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1.
Am J Physiol Lung Cell Mol Physiol ; 322(6): L882-L889, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35537098

RESUMO

Lung resistance (RL) is determined by airway and parenchymal tissue resistance, as well as the degree of heterogeneity in airway constriction. Deep inspirations (DIs) are known to reverse experimentally induced increase in RL, but the mechanism is not entirely clear. The first step toward understanding the effect of DI is to determine how each of the resistance components is affected by DI. In the present study, we measured RL and apparent airway resistance (RAW, which combines the effects of airway resistance and airway heterogeneity) simultaneously before and after a DI in acetylcholine (ACh)-challenged ex vivo sheep lungs. We found that at normal breathing frequency (0.25 Hz) ACh-challenge led to a doubling of RL, 80.3% of that increase was caused by an increase in RAW; the increase in apparent tissue resistance (RT) was insignificant. 57.7% of the increase in RAW was abolished by a single DI. After subtracting RAW from RL, the remaining RT was mostly independent of ACh-challenge and its reduction after a DI came mostly from the change in the mechanical properties of lung parenchyma. We conclude that at normal breathing frequency, RL in an unchallenged lung is mostly composed of RT, and the increase in RL due to ACh-challenge stems mostly from the increase in RAW and that both RAW and RT can be greatly reduced by a DI, likely due to a reduction in true airway resistance and heterogeneity, as well as parenchymal tissue hysteresis post DI.


Assuntos
Resistência das Vias Respiratórias , Tecido Parenquimatoso , Animais , Inalação , Pulmão , Testes de Função Respiratória , Ovinos
2.
Rev. patol. respir ; 25(2): 54-56, Abri - Jun 2022. ilus
Artigo em Espanhol | IBECS | ID: ibc-207326

RESUMO

El secuestro pulmonar es una rara enfermedad congénita del tracto respiratorio, en la cual existe un parénquima pulmonar no funcionante que presenta una circulación arterial aberrante. Puede acompañarse de otras alteraciones torácicas como enfisema lobar, el síndrome de la cimitarra o malformaciones adenomatoides quísticas. El diagnóstico en la edad adulta suele ser incidental, aunque también puede presentarse en un menor número de pacientes como infecciones respiratorias de repetición.(AU)


Pulmonary sequestration is a rare congenital disease of the respiratory tract, in which there is a non-functioning lung parenchyma that presents an aberrant arterial circulation. It can be accompanied by other thoracic alterations such as lobar emphysema, scimitar syndrome or cystic adenomatoid malformations. Diagnosis in adulthood is usually incidental, although it can also present in a smaller number of patients as recurrent respiratory infections.(AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Sequestro Broncopulmonar , Sistema Respiratório , Anormalidades Congênitas , Tecido Parenquimatoso , Doenças Respiratórias/complicações , Doenças Respiratórias/diagnóstico
3.
Acta Clin Croat ; 60(3): 467-475, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35282489

RESUMO

The aim of the study was to investigate morphological traits of hepatic parenchymal tissue repair in response to injury using the conventional technique (closure) and an innovation method (such as hemostatic medication swab packing and modified batching). The experimental study was carried out on laboratory rats of the Winzar breed using light microscopy, standard stains for micropreparations, and morphometry. Histopathologic examination of micropreparations stained by standard methods revealed pronounced dystrophic processes in hepatocytes located near the necrotic zone (albuminous and hydropic degeneration and chromatin fragmentation in the nuclei). Morphometric studies showed a significant decrease (p<0.001) in almost all indicators of the size of cells and nuclei both near necrosis and distant from it on day 28 of the experiment in the experimental group in comparison to the control group. The results obtained pointed to more intense repair processes when applying the innovation method.


Assuntos
Fígado , Tecido Parenquimatoso , Animais , Humanos , Necrose/patologia , Fenótipo , Ratos
4.
Eur J Med Res ; 27(1): 42, 2022 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-35305692

RESUMO

BACKGROUND: Cerebral intraparenchymal masses represent usually a neoplastic, or infectious differential diagnostic workup in neurology or infectious disease units. CASE PRESENTATION: Our patient was an 82-year-old male presenting with seizures, cerebral masses and a history of past treated pulmonary tuberculosis. Initial workup included a differential diagnosis of an infectious mass/multiple abscess. After exclusion of infectious or primary neoplastic origins by negative HIV serology, the absence of immune suppression, endocarditic lesions, negative results of blood cultures and bronchoalveolar lavage, negative cerebrospinal fluid workout on spinal tap led to exclusion of infectious causes. A surgical procedure was performed to access one of the lesions. This yielded a firm, cyst-like mass of histiocytic granulomatous tissue with a conspicuous plasmacellular component and a relevant IgG4 plasmacellular component consistent with IgG4-related disease. Steroid treatment determined conspicuous improvement and led to discharge of the patient. CONCLUSION: Parenchymal IgG4-related disease may be included as a new entity in the differential diagnosis of single or multiple cerebral masses in addition to infectious or neoplastic etiology.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/fisiopatologia , Diagnóstico Diferencial , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/fisiopatologia , Doença Relacionada a Imunoglobulina G4/cirurgia , Tecido Parenquimatoso/fisiopatologia , Idoso , Humanos , Masculino
5.
Medicina UPB ; 41(1): 91-95, mar. 2022. Ilus, tab
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1362719

RESUMO

El angiosarcoma es un tumor vascular maligno poco frecuente. Constituye menos del 2% de todos los sarcomas. Existen varias formas clínicas, una es la producida después de radioterapia, en pacientes que fueron tratadas por un cáncer de mama, con cirugía conservadora y radioterapia. Se presenta como un sarcoma de alto grado, localizado en la piel o en el tejido subcutáneo y, ocasionalmente, el parénquima mamario. El único tratamiento curativo es la cirugía, con tendencia a la recurrencia y a hacer metástasis hematógena, el pronóstico es malo, con alta tasa de mortalidad.


Angiosarcoma is a rare malignant vascular tumor. It constitutes less than 2% of all sarcomas. There are several clinical forms; the one produced after radiation therapy is that associated with patients who were treated for breast cancer with conservative surgery and radiation therapy. It presents as a high-grade sarcoma located on the skin or the subcutaneous tissue and, occasionally, the breast parenchyma. The only curative treatment is surgery, with a tendency to recurrence and visceral hematogenous metastasis, with a poor prognosis and a high mortality rate.


El angiossarcoma é um tumor vascular maligno pouco frequente. Constitui menos de 2% de todos os sarcomas. Existem várias formas clínicas, uma é a produzida depois da radioterapia, em pacientes que foram tratadas por um câncer de mama, com cirurgia conservadora e radioterapia. Se apresenta como um sarcoma de alto grau, localizado na pele ou no tecido subcutâneo e, ocasionalmente, o parênquima mamário. O único tratamento curativo é a cirurgia, com tendência à recorrência e a fazer metástasehematogênica, o prognóstico é mau, com alta taxa de mortalidade.


Assuntos
Humanos , Feminino , Neoplasias da Mama , Radioterapia , Mama , Tela Subcutânea , Tecido Parenquimatoso , Metástase Neoplásica
6.
Immunity ; 55(2): 254-271.e7, 2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35139352

RESUMO

Allergic immunity is orchestrated by group 2 innate lymphoid cells (ILC2s) and type 2 helper T (Th2) cells prominently arrayed at epithelial- and microbial-rich barriers. However, ILC2s and Th2 cells are also present in fibroblast-rich niches within the adventitial layer of larger vessels and similar boundary structures in sterile deep tissues, and it remains unclear whether they undergo dynamic repositioning during immune perturbations. Here, we used thick-section quantitative imaging to show that allergic inflammation drives invasion of lung and liver non-adventitial parenchyma by ILC2s and Th2 cells. However, during concurrent type 1 and type 2 mixed inflammation, IFNγ from broadly distributed type 1 lymphocytes directly blocked both ILC2 parenchymal trafficking and subsequent cell survival. ILC2 and Th2 cell confinement to adventitia limited mortality by the type 1 pathogen Listeria monocytogenes. Our results suggest that the topography of tissue lymphocyte subsets is tightly regulated to promote appropriately timed and balanced immunity.


Assuntos
Inflamação/imunologia , Interferon gama/imunologia , Subpopulações de Linfócitos/imunologia , Células Th2/imunologia , Animais , Morte Celular/imunologia , Movimento Celular/imunologia , Hipersensibilidade/imunologia , Imunidade Inata , Interleucina-33/imunologia , Interleucina-5/metabolismo , Listeria monocytogenes , Listeriose/imunologia , Listeriose/mortalidade , Fígado/imunologia , Pulmão/imunologia , Subpopulações de Linfócitos/metabolismo , Lisofosfolipídeos/imunologia , Camundongos , Tecido Parenquimatoso/imunologia , Esfingosina/análogos & derivados , Esfingosina/imunologia , Células Th1/imunologia , Células Th2/metabolismo
7.
J Immunol ; 208(5): 1259-1271, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35149532

RESUMO

Idiopathic pulmonary fibrosis (IPF) is an irreversible, age-related diffuse parenchymal lung disease of poorly defined etiology. Many patients with IPF demonstrate distinctive lymphocytic interstitial infiltrations within remodeled lung tissue with uncertain pathogenetic relevance. Histopathological examination of explant lung tissue of patients with IPF revealed accentuated lymphoplasmacellular accumulations in close vicinity to, or even infiltrating, remodeled lung tissue. Similarly, we found significant accumulations of B cells interfused with T cells within remodeled lung tissue in two murine models of adenoviral TGF-ß1 or bleomycin (BLM)-induced lung fibrosis. Such B cell accumulations coincided with significantly increased lung collagen deposition, lung histopathology, and worsened lung function in wild-type (WT) mice. Surprisingly, B cell-deficient µMT knockout mice exhibited similar lung tissue remodeling and worsened lung function upon either AdTGF-ß1 or BLM as for WT mice. Comparative transcriptomic profiling of sorted B cells collected from lungs of AdTGF-ß1- and BLM-exposed WT mice identified a large set of commonly regulated genes, but with significant enrichment observed for Gene Ontology terms apparently not related to lung fibrogenesis. Collectively, although we observed B cell accumulations in lungs of IPF patients as well as two experimental models of lung fibrosis, comparative profiling of characteristic features of lung fibrosis between WT and B cell-deficient mice did not support a major involvement of B cells in lung fibrogenesis in mice.


Assuntos
Linfócitos B/imunologia , Fibrose Pulmonar Idiopática/imunologia , Fibrose Pulmonar Idiopática/patologia , Fator de Crescimento Transformador beta1/metabolismo , Animais , Bleomicina/toxicidade , Colágeno/metabolismo , Feminino , Humanos , Fibrose Pulmonar Idiopática/induzido quimicamente , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Tecido Parenquimatoso/patologia , Linfócitos T/imunologia
8.
PLoS One ; 17(2): e0262848, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35143517

RESUMO

BACKGROUND: Pancreatic transplantation is associated with a high rate of early postoperative graft thrombosis. If a thrombosis is detected in time, a potentially graft-saving intervention can be initiated. Current postoperative monitoring lacks tools for early detection of ischemia. The aim of this study was to investigate if microdialysis and tissue pCO2 sensors detect pancreatic ischemia and whether intraparenchymal and organ surface measurements are comparable. METHODS: In 8 anaesthetized pigs, pairs of lactate monitoring microdialysis catheters and tissue pCO2 sensors were simultaneously inserted into the parenchyma and attached to the surface of the pancreas. Ischemia was induced by sequential arterial and venous occlusions of 45-minute duration, with two-hour reperfusion after each occlusion. Microdialysate was analyzed every 15 minutes. Tissue pCO2 was measured continuously. We investigated how surface and parenchymal measurements correlated and the capability of lactate and pCO2 to discriminate ischemic from non-ischemic periods. RESULTS: Ischemia was successfully induced by arterial occlusion in 8 animals and by venous occlusion in 5. During all ischemic episodes, lactate increased with a fold change of 3.2-9.5 (range) in the parenchyma and 1.7-7.6 on the surface. Tissue pCO2 increased with a fold change of 1.6-3.5 in the parenchyma and 1.3-3.0 on the surface. Systemic lactate and pCO2 remained unchanged. The area under curve (AUC) for lactate was 0.97 (95% confidence interval (CI) 0.93-1.00) for parenchymal and 0.90 (0.83-0.97) for surface (p<0.001 for both). For pCO2 the AUC was 0.93 (0.89-0.96) for parenchymal and 0.85 (0.81-0.90) for surface (p<0.001 for both). The median correlation coefficients between parenchyma and surface were 0.90 (interquartile range (IQR) 0.77-0.95) for lactate and 0.93 (0.89-0.97) for pCO2. CONCLUSIONS: Local organ monitoring with microdialysis and tissue pCO2 sensors detect pancreatic ischemia with adequate correlation between surface and parenchymal measurements. Both techniques and locations seem feasible for further development of clinical pancreas monitoring.


Assuntos
Dióxido de Carbono/análise , Isquemia/diagnóstico , Microdiálise , Pâncreas/metabolismo , Animais , Área Sob a Curva , Modelos Animais de Doenças , Ácido Láctico/metabolismo , Tecido Parenquimatoso/metabolismo , Curva ROC , Suínos
9.
Eur Rev Med Pharmacol Sci ; 26(1): 270-277, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35049004

RESUMO

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare new syndrome occurring after the ChAdOx1 nCoV-19 vaccine immunization. Patients with VITT are characterized by a variable clinical presentation, likewise also the outcome of these patients is very variable. Here we report the lung ultrastructural findings in the course of VITT of a 58-year-old male patient. Alveoli were mainly dilated, irregular in shape, and occupied by a reticular network of fibrin, while interalveolar septa appeared thickened. The proliferation of small capillaries gave rise to plexiform structures and pulmonary capillary hemangiomatosis-like features. Near the alveoli occupied by a dense fibrin network, the medium-sized arteries showed a modified wall and an intraluminal thrombus. This scenario looks quite similar to that found during COVID-19, where the lungs suffer from the attack of the antigen-antibodies complexes and the virus respectively. In both diseases, the final outcome is a severe inflammation, activation of the haemostatic system and fibrinolysis.


Assuntos
/efeitos adversos , Lesão Pulmonar/etiologia , Lesão Pulmonar/patologia , Púrpura Trombocitopênica Idiopática/induzido quimicamente , Vacinação/efeitos adversos , COVID-19/prevenção & controle , Fibrina , Humanos , Lesão Pulmonar/diagnóstico por imagem , Lesão Pulmonar/imunologia , Masculino , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , Tecido Parenquimatoso/patologia , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/imunologia
10.
Clin. transl. oncol. (Print) ; 24(1): 13-23, enero 2022.
Artigo em Inglês | IBECS | ID: ibc-203410

RESUMO

Rethinking IDH-wildtype glioblastoma through its unique features can help researchers find innovative and effective treatments. It is currently emerging that, after decades of therapeutic impasse, some traditional concepts regarding IDH-wildtype glioblastoma need to be supplemented and updated to overcome therapeutic resistance. Indeed, multiple clinical aspects and recent indirect and direct experimental data are providing evidence that the supratentorial brain parenchyma becomes entirely and quiescently micro-infiltrated long before primary tumor bulk growth. Furthermore, they are indicating that the known micro-infiltration that occurs during the IDH-wildtype glioblastoma growth and evolution is not at the origin of distant relapses. It follows that the ubiquitous supratentorial brain parenchyma micro-infiltration as a source for the development of widespread distant recurrences is actually due to the silent stage that precedes tumor growth rather than to the latter. All this implies that, in addition to the heterogeneity of the primary bulk, there is a second crucial cause of therapeutic resistance that has never hitherto been identified and challenged. In this regard, the ancestral founder cancer stem cell (CSC) appears as the key cell that can link the two causes of resistance.


Assuntos
Ciências da Saúde , Glioblastoma/prevenção & controle , Fatores R , Células , Tecido Parenquimatoso
11.
Histopathology ; 80(4): 665-676, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34747513

RESUMO

AIMS: Idiopathic pleuroparenchymal fibroelastosis (PPFE) is a rare type of idiopathic interstitial pneumonia, and pathological PPFE is also observed in patients with secondary interstitial pneumonia. This study aimed to evaluate the pathological findings associated with radiological PPFE-like lesions and the clinical and morphological features of patients with pathological PPFE. METHODS AND RESULTS: We retrospectively reviewed the pathology of the explanted lungs from 59 lung transplant recipients with radiological PPFE-like lesions. Pathological PPFE lesions were identified in 14 patients with idiopathic disease and in 12 patients with secondary disease. Pathological PPFE was associated with previous pneumothorax, volume loss in the upper lobes, and a flattened chest. Patients with idiopathic disease and those with secondary disease with pathological PPFE had similar clinical, radiological and pathological findings, whereas fibroblastic foci were more common in patients with idiopathic disease, and patients with secondary disease more frequently showed alveolar septal thickening with elastosis or fibrosis. Post-transplantation survival did not differ between patients with idiopathic and secondary disease with pathological PPFE (log-rank; P = 0.57) and was similar between patients with idiopathic disease with pathological PPFE and those with idiopathic pulmonary fibrosis (IPF) (log-rank; P = 0.62). CONCLUSIONS: Not all patients with interstitial pneumonia with radiological PPFE-like lesions have pathological PPFE. Characteristic clinical features can suggest the presence of pathological PPFE, and idiopathic and secondary cases with pathological PPFE are similar except for fibroblastic foci in idiopathic cases and alveolar septal thickening with elastosis or fibrosis in secondary cases. Patients with pathological PPFE have a similar prognosis to those with IPF after transplantation.


Assuntos
Doenças Pulmonares Intersticiais/diagnóstico , Transplante de Pulmão , Tecido Parenquimatoso/patologia , Pleura/patologia , Adulto , Feminino , Fibrose/complicações , Humanos , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
Urology ; 159: 139-145, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34606882

RESUMO

OBJECTIVE: To analyze predictors, extent and functional implications associated with renal parenchymal volume replacement (PVR) by renal cell carcinoma (RCC) prior to intervention. This phenomenon is well-recognized yet not adequately studied, and, if severe, can influence management. MATERIALS AND METHODS: A retrospective review was performed of partial nephrectomy (PN) and radical nephrectomy (RN) patients with available preoperative nuclear-renal-scan and imaging demonstrating solitary RCC with normal contralateral kidney. Normal renal parenchymal volume of each kidney was measured by free-hand scripting from preoperative axial images. Primary endpoint was percent PVR which was estimated assuming that the contralateral-kidney serves as a control: PVR = (volume contralateral kidney - volume ipsilateral kidney) normalized by volume contralateral kidney. Multivariable linear-regression analysis assessed factors associated with preoperative PVR. Further analysis evaluated the functional effect of PVR prior to surgery. RESULTS: 146 PN and 136 RN patients with necessary studies were analyzed. For RN, the median PVR was 15% and a quarter of patients had PVR ≥27%. In contrast, PVR was negligible in PN patients for whom median preoperative parenchymal volumes were nearly identical in the ipsilateral/contralateral kidneys (179/180cc, respectively). PVR inversely correlated with preoperative renal function in the ipsilateral kidney (P <.01). Tumor-size (P <.01), stage (P = .03), and endophytic properties (P = .03) associated with PVR on multivariable-analysis. CONCLUSION: Our data suggest that substantial replacement of normal parenchyma by RCC occurs in many patients selected for RN and can contribute to preexisting renal-insufficiency. PVR prior to intervention is mainly driven by tumor characteristics in RN patients, but is negligible in most PN patients.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Rim , Invasividade Neoplásica , Nefrectomia , Tecido Parenquimatoso , Cuidados Pré-Operatórios , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/fisiopatologia , Carcinoma de Células Renais/cirurgia , Feminino , Humanos , Rim/diagnóstico por imagem , Rim/fisiopatologia , Testes de Função Renal/métodos , Neoplasias Renais/patologia , Neoplasias Renais/fisiopatologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/diagnóstico por imagem , Invasividade Neoplásica/patologia , Invasividade Neoplásica/fisiopatologia , Estadiamento de Neoplasias , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Tamanho do Órgão , Tecido Parenquimatoso/diagnóstico por imagem , Tecido Parenquimatoso/patologia , Cuidados Pré-Operatórios/métodos , Cuidados Pré-Operatórios/estatística & dados numéricos , Prognóstico , Insuficiência Renal/diagnóstico , Insuficiência Renal/etiologia , Tomografia Computadorizada por Raios X/métodos , Carga Tumoral
13.
Rev. colomb. anestesiol ; 49(4): e400, Oct.-Dec. 2021. graf
Artigo em Inglês | LILACS, COLNAL | ID: biblio-1341243

RESUMO

The accompanying images demonstrate giant pulmonary artery aneurysms in a patient with idiopathic pulmonary arterial hypertension (Image 1). In addition to the main pulmonary artery, both the left and right pulmonary arteries are aneurysmal and are compressing the lung parenchyma (Image 2).


Las imágenes adjuntas muestran aneurismas gigantes de la arteria pulmonar en un paciente con hipertensión arterial pulmonar idiopática (Imagen 1). Además de la arteria pulmonar principal, tanto la arteria pulmonar izquierda como la derecha son aneurismáticas y están comprimiendo el parénquima pulmonar (Imagen 2).


Assuntos
Humanos , Artéria Pulmonar , Radiologia , Aneurisma , Hipertensão Pulmonar Primária Familiar , Tecido Parenquimatoso , Cardiopatias Congênitas
14.
PLoS One ; 16(12): e0261447, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34919595

RESUMO

BACKGROUND: Defining reference intervals in experimental animal models plays a crucial role in pre-clinical studies. The hepatic parameters in healthy animals provide useful information about type and extension of hepatic damage. However, in the majority of the cases, to obtain them require an invasive techniques. Our study combines these determinations with dynamic functional test and imaging techniques to implement a non-invasive protocol for liver evaluation. The aim of the study was to determine reference intervals for hepatic function, perfusion and parenchyma attenuation with analytical and biochemical blood parameters, indocyanine green, ultrasound and computed tomography in six healthy SD rats. METHODS: Six males healthy SD rats were followed for 4 weeks. To determine hepatic function, perfusion and parenchyma attenuation analytical and biochemical blood parameters, indocyanine green, ultrasound and computed tomography were studied. Results were expressed as Means ± standard error of mean (SEM). The significance of differences was calculated by using student t-test, p < 0.05 was considered statistically significant. RESULTS: Indocyanine green clearance 5 and 10 minutes after its injection was 80.12% and 96.59%, respectively. Approximate rate of decay during the first 5 minutes after injection was 38% per minute. Hepatic perfusion evaluation with the high-frequency ultrasound was related to cardiovascular hemodynamic and renal perfusion. Portal area, hepatic artery resistance index, hepatic artery and portal peak systolic velocity and average between hepatic artery and porta was 3.41 ± 0.62 mm2, 0.57 ± 0.04 mm2/s, 693.24±102.53 mm2/s, 150.72 ± 17.80 mm2/s and 4.82 ± 0.96 mm2/s, respectively. Heart rate, cardiac output, left renal artery diammetre and renal blood flow were 331.01 ± 22.22 bpm, 75.58 ± 8.72 mL/min, 0.88 ± 0.04 mm2 and 13.65 ± 1.95 mm2/s. CT-scan hepatic average volume for each rat were 21.08±3.32, 17.57±2.76, 14.87±2.83 and 13.67±2.45 cm3 with an average attenuation coefficient of 113.51±18.08, 129,19±7.18, 141,47±1.95 y 151,67±1.2 HU. CONCLUSION: Indocyanine green and high-frequency ultrasound could be used in rats as a suitable marker of liver function. Computed tomography, through the study of raw data, help to characterize liver parenchyma, and could be a potential tool for early detection of liver parenchymal alterations and linear follow-up of patients. Further studies in rats with liver disease are necessary to verify the usefulness of these parameters.


Assuntos
Verde de Indocianina/metabolismo , Testes de Função Hepática/métodos , Fígado/metabolismo , Tecido Parenquimatoso/metabolismo , Animais , Masculino , Modelos Animais , Ratos , Ratos Sprague-Dawley , Valores de Referência , Tomografia Computadorizada por Raios X , Ultrassonografia
15.
Molecules ; 26(21)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34770956

RESUMO

The microenvironment for tumor growth and developing metastasis should be essential. This study demonstrated that the hyaluronic acid synthase 3 (HAS3) protein and its enzymatic product hyaluronic acid (HA) encompassed in the subcutaneous extracellular matrix can attenuate the invasion of human breast tumor cells. Decreased HA levels in subcutaneous Has3-KO mouse tissues promoted orthotopic breast cancer (E0771) cell-derived allograft tumor growth. MDA-MB-231 cells premixed with higher concentration HA attenuate tumor growth in xenografted nude mice. Human patient-derived xenotransplantation (PDX) experiments found that HA selected the highly migratory breast cancer cells with CD44 expression accumulated in the tumor/stroma junction. In conclusion, HAS3 and HA were detected in the stroma breast tissues at a high level attenuates effects for induced breast cancer cell death, and inhibit the cancer cells invasion at the initial stage. However, the highly migratory cancer cells were resistant to the HA-mediated effects with unknown mechanisms.


Assuntos
Neoplasias da Mama/metabolismo , Hialuronan Sintases/metabolismo , Tecido Parenquimatoso/metabolismo , Animais , Neoplasias da Mama/patologia , Feminino , Humanos , Hialuronan Sintases/deficiência , Hialuronan Sintases/genética , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Tecido Parenquimatoso/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células Tumorais Cultivadas
16.
Vet Res ; 52(1): 132, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663465

RESUMO

The study aim was to determine the expression of genes potentially related to chronic mastitis at the mRNA and protein levels, viz. chemokine C-C motif receptor 1 (CCR1), C-C motif chemokine ligand 2 (CCL2), C-C motif chemokine ligand 5 (CXCL5), tumor necrosis factor α (TNFα), interleukin 1ß (IL-1ß), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 18 (IL-18), in bovine mammary gland parenchyma. The study examines the differences in expression of selected genes between cows with chronic mastitis caused by coagulase-positive (CoPS) or coagulase-negative staphylococci (CoNS) and those with healthy udders (H). Samples were collected from the udder quarters from 40 Polish Holstein-Friesian cows; 54 of these samples were chosen for analysis based on microbiological analysis of milk taken two days before slaughter. They were categorized into three groups: CoPS (N = 27), CoNS (N = 14) and H (N = 13). The RNA expression was analyzed by RT-qPCR and protein concentration by ELISA. No differences in the mRNA levels of seven genes (TNFα, IL-18, CCR1, IL-1ß, CCL2, IL-8, IL-6) and four proteins (TNFα, IL-18, CCR1, IL-1ß) were identified between the CoPS and H groups. Higher transcript levels of CXCL5 (p ≤ 0.05) gene were noted in CoPS than in H. Compared to H, higher concentrations of IL-8 and CXCL5 (p ≤ 0.05) were observed in CoPS (0.05 < p < 0.1) and CCL2 (0.05 < p < 0.1) in CoNS, while lower levels of Il-6 were found in CoPS. This may suggest that during chronic mastitis the organism stops producing pro-inflammatory cytokines, probably to protect the host tissues against their damage during prolonged infection.


Assuntos
Doenças dos Bovinos/metabolismo , Citocinas/genética , Expressão Gênica , Glândulas Mamárias Animais/metabolismo , Tecido Parenquimatoso/metabolismo , Infecções Estafilocócicas/veterinária , Animais , Bovinos , Doenças dos Bovinos/microbiologia , Doença Crônica/veterinária , Citocinas/metabolismo , Feminino , Infecções Estafilocócicas/metabolismo , Infecções Estafilocócicas/microbiologia , Staphylococcus/fisiologia
17.
J Am Soc Nephrol ; 32(10): 2623-2633, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34531177

RESUMO

BACKGROUND: Chronic tubulointerstitial injury on kidney biopsy is usually quantified by the percentage of cortex with interstitial fibrosis/tubular atrophy (IF/TA). Whether other patterns of IF/TA or inflammation in the tubulointerstitium have prognostic importance beyond percentage IF/TA is unclear. METHODS: We obtained, stained, and digitally scanned full cortical thickness wedge sections of renal parenchyma from patients who underwent a radical nephrectomy for a tumor over 2000-2015, and morphometrically analyzed the tubulointerstitium of the cortex for percentage IF/TA, IF/TA density (foci per mm2 cortex), percentage subcapsular IF/TA, striped IF/TA, percentage inflammation (both within and outside IF/TA regions), and percentage subcapsular inflammation. Patients were followed with visits every 6-12 months. Progressive CKD was defined as dialysis, kidney transplantation, or 40% decline from the postnephrectomy eGFR. Cox models assessed the risk of CKD or noncancer mortality with morphometric measures of tubulointerstitial injury after adjustment for the percentage IF/TA and clinical characteristics. RESULTS: Among 936 patients (mean age, 64 years; postnephrectomy baseline eGFR, 48 ml/min per 1.73m2), 117 progressive CKD events and 183 noncancer deaths occurred over a median 6.4 years. Higher IF/TA density predicted both progressive CKD and noncancer mortality after adjustment for percentage IF/TA and predicted progressive CKD after further adjustment for clinical characteristics. Independent of percentage IF/TA, age, and sex, higher IF/TA density correlated with lower eGFR, smaller nonsclerosed glomeruli, more global glomerulosclerosis, and smaller total cortical volume. CONCLUSIONS: Higher density of IF/TA foci (a more scattered pattern with more and smaller foci) predicts higher risk of progressive CKD after radical nephrectomy compared with the same percentage of IF/TA but with fewer and larger foci.


Assuntos
Córtex Renal/patologia , Neoplasias Renais/cirurgia , Túbulos Renais/patologia , Nefrite/patologia , Tecido Parenquimatoso/patologia , Insuficiência Renal Crônica/fisiopatologia , Idoso , Atrofia/patologia , Fibrose , Humanos , Pessoa de Meia-Idade , Nefrectomia , Nefrite/fisiopatologia , Período Pós-Operatório , Insuficiência Renal Crônica/terapia , Fatores de Risco
18.
Stem Cell Reports ; 16(10): 2432-2441, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34559998

RESUMO

Pluripotent stem cell-derived organoids have transformed our ability to recreate complex three-dimensional models of human tissue. However, the directed differentiation methods used to create them do not afford the ability to introduce cross-germ-layer cell types. Here, we present a bottom-up engineering approach to building vascularized human tissue by combining genetic reprogramming with chemically directed organoid differentiation. As a proof of concept, we created neuro-vascular and myo-vascular organoids via transcription factor overexpression in vascular organoids. We comprehensively characterized neuro-vascular organoids in terms of marker gene expression and composition, and demonstrated that the organoids maintain neural and vascular function for at least 45 days in culture. Finally, we demonstrated chronic electrical stimulation of myo-vascular organoid aggregates as a potential path toward engineering mature and large-scale vascularized skeletal muscle tissue from organoids. Our approach offers a roadmap to build diverse vascularized tissues of any type derived entirely from pluripotent stem cells.


Assuntos
Vasos Sanguíneos/citologia , Organoides/irrigação sanguínea , Organoides/citologia , Organoides/fisiologia , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/fisiologia , Engenharia Tecidual/métodos , Vasos Sanguíneos/fisiologia , Técnicas de Cultura de Células/métodos , Diferenciação Celular , Humanos , Neovascularização Fisiológica , Tecido Parenquimatoso/fisiologia , Fatores de Transcrição/metabolismo
19.
Acta Neuropathol Commun ; 9(1): 151, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507620

RESUMO

Little is known about the effects of parenchymal or vascular amyloid ß peptide (Aß) deposition in the brain. We hypothesized that Aß strain-specific information defines whether Aß deposits on the brain parenchyma or blood vessels. We investigated 12 autopsied patients with different severities of Aß plaques and cerebral amyloid angiopathy (CAA), and performed a seeding study using an Alzheimer's disease (AD) mouse model in which brain homogenates derived from the autopsied patients were injected intracerebrally. Based on the predominant pathological features, we classified the autopsied patients into four groups: AD, CAA, AD + CAA, and less Aß. One year after the injection, the pathological and biochemical features of Aß in the autopsied human brains were not preserved in the human brain extract-injected mice. The CAA counts in the mice injected with all four types of human brain extracts were significantly higher than those in mice injected with PBS. Interestingly, parenchymal and vascular Aß depositions were observed in the mice that were injected with the human brain homogenate from the less Aß group. The Aß and CAA seeding activities, which had significant positive correlations with the Aß oligomer ratio in the human brain extracts, were significantly higher in the human brain homogenate from the less Aß group than in the other three groups. These results indicate that exogenous Aß seeds from different Aß pathologies induced Aß deposition in the blood vessels rather than the brain parenchyma without being influenced by Aß strain-specific information, which might be why CAA is a predominant feature of Aß pathology in iatrogenic transmission cases. Furthermore, our results suggest that iatrogenic transmission of Aß pathology might occur due to contamination of brain tissues from patients with little Aß pathology, and the development of inactivation methods for Aß seeding activity to prevent iatrogenic transmission is urgently required.


Assuntos
Peptídeos beta-Amiloides/administração & dosagem , Peptídeos beta-Amiloides/metabolismo , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Tecido Parenquimatoso/irrigação sanguínea , Tecido Parenquimatoso/metabolismo , Idoso , Idoso de 80 Anos ou mais , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Encéfalo/patologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Tecido Parenquimatoso/patologia , Especificidade da Espécie
20.
Proc Natl Acad Sci U S A ; 118(36)2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34479995

RESUMO

Ectopic lymphoid tissue containing B cells forms in the meninges at late stages of human multiple sclerosis (MS) and when neuroinflammation is induced by interleukin (IL)-17 producing T helper (Th17) cells in rodents. B cell differentiation and the subsequent release of class-switched immunoglobulins have been speculated to occur in the meninges, but the exact cellular composition and underlying mechanisms of meningeal-dominated inflammation remain unknown. Here, we performed in-depth characterization of meningeal versus parenchymal Th17-induced rodent neuroinflammation. The most pronounced cellular and transcriptional differences between these compartments was the localization of B cells exhibiting a follicular phenotype exclusively to the meninges. Correspondingly, meningeal but not parenchymal Th17 cells acquired a B cell-supporting phenotype and resided in close contact with B cells. This preferential B cell tropism for the meninges and the formation of meningeal ectopic lymphoid tissue was partially dependent on the expression of the transcription factor Bcl6 in Th17 cells that is required in other T cell lineages to induce isotype class switching in B cells. A function of Bcl6 in Th17 cells was only detected in vivo and was reflected by the induction of B cell-supporting cytokines, the appearance of follicular B cells in the meninges, and of immunoglobulin class switching in the cerebrospinal fluid. We thus identify the induction of a B cell-supporting meningeal microenvironment by Bcl6 in Th17 cells as a mechanism controlling compartment specificity in neuroinflammation.


Assuntos
/metabolismo , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Células Th17/metabolismo , Animais , Linfócitos B/imunologia , Comunicação Celular , Citocinas/metabolismo , Encefalomielite Autoimune Experimental/metabolismo , Feminino , Centro Germinativo/imunologia , Inflamação/metabolismo , Ativação Linfocitária , Masculino , Meninges/imunologia , Meninges/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/metabolismo , /fisiopatologia , Tecido Parenquimatoso/imunologia , Tecido Parenquimatoso/metabolismo , Proteínas Proto-Oncogênicas c-bcl-6/fisiologia , Células Th17/imunologia , Células Th17/fisiologia
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