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1.
Respir Med ; 188: 106612, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34560351

RESUMO

PURPOSE: Pneumonia is a major cause of respiratory-related hospitalization and an important prognostic factor in patients with chronic interstitial lung disease (ILD). However, the relationship between the incidence of pneumonia and human leukocyte antigen (HLA) serotype has not been fully elucidated. Therefore, this study aimed to determine if there is a relationship between HLA serotype and the incidence of pneumonia in Japanese patients with ILD. METHODS: The medical records of patients with ILD treated at any of three centers in Japan were reviewed to determine their HLA-A and HLA-B serotypes. The characteristics of patients with and without pneumonia were compared. Cox regression analysis was performed to identify risk factors for pneumonia and death in these patients. RESULTS: One hundred and forty-four patients with ILD (pneumonia group, n = 27; non-pneumonia group, n = 117) and complete HLA serology data available were included. HLA-B54 positivity was significantly more common in the pneumonia group than in the non-pneumonia group (37.0% vs. 15.4%, p = 0.010). HLA-B54 positivity was also a significant risk factor for pneumonia (hazard ratio [HR] 4.166, 95% confidence interval [CI] 1.862-9.320, p = 0.001) and death (HR 4.050, 95% CI 1.581-10.374, p = 0.004) in patients with ILD. Furthermore, HLA-B54 positivity was a significant risk factor for pneumonia (HR 3.964, 95% CI 1.392-11.090, p = 0.010) and death (HR 8.131, 95% CI 1.763-37.494, p = 0.007) in patients with idiopathic pulmonary fibrosis. CONCLUSION: HLA-B54 positivity was a significant risk factor for pneumonia and death in patients with ILD, including those with idiopathic pulmonary fibrosis.


Assuntos
Antígenos HLA-B/imunologia , Doenças Pulmonares Intersticiais/complicações , Pneumonia/imunologia , Idoso , Biomarcadores/análise , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
2.
Tohoku J Exp Med ; 248(3): 209-216, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31366819

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic joint inflammation and may manifest as interstitial pneumonia (IP). Methotrexate (MTX) is one of the main therapeutic drugs used for RA, but MTX could cause severe side effects, including Pneumocystis jirovecii pneumonia (PCP) and IP. Owing to similar symptoms, it is sometimes difficult to discriminate MTX therapy-associated PCP (MTX-PCP) and MTX therapy-associated IP (MTX-IP). Soluble interleukin-2 receptor (sIL-2R) is considered a marker of T-cell activation, and serum sIL-2R levels are elevated in RA and PCP. This led us to hypothesize that serum sIL-2R is a potential biomarker for discriminating MTX-PCP and MTX-IP. Accordingly, we carried out a retrospective analysis of 20 MITX-PCP cases, 30 MTX-IP cases, and as controls, 16 patients with RA-associated IP (RA-IP) and 13 patients with PCP without MTX treatment (PCP group). C-reactive protein and alveolar-arterial oxygen differences were higher in the MTX-PCP group than those in the RA-IP and MTX-IP groups. Importantly, serum levels of sIL-2R in MTX-PCP were significantly higher than those in other three groups. Based on the receiver operating characteristic curve, the cut-off level of sIL-2R resulting in the highest diagnostic accuracy for MTX-PCP was 1,311.5 U/mL, discriminating between MTX-PCP and other groups with 91.7% sensitivity and 78.6% specificity. Thus, patients with MTX-PCP show a higher degree of systemic inflammation, severe hypoxemia, and increased sIL-2R levels compared with those in MTX-IP cases. In conclusion, serum sIL-2R could be a biomarker for PCP diagnosis among patients with RA under MTX therapy.


Assuntos
Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Metotrexato/uso terapêutico , Pneumocystis carinii/fisiologia , Pneumonia/sangue , Pneumonia/complicações , Receptores de Interleucina-2/sangue , Idoso , Artrite Reumatoide/diagnóstico por imagem , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/diagnóstico por imagem , Pneumonia/microbiologia , Curva ROC , Solubilidade , Tomografia Computadorizada por Raios X
3.
J Med Case Rep ; 13(1): 47, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30819241

RESUMO

BACKGROUND: Parvimonas micra, a Gram-positive anaerobic coccus, is a rare pathogen for psoas abscess. We describe a case of a patient with iliopsoas abscess caused by P. micra. CASE PRESENTATION: An 81-year-old Asian man presented to our department with complaints of fever since the preceding day. Abdominal computed tomography revealed the presence of a low-density mass in the right iliopsoas muscle indicative of a psoas abscess. Computed tomography-guided percutaneous drainage of the psoas abscess was performed. Results of organism cultures of the abscess and blood were positive for P. micra. However, our patient had no known primary focus of infection. On the basis of these findings, a primary psoas abscess caused by P. micra was diagnosed, and treatment with ampicillin/sulbactam 1.5 g, administered intravenously every 8 h, was initiated. By day 7, the patient's white blood cell count normalized. By day 20, his C-reactive protein level was decreased to 0.35 mg/dl. CONCLUSION: Iliopsoas abscesses caused by anaerobic bacteria are relatively rare, and iliopsoas abscesses caused by P. micra are especially rare. Our patient's case revealed that P. micra can cause iliopsoas abscess. Therefore, clinicians should be aware of the possibility that P. micra may cause iliopsoas abscess.


Assuntos
Antibacterianos/uso terapêutico , Drenagem/métodos , Febre/microbiologia , Infecções por Bactérias Gram-Positivas/patologia , Abscesso do Psoas/patologia , Administração Intravenosa , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/terapia , Humanos , Masculino , Abscesso do Psoas/diagnóstico por imagem , Abscesso do Psoas/microbiologia , Abscesso do Psoas/terapia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ultrassonografia de Intervenção
4.
BMC Pulm Med ; 18(1): 6, 2018 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-29338706

RESUMO

BACKGROUND: Tuberculosis and cryptococcosis co-infection usually occurs in immunosuppressed patients with impaired cell-mediated immunity. However, there are few reports about such co-infection in non-HIV patients without underlying diseases. Here, we report a case of miliary tuberculosis with co-existing pulmonary cryptococcosis in non-HIV patient without underlying diseases. CASE PRESENTATION: An 84-year-old Asian female presented to our hospital with complaints of a 1-week history of abdominal pain and appetite loss. Chest computed tomography (CT) showed diffuse micronodules in random patterns in both lung fields. Liver, skin and bone marrow biopsies showed epithelioid cell granuloma. Polymerase chain reaction of gastric aspirate was positive for Mycobacterium tuberculosis. According to these findings, miliary tuberculosis was suspected and antimycobacterial therapy was initiated. After a 6-month treatment course, chest radiograph showed new multiple nodules in the right middle lung field. Chest CT showed that a right S6 small nodule was increased and new multiple nodules appeared in the right lower lobe. Flexible fiberoptic bronchoscopy was subsequently perfomed. Cytology of the bronchial lavage showed a small number of Periodic acid-Schiff-positive bodies, suggesting Cryptococcus species. Moreover, serum cryptococcal antigen testing was positive. According to these findings, pulmonary cryptococcosis was diagnosed, although the culture was negative. Oral fluconazole therapy was subsequently initiated. After a 6-month treatment course, chest radiograph showed gradual improvement. CONCLUSION: Although tuberculosis and cryptococcosis co-infection is relatively rare in immunocompromised hosts, such as those with acquired immunodeficiency syndrome, clinicians should be aware that these infections can co-exist even in non-HIV patients without underlying diseases.


Assuntos
Criptococose/complicações , Pneumopatias Fúngicas/microbiologia , Tuberculose Miliar/complicações , Idoso de 80 Anos ou mais , Criptococose/diagnóstico por imagem , Criptococose/tratamento farmacológico , Feminino , Humanos , Hospedeiro Imunocomprometido , Pneumopatias Fúngicas/diagnóstico por imagem , Pneumopatias Fúngicas/tratamento farmacológico , Tomografia Computadorizada por Raios X , Tuberculose Miliar/diagnóstico , Tuberculose Miliar/tratamento farmacológico
5.
Int J Surg Case Rep ; 41: 212-214, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29096346

RESUMO

INTRODUCTION: Stenotrophomonas maltophilia usually causes nosocomial infections, but intraabdominal abscesses or organ/space surgical site infection (SSI) secondary to this organism has been rarely reported. Here, we reported a rare case of SSI that presented as intraabdominal abscess caused by S. maltophilia. PRESENTATION OF CASE: A 68-year-old woman presented to our hospital with transverse colon cancer. Further work up with abdominal computed tomography (CT) revealed left renal cell carcinoma. Transverse colon resection and left kidney partial resection were performed. On post-operative day 10, she started to have fever at 38°C and repeat abdominal CT showed intraabdominal abscess. Empiric treatment with piperacillin/tazobactam (TAZ/PIPC) was initiated. However, fever persisted and the abscess size did not change despite 10 days of antibiotic. On post-operative day 20, drainage of intraabdominal abscess was performed. TAZ/PIPC was then shifted to meropenem (MEPM). After two days, S. maltophilia was identified in the culture of the abscess, and MEPM was shifted to minocycline (MINO). Fever disappeared after 7days of treatment and abdominal CT after 14 days showed almost complete resolution of the abscess. DISCUSSION: S. maltophilia is a multi-drug resistant, aerobic, non-glucose fermenting, non-sporulating, Gram-negative bacillus. S. maltophilia may cause a variety of infections, but intraabdominal abscesses as a manifestation of SSI due to this organism is relative rare. CONCLUSION: Although usually a non-pathogenic organism or colonizer, S. maltophilia can cause organ/space SSI in an immunocompromised host. Therefore, clinicians should be aware of the possibility that S. maltophilia may cause organ/space SSI.

6.
BMC Infect Dis ; 17(1): 272, 2017 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-28407752

RESUMO

BACKGROUND: ß-D-glucan (BDG) is a helpful diagnostic marker for many invasive fungal infections, but not for nocardiosis. Here, we reported the first case of nocardial infection with high serum level of BDG. CASE PRESENTATION: A 73-year-old man was hospitalized because of fever, headache, and appetite loss after 10 months of steroid and immunosuppressive therapy for cryptogenic organizing pneumonia. With a diagnosis of bacterial pneumonia, treatment with ampicillin/sulbactam was initiated. There was improvement on chest radiograph, but fever persisted. Further work-up revealed multiple brain abscesses on cranial magnetic resonance imaging (MRI). Serum galactomannan and BDG were elevated at 0.6 index and 94.7 pg/ml, respectively. Voriconazole was initiated for presumed aspergillus brain abscess. However, fever persisted and consciousness level deteriorated. Drainage of brain abscess was performed; based on the Gram stain and Kinyoun acid-fast stain, disseminated nocardiosis was diagnosed. Voriconazole was then shifter to trimethoprim/sulfamethoxazole. The presence of Nocardia farcinica was confirmed by the 16S rRNA gene sequence. Treatment course was continued; BDG level normalized after 1 month and cranial MRI showed almost complete improvement after 2 months. CONCLUSION: BDG assay is widely used to diagnose invasive fungal infection; therefore, clinicians should be aware that Nocardia species may show cross-reactivity with BDG assay on serum.


Assuntos
Abscesso Encefálico/microbiologia , Nocardiose/sangue , beta-Glucanas/sangue , Idoso , Ampicilina/administração & dosagem , Anti-Infecciosos/uso terapêutico , Abscesso Encefálico/diagnóstico , Abscesso Encefálico/tratamento farmacológico , Drenagem , Humanos , Masculino , Nocardiose/diagnóstico , Nocardiose/tratamento farmacológico , Sulbactam/administração & dosagem , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem
7.
Kansenshogaku Zasshi ; 90(6): 829-32, 2016 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-30277679

RESUMO

A 42-year-old woman was referred to our hospital with a diagnosis of influenza A and pneumonia out of the influenza season. Chest CT findings resembled interstitial pneumonia, but we initiated anti viral agents and antibiotics. Flexible fiberoptic bronchoscopy was performed on hospital day 3. Based on the results of an RT-PCR analysis of broncho-alveolar lavage, this patient was diagnosed as having influenza viral pneumonia. In the influenza season, we can easily suspect influenza as a differential diagnosis, even if the patient's chest CT findings resemble interstitial pneumonia. Out of the influenza season, clinicians should take into consideration influenza viral pneumonia as a differential diagnosis.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Pneumonia Viral , Adulto , Feminino , Humanos , Influenza Humana/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Estações do Ano , Resultado do Tratamento
8.
J Med Case Rep ; 8: 279, 2014 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-25139636

RESUMO

INTRODUCTION: Pulmonary alveolar proteinosis is a rare pulmonary disease characterized by excessive alveolar accumulation of surfactant due to defective alveolar clearance by macrophages. There are only a few published case reports of pulmonary alveolar proteinosis occurring in association with solid cancers. To the best of our knowledge, there are no previously reported cases of pulmonary alveolar proteinosis associated with breast cancer. CASE PRESENTATION: A 48-year-old Asian woman, a nonsmoker, presented to our institution with a right breast mass. Biopsy examination of the lesion revealed scirrhous carcinoma. A chest computed tomography scan for metastases showed abnormal shadows in both upper lung fields. As a result of flexible fiberscopic bronchoscopy, this patient was diagnosed as having pulmonary alveolar proteinosis. This case was categorized as autoimmune pulmonary alveolar proteinosis due to the positive anti-granulocyte-macrophage colony-stimulating factor antibody. Pulmonary alveolar proteinosis decreased gradually after mastectomy. CONCLUSIONS: The present case involved the coincident occurrence of autoimmune pulmonary alveolar proteinosis with breast cancer; breast cancer may be a factor during pulmonary alveolar proteinosis development.


Assuntos
Doenças Autoimunes/complicações , Neoplasias da Mama/complicações , Proteinose Alveolar Pulmonar/complicações , Doenças Autoimunes/diagnóstico , Biópsia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Broncoscopia , Diagnóstico Diferencial , Feminino , Humanos , Mastectomia Radical Modificada , Pessoa de Meia-Idade , Proteinose Alveolar Pulmonar/diagnóstico , Tomografia Computadorizada por Raios X , Ultrassonografia Mamária
9.
J Infect Chemother ; 20(8): 484-8, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24855912

RESUMO

The novel biological agent recombinant human thrombomodulin (rhTM) has been used clinically in Japan to treat disseminated intravascular coagulation (DIC) since 2008. Previous studies have shown the efficacy of rhTM versus heparin therapy or non-rhTM therapy. We retrospectively evaluated and compared the efficacies of rhTM and gabexate mesilate (GM) in patients diagnosed with sepsis-induced DIC. From September 2010 to October 2012, patients with sepsis-induced DIC who were treated with rhTM (n = 13) or GM (n = 10) at Nagasaki Municipal Hospital were extracted. Patients receiving other anticoagulants in combination were excluded. Clinical information, laboratory data, Sequential Organ Failure Assessment (SOFA) scores, and DIC scores were obtained from the medical records. Mortality at days 7 and 30 after DIC diagnosis and changes in laboratory data and SOFA scores from days 1-7 were evaluated. The groups' clinical characteristics did not differ, except for the relatively higher C-reactive protein (CRP) levels in the rhTM group (P = 0.0508). The survival rates of the rhTM and GM groups on days 7 and 30 were 92.3%, 69.2% and 80%, 70%, respectively, both group indicated similar mortality. However, on day 7, the platelet counts, SOFA scores, and CRP levels significantly improved in the rhTM group; the platelet counts and SOFA scores did not improve significantly in the GM group. The platelet counts of the rhTM group significantly improved compared to the GM group (P = 0.004). Recombinant human thrombomodulin might be more effective for sepsis-induced DIC than GM.


Assuntos
Coagulação Intravascular Disseminada/tratamento farmacológico , Coagulação Intravascular Disseminada/epidemiologia , Gabexato/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Sepse/complicações , Trombomodulina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Proteína C-Reativa/análise , Coagulação Intravascular Disseminada/etiologia , Coagulação Intravascular Disseminada/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Contagem de Plaquetas , Estudos Retrospectivos , Sepse/epidemiologia , Análise de Sobrevida
10.
J Infect Chemother ; 20(8): 506-8, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24855916

RESUMO

Nocardia spp. has not been reported previously as a cause of post-influenza pneumonia. Here we present a first case of post-influenza bacterial pneumonia due to Nocardia farcinica. Initial reason for hospitalization of the 90 year old female patient was a pneumonia with the symptoms of fever and productive cough. A rapid test for influenza antigen was positive for influenza A virus. Treatment with Zanamivir and piperacillin was initiated. However, after 1 week of treatment, the infiltration shadows on chest X-ray had worsened. Because the expectorated sputum collected on admission for culture was found to be positive for Nocardia spp., piperacillin was replaced with trimethoprim/sulfamethoxazole, and a chest X-ray showed some improvement. Although pulmonary nocardiosis with co-infection with influenza A is extremely rare, clinicians should be alert to the possibility.


Assuntos
Coinfecção , Infecções Comunitárias Adquiridas , Vírus da Influenza A , Influenza Humana , Nocardiose , Pneumonia Bacteriana , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Evolução Fatal , Feminino , Humanos , Nocardia , Radiografia Torácica , Escarro/microbiologia
13.
Intern Med ; 50(7): 707-12, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21467702

RESUMO

BACKGROUND: Tobacco smoking is a major risk factor for atherosclerotic and cardiovascular disease. Studies have found evidence that smoking cessation is associated with weight gain, which is itself a leading cause of cardiovascular disease. Aim The present study sought to determine how smoking cessation and associated weight gain affect adiponectin levels and insulin resistance. METHODS: Fifty-two male habitual smokers were treated for 2 months with transdermal nicotine patches, and the 28 subjects who successfully quit smoking were analyzed. Subjects were divided into two sub-groups according to their weight change: weight maintainers and weight gainers. Serum adiponectin levels and the homeostasis model assessment ratio (HOMA-R) were evaluated at the beginning of the study, and at 1 week and 9 weeks after cessation of patch use. RESULTS: In weight gainers (n=18), serum adiponection levels tended to increase at 1 week after the end of treatment (mean difference 0.4 ± 1.0 µg/mL, p=0.08). Moreover, after 9 weeks, adiponectin levels were significantly decreased in weight gainers (mean difference between 1 week and 9 weeks 0.8 ± 0.9 µg/mL, p=0.002). In weight maintainers, adiponectin levels increased slightly after smoking cessation, but changes were not significant. In weight gainers, HOMA-R index was significantly increased (mean difference between baseline and 9 weeks 0.4 ± 0.7, p=0.01), while in weight maintainers, HOMA-R index showed no differences throughout the study. CONCLUSION: Our findings suggest that the adverse effects of weight gain attenuate some of the beneficial effects of smoking cessation.


Assuntos
Adiponectina/sangue , Resistência à Insulina/fisiologia , Abandono do Hábito de Fumar , Aumento de Peso/fisiologia , Adulto , Idoso , Artérias Carótidas/diagnóstico por imagem , Seguimentos , Homeostase/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Nicotina/administração & dosagem , Abandono do Hábito de Fumar/métodos , Adesivo Transdérmico , Túnica Íntima/diagnóstico por imagem , Túnica Média/diagnóstico por imagem , Ultrassonografia
14.
J Clin Gastroenterol ; 44(4): e71-5, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20305466

RESUMO

BACKGROUND: Smoking cessation can lead to changes in appetite and weight gain in some patients; thus, smoking cessation may alter gastrointestinal motility. Effects of smoking cessation on gastric emptying in smokers have not been established. AIM: This study sought to determine how smoking cessation affects gastric emptying in smokers. METHODS: Participant group comprised 53 habitual smokers and 12 healthy nonsmokers. Habitual smokers were treated for 2 months with transdermal nicotine patches. Gastric emptying was studied using C acetate breath tests at the beginning of the study, and at 1 week and 9 weeks after cessation of patch use. Maximal CO2 excretion time (Tmax), CO2 excretion half-life (T1/2), and parameters beta and kappa, representing initial and subsequent gastric-emptying phases, respectively, were determined using conventional formulae. RESULTS: Before smoking cessation, Tmax was reached significantly later in smokers (0.94+/-0.3 h, P=0.014) than in controls (0.89+/-0.1 h). At 1 week after the end of treatment, Tmax was significantly decreased (from 1.05+/-0.32 h to 0.72+/-0.64 h, P=0.003). T1/2 also tended to decrease, but not significantly. Although beta was decreased significantly (from 2.46+/-0.40 to 2.17+/-0.58, P=0.022), kappa was unchanged. However, by 9 weeks after the end of treatment, Tmax (1.28+/-0.69 h) had increased to levels seen before treatment. CONCLUSIONS: Smoking cessation temporarily accelerates gastric emptying, and decreases in beta suggest that initial-phase gastric emptying accelerates after smoking cessation. The temporary acceleration of gastric emptying after smoking cessation may be involved in the temporary increase in appetite and weight gain seen after smoking cessation.


Assuntos
Esvaziamento Gástrico/fisiologia , Abandono do Hábito de Fumar/métodos , Administração Cutânea , Adulto , Idoso , Apetite/efeitos dos fármacos , Testes Respiratórios/métodos , Feminino , Esvaziamento Gástrico/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Nicotina/administração & dosagem , Nicotina/farmacologia , Fumar/efeitos adversos , Resultado do Tratamento , Aumento de Peso/efeitos dos fármacos , Adulto Jovem
15.
Nihon Kokyuki Gakkai Zasshi ; 46(2): 116-9, 2008 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-18318254

RESUMO

A 32-year-old woman was admitted to our hospital because of fever and back pain. Two months previously, she had been given a diagnosis of bacterial pneumonia based on the same symptoms and recovered after antibiotic treatment. Chest CT scans on admission showed a consolidation and thickened pleura in the right lower lobe. Bronchoalveolar lavage fluids showed an alveolar hemorrhage. Lung biopsy specimens showed thickened pulmonary arteries and fibrotic nonspecific interstitial pneumonia (NSIP). Three years later, she was admitted with fever and pain of the left arm and aortitis syndrome was diagnosed. In this case of NSIP pattern associated with aortitis syndrome we speculate that repeated pulmonary infarction and alveolar hemorrhages caused the NSIP pattern.


Assuntos
Doenças Pulmonares Intersticiais/etiologia , Arterite de Takayasu/complicações , Adulto , Feminino , Hemorragia/etiologia , Humanos , Pneumopatias/etiologia , Doenças Pulmonares Intersticiais/patologia , Alvéolos Pulmonares
16.
Life Sci ; 82(3-4): 210-7, 2008 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-18093617

RESUMO

Pirfenidone (5-methyl-1-phenyl-2-(1H)-pyridone) is a novel anti-fibrotic and anti-inflammatory agent that inhibits the progression of fibrosis in animal models and patients with idiopathic pulmonary fibrosis (IPF). Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagen and plays an important role in the pathogenesis of IPF. The present study evaluated the in vitro effects of pirfenidone on expression of HSP47 and collagen type I in cultured normal human lung fibroblasts (NHLF). Expression levels of HSP47 and collagen type I in NHLF stimulated by transforming growth factor (TGF)-beta1 were evaluated genetically, immunologically and immunocytochemically. Treatment with TGF-beta1 stimulated both mRNA and protein expressions of both HSP47 and collagen type I in NHLF, and pirfenidone significantly inhibited this TGF-beta1-enhanced expression in a dose-dependent manner. We concluded that the anti-fibrotic effect of pirfenidone may be mediated not only through direct inhibition of collagen type I expression but also at least partly through inhibition of HSP47 expression in lung fibroblasts, with a resultant reduction of collagen synthesis in lung fibrosis.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Fibroblastos/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP47/metabolismo , Pulmão/efeitos dos fármacos , Piridonas/farmacologia , Fator de Crescimento Transformador beta1/farmacologia , Northern Blotting , Western Blotting , Linhagem Celular , Colágeno Tipo I/antagonistas & inibidores , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Relação Dose-Resposta a Droga , Antagonismo de Drogas , Fibroblastos/patologia , Proteínas de Choque Térmico HSP47/antagonistas & inibidores , Proteínas de Choque Térmico HSP47/genética , Humanos , Imuno-Histoquímica , Pulmão/patologia , RNA Mensageiro/metabolismo
17.
Life Sci ; 80(20): 1839-45, 2007 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-17367817

RESUMO

Neutrophils and lung fibroblasts are thought to play a role in the pathogenesis of pulmonary fibrosis. We reported previously that heat shock protein 47 (HSP47), a collagen-specific molecular chaperon, and collagen-1 synthesis were involved in pulmonary fibrosis, and that plasma levels of alpha-defensins (HNP; human neutrophil peptide), cationic proteins with antimicrobial and cytotoxic activity in neutrophils, were significantly higher in patients with idiopathic pulmonary fibrosis than in control subjects. Here, we investigated the direct effect of HNP-1 in vitro on the expression of HSP47 and collagen-1 in human lung fibroblasts (NHLF). HNP-1 at 5 microg/ml induced fibroblast proliferation but at concentrations >50 microg/ml, HNP-1 reduced cell viability. Incubation of NHLF with 10 to 25 microg/ml of HNP-1 for 24-h increased the expression of HSP47 and collagen-1 mRNAs (p<0.05). The levels of HSP47 protein also increased significantly at 50 microg/ml, and those of collagen-1 protein increased at 10 to 50 microg/ml of HNP-1 (p<0.05). The mitogen-activated protein kinase (MAPK) signaling pathway in NHLF was activated by HNP-1 stimulation, but inhibitor of MEK (PD98059) did not block HNP-1-induced HSP47 protein production. Our results suggest that alpha-defensin is a fibrogenic mediator that promotes collagen synthesis through the upregulation of HSP47 and collagen-1 in lung fibroblasts and participates in the pathogenesis of neutrophil-induced pulmonary fibrosis.


Assuntos
Colágeno Tipo I/metabolismo , Defensinas/farmacologia , Fibroblastos/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP47/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Fibroblastos/metabolismo , Proteínas de Choque Térmico HSP47/genética , Humanos , Pulmão/citologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , alfa-Defensinas/farmacologia
18.
Nihon Kokyuki Gakkai Zasshi ; 43(10): 600-4, 2005 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-16285592

RESUMO

A 59-year-old woman was admitted because of general fatigue, cough and progressive dyspnea about 5 months after treatment with simvastatin for hyperlipidemia. A chest radiograph and computed tomography scans revealed ground glass and reticular opacities in the right middle and lower lung fields. The percentage of peripheral blood eosinophils was elevated. After simvastatin was discontinued and administration of prednisolone was started, eosinophilia and reticular shadows improved. Drug lymphocyte stimulation test (DLST) for simvastatin was positive, so we diagnosed drug induced eosinophilic pneumonia. Now hyperlipidemia is treated frequently with HMG-CoA reductase inhibitor, but there are few reports demonstrating lung injury by this drug. We should be aware of lung side effects of HMG-CoA reductase inhibitor.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Doenças Pulmonares Intersticiais/induzido quimicamente , Sinvastatina/efeitos adversos , Feminino , Humanos , Hiperlipidemias/tratamento farmacológico , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Pessoa de Meia-Idade , Radiografia Torácica , Tomografia Computadorizada por Raios X
19.
Respirology ; 10(4): 548-52, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16135184

RESUMO

A 34-year-old man was admitted to hospital because of persistent shortness of breath and diffuse vascular dilation at both lower fields of his CXR. Bronchiectasis had been suspected during childhood because of abnormal chest shadows. However, a chest CT scan obtained on admission failed to show bronchiectasis, but rather there was a dilation of blood vessels and low attenuation areas in both lower lobes. A pulmonary angiogram showed normal pulmonary arteries in the arterial phase and diffuse dilated veins in the venous phase. Although the patient also had liver cirrhosis type B with portal hypertension, no association could be found between his liver cirrhosis and the lung lesions. This is a rare case of possible congenital or idiopathic diffuse dilatation of the pulmonary veins.


Assuntos
Enfisema Pulmonar/complicações , Enfisema Pulmonar/diagnóstico por imagem , Veias Pulmonares/diagnóstico por imagem , Adulto , Dilatação Patológica/complicações , Dilatação Patológica/diagnóstico por imagem , Humanos , Cirrose Hepática/complicações , Masculino , Radiografia
20.
Respir Res ; 6: 57, 2005 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-15955241

RESUMO

BACKGROUND: Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagens, and its expression is increased in various fibrotic diseases. The aim of this study was to determine whether quantitative immunohistochemical evaluation of the expression levels of HSP47, type I procollagen and alpha-smooth muscle actin (SMA) allows the differentiation of idiopathic usual interstitial pneumonia (UIP) from UIP associated with collagen vascular disease (CVD) and idiopathic nonspecific interstitial pneumonia (NSIP). METHODS: We reviewed surgical lung biopsy specimens of 19 patients with idiopathic UIP, 7 with CVD-associated UIP and 16 with idiopathic NSIP and assigned a score for the expression of HSP47, type I procollagen and alpha-SMA in type II pneumocytes and/or lung fibroblasts (score 0 = no; 1 = weak; 2 = moderate; 3 = strong staining). RESULTS: The expression level of HSP47 in type II pneumocytes of idiopathic UIP was significantly higher than in CVD-associated UIP and idiopathic NSIP. The expression of HSP47 in fibroblasts was significantly higher in idiopathic UIP and idiopathic NSIP than in CVD-associated UIP. The expression of type I procollagen in type II pneumocytes was significantly higher in idiopathic UIP than in idiopathic NSIP. The expression of type I procollagen in fibroblasts was not different in the three groups, while the expression of alpha-SMA in fibroblasts was significantly higher in idiopathic UIP than in idiopathic NSIP. CONCLUSION: Our results suggest the existence of different fibrotic pathways among these groups involved in the expression of HSP47 and type I procollagen.


Assuntos
Fibroblastos/metabolismo , Proteínas de Choque Térmico HSP47/metabolismo , Doenças Pulmonares Intersticiais/classificação , Doenças Pulmonares Intersticiais/metabolismo , Pulmão/metabolismo , Idoso , Idoso de 80 Anos ou mais , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição Tecidual
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