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1.
BMC Complement Med Ther ; 23(1): 301, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37626388

RESUMO

BACKGROUND: Açaí, a Brazilian native fruit, has already been demonstrated to play a role in the progress of breast cancer and cardiotoxicity promoted by chemotherapy agents. Thus, the present study aimed to evaluate the combined use of açaí and the FAC-D chemotherapy protocol in a breast cancer model in vivo. METHODS: Mammary carcinogenesis was induced in thirty female Wistar rats by subcutaneous injection of 25 mg/kg 7,12-dimethylbenzanthracene (DMBA) in the mammary gland. After sixty days, the rats were randomized into two groups: treated with 200 mg/kg of either açaí extract or vehicle, via gastric tube for 45 consecutive days. The FAC-D protocol was initiated after 90 days of induction by intraperitoneal injection for 3 cycles with a 7-day break each. After treatment, blood was collected for haematological and biochemical analyses, and tumours were collected for macroscopic and histological analyses. In the same way, heart, liver, and kidney samples were also collected for macroscopic and histological analyses. RESULTS: Breast cancer was found as a cystic mass with a fibrotic pattern in the mammary gland. The histological analysis showed an invasive carcinoma area in both groups; however, in the saline group, there was a higher presence of inflammatory clusters. No difference was observed regarding body weight, glycaemia, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and urea in either group. However, açaí treatment decreased creatine kinase (CK), creatine kinase MB (CKMB), troponin I and C-reactive protein levels and increased the number of neutrophils and monocytes. Heart histopathology showed normal myocardium in the açaí treatment, while the saline group presented higher toxicity effects with loss of architecture of cardiac tissue. Furthermore, the açaí treatment presented greater collagen distribution, increased hydroxyproline concentration and lower H2AX immunostaining in the heart samples. CONCLUSION: Açaí decreased the number of inflammatory cells in the tumor environment and exhibited protection against chemotherapy drug cardiotoxicity with an increased immune response in animals. Thus, açaí can be considered a promising low-cost therapeutic treatment that can be used in association with chemotherapy agents to avoid heart damage.


Assuntos
Euterpe , Neoplasias , Feminino , Animais , Ratos , Ratos Wistar , Cardiotoxicidade , Coração , Creatina Quinase
2.
Mol Cell Endocrinol ; 564: 111883, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36736881

RESUMO

This study investigated the mechanism of action of clotrimazole (CTZ) and its adverse effects in a model of endometriosis. After autologous endometrial implantation, 18 rats were randomized into two treatment groups: 200 mg/kg CTZ or vehicle for 15 consecutive days. The lesion growth, implant size, glandular atrophy, nitric oxide (NO) serum levels, number of macrophage cells and inducible nitric oxide synthase (iNOS) immunoreactivity were significantly reduced in the CTZ group compared with the control. CTZ (p < 0.05) reduced the lipid peroxidation and protein carbonylation levels in the liver but did not alter the superoxide dismutase (SOD), glutathione (GSH) or glutathione S-transferase (GST) levels in the brain; however, the drug significantly reduced SOD activity and enhanced GST activity in the liver. These results suggest that CTZ interferes with reactive nitrogen species production by downregulating iNOS expression and thus enhances the antioxidant system to promote atrophy and regression of endometriotic lesions, without adverse effects on the brain and/or liver.


Assuntos
Clotrimazol , Endometriose , Feminino , Humanos , Ratos , Animais , Óxido Nítrico Sintase Tipo II/metabolismo , Clotrimazol/farmacologia , Estresse Oxidativo , Antioxidantes/metabolismo , Glutationa/metabolismo , Superóxido Dismutase/metabolismo , Peroxidação de Lipídeos , Óxido Nítrico/metabolismo , Biomarcadores/metabolismo
3.
Appl Magn Reson ; 54(8): 779-791, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38707765

RESUMO

The viscosity measurements are of clinical significance for evaluation of the potential pathological conditions of biological lubricants such as synovial fluids of joints, and for formulation and characterization of peptide- and protein-based biotherapeutics. Due to inherent potential therapeutic activity, protein drugs have proven to be one of the most efficient therapeutic agents in treatment of several life-threatening disorders, such as diabetes and autoimmune diseases. However, home-use applications for treating chronic inflammatory diseases, such as diabetes and rheumatoid arthritis, necessitate the development of high-concentration insulin and monoclonal antibodies formulations for patient self-administration. High protein concentrations can affect viscosity of the corresponding drug solutions complicating their manufacture and administration. The measurements of the viscosity of new insulin analogs and monoclonal antibodies solutions under development is of practical importance to avoid unwanted highly viscous, and therefore, painful for injection drug formulations. Recently, we have demonstrated capability of the electron paramagnetic resonance (EPR) viscometry using viscosity-sensitive 13C-labeled trityl spin probe (13C1-dFT) to report the viscosity of human blood, and interstitial fluids measured in various organs in mice ex-vivo and in anesthetized mice, in vivo. In the present work, we demonstrate utility of the EPR viscometry using 13C1-dFT to measure microviscosity of commercial insulin samples, antibodies solution, and human synovial fluids using small microliter volume samples (5-50 µL). This viscometry analysis approach provides useful tool to control formulations and administration of new biopharmaceuticals, and for evaluation of the state of synovial fluids of importance for clinical applications.

4.
Case Rep Endocrinol ; 2022: 6246867, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35812019

RESUMO

Introduction: Pregnancy in transgender men is an area of increasing study due to data showing that pregnancy can occur in this population despite the reduction in fertility that generally accompanies treatment with gender-affirming hormone therapies. Case: In this case, we describe a healthy 21-year-old transgender man who was able to achieve pregnancy without reproductive assistance after stopping his testosterone therapy for 2 months. Discussion. Our case is important as it highlights how little is known in regards to gender-affirming hormone therapy on fertility. While testosterone is known to reduce fertility by inducing anovulation and altering ovarian histology, its long-term effects on conception rates and pregnancy are largely unknown. Some studies demonstrate that transgender men, treated with gender-affirming hormone therapy (GAHT), including testosterone, have similar oocyte quantity and quality, as well as similar ovarian reserve, when compared to cisgender women, suggesting that resumption of fertility may be possible after cessation of GAHT. Long-term outcomes for the pregnancy and the offspring of those who have been treated with GAHT are unknown. Conclusion: Recent studies have shown that pregnancy is possible for transgender men who desire biological children and have received gender-affirming hormonal therapy without fertility-preserving measures. Further research is needed to help determine rates of fertility, the likelihood of recovery of fertility, conception rates, and long-term pregnancy outcomes. Such information would help guide physicians in providing education and counseling to their transgender patients regarding reproductive options.

5.
Reproduction ; 159(6): 779-786, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32240980

RESUMO

This study aimed to analyse the effects of clotrimazole (CTZ) on estrogen production pathway in endometriosis progression. Experimental endometriosis was induced by autologous transplantation in female Wistar rats, and then the rats were treated with clotrimazole (200 mg/kg) or vehicle, both orally and intraperitoneally, for 15 consecutive days. Serum estrogen levels and vaginal smear analyses were performed and ERα (estrogen receptor alpha) and CYP19 (cytochrome P450 aromatase) levels in the endometriotic lesions were analysed morphologically and immunohistochemically. The clotrimazole group presented a reduction in serum estrogen levels, which were not influenced by the estrous cycle of the animals. The expression of ERα and CYP19 in endometriotic lesions was also reduced in the clotrimazole group compared to the control group. Moreover, clotrimazole treatment decreased the size of the lesions, as confirmed by histological examination, which showed glandular atrophy for both routes of administration. These results suggest that clotrimazole interferes with the estrogen production pathway by downregulating CYP19 and, therefore, reducing serum estrogen levels. Thus, the drug decreases endometriotic lesion size and consequently disease progression.


Assuntos
Aromatase/metabolismo , Clotrimazol/uso terapêutico , Regulação para Baixo/efeitos dos fármacos , Endometriose/tratamento farmacológico , Endométrio/efeitos dos fármacos , Estrogênios/sangue , Animais , Clotrimazol/farmacologia , Modelos Animais de Doenças , Endometriose/metabolismo , Endométrio/metabolismo , Receptor alfa de Estrogênio/metabolismo , Ciclo Estral/efeitos dos fármacos , Feminino , Ratos , Ratos Wistar
6.
Mol Cell Endocrinol ; 486: 1-10, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30753853

RESUMO

This study aimed to analyze galectin-3 importance in endometriotic lesions development and the effect of recombinant Gal-3 carbohydrate recognition domain (Gal3C) in experimental endometriosis treatment. Experimental endometriosis was induced in WT and Gal-3-/- mice. Initially developed lesions were macroscopically and histologically analyzed, including immunohistochemical analysis. Then, WT mice were treated with Gal3C for 15 days. Gal-3 deficiency and Gal3C treatment significantly impaired endometriosis development. A significant decrease in lesions implantation and size, VEGF and VEGFR-2 expression, vascular density and macrophage distribution were observed in Gal-3 absence or inhibition. A greater presence of iNOS positive cells was observed in knockout mice lesions, while the presence of Arginase positive cells was higher in the WT animal lesions. In addition, COX-2 and TGFb1 were reduced by Gal3C treatment. Data showed here indicate a relevant role of Gal-3 in endometriosis development and highlight a target of endometriosis treatment using Gal-3 inhibitor.


Assuntos
Endometriose/tratamento farmacológico , Endometriose/metabolismo , Galectina 3/metabolismo , Terapia de Alvo Molecular , Animais , Biomarcadores/metabolismo , Endométrio/efeitos dos fármacos , Endométrio/patologia , Feminino , Galectina 3/química , Inflamação/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Knockout , Neovascularização Patológica/tratamento farmacológico , Domínios Proteicos , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
7.
PLoS One ; 13(7): e0200101, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29966007

RESUMO

Cancer is an increasingly frequent malignancy worldwide, and despite the advances in drug development, it is still necessary to develop new plant-derived medicines. Euterpe oleracea (açaí) is abundant in South and Central America and has health benefits due to its high levels of phytochemicals, including lignans and polyphenols. The aim of this review was to systematically describe the safety and antitumor effects of açaí in preclinical models using rodents to provide a more comprehensive assessment of açaí for both therapeutic uses and the development of future clinical studies in cancer. Eligible studies were identified using four international databases (PubMed, Medline, Lilacs and SciELO) from their inception date through December 2017. The included studies were analyzed with methodological rigor (QATRS) to enable better quality control for these experimental studies. Sixty publications were identified in the databases, but only 9 articles were eligible: 6 evaluated the pharmacological effects of açaí in animal models of cancer (1 model each of esophageal cancer, urothelial cancer, melanoma and Walker-256 tumor and 2 models of colon cancer), and 3 were toxicological assays using preclinical models with rodents. Overall, 747 animals were analyzed. On a QATRS score scale of 0-20, the quality of the studies ranged from 16 to 20 points. Pulp was the main fraction of açaí administered, and an oral administration route was most common. The açaí dosage administered by gavage ranged from 30 mg/kg to 40,000 mg/kg, and açaí fed in the diet accounted for 2.5% to 5% of the diet. The anticarcinogenic and chemopreventive activities of açaí were observed in all experimental models of cancer and reduced the incidence, tumor cell proliferation, multiplicity and size of the tumors due to the antiinflammatory, antiproliferative and proapoptotic properties of açaí. No genotoxic effects were observed after açaí administration. The results of this review suggest that açaí is safe and can be used as a chemoprotective agent against cancer development. Açaí therapy may be a novel strategy for treating cancer.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Euterpe , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Animais , Humanos
8.
Case Rep Endocrinol ; 2018: 7261264, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29805818

RESUMO

BACKGROUND: Undifferentiated anaplastic carcinoma rarely develops from chronic hyperthyroidism. Although acute hyperthyroidism can develop prior to anaplastic transformation, chronic hyperthyroidism was thought to be a protective measure against thyroid malignancy. METHODS: A 79-year-old female presented acutely to the hospital with dyspnea. She had been taking methimazole for chronic hyperthyroidism due to toxic thyroid nodules, previously biopsied as benign. Upon admission, imaging showed tracheal compression, requiring a total thyroidectomy with tracheostomy for airway management. RESULTS: Pathology demonstrated undifferentiated anaplastic thyroid carcinoma. The patient passed away shortly after hospital discharge. Despite treatment with methimazole for many years, abrupt enlargement of her toxic multinodular goiter was consistent with malignant transformation. Chronic hyperthyroidism and toxic nodules are rarely associated with thyroid malignancy, with only one previous report documenting association with anaplastic thyroid carcinoma. CONCLUSION: Progressive thyroid enlargement and acute worsening of previously controlled hyperthyroidism should promote concern for disease regardless of baseline thyroid function.

9.
BMC Complement Altern Med ; 18(1): 116, 2018 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-29609579

RESUMO

BACKGROUND: Among the processes involved in the breast tumor microenvironment, angiogenesis and inflammation play a central role, and the main factors of these processes are the vascular endothelial growth factor (VEGF), cyclooxygenase 2 (COX-2) and macrophages. Recently, the extract of Euterpe oleracea (açaí), a fruit that is widely found in the Amazon region, already showed antitumorigenic effects in vitro in human breast cancer cell lines. The present study aimed to investigate the effect of açaí on breast cancer using a chemically DMBA (7,12-dimethylbenzanthracene) experimental model. METHODS: One day after initiation of treatment with açaí, mammary carcinogenesis was induced in female Wistar rats using a subcutaneous injection of 25 mg/kg of DMBA in the mammary gland. Forty rats were randomized into two groups: treated with 200 mg/kg of either açaí extract or vehicle, via gastric tube for 16 consecutive weeks. After treatment, the tumor was collected for macroscopic, histological and immunohistochemical (VEGF, vascular endothelial growth factor receptor 2 -VEGFR-2, COX-2 and matrix metalloproteinase -MMP-9) analyses; peritoneal fluid was subjected to flow cytometry (F4-80/MAC-2+) and ELISA immunoassay (VEGF, prostaglandin E2 -PGE2 and interleukin-10 -IL-10). Heart, liver and kidney samples were collected for histological analysis. RESULTS: After 16 weeks of induction, the mammary carcinoma was confirmed by macroscopic and histological evaluation. Survival analysis indicates that açaí increased the survival (P = .0002, long-rank test) and reduced the deaths number (P = .0036, Chi-square test). Açaí treatment decreased the number of inflammatory cells and macrophage positive cells (Mac-2 + F4-80+), as well as promoting a reduction in immunostaining of VEGF, VEGFR-2 and COX-2. The açaí group also exhibited lower concentrations of PGE2, VEGF and IL-10 compared to the control. The histopathological results of the liver and kidneys showed protective effect of açaí, since in the control group, there was an increase in fibrosis, atypical cells and hemorrhagic microenvironment. CONCLUSION: The results of this study demonstrated the antiangiogenic and anti-inflammatory potential of açaí, like due to the decreases of the number of activated macrophages, resulting in the inhibition of DMBA carcinogenicity in breast cancer.


Assuntos
9,10-Dimetil-1,2-benzantraceno/toxicidade , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Carcinógenos/toxicidade , Euterpe/química , Neoplasias Mamárias Experimentais , Extratos Vegetais/farmacologia , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Ratos , Ratos Wistar
10.
Mol Cell Endocrinol ; 476: 17-26, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-29689297

RESUMO

The present work aimed to evaluate molecular, angiogenic and inflammatory changes induced by clotrimazole (CTZ) on endometriosis lesions. For this, thirty female Wistar rats with surgically implanted autologous endometrium were treated with CTZ or vehicle (200 mg/kg) via esophageal gavage for 15 consecutive days. CTZ treatment significantly decreased the growth and the size of the implants, and histological examination indicated regression and atrophy, with no toxicity to the animals. The levels of the angiogenic markers VEGF and VEGFR-2 were significantly decreased in CTZ group. The treatment also promotes a reduction on PGE2 and TNF-α levels. All these effects involve the amelioration of ERK1/2, Akt, AMPK and PERK signaling upon CTZ treatment. In conclusion, CTZ promoted an overall amelioration of endometriosis in a rat model due to the anti-angiogenic properties of the drug. Therefore, our results support the proposal of a clinical trial using CTZ for the treatment of endometriosis.


Assuntos
Clotrimazol/uso terapêutico , Endometriose/tratamento farmacológico , Endométrio/patologia , Próteses e Implantes , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Biomarcadores/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Clotrimazol/efeitos adversos , Clotrimazol/farmacologia , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Endometriose/patologia , Endométrio/irrigação sanguínea , Endométrio/efeitos dos fármacos , Feminino , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/patologia , Ratos Wistar
11.
Case Rep Endocrinol ; 2018: 3652602, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30693115

RESUMO

CONTEXT: To describe a case of invasive ductal carcinoma of the breast in a transgender male receiving testosterone therapy for gender-affirming treatment. CASE DESCRIPTION: A 28-year-old transgender male receiving intramuscular testosterone was found to have a breast mass on ultrasound after self-exam revealed a palpable breast lump. Ultrasound-guided breast biopsy revealed estrogen receptor/progesterone receptor (ER/PR) negative, human epidermal growth factor receptor-2 (HER-2) positive, invasive ductal carcinoma of the left breast. He underwent neoadjuvant and adjuvant chemotherapy along with bilateral mastectomy. At patient request, his testosterone injections were permanently discontinued. CONCLUSION: Fewer than 20 cases of breast cancer in transgender male patients have been reported in medical literature. While studies have shown increased risk of breast cancer in postmenopausal women with higher testosterone levels, data regarding premenopausal women is conflicting and little is known about breast cancer risk in transgender individuals receiving gender-affirming hormone therapy (GAHT), with inconclusive results regarding correlation between testosterone therapy and breast cancer. More research is required to evaluate whether a possible increased risk of breast cancer exists for transgender men receiving gender-affirming therapy.

12.
Artif Cells Nanomed Biotechnol ; 45(3): 598-601, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28211299

RESUMO

The use of monoclonal antibodies and aptamers is growing every single day, as the use of nanoparticle systems. Although most of the products are under investigation, there are a few commercialized products available at the market, for human consume. In this study, we have compared three formulations (aptamer anti-MUC1, monoclonal antibody - Trastuzumab and monoclonal antibodies nanoparticles - PLA/PVA/MMT trastuzumab) to identify their profile as also to understand their behavior into an alive biological system. In this direction the radiolabeling of the products were done and they were all tested in animals (in vivo) in two conditions: healthy rats and breast cancer induced animals. The results showed that the nanoparticle has the better biodistribution profile, followed by the aptamer. We conclude that more studies and a global effort to elucidate the biological behavior of drugs and especially nano-drugs are necessary.


Assuntos
Antineoplásicos/farmacocinética , Aptâmeros de Peptídeos/farmacocinética , Glândulas Mamárias Animais/diagnóstico por imagem , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Cintilografia/métodos , Trastuzumab/farmacocinética , Animais , Antineoplásicos/química , Aptâmeros de Peptídeos/química , Feminino , Humanos , Glândulas Mamárias Animais/metabolismo , Glândulas Mamárias Animais/patologia , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Mucina-1/química , Mucina-1/metabolismo , Nanopartículas/química , Nanopartículas/metabolismo , Poliésteres/química , Álcool de Polivinil/química , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Ratos Wistar , Coloração e Rotulagem/métodos , Tecnécio/química , Tecnécio/farmacocinética , Distribuição Tecidual , Trastuzumab/química
13.
Rio de Janeiro; s.n; 2017. 124 p. ilus, map, tab, graf.
Tese em Português | LILACS, Inca | ID: biblio-943042

RESUMO

O câncer de mama é um problema de saúde pública, com uma alta incidência e sendo a principal causa de morte por câncer em mulheres no Brasil e no mundo. Dentre os processos envolvidos no microambiente tumoral da mama, destacam-se a angiogênese e a inflamação, tendo o fator de crescimento vascular endotelial (VEGF), a ciclo-oxigenase 2 (COX-2) e os macrófagos, como os principais fatores desses processos. Recentemente, o extrato de Euterpe oleracea (açaí), um fruto abundantemente encontrado na região amazônica, apresentou efeito antitumoral in vitro em linhagens de células de carcinoma mamário humano. Desse modo, o presente estudo teve como objetivo estabelecer um modelo experimental de carcinoma mamário e avaliar o potencial efeito farmacológico do açaí no câncer de mama. (...)


Breast cancer is a public health problem with high incidence among women and the leading cause of cancer death in women in Brazil and the world. Among the processes involved in the breast tumor microenvironment, angiogenesis and inflammation plays a central role, with the Vascular Endothelial Growth Factor (VEGF), cyclooxygenase 2 (COX-2) and macrophages, as the main factors of these processes. Recently, the extract of Euterpe oleracea (açaí), a fruit that is widely found in the Amazon region, already showed antitumorigenic effect in vitro in human breast cancer cell lines. The present study aimed to establish a breast carcinoma experimental animal model and investigate the potential pharmacological effect of açaí on breast cancer. Forty female Wistar rats were randomized into two groups: treated with 200 mg/kg of açaí extract or vehicle, via gastric tube for 16 consecutive weeks. (...)


Assuntos
Animais , Ratos , Neoplasias da Mama , Neoplasias da Mama/terapia , Euterpe , Euterpe/toxicidade , Terapêutica , Experimentação Animal , Ensaio de Imunoadsorção Enzimática/métodos , Ratos Wistar
14.
PLoS One ; 11(11): e0166059, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27851787

RESUMO

This study investigated the therapeutic potential of Euterpe oleracea extract (açaí) on the growth and survival of endometriotic lesions using an experimental model. Twenty female Sprague-Dawley rats were randomized into two groups after the implantation and establishment of autologous endometrium onto the peritoneum abdominal wall and treated with 200 mg/kg hydroalcoholic solution extract from açaí stone or vehicle via gastric tube for 30 consecutive days. Body weight, lesion surface areas, histological and immunohistochemistry analyses of vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2) and F4-80 were performed. Levels of VEGF, VEGFR-2, MMP-9 and COX-2 mRNA were measured. Flow cytometry of F4-80 was performed, and ELISA immunoassays measured prostaglandin E2 (PGE2), VEGF and nitric oxide (NO) and concentrations. Macrophage cell line J774.G8 was treated with 10, 20, and 40 µg/mL of açaí for 24, 48 and 72 h, and cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Açaí treatment significantly decreased the implant size, and histological examination indicated atrophy and regression. A reduction in immunostaining and mRNA expression of VEGF, MMP-9 and COX-2 was observed, and F4-80 was lower in the treated group than the control group. The treated group also exhibited lower concentrations of PGE2, VEGF and NO compared to the control group. Macrophages cells treated with 20 and 40 µg/ml of açaí reduced cell viability in about 50% after 24, 48 and 72 h. Our results suggest that açaí effectively suppressed the establishment and growth of endometriotic lesions, and this agent is a promising novel pharmacological therapeutic treatment for endometriosis.


Assuntos
Endometriose/tratamento farmacológico , Euterpe/química , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Linhagem Celular , Endometriose/patologia , Feminino , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Neovascularização Patológica/tratamento farmacológico , Peritônio/efeitos dos fármacos , Peritônio/patologia , Extratos Vegetais/farmacologia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
15.
BMC Complement Altern Med ; 15: 203, 2015 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-26122670

RESUMO

BACKGROUND: Dermal wound healing involves a cascade of complex events including angiogenesis and extracellular matrix remodeling. Several groups have focused in the study of the skin wound healing activity of natural products. The phytomedicine Acheflan®, and its main active constituent is the oil from Cordia verbenacea which has known anti-inflammatory, analgesic and antimicrobial activities. To our knowledge, no investigation has evaluated the effect of Acheflan® in an experimental model of skin wound healing. The present study has explored the wound healing property of Acheflan® and has compared it with topical effectiveness of collagenase and fibrinolysin by using Wistar rat cutaneous excision wound model. METHODS: Animals were divided into four groups: untreated animals are negative control (NC), wounds were treated topically every day with Collagenase ointment (TC), with Fibrinolysin ointment (TF) and with cream Acheflan (TAc). Skin samples were collected on zero, 8th and 15th days after wounding. The healing was assessed by hematoxylin-eosin (HE), picrosirius red, hydoxyproline content and immunohistochemical analysis of the vascular endothelial growth factor (VEGF) and matrix metalloprotease-9 (MMP-9). Statistical analysis was done by ANOVA and Student t-test (p < 0.05). RESULTS: The histological analysis HE of wound in the TAc group was more efficient because it was possible to observe the complete remodeling of the epidermis indicating the regression of lesions compared with the NC. The evaluation of picrosirius staining has demonstrated a significant increase of collagen distribution in the TC and TAc treatments compared with NC and TF groups. These results are corroborated with hydroxyproline content. Skin TC and TAc treated rats have showed an increase of VEGF and MMP-9 compared with NC and TF groups. All parameters were significant (P < 0.05). CONCLUSION: The phytomedicine Acheflan® (oil of Cordia verbenacea) and TC possess higher therapeutic properties for wound healing compared with TF. These ointments seem to accelerate wound healing, probably due to their involvement with the increase of angiogenesis and dermal remodeling.


Assuntos
Extratos Vegetais/farmacologia , Pele , Cicatrização/efeitos dos fármacos , Animais , Imuno-Histoquímica , Ratos , Ratos Wistar , Pele/efeitos dos fármacos , Pele/lesões
16.
Expert Rev Endocrinol Metab ; 9(6): 561-570, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30736194

RESUMO

The emergence of serine-threonine small molecule, multi-targeted kinase inhibitors over the past decade is greatly impacting the therapeutic armamentarium for numerous malignancies, especially thyroid carcinoma. Chief among them are a class of agents referred to as vascular endothelial growth factor signal pathway inhibitors. Sorafenib is a lead compound that has been recently approved by the US FDA for radioactive iodine-refractory differentiated thyroid cancer (DTC). Sorafenib clearly is altering the natural history of DTC. In the largest randomized Phase III study ever conducted in DTC, sorafenib significantly improved progression-free survival compared to placebo (10.8 vs 5.8 months) and had an acceptable and manageable safety profile, though commonly attributed side effects of hand-foot skin reaction, diarrhea and hypertension were more frequent than in other settings. This agent represents a new treatment option for patients with progressive radioactive iodine-refractory DTC.

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