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INTRODUCTION: Caffeine is a widely consumed substance with several effects on bone metabolism. This study aimed to investigate the effect of caffeine on the bone tissue of rats submitted to orthodontic movement. METHODS: Twenty-five male Wistar rats underwent orthodontic movement (21 days) of the first permanent maxillary molars on the left side. The experimental group (caffeine; n = 13) and control group (n = 12) received caffeine and water, respectively, by gavage. Microcomputed tomography was performed to analyze orthodontic movement. Histologic analysis of the inflammatory infiltrate and osteoclast count by tartrate-resistant acid phosphatase were conducted. Maxilla tissue was evaluated for receptor activator of nuclear factor Ò¡B (RANK), RANK ligand (RANKL), and osteoprotegerin by immunohistochemistry. RESULTS: Caffeine exhibited a lower bone volume/tissue volume ratio (78.09% ± 5.83%) than the control (86.84% ± 4.89%; P <0.05). Inflammatory infiltrate was increased in the caffeine group compared with the control group (P <0.05). A higher number of tartrate-resistant acid phosphatase-positive cells was observed in the caffeine (9.67 ± 1.73) than in the control group (2.66 ± 0.76; P <0.01). Immunoexpression of RANK and RANKL in the caffeine group was greater than the control (P <0.05). CONCLUSIONS: The use of caffeine thermogenic induces alveolar bone loss in rats submitted to orthodontic movement via activation of RANK, RANKL, and osteoprotegerin signaling pathways.
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Pérdida de Hueso Alveolar , Cafeína , Osteoprotegerina , Ligando RANK , Receptor Activador del Factor Nuclear kappa-B , Técnicas de Movimiento Dental , Animales , Masculino , Ratas , Pérdida de Hueso Alveolar/metabolismo , Pérdida de Hueso Alveolar/patología , Cafeína/farmacología , Maxilar/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Osteoprotegerina/metabolismo , Ligando RANK/metabolismo , Ratas Wistar , Receptor Activador del Factor Nuclear kappa-B/metabolismo , Transducción de Señal/efectos de los fármacos , Técnicas de Movimiento Dental/efectos adversos , Microtomografía por Rayos XRESUMEN
BACKGROUND: Several studies evidenced the presence of oral alterations in ICU patient. However, data about identification of their risk factors in ICU patients is scarce, especially due to the lack of longitudinal prospective studies. Here, we evaluate the risk factors for the development of oral alterations in a group of ICU patients through a prospective longitudinal cohort. METHODS: During May-December 2019, 43 ICU patients in a tertiary hospital in Brazil were evaluated. Medical record reviews and oral examinations of each patient were made by 3 dentists in five distinct moments. RESULTS: Among all patients, 53.5% (n = 23) were female, with a mean age of 59.8 years (±17.4). The incidence of oral alterations was 51.2% (35.6%-66.8%) and among these (n = 22), hyposalivation (n = 9; 40.9%), and lingual biofilm accumulation (n = 9; 40.9%) were the most common. The mean age of the group with oral alterations (66.9 years) was higher compared to the group without alterations (52.3 years). Furthermore, male patients (p = 0.02), older than 60 years (p = 0.004) and treated with mechanical ventilator (p = 0.03) had a higher risk of oral alterations. CONCLUSIONS: Systemic parameters, as age and mechanical ventilator, could influence the oral environment of ICU patients.
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Unidades de Cuidados Intensivos , Respiración Artificial , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Respiración Artificial/efectos adversos , Factores de RiesgoRESUMEN
BACKGROUND: Histopathologic grading has been routinely used as a complement for clinical staging in the prognostication of patients with oral tongue squamous cell carcinoma (OTSCC). However, this subject remains contentious because there is no universally accepted grading system. OBJECTIVES: This study compared the prognostic significance of four histopathologic grading systems in 80 cases of oral tongue squamous cell carcinoma (OTSCC). METHODS: Clinical and follow-up information of the patients were obtained from medical records. Histopathologic malignancy grading of the tumor invasive front, Histologic risk assessment (HRA), World Health Organization (WHO) grading system, and Budding and Depth of invasion (BD) model were evaluated in the surgical specimens. RESULTS: The HRA, histopathologic malignancy grading and WHO systems did not predict survival. Patients with larger tumor size [Hazard ratio (HR): 2.38; 95% confidence interval (CI): 1.07-5.27; P = 0.026] and patients with BD model high-grade tumors (HR: 2.99; 95% CI: 1.03-8.68; P = 0.034) were significantly associated with a poor 5-year overall survival rate. In the multivariate analysis, tumor size was identified as the only significant independent prognostic factor (HR: 2.23; 95% CI: 1.00-4.99; P = 0.050). None of the grading systems studied was associated with 5-year disease-free survival rates. CONCLUSIONS: BD model was the only histopathologic grading system associated with the outcome of patients with OTSCC, indicating its potential value as an effective tool for the prognostication of OTSCC.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Lengua , Carcinoma de Células Escamosas/patología , Humanos , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello , Neoplasias de la Lengua/patologíaRESUMEN
The enzyme aldehyde dehydrogenase-1 (ALDH-1) is a known putative tumour stem cells (TSC) marker, and these cells are implicated in carcinogenesis and progression of human neoplasms. We aimed to evaluate ALDH-1 expression in benign and malignant salivary gland neoplasms and its clinicopathological and prognostic significance. Expression of ALDH-1 was investigated by immunohistochemistry and confirmed by Western Blot analysis in 154 salivary gland neoplasms (103 malignant and 51 benign neoplasms). The expression was identified in the parenchyma of malignant (n = 88; 85.6%) and benign (100%) neoplasms. Overall, expression in the parenchyma varied considerably and was not associated with clinical parameters in most malignant neoplasms, however, a high expression in mucoepidermoid carcinomas (MEC) was associated with advanced pathological TNM stage (p = 0.047). The presence of ALDH-1 in stromal cells of malignant neoplasms (n = 67; 65.0%) was associated with lymph node metastasis (p = 0.032), tumour recurrence (p = 0.006) and death (p = 0.013). Overall and disease-free survival in 5 and 10 years was lower in patients with diagnosis of adenoid cystic carcinoma, tumour recurrence, advanced staging, and presence of ALDH-1 in the stroma. When adjusted by multivariate analysis, advanced staging and stromal expression were independent prognostic factors affecting disease-free survival. Our findings provide evidence that cells characterized as TSC in the parenchyma and stroma are differentially present among the different types of neoplasms studied and may be related to tumourigenesis, biological behaviour and persistence capacity of malignant tumours of the salivary gland.
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Familia de Aldehído Deshidrogenasa 1/genética , Recurrencia Local de Neoplasia/genética , Neoplasias/genética , Neoplasias de las Glándulas Salivales/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias/patología , Pronóstico , Neoplasias de las Glándulas Salivales/patología , Glándulas Salivales/patología , Adulto JovenRESUMEN
BACKGROUND: This study analyzed the immunoexpression of calcitonin receptor (CTR) and glucocorticoid receptor (GR) in central giant cell lesions (CGCLs) and verified potential associations with patient's response to clinical treatment with intralesional injection of triamcinolone. MATERIALS AND METHODS: Fifty-four cases of CGCLs, including 22 non-aggressive, and 32 aggressive, were investigated by immunohistochemistry. RESULTS: Surgery was the therapeutic choice for 53.1% of the aggressive CGCLs, and 46.9% were submitted to the conservative treatment with intralesional triamcinolone injections. Among patients submitted to conservative treatment, 60% (n = 9) showed favorable response. CTR expression was observed in 68.51%, and GR in 94.44% of the total sample. There were no differences in the expression of CTR, neither GR in mononucleated stromal cells (MSCs) or multinucleated giant cells (MGCs), in relation to aggressiveness, treatment performed for and the response to conservative treatment. Both markers showed a positive correlation between their expression in MSCs and MGCs in the total sample (P < 0.0001). CTR expression on MSCs showed a positive correlation with MGCs in the aggressive and non-aggressive groups (P < 0.0001). CONCLUSIONS: Calcitonin receptor and GR expression were diffuse and similar in non-aggressive and aggressive cases, and it did not influence the response to clinical treatment with triamcinolone in the sample studied.
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Células Gigantes/metabolismo , Granuloma de Células Gigantes/tratamiento farmacológico , Granuloma de Células Gigantes/metabolismo , Inmunohistoquímica , Enfermedades Maxilomandibulares/tratamiento farmacológico , Enfermedades Maxilomandibulares/metabolismo , Receptores de Calcitonina/metabolismo , Receptores de Glucocorticoides/metabolismo , Triamcinolona , Adolescente , Adulto , Niño , Femenino , Expresión Génica , Humanos , Inyecciones Intralesiones , Masculino , Persona de Mediana Edad , Receptores de Calcitonina/genética , Receptores de Glucocorticoides/genética , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Pleomorphic adenoma (PA) is the most frequent benign epithelial lesion of salivary gland origin, showing great histopathological diversity. The aim of this study was to perform a retrospective analysis, with emphasis on histopathologic features of PA of salivary glands. Clinical and histopathologic characteristics of 130 cases of minor and major salivary glands PAs from three Brazilian reference centers were studied. Higher frequency of PAs was observed in female (55.4 %) subjects, with mean age of 49.7 years. The most common affected site was palate (64.5 %) for the PAs of minor salivary glands and parotid for cases affecting major glands (86.2 %). Microscopically, most cases were classified as classic PAs (50 %). Incomplete capsule was observed in 36.2 % of the cases, while 47.2 % showed capsular infiltration. Rounded (66.9 %), angular (49.2 %), oval (46.2 %) and plasmacytoid (39.2 %) cells were widely observed, as well as fibrous (73.8 %) and myxoid (69.2 %) stroma, squamous metaplasia (25.4 %) and cystic degeneration (43.1 %). Crystalloids (3.1 %), increased mitotic activity (5.4 %) and vascular invasion (2.3 %) were rarely observed. PAs arising in minor salivary glands were associated with incomplete capsules, spindle, oval, angular, plasmacytoid and pleomorphic cells, fibrous and hyaline stroma, cystic degeneration, squamous metaplasia and pleomorphism (p < 0.05). No association between capsular features and histological subtype was noted (p ≥ 0.05). These results confirm the findings of previous studies regarding major clinicopathological features of pleomorphic adenomas; and highlighted some important morphologic characteristics like the capsule, vascular invasion, pleomorphism and increased mitotic activity, which can reflect the biological behavior of these tumors.
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Adenoma Pleomórfico/patología , Neoplasias de las Glándulas Salivales/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Metaplasia , Persona de Mediana Edad , Neoplasias de la Parótida/patología , Estudios Retrospectivos , Glándulas Salivales Menores/patología , Adulto JovenRESUMEN
This study aimed to evaluate and compare the immunoexpression of glucose transporter-1 (GLUT-1) and angiogenic index between pleomorphic adenomas (PAs), adenoid cystic carcinomas (ACCs), and mucoepidermoid carcinomas (MECs) of the salivary glands, and establish associations with the respective subtype/histological grade. Twenty PAs, 20 ACCs, and 10 MECs were submitted to morphological and immunohistochemical analysis. GLUT-1 expression was semi-quantitatively evaluated and angiogenic index was assessed by microvessel counts using anti-CD34 antibody. Higher GLUT-1 immunoexpression was observed in the MECs compared to PAs and ACCs (p = 0.022). Mean number of microvessels was 66.5 in MECs, 40.4 in PAs, and 21.2 in ACCs (p < 0.001). GLUT-1 expression and angiogenic index showed no significant correlation in the tumors studied. Results suggest that differences in biological behavior of the studied tumors are related to GLUT-1. Benign and malignant salivary gland tumors differ in the angiogenic index; however, angiogenesis may be independent of the tumor cell's metabolic demand.
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Adenoma Pleomórfico/metabolismo , Carcinoma Adenoide Quístico/metabolismo , Carcinoma Mucoepidermoide/metabolismo , Transportador 2 de Aminoácidos Excitadores/metabolismo , Neovascularización Patológica , Neoplasias de las Glándulas Salivales/metabolismo , Adenoma Pleomórfico/irrigación sanguínea , Adenoma Pleomórfico/patología , Biomarcadores de Tumor/metabolismo , Carcinoma Adenoide Quístico/irrigación sanguínea , Carcinoma Adenoide Quístico/patología , Carcinoma Mucoepidermoide/irrigación sanguínea , Carcinoma Mucoepidermoide/patología , Femenino , Humanos , Inmunohistoquímica , Masculino , Microvasos/patología , Persona de Mediana Edad , Clasificación del Tumor , Neoplasias de las Glándulas Salivales/irrigación sanguínea , Neoplasias de las Glándulas Salivales/patología , Glándulas Salivales/patologíaRESUMEN
BACKGROUND: Actinic cheilitis (AC) is a chronic inflammatory lesion that in some situations can turn into squamous cell carcinoma of the lip. The molecular mechanisms involved in this process are not yet completely understood. This study aimed to investigate the expression pattern of galectins in actinic cheilitis according to the histopathological grading. METHODS: Immunoexpression of galectin-1, galectin-3, galectin-7, and galectin-9 was semiquantitatively analyzed in 65 cases of actinic cheilitis graded as low risk (n = 40) or high risk (n = 25) of malignant transformation. Association between the location of the galectins in the cellular compartments and histopathological grading was analyzed. RESULTS: Galectin-1 was mainly observed in the cell cytoplasm, and was elevated (score 3) in 60% of cases, regardless of the histopathological grade (P > 0.05). Galectin-3 expression was higher in high-risk group than in the low-risk group (P < 0.05), with a predominant expression in the cytoplasm and nucleus of low-risk (67.5%), and only in the cytoplasm of high-risk cases (60%) (P < 0.05). Galectin-7 expression did not show significant differences between low-risk and high-risk groups (P > 0.05). With respect to galectin-9, 89.2% of cases were positive, showing decrease in median of scores as there was an increase in histological grade (P < 0.001), with predominant expression in the nucleus and cytoplasm. CONCLUSIONS: This study is the first indication of galectins involvement in the pathogenesis and morphologic progression of actinic cheilitis, particularly galectin-3 and galectin-9.
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Transformación Celular Neoplásica/metabolismo , Queilitis/metabolismo , Galectinas/biosíntesis , Neoplasias de los Labios/metabolismo , Adulto , Anciano , Carcinoma de Células Escamosas/patología , Membrana Celular/metabolismo , Membrana Celular/patología , Núcleo Celular/metabolismo , Núcleo Celular/patología , Transformación Celular Neoplásica/patología , Queilitis/patología , Citoplasma/metabolismo , Citoplasma/patología , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Inmunohistoquímica , Neoplasias de los Labios/patología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
AIM: This manuscript aims to describe an unusual case of multiple second primary squamous cell carcinomas (SCCs) in several sites of the oral mucosa in a nonsmoker and nondrinker woman and to discuss the diagnostic criteria, clinicopathological aspects and outcome of second primary tumor (SPT). BACKGROUND: Patients treated for SCC of the head and neck are at high risk for developing SPT arising from the same dysplastic mucosal feld. Currently, there is no reliable method to predict which of the patients will develop SPT. CASE DESCRIPTION: A 64-year-old nonsmoker and nondrinker woman developed several second primary oral SCCs in 7 years of follow-up, most of them being synchronic, treated by surgery without and with chemotherapy and radiotherapy. CONCLUSION: Patients treated for SCC require a long-term and careful follow-up as the development of SPT contributes with significantly negative impact on the prognosis. CLINICAL SIGNIFICANCE: This report describes the diagnosis and management of a very unusual case of several SPTs affecting different sites of the oral mucosa in the same patient. Moreover, the patient had no apparent risk factors associated with the development of the oral cancer. Therefore, a brief update concerning SPT and its diagnosis and management is also provided.
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Carcinoma de Células Escamosas/diagnóstico , Neoplasias de la Boca/diagnóstico , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias de la Mama/patología , Carcinoma de Células Escamosas/secundario , Carcinoma de Células Escamosas/terapia , Quimioterapia Adyuvante , Femenino , Estudios de Seguimiento , Neoplasias Gingivales/diagnóstico , Humanos , Leucoplasia Bucal/diagnóstico , Metástasis Linfática/patología , Persona de Mediana Edad , Neoplasias de la Boca/terapia , Terapia Neoadyuvante , Neoplasias Primarias Secundarias/terapia , Neoplasias Palatinas/diagnóstico , Radioterapia AdyuvanteRESUMEN
OBJECTIVE: To evaluate the levels of oxidative stress markers in the saliva of patients with oral lichen planus (OLP). METHODS: A cross-sectional study was conducted with 22 patients diagnosed both clinically and histologically with OLP (reticular or erosive) and 12 individuals without OLP. Non-stimulated sialometry was performed and oxidative stress (myeloperoxidase - MPO and malondialdehyde - MDA) and antioxidant (superoxide dismutase - SOD and glutathione - GSH) markers were determined in the saliva. RESULTS: Among the patients with OLP, most were women (n = 19; 86.4%) and reported to have experienced menopause (63.2%). Patients with OLP were mostly in the active stage of the disease (n = 17; 77.3%) and the reticular form was predominant (n = 15; 68.2%). No statistically significant differences were observed when comparing SOD, GSH, MPO and MDA values between individuals with and without OLP, as well as between erosive and reticular forms of OLP (p > 0.05). Patients with inactive OLP presented higher SOD when compared to those with active disease (p = 0.031). CONCLUSION: Oxidative stress markers in the saliva of patients with OLP were similar to those found in people without OLP, which can be related to the high exposure of the oral cavity environment to several physical, chemical and microbiological stimuli, important generators of the oxidative stress.
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Liquen Plano Oral , Saliva , Humanos , Femenino , Masculino , Liquen Plano Oral/patología , Estudios Transversales , Biomarcadores/metabolismo , Estudios de Casos y Controles , Estrés Oxidativo , Glutatión , Superóxido DismutasaRESUMEN
PURPOSE: To evaluate the effects of the experimental subcutaneous Walker-256 tumor and L-glutamine supplementation, an antioxidant, on the glomerular morphology of rats. METHODS: Twenty Wistar rats were distributed into four groups (n = 5): control (C); control treated with 2% L-glutamine (CG); rats with Walker-256 tumor (WT); and rats with Walker-256 tumor treated with 2% L-glutamine (WTG). Renal histological samples were submitted to periodic acid-Schiff and Masson's Trichrome staining to analyze glomerular density, morphometry of glomerular components and glomerulosclerosis; and to immunohistochemistry for fibroblast growth factor-2 (FGF-2). RESULTS: WT showed 50% reduction in body mass gain and cachexia index > 10%, while WTG demonstrated reduction in cachexia (p < 0.05). WT revealed reduction of glomerular density, increase in the glomerular tuft area, mesangial area, matrix in the glomerular tuft, decrease in the urinary space and synechia, and consequently higher glomerulosclerosis (p < 0.05). L-glutamine supplementation in the WTG improved glomerular density, and reduced glomerular tuft area, urinary space, mesangial area, and glomerulosclerosis compared to WT(p < 0.05). WT showed higher collagen area and FGF-2 expression compared to C (p < 0.05). WTG presented lower collagen fibers and FGF-2 expression compared to WT (p < 0.05). CONCLUSIONS: L-glutamine supplementation reduced cachexia and was beneficial for glomerular morphology of the rats, as well as it reduced kidney damage and improved the remaining glomeruli morphology.
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Glutamina , Neoplasias , Ratas , Animales , Ratas Wistar , Glutamina/farmacología , Caquexia/metabolismo , Caquexia/patología , Factor 2 de Crecimiento de Fibroblastos , Suplementos Dietéticos , ColágenoRESUMEN
OBJECTIVE: To analyze the immunohistochemical expression of the base excision repair (BER) proteins apurinic/apyrimidinic endonuclease 1 (APE1) and X-ray repair cross-complementing protein 1 (XRCC1) and nucleotide excision repair (NER) protein xeroderma pigmentosum group F (XPF) in malignant salivary gland tumors (MSGTs). DESIGN: Sixty-two cases of MSGTs were selected, including 14 acinic cell carcinomas (AcCC), 15 polymorphous adenocarcinomas (PAC), 16 adenoid cystic carcinomas (ACC), and 17 mucoepidermoid carcinomas (MEC). The specimens were submitted to quantitative immunohistochemical analysis. RESULTS: All MSGTs exhibited nuclear or nucleo-cytoplasmic immunostaining of APE1, XRCC1 and XPF, with a high percentage of positive cells (median = 78.31, 70.48 and 75.46, respectively). XRCC1 expression was higher in PAC compared to MEC (p = 0.032). Nuclear APE1 immunostaining was significantly higher than nucleo-cytoplasmic expression in the selected MSGTs (p < 0.0001). APE1 expression was significantly associated with T1-T2 tumors in ACC (p = 0.006). Increased expression of XPF was associated with age older than 60 years in MEC (p = 0.015) and with ACC involving the minor salivary gland (p = 0.012), while a lower expression was found in AcCC and ACC patients treated by surgery combined with adjuvant therapy (p = 0.036 and p = 0.020, respectively). Low expression of XRCC1 in the nucleus (p = 0.028) and concomitant expression of this protein in the nucleus/cytoplasm were associated with a lower overall 5-year survival rate (p = 0.017). CONCLUSIONS: This study showed that BER and NER proteins evaluated are highly expressed in the MSGTs studied, indicating mechanisms of genotoxic control in these tumors. In addition, the dysregulation of XRCC1 expression was a prognostic predictor in MSGTs analyzed.
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Reparación del ADN , Proteínas de Unión al ADN/genética , Neoplasias de las Glándulas Salivales , Adenocarcinoma , Carcinoma de Células Acinares , Carcinoma Adenoide Quístico , Carcinoma Mucoepidermoide , ADN-(Sitio Apurínico o Apirimidínico) Liasa , Humanos , Neoplasias de las Glándulas Salivales/genética , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos XRESUMEN
OBJECTIVES: To analyze the expression profile of DNA repair proteins (XRCC1 and APE1) and histone acetylation (H3K9) in oral and cutaneous lichen planus, in order to investigate potential biological markers that can clarify pathogenesis of these lesions. DESIGN AND RESULTS: The total sample consisted of 89 lichen planus cases (66 oral and 23 cutaneous). Analysis of APE1 and XRCC1 expression was performed by immunohistochemistry in 44 oral and 20 cutaneous lichen planus, whereas the analysis of H3K9 acetylation was performed by immunofluorescence in 42 oral and 11 cutaneous lichen planus. RESULTS: Immunoreactivity for APE1 and XRCC1 was significantly higher in cutaneous lichen planus than in oral lichen planus (P = 0.003 and P = 0.034, respectively). There was a significant and moderate positive correlation between APE1 and XRCC1 in the oral group (Rho = 0.544; P < 0.0001). In oral cases, there were no statistically significant results comparing APE1 and XRCC1 expression between reticular and erosive cases (P > 0.05). Evaluation of H9K3 histone acetylation levels did not reveal significant results comparing oral to cutaneous lichen planus, neither comparing erosive to reticular (P > 0.05). CONCLUSIONS: Changes in the expression profile of the DNA repair proteins exerted greater influence in pathogenesis of cutaneous lichen planus than oral lichen planus, in addition, H3K9 histone acetylation is an epigenetic event found in both lesions.
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Reparación del ADN , Histonas/genética , Liquen Plano Oral/genética , Transcriptoma , Acetilación , ADN-(Sitio Apurínico o Apirimidínico) Liasa/genética , Epigenómica , Humanos , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos X/genéticaRESUMEN
OBJECTIVES: Programmed death ligand-1 (PD-L1) and human leukocyte antigen-G (HLA-G) are considered immune checkpoint molecules that inhibit T-cell effectiveness, contributing to tumor immune escape. This study investigated PD-L1, HLA-G, CD8, and granzyme B (GrB) expression at different stages of lip carcinogenesis. DESIGN AND RESULTS: Forty cases of lip squamous cell carcinoma (LSCC), 55 actinic cheilitis (AC), and 10 healthy lip mucosa (HLM) were submitted to immunohistochemistry. Semiquantitative (PD-L1, HLA-G), and quantitative (CD8, GrB) analysis were performed. PD-L1 and HLA-G expression in neoplastic cells/keratinocytes and stroma/connective tissue was significantly higher in LSCC and AC, compared to HLM (p<0.05). PD-L1 was not associated with clinicopathological features of the lesions. HLA-G expression by malignant cells was significantly higher in LSCCs with distant metastasis (p = 0.041).CD8+ and GrB+ cell numbers progressively increased from HLMs to LSCC, with AC exhibiting intermediate numbers (p<0.01). Most LSCCs showed coexistence of PD-L1+ and CD8+ cells (72.5%). PD-L1 was directly correlated to CD8+ and GrB+ lymphocytic infiltration in LSCCs (p<0.05). Low cytotoxic immune response was associated with lymph node metastasis in LSCC (p<0.05). CONCLUSIONS: PD-L1 and HLA-G-mediated immune evasion mechanisms are likely to occur from early pre-malignant to advanced malignant stages of lip carcinogenesis, which might provide a rationale for therapeutic blockade of these pathways. PD-L1 expression in LSCCs was correlated with the cytotoxic markers, suggesting that PD-L1 may appear as an escape mechanism in response to an active antitumor response.
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Carcinogénesis/inmunología , Neoplasias de los Labios/inmunología , Linfocitos T CD8-positivos/inmunología , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/patología , Queilitis/inmunología , Queilitis/patología , Estudios Transversales , Femenino , Granzimas/inmunología , Antígenos HLA-G/inmunología , Humanos , Evasión Inmune , Inmunohistoquímica , Queratinocitos/inmunología , Queratinocitos/patología , Neoplasias de los Labios/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Mucosa Bucal/inmunología , Mucosa Bucal/patología , Receptor de Muerte Celular Programada 1/inmunología , Estudios Retrospectivos , Células del Estroma/inmunología , Células del Estroma/patología , Microambiente Tumoral/inmunologíaRESUMEN
BACKGROUND: Libidibia ferrea (L. ferrea) is found throughout the northeastern region of Brazil, where it has been used in folk medicine with beneficial effects on many inflammatory disorders. PURPOSE: This study investigated the phytochemical composition of the crude extract and fractions of L. ferrea fruit and evaluated its anti-inflammatory and antinociceptive activities in vivo and effect on cell viability in vitro. METHODS: Characterization of polyphenols present in crude extract (CE), hydroalcoholic fractions of 20-80% ethanol (CE20, CE40, CE60, and CE80), aqueous fraction (AqF), and ethyl acetate (EAF) fractions of L. ferrea fruit was performed by chromatographic analysis. Anti-inflammatory activity was evaluated by using a carrageenan-induced peritonitis model submitted to a leukocyte migration assay and myeloperoxidase activity (MPO) analysis. Total glutathione and malondialdehyde (MDA) levels were assessed to evaluate the oxidative stress level. Antinociceptive activity was evaluated by acetic acid-induced abdominal writhing and hot plate test. In vitro cell viability was determined by using MTT assay in a mouse embryonic fibroblast cell line (3T3 cells). RESULTS: Chromatography revealed the presence of ellagic acid content in EAF (3.06), CE (2.96), and CE40 (2.89). Gallic acid was found in EAF (12.03), CE 20 (4.43), and CE (3.99). L. ferrea crude extract and all fractions significantly reduced leukocyte migration and MPO activity (p<0.001). L. ferrea antioxidant effect was observed through high levels of total glutathione and reduction of MDA levels (p<0.001). Acetic acid-induced nociception was significantly inhibited after administration of L. ferrea crude extract and all fractions (p<0.001). Crude extract and all fractions significantly increased the viability of the 3T3 cell line (p<0.05). CONCLUSIONS: The appropriate extraction procedure preserves the chemical components of L. ferrea fruit, such as gallic acid and ellargic acid. Crude extract and fractions of L. ferrea fruit exhibited anti-inflammatory, antioxidant, antinociceptive activities in vivo and enhanced cell viability in vitro.
RESUMEN
Purpose: To evaluate the effects of the experimental subcutaneous Walker-256 tumor and L-glutamine supplementation, an antioxidant, on the glomerular morphology of rats. Methods: Twenty Wistar rats were distributed into four groups (n = 5): control (C); control treated with 2% L-glutamine (CG); rats with Walker-256 tumor (WT); and rats with Walker-256 tumor treated with 2% L-glutamine (WTG). Renal histological samples were submitted to periodic acid-Schiff and Masson's Trichrome staining to analyze glomerular density, morphometry of glomerular components and glomerulosclerosis; and to immunohistochemistry for fibroblast growth factor-2 (FGF-2). Results: WT showed 50% reduction in body mass gain and cachexia index > 10%, while WTG demonstrated reduction in cachexia (p < 0.05). WT revealed reduction of glomerular density, increase in the glomerular tuft area, mesangial area, matrix in the glomerular tuft, decrease in the urinary space and synechia, and consequently higher glomerulosclerosis (p < 0.05). L-glutamine supplementation in the WTG improved glomerular density, and reduced glomerular tuft area, urinary space, mesangial area, and glomerulosclerosis compared to WT(p < 0.05). WT showed higher collagen area and FGF-2 expression compared to C (p < 0.05). WTG presented lower collagen fibers and FGF-2 expression compared to WT (p < 0.05). Conclusions: L-glutamine supplementation reduced cachexia and was beneficial for glomerular morphology of the rats, as well as it reduced kidney damage and improved the remaining glomeruli morphology.
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Animales , Ratas , Carcinoma 256 de Walker , Ratas Wistar , Glutamina , Glomérulos Renales , AntioxidantesRESUMEN
Subgemmal neurogenous plaque (SNP) is a biphasic neural structure associated with the taste buds. Clinically, SNP usually presents as an asymptomatic, normally colored, papule located in the posterior lateral border of the tongue. Accurate diagnosis is based only on histopathological examination, which shows a superficial neurofibroma-like pattern and a neuroma-like in the deep zone. Appropriate recognition of clinical and morphological aspects of SNPs can avoid their misdiagnosis as neural neoplasms. We report three cases of SNP with detailed clinical, histopathological, and immunohistochemical features.
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Red Nerviosa/patología , Papilas Gustativas/patología , Lengua/inervación , Adulto , Anciano , Biopsia , Diagnóstico Diferencial , Células Epiteliales/patología , Femenino , Humanos , Queratinas/análisis , Tejido Linfoide/patología , Masculino , Mucosa Bucal/patología , Proteínas S100/análisisRESUMEN
Background: Actinic cheilitis is a potentially malignant lesion most commonly found in the lower lip of individuals with chronic exposure to ultraviolet radiation. The aim of this study was to develop and to test a clinical indexthat can be used to assess the severity of actinic cheilitis.Material and Methods: The clinical index of actinic cheilitis was applied to 36 patients. An incisional biopsy wasobtained to grade oral epithelial dysplasias following the World Health Organization (WHO) and binary systems,and to evaluate their association with clinical characteristics by Fishers exact test (P<0.05). The accuracy of theindex was evaluated based on sensitivity, specificity, positive and negative predictive values, and receiver operating curve.Results: The blurring between the border of the lip and the skin was significantly associated with cases withoutdysplasia/mild epithelial dysplasia (P=0.041) and with low risk of malignancy (P=0.005). Ulcers and crusts weresignificantly associated with moderate/severe epithelial dysplasia (P=0.002 and P=0.012, respectively) and highrisk of malignancy (P=0.005 and P=0.045, respectively). Erosion showed a significant association only with highrisk cases of malignancy (P=0.024). The cut-off values of the diagnostic test showing the best performance were10 for the WHO grading system and 11 for the binary system.Conclusions: The index cut-offs with the highest accuracy were considered indicators for a biopsy. Erosion, ulceration and crusts were associated with more severe oral epithelial dysplasias. (AU)
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Humanos , Queilitis/diagnóstico , Queilitis/etiología , Queilitis/patología , Hiperplasia/patología , Labio/patología , Neoplasias de los Labios/diagnóstico , Rayos UltravioletaRESUMEN
Introdução:Pacientes com depressão maior geralmente respondem ao tratamento com medicamentos antidepressivos, no entanto em 10% a 30% dos casos há apenas uma resposta parcial ou nenhuma resposta, entre os fatores que podem influenciar encontra-se o perfil das enzimas hepáticas metabolizadoras dos antidepressivos, tal como a CYP2C19.Objetivo:Caracterizar os indivíduos quanto ao perfil genético dospolimorfismos CYP2C19*2 ou CYP2C19*17 em pacientes com transtorno depressivo maior (TDM) tratados com citalopram ou escitalopram e compará-los em relação a adesão ao tratamento, sintomas de depressão e qualidade de vida.Metodologia:Trata-se de um estudo transversal realizado com 29 pacientes com TDM. Amostras de sangue foram coletadas para genotipagem de CYP2C19 por discriminação alélica TaqMan®. Após caracterização do perfil genético, os indivíduos foram comparados quanto aos dados demográfico e socioeconômico, adesão ao tratamento (TestedeMorisky-Green),sintomas de depressão (escala de Hamilton) e qualidade de vida (WHOQoL-BREF).Resultados:Quatro pacientes (13.8%) apresentaram polimorfismo para CYP2C19*2 e 10 pacientes (34.4%) para CYP2C19*17, com maior prevalência de CYP2C19*17 (p>0.05). Nenhuma associação significativa de características socioeconômicas, demográficas e clínicas entre os genótipos do CYP2C19.No TestedeMorisky-Green, aadesão moderada ao tratamento foi predominante nos pacientes CYP2C19*2 e CYP2C19*17 (p>0.05). Não foi observada associação entre sintomas de depressão e polimorfismos genéticos (p>0.05). Uma associação significativa entre o genótipo polimórfico CC do CYP2C19*17 com a satisfação com a saúde, enquanto o genótipo CT foi associado ao estado "nem satisfeito/nem insatisfeito" (p<0.05). A maioria dos indivíduos CYP2C19*2 e CYP2C19*17 relatou "necessidade de melhorar" em relação aos domínios de qualidade de vida físico, psicológico, social e ambiental (p>0.05).Conclusões:Os pacientes apresentaram maior prevalência do polimorfismo CYP2C19*17, com moderada adesão ao tratamento. Alguns pacientes, mesmo sob efeito da medicação, apresentaram sintomas de depressão moderado a intenso e relataram uma indefinição na satisfação da sua qualidade de vida (AU).
Introduction:Patients with major depression usually respond to treatment with antidepressant drugs, however in 10% to 30% of cases there is only a partial response or no response, among the factors that can influence is the profile of liver enzymes metabolizing antidepressants, such as CYP2C19.Objective:To characterize the individuals regarding the genetic profile ofCYP2C19*2or CYP2C19*17 polymorphisms in patients with major depressive disorder (MDD) treated with citalopram or escitalopram, and to compare themaccording to treatment adherence, symptoms of depression and quality of life.Methodology:This is cross-sectionalstudy carried out with 29 patients with MDD. Blood samples were collected for CYP2C19 genotyping by TaqMan® allelic discrimination. After characterization of the genetic profile, the individuals were compared regarding the demographic and socioeconomic data, treatment adherence (Morisky-GreenTest), symptoms of depression (Hamilton scale) and quality of life (WHOQoL-BREF).Results:Four patients showed (13.8%) CYP219*2 and 10 patients (34.4%) CYP219*17 polymorphisms.,withhigher prevalence of CYP219*17 (p>0.05). No association between socioeconomic, demographic, and clinical features with CYP2C19 genotypes was observed. In Morisky-GreenTest, moderate adherence to treatment was predominant for CYP2C19*2 and CYP219*17 patients (p>0.05). No statistically significant association was observed between symptoms of depression and genetic polymorphisms (p>0.05). A significant association between polymorphic CC genotype of CYP219*17 with health satisfaction, while the CT genotype was associated with "neither satisfied/nor dissatisfied" status (p<0.05). Most of the CYP2C19*2 and CYP2C19*17 subjects reported "need to improve" or "regular" regarding physical, psychological, social, and environmental domainsof quality of life(p>0.05).Conclusions:The patients showed a higher prevalence of CYP219*17 polymorphism, with moderate treatment adherence. Some subjects, even under the effect of the medication, presented moderate to intense symptoms of depression, and reported a lack of definition in the satisfaction of their quality of life (AU).
Introducción:Los pacientes con depresión mayor responder al tratamiento con antidepresivos, en 10% al 30% de los casos existe una respuesta parcial o nula, entre los factores que pueden influir se encuentra el perfil de enzimas hepáticas metabolizadoras de antidepresivos, como CYP2C19.Objetivo: Caracterizar a los individuos en cuanto al perfil genético depolimorfismos CYP2C19 *2 o CYP2C19 * 17 en pacientes con trastorno depresivo mayor (TDM) tratados con citalopram o escitalopram y compararlos en relaciónpara la adherencia al tratamiento, síntomas de depresión y la calidad de vida.Metodología: Estudio transversalcon 29 pacientes con TDM. Se recogieron muestras de sangre para la determinación del genotipo CYP2C19 mediante discriminación alélica TaqMan®, los individuos fueron comparados en cuanto a los datosdemográficosy socioeconómicos, adherencia (Prueba de Morisky-Green), síntomas de depresión (escala de Hamilton) y calidad de vida (WHOQoL-BREF).Resultados: Cuatro pacientes (13,8%) con polimorfismo CYP2C19*2 y 10 (34,4%) con CYP2C19 * 17,(p> 0,05). No existe una asociación significativa de las características socioeconómicas, demográficas y clínicas con los genotipos CYP2C19. La adherencia moderada al tratamiento fue predominante en los pacientes con CYP2C19*2 y CYP2C19*17 (p> 0,05). No hubo asociación entre síntomas de depresión y polimorfismos genéticos (p> 0.05). Una asociación significativa entre el genotipo polimórfico CYP2C19 * 17 CC con la satisfacción con la salud, mientras que el genotipo CT se asoció con el estado "ni satisfecho / no insatisfecho" (p <0.05). La mayoría de CYP2C19 * 2 y CYP2C19 * 17 individuos informaron "necesidad de mejorar" en relación con los dominios físico, psicológico, social y ambientalde calidad de vida(p> 0,05).Conclusiones: Los pacients mostraron una mayor prevalencia del CYP2C19 * 17, con adherencia moderada al tratamiento, síntomas de depresión moderada a intensay informaron una falta de definición en la satisfacción de su calidad de vida (AU).
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Humanos , Citalopram/farmacología , Depresión/tratamiento farmacológico , Trastorno Depresivo Mayor/tratamiento farmacológico , Citocromo P-450 CYP2C19/farmacología , Antidepresivos/farmacología , Calidad de Vida , Brasil , Estudios Transversales/métodos , QuimioterapiaRESUMEN
Abstract Curcumin, contained at Turmeric (Curcumalonga), can exert many beneficial pleiotropic activities in the gastrointestinal tract. This study evaluated the antioxidant and anti-inflammatory activity of C. longa on 5-fluorouracil (5-FU)-induced oral mucositis (OM) in hamsters. Phytochemical analysis of crude C. longa extract (CLE) was performed to detect the presence of curcumin by TLC and HPLC. Golden Syrian hamsters were orally pre-treated with CLE (5, 50, or 100mg/kg). Cheek pouch samples were subjected to macroscopic and histopathological evaluation. ELISA was performed to quantify the inflammatory cytokines IL-1ß and TNF-α. Superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) levels were assessed by ultraviolet-visible spectroscopy analysis. Behavior analysis was conducted by the open field test. Curcumin content in the CLE was 0.55%m/m ± 0.0161 (2.84%). The group treated with 5mg/kg CLE showed healing evidence with macroscopic absence of ulceration (p<0.05) and microscopic aspect of re-epithelialization, discrete inflammatory infiltrate and absence of edema. Treatment with 5mg/kg CLE significantly increased GSH levels, and reduced MDA levels and SOD activity (pË0.05), and decreased IL-1ß (pË0.05) and TNF-α (pË0.01) levels. A significant reduction in walking distance, ambulation, speed, and rearing was observed for motor activity. Curcumin reduced oxidative stress, inflammation, and motor activity in hamsters with 5-FU-induced OM.