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2.
Medicina (Kaunas) ; 55(7)2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31336766

RESUMO

Background and Objectives: Topically administered antiglaucoma medications, especially those containing benzalkonium chloride (BAC), may cause local adverse effects and compromise ocular surface. The aim of the study was to assess the effect of topical prostaglandin F2α analogs (PGAs): preservative-free latanoprost, BAC-preserved latanoprost, preservative-free tafluprost, and BAC-preserved bimatoprost, on selected oxidative stress parameters in the tear film. Materials and Methods: The patients were divided into five groups: group C (n = 25) control group-subjects who did not use topical antiglaucoma medications, group L (n = 22)-patients using topical preservative-free latanoprost, group L+BAC (n = 25)-patients using topical BAC-preserved latanoprost, group T (n = 19)-patients using topical preservative-free tafluprost, and group B+BAC (n = 17)-patients using topical BAC-preserved bimatoprost. The oxidative stress markers in the tear film samples were evaluated: total protein (TP) concentration, advanced oxidation protein products (AOPP) content, total sulfhydryl (-SH) groups content, the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as Total Oxidant Status (TOS), Total Antioxidant Response (TAR), and Oxidative Stress Index (OSI). Results: The TP concentrations in the groups L, L+BAC, and B+BAC were statistically significantly higher in comparison with group C. The SOD and CAT activities in the groups L+BAC and B+BAC were statistically significantly higher when compared to group C. As compared to group C, AOPP and TOS were statistically significantly higher in all the study groups. OSI was found to be statistically significantly higher in the groups L+BAC, T, and B+BAC in comparison with group C. Conclusion: Use of topical PGAs by the patients with ocular hypertension or primary open-angle glaucoma is associated with increased oxidative stress in the tear film which is additionally exacerbated by the presence of BAC in the formulation.


Assuntos
Dinoprosta/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Lágrimas/química , Administração Tópica , Compostos de Benzalcônio/farmacocinética , Compostos de Benzalcônio/farmacologia , Compostos de Benzalcônio/uso terapêutico , Estudos Transversais , Dinoprosta/farmacocinética , Dinoprosta/uso terapêutico , Glaucoma/tratamento farmacológico , Humanos , Latanoprosta/farmacocinética , Latanoprosta/farmacologia , Latanoprosta/uso terapêutico , Estresse Oxidativo/fisiologia , Polônia , Prostaglandinas F/farmacocinética , Prostaglandinas F/farmacologia , Prostaglandinas F/uso terapêutico , Lágrimas/efeitos dos fármacos
3.
Pesqui. vet. bras ; 39(4): 263-270, Apr. 2019. tab, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1002815

RESUMO

Extensive literature is available about the intrinsic denervation of segments of the digestive tube through the application of CB in the serosa of the viscera. However, this technique has some disadvantages like causing peritonitis, flanges and high mortality, limiting its use in humans. The aim of the present study was to evaluate the feasibility of benzalkonium chloride (CB) to induce intrinsic chemical denervation, through applications of CB in the intramural ileum of wistar rats, as well as deepen the knowledge about the evolution of neuronal injury caused in the process. We used 40 rats, divided into two groups (control-GC and benzalkonium-GB) of 20 animals each, divided into four sub-groups according to the time of postoperative assessment of 24, 48 hours, 30 and 90 days. The animals were submitted to intramural microinjections of sterile saline solution 0.9% (GC) or benzalkonium chloride (GB) in ileal portion, and subsequent histopathological analysis and immunohistochemistry for evaluation of neuronal injury. A significant decrease (p<0.05) was found of the neuronal myenteric count over time in groups, GB3, GB4 and GB2. The specific positive immunolabeling for H2AX and Caspase-3 confirmed the results obtained in the histopathological evaluation, denoting the ignition of irreversible cell injury in 24 hours, evolving into neuronal apoptosis in 48 hours after application of the CB 0.3%. Under the conditions in which this work was conducted, it can be concluded that the application of CB 0.3% by means of microinjections intramural in the ileal wall is able to induce intrinsic chemical denervation of the diverticulum of wistar rats and that the main mechanism of neuronal death is induction of apoptosis.(AU)


Existe vasta literatura sobre a desnervação intrínseca de segmentos do tubo digestório através da aplicação de CB na serosa da víscera. Entretanto, essa técnica tem a desvantagem de causar peritonite, formação de bridas e alta mortalidade, não sendo factível para eventuais utilizações em humanos. O objetivo do presente estudo foi avaliar a viabilidade do Cloreto de benzalcônio (CB) induzir desnervação química intrínseca, por meio de aplicações intramurais em íleo de ratos wistar, além de aprofundar o conhecimento sobre a evolução da lesão neuronal causada neste processo. Foram utilizados 40 ratos, distribuídos em dois grupos (controle- GC e benzalcônio- GB) de 20 animais cada, subdivididos em quatro subgrupos de acordo com o tempo de avaliação pós-operatória de 24, 48 horas, 30 e 90 dias. Os animais foram submetidos à microinjeções intramurais de solução salina estéril 0,9% (GC) ou de cloreto de benzalcônio (GB) em porção ileal, e posterior análise histopatológica e imuno-histoquímica, para avaliação da lesão neuronal. Houve diminuição significativa (p<0,05) na contagem neuronal mientérica ao longo do tempo nos grupos GB2, GB3 e GB4. A imunomarcação específica positiva para H2AX e Caspase-3 confirmou os resultados obtidos na avaliação histopatológica, denotando início da lesão celular irreversível em 24 horas, evoluindo para apoptose neuronal em 48 horas após a aplicação do CB 0,3%. Nas condições em que este trabalho foi conduzido, é possível concluir que a aplicação de CB 0,3% por meio de microinjeções intramurais na parede ileal é capaz de induzir desnervação química intrínseca da porção ileal de ratos wistar e que o principal mecanismo de morte neuronal é a indução de apoptose.(AU)


Assuntos
Animais , Ratos , Modelos Animais , Íleo/inervação , Síndrome do Intestino Curto/reabilitação , Compostos de Benzalcônio/uso terapêutico , Ratos Wistar , Denervação Muscular/veterinária
4.
Pain ; 160(2): 307-321, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30412056

RESUMO

Ocular pain is a core symptom of inflammatory or traumatic disorders affecting the anterior segment. To date, the management of chronic ocular pain remains a therapeutic challenge in ophthalmology. The main endogenous opioids (enkephalins) play a key role in pain control but exhibit only transient analgesic effects due to their rapid degradation. The aim of this study was to explore the antinociceptive and anti-inflammatory effects of topical administration of PL265 (a dual enkephalinase inhibitor) on murine models of corneal pain. On healthy corneas, chronic PL265 topical administration did not alter corneal integrity nor modify corneal mechanical and chemical sensitivity. Then, on murine models of corneal pain, we showed that repeated instillations of PL265 (10 mM) significantly reduced corneal mechanical and chemical hypersensitivity. PL265-induced corneal analgesia was completely antagonized by naloxone methiodide, demonstrating that PL265 antinociceptive effects were mediated by peripheral corneal opioid receptors. Moreover, flow cytometry (quantification of CD11b+ cells) and in vivo confocal microscopy analysis revealed that instillations of PL265 significantly decreased corneal inflammation in a corneal inflammatory pain model. Chronic PL265 topical administration also decreased Iba1 and neuronal injury marker (ATF3) staining in the nucleus of primary sensory neurons of ipsilateral trigeminal ganglion. These results open a new avenue for ocular pain treatment based on the enhancement of endogenous opioid peptides' analgesic effects in tissues of the anterior segment of the eye. Dual enkephalinase inhibitor PL265 seems to be a promising topical treatment for safe and effective alleviation of ocular pain and inflammation.


Assuntos
Córnea/patologia , Inibidores Enzimáticos/administração & dosagem , Inflamação/tratamento farmacológico , Dor/tratamento farmacológico , Propionatos/administração & dosagem , Administração Tópica , Animais , Anti-Infecciosos Locais/uso terapêutico , Compostos de Benzalcônio/uso terapêutico , Capsaicina/toxicidade , Córnea/efeitos dos fármacos , Lesões da Córnea/induzido quimicamente , Lesões da Córnea/complicações , Modelos Animais de Doenças , Hiperalgesia/fisiopatologia , Inflamação/induzido quimicamente , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Naloxona/toxicidade , Antagonistas de Entorpecentes/toxicidade , Dor/etiologia , Limiar da Dor/efeitos dos fármacos , Fármacos do Sistema Sensorial/toxicidade , Gânglio Trigeminal/metabolismo , Gânglio Trigeminal/patologia
5.
Int Ophthalmol ; 39(1): 105-109, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29274019

RESUMO

PURPOSE: To validate the hypothesis that BAK induces low-grade inflammation in the anterior chamber, we designed a study to investigate whether switching from BAK-preserved to preservative-free latanoprost in patients with primary open-angle glaucoma (POAG) would reduce the flare levels. PATIENTS: Forty-one eyes of twenty-two patients with primary open-angle glaucoma treated with BAK-preserved latanoprost for at least 6 months as monotherapy were included. Exclusion criteria included any use of topical eye drops other than latanoprost, pseudoexfoliation and pigment dispersion glaucoma, wearing of contact lenses and intraocular surgery in the past year. METHODS: At the start of the study, we measured baseline flare values. We then switched all patients to preservative-free latanoprost. After 1, 2, and 3 months, a routine ophthalmological examination was performed and flare measurement repeated. RESULTS: Thirty-three eyes were followed up throughout the entire 3-month period. One month after the switch to preservative-free latanoprost, a statistically significant mean drop in flare of - 0.96 ph/ms (P = 0.025) was observed. Mean flare decreased further by - 1.31 ph/ms (P = 0.0027) after 2 months and by - 1.25 ph/ms (P = 0.0041) after 3 months. CONCLUSION: The switch from BAK-preserved to preservative-free latanoprost induced a statistically significant reduction in mean flare value. Whereas our previous study showed an increase in flare when initiating treatment with BAK-preserved eye drops, this study shows a decrease in flare upon cessation of BAK-preserved drugs. The combined evidence from the two studies strongly suggests that in humans BAK exerts its effects not only on the ocular surface, but also at the level of the anterior chamber.


Assuntos
Câmara Anterior/diagnóstico por imagem , Compostos de Benzalcônio/uso terapêutico , Substituição de Medicamentos/métodos , Glaucoma de Ângulo Aberto/tratamento farmacológico , Pressão Intraocular/efeitos dos fármacos , Latanoprosta/administração & dosagem , Idoso , Anti-Hipertensivos/administração & dosagem , Feminino , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/administração & dosagem , Conservantes Farmacêuticos , Estudos Prospectivos
6.
Am J Orthod Dentofacial Orthop ; 155(1): 88-97, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30591172

RESUMO

INTRODUCTION: The aim of this study was to determine the effect of an orthodontic bonding adhesive containing benzalkonium chloride (BAC) on enamel demineralization. METHODS: Eighteen female Sprague-Dawley rats, aged 8 to 10 weeks, were inoculated with Streptococcus sobrinus for 5 days. The animals were randomly divided into the control, non-BAC, and BAC groups. The 6 animals in each group did not receive any brackets, received brackets on the maxillary left first molars bonded with conventional adhesive, or received brackets on the maxillary left and right first molars bonded with adhesive incorporated with 0.25% and 0.75% BAC (wt/wt), respectively. After 7 weeks, the maxillae were soaked in murexide stain to observe the surface area (mm2) and percentages of enamel demineralization on the palatal, mesial, buccal, and occlusal surfaces of the maxillary molars using color-based image analysis. RESULTS: The non-BAC and BAC groups exhibited greater enamel demineralization compared with the control group. The surface areas and percentages of enamel demineralization in the BAC group were less compared with the non-BAC group. Less enamel demineralization was noted in the animals treated with 0.75% BAC compared with those given 0.25% BAC in all areas; however, these differences were not great enough to attain statistical significance at the 0.05 level. CONCLUSIONS: The addition of BAC to an orthodontic composite has the potential to reduce the amount and percentage of enamel demineralization. In addition to being an antibacterial agent, BAC may also have an anticariogenic effect. Increased sample sizes and testing of more concentrations of BAC are recommended.


Assuntos
Anti-Infecciosos Locais/uso terapêutico , Compostos de Benzalcônio/uso terapêutico , Cimentos Dentários/uso terapêutico , Desmineralização do Dente/prevenção & controle , Animais , Anti-Infecciosos Locais/farmacologia , Compostos de Benzalcônio/farmacologia , Cárie Dentária/prevenção & controle , Cimentos Dentários/farmacologia , Feminino , Humanos , Ratos , Ratos Sprague-Dawley , Dente/efeitos dos fármacos
7.
Pharm Res ; 36(1): 11, 2018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30411196

RESUMO

PURPOSE: The purpose of this research work was to develop new polycationic compounds based on pyridine and piperidine structures with high antimicrobial activities against bacteria and fungi. Furthermore, the compounds should offer a lower toxicity than the commonly used preservatives for ophthalmic formulations, such as benzalkonium chloride (BAC) and polyquaternium-1 (PQ1). METHODS: Two polymers and three dimeric compounds were developed. Minimum inhibitory concentrations were determined for Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans and Aspergillus brasiliensis. The compounds were characterized regarding their impact on cell viability, cytotoxicity, epithelial integrity and surface tension. MTT and CytoTox-Glo™ assays, permeation studies with mannitol and transepithelial electrical resistance (TEER) measurements were performed on human corneal epithelial or MDCK I cells. BAC and PQ1 were used as references. RESULTS: Three polycationic compounds exhibited high antimicrobial activity against the tested microorganisms comparable to that of BAC. Four compounds were tolerated as well as or better than PQ1. In addition, the TEER, permeability and surface tension were only affected by compounds with amphiphilic properties. CONCLUSION: The pyridine- and piperidine-based polycationic compounds are promising candidates as new preservatives for ophthalmic formulations. Their high antimicrobial efficacy and good tolerability indicate a different mechanism of action compared to BAC.


Assuntos
Anti-Infecciosos , Soluções Oftálmicas , Poliaminas , Conservantes Farmacêuticos , Administração Oftálmica , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/química , Compostos de Benzalcônio/administração & dosagem , Compostos de Benzalcônio/síntese química , Compostos de Benzalcônio/uso terapêutico , Linhagem Celular , Composição de Medicamentos , Células Epiteliais/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/química , Polímeros/administração & dosagem , Polímeros/síntese química , Polímeros/uso terapêutico , Conservantes Farmacêuticos/administração & dosagem , Conservantes Farmacêuticos/química , Pseudomonas aeruginosa/efeitos dos fármacos
8.
Am J Health Syst Pharm ; 75(22): 1791-1797, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30282664

RESUMO

PURPOSE: The results of a study to determine if rates of poor response differ in patients receiving continuous nebulized albuterol (CNA) therapy with or without the preservative benzalkonium chloride are presented. METHODS: A retrospective analysis of the records of all patients who received CNA therapy at a large academic medical center from July 2015 to January 2016 was conducted. Data from patient evaluations performed before and after a change to benzalkonium chloride-containing albuterol were collected. The primary outcome was the rate of poor patient response, defined as a composite endpoint. Secondary outcomes included duration of therapy, dosing requirements, and duration of supplemental oxygen therapy. RESULTS: There was no significant difference in rates of poor response between patients exposed (n = 80) and patients not exposed (n = 48) to benzalkonium chloride (16% and 17%, respectively; p = 0.95). The cohort not exposed to benzalkonium chloride had a median CNA duration of 7.0 hours, as compared with 10.5 hours for the cohort exposed to benzalkonium chloride, but this difference was not significant (p = 0.19). There were no significant differences between the benzalkonium chloride-exposed and nonexposed cohorts in the maximum dosing requirement (12.6 mg/hr versus 12.8 mg/hr, p = 0.89) or median duration of supplemental oxygen use (27.5 hours versus 16.5 hours, p = 0.77). CONCLUSION: A study of hospitalized patients receiving CNA detected no significant difference in the frequency of poor response to therapy between groups receiving benzalkonium chloride-free versus benzalkonium chloride-containing albuterol products.


Assuntos
Albuterol/efeitos adversos , Compostos de Benzalcônio/efeitos adversos , Broncodilatadores/efeitos adversos , Conservantes Farmacêuticos/efeitos adversos , Administração por Inalação , Adolescente , Albuterol/administração & dosagem , Albuterol/uso terapêutico , Compostos de Benzalcônio/administração & dosagem , Compostos de Benzalcônio/uso terapêutico , Broncodilatadores/administração & dosagem , Broncodilatadores/uso terapêutico , Criança , Feminino , Humanos , Masculino , Nebulizadores e Vaporizadores , Conservantes Farmacêuticos/administração & dosagem , Conservantes Farmacêuticos/uso terapêutico , Estudos Retrospectivos , Estado Asmático/tratamento farmacológico , Resultado do Tratamento
9.
Int J Clin Pract ; 72(12): e13272, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30329199

RESUMO

OBJECTIVE: The aim of this multi-centre, randomised, double-blind, placebo-controlled trial was to compare the efficacy and safety of the fixed combination of 0.5 mg tyrothricin, 1.0 mg benzalkonium chloride, and 1.5 mg benzocaine (study drug marketed as Dorithricin® ) in repeat dosing for 3 days to match placebo lozenges in the treatment of acute pharyngitis in adults. METHODS: Patients (pts, aged ≥18 years) with acute pharyngitis, ie, non-streptococcal sore throat and moderate-to-severe pain (intensity NRS ≥ 7; VAS ≥ 50) were assigned to study drug (n = 160) or matching placebo (n = 161). Efficacy was assessed by investigator for 2 hours post initial dose (p.i.d.), and 3 days later (Visit 2). Primary efficacy endpoint was the complete resolution of throat pain and difficulty in swallowing at Visit 2 (3 days p.i.d.). Safety and local tolerability were also assessed. RESULTS: Seventy-two hours (p.i.d.), complete resolution of throat pain and difficulty in swallowing were achieved by 44.6% patients on study drug compared with 27.2% patients on placebo (difference 17.4% (CI [5.8%; 29.7%]; 64% improvement [GEE, P = 0.0022]). Until 2 hours p.i.d., reduction in symptoms was better with study drug (P < 0.005). Treatment satisfaction was higher with study drug (patients'/investigators' assessment (78.9%/78.9% vs 55.0%/55.6% for placebo) and was well tolerated, overall safety profile was comparable to placebo. CONCLUSION: The strength of this randomised controlled trial lies in the endpoint of complete remission after 3 days p.i.d., especially in the light of other trials addressing acute pharyngitis. The results of this study show a significant benefit of the study drug over placebo in the treatment of acute pharyngitis. Local treatment with the fixed combination (0.5 mg tyrothricin, 1.0 mg benzalkonium chloride, and 1.5 mg benzocaine) provides a rapid analgesic effect and is effective in relieving both severe throat pain as well as difficulty in swallowing associated with acute pharyngitis leading to a 64% improved complete remission within 72 hours. The triple active combination is a suitable treatment option for patients in the self-management of acute pharyngitis and sore throat. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03323528.


Assuntos
Compostos de Benzalcônio/uso terapêutico , Benzocaína/uso terapêutico , Dor/tratamento farmacológico , Faringite/tratamento farmacológico , Tirotricina/uso terapêutico , Doença Aguda , Administração Oral , Adulto , Deglutição , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Medição da Dor , Satisfação do Paciente , Faringite/complicações , Resultado do Tratamento , Adulto Jovem
10.
Eye Contact Lens ; 44 Suppl 2: S93-S98, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28617732

RESUMO

PURPOSE: To assess ocular surface changes in participants using latanoprost with benzalkonium chloride (Xalatan) and travoprost with SofZia (Travatan Z). METHODS: In this prospective, open-label, nonrandomized cohort study, participants were classified into two groups: group 1 (n=28) naive to glaucoma therapy, group 2 (n=27) on previous Xalatan monotherapy in both eyes. Both groups started (or continued) Xalatan in the right eye and Travatan Z in the left eye. Baseline, 1-, and 2-month measurements of tear breakup time (TBUT), corneal staining score, conjunctival staining score, conjunctival hyperemia score, tear production, and intraocular pressure were obtained. The Ocular Surface Disease Index questionnaire measured participants' comfort and dryness symptoms. Medication preference was recorded. RESULTS: Data were collected from 55 participants. Tear breakup time at baseline and 1-month follow-up in group 1 was significantly longer than that of group 2 (P=0.005). At 2 months, there was no significant difference in TBUT between the two groups (P=0.779). Tear production in group 1 at all three time points was significantly higher than group 2 (P<0.05). Conjunctival staining score at 2 months in group 1 was significantly higher than group 2 (P=0.031). There was no significant difference in other parameters between the groups at any other time point. No significant difference in any parameter was found between Xalatan and Travatan Z (intragroup comparison). CONCLUSIONS: Significant differences in ocular surface characteristics were detected between groups, but no significant difference was detected between participants treated with Xalatan and Travatan Z.


Assuntos
Anti-Hipertensivos/uso terapêutico , Compostos de Benzalcônio/uso terapêutico , Túnica Conjuntiva/efeitos dos fármacos , Córnea/efeitos dos fármacos , Glaucoma/tratamento farmacológico , Latanoprosta/uso terapêutico , Conservantes Farmacêuticos/uso terapêutico , Travoprost/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/farmacologia , Compostos de Benzalcônio/efeitos adversos , Compostos de Benzalcônio/farmacologia , Túnica Conjuntiva/patologia , Córnea/patologia , Feminino , Glaucoma/patologia , Humanos , Pressão Intraocular , Latanoprosta/efeitos adversos , Latanoprosta/farmacologia , Masculino , Pessoa de Meia-Idade , Conservantes Farmacêuticos/efeitos adversos , Conservantes Farmacêuticos/farmacologia , Estudos Prospectivos , Lágrimas/metabolismo , Travoprost/efeitos adversos , Travoprost/farmacologia
11.
Biomed Res Int ; 2017: 1207208, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28875148

RESUMO

This study investigated the effect of benzalkonium chloride (BAC) modification of two adhesive systems on long-term bond strength to normal and artificially eroded dentin. A total of 128 extracted human molars were sectioned and the buccal and oral surfaces of each molar were ground until the dentin. One half was left untreated (normal dentin) while the other half underwent artificial erosion. Resin composite was bonded to the buccal or oral surface following treatment with Adper Scotchbond 1XT or OptiBond FL without or with 1% BAC incorporation. Shear bond strength (SBS) was measured after 24 h (100% humidity, 37°C) or 1 year (tap water, 37°C). SBS results were statistically analyzed (α = 0.05). SBS was significantly lower to artificially eroded dentin than to normal dentin (p < 0.001). Storage for 1 year had no effect on SBS to normal dentin but led to a significant decrease in SBS to artificially eroded dentin (p < 0.001). BAC incorporation decreased the 24 h SBS to normal dentin (p = 0.018), increased the 24 h SBS to eroded dentin (p = 0.001), and had no effect on the 1-year SBS for either substrate. Consequently, BAC incorporation did not improve bond durability.


Assuntos
Compostos de Benzalcônio/uso terapêutico , Materiais Dentários/uso terapêutico , Erosão Dentária/terapia , Compostos de Benzalcônio/química , Colagem Dentária , Materiais Dentários/química , Análise do Estresse Dentário , Dentina/química , Dentina/patologia , Humanos , Resistência ao Cisalhamento , Erosão Dentária/patologia
12.
Nanomedicine (Lond) ; 12(10): 1177-1185, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28447896

RESUMO

AIM: To develop NB-201, a nanoemulsion compound, as a novel microbicidal agent against methicillin-resistant Staphylococcus aureus (MRSA) infection, which is a common threat to public health but with limited therapeutic options. MATERIALS & METHODS: NB-201 was tested in in vitro and in vivo murine and porcine models infected with MRSA. RESULTS: Topical treatment of MRSA-infected wounds with NB-201 significantly decreased bacterial load and had no toxic effects on healthy skin tissues. NB-201 attenuated neutrophil sequestration in MRSA-infected wounds and inhibited epidermal and deep dermal inflammation. The levels of proinflammatory cytokines were reduced in NB-201-treated MRSA-infected wounds. CONCLUSION: NB-201 can greatly reduce inflammation characteristic of infected wounds and has antimicrobial activity that effectively kills MRSA regardless of the genetic basis of antibiotic resistance.


Assuntos
Antibacterianos/uso terapêutico , Compostos de Benzalcônio/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Polissorbatos/uso terapêutico , Óleo de Soja/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Infecção dos Ferimentos/tratamento farmacológico , Animais , Antibacterianos/farmacologia , Compostos de Benzalcônio/farmacologia , Citocinas/análise , Combinação de Medicamentos , Feminino , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Polissorbatos/farmacologia , Óleo de Soja/farmacologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Suínos , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologia
13.
Anesteziol Reanimatol ; 61: 224-227, 2017 Sep.
Artigo em Russo | MEDLINE | ID: mdl-29465209

RESUMO

Despite the use of modern methods of prevention, at least 10% of patients operated on for ophthalmic indications not develop corneal erosion as the indirect complication of general anesthesia. OBJECTIVE: To reduce the number of ophthalmic complications of general anesthesia by prophylactic use of new mito- chondria-targeted antioxidants - Vizomitin (eye drops). MATERIALS AND METHODS: 70 patients, which was supposed to perform the average duration of operations under general anesthesia were randomized into 3 groups depending on the method specific (pharmacological) prevention of corneal erosions: (1) control (specic (pharmacological) prevention was not carried out), (2), using preparation "natural tear, and (3) "Vizomitin" preparation. Postoperative biomicroscopy was performed to assess the condition of the cornea, tear film stability was measured and the height of the tear meniscus. RESULTS: When using eye drops "Vizomitin" value is an indicator of stability of the tear film on the 3rd day after the operation more than in the control group of patients by 51% (p = 0.012) and patients groups, natural tear by 57% (p = 0.013). Surgical interventions performed under general anesthesia, leading to an increase in the number ofpatients with decreased tear meniscus height index of the control group with 4 to 7 patients (p = 0.30) in the group of natural tear from 3 to 11 patients (p = 0.008) . In the group with drug "Vizomitin" the number of such patients is reduced from 7 to 1 (p = 0.018). CONCLUSION: In the surgical procedures under general anesthesia eye drops "Vizomitin" effectively prevents the devel- opment of corneal erosion.


Assuntos
Anestesia Geral/efeitos adversos , Antioxidantes/uso terapêutico , Compostos de Benzalcônio/uso terapêutico , Córnea/efeitos dos fármacos , Síndromes do Olho Seco/prevenção & controle , Metilcelulose/uso terapêutico , Mitocôndrias/efeitos dos fármacos , Plastoquinona/uso terapêutico , Adulto , Antioxidantes/administração & dosagem , Compostos de Benzalcônio/administração & dosagem , Córnea/patologia , Combinação de Medicamentos , Síndromes do Olho Seco/etiologia , Humanos , Lubrificantes Oftálmicos/administração & dosagem , Lubrificantes Oftálmicos/uso terapêutico , Metilcelulose/administração & dosagem , Pessoa de Meia-Idade , Mitocôndrias/patologia , Plastoquinona/administração & dosagem , Complicações Pós-Operatórias , Resultado do Tratamento , Adulto Jovem
14.
Mil Med ; 181(5 Suppl): 259-64, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27168582

RESUMO

Despite advances in antimicrobial therapies, wound infection remains a global public health concern. We aimed to formulate and assess various nanoemulsions (NEs) for potential effectiveness as stable antimicrobial agents suitable for topic application. A total of 106 NEs were developed that varied with respect to nonionic and cationic surfactants. Stability testing demonstrated that the NEs tested are broadly stable, with 97/106 formulations passing 2-week stability tests. Two NEs, NB-201 and NB-402, were selected to test antimicrobial activity in a wound model in mice. Skin abrasion wounds were infected with Staphylococcus aureus followed by NE treatment. Infected skin was then evaluated by measuring colony forming units. NB-201 reduced median bacterial counts by 4 to 5 log compared to animals treated with saline, whereas NB-402 reduced bacterial counts by 2 to 3 log. Additional stability tests on NB-201 demonstrated that NB-201 is stable in the presence of human serum, and is stable for at least 6 months at 5°C, 25°C, and 40°C. Finally, in in vitro studies, NB-201 was found to be effective against S. aureus at a higher dilution than the commercially available silver sulfadiazine. Altogether these results demonstrate that NB-201 is a stable and effective topical antimicrobial for the treatment of S. aureus.


Assuntos
Compostos de Benzalcônio/farmacologia , Cetilpiridínio/farmacologia , Poloxâmero/farmacologia , Polissorbatos/farmacologia , Óleo de Soja/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Animais , Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/farmacologia , Anti-Infecciosos Locais/uso terapêutico , Compostos de Benzalcônio/administração & dosagem , Compostos de Benzalcônio/uso terapêutico , Cetilpiridínio/administração & dosagem , Cetilpiridínio/uso terapêutico , Combinação de Medicamentos , Camundongos , Modelos Animais , Poloxâmero/administração & dosagem , Poloxâmero/uso terapêutico , Polissorbatos/administração & dosagem , Polissorbatos/uso terapêutico , Sulfadiazina de Prata/administração & dosagem , Sulfadiazina de Prata/farmacologia , Sulfadiazina de Prata/uso terapêutico , Óleo de Soja/administração & dosagem , Óleo de Soja/uso terapêutico , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/prevenção & controle
15.
Neurochem Res ; 41(5): 1138-44, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26738989

RESUMO

Serosal application of benzalkonium chloride (BAC) has been previously applied to produce a model of aganglionosis; however, confusion remains regarding the extent of chemical ablation of enteric myenteric plexus after BAC treatment. The time sequence of BAC-induced effects on the myenteric plexus of the rat colon was determined and followed the morphologic changes. After sacrifice of animals 7, 14, 28, 56, 84 or 168 days postintervention, colonic tissue samples were removed, fixed in formalin, and cut into 5-µm longitudinal sections for histological analysis. The neural analysis was used to re-evaluate BAC treatments for the appropriate model. Compared with rats in sham groups, rats in 0.1 %-30-min BAC group maintained only 15.27 ± 4.80 % of ganglia per section in a 1-cm/5-µm slice and 11.76 ± 2.30 % of ganglionic cells after 28 days, the lower and stable number of ganglionic cells between Day 7 and 84 (from 11.67 ± 2.10 to 19.05 ± 5.10 %). Although an increase, ganglionic cell numbers did not recover at Day168 when compared with the numbers in sham groups. The results showed that characteristics of rats in the 0.1 %-30-min BAC group between Day 7 and 84 most closely kept in stable state, suggesting that these treatment parameters are ideal for producing a hypoganglia model of hypoganglionosis.


Assuntos
Anti-Infecciosos Locais/uso terapêutico , Compostos de Benzalcônio/uso terapêutico , Doença de Hirschsprung/tratamento farmacológico , Animais , Anti-Infecciosos Locais/farmacologia , Compostos de Benzalcônio/farmacologia , Contagem de Células , Colo/inervação , Colo/patologia , Feminino , Doença de Hirschsprung/patologia , Plexo Mientérico/efeitos dos fármacos , Plexo Mientérico/patologia , Ratos Sprague-Dawley , Fatores de Tempo
17.
Cutan Ocul Toxicol ; 35(1): 8-12, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25597371

RESUMO

PURPOSE: To compare the rate of corneal epithelial healing and ocular tolerability following pterygium surgery between gatifloxacin and moxifloxacin. METHODS: In this double masked, prospective, controlled study 40 patients were randomized to receive prophylactic topical gatifloxacin 0.3% or moxifloxacin 0.5% following pterygium surgery. Patients were examined on days 1, 3, 7 and 21 post-operatively or until complete corneal epithelial healing. The primary outcome measure was the area of corneal epithelial defect during the post-operative period. Patients graded post-operative ocular pain, foreign body sensation, tearing, general burning sensation and burning sensation post-antibiotic drops instillation on a scale of 1-5. Conjunctival hyperemia and superficial punctate keratopathy (SPK) were measured on a scale of 0-3. RESULTS: No significant differences between groups were found in terms of corneal epithelial defect percentage over time (p = 0.989) and there was no significant difference between groups on each of the post-operative days. No significant differences were noted in terms of post-operative ocular pain, foreign body sensation, tearing, general burning sensation, burning sensation post-antibiotic drops instillation, conjunctival hyperemia and SPK. CONCLUSIONS: Gatifloxacin and moxifloxacin showed equivalent results in terms of corneal epithelial healing and ocular tolerability following pterygium surgery. This study suggests that there was no apparent added epithelial toxicity due to the presence of benzalkonium chloride in the gatifloxacin preparation when compared to moxifloxacin.


Assuntos
Antibacterianos/uso terapêutico , Epitélio Anterior/efeitos dos fármacos , Fluoroquinolonas/uso terapêutico , Pterígio/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Compostos de Benzalcônio/uso terapêutico , Método Duplo-Cego , Feminino , Fluoroquinolonas/efeitos adversos , Gatifloxacina , Humanos , Masculino , Pessoa de Meia-Idade , Moxifloxacina , Conservantes Farmacêuticos/uso terapêutico , Pterígio/tratamento farmacológico
18.
Adv Ther ; 32(12): 1263-79, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26660938

RESUMO

INTRODUCTION: This article presents the results of an international, multicenter, randomized, double-masked, placebo-controlled clinical study of Visomitin (Mitotech LLC, Moscow, Russian Federation) eye drops in patients with dry eye syndrome (DES). Visomitin is the first registered (in Russia) drug with a mitochondria-targeted antioxidant (SkQ1) as the active ingredient. METHODS: In this multicenter (10 sites) study of 240 subjects with DES, study drug (Visomitin or placebo) was self-administered three times daily (TID) for 6 weeks, followed by a 6-week follow-up period. Seven in-office study visits occurred every 2 weeks during both the treatment and follow-up periods. Efficacy measures included Schirmer's test, tear break-up time, fluorescein staining, meniscus height, and visual acuity. Safety measures included adverse events, slit lamp biomicroscopy, tonometry, blood pressure, and heart rate. Tolerability was also evaluated. RESULTS: This clinical study showed the effectiveness of Visomitin eye drops in the treatment of signs and symptoms of DES compared with placebo. The study showed that a 6-week course of TID topical instillation of Visomitin significantly improved the functional state of the cornea; Visomitin increased tear film stability and reduced corneal damage. Significant reduction of dry eye symptoms (such as dryness, burning, grittiness, and blurred vision) was also observed. CONCLUSION: Based on the results of this study, Visomitin is effective and safe for use in eye patients with DES for protection from corneal damage. FUNDING: Mitotech LLC.


Assuntos
Compostos de Benzalcônio/uso terapêutico , Síndromes do Olho Seco/tratamento farmacológico , Metilcelulose/uso terapêutico , Soluções Oftálmicas/uso terapêutico , Plastoquinona/uso terapêutico , Adulto , Compostos de Benzalcônio/administração & dosagem , Compostos de Benzalcônio/efeitos adversos , Córnea/metabolismo , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Fluoresceína , Humanos , Masculino , Metilcelulose/administração & dosagem , Metilcelulose/efeitos adversos , Pessoa de Meia-Idade , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/efeitos adversos , Plastoquinona/administração & dosagem , Plastoquinona/efeitos adversos , Lágrimas/metabolismo , Resultado do Tratamento , Acuidade Visual
19.
Artigo em Russo | MEDLINE | ID: mdl-26285332

RESUMO

UNLABELLED: This paper reports the results of the clinical observations and special investigations carried out with the involvement of the children presenting with acute respiratory diseases treated with the use of a Myramistin solution for inhalation. MATERIAL AND METHODS: The study included a total of 60 children with the above condition at the age varying between 2 and 17 years. Forty patients inhaled the Myramistin solution through a face mask connected to the nebulizer. The remaining 20 children that comprised the control group inhaled Myramistin in the form of a spray. RESULTS: The study has demonstrated the effectiveness of the proposed method that produced beneficial effect on the clinical symptoms of the respiratory diseases and characteristics of peripheral blood. Moreover, it accelerated the recovery of the patients due to the anti-inflammatory and trophic action of the inhaled solution and promoted normalization of mucociliary clearance. The therapeutic effectiveness of the Myramistin spray was significantly lower than that of the solution. CONCLUSION: The results of the study provided a basis for the development of the optimal technologies for the application of the Myramistin inhalation solution to the treatment of the children presenting with acute respiratory diseases of the upper and lower parts of the respiratory tract.


Assuntos
Compostos de Benzalcônio/administração & dosagem , Transtornos Respiratórios/tratamento farmacológico , Administração por Inalação , Adolescente , Compostos de Benzalcônio/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Nebulizadores e Vaporizadores
20.
Aust Vet J ; 93(7): 248-51, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26113350

RESUMO

BACKGROUND: Guthega skinks have been listed as critically endangered and are considered particularly vulnerable to extinction because of their isolation and restricted distribution. There is no information on their captive husbandry, or the diseases that affect them. CASE REPORT: Cutaneous and systemic mycosis from infection with Lecanicillium spp. was diagnosed in a captive colony of Guthega skinks (Liopholis guthega). Infection resulted in the death of five lizards. Diagnosis of infection was confirmed using a combination of histopathology, fungal culture and DNA sequencing from all affected animals. An additional four similarly affected individuals were successfully treated with a combination of voriconazole (10 mg/kg PO once daily) and shallow baths of benzalkonium chloride and polyhexamethylene biguanide hydrochloride (F10) (1 : 250, 20 min once daily). This is the first report of Lecanicillium spp. infection in reptiles.


Assuntos
Lagartos , Micoses/veterinária , Animais , Anti-Infecciosos Locais/uso terapêutico , Antifúngicos/uso terapêutico , Autopsia/veterinária , Compostos de Benzalcônio/uso terapêutico , Biguanidas/uso terapêutico , Espécies em Perigo de Extinção , Feminino , Masculino , Micoses/diagnóstico , Micoses/tratamento farmacológico , Micoses/mortalidade , Análise de Sequência de DNA/veterinária , Vitória , Voriconazol/uso terapêutico
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