Moderate exercise improves leucocyte function and decreases inflammation in diabetes

P>The genesis and progression of diabetes occur due in part to an uncontrolled inflammation profile with insulin resistance, increased serum levels of free fatty acids (FFA), proinflammatory cytokines and leucocyte dysfunction. In this study, an investigation was made of the effect of a 3-week moderate exercise regimen on a treadmill (60% of VO(2max), 30 min/day, 6 days a week) on inflammatory markers and leucocyte functions in diabetic rats. The exercise decreased serum levels of tumour necrosis factor (TNF)-alpha (6%), cytokine-induced neutrophil chemotactic factor 2 alpha/beta (CINC-2 alpha/beta) (9%), interleukin (IL)-1 beta (34%), IL-6 (86%), C-reactive protein (CRP) (41%) and FFA (40%) in diabetic rats when compared with sedentary diabetic animals. Exercise also attenuated the increased responsiveness of leucocytes from diabetics when compared to controls, diminishing the reactive oxygen species (ROS) release by neutrophils (21%) and macrophages (28%). Exercise did not change neutrophil migration and the proportion of neutrophils and macrophages in necrosis (loss of plasma membrane integrity) and apoptosis (DNA fragmentation). Serum activities of creatine kinase (CK) and lactate dehydrogenase (LDH) were not modified in the conditions studied. Therefore, physical training did not alter the integrity of muscle cells. We conclude that moderate physical exercise has marked anti-inflammatory effects on diabetic rats. This may be an efficient strategy to protect diabetics against microorganism infection, insulin resistance and vascular complications.

Dietary Free Oleic and Linoleic Acid Enhances Neutrophil Function and Modulates the Inflammatory Response in Rats

The high ingestion of oleic (OLA) and linoleic (LNA) acids by Western populations, the presence of inflammatory diseases in these populations, and the importance of neutrophils in the inflammatory process led us to investigate the effects of oral ingestion of unesterified OLA and LNA on rat neutrophil function. Pure OLA and LNA were administered by gavage over 10 days. The doses used (0.11, 0.22 and 0.44 g/kg of body weight) were based on the Western consumption of OLA and LNA. Neither fatty acid affected food, calorie or water intake. The fatty acids were not toxic to neutrophils as evaluated by cytometry using propidium iodide (membrane integrity and DNA fragmentation). Neutrophil migration in response to intraperitoneal injection of glycogen and in the air pouch assay, was elevated after administration of either OLA or LNA. This effect was associated with enhancement of rolling and increased release of the chemokine CINC-2 alpha beta. Both fatty acids elevated l-selectin expression, whereas no effect on beta(2)-integrin expression was observed, as evaluated by flow cytometry. LNA increased the production of proinflammatory cytokines (IL-1 beta and CINC-2 alpha beta) by neutrophils after 4 h in culture and both fatty acids decreased the release of the same cytokines after 18 h. In conclusion, OLA and LNA modulate several functions of neutrophils and can influence the inflammatory process.

The effect of an adventure race on lymphocyte and neutrophil death

The effect of an adventure race (Ecomotion Pr), which lasted for 4-5 days, on neutrophil and lymphocyte death from elite athletes was investigated. Blood was collected from 11 athletes at rest and after the adventure race. The following parameters of cell death were measured in neutrophils and lymphocytes: cell membrane integrity, DNA fragmentation, mitochondrial transmembrane depolarization and reactive oxygen species (ROS) production. Phagocytosis capacity was also evaluated in neutrophils. The adventure race raised the proportion of cells with the loss of membrane integrity; lymphocytes by 14% and neutrophils by 16.4%. The proportion of lymphocytes with DNA fragmentation (2.9-fold) and mitochondrial transmembrane depolarization (1.5-fold) increased. However, these parameters did not change in neutrophils. ROS production remained unchanged in lymphocytes, whereas an increase by 2.2-fold was found in neutrophils due to the race. Despite these changes, the phagocytosis capacity did not change in neutrophils after the race. In conclusion, the Ecomotion Pr race-induced neutrophil death by necrosis (as indicated by the loss of membrane integrity) and led to lymphocyte death by apoptosis (as indicated by increase DNA fragmentation and depolarization of mitochondrial membrane).

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.

In vivo hydroquinone exposure alters circulating neutrophil activities and impairs LPS-induced lung inflammation in mice

Hydroquinone (HQ) is an environmental contaminant which causes immune toxicity. In this study, the effects of exposure to low doses of HQ on neutrophil mobilization into the LPS-inflamed lung were investigated. Male Swiss mice were exposed to aerosolized vehicle (control) or 12.5, 25 or 50 ppm HQ (1 h/day for 5 days). One hour later, oxidative burst, cell cycle. DNA fragmentation and adhesion molecules expressions in circulating neutrophils were determined by flow cytometry, and plasma malondialdehyde (MDA) levels were measured by HPLC. Also, 1 h later the last exposures, inflammation was induced by LPS inhalation (0.1 mg/ml/10 min) and 3 h later, the numbers of leukocytes in peripheral blood and in the bronchoalveolar lavage fluid (BALF) were determined using a Neubauer chamber and stained smears; adhesion molecules expressed on lung microvessel endothelial cells were quantified by immunohistochemistry; myeloperoxidase (MPO) activity was measured in the lung tissue by colorimetric assay; and cytokines in the BALF were determined by ELISA. In vivo HQ exposure augmented plasma MDA levels and oxidative activity of neutrophils, but did not cause alterations in cell cycle and DNA fragmentation. Under these conditions, the number of circulating leukocytes was not altered, but HQ exposure reduced LPS-induced neutrophil migration into the alveolar space, as these cells remained in the lung tissue. The impaired neutrophil migration into BALF may not be dependent on reduced cytokines secretions in the BALF and lung endothelial adhesion molecules expressions. However, HQ exposure increased the expression of beta(2) and beta(3) integrins and platelet-endothelial cell adhesion molecule-1 (PECAM-1) in neutrophils, which were not further enhanced by fMLP in vitro stimulation, indicating that HQ exposure activates circulating neutrophils, impairing further stimulatory responses. Therefore, it has been shown, for the first time, that neutrophils are target of lower levels of in vivo HQ exposure, which may be considered in host defense in infectious diseases. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Autolytic Mycobacterium leprae Hsp65 fragments may act as biological markers for autoimmune diseases

Investigating the proteolytic activity of the recombinant Mycobacterium leprae Heat Shock Protein of 65 kDa (rHsp65), chaperonin 2 (cpn2), we observed that it displays high instability. The fragmentation process starts at the C-terminus followed by progressive degradation of the N-terminus, which leads to a stable fragment comprising the middle region of the molecule. Urea was able to prevent autolysis, probably due to its denaturing action, while EDTA increased degradation levels indicating the need for metal ions. Peptides originated from autolysis were purified and analyzed by mass spectrometry, generating a continuous map. Since the bacteria and mammalian Hsp60 are known to be targets of the immune response and have been implicated in autoimmune diseases and chronic inflammation, the in vivo effect of rHsp65 peptides was evaluated in the spontaneous Systemic Lupus Erythematosus (SLE) model developed by the (NZB/NZW)F(1) mouse hybrids, and their individual anti-rHsp65 IgG2a/IgG1 antibody titer ratio was determined. The results showed orientation toward a T(H)1 responsiveness, and the treatment with the rHsp65 peptides diminished the environmental variance of the survival time of treated animals. These results outline the fact that environmental factors may also act through the modified stability expression of Heat Shock Proteins intervening during autoimmune processes. (C) 2011 Elsevier Ltd. All rights reserved.

Long-term oscillations in the sleep/wake cycle of infants

The development of circadian sleep-wakefulness rhythm was investigated by a longitudinal study of six normal infants. We propose an entropy based measure for the sleep/wake cycle fragmentation. Our results confirm that the sleep/wake cycle fragmentation and the sleep/wake ratio decrease, while the circadian power increases during the maturation process of infants. In addition to these expected linear trends in the variables devised to quantify sleep consolidation, circadian power and sleep/wake ratio, we found that they present infradian rhythms in the monthly range. (C) 2009 Elsevier B.V. All rights reserved.

System size dependence of associated yields in hadron-triggered jets STAR Collaboration

We present results on the system size dependence of high transverse momentum di-hadron correlations at root s(NN) = 200 GeV as measured by STAR at RHIC. Measurements in d + Au, Cu + Cu and Au + Au collisions reveal similar jet-like near-side correlation yields (correlations at small angular separation Delta phi similar to 0, Delta eta similar to 0) for all systems and centralities. Previous measurements have shown Chat the away-side (Delta phi similar to pi) yield is suppressed in heavy-ion collisions. We present measurements of the away-side Suppression as a function of transverse momentum and centrality in Cu + Cu and Au + Au collisions. The suppression is found to be similar in Cu + Cu and An + An collisions at a similar number of participants. The results are compared to theoretical calculations based on the patron quenching model and the modified fragmentation model. The observed differences between data and theory indicate that the correlated yields presented here will further constrain dynamic energy loss models and provide information about the dynamic density profile in heavy-ion collisions. (C) 2009 Elsevier B.V. All rights reserved.

Center of mass energy and system-size dependence of photon production at forward rapidity at RHIC

We present the multiplicity and pseudorapidity distributions of photons produced in Au + Au and Cu + Cu collisions at root(s)NN = 62.4 and 200 GeV. The photons are measured in the region -3.7 < eta < -2.3 using the photon Multiplicity detector in the STAR experiment at RHIC. The number of photons produced per average number of participating nucleon pairs increases with the beam energy and is independent of (lie collision centrality. For collisions with similar average numbers of participating nucleons the photon multiplicities are observed to be similar for An + Au and Cu + Cu collisions at a given beam energy. The ratios of the number of charged particles to photons in the measured pseudorapidity range are found to be 1.4 +/- 0.1 and 1.2 +/- 0.1 for root(s)NN = 62.4 and 200 GeV, respectively. The energy dependence of this ratio could reflect varying contributions from baryons to charged particles, while mesons are the dominant contributors to photon production in the given kinematic region. The photon pseudorapidity distributions normalized by average number of participating nucleon pairs, when plotted as a function of eta-Y(beam), are found to follow a longitudinal scaling independent of centrality and colliding ion species at both beam energies. (C) 2009 Elsevier B.V. All rights reserved.

A new nitrosyl ruthenium complex: Synthesis, chemical characterization, in vitro and in vivo antitumor activities and probable mechanism of action

This study describes the synthesis of a new ruthenium nitrosyl complex with the formula [RuCl(2)NO(BPA)] [BPA = (2-hydroxybenzyl)(2-methylpyridyl)amine ion], which was synthesized and characterized by spectroscopy, cyclic voltammetry, X-ray crystallography, and theoretical calculation data. The biological studies of this complex included in vitro cytotoxic assays, which revealed its activity against two different tumor cell lines (HeLa and Tm5), with efficacy comparable to that of cisplatin, a metal-based drug that is administered in clinical treatment. The in vivo studies showed that [RuCl2NO(BPA)] is effective in reducing tumor mass. Also, our results suggest that the mechanism of action of [RuCl(2)NO(BPA)] includes binding to DNA, causing fragmentation of this biological molecule, which leads to apoptosis. (C) 2011 Elsevier Masson SAS. All rights reserved.

Neoproterozoic geodynamic evolution of SW-Gondwana: a southern African perspective

Our current understanding of the tectonic history of the principal Pan-African orogenic belts in southwestern Africa, reaching from the West Congo Belt in the north to the Lufilian/Zambezi, Kaoko, Damara, Gariep and finally the Saldania Belt in the south, is briefly summarized. On that basis, possible links with tectono-stratigraphic units and major structures on the eastern side of the Rio de la Plata Craton are suggested, and a revised geodynamic model for the amalgamation of SW-Gondwana is proposed. The Rio de la Plata and Kalahari Cratons are considered to have become juxtaposed already by the end of the Mesoproterozoic. Early Neoproterozoic rifting led to the fragmentation of the northwestern (in today`s coordinates) Kalahari Craton and the splitting off of several small cratonic blocks. The largest of these ex-Kalahari cratonic fragments is probably the Angola Block. Smaller fragments include the Luis Alves and Curitiba microplates in eastern Brazil, several basement inliers within the Damara Belt, and an elongate fragment off the western margin, named Arachania. The main suture between the Kalahari and the Congo-So Francisco Cratons is suspected to be hidden beneath younger cover between the West Congo Belt and the Lufilian/Zambezi Belts and probably continues westwards via the Cabo Frio Terrane into the Goias magmatic arc along the Brasilia Belt. Many of the rift grabens that separated the various former Kalahari cratonic fragments did not evolve into oceanic basins, such as the Northern Nosib Rift in the Damara Belt and the Gariep rift basin. Following latest Cryogenian/early Ediacaran closure of the Brazilides Ocean between the Rio de la Plata Craton and the westernmost fragment of the Kalahari Craton, the latter, Arachania, became the locus of a more than 1,000-km-long continental magmatic arc, the Cuchilla Dionisio-Pelotas Arc. A correspondingly long back-arc basin (Marmora Basin) on the eastern flank of that arc is recognized, remnants of which are found in the Marmora Terrane-the largest accumulation of oceanic crustal material known from any of the Pan-African orogenic belts in the region. Corresponding foredeep deposits that emerged from the late Ediacaran closure of this back-arc basin are well preserved in the southern areas, i.e. the Punta del Este Terrane, the Marmora Terrane and the Tygerberg Terrane. Further to the north, present erosion levels correspond with much deeper crustal sections and comparable deposits are not preserved anymore. Closure of the Brazilides Ocean, and in consequence of the Marmora back-arc basin, resulted from a change in the Rio de la Plata plate motion when the Iapetus Ocean opened between the latter and Laurentia towards the end of the Ediacaran. Later break-up of Gondwana and opening of the modern South Atlantic would have followed largely along the axis of the Marmora back-arc basin and not along major continental sutures.

The Guarguaraz Complex and the Neoproterozoic-Cambrian evolution of southwestern Gondwana: Geochemical signatures and geochronological constraints

The Guarguaraz Complex, in western Argentina, comprises a metasedimentary assemblage, associated with mafic sills and ultramafic bodies intruded by basaltic dikes, which are interpreted as Ordovician dismembered ophiolites. Two kinds of dikes are recognized, a group associated with the metasediments and the other ophiolite-related. Both have N-MORB signatures, with epsilon(Nd) between +3.5 and +8.2, indicating a depleted source, and Grenville model ages between 0.99 and 1.62 Ga. A whole-rock Sm-Nd isochron yielded an age of 655 +/- 76 Ma for these mafic rocks, which is compatible with cianobacteria and acritarchae recognized in the clastic metasedimentary platform sequences, that indicate a Neoproterozoic (Vendian)-Cambrian age of deposition. The Guarguaraz metasedimentary-ophiolitic complex represents, therefore, a remnant of an oceanic basin developed to the west of the Grenville-aged Cuyania terrane during the Neoproterozoic. The southernmost extension of these metasedimentary sequences in Cordon del Portillo might represent part of this platform and not fragments of the Chilenia terrane. An extensional event related to the fragmentation of Rodinia is represented by the mafic and ultramafic rocks. The Devonian docking of Chilenia emplaced remnants of ocean floor and slices of the Cuyania terrane (Las Yaretas Gneisses) in tectonic contact with the Neoproterozoic metasediments, marking the Devonian western border of Gondwana. (C) 2009 Elsevier Ltd. All rights reserved.

Lu-Hf and U-Pb age determination of Capivarita Anorthosite in the Dom Feliciano Belt, Brazil

The Capivarita Anorthosite, formed in an intraplate environment and later metamorphosed under amphibolites fades conditions, is exposed in the Dom Feliciano Belt as part of the Brasiliano magmatic arc and occurs as a roof-pedant in, or is even intruded by, 0.6 Ga post-collisional granites. In this work, magmatic and metamorphic minerals were dated using the LA-MC-ICP-MS in situ method. U-Pb magmatic and metamorphic zircon dating yielded an age of 1573 +/- 21 Ma and of 606 +/- 6 Ma, respectively, whereas the igneous titanite dating yielded an age of 1530 +/- 33 Ma and the metamorphic ages were 651 +/- 9 Ma and 601 +/- 5 Ma. The Lu-Hf model ages showed two clusters from 1.81 to 2.03 Ga (calf from +2.21 to +6.42) and 2.55-2.62 Ga (epsilon epsilon Hf from -4.59 to -5.64). This intraplate magmatism can be connected to a very important episode of continental accretion in an extensional setting from the fragmentation of the supercontinent during the Early Mesoproterozoic. (C) 2011 Elsevier B.V. All rights reserved.

Lipid hydroperoxide-induced and hemoglobin-enhanced oxidative damage to colon cancer cells

Epidemiological studies have indicated that Western diets are related to an increase in a series of malignancies. Among the compounds that are credited for this toxic effect are heme and lipid peroxides. We evaluated the effects of hemoglobin (Hb) and linoleic acid hydroperoxides (LAOOH) on a series of toxicological endpoints, such as cytotoxicity, redox status, lipid peroxidation, and DNA damage. We demonstrated that the preincubation of SW480 cells with Hb and its subsequent exposure to LAOOH (Hb + LAOOH) led to an increase in cell death, DCFH oxidation, malonaldehyde formation, and DNA fragmentation and that these effects were related to the peroxide group and the heme present in Hb. Furthermore, Hb and LAOOH alone exerted a toxic effect on the endpoints assayed only at concentrations higher than 100 mu M. We were also able to show that SW480 cells presented a higher level of the modified DNA bases 8-oxo-7,8-dihydro-2`-deoxyguanosine and 1,N(2)-etheno-2`-deoxyguanosine compared to the control. Furthermore, incubations with Hb led to an increase in intracellular iron levels, and this high level of iron correlated with DNA oxidation, as measured as EndoIII- and Fpg-sensitive sites. Thus, Hb from either red meat or bowel bleeding could act as an enhancer of fatty acid hydroperoxide genotoxicity, which contributes to the accumulation of DNA lesions in colon cancer cells. (C) 2011 Elsevier Inc. All rights reserved.

Characterization of O(2) ((1)Delta(g))-Derived Oxidation Products of Tryptophan: A Combination of Tandem Mass Spectrometry Analyses and Isotopic Labeling Studies

The fragmentation mechanisms of singlet oxygen [O(2) ((1)Delta(g))]-derived oxidation products of tryptophan (W) were analyzed using collision-induced dissociation coupled with (18)O-isotopic labeling experiments and accurate mass measurements. The five identified oxidized products, namely two isomeric alcohols (trans and cis WOH), two isomeric hydroperoxides (trans and cis WOOH), and N-formylkynurenine (FMK), were shown to share some common fragment ions and losses of small neutral molecules. Conversely, each oxidation product has its own fragmentation mechanism and intermediates, which were confirmed by (18)O-labeling studies. Isomeric WOH lost mainly H(2)O + CO, while WOOH showed preferential elimination of C(2)H(5)NO(3) by two distinct mechanisms. Differences in the spatial arrangement of the two isomeric WOHs led to differences in the intensities of the fragment ions. The same behavior was also found for trans and cis WOOH. FMK was shown to dissociate by a diverse range of mechanisms, with the loss of ammonia the most favored route. MS/MS analyses, (18)O-labeling, and H(2)(18)O experiments demonstrated the ability of FMK to exchange its oxygen atoms with water. Moreover, this approach also revealed that the carbonyl group has more pronounced oxygen exchange ability compared with the formyl group. The understanding of fragmentation mechanisms involved in O(2) ((1)Delta(g))-mediated oxidation of W provides a useful step toward the structural characterization of oxidized peptides and proteins. (J Am Soc Mass Spectrom 2009, 20, 188-197) (C) 2009 Published by Elsevier Inc. on behalf of American Society for Mass Spectrometry