem , Transporte Biológico/efeitos dos fármacos , Fezes/química , Rim/química , Rim/metabolismo , Ledum/química , Fígado/química , Fígado/metabolismo , Masculino , Neomicina/administração & dosagem , Penicilinas/administração & dosagem , Ratos , Ratos Sprague-Dawley , Estreptomicina/administração & dosagem
7.
Infect Immun ; 87(10)2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31308086

RESUMO

As important players in the host defense system, commensal microbes and the microbiota influence multiple aspects of host physiology. Bordetella pertussis infection is highly contagious among humans. However, the roles of the microbiota in B. pertussis pathogenesis are poorly understood. Here, we show that antibiotic-mediated depletion of the microbiota results in increased susceptibility to B. pertussis infection during the early stage. The increased susceptibility was associated with a marked impairment of the systemic IgG, IgG2a, and IgG1 antibody responses to B. pertussis infection after antibiotic treatment. Furthermore, the microbiota impacted the short-lived plasma cell responses as well as the recall responses of memory B cells to B. pertussis infection. Finally, we found that the dysbiosis caused by antibiotic treatment affects CD4+ T cell generation and PD-1 expression on CD4+ T cells and thereby perturbs plasma cell differentiation. Our results have revealed the importance of commensal microbes in modulating host immune responses to B. pertussis infection and support the possibility of controlling the severity of B. pertussis infection in humans by manipulating the microbiota.


Assuntos
Bordetella pertussis/imunologia , Disbiose/imunologia , Microbioma Gastrointestinal/imunologia , Imunidade Humoral , Simbiose/imunologia , Coqueluche/imunologia , Ampicilina/farmacologia , Animais , Antibacterianos/farmacologia , Anticorpos Antibacterianos/biossíntese , Anticorpos Antibacterianos/classificação , Bacteroidetes/classificação , Bacteroidetes/efeitos dos fármacos , Bacteroidetes/crescimento & desenvolvimento , Bacteroidetes/imunologia , Bordetella pertussis/crescimento & desenvolvimento , Bordetella pertussis/patogenicidade , Disbiose/microbiologia , Disbiose/fisiopatologia , Feminino , Firmicutes/classificação , Firmicutes/efeitos dos fármacos , Firmicutes/crescimento & desenvolvimento , Firmicutes/imunologia , Microbioma Gastrointestinal/efeitos dos fármacos , Imunidade Inata , Imunoglobulina G/biossíntese , Imunoglobulina G/classificação , Metronidazol/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Neomicina/farmacologia , Proteobactérias/classificação , Proteobactérias/efeitos dos fármacos , Proteobactérias/crescimento & desenvolvimento , Proteobactérias/imunologia , Simbiose/efeitos dos fármacos , Vancomicina/farmacologia , Coqueluche/microbiologia , Coqueluche/fisiopatologia
8.
Burns ; 45(6): 1418-1429, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31230802

RESUMO

The delivery of antimicrobial agents to surface wounds has been shown to be of central importance to the wound healing process. In this work, we prepared film forming wound care formulations containing 3 polymers (FTP) that provide broad-spectrum antimicrobial protection for prolonged periods. FTP formulations comprises of a smart gel matrix comprising of pH-degradable and temperature responsive polyacetals (smart polymer) which allow for the FTP films to be hydrophobic at room temperature, preventing accidental rubbing off, and hydrophilic at lower temperatures, allowing for easy removal. Two FTP smart-antimicrobial films were evaluated in this work: FTP-AgSD (Silver sulfadiazine actives), and FTP-NP (Neosporin actives). The in vitro and ex vivo antimicrobial efficacy studies show that FTP-AgSD films are significantly more effective for longer durations against Staphylococcus aureus (3 days), Candida albicans (9 days) and Pseudomonas aeruginosa (4 days) when compared to the cream formulations containing antimicrobials. FTP-NP films showed significantly improved antimicrobial activity for a minimum of 3 days for all pathogens tested. Moreover, when tested ex vivo in porcine skin, FTP-AgSD and FTP-NP showed average improvements of 0.89 log10 and 1.66 log10 respectively over standard cream counterparts. Dermal toxicity studies were carried out in a rat skin excision model which showed a similar wound healing pattern to that in rats treated with standard cream formulations as represented by reduction in wound size, and increase in wound healing markers.


Assuntos
Acetais/uso terapêutico , Anti-Infecciosos Locais/administração & dosagem , Bacitracina/administração & dosagem , Queimaduras/terapia , Neomicina/administração & dosagem , Polímeros/uso terapêutico , Polimixina B/administração & dosagem , Sulfadiazina de Prata/administração & dosagem , Polímeros Responsivos a Estímulos/uso terapêutico , Infecção dos Ferimentos/prevenção & controle , Administração Cutânea , Animais , Queimaduras/microbiologia , Candida albicans/efeitos dos fármacos , Combinação de Medicamentos , Sistemas de Liberação de Medicamentos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Ratos , Staphylococcus aureus/efeitos dos fármacos , Cicatrização , Infecção dos Ferimentos/tratamento farmacológico
9.
J Orthop Res ; 37(10): 2122-2129, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31228216

RESUMO

The gut microbiome (GM) contributes to host development, metabolism, and disease. Perturbations in GM composition, elicited through chronic administration of oral antibiotics (Abx) or studied using germ-free environments, alter bone mass, and microarchitecture. However, studies primarily involved chronic Abx exposure to adult mice prior to evaluating the skeletal phenotype. Children are more prone to infection with bacterial pathogens than adults and are thus treated more frequently with broad-spectrum Abx; consequently, Abx treatment disproportionately occurs during periods of greatest skeletal plasticity to anabolic cues. Because early-life exposures may exert long-lasting effects on adult health, we hypothesized that acute Abx administration during a developmentally sensitive period would elicit lasting effects on the skeletal phenotype. To test this hypothesis, neonatal mice were treated with Abx (P7-P23; oral gavage) or vehicle (water); GM composition, gut physiology, and bone structural and material properties were assessed in adulthood (8 weeks). We found sexually dimorphic effects of neonatal Abx administration on GM composition, gut barrier permeability, and the skeleton, indicating a negative role for neonatal Abx on bone mass and quality. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2122-2129, 2019.


Assuntos
Antibacterianos/administração & dosagem , Osso e Ossos/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Caracteres Sexuais , Ampicilina/administração & dosagem , Animais , Animais Recém-Nascidos , Colo/efeitos dos fármacos , Colo/microbiologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neomicina/administração & dosagem , Permeabilidade , Fenótipo , Vancomicina/administração & dosagem
10.
Spectrochim Acta A Mol Biomol Spectrosc ; 220: 117139, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31146209

RESUMO

The determination of neomycin sulfate was made using photoluminescent amino-functionalized graphene quantum dots (obtained from hydro-exfoliation of a mixture of citric acid and glutathione). From the several ions tested, Fe3+ was the best mediator to enable an off/on photoluminescence effect used for quantification. The mediation of Fe3+ was found to be crucial as it is responsible for the photoluminescence quenching effect, due to the interaction with quantum dots surface, also having large affinity towards neomycin that removes Fe3+ from the surface of GQDs, consequently, promoting restoration of the original nanomaterial photoluminescence. Such signal restoration was proportional to the neomycin sulfate concentration added. The linearized analytical response covered three orders of magnitude (10-7 to 10-5 mol L-1). The proposed method is an alternative to those requiring labor-intensive procedures for chemical the derivatization of neomycin (due to the lack of chromophore groups in aminoglycosides). The method was successfully tested in the analysis of rubella vaccine containing trace residues of neomycin and in pharmaceutical compositions containing neomycin sulfate after solid phase extraction using an aminoglycoside imprinted polymer to improve selectivity in determinations.


Assuntos
Neomicina/análise , Pontos Quânticos/química , Vacina contra Rubéola/análise , Aminoglicosídeos/química , Glutationa/química , Grafite/química , Ferro/química , Limite de Detecção , Medições Luminescentes , Microscopia Eletrônica de Transmissão e Varredura , Impressão Molecular , Sondas Moleculares/química , Espectroscopia Fotoeletrônica , Extração em Fase Sólida/instrumentação , Análise Espectral Raman , Temperatura
11.
Nucleic Acids Res ; 47(9): 4883-4895, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-30957848

RESUMO

The development of synthetic riboswitches has always been a challenge. Although a number of interesting proof-of-concept studies have been published, almost all of these were performed with the theophylline aptamer. There is no shortage of small molecule-binding aptamers; however, only a small fraction of them are suitable for RNA engineering since a classical SELEX protocol selects only for high-affinity binding but not for conformational switching. We now implemented RNA Capture-SELEX in our riboswitch developmental pipeline to integrate the required selection for high-affinity binding with the equally necessary RNA conformational switching. Thus, we successfully developed a new paromomycin-binding synthetic riboswitch. It binds paromomycin with a KD of 20 nM and can discriminate between closely related molecules both in vitro and in vivo. A detailed structure-function analysis confirmed the predicted secondary structure and identified nucleotides involved in ligand binding. The riboswitch was further engineered in combination with the neomycin riboswitch for the assembly of an orthogonal Boolean NOR logic gate. In sum, our work not only broadens the spectrum of existing RNA regulators, but also signifies a breakthrough in riboswitch development, as the effort required for the design of sensor domains for RNA-based devices will in many cases be much reduced.


Assuntos
Aptâmeros de Nucleotídeos/química , RNA/química , Riboswitch/genética , Técnica de Seleção de Aptâmeros , Aptâmeros de Nucleotídeos/genética , Ligantes , Neomicina/química , Conformação de Ácido Nucleico/efeitos dos fármacos , Paromomicina/química , Bibliotecas de Moléculas Pequenas/química , Relação Estrutura-Atividade , Teofilina/química
12.
Methods Mol Biol ; 1973: 147-162, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31016700

RESUMO

Aminoglycoside functionalization as a tool for targeting natural and unnatural nucleic acids holds great promise in their development as diagnostic probes and medicinally relevant compounds. Simple synthetic procedures designed to easily and quickly manipulate amino sugar (neomycin, kanamycin) to more powerful and selective ligands are presented in this chapter. We describe representative procedures for (a) aminoglycoside conjugation and (b) preliminary screening for their nucleic acid binding and selectivity.


Assuntos
Aminoglicosídeos/química , Aminoglicosídeos/metabolismo , Antibacterianos/metabolismo , Canamicina/metabolismo , Neomicina/metabolismo , Ácidos Nucleicos/química , Ácidos Nucleicos/metabolismo , Antibacterianos/química , Canamicina/química , Neomicina/química
13.
PLoS One ; 14(4): e0214877, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30943258

RESUMO

Next generation sequencing (NGS) studies have demonstrated a rich and diverse ocular surface-associated microbiota in people that was previously undetected by traditional culture-based methods. The ocular surface microbiome of horses has yet to be investigated using NGS techniques. This study aimed to determine the bacterial composition of the ocular surface microbiome in healthy horses, and to identify whether there are microbial community changes over time and following topical antibiotic use. One eye of 12 horses was treated 3 times daily for 1 week with neomycin-polymyxin-bacitracin ophthalmic ointment. Contralateral eyes served as untreated controls. The inferior conjunctival fornix of both eyes was sampled at baseline prior to initiating treatment (day 0), after 1 week of treatment (day 7), and 4 weeks after concluding treatment (day 35). Genomic DNA was extracted from ocular surface swabs and sequenced using primers that target the V4 region of bacterial 16S rRNA. At baseline, the most abundant phyla identified were Proteobacteria (46.1%), Firmicutes (24.6%), Actinobacteria (12.6%), and Bacteroidetes (11.2%). The most abundant families included Pasteurellaceae (13.7%), Sphingomonadaceae (7.9%), an unclassified Order of Cardiobacteriales (7.7%), and Moraxellaceae (4.8%). Alpha and beta diversity measurements were unchanged in both treatment and control eyes over time. Overall, the major bacterial taxa on the equine ocular surface remained stable over time and following topical antibiotic therapy.


Assuntos
Antibacterianos/administração & dosagem , Bacitracina/administração & dosagem , Túnica Conjuntiva/microbiologia , Cavalos/microbiologia , Microbiota/efeitos dos fármacos , Neomicina/administração & dosagem , Polimixinas/administração & dosagem , Administração Oftálmica/veterinária , Animais , Bactérias/efeitos dos fármacos , Bactérias/genética , Túnica Conjuntiva/efeitos dos fármacos , Microbiota/genética
14.
Eur Arch Otorhinolaryngol ; 276(6): 1845-1848, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30895432

RESUMO

PURPOSE: To assess the effectiveness and complications of bilateral nasal septal cautery using silver nitrate in anterior nasal epistaxis. METHODS: This prospective study was carried out on 180 consecutive patients presenting with epistaxis to a general ENT clinic. Local anaesthetic cautery was performed using 5% lidocaine hydrochloride and 0.5% phenylephrine hydrochloride spray in all the patients except eight children that were 4 years or younger that were done under general anaesthetic. Visible vessels in Little's areas were cauterised using two silver nitrate sticks each side. Patients were prescribed naseptin cream and followed-up. We classified re-bleeds as follow: 0-1 episodes: significant improvement, 2-3 episodes: moderate improvement, 4 + episodes: no improvement. RESULTS: We analysed 134 (74%) patients who were seen at follow-up. Age range was 5-88 years (mean 25, median 15), there were 89 (67%) males. Children made up 60% (81) of the study population (aged 16 years and under), of these 56 (69%) were male. Significant improvement was seen in 93% (124) of the study population, but there were relapses in two children (1.5%) and only moderate improvement in eight patients (6%). There was no significant complication in the study population, but 11 patients had crusting at the sites of cautery at follow-up. CONCLUSIONS: Bilateral silver nitrate cauterisation is an effective method of treating recurrent epistaxis with low risk of complications.


Assuntos
Assistência Ambulatorial , Anti-Infecciosos Locais/uso terapêutico , Cauterização/métodos , Epistaxe/terapia , Septo Nasal/cirurgia , Nitrato de Prata/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestésicos Locais , Criança , Pré-Escolar , Clorexidina/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Lidocaína/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neomicina/uso terapêutico , Estudos Prospectivos , Recidiva , Adulto Jovem
15.
Nutrients ; 11(3)2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-30862081

RESUMO

Recent evidence suggests that tryptophan, an essential amino acid, may exert biological effects by means of tryptophan-derived gut bacteria products. We evaluated the potential contribution of tryptophan-derived bacterial metabolites to body weight gain. The study comprised three experimental series performed on separate groups of male, Sprague-Dawley rats: (i) rats on standard laboratory diet treated with water solution of neomycin, an antibiotic, or tap water (controls-1); (ii) rats on standard diet (controls-2) or tryptophan-high (TH) or tryptophan-free (TF) diet; and (iii) rats treated with indole-3-propionic acid (I3P), a bacterial metabolite of tryptophan, or a vehicle (controls-3). (i) Rats treated with neomycin showed a significantly higher weight gain but lower stool and blood concentration of I3P than controls-1. (ii) The TH group showed significantly smaller increases in body weight but higher stool and plasma concentration of I3P than controls-2. In contrast, the TF group showed a decrease in body weight, decreased total serum protein and a significant increase in urine output. (iii) Rats treated with I3P showed significantly smaller weight gain than controls-3. Our study suggests that I3P, a gut bacteria metabolite of tryptophan, contributes to changes in body weight gain produced by antibiotics and tryptophan-rich diet.


Assuntos
Indóis/farmacologia , Neomicina/farmacologia , Propionatos/farmacologia , Triptofano/metabolismo , Animais , Indóis/metabolismo , Masculino , Propionatos/metabolismo , Inibidores da Síntese de Proteínas/farmacologia , Ratos , Ratos Sprague-Dawley , Ganho de Peso
16.
Ophthalmic Plast Reconstr Surg ; 35(5): 465-468, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30730433

RESUMO

PURPOSE: To study the effect of periocular steroid use on intraocular pressure (IOP). METHODS: Charts of adult patients with atopic dermatitis or eczema treated with topical periocular steroid creams and ointments from January 1st, 2007 to October 1st, 2017 were reviewed. Patients with the following were excluded: glaucoma, ocular hypertension, known systemic/topical/injectable steroid history, and lack of documented IOP prior to or during treatment with periocular steroid ointment. Patient data were collected regarding gender, treatment regimen, as well as IOP prior to and during treatment. Steroid responders were identified. Statistical analysis was performed using linear mixed effects models adjusting for follow-up time to test the relationship between pre and posttreatment IOP change adjusting for intereye correlations. RESULTS: Thirty-one patients were identified. Twenty-one were treated bilaterally and 10 unilaterally. Five patients were glaucoma suspects. The mean treatment period was 14.2 weeks with a range of 0.1-83.9 weeks. Patients were treated with fluorometholone (42%), loteprednol etabonate (23%), dexamethasone-neomycin-polymyxin B (13%), hydrocortisone 1% or 2.5% (3%), and tobramycin-dexamethasone (19%). In the combined sample, there was no significant IOP change even after adjusting for follow-up time (mean change: +0.44 mm Hg, p = 0.126). However, eyes with baseline IOP ≥ 14 mm Hg had a significant increase (+0.73 mm Hg/year, p = 0.032). Individual steroid responses included the following: 1 intermediate and 30 low responders, of which 19 patients had an IOP change of <1 mm Hg. One patient had a clinically significant intermediate steroid response of 7 mm Hg. CONCLUSIONS: Periocular steroid treatment causes a statistically significant rise in IOP in eyes with higher baseline IOP measurements, the risk of which increases with follow up. While this change is not always correlated with a clinically significant rise in IOP, clinicians should monitor more closely patients at greatest risk of steroid response.


Assuntos
Pressão Intraocular/efeitos dos fármacos , Hipertensão Ocular/induzido quimicamente , Esteroides/efeitos adversos , Administração Tópica , Adolescente , Adulto , Dexametasona/efeitos adversos , Combinação de Medicamentos , Feminino , Humanos , Hidrocarbonetos Fluorados/efeitos adversos , Hidrocortisona/efeitos adversos , Etabonato de Loteprednol/efeitos adversos , Masculino , Neomicina/efeitos adversos , Soluções Oftálmicas/efeitos adversos , Polimixina B/efeitos adversos , Estudos Retrospectivos , Esteroides/administração & dosagem , Adulto Jovem
17.
Med Mal Infect ; 49(3): 194-201, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30792037

RESUMO

OBJECTIVE: An empirical treatment of infectious vaginitis is justified because of its multiple etiologies, the frequent uncertainty of clinical diagnosis and limits of microbiological analysis. Our aim was to comparatively investigate nystatin-neomycin-polymyxin B combination (NNP, Polygynax®) and miconazole. PATIENTS AND METHODS: In this European multicenter, double-blind PRISM trial, participating women presenting with infectious vaginitis were randomized to receive one vaginal capsule containing either NNP for 12 days or miconazole for 3 days followed by 9 days of placebo. RESULTS: The clinical success rate was higher in the NNP group (n=302) than the miconazole group (n=309), with a difference between groups close to statistical significance (91.1% vs. 86.7%, P=0.0906). The risk of treatment failure was 36% lower in the NNP group (odds ratio, 0.64; 95% confidence interval, 0.38-1.07). Vaginal burning on Day 2 and vaginal discharge on Day 4 were significantly less intense in the NNP group than in the miconazole group (39.1 vs. 42.3, P=0.031 and 34.6 vs. 37.6, P=0.031, respectively). Adverse drug reactions were reported by 1.2% and 2.1% of patients in the NNP and miconazole group respectively, with the ratio of adverse drug reactions relative to total adverse events significantly higher in the miconazole group (20.3% vs. 6.9%, P=0.022). CONCLUSION: The widespread use of NNP for several decades and its good efficacy and safety profile, as well as the frequent diagnostic uncertainties due to the various pathogens sustain the initiation of this broad-spectrum empirical treatment in infectious vaginitis.


Assuntos
Arsenicais/administração & dosagem , Miconazol/administração & dosagem , Neomicina/administração & dosagem , Nistatina/administração & dosagem , Polimixinas/administração & dosagem , Vaginite/tratamento farmacológico , Adolescente , Adulto , Arsenicais/efeitos adversos , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/epidemiologia , Método Duplo-Cego , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Miconazol/efeitos adversos , Pessoa de Meia-Idade , Neomicina/efeitos adversos , Nistatina/efeitos adversos , Polimixinas/efeitos adversos , Resultado do Tratamento , Vaginite/epidemiologia , Vaginite/microbiologia , Vaginose Bacteriana/tratamento farmacológico , Vaginose Bacteriana/epidemiologia , Adulto Jovem
18.
mSphere ; 4(1)2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30787120

RESUMO

Coxsackievirus typically infects humans via the gastrointestinal tract, which has a large number of microorganisms collectively referred to as the microbiota. To study how the intestinal microbiota influences enteric virus infection, several groups have used an antibiotic regimen in mice to deplete bacteria. These studies have shown that bacteria promote infection with several enteric viruses. However, very little is known about whether antibiotics influence viruses in a microbiota-independent manner. In this study, we sought to determine the effects of antibiotics on coxsackievirus B3 (CVB3) using an in vitro cell culture model in the absence of bacteria. We determined that an aminoglycoside antibiotic, neomycin, enhanced the plaque size of CVB3 strain Nancy. Neomycin treatment did not alter viral attachment, translation, or replication. However, we found that the positive charge of neomycin and other positively charged compounds enhanced viral diffusion by overcoming the negative inhibitory effect of sulfated polysaccharides present in agar overlays. Neomycin and the positively charged compound protamine also enhanced plaque formation of reovirus. Overall, these data provide further evidence that antibiotics can play noncanonical roles in viral infections and that this should be considered when studying enteric virus-microbiota interactions.IMPORTANCE Coxsackieviruses primarily infect the gastrointestinal tract of humans, but they can disseminate systemically and cause severe disease. Using antibiotic treatment regimens to deplete intestinal microbes in mice, several groups have shown the bacteria promote infection with a variety of enteric viruses. However, it is possible that antibiotics have microbiota-independent effects on viruses. Here we show that an aminoglycoside antibiotic, neomycin, can influence quantification of coxsackievirus in cultured cells in the absence of bacteria.


Assuntos
Antibacterianos/farmacologia , Enterovirus/efeitos dos fármacos , Neomicina/farmacologia , Linhagem Celular , Células Cultivadas , Microbioma Gastrointestinal , Células HeLa , Humanos , Orthoreovirus de Mamíferos/efeitos dos fármacos , Ensaio de Placa Viral , Replicação Viral/efeitos dos fármacos
19.
J Vis Exp ; (143)2019 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-30735171

RESUMO

Telomeres are transcribed, giving rise to telomeric repeat-containing long noncoding RNAs (TERRA), which have been proposed to play important roles in telomere biology, including heterochromatin formation and telomere length homeostasis. Recent findings revealed that TERRA molecules also interact with internal chromosomal regions to regulate gene expression in mouse embryonic stem (ES) cells. In line with this evidence, RNA fluorescence in situ hybridization (RNA-FISH) analyses have shown that only a subset of TERRA transcripts localize at chromosome ends. A better understanding of the dynamics of TERRA molecules will help define their function and mechanisms of action. Here, we describe a method to label and visualize single-telomere TERRA transcripts in cancer cells using the MS2-GFP system. To this aim, we present a protocol to generate stable clones, using the AGS human stomach cancer cell line, containing MS2 sequences integrated at a single subtelomere. Transcription of TERRA from the MS2-tagged telomere results in the expression of MS2-tagged TERRA molecules that are visualized by live-cell fluorescence microscopy upon co-expression of a MS2 RNA-binding protein fused to GFP (MS2-GFP). This approach enables researchers to study the dynamics of single-telomere TERRA molecules in cancer cells, and it can be applied to other cell lines.


Assuntos
RNA Longo não Codificante/genética , RNA/genética , Telômero/genética , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Células Clonais , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Humanos , Camundongos , Neomicina/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Telômero/metabolismo
20.
PLoS One ; 14(1): e0210338, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30620760

RESUMO

This study aimed to evaluate neuropeptide expression after bleaching treatment using histopathological and immunohistochemical analyses and the effects of hydrocortisone and acetaminophen on pulp inflammation, sine dental bleaching and inflammation first occur, and only then, the treatmentt. Sixty-three rats were divided into three groups (n = 21) according to the pain-relieving therapy used: I-control; II-topical application of Otosporin for 10 min after the bleaching treatment; III-oral administration of paracetamol 30 min before whitening and then every 12h. In all the study groups, placebo gel was applied to the left upper jaw (control) and a 35% H2O2-based whitening gel was applied to the right upper jaw for 45 min. Seven animals from each group were euthanized at different time points: 0h after treatment, 24h, and 48h. After euthanasia, the first molar on each side was analyzed by histology and immunohistochemistry to assess the degree of inflammation and verify the presence of the neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP). The data were analyzed using the statistical nonparametric Kruskal-Wallis test followed by Dunn's test for individual comparisons. Extensive areas of necrosis were observed in the groups that received bleaching treatment only, whereas reduced damage were obtained in the group treated with Otosporin. The immunohistochemical analysis showed positive immunolabeling in all groups, including the control, but this was stronger in the groups that received bleaching treatment. The best results were obtained in the group that received treatment with Otosporin. The use of Otosporin after dental bleaching minimized the side effects of this treatment.


Assuntos
Anti-Inflamatórios/uso terapêutico , Polpa Dentária/efeitos dos fármacos , Polpa Dentária/patologia , Pulpite/tratamento farmacológico , Pulpite/etiologia , Clareamento Dental/efeitos adversos , Acetaminofen/uso terapêutico , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Polpa Dentária/metabolismo , Modelos Animais de Doenças , Combinação de Medicamentos , Humanos , Hidrocortisona/uso terapêutico , Imuno-Histoquímica , Masculino , Neomicina/uso terapêutico , Polimixina B/uso terapêutico , Pulpite/patologia , Ratos , Ratos Wistar , Substância P/metabolismo , Clareadores Dentários/efeitos adversos
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