Cordycepin prevents the esophageal stricture formation in the alkali-burn rat model by exerting anti-inflammatory and antifibrotic effects

ABSTRACT Purpose To investigate the efficacy of cordycepin, an adenosine analogue, on prevention of esophageal damage and stricture formation due to esophageal caustic burns in rat model comparing with prednisolone. Methods Caustic esophageal burn was introduced by 37.5% of NaOH to distal esophagus. Thirty-two Wistar albino rats were divided in four groups: sham rats undergone laparotomy, treated with 0.9% NaCl; control rats injured with NaOH without cordycepin treatment; cordycepin group injured with NaOH, treated with 20 mg/kg cordycepin; prednisolone group injured with NaOH, treated with 1 mg/kg prednisolone for 28 days. Efficacy was assessed by histopathological and immunohistochemical analysis of esophageal tissues. Results Cordycepin treatment significantly decreased inflammation, granulation tissue and fibrous tissue formation and prevented formation of esophageal strictures shown by histopathological damage score and stenosis indexes compared to control group (p < 0.01). These effects are relatively more substantial than prednisolone, probably based on attenuation of elevation of proinflammatory cytokines hypoxia-inducible factor 1-alpha (HIF-1?), tumor necrosis factor alpha (TNF-?), proliferative and fibrotic factor fibroblast growth factor 2 (FGF2) and angiogenic factor vascular endothelial growth factor A (VEGFA) (p < 0.05). Conclusions The findings suggest that cordycepin has a complex multifactorial healing process in alkali-burned tissue, more successful than prednisolone in preventing the formation of esophageal strictures and may be used as a therapeutic agent in the acute phase of esophageal alkali-burn.

Therapeutic effects of proanthocyanidin and coenzyme Q10 on nitrogen mustard-induced ocular injury / Efeitos terapêuticos da proantocianidina e da coenzima q10 em lesão ocular induzida por mostarda de nitrogênio

ABSTRACT Purpose: Nitrogen mustard (NM) is a devastating casualty agent in chemical warfare. There is no effective antidote to treat NM-induced ocular injury. We aimed to assess the effects of proanthocyanidin (PAC) and coenzyme Q10 (CoQ10) on NM-induced ocular injury. Methods: Eighteen male rats were divided into the following 4 groups: NM, NM + PAC, NM + CoQ10, and control. The 3 NM groups received a single dose of NM (0.02 mg/μL) on the right eye to induce ocular injury. The control group received saline only. Thirty minutes after the application of NM, the NM + PAC group received PAC (100 mg/kg) via gastric gavage, while the NM + CoQ10 group received CoQ10 (10 mg/kg) via intraperitoneal injection. PAC and CoQ10 were administered once a day for 5 consecutive days. The rats were then sacrificed. Macroscopic images of the eyes were examined and eye tissues were collected for histology. Results: The treatment groups were compared to the control group with regard to both corneal opacity and lid injury scores. The findings were not significantly different for both the NM + PAC and NM + CoQ10 groups. In both the NM + PAC and NM + CoQ10 groups, the histological changes seen in the NM group demonstrated improvement. Conclusions: Our results indicate that PAC and CoQ10 treatments have therapeutic effects on NM-induced ocular injury in a rat model. PAC and CoQ10 may be novel options in patients with NM-induced ocular injury.

RESUMO Objetivo: A mostarda de nitrogênio (MN) é um agente de guerra química devastador. Não existe um antídoto eficaz para tratar lesões oculares induzidas por MN. Nosso objetivo foi avaliar os efeitos da proantocianidina (PAC) e da coenzima Q10 (CoQ10) na lesão ocular induzida por MN. Métodos: Dezoito ratos machos foram divididos em 4 grupos: MN, MN + PAC, MN + CoQ10 e Controle. Três grupos receberam uma dose única de MN (0,02 mg/μL) destilada no olho direito para gerar lesão ocular. Os animais do grupo controle receberam apenas solução salina. Trinta minutos após a aplicação de MN nos animais, o grupo MN + PAC recebeu PAC (100 mg/kg) por gavagem gástrica, enquanto a CoQ10 (10 mg/kg) foi administrada ao grupo MN + CoQ10 por meio de injeção intraperitoneal. A administração de PAC e de CoQ10 foi realizada uma vez por dia, durante 5 dias consecutivos. Os ratos foram, então, sacrificados. Imagens macroscópicas dos olhos foram examinadas e tecidos oculares foram coletados para histologia. Resultados: Os grupos de tratamento foram comparados ao grupo de controle quanto à opacidade da córnea e quanto aos escores de lesão da cobertura da córnea. Os resultados foram insignificantes para ambos os grupos. Ambos, o grupo MN+PAC e o grupo MN+CoQ10, apresentaram melhoras das alterações histológicas observadas no grupo MN. Conclusões: Nossos resultados indicam que os tratamentos com PAC e com CoQ10 têm efeitos terapêuticos sobre lesões oculares induzidas por MN em um modelo em ratos. A proantocianidina e a CoQ10 podem ser uma nova opção nesses casos.

Effects of chitin and sepia ink hybrid sponge on the healing of burning wound rats and its impact on macrophages in vitro

PURPOSE: To detect whether chitin and sepia ink sponge (CS) can promote wound healing and elevate impact of CS on phagocytosis ability of macrophages. METHODS: Forty-eight rats were assigned to four groups: Normal group (Normal), negative control group (Con), chitin and sepia ink sponge group (CS) and positive control Surgicel Gauze(r) group (SG). Deep second-degree burn model was created in rats. Wound area was recorded by digital imaging and determined using Image J software. Samples were collected and kept at -80oC on 3d, 7d, 14d and 21d for cytokines detecting. Transforming growth factor (TGF)-β1, interleukin (IL)-6, matrix metalloproteinase (MMP)-1, hydroxyproline (Hyp) and macrophage activity reflected by tumor necrosis factor (TNF)-α were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Comparing to Con and SG, scabs in CS group fell off and basically healed on 21 day. TGF-β1, IL-6, MMP-1 and Hyp were significantly increased by CS and SG comparing to Con (p < 0.05), CS had more apparently adjustment on TGF-β1 and MMP-1 compared to SG; results in vitro indicated CS significantly promoted phagocytosis ability of macrophages reflected in TNF-α (p < 0.05). CONCLUSION: CS improved wound healing through exerting significant influences on secretion of kinds of cytokines and activating macrophages.

The use of mitomycin C in caustic esophagitis in rats

PURPOSE: To evaluate the topical effects of mitomycin C (MMC) in rats, with or without esophageal dilation, in different moments after esophageal caustic injury with NaOH10%. METHODS: Forty eight Wistar rats were divided into six groups: "GS" infusion of 0.9% saline solution in the esophagus; "CG" infusion of 0.9% saline solution in the esophagus, with temporary ligation of the organ; "NTG" induction of a caustic lesion without treatment; "GmmcD0" MMC applied immediately after the caustic injury; "GmmcD14" MMC applied 14 days after the caustic injury; "Gdil+mmcD14" esophageal dilation and application of MMC 14 days after caustic injury. We performed contrast esophagograms of four animals from each group, seven and 21 days after the caustic injury. On day 28, all animals were sacrificed, and histopathological analyses were performed on the esophageal specimens. RESULTS: The contrast images showed total stenosis in NTG and GmmcD0, improving to partial stenosis in GmmcD0. In GmmcD14 and Gdil+mmcD14, two animals of each group improved to partial stenosis. By histopathological analysis, NTG and GmmcD14 presented intermediate damage and GmmcD0 and Gdil+mmcD14 severe damage. CONCLUSION: The use of mitomycin C had beneficial effects specially when applied immediately after the induction of esophageal lesions.

Ação do bevacizumabe subconjuntival na neovascularização e re-epitelização corneana 25 dias após queimadura química / Effect of subconjunctival bevacizumab on corneal neovascularization and reepithelization 25 days after chemical burn

OBJETIVOS: Avaliar a ação do bevacizumabe subconjuntival em modelo experimental de neovascularização em córnea de coelho. Analisar se o modelo de avaliação empregado é adequado e comparar entre os grupos a extensão dos vasos, inflamação e re-epitelização da córnea. MÉTODOS: Estudo experimental, prospectivo em 20 coelhos submetidos a trauma químico com hidróxido de sódio a 1 N divididos em dois grupos, Imediatamente após a queimadura, o grupo tratado recebeu injeção subconjuntival de 0,15 ml (3,75 mg) de bevacizumabe e o grupo controle, injeção subconjuntival de 0,15 ml de soro fisiológico a 0,9 por cento. Após 25 dias, foi realizada análise fotográfica digital para avaliar a extensão e inflamação/calibre dos vasos segundo critério pré-estabelecido e estudo histopatológico da córnea, no qual foi avaliado o estado do epitélio e o número de polimorfonucleares. RESULTADOS: A extensão dos neovasos corneanos foi menor no grupo estudo em relação ao controle (p<0,001). Não houve diferença significativa entre os grupos na inflamação/calibre dos vasos. A análise histopatológica mostrou que não ocorreu diferença entre os grupos nas variáveis estado do epitélio e número de polimorfonucleares. A análise de concordância para a variável extensão dos vasos e para a variável inflamação/calibre dos vasos teve uma estimativa do coeficiente de Kappa respectivamente de 0,705 e 0,500 indicando bom grau de concordância nas diferentes avaliações cegadas, validando o método empregado. CONCLUSÕES: O modelo de avaliação foi adequado e pode ser reproduzido para avaliar outras drogas na córnea. O bevacizumabe inibiu a neovascularização corneana, porém não foi eficaz em reduzir o processo inflamatório. A droga não atrasou a re-epitelização da córnea.

PURPOSES: To evaluate the effect of subconjunctival bevacizumab in an experimental model of neovascularization in rabbit cornea. Determine its effect on vessels extension, inflammation, epithelialization of the cornea and whether the evaluation method used is appropriate to compare neovascular models. METHODS: Experimental, prospective, randomized, blinded study in twenty rabbits subjected to chemical trauma with sodium hydroxide at 1N divided into two groups. The study group received subconjunctival injection of 0.15 ml (3.75 mg) of bevacizumab and was compared with the control group that received subconjunctival injection of 0.15 ml saline solution. After 25 days, digital photographic analysis was performed to assess the vessel's extension and inflammation/diameter according to pre-established criteria. Histopathology of the cornea, which evaluated the state of the epithelium and the number of polymorphonuclear cells was also studied. RESULTS: The length of the neovessels was greater in the control group compared to the study group (P=<0.001). There was no difference in inflammation/vessel diameter between groups. Histopathology analysis showed that there was no difference between groups for the variables state of the epithelium and number of polymorphonuclear cells. The concordance analysis for the variable extension of the vessels and the variable inflammation/vessel diameter was estimated with Kappa coefficients of 0.705 and 0.500 respectively, indicating a good level of agreement in different evaluations and validating the method. CONCLUSIONS: The experimental model is adequate and can be reproduced to evaluate other drugs in the cornea. Bevacizumab inhibit the neovessels' growth but was not effective in preventing the inflammatory response. The drug did not delay the reepithelialization of the cornea.

Finger burns caused by concentrated hydrofluoric acid, treated with intra-arterial calcium gluconate infusion: case report / Queimadura digital por ácido fluorídrico concentrado tratada com infusão intra-arterial de gluconato de cálcio: relato de caso

CONTEXT: Hydrofluoric acid (HF) is widely used in industry and at home. Severe lesions can occur after contact with highly concentrated solutions, leading to tissue necrosis and bone destruction. Specific treatment is based on neutralization of fluoride ions with calcium or magnesium solutions. CASE REPORT: A 41-year-old male was seen at the emergency department 35 minutes after skin contact with 70 percent HF, showing whitened swollen lesions on the middle and fourth fingers of his right hand with severe pain starting immediately after contact. 2.5 percent calcium gluconate ointment was applied. Twenty-four hours later, the patient was still in severe pain and the lesions had worsened. Considering the high concentration of the solution, early start of severe pain, lesion characteristics and impossibility of administering calcium gluconate subcutaneously because of the lesion location, the radial artery was catheterized and 2 percent calcium gluconate was administered via infusion pump for 36 hours, until the pain subsided. No adverse effects were seen during the procedure. Ten days later, the lesions were stable, without bone abnormalities on X-rays. Six months later, a complete recovery was seen. CONCLUSIONS: Intra-arterial calcium gluconate might be considered for finger burns caused by concentrated HF. Complete recovery of wounded fingers can be achieved with this technique even if started 24 hours after the exposure. However, controlled clinical trials are needed to confirm the effectiveness and safety of this intervention.

CONTEXTO: Ácido fluorídrico é largamente usado na indústria e no ambiente doméstico. Lesões graves podem ocorrer depois de contato com soluções altamente concentradas levando a necrose tecidual e destruição óssea. O tratamento específico é baseado na neutralização dos íons de flúor com soluções de cálcio ou magnésio. RELATO DE CASO: Homem de 41 anos foi atendido na sala de urgência 35 minutos depois de contato da pele com ácido fluorídrico a 70 por cento, apresentando lesões esbranquiçadas e edemaciadas nos dedos médio e quarto da mão direita com dor intensa que iniciou logo após o contato. Pomada de gluconato de cálcio a 2,5 por cento foi aplicada. Depois de 24 horas, o paciente continuava com dor mais intensa e as lesões haviam piorado. Considerando a concentração da solução, o início precoce da dor intensa, as características das lesões e a impossibilidade de administrar gluconato de cálcio no subcutâneo devido ao local da lesão, foi inserido cateter na artéria radial para infusão de gluconato de cálcio a 2 por cento com bomba de infusão por 36 horas até melhora da dor. Nenhum efeito adverso foi observado durante o procedimento. Dez dias depois as lesões encontravam-se estáveis, sem alterações dos ossos vistas nos raios-X. Seis meses depois houve recuperação completa. CONCLUSÃO: Gluconato de cálcio intra-arterial pode ser considerado em queimaduras digitais por ácido fluorídrico. Recuperação completa dos dedos acometidos pode ser obtida com essa técnica mesmo que iniciada 24 horas após a exposição. Porém, ensaios clínicos controlados são necessários para confirmar a efetividade e a segurança desta intervenção.

Accidental scrotal burns from paraquat while handling a patient.

The main risk of paraquat poisoning is from deliberate ingestion. Serious accidental or occupational poisoning is comparatively rare. We report two patients who had accidental exposure to paraquat, resulting in scrotal burns in both and systemic poisoning in one, while attending to a patient who had ingested paraquat for deliberate self harm.

Sistema de puntuación del daño múltiple de órganos en un modelo de quemadura tratado con Aloe b, ozono y factor de crecimiento epidérmico / Scoring system of the multiple organ damage in a burn model treated with Aloe b, ozone and epidermal growth factor

La experiencia alcanzada en el estudio del daño múltiple de órganos (DMO) mostraba la necesidad de establecer una escala semicuantitativa que permitiera cuantificar el valor de las alteraciones observadas. El propósito del presente trabajo fue diseñar un método de estudio del DMO con el empleo de una escala de valores semicuantitativos que se identifique con los daños patomorfológicos y que permita evaluar el DMO en el modelo empleado. Se elaboró un modelo de quemadura seca de un área del 11 por ciento en ratones hembras balb/c de 20 ± 2 g (n= 24) y se aplicó tratamiento con el empleo de inmunomoduladores y citoprotectores. Se estudiaron los órganos con evaluación cualitativa en grados de intensidad. La prueba G fue empleada para conocer la dependencia entre las variables y la prueba t fue usada al comparar porcentajes. La prueba de rango múltiple de Duncan se utilizó en el sistema de puntuación. Se siguieron las normas éticas en el trabajo con los animales. El sistema de puntuación propuesto y aplicado en los animales de los diferentes grupos de estudio permitió excluir el DMO en parte de los animales de los grupos que mejor comportamiento presentaron durante todo el estudio y clasificar el DMO con intensidad entre leve, moderada e intensa

Intoxicación por contacto con óxido de etileno / Intoxication by contac with ethylene oxide

Una lactante eutrófica, durante una cirugía ortopédica tuvo contacto en su muslo derecho con una venda hemostática de látex contaminada con óxido de etileno (OE). Desarrolló una quemadura química intensa en el área expuesta y una intoxicación de efectos generalizados. Se discute el peligro al manipular objetos estrilizados con este método. Además se recomiendan pautas para evitar futuros accidentes

Effect of topically applied Na-hyaluronan on experimental corneal alkali wound healing

The effect of topically applied 1% sodium hyaluronate (Na-HA) on the healing of a standardized corneal alkali wound was studied. The healing of the epithelium, stroma, and endothelium was evaluated separately, using quantitative methods. Central corneal alkali wound was produced in one eye of the rabbits by applying a 5.5-mm round filter paper, soaked in 1 N NaOH, for 60 seconds. 1% Na-HA in the treatment group and phosphate buffered saline (PBS) in the control group were given topically 4 times per day for 2 days, 1- and 3-weeks. Epithelial and endothelial healing was assessed morphometrically from standardized photographs and micrographs, respectively. Stromal healing was determined by counting polymorphonuclear leukocytes (PMN) and keratocytes in the central and marginal wound areas. A positive healing influence was observed in the epithelium. In stromal healing, 1% Na-HA treated corneas showed less PMNs and more keratocytes than the control group, suggesting that topically applied 1% Na-HA may suppress the stromal PMN infiltration and enhance the keratocyte repopulation during corneal alkali wound healing. However, no significant difference was found in morphometric evaluation of endothelial healing between the two groups.

Traumatismos oculares / Eye injuries

O trauma ocular ocupa lugar proeminente na infortunística médica, representando assunto vasto e destacado no estudo da oftalmologia.O presente trabalho faz uma revisao das lesoes traumáticas mais prevalentes, salientando os aspectos clínicos, propedêuticos e terapêuticos mais importantes.Enfase especial é dada aos avanços cirúrgicos que vieram modificar de forma significativa o prognóstico e a recuperaçao funcional de olhos extensamente lesados, no tratamento dos traumatismos do pólo posterior.