RESUMEN
BACKGROUND: Blood culture-negative infective endocarditis is a potentially severe disease that can be associated with infectious agents such as Bartonella spp., Coxiella burnetti, Tropheryma whipplei, and some fungi. CASE PRESENTATION: Reported here are two cases of blood culture-negative infective endocarditis in patients with severe aortic and mitral regurgitation in Brazil; the first case is a 47-year-old white man and the second is a 62-year-old white woman. Bartonella henselae deoxyribonucleic acid was detectable in the blood samples and cardiac valve with vegetation paraffin-fixed tissue samples. Additionally, an investigation was carried out on patients' pets, within the context of One Health, and serum samples collected from cats and dogs were reactive by indirect immunofluorescence assay. CONCLUSIONS: Even though the frequency of bartonellosis in Brazil is unknown, physicians should be aware of the possibility of blood culture-negative infective endocarditis caused by Bartonella, particularly in patients with weight loss, kidney changes, and epidemiological history for domestic animals.
Asunto(s)
Infecciones por Bartonella , Bartonella henselae , Bartonella , Endocarditis Bacteriana , Endocarditis , Humanos , Animales , Gatos , Perros , Endocarditis Bacteriana/microbiología , Infecciones por Bartonella/complicaciones , Infecciones por Bartonella/diagnóstico , Infecciones por Bartonella/microbiología , Endocarditis/complicacionesRESUMEN
BACKGROUND: Dehiscence of intestinal anastomosis results in high morbidity and mortality. The aim of this study was to investigate the effects of locally administered adipose tissue-derived mesenchymal stromal cells in a model of high-risk colonic anastomosis in rats. METHODS: Seven days after induction of colitis with 2,4,6-trinitrobenzene sulfonic acid, Wistar rats were submitted to a transection of the descending colon followed by end-to-end anastomosis and were then treated with 2×106 adipose tissue-derived mesenchymal stromal cells (from the preperitoneal fat) or an acellular culture solution instilled onto the surface of the anastomosis. At day 14, after macroscopic survey of the abdominal cavity, the anastomotic area was submitted to histologic and immunohistochemical analysis, evaluation of myeloperoxidase activity, fibrosis, epithelial integrity, NF-κ B activation, expression of inflammatory cytokines, and extracellular matrix-related genes. RESULTS: Anastomotic leakage and mortality associated with high-risk anastomosis decreased with treatment with adipose tissue-derived mesenchymal stromal cells (P < .03). Application of adipose tissue-derived mesenchymal stromal cells resulted in lower histologic scores (P = .011), decreased deposition of collagen fibers (P = .003), preservation of goblet cells (P = .033), decreased myeloperoxidase activity (P = .012), decreased accumulation of CD4+ T-cells (P = .014) and macrophages (P = .011) in the lamina propria, a decrease in the number of apoptotic cells (P = .008), and the activation of NF-κ B (P = .036). Overexpression of IL-17, TNF-α , IFN-γ, and metalloproteinases in the acellular culture solution-treated, high-risk anastomosis group decreased (P < .05) to near normal values with adipose tissue-derived mesenchymal stromal cells treatment. CONCLUSION: Improvements in outcomes of a high-risk colonic anastomosis with adipose tissue-derived mesenchymal stromal cells therapy reflect the immunomodulatory activity and healing effect of these cells, even after just topical administration and reinforces their use in future translational research.
Asunto(s)
Fuga Anastomótica/prevención & control , Colitis/cirugía , Colon/cirugía , Grasa Intraabdominal/citología , Trasplante de Células Madre Mesenquimatosas/métodos , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos , Fuga Anastomótica/etiología , Animales , Colitis/inducido químicamente , Modelos Animales de Enfermedad , Humanos , Masculino , Ratas , Ratas Wistar , Resultado del Tratamiento , Ácido Trinitrobencenosulfónico/toxicidadRESUMEN
The development of high-frequency endoscopic ultrasound for the investigation of models of esophageal disease may offer insights for future translation to human imaging. With respect to small animal models of esophageal diseases, ultrasound imaging instrumentation must employ frequencies scaled up to maintain the compromise between image resolution and inspected region. In this sense, a 40-MHz endoluminal ultrasound biomicroscopy (eUBM) system and an endoscope were tested as diagnostic methods of imaging rat esophageal lesions in the acute and chronic phases caused by sodium hydroxide. Although endoscopy allowed grading of the esophagus in accordance with a classification specific to the epithelial alterations and including hyperemia, edema, exudates, fibrin and superficial and deep ulcerations, the eUBM images yielded the detection of superficial and deep ulcerations, as well as wall alterations caused by edema and inflammatory infiltrate in the submucosa. Additionally, eUBM enabled wall thickness measurements, which were statistically significantly increased (p < 0.05) in the acute phase.
Asunto(s)
Endoscopía/métodos , Esofagitis/diagnóstico , Esófago/diagnóstico por imagen , Microscopía Acústica/métodos , Animales , Modelos Animales de Enfermedad , Esofagitis/diagnóstico por imagen , Esofagitis/patología , Masculino , Ratas , Ratas WistarRESUMEN
Acute pancreatitis (AP) is an inflammatory disorder that can affect adjacent and/or remote organs. Some evidence indicates that the production of reactive oxygen species is able to induce AP. Protein carbonyl (PC) derivatives, which can also be generated through oxidative cleavage mechanisms, have been implicated in several diseases, but there is little or no information on this biomarker in AP. We investigated the association between some inflammatory mediators and PC, with the severity of ischemia-reperfusion AP. Wistar rats (n = 56) were randomly assigned in the following groups : control; sham, 15- or 180-min clamping of splenic artery, with 24 or 72 h of follow-up. The relationships between serum level of PC and thiobarbituric acid reactive species (TBARS) to myeloperoxidase (MPO) activity in tissue homogenates and to cytokines in culture supernatants of pancreatic samples were analyzed. MPO activity was related to the histology scores and increased in all clamping groups. Tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), and interleukin-6 were higher in the 180-min groups. Significant correlations were found between MPO activity and the concentrations of TNF-α and IL-1ß. PC levels increased in the 15-min to 24-h group. TBARS levels were not altered substantially. MPO activity and TNF-α and IL-1ß concentrations in pancreatic tissue are correlated with AP severity. Serum levels of PC appear to begin to rise early in the course of the ischemia-reperfusion AP and are no longer detected at later stages in the absence of severe pancreatitis. These data suggest that PC can be an efficient tool for the diagnosis of early stages of AP.
Asunto(s)
Biomarcadores/análisis , Pancreatitis Aguda Necrotizante/diagnóstico , Pancreatitis Aguda Necrotizante/patología , Carbonilación Proteica , Daño por Reperfusión/patología , Animales , Citocinas/análisis , Modelos Animales de Enfermedad , Femenino , Peroxidasa/análisis , Ratas WistarRESUMEN
BACKGROUND: Heparanase is the only known mammalian glycosidase capable of cleaving heparan sulfate chains. The expression of this enzyme has been associated with tumor development because of its ability to degrade extracellular matrix and promote cell invasion. METHODS: We analyzed heparanase expression in lung cancer samples to understand lung tumor progression and malignancy. Of the samples from 37 patients, there were 14 adenocarcinomas, 13 squamous cell carcinomas, 5 large cell carcinomas, and 5 small cell carcinomas. Immunohistochemistry was performed to ascertain the expression and localization of heparanase. RESULTS: All of the tumor types expressed heparanase, which was predominantly localized within the cytoplasm and nucleus. Significant enzyme expression was also observed in cells within the tumor microenvironment, such as fibroblasts, epithelial cells, and inflammatory cells. Adenocarcinomas exhibited the strongest heparanase staining intensity and the most widespread heparanase distribution. Squamous cell carcinomas, large cell carcinomas, and small cell carcinomas had a similar subcellular distribution of heparanase to adenocarcinomas but the distribution was less widespread. Heparanase expression tended to correlate with tumor node metastasis (TNM) staging in non-small cell lung carcinoma. CONCLUSION: In this study, we showed that heparanase was localized to the cytoplasm and nucleus of tumor cells and to cells within the microenvironment in different types of lung cancer. This enzyme exhibited a differential distribution based on the type of lung tumor. General significance Elucidating the heparanase expression patterns in different types of lung cancer increased our understanding of the crucial role of heparanase in lung cancer biology. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.
Asunto(s)
Glucuronidasa/metabolismo , Neoplasias Pulmonares/clasificación , Neoplasias Pulmonares/enzimología , Adenocarcinoma/enzimología , Adenocarcinoma/patología , Diferenciación Celular , Membrana Celular/enzimología , Núcleo Celular/enzimología , Núcleo Celular/patología , Femenino , Humanos , Neoplasias Pulmonares/patología , Linfocitos/enzimología , Macrófagos/enzimología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Transporte de Proteínas , Coloración y Etiquetado , Microambiente TumoralRESUMEN
AIM: We sought to investigate whether mammalian or ascidian Styela plicata heparin enemas could diminish inflammation in experimental diversion colitis. METHODS: Wistar-specific pathogen-free rats were submitted to a Hartmann's end colostomy and treated with enemas containing mammalian or Styela plicata heparin, or saline. Enemas were administered 3 times a week in the excluded colon segment from 4 to 8 weeks after operation. The effect of treatment was evaluated using video-endoscopic and histologic scores, measuring the cytokines interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and transforming growth factor-ß production in organ cultures by enzyme-linked immunosorbent assay, quantifying T cells and macrophages, and investigating nuclear factor-kappa B (NF-κB) and external mitogen-activated protein kinase (pERK) activation. RESULTS: Treatment with either mammalian or Styela plicata heparins decreased colonoscopic and histologic scores (P < .02) and restored the densities of collagen fibers and the number of goblet cells (P < .03) in the diverted colon. Both heparin treatments decreased the accumulation of T cells and macrophages (P < .03), and the activation of NF-κB and pERK (P < .04) in the diverted colon. The high levels of cytokines IL-1ß, TNF-α, and IL-6 from the diversion colitis explants decreased (P < .05) to near normal values with heparin treatments. CONCLUSION: The improvement of experimental diversion colitis with heparin treatments indicates the anti-inflammatory effect of these compounds, even after topical administration. Further studies with the nonhemorrhagic heparin obtained from the invertebrate Styela plicata will be necessary to confirm its efficacy for the treatment of human diversion colitis and possibly other forms of colitis.
Asunto(s)
Anticoagulantes/administración & dosificación , Colitis/tratamiento farmacológico , Enema , Heparina/administración & dosificación , Urocordados , Animales , Colitis/patología , Colágeno/metabolismo , Colon/metabolismo , Colon/patología , Colonoscopía , Modelos Animales de Enfermedad , Femenino , Masculino , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
PURPOSE: Endoscopic ultrasound (EUS) imaging of the colon is an important diagnostic tool for early neoplasia, although usually restricted to the rectum in inflammatory bowel disease (IBD). This study aimed to evaluate the ability of an endoluminal ultrasound biomicroscopic (eUBM) system to detect and characterize lesions simulating Crohn's disease in the colon of rats in vivo. METHODS: Colitis was induced with trinitrobenzene sulfonic acid instillated in the distal colon. Eighteen Wistar rats were submitted to eUBM in three time points: week 1 group (18 animals examined on day 3 after colitis induction), week 2 group (12 animals on days 3 and 10), and week 3 group (7 animals on days 3, 10, and 17). This design yielded distinct inflammation intensities. Three untreated rats were used for acquisition of control images. Scores were used for comparison with histology. RESULTS: Scores for eUBM and histology in the different moments of examination achieved a Spearman's rank correlation coefficient of 0.87 (p < 0.001). Findings of wall thickening presented positive predictive value (PPV) and sensitivity of 94 and of 100 %, respectively. Superficial and deep ulcers presented a PPV of 89 and 80 %, respectively, and negative predictive values of 100 and 85 %, respectively. CONCLUSION: Accurate detection and analysis of the lesions was achieved. The model is essential for the clinical development of the technique and a reproducible method for the evaluation of experimental colitis. eUBM might be applicable in different segments of the gut, developing into a novel adjunct method for IBD evaluation.
Asunto(s)
Colitis/diagnóstico por imagen , Endosonografía/métodos , Inflamación/diagnóstico por imagen , Microscopía Acústica/métodos , Animales , Colitis/patología , Colonoscopía , Toma de Decisiones , Inflamación/patología , Masculino , Valor Predictivo de las Pruebas , Ratas , Ratas WistarRESUMEN
BACKGROUND AND AIMS: Oxidative stress is presumed to play an important role in Crohn's disease (CD) pathogenesis. Nevertheless, the evaluation of the intestinal antioxidant capacity through the analysis of glutathione peroxidase activity in CD remains to be determined. METHODS: 20 CD outpatients and 16 volunteers going through colonic cancer screening were enrolled. Colonoscopy with biopsies was performed in all individuals. Samples from inflamed and non-inflamed mucosa were taken when there was CD endoscopic activity. Spectrophotometric assays were performed to measure tissue glutathione peroxidase (GPx) activity, and total (GSHT) and oxidized (GSSG) glutathione in all samples. Demographics and clinical characteristics were collected from clinical charts. RESULTS: Inflamed CD mucosa presented reduced GPx activity compared to non-inflamed CD mucosa (42.94mU/mg protein vs 79.62mU/mg protein, P<0.05) and control mucosa (42.94mU/mg protein vs 95.08mU/mg protein, P<0.001). GSHT concentration was reduced in inflamed mucosa when compared to non-inflamed CD mucosa (0.78µmol/g vs 1.98µmol/g, P<0.01) and the control group (0.78µmol/g vs 2.11µmol/g, P<0.001). A significant correlation was detected between GPx activity and GSSG (r=-0.599), disease duration (r=0.546), and thiopurine treatment (r=-0.480) in non-inflamed CD mucosa. CONCLUSION: Our findings suggest that reduced GPx activity is present in inflamed CD mucosa. In addition, endoscopic activity, disease duration and thiopurine therapy could be associated with mucosal decreased antioxidant activity.
Asunto(s)
Colon/metabolismo , Colon/patología , Enfermedad de Crohn/enzimología , Enfermedad de Crohn/patología , Glutatión Peroxidasa/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Adolescente , Adulto , Anciano , Antioxidantes/metabolismo , Biopsia , Estatura , Índice de Masa Corporal , Peso Corporal , Estudios de Casos y Controles , Colon/química , Colonoscopía , Enfermedad de Crohn/tratamiento farmacológico , Ingestión de Energía , Femenino , Disulfuro de Glutatión/metabolismo , Humanos , Mucosa Intestinal/química , Masculino , Persona de Mediana Edad , Estado Nutricional , Selenio/sangre , Índice de Severidad de la Enfermedad , Factores de Tiempo , Adulto JovenRESUMEN
Pseudomelanosis duodeni (PD) is a rare dark speckled appearance of the duodenum associated with gastrointestinal bleeding, hypertension, chronic heart failure, chronic renal failure and consumption of different drugs. We report four cases of PD associated with chronic renal failure admitted to the gastroenterology outpatient unit due to epigastric pain, nausea, melena and progressive reduction of hemoglobin index. Gastroduodenal endoscopy revealed erosions in the esophagus and stomach, with no active bleeding at the moment. In addition, the duodenal mucosa presented marked signs of melanosis; later confirmed by histopathological study. Even though PD is usually regarded as a benign condition, its pathogenesis and clinical significance is yet to be defined.
Asunto(s)
Enfermedades Duodenales/etiología , Enfermedades Duodenales/patología , Duodeno/patología , Mucosa Intestinal/patología , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/patología , Melaninas/metabolismo , Adulto , Anciano , Femenino , HumanosRESUMEN
BACKGROUND AND AIMS: Mesenchymal stromal cells (MSCs) were shown to have immunomodulatory activity and have been applied for treating immune-mediated disorders. We compared the homing and therapeutic action of cryopreserved subcutaneous adipose tissue (AT-MSCs) and bone marrow-derived mesenchymal stromal cells (BM-MSCs) in rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis. METHODS: After colonoscopic detection of inflammation AT-MSCs or BM-MSCs were injected intraperitoneally. Colonoscopic and histologic scores were obtained. Density of collagen fibres and apoptotic rates were evaluated. Cytokine levels were measured in supernatants of colon explants. For cell migration studies MSCs and skin fibroblasts were labelled with Tc-99m or CM-DiI and injected intraperitonealy or intravenously. RESULTS: Intraperitoneal injection of AT-MSCs or BM-MSCs reduced the endoscopic and histopathologic severity of colitis, the collagen deposition, and the epithelial apoptosis. Levels of TNF-α and interleukin-1ß decreased, while VEGF and TGF-ß did not change following cell-therapy. Scintigraphy showed that MSCs migrated towards the inflamed colon and the uptake increased from 0.5 to 24 h. Tc-99m-MSCs injected intravenously distributed into various organs, but not the colon. Cm-DiI-positive MSCs were detected throughout the colon wall 72 h after inoculation, predominantly in the submucosa and muscular layer of inflamed areas. CONCLUSIONS: Intraperitoneally injected cryopreserved MSCs home to and engraft into the inflamed colon and ameliorate TNBS-colitis.
Asunto(s)
Movimiento Celular , Colitis/terapia , Colon/patología , Criopreservación , Inflamación/patología , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Animales , Apoptosis , Células de la Médula Ósea/citología , Linaje de la Célula , Colitis/complicaciones , Colitis/patología , Colágeno/metabolismo , Colonoscopía , Citocinas/biosíntesis , Modelos Animales de Enfermedad , Inflamación/complicaciones , Inyecciones Intraperitoneales , Inyecciones Intravenosas , Mucosa Intestinal/patología , Masculino , Ratas , Ratas Wistar , Grasa Subcutánea/citología , Ácido Trinitrobencenosulfónico , Cicatrización de HeridasRESUMEN
BACKGROUND: Macrophage migration inhibitory factor (MIF) is essential for controlling parasite burden and survival in a model of systemic Toxoplasma gondii infection. Peroral T. gondii infection induces small intestine necrosis and death in susceptible hosts, and in many aspects resembles inflammatory bowel disease (IBD). Considering the critical role of MIF in the pathogenesis of IBD, we hypothesized that MIF participates in the inflammatory response induced by oral infection with T. gondii. METHODOLOGY/PRINCIPAL FINDINGS: Mif deficient (Mif(-/-)) and wild-type mice in the C57Bl/6 background were orally infected with T. gondii strain ME49. Mif(-/-) mice had reduced lethality, ileal inflammation and tissue damage despite of an increased intestinal parasite load compared to wt mice. Lack of MIF caused a reduction of TNF-α, IL-12, IFN-γ and IL-23 and an increased expression of IL-22 in ileal mucosa. Moreover, suppressed pro-inflammatory responses at the ileal mucosa observed in Mif(-/-) mice was not due to upregulation of IL-4, IL-10 or TGF-ß. MIF also affected the expression of matrix metalloproteinase-9 (MMP-9) but not MMP-2 in the intestine of infected mice. Signs of systemic inflammation including the increased concentrations of inflammatory cytokines in the plasma and liver damage were less pronounced in Mif(-/-) mice compared to wild-type mice. CONCLUSION/SIGNIFICANCE: In conclusion, our data suggested that in susceptible hosts MIF controls T. gondii infection with the cost of increasing local and systemic inflammation, tissue damage and death.
Asunto(s)
Factores Inhibidores de la Migración de Macrófagos/metabolismo , Boca/parasitología , Toxoplasma/fisiología , Toxoplasmosis/patología , Toxoplasmosis/parasitología , Animales , Citocinas/metabolismo , Ileítis/complicaciones , Ileítis/parasitología , Ileítis/patología , Íleon/parasitología , Íleon/patología , Mediadores de Inflamación/metabolismo , Mucosa Intestinal/enzimología , Mucosa Intestinal/parasitología , Mucosa Intestinal/patología , Factores Inhibidores de la Migración de Macrófagos/deficiencia , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Carga de Parásitos , Sepsis/complicaciones , Sepsis/parasitología , Sepsis/patología , Análisis de Supervivencia , Toxoplasmosis/complicacionesRESUMEN
Genital infection by Schistosoma mansoni is usually misdiagnosed in individuals who reside in, or travel to endemic areas. We describe two cases of genital tumor associated with S. mansoni infection manifested by methrorragy. Surgical specimens revealed leiomyomas in both cases associated with S. mansoni. In one of them, granulomas were found in the ovary and in the other they were found in the uterine tube. Although none presented intestinal/hepatic disease, fecal egg excretion was detected in one. Both had elevated pretreatment antibody reactivity to S. mansoni antigen, but follow-up showed different outcomes. Schistosomiasis should be considered as a diagnosis in individuals with methrorragy residing in or having traveled to endemic areas. Since diagnosis follows genital amputation, and cure control is troublesome, improvement of diagnostic tools and follow-up markers are important priorities to decrease schistosomiasis morbidity.
Asunto(s)
Enfermedades del Ovario/diagnóstico , Schistosoma mansoni/aislamiento & purificación , Esquistosomiasis mansoni/diagnóstico , Adulto , Animales , Heces/parasitología , Femenino , Humanos , Enfermedades del Ovario/parasitología , Enfermedades del Ovario/terapia , Recuento de Huevos de Parásitos , Esquistosomiasis mansoni/terapia , Esquistosomicidas/uso terapéuticoRESUMEN
Genital infection by Schistosoma mansoni is usually misdiagnosed in individuals who reside in, or travel to endemic areas. We describe two cases of genital tumor associated with S. mansoni infection manifested by methrorragy. Surgical specimens revealed leiomyomas in both cases associated with S. mansoni. In one of them, granulomas were found in the ovary and in the other they were found in the uterine tube. Although none presented intestinal/hepatic disease, fecal egg excretion was detected in one. Both had elevated pretreatment antibody reactivity to S. mansoni antigen, but follow-up showed different outcomes. Schistosomiasis should be considered as a diagnosis in individuals with methrorragy residing in or having traveled to endemic areas. Since diagnosis follows genital amputation, and cure control is troublesome, improvement of diagnostic tools and follow-up markers are important priorities to decrease schistosomiasis morbidity.
Asunto(s)
Adulto , Animales , Femenino , Humanos , Enfermedades del Ovario/diagnóstico , Schistosoma mansoni/aislamiento & purificación , Esquistosomiasis mansoni/diagnóstico , Heces/parasitología , Enfermedades del Ovario/parasitología , Enfermedades del Ovario/terapia , Recuento de Huevos de Parásitos , Esquistosomiasis mansoni/terapia , Esquistosomicidas/uso terapéuticoRESUMEN
OBJECTIVE: The purpose of this study was to show the feasibility of 50-MHz ultrasound biomicroscopy (UBM) to image the rat colon. METHODS: B-mode images were obtained from ex vivo colon samples (n = 4) collected from Rattus norvegicus (Berkenhout, 1769) rats, with 2,4,6-trinitrobenzene sulfonic acid-induced colitis in 3 of them. Left colon rectangular fragments (5 x 5 mm) were obtained after necropsy, and UBM images were acquired with the samples immersed in saline at 37 degrees C. All layers of the normal intestinal wall were analyzed according to their thickness and the presence of uneven bowel mucosa (ulcers). The folds and layers detected by UBM were correlated with histopathologic analysis. RESULTS: The 4 layers of the normal colon were identified on the UBM images: the mucosa (hyperechoic), muscularis mucosae (hypoechoic), submucosa (hyperechoic), and muscularis externa (hypoechoic). On 2 UBM images, superficial ulcers were detected, approximately 0.5 mm in size, with intestinal involvement limited to the mucosa. The histopathologic analysis verified enlargement of submucosa layers due to an edema associated with sub-mucosa leukocyte infiltration. On 1 UBM image, it was possible to detect a deep ulcer, which was confirmed by the light microscopic analysis. CONCLUSIONS: An ultrasound imaging system was scaled and optimized to visualize the rat colon. Ultrasound biomicroscopy provided axial and lateral resolutions close to 25 and 45 mum, respectively, and adequate penetration depth to visualize the whole thickness of an inflamed colon. The system identified the colon layers and was able to detect mural changes and superficial ulcers on the order of 500 mum.
Asunto(s)
Colitis/diagnóstico por imagen , Modelos Animales de Enfermedad , Aumento de la Imagen/métodos , Microscopía Acústica/métodos , Animales , Humanos , Ratas , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
The anti-inflammatory effect of mammalian heparin analogues, named dermatan sulfate and heparin, isolated from the ascidian Styela plicata was accessed in a TNBS-induced colitis model in rats. Subcutaneous administration of the invertebrate compounds during a 7-day period drastically reduced inflammation as observed by the normalization of the macroscopic and histological characteristics of the colon. At the molecular level, a decrease in the production of TNF-alpha, TGF-beta, and VEGF was observed, as well as a reduction of NF-kappaB and MAPK kinase activation. At the cellular level, the heparin analogues attenuated lymphocyte and macrophage recruitment and epithelial cell apoptosis. A drastic reduction in collagen-mediated fibrosis was also observed. No hemorrhagic events were observed after glycan treatment. These results strongly indicate the potential therapeutic use of these compounds for the treatment of colonic inflammation with a lower risk of hemorrhage when compared with mammalian heparin.
Asunto(s)
Colitis/tratamiento farmacológico , Heparina/análogos & derivados , Heparina/farmacología , Animales , Apoptosis , Cordados , Colágeno/metabolismo , Colon/patología , Fibrosis , Hemorragia/prevención & control , Linfocitos/metabolismo , Macrófagos/metabolismo , Masculino , Modelos Biológicos , Ratas , Ratas WistarRESUMEN
Ectopically ACTH producing tumors may be difficult to localize by conventional radiology and functional imaging may be helpful. Case 1: 31-year-old man was diagnosed with ectopic ACTH-dependent Cushing's syndrome (ECS). Thorax CT revealed a 1.3 cm nodular opacity in upper left lobe, suggestive of residual lesion. [(18)F] fluoro-2-deoxy-D: -glucose ([(18)F] FDG) positron emission tomography ([(18)F] FDG PET) scan revealed mild glycolytic metabolic activity. Pathological examination confirmed an ACTH-positive carcinoid tumor. Case 2: 53-year-old woman presented with very rapid onset ECS. Pituitary MRI was normal. Thorax CT revealed no tumoral lesion. Abdominal and pelvic MRI showed images suggestive of hepatic and iliac, femoral and lumbar secondary implants. [(18)F] FDG PET scan revealed intense uptake in uterus, especially cervix, suggesting this to be the primary tumor site. These cases illustrate the role of [(18)F] FDG PET in the investigation of an ECS where conventional imaging studies were not elucidative in the search for a responsible tumor.
Asunto(s)
Fluorodesoxiglucosa F18 , Neoplasias/diagnóstico , Neoplasias/metabolismo , Tomografía de Emisión de Positrones/métodos , Adulto , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/metabolismo , Carcinoma de Células Pequeñas/diagnóstico , Carcinoma de Células Pequeñas/metabolismo , Femenino , Humanos , Inmunohistoquímica , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
Etiopathogenesis of biliary atresia remains unknown. Among several theories, one proposes that the disorder may be caused by the toxic effect of monohydroxy bile acids on fetal and neonatal hepatobiliary system. In this paper we evaluated toxic effects produced by ingestion of cholic acid, a trihydroxy bile acid, and lithocholic acid, a monohydroxy bile acid in the hepatobiliary system of a hamster during gestational and perinatal periods. A diet composed by 0.5% cholic acid and 0.25% lithocholic acid was administrated to pregnant hamsters. Liver and bile ducts of the adult and newborn animals were analyzed to point out the changes induced by these acids after birth. Because hamsters and humans have a similar bile metabolism, these animals were eligible for the study. The ingestion of 0.5% lithocholic acid, during hamster's gestation, caused maternal intense ductal/ductular proliferation, inflammatory signs, hepatic cells degeneration and regeneration, hyperplasia of extra hepatic ducts epithelium, and abortion. Both 0.5% cholic acid and 0.25% lithocholic acid ingested by pregnant hamsters, caused ductal/ductular proliferation and hepatobiliary inflammatory damage in a different degree of intensity in adult animals and mild intensity in the young; and also the number of the young was reduced in the litter. We found that the ingestion of these bile acids by hamsters, during gestational period caused different degrees of toxicity on maternal and neonatal hepatobiliary systems. The histopathologic findings observed in biliary atresia patients could not be found in newborn hamsters. New experimental models are needed in the attempt to establish a correlation of these acids with neonatal cholestatic diseases.
Asunto(s)
Sistema Biliar/efectos de los fármacos , Ácido Cólico/toxicidad , Ácido Litocólico/toxicidad , Hígado/efectos de los fármacos , Administración Oral , Animales , Animales Recién Nacidos , Atresia Biliar/etiología , Ácido Cólico/administración & dosificación , Cricetinae , Femenino , Ácido Litocólico/administración & dosificación , Masculino , Intercambio Materno-Fetal , EmbarazoRESUMEN
Relatamos o caso de um paciente de 56 anos submetido a transplante pulmonar unilateral esquerdo em decorrência de fibrose pulmonar idiopática (FPI). No pós-operatório imediato, sob intensa imunossupressão, houve progressão rápida da FPI no pulmão nativo direito, confirmada pela biópsia pulmonar videotoracoscópica, necessitando de ventilação mecânica durante 104 dias até a realização de outro transplante pulmonar à direita. Obteve alta hospitalar após o 26º dia do segundo pós-operatório.
We report the case of a 56-year-old patient who underwent left single lung transplantation for idiopathic pulmonary fibrosis (IPF). Despite the high level of immunosuppression after the surgery, there was rapid progression to IPF in the native (right) lung as demonstrated by thoracoscopic lung biopsy. After 104 days on mechanical ventilation (MV), the patient underwent right lung transplant and was discharged from the hospital on postoperative day 26.
Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Trasplante de Pulmón/efectos adversos , Fibrosis Pulmonar , Biopsia , Pulmón/patología , Pulmón , Fibrosis Pulmonar/etiología , Fibrosis Pulmonar/patología , Fibrosis Pulmonar , Tomografía Computarizada por Rayos X/métodosRESUMEN
OBJECTIVE: To quantify elastic fibers (EFs) and smooth muscle (SM) cells, as well as CD4+ and CD8+ T lymphocytes, in stable chronic obstructive pulmonary disease (COPD). METHODS: Surgical specimens were obtained from 15 COPD patients, 18 smokers without airflow limitation, and 14 nonsmokers. Histological and immunohistochemical methods were employed in order to quantify EFs, SM cells, CD4+ T cells, and CD8+ T cells. RESULTS: There was no significant difference in EF numbers among the three groups (p > 0.05). The number of EFs per unit area of lung tissue (mm(2)) and the percentage of EFs in the lung tissue were similar among the three groups. The numbers of SM cells were found to be higher in the COPD patients than in the smokers (p = 0.003) or in the nonsmokers (p = 0.009). There was a tendency toward an increase in CD8+ T-cell counts in the COPD patients. In specimens collected from the COPD patients, CD4+ T-cell counts were lower than in those collected from the smokers (p = 0.015) or from the nonsmokers (p = 0.003). There was a weak correlation between CD4+ T-cell count and the ratio of forced expiratory volume in one second to forced vital capacity (r(2) = 0.003). CONCLUSIONS: The EF counts were similar among the three groups. Hypertrophy/hyperplasia of airway wall SM cells was found in the COPD patients and in the smokers, indicating that airway remodeling occurs in smokers. The CD4/CD8 ratio was lower in the COPD patients.
Asunto(s)
Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/patología , Tejido Elástico/patología , Músculo Liso/citología , Enfermedad Pulmonar Obstructiva Crónica/patología , Fumar/patología , Biopsia , Estudios de Casos y Controles , Estudios Transversales , Femenino , Volumen Espiratorio Forzado/fisiología , Humanos , Inmunohistoquímica , Pulmón/citología , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/sangre , Estadísticas no Paramétricas , Capacidad Vital/fisiologíaRESUMEN
OBJECTIVE: To determine cell profiles, as well as to identify CD4+ and CD8+ lymphocyte subgroups, in induced sputum (IS) and peripheral venous blood (PVB) of patients with chronic obstructive pulmonary disease (COPD). METHODS: Total cell counts and counts of individual cell types, including CD4+ and CD8+ T lymphocytes, were determined in the IS and PVB of 85 subjects (38 with COPD without exacerbation, 29 smokers without obstruction and 18 nonsmokers). Mann-Whitney and Spearman non-parametric tests were used in the statistical analysis, and values of p < 0.05 were considered statistically significant. RESULTS: Comparing the IS of subjects with COPD to that of nonsmokers, neutrophil, eosinophil and CD8+ T lymphocyte counts were higher (respectively p = 0.005, p < 0.05 and p < 0.05), whereas the percentage of macrophages was lower (p = 0.003). There were weak linear correlations (r(2) < 0.1) between each cell type in IS and forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio. Eosinophil and CD8+ T lymphocyte counts were also higher in PVB (p = 0.04 and p = 0.02). CONCLUSIONS: In patients with stable COPD, CD8+ T lymphocyte counts were higher in PVB, whereas total leukocyte counts were similar to those of the other two groups analyzed, suggesting systemic inflammatory involvement. The CD8+ T lymphocyte count in blood can be a useful marker of systemic inflammation and can help identify smokers who already present a COPD inflammatory pattern.