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1.
Med Oncol ; 39(2): 24, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34982270

RESUMO

This work describes the effects of immunotherapy with Protein Aggregate Magnesium-Ammonium Phospholinoleate-Palmitoleate Anhydride in the treatment of non-muscle invasive bladder cancer in an animal model. NMIBC was induced by treating female Fischer 344 rats with N-methyl-N-nitrosourea. After treatment with MNU, the rats were distributed into four experimental groups: Control (without MNU) group, MNU (cancer) group, MNU-BCG (Bacillus Calmette-Guerin) group, and MNU-P-MAPA group. P-MAPA intravesical treatment was more effective in histopathological recovery from cancer state in relation to BCG treatment. Western blot assays showed an increase in the protein levels of c-Myc, COUP-TFII, and wild-type p53 in P-MAPA-treated rats in relation to BCG-treated rats. In addition, rats treated with P-MAPA intravesical immunotherapy showed the highest BAX protein levels and the lowest proliferation/apoptotic ratio in relation to BCG-treated rats, pointing out a preponderance of apoptosis. P-MAPA intravesical treatment increased the wild-type p53 levels and enhanced c-Myc/COUP-TFII-induced apoptosis mediated by p53. These alterations were fundamental for histopathological recovery from cancer and for suppress abnormal cell proliferation. This action of P-MAPA on apoptotic pathways may represent a new strategy for treating NMIBC.


Assuntos
Agentes de Imunomodulação/administração & dosagem , Ácidos Linoleicos/administração & dosagem , Ácidos Oleicos/administração & dosagem , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia , Administração Intravesical , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Imunoterapia/métodos , Invasividade Neoplásica , Proteínas Proto-Oncogênicas c-myc/metabolismo , Ratos Endogâmicos F344 , Proteínas Repressoras/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Proteína X Associada a bcl-2/metabolismo
3.
Lipids ; 55(2): 151-162, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32040876

RESUMO

Nonalcoholic steatohepatitis (NASH) is a common liver disease that occurs in both alcoholics and nonalcoholics. Oxidative stress is a possible causative factor for liver diseases including NASH. Gut microorganisms, especially lactic acid bacteria, can produce unique fatty acids, including hydroxy, oxo, conjugated, and partially saturated fatty acids. The oxo fatty acid 10-oxo-11(E)-octadecenoic acid (KetoC) provides potent cytoprotective effects against oxidative stress through activation of Nrf2-ARE pathway. The aim of this study was to explore the preventive and therapeutic effects of gut microbial fatty acid metabolites in a NASH mouse model. The mice were divided into 3 experimental groups and fed as follows: (1) high-fat diet (HFD) (2) HFD mixed with 0.1% KetoA (10-oxo-12(Z)-octadecenoic acid), and (3) HFD mixed with 0.1% KetoC. After 3 weeks of feeding, plasma parameters, liver histology, and mRNA expression of multiple genes were assessed. There was hardly any difference in fat accumulation in the histological study; however, no ballooning occurred in 2/5 mice of KetoC group. Bridging fibrosis was not observed in the KetoA group, although KetoA administration did not significantly suppress fibrosis score (p = 0.10). In addition, KetoC increased the expression level of HDL related genes and HDL cholesterol levels in the plasma. These results indicated that KetoA and KetoC may partly affect the progression of NASH in mice models.


Assuntos
Bactérias/metabolismo , Redes Reguladoras de Genes/efeitos dos fármacos , Ácidos Linoleicos/administração & dosagem , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Animais , HDL-Colesterol/sangue , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Progressão da Doença , Microbioma Gastrointestinal , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Ácidos Linoleicos/sangue , Ácidos Linoleicos/química , Ácidos Linoleicos/farmacologia , Masculino , Camundongos , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/genética , Estresse Oxidativo/efeitos dos fármacos , Estreptozocina/efeitos adversos
4.
Menopause ; 27(2): 194-198, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31738736

RESUMO

OBJECTIVE: The purpose of this study was to determine the efficacy and safety of evening primrose oil on women's psychological symptoms during menopause. METHODS: A double-blinded randomized placebo-controlled trial carried out from September 2018 to February 2019 in Bandar Abbas, Iran. Eligible women randomly received either 1,000 mg of evening primrose oil capsules daily or matching placebo for 8 weeks. The Main outcome measures were psychological symptoms based on the psychological subscale of the Menopause Rating Scale. Independent samples t test was used for intergroup comparisons and paired samples t test for pre- and post-treatment comparisons. P ≤ 0.05 was considered statistically significant. RESULTS: The 8-week treatment was completed by 189 women. The mean baseline psychological score did not differ among the two groups. After intervention, the psychological score, however, differed significantly among groups (P < 0.01). To distinguish the effect of evening primrose oil, we compared the reduction in the psychological score in each group. Regarding mean differences of the psychological score in both groups, there was a prominent alleviation in the intervention group mean difference: -3.44 (95% confidence interval of difference: -4.01 to -1.20) (P < 0.01). In addition, only one patient reported gastric upset in the intervention group. CONCLUSIONS: This study could provide evidence regarding the potential benefits of evening primrose oil for the psychological symptoms of postmenopausal women. Longer trials are necessary to make more reliable decisions about the use of evening primrose oil and its safety in clinical practice.


Assuntos
Ácidos Linoleicos/administração & dosagem , Transtornos Mentais/tratamento farmacológico , Óleos de Plantas/administração & dosagem , Pós-Menopausa/psicologia , Ácido gama-Linolênico/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Irã (Geográfico) , Transtornos Mentais/etiologia , Pessoa de Meia-Idade , Oenothera biennis , Escalas de Graduação Psiquiátrica , Resultado do Tratamento
5.
Nano Lett ; 19(6): 3505-3518, 2019 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-31034238

RESUMO

Despite recent advances in enhancing photodynamic therapy efficacy, high-efficiency reactive oxygen species (ROS)-based therapy approach, especially in malignancy tumor treatment, remains challenging. Relieving the hypoxia of tumor tissue has been considered to be an attractive strategy for enhancing ROS-based treatment effect. Nevertheless, it is frequently neglected that the hypoxic regions are usually located deep in the tumors and therefore are usually inaccessible. To address these limitations, herein we constructed a sequential intercellular delivery system (MFLs/LAOOH@DOX) that consists of a membrane fusion liposomes (MFLs) doped with linoleic acid hydroperoxide (LAOOH) in the lipid bilayer and antitumor doxorubicin (DOX) encapsulated inside. In this report, LAOOH, one of the primary products of lipid peroxidation in vivo, was selected as ROS-generated agent herein, which depends on Fe2+ rather than oxygen and other external stimuli to produce ROS. Upon the enhanced permeation and retention effect, MFLs/LAOOH@DOX first fused with tumor cell membranes in the perivascular region in synchrony with selective delivery of LAOOH into the plasma membrane and the on-demand intracellular release of DOX. By hitchhiking with extracellular vesicles, LAOOH, as a cell membrane natural ingredient, spread gradually to neighboring cells and throughout the entire tumor eventually. Combined with subsequent administration of nano Fe3O4, ROS was specifically generated on the tumor cell membrane by LAOOH throughout the tumor tissues. This study offers a new method to enhance ROS-based antitumor treatment efficiency.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/análogos & derivados , Ácidos Linoleicos/administração & dosagem , Peróxidos Lipídicos/administração & dosagem , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Animais , Antibióticos Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos , Feminino , Ácidos Linoleicos/uso terapêutico , Peróxidos Lipídicos/uso terapêutico , Camundongos Endogâmicos BALB C , Neoplasias/metabolismo , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/uso terapêutico , Peixe-Zebra
6.
Dermatol Ther ; 31(4): e12599, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29642279

RESUMO

Hidradenitis suppurativa (HS) is a chronic disorder of terminal follicular epithelium in the apocrine gland-bearing areas. The long term therapy is based mainly on topical and/or systemic antibiotic use that could result in antibiotic resistance. The aim of our study was to present the real-life experience based on the efficacy and tolerability of a novel lotion containing triethyl-citrate, ethyl-linoleate, and g-peptide-10 in the treatment of mild to moderate HS that has already shown effectiveness in acne treatment. This was an open-label study on 30 patients of both sexes affected by HS. Patients were divided into two groups: 15 with Hurley I and 15 with Hurley II-III. The subjects were treated with the topical lotion, three-times-daily for eight weeks, with control at 4 (T1 ) and eight weeks (T2 ). Any other concomitant treatment (both topical and/or systemic) was avoided during study period. Improvement was observed in both Sartorius score grading system and inflammatory and noninflammatory lesion counts. The novel lotion has proved to be effective and well-tolerated topical agent alone or in association with other topical and/or systemic tratments in HS, without side effects.


Assuntos
Citratos/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Hidradenite Supurativa/tratamento farmacológico , Ácidos Linoleicos/administração & dosagem , Peptídeos/administração & dosagem , Pele/efeitos dos fármacos , Administração Cutânea , Adolescente , Adulto , Criança , Citratos/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Feminino , Hidradenite Supurativa/diagnóstico , Humanos , Ácidos Linoleicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Peptídeos/efeitos adversos , Indução de Remissão , Índice de Gravidade de Doença , Pele/patologia , Creme para a Pele , Resultado do Tratamento , Adulto Jovem
7.
J Ovarian Res ; 11(1): 8, 2018 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-29343281

RESUMO

BACKGROUND: Toll-like receptors (TLRs) are transmembrane proteins expressed on the surface of ovarian cancer (OC) and immune cells. Identifying the specific roles of the TLR-mediated signaling pathways in OC cells is important to guide new treatments. Because immunotherapies have emerged as the adjuvant treatment for patients with OC, we investigated the effect of a promising immunotherapeutic strategy based on protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride (P-MAPA) combined with cisplatin (CIS) on the TLR2 and TLR4 signaling pathways via myeloid differentiation factor 88 (MyD88) and TLR-associated activator of interferon (TRIF) in an in vivo model of OC. METHODS: Tumors were chemically induced by a single injection of 100 µg of 7,12-dimethylbenz(a)anthracene (DMBA) directly under the left ovarian bursa in Fischer 344 rats. After the rats developed serous papillary OC, they were given P-MAPA, CIS or the combination P-MAPA+CIS as therapies. To understand the effects of the treatments, we assessed the tumor size, histopathology, and the TLR2- and TLR4-mediated inflammatory responses. RESULTS: Although CIS therapy was more effective than P-MAPA in reducing the tumor size, P-MAPA immunotherapy significantly increased the expressions of TLR2 and TLR4. More importantly, the combination of P-MAPA with CIS showed a greater survival rate compared to CIS alone, and exhibited a significant reduction in tumor volume compared to P-MAPA alone. The combination therapy also promoted the increase in the levels of the following OC-related proteins: TLR4, MyD88, TRIF, inhibitor of phosphorylated NF-kB alpha (p-IkBα), and nuclear factor kappa B (NF-kB p65) in both cytoplasmic and nuclear sites. While P-MAPA had no apparent effect on tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6, it seems to increase interferon-γ (IFN-γ), which may induce the Thelper (Th1)-mediated immune response. CONCLUSION: Collectively, our results suggest that P-MAPA immunotherapy combined with cisplatin could be considered an important therapeutic strategy against OC cells based on signaling pathways activated by TLR4.


Assuntos
Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Imuno-Histoquímica , Ácidos Linoleicos/administração & dosagem , NF-kappa B , Gradação de Tumores , Compostos Organofosforados/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/imunologia , Ratos , Receptor 2 Toll-Like/metabolismo , Carga Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Endocr Res ; 43(1): 1-10, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28742409

RESUMO

PURPOSE OF THE STUDY: There was inconsistent evidence about the benefit of vitamin D plus evening primrose oil (EPO) supplement intake on lipid profiles and reduced oxidative stress among women with polycystic ovary syndrome (PCOS). The current study was performed to evaluate the effects of vitamin D plus EPO supplementation on lipid profiles and biomarkers of oxidative stress in vitamin D-deficient women with PCOS. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled trial was performed among 60 vitamin D-deficient women with PCOS. Participants were randomly assigned into two groups to receive either 1000 IU vitamin D3 plus 1000 mg EPO (n = 30) or placebo (n = 30) for 12 weeks. Metabolic profiles were quantified at baseline and after the 12-week intervention. RESULTS: Compared with the placebo group, women in vitamin D and EPO co-supplementation group had significant increases in serum 25-hydroxyvitamin D (25(OH)D) (+10.7 ± 8.4 vs. -0.5 ± 1.6 ng/mL, p < 0.001) and plasma total glutathione (GSH) (+62.7 ± 58.0 vs. -0.7 ± 122.7 µmol/L, p = 0.01), while there were significant decreases in triglycerides (-7.3 ± 23.8 vs. +6.9 ± 26.3 mg/dL, p = 0.03), very low-density lipoprotein (VLDL) cholesterol levels (-1.5 ± 4.7 vs. +1.4 ± 5.3 mg/dL, p = 0.03), total/high-density lipoprotein cholesterol ratio (-0.3 ± 0.4 vs. -0.02 ± 0.4, p = 0.02), and malondialdehyde (MDA) concentration (-0.4 ± 0.4 vs. +0.5 ± 1.8 µmol/L, p = 0.008). CONCLUSION: Overall, vitamin D and EPO co-supplementation for 12 weeks among vitamin D-deficient women with PCOS significantly improved triglycerides, VLDL cholesterol, GSH, and MDA levels.


Assuntos
Colecalciferol/farmacologia , Suplementos Nutricionais , Hipolipemiantes/farmacologia , Ácidos Linoleicos/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Estresse Oxidativo/efeitos dos fármacos , Óleos de Plantas/farmacologia , Síndrome do Ovário Policístico , Deficiência de Vitamina D , Vitamina D/análogos & derivados , Ácido gama-Linolênico/farmacologia , Adulto , Biomarcadores/sangue , Colecalciferol/administração & dosagem , HDL-Colesterol/sangue , HDL-Colesterol/efeitos dos fármacos , VLDL-Colesterol/sangue , VLDL-Colesterol/efeitos dos fármacos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Glutationa/sangue , Glutationa/efeitos dos fármacos , Humanos , Hipolipemiantes/administração & dosagem , Ácidos Linoleicos/administração & dosagem , Malondialdeído/sangue , Oenothera biennis , Óleos de Plantas/administração & dosagem , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/tratamento farmacológico , Triglicerídeos/sangue , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/tratamento farmacológico , Adulto Jovem , Ácido gama-Linolênico/administração & dosagem
10.
BMC Cancer ; 16: 422, 2016 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-27389279

RESUMO

BACKGROUND: The new modalities for treating patients with non-muscle invasive bladder cancer (NMIBC) for whom BCG (Bacillus Calmette-Guerin) has failed or is contraindicated are recently increasing due to the development of new drugs. Although agents like mitomycin C and BCG are routinely used, there is a need for more potent and/or less-toxic agents. In this scenario, a new perspective is represented by P-MAPA (Protein Aggregate Magnesium-Ammonium Phospholinoleate-Palmitoleate Anhydride), developed by Farmabrasilis (non-profit research network). This study detailed and characterized the mechanisms of action of P-MAPA based on activation of mediators of Toll-like Receptors (TLRs) 2 and 4 signaling pathways and p53 in regulating angiogenesis and apoptosis in an animal model of NMIBC, as well as, compared these mechanisms with BCG treatment. RESULTS: Our results demonstrated the activation of the immune system by BCG (MyD88-dependent pathway) resulted in increased inflammatory cytokines. However, P-MAPA intravesical immunotherapy led to distinct activation of TLRs 2 and 4-mediated innate immune system, resulting in increased interferons signaling pathway (TRIF-dependent pathway), which was more effective in the NMIBC treatment. Interferon signaling pathway activation induced by P-MAPA led to increase of iNOS protein levels, resulting in apoptosis and histopathological recovery. Additionally, P-MAPA immunotherapy increased wild-type p53 protein levels. The increased wild-type p53 protein levels were fundamental to NO-induced apoptosis and the up-regulation of BAX. Furthermore, interferon signaling pathway induction and increased p53 protein levels by P-MAPA led to important antitumor effects, not only suppressing abnormal cell proliferation, but also by preventing continuous expansion of tumor mass through suppression of angiogenesis, which was characterized by decreased VEGF and increased endostatin protein levels. CONCLUSIONS: Thus, P-MAPA immunotherapy could be considered an important therapeutic strategy for NMIBC, as well as, opens a new perspective for treatment of patients that are refractory or resistant to BCG intravesical therapy.


Assuntos
Fatores Imunológicos/administração & dosagem , Ácidos Linoleicos/administração & dosagem , Neovascularização Patológica/tratamento farmacológico , Compostos Organofosforados/administração & dosagem , Receptores Toll-Like/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Animais , Vacina BCG/administração & dosagem , Vacina BCG/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Imunoterapia/métodos , Ácidos Linoleicos/farmacologia , Invasividade Neoplásica , Neoplasias Experimentais , Neovascularização Patológica/metabolismo , Compostos Organofosforados/farmacologia , Ratos , Regulação para Cima , Neoplasias da Bexiga Urinária/irrigação sanguínea , Neoplasias da Bexiga Urinária/metabolismo
11.
Int J Clin Exp Pathol ; 8(5): 4427-43, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26191134

RESUMO

The present study describes the role of the ubiquitin ligase Siah-2 and corepressor N-CoR in controlling androgen receptor (AR) and estrogen receptors (ERα and ERß) signaling in an appropriate animal model (Fischer 344 female rats) of non-muscle invasive bladder cancer (NMIBC), especially under conditions of anti-androgen therapy with flutamide. Furthermore, this study describes the mechanisms of a promising therapeutic alternative for NMIBC based on Protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride (P-MAPA) intravesical immunotherapy combined with flutamide, involving the interaction among steroid hormone receptors, their regulators and Toll-like receptors (TLRs). Our results demonstrated that increased Siah-2 and AR protein levels and decreased N-CoR, cytochrome P450 (CYP450) and estrogen receptors levels played a critical role in the urothelial carcinogenesis, probably leading to escape of urothelial cancer cells from immune system attack. P-MAPA immunotherapy led to distinct activation of innate immune system TLRs 2 and 4-mediated, resulting in increase of interferon signaling pathway, which was more effective in recovering the immunosuppressive tumor immune microenvironment and in recovering the bladder histology features than BCG (Bacillus Calmette-Guerin) treatments. The AR blockade therapy was important in the modulating of downstream molecules of TLR2 and TLR4 signaling pathway, decreasing the inflammatory cytokines signaling and enhancing the interferon signaling pathway when associated with P-MAPA. Taken together, the data obtained suggest that interferon signaling pathway activation and targeting AR and Siah-2 signals by P-MAPA intravesical immunotherapy alone and/ or in combination with AR blockade may provide novel therapeutic approaches for NMIBC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Imunoterapia/métodos , Neoplasias da Bexiga Urinária/patologia , Administração Intravesical , Antagonistas de Androgênios/administração & dosagem , Animais , Western Blotting , Modelos Animais de Doenças , Feminino , Flutamida/administração & dosagem , Ácidos Linoleicos/administração & dosagem , Coativadores de Receptor Nuclear/metabolismo , Compostos Organofosforados/administração & dosagem , Ratos , Ratos Endogâmicos F344 , Receptores Androgênicos/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
12.
Sci Rep ; 4: 6550, 2014 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-25298091

RESUMO

A non-invasive method to characterize human mesenchymal stromal cells during adipogenic differentiation was developed for the first time. Seven fatty acid methyl esters (FAMEs), including methyl laurate, methyl myristate, methyl palmitate, methyl linoleate, methyl oleate, methyl elaidate and methyl stearate, were used for characterizing adipogenic differentiation using headspace solid-phase microextraction (HS-SPME) which is a very simple and non-invasive method for the extraction of volatile compounds. Glassware was used for culturing mesenchymal stromal cells rather than the common plasticware to minimize contamination by volatile impurities. The optimal SPME fiber was selected by comparing diverse fibers containing two pure liquid polymers (PDMS and PA) and two porous solids (PDMS/DVB and CAR/PDMS). Using optimized procedures, we discovered that seven FAMEs were only detected in adipogenic differentiated mesenchymal stromal cells and not in the mesenchymal stromal cells before differentiation. These data could support the quality control of clinical mesenchymal stromal cell culture in the pharmaceutical industry in addition to the development of many clinical applications using mesenchymal stromal cells.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Tecido Adiposo/citologia , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Lauratos/administração & dosagem , Ácidos Linoleicos/administração & dosagem , Células-Tronco Mesenquimais/citologia , Ácidos Oleicos/administração & dosagem , Palmitatos/administração & dosagem , Microextração em Fase Sólida
13.
Br J Nutr ; 112(7): 1055-64, 2014 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-25192306

RESUMO

Inflammatory bowel diseases (IBD) are characterised by chronic uncontrolled inflammation of intestinal mucosa. Diet and nutritional factors have emerged as possible interventions for IBD. Microalgae are rich sources of n-3 PUFA and derived oxylipins. Oxylipins are lipid mediators involved in the resolution of many inflammatory disorders. The aim of the present study was to investigate the effects of the oxylipin-containing biomass of the microalga Chlamydomonas debaryana and its major oxylipin constituent, (9Z,11E,13S,15Z)-13-hydroxyoctadeca-9,11,15-trienoic acid ((13S)-HOTE), on acute 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. Lyophilised microalgal biomass and (13S)-HOTE were administered by oral route 48, 24 and 1 h before the induction of colitis and 24 h later, and the rats were killed after 48 h. The treatment with the lyophilised microalga and (13S)-HOTE improved body-weight loss and colon shortening, as well as attenuated the extent of colonic damage and increased mucus production. Cellular neutrophil infiltration, with the subsequent increase in myeloperoxidase levels induced by TNBS, were also reduced after the administration of the lyophilised microalga or (13S)-HOTE. The anti-inflammatory effects of these treatments were confirmed by the inhibition of colonic TNF-α production. Moreover, lyophilised microalga or (13S)-HOTE down-regulated cyclo-oxygenase-2 and inducible nitric oxide synthase expression. The present study was the first to show the prophylactic effects of a lyophilised biomass sample of the microalga C. debaryana and the oxylipin (13S)-HOTE on TNBS-induced acute colitis in rats. Our findings suggest that the microalga C. debaryana or derived oxylipins could be used as nutraceuticals in the treatment of the active phase of IBD.


Assuntos
Chlamydomonas/química , Colite/prevenção & controle , Animais , Anti-Inflamatórios , Biomassa , Colite/induzido quimicamente , Colite/patologia , Colo/efeitos dos fármacos , Colo/enzimologia , Colo/metabolismo , Ciclo-Oxigenase 2/análise , Ácidos Graxos Ômega-3/administração & dosagem , Liofilização , Ácidos Linoleicos/administração & dosagem , Masculino , Neutrófilos/patologia , Óxido Nítrico Sintase Tipo II/análise , Oxilipinas/administração & dosagem , Peroxidase/metabolismo , Ratos , Ratos Wistar , Ácido Trinitrobenzenossulfônico , Fator de Necrose Tumoral alfa/biossíntese
14.
J Environ Biol ; 35(4): 635-40, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25004746

RESUMO

This study was carried out to find out the effect of supplying gamma linolenic acid (GLA) on laying performance and egg quality. A hundred twenty of 30 weeks old hyline brown laying hens with 98% of egg production were completely randomized to 4 different treatment groups by 30 hens (the control group fed with the diet containing beef tallow, 3 treatment groups fed with the diet containing corn oil, the diet containing hemp seed oil and the diet containing evening primrose oil, respectively), and their laying performance and egg production were investigated for 5 weeks. Intake of hemp seed oil or evening primrose helped to increase the retention rate of GLA, which was transmigrated into eggs from blood. GLA was not detected in the blood samples of control group and treatment group fed diet containing corn oil, while it was significantly increased in the blood samples of the treatment groups fed with diet containing hemp seed oil and diet containing evening primrose oil, respectively. GLA retention was not observed in the eggs produced respectively by control group and treatment group fed with diet containing corn oil, whereas it was significantly increased in the eggs produced by the treatment group fed with diet containing hemp seed oil by 1.09% and the treatment group fed with diet containing evening primrose oil by 4.87%. This result suggests that GLA-reinforced functional eggs can be produced by adding hemp seed oil and evening primrose oil to the feed for laying hens and feeding them with it. It is thought that further researches and clinical trials on biochemical mechanism related to atopic dermatitis should be conducted in future.


Assuntos
Cannabis/química , Galinhas/fisiologia , Ovos/análise , Óleos de Plantas/farmacologia , Ácido gama-Linolênico/metabolismo , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Feminino , Cromatografia Gasosa-Espectrometria de Massas/veterinária , Ácidos Linoleicos/administração & dosagem , Ácidos Linoleicos/farmacologia , Oenothera biennis , Óleos de Plantas/administração & dosagem , Ácido gama-Linolênico/administração & dosagem , Ácido gama-Linolênico/farmacologia
15.
Inflammopharmacology ; 22(5): 305-17, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24664592

RESUMO

Rheumatoid arthritis is a chronic inflammatory disease characterized by overproduction of inflammatory mediators along with undermined oxidative defensive mechanisms. Pathological angiogenesis was found to play a critical role in the progression of this disease. The current study was carried out to evaluate the anti-angiogenic, anti-inflammatory, and anti-oxidant effects of evening primrose oil (EPO), rich in gamma linolenic acid (GLA), either alone or in combination with aspirin or celecoxib, on adjuvant-induced arthritis. Arthritis was induced by subcutaneous injection of complete Freund's adjuvant (CFA) in the right hind paw of male albino rats. All treatments were administered orally from day 0 (EPO, 5 g/kg b.w.) or day 4 (celecoxib, 5 mg/kg; aspirin, 150 mg/kg) till day 27 after CFA injection. In the arthritic group, the results revealed significant decrease in the body weight and increase in ankle circumference, plasma angiopoietin-1 (ANG-1) and tumor necrosis factor-alpha (TNF-α) levels. Anti-oxidant status was suppressed as manifested by significant decline in reduced glutathione content along with decreased enzymatic activity of superoxide dismutase and increased lipid peroxidation. Oral administration of EPO exerted normalization of body weight, ANG-1, and TNF-α levels with restoration of activity as shown by reduced malondialdehyde levels. Moreover, histopathological examination demonstrated that EPO significantly reduced the synovial hyperplasia and inflammatory cells invasion in joint tissues, an effect that was enhanced by combination with aspirin or celecoxib. The joint use of GLA-rich natural oils, which possess anti-angiogenic, anti-inflammatory, and anti-oxidant activities, with traditional analgesics represents a promising strategy to restrain the progression of rheumatoid arthritis.


Assuntos
Artrite Experimental/tratamento farmacológico , Aspirina/farmacologia , Ácidos Linoleicos/farmacologia , Óleos de Plantas/farmacologia , Pirazóis/farmacologia , Sulfonamidas/farmacologia , Ácido gama-Linolênico/farmacologia , Administração Oral , Angiopoietina-1/sangue , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Artrite Experimental/patologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Aspirina/administração & dosagem , Celecoxib , Progressão da Doença , Quimioterapia Combinada , Inflamação/tratamento farmacológico , Inflamação/patologia , Ácidos Linoleicos/administração & dosagem , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/patologia , Oenothera biennis , Estresse Oxidativo/efeitos dos fármacos , Óleos de Plantas/administração & dosagem , Pirazóis/administração & dosagem , Ratos , Ratos Wistar , Sulfonamidas/administração & dosagem , Fator de Necrose Tumoral alfa/sangue , Ácido gama-Linolênico/administração & dosagem
16.
Proc Nutr Soc ; 73(1): 73-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24308351

RESUMO

This review considers evidence for a protective effect of PUFA on chronic disease. Estimates of PUFA intakes in prospective cohort studies are usually based on FFQ or biomarkers of intake. Cohort studies suggest that both linoleic and linolenic acid intake are associated with a lower risk of CHD. The intake of fish, the major source of long-chain n-3 PUFA is associated with a lower risk of both stroke and CHD, particularly sudden cardiac death. No relationship with common sites of cancer (breast and colon) and PUFA has been found. However, some recent studies suggest an association of high intakes of n-3 PUFA with risk of prostate cancer. An updated Cochrane review of dietary fat modification (replacing SFA with PUFA) randomised controlled trials to prevent CHD found a 14% lower incidence and a non-significant 7% lower mortality from CHD. The effects of an increased intake of n-3 PUFA on CHD incidence mortality have been tested in patients with pre-existing CHD in randomised controlled trials. Meta-analysis of these trials showed no overall benefit on total mortality or CVD incidence but a trend for lower risk of cardiac death was 0·91 (95% CI 0·85, 0·98). At present, there is little evidence from other trials demonstrating the clear benefits or harm from increased intakes of PUFA. In conclusion, present evidence intakes benefit from partial replacement of SFA with a balanced mixture of n-6 and n-3 PUFA which may contribute to CVD prevention.


Assuntos
Doença das Coronárias/prevenção & controle , Dieta , Ácidos Graxos Ômega-3/uso terapêutico , Comportamento Alimentar , Ácidos Linoleicos/uso terapêutico , Ácidos Linolênicos/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Animais , Doença Crônica/prevenção & controle , Ácidos Graxos/administração & dosagem , Ácidos Graxos Ômega-3/administração & dosagem , Peixes , Humanos , Ácidos Linoleicos/administração & dosagem , Ácidos Linolênicos/administração & dosagem
17.
Dermatol Surg ; 39(8): 1243-51, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23627892

RESUMO

BACKGROUND: Acne affects many adolescents. Conventional therapy often results in side effects and poor adherence, and the treatment does not consider the psychological effect of acne on patients, which is comparable with that of disabling diseases. OBJECTIVES: To evaluate the efficacy and tolerability of a peel (30% salicylic acid, triethyl citrate and ethyl linoleate) combined with a home therapy with three topical agents (triethyl citrate, ethyl linoleate and salicylic acid 0.5% cream, lotion) in moderate acne of the face. DESIGN: Prospective, observational, multicenter, open-label, postmarketing, phase IV study. METHODS: Patients were assessed by comparing Global Acne Grading System (GAGS) score and total lesion count from 15 days before the first peel (T-15 ), after four salicylic peels (every 10 ± 2 days (T0 , T10 , T20 , T30 ), and 20 days after of the end of the study (T50 ). This treatment was associated to a home therapy. RESULTS: Fifty-three patients completed the study. The average GAGS score fell 49% between T-15 and T50 (p < .001). No patient withdrew for adverse events. CONCLUSIONS: This therapy was effective and well-tolerated in all cases. Chemo-exfoliation sessions ensured the continuous monitoring of clinical results and improved patient quality of life.


Assuntos
Acne Vulgar/tratamento farmacológico , Abrasão Química , Salicilatos/administração & dosagem , Adolescente , Adulto , Abrasão Química/métodos , Criança , Citratos/administração & dosagem , Feminino , Humanos , Ácidos Linoleicos/administração & dosagem , Masculino , Estudos Prospectivos , Qualidade de Vida , Adulto Jovem
18.
Cochrane Database Syst Rev ; (4): CD004416, 2013 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-23633319

RESUMO

BACKGROUND: Eczema is a chronic inflammatory skin condition, which usually develops in early childhood. Many children outgrow this disorder as they reach secondary school age, and although It may improve with age, there is no cure. Constant itch makes life uncomfortable for those with this condition, no matter what age they are, so it may have a significant effect on a person's quality of life. Its prevalence seems to be increasing as populations move from rural locations to cities. Some people, who do not see an adequate improvement or fear side-effects of conventional medical products, try complementary alternatives to conventional treatment. This is a review of evening primrose oil (EPO) and borage oil (BO) taken orally (by mouth); these have been thought to be beneficial because of their gamma-linolenic acid content. OBJECTIVES: To assess the effects of oral evening primrose oil or borage oil for treating the symptoms of atopic eczema. SEARCH METHODS: We searched the following databases up to August 2012: Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 1946), EMBASE (from 1974), AMED (from 1985), and LILACS (from 1982). We also searched online trials registers and checked the bibliographies of included studies for further references to relevant trials. We corresponded with trial investigators and pharmaceutical companies to try to identify unpublished and ongoing trials. We performed a separate search for adverse effects of evening primrose oil and borage oil in November 2011. SELECTION CRITERIA: All randomised controlled, parallel, or cross-over trials investigating oral intake of evening primrose oil or borage oil for eczema. DATA COLLECTION AND ANALYSIS: Two review authors independently applied eligibility criteria, assessed risk of bias, and extracted data. We pooled dichotomous outcomes using risk ratios (RR), and continuous outcomes using the mean difference (MD). Where possible, we pooled study results using random-effects meta-analysis and tested statistical heterogeneity using both the Chi(²) test and the I(²) statistic test. We presented results using forest plots with 95% confidence intervals (CI). MAIN RESULTS: A total of 27 studies (1596 participants) met the inclusion criteria: 19 studies assessed evening primrose oil, and 8 studies assessed borage oil. For EPO, a meta-analysis of results from 7 studies showed that EPO failed to significantly increase improvement in global eczema symptoms as reported by participants on a visual analogue scale of 0 to 100 (MD -2.22, 95% CI -10.48 to 6.04, 176 participants, 7 trials) and a visual analogue scale of 0 to 100 for medical doctors (MD -3.26, 95% CI -6.96 to 0.45, 289 participants, 8 trials) compared to the placebo group.Treatment with BO also failed to significantly improve global eczema symptoms compared to placebo treatment as reported by both participants and medical doctors, although we could not conduct a meta-analysis as studies reported results in different ways. With regard to the risk of bias, the majority of studies were of low risk of bias; we judged 67% of the included studies as having low risk of bias for random sequence generation; 44%, for allocation concealment; 59%, for blinding; and 37%, for other biases. IMPLICATIONS FOR PRACTICE: Oral borage oil and evening primrose oil lack effect on eczema; improvement was similar to respective placebos used in trials. Oral BO and EPO are not effective treatments for eczema.In these studies, along with the placebos, EPO and BO have the same, fairly common, mild, transient adverse effects, which are mainly gastrointestinal.The short-term studies included here do not examine possible adverse effects of long-term use of EPO or BO. A case report warned that if EPO is taken for a prolonged period of time (more than one year), there is a potential risk of inflammation, thrombosis, and immunosuppression; another study found that EPO may increase bleeding for people on Coumadin® (warfarin) medication. IMPLICATIONS FOR RESEARCH: Noting that the confidence intervals between active and placebo treatment are narrow, to exclude the possibility of any clinically useful difference, we concluded that further studies on EPO or BO for eczema would be hard to justify.This review does not provide information about long-term use of these products.


Assuntos
Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Eczema/tratamento farmacológico , Ácidos Linoleicos/administração & dosagem , Óleos de Plantas/administração & dosagem , Ácido gama-Linolênico/administração & dosagem , Administração Oral , Adulto , Criança , Humanos , Oenothera biennis , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Arch Anim Nutr ; 65(5): 354-65, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22164957

RESUMO

To examine the effects of dietary conjugated linoleic acids (CLA) on lipid metabolism and antioxidant capacity in laying hens, Hy-Line Brown layers (n = 384, 52 weeks old) were randomly allocated to one of four dietary treatments. Each treatment had six replicates of 16 hens each. All birds were assigned to a corn-soybean meal-based diet containing a mixture of CLA at 0%, 1%, 2% or 4% for six weeks. With increasing dietary CLA, egg weight and feed intake decreased, and yolk colour was darkened. Feed efficiency was improved at 1% and 2% dietary CLA. Serum triglyceride concentration was significantly reduced by CLA in a dose dependent manner. A linear decrease in total cholesterol and low-density lipoprotein cholesterol, and an increase in high-density lipoprotein cholesterol levels were observed after CLA supplementation. With increasing dietary CLA, the deposition of two major isomers of CLA (c9, t11; t10, c12) in yolk lipids increased linearly, the proportion of saturated fatty acids increased and monounsaturated fatty acids decreased significantly. The proportion of polyunsaturated fatty acids was highest at 1% CLA. Compared to the control, CLA supplementation significantly increased the activities of superoxide dismutase and glutathione peroxidase, inhibited hydroxyl radicals and superoxide anion production, and decreased the malonaldehyde concentrations in both serum and liver. The results demonstrated that dietary CLA meliorated serum lipid profiles and enhanced the antioxidant capacity of laying hens.


Assuntos
Antioxidantes/metabolismo , Galinhas/metabolismo , Dieta/veterinária , Ácidos Linoleicos/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Suplementos Nutricionais , Feminino , Ácidos Linoleicos/administração & dosagem
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