Reduced venous endothelial responsiveness after oral lipid overload in healthy volunteers

The aim of this study was to investigate endothelial venous function, mflammatory markers, and systemic oxidative stress after an oral lipid overload (OLO). We studied 18 healthy adults (9 men; age, 29.2 +/- 0.9 years; body mass index, 22.3 +/- 0.4 kg/m(2)). Blood samples were collected in the fasting state and 3, 4, and 5 hour after the OLO (1000 kcal, 58% fat) for metabolic variables, oxidative stress, inflammatory markers, adiponectin, and resistin. Changes in vein diameter to phenylephrine, acetylcholine, and sodium nitroprusside (dorsal hand vein technique) were measured before and after the OLO. Oral lipid overload increased triglycerides (61 +/- 6 vs 134 +/- 17 mg/dL, P <.001), insulin (7.2 +/- 0.8 vs 10.7 +/- 1.3 mu U/mL, P <.05), and resistin (5.38 +/- 0.5 vs 6.81 +/- 0.7 ng/mL, P <.05) and reduced antioxidant capacity (plasma total antioxidant capacity: 186.7 +/- 56 vs 161.8 +/- 50 U Trolox per microliter plasma, P <.01), vascular reactivity (171.3 +/- 85 vs 894.4 +/- 301 ng/mL, P <.001), and maximum acetylcholine venodilation (105.9% +/- 9% vs 61.0% +/- 7%, P <.05). No changes were observed for sodium nitroprusside. Post-OLO triglycerides were positively correlated with phenylephrine dose (rho = 0.38, P <.05) and resistin (rho = 0.43, P <.01) and negatively correlated with the maximum acetylcholine venodilation (rho = -0.36, P <.05). In conclusion, an OLO impaired venoconstriction responsiveness in healthy subjects, probably because of a reduction in the antioxidant capacity. (C) 2008 Elsevier Inc. All rights reserved.

Reversal of Postprandial Endothelial Dysfunction by Cyclooxygenase Inhibition in Healthy Volunteers

The aim of this study was to evaluate the role of cyclooxygenase (COX) in venous vascular reactivity changes after an oral lipid overload (OLO). Venous endothelial function (dorsal hand vein technique) was evaluated in fasting, 30 minutes after COX inhibition (aspirin-fasting), 2 to 4 hours after an OLO (1000 kcal, 58% fat), and again after COX inhibition (aspirin-OLO, 600 mg/200 mL water) in 10 healthy adults (age, 28.1 +/- 1.3 years; body mass index, 22.3 +/- 0.6 kg/m(2)). Fasting, 2- to 4-hour post-OLO, and 60-minute postaspirin plasma glucose, insulin, and lipids were also evaluated. The OLO increased triglycerides and insulin, reduced low-density lipoprotein and high-density lipoprotein, but glycemia and total cholesterol remained unchanged. There were no metabolic differences between OLO and aspirin-OLO. In fasting, aspirin reduced acetylcholine-induced venodilation (107.0% +/- 14% versus 57.3% +/- 11%; P < 0.001). Vascular reactivity was blunted after the OLO (phenylephrine dose: 0.3 +/- 0.2 fasting versus 1.9 +/- 0.8 nmol/min after OLO; P < 0.001) and was partially corrected by aspirin (0.4 +/- 0.2; P < 0.001). Similar changes were observed in maximum venodilation after acetylcholine (107.0% +/- 14% fasting versus 60.4% +/- 9% after OLO, P < 0.001; aspirin-OLO: 95.9% +/- 6%; P < 0.001). The responses to sodium nitroprusside remained unchanged during the study. We conclude that the OLO reduction in the endothelium-dependent venoconstruction and venodilation is partially the result of the action of COX.

Comparative bioavailability of three ibuprofen formulations in healthy human volunteers

Objective: To assess the bioequivalence of three ibuprofen formulations (Test formulation: ibuprofen (400 mg capsule) manufactured by Cardinal Health Brasil 402 Ltda. (Sorocaba, Brazil) and licensed to Boehringer Ingelheim do Brasil Quim. e Farm. Ltda. (Sao Paulo, Brazil); Reference formulation (1): ibuprofen (Advil (R); 2 x 200 mg coated tablet) from Wyeth-Whitehall Ltda. (Itapevi, Brazil); Reference formulation (2): ibuprofen (Alivium (R); 8 ml x 50 mg/ml solution) from Schering Plough S.A. (Rio de Janeiro, Brazil)) in 24 healthy volunteers of both sexes. Methods: The study was conducted using an open, randomized, three-period crossover design with at least 5-day washout interval. Plasma samples were obtained over a 24-h period. Plasma ibuprofen concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) with negative ion electrospray ionization using multiple reaction monitoring (MRM). The following pharmacokinetic parameters were obtained from the ibuprofen plasma concentration vs. time curves: AUC(last), AUC(trunctmax) AUC(inf) and C-max. Results: The limit of quantification for ibuprofen was 0.1 mu g x ml(-1). The geometric mean with corresponding 90% confidence interval (CI) for Test/Reference (1) percent ratios were 114.24% (90% CI = 105.67, 123.50%) for C-max, 98.97% (90% CI = 94.69, 103.44%) for AUC(last) and 99.40% (90% CI = 95.21, 103.78%) for AUCinf. The geometric mean and respective 90% confidence interval (CI) for Test/Reference (2) percent ratios were 108.38% (90% Cl = 100.195, 117.25%) for C-max, 100.79% (90% CI = 96.39, 105.40%) for AUC(last) and 101.26% (90% CI = 96.94, 105.77%) for AUC(inf); t(max) for the 400 mg Test capsule was shorter than that for the 2 x 200 mg Reference (1) tablets (p < 0.002). Conclusion: Since the 90% CI for AUC(last), AUC(inf) and C-max ratios were within the 80 - 125% interval proposed by the US FDA, it was concluded that ibuprofen formulation manufactured by Cardinal Health Brasil 402 Ltda. and licensed to Boehringer Ingelheim do Brasil Quim. e Farm. Ltda. is bioequivalent to the Advil (R) and Alivium (R) formulations with regard to both the rate and the extent of absorption.

Maxillary complete denture movement during chewing in mandibular removable partial denture wearers

To evaluate the pattern of maxillary complete denture movement during chewing for free-end removable partial dentures (RPD) wearers, compared to maxillary and mandibular complete denture wearers. Eighteen edentulous participants (group I) and 10 volunteers with bilateral posterior edentulous mandibles (group II) comprised the sample. Measures of mean denture movement and its variability were obtained by a kinesiographic instrument K6-I Diagnostic System, during the mastication of bread and a polysulphide block. Data were analysed using two-way anova (alpha = 0.05). Upper movement during chewing was significantly lower for group II, regardless of the test food. The test food did not influence the vertical or lateral position of the denture bases, but more anterior dislocation was found when polysulphide blocks were chewed. Group II presented lower intra-individual variability for the vertical axis. Vertical displacement was also more precise with bread as a test food. It can be concluded that mandibular free-end RPD wearers show smaller and more precise movements than mandibular complete denture wearers.

Effect of Two Restorative Materials on Root Dentine Erosion

This study sought to evaluate the microhardness of root dentine adjacent to glass-ionomer and composite resin restorations after erosive challenge. A crossover study was performed in two phases of 4 consecutive days each. One hundred twelve bovine root dentine slabs were obtained, and standardized box-shaped cavities were prepared at center of each specimen. The prepared cavities were randomly restored with glass-ionomer cement or composite resin. The slabs were randomly assigned among 14 volunteers, which wore intraoral palatal device containing four restored root dentin slabs. Starting on the second day, half of the palatal acrylic devices were immersed extraorally in a lemonade-like carbonated soft drink for 90 s, four times daily for 3 days. Alter 3-day wash-out, dentine slabs restored with the alternative material were placed into palatal appliance and the volunteers started the second phase of this study. After erosive challenges. microhardness measurements were performed. Regardless of the restorative material employed, eroded specimens demonstrated lower microhardness value (p < 0.0001). At eroded condition examined in this study, dentine restored with glass-ionomer cement showed higher microhardness values (p < 0.0001). It may be concluded that the glass-ionomer cement decreases the progression of root dentine erosion at restoration margin. (C) 2010 Wiley Periodicals, Inc J Biomed Mater Res Part B Appl Biomater 93B 304-305, 2010

Population genetic structure and dispersal in white-lipped peccaries (Tayassu pecari) from the Brazilian Pantanal

In many mammals social organization promotes genetic structuring, which can be influenced by the dispersal pattern of the species. We analyzed the population genetic structure and dispersal of white-lipped peccaries (Tayassu pecan) from the Pantanal, Brazil. We genotyped 100 individuals at 7 microsatellite loci from 2 adjacent locations with no obvious geographic barrier between them. We found a significant but low F(ST) value, and the Bayesian analysis indicated a unique cluster. No significant differences were observed between mean assignment indices of resident males and females from both locations, and the probability of being born at the location sampled of > 30% of the individuals analyzed was lower than average. Mean relatedness between resident female, male, and opposite-sex pairs was not statistically different in both locations. These results suggest a low degree of genetic differentiation between the locations analyzed, and dispersal by both sexes (contrary to the predicted male-biased dispersal of most mammalian species).

Voluntary action and causality in temporal binding

Previous studies have documented temporal attraction in perceived times of actions and their effects. While some authors argue that voluntary action is a necessary condition for this phenomenon, others claim that the causal relationship between action and effect is the crucial ingredient. In the present study, we investigate voluntary action and causality as the necessary and sufficient conditions for temporal binding. We used a variation of the launching effect proposed by Michotte, in which participants controlled the launch stimulus in some blocks. Volunteers reported causality ratings and estimated the interval between the two events. Our results show dissociations between causality ratings and temporal estimation. While causality ratings are not affected by voluntary action, temporal bindings were only found in the presence of both voluntary action and high causality. Our results indicate that voluntary action and causality are both necessary for the emergence of temporal binding.

Neutrophil death induced by a triathlon competition in elite athletes

Introduction/Purpose: The effect of a triathlon competition on death of neutrophils from elite athletes was investigated. Methods: Blood was collected from 11 sedentary volunteers and 12 triathletes under rest and after a Half Ironman triathlon competition (2-km swimming, 80-km cycling, and 20-km running). Results: The triathlon competition increased DNA fragmentation, phosphatidylserine externalization, and reactive oxygen species production in neutrophils when compared to the results at rest. The proportion of neutrophils with mitochondrial transmembrane depolarization was increased in the triathletes at rest and after competition as compared with sedentary volunteers. Plasma levels of thiobarbituric acid reactive substances were increased in triathletes after competition. Expression of bcl-xL (antiapoptotic) was decreased and that of bax (proapoptotic) was increased, whereas intracellular neutral lipid content was lowered in neutrophils after the triathlon. A positive correlation was found between the proportion of neutrophils with DNA fragmentation and the plasma free fatty acid levels (r = 0.688, P < 0.05), which was elevated by threefold after competition. Plasma levels of oleic, linoleic, and stearic acids were increased in triathletes after the competition when compared with sedentary volunteers. The plasma concentration of these three fatty acids, measured after the triathlon competition, was toxic for 3-h cultured neutrophils obtained from sedentary volunteers. The maximal tolerable (nontoxic) concentration of the fatty acids by 3-h cultured neutrophils was 100 mu mol.L-1 for oleic and linoleic acids and 200 mu mol.L-1 for stearic acid. Conclusion: The triathlon competition induced neutrophil death possibly by apoptosis as indicated by DNA fragmentation and phosphatidylserine externalization. The increase in plasma levels of oleic, linoleic, and stearic acids induced by the competition may be involved in the neutrophil death observed possibly by increasing the production of reactive oxygen species and by decreasing the accumulation of intracellular neutral lipid.

Interlateral asymmetry in the time course of the effect of a peripheral prime stimulus

Evidence exists that both right and left hemisphere attentional mechanisms are mobilized when attention is directed to the right visual hemifield and only right hemisphere attentional mechanisms are mobilized when attention is directed to the left visual hemifield. This arrangement might lead to a rightward bias of automatic attention. The hypothesis was investigated by testing male volunteers, wherein a ""location discrimination"" reaction time task (Experiments 1 and 3) and a ""location and shape discrimination"" reaction time task (Experiments 2 and 4) were used. Unilateral (Experiments 1 and 2) and unilateral or bilateral (Experiments 3 and 4) peripheral visual prime stimuli were used to control attention. Reaction time to a small visual target stimulus in the same location or in the horizontally opposite location was evaluated. Stimulus onset asynchronies (SOAs) were 34, 50, 67, 83 and 100 ms. An important prime stimulus attentional effect was observed as early as 50 ms in the four experiments. In Experiments 2, 3 and 4, this effect was larger when the prime stimulus occurred in the right hemifield than when it occurred in the left hemifield for SOA 100 ms. In Experiment 4, when the prime stimulus occurred simultaneously in both hemifields, reaction time was faster for the right hemifield and for SOA 100 ms. These results indicate that automatic attention tends to favor the right side of space, particularly when identification of the target stimulus shape is required. (c) 2007 Elsevier Inc. All rights reserved.

Effect of olive oil-based emulsion on human lymphocyte and neutrophil death

Background The incorporation of lipid emulsions in parenteral diets is a requirement for energy and essential fatty acid supply to critically ill patients. The most frequently used IV lipid emulsions (LE) are composed with long-chain triacylglycerols rich in omega-6 polyunsaturated fatty acids (PUFA) from soybean oil, but these LE promote lymphocyte and neutrophil death. A new emulsion containing 20% soybean oil and 80% olive oil rich in (omega-9 monounsaturated fatty acids (MUFA) has been hypothesized not to cause impairment of immune function. In this study, the toxicity of an olive oil-based emulsion (OOE) on lymphocytes and neutrophils from healthy volunteers was investigated. Methods: Twenty volunteers were recruited and blood was. collected before a 6-hour infusion of an OOE, immediately after infusion, and again 18 hours postinfusion. Lymphocytes and neutrophils were isolated by gradient density. The cells were studied immediately after isolation and after 24 hours or 48 hours in culture. The following determinations were carried out: triacylglycerol levels and fatty acid composition and levels in plasma, lymphocyte proliferation, production of reactive oxygen species, and parameters of lymphocyte and neutrophil death (viability, DNA fragmentation, phosphatidylserine externalization, mitochondrial depolarization, and neutral lipid accumulation). Results: OOE decreased lymphocyte proliferation, provoked lymphocyte necrosis, and had no effect on the proportion of viable neutrophils. The mechanism of cell death induced by OOE involved neutral lipid accumulation but had no effect on mitochondrial membrane depolarization. Conclusions: The OOE given as a single dose of 500 mL induced low toxicity to lymphocytes from healthy volunteers, probably by necrosis.

Alternative to the stroop color-word test for illiterate individuals

An alternative to the Stroop Color-Word Test (SCWT), denominated the Colored Numbers Test (CNT), was developed to evaluate the selective attention of illiterate individuals. A total of 30 volunteers with basic education (control group) and 30 illiterate volunteers (experimental group) performed the SCWT and the CNT. Volunteers had to name the color of the rectangles in the CNT neutral condition, and in the critical condition they had to either name the color of the numbers or, when the numbers were black, read the numbers. An interference index (II) was calculated for both tests by subtracting the time taken to complete the task in the neutral condition from the time taken to complete the task in the critical condition. The control group showed an II of 14.9s in the SCWT and of 19.1s in the CNT, and the experimental group, which practically presented no interference in the SCWT (II = 0.2s), showed an II of 18.7s in the CNT. These findings suggest that the CNT can he used to evaluate selective attention. Further work should confirm its validity. Its advantage over the SCWT is that it does not depend on the ability to read words, being then suitable for illiterate individuals.

Automatic attention lateral asymmetry in visual discrimination tasks

There is evidence that automatic visual attention favors the right side. This study investigated whether this lateral asymmetry interacts with the right hemisphere dominance for visual location processing and left hemisphere dominance for visual shape processing. Volunteers were tested in a location discrimination task and a shape discrimination task. The target stimuli (S2) could occur in the left or right hemifield. They were preceded by an ipsilateral, contralateral or bilateral prime stimulus (S1). The attentional effect produced by the right S1 was larger than that produced by the left S1. This lateral asymmetry was similar between the two tasks suggesting that the hemispheric asymmetries of visual mechanisms do not contribute to it. The finding that it was basically due to a longer reaction time to the left S2 than to the right S2 for the contralateral S1 condition suggests that the inhibitory component of attention is laterally asymmetric.

Effect of medium/omega-6 long chain triglyceride-based emulsion on leucocyte death and inflammatory gene expression

Lipid emulsion (LE) containing medium/omega-6 long chain triglyceride-based emulsion (MCT/omega-6 LCT LE) has been recommended in the place of omega-6 LCT-based emulsion to prevent impairment of immune function. The impact of MCT/omega-6 LCT LE on lymphocyte and neutrophil death and expression of genes related to inflammation was investigated. Seven volunteers were recruited and infusion of MCT/omega-6 LCT LE was performed for 6 h. Four volunteers received saline and no change was found. Blood samples were collected before, immediately afterwards and 18 h after LE infusion. Lymphocytes and neutrophils were studied immediately after isolation and after 24 and 48 h in culture. The following determinations were carried out: plasma-free fatty acids, triacylglycerol and cholesterol concentrations, plasma fatty acid composition, neutral lipid accumulation in lymphocytes and neutrophils, signs of lymphocyte and neutrophil death and lymphocyte expression of genes related to inflammation. MCT/omega-6 LCT LE induced lymphocyte and neutrophil death. The mechanism for MCT/omega-6 LCT LE-dependent induction of leucocyte death may involve changes in neutral lipid content and modulation of expression of genes related to cell death, proteolysis, cell signalling, inflammatory response, oxidative stress and transcription.

Induction of Lymphocyte Death by Short- and Long-Duration Triathlon Competitions

LEVADA-PIRES, A. C., M. F. CURY-BOAVENTURA, R. GORJAO, S. M. HIRABARA. E. F. PUGGINA, I. L. PELLEGRINOTTI, L. A. DOMINGUES FILHO, R. CURI, and T. C. PITHON-CURI. Induction of Lymphocyte Death by Short- and Long-Duration Triathlon Competitions. Med. Sci. Sporty Exerc., Vol. 4 1, No. 10, pp. 1896-1901, 2009. Purpose: The effect of triathlon competitions on death of lymphocytes from elite athletes was investigated. Material and Methods: Blood was collected from sedentary volunteers and triathletes at rest and after a short-duration triathlon (SDT) and after a long-duration triathlon (LDT-half Ironman) competitions. Results: The athletes had lowered lymphocyte proliferation capacity compared with sedentary volunteers either at rest or after the competitions. There was no difference in the parameters associated with lymphocyte death when sedentary volunteers were compared with triathletes at rest. Lymphocytes from triathletes after SDT competition showed an increase in DNA fragmentation, phosphatidylserine externalization, and mitochondrial transmembrane depolarization and did not alter membrane integrity when compared with cells from athletes at rest. In contrast, the LDT competition raised the proportion of lymphocytes with loss of membrane integrity when compared with cells from athletes at rest and did not change the apoptotic parameters. The LDT competition induced an increase of reactive oxygen species (ROS) production by lymphocytes compared with triathletes at rest. The SDT competition did not alter ROS production by lymphocytes when compared with cells from triathletes at rest. ROS production by lymphocytes after LDT competition was 60% higher than in SDT. Conclusions: Evidence is presented herein that an LDT competition caused lymphocyte death by necrosis, whereas an SDT induced lymphocyte apoptosis. The mechanism for lymphocyte death induced by the triathlon competitions may involve an increase in ROS production at different extents.

Comparative bioavailability of cefuroxime axetil suspension formulations administered with food in healthy subjects

Objective: To assess the comparative bioavailability of two formulations (250 mg/5 mL suspension) of cefuroxime axetil (CAS 64544-07-6), administered with food, in healthy volunteers of both sexes. Methods: The study was conducted using an open, randomized, two-period crossover design with a 1-week washout interval. Plasma samples were obtained for up to 12 h post dose. Plasma cefuroxime axetil concentrations were analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS) with negative ion electrospray ionization using multiple reactions monitoring (MRM). From the cefuroxime axetil plasma concentration vs. time curves, the following pharmacokinetic parameters were obtained: AUC(last) and C(max). Results: The limit of quantification was 0.1 mu g/mL for plasma cefuroxime axetil analysis. The geometric mean and 90% confidence interval CI of test/reference product percent ratios were: 106.1% (100.8%-111.8%) for C(max), 109.4% (104.8%-114.2%) for AUC(last). Conclusion: Since the 90% Cl for AUC(last) and C(max) ratios were within the 80-125 % interval proposed by the US FDA, it was concluded that cefuroxime axetil (test formulation, 250 mg/5 mL suspension) was bioequivalent to a reference formulation under fed conditions, for both the rate and extent of absorption.