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The paper provides an overview of the current understanding of different cells' biology (e.g., keratinocytes, Paneth cells, myoepithelial cells, myofibroblasts, chondroclasts, monocytes, atrial cardiomyocytes), including their origin, structure, function, and role in disease pathogenesis, and of the latest findings in the medical literature concerning the brown adipose tissue and the juxtaoral organ of Chievitz.
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Células Epiteliais , Técnicas Histológicas , Humanos , Bochecha , Queratinócitos , Diagnóstico DiferencialRESUMO
This article focuses on the latest histological knowledge in the field regarding the peripheral lymphoid system [mucosa-associated lymphoid tissue (MALT), bronchus-associated lymphoid tissue (BALT), gut-associated lymphoid tissue (GALT)], the thymus stroma, some of the various corpuscles of the human body (Hassall's corpuscles in thymus, arenaceous corpuscles in pineal gland, corpora amylacea in prostate and other locations) and Fañanas glial cells in the cerebellum.
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Células Epiteliais , Timo , Humanos , MasculinoRESUMO
In the literature, this paper is the first to describe the use of plasma rich in growth factors (PRGF)-Endoret® in hemodialyzed diabetic patients, to promote the healing of after amputation wounds. The PRGF-Endoret® was primarily conceived to be used in maxillofacial surgery, oral implantology, etc., the innovation residing in the blood collection technique (quantity, moment of the week, rhythmicity), which was adapted to the specific conditions of the hemodialyzed patient. Moreover, in the initial phases, the two PRGF fractions were innovatively applied as single alternating layers on the wound surface. Only after the surface of the wound decreased, the two PRGF fractions were applied as overlapping layers. Nevertheless, the paper presents the optimal method to assess the clinical evolution of the wound. Histopathological examination of the biopsy performed during wound preparation for PRGF application brought additional, essential data for orienting the therapeutic approach. The exclusion of calciphylaxis, a disease with high mortality risk, encouraged the application of this method, and also demonstrated the microscopic features in hemodialyzed diabetic patients.
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Diabetes Mellitus , Plasma Rico em Plaquetas , Idoso , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Plasma , CicatrizaçãoRESUMO
Microsatellite instability (MSI) or the deficiency of mismatch repair (MMR) proteins is one of the molecular pathways of colorectal tumorigenesis and may have important clinical implications in predicting the treatment response. We evaluated the relationship between clinicopathological features and MMR proteins [mutL homologue 1 (MLH1), mutS homologue 2 (MSH2), mutS homologue 6 (MSH6), postmeiotic segregation increased 2 (PMS2)], adhesion molecules (E-cadherin, beta-catenin) and caudal-type homeobox 2 (CDX2) in 31 patients with colon adenocarcinoma, using immunohistochemistry. We also aimed to assess the prognostic value of the studied proteins. MLH1 loss was correlated to PMS2 loss (p=0.006) and MSH2 loss (p=0.023); MSH2 loss was significantly associated to MSH6 loss (p=0.011). Tumors with MSH6 loss, together with tumors with PMS2 loss, covered all the patients with MSI status. We found a significant correlation between MSI tumors and mucinous histological type (p=0.03), but no significant associations with other clinicopathological features or with survival rate. There was a significant correlation between E-cadherin expression and differentiation degree (p=0.018) and between beta-catenin expression and lymph node invasion (p=0.046). No significant association between CDX2 loss and any clinical or pathological features was found (p>0.05). No significant differences were identified in overall survival according to E-cadherin, beta-catenin or CDX2 expression (p>0.05). In our study, PMS2 loss was significantly correlated with CDX2 loss (p=0.03). In conclusion, the molecular analysis of biological markers for colon cancer may be important for patient stratification, in order to select the optimal treatment algorithm. Our results suggest that probably the double panel (MSH6 and PMS2) is enough to detect the MSI status, instead of using the quadruple panel.
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Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Encefálicas , Fator de Transcrição CDX2/genética , Caderinas/genética , Neoplasias do Colo/genética , Neoplasias Colorretais/genética , Humanos , Instabilidade de Microssatélites , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Proteína 2 Homóloga a MutS/genética , Síndromes Neoplásicas Hereditárias , Prognóstico , beta Catenina/genéticaRESUMO
In the jaws, the healing process of bone defects occurs differently compared with other anatomical sites where healing is done by the formation of scar tissue. This is due to physiological bone remodeling and continuous bone resorption and apposition. In the case of large cysts, there is an increased risk of postoperative infection due to the retraction of the blood clot on the bony walls. The use of plasma rich in growth factors (PRGF), with or without autologous bone addition, for filling the cystic cavities is beneficial not only for its antimicrobial effect, but also due to simultaneously release of growth factors from platelet alpha granules and adhesive proteins. The aim of our work was to emphasize the spontaneous bone healing of the maxilla and mandible after the enucleation of large and medium-sized cysts in asymptomatic patients of different age. The outcome of three patients who underwent surgery for removal of radicular cysts is presented. Imagistic [cone-beam computed tomography (CBCT)] and histological examination was performed aiming to evaluate the quality of new bone at the site of the bone defect, after different time intervals. By using PRGF approach, the healing of mandibular bone occurred 18 months after cystectomy in a smoker patient, 54-year-old, while the healing of maxillary bone using autologous bone mixed with PRGF occurred after six months in a 63-year-old patient. In a young patient (14 years old), the regeneration period was six months, using PRGF and a fibrin cloth for filling the defect.
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Regeneração Óssea , Cistectomia , Adolescente , Pré-Escolar , Tomografia Computadorizada de Feixe Cônico , Humanos , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgia , Maxila , Pessoa de Meia-IdadeRESUMO
Nowadays, adipose tissue appears to be the most valuable source in regenerative cell therapy, due to the following characteristics: high accessibility, high expression in a large number of individuals, high self-renewal and ability to differentiate, and hematopoietic support to the implant area. Its therapeutic potential has been experimentally observed in a broad spectrum of diseases with high population impact: diabetes, myocardial infarction, Parkinson disease, bone fractures, facial reconstruction or loss of subcutaneous tissue due to congenital abnormalities (e.g., hemifacial microsomy), trauma, burns, and tumors. Over 130 clinical trials using adipose-derived stem cells (ASCs), majority phase I or phase II, have been registered with the National Institutes of Health (NIH), and in the short term no adverse reactions or significant risks were identified. Parallel with regulatory frameworks that control their safety and assess their efficacy, phase III trials are being developed. Although transplantation with adipose tissue is becoming more and more popular, there are still important drawbacks and technical challenges to be addressed, and clinical strategies to be developed. This review explores in a concise manner the present body of knowledge concerning ASCs and their implication in therapy.
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Tecido Adiposo/metabolismo , Células-Tronco/metabolismo , HumanosRESUMO
The current very high success rate of dental implants osseointegration has led to patients having increasingly high expectations in regards to aesthetic outcomes; therefore, effective management of soft tissues and healing of attached gingiva and papillae are essential in the effort to obtain satisfying aesthetic results for the patient. Obtaining papillae to address aesthetic requirements cannot be accomplished without bone reconstruction; an adequate volume of bone is essential in providing necessary long-term dimensional stability. The aim of this work was to highlight the advantages of autogenous bone grafting combined with plasma rich in growth factors (PRGF) in order to improve healing and reduce dehiscence risks. Two clinical cases were presented, both with important (horizontal and vertical) bone loss: in the first case, bone augmentation was performed at the same time as tooth extraction with no surgery needed for reconstruction of dental papillae, keratinized and attached mucosa; in the second case, vertical augmentation was performed by placing the bone graft in contact with an uninfected tooth. In both cases, aesthetic outcomes were as desired at the completion of treatment and also satisfactory at seven years follow-up.
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Transplante Ósseo/métodos , Implantação Dentária Endóssea/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Giant cell granulomas in the oral cavity are reactive hyperplastic lesions that arise either peripherally in the mucoperiosteum or centrally in the bone. The peripheral giant cell granuloma (PGCG) is a benign lesion induced by local chronic irritation. It may develop at any age, and tends to be more frequent in females. Central giant cell granuloma (CGCG) is a reactive lesion of unknown etiology. It commonly occurs in children and young adults. It is also predominant in females and frequently located in the anterior part of the mandible. Histologically, PGCG and CGCG have similar features. The lesions are non-encapsulated proliferations of oval and spindle-shaped mononuclear cells (MCs) and multiple multinucleated giant cells (MGCs) in a vascular supporting stromal tissue, associated with foci of hemorrhage. Despite the similar microscopic features, PGCG and CGCG have different clinical behavior. PGCG is usually reduced in size and asymptomatic. It grows locally, as an exophytic lesion on the alveolar mucosa, but may become slightly infiltrative in the underlying periosteum and bone. After complete excision and curettage, it has a low recurrence rate. Contrarily, CGCG has an aggressive behavior, with rapid growth and intense osteolytic activity causing perforation of the cortical plate, teeth malposition and pain. Moreover, it is characterized by a high recurrence rate. This review focuses on the origin and activating pathways of MCs and MGCs, discusses the mechanisms underlying their biological activity, tries to explain the variable clinical behavior and proposes therapeutic approaches for the granulomas associated with the jaw bones.
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Granuloma/diagnóstico , Granuloma/terapia , Boca/patologia , Células Gigantes/patologia , Granuloma/cirurgia , Humanos , Boca/cirurgia , Osteoclastos/patologia , Transdução de SinaisRESUMO
Vascular endothelial growth factor (VEGF) represents a growth factor with important pro-angiogenic activity, having a mitogenic and an anti-apoptotic effect on endothelial cells, increasing the vascular permeability, promoting cell migration, etc. Due to these effects, it actively contributes in regulating the normal and pathological angiogenic processes. In humans, the VEGF family is composed of several members: VEGF-A (which has different isoforms), VEGF-B, VEGF-C, VEGF-D, VEGF-E (viral VEGF), VEGF-F (snake venom VEGF), placenta growth factor (PlGF), and, recently, to this family has been added endocrine gland-derived vascular endothelial growth factor (EG-VEGF). VEGF binds to tyrosine kinase cell receptors (VEGFRs): VEGFR-1 [Fms-like tyrosine kinase 1 (Flt-1)], VEGFR-2 [kinase insert domain receptor (KDR) in human; fetal liver kinase 1 (Flk-1) in mouse] and VEGFR-3 [Fms-like tyrosine kinase 4 (Flt-4)]. While VEGFR-1 and VEGFR-2 are expressed predominantly on vascular endothelial cells, VEGFR-3 is expressed especially on lymphatic endothelial cells. VEGFR-2 has the strongest pro-angiogenic activity and a higher tyrosine kinase activity than VEGFR-1. Endothelial cells also express co-receptors, such as neuropilin-1 (NP-1) and neuropilin-2 (NP-2), which modulate tyrosine kinase receptor activity. Both VEGF and VEGFRs are expressed not only on endothelial cells, but also on non-endothelial cells. This article aims to highlight the most recent data referring to the VEGF family and its receptors, as well as its implications in the angiogenesis process. At present, blocking angiogenesis in cancer or in other pathological processes, using anti-VEGF and anti-VEGFRs therapies, is considered to be extremely important.
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Inibidores da Angiogênese/farmacologia , Neoplasias/irrigação sanguínea , Neoplasias/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Humanos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismoRESUMO
BACKGROUND AND AIM: Cigarette smoking has negative effects on general health, including oral health. The aim of our study was to assess the correlations between nicotine dependence, exhaled carbon monoxide levels and oral hygiene status. METHODS: Smoker and non-smoker participants were enrolled in this observational study. The Fagerström test was used to classify nicotine dependences: low (score: 0-3), medium (score: 4-6) or high (score: 7-10). The oral hygiene status was classified according to the oral hygiene indices of plaque, calculus and gingival inflammation. Lastly, the exhaled carbon monoxide levels were measured with a MicroSmokelyzer (Bedfont Scientific Ltd., Kent, United Kingdom). RESULTS: Sixty five participants (50 smokers in the study group and 15 non-smokers in the control group) were enrolled between 11th and 29th of January 2016. No statistical differences were observed between the study group and the control group in terms of age (mean age±SD 23.5±1.9 and 24.0±1.5, respectively) or gender (50% and 26.6%, respectively). A statistically significant difference was observed between the 2 groups in terms of plaque, (p=0.036), calculus (p=0.001) and gingival indices (p<0.001). A positive correlation was found between the exhaled levels of carbon monoxide and the general Fagerström score (r=0.97, p<0.001) or the Fagerström score in smokers (r=0.93, p<0.001); a negative correlation was observed between the exhaled carbon monoxide levels and the number of tooth brushings daily (r=-0.41, p=0.001). The plaque index was statistically significantly associated with the exhaled carbon monoxide levels (p=0.008), general Fagerström score (p=0.016) and number of tooth brushings daily (p<0.001). The calculus and gingival indices were statistically significantly associated with the exhaled carbon monoxide levels (p<0.001), general Fagerström score (p<0.001) and score in smoker participants (p=0.029 and p=0.001, respectively) as well as the number of tooth brushings daily (p<0.001). CONCLUSION: Our study found a significant association between the plaque, calculus and gingival indices and smoking. Moreover, nicotine dependence was significantly associated with the number of daily tooth brushings and the gingival index.
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A rare neuroendocrine tumor, the pheochromocytoma (PCC) raises problems due both the limited experience of the researchers in this field and its pathogenic mechanisms, still not fully elucidated. The malignant potential of this tumor cannot be predicted based on its macro- or microscopic aspects, but on the presence of metastases. The aims of this study were: (1) the reevaluation of data for a pertinent and complete tumor diagnostic and prognostic pattern; (2) the statistical correlation of all investigated parameters with the malignant form and the survival rate in order to obtain a possible predictor of malignancy; (3) the potential identification of initially diagnosed benign tumors that become malignant in time. The retrospective study was conducted on 17 patients diagnosed with pheochromocytoma. We investigated: the personal data, the associated neuroendocrine syndromes, the clinical, the laboratory, the macro- and microscopic data [location, size, Hematoxylin-Eosin (HE) pheochromocytoma of the adrenal gland scaled score (PASS score), and immunohistochemical aspects] and the survival rate (analyzed by Kaplan-Meier method and Log-Rank test). The influence of diagnostic parameters on malignancy was calculated taking into consideration the survival rate. By reevaluation of the 17 cases, we tried to emphasize the value of a complex diagnosis pattern for PCCs, based on the correlation between clinical data, laboratory findings and microscopic features. A significant statistical difference between benign and malignant forms was not registered, but there were parameters as age, association with neuroendocrine syndromes, PASS score and specifically Ki-67 mitotic index that had a powerful impact on the survival rate and could be consider as possible predictors of malignancy. The potential of PCC malignant transformation was revealed in our study, by two cases that have metastasized in time.
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Feocromocitoma/diagnóstico , Adulto , Idoso , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Sistemas Neurossecretores/patologia , Feocromocitoma/mortalidade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
In colon cancer, biological markers continue to have a limited prognostic value, the results being controversial. Studies of cell-cycle regulatory proteins and anti-apoptotic proteins aim to identify groups of patients that develop more aggressive tumors and might benefit from an individualized therapy management. The present study evaluates the prognostic role of the p53, Bax, Bcl-2 and cyclin E immunoexpression in colon cancer, using the tissue microarray (TMA) method. Tissue samples were obtained from 31 patients operated for colon cancer, embedded in TMA paraffin blocks and immunohistochemically stained for p53, Bax, Bcl-2 and cyclin E. We evaluated the relationship between the overexpression of these proteins and the clinico-pathological parameters, as well as the effect of these molecular markers on the survival rate. 65.22% of the patients were p53 positive, 39.13% Bcl-2 positive, 78.26% Bax positive and 34.78% cyclin E positive. Bcl-2(+) patients had significantly better differentiated tumors (p=0.043). Significantly poorly differentiated tumors were: Bax(+) patients (p=0.031), Bcl-2(-)÷p53(-) patients (p=0.042), Bcl-2(-)÷Bax(+) patients (p=0.029), and Bcl-2(-)÷p53(-)÷Bax(+) patients (p=0.016). The individual expression of the studied proteins did not influence the survival rate. A significantly lower survival rate was found in the following groups of patients: Bcl-2(-)÷p53(-) (40% vs. 83.3%, p=0.027), p53(-)÷Bax(+) (40% vs. 83.3%, p=0.027), Bcl-2(-)÷p53(-)÷Bax(+) (25% vs. 84.2%, p=0.003). The current study identified groups of patients with a significantly lower survival rate, which consequently are at an increased risk to develop tumors with a more aggressive biological behavior.
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Neoplasias do Colo/metabolismo , Ciclina E/metabolismo , Proteínas Oncogênicas/metabolismo , Análise Serial de Tecidos , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias do Colo/patologia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
Astrocytes represent a heterogeneous population of specialized glial cells responsible not only for accomplishing various important functions in the healthy nervous tissue, but also for reacting to all types of the central nervous system diseases and trauma. GFAP immunostaining is considered to be the most accurate of the routine techniques used for identifying astrocytes; however, silver impregnation techniques, which are inexpensive and approachable, might be a reliable alternative. The present research has brought into question and tried to assess the sensitivity and specificity of these classical methods for identifying and differentiating normal and reactive from tumoral astrocytes. Our study included 10 supratentorial gliomas specimens of various grade and two normal brain samples. We performed a histological study on consecutive seriated sections labeled using four methods: the immunostaining for GFAP (glial fibrillary acidic protein) and the three silver impregnation techniques: Ramón y Cajal, Bielschowsky-Cajal and Gömöri. For each tumoral case, two areas were examined: the tumoral parenchyma and the tumor borders (considered as reactive gliosis) and were both compared to healthy brain parenchyma; for each area, three microscopic fields were assessed and two parameters were recorded: a semi-quantitative score (the astrocytes' density) and a qualitative score (the color intensity). We used a complex statistical analysis in order to process the data and to compare the diagnostic value of silver impregnation techniques versus GFAP immunostaining (the reference method) in terms of tumoral grading and differentiating tumoral from normal and reactive astrocytes. Our results indicated that there data provided by both GFAP immunostaining and silver impregnation techniques were comparable.