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Prostate cancer (CaP) is one of the most common types of cancers worldwide. Despite the existing surgical techniques, prostatectomy patients may experience tumor recurrence. In addition, castration-resistant cancers pose a challenge, especially given their lack of response to standard care. Thus, the development of more efficient therapies has become a field of great interest, and photothermal therapy (PTT) and photodynamic therapy (PDT) are promising alternatives, given their high capacity to cause cell injury and consequent tumor ablation. Phototherapy, along with chemotherapy, has also been shown to be more effective than pharmacotherapy alone. Free molecules used as photosensitizers are rapidly cleared from the body, do not accumulate in the tumor, and are primarily hydrophobic and require toxic solvents. Thus, the use of nanoparticles can be an effective strategy, given their ability to carry or bind to different molecules, protecting them from degradation and allowing their association with other surface ligands, which favors permeation and retention at the tumor site. Despite this, there is still a gap in the literature regarding the use of phototherapy in association with nanotechnology for the treatment of CaP. In this scoping review, it was found that most of the particles studied could act synergistically through PDT and PTT. In addition, fluorescent quenchers can act as diagnostic and therapeutic tools. However, future clinical studies should be performed to confirm the benefits and safety of the combination of nanoparticles and phototherapy for CaP.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Neoplasias da Próstata , Masculino , Humanos , Recidiva Local de Neoplasia , Fototerapia/métodos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Nanopartículas/uso terapêutico , Nanopartículas/química , Linhagem Celular TumoralRESUMO
The present study compares the effects of a low and high doses of simvastatin in a model of peripheral neuropathy by evaluating sensorial, motor, and morphological parameters. First, male Wistar rats were orally treated with vehicle (saline, 1 mL/kg), simvastatin (2 and 80 mg/kg) or morphine (2 mg/kg, s.c.), 1 h before 2.5% formalin injection. Neuropathic pain was induced by crushing the sciatic nerve, and mechanical and cold allodynia, nerve function, histology, MPO and NAG concentrations, as well as mevalonate induced-nociception were evaluated. Animals were orally treated with vehicle, simvastatin, or gabapentin (30 mg/kg) for 18 days. Simvastatin (2 and 80 mg/kg) reduced the inflammatory pain induced by formalin, but failed to decrease the paw edema. Mechanical allodynia was reduced by the simvastatin (2 mg/kg) until the 12th day after injury and until the 18th day by gabapentin. However, both simvastatin and gabapentin treatments failed in attenuated cold allodynia or improved motor function. Interestingly, both doses of simvastatin showed a neuroprotective effect and inhibited MPO activity without altering kidney and hepatic parameters. Additionally, only the higher dose of simvastatin reduced the cholesterol levels and the nociception induced by mevalonate. Our results reinforce the antinociceptive, antiallodynic, and anti-inflammatory effects of oral simvastatin administration, which can strongly contribute to the sciatic nerve morphology preservation. Furthermore, our data suggest that lower and higher doses of simvastatin present beneficial effects that are dependent and independent of the mevalonate pathway, respectively, without causing signs of nerve damage.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperalgesia/tratamento farmacológico , Neuralgia/tratamento farmacológico , Medição da Dor/efeitos dos fármacos , Neuropatia Ciática/tratamento farmacológico , Sinvastatina/uso terapêutico , Animais , Temperatura Baixa/efeitos adversos , Relação Dose-Resposta a Droga , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hiperalgesia/metabolismo , Hiperalgesia/patologia , Masculino , Neuralgia/metabolismo , Neuralgia/patologia , Medição da Dor/métodos , Peroxidase/antagonistas & inibidores , Peroxidase/metabolismo , Ratos , Ratos Wistar , Neuropatia Ciática/metabolismo , Neuropatia Ciática/patologia , Sinvastatina/farmacologia , Resultado do TratamentoRESUMO
Ameloblastoma é uma neoplasia epitelial odontogênica localmente agressiva, com crescimento lento e, na maioria dos casos, benigna. Apresenta alto índice de recorrência se não for corretamente removido (1). Ameloblastoma é o segundo tumor odontogênico mais comum, com distribuição semelhante entre os gêneros. Ocorre principalmente na terceira década de vida e cerca de 91,7% ocorre na mandíbula e 8,3% na maxila (1, 3). A incidência anual da neoplasia varia entre 1,5 a 2,41 casos por milhão (4, 5). Na classificação da OMS de 2005 sobre tumores odontogênicos, o ameloblastoma era dividido em: sólido/ multicístico, extraósseo/ periférico, desmoplásico e unicístico. Na mais recente classificação de 2017 o ameloblastoma é dividido em três tipos: ameloblastoma; ameloblastoma unicístico e ameloblastoma extraósseo/ periférico. Verificou-se nos estudos subsequentes que a classificação anterior não demonstrava significado biológico relevante, sendo alguns reclassificados apenas como sub-tipos histológicos
Ameloblastoma is a slow growing and locally agressive odontogenic neoplasm, most of them are benign. It has a high rate of recurrence if not adequate ressected (1). Ameloblastoma is the second most commun odontogenic tumour. It exhibits no gender predilection. Most cases are diagnosed between 20 and 40 years of age. 91,7% occurs in mandible and 8,3% in maxillary region (1,3). The annual incidence rate ranges from 1,5 to 2,41 per million population (4,5). In the former World Health Organizantion Classification of Odontogenic tumors, published in 2005, ameloblastoma was classified as a benign tumour divided in: Ameloblastoma solid/ multicystic type; Ameloblastoma extraosseous/peripheral type; Ameloblastoma desmoplastic type and Ameloblastoma unicystic type. In the last classification, just published in 2017, it is divided in three types only: Ameloblastoma; Ameloblastoma unicystic type and Ameloblastoma extraosseous/peripheral type. It was concluded in the latter studies that the previous classification did not have a relevant biological significance, some of them being reclassified as histological subtypes
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BACKGROUND: Infusions of aerial parts of Artemisia vulgaris L. (Asteraceae) are used in herbal medicine to treat several disorders, including hepatosis. PURPOSE: Evaluation of in vivo hepatoprotective effects of A. vulgaris infusion (VI) and inulin (VPI; i.e., the major polysaccharide of VI). STUDY DESIGN: The hepatoprotective effect of A. vulgaris extracts on carbon tetrachloride (CCl4)-induced hepatotoxicity and the probable mechanism involved in this protection were investigated in mice. METHODS: A. vulgaris infusion (VI) was prepared according to folk medicine using the aerial parts of the plant. Carbohydrate, protein, and total phenolic content was determined in VI, and its phenolic profile was determined by high-performance liquid chromatography (HPLC). Male Swiss mice were orally pretreated for 7 days with VI or VPI (once per day). On days 6 and 7 of treatment, the mice were intraperitoneally challenged with CCl4. Liver and blood were collected and markers of hepatic damage in plasma and oxidative stress in the liver were analyzed. Hepatic histology and inflammatory parameters were also studied in the liver. The scavenging activity of VI and VPI were evaluated in vitro using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. RESULTS: VI contained 40% carbohydrates, 2.9% proteins and 9.8% phenolic compounds. The HPLC fingerprint analysis of VI revealed chlorogenic, caffeic and dicaffeoylquinic acids as major low-molar-mass constituents. Oral pretreatment with VI and VPI significantly attenuated CCl4-induced liver damage, reduced the activity of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) in plasma, and prevented reactive oxygen species accumulation and lipid peroxidation in the liver. Comparisons with the CCl4-treated group showed that VI and VPI completely prevented necrosis, increased the levels of reduced glutathione (GSH), and reduced tumor necrosis factor alpha (TNF-α) level in the liver. VI and VPI also exhibited high radical scavenging activity in vitro. CONCLUSION: VI and VPI had remarkable hepatoprotective effects in vivo, which were likely attributable to antioxidant and immunomodulatory properties. The present findings support the traditional use of A. vulgaris infusion for the treatment of hepatic disorders.
Assuntos
Artemisia/química , Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Frutanos/uso terapêutico , Fígado/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/uso terapêutico , Animais , Antioxidantes/farmacologia , Frutanos/farmacologia , Masculino , Camundongos , Fitoterapia , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologiaRESUMO
This study evaluated the antitumour activity of the mesoionic compound sydnone 1 (Syd-1) against Walker-256 carcinosarcoma. Tumour cells were subcutaneously inoculated in the hind limb in male Wistar rats. The animals were orally treated for 12 days with Syd-1 (75 mg/kg) or vehicle. At the end of treatment, considerable decreases in tumour volume and tumour weight were observed in treated animals. Samples of these tumours presented increases in apoptotic bodies and pro-apoptotic protein expression (Bax and p53), while the expression of the anti-apoptotic protein Bcl-2 was reduced. A decrease in reduced glutathione levels and an increase in glutathione peroxidase activity were observed in tumour after Syd-1 treatment. However, significant splenomegaly was evident in animals that received Syd-1, most likely attributable to the induction of haemolysis. This study demonstrated the antitumour activity of Syd-1 against Walker-256 carcinosarcoma. Its mechanism of action is linked to the activation of apoptotic pathways that lead to tumour cell death.
Assuntos
Antineoplásicos/farmacologia , Carcinoma 256 de Walker/tratamento farmacológico , Sidnonas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3/genética , Caspase 3/metabolismo , Catalase/metabolismo , Linhagem Celular Tumoral , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Ratos , Ratos Wistar , Baço/efeitos dos fármacos , Baço/patologia , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
Alcoholic liver disease is characterized by a wide spectrum of liver damage, which increases when ethanol is associated with high-fat diets (HFD). This work aimed to establish a model of alcoholic hepatic steatosis (AHS) by using a combination of 10% ethanol and sunflower seeds as the source of HFD. Male rats received water or 10% ethanol and regular chow diet and/or HFD, which consisted of sunflower seeds. The food consumption, liquid intake and body weight of the rats were monitored for 30 days. After this period, blood was collected for biochemical evaluation, and liver samples were collected for histological, mitochondrial enzyme activity and oxidative stress analyses. Our results indicated that the combination of 10% ethanol and HFD induced micro- and macrosteatosis and hepatocyte tumefaction, decreased the levels of reduced glutathione and glutathione S-transferase activity and increased the level of lipoperoxidation and superoxide dismutase activity. The mitochondrial oxidation of NADH and succinate were partially inhibited. Complexes I and II were the main inhibition sites. Hepatic steatosis was successfully induced after 4 weeks of the diet, and the liver function was modified. The combination of 10% ethanol and sunflower seeds as an HFD produced an inexpensive model to study AHS in rats.
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Background: The association between ulcerative colitis and adenocarcinoma determined strategies for patient follow-up and early detection of dysplastic and neoplastic lesions. Aims: To analyze the incidence of dysplasia in patients with ulcerative colitis, comparing clinical data of patients with and without dysplasia and check immunohistochemical expression of p53 protein in dysplasias. Materials and methods: We analyzed biopsy samples and clinical data of 124 patients with ulcerative colitis at Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil. Results: Dysplasia incidence was low (9.67%) and all cases with low-grade dysplasia. Patients clinical data comparison with and without dysplasia did not show significant statistical differences with regard to the race, age at the start of the disease, age at last biopsy, duration and anatomic extent of ulcerative colitis. Significant difference was found between males and females with predominance of males (58.34%) for dysplasia. Seventeenth biopsy samples of 12 patients with dysplasia, 5 (29.4%) were p53 positive. Conclusions: From these results it is concluded that the incidence of dysplasia was low, higher in males and there was positivity of p53 protein in dysplasia. .
Racional: A associação entre retocolite ulcerativa e adenocarcinoma determinou estratégias para seguimento dos pacientes e detecção precoce das lesões displásicas e neoplásicas. Objetivos: Analisar a incidência de displasia nos pacientes com retocolite ulcerativa, comparar dados clínicos dos pacientes com e sem displasia e verificar a expressão imunoistoquimica da proteína p53 nas displasias. Material e Métodos: Foram estudados os exames anatomopatológicos e dados clínicos de 124 pacientes com e sem displasia, portadores de retocolite ulcerativa no Hospital de Clínicas da Universidade Federal do Paraná. Resultados: A incidência de displasia foi de 9,67% e todos os casos foram de displasia de baixo grau. Na comparação dos dados clínicos dos pacientes com e sem displasia não houve diferença estatisticamente significativa com relação à cor, idade no início da doença, idade na última biópsia, extensão da doença e tempo de evolução da doença. Houve diferença estatística com predomínio de pacientes do sexo masculino (58,34%) em relação ao feminino para displasia. Dos 17 exames avaliados de 12 pacientes com displasia, em 5 exames (29,4%) a expressão da proteína p53 foi positiva. Conclusões: Desses resultados conclui-se que a incidência de displasia foi baixa, maior no sexo masculino e houve positividade da proteína p53 nas displasias. .
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Humanos , Masculino , Feminino , Colite Ulcerativa/diagnóstico , Proteína Supressora de Tumor p53 , Neoplasias do Colo/diagnóstico , Proctocolite , Expressão GênicaRESUMO
Introduction: Inflammatory bowel disease comprises two major categories: Crohn's disease and ulcerative rectocolitis, both with different clinical and histological aspects, causing sometimes significant morbidity. Objectives: Choose and apply standardized and quantified histopathological diagnosis method, and compare the results and quality index with the original diagnosis. Materials and methods: 43 histological colonoscopic biopsies of 37 patients were re-evaluated by standardized system. Results and discussion: The original diagnoses were more inconclusive (23.3%) than those standardized (2.3%). The agreement with gold standard (clinical, colonoscopical, and radiological diagnosis) was higher on standardized diagnoses (95.3%) than in original (74.4%), especially in relation to Crohn's disease, which percentages were 92.3% and 46.1%, respectively. The quality index was calculated in conclusive diagnosis of each method. For ulcerative rectocolitis, both methods showed sensitivity and negative predictive value of 100%; otherwise the original diagnosis demonstrated specificity of 85.7%, positive predictive value of 96.3% and accuracy of 97.0%, and the standardized diagnosis 92.3%, 96.7% and 97.6%, respectively. For Crohn's disease, there is specificity and positive predictive value of 100% in both methods; the original diagnosis showed sensitivity of 85.7%, negative predictive value of 96.3% and accuracy of 97%, while for the standardized diagnoses 92.3%, 96.7%, and 97.6%, respectively. Conclusion: The standardized diagnosis presented a higher percentage of correct and conclusive diagnoses than those presented in the original diagnosis, especially for Crohn's disease, as well as equal or slightly higher values in some quality index...
Introdução: Duas são as formas de manifestação da doença intestinal inflamatória: doença de Crohn e retocolite ulcerativa, ambas com evolução clínica, tratamento e aspectos histopatológicos diferentes, causando, por vezes, significativa morbidade. Objetivos: Escolher e aplicar método padronizado e quantificado de diagnóstico histopatológico e comparar os resultados e os índices de qualidade, com os dos diagnósticos originais. Materiais e métodos: Foram reavaliadas histologicamente 43 biópsias colonoscópicas seriadas de 37 pacientes por sistema padronizado. Resultado e discussão: Os diagnósticos originais foram mais inconclusivos (23,3%) do que os padronizados (2,3%). A concordância com o padrão-ouro (diagnóstico clínico, colonoscópico e radiológico) foi maior nos diagnósticos padronizados (95,3%) do que nos originais (74,4%), principalmente em relação à doença de Crohn, cujos percentuais foram de 92,3% e 46,1%, respectivamente. Para retocolite ulcerativa, ambos os métodos apresentaram sensibilidade e valor preditivo negativo de 100%; já nos diagnósticos originais, foram verificados especificidade de 85,7%, valor preditivo positivo de 96,3% e acurácia de 97%, e nos diagnósticos padronizados, 92,3%, 96,7% e 97,6%, respectivamente. Para doença de Crohn, verificaram-se especificidade e valor preditivo positivo de 100% nos dois métodos; nos diagnósticos originais, sensibilidade de 85,7%, valor preditivo negativo de 96,3% e acurácia de 97%, e nos diagnósticos padronizados, 92,3%, 96,7% e 97,6%, respectivamente. Conclusão: O diagnóstico padronizado apresentou maior percentual de diagnósticos corretos e conclusivos do que os apresentados no diagnóstico original, principalmente para doença...
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Humanos , Biópsia/normas , Doença de Crohn/diagnóstico , Proctocolite/diagnóstico , Técnicas e Procedimentos Diagnósticos/normas , Doença de Crohn/patologia , Doenças Inflamatórias Intestinais/diagnóstico , Valor Preditivo dos Testes , Proctocolite/patologiaRESUMO
BACKGROUND AND AIM: Excessive ethanol consumption can lead to development of hepatic steatosis. Since the FXR receptor regulates adipose cell function and liver lipid metabolism, the aim of this work was to examine the effects of the FXR agonist 6ECDCA on alcoholic liver steatosis development and on oxidative stress induced by ethanol consumption. METHODS: Swiss mice (n=24) received a low-protein diet (6%) and a liquid diet containing 10% ethanol or water for 6weeks. In the last 15days mice received oral treatment with 6ECDCA (3mgkg(-1)) or 1% tween (vehicle). The experimental groups (n=6) were: water+tween, water+6ECDCA, ethanol+tween and ethanol+6ECDCA. Moreover, as a diet control, we used a basal group (n=6), fed by a normal-proteic diet (23%) and water. After the treatment period, the animals were anesthetized for sample collection to perform plasma biochemistry assays, hepatic oxidative stress assays, hepatic cholesterol and triglycerides measurements, liver histology and hepatic gene expression. RESULTS: Ethanol associated with low-protein diet induced hepatic oxidative stress, increased plasma transaminases and induced hepatic lipid accumulation. Many of these parameters were reversed by the administration of 6ECDCA, including amelioration of lipid accumulation and lipoperoxidation, and reduction of reactive oxygen species. These effects were possibly mediated by regulation of Srebpf1 and FAS gene expression, both reduced by the FXR agonist. CONCLUSIONS: Our data demonstrated that 6ECDCA reverses the accumulation of lipids in the liver and decreases the oxidative stress induced by ethanol and low-protein diet. This FXR agonist is promising as a potential therapy for alcoholic liver steatosis.
Assuntos
Ácido Quenodesoxicólico/farmacologia , Fígado Gorduroso/tratamento farmacológico , Fármacos Gastrointestinais/farmacologia , Hepatopatias Alcoólicas/tratamento farmacológico , Estresse Oxidativo/fisiologia , Receptores Citoplasmáticos e Nucleares/agonistas , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Catalase/metabolismo , Colesterol/sangue , Etanol/administração & dosagem , Fígado Gorduroso/sangue , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/etiologia , Glutationa Transferase/metabolismo , Histocitoquímica , Hepatopatias Alcoólicas/sangue , Hepatopatias Alcoólicas/etiologia , Hepatopatias Alcoólicas/metabolismo , Masculino , Camundongos , Receptores Citoplasmáticos e Nucleares/metabolismo , Superóxido Dismutase/metabolismo , Triglicerídeos/sangueRESUMO
OBJECTIVE: Evaluate risk factors for colorectal cancer recurrence after surgical treatment. METHODS: Sixty-five patients with colorectal adenocarcinoma, stage I and II (TNM), undergoing curative-intent surgery and followed for five years were studied. Presence of adjuvant/neoadjuvant therapy, tumor differentiation degree, lymphatic and venous vascular infiltration, depth of tumor invasion, and disease staging was analyzed, using recurrence relative risk ratios for each parameter calculated at two years, after two years and five years of follow up. RESULTS:At five years, recurrence was 21.4% (14/65), with equal incidence (10.7%) for the separated periods. Only lymphatic and venous vascular infiltration showed statistically significant association with recurrence during times analyzed. Relative risk (RR) of recurrence was significantly related to the presence of lymphatic infiltration [RR = 6 (1.3 - 28.5) p = 0.01] and venous infiltration [RR = 9.5 (2.6 - 34.9) p < 0.001] after two years of follow-up. At five years follow-up, only venous infiltration remained with significant relative risk for recurrence [RR = 3.9 (1.8 - 8.8) p < 0.001]. In a multivariate analysis, only venous vascular infiltration was associated with recurrence [accuracy 81.5% (p < 0.001)]. CONCLUSION: In this series, the factors associated with risk of colorectal cancer recurrence were the presence of lymphatic and venous vascular infiltration. (AU)
OBJETIVO: Analisar fatores de risco para recidiva de câncer colorretal após tratamento cirúrgico. MÉTODO: Avaliou-se 65 pacientes com adenocarcinoma colorretal, estádio I e II (TNM), submetidos à cirurgia com intenção curativa, acompanhados por cinco anos após a operação. Analisou-se presença de tratamento adjuvante/neoadjuvante, grau de diferenciação do tumor, infiltração vascular linfática e venosa, profundidade de invasão tumoral e estadiamento da doença, estabelecendo-se para cada um o risco relativo de recidiva aos dois anos, após dois anos e aos cinco anos de seguimento. RESULTADOS: Recidiva global em cinco anos foi 21,4% (14/65), com idêntica incidência (10,7%) nos períodos separados. Somente as infiltrações vasculares linfáticas e venosas apresentaram associação estatisticamente significativa com a recidiva nos períodos de análise. Encontrou-se risco relativo (RR) estatisticamente significativo após dois anos relacionados à presença de infiltração linfática [RR = 6 (1,3 - 28,5) p = 0,01] e infiltração venosa [RR = 9,5 (2,6 - 34,9) p < 0,001]. Após cinco anos, apenas a infiltração venosa manteve a significância estatística, com risco relativo elevado para ocorrência de recidiva [RR = 3,9 (1,8 - 8,8) p < 0.001]. Na análise multivariada apenas a presença de infiltração vascular venosa com 81,5% de acerto foi associada à recidiva (p < 0.001). CONCLUSÃO: Nesta série, os únicos fatores associados com risco de recidiva do câncer colorretal foram a presença de infiltração vascular linfática e venosa. (AU)
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Adenocarcinoma/cirurgia , Adenocarcinoma/terapia , Neoplasias Retais/cirurgia , Recidiva , Neoplasias do Colo/cirurgiaRESUMO
BACKGROUND: Several studies suggest that the presence of statins may be beneficial during sepsis, but this idea is controversial. The aim of this study was to investigate the effects of long-term statin treatment in the livers of septic animals, focusing on its antioxidant, antiinflammatory, and metabolic properties. MATERIALS AND METHODS: Male Wistar rats were treated orally with simvastatin, atorvastatin, or vehicle once a d. After 30 d, sepsis was induced by cecal ligation and puncture (CLP) in Control, Simvastatin-treated, and Atorvastatin-treated groups, while the Sham group underwent only laparotomy. The Basal Simvastatin and Basal Atorvastatin groups received only their respective drugs without surgery. Twenty-four h after CLP or laparotomy, samples were collected from anesthetized rats for evaluation of hepatic oxidative stress, liver histology, hepatic mitochondria enzyme activity, leukocyte counts in blood and peritoneal cavity, gene expression of hepatic superoxide dismutase and TNF-2, and plasma biochemistry. RESULTS: Most parameters that we tested exhibited expected changes upon sepsis induction. However, statin treatment only improved liver mitochondrial enzymatic activity. In other parameters, simvastatin and atorvastatin failed to protect the liver against injuries incurred upon the CLP-induced polymicrobial sepsis model. CONCLUSIONS: Pretreatment with simvastatin or atorvastatin alone before sepsis induction improved mitochondrial activity in the liver; however, this result was not reproduced in other biomarkers of liver function and leukocyte migration during sepsis. Future studies should be performed to evaluate whether statins can be combined with other drugs to increase the efficacy of sepsis therapy.
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Hepatócitos/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inflamação/tratamento farmacológico , Sepse/tratamento farmacológico , Animais , Hepatócitos/patologia , Hepatócitos/fisiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Sepse/metabolismo , Sepse/patologia , Superóxido Dismutase/genética , Superóxido Dismutase-1 , Fator de Necrose Tumoral alfa/genéticaRESUMO
A significant increase in cutaneous leishmaniasis (CL) and its geographic expansion has motivated the development of techniques to help with diagnosis of the disease. Here we describe immunocytochemical (ICC) and immunohistochemical (IHC) techniques for the diagnosis of CL in the laboratory. Polyclonal antibodies and a modified avidin-biotin complex (Ultra Streptavidin(®)) for Leishmania (V.) braziliensis or Leishmania (L.) amazonensis were developed for the present study. In vitro culture and histological sections from experimentally infected tissues were submitted to ICC/IHC techniques. The polyclonal antibody specificity, stability and immunostaining were evaluated. The polyclonal antibodies purified by chromatography (Sephadex(®)) and obtained from L. (V.) braziliensis and L. (L.) amazonensis insoluble antigens presented 83.3% sensitivity, when the presence of antigens was evaluated, i.e., higher than histopathology or any equivalent method (in vitro culture). The polyclonal antibody presented 100% specificity when used against species frequently found in CL lesions. The ICC/IHC techniques developed in the current study were able to recognize amastigotes and antigens from in vivo and in vitro cultures and from biopsies, offering additional help in the diagnosis of CL. This methodology could be beneficially adopted in public health laboratories.
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Antígenos de Protozoários/análise , Leishmania braziliensis/imunologia , Leishmania mexicana/imunologia , Leishmaniose Cutânea/diagnóstico , Animais , Anticorpos Antiprotozoários/imunologia , Anticorpos Antiprotozoários/isolamento & purificação , Antígenos de Protozoários/imunologia , Ensaio de Imunoadsorção Enzimática , Humanos , Imuno-Histoquímica , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/parasitologia , Coelhos , Sensibilidade e Especificidade , SolubilidadeRESUMO
Os avanços tecnológicos e metodológicos da biologia molecular criaram a possibilidade de obter DNA de amostras teciduais estocadas em blocos de parafina, alternativa esta que permite estudos retrospectivos de grandes bancos de tecidos contendo inúmeras doenças raras. O objetivo deste trabalho foi a realização de uma breve revisão de alguns fatores inerentes à qualidade do produto extraído proveniente de blocos de parafina armazenados. Os processos envolvidos nas fases de prefixação, fixação, pós-fixação apresentam aspectos que são causa de resultados de produtos finais insatisfatórios. Na fase de prefixação, alterações bioquímicas influenciam na preservação das macromoléculas. As mudanças moleculares causadas pelos fixadores para evitar autólise celular podem ser um limitante no momento da extração de DNA. A qualidade do DNA obtido nas duas primeiras fases é considerada importante para os procedimentos de pós-fixação (extração e purificação do DNA). Existem na literatura vários protocolos, com diferentes passos que podem ser modificados, para a obtenção de DNA de material parafinado. Assim, a compreensão das reações em cada fase é importante para solucionar ou minimizar problemas, que influenciam na qualidade das macromoléculas de DNA.
Technological and methodological advances in molecular biology have enabled the obtainment of DNA from paraffin embedded tissue, thus allowing the use of extensive pathological archive sources and samples of uncommon diseases in retrospective studies. The aim of this work was to carry out a brief review of some factors inherent in the quality of product from paraffin embedded material. The processes involved in the pre-fixation, fixation and post-fixation phases have several aspects that may result in unsatisfactory final products. In the pre-fixation phase, biochemical changes influence the preservation of macromolecules. The molecular changes caused by fixation, an attempt to prevent cell autolysis, may be a limiting factor at the time of DNA extraction. The quality of DNA obtained in the first two phases is regarded important for post-fixation procedures (DNA extraction and purification). In the literature there are several protocols whose steps can be modified to obtain DNA from paraffin embedded material. Therefore, the understanding of reactions at each stage is important in order to solve or minimize problems that interfere in the quality of DNA macromolecules.
Assuntos
Bancos de Espécimes Biológicos/normas , DNA , Fixação de Tecidos/normas , Inclusão em Parafina , Controle de QualidadeRESUMO
RACIONAL: A excisão total do mesorreto é considerada a operação padrão no tratamento dos tumores do reto, apesar de não existir comprovação científica de que ela deva ser usada para todos os estádios da doença. Tem sido demonstrado que em casos escolhidos de tumores retais, resultados promissores podem ser conseguidos com tratamento local por microcirurgia endoscópica transanal. Tais tumores, denominados de câncer retal precoce, são tumores T1 - menores do que 4 cm -, bem diferenciados sem invasão angiolinfática pT1 Sm1. Como o risco de comprometimento linfonodal nesses tumores é de aproximadamente 3 por cento, a ressecção local teria grande chance de ser curativa. OBJETIVO: Apresentar os resultados de uma série prospectiva não randômica de pacientes portadores de câncer retal precoce submetidos ao tratamento local por microcirurgia endoscópica transanal. MÉTODOS: Entre 2002 e 2010, 38 pacientes avaliados por protocolo pré-operatório como portadores câncer retal precoce foram submetidos à ressecção local endoscópica microcirúrgica de toda a parede retal com o tumor quando localizado entre 2 e 8 cm da linha pectínea. A avaliação pré-operatória consistiu de toque retal, retossigmoidoscopia rígida para macrobiópsias, enema opaco e/ou colonoscopia, ultrassonografia endoretal e abdominal, tomografia axial computadorizada do abdome, radiografia do tórax e dosagem sérica do CEA. Realizou-se seguimento pós-operatório endoscópico e ultrassonográfico endoretal a cada três meses nos dois primeiros anos, e a cada seis nos próximos três anos, além de dosagem do CEA a cada seis meses nesse mesmo período de cinco anos. Avaliou-se a recidiva tumoral, morbidade e mortalidade. RESULTADOS: Após avaliação anatomopatológica da lesão, 29 cânceres retais precoces foram categorizados como de baixo risco e nove sendo de alto. O seguimento na série variou de um a sete anos. Recidiva tumoral foi confirmada em dois casos dos 38 (5,26 por cento), uma lesão considerada de alto...
BACKGROUND: The total mesorectal excision is considered the standard operation in the treatment of rectal tumors, although there is no scientific proof that it should be used for all stages of the disease. It has been demonstrated that in selected cases of rectal tumors, promising results can be achieved with local treatment by transanal endoscopic microsurgery. These tumors, called early rectal cancer, T1 tumors, are less than 4 cm, well differentiated without angiolymphatic invasion - pT1 SM1. As the risk of lymph node involvement in these tumors is approximately 3 percent, local resection would have a great chance to be curative. AIM: To present the results of a non-random prospective series of patients with early rectal cancer treated by transanal endoscopic microsurgery. METHODS: Between 2002 and 2010, 38 patients evaluated by preoperative protocol as patients with early rectal cancer underwent endoscopic microsurgical resection of the entire rectal wall including the tumor when located between 2 and 8 cm from the dentate line. The preoperative evaluation consisted of digital rectal examination, rigid sigmoidoscopy macrobiopsies, barium enema and/or colonoscopy, endorectal ultrasound and abdominal computed tomography of the abdomen, chest radiography and serum CEA. Was conducted follow-up with endoscopy and endorectal ultrasound every three months during the first two years, and every six in the next three years, and CEA every six months during the same period of five years. Was evaluated the tumor recurrence, morbidity and mortality. RESULTS: Pathologic evaluation considered 29 categorized as low risk and nine being high. The follow-up in the series ranged from one to seven years. Tumor recurrence was confirmed in two of the 38 cases (5.26 percent), in one the lesion was considered high and another low risk. CONCLUSION: Transanal endoscopic microsurgery associated or not to adjuvant therapy, may be, currently, considered the gold standard in...
Assuntos
Humanos , Masculino , Feminino , Diagnóstico Precoce , Estadiamento de Neoplasias , Excisão de Linfonodo , Microcirurgia , Neoplasias Retais/cirurgia , Neoplasias Retais/diagnóstico , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapiaRESUMO
RACIONAL: A literatura médica aceita ressecção local como opção válida em casos selecionados de tumores de reto. A seleção dos pacientes requer exata estimativa dos riscos e avaliação pré-operatória precisa, tanto no aspecto clínico como histopatológico. OBJETIVO: Avaliar os resultados da microcirurgia endoscópica transanal em seguimento de 18 meses. MÉTODOS: De abril de 2002 a abril de 2006, 50 pacientes com tumores de reto foram submetidos a microcirurgia endoscópica transanal, selecionados por suas características clínicas e histopatológicas. Os critérios de inclusão foram: adenomas sésseis maiores do que 3 cm e menores do que 8 cm não-circunferenciais; neoplasia intra-epitelial de alto grau; carcinoma retal pT1, e em casos especiais pT2. Todos esses tumores foram submetidos ao mesmo procedimento cirúrgico. RESULTADOS: O resultado histopatológico final revelou 9 adenomas, 26 neoplasias intra-epiteliais de alto grau, 13 carcinomas (9 pT1 e 4 pT2) e 2 carcinóides. A menor idade foi de 25 anos e a maior de 92. O menor tumor ressecado tinha 64 mm² (carcinóide) e o maior (adenoma) 90 mm². O tempo médio de operação foi de 90 minutos e o de internamento 5 dias. Houve uma morte não relacionada ao método. Um paciente com carcinoma de baixo risco pT1 apresentou recidiva 18 meses após microcirurgia endoscópica transanal e foi submetido a retossigmoidectomia curativa. Foi observado tumor residual em dois pacientes e a complicação mais grave foi uma fístula retovaginal. A taxa de complicação global foi de 9 por cento. CONCLUSÃO: Atualmente a microcirurgia endoscópica transanal é a técnica de escolha para o tratamento de adenomas sésseis, neoplasias intra-epiteliais de alto grau e carcinoma retal pT1 de baixo risco.
BACKGROUND: The medical literature accepts local resection as a valuable option in selected cases of rectal tumors. Selection of patients requires an exact perioperative estimation of risks with clinical and histopathological examination. Transanal endoscopic microsurgery aims a safe resection of the tumoral area which leads up to the cure. AIM: To evaluate transanal endoscopic microsurgery results in a follow-up time of 18 months. METHODS: From April 2002 to April 2006, 50 patients with rectal tumors were submitted to transanal endoscopic microsurgery, chosen by clinical history and lesion characteristics. The inclusion criteria were: sessile adenomas larger than 3 cm and smaller than 8 cm, not circumferentially distributed; intra epithelial neoplasia of high degree; and rectal carcinoma pT1, and special cases of pT2. All these rectal tumors were submitted to the same surgical act. RESULTS: The final histopathological results reveal 9 adenoma, 26 intra-epithelial neoplasia of high degree, 13 carcinoma (9 pT1-4 pT2) and 2 carcinoid. The lowest age was 25 and the higher, 92 years-old. The smallest resected tumor had 64 mm² (carcinoid) and the largest (adenoma), 90 cm². Operating time was in average 90 minutes and the overall time statement, 5 days. There was one death not related with the method. One patient with low risk carcinoma pT1 presented recurrence 18 months after transanal endoscopic microsurgery and was submitted to curative rectosigmoidectomy. It was proven a residual tumor after local surgery in two patients and the most important complication was one recto-vaginal fistula. The overall complications rate was 9 percent. CONCLUSION: Today transanal endoscopic microsurgery is chosen as the ideal technique for the treatment of sessile adenomas, intraepithelial neoplasia of high degree and rectal carcinoma pT1.
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Adenoma/cirurgia , Carcinoma/cirurgia , Microcirurgia/métodos , Proctoscopia/métodos , Neoplasias Retais/cirurgia , Canal Anal , Adenoma/patologia , Carcinoma/patologia , Seguimentos , Microcirurgia/efeitos adversos , Recidiva Local de Neoplasia , Neoplasia Residual , Estudos Prospectivos , Proctoscopia/efeitos adversos , Neoplasias Retais/complicações , Neoplasias Retais/patologia , Resultado do TratamentoRESUMO
BACKGROUND: The medical literature accepts local resection as a valuable option in selected cases of rectal tumors. Selection of patients requires an exact perioperative estimation of risks with clinical and histopathological examination. Transanal endoscopic microsurgery aims a safe resection of the tumoral area which leads up to the cure. AIM: To evaluate transanal endoscopic microsurgery results in a follow-up time of 18 months. METHODS: From April 2002 to April 2006, 50 patients with rectal tumors were submitted to transanal endoscopic microsurgery, chosen by clinical history and lesion characteristics. The inclusion criteria were: sessile adenomas larger than 3 cm and smaller than 8 cm, not circumferentially distributed; intra epithelial neoplasia of high degree; and rectal carcinoma pT1, and special cases of pT2. All these rectal tumors were submitted to the same surgical act. RESULTS: The final histopathological results reveal 9 adenoma, 26 intra-epithelial neoplasia of high degree, 13 carcinoma (9 pT1-4 pT2) and 2 carcinoid. The lowest age was 25 and the higher, 92 years-old. The smallest resected tumor had 64 mm(2) (carcinoid) and the largest (adenoma), 90 cm(2). Operating time was in average 90 minutes and the overall time statement, 5 days. There was one death not related with the method. One patient with low risk carcinoma pT1 presented recurrence 18 months after transanal endoscopic microsurgery and was submitted to curative rectosigmoidectomy. It was proven a residual tumor after local surgery in two patients and the most important complication was one recto-vaginal fistula. The overall complications rate was 9%. CONCLUSION: Today transanal endoscopic microsurgery is chosen as the ideal technique for the treatment of sessile adenomas, intraepithelial neoplasia of high degree and rectal carcinoma pT1.
Assuntos
Adenoma/cirurgia , Carcinoma/cirurgia , Microcirurgia/métodos , Proctoscopia/métodos , Neoplasias Retais/cirurgia , Adenoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Canal Anal , Carcinoma/patologia , Seguimentos , Humanos , Microcirurgia/efeitos adversos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasia Residual , Proctoscopia/efeitos adversos , Estudos Prospectivos , Neoplasias Retais/complicações , Neoplasias Retais/patologia , Resultado do TratamentoRESUMO
O lúpus eritematoso sistêmico (LES) é doença auto-imune multissistêmica com freqüente comprometimento renal. Ainterpretação dos achados de biópsia renal em portadores de LES é complicada pela sua grande variabilidade morfológica e a possível inconsistência de sua correlação com os dados clínico-laboratoriais. O crescente uso da biópsia renal na avaliação do grau e extensão do comprometimento renal no LES, os avanços no conhecimento de sua patogênese e os estudos de correlação clínico-patológica tornaram necessária a elaboração de um esquema de categorizaçãoe terminologia das lesões. As bases de tal esquema foram lançadas em 1974 e revistas em 1982 e 1995. A fim de acomodar novas visões clínico-patológicas, corrigir inconsistências e tornar mais claras as descrições das lesões e classes de nefrite lúpica, a Sociedade Internacional de Nefrologia (ISN) e a Sociedade de Patologia Renal (RPS) realizaram, em2003, uma revisão da classificação vigente. Este trabalho realiza um breve relato do panorama histórico das classificações propostas desde 1974 e apresenta essa nova proposta que pretende guiar os futuros trabalhos de correlação clínico-patológica.
Assuntos
Humanos , Nefrite Lúpica , Lúpus VulgarRESUMO
Resultados de consultas intra-operatórias obtidas de 200 pacientes portadores de lesöes tireoidianaas. Os laudos anatomopatológicos, pacientes manejados cirurgicamente com consulta intra-operatória entre janeiro de 1993 e maio de 1998, foram revistos. Comparou-se o diagnóstico intra-operatório com o diagnóstico definitivo do material incluído em parafina. Estudo estatístico da acurácia, sensibilidade, especificidade, valor preditivo positivo e negativo foi obtido. Os casos diagnosticados como suspeitos foram excluídos da análise estatística. A análise revelou acurácia de 88,58 por cento sensibilidade de 64,44 por cento, especificidade de 96,4 por cento, valor preditivo positivo de 85,29 por cento e valor preditivo negativo de 89,33 por cento. Os casos diagnosticados intra-operatoriamente como suspeitos foram responsáveis por 8,4 por cento dos diagnósticos, destes 68,75 por cento revelaram-se malignos posteriormente. Este estudo demonstra que apesar da alta especificidade, este método apresenta limitaçäo quando utilizado na avaliaçäo da glândula tireóide. Os principais fatores limitantes säo: (1) dificuldade na detecçäo de invasäo vascular ou capsular; (2) avaliaçäo tecidual restrita no exame per-operatório e (3) atipias nucleares em tireóide näo implicam em malignidade.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide , CongelamentoRESUMO
Propylthiouracil is widely used to treat patients with hyperthyroidism. However, propylthiouracil-induced hepatitis is an uncommon entity. The case of a 15-year-old boy treated with propylthiouracil for hyperthyroidism who developed a cholestatic acute hepatitis is reported. Viral, metabolic and autoimmune liver diseases were excluded and liver biopsy showed a pattern suggestive of drug-induced cholestatic hepatitis. After discontinuing the drug, there was a progressive resolution of symptoms and normalization of liver biochemical tests. Despite its rarity, patients receiving propylthiouracil are exposed to develop severe hepatotoxicity
Assuntos
Humanos , Masculino , Adolescente , Antitireóideos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Colestase Intra-Hepática/diagnóstico , Propiltiouracila/efeitos adversos , Doença Aguda , Antitireóideos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/patologia , Colestase Intra-Hepática/patologia , Hipertireoidismo/tratamento farmacológico , Testes de Função Hepática , Propiltiouracila/uso terapêuticoRESUMO
A imunohistoquímica (IHQ) é um método diagnóstico que tem como objetivo detectar um antígeno tissular ou celular através da utilizaçäo de um anticorpo específico dirigido contra este componente celular. A sua popularizaçäo trouxe grande auxílio diagnóstico em patologia cirúrgica. Com a finalidade de avaliar a nossa experiência no diagnóstico imunohistoquímico, estudamos os 1856 casos enviados à Unidade de IHQ do SAP-HNSGno período de (1988-1997). Todos os casos foram submetidos aos métodos de marcaçäo pela peroxidase-anti-peroxidase ou avidina-biotina-peroxidase. A IHQ contribuiu para a definiçäo diagnóstica em 984 casos (53 por cento); contribuiu para a complementaçäo diagnóstica em 714 casos (5,9 por cento) e propôs um diagnóstico insuspeitado em 48 casos (2,6 por cento). Nos casos em que näo contribuiu, a fixaçäo inadequada do tecido foi uma das principais responsáveis pela falha da técnica. A análise desses dados demonstra que o IHQ é fundamental para a definiçäo e complementaçäo do diagnstico histológico