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1.
Eur J Clin Invest ; 53(11): e14069, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37525474

RESUMO

BACKGROUND: The consumption of high-caloric diets strongly contributes to the development of non-communicable diseases (NCDs), including cardiovascular disease, the leading cause of mortality worldwide. Exercise (along with diet intervention) is one of the primary non-pharmacological approaches to promote a healthier lifestyle and counteract the rampant prevalence of NCDs. The present study evaluated the effects of exercise cessation after a short period training on the cardiac metabolic and mitochondrial function of female rats. METHODS: Seven-week-old female Sprague-Dawley rats were fed a control or a high-fat, high-sugar (HFHS) diet and, after 7 weeks, the animals were kept on a sedentary lifestyle or submitted to endurance exercise for 3 weeks (6 days per week, 20-60 min/day). The cardiac samples were analysed 8 weeks after exercise cessation. RESULTS: The consumption of the HFHS diet triggered impaired glucose tolerance, whereas the HFHS diet and physical exercise resulted in different responses in plasma adiponectin and leptin levels. Cardiac mitochondrial respiration efficiency was decreased by the HFHS diet consumption, which led to reduced ATP and increased NAD(P)H mitochondrial levels, which remained prevented by exercise 8 weeks after cessation. Exercise training-induced cardiac adaptations in redox balance, namely increased relative expression of Nrf2 and downstream antioxidant enzymes persist after an eight-week exercise cessation period. CONCLUSIONS: Endurance exercise modulated cardiac redox balance and mitochondrial efficiency in female rats fed a HFHS diet. These findings suggest that exercise may elicit cardiac adaptations crucial for its role as a non-pharmacological intervention for individuals at risk of developing NCDs.

2.
Int J Mol Sci ; 24(11)2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37298718

RESUMO

Osteomyelitis is an infection of the bone that is often difficult to treat and causes a significant healthcare burden. Staphylococcus aureus is the most common pathogen causing osteomyelitis. Osteomyelitis mouse models have been established to gain further insights into the pathogenesis and host response. Here, we use an established S. aureus hematogenous osteomyelitis mouse model to investigate morphological tissue changes and bacterial localization in chronic osteomyelitis with a focus on the pelvis. X-ray imaging was performed to follow the disease progression. Six weeks post infection, when osteomyelitis had manifested itself with a macroscopically visible bone deformation in the pelvis, we used two orthogonal methods, namely fluorescence imaging and label-free Raman spectroscopy, to characterise tissue changes on a microscopic scale and to localise bacteria in different tissue regions. Hematoxylin and eosin as well as Gram staining were performed as a reference method. We could detect all signs of a chronically florid tissue infection with osseous and soft tissue changes as well as with different inflammatory infiltrate patterns. Large lesions dominated in the investigated tissue samples. Bacteria were found to form abscesses and were distributed in high numbers in the lesion, where they could occasionally also be detected intracellularly. In addition, bacteria were found in lower numbers in surrounding muscle tissue and even in lower numbers in trabecular bone tissue. The Raman spectroscopic imaging revealed a metabolic state of the bacteria with reduced activity in agreement with small cell variants found in other studies. In conclusion, we present novel optical methods to characterise bone infections, including inflammatory host tissue reactions and bacterial adaptation.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Osteomielite , Infecções Estafilocócicas , Camundongos , Animais , Staphylococcus aureus/fisiologia , Osteomielite/patologia , Modelos Animais de Doenças , Inflamação , Infecções Estafilocócicas/microbiologia , Infecção Persistente
3.
Pathologica ; 114(2): 146-151, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35481565

RESUMO

Objective: Respiratory tract infections remain a common problem in clinical practice with high morbidity and mortality worldwide. In Portugal, pneumonia was the third leading death cause in 2018. Due to COVID-19 pandemic, there is a growing concern about the burden of respiratory diseases and preventable risk factors. The present study started before the pandemic and its aim was to determine the occurrence of pneumonia/bronchopneumonia in a postmortem series and to characterize its circumstantial context. Methods: A retrospective anatomopathological study was performed on cases with acute pneumonia/bronchopneumonia at the Medicolegal Portuguese Institute (2011-2017). Results: In an autopsy series of 737 patients, 521 were male and 675 presented comorbidities. The mean age was 63.87 ± 19.8 years. The most common acquisition site was community (65.1%), as natural death (65.5%). Concerning the manner of death, most cases (48.0%) were sudden deaths, followed by accidents (29.2%). A statistically significant association was observed between the medicolegal etiology and the place of infection acquisition, with higher prevalence of natural obitus (91.0%) in community-acquired pneumonia/bronchopneumonia versus higher prevalence of violent obitus in hospital-acquired pneumonia/bronchopneumonia (82.1%) (p < 0.001). Conclusions: Forensic anatomopathological postmortem data may contribute to better understand community and hospital pulmonary infections.


Assuntos
Broncopneumonia , COVID-19 , Pneumonia , Infecções Respiratórias , Adulto , Idoso , Idoso de 80 Anos ou mais , Broncopneumonia/epidemiologia , COVID-19/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia/epidemiologia , Infecções Respiratórias/epidemiologia , Estudos Retrospectivos
4.
Int Endod J ; 54(10): 1687-1698, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33999433

RESUMO

AIM: To investigate the association between root canal treatment outcome, diabetes mellitus, and alterations of the angiogenic process. METHODOLOGY: A retrospective observational study was conducted in healthy (control group, CG) and diabetic (type II diabetes mellitus group, DG) patients after root canal treatment. The follow-up appointments were performed to clinically and radiographically observe symptoms, the healing of periapical lesions and the quality of root fillings. In the animal model study, diabetic Goto-Kakizaki (GK) rats and control Wistar rats were used. After 21 days of pulp exposure and the development of apical periodontitis (AP), the mandibles were removed for scintigraphic, radiographic, histopathological and molecular analyses. Chi-square tests were performed to examine the variables related to endodontic outcome and differences between animal groups were assessed using the Student's t-test. RESULTS: The group of patients with diabetes had a significantly lower rate of success following root canal treatment than the CG (p < .001). Logistic regression suggested that diabetes is a risk factor for success of root canal treatment. In the animal study, GK rats had significantly higher fasting glycaemia at t0 and t21 (p < .001) and triglycerides levels (p < .05) and area under the curve (AUC) during the insulin tolerance test at t21 (p < .001). AP area was significantly greater in GK rats (p < .05). Histologically, diabetic rats had increased signs of periodontal ligament inflammation 21 days after the induction of apical periodontitis, with fibro-hyaline matrix filling and vessel with undefined walls. Wistar rats had significantly increased vascular endothelial growth factor (VEGF) levels and VEGF/Ang-2 ratio 21 days after AP induction (p < .08; p < .07). GK rats had intrinsically lower levels of VEGF than control rats (p < .05), which did not change after AP. CONCLUSION: Diabetes mellitus should be considered as an important factor in the prognosis of root canal treatment and its outcomes over time. Future strategies to improve angiogenesis and tissue repair should be pursued to achieve better root canal treatment outcomes in diabetic patients.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Periodontite Periapical , Animais , Cavidade Pulpar , Diabetes Mellitus Experimental/complicações , Humanos , Periodontite Periapical/terapia , Ratos , Ratos Wistar , Tratamento do Canal Radicular , Fator A de Crescimento do Endotélio Vascular
5.
Pol J Pathol ; 72(4): 346-352, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35308006

RESUMO

Wax models of normal and diseased organs were formerly essential medical teaching tools. The ceroplastic heart models from two 19th century pathology museums at the Universities of Florence (n = 8) and Coimbra (n = 10) were analysed. The Florentine collection comprised congenital malformations as well as infectious and inflammatory disorders. The Coimbra waxworks included congenital defects, cardiac hypertrophy and dilation, valvular pathology and cardiac adiposity. This study focuses on heart diseases and teaching resources in European university hospitals during the 19th century. It also highlights the importance of wax models in medical education both then and today, in an era of informatics and digital photography.


Assuntos
Modelos Anatômicos , Ceras , Humanos , Museus/história , Universidades , Ceras/história
6.
J Environ Manage ; 300: 113697, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34543961

RESUMO

Dysprosium (Dy) is a rare earth element with a high economic and strategic value, and simultaneously an emerging contaminant, whose removal from wastewaters is gaining increasing attention. In this work, the Response Surface Methodology (RSM) combined with a Box-Behnken Design (3 factors-3 levels) was used to optimize the key operational conditions that influence the uptake of Dy by two living seaweed, Ulva sp. and Gracilaria sp.. The initial concentration of Dy (10-500 µg/L), water salinity (10-30), and seaweed dosage (0.5-5.5 g/L) were the independent variables, while the removal efficiency (%) and bioaccumulation (q, µg/g) were the response variables. Results highlighted the high capacity of both species to capture Dy. After 168 h, the optimal conditions that led to a maximum of 91 % of Dy removed by Gracilaria sp. were: 500 µg of Dy per L of water, salinity 10, and 5.5 g of seaweed per L. For Ulva sp., a maximum removal percentage of 79 % was achieved in the conditions: any initial concentration of Dy, salinity 20, and seaweed dosage of 3.7 g/L. Independently of the species, the response surfaces showed that the most important variable for the removal is the seaweed dosage, while for bioaccumulation is the initial concentration of Dy. Using RSM, it was possible to obtain the optimal operating conditions for Dy removal from waters, which is a fundamental step toward the application of the proposed technology at large scale.


Assuntos
Alga Marinha , Ulva , Poluentes Químicos da Água , Disprósio , Água , Poluentes Químicos da Água/análise
7.
Pol J Pathol ; 71(3): 281-282, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33112120

RESUMO

Historical Museums of Anatomical Pathology are a relevant teaching tool for medical undergraduate students and postgraduate residents. The visualization of real specimens allow a deeper comprehension of diseases, namely of rare conditions as in Teratology. This article emphasizes the need to preserve and use Universities Museums, by presenting a XIXth Thoraco-Abdominopagus Fetus.


Assuntos
Museus , Patologia , Feto , Humanos , Patologia/educação , Universidades
8.
Pathophysiology ; 26(3-4): 213-217, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31076239

RESUMO

Acute Fibrinous and Organizing Pneumonitis (AFOP) is a disease with histopathological pattern characterized by the presence of intra-alveolar fibrin in the form of fibrin "balls" and organizing pneumonia represented by inflammatory myofibroblastic polyps. Symptoms of this rare interstitial pulmonary disease can be either acute or sub-acute and it can rapidly progress to death. Diagnosis should be considered in the Intensive Care Unit (ICU) if patients' symptomatology and radiology correlates with non-responding or progressive pneumonia and when morphology, on biopsies, encompasses criteria of diffuse alveolar damage (DAD) and organizing pneumonia (OP) balancing in between. Three clinical cases of patients presenting severe lung disease requiring mechanical ventilation and prolonged intensive care fitted on the variable spectra of AFOP histopathology and had poor outcome: a 23 year-old women had AFOP in the context of antiphospholipid syndrome pulmonary compromise; a 35 year-old man developed a letal intensive care pneumonia with AFOP pattern registered in post-mortem biopsy; and a 79 year-old man died 21 days after intensive care unit treatment of a sub-pleural organizing pneumonia with intra-alveolar fibrin, seen in post-mortem biopsy. The predominance of acute fibrin alveolar deposition pattern is helpful in raising AFOP differential diagnosis while organizing pneumonia pattern establishes a wider range of diagnosis that can go till solitary pulmonary nodule, remaining indefinite to suggest diagnosis. The performance time of biopsy in a larger number of clinical cases may be helpful in establishing the evolutionary morphological pattern, taking in mind the poor outcome of the disease, deserving rapid diagnosis to define treatment.

9.
Pathobiology ; 85(1-2): 96-107, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29635240

RESUMO

Lung cancer diagnosis is a challenge since it is also one of the most frequently diagnosed cancers. Diagnostic challenges are deeply related to the development of personalized therapy and molecular and precise histological characterizations of lung cancer. When addressing these features, it is very important to acknowledge the issue of tumour heterogeneity, as it imposes several questions. First of all, lung cancer is a very heterogeneous disease, at a cellular and histological level. Cellular and histological heterogeneity are addressed with emphasis on the diagnosis, pre-neoplastic lesions, and cell origin, trying to contribute to a better knowledge of carcinogenesis. Molecular intra-tumour and inter-tumour heterogeneity are also addressed as temporal heterogeneity. Lung cancer heterogeneity has implications in pathogenesis understanding, diagnosis, selection of tissue for molecular diagnosis, as well as therapeutic decision. The understanding of tumour heterogeneity is crucial and we must be aware of the implications and future developments regarding this field.


Assuntos
Biomarcadores Tumorais/genética , Heterogeneidade Genética , Neoplasias Pulmonares/genética , Humanos , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Mutação
10.
Rheumatol Int ; 38(8): 1565-1570, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29754327

RESUMO

Vascular involvement in IgG4-related disease (IgG4-RD), is a well-recognized feature and large vessel commitment, especially the aorta, can be the only manifestation of the disease. Being a newly recognized disease, its diagnosis and workup still represents a challenge in clinical practice. A 47-year-old-man with two aortic aneurysms ruptures, one at abdominal and the other at thoracic level, was referred to our rheumatology department. The initial analysis of the surgical specimen obtained 3 years earlier revealed a nonspecific aortitis. Re-evaluation of the biopsy with immunohistology now demonstrated the presence of IgG4 deposits. Evidence-based recommendations regarding diagnosis, treatment and follow-up of IgG4-related large-vessel involvement are lacking. In this particular case, histopathology were crucial. The authors review and discuss vascular involvement in IgG4-RD and respective treatment options.


Assuntos
Aneurisma da Aorta Abdominal/imunologia , Aneurisma da Aorta Torácica/imunologia , Ruptura Aórtica/etiologia , Aortite/imunologia , Doença Relacionada a Imunoglobulina G4/imunologia , Idoso , Aneurisma da Aorta Abdominal/patologia , Aneurisma da Aorta Torácica/patologia , Ruptura Aórtica/imunologia , Ruptura Aórtica/cirurgia , Aortite/sangue , Aortite/complicações , Aortite/tratamento farmacológico , Biomarcadores/sangue , Feminino , Humanos , Doença Relacionada a Imunoglobulina G4/sangue , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Fatores Imunológicos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Plasmócitos/imunologia , Rituximab/administração & dosagem
11.
Pathophysiology ; 25(2): 89-99, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29628185

RESUMO

Colorectal cancer (CRC) is the second most frequent and fatal cancer in Western countries. Understanding its biology with different incidence along the colon and rectum, genetic profile and how these factors contribute to local/distant progression, has been hampered by the lack of a suitable CRC model. We report a reproducible model, using human CRC cell lines (CL) (WiDr, LS1034, C2BBe1) injected (1 × 107 cells/animal) in RNU rats (n = 55) which underwent cecostomy and descending colostomy with mucosal-cutaneous fistula of the sigmoid colon. CL were characterized by immunohistochemistry: CK20, CDX2, P53, vimentin, Ki67, CD44, CD133, E-cadherin, ß-catenin and CEA; cancer stem cells-immune system interaction was studied and tumor progression was assessed with nuclear medicine imaging (99mTc-MIBI). Animals developed locally invasive tumors and with WiDr neural invasion was registered. Cancer stem cells were detected in WiDr (CD44 positive). All the cell lines stimulated the immune system, being WiDr the most aggressive. Imaging studies demonstrated tumor uptake. With this CRC model we can study the microenvironment role and tumor-stroma interactions. All CL developed primary disease, but only the WiDR established neural invasion which may represent a metastatic pathway. This model can help unveiling the underlying metastatic mechanisms, and ultimately test better therapeutic approaches for CRC.

13.
Fetal Pediatr Pathol ; 36(2): 89-105, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27827548

RESUMO

Preterm labor (PTL) accounts for almost 11% of deliveries, and is a major cause of neonatal morbidity and mortality. T regulatory (Treg) cells may prevent fetal rejection by the maternal immune system under the influence of progesterone. Case control study was conducted to determine Treg cells, IL-10, TGF-ß, and membrane progesterone receptorα (mPRα) in the maternal-fetal interface (placenta), including eight pregnant women with threatened PTL (study group) and 16 normal-delivery women (control group). Comparing study group versus control, mean gestational age of delivery differed significantly (p = 0.02), as did endothelial hyperplasia in the upper half (p = 0.035) and the lower half (p = 0.005) of the placenta. Besides, there was higher expression of mPRα and IL-10 in all layers, while Foxp3 expression occurred equally and only in the decidua. TGF-ß expression was similar in both groups. Preterm group placentas showed higher endothelial hyperplasia in both upper and lower halves of the placenta.


Assuntos
Desenvolvimento Fetal/fisiologia , Feto , Trabalho de Parto Prematuro/fisiopatologia , Placenta/fisiopatologia , Nascimento Prematuro/etiologia , Adulto , Estudos de Casos e Controles , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Relações Materno-Fetais , Gravidez , Fator de Crescimento Transformador beta/metabolismo
14.
Rev Port Cir Cardiotorac Vasc ; 24(3-4): 162, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29701393

RESUMO

INTRODUCTION: IgG4-related disease (IgG4-RD) is an immune- -mediated fibro-inflammatory condition with unknown etiology that can affect various organs. Although its prevalence is still unknown, it appears to be more frequent in adult males. Cardiovascular manifestations are rare and can include idiopathic retroperitoneal periaortic fibrosis, inflammatory aortic aneurism, inflammatory periarteritis and inflammatory pericarditis. Vascular involvement is a well-recognized feature and large vessel commitment, especially the aorta, can be the only manifestation of the disease. The gold standard diagnosis is histological. METHODS: A 47-year-old man presented rupture of two aortic aneurysms: one thoracic and one abdominal, and underwent surgical correction. A segment of the aorta artery wall measuring 3x2x0.5cm, exhibited smooth intimate and white vinous adventitia, medium tunic was white, through firm tissue with loss of elasticity. RESULTS: In addition to heterogenous collagenation with destruction of the elastic network of the aortic mediae tunica, there was fibrin deposition and neutrophil overlap. Lymphoid follicles with reactive germinate centers were along the tunica media and adventitia, without phenotype of endothelitis and absence of either macrophages and Langerhans cells (CD1a). Plasmocytes showed immunopositivity to IgG4, with heterogeneous and well defined localization, supporting the diagnosis of igG4 Disease. Serological studies showed negativity for vasculitis, hereditary connective tissue diseases were not component of the clinical set and normal serum IgG4 concentration was determined. CONCLUSION: Few cases of involvement of large vessels by IgG4- -RD have been reported in literature. Serum IgG4 concentration may be normal in one third of patients. In this case, IgG4 immunostaining was crucial for the diagnosis of IgG4-RD aortitis, together with the hyaline destruction of the tunica media (ESP 2015 / Aagaimy 2013). There is still no clinical knowledge for the treatment and monitoring of the involvement of large vessels by IgG4-RD.


Assuntos
Aneurisma Aórtico , Aortite , Imunoglobulina G , Esclerose , Aorta , Aortite/imunologia , Aortite/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Plasmócitos , Esclerose/imunologia , Esclerose/cirurgia
15.
Rev Port Cir Cardiotorac Vasc ; 24(3-4): 166, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29701397

RESUMO

INTRODUCTION: Cardiovascular syphilis can manifest as aortic aneurysms, aortic regurgitation and coronary ostial stenosis. Tertiary syphilis was the most commom reported cause of thoracic aortic aneurysm in the pre-antibiotic era, contributing to 5- 10% of cardiovascular deaths. However, in the 21st century, it has virtually disappered from the devoloping nations. Tertiay syphilis may develop in about one third of cases of untreated syphilis. In the pre-penicilin era, it was calculated that cardiovascular syphilis was responsible for 10-15% of clinical syphilis. METHODS: We present a rare case of syphilitic aortitis in a era of highly effective antibiotics. RESULTS: A 48-year-old man with no known clinical cardiac pathology went to emergency with an episode of chest pain of short duration and great intensity, being hospitalized with a differential diagnosis of coronary disease, ascending aortic aneurysm and aortic valve regurgitation. Two segments of the aorta, 5cm and 9.5cm length were observed, both had thickened wall (1cm), and firm plaques with diferent shapes and sizes. The intima of the aorta appeared rough and pitted, with the appearance of tree bark. There were heterogeneous lesions of the tunica media: hyalinization and calcification, macrophages aggregates, areas of hemorrhage and lymphoplasmacytic infiltrate forming vascular sheaths. Adventitia exhibited hyperplasia of nerve pathways with surrounding lymphoplasmocytic infiltrate. The diagnosis of syphilitic aortitis was purposed and serological analysis revealed positivity for Treponema pallidum. Patient underwent surgical correction of an aortic aneurysm. CONCLUSION: The serological positivity for Treponema pallidum and the histopathological study allowed the currently rare diagnosis of Ascending Aortic Aneurysm by Tertiary Syphilis. In the present scenario with early and widespread use of antibiotics, it is considered a very rare disease.


Assuntos
Aneurisma Aórtico , Insuficiência da Valva Aórtica , Estenose Coronária , Sífilis Cardiovascular , Aneurisma Aórtico/etiologia , Aneurisma Aórtico/cirurgia , Insuficiência da Valva Aórtica/etiologia , Estenose Coronária/etiologia , Estenose Coronária/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Sífilis Cardiovascular/complicações , Sífilis Cardiovascular/diagnóstico , Sífilis Cardiovascular/cirurgia
16.
Rev Port Cir Cardiotorac Vasc ; 24(3-4): 165, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29701396

RESUMO

INTRODUCTION: Takayasu aortitis is a well known yet rare form of large vessel vasculitis. Also known as pulseless disease, occlusive thromboaortopathy, and Martorell syndrome, is a chronic inflammatory aortitis. Vessel inflammation leads to wall thickening, fibrosis, stenosis, and thrombus formation. METHODS: A 64-year-old woman was referred to emergency for lack of pulse in the upper and lower limbs and changes in heart rate. AngioRMN revealed dissection of the ascending aorta while in PET, intense uptake of FDG-F18 involving ascending, crossa, descending thoracic and abdominal segments of the aorta, was evident urgent surgical correction occurred. An aorta ring segment with 2.5cm length, showed whitish and smooth intimate, with linear transversal laceration, with regular borders. Dissection 1cm long of the medial tunica was occupied by a clot in continuity with a thrombus occupying the neoformed lumen. RESULTS: Microscopy examination confirmed hyalinization of the tunica media with impregnation of fibrin / thrombus with blood cell elements. Endothelial inflammatory characteristics together with vasa vasorum and vascular trajectory of the periphery of the tunica media with inflammatory cells involvement allowed the diagnosis of Takayasu aortitis. CONCLUSION: Takayasu aortitis is rare in the presented age group, with early non-specific symptoms. The diagnosis of aortic dissection was crucial, constituting a medical emergency. Heather L-Gomik (2008) supports the hyaline structural alteration of the tunica media. The disease has been recognized for more than 100 years, and patients with Takayasu aortitis remain relatively poor and treatment is suboptimal. Key areas for improvement include the need for increase disease awareness and earlier diagnosis, and improved means for monitoring disease activity. The demonstration of diferential expression of Toll-like receptors in arteries, is particularly intriguing and worthy of further investigation.


Assuntos
Dissecção Aórtica , Arterite de Takayasu , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/cirurgia , Aorta/patologia , Artérias , Feminino , Humanos , Pessoa de Meia-Idade , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/cirurgia
17.
Carcinogenesis ; 36(1): 68-75, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25368033

RESUMO

Lung tumour subtyping, particularly the distinction between adenocarcinoma (AdC) and squamous cell carcinoma (SqCC), is a critical diagnostic requirement. In this work, the metabolic signatures of lung carcinomas were investigated through (1)H NMR metabolomics, with a view to provide additional criteria for improved diagnosis and treatment planning. High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (NMR) spectroscopy was used to analyse matched tumour and adjacent control tissues from 56 patients undergoing surgical excision of primary lung carcinomas. Multivariate modeling allowed tumour and control tissues to be discriminated with high accuracy (97% classification rate), mainly due to significant differences in the levels of 13 metabolites. Notably, the magnitude of those differences were clearly distinct for AdC and SqCC: major alterations in AdC were related to phospholipid metabolism (increased phosphocholine, glycerophosphocholine and phosphoethanolamine, together with decreased acetate) and protein catabolism (increased peptide moieties), whereas SqCC had stronger glycolytic and glutaminolytic profiles (negatively correlated variations in glucose and lactate and positively correlated increases in glutamate and alanine). Other tumour metabolic features were increased creatine, glutathione, taurine and uridine nucleotides, the first two being especially prominent in SqCC and the latter in AdC. Furthermore, multivariate analysis of AdC and SqCC profiles allowed their discrimination with a 94% classification rate, thus showing great potential for aiding lung tumours subtyping. Overall, this study has provided new, clear evidence of distinct metabolic signatures for lung AdC and SqCC, which can potentially impact on diagnosis and provide important leads for future research on novel therapeutic targets or imaging tracers.


Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Espectroscopia de Ressonância Magnética , Metabolômica , Adenocarcinoma/metabolismo , Carcinoma de Células Escamosas/metabolismo , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico
18.
Biochim Biophys Acta ; 1842(1): 32-43, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24161538

RESUMO

Impaired wound healing is an important clinical problem in diabetes mellitus and results in failure to completely heal diabetic foot ulcers (DFUs), which may lead to lower extremity amputations. In the present study, collagen based dressings were prepared to be applied as support for the delivery of neurotensin (NT), a neuropeptide that acts as an inflammatory modulator in wound healing. The performance of NT alone and NT-loaded collagen matrices to treat wounds in streptozotocin (STZ) diabetic induced mice was evaluated. Results showed that the prepared dressings were not-cytotoxic up to 72h after contact with macrophages (Raw 264.7) and human keratinocyte (HaCaT) cell lines. Moreover, those cells were shown to adhere to the collagen matrices without noticeable change in their morphology. NT-loaded collagen dressings induced faster healing (17% wound area reduction) in the early phases of wound healing in diabetic wounded mice. In addition, they also significantly reduced inflammatory cytokine expression namely, TNF-α (p<0.01) and IL-1ß (p<0.01) and decreased the inflammatory infiltrate at day 3 post-wounding (inflammatory phase). After complete healing, metalloproteinase 9 (MMP-9) is reduced in diabetic skin (p<0.05) which significantly increased fibroblast migration and collagen (collagen type I, alpha 2 (COL1A2) and collagen type III, alpha 1 (COL3A1)) expression and deposition. These results suggest that collagen-based dressings can be an effective support for NT release into diabetic wound enhancing the healing process. Nevertheless, a more prominent scar is observed in diabetic wounds treated with collagen when compared to the treatment with NT alone.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Bandagens , Diabetes Mellitus Experimental/metabolismo , Neurotensina/farmacologia , Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Movimento Celular , Colágeno/química , Colágeno Tipo I/genética , Colágeno Tipo I/imunologia , Colágeno Tipo III/genética , Colágeno Tipo III/imunologia , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Experimental/patologia , Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/imunologia , Inflamação/patologia , Inflamação/prevenção & controle , Queratinócitos/efeitos dos fármacos , Queratinócitos/imunologia , Queratinócitos/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Pele/imunologia , Pele/lesões , Pele/metabolismo , Estreptozocina , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
19.
Mutagenesis ; 30(2): 277-86, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25406472

RESUMO

Cellular senescence is a physiological process that serves as a powerful barrier for tumorigenesis. However, senescent cells can be deleterious for the tissue microenvironment. Such is the case of senescent fibroblasts that release several pro-tumorigenic factors that promote malignant transformation in the nearby epithelial cells. Occupational exposure to hexavalent chromium [Cr(VI)] compounds is a cause of respiratory cancers. Although Cr(VI) is known to induce senescence in human foreskin fibroblasts, the role of senescent fibroblasts in the Cr(VI)-induced malignant transformation of human bronchial epithelial cells was never assessed. Thus, to study the evolutionary dynamics generated by the interaction between human bronchial epithelial cells and senescent bronchial fibroblasts, the non-tumorigenic human bronchial epithelial BEAS-2B cells were co-cultured with Cr(VI)-induced senescent human bronchial fibroblasts for 4 weeks. Under the pressure of 0.5 µM Cr(VI), senescent fibroblasts promoted the acquisition of mesenchymal features on BEAS-2B cells, e.g. the fusiform shape and increased Vimentin expression, consistent with the occurrence of an epithelial-mesenchymal transition-like process. Features of transformed cells including larger nuclei, as well as nuclei with heterogeneous size, were also observed. Altogether the results obtained demonstrate that besides acting over the epithelium, Cr(VI) also affects bronchial fibroblasts driving them senescent. As a consequence, a paracrine communication loop is established with the above-placed epithelium prompting the epithelial cells for malignant transformation and thus facilitating the initial steps of tumorigenesis.


Assuntos
Brônquios/efeitos dos fármacos , Senescência Celular , Cromo/toxicidade , Células Epiteliais/fisiologia , Transição Epitelial-Mesenquimal , Fibroblastos/efeitos dos fármacos , Brônquios/citologia , Brônquios/fisiologia , Transformação Celular Neoplásica , Técnicas de Cocultura , Fibroblastos/fisiologia , Humanos
20.
Surg Radiol Anat ; 37(2): 161-5, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24969171

RESUMO

While performing thyroid surgery, the unintentional lesion of parathyroid glands and laryngeal nerves results in a profound alteration in patient's quality of life. To minimize thyroid surgery morbidity, the surgeon must have an in-depth knowledge of the thyroid gland morphology and its anatomical relations in the anterior compartment of the neck. This work intended to simulate total thyroidectomies using cadaver parts and isolate fragments that may correspond to parathyroid glands. The thyroid glands and "eventual" parathyroid glands were then submitted to histological study. Ninety-two cadaver parts were used for macroscopic dissection. A total of 242 fragments were isolated, 154 of which were confirmed through histological study to be parathyroid glands. In 36 cases, all "eventual" parathyroid glands isolated during dissection were confirmed through histological verification. In 40 cases, some glands were confirmed. In 16 cases, none of the "eventual" parathyroid glands was confirmed. The 92 thyroid glands isolated during dissection were also submitted to histological study. In 21 thyroid glands, 16 parathyroid glands were identified in the histological cuts: 8 sub-capsular, 8 extra-capsular, 6 intra-thyroidal. There was no statistical difference between the dimensions of the parathyroid glands. Parathyroid gland identification and preservation are sometimes a challenge during thyroid surgery, difficulty that has been demonstrated during dissection of cadaver parts.


Assuntos
Glândulas Paratireoides/anatomia & histologia , Cadáver , Dissecação , Humanos , Glândulas Paratireoides/ultraestrutura
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