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Background: Malignant tumors are the main cause of death or euthanasia in animals. The oral cavity ranking fourth in number of occurrences. Epidemiological studies with dogs suggest that canine cancer kills 40-50% of individuals aged over 10 years. In view of the interest of academics and professionals in the healthcare of dogs and cats, this paper reports the case of a 10-month-old bitch, which, despite being a young animal, was affected alveolar rhabdomyosarcoma of abrupt evolution. Case: A 10-month-old French Bulldog bitch, weighing 10 kg, was referred to a veterinary hospital in the city of Rio de Janeiro for care. It had a history of mouth bleeding, after chewing a solid mineral material, edema in the region of the right maxilla, and protusion of the gland of the third eyelid. As the clinical examination also revealed a fracture of the maxillary canine, anti-inflammatory and antibiotics were prescribed, to be administered by the owner once a day for 7 days. During the next clinical examination, carried out one week later, an edema was found in the right region of the mouth, which proved difficult to examine. As the patient had already eaten, an appointment was made for the following day for an intervention in the operating room, where the animal could be anesthetized for better observation of the effected region. Blood was collected for hemogram, urea, creatinine, alkaline phosphatase, ALT, and GGT, and an 8 h food fasting and a 4 h water fasting were recommended. On that date, once the dog had been taken to the operating room, was administered the pre anesthesia, in addition to anesthetic induction and manutention. Upon examining the oral cavity, several loose molars were found on the right side, in addition to a tumoral aspect of the gum; thus, it was decided to collect a small sample of the tumoral mass for histopathology. The surgical specimen was placed in a formalin solution and sent to the laboratory for histopathological processing and diagnosis. One week later, the tumor mass was larger and the edema in the right region of the mouth was much larger than on the day of the procedure. Thus, a computerized tomography was requested to further investigate the alterations that had occurred in such a short time. Due to the results of the histopathology and the CT, an immunohistochemical test was suggested which determined the cell profile and morphology and confirmed the diagnosis of alveolar rhabdomyosarcoma according to clinical suspicion. The animal remained in the veterinary hospital for a further 48 h, during which the clinical condition worsened, with the animal suffering heavy bleeding. As the patient was no longer capable of oral intake of food or water, the decision was made with the consent of the owners to induce a painless death to alleviate the suffering of the animal. However, the owners did not authorize a necropsy. Discussion: Veterinary physicians should be conscious of the treatment of serious illnesses that will not result in a benefit for the patient. They should know when to stop the treatment to not cause further pain and suffering to the animals and their owners. Many of the interventions which aim to treat severe malignant neoplasia will not promote an improvement in quality of life or significantly extend the patient's survival, and do not justify the suffering they entail. A painless death remains the best alternative in such cases.
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Animales , Femenino , Perros , Alveolos Pulmonares/patología , Rabdomiosarcoma Alveolar/diagnóstico , Rabdomiosarcoma Alveolar/veterinaria , Neoplasias de la Boca/veterinariaRESUMEN
Resumen La leptospirosis es una de las zoonosis endémicas más importantes en el mundo con un aumento de la incidencia en los últimos años. En el personal militar podría ser catalogada como una enfermedad ocupacional dado sus actividades específicas en áreas rurales. Su presentación clínica es variable siendo en la mayoría de los casos una enfermedad febril autolimitada. De acuerdo con diversos factores dependientes del patógeno y del hospedero pueden presentarse manifestaciones severas de la enfermedad dentro de la cual destaca el compromiso pulmonar con una alta tasa de mortalidad. Existe evidencia del uso de esteroide sistémico como parte del tratamiento de esta complicación. Presentamos el caso de un paciente joven, militar, que debuta con síndrome de hemorragia alveolar difusa secundario a leptospirosis y presenta una excelente respuesta al tratamiento con altas dosis de metilprednisolona, con una discusión del proceso diagnóstico y aspectos fisiopatológicos de esta condición.
Leptospirosis is one of the most important endemic zoonoses in the world with an increase in incidence in recent years. In military personnel it could be classified as an occupational disease given their specific activities in rural areas. Its clinical presentation is variable being in most cases a self-limited febrile disease. According to various factors dependent on the pathogen and the host, severe manifestations of the disease may occur within which the pulmonary involvement with a high mortality rate stands out. There is evidence of systemic steroid use as part of the treatment of this complication. We present a case of a young, military patient who debuts with diffuse alveolar hemorrhage syndrome secondary to leptospirosis and presents an excellent response to treatment with high doses of methylprednisolone, with a discussion of the diagnostic process and pathophysiological aspects of this condition.
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Humanos , Masculino , Adulto Joven , Alveolos Pulmonares/patología , Hemorragia/etiología , Leptospirosis/complicaciones , Enfermedades Pulmonares/etiología , Esteroides/uso terapéutico , Enfermedad de Weil , Zoonosis , Zona Tropical , Leptospirosis/diagnóstico , Leptospirosis/tratamiento farmacológico , Personal Militar , Enfermedades ProfesionalesRESUMEN
Idiopathic pulmonary fibrosis (IPF) is a lethal age-related lung disease whose pathogenesis involves an aberrant response of alveolar epithelial cells (AEC). Activated epithelial cells secrete mediators that participate in the activation of fibroblasts and the excessive deposition of extracellular matrix proteins. Previous studies indicate that matrix metalloproteinase 14 (MMP14) is increased in the lung epithelium in patients with IPF, however, the role of this membrane-type matrix metalloproteinase has not been elucidated. In this study, the role of Mmp14 was explored in experimental lung fibrosis induced with bleomycin in a conditional mouse model of lung epithelial MMP14-specific genetic deletion. Our results show that epithelial Mmp14 deficiency in mice increases the severity and extension of fibrotic injury and affects the resolution of the lesions. Gain-and loss-of-function experiments with human epithelial cell line A549 demonstrated that cells with a deficiency of MMP14 exhibited increased senescence-associated markers. Moreover, conditioned medium from these cells increased fibroblast expression of fibrotic molecules. These findings suggest a new anti-fibrotic mechanism of MMP14 associated with anti-senescent activity, and consequently, its absence results in impaired lung repair. Increased MMP14 in IPF may represent an anti-fibrotic mechanism that is overwhelmed by the strong profibrotic microenvironment that characterizes this disease.
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Células Epiteliales/patología , Fibrosis Pulmonar Idiopática/genética , Metaloproteinasa 14 de la Matriz/genética , Alveolos Pulmonares/metabolismo , Células A549 , Actinas/genética , Actinas/metabolismo , Animales , Bleomicina/administración & dosificación , Senescencia Celular/genética , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Cadena alfa 1 del Colágeno Tipo I , Modelos Animales de Enfermedad , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Fibronectinas/genética , Fibronectinas/metabolismo , Regulación de la Expresión Génica , Humanos , Hipoxantina Fosforribosiltransferasa/genética , Hipoxantina Fosforribosiltransferasa/metabolismo , Fibrosis Pulmonar Idiopática/inducido químicamente , Fibrosis Pulmonar Idiopática/metabolismo , Fibrosis Pulmonar Idiopática/patología , Metaloproteinasa 14 de la Matriz/deficiencia , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Cultivo Primario de Células , Alveolos Pulmonares/efectos de los fármacos , Alveolos Pulmonares/patología , Succinato Deshidrogenasa/genética , Succinato Deshidrogenasa/metabolismo , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
BACKGROUND: Pulmonary involvement in COVID-19 is characterized pathologically by diffuse alveolar damage (DAD) and thrombosis, leading to the clinical picture of Acute Respiratory Distress Syndrome. The direct action of SARS-CoV-2 in lung cells and the dysregulated immuno-coagulative pathways activated in ARDS influence pulmonary involvement in severe COVID, that might be modulated by disease duration and individual factors. In this study we assessed the proportions of different lung pathology patterns in severe COVID-19 patients along the disease evolution and individual characteristics. METHODS: We analysed lung tissue from 41 COVID-19 patients that died in the period March-June 2020 and were submitted to a minimally invasive autopsy. Eight pulmonary regions were sampled. Pulmonary pathologists analysed the H&E stained slides, performing semiquantitative scores on the following parameters: exudative, intermediate or advanced DAD, bronchopneumonia, alveolar haemorrhage, infarct (%), arteriolar (number) or capillary thrombosis (yes/no). Histopathological data were correlated with demographic-clinical variables and periods of symptoms-hospital stay. RESULTS: Patient´s age varied from 22 to 88 years (18f/23 m), with hospital admission varying from 0 to 40 days. All patients had different proportions of DAD in their biopsies. Ninety percent of the patients presented pulmonary microthrombosis. The proportion of exudative DAD was higher in the period 0-8 days of hospital admission till death, whereas advanced DAD was higher after 17 days of hospital admission. In the group of patients that died within eight days of hospital admission, elderly patients had less proportion of the exudative pattern and increased proportions of the intermediate patterns. Obese patients had lower proportion of advanced DAD pattern in their biopsies, and lower than patients with overweight. Clustering analysis showed that patterns of vascular lesions (microthrombosis, infarction) clustered together, but not the other patterns. The vascular pattern was not influenced by demographic or clinical parameters, including time of disease progression. CONCLUSION: Patients with severe COVID-19 present different proportions of DAD patterns over time, with advanced DAD being more prevalent after 17 days, which seems to be influenced by age and weight. Vascular involvement is present in a large proportion of patients, occurs early in disease progression, and does not change over time.
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COVID-19/patología , Lesión Pulmonar/patología , Pulmón/patología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Autopsia , COVID-19/complicaciones , Demografía , Progresión de la Enfermedad , Femenino , Humanos , Infarto/epidemiología , Infarto/patología , Lesión Pulmonar/etiología , Masculino , Persona de Mediana Edad , Alveolos Pulmonares/patología , Trombosis/etiología , Trombosis/patología , Adulto JovenRESUMEN
The COVID-19 pandemic caused a change in our society and put health systems in crisis worldwide. Different risk factors and comorbidities have been found that increase the risk of mortality when acquiring this infection. The use of alternative devices to the cigarette like the electronic cigarettes, the vapers have been studied widely and generators of great controversy since it has been discovered that they also produce different pulmonary affections. When developing the SARS-CoV2 infection, different theories have been generated about the greater predisposition to a worse prognosis of people who use electronic cigarettes; however, the information on this continues in discovery. A group of experts made up of oncologists, infectologists, pulmonologists, and epidemiologists met to review the literature and then generate theories about the impact of electronic cigarettes on SARS-CoV2 infection.
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COVID-19/patología , Sistemas Electrónicos de Liberación de Nicotina , Vapeo/efectos adversos , COVID-19/epidemiología , Susceptibilidad a Enfermedades , Sistemas Electrónicos de Liberación de Nicotina/estadística & datos numéricos , Humanos , Macrófagos/metabolismo , Alveolos Pulmonares/inmunología , Alveolos Pulmonares/patología , Riesgo , SARS-CoV-2 , Vapeo/epidemiología , Adulto JovenRESUMEN
It is currently believed that innate immunity is unable to prevent the spread of SARS-CoV-2 from the upper airways to the alveoli of high-risk groups of patients. SARS-CoV-2 replication in ACE-2-expressing pneumocytes can drive the diffuse alveolar injury through the cytokine storm and immunothrombosis by upregulating the transcription of chemokine/cytokines, unlike several other respiratory viruses. Here we report histopathology data obtained in post-mortem lung biopsies of COVID-19, showing the increased density of perivascular and septal mast cells (MCs) and IL-4-expressing cells (n = 6), in contrast to the numbers found in pandemic H1N1-induced pneumonia (n = 10) or Control specimens (n = 10). Noteworthy, COVID-19 lung biopsies showed a higher density of CD117+ cells, suggesting that c-kit positive MCs progenitors were recruited earlier to the alveolar septa. These findings suggest that MC proliferation/differentiation in the alveolar septa might be harnessed by the shift toward IL-4 expression in the inflamed alveolar septa. Future studies may clarify whether the fibrin-dependent generation of the hyaline membrane, processes that require the diffusion of procoagulative plasma factors into the alveolar lumen and the endothelial dysfunction, are preceded by MC-driven formation of interstitial edema in the alveolar septa.
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Betacoronavirus/inmunología , Infecciones por Coronavirus/inmunología , Mastocitos/inmunología , Neumonía Viral/inmunología , Alveolos Pulmonares/inmunología , Edema Pulmonar/inmunología , Trombosis/inmunología , Adulto , Anciano , Anciano de 80 o más Años , COVID-19 , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Femenino , Humanos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Gripe Humana/inmunología , Gripe Humana/patología , Gripe Humana/virología , Interleucina-4/inmunología , Masculino , Mastocitos/patología , Persona de Mediana Edad , Pandemias , Neumonía Viral/patología , Neumonía Viral/virología , Proteínas Proto-Oncogénicas c-kit/inmunología , Alveolos Pulmonares/patología , Alveolos Pulmonares/virología , Edema Pulmonar/patología , Edema Pulmonar/virología , SARS-CoV-2 , Trombosis/patología , Trombosis/virologíaRESUMEN
OBJECTIVE: The aim of this study was to compare in vivo effect of five pharmacological options on inflammation and pulmonary fibrosis induced by paraquat. METHODS: 54 Wistar SPF rats were used. After 2 h post-intoxication with paraquat ion, groups of 9 animals were randomly assigned to (1) cyclophosphamide plus dexamethasone (2) low molecular weight heparin (3) unfractionated heparin (4) vitamin C every 24 h, (5) atorvastatin or (6) placebo with intraperitoneal saline. Lung inflammation, alveolar injury, hepatocyte damage, hepatic regeneration, acute tubular necrosis and kidney congestion were evaluated. RESULTS: In the control group 100% of animals presented moderate and severe lung inflammation, while in the groups with atorvastatin and intratracheal heparin this proportion was lower (55.5%; CI 26.6-81.3%) (p = 0.025). A lower degree of moderate or severe hepatic regeneration was evident in the treatment groups with atorvastatin (p = 0.009). In this study was demonstrated that statins and heparin might have a protective effect in the paraquat-induced destructive phase. More evidence is needed to evaluated of dose-response effects of these drugs before to study in clinical trials.
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Quimioterapia/métodos , Pulmón/efectos de los fármacos , Neumonía/tratamiento farmacológico , Alveolos Pulmonares/efectos de los fármacos , Fibrosis Pulmonar/tratamiento farmacológico , Animales , Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Atorvastatina/farmacología , Ciclofosfamida/farmacología , Dexametasona/farmacología , Quimioterapia Combinada , Heparina/farmacología , Heparina de Bajo-Peso-Molecular/farmacología , Pulmón/patología , Paraquat/toxicidad , Neumonía/patología , Alveolos Pulmonares/patología , Fibrosis Pulmonar/inducido químicamente , Ratas Wistar , Resultado del TratamientoRESUMEN
Alveolar capillary dysplasia typically presents with neonatal pulmonary hypertension and early mortality. However, there is growing evidence for a subset of disease with atypical late onset and/or prolonged survival. Here, we present the variable clinical, genetic, and pathology findings of 4 such patients.
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Pulmón/patología , Síndrome de Circulación Fetal Persistente/genética , Síndrome de Circulación Fetal Persistente/patología , Alveolos Pulmonares/anomalías , Biopsia , Resultado Fatal , Femenino , Factores de Transcripción Forkhead/genética , Humanos , Hipertensión Pulmonar/etiología , Lactante , Trasplante de Pulmón , Masculino , Mutación , Alveolos Pulmonares/patología , Edema Pulmonar/etiologíaAsunto(s)
Endoscopía/métodos , Microscopía Confocal/métodos , Lesiones Precancerosas/diagnóstico por imagen , Lesiones Precancerosas/patología , Neoplasias del Sistema Respiratorio/diagnóstico por imagen , Neoplasias del Sistema Respiratorio/patología , Elastina , Humanos , Estudios Prospectivos , Alveolos Pulmonares/diagnóstico por imagen , Alveolos Pulmonares/patología , Reproducibilidad de los ResultadosRESUMEN
Pulmonary complications are frequent in patients with sickle cell disease (SCD), but few studies have described lung pathology in SCD. We studied the lung tissue of 30 deceased SCD patients (1994-2012). Demographics, genotype, clinical characteristics, cause of death and associated conditions are presented. We quantified the presence of pulmonary arterial changes, thrombosis and venous thickening. Alveolar capillary abnormalities were demonstrated using CD34 expression and confocal microscopy. Autopsy and echocardiography reports were reviewed to classify heart abnormalities. Tissue expression of markers of endothelial activation (vascular cell adhesion molecule 1, intercellular adhesion molecule 1 and vascular endothelial growth factor) was quantified in pulmonary vessels. Median age was 33 years; genotype was SS in 19, SC in 7 and Sß in 4, and there were 18 males. Hypertensive arterial changes were present in 76% of the patients, recent thrombosis in 80% and old thrombosis in 43%. Venous thickening was present in 23% and pulmonary capillary haemangiomatosis foci in 87%. Ten percent of the patients presented right ventricular hypertrophy. There was no increased expression of endothelial activation markers when compared to controls. SCD affects the whole pulmonary vascular tree and reflects the multiple burden on lung vasculature imposed by the disease upon time.
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Anemia de Células Falciformes/complicaciones , Enfermedades Pulmonares/etiología , Adolescente , Adulto , Anemia de Células Falciformes/patología , Capilares/patología , Niño , Ecocardiografía/métodos , Femenino , Humanos , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/patología , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/etiología , Enfermedades Pulmonares/patología , Masculino , Microscopía Confocal , Persona de Mediana Edad , Alveolos Pulmonares/patología , Arteria Pulmonar/patología , Trombosis/etiología , Trombosis/patología , Adulto JovenAsunto(s)
Humanos , Lesiones Precancerosas/patología , Lesiones Precancerosas/diagnóstico por imagen , Neoplasias del Sistema Respiratorio/patología , Neoplasias del Sistema Respiratorio/diagnóstico por imagen , Microscopía Confocal/métodos , Endoscopía/métodos , Alveolos Pulmonares/patología , Alveolos Pulmonares/diagnóstico por imagen , Estudios Prospectivos , Reproducibilidad de los Resultados , ElastinaRESUMEN
PURPOSE: To investigate the apoptotic mechanisms in rabbits with blast-induced acute lung injury (ALI). METHODS: A total of 40 rabbits were randomly divided into a blank control group (A, n=10) and an experimental group (EXP, n=30). Explosion-induced chest-ALI models were prepared and sampled at different time points (4, 12, and 24h after modeling, T1-T3) to test the lung dry weight/wet weight ratio (W/D) and arterial oxygen pressure (PaO2), apoptosis of lung tissue by the TUNEL assay, and Caspase-3, Bax, and Bcl-2 levels by immunohistochemical analysis. Furthermore, lung tissue was sampled to observe pathological morphology by microscopy. RESULTS: Under a light microscope, Group EXP exhibited obvious edema in the pulmonary interstitial substance and alveoli, a large number of red blood cells, inflammatory cells, and serous exudation in the alveolar cavity, as well as thickening of the pulmonary interstitial fluid. Compared to Group A, the W/D ratio was significantly increased in Group EXP (P<0.01), while PaO2 was significantly reduced (P<0.01). The apoptosis index was significantly increased (P<0.01), and caspase-3 and Bax/Bcl-2 levels were increased (P<0.01). CONCLUSION: Apoptosis plays an important role in the occurrence and development of acute lung injury in rabbits by participating in lung injury and promoting the progression of ALI.
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Lesión Pulmonar Aguda/fisiopatología , Apoptosis/fisiología , Traumatismos por Explosión/fisiopatología , Lesión Pulmonar Aguda/sangre , Lesión Pulmonar Aguda/patología , Animales , Traumatismos por Explosión/sangre , Traumatismos por Explosión/patología , Caspasa 3/sangre , Modelos Animales de Enfermedad , Femenino , Masculino , Proteínas Proto-Oncogénicas c-bcl-2/sangre , Alveolos Pulmonares/patología , Conejos , Distribución Aleatoria , Proteína X Asociada a bcl-2/sangreRESUMEN
Abstract Purpose: To investigate the apoptotic mechanisms in rabbits with blast-induced acute lung injury (ALI). Methods: A total of 40 rabbits were randomly divided into a blank control group (A, n=10) and an experimental group (EXP, n=30). Explosion-induced chest-ALI models were prepared and sampled at different time points (4, 12, and 24h after modeling, T1-T3) to test the lung dry weight/wet weight ratio (W/D) and arterial oxygen pressure (PaO2), apoptosis of lung tissue by the TUNEL assay, and Caspase-3, Bax, and Bcl-2 levels by immunohistochemical analysis. Furthermore, lung tissue was sampled to observe pathological morphology by microscopy. Results: Under a light microscope, Group EXP exhibited obvious edema in the pulmonary interstitial substance and alveoli, a large number of red blood cells, inflammatory cells, and serous exudation in the alveolar cavity, as well as thickening of the pulmonary interstitial fluid. Compared to Group A, the W/D ratio was significantly increased in Group EXP (P<0.01), while PaO2 was significantly reduced (P<0.01). The apoptosis index was significantly increased (P<0.01), and caspase-3 and Bax/Bcl-2 levels were increased (P<0.01). Conclusion: Apoptosis plays an important role in the occurrence and development of acute lung injury in rabbits by participating in lung injury and promoting the progression of ALI.
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Animales , Masculino , Femenino , Conejos , Traumatismos por Explosión/fisiopatología , Apoptosis/fisiología , Lesión Pulmonar Aguda/fisiopatología , Alveolos Pulmonares/patología , Traumatismos por Explosión/patología , Traumatismos por Explosión/sangre , Distribución Aleatoria , Proteínas Proto-Oncogénicas c-bcl-2/sangre , Modelos Animales de Enfermedad , Proteína X Asociada a bcl-2/sangre , Caspasa 3/sangre , Lesión Pulmonar Aguda/patología , Lesión Pulmonar Aguda/sangreRESUMEN
Gestational exposure to air pollution is associated with negative outcomes in newborns and children. In a previous study, we demonstrated a synergistic negative effect of pre- and postnatal exposure to PM2.5 on lung development in mice. However, the means by which air pollution affects development of the lung have not yet been identified. In this study, we exposed pregnant BALB/c mice and their offspring to concentrated urban PM2.5 (from São Paulo, Brazil; target dose 600⯵g/m3 for 1â¯h daily). Exposure was started on embryonic day 5.5 (E5.5, time of placental implantation). Lung tissue of fetuses and offspring was submitted to stereological and transcriptomic analyses at E14.5 (pseudoglandular stage of lung development), E18.5 (saccular stage) and P40 (postnatal day 40, alveolarized lung). Additionally, lung function and cellularity of bronchoalveolar lavage (BAL) fluid were studied in offspring animals at P40. Compared to control animals that were exposed to filtered air throughout gestation and postnatal life, PM-exposed mice exhibited higher lung elastance and a lower alveolar number at P40 whilst the total lung volume and cellularity of BAL fluid were not affected. Glandular and saccular structures of fetal lungs were not altered upon gestational exposure; transcriptomic signatures, however, showed changes related to DNA damage and its regulation, inflammation and regulation of cell proliferation. A differential expression was validated at E14.5 for the candidates Sox8, Angptl4 and Gas1. Our data substantiate the in utero biomolecular effect of gestational exposure to air pollution and provide first-time stereological evidence that pre- and early life-postnatal exposure compromise lung development, leading to a reduced number of alveoli and an impairment of lung function in the adult mouse.
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Contaminación del Aire/efectos adversos , Pulmón/fisiopatología , Material Particulado/efectos adversos , Material Particulado/análisis , Alveolos Pulmonares/patología , Proteína 4 Similar a la Angiopoyetina/biosíntesis , Animales , Brasil , Proteínas de Ciclo Celular/biosíntesis , Daño del ADN/efectos de los fármacos , Elasticidad/fisiología , Femenino , Proteínas Ligadas a GPI/biosíntesis , Regulación de la Expresión Génica/efectos de los fármacos , Pulmón/crecimiento & desarrollo , Pulmón/metabolismo , Pulmón/patología , Masculino , Ratones , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Factores de Transcripción SOXE/biosíntesis , Factores de TiempoRESUMEN
The response of lungs with emphysema to an acute lung injury (ALI) remains unclear. This study compared the lung response to intratracheal instillation of lipopolysaccharide (LPS) in rats with and without emphysema. Twenty-four Wistar rats were randomized to four groups: control group (C-G), ALI group (ALI-G), emphysema group (E-G), emphysema and ALI group (E-ALI-G). Euthanasia and the following analysis were performed 24 h after ALI induction: lung histology, bronchoalveolar lavage (BAL), mRNA expression of inflammatory mediators, and blood gas measures. The histological analysis showed that animals of ALI-G (0.55 ± 0.15) and E-ALI-G (0.69 ± 0.08) had a higher ALI score compared to C-G (0.12 ± 0.04) and E-G (0.16 ± 0.04) (p < 0.05). The analysis of each component of the score demonstrated that ALI-G and E-ALI-G had greater alveolar and interstitial neutrophil infiltration, as well as greater amount of alveolar proteinaceous debris. Comparing the two groups that received LPS, there was a trend of higher ALI in the E-ALI-G, specially due to a higher neutrophil infiltration in the alveolar spaces and a higher septal thickening. Total cell count (E-G = 3.09 ± 0.83; ALI-G = 4.45 ± 1.9; E-ALI-G = 5.9 ± 2.1; C-G = 0.73 ± 0.37 × 105) and neutrophil count (E-G = 0.69 ± 0.35; ALI-G = 2.53 ± 1.09; E-ALI-G = 3.86 ± 1.4; C-G = 0.09 ± 0.07 × 105) in the BAL were higher in the groups E-G, ALI-G, and E-ALI-G when compared to C-G (p < 0.05). The IL-6, TNF-α, and CXCL2 mRNA expressions were higher in the animals that received LPS (ALI-G and E-ALI-G) compared to the C-G and E-G (p < 0.05). No statistically significant difference was observed in the BAL cellularity and in the expression of inflammatory mediators between the ALI-G and the E-ALI-G. The severity of ALI in response to intratracheal instillation of LPS did not show difference in rats with and without intratracheal-induced emphysema.
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Lesión Pulmonar Aguda/inducido químicamente , Lipopolisacáridos , Elastasa Pancreática , Alveolos Pulmonares/patología , Enfisema Pulmonar/inducido químicamente , Lesión Pulmonar Aguda/genética , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/patología , Animales , Líquido del Lavado Bronquioalveolar/química , Permeabilidad Capilar , Quimiocina CXCL2/genética , Quimiocina CXCL2/metabolismo , Modelos Animales de Enfermedad , Mediadores de Inflamación/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/patología , Masculino , Infiltración Neutrófila , Alveolos Pulmonares/metabolismo , Enfisema Pulmonar/genética , Enfisema Pulmonar/metabolismo , Enfisema Pulmonar/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Wistar , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia ArribaRESUMEN
Acute respiratory distress syndrome is a challenging entity for the intensivist. The pathological hallmark of the acute phase is diffuse alveolar damage, which is present in approximately half of living patients with acute respiratory distress syndrome. It is clear that respiratory support for acute respiratory distress syndrome has gradually been improving over recent decades. However, it is also evident that these procedures are beneficial, as they reduce lung injury and keep the patient alive. This could be interpreted as a time-gaining strategy until the trigger or causal or risk factor improves, the inflammatory storm decreases and the lung heals. However, all except two pharmacological treatments (neuromuscular blockers and steroids) were unable to improve the acute respiratory distress syndrome outcome. The hypothesis that pharmacological negative results may be explained by the histological heterogeneity of acute respiratory distress syndrome has been supported by the recent demonstration that acute respiratory distress syndrome with diffuse alveolar damage constitutes a specific clinical-pathological entity. Given that diffuse alveolar damage is a pathological diagnosis and that open lung biopsy (the most common technique to obtain lung tissue) has several side effects, it is necessary to develop surrogate biomarkers for diffuse alveolar damage. The aim of this narrative review is to address the following three topics related to acute respiratory distress syndrome: (a) the relationship between acute respiratory distress syndrome and diffuse alveolar damage, (b) how diffuse alveolar damage could be surrogated in the clinical setting and
A síndrome do desconforto respiratório agudo é um desafio para o intensivista. A característica principal desta doença aguda é o dano alveolar difuso, presente em cerca de metade dos pacientes com a síndrome. É claro que o suporte respiratório à síndrome do desconforto respiratório agudo tem melhorado gradualmente nas últimas décadas. É também evidente que todos estes procedimentos são benéficos, já que reduzem a lesão pulmonar e mantêm o paciente vivo. Isto deve ser interpretado como uma estratégia de ganho de tempo, até que o fator desencadeante ou de risco causal melhore, assim como a tempestade inflamatória diminua e o pulmão se cure. Por outro lado, todos - exceto dois tratamentos farmacológicos (bloqueadores neuromusculares e esteroides) - são incapazes de melhorar o desfecho da síndrome do desconforto respiratório agudo. A hipótese de que os resultados farmacológicos negativos podem ser explicados pela heterogeneidade histológica da síndrome do desconforto respiratório agudo tem sido apoiada pelas recentes demonstrações de que a síndrome com dano alveolar difuso tem característica clínico-patológica específica. O dano alveolar difuso é um diagnóstico patológico, e a biópsia pulmonar a céu aberto (a técnica mais comum para obtenção de tecido pulmonar) tem efeitos colaterais graves, sendo necessário que se desenvolvam biomarcadores substitutos para o dano alveolar difuso. O objetivo desta revisão é discutir três tópicos relacionados à síndrome do desconforto respiratório agudo: o relacionamento entre a síndrome do desconforto respiratório agudo e o dano alveolar difuso; como o dano alveolar difuso pode ser representado no quadro clínico; e como o enriquecimento pode melhorar os resultados de estudos clínicos farmacológicos realizados com pacientes com a síndrome e com dano alveolar difuso.
Asunto(s)
Unidades de Cuidados Intensivos , Alveolos Pulmonares/patología , Síndrome de Dificultad Respiratoria/terapia , Biomarcadores/metabolismo , Biopsia/métodos , Cuidados Críticos/métodos , Humanos , Síndrome de Dificultad Respiratoria/fisiopatología , Factores de RiesgoRESUMEN
RESUMO A síndrome do desconforto respiratório agudo é um desafio para o intensivista. A característica principal desta doença aguda é o dano alveolar difuso, presente em cerca de metade dos pacientes com a síndrome. É claro que o suporte respiratório à síndrome do desconforto respiratório agudo tem melhorado gradualmente nas últimas décadas. É também evidente que todos estes procedimentos são benéficos, já que reduzem a lesão pulmonar e mantêm o paciente vivo. Isto deve ser interpretado como uma estratégia de ganho de tempo, até que o fator desencadeante ou de risco causal melhore, assim como a tempestade inflamatória diminua e o pulmão se cure. Por outro lado, todos - exceto dois tratamentos farmacológicos (bloqueadores neuromusculares e esteroides) - são incapazes de melhorar o desfecho da síndrome do desconforto respiratório agudo. A hipótese de que os resultados farmacológicos negativos podem ser explicados pela heterogeneidade histológica da síndrome do desconforto respiratório agudo tem sido apoiada pelas recentes demonstrações de que a síndrome com dano alveolar difuso tem característica clínico-patológica específica. O dano alveolar difuso é um diagnóstico patológico, e a biópsia pulmonar a céu aberto (a técnica mais comum para obtenção de tecido pulmonar) tem efeitos colaterais graves, sendo necessário que se desenvolvam biomarcadores substitutos para o dano alveolar difuso. O objetivo desta revisão é discutir três tópicos relacionados à síndrome do desconforto respiratório agudo: o relacionamento entre a síndrome do desconforto respiratório agudo e o dano alveolar difuso; como o dano alveolar difuso pode ser representado no quadro clínico; e como o enriquecimento pode melhorar os resultados de estudos clínicos farmacológicos realizados com pacientes com a síndrome e com dano alveolar difuso.
ABSTRACT Acute respiratory distress syndrome is a challenging entity for the intensivist. The pathological hallmark of the acute phase is diffuse alveolar damage, which is present in approximately half of living patients with acute respiratory distress syndrome. It is clear that respiratory support for acute respiratory distress syndrome has gradually been improving over recent decades. However, it is also evident that these procedures are beneficial, as they reduce lung injury and keep the patient alive. This could be interpreted as a time-gaining strategy until the trigger or causal or risk factor improves, the inflammatory storm decreases and the lung heals. However, all except two pharmacological treatments (neuromuscular blockers and steroids) were unable to improve the acute respiratory distress syndrome outcome. The hypothesis that pharmacological negative results may be explained by the histological heterogeneity of acute respiratory distress syndrome has been supported by the recent demonstration that acute respiratory distress syndrome with diffuse alveolar damage constitutes a specific clinical-pathological entity. Given that diffuse alveolar damage is a pathological diagnosis and that open lung biopsy (the most common technique to obtain lung tissue) has several side effects, it is necessary to develop surrogate biomarkers for diffuse alveolar damage. The aim of this narrative review is to address the following three topics related to acute respiratory distress syndrome: (a) the relationship between acute respiratory distress syndrome and diffuse alveolar damage, (b) how diffuse alveolar damage could be surrogated in the clinical setting and (c) how enrichment in diffuse alveolar damage may improve the results of pharmacological clinical trials tried out on patients with acute respiratory distress syndrome.
Asunto(s)
Humanos , Alveolos Pulmonares/patología , Síndrome de Dificultad Respiratoria/terapia , Unidades de Cuidados Intensivos , Síndrome de Dificultad Respiratoria/fisiopatología , Biopsia/métodos , Biomarcadores/metabolismo , Factores de Riesgo , Cuidados Críticos/métodosRESUMEN
BACKGROUND: Diffuse alveolar damage (DAD), which is the histological surrogate for acute respiratory distress syndrome (ARDS), has a multifactorial aetiology. Therefore it is possible that the immunopathology differs among the various presentations of DAD. The aim of this study is to compare lung immunopathology of viral (influenza A(H1N1)pdm09) to non-viral, extrapulmonary aetiologies in autopsy cases with DAD. METHODS: The lung tissue of 44 patients, was divided in the H1N1 group (n = 15) characterized by severe pulmonary injury due to influenza A(H1N1)pdm09 infection; the ARDS group (n = 13), characterized by patients with DAD due to non-pulmonary causes; and the Control group (n = 16), consisting of patients with non-pulmonary causes of death. Immunohistochemistry and image analysis were used to quantify, in the parenchyma and small airways, several immune cell markers. RESULTS: Both DAD groups had higher expression of neutrophils and macrophages in parenchyma and small airways. However, there was a higher expression of CD4+ and CD8+ T lymphocytes, CD83+ dendritic cells, granzyme A+ and natural killer + cell density in the lung parenchyma of the H1N1 group (p < 0.05). In the small airways, there was a lower cell density of tryptase + mast cells and dendritic + cells and an increase of IL-17 in both DAD groups (p < 0.05). CONCLUSION: DAD due to viral A(H1N1)pdm09 is associated with a cytotoxic inflammatory phenotype, with partially divergent responses in the parenchyma relative to the small airways. In non-viral DAD, main immune cell alterations were found at the small airway level, reinforcing the role of the small airways in the pathogenesis of the exudative phase of DAD.
Asunto(s)
Células Dendríticas/patología , Inmunidad Celular/inmunología , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Alveolos Pulmonares/patología , Síndrome de Dificultad Respiratoria/patología , Linfocitos T/patología , Adulto , Anciano , Células Dendríticas/inmunología , Femenino , Humanos , Gripe Humana/inmunología , Gripe Humana/patología , Masculino , Persona de Mediana Edad , Alveolos Pulmonares/inmunología , Síndrome de Dificultad Respiratoria/inmunología , Estudios Retrospectivos , Linfocitos T/inmunologíaRESUMEN
BACKGROUND: Diffuse alveolar haemorrhage (DAH) is a manifestation of several immune and nonimmune diseases. OBJECTIVE: The objective of this study was to characterize the clinical characteristics and short-term outcomes of patients with immune-mediated DAH requiring hospital admission. METHODS: A retrospective study from December 2010 to December 2015, was conducted by analyzing the clinical records of 39 patients with DAH with a proven immunological origin. The diagnosis of individual collagen vascular diseases (CVD) was made according to the criteria of the corresponding societies. RESULTS: Thirty-nine patients were included (median age 44.8 years, range 16-76). The main causes of DAH were ANCA-related vasculitis (74.3%) mainly granulomatosis with polyangiitis (n = 14) and microscopic polyangiitis (n = 13). Thirty patients (76.9%) had hemoptysis. An alveolar airspace filling pattern was found in most of patients (59%). All the patients had a drop in hemoglobin level that ranged from 1.0 to 3.0 g/dL. BAL fluid was macroscopically bloody in 43.6% of patients (n = 17) and showed siderophagic alveolitis on BAL cytology in 100%. All patients received high doses of corticosteroids. Other additional treatments were antibiotics (53,8%, n = 21), intravenous cyclophosphamide (87.2%, n = 34), plasma exchange (35.9%, n = 14); intravenous immunoglobulin (12.8%, n = 5) and rituximab in 5 patients (12.8%). Mortality rate was higher amongst patients who required dialysis (50.0 vs 15.4%, p = 0.045), with SaO2 <90% at admission (50.0 vs 5.3%, p = 0.003) or those who required mechanical ventilation (76.9 vs 6.8%, p = < 0.001). CONCLUSION: DAH may present without hemoptysis and requires an early bronchoscopy to confirm the diagnosis and exclude infection. Other characteristics could be included in the abstract which are relevant to the paper. (relation between mortality, dialysis, ventilation, etc.).
Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Hemorragia/etiología , Enfermedades Pulmonares/patología , Alveolos Pulmonares/irrigación sanguínea , Administración Intravenosa , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Anciano , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Broncoscopía/métodos , Enfermedades del Tejido Conjuntivo/complicaciones , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Femenino , Hemoptisis/diagnóstico , Hemoptisis/etiología , Hemorragia/complicaciones , Hemorragia/inmunología , Hemorragia/mortalidad , Hospitalización/estadística & datos numéricos , Humanos , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Alveolos Pulmonares/patología , Respiración Artificial/métodos , Estudios Retrospectivos , Adulto JovenRESUMEN
Elastase (PPE) is usually used for emphysema models, whereas bleomycin (BLM) is used for fibrosis models. The aim of this study was to investigate the effect of BLM in PPE-induced emphysema, as well as the effect of PPE in BLM-induced fibrosis. C57BL/6 mice were divided into five groups: control, PPE, BLM, PPE + BLM, and BLM + PPE. Mice received saline, PPE (3 U/mouse), or BLM (20 U/kg) by intranasal instillation. Mice from the BLM and BLM + PPE groups received BLM on day 0 and saline or PPE on day 21, respectively. Those in the PPE and PPE + BLM groups received PPE on day 0 and saline or BLM on day 21, respectively. Mice were euthanized on day 42. We performed histology, morphometry in lung sections and ELISA, zymography and western blotting in BAL samples or lung homogenates. In the lungs of PPE + BLM and BLM + PPE groups, we observed inflammation, oxidative stress and expression of MMP-2 and MMP-9. The alveolar enlargement was reduced in the PPE + BLM group, suggesting that the BLM could participate in the alveolar remodeling process. The significance of this result supports future therapeutic approaches targeting extracellular-matrix deposition in patients with emphysema as a way to repair the enlargement of alveoli and airspaces.