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1.
Porto Biomed J ; 9(1): 244, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38344456

RESUMO

Background: Some patients with breast cancer submitted to breast-conserving surgery might benefit from a postlumpectomy imaging examination previously to radiation therapy. This aims to document the complete removal of cancer and might be accomplished using mammogram with breast and axillary ultrasonography. These modalities study not only the affected side but also the contralateral side. In fact, it is well-documented that women with breast cancer have an increased risk for contralateral breast cancer. Thus, we intended to evaluate the value of postlumpectomy imaging undertaken before adjuvant radiotherapy regarding the evaluation of the contralateral breast and axilla. Methods: In this retrospective study, medical records for patients with breast cancer submitted to breast-conserving surgery and referred to our radiotherapy unit between 2018 and 2019 were reviewed. All patients had to be submitted to bilateral mammogram with breast and axillary ultrasonography previously to radiotherapy. Patients with bilateral disease or with a history of breast cancer were excluded. Results: One thousand two hundred forty patients were analyzed. 19 (1.5%) had suspicious findings for contralateral breast disease, and 8 (0.6%) had a re-excision positive for residual malignancy. Higher age, invasive lobular carcinoma associated or not with lobular carcinoma in situ, and presence of lobular carcinoma in situ were associated with an increased risk for residual disease. Conclusion: Contralateral evaluation as part of postlumpectomy imaging revealed itself useful at detecting contralateral cancer, with some demographic and clinical features being associated with an increased risk for residual disease.

2.
Adv Radiat Oncol ; 9(3): 101404, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38292889

RESUMO

Purpose: Most of radiation oncology centers rely on set-up skin markings for patient setup during treatment delivery. Permanent dark-ink tattooing is the most popular marking method. COMFORTATTOO is a unicentric, randomized trial testing 2 permanent methods: lancets against an electric marking pen (Comfort Marker 2.0, CM). One substudy was undertaken to test if using the CM translates into a cosmesis, fading, or satisfaction benefit compared with the lancets. Methods and Materials: Patients aged 18 years or older referred to our department to receive RT were recruited. They were randomly assigned, in a 1:1 ratio, to receive set-up markings using lancets or CM. This substudy aimed to recruit all the living participants included in the main study. The primary endpoints were tattoos cosmesis, tattoos fading, and patients' satisfaction 6 months after finishing the RT. Cosmetic and fading assessments were scored on a 5-point ascending scale and patients' satisfaction on a 10-point ascending scale. The trial is registered at ClinicalTrials.gov (number NCT05371795). Results: Between April and September 2022, 92 patients were enrolled (45 assigned to lancets and 47 to CM) and assessed for the outcomes. Patients receiving CM had significantly better cosmetic markings, with a median score of 4.4 (vs 3.7 for lancets, P<.001). On the fading assessment, the CM was associated with lower scores compared with the lancets (median score of 1.3 and 3.3, respectively; P<.001). No differences in patients' satisfaction were observed with either method (median score of 10 for both arms, P=.952). Conclusions: Our substudy results demonstrated that, 6 months after the end of RT, the CM produces better cosmetic markings with less fading compared with the lancets. These differences didn't translate into patients' satisfaction superiority toward any method.

3.
Rev. bras. cir. plást ; 37(3): 354-363, jul.set.2022. ilus
Artigo em Inglês, Português | LILACS-Express | LILACS | ID: biblio-1398732

RESUMO

A mão em fenda é uma deformidade congênita rara caracterizada por uma deficiência longitudinal dos raios centrais da mão, podendo estar associada a outras malformações. Devido ao amplo espectro de manifestações, o tratamento de mãos em fenda é desafiador. Este estudo objetiva apresentar as classificações, técnicas cirúrgicas mais indicadas e seguimentos adotados conforme a manifestação clínica. Foi realizada uma pesquisa nos bancos de dados Web of Science, PubMed, Scopus, Cochrane e Embase, descritores e termos relacionados à anomalia mão em fenda típica. Trinta e dois artigos foram incluídos, sendo analisados quanto a classificação da anomalia, classificação da gravidade de expressão, técnicas cirúrgicas e estudos com informações da intervenção cirúrgica adotada para uma coorte de pacientes. Considerando que estudos sobre mão em fenda são diretamente afetados pelas descobertas embriológicas, genéticas e de biologia molecular, diferentes classificações foram descritas e diversos estudos de complementação de técnicas cirúrgicas já existentes foram encontrados. Estudos inovadores são escassos. A padronização na descrição das técnicas e resultados, além de pesquisas de melhor qualidade, poderiam elucidar lacunas ainda existentes em torno das opções de tratamento.


Cleft hand is a rare congenital deformity characterized by a longitudinal deficiency of the central rays of the hand, which may be associated with other malformations. Due to the wide spectrum of manifestations, the treatment is challenging. This study aims to present the most suitable classifications, surgical techniques and follow-up adopted according to the clinical manifestation. A search was performed in the databases Web of Science, PubMed, Scopus, Cochrane and Embase, descriptors and terms related to the hand anomaly in a typical cleft. Thirty-two articles were included and analyzed regarding the classification of the anomaly, classification of the severity of expression, surgical techniques and studies with information on the surgical intervention adopted for a cohort of patients. Considering that studies about cleft hand could be directly affected by embryological, genetic and molecular biology discoveries, different classifications have been described and several studies to complement existing surgical techniques have been found. Innovative studies are scarce. Standardization in the description of techniques and results, in addition to better quality research, could elucidate gaps that still exist around treatment options.

4.
Radiol Bras ; 55(1): 47-53, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35210664

RESUMO

High-resolution ultrasound is the imaging method of choice for the evaluation of thyroid nodules. The method has recently come to be used widely and often, which has increased the rate of thyroid nodule detection. In 2017, the American College of Radiology (ACR) established a risk-stratification system designated the Thyroid Imaging Reporting and Data System (TI-RADS) to be a practical guide for widespread use, with a single lexicon and standardization of ultrasound reports of thyroid nodules. The objective of this study was to present a practical approach, using examples to illustrate the criteria evaluated by the 2017 ACR TI-RADS, in order to help minimize uncertainties regarding its application by sonographers.


A ultrassonografia de alta resolução é a modalidade de escolha para avaliação de imagem dos nódulos tireoidianos, e sua recente aplicação ampla e difusa tornou a detecção de nódulos tireoidianos mais frequentes. O American College of Radiology (ACR) estabeleceu um sistema de estratificação de risco denominado Thyroid Imaging, Reporting and Data System (TI-RADS) para ser um guia prático para utilização ampla com um léxico único e padronização de relatórios ultrassonográficos de nódulos tireoidianos. O objetivo deste trabalho é fazer uma abordagem prática com base em exames para ilustrar e exemplificar os critérios avaliados pelo TI-RADS-ACR 2017, a fim de ajudar a reduzir os pontos de dúvidas de sua aplicação pelos profissionais ultrassonografistas.

5.
Radiol. bras ; 55(1): 47-53, Jan.-Feb. 2022. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1360663

RESUMO

Abstract High-resolution ultrasound is the imaging method of choice for the evaluation of thyroid nodules. The method has recently come to be used widely and often, which has increased the rate of thyroid nodule detection. In 2017, the American College of Radiology (ACR) established a risk-stratification system designated the Thyroid Imaging Reporting and Data System (TI-RADS) to be a practical guide for widespread use, with a single lexicon and standardization of ultrasound reports of thyroid nodules. The objective of this study was to present a practical approach, using examples to illustrate the criteria evaluated by the 2017 ACR TI-RADS, in order to help minimize uncertainties regarding its application by sonographers.


RESUMO A ultrassonografia de alta resolução é a modalidade de escolha para avaliação de imagem dos nódulos tireoidianos, e sua recente aplicação ampla e difusa tornou a detecção de nódulos tireoidianos mais frequentes. O American College of Radiology (ACR) estabeleceu um sistema de estratificação de risco denominado Thyroid Imaging, Reporting and Data System (TI-RADS) para ser um guia prático para utilização ampla com um léxico único e padronização de relatórios ultrassonográficos de nódulos tireoidianos. O objetivo deste trabalho é fazer uma abordagem prática com base em exames para ilustrar e exemplificar os critérios avaliados pelo TI-RADS-ACR 2017, a fim de ajudar a reduzir os pontos de dúvidas de sua aplicação pelos profissionais ultrassonografistas.

7.
J Hand Surg Glob Online ; 3(6): 352-355, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35415587

RESUMO

Bucket-handle injury to the triangular fibrocartilage complex is a rare and poorly described condition in the literature that is not included in the Palmer classification. A young man presented with right wrist torsional trauma while playing sports. He progressed with local pain and limited range of motion with a supination block. Magnetic resonance imaging revealed a bucket-handle injury to the central portion of the triangular fibrocartilage complex with a volar flap, measuring 0.6 cm × 0.6 cm. The patient underwent wrist arthroscopy with debridement, removal of a loose body, and resection of the bucket-handle lesion. In the postoperative period, pain alleviation and a considerable gain in range of motion occurred. The patient was able to resume his participation in sporting activities 3 months after surgery. There is no consensus about the treatment of bucket-handle injuries to the triangular fibrocartilage complex because of the small number of cases described in the literature.

9.
Diabet Foot Ankle ; 8(1): 1270076, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28326158

RESUMO

The aim of this case report was to describe a successful diabetic limb salvage procedure in the treatment of an infected diabetic foot ulcer through a multidisciplinary team approach and complex surgical reconstruction involving a femoral head bone allograft and musculocutaneous latissimus dorsi free flap. The decision to proceed with aggressive staged efforts at diabetic limb salvage should be made only after careful consultation with the patient, his or her family, and the rest of the multidisciplinary healthcare team.

10.
Acta Ortop Bras ; 24(1): 35-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26997912

RESUMO

OBJECTIVE: The aim of this study is to compare micro-sutures commonly used in our midst. METHODS: In this double-blind study, 30 Wistar rats were operated randomly divided into three groups matched according to the suture used (Nylon 10-0, 75micron, brands Microsuture((r)), Polysuture((r)) and Ethicon((r))). We analyzed the number of surgical nodes required, bleeding, surgical time and histological evaluation. RESULTS: There was no significant difference between the amount of stitches of arterial suture per anastomosis. Surgical time was longer in Microsuture((r)) group as compared to Polysuture((r)) (p ≤ 0.05). Bleeding in Microsuture((r)) group was higher when compared to the others (p <0.01). In the histological analysis, the Microsuture((r)) group showed a greater tendency to develop fibrosis and aneurysm in surgical site than the others (p <0.01 and p≤0,05, respectively). Similarly, the Ethicon((r)) group showed less tendency to myointimal proliferation than the rest. (p = 0.025). CONCLUSION: The results confirm the relevance of the choice of surgical thread as an independent determining factor for the success of the procedure, besides serving as a rational subsidy for a better cost-benefit analysis. Level of Evidence I, Experimental Study, Controlled Animal Study.

11.
Acta ortop. bras ; 24(1): 35-38, Jan.-Feb. 2016. tab
Artigo em Inglês | LILACS | ID: lil-771857

RESUMO

ABSTRACT Objective: The aim of this study is to compare micro-sutures commonly used in our midst. Methods: In this double-blind study, 30 Wistar rats were operated randomly divided into three groups matched according to the suture used (Nylon 10-0, 75micron, brands Microsuture(r), Polysuture(r) and Ethicon(r)). We analyzed the number of surgical nodes required, bleeding, surgical time and histological evaluation. Results: There was no significant difference between the amount of stitches of arterial suture per anastomosis. Surgical time was longer in Microsuture(r) group as compared to Polysuture(r) (p ≤ 0.05). Bleeding in Microsuture(r) group was higher when compared to the others (p <0.01). In the histological analysis, the Microsuture(r) group showed a greater tendency to develop fibrosis and aneurysm in surgical site than the others (p <0.01 and p≤0,05, respectively). Similarly, the Ethicon(r) group showed less tendency to myointimal proliferation than the rest. (p = 0.025). Conclusion: The results confirm the relevance of the choice of surgical thread as an independent determining factor for the success of the procedure, besides serving as a rational subsidy for a better cost-benefit analysis. Level of Evidence I, Experimental Study, Controlled Animal Study.

12.
Nutrients ; 6(12): 5572-82, 2014 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-25470379

RESUMO

Despite the antioxidant potential of vitamin A, recent studies reported that chronic retinol ester supplementation can also exert pro-oxidant effects and neurotoxicity in vivo and raises the mortality rates among healthy subjects. Our aim was to find evidence for a safer (i.e., less toxic) molecule with provitamin A activity. Therefore, we investigated whether chronic supplementation of healthy Wistar rats with ß-carotene (0.6, 3, and 6 mg/kg/day) would demonstrate antioxidant characteristics without leading to pro-oxidant side effects in the brain. Total reactive antioxidant potential (TRAP), thiobarbituric reactive species level (TBARS), and total reduced thiol content (SH) were evaluated in plasma. TBARS and SH were additionally evaluated in selected brain regions together with superoxide dismutase (SOD) and catalase (CAT) activity. In the present study, we show that ß-carotene is able to exert antioxidant activity in plasma without triggering pro-oxidant events in the brain, providing evidence that may justify its further evaluation as a safer nutritional supplement with provitamin A activity.


Assuntos
Antioxidantes/administração & dosagem , Encéfalo/efeitos dos fármacos , Suplementos Nutricionais , Vitamina A/administração & dosagem , beta Caroteno/administração & dosagem , Animais , Antioxidantes/efeitos adversos , Biomarcadores/sangue , Encéfalo/metabolismo , Catalase/metabolismo , Suplementos Nutricionais/efeitos adversos , Masculino , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Medição de Risco , Fatores de Risco , Compostos de Sulfidrila/sangue , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fatores de Tempo , Vitamina A/efeitos adversos , beta Caroteno/efeitos adversos
13.
Anticancer Agents Med Chem ; 14(8): 1128-35, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25115457

RESUMO

Cellular and molecular mechanisms related to lung cancer have been extensively studied in recent years, but the availability of effective treatments is still scarce. Hecogenin acetate, a natural saponin presenting a wide spectrum of reported pharmacological activities, has been previously evaluated for its anticancer/antiproliferative activity in some in vivo and in vitro models. Here, we investigated the effects of hecogenin acetate in a human lung cancer cell line. A549 non-small lung cancer cells were exposed to different concentrations of hecogenin acetate and reactive species production, ERK1/2 activation, matrix metalloproteinase expression, cell cycle arrest and cell senescence parameters were evaluated. Hecogenin acetate significantly inhibited increase in intracellular reactive species production induced by H2O2. In addition, hecogenin acetate blocked ERK1/2 phosphorylation and inhibited the increase in MMP-2 caused by H2O2. Treatment with hecogenin acetate induced G0/G1-phase arrest at two concentrations (75 and 100 µM, 74% and 84.3% respectively), and increased the staining of senescence-associated ß -galactosidase positive cells. These data indicate that hecogenin acetate is able to exert anti-cancer effects by modulating reactive species production, inducing cell cycle arrest and senescence and also modulating ERK1/2 phosphorylation and MMP-2 production.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Senescência Celular/efeitos dos fármacos , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Espécies Reativas de Oxigênio/metabolismo , Compostos de Espiro/farmacologia , Esteroides/farmacologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Invasividade Neoplásica/patologia , Estresse Oxidativo/efeitos dos fármacos , Fosforilação
14.
Cell Stress Chaperones ; 19(6): 913-25, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24817194

RESUMO

Expression of intracellular HSP70 is associated with cytoprotective effects against a wide range of stressful stimuli, such as inflammation, oxidative stress, hypoxia, endotoxins, infections, and fever. This cytoprotective effect is mainly attributed to their ability to stabilize protein structures through chaperone-like reversible interactions. HSP70 was recently detected in the extracellular medium, and its presence in serum is commonly associated with pathological situations, where it exerts modulatory effects on cells of the immune system. Previously, we have described the relationship between serum HSP70 levels, oxidant status, and clinical outcome of septic patients; the group of patients with higher prooxidant status and higher serum HSP70 had also higher mortality. To investigate the possible association between oxidized HSP70 and cytoprotection or cell death, we incubated RAW 264.7 macrophages with oxidized HSP70 and evaluated nitrite production, cell proliferation, cell viability, TNF-α release, and phagocytic activity. We also evaluated structural modifications caused by oxidation in purified HSP70. Oxidation of HSP70 altered its protein structure; besides, the modulatory effect of oxidized HSP70 on RAW264.7 cells was different from that of native HSP70. Macrophages treated with oxidized HSP70 presented lower proliferation and viability, lower phagocytic activity, and lower TNF-α release. These results indicate that oxidation of extracellular HSP70 modified its signaling properties, causing alterations on its modulatory effects on macrophage function and viability.


Assuntos
Proteínas de Choque Térmico HSP70/metabolismo , Ativação de Macrófagos , Macrófagos/metabolismo , Animais , Linhagem Celular , Proliferação de Células , Sobrevivência Celular , Proteínas de Choque Térmico HSP70/química , Mediadores da Inflamação/metabolismo , Macrófagos/imunologia , Macrófagos/patologia , Camundongos , Nitritos/metabolismo , Oxirredução , Fagocitose , Conformação Proteica , Transdução de Sinais , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/metabolismo
15.
Oxid Med Cell Longev ; 2013: 791795, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23766861

RESUMO

SCOPE: To elucidate the morphological and biochemical in vitro effects exerted by caffeine, taurine, and guarana, alone or in combination, since they are major components in energy drinks (EDs). METHODS AND RESULTS: On human neuronal SH-SY5Y cells, caffeine (0.125-2 mg/mL), taurine (1-16 mg/mL), and guarana (3.125-50 mg/mL) showed concentration-dependent nonenzymatic antioxidant potential, decreased the basal levels of free radical generation, and reduced both superoxide dismutase (SOD) and catalase (CAT) activities, especially when combined together. However, guarana-treated cells developed signs of neurite degeneration in the form of swellings at various segments in a beaded or pearl chain-like appearance and fragmentation of such neurites at concentrations ranging from 12.5 to 50 mg/mL. Swellings, but not neuritic fragmentation, were detected when cells were treated with 0.5 mg/mL (or higher doses) of caffeine, concentrations that are present in EDs. Cells treated with guarana also showed qualitative signs of apoptosis, including membrane blebbing, cell shrinkage, and cleaved caspase-3 positivity. Flow cytometric analysis confirmed that cells treated with 12.5-50 mg/mL of guarana and its combinations with caffeine and/or taurine underwent apoptosis. CONCLUSION: Excessive removal of intracellular reactive oxygen species, to nonphysiological levels (or "antioxidative stress"), could be a cause of in vitro toxicity induced by these drugs.


Assuntos
Cafeína/farmacologia , Bebidas Energéticas , Neurônios/metabolismo , Neurônios/patologia , Paullinia/química , Espécies Reativas de Oxigênio/metabolismo , Taurina/farmacologia , Antioxidantes/metabolismo , Catalase/metabolismo , Contagem de Células , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sequestradores de Radicais Livres/metabolismo , Humanos , Radical Hidroxila/metabolismo , Espaço Intracelular/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Modelos Biológicos , Degeneração Neural/patologia , Neuritos/efeitos dos fármacos , Neuritos/metabolismo , Neuritos/patologia , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Óxido Nítrico/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismo
16.
ISRN Toxicol ; 2013: 459530, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23724298

RESUMO

Objective. To evaluate antinocicpetive and redox properties of the monoterpenes (+)-camphene, p-cymene, and geranyl acetate in in vivo and in vitro experimental models. Methods. Evaluation of the in vitro antioxidant activity of (+)-camphene, p-cymene, and geranyl acetate using different free radical-generating systems and evaluation of antinociceptive actions by acetic acid-induced writhing and formalin-induced nociception tests in mice. Results. p-Cymene has the strongest antinociceptive effect, but (+)-camphene and geranyl acetate also present significant activity at high doses (200 mg/kg). (+)-Camphene had the strongest antioxidant effect in vitro at TBARS and TRAP/TAR assays and also had the highest scavenging activities against different free radicals, such as hydroxyl and superoxide radicals. Sodium nitroprussiate-derived NO production was enhanced by (+)-camphene. Geranyl acetate and p-cymene also presented some antioxidant effects, but with a varying profile according the free radical-generating system studied. Conclusion. (+)-Camphene, p-cymene, and geranyl acetate may present pharmacological properties related to inflammation and pain-related processes, being potentially useful for development of new therapeutic strategies, with limited possibilities for p-cymene and geranyl acetate.

17.
Cell Signal ; 25(4): 939-54, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23333461

RESUMO

As an essential component of the diet, retinol supplementation is often considered harmless and its application is poorly controlled. However, recent works demonstrated that retinol may induce a wide array of deleterious effects, especially when doses used are elevated. Controlled clinical trials have demonstrated that retinol supplementation increased the incidence of lung cancer and mortality in smokers. Experimental works in cell cultures and animal models showed that retinol may induce free radical production, oxidative stress and extensive biomolecular damage. Here, we evaluated the effect of retinol on the regulation of the receptor for advanced glycation end-products (RAGE) in the human lung cancer cell line A549. RAGE is constitutively expressed in lungs and was observed to be down-regulated in lung cancer patients. A549 cells were treated with retinol doses reported as physiologic (2 µM) or therapeutic (5, 10 or 20 µM). Retinol at 10 and 20 µM increased free radical production, oxidative damage and antioxidant enzyme activity in A549 cells. These doses also downregulated RAGE expression. Antioxidant co-treatment with Trolox®, a hydrophilic analog of α-tocopherol, reversed the effects of retinol on oxidative parameters and RAGE downregulation. The effect of retinol on RAGE was mediated by p38 MAPK activation, as blockade of p38 with PD169316 (10 µM), SB203580 (10 µM) or siRNA to either p38α (MAPK14) or p38ß (MAPK11) reversed the effect of retinol on RAGE. Trolox also inhibited p38 phosphorylation, indicating that retinol induced a redox-dependent activation of this MAPK. Besides, we observed that NF-kB acted as a downstream effector of p38 in RAGE downregulation by retinol, as NF-kB inhibition by SN50 (100 µg/mL) and siRNA to p65 blocked the effect of retinol on RAGE, and p38 inhibitors reversed NF-kB activation. Taken together, our results indicate a pro-oxidant effect of retinol on A549 cells, and suggest that modulation of RAGE expression by retinol is mediated by the redox-dependent activation of p38/NF-kB signaling pathway.


Assuntos
Regulação para Baixo/efeitos dos fármacos , NF-kappa B/metabolismo , Receptores Imunológicos/metabolismo , Vitamina A/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Humanos , Imidazóis/farmacologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Proteína Quinase 11 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 11 Ativada por Mitógeno/genética , Proteína Quinase 11 Ativada por Mitógeno/metabolismo , Proteína Quinase 14 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 14 Ativada por Mitógeno/genética , Proteína Quinase 14 Ativada por Mitógeno/metabolismo , NF-kappa B/antagonistas & inibidores , Oxirredução , Peptídeos/farmacologia , Fosforilação/efeitos dos fármacos , Piridinas/farmacologia , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptor para Produtos Finais de Glicação Avançada , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , alfa-Tocoferol/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/genética
18.
Mol Cell Biochem ; 372(1-2): 127-35, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22983815

RESUMO

The outcome of sepsis occurs due to influence of environmental and genetic factors besides genes variants whose expression support its outcome or not. Oxidative stress is associated to the pathogenicity of sepsis, occurring when there is a reactive species overproduction associated with inflammation. The aim of this study was to characterize the cellular redox status of human peripheral blood mononuclear cells (PBMCs) with either -9Ala (AA) or -9Val (VV) SOD2 genotypes and evaluate their response to oxidative stress induced by lipopolysaccharide (LPS). The PBMCs were isolated from the blood of 30 healthy human volunteers (15 volunteers for each allele) and the following assays were performed: antioxidant enzyme activities (superoxide dismutase; catalase; glutathione peroxidase), total radical-trapping antioxidant parameter, non-enzymatic antioxidant capacity (total antioxidant reactivity), and quantification of conjugated dienes (lipid peroxidation). At basal conditions (i.e., not stimulated by LPS), cells from 47C allele carriers showed higher activities of CAT and SOD, as well as higher TAR compared to 47T allele. However, when 47CC cells were challenged with LPS, we observed a higher shift toward a pro-oxidant state compared to 47TT cells. The CAT activity and lipid peroxidation were increased in cells with both alleles, but SOD activity increased significantly only in 47TT cells. These results demonstrate that SOD2 polymorphisms are associated with different cellular redox environments at both basal and LPS-stimulated states, and identification of this polymorphism may be important for a better understanding of pro-inflammatory conditions.


Assuntos
Leucócitos Mononucleares/enzimologia , Lipopolissacarídeos/farmacologia , Polimorfismo de Nucleotídeo Único , Superóxido Dismutase/genética , Adulto , Substituição de Aminoácidos , Catalase , Células Cultivadas , Feminino , Radicais Livres/metabolismo , Glutationa Peroxidase/metabolismo , Heterozigoto , Humanos , Líquido Intracelular/enzimologia , Leucócitos Mononucleares/imunologia , Peroxidação de Lipídeos , Masculino , Nitritos/metabolismo , Estresse Oxidativo , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
19.
Eur J Pharm Biopharm ; 83(2): 156-67, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23219677

RESUMO

In this study, we developed curcumin-loaded lipid-core nanocapsules (C-LNCs) in an attempt to improve the antiglioma activity of this polyphenol. C-LNC showed nanotechnological properties such as nanometric mean size (196 nm), 100% encapsulation efficiency, polydispersity index below 0.1, and negative zeta potential. The in vitro release assays demonstrated a controlled release of curcumin from lipid-core nanocapsules. In C6 and U251MG gliomas, C-LNC promoted a biphasic delivery of curcumin: the first peak occurred early in the treatment (1-3h), whereas the onset of the second phase occurred after 48 h. In C6 cells, the cytotoxicity of C-LNC was comparable to non-encapsulated curcumin only after 96 h, whereas C-LNCs were more cytotoxic than non-encapsulated curcumin after 24h of incubation in U251MG. Induction of G2/M arrest and autophagy were observed in C-LNC as well as in free-curcumin treatments. In rats bearing C6 gliomas, C-LNC (1.5mg/kg/day, i.p.) decreased the tumor size and malignance and prolonged animal survival when compared to same dose of non-encapsulated drug. In addition, serum markers of tissue toxicity and histological parameters were not altered. Considered overall, the data suggest that the nanoencapsulation of curcumin in LNC is an important strategy to improve its pharmacological efficacy in the treatment of gliomas.


Assuntos
Curcumina/administração & dosagem , Glioma/tratamento farmacológico , Lipídeos/administração & dosagem , Nanocápsulas/administração & dosagem , Animais , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Masculino , Tamanho da Partícula , Ratos , Ratos Wistar
20.
Oxid Med Cell Longev ; 2012: 819310, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23259029

RESUMO

This study evaluated the oxidative stress through enzymatic and nonenzymatic biomarkers in diabetic patients with and without hypertension and prediabetics. The SOD and CAT (in erythrocytes) and GPx (in plasma) enzymatic activities, plasma levels of lipid peroxidation, and total thiols were measured in the blood of 55 subjects with type 2 diabetes and 38 subjects without diabetes (9 pre-diabetics and 29 controls) aged 40-86 years. The total SOD activity and the lipid peroxidation were higher in diabetics compared to nondiabetics. In stratified groups, the total SOD activity was different for the hypertensive diabetics compared to the prediabetics and normotensive controls. Lipid peroxidation was significantly higher in both groups of diabetics (hypertensive and normotensive) compared to prediabetic groups and hypertensive and normotensive controls. There was no significant difference in the CAT and GPx activities, as well as in the concentration of total thiols in the groups studied. Present data strongly suggest the involvement of oxidative stress in the pathophysiology of diabetes, revealing that the increased lipid peroxidation has a close relationship with high glucose levels, as observed by the fasting glucose and HbA1c levels. The results evidence the correlation between lipid peroxidation and DM, irrespective of the presence of hypertension.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/enzimologia , Peroxidação de Lipídeos , Estresse Oxidativo , Superóxido Dismutase/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antioxidantes/metabolismo , Glicemia/metabolismo , Catalase/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Jejum/sangue , Feminino , Glutationa Peroxidase/sangue , Hemoglobinas Glicadas/metabolismo , Humanos , Hipertensão/sangue , Hipertensão/complicações , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
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