P-MAPA activates TLR2 and TLR4 signaling while its combination with IL-12 stimulates CD4+ and CD8+ effector T cells in ovarian cancer.

AIMS: Ovarian cancer (OC) is the most lethal gynecological malignancies and many women develop chemoresistance associated with the inflammatory process. We investigated the effects of P-MAPA and IL-12 on the inflammatory and immune responses in a chemically-induced OC model. MAIN METHODS: OCs were induced with 7,12-dimethylbenz(a)anthracene into the ovarian bursa, and the animals were given P-MAPA (5 mg/kg bw., i.p., twice a week), or IL-12 (300 ng/kg bw., i.p., one a week) for 60 days, or both P-MAPA and IL-12. Immunohistochemistry, western blot, flow cytometry, and multiplex assay were used to examine the effectiveness of immunotherapies in OC. KEY FINDINGS: The combinatory therapy improved the general OC features, reducing inflammatory cells and adipocyte accumulation, in addition to revealing a soft and mobile tissue with no adherences and peritoneal implants. P-MAPA treatment increased the levels of TLR2, TLR4 and TRIF in OCs while decreasing the number of regulatory T (Treg) cells. Additionally, the association of P-MAPA with IL-12 significantly increased the number of CD4+ and CD8+ T effector cells in draining lymph nodes. Regarding the inflammatory mediators, P-MAPA enhanced the levels of the pro-inflammatory cytokine IL-17 while P-MAPA+IL-12 increased the levels of IL-1ß. Treatment with IL-12 enhanced the cytokine levels of IL-17, TNF-α, IL-1ß, and IL-2 in addition to the chemokine MIP-1α. SIGNIFICANCE: We conclude that P-MAPA upregulated TLR2 and TLR4 signaling, possibly activating the non-canonical pathway, while attenuating the tumor immunosuppression. Also, the combination of P-MAPA with IL-12 improves the antitumor immunoresponse, opening a new therapeutic approach for fighting OC.

Características clínicas e psicológicas em mulheres portadoras de mastologia cíclica tratadas com os ácidos gamalinolênico e linoléico / Clinical and psychological characteristics of women with moderate to severe mastalgia treated with gamma linolenic and linoleic acids

Para avaliar a resposta da mastalgia clínica moderada a severa à terapêutica com ácidos gaminolênico e linoléico(AGEs), foi realizado estudo do tipo ensaio clínico não- aleatório, envolvendo 30 pacientes atendidas no Ambulatório de Mastologia do Hospital Universitário Oswaldo Cruz, no período de fevereiro de 2001 a julho de 2002. As pacientes receberam orientação verbal e iniciaram tratamento com AGEs por três meses. Os graus de resposta terapêutica do Cardiff Breast Score foram determinados através da avaliação da dor mamária pela escala visual analógica(EVA). Ao final do tratamento, 22(73,3 por cento)pacientes foram responsivas e oito(26,7 por cento)não-responsivas. As mulheres com idade > 29 anos, tempo de mastalgia < 5 anos, menarca < 13 anos, ausência de nuliparidade, idade ao primeiro parto > 22 anos, tempo de lactação = 6 meses, referência de não ser a primeira consulta ao mastologista, percepção de irritação, depressão ou estresse devido à mastalgia, mais freqüentemente tiveram redução completa ou parcial da mastalgia cíclica, embora sem associação estatística com a resposta terapêutica. Concluiu-se que fatores clínicos e psicológicos pareceram influenciar a resposta terapêutica, assim como o composto de AGEs pareceu ser efetivo na dor mamária cíclica, constituindo-se numa boa opção como droga de primeira linha

Lipídios em terapia nutricional pediátrica / Lipids in pediatric nutritional therapy

As funçöes dos lipídios na nutriçäo dos pacientes pediátricos säo discutidas neste artigo, com ênfase na absorçäo, no aproveitamento energético e, principalmente, no metabolismo dos acidos graxos essenciais e sua relaçäo com o desenvolvimento infantil. A mudança de composiçäo dos lipídios nas fórmulas enterais e parenterais pode alterar o aproveitamento energético e o metabolismo dos ácidos graxos essenciais. A adiçäo de ácido linoléico e alfa-linolênico nas fórmulas enterais infantis é suficiente para evitar sinais clínicos de carência destes nutrientes; entretanto, este fornecimento näo é garantia de resultar em status adequado de ácido araquidônico e docosahexaenóico, que säo componebtes estruturais das membranas celulares. Os prematuros alimentados com fórmulas suplementadas de ácidos graxos essenciais apresentam nLveis de ácidos graxos no plasma e nos eritrócitos mais elevados do que aqueles alimentados com fórmulas convencionais, mas abaixo dos prematuros alimentados com leite humano. A performance nos testes de desenvolvimento dos prematuros alimentados com fórmulas suplementadas de ácidos graxos é melhor do que a daqueles alimentados com fórmula sem suplementaçäo. Novas fórmulas enterais e parenterais com a adiçäo de ácidos graxos específicos abrem perspectivas atraentes para pesquisas das relaçöes entre a composiçäo da membrana celular e o desenvolvimento infantil.(au)

Effect of dietary linoleic/alpha-linolenic acid ratio on growth and visual function of term infants.

OBJECTIVES: To determine the effect of alpha-linolenic acid (ALA) intake (or the dietary linoleic acid [LA]/ALA ratio) on the growth and visual function of term infants. STUDY DESIGN: Normal term infants were assigned randomly and in masked fashion at birth to receive formulas with approximately 16% of total fatty acids as LA and 0.4%, 1.0%, 1.7%, or 3.2% of fatty acids as ALA (LA/ALA ratios of 44, 18.2, 9.7, and 4.8) for the first 4 months of life. The fatty acid pattern of plasma phospholipids was determined shortly after birth and at approximately 21, 60, and 120 days of age. Anthropometric data were obtained at the same times and also at approximately 240 days of age. Transient visual evoked responses (VERs) were measured at approximately 120 and 240 days of age. For comparisons, anthropometric and VER data also were obtained in infants who were exclusively breast-fed for the first 4 months of life. RESULTS: Infants who received the formula with 3.2% ALA (LA/ALA ratio, 4.8) had higher plasma concentrations of phospholipid docosahexaenoic acid (DHA) but lower concentrations of arachidonic acid at 21, 60, and 120 days of age. Mean weight of this group at 120 days of age was 760 gm less (p < 0.05) than the mean weight of the group that received the formula with 0.4% ALA (LA/ALA ratio, 44). Despite differences in plasma phospholipid DHA contents among groups, neither VER latency nor amplitude differed significantly among formula groups or between any formula group and age-matched, breast-fed infants. CONCLUSIONS: The highest versus the lowest ALA intake (or the lowest vs the highest LA/ALA ratio) resulted in higher plasma phospholipid DHA content from 21 to 120 days of age but was not associated with improved visual function as assessed by transient VER. Moreover, mean body weight of infants who received the highest versus lowest ALA intake was less at 120 days (p < 0.05). These data suggest that the lower LA/ALA ratios currently recommended for infant formulas should not be adopted until the effect of such ratios on growth are evaluated more completely.

Aplicaçäo do triglicerídeos de cadeia média (TCM) na prevençäo de úlceras de decúbito / The using of MCT in the ulcer prevent

Aproximadamente 75.000 das 1.000.000 pessoas hospitalizadas a cada ano desenvolvem Ulceras de Decúbito. Graças à tecnologia avançada, hoje temos várias opçöes de tratamento destas úlceras, ainda que isto seja dispendioso para os pacientes e hospitais. Porém, melhor que desenvolver um processo curativo, é poder desenvolver um processo preventivo eficáz. Com o objetivo de avaliar a eficácia do uso tópico de triglicerídeos de cadeia média (TCM) na prevençäo de Ulceras de Decúbito, a autora utilizou o método duplo-cego em 86 pacientes, onde 50 por cento foi submetido ao uso de soluçäo com TCM e 50 por cento ao uso de Soluçäo Glicerinada. Em ambos os casos, houve diminuiçäo da instalaçäo de Ulceras de Decúbito porém, dos pacientes que se submeteram ao uso da soluçäo com TCM, apenas 2 (dois) desenvolveram Ulcera de Decúbito (Grau 1); e dos pacientes que se submeteram ao uso de Soluçäo com Glicerina, 12 (doze) desenvolveram Ulcera de Decúbito (Graus 1 e 2). Concluiu-se que o TCM é de grande auxílio na prevençäo de Ulceras de Decúbito, tem excelente absorçäo para uso tópico, forma uma película protetora à pele, previne escoriaçöes devido à sua alta capacidade de hidrataçäo e proporciona nutriçäo celular local.

Essential fatty acid deficiency in neonates: inability to reverse deficiency by topical applications of EFA-rich oil.

Correction of essential fatty acid deficiency by transcutaneous absorption of topically applied EFA-rich oil has been reported. We measured serum EFA levels in two groups of neonates receiving fat-free total parenteral nutrition: nine control patients after 16 and 25 days of TPN, and six patients before and 12 days after beginning cutaneous application of 100 mg/kg/day of linoleic acid as sunflower seed oil. Progressive biochemical EFA deficiency occurred in all but one of the control patients. Of the six patients receiving 100 mg/kg/day of linoleic acid, one patient with mild deficiency improved, but progressive EFA deficiency occurred in the other five patients. Serum EFA levels were also measured in four patients following 76 days of TPN and daily application of high doses of topical safflower oil, all of whom had severe biochemical EFA deficiency. The topical application of EFA-rich oil cannot be assumed to be uniformly effective in reversing or preventing EFA deficiency. The transcutaneous absorption of essential fatty acids must be documented by appropriate measurements of EFA in serum lipids.