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1.
Plast Reconstr Surg Glob Open ; 7(2): e2030, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30881820

RESUMO

BACKGROUND: There are studies demonstrating an increased expression of cyclooxygenase (COX) in keloids and hypertrophic scars, suggesting that anti-inflammatory drugs could be used in their treatment. However, a precise relationship between COX and pathological scarring has not been established in the literature yet. This study aims to evaluate the immunohistochemical expression of COXs in these scars. METHODS: Prospective study, including 54 patients (aged 18-60 years) undergoing scar excision: 18 normal scars (group 1), 18 hypertrophic scar (group 2), and 18 keloids (group 3). The group classification was performed by clinical criteria. Scars samples were collected and anatomopathological examination (through hematoxylin-eosin method) was performed to confirm the scar type. Immunohistochemistry was performed to assess the expression of COX1 and COX2 in epidermis and dermis. Results were compared among all groups and between group I versus II and III together (abnormal scars). RESULTS: For COX1, in the epidermis, there was no significant difference in the immunohistochemical expression when comparing the 3 groups. In the dermis, groups 2 and 3 had greater expression than group 1, with a significant difference being found when comparing all groups (P = 0.014), and in the comparison between normal versus abnormal scars (P = 0.004). For COX2, there was no significant difference between the groups in both the epidermis and dermis. CONCLUSIONS: The immunohistochemical expression of COX1 was greater in the dermis of abnormal scars when compared with normal scars. Future studies can be performed involving COX blockade as a perspective of these scars treatment.

2.
Ann Vasc Surg ; 52: 216-224, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29758327

RESUMO

BACKGROUND: Aortoiliac occlusive disease (AOD) and abdominal aortic aneurysm (AAA) are very important cardiovascular diseases that present different aspects of pathophysiology; however, oxidative stress and inflammatory response seem be relevant in both of them. Our objective was to evaluate oxidative damage and degree of inflammatory infiltrate in aortas of patients surgically treated for AOD and AAA. MATERIALS AND METHODS: Levels of reactive oxygen species (ROS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and myeloperoxidase (MPO) expression as well as nitrite levels and superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in aortas of patients with AOD (n = 16) or AAA (n = 14), while the control group was formed by cadaveric organ donors (n = 10). We also analyzed the degree of inflammatory infiltrate in these aortas. RESULTS: There was an increase in ROS levels and NADPH oxidase activity in patients with AOD and AAA when compared with the control group, and the AOD group demonstrated higher ROS production and NADPH oxidase activity and also nitrite levels when compared with the AAA group (P < 0.001). On the other hand, an increase of SOD activity in the AOD group and CAT activity in the AAA group was observed. Inflammatory infiltrate and MPO expression were higher in the AOD group when compared with the control group (P < 0.05). CONCLUSIONS: Oxidative stress is relevant in both AOD and AAA, though AOD presented higher ROS levels and NADPH activity. Increased activities of antioxidant enzymes may be a compensatory phenomenon which occurs in aortas of patients with AOD and AAA. Perhaps, a relationship between oxidative stress and degree of inflammatory infiltrate may exist in the pathophysiology of AOD and AAA.


Assuntos
Aorta Abdominal/enzimologia , Aneurisma da Aorta Abdominal/enzimologia , Arteriopatias Oclusivas/enzimologia , Estresse Oxidativo , Idoso , Antioxidantes/análise , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/diagnóstico , Arteriopatias Oclusivas/diagnóstico , Biomarcadores/análise , Estudos de Casos e Controles , Catalase/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , NADPH Oxidases/análise , Nitritos/análise , Peroxidase/análise , Estudos Prospectivos , Espécies Reativas de Oxigênio/análise , Superóxido Dismutase/análise
3.
J Cancer Res Clin Oncol ; 140(3): 461-70, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24449404

RESUMO

PURPOSE: The expression levels of human antioxidant genes (HAGs) and oxidative markers were investigated in light of lung adenocarcinoma aggressiveness and patient outcome. METHODS: We assayed in vitro the tumoral invasiveness and multidrug resistance in human lung adenocarcinoma (AdC) cell lines (EKVX and A549). Data were associated with several redox parameters and differential expression levels of HAG network. The clinicopathological significance of these findings was investigated using microarray analysis of tumor tissue and by immunohistochemistry in archival collection of biopsies. RESULTS: An overall increased activity (expression) of selected HAG components in the most aggressive cell line (EKVX cells) was observed by bootstrap and gene set enrichment analysis (GSEA). In vitro validation of oxidative markers revealed that EKVX cells had high levels of oxidative stress markers. In AdC cohorts, GSEA of microarray datasets showed significantly high levels of HAG components in lung AdC samples in comparison with normal tissue, in advanced stage compared with early stage and in patients with poor outcome. Cox multivariate regression analysis in a cohort of early pathologic (p)-stage of AdC cases showed that patients with moderate levels of 4-hydroxynonenal, a specific and stable end product of lipid peroxidation, had a significantly less survival rate (hazard ratio of 8.87) (P < 0.05). CONCLUSIONS: High levels of oxidative markers are related to tumor aggressiveness and can predict poor outcome of early-stage lung adenocarcinoma patients.


Assuntos
Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Aldeídos/metabolismo , Antioxidantes/metabolismo , Peroxidação de Lipídeos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma de Pulmão , Adulto , Idoso , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Estadiamento de Neoplasias , Razão de Chances , Oxirredução , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
4.
Mol Cell Endocrinol ; 375(1-2): 14-26, 2013 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-23693027

RESUMO

Congenital hypothyroidism is associated with delay in cell migration and proliferation in brain tissue, impairment of synapse formation, misregulation of neurotransmitters, hypomyelination and mental retardation. However, the mechanisms underlying the neuropsychological deficits observed in congenital hypothyroidism are not completely understood. In the present study we proposed a mechanism by which hypothyroidism leads to hippocampal neurotoxicity. Congenital hypothyroidism induces c-Jun-N-terminal kinase (JNK) pathway activation leading to hyperphosphorylation of the glial fibrillary acidic protein (GFAP), vimentin and neurofilament subunits from hippocampal astrocytes and neurons, respectively. Moreover, hyperphosphorylation of the cytoskeletal proteins was not reversed by T3 and poorly reversed by T4. In addition, congenital hypothyroidism is associated with downregulation of astrocyte glutamate transporters (GLAST and GLT-1) leading to decreased glutamate uptake and subsequent influx of Ca(2+) through N-methyl-D-aspartate (NMDA) receptors. The Na(+)-coupled (14)C-α-methyl-amino-isobutyric acid ((14)C-MeAIB) accumulation into hippocampal cells also might cause an increase in the intracellular Ca(2+) concentration by opening voltage-dependent calcium channels (VDCC). The excessive influx of Ca(2+) through NMDA receptors and VDCCs might lead to an overload of Ca(2+) within the cells, which set off glutamate excitotoxicity and oxidative stress. The inhibited acetylcholinesterase (AChE) activity might also induce Ca(2+) influx. The inhibited glucose-6-phosphate dehydrogenase (G6PD) and gamma-glutamyl transferase (GGT) activities, associated with altered glutamate and neutral amino acids uptake could somehow affect the GSH turnover, the antioxidant defense system, as well as the glutamate-glutamine cycle. Reduced levels of S100B and glial fibrillary acidic protein (GFAP) take part of the hypothyroid condition, suggesting a compromised astroglial/neuronal neurometabolic coupling which is probably related to the neurotoxic damage in hypothyroid brain.


Assuntos
Acetilcolinesterase/metabolismo , Hipotireoidismo Congênito/enzimologia , Hipocampo/enzimologia , Estresse Oxidativo , Animais , Astrócitos/metabolismo , Contagem de Células , Hipotireoidismo Congênito/patologia , Transportador 1 de Aminoácido Excitatório/metabolismo , Transportador 2 de Aminoácido Excitatório/metabolismo , Proteínas Ligadas por GPI/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Ácido Glutâmico/metabolismo , Hipocampo/crescimento & desenvolvimento , Hipocampo/patologia , Masculino , Neurônios/metabolismo , Ratos , Ratos Wistar , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo , Hormônios Tireóideos/sangue
5.
Burns ; 38(8): 1143-50, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22998897

RESUMO

Autografts represent the gold standard for the treatment of full thickness burns. Factors such as lack of suitable donor sites and poor skin quality, however, have led to the development of artificial dermal substitutes. The investigation of mechanisms leading to enhanced functionality of these skin substitutes has been attracting great attention. This study aimed to investigate the effect of autologous stem cells on the integration and vascularization of a dermal substitute in full-thickness skin wounds, in a murine model. Two cell populations were compared, whole bone marrow cells and cultivated mesenchymal stem cells, isolated from mice transgenic for the enhanced green fluorescent protein, which allowed tracking of the transplanted cells. The number of cells colonizing the dermal substitute, as well as vascular density, were higher in mice receiving total bone marrow and particularly mesenchymal stem cells, than in control animals. The effect was more pronounced in animals treated with mesenchymal stem cells, which located primarily in the wound bed, suggesting a paracrine therapeutic mechanism. These results indicate that combining mesenchymal stem cells with artificial dermal substitutes may represent an important potential modality for treating full thickness burns, even in allogeneic combinations due to the immunoregulatory property of these cells.


Assuntos
Transplante de Células-Tronco Mesenquimais/métodos , Pele Artificial , Cicatrização/fisiologia , Ferimentos e Lesões/terapia , Animais , Transplante de Medula Óssea , Contagem de Células , Técnicas de Cultura de Células , Terapia Combinada/métodos , Modelos Animais de Doenças , Camundongos , Camundongos Transgênicos , Transplante Autólogo , Ferimentos e Lesões/patologia
6.
Exp Brain Res ; 215(2): 163-72, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21969209

RESUMO

Neonatal handling reduces the stress response in adulthood due to a feedback mechanism. The present study analyzed the effects of repeated neonatal environmental intervention (daily handling during the first 10 days after birth) on neuron-, astroglial cell density, and cellular proliferation of the hippocampal (CA1, CA2, and CA3) pyramidal cell layers in female rats. Pups were divided into two groups, nonhandled and handled, which were submitted to repeated handling sessions between postnatal days 1 and 10. Histological and immunohistochemical procedures were used to determine changes in neuron density, astroglial cell density, and cellular proliferation. We found an increase in neuron density in each pyramidal cell layer of the hippocampus (CA1, CA2, and CA3) in female rats (11 and 90 day old) that were handled during the neonatal period. Furthermore, we found an increase in astroglial cell density in both hemispheres of the brain in the handled group. Finally, we observed an increase in cellular proliferation in both hippocampi (CA1, CA2, and CA3) of the brain in female pups (11 days old) handled during the neonatal period. This study demonstrates that an early-life environmental intervention may induce morphological changes in a structure involved with several functions, including the stress response. The results of the current study suggest that neonatal handling may influence the animals' responses to environmental adversities later in life.


Assuntos
Astrócitos/fisiologia , Proliferação de Células , Ambiente Controlado , Hipocampo/citologia , Hipocampo/crescimento & desenvolvimento , Neurogênese/fisiologia , Neurônios/fisiologia , Animais , Animais Recém-Nascidos , Astrócitos/citologia , Contagem de Células , Feminino , Masculino , Neurônios/citologia , Gravidez , Ratos , Ratos Wistar
7.
J Cancer Res Clin Oncol ; 137(9): 1309-16, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21735353

RESUMO

PURPOSE: Cofilin is a cytoskeletal protein whose overexpression has been associated with aggressiveness in several types of malignancies. Here, we established and optimized a simple semi-quantitative immunohistochemistry (SQ-IHC) method for cofilin quantification in tumor biopsies, and applied it in a retrospective cohort of NSCLC patients aiming at validating the use of cofilin-1 as a prognostic biomarker. METHODS: The SQ-IHC method for cofilin-1 quantification was established and applied in a NSCLC cohort. An archival collection of biopsies from 50 patients with clinicopathological information and 5 years follow-up was accessed. Association between cofilin-1 immunocontent and clinical outcome was assessed using standard Kaplan-Meier mortality curves and the log-rank test. To evaluate the robustness of our findings, three different partitional clustering strategies were used to stratify patients into two groups according to the biomarker expression level (hierarchical clustering, Kmeans and median cutoff). RESULTS: In all the three different partitional clustering we used, survival analysis showed that patient with high cofilin-1 immunocontent had a lower overall survival rate (P < 0.05), and could be used to discriminate between good and bad prognosis. No other correlation was found when the variables age, sex or histological type were tested in association with patients outcome or with cofilin immunocontent. CONCLUSIONS: Our method showed good sensitivity/specificity to indicate the outcome of patients according to their cofilin immunocontent in biological samples. Its application in a retrospective cohort and the results presented here are an important step toward the validation process of cofilin-1 as a prognostic biomarker.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Cofilina 1/fisiologia , Neoplasias Pulmonares/diagnóstico , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/fisiologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Cofilina 1/análise , Cofilina 1/metabolismo , Estudos de Coortes , Estudos de Avaliação como Assunto , Feminino , Seguimentos , Humanos , Imuno-Histoquímica/métodos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sensibilidade e Especificidade , Análise de Sobrevida
8.
Horm Behav ; 56(1): 93-100, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19324045

RESUMO

Early-life environmental events can induce profound long-lasting changes in several behavioral and neuroendocrine systems. The neonatal handling procedure, which involves repeated brief maternal separations followed by experimental manipulations, reduces stress responses and sexual behavior in adult rats. The purpose of this study was to analyze the effects of neonatal handling on social behaviors of male and female rats in adulthood, as manifest by the results of social memory and social interaction tests. The number of oxytocin (OT) and vasopressin (VP) neurons in the paraventricular (PVN) and supraoptic (SON) nuclei of hypothalamus were also analyzed. The results did not demonstrate impairment of social memory. Notwithstanding, handling did reduce social investigative interaction and increase aggressive behavior in males, but did not do so in females. Furthermore, in both males and females, handling was linked with reduced number of OT-neurons in the parvocellular region of the PVN, while no differences were detected in the magnocellular PVN or the SON. On the other hand, handled males exhibited increased number of VP-neurons in the magnocellular zone of the PVN. We may conclude that the repeated brief maternal separations can reduce affiliative social behavior in adult male rats. Moreover, the disruption of the mother-infant relationship caused by the handling procedure induced long-lasting morphological changes in critical neuroendocrine areas that are involved in social bonding in mammals.


Assuntos
Memória , Neurônios/metabolismo , Ocitocina/metabolismo , Comportamento Social , Estresse Psicológico/fisiopatologia , Vasopressinas/metabolismo , Análise de Variância , Animais , Animais Recém-Nascidos , Feminino , Imuno-Histoquímica , Masculino , Privação Materna , Núcleo Hipotalâmico Paraventricular/crescimento & desenvolvimento , Núcleo Hipotalâmico Paraventricular/metabolismo , Ratos , Ratos Wistar , Caracteres Sexuais , Núcleo Supraóptico/crescimento & desenvolvimento , Núcleo Supraóptico/metabolismo
9.
Brain Res ; 1247: 92-9, 2009 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-18977206

RESUMO

Early-life events may induce alterations in neuronal function in adulthood. A crucial aspect in studying long-lasting effects induced by environmental interventions imposed to the animal several weeks before is finding a stable change that could be causally related to the phenotype observed in adulthood. In order to explain an adult trait, it seems necessary to look back to early life and establish a temporal line between events. The neonatal handling procedure is an experimental tool to analyze the long-lasting impact of early-life events. Aside from the neuroendocrine response to stress, neonatal handling also alters the functionality of the hypothalamus-pituitary-gonad (HPG) axis. Reductions in ovulation and surge of the luteinizing hormone (LH) on the proestrous day were shown in female rats. Considering the importance of the medial preoptic area (MPA) for the control of ovulation, the present study aimed to verify the effects of neonatal handling on the numerical density and cell size in the MPA in 11-day-old and 90-day-old female rats. Cellular proliferation was also assessed using BrdU (5-bromo-2'-deoxyuridine) in 11-day-old pups. Results showed that neonatal handling induces a stable reduction in the number of cells and in the size of the cell soma, which were lower in handled females than in nonhandled ones at both ages. Cellular proliferation in the MPA was also reduced 24 h after the last manipulation. The repeated mother-infant disruption imposed by the handling procedure "lesioned" the MPA. The dysfunction in the ovulation mechanisms induced by the handling procedure could be related to that neuronal loss. The study also illustrates the impact of an environmental intervention on the development of the brain.


Assuntos
Manobra Psicológica , Sistema Hipotálamo-Hipofisário/fisiopatologia , Neurônios/metabolismo , Ovulação/fisiologia , Área Pré-Óptica/fisiopatologia , Estresse Psicológico/fisiopatologia , Animais , Animais Recém-Nascidos , Bromodesoxiuridina , Contagem de Células , Proliferação de Células , Tamanho Celular , Modelos Animais de Doenças , Meio Ambiente , Ciclo Estral/fisiologia , Feminino , Hormônio Luteinizante/sangue , Hormônio Luteinizante/metabolismo , Privação Materna , Neurônios/patologia , Área Pré-Óptica/crescimento & desenvolvimento , Ratos , Ratos Wistar , Tempo
10.
Brain Res ; 1170: 20-30, 2007 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-17692831

RESUMO

Early-life events can exert profound long-lasting effects on several behaviors such as fear/anxiety, sexual activity, stress responses and reproductive functions. Present study aimed to examine the effects of neonatal handling on the volume and number of cells in the hypothalamic paraventricular nucleus (pPVN, parvocellular and mPVN, magnocellular regions) and the supraoptic nucleus (SON) in female rats at 11 and 90 days of age. Moreover, in the same areas, immunohistochemistry for oxytocin (OT) and glial fibrillary acidic protein (GFAP) were analyzed in the adult animals. Daily handling during the first 10 postnatal days reduced the number of cells in the pPVN and SON at both the 11 and 90 days. Handling decreased the number of OT-positive parvocellular cells in the PVN in adult females. No significant differences were detected on the optical density (OD) of GFAP-positive cells between the handled and nonhandled adult females. The effect of handling on cell loss was observed 24 h after the 10-day handling period and persisted into adulthood, indicating a stable morphological trace. Results suggest that neonatal handling can induce plastic changes in the central nervous system.


Assuntos
Envelhecimento/fisiologia , Manobra Psicológica , Hipotálamo/fisiologia , Plasticidade Neuronal/fisiologia , Estresse Psicológico/metabolismo , Animais , Animais Recém-Nascidos , Morte Celular/fisiologia , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Hipotálamo/anatomia & histologia , Ocitocina/metabolismo , Núcleo Hipotalâmico Paraventricular/citologia , Núcleo Hipotalâmico Paraventricular/metabolismo , Ratos , Caracteres Sexuais , Estresse Psicológico/fisiopatologia , Núcleo Supraóptico/citologia , Núcleo Supraóptico/metabolismo , Tempo
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