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1.
Article in English | WPRIM | ID: wpr-928653

ABSTRACT

To investigate the therapeutic effect and mechanism of Qingfei oral liquid in idiopathic pulmonary fibrosis. Seventy-two male SD rats were divided into control group, model group, pirofenidone group and Qingfei group with 18 animals in each group. The idiopathic pulmonary fibrosis was induced in last three groups by intratracheal injection of bleomycin; pirofenidone group was given oral administration of pirofenidone b.i.d for 21 d, and Qingfei group was given Qingfei oral liquid 3.6 mL/kg q.d for Lung tissues were obtained for HE staining, Masson staining and transforming growth factor (TGF)-β immunohistochemical staining. Superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) were detected in tissue homogenates. The BATMAN-TCM database was used to retrieve the chemical components and their corresponding targets of Qingfei oral solution by network pharmacology method, and then the component-target-disease network diagram was constructed. Finally, the pathway enrichment analysis was carried out to explore the molecular mechanism of Qingfei oral liquid against idiopathic fibrosis. Histopathology results showed that Qingfei oral liquid had a similar relieving effect on pulmonary fibrosis as the positive drug pirfenidone; TGF-β secretion had a significant reduction in lung tissues of Qingfei group; and Qingfei oral liquid had better regulatory effect on SOD, MDA and GSH than pirfenidone. The results of component-target-disease network and pathway enrichment analysis showed that the related molecular pathways were concentrated in inflammation, extracellular matrix and cytokines. Qingfei oral liquid has a good therapeutic effect on idiopathic pulmonary fibrosis in rats via regulation of inflammation, extracellular matrix and cytokines.


Subject(s)
Animals , Bleomycin/pharmacology , Cytokines , Drugs, Chinese Herbal , Glutathione , Idiopathic Pulmonary Fibrosis/drug therapy , Inflammation , Lung/pathology , Male , Network Pharmacology , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/metabolism , Transforming Growth Factor beta/pharmacology
2.
Cambios rev. méd ; 20(2): 53-59, 30 Diciembre 2021. ilus, tabs.
Article in Spanish | LILACS | ID: biblio-1368287

ABSTRACT

INTRODUCCIÓN. Los linfangiomas son una malformación infrecuente a escala mundial y constituye una preocupación para los padres del infante; está asociado a problemas estéticos y a posibles efectos deletéreos debido a la obstrucción o compresión de órganos vitales. Se ha descrito a la escleroterapia como la mejor opción de tratamiento. OBJETIVO. Determinar la eficiencia del tratamiento con bleomicina en linfangiomas en la población pediátrica de 0 a 18 años. MATERIALES Y MÉTODOS. Estudio transversal analítico retrospectivo. Población y muestra conocida de 20 datos de Historias Clínicas electrónicas de pacientes diagnosticados con linfangiomas y tratados con bleomicina en el Hospital de Especialidades Carlos Andrade Marín, desde enero 2015 a enero 2018. Criterios de inclusión: pacientes de 0 a 18 años de edad con diagnóstico de linfangioma mediante ecografía y angiotomografía computarizada. Criterios de exclusión: pacientes mayores de 18 años de edad o sospecha diagnóstica de linfangioma sin estudios de imagen, y/o que no acudieron a la cita de control, pacientes diagnosticados de linfangioma que no recibieron bleomicina para su tratamiento, niños con otras malformaciones vasculares. El análisis de datos se realizó en el programa estadístico International Business Machines Statistical Package for the Social Sciences. RESULTADOS. La mediana de edad en mujeres fue de 6,25 años y 3,8 años en hombres. 10 pacientes fueron hombres. El promedio de seguimiento fue de 26,86 +/- 16,78 meses. El tamaño promedio de los linfangiomas fue de 5,77 +/- 3,73 cm. La localización más frecuente fue cervical con un 52,38%. La mayoría fueron macronodulares con un 85,71%. La respuesta fue buena o excelente en el 81,00% de los casos con la primera infiltración y subió al 95,00% con la segunda y tercera, según requerimiento. CONCLUSIÓN. El tratamiento de los linfangiomas con bleomicina fue muy efectivo en la población estudiada.


INTRODUCTION. Lymphatic malformation is a rare malformation worldwide and is a concern for the parents of the infant; it is associated with aesthetic problems and possible deleterious effects due to obstruction or compression of vital organs. Sclerotherapy has been described as the best treatment option. OBJECTIVE. To determine the efficiency of bleomycin treatment in lymphangiomas in the pediatric population aged 0 to 18 years. MATERIALS AND METHODS. Retrospective analytical cross-sectional study. Population and known sample of 20 data from Electronic Medical Records of patients diagnosed with lymphangiomas and treated with bleomycin at the Carlos Andrade Marín Specialties Hospital, from January 2015 to January 2018. Inclusion criteria: patients aged 0 to 18 years with diagnosis of lymphangioma by ultrasound and computed angiotomography. Exclusion criteria: patients older than 18 years of age or diagnostic suspicion of lymphangioma without imaging studies, and/or who did not attend the control appointment, patients diagnosed with lymphangioma who did not receive bleomycin for treatment, children with other vascular malformations. Data analysis was performed in the statistical program International Business Machines Statistical Package for the Social Sciences. RESULTS. The median age in women was 6,25 years and 3,8 years in men. Ten patients were men. The average follow-up was 26,86 +/- 16,78 months. The average size of the lymphatic malformations was 5,77 +/- 3,73 cm. The most frequent location was cervical with 52,38%. Most were macronodular with 85,71%. The response was good or excellent in 81,00% of cases with the first infiltration and rose to 95,00% with the second and third, as required. CONCLUSION. The treatment of lymphangiomas with bleomycin was very effective in the population studied.


Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Congenital Abnormalities , Bleomycin , Epidemiologic Factors , Child Health Services , Adolescent Health Services , Lymphangioma , Pediatrics , Axilla , Diagnostic Imaging , Diagnosis , Inguinal Canal , Neck
3.
Bol. latinoam. Caribe plantas med. aromát ; 20(3): 315-323, may. 2021. ilus, tab
Article in English | LILACS | ID: biblio-1343489

ABSTRACT

To investigate effectsof Yangyinyiqi Mixture on pulmonary fibrosis caused by bleomycin. SD ratswere divided randomly into: model group(distilled water,1 mL·0.1 kg-1), dexamethasone acetate group (dexamethasone acetate, the dosage was reduced gradually), low-dose group (Yangyinyiqi Mixture, 11 g·kg-1), moderate-dose group (Yangyinyiqi Mixture, 22 g·kg-1), high-dose group (Yangyinyiqi Mixture, 44 g·kg-1) and control group (distilled water, 1 mL·0.1 kg-1). Yangyinyiqi Mixture and dexamethasone acetate were intragastrically administrated. Lung tissue was collected for histopathological examination. Compared with control group, collagen markedly increased and HYP content significantly increased on 7th day in model group (p<0.01). On 28th day, collagen was diffusely deposited, alveolar was destroyed, and HYP content significantly increased (p<0.01). Compared with model group, bleomycin-induced suffering injury caused MMP-9 expression levels to rapidly increase (7and 14 days, p<0.01). TIMP-1 markedly increased (7and 14 days, p<0.01) and stayed at a high level to28th day. Yangyinyiqi Mixture exerted an effect against pulmonary fibrosis, which could involved prevention of collagen deposition through inhibitingMMP-9 and TIMP-1 expression.


El trabajo investiga los efectos de la mezcla Yangyinyiqi sobre la fibrosis pulmonary causada por bleomicina. Ratas SD se dividieron aleatoriamente en: grupo modelo (agua destilada, 1 mL·0.1 kg-1), grupo acetate de dexametasona (acetate de dexametasona, la dosis se redujo gradualmente), grupo de dosis baja (mezcla Yangyinyiqi, 11 g·kg-1), grupo de dosis moderada (mezcla Yangyinyiqi, 22 g·kg-1), grupo de dosis alta (mezcla Yangyinyiqi, 44 g·kg-1) y grupo control (agua destilada, 1 Ml·0.1 kg-1). La mezcla de Yangyinyiqi y el acetate de dexametasona se administraron por vía intragástrica. Se recolectó tejido pulmonary para examen histopatológico. En comparación con el grupo control, el colágeno aumentó notablemente y el contenido de HYP aumentó significativamente el séptimo día en el grupo modelo (p<0.01). El día 28, el colágeno se depositó difusamente, se produjo destrucción alveolar y el contenido de HYP aumento significativamente (p<0.01). En comparación con el grupo modelo, la lesión inducida por bleomicina causó que los niveles de expression de MMP-9 aumentaron rápidamente (7 y 14 días, p<0.01). TIMP-1 aumentó notablemente (7 y 14 días, p<0.01) y se mantuvo en un nivel alto hasta el día 28. La mezcla Yangyinyiqi ejerció un efecto contra la fibrosis pulmonary, lo que podría implicar la prevención del deposito de colágenio mediante la inhibición de la expression de MMP-9 y TIMP-1.


Subject(s)
Animals , Male , Rats , Pulmonary Fibrosis/drug therapy , Drugs, Chinese Herbal/administration & dosage , Tissue Inhibitor of Metalloproteinases/metabolism , Matrix Metalloproteinase 9/metabolism , Bleomycin , Dexamethasone/administration & dosage , Blotting, Western , Rats, Sprague-Dawley , Matrix Metalloproteinase 1 , Disease Models, Animal , Hydroxyproline/analysis
4.
Chinese Medical Journal ; (24): 2175-2185, 2021.
Article in English | WPRIM | ID: wpr-921109

ABSTRACT

BACKGROUND@#Macrophages are involved in the pathogenesis of idiopathic pulmonary fibrosis, partially by activating lung fibroblasts. However, how macrophages communicate with lung fibroblasts is largely unexplored. Exosomes can mediate intercellular communication, whereas its role in lung fibrogenesis is unclear. Here we aim to investigate whether exosomes can mediate the crosstalk between macrophages and lung fibroblasts and subsequently induce fibrosis.@*METHODS@#In vivo, bleomycin (BLM)-induced lung fibrosis model was established and macrophages infiltration was examined. The effects of GW4869, an exosomes inhibitor, on lung fibrosis were assessed. Moreover, macrophage exosomes were injected into mice to observe its pro-fibrotic effects. In vitro, exosomes derived from angiotensin II (Ang II)-stimulated macrophages were collected. Then, lung fibroblasts were treated with the exosomes. Twenty-four hours later, protein levels of α-collagen I, angiotensin II type 1 receptor (AT1R), transforming growth factor-β (TGF-β), and phospho-Smad2/3 (p-Smad2/3) in lung fibroblasts were examined. The Student's t test or analysis of variance were used for statistical analysis.@*RESULTS@#In vivo, BLM-treated mice showed enhanced infiltration of macrophages, increased fibrotic alterations, and higher levels of Ang II and AT1R. GW4869 attenuated BLM-induced pulmonary fibrosis. Mice with exosomes injection showed fibrotic features with higher levels of Ang II and AT1R, which was reversed by irbesartan. In vitro, we found that macrophages secreted a great number of exosomes. The exosomes were taken by fibroblasts and resulted in higher levels of AT1R (0.22 ± 0.02 vs. 0.07 ± 0.02, t = 8.66, P = 0.001), TGF-β (0.54 ± 0.05 vs. 0.09 ± 0.06, t = 10.00, P < 0.001), p-Smad2/3 (0.58 ± 0.06 vs. 0.07 ± 0.03, t = 12.86, P < 0.001) and α-collagen I (0.27 ± 0.02 vs. 0.16 ± 0.01, t = 7.01, P = 0.002), and increased Ang II secretion (62.27 ± 7.32 vs. 9.56 ± 1.68, t = 12.16, P < 0.001). Interestingly, Ang II increased the number of macrophage exosomes, and the protein levels of Alix (1.45 ± 0.15 vs. 1.00 ± 0.10, t = 4.32, P = 0.012), AT1R (4.05 ± 0.64 vs. 1.00 ± 0.09, t = 8.17, P = 0.001), and glyceraldehyde-3-phosphate dehydrogenase (2.13 ± 0.36 vs. 1.00 ± 0.10, t = 5.28, P = 0.006) were increased in exosomes secreted by the same number of macrophages, indicating a positive loop between Ang II and exosomes production.@*CONCLUSIONS@#Exosomes mediate intercellular communication between macrophages and fibroblasts plays an important role in BLM-induced pulmonary fibrosis.


Subject(s)
Angiotensin II , Animals , Bleomycin/toxicity , Exosomes , Fibroblasts , Lung , Macrophages , Mice , Mice, Inbred C57BL , Pulmonary Fibrosis/chemically induced , Receptor, Angiotensin, Type 1
5.
Frontiers of Medicine ; (4): 313-329, 2021.
Article in English | WPRIM | ID: wpr-880974

ABSTRACT

The medical fungus Hirsutella sinensis has been used as a Chinese folk health supplement because of its immunomodulatory properties. Our previous studies established the antifibrotic action of Hirsutella sinensis mycelium (HSM) in the lung. The epithelial-mesenchymal transition (EMT) is involved in the pathogenesis of idiopathic pulmonary fibrosis. The present study investigates the role of HSM in mediating EMT during the development of pulmonary fibrosis. HSM significantly inhibits bleomycin (BLM)-induced pulmonary fibrosis by blocking the EMT. In addition, the expression levels of midkine are increased in the lungs of the BLM-induced group. Further analysis of the results indicates that the mRNA level of midkine correlated positively with EMT. HSM markedly abrogates the transforming growth factor β-induced EMT-like phenotype and behavior in vitro. The activation of midkine related signaling pathway is ameliorated following HSM treatment, whereas this extract also caused an effective attenuation of the induction of EMT (caused by midkine overexpression) in vitro. Results further confirm that oral medication of HSM disrupted the midkine pathway in vivo. Overall, findings suggest that the midkine pathway and the regulation of the EMT may be considered novel candidate therapeutic targets for the antifibrotic effects caused by HSM.


Subject(s)
Bleomycin , Epithelial-Mesenchymal Transition , Humans , Midkine , Mycelium , Pulmonary Fibrosis/drug therapy
6.
Article in Chinese | WPRIM | ID: wpr-880825

ABSTRACT

OBJECTIVE@#To study the changes in mRNA and long non-coding RNA (lncRNA) expression profiles in a mouse model of bleomycin-induced lung fibrosis and identify lung fibrosis-related mRNA for coding-noncoding coexpression (CNC) bioinformatics analysis of the differential lncRNAs.@*METHODS@#Lung fibrosis was induced by intratracheal injection of bleomycin in 10 C57BL/6 mice and another 10 mice with intratracheal injection of saline served as the control group. Lung tissues were harvested from the mice at 14 days after the injections and lung fibrosis was assessed using Masson and HE staining. LncRNA chip technology was used to screen the differentially expressed mRNAs and lncRNAs in mice with lung fibrosis, and GO and KEGG pathway analyses of the differential mRNAs were performed using NCBI database and UCSC database to identify possible fibrosis-related mRNAs, which were validated by qRT-PCR to construct a coding and non-coding co- expression network with the differential lncRNAs.@*RESULTS@#Compared with the control mice, the mice with intratracheal injection of bleomycin showed obvious lung fibrosis. The results of gene chip analysis showed that 127 mRNAs were upregulated and 184 mRNAs were down-regulated in the model group as compared with the control group. GO and pathway analysis suggested that the differentially expressed genes participated mainly in immune response, cell differentiation, and cytoskeletons; the involved signal pathways were associated mainly with cytokine and cytokine receptor interaction and chemokine signal transduction. Bioinformatics analysis identified a significant coexpression network between the fibrosisrelated mRNA and the differentially expressed lncRNA.@*CONCLUSIONS@#In mice with lung fibrosis, the differential expressions of fibrosis-related mRNAs in the lung tissues are closely correlated with the co- expressions of a large number of differential lncRNAs, which points to a new direction for investigation of the pathogenesis of pulmonary fibrosis.


Subject(s)
Animals , Bleomycin/toxicity , Gene Expression Profiling , Gene Regulatory Networks , Mice , Mice, Inbred C57BL , Pulmonary Fibrosis/genetics , RNA, Long Noncoding/genetics , RNA, Messenger/genetics
7.
Rev. cuba. med ; 59(4): e1577, oct.-dic. 2020. tab, graf
Article in Spanish | LILACS, CUMED | ID: biblio-1144505

ABSTRACT

Introducción: El derrame pleural recidivante maligno se reproduce en breve tiempo y requiere el diagnóstico etiológico positivo de malignidad, la etiología más frecuente es el cáncer de pulmón. La pleurodesis química es el tratamiento de elección con la aplicación intrapleural de sustancias sinfisiantes. Objetivo: Describir la respuesta clínica y radiológica de los enfermos con derrame pleural recidivante maligno con el uso de bleomicina. Método: Estudio observacional comparativo en 30 pacientes con derrame pleural recidivante maligno divididos en dos grupos, en uno se aplicó la bleomicina intrapleural y al otro yodo povidona. Resultado: El 33,3 por ciento fueron del sexo masculino, 60 por ciento perteneció al grupo de edades de 60-69 años. El grupo tratado con bleomicina presentó una respuesta clínica favorable en los síntomas, p<0,005 después de la pleurodesis. En la evaluación de la respuesta radiológica, 66,6 por ciento pacientes tratados con la bleomicina tuvieron una resolución completa. Conclusiones: Se logró una buena respuesta clínica-radiológica con la pleurodesis química similar entre ambas modalidades de tratamiento. Se obtuvieron mejores resultados y menos reacciones adversas con la bleomicina intrapleural(AU)


Introduction: The malignant recurrent pleural effusion reproduces in short time and it requires a positive etiological diagnosis of malignancy, the most frequent etiology is lung cancer. Chemical pleurodesis is the treatment of choice with the intrapleural application of symphysiating substances. Objective: To describe the clinical and radiological response of patients with malignant recurrent pleural effusion with the use of bleomycin. Method: A comparative observational study in 30 patients with recurrent malignant pleural effusion was carried out. They were divided into two groups, one used intrapleural bleomycin and the other group used povidone iodine. Result: 33.3 percent were male, 60 percent belonged to the 60-69 age group. The group treated with bleomycin presented favorable clinical response in symptoms, p <0.005 after pleurodesis. At the evaluation of the radiological response, 66.6 percent patients treated with bleomycin had a complete resolution. Conclusions: Good clinical-radiological response was achieved with similar chemical pleurodesis between both treatment modalities. Better results and fewer adverse reactions were obtained with intrapleural bleomycin(AU)


Subject(s)
Humans , Male , Female , Bleomycin/therapeutic use , Pleural Effusion, Malignant/drug therapy , Lung Neoplasms/etiology , Observational Study
8.
Rev. méd. Chile ; 147(4): 437-443, abr. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1014244

ABSTRACT

Background: Hodgkin lymphoma has a high rate of curability, even in advanced stages. Aim: To assess the results of Hodgkin lymphoma treatment using the ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy regimen. Material and Methods: Analysis of a database held by the Chilean Ministry of Health, including all patients treated at accredited cancer treatment centers. Results: Data for 915 patients, median age 35 years (range 15-86 years) and followed for a median of 97 months (range 1-347 months) were analyzed. Forty-one percent had localized disease. Overall survival at five years for localized and advanced stages was 92% and 74%, respectively. The figures for progression free survival were 87% and 64%, respectively. Patients with relapse who received autologous stem cell transplantation (ASCT) had a five year overall survival of 92%, compared to 64% among those who did not undergo this procedure (p < 0.01). The Guarantees in Health Program set up by the Ministry of Health, was associated with earlier stage disease at diagnosis. Conclusions: The ABVD regimen achieves high rates of cure in localized stages of the disease but the results in advanced stages are not optimal. ASCT significantly improves survival in patients with relapse. The Guarantees in Health Program is associated with earlier diagnosis of the disease.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Hodgkin Disease/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Time Factors , Vinblastine/therapeutic use , Bleomycin/therapeutic use , Hodgkin Disease/mortality , Hodgkin Disease/pathology , Doxorubicin/therapeutic use , Chile , Treatment Outcome , Hematopoietic Stem Cell Transplantation/methods , Disease-Free Survival , Dacarbazine/therapeutic use , Kaplan-Meier Estimate
9.
Prensa méd. argent ; 105(1): 41-46, mar 2019.
Article in Spanish | LILACS, BINACIS | ID: biblio-1026344

ABSTRACT

This article details the treatment of lymphangioma of the face with intralesional bleomycin: with a case report and literature review. Surgical treatment of lymphangioma of the face is a difficult task to achieve, due to close vicinity of the lesion to the facial nerve and possibility of scar tissue formation. Inefficient surgical removals generally will give rise to high recurrence rates because of infiltrative and diffuse extension of the lesion. However, complete cure has been described by non-surgical methods with intralesional bleomycin injection under ultrasonographic guidance. Lymphangioma is a rare congenital malformation of the lymphatic system, frequently seen in the head and neck. Percutaneous sclerotherapy of lymphangioma involves the injection of sclerosing substances into the lymphangioma. This study aims to evaluate the effectiveness of intralesional bleomycin sclerotherapy in the treatment of lymphangioma, and to determine the incidence of complications in the treatment. Intralesional bleomycin therapy was very effective in the treatment of lymphangioma. Bleomycin administered as intralesional injection was found to be safe as there was no lesions complicating or side effects observed in the study.


Subject(s)
Humans , Female , Adolescent , Bleomycin/therapeutic use , Sclerotherapy , Facial Injuries/therapy , Lymphangioma/therapy
10.
Int. braz. j. urol ; 45(1): 74-82, Jan.-Feb. 2019. tab, graf
Article in English | LILACS | ID: biblio-989965

ABSTRACT

ABSTRACT Purpose: The current first - line treatment for non - seminomatous germ cell tumor (NSGCT) consists of four cycles of cisplatin, etoposide, and bleomycin (BEP), which results in 5 - year overall survival < 60% in patients with poor - risk features. Autologous hematopoietic stem cell transplantation (auto - HSCT) as a method for overcoming high toxicity after high dose chemotherapy (HDC) has been explored in different solid tumors, but has remained standard practice only for NSGCT. Our objective was to describe outcomes of patients with poor - risk NSGCT who underwent first - line autologous HSCT in a tertiary center in Mexico. Patients and Methods: Twenty nine consecutive patients with NSGCT who received first - line, non - cryopreserved autologous HSCT at the National Institute of Medical Sciences and Nutrition Salvador Zubiran in Mexico City, Mexico, from November 1998 to June 2016, were retrospectively analyzed. Results: The median age at transplantation was 23 (15 - 39) years. Most patients (n = 18, 62%) had testicular primary tumor, and 23 had metastases (79%). Complete response after auto - HSCT was observed in 45%. Non - relapse mortality was 0. Five - year relapse / progression free and overall survival were 67% and 69%, respectively. Conclusions: This small single limited - resource institution study demonstrated that patients with poor - risk NSGCT are curable by first - line HDC plus autologous HSCT and that this procedure is feasible and affordable to perform using non - cryopreserved hematopoietic stem cells.


Subject(s)
Testicular Neoplasms/therapy , Bleomycin/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cisplatin/administration & dosage , Neoplasms, Germ Cell and Embryonal/therapy , Hematopoietic Stem Cell Transplantation/methods , Etoposide/administration & dosage , Retrospective Studies , Treatment Outcome , Combined Modality Therapy , Kaplan-Meier Estimate
11.
Article in Chinese | WPRIM | ID: wpr-776551

ABSTRACT

OBJECTIVE@#To investigate the effects of Yiqi Huayu Hutan decoction on pulmonary fibrosis of rats which induced by bleomycin.@*METHODS@#The rat model of pulmonary fibrosis was induced by intratracheal injection of bleomycin hydrochloride (5 mg/kg). Sixty SD rats were randomly divided into the normal group (group N), the model group (group M), the positive control group (group Y), group of low concentration (group LC), group of medium concentration (group MC) and group of high concentration of Yiqi Huayu Hutan decoction (group HC). After 4 weeks, the experimental groups were treated with low concentration decoction, medium concentration decoction and high concentration decoction respectively, and the Y group was treated with hydrocortisone acetate, the Group N and group M were treated with saline by intragastric administration. Twelve weeks later, rats were killed and the pathomorphism of pulmonary tissues of each group was observed by HE staining and Masson staining. Further, the expressions of transforming growth factor-β1(TGF-β1), Snail1, E-cadherin and Fibronectin in pulmonary tissues of each group were detected by qTR-PCR and Western blot.@*RESULTS@#Compared with the model group, the collagen sediment in the interstitial was reduced in the experimental groups, especially in the group of medium concentration, which was observed by HE staining and Masson staining .Compared with the model group, the expressions of TGF-β1, Snail1 and Fibronectin protein in pulmonary tissues of the treatment groups were decreased in the experimental group, especially in the group of medium concentration, which were detected by qRT-PCR and Western blot.@*CONCLUSION@#Yiqi Huayu Hutan decoction can significantly improve the pulmonary fibrosis which is induced by bleomycin, and the mechanism is related to the inhibition of the expression of TGF-β/Snail pathway of transcription TGF-β1.


Subject(s)
Animals , Bleomycin , Cadherins , Metabolism , Drugs, Chinese Herbal , Pharmacology , Fibronectins , Metabolism , Idiopathic Pulmonary Fibrosis , Drug Therapy , Lung , Metabolism , Pathology , Random Allocation , Rats , Rats, Sprague-Dawley , Snail Family Transcription Factors , Metabolism , Transforming Growth Factor beta1 , Metabolism
12.
Article in Chinese | WPRIM | ID: wpr-776499

ABSTRACT

OBJECTIVE@#To study the preventive and therapeutic effects of safflower water extract on systemic scleroderma (SSc) in mice and its mechanism.@*METHODS@#Sixty BALB/C mice were randomly divided into the control group, model group, prednisone group and safflower low, middle, high dose groups, 10 mice in each group.The control group was injected with normal saline, and the other five groups were subcutaneously injected with bleomycin hydrochloride with 100 μl at the concentration of 200 μg /ml on the back, once a day for 28 days to establish the SSc models.At the same time, the control group and model group were treated with normal saline (10 ml/kg), the prednisone group was treated with prednisone 4.5 mg/kg (10 ml/kg), and the low, middle, and high dose safflower groups were treated with safflower at the doses of 1.5, 3, 6 g/kg (10 ml/kg), and all groups were treated for 28 days.After 28 days, all mice were decapitated. The blood samples and back skin of the BLM injection part were collected.After that, all the tissue slices were taken to measure the dermal thickness, and the content of hydroxyproline (HYP) in the skin tissues was detected by hydrolysis method.The contents of tissue growth factor (CTGF) and transforming growth factor-β (TGF-β ) in the skin tissues and the levels of interleukin-6 (IL-6) and interleukin-17 (IL-17) in serum were determined by ELISA.@*RESULTS@#Compared with the control group, the dermal thickness of the model group was increased(P<0.05), the contents of CTGF, TGF-β and HYP in the skin tissues and the levels of IL-6 and IL-17 in the serum of the model group were increased(P<0.05); compared with the model group, the dermal thickness in the prednisone group and safflower groups was decreased (P<0.05), the levels of CTGF, TGF-β and HYP in the skin tissues and the serum levels of IL-6 and IL-17 in the prednisone group and safflower groups were decreased (P<0.05).@*CONCLUSION@#Safflower water extract can improve skin condition (or dermal thickness) in SSc mice, and its mechanism may be related to reducing immune inflammatory response.


Subject(s)
Animals , Bleomycin , Carthamus tinctorius , Chemistry , Connective Tissue Growth Factor , Metabolism , Disease Models, Animal , Hydroxyproline , Interleukin-17 , Metabolism , Interleukin-6 , Metabolism , Mice , Mice, Inbred BALB C , Plant Extracts , Pharmacology , Random Allocation , Scleroderma, Systemic , Drug Therapy , Skin , Pathology , Transforming Growth Factor beta1 , Metabolism
13.
Article in English | WPRIM | ID: wpr-763012

ABSTRACT

Sphingosine 1-phosphate (S1P) levels are often found to be elevated in serum, bronchoalveolar lavage, and lung tissue of idiopathic pulmonary fibrosis patients and experimental mouse models. Although the roles of sphingosine kinase 1 and S1P receptors have been implicated in fibrosis, the underlying mechanism of fibrosis via Sphingosine 1-phosphate receptor 2 (S1P₂) has not been fully investigated. Therefore, in this study, the roles of S1P₂ in lung inflammation and fibrosis was investigated by means of a bleomycin-induced lung fibrosis model and lung epithelial cells. Bleomycin was found to induce lung inflammation on day 7 and fibrosis on day 28 of treatment. On the 7(th) day after bleomycin administration, S1P₂ deficient mice exhibited significantly less pulmonary inflammation, including cell infiltration and pro-inflammatory cytokine induction, than the wild type mice. On the 28(th) day after bleomycin treatment, severe inflammation and fibrosis were observed in lung tissues from wild type mice, while lung tissues from S1P₂ deficient mice showed less inflammation and fibrosis. Increase in TGF-β1-induced extracellular matrix accumulation and epithelial-mesenchymal transition were inhibited by JTE-013, a S1P₂ antagonist, in A549 lung epithelial cells. Taken together, pro-inflammatory and pro-fibrotic functions of S1P₂ were elucidated using a bleomycin-induced fibrosis model. Notably, S1P₂ was found to mediate epithelial-mesenchymal transition in fibrotic responses. Therefore, the results of this study indicate that S1P₂ could be a promising therapeutic target for the treatment of pulmonary fibrosis.


Subject(s)
Animals , Bleomycin , Bronchoalveolar Lavage , Epithelial Cells , Epithelial-Mesenchymal Transition , Extracellular Matrix , Fibrosis , Humans , Idiopathic Pulmonary Fibrosis , Inflammation , Lung , Mice , Phosphotransferases , Pneumonia , Pulmonary Fibrosis , Receptors, Lysosphingolipid , Sphingosine
14.
Article in English | WPRIM | ID: wpr-719618

ABSTRACT

BACKGROUND: Transforming growth factor β (TGF-β), retinoic acid (RA), p38 mitogen-activated protein kinase (MAPK), and MEK signaling play critical roles in cell differentiation, proliferation, and apoptosis. We investigated the effect of RA and the role of these signaling molecules on the phosphorylation of Smad2/3 (p-Smad2/3) induced by TGF-β1. METHODS: A549 epithelial cells and CCD-11Lu fibroblasts were incubated and stimulated with or without all-trans RA (ATRA) and TGF-β1 and with MAPK or MEK inhibitors. The levels of p-Smad2/3 were analyzed by western blotting. For animal models, we studied three experimental mouse groups: control, bleomycin, and bleomycin+ATRA group. Changes in histopathology, lung injury score, and levels of TGF-β1 and Smad3 were evaluated at 1 and 3 weeks. RESULTS: When A549 cells were pre-stimulated with TGF-β1 prior to RA treatment, RA completely inhibited the p-Smad2/3. However, when A549 cells were pre-treated with RA prior to TGF-β1 stimulation, RA did not completely suppress the p-Smad2/3. When A549 cells were pre-treated with MAPK inhibitor, TGF-β1 failed to phosphorylate Smad2/3. In fibroblasts, p38 MAPK inhibitor suppressed TGF-β1-induced p-Smad2. In a bleomycin-induced lung injury mouse model, RA decreased the expression of TGF-β1 and Smad3 at 1 and 3 weeks. CONCLUSION: RA had inhibitory effects on the phosphorylation of Smad induced by TGF-β1 in vitro, and RA also decreased the expression of TGF-β1 at 1 and 3 weeks in vivo. Furthermore, pre-treatment with a MAPK inhibitor showed a preventative effect on TGF-β1/Smad phosphorylation in epithelial cells. As a result, a combination of RA and MAPK inhibitors may suppress the TGF-β1-induced lung injury and fibrosis.


Subject(s)
Animals , Apoptosis , Bleomycin , Blotting, Western , Cell Differentiation , Epithelial Cells , Fibroblasts , Fibrosis , In Vitro Techniques , Lung Injury , Mice , Mitogen-Activated Protein Kinase Kinases , Mitogen-Activated Protein Kinases , Models, Animal , p38 Mitogen-Activated Protein Kinases , Phosphorylation , Protein Kinases , Smad Proteins , Transforming Growth Factor beta , Transforming Growth Factors , Tretinoin
15.
Article in English | WPRIM | ID: wpr-742449

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis involves irreversible alveolar destruction. Although alveolar epithelial type II cells are key functional participants within the lung parenchyma, how epithelial cells are affected upon bleomycin (BLM) exposure remains unknown. In this study, we determined whether BLM could induce cell cycle arrest via regulation of Schlafen (SLFN) family genes, a group of cell cycle regulators known to mediate growth-inhibitory responses and apoptosis in alveolar epithelial type II cells. METHODS: Mouse AE II cell line MLE-12 were exposed to 1–10 µg/mL BLM and 0.01–100 µM baicalein (Bai), a G1/G2 cell cycle inhibitor, for 24 hours. Cell viability and levels of pro-inflammatory cytokines were analyzed by MTT and enzyme-linked immunosorbent assay, respectively. Apoptosis-related gene expression was evaluated by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Cellular morphology was determined after DAPI and Hoechst 33258 staining. To verify cell cycle arrest, propidium iodide (PI) staining was performed for MLE-12 after exposure to BLM. RESULTS: BLM decreased the proliferation of MLE-12 cells. However, it significantly increased expression levels of interleukin 6, tumor necrosis factor α, and transforming growth factor β1. Based on Hoechst 33258 staining, BLM induced condensation of nuclear and fragmentation. Based on DAPI and PI staining, BLM significantly increased the size of nuclei and induced G2/M phase cell cycle arrest. Results of qRT-PCR analysis revealed that BLM increased mRNA levels of BAX but decreased those of Bcl2. In addition, BLM/Bai increased mRNA levels of p53, p21, SLFN1, 2, 4 of Schlafen family. CONCLUSION: BLM exposure affects pulmonary epithelial type II cells, resulting in decreased proliferation possibly through apoptotic and cell cycle arrest associated signaling.


Subject(s)
Animals , Apoptosis , Bisbenzimidazole , Bleomycin , Cell Cycle Checkpoints , Cell Cycle , Cell Line , Cell Survival , Cytokines , Enzyme-Linked Immunosorbent Assay , Epithelial Cells , Gene Expression , Genes, vif , Humans , Idiopathic Pulmonary Fibrosis , Interleukin-6 , Lung , Mice , Propidium , RNA, Messenger , Transforming Growth Factors , Tumor Necrosis Factor-alpha
16.
Neurointervention ; : 53-60, 2019.
Article in English | WPRIM | ID: wpr-741673

ABSTRACT

PURPOSE: We analyzed results of percutaneous sclerotherapy for venous malformations (VMs) in head, neck and extremities. MATERIALS AND METHODS: Thirty-five patients with head and neck and extremities VM treated by sclerotherapy with bleomycin and sodium tetradecyl sulphate (STS) were retrospectively reviewed. A pre-treatment magnetic resonance imaging was done for all patients to diagnose the lesion. Each lesion received 1 to 11 sessions (average, 2.7; standard deviation [SD], 2.03). We evaluated percentage reduction in swelling size and a Likert scale review of subjective feelings of the patients. RESULTS: Sixteen had a complete obliteration; by sclerotherapy alone (n=13) and surgery after a 75% reduction (n=3). Ten patients had a significant reduction up to 75% and three patients by 50%. Four had a minimal decrease with reduction of 25% or less. Follow-up duration of the patients varied from a minimum of 6 months up to 3 years (average, 15.7 months; SD, 7.8 months). Of all patients, three refused further treatment and were lost to follow-up, while another two were referred to a dermatologist. Thirteen patients reported feeling excellent after the sessions. Eight patients claimed to feel slightly better compared to before the sessions started. Only three patients complained of feeling the same before and after the sessions. None of the patients still in follow-up have reported a recurrence of a lesion thus far. CONCLUSION: Sclerotherapy using bleomycin and STS as sclerosants is a safe and effective primary treatment for VMs in the head and neck as well as in extremities.


Subject(s)
Bleomycin , Extremities , Follow-Up Studies , Head , Humans , Lost to Follow-Up , Magnetic Resonance Imaging , Neck , Recurrence , Retrospective Studies , Sclerosing Solutions , Sclerotherapy , Sodium , Vascular Malformations
17.
Article in English | WPRIM | ID: wpr-759745

ABSTRACT

A 40-year-old man presented with pruritic, multiple, variable-sized, erythematous umbilicated papules on the trunk and both extremities for 4 months. He was diagnosed with Hodgkin's lymphoma (stage IIA) after histopathologic examination of a neck mass that developed a month ago. A punch biopsy was performed on his right lower leg. Histological examination showed transepidermal elimination of the degenerated collagen. Masson's trichrome staining was performed to distinguish collagen fibers from the muscular tissue; using Masson's stain, the collagen appeared as a bluish color crossing from the dermis to the epidermis. The diagnosis of acquired reactive perforating collagenosis was made. The skin lesions showed much improvement after 6 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy. Acquired perforating disorders are a group of cutaneous disorders that occur in adults with chronic kidney disease or diabetes mellitus. Cases of acquired perforating disorders associated with Hodgkin's lymphoma have been rarely reported in the English literature. To our knowledge, this is the first case of acquired reactive perforating collagenosis in a Korean patient with Hodgkin's lymphoma.


Subject(s)
Adult , Biopsy , Bleomycin , Collagen , Dacarbazine , Dermis , Diabetes Mellitus , Diagnosis , Doxorubicin , Drug Therapy , Epidermis , Extremities , Hodgkin Disease , Humans , Leg , Neck , Renal Insufficiency, Chronic , Skin , Vinblastine
18.
Rev. chil. pediatr ; 89(2): 257-260, abr. 2018. graf
Article in Spanish | LILACS | ID: biblio-900096

ABSTRACT

INTRODUCCIÓN: La Dermatitis Flagelada es una patología infrecuente, con lesiones cutáneas características, que se desarrolla por el uso de Bleomicina. Clínicamente se presenta como maculas eritematosas o hiperpigmentadas de disposición lineal con patrón flagelar, en tronco y/o extremidades superiores. Presenta evolución autolimitada por lo que su tratamiento varía desde conducta expectante hasta uso de corticoides tópicos u orales. OBJETIVO: Presentación de un caso clínico de Dermatitis flagelada secundaria a Bleomicina en paciente pediátrico con antecedentes de neoplasia de sistema nervioso central. CASO CLÍNICO: Escolar de 8 años, sexo femenino, con antecedentes de tumor prima rio de células germinales mixto intracraneal (selar y supraselar) y panhipopituitarismo secundario. Recibe tratamiento quimioterapéutico según protocolo PEB, con uso de Bleomicina EV por 3 días. A los 2 días posteriores, inicia prurito intermitente, asociado a máculas eritematosas y pigmentadas de distribución lineal, siguiendo patrón flagelado, con aislados signos de excoriación, en región abdominal y dorso alto. Se indica tratamiento tópico con corticoides de moderada potencia por 10 días, con respuesta clínica satisfactoria. CONCLUSIONES: Se debe tener una alta sospecha diagnóstica en pacientes pediátricos con historia de administración previa del fármaco y aparición de lesiones cutáneas características, lo que permitirá una conducta adecuada respecto a su manejo y a la continuidad de la quimioterapia.


INTRODUCTION: Flagellated dermatitis is an infrequent pathology, with characteristic skin lesions, which is developed due to the use of bleomycin. Clinically it occurs as erythematous or hyperpigmented maculae of linear disposition with flagellar pattern, in trunk and/or upper extremities. It presents self-limited evolution, therefore, its treatment varies from expectant management to the use of topical or oral corticosteroids. OBJECTIVE: Presentation of a clinical case of flagellated dermatitis secondary to bleomycin in a pediatric patient with history of central nervous system neoplasia. CLINICAL CASE: 8 years, schoolchild, female, with a history of primary intracranial mixed germ cell tumor (sellar and suprasellar) and secondary panhypopituitarism. She receives chemotherapeutic treatment according to the PEB protocol, with use of IV bleomycin during three days. After two days, intermittent pruritus begins, associated with erythematous and pigmented maculae of linear distribution, followed by a flagellated pattern, with isolated signs of excoriation, in the abdominal region and upper back. Topical treatment with mild potency corticosteroids is indicated for ten days, with a satisfactory clinical response. CONCLUSIONS: There should be a high diagnostic suspi cion in pediatric patients with a history of prior administration of the drug and the appearance of characteristic skin lesions, which will allow adequate behavior regarding its management and the continuity of chemotherapy.


Subject(s)
Humans , Female , Child , Bleomycin/adverse effects , Drug Eruptions/diagnosis , Antibiotics, Antineoplastic/adverse effects , Drug Eruptions/etiology
19.
Rev. méd. Chile ; 146(4): 523-527, abr. 2018. graf
Article in Spanish | LILACS | ID: biblio-961424

ABSTRACT

Toxic epidermal necrolysis (TEN) is a lethal entity, characterized by extensive epidermal necrosis and multiorgan failure. Hemophagocytic syndrome (HFS) is also a rare and lethal syndrome characterized by hyperinflammation that leads to the appearance of fever, pancytopenia, organomegaly and hemophagocytosis. The concomitance of these diseases is extremely uncommon. We report a 38 years old female, who during the course of a HFS secondary to Hodgkin Lymphoma (HL), presented a TEN secondary to antibiotics. She was admitted due to a consumptive syndrome, lymphadenopathy, visceromegaly and severe pancytopenia. Laboratory and bone marrow tests confirmed HFS. Due to constant fever, imipenem was indicated. On the third day she started with pain and skin rash. She evolved with positive Nikolsky sign. Cutaneous biopsy was concordant with extensive TEN, which was managed with intravenous immunoglobulin and dexamethasone. A complete response and normalization of the blood count were achieved. Finally, the lymph node biopsy showed HL of mixed cellularity type, which was managed with 8 cycles of ABVD chemotherapy, achieving complete remission.


Subject(s)
Humans , Female , Adult , Hodgkin Disease/complications , Stevens-Johnson Syndrome/etiology , Lymphohistiocytosis, Hemophagocytic/etiology , Vinblastine , Bleomycin , Hodgkin Disease/pathology , Hodgkin Disease/drug therapy , Antineoplastic Combined Chemotherapy Protocols , Doxorubicin , Imipenem/adverse effects , Stevens-Johnson Syndrome/pathology , Stevens-Johnson Syndrome/drug therapy , Treatment Outcome , Dacarbazine , Lymphohistiocytosis, Hemophagocytic/pathology , Lymphohistiocytosis, Hemophagocytic/drug therapy , Anti-Bacterial Agents/adverse effects
20.
Clinics ; 73: e433, 2018. tab, graf
Article in English | LILACS | ID: biblio-974931

ABSTRACT

OBJECTIVES: This retrospective study performed a comprehensive analysis of the usage of intra-arterial chemotherapy (iaCh) for locally recurrent UICC stage IV oral squamous cell carcinoma (OSCC) over two decades at the Department of Cranio-Maxillofacial and Oral Surgery at the University Hospital Vienna to assess the utility of its future use. METHODS: Between 1994 and 2014, iaCh was indicated in 48 OSCC cases. In these, the two most frequent iaCh schemes, cisplatin/5-fluorouracil (Cis/5-FU) and methotrexate/bleomycin (MTX/Bleo), were chosen for further analysis. The effect on survival of two distinct intra-arterial protocols and their covariates were analyzed with the Kaplan-Meier method as well as univariate and multivariate Cox proportional hazard regression models. RESULTS: The mean follow-up period was 29.91 months. The two intra-arterial chemotherapy groups did not differ significantly in sample size, demographic data or therapeutic covariates. The Cis/5-FU iaCh regimen was associated with significantly better overall survival (median OS 2.6 years vs. 1.3 years; p=0.002) and had a beneficial effect on survival (HR=3.62, p=0.015). Side effects occurred at a frequency similar to that described in the literature for intravenous chemotherapy (ivCh). CONCLUSIONS: These results suggest a preference for administering Cis/5-FU for iaCh. Nevertheless, due to economic considerations in healthcare expenditures, there is no future for iaCh in the treatment of head and neck carcinomas because ivCh is known to be equivalent.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Young Adult , Mouth Neoplasms/drug therapy , Carcinoma, Squamous Cell/drug therapy , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bleomycin/administration & dosage , Infusions, Intra-Arterial , Methotrexate/administration & dosage , Retrospective Studies , Cisplatin/administration & dosage , Treatment Outcome , Kaplan-Meier Estimate , Fluorouracil/administration & dosage , Neoplasm Recurrence, Local , Neoplasm Staging
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