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Articular ultrasound of 6500 joint recesses was performed for the purpose of identifying which joint had the highest measurements among small-sized (SSJ), medium-sized (MSJ) and large-sized (LSJ) joints. Quantitative measurements of synovial hypertrophy (QSR) and semiquantitative measurements of synovial hypertrophy (SSH), power Doppler (SPD) and bone erosion (SBE) (score: 0-3) were made. Higher measurements (p < 0.01) of QSR were obtained in the second metatarsophalangeal joint (MTP), talonavicular joint, and hip. The highest SSH scores (2/3) were obtained in the second MTP, talonavicular joint, hip and knee; the highest SPD scores (1/2/3) in the first MTP, second MTP, dorsal second metacarpophalangeal (MCP) and radiocarpal recesses; and the highest SBE scores (2/3) in the radiocarpal, ulnocarpal and posterior recesses of the glenohumeral joint. In conclusion, higher measurements of synovial hypertrophy were found in the first and second MTPs (SSJ), talonavicular recess (MSJ) and hip (LSJ). Synovial blood flow was frequent in the first MTP and radiocarpal recess. Bone erosion stood out only in the glenohumeral joint., (Copyright © 2017. Published by Elsevier Inc.)

The Paiva's blenny Lupinoblennius paivai is redescribed and its range redefined along the Brazilian coast. It differs from its congeners by the presence of three cephalic pores between the dorsal-fin base and lateral line, dorsal-fin elements XII, 12, anal-fin elements II, 16, pectoral-fin rays 14 and 10 + 20 vertebrae. It is here reported from Amazon estuaries (Marajó and Mosqueiro islands, Pará State), increasing its range by c. 3000 km. Lupinoblennius paivai is one of the few blenniid species able to tolerate low salinities. New data about its meristics and morphometrics are presented, as well as a new habitat type., (© 2017 The Fisheries Society of the British Isles.)

Zika virus (ZIKV) infection is a global health emergency that causes significant neurodegeneration. Neurodegenerative processes may be exacerbated by N -methyl-d-aspartate receptor (NMDAR)-dependent neuronal excitoxicity. Here, we have exploited the hypothesis that ZIKV-induced neurodegeneration can be rescued by blocking NMDA overstimulation with memantine. Our results show that ZIKV actively replicates in primary neurons and that virus replication is directly associated with massive neuronal cell death. Interestingly, treatment with memantine or other NMDAR blockers, including dizocilpine (MK-801), agmatine sulfate, or ifenprodil, prevents neuronal death without interfering with the ability of ZIKV to replicate in these cells. Moreover, in vivo experiments demonstrate that therapeutic memantine treatment prevents the increase of intraocular pressure (IOP) induced by infection and massively reduces neurodegeneration and microgliosis in the brain of infected mice. Our results indicate that the blockade of NMDARs by memantine provides potent neuroprotective effects against ZIKV-induced neuronal damage, suggesting it could be a viable treatment for patients at risk for ZIKV infection-induced neurodegeneration. IMPORTANCE Zika virus (ZIKV) infection is a global health emergency associated with serious neurological complications, including microcephaly and Guillain-Barré syndrome. Infection of experimental animals with ZIKV causes significant neuronal damage and microgliosis. Treatment with drugs that block NMDARs prevented neuronal damage both in vitro and in vivo These results suggest that overactivation of NMDARs contributes significantly to the neuronal damage induced by ZIKV infection, and this is amenable to inhibition by drug treatment., (Copyright © 2017 Costa et al.)

The objective of this study was to estimate the energy and protein requirements of crossbred (Holstein × Gyr) growing bulls. Twenty-four 10-mo-old bulls [initial body weight (BW) = 184 ± 23.4 kg] were used in a comparative slaughter trial. Six bulls were slaughtered at the beginning of the experiment as the reference group, to estimate initial empty body weight (EBW) and energy and protein contents of the remaining animals. The remaining bulls were assigned to a completely randomized design with 3 levels of dry matter intake and 6 replicates. The levels of dry matter intake were 1.2% of BW, 1.8% of BW, and ad libitum to target orts equal to 5% of the total amount that was fed. The remaining bulls were slaughtered at the end of the experiment. The bulls were fed a diet consisting of 59.6% corn silage and 40.4% concentrate on a dry matter basis. The equation that determined the relationship between EBW and BW was EBW = (0.861 ± 0.0031) × BW. The relationship between empty body gain (EBG) and average daily gain (ADG) was demonstrated by the following equation: EBG = (0.934 ± 0.0111) × ADG. Net energy for maintenance (NE M ) was 74.8 ± 2.89 kcal/kg of EBW 0.75 per day, and metabolizable energy for maintenance (ME M ) was 120.8 kcal/kg of EBW 0.75 per day. The detected efficiency of use of metabolizable energy for maintenance (k m ) was 61.9%. The equation used to estimate net energy for gain (NE G ) was as follows: NE G = (0.049 ± 0.0011) × EBW 0.75 × EBG 0.729 ± 0.0532 . The efficiency of use of metabolizable energy for gain (k g ) was 35.7%. The metabolizable protein for maintenance (MP M ) was 3.05 g/kg of BW 0.75 . The equation used to estimate net protein requirements for gain (NP G ) = (87.138 ± 65.1378 × EBG) + [(40.436 ± 21.3640) × NE G ]. The efficiency of use of metabolizable protein for gain (k) was 35.7%. We concluded that the estimates of energy and protein requirements presented herein are more appropriate than the National Research Council dairy cattle model and the Brazilian BR-CORTE system to balance the diets of crossbred (Holstein × Gyr) growing bulls., (Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Little is known regarding the role of suppressor of cytokine signaling (SOCS) in the control of cytokine signaling in cardiomyocytes. We investigated the consequences of SOCS2 ablation for leukemia inhibitory factor (LIF)-induced enhancement of intracellular Ca 2+ ([Ca 2+ ] i ) transient by performing experiments with cardiomyocytes from SOCS2-knockout (ko) mice. Similar levels of SOCS3 transcripts were seen in cardiomyocytes from wild-type and SOCS2-ko mice, while SOCS1 mRNA was reduced in SOCS2-ko. Immunoprecipitation experiments showed increased SOCS3 association with gp130 receptor in SOCS2-ko myocytes. Measurements of Ca 2+ in wild-type myocytes exposed to LIF showed a significant increase in the magnitude of the Ca 2+ transient. This change was absent in LIF-treated SOCS2-ko cells. LIF activation of ERK and STAT3 was observed in both wild-type and SOCS2-ko cells, indicating that in SOCS2-ko, LIF receptors were functional, despite the lack of effect in the Ca 2+ transient. In wild-type cells, LIF-induced increase in [Ca 2+ ] i and phospholamban Thr17 [PLN(Thr17)] phosphorylation was inhibited by KN-93, indicating a role for CaMKII in LIF-induced Ca 2+ raise. LIF-induced phosphorylation of PLN(Thr17) was abrogated in SOCS2-ko myocytes. In wild-type cardiomyocytes, LIF treatment increased L-type Ca 2+ current ( I Ca,L ), a key activator of CaMKII in response to LIF. Conversely, SOCS2-ko myocytes failed to activate I Ca,L in response to LIF, providing a rationale for the lack of LIF effect on Ca 2+ transient. Our data show that absence of SOCS2 turns cardiomyocytes unresponsive to LIF-induced [Ca 2+ ] raise, indicating that endogenous levels of SOCS2 are crucial for full activation of LIF signaling in the heart., (Copyright © 2017 the American Physiological Society.)

Objectives: To evaluate local joint variables after intra-articular injection with triamcinolone hexacetonide in rheumatoid arthritis patients., Methods: We blindly and prospectively (baseline, 1, 4, 12 and 24 weeks) evaluated metacarpophalangeal, wrist, elbow, shoulder, knee and ankle joints after triamcinolone hexacetonide intra-articular injection by the following outcome measures: visual analogue scale 0-10cm (VAS) for rest pain (VASR); VAS for movement pain (VASM); VAS for joint swelling (VASSw); flexion (FlexG) and extension (ExtG)., Results: 289 patients (635 joints) were studied. VASSw (p<0.001) and VASR (0.001

Current treatments for chronic Chagas cardiomyopathy, a disease with high mortality rates and caused by the protozoan Trypanosoma cruzi , are unsatisfactory. Myocardial inflammation, including endothelial activation, is responsible for the structural and functional damage seen in the chronic phase. The clinical efficacy of benznidazole could be improved by decreasing chronic inflammation. Statins, which have anti-inflammatory properties, may improve the action of benznidazole. Here, the action of simvastatin in a murine model of chronic Chagas cardiomyopathy and the link with the production of the proresolving eicosanoid 15-epi-lipoxin A4, produced by 5-lipoxygenase, are evaluated. Simvastatin decreased the expression of the adhesion molecules E-selectin, intracellular adhesion molecule type 1 (ICAM-1), and vascular cell adhesion molecule type 1 (VCAM-1) in T. cruzi -infected mice. However, when this drug was administered to 5-lipoxygenase-deficient mice, the anti-inflammatory effect was not observed unless exogenous 15-epi-lipoxin A4 was administered. Thus, in chronic Chagas disease, 5-epi-lipoxin A4 induced by simvastatin treatment could improve the pathophysiological condition of patients by increasing the trypanocidal action of benznidazole., (Copyright © 2017 American Society for Microbiology.)

Objectives: To assess the correlation between inflammatory sonographic findings (grayscale synovial hypertrophy and power Doppler) and clinical and functional assessments in hand osteoarthritis (symptomatic interphalangeal joints) and to correlate the intraobserver and interobserver reliability of these findings., Methods: A prospective double-blind study of 60 interphalangeal joints was conducted. The joints were assessed 6 times per year by clinician and sonographer observers., Results: A total of 720 measurement recesses were included (360 palmar and 360 dorsal). Small correlations and a few associations were found. Proximal interphalangeal joint quantitative measurements of the dorsal recess showed a statistical correlation with joint swelling (P = .043) and pulp-to-pulp pinch strength (P = .043); in the palmar recess, statistical correlations were seen for joint swelling (P = .007), the Australian/Canadian (AUSCAN) Function Index (P = .044), and grip and finger strength (P = .037, .003, .019, and .017). In dorsal semiquantitative assessments, there were associations between sonographic findings and joint swelling (P = .010) and pinch strength (P = .027, .003, and .014); in the palmar recess, we found associations with the AUSCAN Index (P = .048) and grip and finger strength (P = .031, .006, and 0.041). No correlations or associations were found in distal interphalangeal joints. Power Doppler signals were found in only 1.7% of the sample, precluding statistical analysis. Excluding palmar semiquantitative assessments in distal interphalangeal joints (P = .623), sonographic findings were reliable (intraclass correlation coefficients, 0.474-0.857; κ = 0.390-0.673)., Conclusions: Joint swelling, grip and pinch strength, and the AUSCAN Index were weakly correlated and associated with sonographic findings in proximal interphalangeal joints. Intraobserver and interobserver sonographic assessments were reliable., (© 2016 by the American Institute of Ultrasound in Medicine.)

Chagas disease is caused by the trypanosomatid Trypanosoma cruzi, which chronically causes heart problems in up to 30% of infected patients. Chagas disease was initially restricted to Latin America. However, due to migratory events, this disease may become a serious worldwide health problem. During Chagas disease, many patients die of cardiac arrhythmia despite the apparent benefits of anti-arrhythmic therapy (e.g., amiodarone). Here, we assimilate the cardiac form of Chagas disease to an inflammatory cardiac disease. Evidence from the literature, mostly provided using experimental models, supports this view and argues in favor of new strategies for treating cardiac arrhythmias in Chagas disease by modulating cytokine production and/or action. But the complex nature of myocardial inflammation underlies the need to better understand the molecular mechanisms of the inflammatory response during Chagas disease. Here, particular attention has been paid to tumor necrosis factor alpha (TNF) and transforming growth factor beta (TGF-β) although other cytokines may be involved in the chagasic cardiomyopathy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The objective was to quantify the energy and protein nutritional requirements of Holstein × Gyr crossbred preweaned dairy calves until 64 d of age. Thirty-nine Holstein × Gyr crossbred male calves with an average initial live weight (mean ± SEM; for all next values) of 36 ± 1.0 kg were used. Five calves were slaughtered at 4 d of life to estimate the animals' initial body composition (reference group). The remaining 34 calves were distributed in a completely randomized design in a 3 × 2 factorial arrangement consisting of 3 levels of milk (2, 4, or 8 L/d) and 2 levels of starter feed (presence or absence in diet). At 15 and 45 d of life, 4 animals from each treatment were subjected to digestibility trials with total collection of feces (for 72 h) and urine (for 24 h). At 64 d of age, all animals were slaughtered, their gastro-intestinal tract was washed to determine the empty body weight (EBW; kg), and their body tissues were sampled for subsequent analyses. The net energy requirement for maintenance was estimated using an exponential regression between metabolizable energy intake and heat production (both in Mcal/EBW 0.75 per d) and was 74.3 ± 5.7 kcal/EBW 0.75 per d, and was not affected by inclusion of starter feed in the diet. The metabolizable energy requirement for maintenance was determined at the point of zero energy retention in the body and was 105.2 ± 5.8 kcal/EBW 0.75 per d. The net energy for gain was estimated using the EBW and the empty body gain (EBG; kg/d) as 0.0882 ± 0.0028 × EBW 0.75 × EBG 0.9050±0.0706 . The metabolizable energy efficiency for gain (k g ) of the milk was 57.4 ± 3.45%, and the k g of the starter feed was 39.3 ± 2.09%. The metabolizable protein requirement for maintenance was 3.52 ± 0.34 g/BW 0.75 per d. The net protein required for each kilogram gained was estimated as 119.1 ± 32.9 × EBW 0.0663±0.059 . The metabolizable protein efficiency for gain was 77 ± 8.5% and was not affected by inclusion of starter feed in the diet. In conclusion, the energy efficiency for gain of milk is higher than that of starter and the net protein required per unit protein gain increases with empty body weight., (Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background: Stroke is the second leading cause of death and a major cause of disability of adults worldwide. Inflammatory processes are known to contribute to the pathophysiology of cerebral ischemia, especially following reperfusion. Chemokines and their receptors are involved in migration of leukocytes and have been implicated in the pathogenesis of ischemic stroke., Objective: In the present study, we investigated the effects of C-C chemokine receptor type 5 (CCR5) deficiency on neurological outcome, brain damage and expression of pro-inflammatory chemokines: chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (CC motif) ligand 3 (CCL3) and chemokine (C-C motif) ligand 5 (CCL5), and the brain-derived neurotrophic factor (BDNF)., Methods: Adult male C57BL/6 (wild-type) (WT) and CCR5 deficient mice were subjected to transient cerebral ischemia induced by 25 min of bilateral common carotid artery occlusion (BCCAO) followed by 24 hours of reperfusion. Mice were divided into four groups: WT sham group, which underwent sham operation; WT ischemic group, which was subjected to transient bilateral common carotid artery occlusion, CCR5-/- sham group, which underwent sham operation, and CCR5-/- ischemic group, which was subjected to transient BCCAO., Results: In CCR5 deficiency, we observed a significant improvement in the neurological deficits associated with decreased brain infarcted area as evaluated by triphenyltetrazolium chloride (TTC). Moreover, CCR5 deficiency revealed decreased percentage of necrotic cavities areas and frequency of ischemic neurons by histometric analysis. In addition, CCR5-/- ischemic animals showed lower brain levels of the chemokine CXCL1 and higher levels of BDNF by ELISA, compared with WT BCCAo mice., Conclusion: Taken together, our results suggest a potential neuroprotection in the absence of CCR5 receptor during global brain ischemia and reperfusion injury., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

The objective of this study was to assess the oxygen pulse and heart rate (O 2 P-HR) technique using the respiration chamber (RC) and comparative slaughter (CS) methods for measuring the heat production (HP) of crossbred (Holstein × Gyr) yearling bulls. Twenty-four bulls were used. Six bulls were slaughtered at the beginning of the experiment as a reference group to estimate the initial empty body weight (BW) and energy content of the remaining animals. The remaining bulls were assigned to a completely randomized design with 3 levels of dry matter intake, with 6 replicates. The levels of dry matter intake were 1.2% of BW, 1.8% of BW and ad libitum, with target orts of 5%. The bulls were fed a diet consisting of 59.6% corn silage and 40.4% concentrate on a dry matter basis. The HP (kcal/BW 0.75 ) was measured using 3 techniques, first using O 2 P-HR, followed by the RC and CS methods. The HP did not differ among assessed techniques, averaging 162.7kcal/BW 0.75 . The intercepts of the linear regressions (mean ± SE) were 64.82±25.515 (H 0 : intercept=0; P=0.024), 33.77±13.418 (H 0 : intercept=0), and 50.02±27.495 (H 0 : intercept=0) for O 2 P-HR versus RC, CS versus RC, and O 2 P-HR versus CS, respectively. The slopes of the linear regressions were 0.59±0.153 (H 0 : slope=1), 0.88±0.081 (H 0 : slope=1), and 0.62±0.155 (H 0 : slope=1) for O 2 P-HR versus RC, CS versus RC, and O 2 P-HR versus CS, respectively. The coefficients of determination were 0.52, 0.90, and 0.52 for O 2 P-HR versus RC, CS versus RC, and O 2 P-HR versus CS, respectively. The concordance correlation coefficients, 0.70 and 0.68, were moderate for O 2 P-HR versus RC and O 2 P-HR versus CS, respectively, but high, 0.90, for CS versus RC. The between-animal coefficient of variation was greater for the O 2 P-HR method (16.6%) compared with RC (7.7%) or CS (6.7%). We conclude that there was an agreement among the HP measurements detected using the assessed methods and that O 2 P-HR is able to predict HP in cattle with great accuracy but only moderate precision. Therefore, the O 2 P-HR method may have limitations in terms of assessing HP in low numbers of replications due to greater between-animal coefficient of variation than either the RC or CS methods., (Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate the effects on feed intake, calf performance, feed efficiency, fecal score, passage rate, apparent nutrient digestibility, development of rumen and other organs, and body composition of increasing the total solids content of liquid feed (whole milk) by adding increasing amounts of milk replacer powder during the preweaning period. Crossbred Holstein-Gyr calves (n=32) were assigned to 1 of 4 treatments (n=8 per group), which consisted of different total solids concentrations: 12.5, 15.0, 17.5, and 20.0% of liquid feed. Calves received 6 L of liquid per day, divided into 2 equal meals (0800 and 1600 h) and provided in buckets, from 5 to 55d of age. Starter and water were provided ad libitum during the entire experiment. At 56d of age, animals were killed. Laboratory analysis determined that the actual total solids contents of the liquid feed were 13.5, 16.1, 18.2, and 20.4%, for the proposed 12.5, 15.0, 17.5, and 20.0% total solids treatments, respectively. The osmolality of liquid feed treatments was 265 to 533 mOsm/L. Fecal score was similar among treatments, except for wk 2 and 7. Intake of liquid feed was similar among treatments from 6wk of age. During wk 4, 5, and 6, we detected a linear decrease in starter intake. After wk 7, we observed greater starter intake for calves fed approximately 16.1% total solids. Water intake, feed efficiency, and withers height were similar among treatments. Increasing concentrations of total solids in liquid feed quadratically affected average daily gain, final body weight, and empty body weight. We observed a greater average daily gain for calves fed approximately 20.4% total solids. Passage rate, nutrient digestibility, development of pre-stomachs and intestine, and body composition were similar among treatments. Increasing the concentration of total solids in liquid feed up to 20.4% reduced starter intake between 4 and 6wk of life, but increased average daily gain. It did not affect passage rate, nutrient digestibility, ruminal and organ development, or body composition in calves during the preweaning period, indicating that this strategy may be a viable alternative for feeding without increasing the total volume of liquid feed provided to dairy calves., (Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

In the present study, we investigated whether the daily fluctuations of internal body temperature (T b ) and spontaneous locomotor activity (SLA) interact with the thermal and neuronal adjustments induced by high-intensity aerobic exercise until fatigue. The body temperature and SLA of adult Wistar rats ( n = 23) were continuously recorded by telemetry for 48 h. Then, the rats were subjected to a protocol of graded exercise until fatigue or rest on the treadmill during light and dark-phases. T b , tail skin temperature and ambient temperature during each experimental session were recorded. At the end of the last experimental session, the animals were anaesthetized; the brains were perfused and removed for immunohistochemical analysis of c-fos neuronal activation. The daily rhythms of SLA and T b were strongly correlated ( r = 0.88 and p < 0.001), and this was followed by a daily oscillation in both the ratio and the correlation index between these variables ( p < 0.001). Exercise capacity was associated with a lower resting T b ( p < 0.01) and was higher in the light-phase ( p < 0.001), resulting in an increased capacity to accumulate heat during exercise ( p < 0.01). Independent of time-of-day, high intensity exercise strongly activated the hypothalamic paraventricular nucleus (PVN), the supra-optic nucleus (SON) and the locus coeruleus (LC) ( p < 0.001) but not the suprachiasmatic nucleus (SCN). Taken together, our results points toward a role of the circadian system in a basal activity control of the thermoregulatory system as an important component for the onset of physical activities. In fact, rather than directly limiting the adjustments induced by exercise the present study brings new evidence that the effect of time-of-day on exercise performance occurs at the threshold level for each thermoregulatory system effector activity. This assumption is based on the observed resilience of the central clock to high-intensity exercise and the similarities in exercise-induced neuronal activation in the PVN, SON, and LC.

The aim of this study was to evaluate the effects on feed intake, heifer performance, and health of increasing the total solids (TS) content of liquid feed (whole milk) by adding increasing amounts of milk replacer powder during the pre- and postweaning periods. Crossbred Holstein-Gyr heifers (n=60) were assigned to 1 of 4 treatments (n=15 per group), which consisted of different TS concentrations: 12.5, 15.0, 17.5, and 20.0% of liquid feed. Heifers received 6 L of liquid feed per day, divided into 2 equal meals (0800 and 1600h) and provided in buckets, from 5 to 55d of age. From 56 to 59d of age, the total amount of liquid feed was reduced by half, maintaining only morning feedings. Heifers were weaned at 60d and monitored until 90d of age. Water and starter were provided ad libitum during the entire experiment. Corn silage was included in the diet during the postweaning period (70d of age). Feed intake and health scores were evaluated daily. Body weight and body frame development were recorded weekly. Starting at 14d, ruminal pH was measured every other week. Laboratory analysis determined that the actual TS contents of the liquid feed were 13.5, 16.1, 18.2, and 20.4%, for the proposed 12.5, 15.0, 17.5, and 20.0% TS treatments, respectively. The osmolality of liquid feed treatments was 265 to 533mOsm/L. Intake of liquid feed was similar among treatments from 4wk of age. During the preweaning period, starter intake, fecal score, and days with diarrhea were similar among treatments. Ruminal pH at weaning averaged 6.2 and was similar among treatments. Increasing concentrations of TS in the liquid feed were associated with linear increases in average daily gain, final body weight, and growth performance, but linear decreases in feed efficiency. During the postweaning period, intake of starter, corn silage, and water were similar among treatments, as well as average daily gain and feed efficiency. Final body weight and growth performance during the postweaning period also increased linearly with concentration of TS in liquid feed. Increasing the concentration of TS in liquid feed up to 20.4% increased performance and body frame development in dairy heifers during the pre- and postweaning periods and had no effects on solid feed intake or health., (Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The most severe manifestation of Herpes Simplex Type 1 virus (HSV-1) infection is encephalitis characterized by arousal impairment and seizures that can evolve to coma and death. Previous studies reported the involvement of suppressor of cytokine signaling (SOCS) proteins, specifically SOCS1 and SOCS3, in HSV-1 infection, suggesting that other members of this family could be involved in the immune response against HSV-1. No previous study has reported the role of SOCS2 in HSV-1 infection. In the current study, C57BL/6 wild-type mice (WT) and mice deficient in SOCS2 gene (SOCS2 -/- ) were subjected to intracranial inoculation with 10 2 plaque forming units (PFU) of HSV-1. Survival curve, neuroinflammatory parameters and neuropathology were evaluated. Infected SOCS2 -/- mice had increased survival in comparison with infected WT animals. This better outcome was associated with reduced leukocyte infiltration, concentration of cytokines, and structural changes in the brain. SOCS2 seems to play a detrimental role in HSV-1 encephalitis. Moreover, the control of neuroinflammatory response in HSV-1 infection was of paramount importance to clinical outcome., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in controlling several aspects of immune responses, including the activation and differentiation of specific T cell subsets and antigen-presenting cells, thought to be relevant in the context of experimental Trypanosoma cruzi infection. The relevance of AhR for the outcome of T. cruzi infection is not known and was investigated here. We infected wild-type (WT) mice and AhR knockout (AhR KO) mice with T. cruzi (Y strain) and determined levels of parasitemia, myocardial inflammation and fibrosis, expression of AhR/cytokines/suppressor of cytokine signaling (SOCS) (spleen/heart), and production of nitric oxide (NO), reactive oxygen species (ROS), and peroxynitrite (ONOO(-)) (spleen). AhR expression was increased in the heart of infected WT mice. Infected AhR KO mice displayed significantly reduced parasitemia, inflammation, and fibrosis of the myocardium. This was associated with an anticipated increased immune response characterized by increased levels of inflammatory cytokines and reduced expression of SOCS2 and SOCS3 in the heart. In vitro, AhR deficiency caused impairment in parasite replication and decreased levels of ROS production. In conclusion, AhR influences the development of murine Chagas disease by modulating ROS production and regulating the expression of key physiological regulators of inflammation, SOCS1 to -3, associated with the production of cytokines during experimental T. cruzi infection., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

The role of suppressors of cytokine signaling (SOCS) in meningoencephalitis caused by Bovine herpesvirus 5 (BoHV-5) was evaluated by intracranial infection in C57BL/6 wild-type mice (WT) and SOCS2 deficient mice (SOCS2(-/-)). Both infected groups presented weight loss, ruffled fur and hunched posture. Additionally, infected SOCS2(-/-) mice showed swollen chamfer and progressive depression. Infected WT animals developed mild meningitis, characterized by infiltration of mononuclear cells. Moreover, viral DNA was detected in liver and lung from infected WT group. This group also showed elevated brain levels of IFN-γ, IL-10, CXCL1 and CCL5, when compared with non-infected WT animals. Brain inflammation was exacerbated in infected SOCS2(-/-) mice with widespread distribution of the virus and increased brain levels of TNF-α, IFN-γ, IL-10, IL-12, CXCL1 and CCL5, when compared with WT infected mice. Moreover, infected SOCS2 deficient mice exhibited reduced brain mRNA expression of IFNα and IFNβ and increased expression of mRNA of SOCS1, compared with infected WT mice. Taken together, our study provides an insight into the role of SOCS2 in modulating the immune response to BoHV-5 infection., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Malaria is considered a neglected disease and public health problem, affecting >200 million people worldwide. In the present study we used the Plasmodium berghei ANKA (PbA) model of experimental cerebral malaria (CM) in C57BL/6 mice. After rescue from CM and parasite clearance, animals were submitted to a seizure susceptibility test (45 days after infection) using a low dose of pentylenetetrazol (PTZ, 30 mg/kg) and monitored with use of behavioral and electroencephalography (EEG) methods. Mice rescued from CM presented a reduced latency to myoclonic and tonic-clonic seizures and an increased duration of tonic-clonic seizures. In addition, quantitative analysis of EEG revealed a decrease in relative power at beta frequency band in PbA-infected animals after PTZ injection. Our results suggest that CM may lead to increased susceptibility to seizures in mice., (Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.)

A respiration system consisting of 4 climate-controlled chambers and 1 set of flowmeters and analyzers was constructed and validated. Each chamber had volume of 21.10m(3) (3.68×2.56×2.24m) and was made from steel with double-glazed windows on either side enabling visual contact between animals. The chambers are independently climate-controlled and can maintain temperature and relative humidity in a range from 5 to 45°C and 30 to 80%, respectively. A flow generator and mass flowmeter continuously pull air from each chamber and a slight negative pressure inside the chamber is ensured. Air from all chambers and ambient air share a common gas analysis and data acquisition system for monitoring O2, CO2, and CH4 concentrations over the measurement period, with the cycle time set to 20min. Analyzers are regularly calibrated and the chambers have mean recoveries of 99.0 and 98.0% for CO2 and CH4, respectively. The chambers are equipped with infrared cameras and electronic feed and water bins for intake measurements, as well as sensors for monitoring animal position and heart rate. Data acquisition and analysis software is used to calculate the rate of consumption of O2 and production of CO2 and CH4. The dynamic respiration measurements are integrated with feed intake data and other sensors. The daily gas exchanges are estimated by integration to determine methane emission and heat production. We conducted a trial with 12 lactating 3/4 Holstein × 1/4 Gyr crossbred dairy cows (6 multiparous and 6 primiparous) under 2 feeding regimens (ad libitum or restricted) to validate the system. Two 22-h respiration measurements were obtained from each cow. Restricted-fed cows showed lower values for milk yield, methane emission, and heat production compared with ad libitum-fed animals. We found no difference between groups for CH4 produced per kilogram of dry matter intake. Repeatability for CH4 emission and heat production was high (0.97 and 0.92, respectively). The respiration system described herein is a useful tool for measuring the dynamic and accumulated data of heat production, methane emission, and feed intake., (Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Chagas disease, caused by the triatominae Trypanosoma cruzi, is one of the leading causes of heart malfunctioning in Latin America. The cardiac phenotype is observed in 20-30% of infected people 10-40 years after their primary infection. The cardiac complications during Chagas disease range from cardiac arrhythmias to heart failure, with important involvement of the right ventricle. Interestingly, no studies have evaluated the electrical properties of right ventricle myocytes during Chagas disease and correlated them to parasite persistence. Taking advantage of a murine model of Chagas disease, we studied the histological and electrical properties of right ventricle in acute (30 days postinfection [dpi]) and chronic phases (90 dpi) of infected mice with the Colombian strain of T. cruzi and their correlation to parasite persistence. We observed an increase in collagen deposition and inflammatory infiltrate at both 30 and 90 dpi. Furthermore, using reverse transcriptase polymerase chain reaction, we detected parasites at 90 dpi in right and left ventricles. In addition, we observed action potential prolongation and reduced transient outward K(+) current and L-type Ca(2+) current at 30 and 90 dpi. Taking together, our results demonstrate that T. cruzi infection leads to important modifications in electrical properties associated with inflammatory infiltrate and parasite persistence in mice right ventricle, suggesting a causal role between inflammation, parasite persistence, and altered cardiomyocyte function in Chagas disease. Thus, arrhythmias observed in Chagas disease may be partially related to altered electrical function in right ventricle., (© The American Society of Tropical Medicine and Hygiene.)

Plasmodium falciparum infection results in severe malaria in humans, affecting various organs, including the liver, spleen and brain, and resulting in high morbidity and mortality. The Plasmodium berghei ANKA (PbA) infection in mice closely recapitulates many aspects of human cerebral malaria (CM); thus, this model has been used to investigate the pathogenesis of CM. Suppressor of cytokine signaling 2 (SOCS2), an intracellular protein induced by cytokines and hormones, modulates the immune response, neural development, neurogenesis and neurotrophic pathways. However, the role of SOCS2 during CM remains unknown. SOCS2 knockout (SOCS2(-/-)) mice infected with PbA show an initial resistance to infection with reduced parasitemia and production of TNF, TGF-β, IL-12 and IL-17 in the brain. Interestingly, in the late phase of infection, SOCS2(-/-) mice display increased parasitemia and reduced Treg cell infiltration, associated with enhanced levels of Th1 and Th17 cells and related cytokines IL-17, IL-6, and TGF-β in the brain. A significant reduction in protective neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF), was also observed. Moreover, the molecular alterations in the brain of infected SOCS2(-/-) mice were associated with anxiety-related behaviors and cognition impairment. Mechanistically, these results revealed enhanced nitric oxide (NO) production in PbA-infected SOCS2(-/-) mice, and the inhibition of NO synthesis through l-NAME led to a marked decrease in survival, the disruption of parasitemia control and more pronounced anxiety-like behavior. Treatment with l-NAME also shifted the levels of Th1, Th7 and Treg cells in the brains of infected SOCS2(-/-) mice to the background levels observed in infected WT, with remarkable exception of increased CD8(+)IFN(+) T cells and inflammatory monocytes. These results indicate that SOCS2 plays a dual role during PbA infection, being detrimental in the control of the parasite replication but crucial in the regulation of the immune response and production of neurotrophic factors. Here, we provided strong evidence of a critical relationship between SOCS2 and NO in the orchestration of the immune response and development of CM during PbA infection., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: This study aimed to present seven cases of avascular necrosis of the sesamoid and report the role of bone scintigraphy in the diagnosis of these patients., Methods: Seven patients with clinical suspicion of avascular necrosis of the sesamoid underwent three-phase bone scintigraphy with 30 mCi of (99m)Tc-MDP., Results: Most of the patients were young female adults with complaints of limiting pain in the forefoot, who were making use of inappropriate footwear and/or had a history of injury with or without fracture. There was no predominance of either of the feet or between the femoral or tibial sesamoid. Two patients (28.57%) had a bipartite tibial sesamoid and one (14.29%) had splitting of the tibial and fibular sesamoids. In 100% of the patients, three-phase bone scintigraphy, combined with other propaedeutic methods, proved to be crucial for the diagnosis. The initial procedure in all cases was conservative. In four cases (57.14%), there was no remission of symptoms, and surgical excision of the necrotized sesamoid tissue was performed. In all the patients, the therapy used was effective, with complete remission of symptoms, without complications or deformities of the forefoot., Conclusions: Three-phase bone scintigraphy becomes a cornerstone of the propaedeutics when avascular necrosis of the sesamoid is suspected, through contributing towards early and accurate diagnosis and enabling allowing appropriate specialized treatment.

Over 100 years have elapsed since the discovery of Chagas disease and there is still much to learn regarding pathogenesis and treatment. Although there are antiparasitic drugs available, such as benznidazole and nifurtimox, they are not totally reliable and often toxic. A recently released negative clinical trial with benznidazole in patients with chronic Chagas cardiomyopathy further reinforces the concerns regarding its effectiveness. New drugs and new delivery systems, including those based on nanotechnology, are being sought. Although vaccine development is still in its infancy, the reality of a therapeutic vaccine remains a challenge. New ECG methods may help to recognize patients prone to developing malignant ventricular arrhythmias. The management of heart failure, stroke and arrhythmias also remains a challenge. Although animal experiments have suggested that stem cell based therapy may be therapeutic in the management of heart failure in Chagas cardiomyopathy, clinical trials have not been promising.

Objective: To evaluate the effectiveness and tolerance of intraarticular injection (IAI) of triamcinolone hexacetonide (TH) for the treatment of osteoarthritis (OA) of hand interphalangeal (IP) joints., Methods: Sixty patients who underwent IAI at the most symptomatic IP joint were randomly assigned to receive TH/lidocaine (LD; n = 30) with TH 20 mg/ml and LD 2%, or just LD (n = 30). The injected joint was immobilized with a splint for 48 h in both groups. Patients were assessed at baseline and at 1, 4, 8, and 12 weeks by a blinded observer. The following variables were assessed: pain at rest [visual analog scale (VAS)r], pain at movement (VASm), swelling (physician VASs), goniometry, grip and pinch strength, hand function, treatment improvement, daily requirement of paracetamol, and local adverse effects. The proposed treatment (IAI with TH/LD) was successful if statistical improvement (p < 0.05) was achieved in at least 2 of 3 VAS. Repeated-measures ANOVA test was used to analyze intervention response., Results: Fifty-eight patients (96.67%) were women, and the mean age was 60.7 years (± 8.2). The TH/LD group showed greater improvement than the LD group for VASm (p = 0.014) and physician VASs (p = 0.022) from the first week until the end of the study. In other variables, there was no statistical difference between groups. No significant adverse effects were observed., Conclusion: The IAI with TH/LD has been shown to be more effective than the IAI with LD for pain on movement and joint swelling in patients with OA of the IP joints. Regarding pain at rest, there was no difference between groups., Trial Registration Number: ClinicalTrials.gov (NCT02102620).

Background: Cerebral malaria (CM) is debilitating and sometimes fatal. Disease severity has been associated with poor treatment access, therapeutic complexity and drug resistance and, thus, alternative therapies are increasingly necessary. In this study, the effect of the administration of Agaricus blazei, a mushroom of Brazilian origin in a model of CM caused by Plasmodium berghei, strain ANKA, was investigated in mice., Methods: C57BL/6 mice were pre-treated with aqueous extract or fractions of A. blazei, or chloroquine, infected with P. berghei ANKA and then followed by daily administration of A. blazei or chloroquine. Parasitaemia, body weight, survival and clinical signs of the disease were evaluated periodically. The concentration of pro-and anti-inflammatory cytokines, histopathology and in vitro analyses were performed., Results: Mice treated with A. blazei aqueous extract or fraction C, that shows antioxidant activity, displayed lower parasitaemia, increased survival, reduced weight loss and protection against the development of CM. The administration of A. blazei resulted in reduced levels of TNF, IL-1β and IL-6 production when compared to untreated P. berghei-infected mice. Agaricus blazei (aqueous extract or fraction C) treated infected mice displayed reduction of brain lesions. Although chloroquine treatment reduced parasitaemia, there was increased production of proinflammatory cytokines and damage in the CNS not observed with A. blazei treatment. Moreover, the in vitro pretreatment of infected erythrocytes followed by in vivo infection resulted in lower parasitaemia, increased survival, and little evidence of clinical signs of disease., Conclusions: This study strongly suggests that the administration of A. blazei (aqueous extract or fraction C) was effective in improving the consequences of CM in mice and may provide novel therapeutic strategies.

Purpose of Review: American trypanosomiasis, or Chagas disease, is a lifelong and persistent infection caused by the protozoan Trypanosoma cruzi and is the most significant cause of morbidity and mortality in South and Central America. Owing to immigration and additional risks from blood transfusion and organ transplantation, the number of reported cases of Chagas disease has increased recently in Europe and the USA. The disease is caused by a moderate to intense lasting inflammatory response that triggers local expression of inflammatory mediators and activates and recruits leukocytes to various tissues to eliminate the parasites., Recent Findings: This long-term inflammatory process triggers biochemical, physiological and morphological alterations and clinical changes in the digestive, nervous and cardiac (e.g. myocarditis, arrhythmias, congestive heart failure, autonomic dysfunctions and microcirculatory disturbances) systems. Indeed, the pathogenesis of Chagas disease is intricate and multifactorial, and the roles of the parasite and the immune response in initiating and maintaining the disease are still controversial., Summary: In this review, we discuss the current knowledge of 'strategies' employed by the parasite to persist in the host and host defence mechanisms against Trypanosoma cruzi infection, which can result in equilibrium (absence of the disease) or disease development, mainly in the cardiac systems.

The objective of this study was to validate an electronic system for monitoring individual feeding behavior and feed intake (Intergado Ltd., Contagem, Minas Gerais, Brazil) in freestall-housed dairy cattle. No data have been published that validate either the behavioral measurement or the feed intake of this system. Feeding behavior data were recorded for 12 Holstein cows over 5d using an Intergado system and time-lapse video. The cows were fitted with an ear tag containing a unique passive transponder and provided free access to 12 feed bins. The system documented the visit duration and feed intake by recording the animal identification number, bin number, initial and final times, and the difference between feed weight at start and end of each feed bin visit. These data were exported to Intergado web software and reports were generated. Electronic data on animal behavior were compared with video data collected during the same evaluation period. An external scale was used to manually measure and validate the electronic system's ability to monitor dairy cow feed intake for each feed bin visit. The feed intake was manually measured for 4-h time periods and compared with the sum of the feed intake recorded by the monitoring system for each cow visit during the same time period. Video and manual weight data were regressed on the electronic feeding behavior and feeding intake data to evaluate the precision of the monitoring system. The Intergado system presented high values for specificity (99.9%) and sensitivity (99.6%) for cow detection. The visit duration and feed intake per visit collected using the electronic monitoring system were similar to the video and manual weighing data, respectively. The difference between the feed intake measured manually and the sum of the electronically recorded feed intake was less than 250g (25,635±2,428 and 25,391±2,428g estimated using manual weighing and the electronic system, respectively). In conclusion, the Intergado system is a reasonable tool to monitor feeding behavior and feed intake for freestall-housed dairy cows., (Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Objectives: Identify good response predictors to intra-articular injection (IAI) with triamcinolone hexacetonide (TH)., Methods: This study was carried out in rheumatoid arthritis (RA) patients (American College of Rheumatology criteria) submitted to IAI (mono, pauci or polyarticular injection)., Assessment: A "blinded" observer prospectively evaluated joints at one week (T1), four weeks (T4), twelve weeks (T12) and 24 weeks (T24) after IAI. Outcome measurements included Visual Analogue Scale (0-10 cm) at rest, in movement and for swollen joints. Clinical, demographic and variables related to injection at baseline were analyzed according to IAI response., Results: We studied 289 patients with RA (635 joints) with a mean age of 48.7 years (±10.68), 48.5% of them Caucasians, VAS for global pain=6.52 (±1.73). Under univariate analysis, the variables relating the best responses following IAI (improvement > 70%) were: "elbow and metacarpophalangeal (MCP) IAI, and functional class II". Under multivariate analysis, "males" and "non-whites" were the predictors with the best response to IAI at T4, while "elbow and MCP IAI", "polyarticular injection", "use of methotrexate" and "higher total dose of TH" obtained the best response at T24., Conclusion: Several predictors of good response to IAI in patients with RA were identified. The best-response predictors for TH IAI of long term were "apply elbow and MCP IAI" and "apply polyarticular injection"., (Copyright © 2014 Elsevier Editora Ltda. All rights reserved.)

This study investigated how feeding regimen (FR) alters apparent total-tract digestibility, performance, N balance, excretion of purine derivatives, and fat deposition in Holstein × Gyr cows at different days of gestation (DG). Forty-four pregnant multiparous Holstein × Gyr cows with an average initial body weight of 480±10.1 kg and an initial age of 5±0.5 yr old were allocated to 1 of 2 FR: ad libitum (AL; n=20) and maintenance level (ML; n=24). Maintenance level was considered to be 1.15% of body weight on a dry matter (DM) basis and met 100% of the energy requirements, whereas AL provided 190% of total net energy requirements. Data for hot and cold carcass dressing, fat deposition, average daily gain, empty body gain, and average daily gain without the gravid uterus were analyzed as a 4×2 factorial design. Intake, apparent total-tract digestibility, N balance, urinary concentration of urea, and purine derivatives data were analyzed as repeated measurements taken over the 28-d period (122, 150, 178, 206, 234, and 262 d of gestation). Cows were individually fed a corn silage-concentrate based diet composed of 93% roughage and 7% concentrate (DM basis) as a total mixed ration. Pregnant cows were slaughtered on 4 different DG: 139 (n=11), 199 (n=11), 241 (n=11), and 268 d (n=11). Overall, DM intake decreased as DG increased. This decrease observed in DM intake may be associated with the reduction in ruminal volume caused by the rapid increase in fetal size during late gestation. We observed an interaction for DM and organic matter apparent total-tract digestibility between FR and DG; at 150, 178, and 206 d of gestation, ML-fed cows had greater DM and organic matter apparent total-tract digestibility values than AL-fed cows. Rib fat thickness, mesentery, and kidney, pelvic, and heart fat were greater in AL-fed than in ML-fed cows at all DG, with the exception of rib fat thickness on d 139. Ad libitum-fed cows excreted more N in their feces and urine compared with ML-fed cows. Pregnant cows that were fed at maintenance had greater digestibility during some DG, excreted less N in feces and less N and urea in urine, and deposited less fat in the body. We therefore recommend ML (1.15% of body weight with 93% of roughage) as a FR for pregnant dry cows; however, during the last month of gestation, AL seems to be the most appropriate FR to avoid loss of body weight., (Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The objective was to evaluate the effect of supplying different levels of raw milk, alone or in combination, with access to a starter feed, on the intake, digestibility, daily gain, N balance, and body composition of Holstein × Gyr crossbred suckling calves until 64 d of age. Thirty-nine male calves aged 4 d with an average initial live weight of 36 ± 1.0 kg were used. Five calves were defined as a reference group and slaughtered at 4 d of age to estimate the initial body composition of the animals. The other calves were distributed according to a completely randomized design in a 3 × 2 factorial arrangement consisting of 3 levels of milk (2, 4, or 8 L/d) and 2 levels of starter feed (presence or absence in diet). At 15 and 45 d of age, 4 animals from each treatment were subjected to digestibility trials with total collection of feces and urine and sampling of feeds. At 64 d of age, all animals were slaughtered and their body tissues were sampled for analyses. Total dry matter and nutrient intake increased linearly and starter intake decreased linearly in response to the supply of increasing amounts of milk. The digestibility coefficient of organic matter was not affected by the inclusion of starter feed and increased linearly as milk supply was elevated. Daily gain was greater at increased milk supply levels and also greater when starter was supplied, without any interaction between milk supply level and the presence or absence of starter. Fecal N excretion and N retention were higher in the animals fed starter feed. Fecal N excretion was not affected by milk levels, whereas N retention was affected. Body protein and ash contents decreased linearly according to increased milk allowance. In contrast, fat body content increased linearly according to milk supply. The presence of starter feed in the diet was responsible for the increased body fat content, but had no effect on protein or ash content. In conclusion, weight gain and N retention in calves up to 64 d of age increased with milk supply. Ad libitum access to starter further increased weight gain and N retention and no interaction with milk allowance level occurred. However, greater levels of milk are also associated with reduced starter feed intake, in addition to increased body fat content., (Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

To determine ultrasound measurements indicative of abnormalities in small, medium and large joints, we conducted a cross-sectional study comparing 60 patients with rheumatoid arthritis (RA) and 78 healthy volunteers. A MyLab 60 ultrasound machine (Esaote) and a linear multifrequency probe were used. Quantitative measurements of synovial recesses and semiquantitative measurements of synovial hyperplasia, power Doppler and bone erosion (scores = 0-3) were performed. The cutoff values for synovial recesses indicating RA (receiver operating characteristic curve, area under the curve >0.800) were found to be (radiocarpal) 3.78 mm and (ulnocarpal) 3.07 mm. Those measurements with the greatest chance of indicating RA (logistic regression analysis expressed as odds ratios [ORs]) were (p < 0.001) measurements of synovial hyperplasia (ulnocarpal, OR = 100, and radiocarpal, OR = 70); synovial power Doppler (radiocarpal, OR = 66); synovial bone erosion (radiocarpal, OR = 324); fifth metatarsophalangeal joint (OR = 100); and second metacarpophalangeal joint (OR = 92). We concluded that for both quantitative and semiquantitative ultrasound measurements, radiocarpal abnormalities increase the chance of detecting RA., (Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Cerebral malaria (CM) is a severe complication resulting from Plasmodium falciparum infection that might cause permanent neurological deficits. Cannabidiol (CBD) is a nonpsychotomimetic compound of Cannabis sativa with neuroprotective properties. In the present work, we evaluated the effects of CBD in a murine model of CM. Female mice were infected with Plasmodium berghei ANKA (PbA) and treated with CBD (30mg/kg/day - 3 or 7days i.p.) or vehicle. On 5th day-post-infection (dpi), at the peak of the disease), animals were treated with single or repeated doses of Artesunate, an antimalarial drug. All groups were tested for memory impairment (Novel Object Recognition or Morris Water Maze) and anxiety-like behaviors (Open field or elevated plus maze test) in different stages of the disease (at the peak or after the complete clearance of the disease). Th1/Th2 cytokines and neurotrophins (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) were measured in the prefrontal cortex and hippocampus of experimental groups. PbA-infected mice displayed memory deficits and exhibited increase in anxiety-like behaviors on the 5dpi or after the clearance of the parasitemia, effects prevented by CBD treatment. On 5dpi, TNF-α and IL-6 increased in the hippocampus, while only IL-6 increased in the prefrontal cortex. CBD treatment resulted in an increase in BDNF expression in the hippocampus and decreased levels of proinflammatory cytokines in the hippocampus (TNF-α) and prefrontal cortex (IL-6). Our results indicate that CBD exhibits neuroprotective effects in CM model and might be useful as an adjunctive therapy to prevent neurological symptoms following this disease., (Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.)

The aim of this study was to verify the possible interactions between exercise capacity and spontaneous locomotor activity (SLA) during the oscillation of core body temperature (Tb) that occurs during the light/dark cycle. Wistar rats (n=11) were kept at an animal facility under a light/dark cycle of 14/10h at an ambient temperature of 23°C and water and food ad libitum. Initially, in order to characterize the daily oscillation in SLA and Tb of the rats, these parameters were continuously recorded for 24h using an implantable telemetric sensor (G2 E-Mitter). The animals were randomly assigned to two progressive exercise test protocols until fatigue during the beginning of light and dark-phases. Fatigue was defined as the moment rats could not keep pace with the treadmill. We assessed the time to fatigue, workload and Tb changes induced by exercise. Each test was separated by 3days. Our results showed that exercise capacity and heat storage were higher during the light-phase (p<0.05). In contrast, we observed that both SLA and Tb were higher during the dark-phase (p<0.01). Notably, the correlation analysis between the amount of SLA and the running capacity observed at each phase of the daily cycle revealed that, regardless of the time of the day, both types of locomotor physical activity have an important inherent component (r=0.864 and r=0.784, respectively, p<0.01) without a direct relationship between them. This finding provides further support for the existence of specific control mechanisms for each type of physical activity. In conclusion, our data indicate that the relationship between the body temperature and different types of physical activity might be affected by the light/dark cycle. These results mean that, although exercise performance and spontaneous locomotor activity are not directly associated, both are strongly influenced by daily cycles of light and dark., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Brucella abortus is a Gram-negative bacterium that infects humans and cattle, causing a chronic inflammatory disease known as brucellosis. A Th1-mediated immune response plays a critical role in host control of this pathogen. Recent findings indicate contrasting roles for lipid mediators in host responses against infections. 5-Lipoxygenase (5-LO) is an enzyme required for the production of the lipid mediators leukotrienes and lipoxins. To determine the involvement of 5-LO in host responses to B. abortus infection, we intraperitoneally infected wild-type and 5-LO-deficient mice and evaluated the progression of infection and concomitant expression of immune mediators. Here, we demonstrate that B. abortus induced the upregulation of 5-LO mRNA in wild-type mice. Moreover, this pathogen upregulated the production of the lipid mediators leukotriene B4 and lipoxin A4 in a 5-LO-dependent manner. 5-LO-deficient mice displayed lower bacterial burdens in the spleen and liver and less severe liver pathology, demonstrating an enhanced resistance to infection. Host resistance paralleled an increased expression of the proinflammatory mediators interleukin-12 (IL-12), gamma interferon (IFN-γ), and inducible nitric oxide synthase (iNOS) during the course of infection. Moreover, we demonstrated that 5-LO downregulated the expression of IL-12 in macrophages during B. abortus infection. Our results suggest that 5-LO has a major involvement in B. abortus infection, by functioning as a negative regulator of the protective Th1 immune responses against this pathogen., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Cognitive dysfunction is a major sign of cerebral malaria (CM). However, the underlying mechanisms of CM cognitive outcome remain poorly understood. A body of evidence suggests that adult neurogenesis may play a role in learning and memory processes. It has also been reported that these phenomena can be regulated by the immune system. We hypothesized that memory dysfunction in CM results from hippocampal neurogenesis impairment mediated by the deregulated immune response during the acute phase of CM. C57Bl/6 mice were infected with Plasmodium berghei ANKA (PbA) strain, using a standardized inoculation of 10(6) parasitized erythrocytes. Long-term working memory was evaluated using the novel object recognition test. The mRNA expression of brain-derived neurotrophic factor (BDNF), tropomyosin-receptor-kinase (TRK-B) and nerve growth factor (NGF) in the frontal cortex and hippocampus was estimated by real-time polymerase chain reaction (PCR). The protein levels of cytokine interleukin-2 (IL-2), IL-4, IL-6, IL-10, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and CCL11 and neurotrophins BDNF and NGF were determined using a cytometric bead array (CBA) kit or enzyme-linked immunosorbent assay. Cell viability in the hippocampus was analyzed by Confocal Microscopy. Neurogenesis in the dentate gyrus was determined through quantification of doublecortin (DCX) positive cells. PbA-infected mice presented working memory impairment on day 5 post-infection. At this same time point, CM mice exhibited a decrease in DCX-positive cells in the dentate gyrus in parallel with increased cell death and elevated inflammatory cytokines (IL-6, TNF-α, IFN-γ and CCL11) in the hippocampus and frontal cortex. A significant reduction of BDNF mRNA expression was also found. IL-6 and TNF-α correlated negatively with BDNF and NGF levels in the hippocampus of CM mice. In summary, we provide further evidence that neuroinflammation following PbA-infection influences neurotrophin expression, impairs adult hippocampal neurogenesis and increases hippocampal cell death in association with memory impairment following CM course. The current study identified potential mediators of memory impairment in CM., (Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.)

A Brazilian Health Technology Assessment Bulletin (BRATS) article regarding scientific evidence of the efficacy and safety of methylphenidate for treating attention deficit hyperactivity disorder (ADHD) has caused much controversy about its methods. Considering the relevance of BRATS for public health in Brazil, we critically reviewed this article by remaking the BRATS search and discussing its methods and results. Two questions were answered: did BRATS include all references available in the literature? Do the conclusions reflect the reviewed articles? The results indicate that BRATS did not include all the references from the literature on this subject and also that the proposed conclusions are different from the results of the articles chosen by the BRATS authors themselves. The articles selected by the BRATS authors showed that using methylphenidate is safe and effective. However, the BRATS final conclusion does not reflect the aforementioned and should not be used to support decisions on the use of methylphenidate.

Background: There are limited studies on the prevalence and risk factors associated with hepatitis C virus (HCV) infection. Objective Identify the prevalence and risk factors for HCV infection in university employees of the state of São Paulo, Brazil., Methods: Digital serological tests for anti-HCV have been performed in 3153 volunteers. For the application of digital testing was necessary to withdraw a drop of blood through a needlestick. The positive cases were performed for genotyping and RNA. Chi-square and Fisher's exact test were used, with P-value <0.05 indicating statistical significance. Univariate and multivariate logistic regression were also used., Results: Prevalence of anti-HCV was 0.7%. The risk factors associated with HCV infection were: age >40 years, blood transfusion, injectable drugs, inhalable drugs (InDU), injectable Gluconergam®, glass syringes, tattoos, hemodialysis and sexual promiscuity. Age (P=0.01, OR 5.6, CI 1.4 to 22.8), InDU (P<0.0001, OR=96.8, CI 24.1 to 388.2), Gluconergam® (P=0.0009, OR=44.4, CI 4.7 to 412.7) and hemodialysis (P=0.0004, OR=90.1, CI 7.5 - 407.1) were independent predictors. Spatial analysis of the prevalence with socioeconomic indices, Gross Domestic Product and Human Development Index by the geoprocessing technique showed no positive correlation., Conclusions: The prevalence of HCV infection was 0.7%. The independent risk factors for HCV infection were age, InDU, Gluconergan® and hemodialysis. There was no spatial correlation of HCV prevalence with local economic factors.

Trogocytosis was originally thought to be restricted to the interaction of cells of the immune system with cancer cells. Such membrane exchanges are probably a general process in cell biology, and membrane exchange has been demonstrated to occur between non-immune cells within an organism. Herein, we report that membrane and protein exchange, consistent with trogocytosis, between Trypanosoma cruzi (both the Brazil and Tulahuen strains) and the mammalian cells it infects. Transfer of labeled membrane patches was monitored by labeling of either parasites or host cells, i.e. human foreskin fibroblasts and rat myoblasts. Trypomastigotes and amastigotes transferred specific surface glycoproteins to the host cells along with membranes. Exchange of membranes between the parasite and host cells occurred during successful invasion. Extracellular amastigotes did not transfer membrane patches and were did not transfer either membranes or proteins to the host cells. Membrane exchange was also found to occur between interacting epimastigotes in cell-free culture and may be important in parasite-parasite interactions as well. Further studies should provide new insights into pathogenesis and provide targets for therapeutic intervention., (Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Stroke is one of the most frequent causes of death and disability worldwide causing a major clinical and socioeconomic impact. Although the pathophysiology of brain ischemia and reperfusion is complex, the inflammatory process plays an important role in pathogenesis, contributing to the expansion of brain injury. The 5-lipoxygenase (5-LOX) is a key enzyme in the biosynthesis of the leukotrienes and has been implicated and in the central nervous system (CNS) disorders such as Alzheimer's disease and acute ischemic stroke. Zileuton, a selective 5-LOX inhibitor, has antiinflammatory properties and exerts an inhibitory effect on inflammatory diseases. The objective of this study was to evaluate the effects of blocking 5-LOX activity in a murine model of transient and global brain ischemia. Zileuton improved neurological deficits and significantly decrease volume and density of lesion, compared to vehicle-ischemic animals measured by magnetic resonance imaging (MRI). In addition, the blockage of 5-LOX reduced infarct area and histopathological changes. Furthermore, by enzyme immunoassay (ELISA) increased brain levels of tumor necrosis factor-alpha (TNFalpha), interferon-gamma (IFN-gamma), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C-C motif) ligand 3 (CCL3) and chemokine (C-C motif) ligand 5 (CCL5) were detected in the vehicle-ischemic group, whereas in Zileuton-ischemic group presented reduction of these mediators. The concentration of the antiinflammatory cytokine interleukin-10 (IL-10) was increased after 5-LOX inhibition. Our results suggest that Zileuton decreases brain damage and reduces inflammatory cytokines expression in the CNS which contributes, at least in part, to improve the neurological outcome of brain ischemia.

5-Lipoxygenase (5-LO) metabolites are important pro-inflammatory lipid mediators. However, much still remains to be understood about the role of such mediators in bone remodeling. This study aimed to investigate the effect of 5-LO metabolites, LTB4 and CysLTs, in a model of mechanical loading-induced bone remodeling. Strain-induced tooth movement and consequently alveolar bone resorption/apposition was achieved by using a coil spring placed on molar and attached to incisors of C57BL6 (wild-type-WT), 5-LO deficient mice (5-LO(-/-)) and mice treated with 5-LO inhibitor (zileuton-ZN) or with antagonist of CysLTs receptor (montelukast-MT). The amount of bone resorption and the number of osteoclasts were determined morphometrically. The expression of inflammatory and bone remodeling markers in periodontium was analyzed by qPCR. Osteoclast differentiation and TNF-α production were evaluated in vitro using RAW 264.7 cells treated with LTB4 or LTD4. Bone resorption, TRAP(+) cells and expression of Tnfa, Il10 and Runx2 were significantly diminished in 5-LO(-/-), ZN- and MT-treated mice. The expression of Rank was also reduced in 5-LO(-/-) and MT-treated mice. Accordingly, LTB4 and LTD4 in association with RANKL promoted osteoclast differentiation and increased TNF-α release in vitro. These data demonstrate that the absence of 5-LO metabolites, LTB4 and CysLTs reduces osteoclast recruitment and differentiation, consequently diminishing bone resorption induced by mechanical loading. Thus, 5-LO might be a potential target for controlling bone resorption in physiological and pathological conditions., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: To describe quantitative and semiquantitative sonographic joint measurements in healthy adults and compare them with demographic parameters., Methods: A cross-sectional study was conducted. Bilateral sonographic measurements of small, medium, and large joints were performed in 130 healthy volunteers, stratified into 5 age groups (A, 18-29; B, 30-39; C, 40-49; D, 50-59; and E, 60-80 years). Quantitative synovial hypertrophy measurements and semiquantitative synovial hypertrophy, power Doppler, bone erosion (score 0-3), and articular cartilage (score 0-4) measurements were performed by a blinded radiologist using a 6-18-MHz linear array transducer. The sonographic measurements were correlated with demographic parameters. The significant P value was set at .05., Results: A total of 6500 joint recesses were studied; the mean age ± SD of the participants was 44.8 ± 14.6 years, and 76.9% were women. The highest quantitative synovial hypertrophy values were found in the hip (6.4 mm) and talonavicular joint (2.6 mm). The joint recesses with a greater frequency of hypothetical pathologic semiquantitative scores were second metatarsophalangeal (78.8%) and first metatarsophalangeal (69.3%) for synovial hypertrophy, radiocarpal (17.7%) and first metatarsophalangeal (15.8%) for power Doppler, and posterior glenohumeral (23.1%) and ulnocarpal (4.2%) for bone erosion. The highest quantitative synovial hypertrophy values and the lowest semiquantitative synovial hypertrophy, power Doppler, bone erosion, and articular cartilage scores were observed in age group E (P < .046). There were positive correlations between the sonographic measurements and height, age, weight, and body mass index in 30.4%, 34.8%, 43.5%, and 47.8%, respectively, of all the joint recesses studied., Conclusions: Sonographic changes in healthy peripheral joints were observed predominantly in the oldest group., (© 2013 by the American Institute of Ultrasound in Medicine.)

Endothelins are potent regulators of vascular tone, which also have mitogenic, apoptotic, and immunomodulatory properties (Rubanyi and Polokoff, 1994; Kedzierski and Yanagisawa, 2001; Bagnato et al., 2011). Three isoforms of endothelin have been identified to date, with endothelin-1 (ET-1) being the best studied. ET-1 is classically considered a potent vasoconstrictor. However, in addition to the effects of ET-1 on vascular smooth muscle cells, the peptide is increasingly recognized as a pro-inflammatory cytokine (Teder and Noble, 2000; Sessa et al., 1991). ET-1 causes platelet aggregation and plays a role in the increased expression of leukocyte adhesion molecules, the synthesis of inflammatory mediators contributing to vascular dysfunction. High levels of ET-1 are found in alveolar macrophages, leukocytes (Sessa et al., 1991) and fibroblasts (Gu et al., 1991). Clinical and experimental data indicate that ET-1 is involved in the pathogenesis of sepsis (Tschaikowsky et al., 2000; Goto et al., 2012), viral and bacterial pneumonia (Schuetz et al., 2008; Samransamruajkit et al., 2002), Rickettsia conorii infections (Davi et al., 1995), Chagas disease (Petkova et al., 2000, 2001), and severe malaria (Dai et al., 2012; Machado et al., 2006; Wenisch et al., 1996a; Dietmann et al., 2008). In this minireview, we will discuss the role of endothelin in the pathogenesis of infectious processes., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The protozoan parasite Trypanosoma cruzi causes Chagas disease. Cardiac and adipose tissues are among the early targets of infection and are sites of persistent infection. In the heart and adipose tissue, T. cruzi infection results in an upregulation of pro-inflammatory mediators. In the heart, infection is associated with an increase in the markers of oxidative stress. To date, markers of oxidative stress have not been evaluated in adipose tissue in this infection. Brown and white adipose tissues were obtained from CD-1 mice infected with the Brazil strain of T. cruzi for 15, 30, and 130 days post infection. Protein carbonylation and lipid peroxidation assays were performed on these samples. There was an upregulation of these markers of oxidative stress at all time-points in both white and brown adipose tissue. Determinants of anti-oxidative stress were downregulated at similar time-points. This increase in oxidative stress during T. cruzi infection most likely has a deleterious effect on host metabolism and on the heart.

Infection with Plasmodium falciparum may result in severe disease affecting various organs, including liver, spleen, and brain, resulting in high morbidity and mortality. Plasmodium berghei Anka infection of mice recapitulates many features of severe human malaria. The aryl hydrocarbon receptor (AhR) is an intracellular receptor activated by ligands important in the modulation of the inflammatory response. We found that AhR-knockout (KO) mice infected with P. berghei Anka displayed increased parasitemia, earlier mortality, enhanced leukocyte-endothelial cell interactions in the brain microvasculature, and increased inflammation in brain (interleukin-17 [IL-17] and IL-6) and liver (gamma interferon [IFN-γ] and tumor necrosis factor alpha [TNF-α]) compared to infected wild-type (WT) mice. Infected AhR-KO mice also displayed a reduction in cytokines required for host resistance, including TNF-α, IL-1β, and IFN-γ, in the brain and spleen. Infection of AhR-KO mice resulted in an increase in T regulatory cells and transforming growth factor β, IL-6, and IL-17 in the brain. AhR modulated the basal expression of SOCS3 in spleen and brain, and P. berghei Anka infection resulted in enhanced expression of SOCS3 in brain, which was absent in infected AhR-KO mice. These data suggest that AhR-mediated control of SOCS3 expression is probably involved in the phenotype seen in infected AhR-KO mice. This is, to our knowledge, the first demonstration of a role for AhR in the pathogenesis of malaria., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

The endocannabinoid system plays an important role in thermal control and modulates several behaviors, such as locomotion and food intake (FI) that may affect the body temperature (Tb). To test whether the changes in Tb induced by anandamide (AEA) are related to behavioral changes, adult Wistar rats received an intracerebroventricular injection of AEA (0.1, 1.0 and 10.0 μg) and vehicle. Total FI was weighted daily, and Tb and spontaneous locomotor activity (SLA) were simultaneously and continuously recorded. AEA induced an increase in Tb without changing SLA and FI. For all doses tested, the Tb average in the post-injection period was higher than in the pre-injection period. The higher thermal effect was verified using a dose of 10.0 μg AEA, starting within the first hour post-injection, and was maintained for 8h after treatment. A dose-dependent thermal effect was observed (r=0.953; p<0.05) at 1h post-injection. Hypoactivity was verified only at a dose of 1.0 μg AEA. As expected, both the Tb and SLA values during the dark phase were always higher than during the light phase and were positively correlated (r=0.834, p<0.001); however, this correlation was inverted (r=-0.852, p<0.01) after the rats received 10.0 μg AEA. In summary, our results suggest that brain AEA induces an increase in Tb, and that this effect may occur independently of changes in both locomotion and FI. Moreover, it is possible that the hypolocomotion induced by AEA could be an adaptive response to the increased Tb., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: To compare hand US between systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients., Methods: Hands (1st-5th metacarpophalangeal [MCP] and 1st-5th proximal interphalangeal [PIP] joints) and wrists (radiocarpal and distal radioulnar joints) of 62 "no rhupus" SLE and 60 RA patients were compared through US (linear probe, 6-18 MHz). The findings were compared to clinical, functional, serological outcomes, and disease activity indices., Results: 2108 and 2040 joint recesses were evaluated in SLE and AR patients, respectively. Synovitis was found in 46.8% and 75% of wrists, 83.9% and 86.7% of MCPs and 58.1% and 70% of PIPs in the SLE and RA groups, respectively. More significant US findings were found in RA group. Greater values of synovitis (mm) in RA group were only found in the joint recesses of wrist (p < 0.001-0.002). In SLE group, US findings were associated with "puffy hands," Health Assessment Questionnaire score and dynamometry. Twenty-two SLE patients (35.5%) had erosion in any of joints studied. SLE patient subgroup with US erosion was associated with hematological involvement and Jaccoud's arthropathy., Conclusions: US of "no rhupus" SLE and RA patients is different, especially in wrists. In SLE patients the clinical variable most associated with US findings was "puffy hands."

The use of triple therapy for hepatitis C not only increases the rate of sustained virological responses compared with the use of only interferon and ribavirin (RBV) but also leads to an increased number of side effects. The subject of this study was a 53-year-old male who was cirrhotic with hepatitis C virus genotype 1 A and was a previous null non-responder. We initially attempted retreatment with boceprevir (BOC), Peg-interferon and RBV, and a decrease in viral load was observed in the 8(th) week. In week 12, he presented with disorientation, flapping, fever, tachypnea, arterial hypotension and tachycardia. He also exhibited leucopenia with neutropenia. Cefepime and filgrastim were initiated, and treatment for hepatitis C was suspended. A myelogram revealed hypoplasia, cytotoxicity and maturational retardation. After 48 h, he developed bilateral inguinal erythema that evolved throughout the perineal area to the root of the thighs, with exulcerations and an outflow of seropurulent secretions. Because we hypothesized that he was suffering from Fournier's Syndrome, treatment was replaced with the antibiotics imipenem, linezolid and clindamycin. After this new treatment paradigm was initiated, his lesions regressed without requiring surgical debridement. Triple therapy requires knowledge regarding the management of adverse effects and drug interactions; it also requires an understanding of the importance of respecting the guidelines for the withdrawal of treatment. In this case report, we observed an adverse event that had not been previously reported in the literature with the use of BOC.

Chagas disease, caused by Trypanosoma cruzi (Tc), is an important cause of heart disease. Resistance to Tc infection is multifactorial and associated with Th1 response. IL-18 plays an important role in regulation of IFN-γ production/development of Th1 response. However, the role of IL-18 in the setting of Tc infection remains unclear. Therefore, we investigated the role of IL-18 in the modulation of immune response and myocarditis in Tc infection. C57BL/6 and IL-18 KO mice were infected with Tc (Y or Colombian strain) and parasitemia, immune response and pathology were evaluated. Y strain infection of IL-18 KO did not alter any parameters when compared with C57BL/6 mice. However, during the acute phase (20 and 40 days post infection-dpi), Colombian strain infected-IL-18 KO mice displayed higher serum levels of IL-12 and IFN-γ, respectively, and at the chronic phase (100 dpi) an increase in splenic IFN-γ-producing CD4(+) and CD8(+) T memory cells. There was an IL-10, FOXP3 and CD4(+)CD25(+) cells reduction during acute infection in spleen. Additionally, there was a significant reduction in leukocyte infiltration and parasite load in myocardium of chronically infected IL-18 KO mice. Collectively, these data indicate that IL-18 contributes to the pathogenesis of Tc-induced myocarditis when infected with Colombian but not Y strain. These observations also underscore that parasite and host strain differences are important in evaluation of experimental Tc infection pathogenesis., (Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)