Dietary fatty acids and the time elapsed from their intake are related to their composition in rat submandibular gland and salivary flow rates.

OBJECTIVES: The aim of this study was to analyze the influence of dietary fatty acids (FAs) and the time elapsed from their intake on FA tissue profile of rat submandibular gland (SG) and on its salivary flow rate (SFR). Do dietary FAs depending on the intake time modify their profile in SG and consequently the SFR? MATERIALS AND METHODS: Thirty-six adult male Wistar rats were fed on control diet (corn oil, CD, 18:2 n-6 FA) for 7 days and then divided into CD and two groups with replacement of corn oil by olive (OD, 18:1 n-9 FA) or chia (ChD, 18:3 n-3 FA) oils (1 and 30 day intake). Submandibular ducts were canalized to collect saliva for 20 min (µL/min). SG were examined (optical/electron microscopy; ImageJ 1.48 software). RESULTS: SFR values were 6.18 ± 0.34 (CD1), 6.04 ± 0.31 (OD1), and 6.00 ± 0.50 (ChD1) (p > 0.05). At 30-day intake, higher SFR values in ChD (7.82 ± 0.7) with respect to CD (4.68 ± 0.44; p < 0.001) and OD (6.08 ± 0.2; p = 0.038) were found. ChD30 showed a higher serous acinous area percentage than CD30 and OD30, whereas mucous acinous density was greater in CD30 than in OD30 and ChD30 (p < 0.05). α-Linolenic (ALA) and eicosapentaenoic and docosahexaenoic acid levels were only detected in SG of ChD30, while arachidonic acid was lower in this group as compared with CD30 and OD30 (p < 0.05). CONCLUSIONS: SG FA composition and its SFR appear to be modulated by dietary FAs and the time elapsed from their consumption. SFR is highest with n-3 ALA-rich ChD at 30-day intake. CLINICAL RELEVANCE: Diet could contribute to improve secretory dysfunctions.

Molecular Basis of the Beneficial Actions of Resveratrol.

Resveratrol modulates the transcription factor NF-κB, cytochrome P450 isoenzyme CYP1A1, expression and activity of cyclooxygenase (COX) enzymes, Fas/Fas ligand mediated apoptosis, p53, mTOR and cyclins and various phospho-diesterases resulting in an increase in cytosolic cAMP levels. Cyclic AMP, in turn, activates Epac1/CaMKKß/AMPK/SIRT1/PGC-1α pathway that facilitates increased oxidation of fatty acids, mitochondrial respiration and their biogenesis and gluconeogenesis. Resveratrol triggers apoptosis of activated T cells and suppresses tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17) and other pro-inflammatory molecules and inhibits expression of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) that may explain its anti-inflammatory actions. Polyunsaturated fatty acids (PUFAs) and their anti-inflammatory metabolites lipoxin A4, resolvins, protectins and maresins have a significant role in obesity, type 2 diabetes mellitus (T2DM), metabolic syndrome and cancer. We observed that PUFAs (especially arachidonic acid, AA) and BDNF (brain-derived neurotrophic factor) protect against the cytotoxic actions of alloxan, streptozotocin, benzo(a)pyrene (BP) and doxorubicin. Thus, there is an overlap in the beneficial actions of resveratrol, PUFAs and BDNF suggesting that these molecules may interact and augment synthesis and action of each other. This is supported by the observation that resveratrol and PUFAs modulate gut microbiota and influence stem cell proliferation and differentiation. Since resveratrol is not easily absorbed from the gut it is likely that it may act on endocannabinoid and light, odor, and taste receptors located in the gut, which, in turn, convey their messages to the various organs via vagus nerve.

Eicosapentaenoic acid prevents salt sensitivity in diabetic rats and decreases oxidative stress.

OBJECTIVES: Salt sensitivity (SS) is associated with increased cardiovascular risk in patients with Type 2 diabetes mellitus (T2-DM) due to an increase in renal oxidation. ω-3 polyunsaturated fatty acids have shown antioxidant effects, but a typical Western diet contains limited content. In particular, ω-3 polyunsaturated fatty acids are able to activate nuclear factor erythroid 2-related factor 2 (Nrf-2) to prevent diabetes mellitus-related complications by mitigating oxidative stress. Therefore, we hypothesized that eicosapentaenoic acid (EPA; ω-3) modulates SS in rats with T2-DM by decreasing renal oxidative stress via Nrf-2 activation and enhancing the antiinflammatory response via interleukin (IL) 6 modulation. METHODS: Three-month-old male rats (n = 40) were fed with a Normal Na-diet (NNaD) and randomly selected into four groups: Healthy Wistar nondiabetic rats (Wi), diabetic controls (eSS), arachidonic acid-treated eSS (AA; ω-6), and EPA-treated eSS (ω-3). After 1 year, rats were placed in metabolic cages for 7 d and fed a NNaD, followed by a 7-d period with a High Na-diet (HNaD). Systolic blood pressure, body weight, serum IL-6 and reactive oxygen species (ROS) levels were determined at the end of each 7-d period. Glycated hemoglobin (HbA1c), triacylglycerol, creatinine, and cholesterol levels were determined. ROS levels and Nrf-2 expression in kidney lysates were also assayed. Histologic changes were evaluated. A t test or analysis of variance was used for the statistical analysis. RESULTS: After a HNaD, systolic blood pressure increased in both the control eSS and AA groups, but not in the EPA and Wi groups. However, HbA1c levels remained unchanged by the treatments, which suggests that the observed beneficial effect was independent of HbA1c levels. The IL-6 levels were higher in the eSS and AA groups, but remained unaltered in EPA and Wi rats after a HNaD diet. Interestingly, EPA protected against serum ROS in rats fed the HNaD, whereas AA did not. In kidney lysates, ROS decreased significantly in the EPA group compared with the eSS group, and Nrf-2 expression was consistently higher compared with the AA and eSS groups. Diabetic rats presented focal segmental sclerosis, adherence to Bowman capsule, and mild-to-moderate interstitial fibrosis. EPA and AA treatment prevented kidney damage. CONCLUSIONS: An adequate ω3-to-ω6 ratio prevents SS in diabetic rats by a mechanism that is independent of glucose metabolism but associated with the prevention of renal oxidative stress generation. These data suggest that EPA antioxidant properties may prevent the development of hypertension or kidney damage.

Role of ω3 polyunsaturated fatty acids in diabetic retinopathy: a morphological and metabolically cross talk among blood retina barriers damage, autoimmunity and chronic inflammation.

Vision disorders are one of the most serious complications of diabetes mellitus (DM) affecting the quality of life of patients and eventually cause blindness. The ocular lesions in diabetes mellitus are located mainly in the blood vessels and retina layers. Different retina lesions could be grouped under the umbrella term of diabetic retinopathies (DMRP).We propose that one of the main causes in the etiopathogenesis of the DMRP consists of a progressive loss of the selective permeability of blood retinal barriers (BRB). The loss of selective permeability of blood retinal barriers will cause a progressive autoimmune process. Prolonged autoimmune injures in the retinal territory will triggers and maintains a low-grade chronic inflammation process, microvascular alterations, glial proliferation and subsequent fibrosis and worse, progressive apoptosis of the photoreceptor neurons.Patients with long-standing DM disturbances in retinal BRBs suffer of alterations in the enzymatic pathways of polyunsaturated fatty acids (PUFAs), increase release of free radicals and pro-inflammatory molecules and subsequently incremented levels of vascular endothelial growth factor. These facts can produce retinal edema and photoreceptor apoptosis.Experimental, clinical and epidemiological evidences showing that adequate metabolic and alimentary controls and constant practices of healthy life may avoid, retard or make less severe the appearance of DMRP. Considering the high demand for PUFAs ω3 by photoreceptor complexes of the retina, it seems advisable to take fish oil supplements (2 g per day). The cellular, subcellular and molecular basis of the propositions exposed above is developed in this article.Synthesizer drawings the most relevant findings of the ultrastructural pathology, as well as the main metabolic pathways of the PUFAs involved in balance and disbalanced conditions are provided.

Diabetic encephalopathy: beneficial effects of supplementation with fatty acids ω3 and nordihydroguaiaretic acid in a spontaneous diabetes rat model.

BACKGROUND: Diabetic encephalopathy is a chronic complications of diabetes mellitus that affects the central nervous system. We evaluated the effect of ω3 and ω6 polyunsaturated fatty acids (PUFAs) supplementation plus the antioxidant agent nordihydroguaiaretic acid (NDGA) on the etiopathology of diabetic encephalopathy in eSS rats, a spontaneous model of type 2 diabetes. METHODS: One hundred twenty spontaneous diabetic eSS male rats and 38 non-diabetic Wistar, used as healthy control, received monthly by intraperitoneal route, ω3 or ω6 PUFA (6.25 mg/kg) alone or plus NDGA (1.19 mg/kg) for 12 months. Diabetic rats had a worse performance in behavioural Hole-Board test. Histopathological analysis confirmed lesions in diabetic rats brain tissues. We also detected low expression of synaptophysin, a protein linked to release of neurotransmitters, by immunohistochemically techniques in eSS rats brain. Biochemical and histopathological studies of brain were performed at 12th month. Biochemical analysis showed altered parameters related to metabolism. High levels of markers of oxidative stress and inflammation were detected in plasma and brain tissues. Data were analysed by ANOVA test and paired t test was used by comparison of measurements of the same parameter at different times. RESULTS: The data obtained in this work showed that behavioural, biochemical and morphological alterations observed in eSS rats are compatible with previously reported indices in diabetic encephalopathy and are associated with increased glucolipotoxicity, chronic low-grade inflammation and oxidative stress burden. Experimental treatments assayed modulated the values of studied parameters. CONCLUSIONS: The treatments tested with ω3 or ω3 plus NDGA showed improvement in the values of the studied parameters in eSS diabetic rats. These observations may form the basis to help in prevent and manage the diabetic encephalopathy.

Effects of bioavailable phenolic compounds from Ilex paraguariensis on the brain of mice with lung adenocarcinoma.

Lung carcinoma is one of the most common cancers and has a high mortality. Recently, we showed that it produces neurological paraneoplastic syndrome, with Ilex paraguariensis (IP) extract exerting palliative effects due to its content of phenolic compounds. It is possible, therefore, that these diet agents can arrive at the brain and exert neuroprotection, after the oral intake of IP. Here, the aim was to investigate the protective role of bioavailable IP compounds on the telencephalon and diencephalon in lung adenocarcinoma-bearing BALB/cJ males. Mice aged 2 months were treated for 3 weeks with 0-100 IP mg·kg-1 ·day-1 . HPLC-UV revealed the presence of chlorogenic acid and quercetin in brain regions, liver, and tumour, in an IP dose-dependent manner. Brain was also evaluated histologically, and interleukin-6 was measured by ELISA. Chlorogenic acid was the major compound found in brain, whereas quercetin was observed at the diencephalon to a lesser extent. Both compounds were involved in IP dose-dependent diencephalic interleukin-6 reduction. Histology suggested cellular protection with less apoptosis in chlorogenic-exposed areas. Taken together, chlorogenic acid and quercetin from dietary IP were bioavailable and bioactive in brain, thereby attenuating lung cancer-related neuroinflammation and damage. These findings support plant-based strategies to improve prognosis.

Neuroprotective Effect of Ilex Paraguariensis Intake on Brain Myelin of Lung Adenocarcinoma-Bearing Male Balb/c Mice.

Ilex paraguariensis (IP) is widely consumed as tea with high nutritional value. This plant contains several bioactive phenolic compounds, which are antioxidant and anti-inflammatory. On the other hand, lung adenocarcinoma (LAC) deleteriously involves neoplastic progression, inflammatory paraneoplastic syndromes, and death. Given that brain is a frequent target of this illness, our objective was to determine the neuroprotective effect of IP consumption in LAC-bearing mice. They were orally treated with 50 mg of IP extract/kg/day (IP50) for 3 weeks. Results (phenolic compounds, lipid peroxides, interleukin 6-IL-6-, tumor necrosis factor alpha -TNFα-, and luxol-stained myelination) were compared with respect to untreated controls (C) by the T test. IP50 significantly lowed brain IL-6 (2858.12 ± 57.81 pg g-1 vs. 3801.30 ± 27.34 pg g-1), whereas other variables differed in a less extent. C brains showed demyelination (low luxol-staining contrast between gray and white matters), with IP50 increasing myelination (P < 0.05). In conclusion, LAC deleterious effects on murine brain were prevented by dietary IP, which is an original discovery to develop a nutritional approach against cancer neurological compromise.

Omega-3 and Omega-6 salivary fatty acids as markers of dietary fat quality: A cross-sectional study in Argentina.

The use of saliva for analyzing biological compounds has recently been expanded. The aim of this study was to analyze the correlation between specific dietary sources of n3 and n6 fatty acids (FA) and their salivary levels to evaluate their role as intake markers. Seventynine healthy volunteers were included. A validated food frequency questionnaire was used for data collection and Interfood v.1.3 software was employed to quantify food intake. Salivary samples were collected following international standards and FA profile was determined by gas liquidchromatography. Multiple linear regression analyses were performed for dependent variables (salivary FA profile) to detect independent associations with n3 and n6 FA food source intake, adjusted by age, gender, bodymass index, total energy intake, regular exercise, alcohol intake and smoking. Salivary concentrations of alphalinolenic acid (ALA) 18:3 n3 were significantly associated with nuts intake (ß=0.05, 95% CI 0.020.07, p=0.04). Salivary concentrations of linoleic acid (LA) 18:2 n6 and arachidonic acid (AA) 20:4 n6 were associated with the intake of n6 vegetable oils and red meat, cold meat and viscera (ß=0.80, 95% CI 0.060.09 p=0.03; ß=0.40, 95% CI 0.300.50, p=0.02, respectively). This study supports the hypothesis that salivary concentrations of n3 and n6 FA are related to food intake. Monitoring dietary FA though salivary markers is relevant for nutrition epidemiology and for prevention and management of several diseases related to fat intake.

El uso de biomarcadores salivales está en continua expansión. El objetivo de este estudio fue analizar la asociación entre fuentes alimentarias de ácidos grasos (AG) n3 y n6 y sus concentraciones salivales como marcador de ingesta. Parti ci paron 79 voluntarios sanos. Se aplicó un cuestionario validado de frecuencia de consumo alimentario y el software Interfood v.1.3 para su procesa miento. Las muestras saliva les se recogieron según estándares internacionales y se determinó el perfil de AG salivales por cromatografía gaseosa. Se desarrolló un modelo de regresión lineal múltiple ajustado por sexo, edad, índice de masa corporal, valor energético total, actividad física, consumo de tabaco y alcohol para analizar la asociación entre el perfil de AG salivales y la ingesta de alimentos fuente de AG n3 y n6. Las concentraciones salivales del AG alfalinolénico (ALA) 18:3 n3 se asociaron positivamente con la ingesta de nueces (ß=0.05, IC 95% 0.020.07, p=0.04), mientras que las concentraciones salivales de ácido linoleico (AL) 18:2 n6 y araquidónico (AA) 20:4 n6 se asociaron con el consumo de aceites ricos en n6 (ß=0.80, 95% IC 0.060.09 p=0.03) y de carnes rojas, fiambres y embutidos y vísceras, (ß=0.40, IC 95% 0.300.50, p=0.02). De acuerdo a estos resultados, las concen traciones salivales de AG n3 y n6 se relacionan a la ingesta de sus alimentos fuente. El monitoreo de la ingesta lipídica a través de biomarcadores salivales constituye un aporte a la epidemiología nutricional y a la prevención y tratamiento de patologías vinculadas a la ingesta de grasas.

Modulation of Fatty Acids and Interleukin-6 in Glioma Cells by South American Tea Extracts and their Phenolic Compounds.

Dietary phenolic compounds are plant metabolites with beneficial effects on the central nervous system. Thus, our aim was to identify anti-inflammatory compounds from South American plants on glia, which regulates neuro-immune response. The compounds were extracted from Lantana grisebachii (LG), Aspidosperma quebracho-blanco (AQB), and Ilex paraguariensis (IP) teas and identified by HPLC-DAD-MS. Extracts (0-200 µg/ml) were tested on human T98-G and rat C6 glioma lines. Cellular viability (by the resazurin assay), fatty acid profile (by gas chromatography) and pro-inflammatory interleukin-6 release (IL-6 by ELISA) were determined. Data were analyzed by partial least-square regression to discriminate bioactive compounds. Twenty-one compounds were determined in LG, mainly iridoids, which were linked to ω-3 and ω-6 polyunsaturated fatty acids, but not to IL-6 release. Thirty-one compounds were found in AQB, mostly hydroxybenzoic derivatives, which were positively related to IL-6 release. Twenty-three compounds were identified in IP, including caffeoylquinic derivatives and mainly chlorogenic acid. They increased the ω-7 palmitoleic fatty acid, which was related to IL-6 decrease. These results enhances phytochemical knowledge of widely available plants, and suggest the lipid-related anti-inflammatory activity of IP phenolic compounds, which give nutritional relevance to the tea.

Omega-3 and Omega-6 salivary fatty acids as markers of dietary fat quality: a cross-sectional study in Argentina

The use of saliva for analyzing biological compounds has recently been expanded. The aim of this study was to analyze the correlation between specific dietary sources of n3 and n6 fatty acids (FA) and their salivary levels to evaluate their role as intake markers. Seventynine healthy volunteers were included. A validated food frequency questionnaire was used for data collection and Interfood v.1.3 software was employed to quantify food intake. Salivary samples were collected following international standards and FA profile was determined by gas liquidchromatography. Multiple linear regression analyses were performed for dependent variables (salivary FA profile) to detect independent associations with n3 and n6 FA food source intake, adjusted by age, gender, bodymass index, total energy intake, regular exercise, alcohol intake and smoking. Salivary concentrations of alphalinolenic acid (ALA) 18:3 n3 were significantly associated with nuts intake (ß=0.05, 95% CI 0.020.07, p=0.04). Salivary concentrations of linoleic acid (LA) 18:2 n6 and arachidonic acid (AA) 20:4 n6 were associated with the intake of n6 vegetable oils and red meat, cold meat and viscera (ß=0.80, 95% CI 0.060.09 p=0.03; ß=0.40, 95% CI 0.300.50, p=0.02, respectively). This study supports the hypothesis that salivary concentrations of n3 and n6 FA are related to food intake. Monitoring dietary FA though salivary markers is relevant for nutrition epidemiology and for prevention and management of several diseases related to fat intake (AU)

El uso de biomarcadores salivales está en continua expansión. El objetivo de este estudio fue analizar la asociación entre fuentes alimentarias de ácidos grasos (AG) n3 y n6 y sus concentraciones salivales como marcador de ingesta. Parti ci paron 79 voluntarios sanos. Se aplicó un cuestionario validado de frecuencia de consumo alimentario y el software Interfood v.1.3 para su procesa miento. Las muestras saliva les se recogieron según estándares internacionales y se determinó el perfil de AG salivales por cromatografía gaseosa. Se desarrolló un modelo de regresión lineal múltiple ajustado por sexo, edad, índice de masa corporal, valor energético total, actividad física, consumo de tabaco y alcohol para analizar la asociación entre el perfil de AG salivales y la ingesta de alimentos fuente de AG n3 y n6. Las concentraciones salivales del AG alfalinolénico (ALA) 18:3 n3 se asociaron positivamente con la ingesta de nueces (ß=0.05, IC 95% 0.020.07, p=0.04), mientras que las concentraciones salivales de ácido linoleico (AL) 18:2 n6 y araquidónico (AA) 20:4 n6 se asociaron con el consumo de aceites ricos en n6 (ß=0.80, 95% IC 0.060.09 p=0.03) y de carnes rojas, fiambres y embutidos y vísceras, (ß=0.40, IC 95% 0.300.50, p=0.02). De acuerdo a estos resultados, las concen traciones salivales de AG n3 y n6 se relacionan a la ingesta de sus alimentos fuente. El monitoreo de la ingesta lipídica a través de biomarcadores salivales constituye un aporte a la epidemiología nutricional y a la prevención y tratamiento de patologías vinculadas a la ingesta de grasas (AU)

Long chain polyunsaturated fatty acids (LCPUFAs) and nordihydroguaiaretic acid (NDGA) modulate metabolic and inflammatory markers in a spontaneous type 2 diabetes mellitus model (Stillman Salgado rats).

BACKGROUND: Diabetes mellitus (DM) is a complex disease with alterations in metabolic and inflammatory markers. Stillman Salgado rats (eSS) spontaneously develop type 2 DM by middle age showing progressive impairment of glucose tolerance with hyperglycemia, hypertriglyceridemia and hyperinsulinemia. We analyzed the effects of supplementation of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) with or without nordihydroguaiaretic acid (NDGA) added, an antioxidant and lipoxygenase inhibitor, on metabolic and inflammatory parameters in eSS rats to evaluate whether they can delay development and/or prevent progression of DM. METHODS: After weaning, eSS rats received, intraperitoneally, once a month ω-3 (EPA 35% and DHA 40%-6.25 mg/Kg) or ω-6 (90% arachidonic acid- 6. 25 mg/Kg) for twelve months. Two additional groups of rats received 1.9 mg/kg NDGA added to ω-3 and ω-6 fatty acids. Blood samples were collected at day 40, and at the end of the 6th month and 12th month of age to determine plasma triglycerides (TGs), total plasma fatty acids (FA), A1C hemoglobin (HbA1C), C-reactive protein (CRP), gamma glutamyl transpeptidase (GGT), lipo and hydro peroxides, nitrites and IL-6 (in plasma and liver, kidney, and pancreas) and underwent oral glucose tolerance test (OGTT) as well. Wistar and eSS rats that received saline solution were used as controls. RESULTS: Plasma lipids profile, TG, fasting and post-prandial blood glucose levels, and glycosylated HbA1C showed significant improvements in ω-3 and ω-3 + NDGA treated animals compared to eSS control group. ω-3 and ω-3 + NDGA groups showed an inverse correlation with fasting blood glucose and showed lower plasma levels of GGT, TG, and CRP. eSS rats treated with ω-3 LCPUFAs showed reduced level of inflammatory and oxidative indices in plasma and liver, kidney and pancreas tissues in comparison with eSS control (non-treated) and ω-6 treated groups. CONCLUSIONS: eSS rats are a useful model to study type 2 DM pathophysiology and related inflammatory indices. ω-3 + NDGA supplementation, at the doses tested, ameliorated inflammatory, metabolic and oxidative stress markers studied.

Beneficial action of resveratrol: How and why?

Flavonoid resveratrol modulates the transcription factor NF-κB; inhibits the cytochrome P450 isoenzyme CYP1 A1; suppresses the expression and activity of cyclooxygenase enzymes; and modulates Fas/Fas-ligand-mediated apoptosis, p53, mammalian target of rapamycin, and cyclins and various phosphodiesterases. This increases the cytosolic cAMP that activates Epac1/CaMKKß/AMPK/SIRT1/PGC-1α pathway, which in turn facilitates increased oxidation of fatty acids, mitochondrial biogenesis, mitochondrial respiration, and gluconeogenesis. Resveratrol triggers apoptosis of activated T cells and suppresses tumor necrosis factor-α, interluekin-17 (IL-17), and other proinflammatory molecules, and thus is of benefit in autoimmune diseases. In addition, resveratrol inhibits expression of hypoxia-inducible factor-1α and vascular endothelial growth factor, explaining its effective action against cancer. Brain-derived neurotrophic factor (BDNF) that is involved in the pathogenesis of obesity, type 2 diabetes mellitus, and metabolic syndrome is also altered in depression, schizophrenia, bipolar disorder, and autism. We noted that BDNF protects against cytotoxic actions of alloxan, streptozotocin, and benzo(a)pyrene. Resveratrol prevents bisphenol A-induced autism, type 2 diabetes mellitus, and metabolic syndrome, suggesting that it may augment BDNF synthesis and action. We also observed that BDNF levels are low in type 2 diabetes mellitus and that BDNF enhances production of antiinflammatory lipid, lipoxin A4, whose levels are low in diabetes mellitus. Thus, resveratrol may augment production of lipoxin A4. Resveratrol alters gut microbiota and influences stem cell proliferation and differentiation. These pleiotropic actions of resveratrol may explain the multitude of its actions and benefits.

Polyunsaturated fatty acids and gliomas: a critical review of experimental, clinical, and epidemiologic data.

Certain polyunsaturated fatty acids (PUFAs) called essential fatty acids (EFAs) cannot be biosynthesized by the body and hence, need to be obtained from diet. These PUFAs and their metabolites have multiple physiological functions that are altered in tumor cells due to a decreased expression of Δdelta-6-desaturase, which is an essential step in their metabolism. As a result, tumor cells would be protected from the toxic effect caused by free radicals, one product of EFA metabolism. EFAs have been proposed to have therapeutic potential in the treatment of glioblastoma. Gliomas are the most common primary tumors of the central nervous system in children and adults. High-grade gliomas remain a therapeutic challenge in neuro-oncology because there is no treatment that achieves a significant improvement in survival. Novel therapeutic strategies that use PUFAs for the treatment of gliomas have been assessed in cell cultures, rodent glioma models, and humans, with encouraging results. Here we review the latest progress made in the field.

In Vitro Infection of Trypanosoma cruzi Causes Decrease in Glucose Transporter Protein-1 (GLUT1) Expression in Explants of Human Placental Villi Cultured under Normal and High Glucose Concentrations.

Trypanosoma cruzi, the etiologic Chagas' disease agent, induces changes in protein pattern of the human placenta syncytiotrophoblast. The glucose transporter protein-1 (GLUT1) is the primary isoform involved in transplacental glucose transport. We carried out in vitro assays to determine if T. cruzi infection would induce changes in placental GLUT1 protein expression under normal and high concentration of glucose. Using Western blot and immunohistological techniques, GLUT1 expression was determined in normal placental villi cultured under normal or high concentrations of glucose, with or without in vitro T. cruzi infection, for 24 and 48 hours. High glucose media or T. cruzi infection alone reduced GLUT1 expression. A yet more accentuated reduction was observed when infection and high glucose condition took place together. We inform, for the first time, that T. cruzi infection may induce reduction of GLUT1 expression under normal and high glucose concentrations, and this effect is synergic to high glucose concentrations.

Is insulin resistance a disorder of the brain?

There is reasonable evidence to suggest that insulin resistance may have its origins in the hypothalamus. Insulin secretion is regulated by sympathetic and parasympathetic nervous systems and modulates the concentrations of hypothalamic neuropeptides and monoaminergic neurotransmitters, and, in return, hypothalamic monoamines regulate the secretion of insulin by pancreatic beta cells. A lesion of the ventromedial hypothalamus produces all the features of the metabolic syndrome including insulin resistance and hyperinsulinemia. These and other evidence suggest that insulin resistance may very well be a disease of the brain.

L-arginine, NO and asymmetrical dimethylarginine in hypertension and type 2 diabetes.

Both hypertension and type 2 diabetes mellitus are common and there are no reliable markers either to predict their development or complications. High fat diet and carbohydrate-rich diet enhance serum asymmetrical dimethylarginine (ADMA) levels, an endogenous inhibitor of nitric oxide synthesis. ADMA levels are elevated in patients with hypertension, poor control of hyperglycemia, diabetic microangiopathy and macroangiopathy and dyslipidemia. One of the earliest signs of vascular dysfunction and insulin resistance, which are present in hypertension and type 2 diabetes mellitus, is an elevation in serum ADMA levels. Displacing plasma ADMA by oral supplementation of L-arginine restores endothelial dysfunction by augmenting endothelial nitric oxide generation. Strict control of hyperglycemia decreases serum ADMA levels. These and other studies suggest that serum ADMA levels could be used to predict the development of hypertension and type 2 diabetes mellitus in those who are at high-risk to develop these diseases.

Role of PUFAs, the precursors of endocannabinoids, in human obesity and type 2 diabetes.

Polyunsaturated fatty acids (PUFAs) serve as precursors of the endocannabinoids (ECs) that are bioactive lipids molecules. Recent studies revealed that ECs participate in several physiological and pathological processes including obesity and type 2 diabetes mellitus. Here we review the experimental and clinical aspects of the role of endocannabinoids in obesity and type 2 diabetes mellitus and the modification of the endocannabinoids by exogenously administered PUFAs. Based on these evidences, we propose that the endocannabinoid system (ECS) can be modulated by exogenous manipulation of PUFAs that could help in the prevention and management of human diseases such as obesity, metabolic syndrome and type 2 diabetes mellitus.

[Cellular components and placental alkaline phosphatase in Trypanosoma cruzi infection ]. / Componentes celulares y fosfatasa alcalina placentaria en la infección por T. cruzi.

Trypanosoma cruzi induces changes in the protein pattern of human placenta syncytiotrophoblast. Placental alkaline phosphatase (PLAP) is a glycoenzyme anchored to the membrane by a glycosyl-phosphatidylinositol molecule. PLAP activity and its presence was altered by the parasite in cultures of human placental villi and HEp2 cells with T.cruzi. The cells treated before the cultures with agents which affect PILAP or glycosyl-phosphatidylinositol (antibodies, PL-C, genistein, lithium) presented less parasitic invasion than the control ones. It was also observed a modification in the pattern of actine filaments of the host cells infected. We concluded that PLAP would participate in the process of T. cruzi invasion into placental syncitiotrophoblast cells, by a mechanism that involves hydrolysis of the glycosyl-phosphatidylinositol molecules, the activation of tyrosine kinase proteins, the increase of cytosolic calcium and the rearrangement of actine filaments of the host cells.