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1.
Life Sci ; 314: 121287, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36526044

RESUMO

AIMS: Photodynamic therapy (PDT) is a treatment modality for several cancers involving the administration of a tumour-localising photosensitiser (PS) and its subsequent activation by light, resulting in tumour damage. Ras oncogenes have been strongly associated with chemo- and radio-resistance. Based on the described roles of adhesion and cell morphology on drug resistance, we studied if the differences in shape, cell-extracellular matrix and cell-cell adhesion induced by Ras transfection, play a role in the resistance to PDT. MATERIALS AND METHODS: We employed the human normal breast HB4a cells transfected with H-RAS and a panel of five PSs. KEY FINDINGS: We found that resistance to PDT of the HB4a-Ras cells employing all the PSs, increased between 1.3 and 2.5-fold as compared to the parental cells. There was no correlation between resistance and intracellular PS levels or PS intracellular localisation. Even when Ras-transfected cells present lower adherence to the ECM proteins, this does not make them more sensitive to PDT or chemotherapy. On the contrary, a marked gain of resistance to PDT was observed in floating cells as compared to adhesive cells, accounting for the higher ability conferred by Ras to survive in conditions of decreased cell-extracellular matrix interactions. HB4a-Ras cells displayed disorganisation of actin fibres, mislocalised E-cadherin and vinculin and lower expression of E-cadherin and ß1-integrin as compared to HB4a cells. SIGNIFICANCE: Knowledge of the mechanisms of resistance to photodamage in Ras-overexpressing cells may lead to the optimization of the combination of PDT with other treatments.


Assuntos
Neoplasias da Mama , Fotoquimioterapia , Humanos , Feminino , Adesão Celular , Genes ras , Neoplasias da Mama/patologia , Fármacos Fotossensibilizantes/farmacologia , Caderinas
3.
J Curr Glaucoma Pract ; 16(3): 199-204, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36793259

RESUMO

Aim: To describe a case of an acute attack of glaucoma due to scleral melting in the area where a trabeculectomy was previously done. This condition resulted from the blockage of the surgical opening due to an iris prolapse in an eye that was previously supplemented with mitomycin C (MMC) during a filtering surgery and bleb needling revision. Case description: A 74-year-old Mexican female with a prior glaucoma diagnosis who assisted to an appointment presenting an acute ocular hypertensive crisis after several months of adequately controlled intraocular pressure (IOP). Ocular hypertension had been regulated after undergoing a trabeculectomy and bleb needling revision; both supplemented with MMC. The severe IOP increase occurred due to uveal tissue blockage in the filtering site, related to melting of the sclera in the same area. The patient was successfully treated through the use of a scleral patch graft and the implantation of an Ahmed valve. Conclusion: An acute attack of glaucoma associated with scleromalacia after trabeculectomy and needling has not been previously reported and is currently attributed to MMC supplementation. Nevertheless, the use of a scleral patch graft and further glaucoma surgery seems to be an efficient way to treat this condition. Clinical significance: Even though this complication was appropriately managed with this patient, we want to prevent further cases like this through the judicious and careful use of MMC. How to cite this article: Paczka JA, Ponce-Horta AM, Tornero-Jimenez A. Acute Attack of Glaucoma after Scleral Melting and Iris Blockage of the Surgical Ostium: A Case Report of a Complication derived from a Mitomycin C Supplemented Trabeculectomy. J Curr Glaucoma Pract 2022;16(3):199-204.

4.
Arq. bras. oftalmol ; Arq. bras. oftalmol;84(5): 481-489, Sept.-Oct. 2021. graf
Artigo em Inglês | LILACS | ID: biblio-1339205

RESUMO

ABSTRACT Purpose: This study aimed to optimize the effective doses of mitomycin C, 5-fluorouracil, and their combination on cultivated basal cell carcinoma. Methods: Cultivated basal cell carcinoma and fibroblastic cells were treated with different concentrations of mitomycin C, 5-fluorouracil, and their combination. Cell viability, cell cycle, apoptosis, and expression levels of TP53, CDKN1A, and CDK6 were investigated. The most effective drug with its optimum dosage was administered via multiple intralesional injections to a 65-year-old woman with advanced periorbital nodulo-ulcerative BCC. Results: The concentrations of 0.00312 and 0.312 mg/mL were considered optimum for mitomycin C and 5-fluorouracil, respectively. The mean viabilities of basal cell carcinoma treated with mitomycin C alone and its combination with 5-fluorouracil were significantly less than those of the controls (p=0.002 and p=0.04, respectively). The cell cycle of all the treated basal cell carcinoma groups was arrested in the S phase. The apoptotic rates (p=0.002) of mitomycin C treated basal cell carcinoma were higher than those of the other treated cells, and their TP53 was significantly upregulated (p=0.0001). Moreover, CDKN1A was upregulated, whereas CDK6 was downregulated in basal cell carcinoma treated with either 5-fluorouracil (p=0.0001 and p=0.01, respectively) or the combination of 5-fluorouracil and mitomycin C (p=0.007 and p=0.001, respectively). Basal cell carcinoma lesions were significantly alleviated following mitomycin C injections in the reported patient. Conclusion: Our in vitro results revealed that the effective doses of mitomycin C and 5-fluorouracil on cultivated basal cell carcinoma were optimized. Mitomycin C was more effective in inducing the apoptosis of basal cell carcinoma than 5-fluorouracil and their combination. The intralesional injections of the optimum dose of mitomycin C could be proposed for the nonsurgical treatment of advanced eyelid basal cell carcinoma.


RESUMO Objetivo: Otimizar a dose efetiva de mitomicina C, 5fluorouracil e da combinação de ambos em culturas de células de carcinoma basocelular (CBC). Métodos: Culturas de células de células de carcinoma basocelular e de fibroblastos foram tratadas com diferentes concentrações de mitomicina C, 5fluorouracil e combinação de ambos. Além disto, foram investigados a viabilidade celular, o ciclo celular, a apoptose e a expressão dos genes TP53, CDKN1A e CDK6. O medicamento mais eficaz, em sua dosagem otimizada, foi administrado em últiplas injeções intralesionais em uma mulher de 65 anos com carcinoma basocelular nódulo-ulcerativo periorbital avançado. Resultados: A concentração de 0,00312 mg/mL de mitomicina C e a de 0,312 mg/mL de 5fluorouracil foram consideradas as ideias. A viabilidade média das células de carcinoma basocelular tratadas com mitomicina C isoladamente e em combinação foi significativamente menor que nas células de controle (respectivamente, p=0,002 e p=0,04). Todos os grupos de carcinoma basocelular tratados demonstraram interrupção do ciclo celular na fase S. As células de carcinoma basocelular tratadas com mitomicina C mostraram maiores taxas de apoptose (p=0,002) e significativa regulação positiva do gene TP53 (p=0,0001). Além disso, o gene CDKN1A foi positivamente regulado e o gene CDK6 foi negativamente regulado em células de carcinoma basocelular tratadas com 5fluorouracil (respectivamente, p=0,0001 e p=0,01) ou com a combinação de medicamentos (respectivamente, p=0,007 e p=0,001). Injeções posteriores de mitomicina C na paciente em questão levaram à melhora significativa da lesão do carcinoma basocelular. Conclusão: Nossos resultados in vitro otimizaram as doses efetivas de mitomicina C e 5fluorouracil na cultura de células de carcinoma basocelular e mostraram que a mitomicina C tem mais eficácia na apoptose de células de carcinoma basocelular do que o 5fluorouracil e a combinação de ambos. Injeções intralesionais de doses otimizadas de mitomicina C podem ser propostas para o tratamento não cirúrgico do células de carcinoma basocelular avançado de pálpebra.


Assuntos
Idoso , Feminino , Humanos , Neoplasias Cutâneas , Carcinoma Basocelular , Carcinoma Basocelular/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Análise de Sobrevida , Mitomicina , Fluoruracila
5.
Rev. cuba. oftalmol ; 34(3): e1071, 2021. tab
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1352029

RESUMO

Objetivo: Evaluar la utilidad de dos concentraciones de mitomicina C para la prevención del haze en la queratectomía fotorrefractiva. Métodos: Se realizó un estudio experimental aleatorizado en 26 ojos de 17 pacientes con defectos miópicos. Los pacientes fueron asignados a dos grupos según las dosis de mitomicina C (0,02 por ciento grupo 1 y 0,002 por ciento grupo 2). La variable de respuesta principal fue la presencia de haze. Se buscó correlación entre la magnitud del haze con grado de ametropía tratada, profundidad de ablación, microscopia endotelial y resultados visuales y refractivos. Resultados: A los 6 meses la mayoría de los pacientes del grupo 1 no presentó haze (ocho ojos / 57 por ciento), y del grupo 2 mantuvieron haze 0,5 (6 ojos / 50 por ciento). En la ametropía severa el haze en el grupo 2 fue mayor que en el grupo 1 durante todo el posoperatorio, y se observó la mayor diferencia al sexto mes con 0,5 ± 0,4 vs. 1,5 ± 0,32. En ablaciones > 75 micras el grupo dos terminó con más haze que el uno, con 0,5 ± 0,44 vs. 1,75 ± 0,76. La agudeza visual sin corrección se vio más afectada en el grupo 2. No hubo daño endotelial en ningún grupo. Conclusión: La presencia de haze predomina en los casos tratados con dosis 0,002 por ciento de mitomicina C, comparada con la dosis 0,02 por ciento, aunque en este caso ambos grupos mantuvieron un resultado visual y refractivo adecuado y baja toxicidad endotelial.


Objective: Evaluate the usefulness of two concentrations of mitomycin C for haze prevention in photorefractive keratectomy. Methods: An experimental randomized study was conducted of 26 eyes of 17 patients with myopic defects. The patients were divided into two groups according to their mitomycin C doses (Group 1: 0.02 percent and Group 2: 0.002 percent). The main response variable was the presence of haze. Verification was performed of the correlation between haze magnitude and the degree of the ametropia treated, ablation depth, endothelial microscopy, and visual and refractive results. Results: At six months most patients in Group 1 did not have any haze (eight eyes / 57 percent), whereas 0.5 (6 eyes / 50 percent) in Group 2 still had haze. In severe ametropia, haze was larger in Group 2 than in Group 1 throughout the postoperative period, the greatest difference being observed in the sixth month with 0.5 ± 0.4 vs 1.5 ± 0.32. In ablations > 75 microns, Group 2 ended with more haze than Group 1, with 0.5 ± 0.44 vs 1.75 ± 0.76. Uncorrected visual acuity was more affected in Group 2. No endothelial damage occurred in either group. Conclusion: The presence of haze prevails in cases treated with 0.002 percent doses of mitomycin C, as compared with 0.02 percent doses, though in this case both groups maintained an appropriate visual and refractive result and low endothelial toxicity(AU)


Assuntos
Humanos , Erros de Refração/etiologia , Mitomicina/uso terapêutico , Ceratectomia Fotorrefrativa/métodos
6.
Am J Ophthalmol Case Rep ; 23: 101120, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34095607

RESUMO

To report a case of a 20-year-old woman who developed massive and progressive corneal remodeling in both eyes after bilateral PRK with mitomycin and CXL as an elective refractive procedure for mild keratoconus. The patient had 6 years of follow up, initially presenting with focal steepening of up to 20 diopters on both eyes one-and-a-half- years postoperatively that spontaneously reversed over the next five years while the high order aberrations worsened. At the present time, the patient depends on bilateral scleral contact lenses for her day-to-day activities. The use of combined elective PRK with mitomycin and prophylactic CXL could lead to progressive corneal deformation. Additional reports would help to establish the role of this combination procedure among the armamentarium to visually rehabilitate patients with keratoconus.

7.
Arq. gastroenterol ; Arq. gastroenterol;58(2): 253-261, Apr.-June 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1285318

RESUMO

ABSTRACT BACKGROUND: Caustic ingestion and development of esophageal strictures are recognized major public health problems in childhood. Different therapeutic methods have been proposed in the management of such strictures. OBJECTIVE: To evaluate efficacy and risk of endoscopic topical application of mitomycin C in the treatment of caustic esophageal strictures. METHODS: We searched MEDLINE, EMBASE, Central Cochrane, and LILACS databases. The outcomes evaluated were dysphagia resolution rate, number of dilations performed in resolved cases, and the number of dilations performed in all patients. RESULTS: Three randomized clinical trials were included for final analysis with a total of 190 patients. Topical mitomycin C application group showed a significant increase in dysphagia resolution rate, corresponding to a 42% higher dysphagia resolution as compared to endoscopic dilation alone, with statistical significance between the two groups (RD: 0.42 - [CI: 0.29-0.56]; P-value <0.00001). The mean number of dilations performed in resolved cases were significantly less in the topical mitomycin C application group, compared to endoscopic dilations alone, with statistical significance between the two groups (MD: 2.84 [CI: 1.98-3.69]; P-value <0.00001). When comparing the number of dilations in all patients, there was no statistical difference between the two groups (MD: 1.46 [CI: -1.53-4.44]; P-value =0.34). CONCLUSION: Application of topical mitomycin C with endoscopic dilations in caustic esophageal strictures was more effective in dysphagia resolution than endoscopic therapy alone in the pediatric population. Moreover, topical mitomycin C application also reduced the number of dilation sessions needed to alleviate dysphagia without rising morbidity.


RESUMO CONTEXTO: A ingestão de soda cáustica e o desenvolvimento de estenoses esofágicas são reconhecidos como importantes problemas de saúde pública na infância. Diferentes métodos terapêuticos têm sido propostos no manejo dessas estenoses. OBJETIVO: Avaliar a eficácia e o risco da aplicação endoscópica tópica de mitomicina C no tratamento de estenoses esofágicas cáusticas. MÉTODOS: Buscamos as bases de dados MEDLINE, EMBASE, Central Cochrane e LILACS. Os desfechos avaliados foram taxa de resolução da disfagia, número de dilatações realizadas nos casos resolvidos e número de dilatações realizadas em todos os pacientes. RESULTADOS: Três ensaios clínicos randomizados foram incluídos para análise final com um total de 190 pacientes. O grupo de aplicação de mitomicina C tópica apresentou aumento significativo na taxa de resolução da disfagia, correspondendo a uma resolução da disfagia 42% maior em comparação à dilatação endoscópica isolada, com significância estatística entre os dois grupos (RD: 0,42 - [IC: 0,29-0,56]; P-valor <0,00001). O número médio de dilatações realizadas em casos resolvidos foi significativamente menor no grupo de aplicação tópica de mitomicina C, em comparação com as dilatações endoscópicas isoladas, com significância estatística entre os dois grupos (MD: 2,84 [IC: 1,98-3,69]; P-valor <0,00001). Ao comparar o número de dilatações em todos os pacientes, não houve diferença estatística entre os dois grupos (MD: 1,46 [IC: -1,53-4,44]; valor de P=0,34). CONCLUSÃO: A aplicação de mitomicina C tópica com dilatações endoscópicas em estenoses esofágicas cáusticas foi mais eficaz na resolução da disfagia do que a terapia endoscópica isolada na população pediátrica. Além disso, a aplicação tópica de mitomicina C também reduziu o número de sessões de dilatação necessárias para aliviar a disfagia sem aumentar a morbidade.


Assuntos
Humanos , Criança , Cáusticos/toxicidade , Estenose Esofágica/induzido quimicamente , Estenose Esofágica/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Administração Tópica , Esofagoscopia , Resultado do Tratamento , Mitomicina/uso terapêutico
8.
Rev. cuba. hematol. inmunol. hemoter ; 37(1): e1260, ene.-mar. 2021. tab, graf
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1251714

RESUMO

Introducción: La anemia de Fanconi es una enfermedad genética rara, de herencia autosómica o ligada al X, caracterizada por inestabilidad genómica e hipersensibilidad a los agentes de entrecruzamiento del ADN, como el diepoxibutano y la mitomicina C (MMC). La respuesta anormal a estas sustancias, que constituye un marcador celular único y se manifiesta como un incremento de la frecuencia de roturas cromosómicas, es la base de su diagnóstico. Objetivo: Realizar el análisis de roturas cromosómicas inducidas por la mitomicina C en linfocitos de sangre periférica de pacientes cubanos con sospecha de anemia de Fanconi. Métodos: Se realizó estudio de roturas cromosómicas inducidas por la mitomicina C a diferentes concentraciones en cultivos de linfocitos T provenientes de sangre venosa periférica en 32 pacientes con sospecha clínica de anemia de Fanconi e igual cantidad de sujetos controles. Resultados: Al finalizar el análisis seis pacientes (20 por ciento) fueron diagnosticados con anemia de Fanconi. De ellos, cuatro presentaron alto porcentaje de rupturas y dos un mosaicismo somático. Desde el punto de vista clínico, cuatro mostraban anemia aplásica y dos exhibían únicamente rasgos dismórficos típicos de la enfermedad. Conclusiones: El ensayo de roturas cromosómicas inducidas por la mitomicina C permitió el diagnóstico definitivo de anemia de Fanconi en pacientes con antecedentes de anemia aplásica, aún sin anomalías congénitas. Este constituye el primer estudio de este tipo en un grupo de pacientes cubanos(AU)


Introduction: Fanconi anemia is a rare genetic disease of autosomal inheritance or X-linked, characterized by genomic instability and hypersensitivity to DNA cross-linking agents like diepoxybutane and mitomycin C (MMC). The basis for its diagnosis is an abnormal response to these substances, which constitutes a unique cell marker and manifests as an increased chromosomal breakage rate. Objective: To perform the analysis of the chromosomal breakages induced by mitomycin C in peripheral blood lymphocytes of Cuban patients with suspicion of Fanconi anemia. Methods: A study was conducted of chromosomal breakages induced by mitomycin C at various concentrations in cultures of T lymphocytes from venous peripheral blood of 32 patients with clinical suspicion of Fanconi anemia and an equal number of control subjects. Results: At the end of the analysis, six patients (20 percent) were diagnosed with Fanconi anemia. Of these, four showed a high percentage of breakages and two had somatic mosaicism. From a clinical point of view, four had aplastic anemia and two only presented dysmorphic features typical of the disease. Conclusions: Evaluation of the chromosomal breakages induced by mitomycin C led to the definitive diagnosis of Fanconi anemia in patients with a history of aplastic anemia, even in the absence of congenital anomalies. This is the first study of its type in a group of Cuban patients(AU)


Assuntos
Humanos , Anormalidades Congênitas , Linfócitos , Instabilidade Genômica , Anemia de Fanconi , Doenças Genéticas Inatas , Hipersensibilidade , Cuba/epidemiologia
9.
Arch Soc Esp Oftalmol (Engl Ed) ; 96(4): 202-209, 2021 Apr.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33342630

RESUMO

PURPOSE: Describe and compare the effects of intraoperative application of Polyvinylpyrrolidone Collagen (PVP) versus Mitomycin C (MMC) on the pattern of change in mean IOP reduction and mean number of medications over 36-months follow-up in patients with primary open angle glaucoma (POAG) undergoing trabeculectomy. METHODS: Prospective, randomized, comparative study. Twenty-six eyes of 26 patients with POAG and no previous incisional glaucoma surgery underwent trabeculectomy and were randomized to PVP or MMC and completed a 36-month follow-up. Main outcome measures were IOP and number of glaucoma medications. Multivariate longitudinal analysis was performed by fitting a linear trend model adjusting for baseline response for the IOP outcome and a log-linear regression model with within-subject associations for the number of hypotensive medications outcome. Sensitivity analysis was performed to assess lower and higher order polynomial trends over time in IOP. RESULTS: The univariate analysis revealed that the mean IOP reduction from baseline to 36 months was 7.62mmHg (3.05; 12.18) in the MMC group and 8.15mmHg (-0.64; 16.95) in the PVP group. Mean percentage IOP reduction from baseline was 37.09% (15.93; 58.17) and 36.08% (5.16; 67.20) in the PVP group. Mean change in number of medications from baseline to 36 months was -0.92 medications (-3.38; +1.54) for the MMC group and -1 medication (-3.12; +1.12) for the PVP group. Both groups had a statistically significant decline in mean IOP over the follow-up period (p<0.001) but there was no discernible difference between the two exposure groups in the rate of change in IOP (p=0.5975). Sensitivity analysis showed that a linear trend model is adequate to describe the IOP reduction over the follow-up period. Both groups had a statistically significant change in the number of hypotensive medications used between baseline and month 36 (p<0.05) but there was no discernible difference between exposure groups (p=0.2917). Both the PVP and MMC groups showed an initial reduction in number of medications until month 12 and a relatively linear increase towards month 36. A longer follow-up may be warranted to reveal differences in the number of medications between the two exposure groups. Postoperative complications were less frequent in the PVP group. CONCLUSIONS: The use of PVP during trabeculectomy achieves and maintains a statistically significant IOP reduction from baseline to 36 months and decreases the number of glaucoma medications. Secondary outcome measures showed a lower incidence of adverse events in the PVP group.

10.
Medicentro (Villa Clara) ; 24(3): 564-577, jul.-set. 2020. tab
Artigo em Espanhol | LILACS | ID: biblio-1125016

RESUMO

RESUMEN Introducción: la dacriocistorrinostomía externa es la técnica más empleada por la mayoría de los cirujanos oculoplásticos para tratar a los pacientes con obstrucción del canal nasolagrimal. Es posible que los galenos cometan algunos errores en este tipo de cirugía, a pesar de los grandes avances en las tecnologías ópticas, las técnicas quirúrgicas y el uso de modernos materiales de intubación. La principal causa de los errores es el cierre de la osteotomía por tejido cicatrizal o de granulación, con la formación de sinequias en la cavidad nasal. La mitomicina C es el antibiótico alquilante más estudiado en la prevención del exceso de cicatrización en el área de la osteotomía; sin embargo, existen acuerdos y desacuerdos entre estudiosos del tema sobre la eficacia, dosis y tiempo de exposición de este medicamento. El papel de cada una de estas variables en el resultado final de la cirugía es controversial. Objetivo: brindar evidencias sobre el papel de la aplicación transoperatoria de la mitomicina C en la dacriocistorrinostomía externa. Métodos: se realizó una revisión de la bibliografía actualizada disponible en idioma español e inglés. Se consultaron los textos completos y resúmenes en las bases de datos: PubMed, Ebsco, Google Académico y Scielo. También se revisaron novedosos artículos en prestigiosas revistas especializadas. Conclusiones: la mayoría de los autores coinciden en que este medicamento contribuye a elevar la tasa de éxito de la dacriocistorrinostomía externa; aunque su aplicación es segura, todavía se estudian algunas variables que mejorarían su eficacia.


ABSTRACT Introduction: external dacryocystorhinostomy is the most used technique by oculoplastic surgeons to treat patient with nasolacrimal duct obstruction. Physicians may make some mistakes in this type of surgery despite great advances in optical technologies, surgical techniques and the use of modern materials for intubation, The main cause of errors is the closure of the osteotomy due to scar tissue or granulation with synechia formation in the nasal cavity. Mitomycin-C is the most studied alkylating antibiotic in the prevention of excessive scarring in the osteotomy area; however, there are some agreements and disagreements among scholars on the efficacy, dosage and time of exposure of this drug. The role of each of these variables in the final outcome of the surgery is controversial. Objective: to provide some evidences about the transoperative application of Mitomycin-C in external dacryocystorhinostomy. Methods: a review of the updated bibliography available in Spanish and English languages was carried out. Complete texts and abstracts were consulted in the databases: PubMed, Ebsco, Google Scholar and Scielo. Novel articles were also reviewed in prestigious specialized journals. Conclusions: must authors agree that this drug appears to improve the success rate of external dacryocystorhinostomy. Although its application is safe, some variables are still being studied that would improve its efficacy.


Assuntos
Cirurgia Geral , Dacriocistorinostomia , Mitomicina , Aparelho Lacrimal , Obstrução dos Ductos Lacrimais
11.
J Struct Biol ; 212(1): 107595, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32736071

RESUMO

Tailed bacteriophages are one of the most widespread biological entities on Earth. Their singular structures, such as spikes or fibers are of special interest given their potential use in a wide range of biotechnological applications. In particular, the long fibers present at the termini of the T4 phage tail have been studied in detail and are important for host recognition and adsorption. Although significant progress has been made in elucidating structural mechanisms of model phages, the high-resolution structural description of the vast population of marine phages is still unexplored. In this context, we present here the crystal structure of C24, a putative receptor-binding tip-like protein from Bizionia argentinensis JUB59, a psychrotolerant bacterium isolated from the marine surface waters of Potter Cove, Antarctica. The structure resembles the receptor-binding tip from the bacteriophage T4 long tail fiber yet showing marked differences in its domain organization, size, sequence identity and metal binding nature. We confirmed the viral origin of C24 by induction experiments using mitomycin C. Our results reveal the presence of a novel uncharacterized prophage in the genome of B. argentinensis JUB59, whose morphology is compatible with the order Caudovirales and that carries the nucleotide sequence of C24 in its genome. This work provides valuable information to expand our current knowledge on the viral machinery prevalent in the oceans.


Assuntos
Bacteriófagos/genética , Flavobacteriaceae/virologia , Regiões Antárticas , Genoma Bacteriano/genética , Genoma Viral/genética , Ligação Proteica/genética
12.
Int. arch. otorhinolaryngol. (Impr.) ; 24(2): 212-216, Apr.-June 2020. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1134120

RESUMO

Abstract Introduction Knowing a concentration at which cytostatic drugs are toxic for the nasal fibroblasts will enable the use cytostatic drugs in the clinical practice to prevent excessive cicatrization. Objective To determine the cytostatic concentrations of mitomycin С, doxorubicin, and 5-fluorouracil affecting nasal mucosa fibroblasts. Methods We obtained material during an endonasal dacryocystorhinostomy with the patient's informed consent. The cells were cultivated. Second- to fourth-passage cells were used in the experiments. The cells were stained for vimentin and cluster of differentiation 90 (CD90). An MTS test 3 (3-(4,5-dimethylthiazole-2-yl)-5-(3-carboxymethoxyphenyl)- 2-(4-sulfophenyl)-2H-tetrazolium); cell viability test was performed. Results The cytostatic drugs have a toxic effect on cultivated fibroblasts of the nasal mucosa. This effect is dose-dependent. In terms of reducing the level of tissue fibrotisation in the nasal cavity, the most justified approach is to carry out an experimental study of the effect of mitomycin C, doxorubicin, and 5-fluorouracil at the concentrations of 0.25mg/ml, 0.25mg/ml, and 12.5mg/ml respectively. Conclusion The authors argue that it is inappropriate to use these cytostatic drugs to conduct studies with the goal of analyzing their antifibrotic effect on the nasal mucosa at concentrations that are either lower or higher than the aforementioned ones.

13.
Int Arch Otorhinolaryngol ; 24(2): e206-e210, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32256842

RESUMO

Introduction Knowing a concentration at which cytostatic drugs are toxic for the nasal fibroblasts will enable the use cytostatic drugs in the clinical practice to prevent excessive cicatrization. Objective To determine the cytostatic concentrations of mitomycin С, doxorubicin, and 5-fluorouracil affecting nasal mucosa fibroblasts. Methods We obtained material during an endonasal dacryocystorhinostomy with the patient's informed consent. The cells were cultivated. Second- to fourth-passage cells were used in the experiments. The cells were stained for vimentin and cluster of differentiation 90 (CD90). An MTS test 3 (3-(4,5-dimethylthiazole-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium); cell viability test was performed. Results The cytostatic drugs have a toxic effect on cultivated fibroblasts of the nasal mucosa. This effect is dose-dependent. In terms of reducing the level of tissue fibrotisation in the nasal cavity, the most justified approach is to carry out an experimental study of the effect of mitomycin C, doxorubicin, and 5-fluorouracil at the concentrations of 0.25 mg/ml, 0.25 mg/ml, and 12.5 mg/ml respectively. Conclusion The authors argue that it is inappropriate to use these cytostatic drugs to conduct studies with the goal of analyzing their antifibrotic effect on the nasal mucosa at concentrations that are either lower or higher than the aforementioned ones.

14.
Ophthalmol Ther ; 9(2): 305-319, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32342404

RESUMO

PURPOSE: To evaluate the effect of mitomycin-C (MMC) on the success of external (Ex-DCR) or endoscopic dacryocystorhinostomy (En-DCR). METHOD: A systematic review of randomized clinical trials of Ex- or En-DCR with and without the use of MMC to treat primary acquired nasolacrimal duct obstruction (NLDO) was done. Two authors independently searched six databases from 1990 to 2019, using the terms "dacryocystorhinostomy" and "mitomycin-C." Statistical and meta-analyses were performed using RevMan 5.3 software. RESULTS: Twenty-seven studies involving 2158 surgeries were included in this systematic review. The Ex-DCR group comprised 14 studies [odds ratio (OR): 2.74; 95% confidence intervals (CI) 1.54-4.87; I2 = 30%], while the En-DCR group 13 studies (OR: 1.69; 95% CI 1.21-2.37; I2 = 0%). The use of MMC slightly increased the success rate of Ex- or En-DCR (OR: 2.1; 95% CI 1.52-2.9; I2 = 14%). CONCLUSION: The intraoperative use of MMC is safe and slightly improves the success rate of Ex- or En-DCR. However, the evidence was very weak.

15.
Int. arch. otorhinolaryngol. (Impr.) ; 24(1): 112-124, Jan.-Mar. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1090547

RESUMO

Abstract Introduction Mitomycin C is a natural antibiotic that has been used to inhibit the proliferation of fibroblasts in scar tissue. Objective To evaluate the effectiveness and safety of topical Mitomycin C as an adjuvant in the endoscopic treatment of laryngotracheal stenoses. Data synthesis A systematic review of experimental or observational studies that have evaluated the treatment of laryngotracheal stenoses with the use of topical Mitomycin C was performed. Databases researched: LILACS, PubMed, Embase, Cochrane and Web of Science. Outcomes: resolution (symptom-free time ≥ one year), number of procedures required, and complications resulting from the procedure. A total of 15 studies (involving 387 patients) were selected. Mitomycin C was administered to every patient in 11 studies, and in 4 other studies, the patients were separated into 2 groups, 1 receiving mitomycin C, and the other not. The resolution of the stenosis evaluated in 12 studies in which the patients received mitomycin C was of 69% (95% confidence interval [95%CI]: 61-76%; I2 = 17.3%). A total of 52% of the patients (95%CI: 39-64%, 11 studies; I2 = 64.7%) were submitted to a single endoscopic procedure, and 48% (95%CI: 36-61%, 11 studies; I2 = 64.7%) were submitted to more than 1 procedure. Complications (mediastinal and subcutaneous emphysema, dysphonia, laceration or vocal fold paralysis and acute light obstruction) were reported in 9% of the patients (95%CI: 3-18%, 9 studies; I2 = 79.8%). Conclusions The evidence suggests that mitomycin C is an effective and safe option in the endoscopic treatment of laryngotracheal stenosis.


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Estenose Traqueal/terapia , Laringoestenose/terapia , Mitomicina/uso terapêutico , Laringoscopia/métodos , Administração Tópica , Resultado do Tratamento , Mitomicina/administração & dosagem , Terapia Combinada
16.
Int Arch Otorhinolaryngol ; 24(1): e112-e124, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31915466

RESUMO

Introduction Mitomycin C is a natural antibiotic that has been used to inhibit the proliferation of fibroblasts in scar tissue. Objective To evaluate the effectiveness and safety of topical Mitomycin C as an adjuvant in the endoscopic treatment of laryngotracheal stenoses. Data synthesis A systematic review of experimental or observational studies that have evaluated the treatment of laryngotracheal stenoses with the use of topical Mitomycin C was performed. Databases researched: LILACS, PubMed, Embase, Cochrane and Web of Science. Outcomes: resolution (symptom-free time ≥ one year), number of procedures required, and complications resulting from the procedure. A total of 15 studies (involving 387 patients) were selected. Mitomycin C was administered to every patient in 11 studies, and in 4 other studies, the patients were separated into 2 groups, 1 receiving mitomycin C, and the other not. The resolution of the stenosis evaluated in 12 studies in which the patients received mitomycin C was of 69% (95% confidence interval [95%CI]: 61-76%; I 2 = 17.3%). A total of 52% of the patients (95%CI: 39-64%, 11 studies; I 2 = 64.7%) were submitted to a single endoscopic procedure, and 48% (95%CI: 36-61%, 11 studies; I 2 = 64.7%) were submitted to more than 1 procedure. Complications (mediastinal and subcutaneous emphysema, dysphonia, laceration or vocal fold paralysis and acute light obstruction) were reported in 9% of the patients (95%CI: 3-18%, 9 studies; I 2 = 79.8%). Conclusions The evidence suggests that mitomycin C is an effective and safe option in the endoscopic treatment of laryngotracheal stenosis.

17.
J Endourol Case Rep ; 6(4): 315-318, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33457662

RESUMO

Background: Mitomycin C (MMC) extravasation after transurethral resection of bladder tumor (TURBT) is a rare and highly morbid complication. Management of these cases may require a multidisciplinary approach with strategies ranging from conservative management to surgical intervention. Case Presentation: We present a 48-year-old woman who received a TURBT for a 5 mm bladder tumor. Procedure was uneventful and no bladder perforation was noticed. A single dose of instillation of MMC was performed after surgery resulting in extravasation, consequent ipsilateral pudendal neuralgia, and ureterohydronephrosis. Treatment included a second TURBT, Double-J stent placement, and multiple pain management schemes. After 8 months the patient had complete resolution of pain and ureterohydronephrosis. Conclusion: Perioperative chemotherapy is the standard of care in low-risk bladder cancer. Extravasation of MMC, although rare, can produce severe complications, sometimes irreversible. Other treatment options, such as gemcitabine, are less frequently used despite being less irritant and having similar efficacy. Further studies are needed to compare single-dose instillation regimens.

18.
J Curr Glaucoma Pract ; 13(2): 50-54, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564793

RESUMO

AIM: The aim of this study is to compare the outcomes, success rates, complications, and number of interventions of the trabeculectomy surgery with mitomycin C (MMC) in two different techniques: conventional soaked sponges and sub-Tenon injection. MATERIALS AND METHODS: An observational retrospective study was performed with 79 eyes of 64 participants who underwent a glaucoma surgery with MMC. The conventional sponge soaked with MMC 0.03% for 3 minutes over the scleral flap (group I) and the subtenon injection of 0.1 mL of MMC 0.03% (group II) techniques were used to deliver the MMC. The data collected were patient demographics, preoperative intraocular pressure (IOP), central corneal thickness (CCT), number of pre- and postoperative ocular hypotensive drugs, postoperative complications, number of interventions, and need of further glaucoma surgery. RESULTS: Seventy-nine eyes were divided into two: 39 eyes (49.37%) in group I and 40 eyes (50.63%) in group II. Trabeculectomy was performed in 53.17% and phacotrabeculectomy in 46.83%. The IOP decreased from 18.0 ± 11.0 mm Hg at the baseline to 10.0 ± 3.0 mm Hg at the last visit in group I and, in group II, from 16.0 ± 10.0-13.0 ± 6.0 mm Hg (median ± ID), p < 0.001. There were no significant differences between the groups regarding demographics, median follow-up, IOP in baseline, CCT, drugs reduction, success criteria adopted, postsurgical interventions, surgical complications, and need for new procedures (p > 0.05). CONCLUSION: Sub-Tenon injection of MMC is a safe and as effective as the conventional soaked sponge method in trabeculectomies. This method reduces surgical time and sponge-related risks with equivalent surgical efficacy. CLINICAL SIGNIFICANCE: As trabeculectomy is still the most common surgical procedure to reduce IOP and scar formation is one of the main causes of surgical failure, it is important to develop surgical techniques to improve its outcomes. HOW TO CITE THIS ARTICLE: Guimarães MEV, de Pádua Soares Bezerra B, et al. Glaucoma Surgery with Soaked Sponges with Mitomycin C vs Sub-Tenon Injection: Short-term Outcomes. J Curr Glaucoma Pract 2019;13(2):50-54.

19.
Rev. cuba. oftalmol ; 32(2): e717, abr.-jun. 2019. tab
Artigo em Espanhol | LILACS | ID: biblio-1093685

RESUMO

RESUMEN Objetivo: Evaluar los resultados relacionados con la efectividad y la seguridad en el tratamiento con queratectomía subepitelial asistida por láser con mitomicina C versus queratectomía fotorreactiva con mitomicina C en ojos con miopía o astigmatismo miópico compuesto. Métodos: Se realizó un estudio experimental, longitudinal y prospectivo en el Instituto Cubano de Oftalmología Ramón Pando Ferrer entre abril del año 2016 y abril de 2017. Se empleó un muestreo aleatorio simple por el cual se obtuvo la técnica quirúrgica a realizar. El primer ojo operado fue el derecho y a la semana se realizó la cirugía en el ojo izquierdo, en el cual se aplicó la otra técnica quirúrgica. Esto permitió realizar en cada paciente ambas técnicas quirúrgicas. La muestra quedó constituida por 146 ojos (73 pacientes) que cumplían con los criterios de selección. Resultados: El comportamiento preoperatorio entre los dos grupos fue muy similar. En ninguno de los casos existieron diferencias en las variables que se evaluaron (agudeza visual sin corrección, agudeza visual mejor corregida, esfera, cilindro y equivalente esférico). La diferencia entre los valores preoperatorios y los encontrados a los 6 meses del tratamiento quirúrgico en cada grupo fueron estadísticamente significativos (p= 0,000) para todas las variables analizadas, excepto para la agudeza visual mejor corregida en el grupo de ojos tratados con láser con mitomicina C (p= 0,083). El haze y el defecto de epitelización fueron los dos tipos de complicaciones observadas. Conclusiones: Se demostró que ambas técnicas quirúrgicas son efectivas y seguras(AU)


ABSTRACT Objective: Evaluate the effectiveness and safety of laser-assisted subepithelial keratectomy with mitomycin C vs. photoreactive keratectomy with mitomycin C in eyes with myopia or compound myopic astigmatism. Methods: An experimental prospective longitudinal study was conducted at Ramón Pando Ferrer Cuban Institute of Ophthalmology from April 2016 to April 2017. Simple random sampling was used to decide on the surgical technique to be applied. Surgery was first performed on the right eye using one of the techniques, and then one week later on the left eye with the other technique. That way each patient could undergo both surgical techniques. The sample was composed of 146 eyes (73 patients) meeting the inclusion criteria. Results: Preoperative behavior was very similar in the two groups. In neither case were differences found in the variables analyzed (uncorrected visual acuity, best corrected visual acuity, sphere, cylinder and spherical equivalent). The differences between preoperative values and those found six months after surgery in each group were statistically significant for all the variables analyzed (p= 0.000), except for best corrected visual acuity in the group of eyes treated with laser with mitomycin C (p= 0.083). Haze and epithelization defect were the two types of complications observed. Conclusions: It was demonstrated that both surgical techniques are effective and safe(AU)


Assuntos
Humanos , Feminino , Adulto , Mitomicina/uso terapêutico , Ceratectomia Fotorrefrativa/métodos , Ceratectomia Subepitelial Assistida por Laser/métodos , Lasers de Excimer/uso terapêutico , Miopia/cirurgia , Estudos Prospectivos , Estudos Longitudinais
20.
Gene ; 703: 50-57, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-30965126

RESUMO

Desulfovibrio alaskensis is a Gram-negative bacterial species that belongs to the group of Sulphate Reducing Bacteria (SRB) and presents prophages in genomes, a common characteristic of the genus Desulfovibrio. Genetic material can be transported by outer membrane vesicles, however, no data regarding the production of these vesicles has been reported for D. alaskensis. To verify the expression of D. alaskensis prophages and their involvement with outer membrane vesicles, the DSM16109 strain was used. The DSM16109 strain had three prophages and presented reduced growth after mitomycin C addition when compared to the control culture. This reduction was accompanied by the presence of virus-like particles (VLPs), indicating mitomycin C dependent prophage induction. The increase in the number of cap gene copies and transcriptions of the three prophages was verified in the control sample, however, without the formation of VLPs. Prophage genes were identified in outer membrane vesicles from cultures treated and not treated with mitomycin C. DSM16109 prophages are expressed spontaneously but only in the presence of mitomycin C was it possible to observe VLP formation. Due to the genetic material detection from the prophages within outer membrane vesicles, this property may be related to the horizontal transfer of viral genes.


Assuntos
Desulfovibrio/virologia , Transferência Genética Horizontal , Prófagos/genética , Vesículas Transportadoras/genética , Desulfovibrio/crescimento & desenvolvimento , Mitomicina/farmacologia , Transcrição Gênica , Proteínas Virais/genética
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