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1.
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
2.
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
3.
Rev. Inst. Nac. Hig ; 50(1-2): 14-21, Diciembre 2019. tab
Article in Spanish | LILACS, LIVECS | ID: biblio-1118362

ABSTRACT

El Paraquat (PQ) es un herbicida de contacto bipiridilico ampliamente utilizado en agricultura. La intoxicación en humanos por este agente ocasiona fibrosis pulmonar. Evaluamos los cambios histológicos pulmonares de ratas intoxicadas con PQ y tratadas con N-aceticisteina (NAC) administrada vía inhalatoria. Realizamos un estudio experimental descriptivo con 25 ratas adultas, machos cepa Wistar, divididas en cinco grupos. Al grupo I no se les administro ni PQ ni NAC. Grupo II, recibió NAC inhalada a 15mg/kg diaria c/12 horas. Grupo III, PQ vía oral (VO) 15mg/kg. Grupo IV, PQ a 15mg/kg, por VO y a la hora NAC 150mg/kg. Grupo V, PQ a 15mg/kg, por VO y a las seis horas NAC dosis de 150mg/kg. Los pulmones fueron extraídos y se evaluaron mediante cortes histológicos. Resultados: Los grupos I y II (supervivencia del 100%, n=10) no desarrollaron sintomatología de intoxicación. Grupos III, IV y V predominaron síntomas respiratorios, diversos grados de edema pulmonar, enfisema, congestión vascular y hemorragia intra-alveolar focal. La eficacia de la NAC sobre la intoxicación por PQ en términos de sobrevivencia al primer día, fue del 100% y al segundo día, fue del 80% (p= 0,005; prueba Chi-cuadrado). El PQ indujo un proceso inflamatorio (agudo-crónico) por infiltrado de segmentados neutrófilos y linfocitos, lo cual fue revertido parcialmente por la administración inhalada de NAC. Conclusión: Los cambios histopatológicos observados a nivel pulmonar fueron aminorados por el tratamiento con NAC, lo que sugiere un posible efecto protector de este fármaco sobre el daño oxidativo inducido por el herbicida


Paraquat (PQ) is a bipyridyl contact herbicide widely used in agriculture. Intoxication in humans by this agent causes pulmonary fibrosis. We evaluated pulmonary histological changes of rats intoxicated with PQ and treated with N-acetycysteine (NAC) administered via inhalation. We conducted a descriptive experimental study with 25 adult rats, male Wistar strain, divided into five groups. Group I was not administered PQ or NAC. Group II, received NAC inhaled at 15mg/kg daily c/12 hours. Group III, PQ orally (VO) 15mg/ kg. Group IV, PQ at 15mg/kg, by VO and at hour NAC 150mg/ kg. Group V, PQ at 15mg/kg, by VO and at six hours NAC dose of 150mg/kg. The lungs were extracted and evaluated by histological sections. Results: Groups I and II (100% survival, n=10) did not develop intoxication symptoms. Groups III, IV and V predominantly respiratory symptoms, various degrees of pulmonary edema, emphysema, vascular congestion and focal intra-alveolar hemorrhage. The efficacy of NAC on PQ poisoning in terms of survival on the first day was 100% and on the second day it was 80% (p = 0.005, Chi-square test). The PQ induced an inflammatory process (acute-chronic) by infiltration of segmented neutrophils and lymphocytes, which was partially reversed by the inhaled administration of NAC. Conclusion: The histopathological changes observed at the pulmonary level were reduced by the treatment with NAC, which suggests a possible protective effect of this drug on the oxidative damage induced by the herbicide.


Subject(s)
Animals , Male , Rats , Paraquat/poisoning , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , Acetylcysteine/therapeutic use , Free Radical Scavengers/therapeutic use , Herbicides/poisoning , Paraquat/administration & dosage , Acetylcysteine/administration & dosage , Time Factors , Administration, Inhalation , Survival Analysis , Free Radical Scavengers/administration & dosage , Treatment Outcome , Rats, Wistar , Models, Animal , Herbicides/administration & dosage
4.
Rev. méd. Chile ; 146(7): 938-941, jul. 2018. tab, graf
Article in Spanish | LILACS | ID: biblio-961482

ABSTRACT

Paraquat, a non-selective bipyridyl pesticide, is one of the leading causes of death from intoxication in many parts of Asia and America. It is the second most sold herbicide worldwide, being widely used in Chile. Its ingestion generates toxicity due to the release of superoxide radicals, mainly affecting kidneys, lungs and liver. There is no antidote available. We report a 31 years old male who ingested Paraquat for suicidal purposes. He developed an acute renal and hepatic failure and a rapidly progressive severe respiratory failure with images compatible with acute pulmonary fibrosis. No response to immunosuppressive treatment was observed. He died eight days after admission. The use of cyclophosphamide associated with glucocorticoids could lower risk of death the in these patients, although the pathophysiology of respiratory failure is still under study.


Subject(s)
Humans , Male , Adult , Paraquat/poisoning , Pulmonary Fibrosis/chemically induced , Herbicides/poisoning , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/diagnostic imaging , Suicide , Methylprednisolone/therapeutic use , Chile , Fatal Outcome , Cyclophosphamide/therapeutic use , Glucocorticoids/therapeutic use , Immunosuppressive Agents/therapeutic use
5.
Braz. j. med. biol. res ; 48(6): 545-552, 06/2015. tab, graf
Article in English | LILACS | ID: lil-748222

ABSTRACT

Abnormal high mobility group protein B1 (HMGB1) activation is involved in the pathogenesis of pulmonary fibrosis. Pulmonary rehabilitation mixture (PRM), which combines extracts from eight traditional Chinese medicines, has very good lung protection in clinical use. However, it is not known if PRM has anti-fibrotic activity. In this study, we investigated the effects of PRM on transforming growth factor-β1 (TGF-β1)-mediated and bleomycin (BLM)-induced pulmonary fibrosis in vitro and in vivo. The effects of PRM on TGF-β1-mediated epithelial-mesenchymal transition (EMT) in A549 cells, on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on BLM-induced pulmonary fibrosis in vivo were investigated. PRM treatment resulted in a reduction of EMT in A549 cells that was associated with attenuating an increase of vimentin and a decrease of E-cadherin. PRM inhibited the proliferation of HLF-1 at an IC50 of 0.51 µg/mL. PRM ameliorated BLM-induced pulmonary fibrosis in rats, with reduction of histopathological scores and collagen deposition, and a decrease in α-smooth muscle actin (α-SMA) and HMGB1 expression. An increase in receptor for advanced glycation end-product (RAGE) expression was found in BLM-instilled lungs. PRM significantly decreased EMT and prevented pulmonary fibrosis through decreasing HMGB1 and regulating RAGE in vitro and in vivo. PRM inhibited TGF-β1-induced EMT via decreased HMGB1 and vimentin and increased RAGE and E-cadherin levels. In summary, PRM prevented experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway.


Subject(s)
Animals , Humans , Male , Drugs, Chinese Herbal/pharmacology , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/prevention & control , Antibiotics, Antineoplastic , Receptor for Advanced Glycation End Products/drug effects , Apoptosis/drug effects , Bleomycin , Blotting, Western , Cells, Cultured , Collagen/drug effects , Complex Mixtures/pharmacology , Drugs, Chinese Herbal/therapeutic use , Epithelial-Mesenchymal Transition/drug effects , Fibroblasts/drug effects , HMGB1 Protein/drug effects , Hydroxyproline/analysis , Immunohistochemistry , Lung/drug effects , Lung/pathology , Platelet-Derived Growth Factor/drug effects , Pulmonary Fibrosis/pathology , Random Allocation , Rats, Sprague-Dawley , Reproducibility of Results , Transforming Growth Factor beta1/drug effects
6.
Article in English | WPRIM | ID: wpr-62924

ABSTRACT

Pulmonary fibrosis is a fatal progressive disease with no effective therapy. Transforming growth factor (TGF)-beta1 has long been regarded as a central mediator of tissue fibrosis that involves multiple organs including skin, liver, kidney, and lung. Thus, TGF-beta1 and its signaling pathways have been attractive therapeutic targets for the development of antifibrotic drugs. However, the essential biological functions of TGF-beta1 in maintaining normal immune and cellular homeostasis significantly limit the effectiveness of TGF-beta1-directed therapeutic approaches. Thus, targeting downstream mediators or signaling molecules of TGF-beta1 could be an alternative approach that selectively inhibits TGF-beta1-stimulated fibrotic tissue response while preserving major physiological function of TGF-beta1. Recent studies from our laboratory revealed that TGF-beta1 crosstalk with epidermal growth factor receptor (EGFR) signaling by induction of amphiregulin, a ligand of EGFR, plays a critical role in the development or progression of pulmonary fibrosis. In addition, chitotriosidase, a true chitinase in humans, has been identified to have modulating capacity of TGF-beta1 signaling as a new biomarker and therapeutic target of scleroderma-associated pulmonary fibrosis. These newly identified modifiers of TGF-beta1 effector function significantly enhance the effectiveness and flexibility in targeting pulmonary fibrosis in which TGF-beta1 plays a significant role.


Subject(s)
Animals , Drug Design , Hexosaminidases/antagonists & inhibitors , Humans , Lung/drug effects , Molecular Targeted Therapy , Pulmonary Fibrosis/drug therapy , Receptor Cross-Talk , ErbB Receptors/antagonists & inhibitors , Receptors, Transforming Growth Factor beta/antagonists & inhibitors , Signal Transduction , Transforming Growth Factor beta1/antagonists & inhibitors
7.
Article in English | WPRIM | ID: wpr-228626

ABSTRACT

Glucocorticosteroid-induced osteoporosis is the most frequent of all secondary types of osteoporosis, and can increase the risk of vertebral compression fractures (VCFs). There are promising additions to current medical treatment for appropriately selected osteoporotic patients. Few studies have reported on the efficiency of percutaneous vertebroplasty (PVP) or kyphoplasty for whole thoracic and lumbar glucocorticosteroid-induced osteoporotic vertebral compression fractures. We report a case of a 67-year-old man with intractable pain caused by successional VCFs treated by PVP.


Subject(s)
Aged , Arthritis, Rheumatoid/drug therapy , Fractures, Compression/diagnostic imaging , Glucocorticoids/adverse effects , Humans , Kyphoplasty , Lumbar Vertebrae/diagnostic imaging , Male , Osteoporosis/chemically induced , Pulmonary Fibrosis/drug therapy , Thoracic Vertebrae/diagnostic imaging , Vertebroplasty
8.
Yonsei Medical Journal ; : 437-444, 2013.
Article in English | WPRIM | ID: wpr-89564

ABSTRACT

PURPOSE: The present study was designed to determine whether rapamycin could inhibit transforming growth factor beta1 (TGF-beta1)-induced fibrogenesis in primary lung fibroblasts, and whether the effect of inhibition would occur through the mammalian target of rapamycin (mTOR) and its downstream p70S6K pathway. MATERIALS AND METHODS: Primary normal human lung fibroblasts were obtained from histological normal lung tissue of 3 patients with primary spontaneous pneumothorax. Growth arrested, synchronized fibroblasts were treated with TGF-beta1 (10 ng/mL) and different concentrations of rapamycin (0.01, 0.1, 1, 10 ng/mL) for 24 h. We assessed m-TOR, p-mTOR, S6K1, p-S6K1 by Western blot analysis, detected type III collagen and fibronectin secreting by ELISA assay, and determined type III collagen and fibronectin mRNA levels by real-time PCR assay. RESULTS: Rapamycin significantly reduced TGF-beta1-induced type III collagen and fibronectin levels, as well as type III collagen and fibronectin mRNA levels. Furthermore, we also found that TGF-beta1-induced mTOR and p70S6K phosphorylation were significantly down-regulated by rapamycin. The mTOR/p70S6K pathway was activated through the TGF-beta1-mediated fibrogenic response in primary human lung fibroblasts. CONCLUSION: These results indicate that rapamycin effectively suppresses TGF-beta1-induced type III collagen and fibronectin levels in primary human lung fibroblasts partly through the mTOR/p70S6K pathway. Rapamycin has a potential value in the treatment of pulmonary fibrosis.


Subject(s)
Cells, Cultured , Collagen Type III/metabolism , Fibroblasts/drug effects , Fibronectins/metabolism , Humans , Lung/cytology , Pulmonary Fibrosis/drug therapy , Signal Transduction/drug effects , Sirolimus/pharmacology , TOR Serine-Threonine Kinases/metabolism , Transforming Growth Factor beta1/antagonists & inhibitors
9.
Pulmäo RJ ; 22(1): 46-50, 2013.
Article in Portuguese | LILACS | ID: lil-677125

ABSTRACT

As doenças fibrosantes pulmonares representam um importante desafio considerando seu curso progressivo para insuficiência respiratória e o grave comprometimento da qualidade de vida dos pacientes acometidos. A fibrose pulmonar idiopática (FPI), doença fibrosante mais prevalente, apesar de inúmeras pesquisas na busca de alvos moleculares e novas drogas, permanece sem um tratamento eficaz e seguro.A análise da patogenia da FPI e a avaliação da severidade da doença estão relacionadas às propostas de tratamento medicamentoso. Abordamos o uso das terapias anti-inflamatórias, drogas antifibróticas e antioxidantes, com ênfase no papel atual dos corticosteroides e imunossupressores, na análise do risco do uso das drogas, além de uma revisão de medicamentos de uso recente. Os tratamentos não medicamentosos, outro aspecto importante na condução dos pacientes portadores de fibrose pulmonar, são revistos em seu papel no alívio dos sintomas e na prevenção de complicações, além da elaboração de um paralelo entre a FPI e outras doenças fibrosantes pulmonares. Concluímos que, apesar de não haver uma droga específica plenamente eficaz para o tratamento da FPI, muito pode ser feito para o alívio do paciente, e que o plano terapêutico deve incluir a análise da gravidade da doença e os desejos e necessidades individuais dos pacientes.


Subject(s)
Humans , Male , Female , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/therapy , Physiological Effects of Drugs , Pharmacologic Actions , Respiratory Tract Diseases
10.
Biol. Res ; 45(4): 345-350, 2012. ilus
Article in English | LILACS | ID: lil-668684

ABSTRACT

Statins reduce cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase and have a major place in the treatment of atherosclerotic disease. Recent studies have shown anti-inflammatory properties of statins. The purpose of this study was to evaluate the anti-inflammatory effect of simvastatin on bleomycin (BLM)-induced pulmonary fibrosis in rats. A total of 31 female Sprague-Dawley rats were divided into four groups: (1) intratracheal (IT) phosphate-buffered saline (PBS) + intraperitoneal (IP) PBS (n=7); (2) IT BLM + IP PBS (n=8); (3) IT BLM + low dose (LD) simvastatin (1 mg/kg daily, n=8); (4) IT BLM + high dose (HD) simvastatin (5 mg/kg daily, n=8). Simvastatin was administered IP for 15 days, beginning 1 day prior to IT BLM. The effect of simvastatin on pulmonary fibrosis was studied by measurements of IL-13, PDGF, IFN-γ, TGF-p1 levels in bronchoalveolar lavage (BAL) fluid and lung tissue hydroxyproline (HPL) content and by histopathological examination (Ashcroft score). BLM caused significant change in BAL fluid cytokine levels and increased both HPL content and histopathological score (p<0.001 for all). While LD simvastatin had no effect on cytokine levels, HD significantly reduced IL-13 (15.12 ±7.08 pg/ml vs. 4.43±2.34 pg/mL; p<0.05) and TGF-β1 levels (269.25 ±65.42 pg/mL vs. 131.75±32.65 pg/mL; p<0.05). Neither HD nor LD simvastatin attenuated HPL content or Ashcroft score. In conclusion, this study showed that LD simvastatin had no effect on a BLM-induced pulmonary fibrosis model, while the high dose caused partial improvement in profibrotic cytokine levels.


Subject(s)
Animals , Female , Rats , Anti-Inflammatory Agents/therapeutic use , Pulmonary Fibrosis/drug therapy , Simvastatin/therapeutic use , Bleomycin , Bronchoalveolar Lavage Fluid , Disease Models, Animal , Drug Evaluation, Preclinical , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/pathology , Rats, Sprague-Dawley , Transforming Growth Factor beta1
12.
J. bras. pneumol ; 34(11): 891-899, nov. 2008. ilus, tab
Article in Portuguese | LILACS | ID: lil-623376

ABSTRACT

OBJETIVO: Avaliar a influência do biofármaco DNA-hsp65 em um modelo de distúrbio fibrosante pulmonar experimental. MÉTODOS: Foram estudados 120 camundongos machos C57BL/6, divididos em quatro grupos: grupo SS, animais tratados com salina (placebo) e injetados com salina intratraqueal (IT); grupo SB, tratados com salina (placebo) e injetados com bleomicina IT; grupo PB, tratados com plasmídeo, sem gene bacteriano, e injetados com bleomicina IT; e grupo BB, tratados com DNA-hsp65 e injetados com bleomicina IT. A bleomicina foi injetada 15 dias após a última imunização, e os animais sacrificados seis semanas após o uso da droga IT. O pulmão esquerdo retirado foi utilizado para análise morfológica, e o pulmão direito para dosagens de hidroxiprolina. RESULTADOS: A proporção de camundongos que apresentaram morte não-programada depois de 48 h da injeção IT foi maior no grupo SB em comparação ao grupo SS (57,7% vs. 11,1%). A área percentual média de interstício septal foi maior nos grupos SB e PB (53,1 ± 8,6% e 53,6 ± 9,3%, respectivamente) em comparação aos grupos SS e BB (32,9 ± 2,7% e 34,3 ± 6,1%, respectivamente). Os grupos SB, PB e BB mostraram aumentos nos valores médios da área de interstício septal corada por picrosirius em comparação ao grupo SS (SS: 2,0 ± 1,4%; SB: 8,2 ± 4,9%; PB: 7,2 ± 4,2%; e BB:6,6±4,1%).O conteúdo pulmonar de hidroxiprolina no grupo SS foi inferior ao dos demais grupos (SS: 104,9 ± 20,9 pg/pulmão; SB: 160,4 ±47,8 pg/pulmão; PB:170,0 ± 72,0 pg/pulmão; e BB: 162,5 ± 39,7 pg/pulmão). CONCLUSÕES: A imunização com o biofármaco DNA-hsp65 interferiu na deposição de matriz não-colágena em um modelo de lesão pulmonar induzida por bleomicina.


OBJECTIVE: To evaluate the effects of immunization with a DNA-hsp65 vaccine in an experimental model of pulmonary fibrosis. METHODS: A total of 120 male C57BL/6 mice were distributed into four groups: SS, injected with saline (placebo) and then receiving intratracheal (IT) instillation of saline; SB, injected with saline (placebo) and then receiving IT instillation of bleomycin; PB, treated with plasmid only, without bacterial genome, and then receiving IT instillation of bleomycin; and BB, treated with the vaccine and then receiving IT instillation of bleomycin. Bleomycin was instilled 15 days after the last immunization, and the animals were killed six weeks thereafter. The left and right lungs were removed, the former for morphological analysis and the latter for hydroxyproline measurements. RESULTS: The proportion of deaths within the first 48 h after the IT instillation (deaths attributed to the surgical procedure) was higher in the SB group than in the SS group (57.7% vs. 11.1%). The mean area of pulmonary interstitial septa was greater in the SB and PB groups (53.1 ± 8.6% and 53.6±9.3%, respectively) than in the SS and BB groups (32.9 ± 2.7% and 34.3 ± 6.1%, respectively). The mean area of interstitial septa stained by picrosirius was greater in the SB, PB and BB groups than in the SS group (8.2 ± 4.9%, 7.2 ± 4.2% and 6.6 ± 4.1%, respectively, vs. 2.0±1.4%). The total hydroxyproline content in the lung was significantly lower in the SS group (104.9 ± 20.9 pg/lung) than in the other groups (SB: 160.4 ± 47.8 pg/lung; PB: 170.0 ± 72.0 pg/lung; and BB: 162.5 ± 39.7 pg/lung). CONCLUSIONS: Immunization with the DNA-hsp65 vaccine reduced the deposition of noncollagen matrix in a model of bleomycin-induced lung lesion.


Subject(s)
Animals , Male , Mice , Bacterial Proteins/therapeutic use , Chaperonins/therapeutic use , Pulmonary Fibrosis/drug therapy , Vaccines, DNA/therapeutic use , Antibiotics, Antineoplastic , Bleomycin , Bacterial Proteins/immunology , Chaperonins/immunology , Disease Models, Animal , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/immunology , Random Allocation , Vaccines, DNA/immunology
13.
Pakistan Journal of Medical Sciences. 2008; 24 (6): 813-820
in English | IMEMR | ID: emr-101047

ABSTRACT

To evaluate the protective effect of cetrizine against bleomycin induced pulmonary fibrosis in rats. Male Sprague-Dawley rats [n=30], received an intratracheal injection of bleomycin [7.5 IU/kg] in saline solution for induction of pulmonary fibrosis. Two treatment groups received daily cetirizine five and 20mg/kg/day, seven days before and four weeks after administering a single-dose bleomycin [7.5IU/kg]. The cytokines [IL-8, TNF-alpha, TGF-alpha1] through ELISA kits, the amount of collagen in the lungs [hydroxyproline content], and pharmacological activity of the lung strip tissues were determined. The cytokine levels have been decreased in the treated groups by cetirizine 5 [p< 0.05] and 20 [p<0.01] mg/kg/day, in comparison to positive control group. Cetirizine may have a protective effect against bleomycine induced pulmonary fibrosis as evident by the reduction of the severity of lung tissue changes, collagen amounts and cytokines levels caused by bleomycine in rats lungs tissues


Subject(s)
Male , Animals, Laboratory , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , Bleomycin/adverse effects , Rats, Sprague-Dawley , Protective Agents
14.
J. bras. pneumol ; 32(3): 249-260, maio-jun. 2006. ilus, graf
Article in English | LILACS | ID: lil-446349

ABSTRACT

Embora diagnósticos de fibrose pulmonar idiopática continuem sendo devastadores, avanços recentes têm melhorado nossa compreensão a respeito de muitas das facetas desta doença. Estas descobertas, juntamente com o aumento da disponibilidade geral de ensaios terapêuticos, encerram a promessa de um futuro mais promissor para pacientes com fibrose pulmonar idiopática. Por exemplo, nós temos agora uma compreensão mais abrangente a respeito dos critérios diagnósticos e da história natural da doença. Vários estudos têm mostrado que a mensuração simples da fisiologia pulmonar ou troca gasosa pode ser usada para prever a sobrevida do paciente. Através da identificação de várias vias moleculares que têm papéis importantes na patogênese da fibrose pulmonar idiopática, os pesquisadores têm produzido uma lista crescente de possíveis novos alvos terapêuticos para a doença. Vários ensaios terapêuticos prospectivos e controlados têm sido realizados. Outros estão em andamento ou ainda estão em fase de planejamento. Estes esforços têm avançado nosso conhecimento atual sobre fibrose pulmonar idiopática e levantado novas questões importantes, assim como têm gerado o interesse e o impulso necessários para avançar terreno na luta contra esta doença desafiadora. Este artigo oferece ao leitor um panorama dos avanços recentes nas pesquisas sobre fibrose pulmonar idiopática, tendo como foco a história natural, patogênese e tratamento.


Although idiopathic pulmonary fibrosis remains a devastating diagnosis, recent advances have improved our understanding of many facets of this disease. These breakthroughs, combined with the increased general availability of therapeutic trials, hold the promise of a brighter future for idiopathic pulmonary fibrosis patients. For example, we now have a more comprehensive understanding of the diagnostic criteria and natural history of the disease. Several studies have shown that simple measurement of pulmonary physiology or gas exchange can be used to predict patient survival. By identifying several molecular pathways that play significant roles in the pathogenesis of idiopathic pulmonary fibrosis, investigators have produced a growing list of novel potential therapeutic targets for the disease. Several prospective, controlled therapeutic trials have been conducted. Others are ongoing or are still in the planning stages. These efforts have advanced our current knowledge of idiopathic pulmonary fibrosis and have raised new important questions, as well as having generated the interest and momentum needed to gain additional ground in the fight against this challenging disease. This article offers the reader a view of the recent advances in idiopathic pulmonary fibrosis research, with a focus on natural history, pathogenesis and treatment.


Subject(s)
Humans , Pulmonary Fibrosis , Clinical Trials as Topic , Prognosis , Pulmonary Fibrosis/diagnosis , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/etiology
15.
Egyptian Rheumatology and Rehabilitation. 2003; 30 (3): 311-322
in English | IMEMR | ID: emr-62009

ABSTRACT

Low dose methotrexate [MTX] treatment is used extensively as a second-line therapy in RA. Two forms of interstitial lung diseases are related to low dose MTX therapy, the first is acute methotrexate pneumonitis which is a life-threatening complication that occurs in less than 10% of RA patients treated with MTX. The other interstitial lung affection is chronic pulmonary fibrosis [PF]. To evaluate whether chronic PF can be a significant complication in RA patient treated with low dose methotrexate [MTX]. The study was performed on 40 RA patients who fulfilled the American College of Rheumatology classification criteria for RA, The patients were classified into two separate groups. The first group consisted of 20 RA patients who were being treated with low dose MTX at the time of initial assessment, while the other group comprised another 20 RA patients who were not being treated with MTX, but treated with second-line therapy other than MTX. Pulmonary function tests were performed for all patients at the time of initial assessment using the standard protocol. All patients underwent HRCT chest scanning. Supine views were taken in serial slices 10 mm apart and 1 mm in width. According to the study design, the patients were followed over 18 months from the time of the initial assessment. Clinically, the patients were assessed regularly at time intervals of 3 months particularly for development of any chest illness together with the patient compliance of drug therapy and its effect on disease. Follow up chest radiographs and HRCT were performed at the end point. The age of the patients and disease duration in the MTX group were 52.1+ 2.9 years and 8.9 +/- .2 years respectively while in the other group they were 50.8 +/- 2.1 years and 9.2 +/- 5.1 years respectively. Pulmonary function results at baseline assessment expressed no significant differences between the two groups with p value > 0.05. On initial HRCT chest scanning, 3 patients were found to have PF interstitial lung disease pattern, two of them were being treated with MTX. There was no significant difference in the dose and duration of MTX treatment between the two RA patients treated with MTX and has PF on initial evaluation and those who were being treated with the drug and had no evidence of PF on HRCT on chest scanning at the initial evaluation. Change in pulmonary function tests from the time of initial assessment to the end of the study was not clinically or statistically significant in both groups [p value > 0.05]. Furthermore, there was no clinical or pulmonary function evidence that MTX had any deteriorating effect on PF detected in two patients on initial assessment even when compared with the patients who were not being treated with it. This study showed no clinical, physiological or radiological evidence that low dose MTX treatment used successfully in treatment of RA is associated with chronic fibrotic lung disease


Subject(s)
Humans , Male , Female , Pulmonary Fibrosis/drug therapy , Chronic Disease , Methotrexate , Respiratory Function Tests , C-Reactive Protein , Tomography, X-Ray Computed
17.
Rev. méd. Chile ; 126(11): 1345-53, nov. 1998. tab, graf
Article in Spanish | LILACS | ID: lil-243727

ABSTRACT

Background: Experimental and clinical evidences suggest that colchicine can be effective in the treatment of patients with idiopathic pulmonary fibrosis. Aim: To assess the effect of colchicine in the treatment of idiopathic pulmonary fibrosis. Patients and methods: Patients with clinically diagnosed idiopathic pulmonary fibrosis were treated with colchicine in doses of 0.5 to 1 mg/day, according to tolerance and followed for periods ranging from 7 to 40 months. The clinical and radiological score reported by Watters et al was used for the longitudinal assessment of patients. Maintenance or improvement in forced vital capacity and maintenance or decrease in alveolar arterial O2 gradient during follow up, were considered as positive therapeutic responses. Results: Seventeen patients (10 male, aged 61 to 81 years old) were studied. Their basal score for dyspnea was 5.8 (over 20), for the chest X ray examination was 2.4 (over 3) and for CT scan was 2.8 (over 3). Basal FVC was 77 percent of predicted value (range 51-108 percent), basal FEV, was 82 percent (range 59-117 percent) and FEV1/FVC was 0.82 (range 0.68-0.95). PaO2 at rest was 78 mm Hg (ranges 63-97). Alveolar-arterial PO2 gradient was 16 mm Hg (range 5-31.6) at rest and 31 mm Hg (range 5.7-51.4) after exercise. Six patients (35 percent) had a positive response to therapy. Conclusions: The response rates of these patients to colchicine are at least similar to those obtained with steroids, but with less side effects


Subject(s)
Humans , Male , Female , Middle Aged , Colchicine/administration & dosage , Pulmonary Fibrosis/drug therapy , Dyspnea/drug therapy , Pulmonary Fibrosis/diagnosis , Pulmonary Gas Exchange/drug effects , Spirometry , Vital Capacity/drug effects
18.
Rev. chil. enferm. respir ; 13(2): 93-101, abr.-jun. 1997. ilus, tab
Article in Spanish | LILACS | ID: lil-211843

ABSTRACT

La administración intratraqueal de bleomicina (BLM) induce una fibrosis pulmonar en la rata detectable al cabo de 14 días. Tanto la ciclosporina-A como la Prednisona (administrada contemporáneamente con la bleomicina y luego diariamente hasta 14 ó 30 días después de BLM) disminuyen en cerca del 50 por ciento la fibrosis pulmonar inducida por bleomicina (Puntaje histopatológico). El Própósito de este estudio fue determinar si la ciclosporina y la prednisona administradas una vez que la fibrosís pulmonar estaba ya establecida eran capaces de inhíbirla. 1 U de BLM/100 g de peso corporal fue administrada intratraquealmente y las ratas se sacrificaron 14 y 30 días después. Se inyectó ciclosporina (0,15 mg/lOO g/día, ip) y/o prednisona (0,1 mg/1OO g/día, ip) desde el día 14 al 30 post-BLM. Prednisona o ciclosporina disminuyeron en cerca del 50 por ciento la fíbrosis pulmonar inducida por BLM. Sin embargo, la asociación prednisona + ciclosporina redujo la fíbrosis en sólo 40 por ciento. La disminución de la fibrosis pulmonar estuvo asociada a cambios en el líquido del lavado broncoalveolar: recuento celular, contenido de proteínas y fosfolípídos y actividad gama glutamil transpeptídasa. Se concluye que la prednisona y la ciclosporina son capaces de disminuir una fibrosís pulmonar ya establecida inducida por BLM en la rata


Subject(s)
Animals , Rats , Bleomycin/adverse effects , Cyclosporine/pharmacology , Prednisolone/pharmacology , Pulmonary Fibrosis/chemically induced , Bronchoalveolar Lavage , Instillation, Drug , Lung/pathology , Pulmonary Fibrosis/drug therapy
19.
Rev. méd. Chile ; 125(6): 690-5, jun. 1997. tab, ilus
Article in Spanish | LILACS | ID: lil-197768

ABSTRACT

There are few reports on the use of cyclosporine in idiopathic pulmonary fibrosis, in experimental animals or humans. We report three patients with advanced pulmonary fibrosis in whom steroid therapy failed and that received cyclosporine in a dose of 3 to 5 mg/kg for three to five months. One patient developed systemic hypertension that subsided reducing the dose of cyclosporine. No positive changes in dyspnea were obtained and pulmonary function tests deteriorated during the treatment period. We conclude that cyclosporine treatment had no clinical benefit in these patients with pulmonary fibrosis


Subject(s)
Humans , Female , Middle Aged , Cyclosporine/administration & dosage , Pulmonary Fibrosis/drug therapy , Adrenal Cortex Hormones/pharmacokinetics , Pulmonary Fibrosis/pathology , Treatment Outcome
20.
Rev. chil. enferm. respir ; 11(1): 16-24, ene.-mar. 1995. tab, ilus
Article in Spanish | LILACS | ID: lil-194534

ABSTRACT

La instilación endotraqueal de bleomicina (BLM) en ratas produce daño pulmonar difuso. A los 3 dias de la administración de BLM se observa edema e inflamación y a los 14 y 30 días fibrosis intersticial. Basándonos en que la liberación de radicales libres del O2 ha sido involucrada en el daño pulmonar inducido por bleomicina, nuestro objetivo fue evaluar el efecto asociado de dos antioxidantes: alopurinol y superóxido dismutasa (SOD) sobre la respuesta pulmonar a BLM. Utilizamos 5 series de ratas: a)BLM 1 u/100 g de peso corporl fue instilada por vía intratraqueal. b) Tratada con BLM y alopurinol (2mg/100 g intraperitoneal, 30 min antes de la BLM. c) Tratada con BLM + alopurinol y SOD (0.3 mg/100 g intraperitoneal, 5 min antes de la BLM); d) Controles (0.3 ml de NaCl al 0.9 porciento/100 g vía intratraqueal); e) NaCl 0.9 porciento + alopurinol + SOD. Luego de 3, 14, 30 días se estudió la hispatología pulmonar y el lavado broncoalveolar se determinó: número de células, contenido de proteínas y fosfolípidos y actividad de gama glutamiltranspeptidasa. Encontramos que el alopurinol asociado a la SOD disminuyó en porcentaje hispatológico de la fibrosis pulmonar inducida por la BLM a los 14 y 30 días. Además, esta asociación redujo en aumento en el recuento celular y en el contenido de fosfolípidos del lavado broncoalveolar, sin que modificara el aumento de proteínas y de la actividad de la gama glutamiltranspeptidasa observado en las ratas tratadas con BLM


Subject(s)
Animals , Rats , Allopurinol/administration & dosage , Bleomycin/adverse effects , Pulmonary Fibrosis/drug therapy , Superoxide Dismutase/administration & dosage , Lung Diseases, Interstitial/etiology , Lung Diseases, Interstitial/drug therapy
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