Brazil nut ingestion increased plasma selenium but had minimal effects on lipids, apolipoproteins, and high-density lipoprotein function in human subjects

The Brazil nut (Bertholletia excelsa) of the Amazon region is consumed worldwide. It is rich in both monounsaturated fatty acids and polyunsaturated fatty acids and is known for its high selenium content. This study tested the hypothesis whether the consumption of this nut could affect the plasma lipids and apolipoproteins and some functional properties of the antiatherogenic high-density lipoprotein (HDL). Fifteen normolipidemic subjects aged 27.3 +/- 3.9 years and with body mass index of 23.8 +/- 2.8 kg/m(2) consumed 45 g of Brazil nuts per day during a 15-day period. On days 0 and 15, blood was collected for biochemical analysis, determination of HDL particle size, paraoxonase 1 activity, and lipid transfer from a lipoprotein-like nanoparticle to the HDL fraction. Brazil nut ingestion did not alter HDL, low-density lipoprotein cholesterol, triacylglycerols, apolipoprotein A-1, or apolipoprotein B concentrations. HDL particle diameter and the activity of antioxidative paraoxonase 1, mostly found in the HDL fraction, Were also unaffected. Supplementation increased the reception of cholesteryl esters (P <.05) by the HDL yet did not alter the reception of phospholipids, free cholesterol, or triacylglycerols. As expected, plasma selenium was significantly increased. However, the consumption of Brazil nuts for short duration by normolipidemic subjects in comparable amounts to those tested for other nuts did not alter serum lipid profile. The only alteration in HDL function was the increase in cholesteryl ester transfer. This latter finding may be beneficial because it would improve the nonatherogenic reverse cholesterol transport pathway. (c) 2008 Elsevier Inc. All rights reserved.

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.

Glutamine in vitro supplementation partly reverses impaired macrophage function resulting from early weaning in mice

Objective: Glutamine is one of the most abundant amino acids found in maternal milk, and its concentration increases throughout lactation. Because glutamine is essential for macrophage functionality, it is hereby suggested that early weaning in conjunction with the absence of glutamine consumption impairs the functioning of macrophages, which could in turn be reversed with an in vitro supplementation with glutamine. Methods: Swiss Webster mice were early weaned at 14 d of age (EW group) or at 21 d of age (control group, n = 8 per group). The EW group was fed a glutamine-free diet from days 14 to 21 of life. Results: Mice in the EW group presented a significant decrease in plasma and muscle concentrations of glutamine and an increase in the activity of glutamine synthetase in the muscle. Peritoneal macrophages obtained from animals in the EW group presented a significant increase in the production of interleukin (IL)-10 and a significant decrease in the synthesis of IL-1 beta, IL-6, tumor necrosis factor-a, nitric oxide, and hydrogen peroxide and in their ability to adhere, spread, phagocytize, and kill fungi. Glutamine in vitro supplementation reversed the decrease in IL-6, nitric oxide, and hydrogen peroxide synthesis and the decrease in the capacity to adhere, spread, and phagocytize in animals of the EW group. Conclusion: These new. data may imply that a lack of glutamine intake in early weaned mice hampers the functioning of peritoneal macrophages. (C) 2008 Elsevier Inc. All rights reserved.

Hydrolysis Influence on Phytochemical Composition, Antioxidant Activity, Plasma Concentration, and Tissue Distribution of Hydroethanolic Ilex paraguariensis Extract Components

The infusion of aerial parts of Ilex paraguariensis is widely consumed. Its antioxidant activity suggests an important role of this plant in the treatment/prevention of oxidative stress related diseases. Plant extract active compounds are frequently found in esterified form that may be poorly absorbed. Hydrolysis of the extract is a possible approach to increase its bioavailability. The aim of this study was to perform a phytochemical analysis and evaluate in rats the plasma concentration and tissue distribution of antioxidant compounds in the hydroethanolic extract of Ilex paraguariensis, before and after enzymatic hydrolysis. Both extracts presented high antioxidant activity and phenolic content. Rats given single or repeated doses of the hydrolyzed extract showed increased plasma antioxidant activity and higher plasma levels of caffeic acid. However, no changes of endogenous antioxidants were observed. In conclusion, hydrolysis of the extract of Ilex paraguariensis is a strategy to improve its bioavailability and in vivo antioxidant activity.

Methylenedioxymethamphetamine (Ecstasy) Decreases Neutrophil Activity and Alters Leukocyte Distribution in Bone Marrow, Spleen and Blood

Objective: Looking for possible neuroimmune relationships, we analyzed the effects of methylenedioxymethamphetamine (MDMA) administration on neuroendocrine, neutrophil activity and leukocyte distribution in mice. Methods: Five experiments were performed. In the first, mice were treated with MDMA (10 mg/kg) 30, 60 min and 24 h prior to blood sample collection for neutrophil activity analysis. In the second experiment, the blood of nave mice was collected and incubated with MDMA for neutrophil activity in vitro analysis. In the third and fourth experiments, mice were injected with MDMA (10 mg/kg) and 60 min later, blood and brain were collected to analyze corticosterone serum levels and hypothalamic noradrenaline (NA) levels and turnover. In the last experiment, mice were injected with MDMA 10 mg/kg and 60 min later, blood, bone marrow and spleen were collected for leukocyte distribution analysis. Results: Results showed an increase in hypothalamic NA turnover and corticosterone serum levels 60 min after MDMA (10 mg/kg) administration, a decrease in peripheral blood neutrophil oxidative burst and a decrease in the percentage and intensity of neutrophil phagocytosis. It was further found that MDMA (10 mg/kg) treatment also altered leukocyte distribution in blood, bone marrow and spleen. In addition, no effects were observed for MDMA after in vitro exposure both in neutrophil oxidative burst and phagocytosis. Conclusion: The effects of MDMA administration (10 mg/kg) on neutrophil activity and leukocyte distribution might have been induced indirectly through noradrenergic neurons and/or hypothalamic-pituitary-adrenal axis activations. Copyright (C) 2009 S. Karger AG, Basel

Comparison of Bidirectional Lamivudine and Zidovudine Transport Using MDCK, MDCK-MDR1, and Caco-2 Cell Monolayers

Bidirectional transport studies were conducted using Caco-2, MDCK, and MDCK-MDR1 to determine P-gp influences in lamivudine and zidovudine permeability and evaluate if zidovudine permeability changes with the increase of zidovudine concentration and/or by association of lamivudine. Transport of lamivudine and zidovudine separated and coadministrated across monolayers based on these cells were quantified using LC-MS-MS. Drug efflux by P-gp was inhibited using GG918. Bidirectional transport of lamivudine and zidovudine was performed across MDCK-MDR1 and Caco-2 cells. Statistically significant transport decrease in B -> A direction was observed using MDCK-MDR1 for zidovudine and MDCK-MDR1 and Caco-2 for lamivudine. Results show increased transport in B -> A and A -> B directions as concentration increases but data from P(app) increase in both directions for both drugs in Caco-2, decrease in MDCK, and does not change significantly in MDCK-MDR1. Zidovudine transport in A -> B direction increases when coadministrated with increasing lamivudine concentration but does not change significantly in B -> A direction. Zidovudine and lamivudine are P-gp substrates, but results assume that P-gp does not affect significantly lamivudine and zidovudine. Their transport in monolayers based on Caco-2 cells increase proportionally to concentration (in both directions) and zidovudine transport in Caco-2 cell monolayer does not show significant changes with lamivudine increasing concentrations. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4413-4419, 2009

Impact of cholesterol on ABC and SLC transporters expression and function and its role in disposition variability to lipid-lowering drugs

This report focuses on the effects of cholesterol on the expression and function of the ATP-binding cassette (ABCB1, ABCG2 and ABCC2) and solute-linked carrier (SLCO1B1 and SLCO2B1) drug transporters with a particular focus on the potential impact of cholesterol on lipid-lowering drug disposition. Statins are the most active agents in the treatment of hypercholesterolemia. However, considerable interindividual variation exists in the response to statin therapy. Therefore, it would be huge progress if factors were identified that reliably differentiate between responders and nonresponders. Many studies have suggested that plasma lipid concentrations can affect drug disposition of compounds, such as ciclosporin and amphotericin B. Both compounds are able to affect the expression and function of ABC transporters. Although still speculative, these effects might be owing to the regulation of drug transporters by plasma cholesterol levels. Studies with normo- and hyper-cholesterolemic individuals, before and after atorvastatin treatment, have demonstrated that plasma cholesterol levels are correlated with drug transporter expression, as well as being related to atorvastatin`s cholesterol-lowering effect. The mechanism influencing the correlation between cholesterol levels and the expression and function of drug transporters remains unclear. Some studies provide strong evidence that nuclear receptors, such as the pregnane X receptor and the constitutive androstane receptor, mediate this effect. In the near future, pharmacogenomic studies with individuals in a pathological state should be performed in order to identify whether high plasma cholesterol levels might be a factor contributing to interindividual oral drug bioavailability.

Mitochondrial function in the yeast form of the pathogenic fungus Paracoccidioides brasiliensis

Differences between the respiratory chain of the fungus Paracoccidioides brasiliensis and its mammalian host are reported. Respiration, membrane potential, and oxidative phosphorylation in mitochondria from P. brasiliensis spheroplasts were evaluated in situ, and the presence of a complete (Complex I-V) functional respiratory chain was demonstrated. In succinate-energized mitochondria, ADP induced a transition from resting to phosphorylating respiration. The presence of an alternative NADH-ubiquinone oxidoreductase was indicated by: (i) the ability to oxidize exogenous NADH and (ii) the lack of sensitivity to rotenone and presence of sensitivity to flavone. Malate/NAD(+)-supported respiration suggested the presence of either a mitochondrial pyridine transporter or a glyoxylate pathway contributing to NADH and/or succinate production. Partial sensitivity of NADH/succinate-supported respiration to antimycin A and cyanide, as well as sensitivity to benzohydroxamic acids, suggested the presence of an alternative oxidase in the yeast form of the fungus. An increase in activity and gene expression of the alternative NADH dehydrogenase throughout the yeast`s exponential growth phase was observed. This increase was coupled with a decrease in Complex I activity and gene expression of its subunit 6. These results support the existence of alternative respiratory chain pathways in addition to Complex I, as well as the utilization of NADH-linked substrates by P. brasiliensis. These specific components of the respiratory chain could be useful for further research and development of pharmacological agents against the fungus.

Chronic hyperhomocysteinemia impairs vascular function in ovariectomized rat carotid arteries

Homocysteine is an independent risk factor for coronary heart disease, as well as for cerebrovascular and peripheral vascular diseases. The purpose of this study was to investigate the effects of hyperhomocysteinemia (HHcy) on vascular reactivity within carotid artery segments isolated from ovariectomized female rats. Treatment with dl-Hcy thiolactone (1 g/kg body weight per day) reduced the phenylephrine-induced contraction of denuded rings. However, the treatment did not alter KCl-induced contractions, or relaxations induced by sodium nitroprusside or acetylcholine. We report elevated expressions of iNOS, eNOS, and nitrotyrosine in homocysteine-treated rat artery sections. Moreover, the inhibition of NOS by l-NAME, 1,400 W, or l-NNA restored phenylephrine-induced vasoconstriction in carotid artery segments from Hcy-treated rats. In conclusion, our findings show that severe HHCy can promote an acute decrease in the endothelium-independent contractile responses of carotid arteries to adrenergic agonists. This effect was restored by nitric oxide synthase inhibitors, which further supports the involvement of nitric oxide in HHcy-derived vascular dysfunction.

Discriminant analysis of trace elements in normal, benign and malignant breast tissues measured by total reflection X-ray fluorescence

In this work total reflection X-ray fluorescence spectrometry has been employed to determine trace element concentrations in different human breast tissues (normal, normal adjacent, benign and malignant). A multivariate discriminant analysis of observed levels was performed in order to build a predictive model and perform tissue-type classifications. A total of 83 breast tissue samples were studied. Results showed the presence of Ca, Ti, Fe, Cu and Zn in all analyzed samples. All trace elements, except Ti, were found in higher concentrations in both malignant and benign tissues, when compared to normal tissues and normal adjacent tissues. In addition, the concentration of Fe was higher in malignant tissues than in benign neoplastic tissues. An opposite behavior was observed for Ca, Cu and Zn. Results have shown that discriminant analysis was able to successfully identify differences between trace element distributions from normal and malignant tissues with an overall accuracy of 80% and 65% for independent and paired breast samples respectively, and of 87% for benign and malignant tissues. (C) 2009 Elsevier B.V. All rights reserved.

Paste Residence Time in a Spouted Bed Dryer. IV: Effect of the Inert Particle Size Distribution

The residence time distribution and mean residence time of a 10% sodium bicarbonate solution that is dried in a conventional spouted bed with inert bodies were measured with the stimulus-response method. Methylene blue was used as a chemical tracer, and the effects of the paste feed mode, size distribution of the inert bodies, and mean particle size on the residence times and dried powder properties were investigated. The results showed that the residence time distributions could be best reproduced with the perfect mixing cell model or N = 1 for the continuous stirred tank reactor in a series model. The mean residence times ranged from 6.04 to 12.90 min and were significantly affected by the factors studied. Analysis of variance on the experimental data showed that mean residence times were affected by the mean diameter of the inert bodies at a significance level of 1% and by the size distribution at a level of 5%. Moreover, altering the paste feed from dripping to pneumatic atomization affected mean residence time at a 5% significance level. The dried powder characteristics proved to be adequate for further industrial manipulation, as demonstrated by the low moisture content, narrow range of particle size, and good flow properties. The results of this research are significant in the study of the drying of heat-sensitive materials because it shows that by simultaneously changing the size distribution and average size of the inert bodies, the mean residence times of a paste can be reduced by half, thus decreasing losses due to degradation.

Central Cardiovascular Anatomy and Function in Crocodilia

Abstract: Among the vertebrates, crocodilians have the most complex anatomy of the heart and outflow channels. Their cardiovascular anatomy may also be the most func­tionally sophisticated, combining as it does the best features of both reptilian and mammalian (and avian) systems. The puzzlingly complex "plumbing" of crocodilians has fascinated ana­tomists and physiologists for a very long time, the first paper being that by Panizza (1833). Gradually, with the application of successive techniques of investigation as they became available, its functional significance has become reasonably clear, and the complexity is now revealed as a cardiovascular system of considerable elegance. In this paper I will review the main anatomical features of the heart and outflow channels, discuss what is known about the way they work, and speculate about the probable functional significance.

Dimensionless spray flux in wet granulation: Monte-Carlo simulations and experimental validation

Dimensionless spray flux Ψa is a dimensionless group that characterises the three most important variables in liquid dispersion: flowrate, drop size and powder flux through the spray zone. In this paper, the Poisson distribution was used to generate analytical solutions for the proportion of nuclei formed from single drops (fsingle) and the fraction of the powder surface covered by drops (fcovered) as a function of Ψa. Monte-Carlo simulations were performed to simulate the spray zone and investigate how Ψa, fsingle and fcovered are related. The Monte-Carlo data was an excellent match with analytical solutions of fcovered and fsingle as a function of Ψa. At low Ψa, the proportion of the surface covered by drops (fcovered) was equal to Ψa. As Ψa increases, drop overlap becomes more dominant and the powder surface coverage levels off. The proportion of nuclei formed from single drops (fsingle) falls exponentially with increasing Ψa. In the ranges covered, these results were independent of drop size, number of drops, drop size distribution (mono-sized, bimodal and trimodal distributions), and the uniformity of the spray. Experimental data of nuclei size distributions as a function of spray flux were fitted to the analytical solution for fsingle by defining a cutsize for single drop nuclei. The fitted cutsizes followed the spray drop sizes suggesting that the method is robust and that the cutsize does indicate the transition size between single drop and agglomerate nuclei. This demonstrates that the nuclei distribution is determined by the dimensionless spray flux and the fraction of drop controlled nuclei can be calculated analytically in advance.

Liquid distribution as a means to describing the granule growth mechanism

Copper concentrate (chalcopyrite) was granulated in a rotating drum with a diameter of 0.3 m and a length of 0.2 m. Water was used as the binder and it was sprayed onto the powder bed with a nozzle. This material exhibited induction type behaviour, which was defined by Iveson and Litster [AIChE J. 44 (1998) 1510]. Induction type behaviour is characterized by the occurrence of an induction stage, during which the granules are gradually being compacted and little or no growth occurs. At the end of this induction stage, binder liquid is squeezed from the interior of the granules onto the granule surface and the granules are then surface-wet. This results in a rapid growth rate of the granules. Different types of experiments were conducted. The influence of the nozzle pressure and the distance from the nozzle to the powder bed on the growth behaviour of the granules as well as on the binder distribution was examined. The results of these experiments led to the postulation of a modified mechanism for induction type behaviour: it was found that after the binder was delivered, there were large granules containing a high amount of binder and small granules containing less binder. During the induction stage, the granules are compacted and binder liquid continuously appears at the surface of the large granules. These wet spots that are continuously being formed pick up the dry and small granules. When all the small granules have been picked up, further expulsion of binder liquid onto the granules' surface results in granules that remain surface-wet. This phenomenon marks the end of the induction stage and it coincides with the disappearance of the small granules. The hypothesis was tested by selectively removing the smaller granules during an experiment. As expected, this resulted in a shorter induction time.

Analytical solution of forced convection in a duct of rectangular cross-section saturated by a porous medium

A theoretical analysis is presented to investigate fully developed (both thermally and hydrodynamically) forced convection in a duct of rectangular cross-section filled with a hyper-porous medium. The Darcy-Brinkman model for flow through porous media was adopted in the present analysis. A Fourier series type solution is applied to obtain the exact velocity and temperature distribution within the duct. The case of uniform heat flux on the walls, i.e. the H boundary condition in the terminology of Kays and Crawford [1], is treated. Values of the Nusselt number and the friction factor as a function of the aspect ratio, the Darcy number, and the viscosity ratio are reported.