Inhibition Of Tumor Necrosis Factor-alpha And Cyclooxigenase-2 By Isatin: A Molecular Mechanism Of Protection Against Tnbs-induced Colitis In Rats.

Isatin, an indole alkaloid has been shown to have anti-microbial, anti-tumor and anti-inflammatory effects. Due to its findings, we evaluated whether this alkaloid would have any effect on TNBS-induced colitis. Animals (male Unib:WH rats, aged 8 weeks old) were induced colitis through a rectal administration of 2,4,6-trinitrobenzene sulphonic acid using a catheter inserted 8 cm into the rectum of the animals. The rats were divided into two major groups: non-colitic and colitic. The colitic group was sub-divided into 6 groups (10 animals per group): colitic non-treated, Isatin 3; 6; 12.5; 18.75 and 25 mg/kg. Our main results showed that the oral treatment with Isatin 6 and 25 mg/kg were capable of avoiding the increase in TNF-α, COX-2 and PGE₂ levels when compared to the colitic non-treated group. Interestingly, the same doses (6 and 25 mg/kg) were also capable of preventing the decrease in IL-10 levels comparing with the colitic non-treated group. The levels of MPO, (an indirect indicator of neutrophil presence), were also maintained lower than those of the colitic non-treated group. Isatin also prevented the decrease of SOD activity and increase of GSH-Px and GSH-Rd activity as well as the depletion of GSH levels. In conclusion, both pre-treatments (6 and 25 mg/kg) were capable of protecting the gut mucosa against the injury caused by TNBS, through the combination of antioxidant and anti-inflammatory properties, which, together, showed a protective activity of the indole alkaloid Isatin.

Assessment Of Sleep Bruxism, Orthodontic Treatment Need, Orofacial Dysfunctions And Salivary Biomarkers In Asthmatic Children.

To evaluate the sleep bruxism, malocclusions, orofacial dysfunctions and salivary levels of cortisol and alpha-amylase in asthmatic children. 108 7-9-yr-old children were selected from Policlinic Santa Teresinha Doutor Antonio Haddad Dib (asthmatics, n=53) and from public schools (controls, n=55), Piracicaba, SP, Brazil. Sleep bruxism diagnosis was confirmed by parental report of grinding sounds and the presence of shiny and polish facets on incisors and/or first permanent molars. The index of orthodontic treatment need was used for occlusion evaluation. Orofacial dysfunctions were evaluated using the nordic orofacial test-screening (NOT-S). Salivary cortisol and alpha-amylase were expressed as awakening response (AR), calculated as the difference between levels immediately after awakening and 30min after waking, and diurnal decline (DD), calculated as the difference between levels at 30min after waking and at bedtime. Data were analyzed using Shapiro-Wilk/Kolmogorov-Smirnov, Chi-square, unpaired t test/Mann-Whitney and paired t/Wilcoxon tests. Sleep bruxism was more prevalent in children with asthma than controls (47.2% vs. 27.3%, p<0.05). Asthmatics had higher scores of NOT-S total and interview (p<0.05). Dysfunctions on sensory function and chewing and swallowing were more frequent in asthmatics (p<0.05). Salivary cortisol AR on weekend was significantly higher for asthmatics (p<0.05). Salivary cortisol DD was significantly higher on weekday than weekend for controls (p<0.05). There were no significant differences in alpha-amylase values in and between groups. The presence of asthma in children was associated with sleep bruxism, negative perception of sensory, chewing and swallowing functions, and higher concentrations of salivary cortisol on weekend.

Flexural strength and hardness of direct and indirect composites

The objective of this study was to evaluate the flexural strength (σf) and hardness (H) of direct and indirect composites, testing the hypotheses that direct resin composites produce higher σf and H values than indirect composites and that these properties are positively related. Ten bar-shaped specimens (25 mm x 2 mm x 2 mm) were fabricated for each direct [D250 - Filtek Z250 (3M-Espe) and D350 - Filtek Z350 (3M-Espe)] and indirect [ISin - Sinfony (3M-Espe) and IVM - VitaVM LC (Vita Zahnfabrik)] materials, according to the manufacturer's instructions and ISO4049 specifications. The σf was tested in three-point bending using a universal testing machine (EMIC DL 2000) at a crosshead speed of 0.5 mm/min (ISO4049). Knoop hardness (H) was measured on the specimens' fragments resultant from the σf test and calculated as H = 14.2P/l², where P is the applied load (0.1 kg; dwell time = 15 s) and l is the longest diagonal of the diamond shaped indent (ASTM E384). The data were statistically analyzed using Anova and Tukey tests (α = 0.05). The mean σf and standard deviation values (MPa) and statistical grouping were: D250 - 135.4 ± 17.6a; D350 - 123.7 ± 11.1b; ISin - 98.4 ± 6.4c; IVM - 73.1 ± 4.9d. The mean H and standard deviation values (kg/mm²) and statistical grouping were: D250 - 98.12 ± 1.8a; D350 - 86.5 ± 1.9b; ISin - 28.3 ± 0.9c; IVM - 30.8 ± 1.0c. The direct composite systems examined produce higher mean σf and H values than the indirect composites, and the mean values of these properties were positively correlated (r = 0.91), confirming the study hypotheses.

Phase transitions in biodegradable films based on blends of gelatin and poly (vinyl alcohol)

The aim of this work was to study the effect of the hydrolysis degree (HD) and the concentration (C PVA) of two types of poly (vinyl alcohol) (PVA) and the effect of the type and the concentration of plasticizers on the phase properties of biodegradable films based on blends of gelatin and PVA, using a response-surface methodology. The films were made by casting and the studied properties were their glass (Tg) and melting (Tm) transition temperatures, which were determined by diferential scanning calorimetry (DSC). For the data obtained on the first scan, the fitting of the linear model was statistically significant and predictive only for the second melting temperature. In this case, the most important effect on the second Tm of the first scan was due to the HD of the PVA. In relation to the second scan, the linear model could be fit to Tg data with only two statistically significant parameters. Both the PVA and plasticizer concentrations had an important effect on Tg. Concerning the second Tm of the second scan, the linear model was fit to data with two statistically significant parameters, namely the HD and the plasticizer concentration. But, the most important effect was provoked by the HD of the PVA.

Influência de diferentes sistemas de solvente água-etanol sobre as propriedades físico-químicas e espectroscópicas dos compostos macrocíclicos feofitina e clorofila α

This work focus on the influence of solvent on the photophysical properties of chlorophyll α and pheophytin. Both compounds are related to the photosynthesis process and are considered prototypes of photosensitizers in Photodynamic Therapy. Fluorescence measurements were developed using water/ethanol mixtures at different compositions, since both solvents could be employed in biological applications. The spectroscopic properties of these compounds undergo profound changes depending on water content in the ethanol due to auto-aggregation processes. The major hydrophobicity and the lower dielectric constant of ethanol when compared with water precluded significantly the auto-aggregation process of these compounds.

Aging and fluctuation-dissipation ratio in a nonequilibrium q-state lattice model

A generalized version of the nonequilibrium linear Glauber model with q states in d dimensions is introduced and analyzed. The model is fully symmetric, its dynamics being invariant under all permutations of the q states. Exact expressions for the two-time autocorrelation and response functions on a d-dimensional lattice are obtained. In the stationary regime, the fluctuation-dissipation theorem holds, while in the transient the aging is observed with the fluctuation-dissipation ratio leading to the value predicted for the linear Glauber model.

Lack of Galectin-3 Disturbs Mesenteric Lymph Node Homeostasis and B Cell Niches in the Course of Schistosoma mansoni Infection

Galectin-3 is a beta-galactoside-binding protein that has been shown to regulate pathophysiological processes, including cellular activation, differentiation and apoptosis. Recently, we showed that galectin-3 acts as a potent inhibitor of B cell differentiation into plasma cells. Here, we have investigated whether galectin-3 interferes with the lymphoid organization of B cell compartments in mesenteric lymph nodes (MLNs) during chronic schistosomiasis, using WT and galectin-3(-/-) mice. Schistosoma mansoni synthesizes GalNAc beta 1-4(Fuc alpha 1-3) GlcNAc(Lac-DiNAc) structures (N-acetylgalactosamine beta 1-4 N-acetylglucosamine), which are known to interact with galectin-3 and elicit an intense humoral response. Antigens derived from the eggs and adult worms are continuously drained to MLNs and induce a polyclonal B cell activation. In the present work, we observed that chronically-infected galectin-3(-/-) mice exhibited a significant reduced amount of macrophages and B lymphocytes followed by drastic histological changes in B lymphocyte and plasma cell niches in the MLNs. The lack of galectin-3 favored an increase in the lymphoid follicle number, but made follicular cells more susceptible to apoptotic stimuli. There were an excessive quantity of apoptotic bodies, higher number of annexin V(+)/PI(-) cells, and reduced clearance of follicular apoptotic cells in the course of schistosomiasis. Here, we observed that galectin-3 was expressed in nonlymphoid follicular cells and its absence was associated with severe damage to tissue architecture. Thus, we convey new information on the role of galectin-3 in regulation of histological events associated with B lymphocyte and plasma cell niches, apoptosis, phagocytosis and cell cycle properties in the MLNs of mice challenged with S. mansoni.

Dopamine-beta hydroxylase polymorphism and cocaine addiction

Cocaine addiction involves a number of medical, psychological and social problems. Understanding the genetic aetiology of this disorder will be essential for design of effective treatments. Dopamine-beta hydroxylase (DbH) catalyzes the conversion of dopamine to norepinephrine and could, therefore, have an influence on both cocaine action and the basal sensitivity of neurotransmitter systems to cocaine. Recently, the - 1021C> T polymorphism have been found to strongly correlated with individual variation in plasma DbH activity. To test the influence of this polymorphism on the susceptibility of cocaine addiction, we decided to genotype it in a sample of 689 cocaine addicts and 832 healthy individuals. Genotypic and allelic analyses did not show any evidence of association with cocaine addiction, even after correcting for the effect of population stratification and other possible confounders. Our results do not support a major role of the - 1021C> T polymorphism or the gene itself in the development of cocaine addiction but further examination of other variants within this gene will be necessary to completely rule out an effect.

Central nitrergic system regulation of neuroendocrine secretion, fluid intake and blood pressure induced by angiotensin-II

Background: Nitric oxide (NO) synthesis has been described in several circumventricular and hypothalamic structures in the central nervous system that are implicated in mediating central angiotensin-II (ANG-II) actions during water deprivation and hypovolemia. Neuroendocrine and cardiovascular responses, drinking behavior, and urinary excretions were examined following central angiotensinergic stimulation in awake freely-moving rats pretreated with intracerebroventricular injections of N omega-nitro-L-arginine methyl ester (L-NAME, 40 mu g), an inhibitor of NO synthase, and L-arginine (20 ug), a precursor of NO. Results: Injections of L-NAME or ANG-II produced an increase in plasma vasopressin (VP), oxytocin (OT) and atrial natriuretic peptide (ANP) levels, an increase in water and sodium intake, mean arterial blood pressure and sodium excretion, and a reduction of urinary volume. L-NAME pretreatment enhanced the ANG-II response, while L-arginine attenuated VP and OT release, thirst, appetite for sodium, antidiuresis, and natriuresis, as well as pressor responses induced by ANG-II. Discussion and conclusion: Thus, the central nitrergic system participates in the angiotensinergic responses evoked by water deprivation and hypovolemia to refrain neurohypophysial secretion, hydromineral balance, and blood pressure homeostasis.

Characterization of Novel OmpA-Like Protein of Leptospira interrogans That Binds Extracellular Matrix Molecules and Plasminogen

Leptospira interrogans is the etiological agent of leptospirosis, a zoonotic disease of human and veterinary concern. The identification of novel proteins that mediate host-pathogen interactions is important for understanding the bacterial pathogenesis as well as to identify protective antigens that would help fight the disease. We describe in this work the cloning, expression, purification and characterization of three predicted leptospiral membrane proteins, LIC10258, LIC12880 (Lp30) and LIC12238. We have employed Escherichia coli BL21 (SI) strain as a host expression system. Recently, we have identified LIC12238 as a plasminogen (PLG)-binding receptor. We show now that Lp30 and rLIC10258 are also PLG-receptors of Leptospira, both exhibiting dose-dependent and saturating binding (K(D), 68.8 +/- 25.2 nM and 167.39 +/- 60.1 nM, for rLIC10258 and rLIC12880, respectively). In addition, LIC10258, which is a novel OmpA-like protein, binds laminin and plasma fibronectin ECM molecules and hence, it was named Lsa66 (Leptospiral surface adhesin of 66 kDa). Binding of Lsa66 to ECM components was determined to be specific, dose-dependent and saturable, with a KD of 55.4 +/- 15.9 nM to laminin and of 290.8 +/- 11.8 nM to plasma fibronectin. Binding of the recombinant proteins to PLG or ECM components was assessed by using antibodies against each of the recombinant proteins obtained in mice and confirmed by monoclonal anti-polyhistidine antibodies. Lsa66 caused partial inhibition on leptospiral adherence to immobilized ECM and PLG. Moreover, this adhesin and rLIC12238 are recognized by antibodies in serum samples of confirmed leptospirosis cases. Thus, Lsa66 is a novel OmpA-like protein with dual activity that may promote the attachment of Leptospira to host tissues and may contribute to the leptospiral invasion. To our knowledge, this is the first leptospiral protein with ECM and PLG binding properties reported to date.

Genetic parameters for productive life traits and reproductive efficiency traits at 6 years in Nellore cattle

The objective of the present study was to estimate (co)variance components for length of productive life (LPL) and some alternative reproductive traits of 6-year-old Nellore cattle. The data set contained 57,410 records for age at first calving from Nellore females and was edited to remove animal records with uncertain paternity and cows with just one piece of calving information. Only animals with age at first calving ranging from 23 to 48 months and calving intervals between 11 and 24 months were kept for analysis. LPL and life production ( LP) were used to describe productive life. LPL was defined as the number of months a cow was kept in the herd until she was 6 years old, given that she was alive at first calving and LP was defined as total number of calves in that time. Four traits were used to describe reproductive traits: two breeding efficiencies on original scale were estimated using Wilcox and Tomar functions (BEW and BET, respectively), and two breeding efficiencies transformed (ASBEW and ASBET, respectively), using the function [arcsine (square root (BEi/100))]. Estimates of heritability for measures of LPL and LP were low and ranged from 0.04 to 0.05. Estimates of heritability for breeding efficiencies on original and transformed scales oscillated from 0.18 to 0.32. Estimates of genetic correlations ranged from -0.57 to 0.79 for LPL and other traits and from 0.28 to 0.63 for LP and other traits.

Cluster and cluster galaxy evolution history from IR to X-ray observations of the young cluster RX J1257.2+4738 at z=0.866

Context. The cosmic time around the z similar to 1 redshift range appears crucial in the cluster and galaxy evolution, since it is probably the epoch of the first mature galaxy clusters. Our knowledge of the properties of the galaxy populations in these clusters is limited because only a handful of z similar to 1 clusters are presently known. Aims. In this framework, we report the discovery of a z similar to 0.87 cluster and study its properties at various wavelengths. Methods. We gathered X-ray and optical data (imaging and spectroscopy), and near and far infrared data (imaging) in order to confirm the cluster nature of our candidate, to determine its dynamical state, and to give insight on its galaxy population evolution. Results. Our candidate structure appears to be a massive z similar to 0.87 dynamically young cluster with an atypically high X-ray temperature as compared to its X-ray luminosity. It exhibits a significant percentage (similar to 90%) of galaxies that are also detected in the 24 mu m band. Conclusions. The cluster RXJ1257.2+4738 appears to be still in the process of collapsing. Its relatively high temperature is probably the consequence of significant energy input into the intracluster medium besides the regular gravitational infall contribution. A significant part of its galaxies are red objects that are probably dusty with on-going star formation.

Female sex hormones mediate the allergic lung reaction by regulating the release of inflammatory mediators and the expression of lung E-selectin in rats

Background: Fluctuations of estradiol and progesterone levels caused by the menstrual cycle worsen asthma symptoms. Conflicting data are reported in literature regarding pro and anti-inflammatory properties of estradiol and progesterone. Methods: Female Wistar rats were ovalbumin (OVA) sensitized 1 day after resection of the ovaries (OVx). Control group consisted of sensitized-rats with intact ovaries (Sham-OVx). Allergic challenge was performed by aerosol (OVA 1%, 15 min) two weeks later. Twenty four hours after challenge, BAL, bone marrow and total blood cells were counted. Lung tissues were used as explants, for expontaneous cytokine secretion in vitro or for immunostaining of E-selectin. Results: We observed an exacerbated cell recruitment into the lungs of OVx rats, reduced blood leukocytes counting and increased the number of bone marrow cells. Estradiol-treated OVx allergic rats reduced, and those treated with progesterone increased, respectively, the number of cells in the BAL and bone marrow. Lungs of OVx allergic rats significantly increased the E-selectin expression, an effect prevented by estradiol but not by progesterone treatment. Systemically, estradiol treatment increased the number of peripheral blood leukocytes in OVx allergic rats when compared to non treated-OVx allergic rats. Cultured-BAL cells of OVx allergic rats released elevated amounts of LTB(4) and nitrites while bone marrow cells increased the release of TNF-alpha and nitrites. Estradiol treatment of OVx allergic rats was associated with a decreased release of TNF-alpha, IL-10, LTB4 and nitrites by bone marrow cells incubates. In contrast, estradiol caused an increase in IL-10 and NO release by cultured-BAL cells. Progesterone significantly increased TNF-alpha by cultured BAL cells and bone marrow cells. Conclusions: Data presented here suggest that upon hormonal oscillations the immune sensitization might trigger an allergic lung inflammation whose phenotype is under control of estradiol. Our data could contribute to the understanding of the protective role of estradiol in some cases of asthma symptoms in fertile ans post-menopausal women clinically observed.

Complete Genome Viral Phylogenies Suggests the Concerted Evolution of Regulatory Cores and Accessory Satellites

We consider the concerted evolution of viral genomes in four families of DNA viruses. Given the high rate of horizontal gene transfer among viruses and their hosts, it is an open question as to how representative particular genes are of the evolutionary history of the complete genome. To address the concerted evolution of viral genes, we compared genomic evolution across four distinct, extant viral families. For all four viral families we constructed DNA-dependent DNA polymerase-based (DdDp) phylogenies and in addition, whole genome sequence, as quantitative descriptions of inter-genome relationships. We found that the history of the polymerase gene was highly predictive of the history of the genome as a whole, which we explain in terms of repeated, co-divergence events of the core DdDp gene accompanied by a number of satellite, accessory genetic loci. We also found that the rate of gene gain in baculovirus and poxviruses proceeds significantly more quickly than the rate of gene loss and that there is convergent acquisition of satellite functions promoting contextual adaptation when distinct viral families infect related hosts. The congruence of the genome and polymerase trees suggests that a large set of viral genes, including polymerase, derive from a phylogenetically conserved core of genes of host origin, secondarily reinforced by gene acquisition from common hosts or co-infecting viruses within the host. A single viral genome can be thought of as a mutualistic network, with the core genes acting as an effective host and the satellite genes as effective symbionts. Larger virus genomes show a greater departure from linkage equilibrium between core and satellites functions.

Effect of weak dipolar interaction on the magnetic properties of Ni nanoparticles assembly analyzed with different protocols

The effect of weak dipolar interactions (DIs) between Ni nanoparticles (NPs) in samples with different Ni concentrations was investigated by performing a detailed characterization of their structural and magnetic properties. From the determination of several physical parameters of Ni NP assemblies, it was found that the ac and dc magnetic susceptibility measurements are valuable for identifying the DIs between NPs while hysteresis loops measurements showed to be very insensitive, provided that the strength of the DI field is much smaller than the maximum coercive field. Therefore, the sensitivity of the observed static and dynamical magnetic properties to the effect of weak DI depends on the measurement protocols used. (C) 2011 American Institute of Physics. [doi:10.1063/1.3556767]