Eucalyptol promotes lung repair in mice following cigarette smoke-induced emphysema.

BACKGROUND: Eucalyptol is a monoterpenoid oil present in many plants, principally the Eucalyptus species, and has been reported to have anti-inflammatory and antioxidative effects. HYPOTHESIS/PURPOSE: Since the potential effect of eucalyptol on mouse lung repair has not yet been studied, and considering that chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide, the aim of this study was to investigate eucalyptol treatment in emphysematous mice. STUDY DESIGN: Male mice (C57BL/6) were divided into the following groups: control (sham-exposed), cigarette smoke (CS) (mice exposed to 12 cigarettes a day for 60 days), CS + 1 mg/ml (CS mice treated with 1 mg/ml eucalyptol for 60 days), and CS + 10 mg/ml (CS mice treated with 10 mg/ml eucalyptol for 60 days). Mice in the CS and control groups received vehicle for 60 days. Eucalyptol (or the vehicle) was administered via inhalation (15 min/daily). Mice were sacrificed 24 h after the completion of the 120-day experimental procedure. METHODS: Histology and additional lung morphometric analyses, including analysis of mean linear intercept (Lm) and volume density of alveolar septa (Vv[alveolar septa]) were performed. Biochemical analyses were also performed using colorimetric assays for myeloperoxidase (MPO), malondialdehyde (MDA), and superoxide dismutase (SOD) activity, in addition to using ELISA kits for the determination of inflammatory marker levels (tumor necrosis factor alpha [TNF-α], interleukin-1 beta [IL-1ß], interleukin 6 [IL-6], keratinocyte chemoattractant [KC], and tumor growth factor beta 1 [TGF-ß1]). Finally, we investigated protein levels by western blotting (nuclear factor (erythroid-derived 2)-like 2 [Nrf2], nuclear factor kappa B [NF-κB], matrix metalloproteinase 12 [MMP-12], tissue inhibitor of matrix metalloproteinase 1 [TIMP-1], neutrophil elastase [NE], and elastin). RESULTS: Eucalyptol promoted lung repair at the higher dose (10 mg/ml), with de novo formation of alveoli, when compared to the CS group. This result was confirmed with Lm and Vv[alveolar septa] morphometric analyses. Moreover, collagen deposit around the peribronchiolar area was reduced with eucalyptol treatment when compared to the CS group. Eucalyptol also reduced all inflammatory (MPO, TNF-α, IL-1ß, IL-6, KC, and TGF-ß1) and redox marker levels (MDA) when compared to the CS group (at least p < 0.05). In general, 10 mg/ml eucalyptol was more effective than 1 mg/ml and, at both doses, we observed an upregulation of SOD activity when compared to the CS group (p < 0.001). Eucalyptol upregulated elastin and TIMP-1 levels, and reduced neutrophil elastase (NE) levels, when compared to the CS group. CONCLUSION: In summary, eucalyptol promoted lung repair in emphysematous mice and represents a potential therapeutic phytomedicine in the treatment of COPD.

Emphysematous and granulomatous submucosal rumenitis in a feedlot Nellore stee

Background: Emphysematous rumenitis is a condition characterized by gas filled bubbles or cysts in the ruminal mucosa. Although a similar pathology is reported from swine and humans, the incidence of this disease in cattle seems to be scarce. The etiology of emphysematous rumenitis is uncertain once many factors can be involved in its pathogeny, a single cause is difficult to ascertain. This lesion usually fails to display specific clinical signs; however, some degree of malabsorption and weight loss is expected. We described a case of emphysematous granulomatous submucosal rumenitis in a 2.5-yearold feedlot Nellore steer that presented reduction on daily weight gain.Case: Rumen fragments of a 2.5-year-old Nellore steer were submitted for histopathological evaluation at the Sector of Pathological Anatomy (SAP) of the Rural Federal University of Rio de Janeiro, Brazil. The specimens were part of an experimental trial to evaluate the effect of phosphorus (P) supplementation on nutrient intake, performance and P balance in fifty feedlot Nellore steers. Following a short adaptation period, in which behavioral observations were made twice daily to assess possible adverse factors, all steers were fed with balanced diet for one hundred and sixteen days. The steers were then slaughtered in order to evaluate macroscopic changes in the gastrointestinal system. Rumen and abomasum of each steer was emptied, washed with tap water and grossly examined. One steer presented ruminal lesion, while the other forty-nine did not show any ruminal injury. Throughout the experiment the affected steer showed reduction of daily weight gain; but during clinical examination no additional clinical sign was seen. At gross inspection, a reduction in the amount of muscular and adipose tissue was seen. Multiple coalescent bullous elevated structures measuring three to ten mm diameter were covering about 40% of the ruminal surface.[...]

Emphysematous and granulomatous submucosal rumenitis in a feedlot Nellore stee

Background: Emphysematous rumenitis is a condition characterized by gas filled bubbles or cysts in the ruminal mucosa. Although a similar pathology is reported from swine and humans, the incidence of this disease in cattle seems to be scarce. The etiology of emphysematous rumenitis is uncertain once many factors can be involved in its pathogeny, a single cause is difficult to ascertain. This lesion usually fails to display specific clinical signs; however, some degree of malabsorption and weight loss is expected. We described a case of emphysematous granulomatous submucosal rumenitis in a 2.5-yearold feedlot Nellore steer that presented reduction on daily weight gain.Case: Rumen fragments of a 2.5-year-old Nellore steer were submitted for histopathological evaluation at the Sector of Pathological Anatomy (SAP) of the Rural Federal University of Rio de Janeiro, Brazil. The specimens were part of an experimental trial to evaluate the effect of phosphorus (P) supplementation on nutrient intake, performance and P balance in fifty feedlot Nellore steers. Following a short adaptation period, in which behavioral observations were made twice daily to assess possible adverse factors, all steers were fed with balanced diet for one hundred and sixteen days. The steers were then slaughtered in order to evaluate macroscopic changes in the gastrointestinal system. Rumen and abomasum of each steer was emptied, washed with tap water and grossly examined. One steer presented ruminal lesion, while the other forty-nine did not show any ruminal injury. Throughout the experiment the affected steer showed reduction of daily weight gain; but during clinical examination no additional clinical sign was seen. At gross inspection, a reduction in the amount of muscular and adipose tissue was seen. Multiple coalescent bullous elevated structures measuring three to ten mm diameter were covering about 40% of the ruminal surface.[...](AU)

Emphysematous pyelonephritis in a transplanted kidney

Emphysematous pyelonephritis is a rare infection characterized by necrosis and gas accumulation in the renal parenchyma, adjacent tissues, and/or urinary collecting system. This entity is rarely reported in transplanted kidneys. Computed tomography imaging is necessary for diagnosis and risk classification. The authors described the case of a 58-year-old man who underwent a kidney transplant and presented sepsis from a urinary tract infection. An abdominal tomography showed some characteristics of emphysematous pyelonephritis associated with an abscess. A graft biopsy, performed 45 days after the transplant, failed to show signs of infection, and tubule-interstitial and vascular rejection were ruled out. The patient had a poor outcome, and a nephrectomy was needed, the pathological analysis of which yielded the diagnosis of chronic pyelonephritis with necrotizing papillitis. The patient became hemodynamically unstable and died. The authors highlight the current tomographic criteria for the diagnosis and treatment of emphysematous pyelonephritis and question the validity of accepting the same standards used to guide the treatment of patients without transplants, and call attention to the importance of the clinical status for the indication of nephrectomy in cases of emphysematous pyelonephritis.

Fissure Integrity and Volume Reduction in Emphysema: A Retrospective Study.

BACKGROUND: One-way endobronchial valves (EBVs) relieve symptoms of emphysema, particularly in patients without collateral ventilation between the target and adjacent lobes. Pretreatment knowledge of fissure integrity could serve as an aid in indicating EBV interventions. OBJECTIVE: This study aimed to investigate the relationship between software-measured lung fissure integrity and clinically relevant lung volume reduction (≥350 ml) in emphysema patients treated with one-way EBVs using a lobar exclusion strategy. METHODS: Of 108 patients treated between March 2008 and July 2014, 38 had both baseline and follow-up computed tomography (CT) scans acquired following a specific protocol for quantitative CT analysis and were included in the study (total of 39 treatments, two lungs treated in 1 patient). Outcome measures were fissure integrity measured on baseline CT scans, difference between pre- and postoperative lung volume (considering the lowest measured postoperative volume), and correlation between fissure integrity and volume change. RESULTS: Fissure integrity ≥75% correlated with volume reduction ≥350 ml (Spearman coefficient: -0.65; p < 0.01). The mean and median volume reductions were 1,223.96 ± 907.5 ml and 663 ml, respectively, for lungs with fissure integrity ≥75% (n = 31). The accuracy of fissure integrity ≥75% in predicting a volume reduction was 87.2%. The positive predictive value of fissure integrity ≥75% to predict a volume reduction ≥350 ml was 83.9%, and it was 70% for fissure integrity 75-90% and 90.5% for fissure integrity >90%. CONCLUSIONS: A target lobe volume reduction using EBVs is possible with lung fissure integrity ≥75%. For patients with fissure integrity between 75 and 90%, a further evaluation of interlobar ventilation should be performed. A clinically relevant volume reduction following treatment with EBVs is likely with any level of fissure integrity >90%.

Gastritis enfisematosa como causa infrecuente de abdomen agudo / Emphysematous gastritis as an infrequent cause of acute abdominal pain

La gastritis enfisematosa (GE) es una entidad poco frecuente, descripta por primera vez por Fraenkel en 1889. Se caracteriza por la invasión de la pared gástrica por gérmenes productores de gas, y se asocia a una alta morbimortalidad. Se describen en la bibliografía diferentes factores de riesgo que favorecerían su desarrollo, entre ellos ingesta de cáusticos, diabetes, abuso de alcohol, isquemia gástrica y cirugía de estómago. El cuadro clínico se caracteriza por dolor abdominal agudo y progresivo asociado a repercusión sistémica, sepsis severa, shock séptico, disfunción orgánica múltiple y muerte. Los métodos de diagnóstico por imágenes cumplen un rol fundamental en su abordaje, siendo la tomografía computada multidetector (TCMD) el método de elección, ya que cuenta con la capacidad de mostrar la presencia de gas en el interior de la pared gástrica (neumatosis gástrica) en asociación con el aumento de su espesor, siendo estos dos hallazgos la clave en el diagnóstico. También se encuentra presente un aumento de la densidad del tejido perigástrico compatible con cambios de tipo inflamatorio o infeccioso, y en algunas ocasiones se asocia a neumatosis portal. Se realiza una actualización del tema enfatizando el rol de la TCMD para su diagnóstico.(AU)

Emphysematous gastritis (EG) is a rare entity first described in 1889. It is characterized by the invasion of the gastric wall by gas-producing bacteria, and is associated with high morbidity and mortality. The clinical picture is characterized by acute abdominal pain associated with progressive systemic repercussions, severe sepsis, septic shock, multiple organ dysfunction, and death. Imaging methods play a fundamental role in the diagnosis. Multidetector Computed Tomography (MDCT) is the method of choice, since it has the ability to show the presence of gas within the gastric wall (gastric pneumatosis) in association with increased wall thickness. These two features are key findings for diagnosis. Increased density of perigastric tissue is frequently present, due to infectious or inflammatory changes; sometimes portal pneumatosis is present as well. An update on EG is presented, emphasizing the role of MDCT in diagnosis.(AU)

Gastritis enfisematosa como causa infrecuente de abdomen agudo / Emphysematous gastritis as an infrequent cause of acute abdominal pain

La gastritis enfisematosa (GE) es una entidad poco frecuente, descripta por primera vez por Fraenkel en 1889. Se caracteriza por la invasión de la pared gástrica por gérmenes productores de gas, y se asocia a una alta morbimortalidad. Se describen en la bibliografía diferentes factores de riesgo que favorecerían su desarrollo, entre ellos ingesta de cáusticos, diabetes, abuso de alcohol, isquemia gástrica y cirugía de estómago. El cuadro clínico se caracteriza por dolor abdominal agudo y progresivo asociado a repercusión sistémica, sepsis severa, shock séptico, disfunción orgánica múltiple y muerte. Los métodos de diagnóstico por imágenes cumplen un rol fundamental en su abordaje, siendo la tomografía computada multidetector (TCMD) el método de elección, ya que cuenta con la capacidad de mostrar la presencia de gas en el interior de la pared gástrica (neumatosis gástrica) en asociación con el aumento de su espesor, siendo estos dos hallazgos la clave en el diagnóstico. También se encuentra presente un aumento de la densidad del tejido perigástrico compatible con cambios de tipo inflamatorio o infeccioso, y en algunas ocasiones se asocia a neumatosis portal. Se realiza una actualización del tema enfatizando el rol de la TCMD para su diagnóstico.

Emphysematous gastritis (EG) is a rare entity first described in 1889. It is characterized by the invasion of the gastric wall by gas-producing bacteria, and is associated with high morbidity and mortality. The clinical picture is characterized by acute abdominal pain associated with progressive systemic repercussions, severe sepsis, septic shock, multiple organ dysfunction, and death. Imaging methods play a fundamental role in the diagnosis. Multidetector Computed Tomography (MDCT) is the method of choice, since it has the ability to show the presence of gas within the gastric wall (gastric pneumatosis) in association with increased wall thickness. These two features are key findings for diagnosis. Increased density of perigastric tissue is frequently present, due to infectious or inflammatory changes; sometimes portal pneumatosis is present as well. An update on EG is presented, emphasizing the role of MDCT in diagnosis.

A comparative study of extracellular matrix remodeling in two murine models of emphysema.

A single instillation of porcine pancreatic elastase (PPE) results in significant airspace enlargement on the 28th day after instillation, whereas cigarette smoke (CS) exposure requires 6 months to produce mild emphysema in rodents. Considering that there are differences in the pathogenesis of parenchymal destruction in these different experimental models, it is likely that there may be different patterns of extracellular matrix (ECM) remodeling. To evaluate ECM remodeling, C57BL/6 mice were submitted to either a nasal drop of PPE (PPE 28 Days) or exposed for 6 months to cigarette smoke (CS 6 months). Control groups received either an intranasal instillation of saline solution (Saline 28 Days) or remained without any smoke inhalation for six months (Control 6 months). We measured the mean linear intercept and the volume proportion of collagen type I, collagen type III, elastin and fibrillin. We used emission-scanning confocal microscopy to verify the fiber distribution. Both models induced increased mean linear intercept in relation to the respective controls, being larger in the elastase model in relation to the CS model. In the CS model, emphysema was associated with an increase in the volume proportion of fibrillin, whereas in the PPE model there was an increase in the parenchymal elastin content. In both models, there was an increase in collagen type III, which was higher in the CS-exposed mice. We concluded that ECM remodeling is different in the two most used experimental models of emphysema.

Protective effects of bone marrow mononuclear cell therapy on lung and heart in an elastase-induced emphysema model.

We hypothesized that bone marrow-derived mononuclear cell (BMDMC) therapy protects the lung and consequently the heart in experimental elastase-induced emphysema. Twenty-four female C57BL/6 mice were intratracheally instilled with saline (C group) or porcine pancreatic elastase (E group) once a week during 4 weeks. C and E groups were randomized into subgroups receiving saline (SAL) or male BMDMCs (2 × 10(6), CELL) intravenously 3h after the first saline or elastase instillation. Compared to E-SAL group, E-CELL mice showed, at 5 weeks: lower mean linear intercept, neutrophil infiltration, elastolysis, collagen fiber deposition in alveolar septa and pulmonary vessel wall, lung cell apoptosis, right ventricle wall thickness and area, higher endothelial growth factor and insulin-like growth factor mRNA expressions in lung tissue, and reduced platelet-derived growth factor, transforming growth factor-ß, and caspase-3 expressions. In conclusion, BMDMC therapy was effective at modulating the inflammatory and remodeling processes in the present model of elastase-induced emphysema.

N-(2-mercaptopropionyl)-glycine but not allopurinol prevented cigarette smoke-induced alveolar enlargement in mouse.

We investigated the possible protective effects of the Allopurinol (A), N-(2-mercaptopropionyl)-glycine (M) and N-acetylcysteine (N) against lung injury caused by long-term exposure to cigarette smoke (CS) in mouse. C57BL6 mice were exposed to 12 cigarettes a day for 60 days and concomitantly treated with either one of the antioxidant drugs diluted in saline (CS+A-50 mg/kg; CS+M-200 mg/kg/day; CS+N-200 mg/kg/day). Control groups were sham-smoked (AA). Long-term CS exposure results in extensive parenchyma destruction in CS group. Both CS+N and CS+M groups showed preserved alveolar structure and showed preserved lung function when compared to CS group. Macrophage and neutrophil counts were decreased in CS+M, and CS+N groups when compared to CS group (p<0.05). Antioxidant enzyme activities were reduced in all treated groups. CS+A showed the highest reduction in catalase activity (-25%, p<0.01). We conclude that M treatment reduced long-term CS-induced inflammatory lung parenchyma destruction and lung function, comparable to N treatment, however, antioxidant administration did not reverse CS-induced antioxidant enzyme activity reduction.

Spirometric assessment of lung transplant patients: one year follow-up.

OBJECTIVE: The purpose of this study was to compare spirometry data between patients who underwent single-lung or double-lung transplantation the first year after transplantation. INTRODUCTION: Lung transplantation, which was initially described as an experimental method in 1963, has become a therapeutic option for patients with advanced pulmonary diseases due to improvements in organ conservation, surgical technique, immunosuppressive therapy and treatment of post-operative infections. METHODS: We retrospectively reviewed the records of the 39 patients who received lung transplantation in our institution between August 2003 and August 2006. Twenty-nine patients survived one year post-transplantation, and all of them were followed. RESULTS: The increase in lung function in the double-lung transplant group was more substantial than that of the single-lung transplant group, exhibiting a statistical difference from the 1st month in both the forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC) in comparison to the pre-transplant values (p <0.05). Comparison between double-lung transplant and single lung-transplant groups of emphysema patients demonstrated a significant difference in lung function beginning in the 3rd month after transplantation. DISCUSSION: The analyses of the whole group of transplant recipients and the sub-group of emphysema patients suggest the superiority of bilateral transplant over the unilateral alternative. Although the pre-transplant values of lung function were worse in the double-lung group, this difference was no longer significant in the subsequent months after surgery. CONCLUSION: Although both groups demonstrated functional improvement after transplantation, there was a clear tendency to greater improvement in FVC and FEV1 in the bilateral transplant group. Among our subjects, double-lung transplantation improved lung function.

Spirometric assessment of lung transplant patients: one year follow-up

OBJECTIVE: The purpose of this study was to compare spirometry data between patients who underwent single-lung or double-lung transplantation the first year after transplantation. INTRODUCTION: Lung transplantation, which was initially described as an experimental method in 1963, has become a therapeutic option for patients with advanced pulmonary diseases due to improvements in organ conservation, surgical technique, immunosuppressive therapy and treatment of post-operative infections. METHODS: We retrospectively reviewed the records of the 39 patients who received lung transplantation in our institution between August 2003 and August 2006. Twenty-nine patients survived one year post-transplantation, and all of them were followed. RESULTS: The increase in lung function in the double-lung transplant group was more substantial than that of the single-lung transplant group, exhibiting a statistical difference from the 1st month in both the forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC) in comparison to the pre-transplant values (p <0.05). Comparison between double-lung transplant and single lung-transplant groups of emphysema patients demonstrated a significant difference in lung function beginning in the 3rd month after transplantation. DISCUSSION: The analyses of the whole group of transplant recipients and the sub-group of emphysema patients suggest the superiority of bilateral transplant over the unilateral alternative. Although the pre-transplant values of lung function were worse in the double-lung group, this difference was no longer significant in the subsequent months after surgery. CONCLUSION: Although both groups demonstrated functional improvement after transplantation, there was a clear tendency to greater improvement in FVC and FEV1 in the bilateral transplant group. Among our subjects, double-lung transplantation improved lung function.

Exposure to ambient levels of particles emitted by traffic worsens emphysema in mice.

OBJECTIVES: We investigated effects of chronic exposure (2 months) to ambient levels of particulate matter (PM) on development of protease-induced emphysema and pulmonary remodeling in mice. METHODS: Balb/c mice received nasal drop of either papain or normal saline and were kept in two exposure chambers situated in an area with high traffic density. One of them received ambient air and the other had filters for PM. RESULTS: mean concentration of PM10 was 2.68 +/- 0.38 and 33.86 +/- 2.09 microg/m3, respectively, in the filtered and ambient air chambers (p < 0.001). After 2 months of exposure, lungs from papain-treated mice kept in the chamber with ambient air presented greater values of mean linear intercept, an increase in density of collagen fibers in alveolar septa and in expression of 8-isoprostane (p = 0.002, p < 0.05 and p = 0.002, respectively, compared to papain-treated mice kept in the chamber with filtered air). We did not observe significant differences between these two groups in density of macrophages and in amount of cells expressing matrix metalloproteinase-12. There were no significant differences in saline-treated mice kept in the two chambers. CONCLUSIONS: We conclude that exposure to urban levels of PM worsens protease-induced emphysema and increases pulmonary remodeling. We suggest that an increase in oxidative stress induced by PM exposure influences this response. These pulmonary effects of PM were observed only in mice with emphysema.

El lóbulo secundario como expresión anatómica de las enfermedades pulmonares / The secondary lobe as anatomic landmark for different pulmonary diseases

El propósito de éste ensayo iconográfico es presentar el espectro de los hallazgos patológicos del parénquima pulmonar, basándose en el conocimiento del lóbulo secundario y sus componentes. Realizar su evaluación con la tomografía computada con alta resolución (TCAR) y compararlos con los hallazgos histopatológicos. Por definición el lóbulo secundario es la pequeña porción de tejido pulmonar marginada por septos de tejido conectivo y suplida por 2 a 5 o más bronquiolos terminales de acuerdo a su localización central o periférica. Las distintas enfermedades se pueden manifestar como consecuencia de: 1. Obstrucción bronquiolar (transitoria o definitiva). 2. Por afección intra alveolar o de su pared. 3. Por afección del tejido de sostén. 4. Por compromiso de las estructuras vasculares y o linfáticas. La etiología puede ser: idiopática, infecciosa, por inhalación, neoplásica, alérgica, por afección del colágeno, secundarias a la administración de drogas y o postransplantes. El reconocimiento de los componentes del lóbulo secundario, mediante la tomografía computada con cortes finos de alta resolución, es el método dinámico de elección para la caracterización de las enfermedades pulmonares, permitiendo efectuar diagnósticos diferenciales más precisos, cuando se los relaciona con los hallazgos clínicos. La inclusión en el estudio de rutina de cortes en espiración, es el complemento imprescindible para resaltar trastornos de la perfusión que pueden pasar inadvertidos en inspiración profunda. La intención de éste trabajo es revisar algunas de éstas patologías donde la TCAR puede ser de gran utilidad y realizar una interrelación con lo observado por la histopatología (AU)