Assuntos
Anemia Hemolítica Autoimune/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Anemia Hemolítica Autoimune/fisiopatologia , Artralgia/fisiopatologia , Hematúria/fisiopatologia , Humanos , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pleurisia/fisiopatologia , Insuficiência Renal/fisiopatologiaRESUMO
Streptococcus pneumoniae is the leading cause of hospital community-acquired pneumonia. Patients with pneumococcal pneumonia may develop complicated parapneumonic effusions or empyema that can lead to pleural organization and subsequent fibrosis. The pathogenesis of pleural organization and scarification involves complex interactions between the components of the immune system, coagulation, and fibrinolysis. EPCR (endothelial protein C receptor) is a critical component of the protein C anticoagulant pathway. The present study was performed to evaluate the role of EPCR in the pathogenesis of S. pneumoniae infection-induced pleural thickening and fibrosis. Our studies show that the pleural mesothelium expresses EPCR. Intrapleural instillation of S. pneumoniae impairs lung compliance and lung volume in wild-type and EPCR-overexpressing mice but not in EPCR-deficient mice. Intrapleural S. pneumoniae infection induces pleural thickening in wild-type mice. Pleural thickening is more pronounced in EPCR-overexpressing mice, whereas it is reduced in EPCR-deficient mice. Markers of mesomesenchymal transition are increased in the visceral pleura of S. pneumoniae-infected wild-type and EPCR-overexpressing mice but not in EPCR-deficient mice. The lungs of wild-type and EPCR-overexpressing mice administered intrapleural S. pneumoniae showed increased infiltration of macrophages and neutrophils, which was significantly reduced in EPCR-deficient mice. An analysis of bacterial burden in the pleural lavage, the lungs, and blood revealed a significantly lower bacterial burden in EPCR-deficient mice compared with wild-type and EPCR-overexpressing mice. Overall, our data provide strong evidence that EPCR deficiency protects against S. pneumoniae infection-induced impairment of lung function and pleural remodeling.
Assuntos
Receptor de Proteína C Endotelial/deficiência , Pulmão/metabolismo , Pleura/metabolismo , Derrame Pleural/metabolismo , Pleurisia/metabolismo , Pneumonia Pneumocócica/metabolismo , Streptococcus pneumoniae/patogenicidade , Animais , Carga Bacteriana , Células Cultivadas , Modelos Animais de Doenças , Receptor de Proteína C Endotelial/genética , Feminino , Fibrose , Interações Hospedeiro-Patógeno , Humanos , Pulmão/microbiologia , Pulmão/patologia , Pulmão/fisiopatologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infiltração de Neutrófilos , Neutrófilos/metabolismo , Neutrófilos/microbiologia , Pleura/microbiologia , Pleura/patologia , Derrame Pleural/microbiologia , Derrame Pleural/patologia , Derrame Pleural/fisiopatologia , Pleurisia/microbiologia , Pleurisia/patologia , Pleurisia/fisiopatologia , Pneumonia Pneumocócica/microbiologia , Pneumonia Pneumocócica/patologia , Pneumonia Pneumocócica/fisiopatologiaRESUMO
Pleural organization may occur after empyema or complicated parapneumonic effusion and can result in restrictive lung disease with pleural fibrosis (PF). Pleural mesothelial cells (PMCs) may contribute to PF through acquisition of a profibrotic phenotype, mesothelial-mesenchymal transition (MesoMT), which is characterized by increased expression of α-SMA (α-smooth muscle actin) and other myofibroblast markers. Although MesoMT has been implicated in the pathogenesis of PF, the role of the reactive oxygen species and the NOX (nicotinamide adenine dinucleotide phosphate oxidase) family in pleural remodeling remains unclear. Here, we show that NOX1 expression is enhanced in nonspecific human pleuritis and is induced in PMCs by THB (thrombin). 4-Hydroxy-2-nonenal, an indicator of reactive oxygen species damage, was likewise increased in our mouse model of pleural injury. NOX1 downregulation blocked THB- and Xa (factor Xa)-mediated MesoMT, as did pharmacologic inhibition of NOX1 with ML-171. NOX1 inhibition also reduced phosphorylation of Akt, p65, and tyrosine 216-GSK-3ß, signaling molecules previously shown to be implicated in MesoMT. Conversely, ML-171 did not reverse established MesoMT. NOX4 downregulation attenuated TGF-ß- and THB-mediated MesoMT. However, NOX1 downregulation did not affect NOX4 expression. NOX1- and NOX4-deficient mice were also protected in our mouse model of Streptococcus pneumoniae-mediated PF. These data show that NOX1 and NOX4 are critical determinants of MesoMT.
Assuntos
Transição Epitelial-Mesenquimal , NADPH Oxidase 1/metabolismo , Pleura/enzimologia , Pleurisia/enzimologia , Pneumonia Pneumocócica/enzimologia , Espécies Reativas de Oxigênio/metabolismo , Streptococcus pneumoniae/patogenicidade , Animais , Células Cultivadas , Modelos Animais de Doenças , Fator Xa/metabolismo , Fibrose , Interações Hospedeiro-Patógeno , Humanos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NADPH Oxidase 1/deficiência , NADPH Oxidase 1/genética , NADPH Oxidase 4/genética , NADPH Oxidase 4/metabolismo , Pleura/microbiologia , Pleura/patologia , Pleurisia/microbiologia , Pleurisia/patologia , Pleurisia/fisiopatologia , Pneumonia Pneumocócica/microbiologia , Pneumonia Pneumocócica/patologia , Transdução de Sinais , Trombina/metabolismoRESUMO
Pulmonary manifestations of inflammatory bowel disease are increasingly recognized in patients with ulcerative colitis and Crohn's disease. Most commonly, incidental abnormalities are noted on chest imaging or pulmonary function tests. Although clinically significant pulmonary disease is less common, it can carry significant morbidity for patients. We review the presenting symptoms, workup, and management for several of the more common forms of inflammatory bowel disease-related pulmonary disease. Increased awareness of the spectrum of extraintestinal inflammatory bowel disease will help providers more readily recognize this phenomenon in their own patients and more comprehensively address the protean sequelae of inflammatory bowel disease.
Assuntos
Doenças Inflamatórias Intestinais/complicações , Pneumopatias/etiologia , Bronquiectasia/etiologia , Bronquiectasia/fisiopatologia , Bronquiolite/etiologia , Bronquiolite/fisiopatologia , Bronquite Crônica/etiologia , Bronquite Crônica/fisiopatologia , Humanos , Imunossupressores/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/fisiopatologia , Pneumopatias/fisiopatologia , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Pleurisia/etiologia , Pleurisia/fisiopatologia , Eosinofilia Pulmonar/etiologia , Eosinofilia Pulmonar/fisiopatologia , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/fisiopatologia , Traqueíte/etiologia , Traqueíte/fisiopatologia , Inibidores do Fator de Necrose Tumoral/efeitos adversosRESUMO
INTRODUCTION: Adult spirometry following community-acquired childhood pneumonia has variably been reported as showing obstructive or non-obstructive deficits. We analysed associations between doctor-diagnosed childhood pneumonia/pleurisy and more comprehensive lung function in a middle-aged general population cohort born in 1961. METHODS: Data were from the prospective population-based Tasmanian Longitudinal Health Study cohort. Analysed lung function was from ages 7 years (prebronchodilator spirometry only, n=7097), 45 years (postbronchodilator spirometry, carbon monoxide transfer factor and static lung volumes, n=1220) and 53 years (postbronchodilator spirometry and transfer factor, n=2485). Parent-recalled histories of doctor-diagnosed childhood pneumonia and/or pleurisy were recorded at age 7. Multivariable linear and logistic regression were used. RESULTS: At age 7, compared with no episodes, childhood pneumonia/pleurisy-ever was associated with reduced FEV1:FVC for only those with current asthma (beta-coefficient or change in z-score=-0.20 SD, 95% CI -0.38 to -0.02, p=0.028, p interaction=0.036). At age 45, for all participants, childhood pneumonia/pleurisy-ever was associated with a restrictive pattern: OR 3.02 (1.5 to 6.0), p=0.002 for spirometric restriction (FVC less than the lower limit of normal plus FEV1:FVC greater than the lower limit of normal); total lung capacity z-score -0.26 SD (95% CI -0.38 to -0.13), p<0.001; functional residual capacity -0.16 SD (-0.34 to -0.08), p=0.001; and residual volume -0.18 SD (-0.31 to -0.05), p=0.008. Reduced lung volumes were accompanied by increased carbon monoxide transfer coefficient at both time points (z-score +0.29 SD (0.11 to 0.49), p=0.001 and +0.17 SD (0.04 to 0.29), p=0.008, respectively). DISCUSSION: For this community-based population, doctor-diagnosed childhood pneumonia and/or pleurisy were associated with obstructed lung function at age 7 for children who had current asthma symptoms, but with evidence of 'smaller lungs' when in middle age.
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Asma/fisiopatologia , Pleurisia/fisiopatologia , Pneumonia/fisiopatologia , Adolescente , Adulto , Criança , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , TasmâniaRESUMO
BACKGROUND AND OBJECTIVES: Plasminogen activator inhibitor-1 (PAI-1) is a fibrinolytic system enzyme whose role in various fibrinolytic processes is currently unknown. In clinical manifestations of pleural liquids of diverse etiology, various levels of fibrinolytic activity can be observed-parapneumonic processes tend to loculate in fibrin septa, while malignant pleural effusion (MPE) does not. The purpose of this study was to determine possible differences in PAI-1 levels in pleural effusions of varied etiology. MATERIAL AND METHODS: PAI-1 level in pleural effusion and serum was determined in 144 patients with pleural effusions of various etiology (cardiac hydrothorax-42 patients (29.2%), MPE-67 patients (46.5%), parapneumonic pleuritis-27 (18.8%), tuberculous pleuritis-6 patients (4.1%), pancreatogenic pleuritis-1 patient (0.7%) and pulmonary artery thromboembolism with pleuritis-1 patient (0.7%)). RESULTS: The median PAI-1 level (ng/mL) was the highest in the parapneumonic pleuritis group both in the effusion and the serum, with values of 291 (213-499) ng/mL and 204 (151-412) ng/mL, respectively, resulting in a statistically significant difference (p < 0.001) from the cardiac hydrothorax and MPE groups. However, there was no statistically significant difference between PAI-1 levels in the pleural effusion and serum in the cardiac hydrothorax and MPE groups. CONCLUSION: The PAI-1 level in MPE and cardiac hydrothorax was statistically significantly lower than in parapneumonic pleuritis.
Assuntos
Hidrotórax/sangue , Inibidor 1 de Ativador de Plasminogênio/análise , Derrame Pleural Maligno/sangue , Pleurisia/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hidrotórax/fisiopatologia , Letônia , Masculino , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/sangue , Derrame Pleural Maligno/fisiopatologia , Pleurisia/fisiopatologiaRESUMO
Detecting Mycoplasma bovis on cattle farms represents a challenge in the absence of an outbreak or cases of M. bovis mastitis, yet identification of an infection is essential to control the spread of the disease successfully. The objectives of this study were: (1) to determine whether meat inspection records can aid identification of cattle farms supporting M. bovis infection, and (2) to compare the average daily weight gain estimated from carcass weight for cattle originating from farms differing in M. bovis test-status. Meat inspection records were collected from two abattoirs in 2015; 80 677 animals in total. All the dairy and mixed breed cows and bulls used for meat production were categorized according to known M. bovis infection status of the farms from which the cattle were derived; positive, contact or control farms. The associations between animals from different M. bovis categories and lung lesions of bulls and cows (pneumonia and pleuritis), identified during meat inspection, and estimated average daily gain (ADG) of bulls, were investigated. The odds ratios for lung lesions, especially pleuritis, were higher in M. bovis test-positive or contact farms compared with control farms. Additionally, odds ratios for pleuritis were higher among animals from M. bovis test-positive farms and animals from contact slaughtering farms originating from M. bovis-free rearing farms. Bulls originating from M. bovis test-positive farms had higher estimated average daily gain than cattle from control farms. Meat inspection records can be used alongside other methods to detect M. bovis-positive farms where M. bovis causes lung lesions.
Assuntos
Doenças dos Bovinos/microbiologia , Inspeção de Alimentos , Carne , Infecções por Mycoplasma/veterinária , Mycoplasma bovis , Doenças Respiratórias/veterinária , Aumento de Peso , Matadouros , Animais , Bovinos , Doenças dos Bovinos/patologia , Doenças dos Bovinos/fisiopatologia , Indústria de Laticínios , Feminino , Finlândia , Pulmão/patologia , Masculino , Infecções por Mycoplasma/diagnóstico , Infecções por Mycoplasma/patologia , Infecções por Mycoplasma/fisiopatologia , Pleurisia/patologia , Pleurisia/fisiopatologia , Pleurisia/veterinária , Pneumonia/patologia , Pneumonia/fisiopatologia , Pneumonia/veterinária , Doenças Respiratórias/microbiologia , Doenças Respiratórias/patologia , Doenças Respiratórias/fisiopatologiaAssuntos
Doenças Autoimunes , Implantes de Mama/efeitos adversos , Remoção de Dispositivo/métodos , Pericardite , Pleurisia , Géis de Silicone/efeitos adversos , Doenças Autoimunes/sangue , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/etiologia , Doenças Autoimunes/terapia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Pericardite/diagnóstico por imagem , Pericardite/etiologia , Pericardite/fisiopatologia , Pericardite/cirurgia , Pleurisia/diagnóstico por imagem , Pleurisia/fisiopatologia , Pleurisia/cirurgia , Radiografia Torácica/métodos , Cintilografia/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
PURPOSE OF REVIEW: Familial Mediterranean fever (FMF) is the oldest and most common of the hereditary autoinflammatory diseases (AIDs). A large body of information has been accumulated over recent years on the pathophysiology, diagnosis and treatment of these diseases. The purpose of this review is to bring an up-to-date summary of the clinic manifestations, diagnostic criteria and treatment of FMF. RECENT FINDINGS: An overview of the pathophysiologic basis of FMF as part of the AID is discussed. Over the last year, attempts to establish new criteria for childhood FMF, new guidelines for treatment and follow-up of disease and novel treatment for FMF were made. A comparison of the different disease severity scores for research purposes suggests that a new score is needed. New evidence for antiinterleukin-1 blockade as a new treatment modality is described. SUMMARY: New diagnostic criteria, disease severity score, treatment and follow-up guidelines have been proposed, and need validation in the next several years.
Assuntos
Antirreumáticos/uso terapêutico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Moduladores de Tubulina/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Colchicina/uso terapêutico , Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/genética , Febre Familiar do Mediterrâneo/fisiopatologia , Febre/etiologia , Febre/fisiopatologia , Doenças Hereditárias Autoinflamatórias , Humanos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Peritonite/etiologia , Peritonite/fisiopatologia , Pleurisia/etiologia , Pleurisia/fisiopatologia , Pirina/genética , Proteínas Recombinantes de Fusão/uso terapêutico , Sinovite/etiologia , Sinovite/fisiopatologiaRESUMO
O objetivo do presente estudo foi identificar a frequência de lesões macroscópicas e microscópicas e dos agentes bacterianos envolvidos em pericardites em suínos no abate no Estado do Rio Grande do Sul. As amostras foram coletadas em frigoríficos de suínos com Serviço de Inspeção Federal (SIF) entre fevereiro a outubro de 2010 e a condenação por pericardite dos animais acompanhados foi de 3,9 por cento(299/7.571). No total foram investigados 91 casos de pericardites, 89% deles foram classificados como crônicos por histopatologia e pleurite crônica foi observada em 47 porcento dos pulmões correspondentes, todavia não houve associação significativa entre as duas lesões. Os agentes bacterianos isolados a partir dos corações foram Streptococcus spp., Pasteurella multocida, Haemophilus parasuis e Streptococcus suis. DNA bacterianos mais detectados pela PCR foram de Mycoplasma hyopneumoniae e Actinobacillus pleuropneumoniae. Houve associação significativa entre isolamento de P. multocida e Streptococcus sp. nos corações e pulmões correspondentes. Esses resultados sugerem que a infecção no pulmão possa ter servido de porta de entrada para a colonização do pericárdio adjacente. Apesar de M. hyopneumoniae ter sido o agente detectado com maior frequência pela PCR em corações e pulmões correspondentes, não houve associação significativa da detecção dos agentes nos órgãos. Isto sugere que as infecções foram eventos independentes. Os demais agentes investigados não apresentaram associação significativa entre isolamento ou detecção de DNA em coração e pulmão correspondente. Outro achado importante foi a presença de coinfecções bacterianas em 2 por cento dos corações e por PCR foi detectado DNA bacteriano de dois ou mais agentes em 16,5 por cento dos corações. Esses resultados sugerem que as coinfecções em pericardites precisam ser melhor estudadas.
The objective of the study was to identify the frequency of macroscopic and microscopic lesions and bacterial agents involved with pericarditis in slaughter pigs in the State of Rio Grande do Sul, Brazil. The samples were collected in slaughterhouses with Federal Inspection Service (SIF) between February and October, 2010. Condemnation due to pericarditis in the examined animals was 3.9 percent (299/7,571). Ninety one cases of pericarditis were examined and by histopathology 89% were chronic and 47 percent of the corresponding lungs showed chronic pleuritis, but there was no significant association between both lesions. The bacterial agents isolated from the hearts were Streptococcus spp., Pasteurella multocida, Haemophilus parasuis and Streptococcus suis. Bacterial DNA from Mycoplasma hyopneumoniae and Actinobacillus pleuropneumoniae were the most frequently detected by PCR. There was significant association between isolation of P. multocida and Streptococcus spp. in the hearts and corresponding lungs. The results suggest that lung infection could act as a port of entry to the colonization of the adjacent pericardium. In spite of the fact that M. hyopneumoniae was the agent more frequently identified by PCR in the heart and corresponding lung, there was no significant association of the agent in the organs. This suggests that the infections were independent events. The other agents investigated did not show significant association between isolation or DNA detection in heart and corresponding lungs. Another important finding was the presence of coinfection between bacterial agents in 2 percent of the hearts and by PCR were identified bacterial DNA of two or more agents in 16.5 percent of the hearts. These results suggest that coinfections in cases of pericarditis need further investigation.
Assuntos
Animais , Doenças dos Suínos/microbiologia , Genes Bacterianos , Pericardite/fisiopatologia , Pericardite/veterinária , Pleurisia/fisiopatologia , Pleurisia/veterinária , Reação em Cadeia da Polimerase/veterinária , Mycoplasma hyopneumoniae/isolamento & purificação , Pasteurella multocida/isolamento & purificação , Streptococcus suis/isolamento & purificaçãoAssuntos
Antibacterianos/administração & dosagem , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica , Implante de Prótese Vascular , Hemotórax , Pleurisia , Infecção da Ferida Cirúrgica , Acinetobacter baumannii/isolamento & purificação , Idoso , Aorta Torácica/patologia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/fisiopatologia , Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/métodos , Terapia Combinada , Enterobacter cloacae/isolamento & purificação , Feminino , Hemotórax/etiologia , Hemotórax/fisiopatologia , Hemotórax/cirurgia , Humanos , Pleurisia/etiologia , Pleurisia/fisiopatologia , Pleurisia/terapia , Radiografia , Reoperação/métodos , Índice de Gravidade de Doença , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/fisiopatologia , Infecção da Ferida Cirúrgica/cirurgia , Resultado do TratamentoRESUMO
Systemic lupus erythematosus (SLE) is a systemic inflammatory disease, characterized serologically by an autoantibody response to nucleic antigens, and clinically by injury and/or malfunction in any organ system. During their disease course, up to 50% of SLE patients will develop lung disease. Pulmonary manifestations of SLE include pleuritis (with or without effusion), inflammatory and fibrotic forms of interstitial lung disease, alveolar hemorrhage, shrinking lung syndrome, pulmonary hypertension, airways disease, and thromboembolic disease. Two major themes inform our understanding of SLE-associated pulmonary manifestations: first, the presence of specific autoantibodies correlates with the presence of certain pulmonary manifestations and second, vascular injury marks a common pathophysiologic thread among the various SLE-related lung diseases. This review will focus on the clinical presentation, pathogenesis, pathology, management, and prognosis of these SLE-associated lung conditions.
Assuntos
Autoanticorpos/imunologia , Pneumopatias/etiologia , Lúpus Eritematoso Sistêmico/complicações , Humanos , Pneumopatias/epidemiologia , Pneumopatias/fisiopatologia , Lúpus Eritematoso Sistêmico/imunologia , Pleurisia/etiologia , Pleurisia/imunologia , Pleurisia/fisiopatologia , Prognóstico , Tromboembolia/etiologia , Tromboembolia/imunologia , Tromboembolia/fisiopatologiaRESUMO
The histamine H4 receptor (H4R), recently cloned and identified, is a G-protein coupled histamine receptor family expressed in immune cells which plays an important role in inflammation. Recent data evidentiated that H4R antagonists can decrease airway inflammation and hyperreactivity in animal models of asthma. In the present study we evaluated the effect of the selective H4R antagonist JNJ7777120 (JNJ) in carrageenan-induced pleurisy, an in vivo model of inflammation, well characterized for cellular and molecular mechanisms. Intra-pleural administration of λ-carrageenan (1% w/v in 0.2 ml sterile saline) determined an intense recruitment of leucocytes in pleural exudates and in lung tissues, activated inducible nitric oxide (NO) synthase and cyclooxygenase-2, thus increasing the generation of harmful autacoids such as NO and pro-inflammatory prostaglandins, PgE2 and 6-ketoPgF(1α), increased cellular and DNA oxidative stress, measured as malondialdehyde and 8-OH-deoxyguanosine and the local generation of IL-1ß and TNF-α. Moreover, the activity of caspase-3, an early marker of apoptosis was also activated by λ-carrageenan injection. The pre-treatment with JNJ (5-10 mg Kg⻹ b.wt., given intrapleurally), 60 min before carrageenan markedly reduced all the studied parameters. This study clearly demonstrated that histamine H4R antagonists have anti-inflammatory effects and could have potential therapeutic application for the treatment of inflammatory diseases.
Assuntos
Indóis/farmacologia , Inflamação/tratamento farmacológico , Piperazinas/farmacologia , Pleurisia/tratamento farmacológico , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Animais , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Carragenina/toxicidade , Caspase 3/metabolismo , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Antagonistas dos Receptores Histamínicos/farmacologia , Inflamação/fisiopatologia , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Pleurisia/fisiopatologia , Ratos , Ratos Wistar , Receptores Histamínicos , Receptores Histamínicos H4RESUMO
OBJECTIVE: The pathophysiology of shrinking lung syndrome (SLS) is poorly understood. We sought to define the structural basis for this condition through the study of pulmonary mechanics in affected patients. METHODS: Since 2007, most patients evaluated for SLS at our institutions have undergone standardized respiratory testing including esophageal manometry. We analyzed these studies to define the physiological abnormalities driving respiratory restriction. Chest computed tomography data were post-processed to quantify lung volume and parenchymal density. RESULTS: Six cases met criteria for SLS. All presented with dyspnea as well as pleurisy and/or transient pleural effusions. Chest imaging results were free of parenchymal disease and corrected diffusing capacities were normal. Total lung capacities were 39%-50% of predicted. Maximal inspiratory pressures were impaired at high lung volumes, but not low lung volumes, in 5 patients. Lung compliance was strikingly reduced in all patients, accompanied by increased parenchymal density. CONCLUSION: Patients with SLS exhibited symptomatic and/or radiographic pleuritis associated with 2 characteristic physiological abnormalities: (1) impaired respiratory force at high but not low lung volumes; and (2) markedly decreased pulmonary compliance in the absence of identifiable interstitial lung disease. These findings suggest a model in which pleural inflammation chronically impairs deep inspiration, for example through neural reflexes, leading to parenchymal reorganization that impairs lung compliance, a known complication of persistently low lung volumes. Together these processes could account for the association of SLS with pleuritis as well as the gradual symptomatic and functional progression that is a hallmark of this syndrome.
Assuntos
Dispneia/etiologia , Pneumopatias/etiologia , Pulmão/fisiopatologia , Pleurisia/complicações , Adolescente , Adulto , Dispneia/diagnóstico por imagem , Dispneia/fisiopatologia , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pneumopatias/diagnóstico por imagem , Pneumopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pleurisia/diagnóstico por imagem , Pleurisia/fisiopatologia , Radiografia , Testes de Função Respiratória , SíndromeRESUMO
BACKGROUND: According to cytotoxic and mutagenic properties, nitrogranulogen (NTG) changes the character of inflammatory reactions. Our previous studies have shown that NTG can enhance immunological defense reactions, because of its high affinity to DNA, and causes disorders in the synthesis of acute phase proteins (e.g., haptoglobin, transferrin, fibrinogen and complement protein C3) [15]. The aim of the current studies was to determine the influence of three different NTG doses: 5 µg/kg b.w. (body weight), 50 µg/kg b.w. and 600 µg/kg b.w. (cytotoxic dose) on the values of hematological blood parameters: RBC, HGB, HCT, RDW, MCV, MCH, MCHC, PLT, MPV, PCT, PDW, WBC, NEUT, LYMPH, MONO, EOS and BASO in pleuritis-induced rats. METHODS: The animals were randomized into five groups: Group I - control group; Group II - IP (induced pleuritis) group; Group III - NTG5 group; Group IV - NTG50 group; Group V - NTG600 group. The blood was collected from all the groups at the 24(th) h, 48(th) h, and 72(nd) h after the initiation of the carrageenin-induced inflammatory reaction. RESULTS: These investigations have revealed that NTG administered at the dose of 5 µg/kg b.w. caused the drop of the leukocyte and lymphocyte numbers and the rise of the neutrophil number at the 72(nd) h of the experimental-induced inflammatory reaction. Moreover, the dose of: 5 µg/kg b.w. was an immunomodulatory property and it also increased the erythrocytic parameters. On the contrary, NTG applied at the doses of 50 µg/kg and 600 µg/kg b.w. contributed to the drop of both: the erythrocytic and leukocytic parameters during the whole time of the inflammatory reaction. CONCLUSIONS: The results suggest that nitrogranulogen affects the erythropoiesis.
Assuntos
Alquilantes/farmacologia , Inflamação/tratamento farmacológico , Mecloretamina/farmacologia , Pleurisia/tratamento farmacológico , Alquilantes/administração & dosagem , Animais , Carragenina , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Eritropoese/efeitos dos fármacos , Feminino , Inflamação/fisiopatologia , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Mecloretamina/administração & dosagem , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Pleurisia/fisiopatologia , Distribuição Aleatória , Ratos , Ratos Endogâmicos BUF , Fatores de TempoRESUMO
Shrinking lung syndrome (SLS) is an uncommon feature of systemic lupus erythematosus (SLE) characterized by dyspnea, pleuritic chest pain, diaphragmatic elevation, restrictive ventilatory defect and reduced respiratory muscle strength as measured by volitional tests. We report the case of a 28-year-old woman with overlapping features of SLE and Sjögren syndrome who developed severe SLS while receiving corticosteroids and azathioprine for severe polyarthritis. She was treated with a combination of rituximab and cyclophosphamide, which led to a dramatic improvement in her clinical condition and respiratory function tests. The increase in vital capacity was one of the highest among 35 published cases of SLS. Thus, restoring a near-normal lung function is an achievable goal in SLS, and the use of rituximab, with or without concomitant cyclophosphamide, certainly deserves further study in this setting.
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Anticorpos Monoclonais Murinos/administração & dosagem , Ciclofosfamida/administração & dosagem , Pneumopatias , Lúpus Eritematoso Sistêmico , Testes de Função Respiratória/métodos , Síndrome de Sjogren , Adulto , Antirreumáticos/administração & dosagem , Dor no Peito/etiologia , Dor no Peito/fisiopatologia , Monitoramento de Medicamentos/métodos , Quimioterapia Combinada , Dispneia/etiologia , Dispneia/fisiopatologia , Feminino , Humanos , Pneumopatias/tratamento farmacológico , Pneumopatias/etiologia , Pneumopatias/fisiopatologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/fisiopatologia , Pleura/fisiopatologia , Pleurisia/tratamento farmacológico , Pleurisia/etiologia , Pleurisia/fisiopatologia , Músculos Respiratórios/fisiopatologia , Rituximab , Índice de Gravidade de Doença , Síndrome de Sjogren/complicações , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/fisiopatologia , Resultado do TratamentoRESUMO
PURPOSE: To evaluate long-term results of decortications in patients with symptomatic restrictive pleurisy and trapped lung after coronary bypass grafting. METHODS: Twenty consecutive patients undergoing lung decortications for trapped lung after coronary bypass grafting were prospectively evaluated. Pulmonary function tests were used as objective criteria, and quality of life was assessed by the Medical Research Council dyspnea scale. A p value <0.05 was considered significant. RESULTS: Twenty patients, 3 women and 17 men, with a median age of 59 years were evaluated. The median time interval between coronary bypass grafting and decortications was 9.3 months. The mean preoperative forced expiratory volume in one second and forced vital capacity were 63.8% ± 7.4% and 50.5% ± 6.6% of the predicted value, respectively, and the improvement rates after decortications were 14.97% ± 6.3% and 17.62% ± 6.38%, respectively. Dyspnea scores improved after decortications (p <0.05). The median follow-up was 25 months. After surgery, 3 patients developed superficial wound infections, and out of 7 patients with prolonged air leaks, 2 underwent re-operation. After surgery, one patient died on day 34 and another, after 3 years. CONCLUSION: Lung decortications, re-expanding the affected lung, ensures symptom remission and improves quality of life of patients with trapped lung after coronary bypass grafting in the long-term.
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Ponte de Artéria Coronária/efeitos adversos , Pleurisia/cirurgia , Atelectasia Pulmonar/cirurgia , Procedimentos Cirúrgicos Pulmonares , Adulto , Idoso , Ponte de Artéria Coronária/mortalidade , Dispneia/etiologia , Dispneia/cirurgia , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Pleurisia/diagnóstico , Pleurisia/etiologia , Pleurisia/mortalidade , Pleurisia/fisiopatologia , Valor Preditivo dos Testes , Estudos Prospectivos , Atelectasia Pulmonar/diagnóstico , Atelectasia Pulmonar/etiologia , Atelectasia Pulmonar/mortalidade , Atelectasia Pulmonar/fisiopatologia , Procedimentos Cirúrgicos Pulmonares/efeitos adversos , Procedimentos Cirúrgicos Pulmonares/mortalidade , Qualidade de Vida , Recuperação de Função Fisiológica , Reoperação , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Turquia , Capacidade VitalRESUMO
Undifferentiated connective tissue diseases (UCTDs) are clinical entities characterised by signs and symptoms suggestive of a systemic autoimmune disease, which do not fulfil the diagnostic criteria for a defined connective tissue disease. Lung involvement can complicate the course and management of the disease, often determining a worse outcome. Respiratory dysfunction as the first clinical manifestation has seldom been reported.We describe a case of a female patient who developed significant respiratory dysfunction as the principal clinical sign. Video-assisted thoracoscopy was performed and a histological pattern of nonspecific interstitial pneumonia (NSIP) was found. A pathological diagnosis suggested careful follow-up with extensive immunological screening which then detected Raynaud's phenomenon and positivity of antinuclear antibodies. After a multidisciplinary discussion (pneumologist, radiologist, pathologist and rheumatologist) a final diagnosis of NSIP associated with UCTD was made. The diagnosis of UCTD should be considered when NSIP is diagnosed even in cases with evident first clinical manifestations of severe respiratory dysfunction. A multidisciplinary approach in the field of interstitial lung disease with NSIP, also including rheumatologic expertise, is fundamental to achieve a prompt and correct diagnosis.
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Doenças do Tecido Conjuntivo/diagnóstico , Doenças Pulmonares Intersticiais/diagnóstico , Pulmão/patologia , Insuficiência Respiratória/diagnóstico , Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/fisiopatologia , Diagnóstico Diferencial , Feminino , Humanos , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/fisiopatologia , Pessoa de Meia-Idade , Pleurisia/complicações , Pleurisia/patologia , Pleurisia/fisiopatologia , Radiografia Torácica , Testes de Função Respiratória , Insuficiência Respiratória/complicações , Insuficiência Respiratória/fisiopatologiaRESUMO
Abstract Pleural inflammation underlies the formation of most exudative pleural effusions and the plasma kallikrein-kinin system (KKS) is known to contribute. Mesothelial cells are the predominant cell type in the pleural cavity, but their potential role in plasma KKS activation and BK production has not been studied. Bradykinin concentrations were higher in pleural fluids than the corresponding serum samples in patients with a variety of diseases. Bradykinin concentrations did not correlate with disease diagnosis, but were elevated in exudative effusions. It was demonstrated, using a range of primary and transformed mesothelial and mesothelioma cell lines, that cells assembled high molecular weight kininogen and plasma prekallikrein to liberate bradykinin, a process inhibited by novobiocin, a heat shock protein 90 (HSP90) inhibitor, cysteine, bradykinin and protamine sulphate. Of the common plasma prekallikrein activators, mesothelial cells expressed HSP90, but not prolylcarboxypeptidase or Factor XII. Calcium mobilisation was induced in some mesothelium-derived cell lines by bradykinin. Des-Arg(9)-bradykinin was inactive, indicating that mesothelial cells are responsive to bradykinin, mediated via the bradykinin receptor subtype 2. In summary, pleural mesothelial cells support the assembly and activation of the plasma KKS by a mechanism dependent on HSP90, and may contribute to KKS-mediated inflammation in pleural disease.
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Células Epiteliais/metabolismo , Sistema Calicreína-Cinina , Pleura/citologia , Pleura/imunologia , Pleurisia/fisiopatologia , Animais , Líquidos Corporais/química , Bradicinina/análise , Bradicinina/farmacologia , Cálcio/metabolismo , Linhagem Celular Tumoral , Citocinas/metabolismo , Células Epiteliais/efeitos dos fármacos , Epitélio/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas de Membrana/metabolismo , Camundongos , Vasodilatadores/farmacologiaRESUMO
This work studied the intravenous injection formulation of nanostructured lipid carriers (NLCs) loaded with dexamethasone acetate (DA), a poorly water-soluble drug. The goal of this study was to design nanoparticles which could improve therapeutic efficacy of DA on inflammations. Based on the optimized results of single-factor screening experiment, DA-loaded NLCs (DA-NLCs) prepared by an emulsification-ultrasound method were found to be relatively uniform in size (178 ± 4 nm) with a negative zeta potential (-38 ± 4 mV). The average drug entrapment efficiency was 91 ± 3 %. In vitro release tests indicated DA-NLCs possessed a sustained release characteristic and the accumulative release percentage was near 80 % at 23 h. DA-NLCs exhibited an average peak concentration of DA (7.6 µg/ml) in the pleural exudate after intravenous administration to an experimental model of γ-carrageenan-induced pleuritis rats, which was 8.3 times higher than that of free DA (0.9 µg/ml). The γ-carrageenan-induced edema test showed that the anti-acute inflammatory activity of DA-NLCs was stronger than that of free drug at the same drug concentration (P<0.05). In addition, biodistribution results clearly indicated that DA-NLCs preferentially accumulated in mice livers and lungs after intravenous injection. These results revealed that injectable NLCs may serve as a promising carrier for DA, greatly enhancing the selective effect on inflammatory sites, reducing systematic side effects and may be a potential carrier to increase therapeutic efficacy on inflammatory diseases.