RESUMEN
BACKGROUND: The development of rosacea is suggested to be closely associated with lipid metabolism, inflammation, and anxiety/depression. Gamma linolenic acid (GLA) is a key factor participating in lipid metabolism, which is also confirmed to regulate the inflammatory response. However, the associations of serum GLA levels with rosacea severity and psychological status still remain unclear. OBJECTIVE AND LIMITATIONS OF THE STUDY: The present study aimed to investigate the associations of gamma linolenic acid (GLA), a key factor participating in lipid metabolism and the inflammatory response, with rosacea severity and psychological status. The present study still had some limitations. First, this study is a cross-sectional study and does not provide longitudinal evidence about the relationship between GLA and rosacea; Second, the cohort in this study is also relatively small, and a larger cohort is needed in further investigation to reveal the potential role of lipid metabolism in the pathogenesis of rosacea. METHODS: A total of 62 rosacea patients were consecutively recruited. Patient's Self-Assessment (PSA) scale and Clinician Erythema Assessment (CEA) as well as 7-item Generalized Anxiety Disorder (GAD-7) and 9-item Patient Health Questionnaire (PHQ-9) were conducted to evaluate the degree of erythema severity and anxiety/depression, respectively. Serum GLA levels were determined by gas chromatography mass. RESULTS: Lower levels of serum GLA in rosacea patients were observed (p<0.001), and subgroup analysis revealed that patients with higher-level GLA had lower scores of PSA, CEA, GAD-7 and PHQ-9. Moreover, Spearman correlation analysis uncovered that serum GLA levels were negatively associated with PSA, CEA, GAD-7 as well and PHQ-9 scores, respectively. Linear regression model found that serum GLA levels at baseline were a predictive factor for prognosis of clinical outcomes after 1-month conventional treatment. CONCLUSION: The present study indicates that lower levels of serum GLA in rosacea patients are negatively associated with the degree of erythema and anxiety/depression status.
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Rosácea , Ácido gammalinolénico , Humanos , Ácido gammalinolénico/uso terapéutico , Depresión/etiología , Estudios Transversales , Índice de Severidad de la Enfermedad , Rosácea/complicaciones , Rosácea/psicología , Eritema/etiología , Eritema/tratamiento farmacológico , Ansiedad/etiologíaRESUMEN
OBJECTIVE: Systemic arterial hypertension and obesity are major public health problems that increase risks of serious cardiovascular diseases and kidney failure as well as increase mortality. Substances that can alleviate these problems are desirable. We evaluated the beneficial effects of nutritional supplementation with gamma-linolenic acid in postmenopausal hypertensive women. METHODS: This was a prospective, double-blind, placebo-controlled, randomized study involving 96 postmenopausal women. Participants were divided into two groups either receiving 1,000âmg of borage oil rich in gamma-linolenic acid + vitamin E (drug) or only vitamin E (placebo) capsules for 6 months. They were followed up monthly to assess the impact on systemic blood pressure and body composition. To verify group homogeneity, Fisher's exact and Student t tests were performed. To evaluate differences in various parameters between the two groups and at various times, repeated measures analysis of variance was performed, with Bonferroni correction. RESULTS: The power of the test was calculated based on the difference in the mean systolic blood pressure between baseline and after 6 months of treatment in the placebo group and in the drug group. A 92.9% test power was found with a 95% confidence interval. There was a significant reduction in the systolic and diastolic pressure as well as a significant change in waist-hip ratio (Pâ<â0.01) in the drug group as compared with the placebo group. CONCLUSIONS: Supplementation with borage oil rich in gamma-linolenic acid had significant beneficial short-term effects without showing any adverse effect. There remains a need for further studies to evaluate long-term benefits.
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Hipertensión , Ácido gammalinolénico , Tejido Adiposo , Suplementos Dietéticos , Método Doble Ciego , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Posmenopausia , Estudios ProspectivosRESUMEN
This paper proposes the use of random forest for adulteration detection purposes, combining the random forest algorithm with the artificial generation of outliers from the authentic samples. This proposal was applied in two food adulteration studies: evening primrose oils using ATR-FTIR spectroscopy and ground nutmeg using NIR diffuse reflectance spectroscopy. The primrose oil was adulterated with soybean, corn and sunflower oils, and the model was validated using these adulterated oils and other different oils, such as rosehip and andiroba, in pure and adulterated forms. The ground nutmeg was adulterated with cumin, commercial monosodium glutamate, soil, roasted coffee husks and wood sawdust. For the primrose oil, the proposed method presented superior performance than PLS-DA and similar performance to SIMCA and for the ground nutmeg, the random forest was superior to PLS-DA and SIMCA. Also, in both applications using the random forest, no sample was excluded from the external validation set.
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Contaminación de Alimentos/análisis , Ácidos Linoleicos/química , Aceites de Plantas/química , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Ácido gammalinolénico/química , Aceite de Maíz/análisis , Límite de Detección , Myristica/química , Oenothera biennis , Aceite de Soja/análisis , Aceite de Girasol/análisisRESUMEN
This study aimed at evaluating the polycyclic aromatic hydrocarbons (PAHs) contamination of commercial vegetable oils and examined the identity through the fatty acids profiles. Coconut, safflower, evening primrose, and linseed oils marketed in São Paulo (Brazil) were investigated totaling 69 samples. Four PAHs, benzo[a]anthracene (BaA), chrysene (Chr), benzo[b]fluoranthene (BbF), and benzo[a]pyrene (BaP), were detected in 96% of the samples at individual levels ranging from not detected to 14.99⯵gâ¯kg-1. Chrysene was the abundant hydrocarbon found among all types of oils, with the highest median values. The results of the fatty acid profiles revealed that 43% showed different profiles according to the ones on their labels, with a higher incidence of adulteration of evening primrose oils. The maximum tolerable limits by European Regulation No. 835/2011 were exceeded for BaP in 12%, and for total 4 PAHs in 28%, with a greater contribution of adulterated samples.
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Ácidos Grasos/análisis , Contaminación de Alimentos/análisis , Aceite de Linaza/análisis , Aceites de Plantas/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Brasil , Crisenos , Aceite de Coco/análisis , Análisis de los Alimentos , Ácidos Linoleicos/análisis , Oenothera biennis , Aceites de Plantas/química , Aceite de Cártamo/análisis , Ácido gammalinolénico/análisisRESUMEN
PURPOSE: To investigate the effects of Borage oil on cardiac remodeling after myocardial infarction (MI). METHODS: Male Wistar rats underwent ligation of the left coronary artery and divided into three groups: MI (control), BO-18 (18 mg/kg of borage oil) and BO-180 (180 mg/kg of borage oil). After seven days, heart was arrested in diastole and processed for histological evaluation of: MI size, LV dilation, myocyte hypertrophy, inflammatory infiltration and fibrosis in MI region and in remote region. The relative weight of the lung was used as a marker of heart failure. The MI size was comparable among groups. RESULTS: Compared to control, BO treated groups showed lower weight of heart and lungs, reduced LV dilation and myocyte hypertrophy. Hemodynamic measurements were comparable. The treatment attenuated the inflammatory infiltration and fibrosis in remote myocardium. CONCLUSION: Borage oil attenuates progression of cardiac remodeling after myocardial infarction and congestive heart failure.
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Antiinflamatorios/farmacología , Ventrículos Cardíacos/patología , Infarto del Miocardio/patología , Aceites de Plantas/farmacología , Remodelación Ventricular/efectos de los fármacos , Ácido gammalinolénico/farmacología , Animales , Fibrosis , Insuficiencia Cardíaca/patología , Pulmón/patología , Masculino , Modelos Animales , Miocitos Cardíacos/efectos de los fármacos , Tamaño de los Órganos , Ratas WistarRESUMEN
ABSTRACT PURPOSE: To investigate the effects of Borage oil on cardiac remodeling after myocardial infarction (MI). METHODS: Male Wistar rats underwent ligation of the left coronary artery and divided into three groups: MI (control), BO-18 (18 mg/kg of borage oil) and BO-180 (180 mg/kg of borage oil). After seven days, heart was arrested in diastole and processed for histological evaluation of: MI size, LV dilation, myocyte hypertrophy, inflammatory infiltration and fibrosis in MI region and in remote region. The relative weight of the lung was used as a marker of heart failure. The MI size was comparable among groups. RESULTS: Compared to control, BO treated groups showed lower weight of heart and lungs, reduced LV dilation and myocyte hypertrophy. Hemodynamic measurements were comparable. The treatment attenuated the inflammatory infiltration and fibrosis in remote myocardium. CONCLUSION: Borage oil attenuates progression of cardiac remodeling after myocardial infarction and congestive heart failure.
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Animales , Masculino , Aceites de Plantas/farmacología , Ácido gammalinolénico/farmacología , Remodelación Ventricular/efectos de los fármacos , Ventrículos Cardíacos/patología , Antiinflamatorios/farmacología , Infarto del Miocardio/patología , Tamaño de los Órganos , Fibrosis , Ratas Wistar , Modelos Animales , Miocitos Cardíacos/efectos de los fármacos , Insuficiencia Cardíaca/patología , Pulmón/patologíaRESUMEN
AIM: Gliomas are primary brain tumours. Gamma-linolenic acid (GLA) exerts anti-proliferative effects. Several ruthenium-containing complexes have antiproliferative effects and can be used as adjuvant therapies in cisplatin-resistant cancer. The present study reports on the anti-proliferative properties and effects on tumour morphology of a novel diruthenium-GLA complex (Ru2GLA) and its comparison with GLA in the C6 rat glioma model both in vitro and in vivo. MATERIALS AND METHODS: In vitro and in vivo experiments were performed on C6 glioma rat cells, and in an orthotopic model. RESULTS: Ru2GLA (100 µM) appears to be an inhibitor of C6 rat glioma cell proliferation. The nuclear area of Ru2GLA-treated cells was 2.18-times larger than that of control cells, suggesting DNA replication occurred but mitosis was blocked in the G2-M phase. Ru2GLA (2 mM) inhibited C6 cell proliferation in vivo and the changes in tumor morphology confirm both cellular uptake and collagen fibre-binding in the extracellular matrix. CONCLUSION: Ru2GLA appears to be a low-toxicity drug and a potential candidate for anti-proliferative therapy of glioma.
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Glioma/patología , Rutenio/farmacología , Ácido gammalinolénico/farmacología , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Matriz Extracelular/metabolismo , Femenino , Glioma/tratamiento farmacológico , Glioma/ultraestructura , Ratas , Rutenio/administración & dosificación , Carga Tumoral/efectos de los fármacos , Ácido gammalinolénico/administración & dosificaciónRESUMEN
Cats have limited Δ6 desaturase activity. However, γ-linolenate (GLA) feeding may by-pass the Δ6 desaturase step allowing arachidonate (ARA) accumulation via Δ5-desaturation. Alternatively, high dietary linoleate (LNA) may induce limited Δ6 desaturase also resulting in ARA accumulation. Fatty acid profiles were determined after feeding high LNA, high GLA, or adequate LNA diets. Adult female cats (n = 29) were assigned to one of three groups and fed for 8 weeks. Plasma samples were collected at weeks 0, 2, 4 and 8 for plasma triacylglycerol (TAG), total cholesterol (TC), lipoprotein (LP), and plasma and red blood cell membrane phospholipid fatty acid determinations. Time, but no diet, effects were observed for TAG, TC, and LP fractions at weeks 2 and 4 with significant increases likely due to increased dietary fat. However, all values were within feline normal limits. The GLA diet resulted in increased dihomo-γ-linolenic acid (DGLA) and ARA as early as week 2, supporting a ∆5 desaturase. Further evidence of Δ5 desaturase was found at high dietary LNA with the appearance of a novel fatty acid, 20:3 ∆7, 11, 14, apparently formed via ∆5 desaturation and chain elongation of LNA. However, Δ6 desaturase induction at high dietary LNA concentration was not observed. Cats are able to maintain plasma and red blood cell ARA when fed a practical diet containing GLA using what appears to be an active Δ5 desaturase enzyme.
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Ácido Araquidónico/sangre , Grasas Insaturadas en la Dieta/metabolismo , Ácido Graso Desaturasas/metabolismo , Ácido Linoleico/sangre , Ácido gammalinolénico/sangre , Ácido 8,11,14-Eicosatrienoico/sangre , Animales , Peso Corporal , Gatos , Femenino , Cromatografía de Gases y Espectrometría de Masas , Metabolismo de los Lípidos , Hígado/metabolismoRESUMEN
To investigate the effect of n-3 polyunsaturated fatty acid (PUFA) supplementation on the fatty acid composition of erythrocyte phospholipids and breast milk lipids, pregnant Brazilian women in the 30th week of gestation were randomized to supplement their usual diet with 2 g/day of fish oil (FO group) or primrose oil (PO group, control) capsules for 15 days. Erythrocyte phospholipids from FO group had proportionally higher docosahexaenoicacid and eicosapentaenoic acid levels and furthermore, the ratio of n-6/n-3 PUFA was significantly lower in the breast milk lipids compared with the control group. Assessment of plasma anti-oxLDL autoantibodies and thiobarbituric acid-reactive substance concentration demonstrated that both groups had the same levels and they were unaltered by supplementations.
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Suplementos Dietéticos , Ácidos Grasos Omega-3/farmacología , Ácidos Linoleicos/farmacología , Leche Humana/metabolismo , Fosfolípidos/sangre , Aceites de Plantas/farmacología , Embarazo/metabolismo , Ácido gammalinolénico/farmacología , Adulto , Autoanticuerpos/sangre , Brasil , LDL-Colesterol/sangre , LDL-Colesterol/inmunología , Dieta , Grasas de la Dieta/metabolismo , Ácidos Docosahexaenoicos/metabolismo , Ácidos Docosahexaenoicos/farmacología , Ácido Eicosapentaenoico/metabolismo , Ácido Eicosapentaenoico/farmacología , Eritrocitos/metabolismo , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Omega-6/metabolismo , Femenino , Humanos , Ácidos Linoleicos/metabolismo , Oenothera biennis , Aceites de Plantas/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Adulto Joven , Ácido gammalinolénico/metabolismoRESUMEN
A mastalgia é uma queixa comum nos consultórios de mastologia. Devido à intensidade da dorou pelo medo do câncer de mama, mulheres com mastalgia buscam orientação com o mastologista.Nesse sentido, o mastologista deve estar familiarizado com o tema. Considerando que aqueixa de dor mamária está entre as mais frequentes em mastologia, conduziu-se uma revisão daliteratura, enfatizando-se a abordagem terapêutica da mastalgia.
Mastalgia is a common complaint in mastology offices. Women who are experiencing mastalgia seekclarification with the breast cancer specialist due to the intensity of the pain or because they fear breastcancer. Therefore, the specialist shall understand such issue. Considering that the complaint concerningbreast pain is one of the most frequent complaints in mastology, a literature review was carried outemphasizing the therapeutic approach of mastalgia.
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Borago , Bromocriptina/uso terapéutico , Danazol/uso terapéutico , Enfermedades de la Mama/terapia , Gonadotropinas/uso terapéutico , Lisurida/uso terapéutico , Mastodinia/terapia , Primula , Tamoxifeno/uso terapéutico , Ácido gammalinolénico/uso terapéuticoRESUMEN
INTRODUCTION: Enteral nutrition (EN) with eicosapentaenoic acid (EPA)/γ-linolenic acid (GLA) is recommended for mechanically ventilated patients with severe lung injury. EPA/GLA has anti-inflammatory benefits, as evidenced by its association with reduction in pulmonary inflammation, improvement in oxygenation and improved clinical outcomes in patients with severe forms of acute lung injury. This study was a prospective, multicenter, randomized, double-blinded, controlled trial designed to investigate whether EPA/GLA could have an effective role in the treatment of patients with early sepsis (systemic inflammatory response syndrome with confirmed or presumed infection and without any organ dysfunction) by reducing the progression of the disease to severe sepsis (sepsis associated with at least one organ failure) or septic shock (sepsis associated with hypotension despite adequate fluid resuscitation). Secondary outcomes included the development of individual organ failure, increased ICU and hospital length of stay, need for mechanical ventilation and 28-day all-cause mortality. METHODS: Randomization was concealed, and patients were allocated to receive, for seven days, either an EPA/GLA diet or an isocaloric, isonitrogenous control diet not enhanced with lipids. Patients were continuously tube-fed at a minimum of 75% of basal energy expenditure × 1.3. To evaluate the progression to severe sepsis and/or septic shock, daily screening for individual organ failure was performed. All clinical outcomes were recorded during a 28-day follow-up period. RESULTS: A total of 115 patients in the early stages of sepsis requiring EN were included, among whom 106 were considered evaluable. Intention-to-treat (ITT) analysis demonstrated that patients fed the EPA/GLA diet developed less severe sepsis and/or septic shock than patients fed the control diet (26.3% versus 50%, respectively; P = 0.0259), with similar results observed for the evaluable patients (26.4% versus 50.9% respectively; P = 0.0217). The ITT analysis demonstrated that patients in the study group developed cardiovascular failure (36.2% versus 21%, respectively; P = 0.0381) and respiratory failure (39.6% versus 24.6%, respectively; P = 0.0362) less often than the control group. Similarly, when considering only the evaluable patients, fewer patients developed cardiovascular failure (20.7% versus 37.7%, respectively; P = 0.03) and respiratory failure (26.4% versus 39.6%, respectively; P = 0.04). The percentage of patients fed the EPA/GLA diet requiring invasive mechanical ventilation was reduced compared with controls (ITT patients: 18.9% versus 33.9%, respectively; P = 0.394; evaluable patients: 17.5% versus 34.5%, respectively; P = 0.295). Patients nourished with the EPA/GLA diet remained in the ICU fewer days than the control population (ITT patients: 21.1 ICU-free days versus 14.7 ICU-free days, respectively; P < 0.0001; evaluable patients: 20.8 ICU-free days versus 14.3 ICU-free days, respectively; P < 0.0001) and fewer days at the hospital (ITT patients: 19.5 hospital-free days versus 10.3 hospital-free days, respectively; P < 0.0001; evaluable patients: 19.1 hospital-free days versus 10.2 hospital-free days, respectively; P < 0.001) (all numbers expressed as means). No significant differences in 28-day all-cause mortality were observed (ITT patients: 26.2% EPA/GLA diet versus 27.6% control diet, respectively; P = 0.72; evaluable: 26.4 EPA/GLA diet versus 30.18 control diet, respectively; P = 0.79). CONCLUSIONS: These data suggest that EPA/GLA may play a beneficial role in the treatment of enterally fed patients in the early stages of sepsis without associated organ dysfunction by contributing to slowing the progression of sepsis-related organ dysfunction, especially with regard to cardiovascular and respiratory dysfunction. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00981877.
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Antioxidantes/administración & dosificación , Ácido Eicosapentaenoico/administración & dosificación , Nutrición Enteral/métodos , Sepsis/terapia , Ácido gammalinolénico/administración & dosificación , Anciano , Anciano de 80 o más Años , Antioxidantes/metabolismo , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sepsis/metabolismo , Factores de Tiempo , Resultado del TratamientoRESUMEN
Introdução: Acne é uma dermatose que apresenta o padrão do sebo alterado, tanto quali, quanto quantitativamente. Objetivos: Estudar as possíveis alterações quali e quantitativas dos ácidos graxos encontrados no sebo de portadores de acne vulgar graus II ou III mediante ao uso diário de limeciclina e/ou suplemento oral a base de ácidos linoleico, gamalinolênico e oleico. Métodos: Quarenta e cinco sujeitos de pesquisa masculinos, de 12 a 40 anos de idade, portadores de acne vulgar graus II ou III, submeteram-se a 90 dias de uso de: Grupo A, 300mg/dia de limeciclina; Grupo B, 540mg de ácidos gamalinolênico, 1.200mg linoleico e 510mg oleico/dia; Grupo C: Grupos A+B. A cada 30 dias, eles tinham amostra de sebo da fronte coletada para análise cromatográfica dos ácidos graxos nele presentes. Resultados: Quarenta sujeitos de pesquisa (88,9 por cento) concluíram o estudo, os quais ingeriram todas as doses dos produtos, sem apresentarem eventos adversos em qualquer dos Grupos. O número de comedões, pústulas e cistos reduziu com o tempo (p<0,001, para todos), nos três Grupos. Com relação ao número total de lesões, houve uma maior quantidade de lesões em pacientes do Grupo B, quando comparados aos do Grupo A (p=0,033) e aos do Grupo C (p=0,030). Sete ácidos graxos apresentaram mudanças de seu padrão durante o estudo. De um modo geral, as mudanças que se tornaram mais evidentes foram: 1) a concentração de esqualeno no SB não reduziu em qualquer Grupo de estudo; 2) C12:0, C14:0 e C16:1 tiveram suas respectivas concentrações aumentadas nos três Grupos com o tempo de terapêuticas; 3) há indicativo de aumento de C18:1n9c+C18:1n9t na associação das duas classes terapêuticas estudadas; 4) limeciclina e/ou ingestão de ácido linoleico não aumentaram a participação do ácido linoleico no sebo; 5) ácido -linolênico teve sua concentração aumentada e, depois diminuída com o uso de LM e/ou com sua própria suplementação oral...
Introduction: Acne is a dermatosis that presents an altered sebum pattern, quantitatively and qualitatively. Objectives: To study the possible quantitative and qualitative changes of fatty acids found in the sebum of patients with acne vulgaris grade II or III, through the daily use of lymecycline and/or oral supplementation based on linoleic, gamma-linolenic, and oleic acids. Methods: Fortyfive male research subjects, ages 12 to 40, presenting acne vulgaris grade II or III, were submitted to a 90-day use of: Group 1, 300mg of lymecycline per day; Group 2, 540mg of gamma-linolenic acid, 1,200mg of linoleic acid, and e 510mg of oleic acid per day; Group 3: Groups A+B. Every 30 days, a sample of the sebum of their forehead was collected for chromatographic analysis of the fatty acids contained therein. Results: Forty research subjects (88.9 percent ) concluded the study. They ingested all dosages of the products, without presenting side effects in any of the Groups. The number of comedones, pustules, and cysts reduced with time (p<0.001, for all), in all the 3 Groups. With respect to the total number of lesions, Group B´s patients presented a larger quantity of lesions, as compared to those of Group A (p=0.033) and Group C (p=0.030). Seven fatty acids presented pattern changes during the study. In general, the changes that became more evident were: 1) the squalene concentration in the sebum did not diminish in any Group under study; 2) C12:0, C14:0, and C16:1 had their respective concentrations increased in the 3 Groups over the time of the treatments; 3) there is an indication for increasing of C18:1n9t+C18:1n9c when both of therapies are associated; 4) lymecycline and/or the ingestion of linoleic acid did not increase the participation of linoleic acid in the sebum; and 5) gama-linolenic acid had its concentration increased during the first 60-day and diminished during the last 30-day therapies period using lymecycline and/or with its own oral supplementation...
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Humanos , Masculino , Adolescente , Adulto , Acné Vulgar , Ácidos Grasos Esenciales , Ácido gammalinolénico , Ácido Linoleico , Limeciclina , Ácido Oléico , Glándulas Sebáceas , SeboRESUMEN
The present study reports the synthesis of a novel compound with the formula [Ru(2)(aGLA)4Cl] according to elemental analyses data, referred to as Ru(2)GLA. The electronic spectra of Ru(2)GLA is typical of a mixed valent diruthenium(II,III) carboxylate. Ru(2)GLA was synthesized with the aim of combining and possibly improving the anti-tumour properties of the two active components ruthenium and gamma-linolenic acid (GLA). The properties of Ru(2)GLA were tested in C6 rat glioma cells by analysing cell number, viability, lipid droplet formation, apoptosis, cell cycle distribution, mitochondrial membrane potential and reactive oxygen species. Ru(2)GLA inhibited cell proliferation in a time and concentration dependent manner. Nile Red staining suggested that Ru(2)GLA enters the cells and ICP-AES elemental analysis found an increase in ruthenium from <0.02 to 425 mg/Kg in treated cells. The sub-G1 apoptotic cell population was increased by Ru(2)GLA (22 +/- 5.2%) when analysed by FACS and this was confirmed by Hoechst staining of nuclei. Mitochondrial membrane potential was decreased in the presence of Ru(2)GLA (44 +/- 2.3%). In contrast, the cells which maintained a high mitochondrial membrane potential had an increase (18 +/- 1.5%) in reactive oxygen species generation. Both decreased mitochondrial membrane potential and increased reactive oxygen species generation may be involved in triggering apoptosis in Ru(2)GLA exposed cells. The EC(50) for Ru(2)GLA decreased with increasing time of exposure from 285 microM at 24 h, 211 microM at 48 h to 81 microM at 72 h. In conclusion, Ru(2)GLA is a novel drug with antiproliferative properties in C6 glioma cells and is a potential candidate for novel therapies in gliomas.
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Antineoplásicos/farmacología , Apoptosis , Glioma/tratamiento farmacológico , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Compuestos Organometálicos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Rutenio/química , Ácido gammalinolénico/química , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Bencimidazoles/farmacología , Línea Celular Tumoral , Proliferación Celular , Citometría de Flujo , Fase G1 , Glioma/metabolismo , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Oxazinas/farmacología , Ratas , Espectrofotometría Atómica , Coloración y EtiquetadoRESUMEN
Gamma-linolenic acid (GLA, 18:3, cis- 6,9,12-octadecatrienoic acid), an important compound in n-6 eicosanoid family biosynthesis, occurs in the lipids of a few plant and microbial sources. This study focused on the screening of microbial strains with suitable lipase activity for enrichment of GLA by selective hydrolysis of the borage oil (21.6 percent of GLA/total fatty acids). Firstly, 352 microrganisms were tested for their lipolytic capacity using screening techniques on agar plates containing borage oil, strains were then selected and screened for their activity (U/mg) using both submerged fermentation (SmF) and solid state fermentation (SSF). The rate of hydrolysis and the selective preference of these hydrolytic enzymes towards fatty acids, with a special focus on enrichment of GLA were studied and compared with those obtained by two commercially-available lipases. Only one of the lipases tested during this study displayed selectivity, discriminating the GLA during the hydrolysis reaction. Using the enzymatic extract from Geotrichum candidum as a biocatalyst of the reaction, it was possible to obtain a percentage of 41.7 percent of GLA in acylglycerols fraction when the borage oil was treated in a fixed-bed reactor for 24 hours at 30ºC.
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Ácido gammalinolénico/análisis , Ácido gammalinolénico/aislamiento & purificación , Borago , Fermentación , Geotrichum/enzimología , Geotrichum/aislamiento & purificación , Técnicas In Vitro , Lipasa/análisis , Lipasa/aislamiento & purificación , Catalizador , Activación Enzimática , Hidrólisis , Métodos , MétodosRESUMEN
BACKGROUND: Gamma-linolenic acid is a known inhibitor of tumour cell proliferation and migration in both in vitro and in vivo conditions. The aim of the present study was to determine the mechanisms by which gamma-linolenic acid (GLA) osmotic pump infusion alters glioma cell proliferation, and whether it affects cell cycle control and angiogenesis in the C6 glioma in vivo. METHODS: Established C6 rat gliomas were treated for 14 days with 5 mM GLA in CSF or CSF alone. Tumour size was estimated, microvessel density (MVD) counted and protein and mRNA expression measured by immunohistochemistry, western blotting and RT-PCR. RESULTS: GLA caused a significant decrease in tumour size (75 +/- 8.8%) and reduced MVD by 44 +/- 5.4%. These changes were associated with reduced expression of vascular endothelial growth factor (VEGF) (71 +/- 16%) and the VEGF receptor Flt1 (57 +/- 5.8%) but not Flk1. Expression of ERK1/2 was also reduced by 27 +/- 7.7% and 31 +/- 8.7% respectively. mRNA expression of matrix metalloproteinase-2 (MMP2) was reduced by 35 +/- 6.8% and zymography showed MMP2 proteolytic activity was reduced by 32 +/- 8.5%. GLA altered the expression of several proteins involved in cell cycle control. pRb protein expression was decreased (62 +/- 18%) while E2F1 remained unchanged. Cyclin D1 protein expression was increased by 42 +/- 12% in the presence of GLA. The cyclin dependent kinase inhibitors p21 and p27 responded differently to GLA, p27 expression was increased (27 +/- 7.3%) while p21 remained unchanged. The expression of p53 was increased (44 +/- 16%) by GLA. Finally, the BrdU incorporation studies found a significant inhibition (32 +/- 11%) of BrdU incorporation into the tumour in vivo. CONCLUSION: Overall the findings reported in the present study lend further support to the potential of GLA as an inhibitor of glioma cell proliferation in vivo and show it has direct effects upon cell cycle control and angiogenesis. These effects involve changes in protein expression of VEGF, Flt1, ERK1, ERK2, MMP2, Cyclin D1, pRb, p53 and p27. Combination therapy using drugs with other, complementary targets and GLA could lead to gains in treatment efficacy in this notoriously difficult to treat tumour.
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Ciclo Celular/efectos de los fármacos , Neovascularización Patológica/tratamiento farmacológico , Ácido gammalinolénico/farmacología , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ciclina D1 , Glioma/tratamiento farmacológico , Glioma/patología , Metaloproteinasa 2 de la Matriz , Proteína Quinasa 3 Activada por Mitógenos , Antígeno Nuclear de Célula en Proliferación , Ratas , Proteína de Retinoblastoma , Proteína p53 Supresora de Tumor , Factor A de Crecimiento Endotelial Vascular , Receptor 1 de Factores de Crecimiento Endotelial VascularRESUMEN
BACKGROUND: This meta-analysis of clinical trials compares an inflammation-modulating diet enriched with eicosapentaenoic acid (EPA), gamma-linolenic acid (GLA), and elevated antioxidants (EPA + GLA) vs a control diet to determine the effectiveness of this specialized diet on oxygenation and clinical outcomes in mechanically ventilated patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). METHODS: MEDLINE, EMBASE, Cochrane Clinical Trials Register, and the U.S. National Institute of Health Clinical Trials databases were searched. The outcome measures assessed were 28-day in-hospital mortality, 28-day ventilator-free and intensive care unit (ICU)-free days, and the development of new organ failures. An evaluation of oxygenation and ventilatory variables was also performed. Outcomes were analyzed using both fixed-effects and random-effects models. RESULTS: Three randomized controlled studies (n = 411 patients) were included in this meta-analysis. Among the most important findings of this evaluation is a significant reduction in the risk of mortality (odds ratio [OR] = 0.40; 95% confidence interval [CI] = 0.24-0.68; P = .001), with significant reductions in the risk of developing new organ failures (OR = 0.17; 95% CI = 0.08-0.34; P < .0001), time on mechanical ventilation (standardized mean difference [SMD] = 0.56; 95% CI = 0.32-0.79; P < .0001), and ICU stay (SMD = 0.51; 95% CI = 0.27-0.74; P < .0001) in patients who received EPA + GLA. CONCLUSIONS: The meta-analysis showed a significant reduction in the risk of mortality as well as relevant improvements in oxygenation and clinical outcomes of ventilated patients with ALI/ARDS given EPA + GLA.
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Lesión Pulmonar Aguda/terapia , Ácido Eicosapentaenoico/uso terapéutico , Nutrición Enteral/métodos , Mortalidad Hospitalaria , Insuficiencia Multiorgánica/epidemiología , Síndrome de Dificultad Respiratoria/terapia , Ácido gammalinolénico/uso terapéutico , Lesión Pulmonar Aguda/complicaciones , Lesión Pulmonar Aguda/mortalidad , Intervalos de Confianza , Dieta , Ácido Eicosapentaenoico/administración & dosificación , Humanos , Tiempo de Internación , Insuficiencia Multiorgánica/etiología , Oportunidad Relativa , Intercambio Gaseoso Pulmonar , Ensayos Clínicos Controlados Aleatorios como Asunto , Respiración Artificial , Síndrome de Dificultad Respiratoria/complicaciones , Síndrome de Dificultad Respiratoria/mortalidad , Resultado del Tratamiento , Ácido gammalinolénico/administración & dosificaciónAsunto(s)
Ácidos Linoleicos/efectos adversos , Materia Medica/efectos adversos , Parto , Aceites de Plantas/efectos adversos , Plantas Medicinales , Púrpura/inducido químicamente , Ácido gammalinolénico/efectos adversos , Adulto , Bebidas , Femenino , Humanos , Recién Nacido , Ácidos Linoleicos/administración & dosificación , Materia Medica/administración & dosificación , Oenothera biennis , Extractos Vegetales/administración & dosificación , Extractos Vegetales/efectos adversos , Hojas de la Planta , Aceites de Plantas/administración & dosificación , Embarazo , Púrpura/sangre , Ácido gammalinolénico/administración & dosificaciónRESUMEN
The effects of oleic, linoleic, and gamma-linolenic acids on the production of ROS by unstimulated and PMA-stimulated neutrophils were investigated by using five techniques: luminol- and lucigenin-amplified chemiluminescence, cytochrome c, hydroethidine, and phenol red reduction. Using lucigenin-amplified chemiluminescence, an increase in extracellular superoxide levels was observed by the treatment of neutrophils with the fatty acids. There was also an increase in intracellular ROS levels under similar conditions as measured by the hydroethidine technique. An increment in the intra- and extracellular levels of H2O2 was also observed in neutrophils treated with oleic acid as measured by phenol red reduction assay. In the luminol technique, peroxidase activity is required in the reaction of luminol with ROS for light generation. Oleic, linoleic, and gamma-linolenic acids inhibited the myeloperoxidase activity in stimulated neutrophils. So, these fatty acids jeopardize the results of ROS content measured by this technique. Oleic, linoleic, and gamma-linolenic acids per se led to cytochrome c reduction and so this method also cannot be used to measure ROS production induced by fatty acids. Oleic, linoleic, and gamma-linolenic acids do stimulate ROS production by neutrophils; however, measurements using the luminol-amplified chemiluminescence and cytochrome c reduction techniques require further analysis.
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Ácidos Linoleicos/metabolismo , Neutrófilos/metabolismo , Ácido Oléico/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ácido gammalinolénico/metabolismo , Animales , Grupo Citocromo c/metabolismo , Citometría de Flujo , Humanos , Cinética , Masculino , Oxidación-Reducción , Ratas , Ratas WistarRESUMEN
OBJECTIVES: Enteral diets enriched with eicosapentaenoic acid (EPA), gamma-linolenic acid (GLA), and antioxidants have previously been shown to improve outcomes in patients with acute respiratory distress syndrome. Several studies using animal models of sepsis demonstrate that enteral nutrition enriched with omega-3 fatty acids reduces mortality rate. This study investigated whether an enteral diet enriched with EPA, GLA, and antioxidant vitamins can improve outcomes and reduce 28-day all-cause mortality in patients with severe sepsis or septic shock requiring mechanical ventilation. DESIGN: Prospective, double-blind, placebo-controlled, randomized trial. SETTING: Three different intensive care units of a tertiary hospital in Brazil. PATIENTS: The study enrolled 165 patients. INTERVENTIONS: Patients were randomized to be continuously tube-fed with either a diet enriched with EPA, GLA, and elevated antioxidants or an isonitrogenous and isocaloric control diet, delivered at a constant rate to achieve a minimum of 75% of basal energy expenditure x 1.3 during a minimum of 4 days. MEASUREMENTS AND MAIN RESULTS: Patients were monitored for 28 days. Patients who were fed with the study diet experienced a significant reduction in mortality rate compared with patients fed with the control diet, the absolute mortality reduction amounting to 19.4% (p = .037). The group who received the study diet also experienced significant improvements in oxygenation status, more ventilator-free days (13.4 +/- 1.2 vs. 5.8 +/- 1.0, p < .001), more intensive care unit (ICU)-free days (10.8 +/- 1.1 vs. 4.6 +/- 0.9, p < .001), and a lesser development of new organ dysfunctions (p < .001). CONCLUSIONS: In patients with severe sepsis or septic shock and requiring mechanical ventilation and tolerating enteral nutrition, a diet enriched with EPA, GLA, and elevated antioxidants contributed to better ICU and hospital outcomes and was associated with lower mortality rates.
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Nutrición Enteral , Síndrome de Dificultad Respiratoria/terapia , Sepsis/terapia , Choque Séptico/terapia , Anciano , Antioxidantes/uso terapéutico , Ácido Ascórbico/uso terapéutico , Brasil/epidemiología , Método Doble Ciego , Ácido Eicosapentaenoico/uso terapéutico , Femenino , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/prevención & control , Estudios Prospectivos , Intercambio Gaseoso Pulmonar , Respiración Artificial , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/mortalidad , Sepsis/complicaciones , Sepsis/mortalidad , Choque Séptico/complicaciones , Choque Séptico/mortalidad , Vitamina E/uso terapéutico , Ácido gammalinolénico/uso terapéuticoRESUMEN
Fatty acids have been shown to cause death of rat and human primary pancreatic beta cells and of insulin-producing cell lines. These studies focused mainly on saturated and monounsaturated FA such as palmitic, stearic and oleic acids. In this study, we have performed a comparison of the toxicity of a wider range of FA. The toxicity of different FA to insulin-producing RINm5F cells was assessed by flow cytometry measuring loss of plasma membrane integrity and increase in DNA fragmentation. Additionally, the FA induced neutral lipid accumulation and the FA composition were determined. Palmitic, linoleic, gamma-linolenic, oleic, stearic, and eicosapentaenoic acid caused DNA fragmentation of insulin-producing RINm5F cells. Loss of membrane integrity was mainly caused by linoleic and gamma-linolenic acid. There was no correlation between cytotoxicity and the abundance of the FA in the cells as determined by HPLC analysis. Taken as whole, the toxic effect of the FA on insulin-producing RINm5F cells varied irrespective of the chain length and the degree of unsaturation. In these cells PA and LA exhibited the highest toxicity, whereas AA was not toxic. In addition, the toxicity of most tested FA was inversely related to low NLA, except for AA and EPA. The results of this study contribute to the understanding of the role of FA in the impairment of pancreatic beta cell function that occurs in type 2 diabetes and obesity.