Multiple sclerosis and herpesvirus interaction

Multiple sclerosis is the most common autoimmune inflammatory demyelinating disease of the central nervous system, and its etiology is believed to have both genetic and environmental components. Several viruses have already been implicated as triggers and there are several studies that implicate members of the Herpesviridae family in the pathogenesis of MS. The most important characteristic of these viruses is that they have periods of latency and exacerbations within their biological sanctuary, the central nervous system. The Epstein-Barr, cytomegalovirus, human herpesvirus 6 and human herpesvirus 7 viruses are the members that are most studied as being possible triggers of multiple sclerosis. According to evidence in the literature, the herpesvirus family is strongly involved in the pathogenesis of this disease, but it is unlikely that they are the only component responsible for its development. There are probably multiple triggers and more studies are necessary to investigate and define these interactions.

Cooperative interventions and the interaction of Community Health Agents within the Family Health team

This qualitative study examines the social relationships between the Community Health Agents (CHAs) and the Family Health team (FH), highlighting cooperative interventions and interactions among workers. A total of 23 participant observations and 11 semi-structured interviews were conducted with an FH team in a city in the interior of Sao Paulo, Brazil. The results revealed that CHAs function as a link in the development of operational actions to expedite teamwork. These professionals, while creating bonds, articulate connections of teamwork and interact with other workers, developing common care plans and bringing the team and community together, as well as adapting care interventions to meet the real needs of people. In communication practice, when talking about themselves they talk about the community itself because they are the community's representatives and spokespersons on the team. The conclusion is that the CHA may be a strategic worker if his/her actions include more political and social dimensions of work in healthcare.

Effect of amino-terminated substrates onto surface properties of cellulose esters and their interaction with lectins

Films of cellulose acetate butyrate (CAB) and carboxymethylcellulose acetate butyrate (CMCAB) were deposited from ethyl acetate solutions onto bare silicon wafers (Si/SiO2) or amino-terminated surfaces (APS) by means of equilibrium adsorption. All surfaces were characterized by means of ellipsometry, atomic force microscopy (AFM) and contact angle measurements. The presence of amino groups on the support surface favored the adsorption of CAB and CMCAB, inducing the orientation almost polar groups to the surface and the exposition of alkyl group to the air. Such molecular orientation caused increase of the dispersive component of surface energy (gamma(d)(s)) and decrease of the polar component of surface energy (gamma(p)(s)) of cellulose esters in comparison to those values determined for films deposited onto bare Si/SiO2 wafers. Adsorption behavior of jacalin or concanavalin A onto CAB and CMCAB films was also investigated. The adsorbed amounts of lectins were more pronounced on cellulose esters with high (gamma(p)(s)) and total surface energy (gamma(t)(s)) values. (C) 2011 Elsevier B.V. All rights reserved.

A Comparative Analysis between Ultrasonometry and Computer-Aided Tomography to Evaluate Bone Healing

An ultrasonometric and computed-tomographic study of bone healing was undertaken using a model of a transverse mid-shaft osteotomy of sheep tibiae fixed with a semi-flexible external fixator. Fourteen sheep were operated and divided into two groups of seven according to osteotomy type, either regular or by segmental resection. The animals were killed on the 90th postoperative day and the tibiae resected for the in vitro direct contact transverse and axial measurement of ultrasound propagation velocity (UV) followed by quantitative computer-aided tomography (callus density and volume) through the osteotomy site. The intact left tibiae were used for control, being examined in a symmetrical diaphyseal segment. Regular osteotomies healed with a smaller and more mature callus than resection osteotomies. Axial UV was consistently and significantly higher (p?=?0.01) than transverse UV and both transverse and axial UV were significantly higher for the regular than for the segmental resection osteotomy. Transverse UV did not differ significantly between the intact and operated tibiae (p?=?0.20 for regular osteotomy; p?=?0.02 for resection osteotomy), but axial UV was significantly higher for the intact tibiae. Tomographic callus density was significantly higher for the regular than for the resection osteotomy and higher than both for the intact tibiae, presenting a strong positive correlation with UV. Callus volume presented an opposite behavior, with a negative correlation with UV. We conclude that UV is at least as precise as quantitative tomography for providing information about the healing state of both regular and resection osteotomy. (C) 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:10761082, 2012

Evidence supporting a protective role for Th9 and Th22 cytokines in human and experimental periapical lesions

Introduction: The development of periapical granulomas is dependent on the host response and involves Th1, Th2, Th17, and Treg-related cytokines. The discovery of new Th9 and Th22 subsets, with important immunomodulatory roles mediated by interleukin (IL)-9 and IL-22, respectively, emphasizes the need for reevaluation of current cytokine paradigms in context of periapical lesions. We investigated the expression of IL-9 and IL-22 in active and stable human granulomas and throughout experimental lesion development in mice. Methods: Periapical granulomas (N = 83) and control specimens (N = 24) were evaluated regarding the expression of IL-9 and IL-22 via realtime polymerase chain reaction. Experimental periapical lesions were induced in mice (pulp exposure and bacterial inoculation) and the lesions evolution correlation with IL-9 and IL-22 expression kinetics was evaluated. Results: IL-9 and IL-22 mRNA expression was higher in periapical lesions than in control samples; higher levels of IL-9 and IL-22 were observed in inactive than in active lesions. In the experimental lesions model, increasing levels of IL-9 and IL-22 mRNA were detected in the lesions, and inverse correlations were found between IL-9 and IL-22 and the increase of lesion area in the different time point intervals. Conclusions: Our results suggest that Th9 and Th22 pathways may contribute to human and experimental periapical lesion stability

Jacalin interaction with human immunoglobulin A1 and bovine immunoglobulin G1: Affinity constant determined by piezoelectric biosensoring

The affinity of the d-galactose-binding lectin from Artocarpus heterophyllus lectin, known as jacalin, with immonuglobulins (Igs) was determined by biofunctionalization of a piezoelectric transducer. This piezoelectric biofunctionalized transducer was used as a mass-sensitive analytical tool, allowing the real-time binding analysis of jacalin-human immunoglobulin A1 (IgA(1)) and jacalin-bovine IgG(1) interactions from which the apparent affinity constant was calculated. The strategy was centered in immobilizing jacalin on the gold electrode's surface of the piezoelectric crystal resonator using appropriate procedures based on self-assembling of 11-mercaptoundecanoic acid and 2-mercaptoethanol thiol's mixture, a particular immobilization strategy by which it was possible to avoid cross-interaction between the proteins over electrode's surface. The apparent affinity constants obtained between jacalin-human IgA(1) and jacalin-bovine IgG(1) differed by 1 order of magnitude [(8.0 +/- 0.9) x 10(5) vs (8.3 +/- 0.1) x 10(6) L mol(-1)]. On the other hand, the difference found between human IgA(1) and human IgA(2) interaction with jacalin, eight times higher for IgA(1), was attributed to the presence of O-linked glycans in the IgA(1) hinge region, which is absent in IgA(2). Specific interaction of jacalin with O-glycans, proved to be present in the human IgA(1) and hypothetically present in bovine IgG(1) structures, is discussed as responsible for the obtained affinity values.

Cross-reactivity of antipneumococcal surface protein C (PspC) antibodies with different strains and evaluation of inhibition of human complement factor H and secretory IgA binding via PspC

Pneumococcal surface protein C (PspC) is an important candidate for a cost-effective vaccine with broad coverage against pneumococcal diseases. Previous studies have shown that Streptococcus pneumoniae is able to bind to both human factor H (FH), an inhibitor of complement alternative pathway, and human secretory IgA (sIgA) via PspC. PspC was classified into 11 groups based on variations of the gene. In this work, we used three PspC fragments from different groups (PspC3, PspC5, and PspC8) to immunize mice for the production of antibodies. Immunization with PspC3 induced antibodies that recognized the majority of the clinical isolates as analyzed by Western blotting of whole-cell extracts and flow cytometry of intact bacteria, while anti-PspC5 antibodies showed cross-reactivity with the paralogue pneumococcal surface protein A (PspA), and anti-PspC8 antibodies reacted only with the PspC8-expressing strain. Most of the isolates tested showed strong binding to FH and weaker interaction with sIgA. Preincubation with anti-PspC3 and anti-PspC5 IgG led to some inhibition of binding of FH, and preincubation with anti-PspC3 partially inhibited sIgA binding in Western blotting. The analysis of intact bacteria through flow cytometry showed only a small decrease in FH binding after incubation of strain D39 with anti-PspC3 IgG, and one clinical isolate showed inhibition of sIgA binding by anti-PspC3 IgG. We conclude that although anti-PspC3 antibodies were able to recognize PspC variants from the majority of the strains tested, partial inhibition of FH and sIgA binding through anti-PspC3 antibodies in vitro could be observed for only a restricted number of isolates.

Endurance exercise training increases APPL1 expression and improves insulin signaling in the hepatic tissue of diet-induced obese mice, independently of weight loss

Hepatic insulin resistance is the major contributor to fasting hyperglycemia in type 2 diabetes. The protein kinase Akt plays a central role in the suppression of gluconeogenesis involving forkhead box O1 (Foxo1) and peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1a), and in the control of glycogen synthesis involving the glycogen synthase kinase beta (GSK3 beta) in the liver. It has been demonstrated that endosomal adaptor protein APPL1 interacts with Akt and blocks the association of Akt with its endogenous inhibitor, tribbles-related protein 3 (TRB3), improving the action of insulin in the liver. Here, we demonstrated that chronic exercise increased the basal levels and insulin-induced Akt serine phosphorylation in the liver of diet-induced obese mice. Endurance training was able to increase APPL1 expression and the interaction between APPL1 and Akt. Conversely, training reduced both TRB3 expression and TRB3 and Akt association. The positive effects of exercise on insulin action are reinforced by our findings that showed that trained mice presented an increase in Foxo1 phosphorylation and Foxo1/PGC-1a association, which was accompanied by a reduction in gluconeogenic gene expressions (PEPCK and G6Pase). Finally, exercised animals demonstrated increased at basal and insulin-induced GSK3 beta phosphorylation levels and glycogen content at 24?h after the last session of exercise. Our findings demonstrate that exercise increases insulin action, at least in part, through the enhancement of APPL1 and the reduction of TRB3 expression in the liver of obese mice, independently of weight loss. J. Cell. Physiol. 227: 29172926, 2012. (C) 2011 Wiley Periodicals, Inc.

Novel aryl beta-aminocarbonyl derivatives as inhibitors of Trypanosoma cruzi trypanothione reductase: binding mode revised by docking and GRIND2-based 3D-QSAR procedures

Trypanothione reductase has long been investigated as a promising target for chemotherapeutic intervention in Chagas disease, since it is an enzyme of a unique metabolic pathway that is exclusively present in the pathogen but not in the human host, which has the analog Glutathione reductase. In spite of the present data-set includes a small number of compounds, a combined use of flexible docking, pharmacophore perception, ligand binding site prediction, and Grid-Independent Descriptors GRIND2-based 3D-Quantitative Structure-Activity Relationships (QSAR) procedures allowed us to rationalize the different biological activities of a series of 11 aryl beta-aminocarbonyl derivatives, which are inhibitors of Trypanosoma cruzi trypanothione reductase (TcTR). Three QSAR models were built and validated using different alignments, which are based on docking with the TcTR crystal structure, pharmacophore, and molecular interaction fields. The high statistical significance of the models thus obtained assures the robustness of this second generation of GRIND descriptors here used, which were able to detect the most important residues of such enzyme for binding the aryl beta-aminocarbonyl derivatives, besides to rationalize distances among them. Finally, a revised binding mode has been proposed for our inhibitors and independently supported by the different methodologies here used, allowing further optimization of the lead compounds with such combined structure- and ligand-based approaches in the fight against the Chagas disease.

Nd:YAG Laser Irradiation of Etched/Unetched Dentin Through an Uncured Two-step Etch-and-Rinse Adhesive and its Effect on Microtensile Bond Strength

Purpose: To evaluate whether Nd:YAG laser irradiation of etched and unetched dentin through an uncured adhesive affected the microtensile bond strength (pTBS). Materials and Methods: Flat dentin surfaces were created in 19 extracted human third molars. Adper Single Bond (SB) adhesive was applied over etched (groups 1 to 3) or unetched dentin (groups 4 to 6). The dentin was then irradiated with a Nd:YAG laser through the uncured adhesive, using 0.75 or 1 W power settings, except for the control groups (groups 1 and 4). The adhesive was light cured and composite crowns were built up. After 24 h, the teeth were sectioned into beams, with cross-sectional areas of 0.49 mm(2), and were stressed under tension. Data were statistically analyzed using two-way ANOVA and Tukey's test (alpha = 5%). Dentin surfaces of fractured specimens and the interfaces of untested beams were observed under scanning electron microscopy (SEM). Results: Acid etching, laser irradiation, and their interaction significantly affected bonding (p < 0.05). Laser irradiation did not improve bonding of etched dentin to resin (p > 0.05). However, higher pTBS means were found on unetched lased dentin (groups 5 and 6), but only in comparison to group 4, where neither lasing nor etching was performed. Groups 4 to 6 showed the lowest pTBS means among all groups tested (p < 0.05). Laser irradiation did not change the characteristics of the hybrid layers created, while solidification globules were observed on lased dentin surfaces under SEM. Conclusion: Laser irradiation of dentin through the uncured adhesive did not significantly improve the pTBS in comparison to the suggested manufacturer's technique.

The effect of implant design on insertion torque and immediate micromotion

Objectives: To evaluate the effect of insertion torque on micromotion to a lateral force in three different implant designs. Material and methods: Thirty-six implants with identical thread design, but different cutting groove design were divided in three groups: (1) non-fluted (no cutting groove, solid screw-form); (2) fluted (901 cut at the apex, tap design); and (3) Blossomt (Patent pending) (non-fluted with engineered trimmed thread design). The implants were screwed into polyurethane foam blocks and the insertion torque was recorded after each turn of 901 by a digital torque gauge. Controlled lateral loads of 10N followed by increments of 5 up to 100N were sequentially applied by a digital force gauge on a titanium abutment. Statistical comparison was performed with two-way mixed model ANOVA that evaluated implant design group, linear effects of turns and displacement loads, and their interaction. Results: While insertion torque increased as a function of number of turns for each design, the slope and final values increased (Po0.001) progressively from the Blossomt to the fluted to the non-fluted design (M +/- standard deviation [SD] = 64.1 +/- 26.8, 139.4 +/- 17.2, and 205.23 +/- 24.3 Ncm, respectively). While a linear relationship between horizontal displacement and lateral force was observed for each design, the slope and maximal displacement increased (Po0.001) progressively from the Blossomt to the fluted to the non-fluted design (M +/- SD 530 +/- 57.7, 585.9 +/- 82.4, and 782.33 +/- 269.4 mm, respectively). There was negligible to moderate levels of association between insertion torque and lateral displacement in the Blossomt, fluted and non-fluted design groups, respectively. Conclusion: Insertion torque was reduced in implant macrodesigns that incorporated cutting edges, and lesser insertion torque was generally associated with decreased micromovement. However, insertion torque and micromotion were unrelated within implant designs, particularly for those designs showing the least insertion torque.

Sperm head morphometry in ejaculates of adult marmosets (Callithrix jacchus): a model for studying sperm subpopulations and among-donor variations

In humans and other mammals, sperm morphology has been considered one of the most important predictive parameters of fertility. The objective was to determine the presence and distribution of sperm head morphometric subpopulations in a nonhuman primate model (Callithrix jacchus), using an objective computer analysis system and principal component analysis (PCA) methods to establish the relationship between the subpopulation distribution observed and among-donor variation. The PCA method revealed a stable number of principal components in all donors studied, that represented more than 85% of the cumulative variance in all cases. After cluster analysis, a variable number (from three to seven) sperm morphometric subpopulations were identified with defined sperm dimensions and shapes. There were differences in the distribution of the sperm morphometric subpopulations (P < 0.001) in all ejaculates among the four donors analyzed. In conclusion, in this study, computerized sperm analysis methods combined with PCA cluster analyses were useful to identify, classify, and characterize various head sperm morphometric subpopulations in nonhuman primates, yielding considerable biological information. In addition, because all individuals were kept in the same conditions, differences in the distribution of these subpopulations were not attributed to external or management factors. Finally, the substantial information derived from subpopulation analyses provided new and relevant biological knowledge which may have a practical use for future studies in human and nonhuman primate ejaculates, including identifying individuals more suitable for assisted reproductive technologies. (c) 2012 Elsevier Inc. All rights reserved.

Children with Type 1 Diabetes Mellitus and their friends: the influence of this interaction in the management of the disease

Friends' support is a key element in the management of Type 1 Diabetes Mellitus. This study describes the influence of friends on the lives of children with Diabetes Mellitus and its implications for managing the disease. Empirical data were collected through semi-structured interviews, supported with the use of puppets, with 19 children aged between seven and 12 years old. The qualitative analysis of the testimonies allowed understanding the phenomenon from two perspectives: the attitude of friends towards the child, positively or negatively affecting the disease's management, and the attitude of the child toward friends. The knowledge of those involved and the interaction between the children with DM1 and their friends impacts the management of the disease. Understanding the implications of these interactions contributes to the delivery of qualified nursing care to this population.

Uptake of oxLDL and IL-10 production by macrophages requires PAFR and CD36 recruitment into the same lipid rafts

Macrophage interaction with oxidized low-density lipoprotein (oxLDL) leads to its differentiation into foam cells and cytokine production, contributing to atherosclerosis development. In a previous study, we showed that CD36 and the receptor for platelet-activating factor (PAFR) are required for oxLDL to activate gene transcription for cytokines and CD36. Here, we investigated the localization and physical interaction of CD36 and PAFR in macrophages stimulated with oxLDL. We found that blocking CD36 or PAFR decreases oxLDL uptake and IL-10 production. OxLDL induces IL-10 mRNA expression only in HEK293T expressing both receptors (PAFR and CD36). OxLDL does not induce IL-12 production. The lipid rafts disruption by treatment with βCD reduces the oxLDL uptake and IL-10 production. OxLDL induces co-immunoprecipitation of PAFR and CD36 with the constitutive raft protein flotillin-1, and colocalization with the lipid raft-marker GM1-ganglioside. Finally, we found colocalization of PAFR and CD36 in macrophages from human atherosclerotic plaques. Our results show that oxLDL induces the recruitment of PAFR and CD36 into the same lipid rafts, which is important for oxLDL uptake and IL-10 production. This study provided new insights into how oxLDL interact with macrophages and contributing to atherosclerosis development.