Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 96
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Exp Eye Res ; 248: 110074, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39251120

RESUMO

Reactive oxygen species (ROS) play a significant role in toxicity to the retina in a variety of diseases. N-acetylcysteine (NAC), N-acetylcysteine amide (NACA) and the dimeric di-N-acetylcysteine amide (diNACA) were evaluated in terms of protecting retinal cells, in vitro, in a variety of stress models. Three types of rat retinal cell cultures were utilized in the study: macroglial-only cell cultures, neuron-only retinal ganglion cell (RGC) cultures, and mixed cultures containing retinal glia and neurons. Ability of test agents to attenuate oxidative stress in all cultures was ascertained. In addition, capability of agents to protect against a variety of alternate clinically-relevant stressors, including excitotoxins and mitochondrial electron transport chain inhibitors, was also evaluated. Capacity of test agents to elevate cellular levels of reduced glutathione under normal and compromised conditions was also determined. NAC, NACA and diNACA demonstrated concentration-dependent cytoprotection against oxidative stress in all cultures. These three compounds, however, had differing effects against a variety of alternate insults to retinal cells. The most protective agent was NACA, which was most potent against the most stressors (including oxidative stress, mitochondrial impairment by antimycin A and azide, and glutamate-induced excitotoxicity). Similar to NAC, NACA increased glutathione levels in non-injured cells, although diNACA did not, suggesting a different, unknown mechanism of antioxidant activity for the latter. In support of this, diNACA was the only agent to attenuate rotenone-induced toxicity in mitochondria. NAC, NACA and diNACA exhibited varying degrees of antioxidant activity, i.e., protected cultured rat retinal cells from a variety of stressors which were designed to mimic aspects of the pathology of different retinal diseases. A general rank order of activity was observed: NACA ≥ diNACA > NAC. These results warrant further exploration of NACA and diNACA as antioxidant therapeutics for the treatment of retinal diseases, particularly those involving oxidative stress. Furthermore, we have defined the battery of tests carried out as the "Wood, Chidlow, Wall and Casson (WCWC) Retinal Antioxidant Indices"; we believe that these are of great value for screening molecules for potential to reduce retinal oxidative stress in a range of retinal diseases.

2.
Exp Eye Res ; 234: 109610, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37536438

RESUMO

Oxidative stress plays a central role in cataract formation suggesting that antioxidants might slow cataract progression. The anticataract activity of N-acetylcysteine amide (NACA) and (2 R, 2 R')-3,3'-disulfanediyl bis(2-acetamidopropanamide) (diNACA) and/or N-acetylcysteine (NAC), were evaluated in porcine and rat lens models. Cataractogenesis via oxidation was induced with H2O2 and/or glucose oxidase (GO). Porcine lenses were incubated in 0.1 mM, 1 mM, or 10 mM NAC, NACA or diNACA for 24 h. Lenses were then transferred to media containing 0.75 mM H2O2 and 4.63U of GO in order to maintain a constant H2O2 level for an additional 8 h. At the end of incubation, lenses were imaged under darkfield microscopy. Separately, rat lenses were extracted from 3-week-old Wistar rats and incubated with either 10 mM NACA or 10 mM diNACA for 24 h prior to treatment with 0.2U GO to generate a steady source of ∼0.6 mM H2O2. Rat lenses were analyzed by LC-MS/MS to quantify changes in cysteine, cystine, glutathione (GSH) or oxidised glutathione (GSSG) levels in the lens epithelium, cortex or core. Pre-treatment with NACA or diNACA followed by oxidation with H2O2 and/or GO to stimulate cataract formation afforded rapid assessment in ex vivo porcine (32 h) and rat (48 h) lens models. Pre-treatment of isolated porcine lenses with 0.1 mM, 1 mM or 10 mM of either NAC, NACA or diNACA followed by H2O2/GO treatment resulted in reduced lens opacity relative to the lenses exposed to H2O2/GO, with NACA and diNACA reducing opacities to a greater extent than NAC. Rat lenses incubated with 10 mM NACA or 10 mM diNACA without exposure to H2O2 showed no signs of opacities. Pre-treatment of rat lenses with 10 mM NACA or 10 mM diNACA, followed by GO cataract induction resulted in reduced opacities compared to control (GO alone). LC-MS/MS analyses revealed that NACA, but not diNACA, increased cysteine, cystine and GSH levels in rat lens epithelium and cortex regions. Taken together, both NACA and diNACA inhibited cataract formation to a greater extent than NAC (all at 1-10 mM) in an ex vivo porcine lens model. Both NACA and diNACA (both at 10 mM) reduced cataract formation in rat lenses. Based on LC-MS/MS analyses, NACA-induced reduction in opacity observed in rat lenses was attributed to enhanced cysteine and GSH levels while the diNACA-induced reduction in opacity induced did not consistently increase cysteine, cystine and GSH levels and, therefore, appears to involve a different antioxidant mechanism. These screening studies warrant further testing of NACA and diNACA as anticataract agents.


Assuntos
Catarata , Cristalino , Ratos , Animais , Suínos , Acetilcisteína/efeitos adversos , Peróxido de Hidrogênio/farmacologia , Cistina/efeitos adversos , Cromatografia Líquida , Ratos Wistar , Espectrometria de Massas em Tandem , Cristalino/metabolismo , Catarata/induzido quimicamente , Antioxidantes , Estresse Oxidativo , Glutationa/metabolismo , Proteínas , Dissulfeto de Glutationa
3.
Environ Sci Technol ; 46(10): 5336-43, 2012 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-22540536

RESUMO

Data were collected at a wastewater treatment plant (WWTP) in Burlington, Vermont, USA, (serving 30,000 people) to assess the relative contribution of CSO (combined sewer overflow) bypass flows and treated wastewater effluent to the load of steroid hormones and other wastewater micropollutants (WMPs) from a WWTP to a lake. Flow-weighted composite samples were collected over a 13 month period at this WWTP from CSO bypass flows or plant influent flows (n = 28) and treated effluent discharges (n = 22). Although CSO discharges represent 10% of the total annual water discharge (CSO plus treated plant effluent discharges) from the WWTP, CSO discharges contribute 40-90% of the annual load for hormones and WMPs with high (>90%) wastewater treatment removal efficiency. By contrast, compounds with low removal efficiencies (<90%) have less than 10% of annual load contributed by CSO discharges. Concentrations of estrogens, androgens, and WMPs generally are 10 times higher in CSO discharges compared to treated wastewater discharges. Compound concentrations in samples of CSO discharges generally decrease with increasing flow because of wastewater dilution by rainfall runoff. By contrast, concentrations of hormones and many WMPs in samples from treated discharges can increase with increasing flow due to decreasing removal efficiency.


Assuntos
Monitoramento Ambiental , Hormônios/análise , Esgotos/química , Eliminação de Resíduos Líquidos , Movimentos da Água , Poluentes Químicos da Água/análise , Vermont , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água
4.
Orphanet J Rare Dis ; 17(1): 231, 2022 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-35710564

RESUMO

BACKGROUND: Cystinosis is a rare autosomal recessive lysosomal storage disease, associated with high morbidity and mortality. Mutations in the CTNS gene disable a membrane protein responsible for the transport of cystine out of the lysosome. Loss of transporter function leads to intralysosomal cystine accumulation and long-term damage to various tissues and organs, including the kidneys, eyes, liver, muscles, pancreas, and brain. The only cystine-depletion therapy for treatment of cystinosis is cysteamine which requires frequent administration of high doses and often causes gastrointestinal pain as well as pungent sulfurous odor in patients. The current in vitro study evaluated antioxidants, N-acetylcysteine amide (NACA; NPI-001) and (2R,2R')-3,3'-disulfanediyl bis(2-acetamidopropanamide) (diNACA; NPI-002), as potential treatments for cystinosis. METHODS: Cytotoxicity of cysteamine, NACA and diNACA was evaluated in cultured human cystinotic fibroblasts (HCFs). HCFs were cultured in 96 well plates incubated for 0-72 h in the presence of 25, 50 or 75 µM each of either cysteamine, NACA or diNACA along with an untreated control. Media was removed and cell viability assessed. Next, cystine-depleting activities of cysteamine, NACA and diNACA were screened in HCFs cell culture utilizing an inexpensive, proven colorimetric assay. HCFs were seeded and allowed to reach approximately 80% confluence before the addition of the test articles: 50 µM of either cysteamine, NACA or diNACA in media along with an untreated control. HCFs were incubated, harvested, and cystine was reduced to cysteine, the concentration of which was then determined per quantity of protein compared to a cysteine standard. Statistically significant cystine depletion was determined by paired t-test versus untreated control (p < 0.05). RESULTS: Neither cysteamine, NACA nor diNACA at 25, 50 or 75 µM caused cytotoxicity in HCFs. Treatment with all tested concentrations (25, 50 or 75 µM) of either NACA or diNACA at 48 or 72 h resulted in statistically significant increases in cell viability, relative to untreated control, whereas the higher concentrations (50 or 75 µM) of cysteamine achieved statistical significance at both timepoints but not the lowest concentration (25 µM). All test articles depleted cystine from HCFs compared to control. NACA depletion of cystine was statistically superior to cysteamine at 6, 24 and 48 h and numerically greater at 72 h. DiNACA depletion of cystine was statistically superior to cysteamine at 6 and 48 h, slightly numerically greater at 24 h and slightly less at 72 h. CONCLUSIONS: NACA and diNACA were non cytotoxic to HCFs and significantly increased cell viability. Cystine reduction was determined as percent of control after incubation with 50 µM of NACA, diNACA or cysteamine in HCFs cell culture for 6, 24, 48 and 72 h. Of the three test articles, NACA exhibited most rapid and greatest potency in cystine reduction. Rank order potency for cystine reduction over time was observed, NACA > diNACA ≥ cysteamine. Therefore, further study of NACA and diNACA as potential treatments for cystinosis is warranted.


Assuntos
Cistinose , Técnicas de Cultura de Células , Cisteamina/farmacologia , Cisteamina/uso terapêutico , Cisteína/metabolismo , Cisteína/uso terapêutico , Cistina/metabolismo , Cistina/uso terapêutico , Cistinose/tratamento farmacológico , Cistinose/genética , Cistinose/metabolismo , Fibroblastos/metabolismo , Humanos
5.
Br J Oral Maxillofac Surg ; 58(7): 812-818, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32409131

RESUMO

Is there a variation in facial ideals depending on ethnic background that affects judgements of outcome in orthognathic surgery? How does the evaluation correlate with patient-reported outcome measures? Two evaluation panels, Singaporean and Swedish, judged photographs of patients undergoing orthognathic surgery taken before and after operation. Improvement in facial aesthetics was calculated between the two ratings. The result was compared between the panels and correlated with health-related quality of life (QoL) measures. Thirty male and 27 female patients aged between 18 and 28 years (mean 21) were included, and 52 subjects were eligible for comparison of health-related QoL. The photographic evaluation showed that both panels judged there to be significant improvement in facial aesthetics after treatment (p<0.001). The Singaporean panel rated the overall facial appearance higher than the Swedish panel when evaluating photographs both before (p=0.025) and after (p=0.032) operation. Improvement of the overall facial appearance showed no significant difference between the panels (p>0.30). No correlation between health-related QoL and improvement of facial appearance was found by either panel. Subjective evaluation of facial aesthetics in orthognathic surgery is unaffected by the observer's ethnic origin. Independently of their ethnicity, the evaluation juries found that facial aesthetics improved after orthognathic surgery. Improvement reported by the juries corresponded to that reported by patients.


Assuntos
Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Adolescente , Adulto , Estética Dentária , Etnicidade , Feminino , Humanos , Masculino , Qualidade de Vida , Adulto Jovem
6.
J Clin Invest ; 130(3): 1527-1541, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-31805012

RESUMO

BACKGROUNDIn retinitis pigmentosa (RP), rod photoreceptors degenerate from 1 of many mutations, after which cones are compromised by oxidative stress. N-acetylcysteine (NAC) reduces oxidative damage and increases cone function/survival in RP models. We tested the safety, tolerability, and visual function effects of oral NAC in RP patients.METHODSSubjects (n = 10 per cohort) received 600 mg (cohort 1), 1200 mg (cohort 2), or 1800 mg (cohort 3) NAC bid for 12 weeks and then tid for 12 weeks. Best-corrected visual acuity (BCVA), macular sensitivity, ellipsoid zone (EZ) width, and aqueous NAC were measured. Linear mixed-effects models were used to estimate the rates of changes during the treatment period.RESULTSThere were 9 drug-related gastrointestinal adverse events that resolved spontaneously or with dose reduction (maximum tolerated dose 1800 mg bid). During the 24-week treatment period, mean BCVA significantly improved at 0.4 (95% CI: 0.2-0.6, P < 0.001), 0.5 (95% CI: 0.3-0.7, P < 0.001), and 0.2 (95% CI: 0.02-0.4, P = 0.03) letters/month in cohorts 1, 2, and 3, respectively. There was no significant improvement in mean sensitivity over time in cohorts 1 and 2, but there was in cohort 3 (0.15 dB/month, 95% CI: 0.04-0.26). There was no significant change in mean EZ width in any cohort.CONCLUSIONOral NAC is safe and well tolerated in patients with moderately advanced RP and may improve suboptimally functioning macular cones. A randomized, placebo-controlled trial is needed to determine if oral NAC can provide long-term stabilization and/or improvement in visual function in patients with RP.TRIAL REGISTRATIONNCT03063021.FUNDINGMr. and Mrs. Robert Wallace, Mr. and Mrs. Jonathan Wallace, Rami and Eitan Armon, Marc Sumerlin, Cassandra Hanley, and Nacuity Pharmaceuticals, Inc.


Assuntos
Acetilcisteína/administração & dosagem , Células Fotorreceptoras Retinianas Cones/metabolismo , Retinose Pigmentar/tratamento farmacológico , Acuidade Visual/efeitos dos fármacos , Acetilcisteína/efeitos adversos , Administração Oral , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Retinose Pigmentar/metabolismo , Retinose Pigmentar/patologia , Retinose Pigmentar/fisiopatologia
7.
Pediatr Infect Dis J ; 28(2): 141-4, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19116600

RESUMO

The objective of this article is to review the literature related to ciprofloxacin 0.3% and dexamethasone 0.1% sterile otic suspension. A systematic literature search utilizing Medline was conducted to identify peer-reviewed articles related to safety and efficacy. A total of 47 publications were identified and reviewed herein. The literature supports the use of antibiotic/antiiflammatory combination ear drops in the treatment of both acute otitis externa and acute otitis media in pediatric patients with tympanostomy tubes. Ciprofloxacin/dexamethasone has been demonstrated as safe and effective with regard to clinical cures and microbiological eradication of pathogens in either disease with low treatment failure rates. Additionally, the literature also provides clear evidence for the contribution of dexamethasone when added to ciprofloxacin for the topical treatment of ear infections.


Assuntos
Anti-Infecciosos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Ciprofloxacina/administração & dosagem , Dexametasona/administração & dosagem , Otite Externa/tratamento farmacológico , Otite Média/tratamento farmacológico , Administração Tópica , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Ciprofloxacina/uso terapêutico , Dexametasona/uso terapêutico , Combinação de Medicamentos , Humanos
8.
Clin Ther ; 31(1): 99-107, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19243710

RESUMO

BACKGROUND: Seasonal allergic rhinitis (SAR) is an allergen-induced inflammatory reaction that occurs during periods of high pollen count. Current treatments for SAR include allergen avoidance, systemic antihistamines, and steroidal and nonsteroidal intranasal sprays. Olopatadine is a selective antihistamine and an inhibitor of proinflammatory mediators from human mast cells. An intranasal formulation of olopatadine has been developed for the treatment of SAR. OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of olopatadine hydrochloride nasal spray 0.6% (OLO) relative to azelastine hydrochloride nasal spray 0.1% (AZE) and an inactive vehicle in the treatment of SAR. METHODS: This Phase III, multicenter, randomized, double-blind, active- and placebo-controlled, parallel-group study was conducted at 21 centers across the United States. Eligible patients were aged > or =12 years and had a history of SAR and verified allergy to a prevalent local allergen. After a run-in period during which inactive vehicle was administered, patients were randomly assigned to OLO, AZE (active control), or inactive vehicle (identical to OLO; placebo control), 2 sprays in each nostril BID for 16 days. The timing of enrollment was correlated with the start of the allergy season at each site. Symptoms were recorded twice daily in an electronic diary. Efficacy assessments included changes in mean daily reflective total nasal symptom scores (TNSS). Tolerability was evaluated based on adverse events (AEs) and nasal, physical, and cardiovascular parameters. RESULTS: A total of 544 patients were randomized. The mean age was 36 years (range, 12-77 years); men and boys represented 32.2% of the population; and the patients were predominantly white (75.4%). The mean reductions from baseline in reflective TNSS were 26.8%, 29.9%, and 18.4% with OLO, AZE, and inactive vehicle, respectively (P = 0.003 OLO vs inactive vehicle; 95% CI, -2.5% to 8.7% OLO vs AZE [non-inferiority]). The most commonly reported treatment-related AE in the OLO and AZE groups was bitter taste (12.2% [22/180] and 19.7% [37/188], respectively). The prevalence and intensity of bitter taste were significantly lower with OLO than with AZE (P = 0.05 and P = 0.005, respectively). In the group that received inactive vehicle, the prevalence of bitter taste was 1.7% (3/176). The prevalences of other treatment-related AEs, including epistaxis and nasal discomfort, were < or =3.7% in each group and did not differ significantly between groups. CONCLUSIONS: In this small study in patients aged > or =12 years with SAR, the percentage reduction from baseline in TNSS was significantly greater with OLO (2 sprays in each nostril BID) compared with vehicle and not significantly different from that with AZE. OLO and AZE were similarly well tolerated, with the exception of prevalence and intensity of bitter taste, which were significantly lower with OLO.


Assuntos
Antialérgicos/uso terapêutico , Dibenzoxepinas/uso terapêutico , Ftalazinas/uso terapêutico , Administração Intranasal , Adolescente , Adulto , Idoso , Antialérgicos/administração & dosagem , Antialérgicos/efeitos adversos , Criança , Dibenzoxepinas/administração & dosagem , Dibenzoxepinas/efeitos adversos , Método Duplo-Cego , Epistaxe/induzido quimicamente , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cloridrato de Olopatadina , Ftalazinas/administração & dosagem , Ftalazinas/efeitos adversos , Rinite Alérgica Sazonal/tratamento farmacológico , Paladar , Estados Unidos/epidemiologia , Adulto Jovem
9.
Allergy Asthma Proc ; 30(6): 612-23, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20031007

RESUMO

Olopatadine (OLO) nasal spray 0.6% is indicated for treatment of seasonal allergic rhinitis (SAR) in subjects > or = 12 years of age. This study was designed to present the results of two studies that evaluated the efficacy, safety, and pharmacokinetics (PK) of OLO in children with allergic rhinitis (AR). These were multicenter, double-blind, randomized, parallel-group studies in subjects 6 to <12 years of age (study 1) and 2 to <6 years of age (study 2) with SAR (study 1) or AR (study 2). In study 1, nasal and ocular symptoms were scored for efficacy, and study 2 included PK analyses. In both studies, subjects were evaluated based on physical/nasal examinations and adverse events (AEs). Overall, 1188 subjects (study 1) and 132 subjects (study 2) were randomized, respectively. OLO (1 or 2 sprays/nostril, b.i.d.) was superior to vehicle in the percent decrease in reflective total nasal symptom scores (p < or = 0.0120). OLO 1 spray/nostril b.i.d. was also superior to vehicle in the percent decreases in reflective total ocular symptom scores (p < or = 0.0084), change from baseline in Pediatric Rhinoconjunctivitis Quality-of-Life Questionnaire scores (p < or = 0.0377), Caregiver Treatment Satisfaction Questionnaire scores (p < or = 0.0450), and proportions of subjects reporting improvements in Subject Global Assessments (p = 0.0035). The most frequently reported treatment-related events in the OLO group were bad/bitter taste and epistaxis. In subjects 6 to <12 years of age, OLO was superior to vehicle in the treatment of SAR. In subjects 2 to <12 years of age, OLO had an overall low rate of AEs and low systemic exposure.


Assuntos
Dibenzoxepinas , Antagonistas não Sedativos dos Receptores H1 da Histamina , Rinite Alérgica Sazonal/tratamento farmacológico , Administração Intranasal , Criança , Pré-Escolar , Conjuntivite Alérgica/tratamento farmacológico , Dibenzoxepinas/administração & dosagem , Dibenzoxepinas/efeitos adversos , Dibenzoxepinas/farmacocinética , Epistaxe/etiologia , Epistaxe/prevenção & controle , Feminino , Antagonistas não Sedativos dos Receptores H1 da Histamina/administração & dosagem , Antagonistas não Sedativos dos Receptores H1 da Histamina/efeitos adversos , Antagonistas não Sedativos dos Receptores H1 da Histamina/farmacocinética , Humanos , Masculino , Obstrução Nasal/tratamento farmacológico , Cloridrato de Olopatadina , Qualidade de Vida , Rinite Alérgica Sazonal/fisiopatologia , Rinite Alérgica Sazonal/psicologia , Inquéritos e Questionários , Resultado do Tratamento
10.
AAPS PharmSciTech ; 10(4): 1313-20, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19888658

RESUMO

The shelf-life of a previously developed two-part liquid-liquid enzyme ceruminolytic product was improved maintaining the same final reconstituted composition and re-formulating the liquid enzyme portion as a drug granulate by a double wet granulation process. The critical steps for the preparation of the granulate were studied (mixing/granulating times and drying) determining the proteolytic activity, the residual ethanol, and the moisture content of the granulates. The original liquid-liquid formulation had been proven effective as a ceruminolytic agent, but only had stability of greater than 75% enzyme activity for up to 18 months and up to 1 day at room temperature after combining the two parts. The resulting improved product was proven to be stable for up to 24 months at 30 degrees C, and up to 3 days at room temperature after combining the two parts. Therefore, maintaining the enzyme in a granulated form until reconstitution afforded an improvement in stability compared with the original two-part liquid-liquid formulation.


Assuntos
Estabilidade Enzimática , Tecnologia Farmacêutica , Química Farmacêutica , Armazenamento de Medicamentos , Soluções
11.
Artigo em Inglês | MEDLINE | ID: mdl-30708342

RESUMO

Studies of N-acetylcysteine amide (NACA) in nonclinical models have demonstrated various antioxidant, anti-apoptotic, anti-inflammatory and neuroprotective effects, and it is currently being developed as a treatment for retinitis pigmentosa. Sensitive LC-MS/MS methods were developed and validated to quantitate reduced and total NACA and its major metabolite, N-acetylcysteine (NAC), in human plasma to support clinical studies involving NACA. To trap and stabilize reduced NACA and NAC at the time of collection, whole blood was immediately treated with 2-chloro-1-methylpyridinium iodide (CMPI) to convert free thiols to 1-methylpyridinyl thioether derivatives. Plasma was harvested and frozen until samples were assayed using protein precipitation and an LC-MS/MS separation based on hydrophilic-interaction chromatography (HILIC). To process NACA and NAC present as disulfides, an intermediate portion of the extract was further subjected to reduction with tris(2-carboxyethyl) phosphine; the released thiols were then reacted with CMPI, extracted, and analyzed as before, to measure total thiols. The method for NACA and NAC, whether free/reduced or total, covered a range from 50 ng/mL to 50 µg/mL in human plasma and required a single 25 µL plasma sample. Up to 180 samples could be assayed in a single session. The inter-run mean bias and precision (%CV) were within ±5% for the free thiol method and within ±8.5% for the total thiol method. Benchtop, freeze/thaw, and long-term stability were evaluated and acceptable. The NAC/NACA method applied to a clinical study demonstrated incurred sample reproducibility of 95.5% for NAC and 99.1% for NACA.


Assuntos
Acetilcisteína/análogos & derivados , Acetilcisteína/sangue , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Acetilcisteína/química , Estabilidade de Medicamentos , Humanos , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes
12.
Br J Oral Maxillofac Surg ; 57(4): 352-358, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30962030

RESUMO

The aim of this randomised controlled trial was to compare the costs and benefits of computer-based 2-dimensional and 3-dimensional predictions in orthognathic surgery. Subjects aged 18-30 years with severe class III malocclusion had their treatment planned with both 2- and 3-dimensional techniques. They were randomised in a 1:1 ratio for one or other planning technique. Costs (financial, time, and dose of radiation) were compared with benefits (accuracy and health-related quality of life (HRQoL)). In total, 57 subjects (27 women and 30 men, mean (range) age 21 (18-28) years) completed the study. Comparisons showed no significant difference in total time spent, but a large advantage for the 2-dimensional technique in financial costs (p < 0.001); it also required a significantly lower dose of radiation (p < 0.001). The cost-effectiveness analysis showed a reduction in time of 0.53 minutes/HRQoL-point gained, and an increased economic cost of US$15/HRQoL point gained for the 3-dimensional technique. It also showed that the two techniques consumed an equal amount of time, but that the 2-dimensional technique had lower financial costs, and the 3-dimensional technique a larger dose of radiation.


Assuntos
Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Adolescente , Adulto , Análise Custo-Benefício , Feminino , Humanos , Masculino , Técnicas de Planejamento , Qualidade de Vida , Cirurgia Assistida por Computador , Adulto Jovem
13.
Br J Oral Maxillofac Surg ; 57(4): 345-351, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31000205

RESUMO

The outcome of treatment in orthognathic surgery is dependent on preoperative surgical planning. The main purpose of the present study was to evaluate from photographs the improvement in facial appearance after orthognathic surgery. In addition, the outcomes of two different planning techniques, 2-dimensional and 3-dimensional, were compared and the correlation between the outcome and health-related quality of life (HRQoL) assessed. The study was a randomised controlled trial with the intervention being either 2-dimensional or 3-dimensional treatment planning. An evaluation panel compared photographs taken before and after operation on patients with severe class III malocclusion. The change in facial appearance was rated, the two planning techniques compared, and the result correlated with previously published findings on cephalometric accuracy and HRQoL in the same group. Completed 12-month follow-up resulted in the inclusion of 57 subjects aged between 18 and 28 years at the time of operation (mean 21 years). We found significant differences between the two evaluations (p = 4.4E-9) but no significant difference in facial improvement between the planning techniques (p = 0.54). However, there was a correlation between cephalometric measurement of accuracy in the anterior maxilla and evaluation of improvement of facial appearance (p = 0.024, r = 0.30), but we found no correlation +between HRQoL and the evaluation of facial appearance (p = 0.31, r = -0.14). We conclude that there was an improvement in facial aesthetics after orthognathic surgery that was independent of the planning technique used.


Assuntos
Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Adolescente , Adulto , Cefalometria , Estética Dentária , Humanos , Imageamento Tridimensional , Má Oclusão Classe III de Angle , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Resultado do Tratamento , Adulto Jovem
14.
Otolaryngol Head Neck Surg ; 138(3): 340-6, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18312882

RESUMO

OBJECTIVE: To test whether intranasal ciprofloxacin/dexamethasone or dexamethasone alone affects the course of acute bacterial rhinosinusitis in mice. STUDY DESIGN: We performed a randomized, double-blind, parallel, placebo-controlled study in mice. SUBJECTS AND METHODS: Three groups of 10 C57Bl/6 mice were infected with Streptococcus pneumoniae, and then 1 day later randomized to treatment with placebo, ciprofloxacin plus dexamethasone, or dexamethasone. The mice were killed 3 or 10 days after treatment was begun. RESULTS: The placebo-treated mice became infected and developed an inflammatory cell infiltration in their sinuses. None of the treatments significantly affected the course of the illness. CONCLUSION: The lack of topical, intranasal efficacy of ciprofloxacin and dexamethasone could be attributed to subpotent dosage, rapid nasal clearance, or inability of the drops to reach the site of infection. Treatment with dexamethasone neither improved nor worsened the bacterial infection.


Assuntos
Anti-Infecciosos/administração & dosagem , Ciprofloxacina/administração & dosagem , Dexametasona/administração & dosagem , Infecções Pneumocócicas/tratamento farmacológico , Rinite/tratamento farmacológico , Rinite/microbiologia , Sinusite/tratamento farmacológico , Sinusite/microbiologia , Administração Tópica , Animais , Contagem de Colônia Microbiana , Quimioterapia Combinada , Feminino , Citometria de Fluxo , Camundongos , Camundongos Endogâmicos C57BL , Coleta de Tecidos e Órgãos
15.
Int J Pediatr Otorhinolaryngol ; 72(1): 97-102, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18035427

RESUMO

OBJECTIVE: Describe the pharmacokinetics of ciprofloxacin and dexamethasone after administration of CIPRODEX Otic Suspension (CIP/DEX) into the middle ears of children. DESIGN: Open-label, single-dose, pharmacokinetic studies, administering four drops of CIP/DEX instilled into each middle ear through the tympanostomy tubes immediately following tube placement. Blood was collected for 6h and analyzed for ciprofloxacin and dexamethasone concentrations using a validated liquid chromatography and tandem mass spectrometry (LC/MS/MS) method. SETTING: The study was conducted through a referral pediatric otolaryngology practice with actual surgical procedures performed in an ambulatory care center. PATIENTS: Twenty-five randomly selected patients, 1-14 years of age (mean age, 5 years), receiving tympanostomy tubes. RESULTS: Peak ciprofloxacin plasma levels were observed at about 1h, with a mean C(max) of 1.33+/-0.96 ng/mL (range <0.5-3.45 ng/mL) and an estimated half-life of 3.0+/-1.2h. Peak dexamethasone plasma levels were observed within 2h with a mean C(max) of 0.90+/-1.04 ng/mL (range <0.05-5.10 ng/mL) and an estimated half-life of 3.9+/-2.9h. CONCLUSION: These results demonstrated low systemic exposure of ciprofloxacin and dexamethasone following topical otic administration in pediatric patients.


Assuntos
Ciprofloxacina/administração & dosagem , Ciprofloxacina/farmacocinética , Dexametasona/administração & dosagem , Dexametasona/farmacocinética , Adolescente , Criança , Pré-Escolar , Cromatografia Líquida , Combinação de Medicamentos , Orelha Média , Feminino , Meia-Vida , Humanos , Lactente , Masculino , Ventilação da Orelha Média/instrumentação , Espectrometria de Massas em Tandem
16.
Am J Otolaryngol ; 29(4): 255-61, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18598837

RESUMO

OBJECTIVE: To demonstrate clinical equivalence (statistical noninferiority) of topical ciprofloxacin and hydrocortisone (CHC, Cipro HC) and topical neomycin/polymyxin b/hydrocortisone (NPH, Cortisporin) with systemic amoxicillin (AMX, Amoxil), for treatment of acute otitis externa (AOE). DESIGN: Randomized, active-control, observer-blind, multicenter trial. PATIENTS: Altogether, 206 patients were enrolled (CHC, 106; NPH + AMX, 100). Patients were > or =1 year of age, had AOE >2 days with at least mild symptoms, and gave informed consent. All were evaluable for safety, and 151 were evaluable for efficacy. INTERVENTIONS: Ciprofloxacin and hydrocortisone 3 drops twice daily for 7 days (adults and children) or NPH 4 drops (adults) or 2 drops (children) with AMX 250 mg (adults and children) 3 times daily for 10 days, as directed in approved product labeling. MAIN OUTCOME MEASURES: The primary efficacy variable was response to therapy 7 days after treatment ended (test of cure). Secondary variables included time to end of pain, symptom scores (otalgia and tenderness) and microbiological eradication. Noninferiority was declared if the lower confidence limit around the measurement difference was above -10 (nearer zero). RESULTS: Response to therapy was higher for CHC (95.71% vs 89.83%) but was statistically noninferior (lower confidence limit, -4.98) to NPH + AMX. Median time to end of pain was 6 days for both groups. Noninferiority was declared for symptom scores at all measurement periods and for microbiological eradication. No serious adverse events related to treatment were reported. CONCLUSIONS: Ciprofloxacin and hydrocortisone is clinically equivalent to NPH + AMX for the treatment of AOE in adults and children. However, low systemic exposure, absence of ototoxicity, and less frequent dosing clearly favor Cipro HC.


Assuntos
Amoxicilina/administração & dosagem , Antibacterianos/administração & dosagem , Anti-Infecciosos/administração & dosagem , Ciprofloxacina/administração & dosagem , Hidrocortisona/administração & dosagem , Neomicina/administração & dosagem , Otite Externa/tratamento farmacológico , Polimixinas/administração & dosagem , Doença Aguda , Administração Oral , Administração Tópica , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Equivalência Terapêutica , Resultado do Tratamento
17.
Clin Ther ; 29(9): 1950-6, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18035194

RESUMO

OBJECTIVE: This study aimed to compare the clinical outcome of patients receiving topical ciprofloxacin 0.3%/dexamethasone 0.1% (CD) otic suspension with that of those receiving polymyxin B/neomycin/ hydrocortisone (PNH) otic suspension for the treatment of acute otitis externa (AOE). METHODS: Data from 2 institutional review board-approved, multicenter, observer-masked, parallel-group, randomized, noninferiority clinical trials conducted at 76 institutions across the United States between April 1998 and July 1999 were pooled together for this analysis. Patients > or =1 year of age diagnosed with AOE were considered for inclusion in the studies. Patients with AOE >4 weeks' duration, a perforated tympanic membrane, chronic suppurative otitis media, or use of either antibiotics or steroids within the previous 7 days were excluded from the studies. Patients were randomly assigned to receive CD or PNH for 7 days. CD was administered as 3 drops in children and 4 drops in patients > or =12 years of age BID. PNH was administered as 3 drops in children and 4 drops in patients > or =12 years of age TID. The clinical investigators were blinded to treatment assignment. Due to the different dosing regimens, patients were not blinded, but they also were not directly informed of their treatment assignments. Otic inflammation, tenderness, edema, and discharge were clinically assessed on days 3, 8, and 18 of the studies. Otic inflammation and edema were evaluated using a 4-point scale (none = 0; mild = 1; moderate = 2; and severe = 3). Otic tenderness and discharge were rated on a binomial scale (absent = 0 and present = 1). The clinical assessments were aggregated into a 9-point composite clinical scale (range, 0-8) to compare baseline severity between groups. For the final outcomes assessment in this study, the aggregated clinical scores were dichotomized into cured (0) versus noncured (>0) and analyzed using a Kaplan-Meier survival technique. A log-rank test was used to compare the cure curves between treatment groups. Kaplan-Meier summary statistics provide the mean and median times to cure, and the mean times to cure for the 25th and 75th patient quartiles. Tolerability was assessed by monitoring patients for adverse events at each visit. RESULTS: Data from 1072 patients (1242 ears) were included in the analysis (CD, 537 patients; PNH, 535 patients). Baseline AOE severity and demographic characteristics were similar between the 2 treatment groups. The mean patient age was 21.7 and 22.0 years in the CD and PNH groups, respectively. Both groups were similar with respect to sex, with 50.7% and 53.5% females in the CD and PNH groups, respectively. The racial composition was predominately white (88.6% vs 84.9% in the CD and PNH groups, respectively). The log-rank test revealed a significant difference in the AOE cure curves between the CD and PNH groups (P = 0.038). The proportions cured in the AOE at-risk groups at the day-3, -8, and -18 assessments in the CD and PNH treatment groups were 0.14 and 0.10, 0.75 and 0.72, and 0.98 and 0.97, respectively. The Kaplan-Meier summary statistics indicated that the mean time to cure was 0.6 day less with CD compared with PNH (9.7 vs 10.3 days). Treatment-related adverse event rates were similar between the 2 groups and occurred in 3.8% of the patients. The most common adverse events included otic pruritus (2.1%), otic congestion (0.6%), otic debris (0.5%), otic pain (0.3%), superimposed ear infection (0.3%), and erythema (0.1%). CONCLUSION: These data from 2 previous studies suggest that time to cure was significantly less with CD compared with PNH in patients with AOE.


Assuntos
Ciprofloxacina/uso terapêutico , Dexametasona/uso terapêutico , Hidrocortisona/uso terapêutico , Neomicina/uso terapêutico , Otite Externa/tratamento farmacológico , Polimixina B/uso terapêutico , Administração Tópica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Criança , Pré-Escolar , Ciprofloxacina/administração & dosagem , Dexametasona/administração & dosagem , Combinação de Medicamentos , Humanos , Pessoa de Meia-Idade , Neomicina/administração & dosagem , Polimixina B/administração & dosagem , Suspensões , Resultado do Tratamento
18.
Otolaryngol Head Neck Surg ; 137(6): 918-24, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18036421

RESUMO

OBJECTIVE: Seasonal allergic rhinitis (SAR) is a highly prevalent disease. This study was conducted to evaluate the onset and duration of action of three concentrations of olopatadine nasal spray. METHODS: This was a randomized, double-blind, single-dose, placebo-controlled study, conducted in an environmental exposure chamber in patients with SAR. A total of 320 patients were exposed to ragweed allergen in the chamber and randomized to olopatadine nasal spray 0.2%, 0.4%, 0.6%, or placebo nasal spray. Symptoms (sneezing, runny, itchy, and stuffy nose) were self-assessed during a 12-hour study period. RESULTS: All concentrations of olopatadine nasal spray provided clinically meaningful reductions in total nasal symptom scores at 30 minutes compared to the placebo. Olopatadine nasal spray 0.6% was significantly more effective (P < 0.05) than placebo nasal spray at all time-points starting at 90 minutes post-dose and continuing over 12 hours. CONCLUSIONS: Olopatadine nasal spray 0.6% demonstrated a fast onset of action and maintained an effect for at least 12 hours after dosing.


Assuntos
Antialérgicos/administração & dosagem , Dibenzoxepinas/administração & dosagem , Rinite Alérgica Sazonal/prevenção & controle , Administração Intranasal , Adolescente , Adulto , Aerossóis , Idoso , Alérgenos/efeitos adversos , Ambrosia/efeitos adversos , Método Duplo-Cego , Ambiente Controlado , Exposição Ambiental , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cloridrato de Olopatadina , Satisfação do Paciente , Placebos , Pólen/efeitos adversos , Rinite Alérgica Sazonal/classificação , Segurança , Fatores de Tempo , Resultado do Tratamento
19.
Adv Ther ; 24(3): 671-5, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17660178

RESUMO

Ciprofloxacin 0.3%/dexamethasone 0.1% (CIP/DEX) and neomycin 0.35%(polymyxin B 10,000 IU/mL/hydrocortisone 1.0% (NPH) were compared for relief of pain in patients with acute otitis externa. Patients received 7 d of treatment with CIP/DEX twice daily or NPH 3 times daily. Ear pain was assessed by patients/caregivers twice daily and by the study investigator on days 3, 8, and 18 (4-point scale). Higher percentages of CIP/DEX-treated patients had relief of severe pain over time (P=.0013) and relief of significant pain (moderate or severe pain) over time (P=.0456), compared with NPH-treated patients. The percentage of CIP/DEXtreated patients with severe pain decreased rapidly within the first 12 h; this contrasted with an increase in pain among NPH-treated patients. CIP/DEX-treated patients had significantly less inflammation (P=.0043) and edema (P=.0148) than NPH-treated patients. Overall, these results support greater pain relief attained over the first 3 d in patients with acute otitis externa treated with CIP/DEX compared with NPH and a rapid reduction in severe pain after initiation of treatment.


Assuntos
Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Otite Externa/tratamento farmacológico , Dor/tratamento farmacológico , Adulto , Anti-Infecciosos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Ciprofloxacina/administração & dosagem , Ciprofloxacina/farmacologia , Dexametasona/administração & dosagem , Dexametasona/farmacologia , Quimioterapia Combinada , Humanos , Hidrocortisona/administração & dosagem , Hidrocortisona/farmacologia , Lactente , Neomicina/administração & dosagem , Neomicina/farmacologia , Polimixinas/administração & dosagem , Polimixinas/farmacologia , Método Simples-Cego
20.
Acta Otolaryngol ; 126(9): 910-5, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16864486

RESUMO

CONCLUSION: The lipopolysaccharide (LPS)-induced chinchilla otitis media (OM) model was proven useful in screening anti-inflammatory agents for topical use. Both 1% rimexolone and 1% dexamethasone are effective in reducing the volume of middle ear effusion and mucosal thickness compared with control groups. Topical corticosteroid therapy was efficacious in reducing middle ear mucosal inflammation. OBJECTIVE: OM is one of the most common diseases in the pediatric population. Our previous studies have shown that treatment with systemic antibiotics and corticosteroids was more efficacious than antibiotics alone. The purpose of this study was to determine the effectiveness of topically applied corticosteroids on the outcome of OM. The long-term goal of this study was to develop a better method of OM treatment by demonstrating effectiveness of topically applied anti-inflammatory agents, such as corticosteroids, avoiding systemic side effects. MATERIALS AND METHODS: Three experimental groups were studied in chinchillas. OM with effusion was induced in all groups by injecting LPS. Group 1 consisted of controls in three subgroups as follows. Control-LPS alone, vehicle of dexamethasone (control-dexa), vehicle of rimexolone (control-rimex). Group 2 was treated with dexamethasone and included subgroups of separate concentrations of dexamethasone: 0.1% and 1% suspensions. Group 3 was treated with rimexolone and included subgroups of separate concentrations of rimexolone: 0.1% and 1% suspensions. A total of 58 animals were used: 18 for controls and 40 for experimental groups. All test substances (saline, control-dexa, control-rimex, dexamethasone and rimexolone, 200 microl) were injected at -2, 48 and 60 h; LPS was injected at 0 h. Animals were monitored by daily otomicroscopy. After 4 days, samples of middle ear effusion (MEE) were collected for analysis and temporal bones were harvested for histopathological studies. RESULTS: At the end of 4 days, only in five ears (3/20 with 1% dexamethasone, 1/20 with 1% rimexolone, and 1/20 with 0.1% rimexolone) had the fluid diminished to the point of being unobservable. The volume of MEE, thickness of mucoperiosteum, and the degree of inflammation of middle ear mucosa with 1% dexamethasone and 1% rimexolone was significantly less compared with other groups.


Assuntos
Dexametasona/farmacologia , Glucocorticoides/farmacologia , Otite Média com Derrame/tratamento farmacológico , Pregnadienos/farmacologia , Administração Tópica , Animais , Chinchila , Modelos Animais de Doenças , Feminino , Masculino , Microscopia , Mucosa/efeitos dos fármacos , Mucosa/patologia , Otite Média com Derrame/patologia , Periósteo/efeitos dos fármacos , Periósteo/patologia , Distribuição Aleatória , Osso Temporal/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA