Dietary glutamine supplementation affects macrophage function, hematopoiesis and nutritional status in early weaned mice

Background Et aims: To investigate the effect that early weaning associated with the ingestion of either a glutamine-free or supplemented diet has on the functioning of peritoneal. macrophages, hematopoiesis and nutritional status of mice. Methods: Swiss Webster mice were early weaned on their 14th day of life and distributed to two groups, being fed either a glutamine-free diet (-GLN) or a glutamine-supplemented diet (+GLN). Animals belonging to a control group (CON) were weaned on their 21st day of life. Results: The -GLN and +GLN groups had a lower lean body mass, carcass protein and ash content, plasma glutamine concentration and lymphocyte counts both in the peripheral blood and bone marrow when compared to the CON group (P < 0.05). Dietary supplementation with glutamine reversed both the lower concentrations of protein and DNA in the muscle and liver, as well. as the reduced capacity of spreading and synthesizing nitric oxide, hydrogen peroxide, TNF-alpha, IL-1 beta and IL-6 in cultures of peritoneal. macrophages obtained from the -GLN group (P < 0.05). Conclusion: These data indicate that the ingestion of glutamine modulates the function of peritoneal macrophages in early weaned mice. However, a glutamine-supplemented diet cannot substitute maternal milk in respect to immunological and metabolic parameters. (C) 2008 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Pleiotropic Effects With Equivalent Low-density Lipoprotein Cholesterol Reduction: Comparative Study Between Simvastatin and Simvastatin/Ezetimibe Coadministration

Background: Coadministration of any statin with ezetimibe is as effective as using high doses of the same statin in the reduction Of tow-density lipoprotein cholesterol (LDL-c). There may be other effects called pleiotropics. Objective: To compare the effectiveness of 2 different treatments that obtain equivalent LDL-c reductions (80 mg of simvastatin, once a clay and coadministration of 10 mg of simvastatin and 10 mg of ezetimibe, once a day) over endothelial function and inflammation. Methods: Twenty-three randomized patients with hypercholesterolemia in a 2 X 2 crossover protocol were Studied. Endothelial function was analyzed by ultrasound assessment of endothelial dependent flow-mediated vasodilation of the brachial artery, and inflammation was estimated by high-sensitivity C-reactive protein (hs-CRP). Results: LDL-c reduction was similar between the 2 treatments with simvastatin/ezetimibe and with simvastatin (P < 0.001); no difference between treatments was found (P = 0.968). Both treatments improved significantly the endothelial function [3.61% with simvastatin/ezetimibe (P = 0.003) and 5.08%. with simvastatin (P < 0.001)]; no difference was found between the 2 treatments (P = 0.291). hs-CRP had a 23% reduction with simvastatin/ezetimibe (P = 0.004) and a 30% reduction with simvastatin alone (P = 0.01), with no significant difference between the 2 treatments (P = 0.380). Conclusion: The 2 forms of treatment presented similar pleiotropic effects: improvement in endothelial function and decrease in hsCRP levels.

Apoptosis induction by 4-nerolidylcatechol in melanoma cell lines

Pothomorphe umbellata, a native Brazilian plant, is popularly known to be effective in the treatment of skin lesions. This benefit is attributed to 4-nerolidylcatechol (4-NC) a compound extracted from P. umbellata. Since melanomas show prominent resistance to apoptosis and exhibit extreme chemoresistance to multiple forms of therapy, novel compounds addressing induction of cell death are worth investigating. Here, we evaluated effects on cell cycle progression and possible cytotoxic activity of 4-NC in melanoma cell lines as well as human dermal fibroblasts. Inhibitory effects on cell invasion and MMP activity were also investigated. 4-NC showed cytotoxic activity for all melanoma cell lilies tested (IC(50) = 20-40 mu M, 24 h for tumoral cell lines: IC(50) = 50 mu M for fibroblast cell line) associated with its capacity to induce apoptosis. Furthermore, this is the first time that 4-NC is described as an inhibitor of cell invasiveness, due mainly to a G I cell cycle arrest and inhibition of MMP-2 activity in melanoma cell lines. (C) 2008 Elsevier Ltd. All rights reserved.

Acute ingestion of yerba mate infusion (Ilex paraguariensis) inhibits plasma and lipoprotein oxidation

Yerba mate extract (Ilex paraguariensis) is a Source of phenolic compounds that possesses in vitro antioxidant activities and may contribute to a reduction in the risk of cardiovascular disease. In this Study we examined the acute effects of the consumption of mate infusion on ex vivo plasma and low-density lipoprotein (LDL) oxidation, plasma antioxidant capacity, and platelet aggregation. Twelve healthy fasted subjects ingested 500 mL. of mate infusion and blood samples were collected before and I h after mate intake. Lipid peroxidation of plasma and LDL was monitored by the measurement of cholesteryl-ester hydroperoxides (CE-OOH) and cholesterol oxides. The plasma antioxidant capacity was measured as ferric-reducing antioxidant potential (FRAP). Platelet aggregation was evaluated in platelet-rich plasma Stimulated with adenosine diphosphate and coagulation was tested in platelet-poor plasma. Ingestion of mate infusion diminished the ex vivo oxidizability of both plasma and LDL particles. After mate intake, the CE-OOH levels were around 50% lower in plasma oxidized with copper or 2,2`-azobis[-2-amidine-propane-hydrochloride] (AAPH) and the lag time to plasma oxidation increased 2-fold (P < 0.05). Copper- and AAPH-induced LDL peroxidation were also inhibited by around 50% and 20%, respectively, after mate Consumption (P < 0.05). The levels of various oxysterols were significantly reduced in oxidized-plasma and LDL (P < 0.05) and FRAP increased by 7.7% after mate intake (P < 0.01). However. mate consumption did not inhibit platelet aggregation or blood coagulation. In summary, intake of yerba mate infusion improved the antioxidant capacity and the resistance of plasma and LDL particles to ex vivo lipid peroxidation. (C) 2008 Elsevier Ltd. All rights reserved.

Relationships between gene polymorphisms of folate-related proteins and vitamins and metabolites in pregnant women and neonates

Background: The methylenetetrahydrofolate reductase (MTHFR), glutamate carboxypeptidase II (GCPII) and reduced folate carrier (RFC1) gene polymorphisms were associated with folate status. We investigated the effects of these polymorphisms on serum folate (SF) and folate-related metabolites in mothers and their neonates. Methods: Cobalamin (Cbl), SF, total homocysteine (tHcy), methylmalonic acid (MMA), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) were measured in 275 healthy women and their neonates. MTHFR C677T, GCPII C1561T and RFC1 A80G polymorphisms were determined by PCR-RFLP. Results: Maternal tHcy was affected individually by MTHFR C677T and GCPII C1561T polymorphisms and by combined genotypes MTHFR 677TT/GCPII 1561CC and MTHFR 677TT/RFC1 80AG. The MTHFR and RFC1 polymorphisms were not associated with variations in vitamins or SAM, SAH and MMA in neonates. Neonatal tHcy was predicted directly by maternal tHcy and inversely by maternal SF, neonatal Cbl and neonatal RFC1 80G allele (AG+GG genotypes). Maternal MMA and SAM/SAH were predicted by creatinine and Cbl, respectively. Neonatal MMA was predicted by maternal MMA and GCPII 1561T allele (CT+TT genotypes) and by neonatal Cbl. Conclusions: Maternal tHcy was affected by MTHFR C677T, RFC1 A80G and GCPII C1561T polymorphisms. Maternal GCPII C1561T variant was associated with neonatal MMA. Neonatal RFC1 A80G polymorphism influenced tHcy in neonates. (C) 2008 Elsevier B.V. All rights reserved.

Novel deoxy-selenylconduritols: chemoenzymatic synthesis and biological evaluation

The first synthesis of two selenyldeoxycyclitols (4-bromo-2-phenylselenyl conduritol F and 6-phenylselenylconduritol F) is reported via a chemoenzymatic enantioselective route. The key step of the synthesis is the selenolysis of a vinyl epoxide. The new compounds were evaluated for their capacity to inhibit the growth of different microorganisms using a modification of the agar diffusion technique with thin layer chromatography plates as support. (C) 2009 Elsevier Ltd. All rights reserved.

Broad spectrum bioactive sunscreens

The development of sunscreens containing reduced concentration of chemical UV filters, even though, possessing broad spectrum effectiveness with the use of natural raw materials that improve and infer UV absorption is of great interest. Due to the structural similarities between polyphenolic compounds and organic UV filters, they might exert photoprotection activity. The objective of the present research work was to develop bioactive sunscreen delivery systems containing rutin, Passiflora incarnata L. and Plantago lanceolata extracts associated or not with organic and inorganic UV filters. UV transmission of the sunscreen delivery system films was performed by using diffuse transmittance measurements coupling to an integrating sphere. In vitro photoprotection efficacy was evaluated according to the following parameters: estimated sun protection factor (SPF); Boot`s Star Rating category; UVA/UVB ratio; and critical wavelength (lambda(c)). Sunscreen delivery systems obtained SPF values ranging from 0.972 +/- 0.004 to 28.064 +/- 2.429 and bioactive compounds interacted with the UV filters positive and negatively. This behavior may be attributed to: the composition of the delivery system: the presence of inorganic UV filter and quantitative composition of the organic UV filters; and the phytochemical composition of the P. incarnate L and P. lanceolato extracts. Among all associations of bioactive compounds and UV filters, we found that the broad spectrum sunscreen was accomplished when 1.68% (w/w) P incarnata L. dry extract was in the presence of 7.0% (w/w) ethylhexyl methoxycinnamate, 2.0% (w/w) benzophenone-3 and 2.0% (w/w) TiO(2). It was demonstrated that this association generated estimated SPF of 20.072 +/- 0.906 and it has improved the protective defense against UVA radiation accompanying augmentation of the UVA/UVB ratio from 0.49 to 0.52 and lambda(c) from 364 to 368.6 nm. (c) 2008 Elsevier B.V. All rights reserved.

Liquid-liquid extraction of proteases from fermented broth by PEG/citrate aqueous two-phase system

This work deals with the use of an aqueous two-phase system (ATPS) of PEG/citrate to remove proteases from a Clostridium perfringens fermentation broth. To plan the experimental tests and evaluate the corresponding results, three successive experimental designs were employed, for which the PEG molar mass (M-PEG) and concentration (C-PEG), the citrate concentration (C-C) and the pH were selected as independent variables, while the purification factor (PF), the partition coefficient (K), the activity yield (Y) and the selectivity (S) were selected as responses. PF of proteases in the top phase was shown to increase with increasing MPEG and decreasing Cc, whereas a completely opposite trend was observed for K. On the other hand, Y was favored by simultaneous decreases in both these variables, while S decreased with increasing Cc. Therefore, selecting a simultaneous increase in PF and Y as the most desirable result, the best performance of the system was obtained using M-PEG = 10-000 g/mol C-PEG = 22% (w/w) and C-c = 8.0% (w/w) at pH 8.5. Under these conditions, the activity yield was very high (131 %) but the purification factor (4.2) and the selectivity (4.3) were lower than those ensured by more selective purification methods. According to these results, the ATPS seems to be an interesting alternative primary concentration/decontamination step for vaccine preparation from C. perfringens fermented broth. (C) 2007 Elsevier B.V. All rights reserved.

qNMR: An applicable method for the determination of dimethyltryptamine in ayahuasca, a psychoactive plant preparation

Ayahuasca is an Amazonian plant beverage obtained by infusing the pounded stems of Banisteriopsis caapi in combination with the leaves of Psychotria viridis. P. viridis contains the psychedelic indole N,N-dimethyltryptamine (DMT). This association has a wide range of use in religious rituals around the world. In the present work, an easy, fast and non-destructive method by Nuclear Magnetic Resonance of proton ((1)H NMR) for quantification of DMT in ayahuasca samples was developed and validated. 2,5-Dimethoxybenzaldehyde (DMBO) was used as internal standard (IS). For this purpose, the area ratios produced by protons of DMT (N(CH(3))(2)) at 2.70 ppm, singlet, (6H) and for DMBO (Ar(OCH(3))(2)) at 3.80 and 3.89 ppm, doublet, (6H) were used for quantification. The lower limit of quantification (LLOQ) was 12.5 mu g/mL and a good intra-assay precision was also obtained (relative standard deviation < 5.1%). The present (1)H NMR method is not time consuming and can be readily applied to monitor this tryptamine in plant preparations. We believe that qNMR can be used for identification and quantification of many plant-based products and metabolites with important advantages, while comparing with other analytical techniques. (C) 2010 Phytochemical Society of Europe. Published by Elsevier B. V. All rights reserved.

Bioactivity of nitrolinoleate: effects on adhesion molecules and CD40-CD40L system

The vascular effects of nitrolinoleate (LNO(2)), an endogenous product of linoleic acid (LA) nitration by nitric oxide-derived species and a potential nitrosating agent, were investigated on rat endothelial-leukocyte interactions. Confocal microscopy analysis demonstrated that LNO(2) was capable to deliver free radical nitric oxide ((center dot)NO) into cells, 5 min after its administration to cultured cells, with a peak of liberation at 30 min. THP-1 monocytes incubated with LNO(2) for 5 min presented nitrosation of CD40, leading to its inactivation. Other anti-inflammatory actions of LNO(2) were observed in vivo by intravital microscopy assays. LNO(2) decreased the number of adhered leukocytes in postcapillary venules of the mesentery network. In addition to this, LNO(2) reduced mRNA and protein expression of 2-integrin in circulating leukocytes, as well as VCAM-1 in endothelial cells isolated from postcapillary venules, confirming its antiadhesive effects on both cell types. Moreover, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, a nitric oxide scavenger, partially abolished the inhibitory action of LNO(2) on leukocyte-endothelium interaction, suggesting that the antiadhesion effects of LNO(2) involve a dual role in leukocyte adhesion, acting as a nitric oxide donor as well as through nitric oxide-independent mechanisms. In conclusion, LNO(2) inhibited adhesion molecules expression and promoted (center dot)NO inactivation of the CD40-CD40L system, both important processes of the inflammatory response. (C) 2010 Elsevier Inc. All rights reserved.

Brazilian flavonoid database: Application of quality evaluation system

Much information on flavonoid content of Brazilian foods has already been obtained; however, this information is spread in scientific publications and non-published data. The objectives of this work were to compile and evaluate the quality of national flavonoid data according to the United States Department of Agriculture`s Data Quality Evaluation System (USDA-DQES) with few modifications, for future dissemination in the TBCA-USP (Brazilian Food Composition Database). For the compilation, the most abundant compounds in the flavonoid subclasses were considered (flavonols, flavones, isoflavones, flavanones, flavan-3-ols, and anthocyanidins) and the analysis of the compounds by HPLC was adopted as criteria for data inclusion. The evaluation system considers five categories, and the maximum score assigned to each category is 20. For each data, a confidence code (CC) was attributed (A, B, C and D), indicating the quality and reliability of the information. Flavonoid data (773) present in 197 Brazilian foods were evaluated. The CC ""C"" (as average) was attributed to 99% of the data and ""B"" (above average) to 1%. The main categories assigned low average scores were: number of samples; sampling plan and analytical quality control (average scores 2, 5 and 4, respectively). The analytical method category received an average score of 9. The category assigned the highest score was the sample handling (20 average). These results show that researchers need to be conscious about the importance of the number and plan of evaluated samples and the complete description and documentation of all the processes of methodology execution and analytical quality control. (C) 2010 Elsevier Inc. All rights reserved.

Involvement of oxidative stress in the hepatotoxicity induced by aromatic antiepileptic drugs

The use of the classic aromatic antiepileptic drugs (AAEDs) has recently been expanded to a broad spectrum of psychiatric and neurological disorders. However, the clinical use of these drugs is limited by several adverse effects, mainly idiosyncratic hepatotoxicity. AAED-induced hepatotoxicity has been attributed to a defective detoxification by the epoxide hydrolase and accumulation of arene oxides. The underlying mechanism has been proposed as immune-mediated, but direct toxicity has also been suggested. In general, idiosyncratic drug-induced hepatotoxicity may be mediated, at least in part, by oxidative stress. On the other hand, the oxidative stress induced by the AAED metabolites has not been demonstrated yet. Therefore, in the present study we have evaluated the induction of oxidative stress by three classical AAEDs: carbamazepine. phenytoin and phenobarbital as well as by their metabolites. The toxic effects of the metabolites were evaluated by incubating the drug with rat liver microsomes. The AAED-induced oxidative stress was demonstrated by the increased malondialdehyde levels, oxidation of cardiolipin; oxidation of sulfhydryl proteins and alteration of the cellular redox status. Results suggest that the hepatotoxicity associated with AAED might be mediated by the oxidative stress induced by the drugs metabolites. (C) 2008 Elsevier Ltd. All rights reserved

Protective effects of Mangifera indica L extract (Vimang), and its major component mangiferin, on iron-induced oxidative damage to rat serum and liver

In vivo preventive effects of a Mangifera indica L extract (Vimang) or its major component mangiferin on iron overload injury have been studied in rats given respectively, 50, 100, 250 mg kg(-1) body weight of Vimang, or 40 mg kg(-1) body weight of mangiferin, for 7 days prior to, and for 7 days following the administration of toxic amounts of iron-dextran. Both Vimang or mangiferin treatment prevented iron overload in serum as well as liver oxidative stress, decreased serum and liver lipid peroxidation, serum GPx activity, and increased serum and liver GSH, serum SOD and the animals overall antioxidant condition. Serum iron concentration was decreased although at higher doses, Vimang tended to increase it; percent tranferrin saturation, liver weight/body mass ratios, liver iron content was decreased. Treatment increased serum iron-binding capacity and decreased serum levels of aspartate-amine transferase (ASAT) and alanine-amine transferase (ALAT), as well as the number of abnormal Kupffer cells in iron-loaded livers. It is suggested that besides acting as antioxidants, Vimang extract or its mangiferin component decrease liver iron by increasing its excretion. Complementing earlier in vitro results from our group, it appears possible to support the hypothesis that Vimang and mangiferin present therapeutically useful effects in iron overload related diseases. (C) 2007 Elsevier Ltd. All rights reserved.

Balloon catheter injury abolishes phenylephrine-induced relaxation in the rat contralateral carotid

BACKGROUND AND PURPOSE The consequences of compensatory responses to balloon catheter injury in rat carotid artery, on phenylephrine-induced relaxation and contraction in the contralateral carotid artery were studied. EXPERIMENTAL APPROACH Relaxation and contraction concentration-response curves for phenylephrine were obtained for contralateral carotid arteries in the presence of indomethacin (COX inhibitor), SC560 (COX-1 inhibitor), SC236 (COX-2 inhibitor) or 4-hydroxytetramethyl-L-piperidine-1-oxyl (tempol; superoxide dismutase mimetic). Reactive oxygen species were measured in carotid artery endothelial cells fluorimetrically with dihydroethidium. KEY RESULTS Phenylephrine-induced relaxation was abolished in contralateral carotid arteries from operated rats (E(max) = 0.01 +/- 0.004 g) in relation to control (E(max) = 0.18 +/- 0.005 g). Phenylephrine-induced contractions were increased in contralateral arteries (E(max) = 0.54 +/- 0.009 g) in relation to control (E(max) = 0.38 +/- 0.014 g). SC236 restored phenylephrine-induced relaxation (E(max) = 0.17 +/- 0.004 g) and contraction (E(max) = 0.34 +/- 0.018 g) in contralateral arteries. Tempol restored phenylephrine-induced relaxation (E(max) = 0.19 +/- 0.012 g) and contraction (E(max) = 0.42 +/- 0.014 g) in contralateral arteries, while apocynin did not alter either relaxation (E(max) = 0.01 +/- 0.004 g) or contraction (E(max) = 0.54 +/- 0.009 g). Dihydroethidium fluorescence was increased in contralateral samples (18 882 +/- 435 U) in relation to control (10 455 +/- 303 U). SC236 reduced the fluorescence in contralateral samples (8250 +/- 365 U). CONCLUSIONS AND IMPLICATIONS Balloon catheter injury abolished phenylephrine-induced relaxation and increased phenylephrine-induced contraction in contralateral carotid arteries, through O(2)(-) derived from COX-2.

A new nitrosyl ruthenium complex nitric oxide donor presents higher efficacy than sodium nitroprusside on relaxation of airway smooth muscle

Nitric oxide (NO) has been demonstrated to be the primary agent in relaxing airways in humans and animals. We investigated the mechanisms involved in the relaxation induced by NO-donors, ruthenium complex [Ru(terpy)(bdq)NO(+)](3+) (TERPY) and sodium nitroprusside (SNP) in isolated trachea of rats contracted with carbachol in an isolated organs chamber. For instance, we verified the contribution of K(+) channels, the importance of sGC/cGMP pathway, the influence of the extra and intracellular Ca(2+) sources and the contribution of the epithelium on the relaxing response. Additionally, we have used confocal microscopy in order to analyze the action of the NO-donors on cytosolic Ca(2+) concentration. The results demonstrated that both compounds led to the relaxation of trachea in a dependent-concentration way. However, the maximum effect (E(max)) of TERPY is higher than the SNP. The relaxation induced by SNP (but not TERPY) was significantly reduced by pretreatment with ODQ (sGC inhibitor). Only TERPY-induced relaxation was reduced by tetraethylammonium (K(+) channels blocker) and by pre-contraction with 75 mM KCl (membrane depolarization). The response to both NO-donors was not altered by the presence of thapsigargin (sarcoplasmic reticulum Ca(2+)-ATPase inhibitor). The epithelium removal has reduced the relaxation only to SNP, and it has no effect on TERPY. The both NO-donors reduced the contraction evoked by Ca(2+) influx, while TERPY have shown a higher inhibitory effect on contraction. Moreover, the TERPY was more effective than SNP in reducing the cytosolic Ca(2+) concentration measured by confocal microscopy. In conclusion, these results show that TERPY induces airway smooth muscle relaxation by cGMP-independent mechanisms, it involves the fluxes of Ca(2+) and K(+) across the membrane, it is more effective in reducing cytosolic Ca(2+) concentration and inducing relaxation in the rat trachea than the standard drug, SNP. (C) 2011 Elsevier B.V. All rights reserved.