Type 2 diabetes mellitus is a chronic disease characterized by insulin resistance; inflammation; oxidative stress; vascular damage; and dysfunction of glucose, protein, and lipid metabolisms. However, comparatively less attention has been paid to neurologic alterations seen in elderly individuals with type 2 diabetes. We review clinical, metabolic, and biochemical aspects of diabetic encephalopathy (DE) and propose that quality of dietary lipids is closely linked to DE. This implies that preventive nutritional interventions may be designed to improve DE.

La dosis en terapia fotodinámica es proporcional a la fluencia de energía (distribución espacial de luz) y a la concentración de sustancias fotosensibles en los tejidos. El conocimiento de las propiedades ópticas del tejido (coeficiente de absorción, coeficiente de scattering) es necesario para calcular la distribución espacial de la luz in vivo. En muchos tejidos blandos en el rango visible del espectro el scattering es anisotrópico en el eje de incidencia del haz láser, y el camino libre medio entre interacciones es pequeño. Se han realizado mediciones por métodos directos del coeficiente de atenuación total y de la función fase de scattering en tejidos animales (blandos), con una longitud de onda de 632.8 nm. Los resultados demuestran que para los tejidos estudiados el scattering óptico es fuertemente "picudo" hacia adelante, con un coseno medio comprendido entre 0.90 y 0.99, y el coeficiente de atenuación toma valores entre 10 y 100 mm-1.

Urinary tract tumors are tenth in frequency, and many environmental carcinogens are excreted by urine. Interplay between chronic inflammatory urolithiasis and urothelial carcinogenesis is not well understood. Experimental evidences show that dietary melamine induce these events even at low concentrations. This is important because thousands of children were exposed to melamine through intentionally contaminated milk formula worldwide. We propose that an increased risk for urinary tumors in adult life may occur and screenings for early urinary signs may be necessary. Therefore, urothelial biology, melamine carcinogenic potential, and related epidemiology are discussed, recommending a preventive dietary polyunsaturated fatty acid-based supplementation, since they modulate such interplay in rodents.

El cancer se origina por mutaciones, competicion y seleccion natural en celulas somaticas de tejidos de diferentes organos,siendo un proceso complejo y multifactorial que ocurre en una secuencia de etapas: iniciacion, promocion y progresion (1). Factores hereditarios,geneticos y epigeneticos como los lipidos dietarios, estres oxidativo, hormonas, pesticidas y otros, influyen tanto en el desarrollo como en la inhibicion de esta enfermedad (2). Datos epidemiologicos y experimentales tanto nuestros como de otros laboratorios han demostrado que el consumo de dietas ricas en acidos grasos de la familia n-3, n-6 o n-9 cambian la fluidez, la actividad de enzimas, el nivel de proteinas y favorecen la formacion de moleculas bioactivas derivadas de los lipidos como los eicosanoides y endocanabinoides que modulan el proceso carcinogenico (3-15). Estos derivados lipidicos activan vias de senalizacion produciendo cambios especificos en la expresion genica, un proceso fundamental durante la transformacion neoplasica (1-2).Tambien ha sido demostrado que estos cambios en la expresion genica inducidos por derivados lipidicos modulan funciones en celulas cancerosas como proliferacion y muerte celular, migracion y produccion de matriz extracelular (16-17). A pesar de estos conocimientos, la identidad de los derivados lipidicos implicados en la modulacion de la expresion genica durante la transformacion neoplasica asi como los mecanismos utilizados por estas moleculas permanecen aun poco conocidos. HIPOTESIS: En los modelos a utilizar en el presente proyecto, la variacion lipidica de las membranas que se induzca por manipulacion dietaria deberan generar tambien variaciones en los eicosanoides . endocanabinoides y otros peroxidos que afecten factores de transcripcion nucleares como el p53 y GLI incidiendo en los mecanismos responsables de la muerte y proliferacion de celulas cancerosas. OBJETIVOS: Nos proponemos establecer el impacto de dietas enriquecidas con acidos grasos de las familias n-3, n-6 o n-9 sobre modelos experimentales in-vivo e in-vitro. Se estudiaran los acidos grasos de membrana plasmatica, la generacion de eicosanoides y endocanabinoides derivados de las vias COX y LOX Ademas se determinara el efecto de los peroxidos en la expresion y actividad de los factores nucleares de transcripcion p53 y GLI como mecanismos responsables de la muerte y proliferacion celular. MATERIALES Y METODO: Se utilizara un modelo in-vivo de cancer de mama empleando ratones C57BL6J inducidos con DMBA que se alimentaran con una dieta base semi-sintetica suplemetada con diferentes PUFAs (Chia: n-3, Maiz: n-6 y Oleico: n-9 , empleada en estudios previos (8).Modelos in vitro: se utilizaran lineas celulares cancerigenas humanas de mama MCF-7 y MDA, las cuales se trataran exogenamente con diferentes PUFAS (GLA:n-6,EPA:n-3, Oleico n-9)(9). Se determinaran acidos grasos de membranas por Cromatografia de gas (CG)(10-11). El analisis de eicosanoides en celulas tumorales se realizara por HPLC (9-11). Los endocanabinoides por GC-Espectometria de Masa (18).La formacion de peroxidos intracelulares se determinara por analisis de Glutation reducido (GSH)(16).La apoptosis se medira por actividad caspasas y por Citometria de flujo usando Annexina V FICT (19).La expresion celular de Tp53 y GLI se realizara por Western Blot, PCR e inmunohistoquimica (20-21).RESULTADOS ESPERADOS: Se espera que los lipidos anadidos en las dietas de ratones inyectados con DMBA o al medio de cultivo de celulas tumorales de mama o pancreas modifiquen los acidos grasos de membrana y sus derivados lipidicos los eicosanoides y endocanabionoides que suponemos afectaran la activacion y expresion de factores de transcripcion regulando la carcinogenesis. IMPORTANCIA: Disenar nuevos modelos experimentales para implementar en terapias genicas y aplicar los resultados sobre factores nutricionales que pudieran actuar como inhibidores o promotores del desarrollo del cancer en humanos.

The essential PUFAs (polyunsaturated fatty acids) serve as precursors of several bioactive lipids molecules including the endocannabinoids (ECS). This article reviews the components of the endocannabinoid system, and their functions. Furthermore, a brief overview on the relationship of this system with some physiological and pathological processes, with focus on metabolic and mental disorders is discussed. Experimental and clinical effects of modification of the ECS and results of the exogenous manipulation of PUFAs and consequent modulation on ECS are also outlined. Finally, we propose that the ECS system can be favourably modulated by exogenous manipulation of PUFAs that could help in the prevention and management of several diseases.

Objective. To determine the role of the habitual use of the most common artificial sweeteners (AS) in the development of urinary tract tumors (UTT) in Argentina.Methods. Case-control study of 197 patients with histologically confirmed UTT of transitional varieties, and 397 controls with acute, non-neoplastic, and non-urinary tract diseases, admitted to the same hospitals in Cordoba (Argentina) between 1999 and 2006. All subjects were interviewed about their use of AS and their exposure to other known or suspected risk factors for UTT.Results. Fifty-one UTT patients (26%) and 87 controls (22%) used AS. The risk of UTT was significantly increased in long-term ( 10 years) AS users compared with none-AS users. The OR (95% CI) for long-term consumers was 2.18 (1.22-3.89) and for short-term users was 1.10 (0.61-2.00) after adjustment for age, gender, BMI, social status. and years of tobacco use.Conclusion. Regular use of AS for 10 years or more was positively associated with UTT. (C) 2008 Elsevier Inc. All rights reserved.

The amount and type of dietary fats represent risk factors for several cancers. Essential PUFAs serve as precursors of several biologically active molecules, mainly endocannabinoids and eicosanoids, which participate in tumorigenic processes. However, their mechanisms still remain unclear. This article reviews the current knowledge and experimental results on the effects of dietary manipulation of n-3, n-6 essential fatty acids (EFA) including the conjugated linoleic acid (CLA), on eicosanoid and endocannabinoid production, and their correlation with cancer development. The oxidative pathways of Arachidonic acid (AA) when it is released from phospholipids as Lipoxygenases (LOXs), cyclooxygenases (COX) and Cytochrome P-450s (CYP450) to eicosanoids, and the non-oxidative pathway to endocannabinoid synthesis are summarized. COXs, LOXs, and CYP 450s, endocannabinoids, thereby generating oxygenated products that resemble eicosanoids with the slight difference that endocannabinoid- derived products retain amide or ester functionalities at C1. Competition between n-3 and n-6 FA families gives rise to a variation in the ratio of the eicosanoid products, but the significance of these changes are as yet poorly understood. Finally, we propose that the apparently contradictory results in the field of eicosanoids, endocannabionidsand cancer should be considered due to difficulties arising from the lack of nutritional evaluation.

Bladder tumors predominantly occur in high-income countries. However, South America deserves particular attention since is it is made up of countries with striking differences in their GNP per capita, representing a "chessboard" field for the study of tumor risk related to the environment. In recent times, a so-called "healthy" culture has emerged with people beginning to be conscious of the effects of food and nutrition on well-being and the risk of disease linked to being overweight. As a result of the so-called "healthy" culture, many people have substituted sugar for different types of Artificial Sweeteners (AS) which also have lower costs of production and commercialization. This article reviews and critically discusses the current literature regarding the correlations between AS and Urinary Tract Tumors worldwide, particularly taking into account recent data of case-control studies in South America, an area having distinctive dietary habits and food culture.

We investigated the effects of certain dietary polyunsaturated fatty acids (PUFAs) and related eicosanoids on the growth and metastasis formation of a murine mammary gland adenocarcinoma. Salvia hispanica (ChO) and Carthamus tinctorius (SaO) vegetable oil sources of omega-3 and -6 PUFAs and a commercial diet as control (CO), were used. We analysed fatty acids of neoplastic cells (NC) membranes by GLC; the eicosanoids 12- HETE and 12-HHT (LOX and COX metabolites) by HPLC and apoptosis and T-lymphocyte infiltration by flow cytometry and microscopy. NC from ChO groups showed lower levels of arachidonic acid and of both eicosanoids compared to SaO and CO (p<0.05). The ChO diet decreased the tumor weight and metastasis number (p<0.05). Apoptosis and T-lymphocyte infiltration were higher and mitosis decreased with respect to the other diets (p<0.05). Present data showed that ChO, an ancient and almost unknown source of omega-3, inhibits growth and metastasis in this tumor model.

We have previously shown that a single i.p. injection of nitrosomethylurea (NMU) in 3-day-old rats orally treated with the pesticide mancozeb (MZ), the flavonoid quercetin (Q) or in combination (MZ-Q) induces hyperplasia, atypical acinar cell proliferation and carcinoma in situ (CIS) in the pancreas. This work studies the effect of oral administration of phenobarbital (PB) on this model of pancreatic carcinogenesis. The animals were fed on a diet supplemented by NIZ or/and Q from the 10th day of pregnancy, thorough lactation and as pups after weaning until being sacrificed at week 24. Saline injection with non-supplemented diet was used for the control group (SAL). The experimental groups were (1) SAL (control), (2) SAL-PB, (3) NMU, (4) NMU-PB, (5) MZ-NMU, (6) MZ-NMU-PB, (7) Q-NMU, (8) Q-NMU-PB, (9) MZ-Q-NMU and (10) MZ-Q-NMU-PB. Acinar cell hyperplasia was found in all groups of NMU-treated rats. Dysplastic foci (DYS) were seen in groups 3-10 at the following percentages: 19, 48, 71, 27, 71, 35, 100 and 30, respectively. CIS were recorded in groups 4 to 10 at percentages: 4, 36, 13, 11, 0, 16, 5, respectively. Conclusion: Although PB, Q or NIZ given alone enhance DYS lesions in NMU-treated rats, the MZ/Q/PB combined treatments may increase (mainly in males) or decrease (mainly in female) the DYS and CIS proportion. Because PB, NIZ and Q influence P450 enzymes, we suggest that these enzymes play a role in the carcinogenesis process. (c) 2006 Elsevier Ltd. All rights reserved.

Conjugated linoleic acids (CLAs) are a group of octadecadienoic acids (18:2) that are naturally present in food products and may have beneficial health effects. Liposomes and ethanol solutions were prepared by mixing synthetic phosphatidylcholines (PCs) with c9,t11-CLA, t10,c12-CLA, and linoleic acid (LA) in the sn-2 position into natural PCs from soybean, egg yolk, rat brain, and rat heart at 5 mol %. The oxygen diffusion-concentration products were measured using electron spin resonance spin-label oximetry methods. Individual synthetic PCs, the phospholipid matrix, and the tested lipid systems all exhibited influence on oxygen diffusion-concentration products during lipid peroxidation. Incorporating 5 mol % PC(c9,t11-CLA) into soy and egg yolk PC increased oxygen consumption in liposome suspensions while it was decreased in rat heart and brain PCs. On the other hand, PC(t10,c12-CLA) increased oxygen consumption in mixtures with egg yolk and rat heart PC but decreased it in soybean and rat brain PC. By comparison, PC(LA) decreased oxygen consumption in every case. In ethanol solutions, all of the synthetic PCs suppressed the capacity to generate peroxide radicals in the order of LA > c9,t11-CLA > t10,c12-CLA. In addition, PCs containing individual CLA isomers and LA differed in their capacities to react with and quench DPPH radicals in both ethanol solution and liposome, suggesting differences between CLA isomers and LA in DPPH radical-fatty acid interactions. Incorporation of CLA isomers and LA into dimyristyl-PC reduced the phase transition temperature from 23.6 to 23.1 and 23.3 degrees C, respectively. The results of this study provide evidence that the behavior of CLA isomers differs in the microenvironment of membranes possibly due to structural differences that affect the permeability of membranes to oxygen and lipid peroxidation.

Chronic toxic effects of arsenic resulting from drinking water are a human health problem, especially in South-America and Asia. Arsenic is capable of influencing various cellular processes, causing adverse effects, including cancer. Although the exact mechanism of the action is not known, a correlation between oxidative stress, tumour promotion and arsenic exposure has been observed. We examined the effects of silymarin and quercetin, in counteracting oxidative stress produced by acute or sub-chronic sodium arsenite exposure. The stress responses to arsenite included an increase in the heat shock protein 70 kDa expression, lipid peroxidation assayed by conjugated dienes measure, and gamma-glutamyl-transpeptidase activity. We found that all these stress responses were eliminated by silymarin and quercetin in acute experiments. Both flavonoids diminished the conjugated dienes formation during sub-chronic cultures. Our results suggest that these antioxidant flavonoids, which may be easily incorporated into the diet, may afford a protective effect against arsenite-induced cytotoxicity.

Dietary fat influences dimethylbenzanthracene (DMBA)-induced tumorigenesis of several organs, including the salivary glands. There is not enough evidence to suggest that soy oil could also affect growth of salivary tumors. The main purpose of this work therefore was to study the effects of dietary soy oil on macroscopic parameters of chemically induced murine salivary gland tumors. Eighty BALB/c male mice were assigned to four groups: soy oil (SO), corn oil (CO, control), fish oil (FO) and olein (O). Two weeks later, tumors were induced by 9,10-dimethyl-1,2-benzanthracene (DMBA). At the 13th post-injection week, the animals were sacrificed. In vivo tumor diameter, gland volume (total resected mass), tumor volume (microscopically measured), tumor remission and tumor histopathology were analyzed. The initial in vivo tumor diameter, gland and tumor volume were significantly greater in soy oil than in fish oil group. 26.7% of animals on the soy oil diet showed tumor remission. Sarcomas were more often found in the SO group, carcinomas in FO and the mixed-type tumors both in SO and CO groups. This study shows that the soy oil treatment resulted in larger tumors, some of which later became undetectable. It is necessary to further investigate these divergent results.

Dietary arachidonic acid (AA) and eicosanoids influence neoplastic cell (NC) growth, differentiation and apoptosis. Plasma membrane fatty acid and cyclooxygenase (COX) and lipoxygenase (LOX) products were investigated in lung alveolar carcinoma cells from mice fed on different diets. Two groups were fed on a basic diet plus 6% of: corn oil (rich in 18:2n-6; CO) and on olein oil (rich in 18:1n-9; O), respectively. Control group (C) received commercial diet. NC fatty acids were analyzed by GLC, and apoptosis by flow cytometry and microscopy. In NC from CO group AA levels and LOX metabolites were increased, whereas COX metabolites decreased. NC from CO compared to O group diet showed a higher count of apoptosis and increased LOX:COX ratio. High levels of AA and decreased COX eicosanoids has been involved in anti-tumoral mechanisms by increasing tumor cell apoptosis. Present data emphasizes the implications of the dietary fatty acids on the neoplastic process in this tumoral model.

The purpose of this work was to analyze the effect of diets that contain several oils whose composition in fatty acids were different, on the kinetic parameters of the gamma-glutamyltranspeptidase (GGTP) and the lipoperoxidation of the epididymis because GGTP controls the level of the glutathione that is an molecule that regulates the level of oxidation protecting the maturation and survival of sperm in the lumen of the epididymis. The caput portion of the epididymis was chosen because the epithelium of this segment synthesizes GGTP. Weaned BALB-c mice were fed a commercial or semi-synthetic diet that contained 5% added olein. The mice were maintained on corn oil or fish oil diet for the first 4-8 months of age. The kinetic variables of the GGTP enzyme, analyzed by means of multiple regression analysis using dummy variables, showed that values were similar in olein and corn oil samples, whereas in samples from the fish oil fed group the enzyme behaved as that in animals maintained on commercial diets. Although there were no variations in maximum velocity (Vm) of the enzyme, the Km value, was greater (P < 0.0001) for the mice fed the olein and corn diets. These groups contained greater percentages of the monounsaturated fatty acids, palmitoleic (16:1 n-7) and oleic acid, 18:1 n-9. Similarly, the amount of lipid peroxidation was also greater in the olein and corn oil groups with respect to commercial and fish groups. The significant increment in Km of GGTP in the olein and corn groups was correlated with greater amount of monounsaturated fatty acids and lipid peroxidation in the epididymis. In conclusion, modifications of dietary lipid sources differentially modulated the epididymis tissue fatty acid profile, lipid peroxidation amounts, and the Km of GGTP. These effects may alter the metabolism of the natural substrate of GGTP, glutathione, a tripeptide with a powerful antioxidant activity, which is necessary in maintaining the oxidative state of the sperm microenvironment, thereby favoring maturation of the male gametes.

Objective: Since conventional food questionnaires are not precise in assessing the dietary fatty acids, the purpose of this study was to determine the relationship between the salivary fatty acid profile and the alimentary habits of two different groups in an attempt to develop a more reliable way to determine the lipidic intake.Design: Twenty adults of both sexes, with mixed (M) or vegetarian (V) diets were studied. Data about the fat intake were obtained by means of a Food Frequency Questionnaire (FFQ) and the presence of the main salivary fatty acids was determined by gas chromatography.Results: A greater salivary concentration of alpha-linolenic acid (18:3 n-3) (2.82) was found in V than in M subjects (1.65) (p = 0.001), whilst arachidonic acid (20:4 n-6) was lower in V (3.93) than in M (4.52) (p = 0.045). The same difference regarding arachidonic acid was observed in the dietary fatty acid intake, also showing a significant correlation between its dietary and salivary levels in vegetarian subjects.Conclusions: These results show that salivary arachidonic acid, relevant for their eicosanoid production related to the tumourigenesis process and cardiovascular diseases, is influenced by dietary fats. (C) 2004 Elsevier Ltd. All rights reserved.