RESUMO
The purpose of this study was to examine the effect of topical and/or oral angiotensin converting enzyme II inhibitor and TGF-beta signaling blocker losartan on corneal stromal fibrosis that developed in rabbit corneas after Descemetorhexis removal of central Descemet's membrane and corneal endothelium. Twenty-eight New Zealand white rabbits were included and either had 8 mm central Descemetorhexis or sham control surgery without Descemetorhexis in one eye. Groups of 4 eyes without Descemetorhexis were treated for one month with no medications, topical losartan or oral losartan. Groups of 4 eyes with Descemetorhexis were treated with topical and oral vehicle, topical losartan, oral losartan, or both topical losartan and oral losartan for one month. Standardized slit lamp photos were obtained with central opacity intensity measured with ImageJ. The posterior fibrotic zone of corneas was measured on immunohistochemistry for alpha-smooth muscle actin (SMA) and keratocan using QuPath analysis. Collagen type IV expression in the posterior cornea was quantitated with ImageJ and duplex immunohistochemistry for collagen type IV and TGF beta-1. After Descemetorhexis, topical, but not oral, losartan decreased the intensity of central stromal opacity, reduced peripheral corneal scarring, and decreased alpha-smooth muscle actin myofibroblast fibrosis area compared to corneas that had Descemetorhexis and treatment with vehicles alone. Topical losartan decreased posterior stromal cellular, non-Descemet's membrane, collagen type IV production, that is likely stimulated by TGF beta as part of a negative regulatory feedback mechanism, compared to vehicle treatment at one month after Descemetorhexis. Topical losartan is likely to be effective in reducing corneal scarring fibrosis produced by traumatic injury, microbial infection, and some corneal diseases and surgeries.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Cicatriz/tratamento farmacológico , Colágeno Tipo IV/metabolismo , Doenças da Córnea/tratamento farmacológico , Substância Própria/patologia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Losartan/administração & dosagem , Actinas/metabolismo , Administração Oftálmica , Animais , Cicatriz/metabolismo , Doenças da Córnea/metabolismo , Substância Própria/metabolismo , Feminino , Fibrose/prevenção & controle , Imuno-Histoquímica , Soluções Oftálmicas , Proteoglicanas/metabolismo , Coelhos , Microscopia com Lâmpada de FendaRESUMO
INTRODUCCIÓN Y OBJETIVOS: El embarazo en cicatriz de cesárea previa (ECC) es una entidad poco frecuente que puede tener graves consecuencias. Hasta la fecha no existen esquemas estandarizados de tratamiento y su manejo óptimo sigue siendo controvertido. Nuestro objetivo es realizar una revisión de la literatura publicada sobre el manejo del ECC y proponer un algoritmo. También exponemos tres casos de ECC resueltos con diferentes tratamientos en el Hospital Universitario Infanta Elena MÉTODOS: Búsqueda de la literatura en bases de datos utilizando las palabras clave: "embarazo en cicatriz cesárea"," gestación ectópica en cicatriz cesárea", "tratamiento", "manejo". RESULTADOS: Las opciones terapéuticas pueden ser médicas, quirúrgicas o una combinación de ambas. Los tratamientos quirúrgicos tienen altas tasas de éxito, sin embargo, son más invasivos y no están exentos de riesgo. La combinación de tratamientos parece aumentar la tasa de éxito, no obstante, podría implicar un mayor riesgo de efectos secundarios y costes. CONCLUSIONES: El manejo de los ECC debe de ser individualizado, basado en la evidencia científica, en los medios disponibles y la experiencia de los profesionales en los distintos procedimientos, guiándonos por el tipo de ECC y su grado de vascularización e invasión, grosor del miometrio, niveles de beta-hCG, presencia de actividad cardiaca, clínica y estabilidad hemodinámica de la paciente. Deben tenerse en cuenta las circunstancias y patología intercurrente de la mujer, así como su deseo genésico o de preservación del útero.
INTRODUCTION AND OBJECTIVES: Cesarean scar pregnancy (CSP) is a rare entity that can cause serious consequences. Up to now, there are no standardized treatment schemes, and its optimal management remains controversial. Our objetive is to review the literature regarding CSP management and propose an algorithm. We also present three cases of CSP resolved with different treatments at Hospital Universitario Infanta Elena. METHODS: Literature search in databases using the following keywords: pregnancy with cesarean section, ectopic pregnancy with cesarean section, treatment, management. RESULTS: The therapeutic options can be medical, surgical or a combination of both. Surgical treatments have high success rates; however, they are more invasive and are not without risk. The combination of treatments seems to increase the success rate; however, it could imply a higher risk of side effects and costs. CONCLUSIONS: The management of CSP must be individualized; based on scientific evidence, on the means available, and on the experience of the professionals in the different procedures; guided by the type of CSP and its degree of vascularization and invasion, by the thickness of the myometrium, beta-hCG levels, presence of cardiac activity, and by clinical and hemodynamic stability of the patient. The circumstances and intercurrent pathology of the patient must be considered, as well as her desire for future pregnancy or preservation of the uterus.
Assuntos
Humanos , Feminino , Gravidez , Adulto , Gravidez Ectópica/terapia , Cesárea/efeitos adversos , Cicatriz/etiologia , Cicatriz/terapia , Gravidez Ectópica/cirurgia , Gravidez Ectópica/tratamento farmacológico , Metotrexato/uso terapêutico , Cicatriz/cirurgia , Cicatriz/tratamento farmacológico , Embolização da Artéria Uterina , Ablação por Ultrassom Focalizado de Alta Intensidade , HisterectomiaRESUMO
Sesquiterpene lactones (SL) are natural bioactive molecules indicated as potential scaffolds for anti-inflammatory and analgesic drug design. However, their anti-inflammatory applicability remains underestimated since the impact of SL on inflammatory nociception and tissue repair are overlooked. Thus, we used an integrated in silico, in vitro and in vivo framework to investigate the impact of tagitinin F (TAG-F) on lipopolysaccharide (LPS)-challenged macrophages, excisional skin wounds, and carrageenan-induced paw edema and mechanical hyperalgesia in mice. RAW 264.7 macrophages in culture were challenged with LPS and treated with TAG-F (5, 10, 50 and 100 µM). The paw of BALB/c mice was injected with carrageenan and treated with 0.5% and 1% TAG-F. Excisional wounds were also produced in BALB/c mice and treated with 0.5% and 1% TAG-F. Our results indicated a consistent concentration-dependent downregulation in 5-lipoxygenase, cyclooxygenase 1 and 2 (COX-1 and COX-2), matrix metalloproteinase 1 and 2 (MMP-1 and MMP-2) activities; as well as attenuation in prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and tumor necrosis factor-α (TNF-α) production in both in vitro and in vivo models. In vivo, TAG-F also attenuated carrageenan-induced paw edema and mechanical hyperalgesia in mice. From the excisional skin wound, TAG-F was still effective in reducing neutrophils and macrophages infiltration and stimulating collagen deposition in the scar tissue, accelerating tissue maturation. Together, our findings indicate that the anti-inflammatory effect of TAG-F is more comprehensive than previously suggested, exerting a significant impact on the control of edema, inflammatory pain and modulating central metabolic processes linked to skin wound healing.
Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Cicatriz/tratamento farmacológico , Edema/tratamento farmacológico , Hiperalgesia/tratamento farmacológico , Sesquiterpenos/uso terapêutico , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Araquidonato 5-Lipoxigenase/metabolismo , Carragenina , Cicatriz/metabolismo , Colágeno/metabolismo , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Edema/induzido quimicamente , Leucotrieno B4/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Células RAW 264.7 , Sesquiterpenos/farmacologia , Tato , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Treatment of tracheal stenosis is occasionally performed in combination with wound healing modulators to manipulate new extracellular matrix (ECM) formation and prevent fibrosis. Hyaluronic acid (HA) and collagen-polyvinylpyrrolidone (collagen-PVP) decrease fibrosis in experimental tracheal healing. However, they have not been used clinically as their effect on ECM components, which modify tracheal scarring, has not been described. Objective. To evaluate the effect of the application of HA, collagen-PVP, a mixture of HA and collagen-PVP (HA+collagen-PVP), and mitomycin C on the expression of decorin, matrix metalloproteinase 1 (MMP1), and MMP9, as well as the type of collagen and deposits formed in the scar after resection and end-to-end anastomosis (REEA) of the cervical trachea using an experimental model. Materials and Methods. Thirty dogs underwent REEA of the cervical trachea and were treated with different wound healing modulators: group I (n = 6), control; group II (n = 6), HA; group III (n = 6), collagen-PVP; group IV (n = 6), HA+collagen-PVP; and group V (n = 6), mitomycin C. The dogs were evaluated clinically and endoscopically for 4 weeks. Subsequently, macroscopic and microscopic changes, expression of ECM proteins, and collagen deposition in tracheal scars were analysed. Results. Groups II, III, and IV showed reduced endoscopic, macroscopic, and microscopic inflammation, improved neovascularization, high decorin expression (p < 0.01, analysis of variance (ANOVA)), and moderate expression of MMP1 (p < 0.003, ANOVA) and type I and III collagen (p < 0.05, Kruskal-Wallis). Groups IV and V developed fewer collagen deposits (p < 0.001, ANOVA). Conclusion. Treatment with HA and collagen-PVP improved post-REEA healing by increasing neovascularization, stimulating the expression of decorin, and regulating the expression of MMP1, as well as type I and III collagen and their deposition.
Assuntos
Cicatriz/tratamento farmacológico , Colágeno/administração & dosagem , Ácido Hialurônico/administração & dosagem , Complicações Pós-Operatórias/tratamento farmacológico , Povidona/administração & dosagem , Estenose Traqueal/cirurgia , Anastomose Cirúrgica , Animais , Cicatriz/etiologia , Cicatriz/patologia , Colágeno/metabolismo , Decorina/metabolismo , Modelos Animais de Doenças , Cães , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Feminino , Fibrose , Humanos , Masculino , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Mitomicina/administração & dosagem , Complicações Pós-Operatórias/metabolismo , Complicações Pós-Operatórias/patologia , Traqueia/efeitos dos fármacos , Traqueia/patologia , Traqueia/cirurgia , Cicatrização/efeitos dos fármacosRESUMO
PURPOSE: To evaluate the safety and potential healing efficacy of the topical ocular administration of a gelatin membrane containing usnic acid/liposomes (UALs) for corneal cicatrization. UALs have shown healing activity in animal models of dermal burn lesions. We evaluated the safety of topical ocular administration of UAL and its potential healing efficacy as an ophthalmic treatment on chemical lesions in rabbit eyes. METHOD: The Draize test was used to check for ocular toxicity and the score was zero at each observation, indicating the ocular safety of a gelatin membrane containing usnic acid/liposome. Its potential healing efficacy as an ophthalmic treatment on chemical lesions in rabbit eyes was also assessed. RESULTS: After epithelial removal and treatment with UAL, there was a 49.4 % reduction in injury under in vivo conditions compared with a 36.6 % reduction in the control, a gelatin membrane containing liposome without usnic acid. Histological analysis of ocular surface chemical injury-tissue sections after treatment with UAL supported these observations. The corneal expression of VEGF and TGF-ß1increased by 70 % and 50 % respectively following treatment with UAL gelatin membrane. CONCLUSION: These results indicate the potential therapeutic application of UAL gelatin membranes as an ophthalmic treatment that may be used for corneal cicatrization.
Assuntos
Benzofuranos/administração & dosagem , Cicatriz/tratamento farmacológico , Córnea/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Cicatrização/efeitos dos fármacos , Administração Oftálmica , Animais , Benzofuranos/química , Galinhas , Córnea/irrigação sanguínea , Feminino , Gelatina/administração & dosagem , Gelatina/química , Lipossomos/administração & dosagem , Lipossomos/química , Neovascularização Fisiológica/efeitos dos fármacos , Soluções Oftálmicas/químicaRESUMO
Cicatrizing conjunctivitis is the final consequence of several diseases. The most severe among them are cicatricial pemphigoid and chronic Stevens-Johnson syndrome. Systemic immunosuppressive drugs and steroids are usually an effective approach to these diseases. However, a few patients follow a recalcitrant course unremitting to usual therapy. We describe the treatment with rituximab of seven patients with cicatricial pemphigoid and two with chronic Stevens-Johnson syndrome. Eight of them also received gammaglobulin and all achieved clinical remission. Three relapsed and required two or three new courses of rituximab with good control of disease activity. Rituximab proved to be an efficacious drug for chronic recalcitrant cicatrizing conjunctivitis.
La conjuntivitis cicatrizal es la consecuencia de distintas enfermedades oculares. Entre ellas, las más graves son el penfigoide cicatrizal y el síndrome de Stevens-Johnson crónico. El tratamiento de estas enfermedades con corticoides e inmunosupresores es habitualmente exitoso, pero unos pocos pacientes siguen un curso recalcitrante. En los últimos años se introdujo el uso de rituximab, asociado o no a gammaglobulina endovenosa, en forma abierta, para el control de la inflamación conjuntival. Describimos aquí el tratamiento de siete pacientes con penfigoide y dos con Stevens-Johnson recalcitrante, con rituximab. Ocho recibieron también gammaglobulina y todos alcanzaron la remisión de la actividad. Tres recayeron y recibieron dos o tres nuevos cursos de la medicación con mejoría sintomática. El rituximab probó ser una droga efectiva para el tratamiento de la conjuntivitis cicatrizal crónica recalcitrante.
Assuntos
Cicatriz/tratamento farmacológico , Conjuntivite/tratamento farmacológico , Fatores Imunológicos/administração & dosagem , Penfigoide Mucomembranoso Benigno/complicações , Rituximab/administração & dosagem , Síndrome de Stevens-Johnson/complicações , Adulto , Idoso , Doença Crônica , Cicatriz/etiologia , Conjuntivite/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
La conjuntivitis cicatrizal es la consecuencia de distintas enfermedades oculares. Entre ellas, las más graves son el penfigoide cicatrizal y el síndrome de Stevens-Johnson crónico. El tratamiento de estas enfermedades con corticoides e inmunosupresores es habitualmente exitoso, pero unos pocos pacientes siguen un curso recalcitrante. En los últimos años se introdujo el uso de rituximab, asociado o no a gammaglobulina endovenosa, en forma abierta, para el control de la inflamación conjuntival. Describimos aquí el tratamiento de siete pacientes con penfigoide y dos con Stevens-Johnson recalcitrante, con rituximab. Ocho recibieron también gammaglobulina y todos alcanzaron la remisión de la actividad. Tres recayeron y recibieron dos o tres nuevos cursos de la medicación con mejoría sintomática. El rituximab probó ser una droga efectiva para el tratamiento de la conjuntivitis cicatrizal crónica recalcitrante.
Cicatrizing conjunctivitis is the final consequence of several diseases. The most severe among them are cicatricial pemphigoid and chronic Stevens-Johnson syndrome. Systemic immunosuppressive drugs and steroids are usually an effective approach to these diseases. However, a few patients follow a recalcitrant course unremitting to usual therapy. We describe the treatment with rituximab of seven patients with cicatricial pemphigoid and two with chronic Stevens-Johnson syndrome. Eight of them also received gammaglobulin and all achieved clinical remission. Three relapsed and required two or three new courses of rituximab with good control of disease activity. Rituximab proved to be an efficacious drug for chronic recalcitrant cicatrizing conjunctivitis.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Cicatriz/tratamento farmacológico , Penfigoide Mucomembranoso Benigno/complicações , Síndrome de Stevens-Johnson/complicações , Conjuntivite/tratamento farmacológico , Rituximab/administração & dosagem , Fatores Imunológicos/administração & dosagem , Doença Crônica , Cicatriz/etiologia , Resultado do Tratamento , Conjuntivite/etiologiaRESUMO
Surgical extraction of impacted lower wisdom teeth is a frequent minor intraoral surgical process. It is regularly linked with aching and postoperative consequences as pain and swelling. The aim of this study is to evaluate the efficacy of two methods in reducing swelling and pain subsequent to the removal of impacted wisdom teeth. This randomized study incorporated 20 patients with impacted wisdom teeth of different surgical complexity. Topical hyaluronic acid gel 2g/2ml with aloe vera (Kin®Care) was given to the patients to be applied to the surgical area three times a day, or diclofenac sodium tablet 50mg (Voltaren®) to be taken every eight hours, for one week. Swelling was estimated using a strip gauge technique, and pain with a visual analogue scale. Evaluations were made on day one of surgical treatment and on 72hrs and one week later. Statistically no significant differences were identified regarding the swelling and pain values between the two treatment groups on the third and seventh day after surgery. Hyaluronic acid gel was as efficient as diclofenac tablets in reducing the two parameters. The use of hyaluronic acid may be advantageous in medically compromised patient such as those with hypertension, chronic asthma, gastric ulcers or in those with any contraindications to using non-steroidal anti-inflammatory drugs, or in pregnant patients to reduce pain and swelling subsequent to impacted wisdom teeth surgery.