Actions of the Kunitz-type serine protease inhibitor Amblyomin-X on VEGF-A-induced angiogenesis

Amblyomin-X is a Kunitz-type serine protease inhibitor (Kunitz-type SPI) designed from the cDNA library of the Amblyomma cajennense tick, which displays in vivo anti-tumor activities. Here, the mechanisms of actions of Amblyomin-X in vascular endothelial growth factor A (VEGF-A)-induced angiogenesis were characterized. Topical application of Amblyomin-X (10 or 100 ng/10 mu l; each 48 h) inhibited VEGF-A-induced (10 ng/10 mu l; each 48 h) angiogenesis in the dorsal subcutaneous tissue in male Swiss mice. Moreover, similar effect was observed in the VEGF-A-induced angiogenesis in the chicken chorioallantoic membrane (CAM). Additional in vitro assays in t-End cells showed that Amblyomin-X treatment delayed the cell cycle, by maintaining them in G0/G1 phase, and inhibited cell proliferation and adhesion, tube formation and membrane expression of the adhesion molecule platelet-endothelial cell adhesion molecule-1 (PECAM-I), regardless of mRNA synthesis. Together, results herein reveal the role of Kunitz-type SPI on in vivo VEGF-A-induced angiogenesis, by exerting modulatory actions on endothelial cell proliferation and adhesion, especially on membrane expression of PECAM-1. These data provide further mechanisms of actions of Kunitz-type SPI, corroborating their relevance as scientific tools in the design of therapeutic molecules. (C) 2012 Elsevier Ltd. All rights reserved.

Actions of translocator protein ligands on neutrophil adhesion and motility induced by G-protein coupled receptor signaling

The 18 kDa translocator protein (TSPO) also known as the peripheral benzodiazepine receptor (PBR), mediates the transportation of cholesterol and anions from the outer to the inner mitochondrial membrane in different cells types. Although recent evidences indicate a potential role for TSPO in the development of inflammatory processes, the mechanisms involved have not been elucidated. The present study investigated the ability of the specific TSPO ligands, the isoquinoline carboxamide PK11195 and benzodiazepine Ro5-4864, on neutrophil recruitment promoted by the N-formylmethionyl-leucyl-phenylalanine peptide (fMLP), an agonist of G-protein coupled receptor (GPCR). Pre-treatment with Ro5-4864 abrograted fMLP-induced leukocyte-endothelial interactions in mesenteric postcapillary venules in vivo. Moreover, in vitro Ro5-4864 treatment prevented fMLP-induced: (i) L-selectin shedding and overexpression of PECAM-1 on the neutrophil cell surface; (ii) neutrophil chemotaxis and (iii) enhancement of intracellular calcium cations (iCa(+2)). Intriguingly, the two latter effects were augmented by cell treatment with PK11195. An allosteric agonist/antagonist relation may be suggested, as the effects of Ro5-4864 on fMLP-stimulated neutrophils were reverted by simultaneous treatment with PK11195. Taken together, these data highlight TSPO as a modulator of pathways of neutrophil adhesion and locomotion induced by GPCR, connecting TSPO actions and the onset of an innate inflammatory response. (C) 2011 Elsevier Inc. All rights reserved.

Relationship of aerobic and neuromuscular indexes with specific actions in judo

Objective. - The aim of this study was to verify the relationship of aerobic and neuromuscular indexes with specific situations in judo. Method. - Eighteen male judokas took part in the study. The following assessments were performed: vertical jump (CMJ) on a force platform; Special Judo Fitness Test (SJFT) to obtain the number of throws and percentage of the maximal heart rate (%HRmax) one minute after the test; match simulation to obtain the peak blood lactate (LACmax) and the percentage of the blood lactate removal (BLR); incremental test to obtain the velocity at the anaerobic threshold (vAT) and peak velocity (PV) reached in the test. Results. - A significant correlation was observed between the number of throws in the SJFT, the vAT (r = 0.60; P < 0.01), PV (r = 0.70; P < 0.01) and CMJ (r = 0.74; P < 0.01). A significant inverse correlation was found between the LACmax and vAT (r = -0.59; P = 0.01). Conclusions. - It can be concluded that the performance in the SJFT was determined by the aerobic capacity and power and the muscle power. Athletes with greater aerobic ability (vAT) presented lower blood lactate accumulation after the match. (c) 2011 Elsevier Masson SAS. All rights reserved.

Partial projective representations and partial actions II

This paper is a continuation of Dokuchaev and Novikov (2010) [8]. The interaction between partial projective representations and twisted partial actions of groups considered in Dokuchaev and Novikov (2010) [8] is treated now in a categorical language. In the case of a finite group G, a structural result on the domains of factor sets of partial projective representations of G is obtained in terms of elementary partial actions. For arbitrary G we study the component pM'(G) of totally-defined factor sets in the partial Schur multiplier pM(G) using the structure of Exel's semigroup. A complete characterization of the elements of pM'(G) is obtained for algebraically closed fields. (C) 2011 Elsevier B.V. All rights reserved.

Physical exercise and pancreatic islets Acute and chronic actions on insulin secretion

Diabetes mellitus (DM) is a great public health problem, which attacks part of the world population, being characterized by an imbalance in body glucose homeostasis. Physical exercise is pointed as a protective agent and is also recommended to people with DM. As pancreatic islets present an important role in glucose homeostasis, we aim to study the role of physical exercise (chronic adaptations and acute responses) in pancreatic islets functionality in Wistar male rats. First, animals were divided into two groups: sedentary (S) and aerobic trained (T). At the end of 8 weeks, half of them (S and T) were submitted to an acute exercise session (exercise until exhaustion), being subdivided as acute sedentary (AS) and acute trained (AT). After the experimental period, periepididymal, retroperitoneal and subcutaneous fat pads, blood, soleus muscle and pancreatic islets were collected and prepared for further analysis. From the pancreatic islets, total insulin content, insulin secretion stimulated by glucose, leucine, arginine and carbachol were analyzed. Our results pointed that body adiposity and glucose homeostasis improved with chronic physical exercise. In addition, total insulin content was reduced in group AT, insulin secretion stimulated by glucose was reduced in trained groups (T and AT) and insulin secretion stimulated by carbachol was increased in group AT. There were no significant differences in insulin secretion stimulated by arginine and leucine. We identified a possible modulating action on insulin secretion, probably related to the association of chronic adaptation with an acute response on cholinergic activity in pancreatic islets.

Judiciary as the last resort to protect children and adolescents: intersectoral actions, investment in human resources, and structuring of services

This study aimed to identify the work developed by the Judiciary to prevent sexual violence against children and adolescents within the family. The approach to social representations in a cultural perspective was used. The field study consisted in the 1st and 2nd Court of Crimes against Children and Adolescents, at the State Supreme Court of Pernambuco, Brazil. Participant observation, semi-structured interviews, and focus group with 17 subjects were the techniques for data collection, analyzed through the interpretation of meanings, allowing the identification of the category "The Judiciary as the ultimate level" and the following subcategories: "The public policies to prevent violence" and "The structure and dynamics of Courts". This study allows the visualization of the Judiciary's limitations with regard to the full protection and absolute priority, and that the work along with the victims demands investments in structure and human resources.

PReS-FINAL-2170: Work disability in adult patients with juvenile idiopathic arthritis (JIA)

Introduction Approximately 20% JIA patients enters adulthood with clinically active disease and disabled, therefore work condition may be affected. Objectives To assess the prevalence of work disability among adult patients with JIA regularly attending a tertiary heumatology center and to determine possible associated risk factors. Methods This was a cross-sectional study that enrolled 43 JIA patients according to 2004 revised ILAR criteria. A questionnaire was developed in order to evaluate working status and labor activity: occupation, current/previous work, employment status and withdrawal rate were actively searched. Demographic data, JIA characteristics, clinical activity (DAS28>2.6), therapeutic intervention, comorbidities, physical activity, sedentarism (WHO definitions), functional class (1991 ACR criteria), HAQ and SF-36 were recorded. The prevalence of work disability was calculated using 95% confidence interval, and compared to all parameters; qualitative variables were analyzed using tests of association (chi-square test) and quantitative variables by Mann-Whitney or student test. Results Patients' mean age was 29+7.4 yrs (range 19-41) with mean JIA duration = 17.2+12.3 yrs (range 3-33); 63% were males and 37% females. JIA subtypes were 64% polyarticular, 11% oligoarticular, 9% systemic, 9% ERA, 2% extended oligoarticular, 2% psoriatic arthritis; 7% had uveitis. Serum RF was positive in 21% and ANA in 21%. The majority (72%, n = 31) of JIA patients were employed, whereas 28% (n = 12) were currently not working. In the latter group, 83% (10/12) were retired due to JIA related disability. Further analysis comparing those currently working vs. Those not working revealed similar age (25,3 yrs vs.29,5 yrs, p = 0,09). Although not significantly, most patients currently working had Poly onset JIA (22 vs. 6 p = 0,37), higher frequencies of good education level >12 yrs of school (31 vs.9, p = 0,38), functional class I (p = 0,96), practiced regular physical activity (9 vs. 0, p = 0,89), were singles (26 vs. 8, p = 0,15). Both groups had comparable HAQ and DAS 28 scores (0,62 vs. 0.59, p = 0,47 and 2,51 vs.2,07, p = 0,64) and similar arthroplasty rate (8 vs. 4, p = 0,427). Frequencies of hypertension (3 vs.1, p = 0,999), dyslipidemia (1 vs. 1, p = 0,125), diabetes (1 vs. 0 p = 0,999), depression (1 vs. 0, p = 0,999) and smokers (3 vs. 1, p = 0,99) were alike in both groups. Remarkably, employed patients had higher SF 36 mental health component (84.0 vs. 70.42, P = 0.01). Conclusion High prevalence of almost 1/3 work disability and of retirement due to disease related incapacity remain major problems for adult JIA individuals. We also identified worse mental health in employed patients indicating that further research is needed, in addition to intense affirmative disability actions in order to remove possible disabling barriers and to adapt restrictive environments for these patients. Moreover, enhanced strategies and policy for inclusion of JIA patients in the job market is urged.

Bias and learning in temporal binding: intervals between actions and outcomes are compressed by prior bias

It has consistently been shown that agents judge the intervals between their actions and outcomes as compressed in time, an effect named intentional binding. In the present work, we investigated whether this effect is result of prior bias volunteers have about the timing of the consequences of their actions, or if it is due to learning that occurs during the experimental session. Volunteers made temporal estimates of the interval between their action and target onset (Action conditions), or between two events (No-Action conditions). Our results show that temporal estimates become shorter throughout each experimental block in both conditions. Moreover, we found that observers judged intervals between action and outcomes as shorter even in very early trials of each block. To quantify the decrease of temporal judgments in experimental blocks, exponential functions were fitted to participants’ temporal judgments. The fitted parameters suggest that observers had different prior biases as to intervals between events in which action was involved. These findings suggest that prior bias might play a more important role in this effect than calibration-type learning processes.

The cardiovascular actions of fractalkine/CX3CL1 in the hypothalamic paraventricular nucleus are attenuated in rats with heart failure

The paraventricular nucleus (PVN) of the hypothalamus plays an important role in the regulation of sympathetic nerve activity, which is significantly elevated in chronic heart failure (CHF). Fractalkine (FKN) and its cognate receptor, CX3CR1, are constitutively expressed in the central nervous system, but their role and physiological significance are not well known. The aims of the present study were to determine whether FKN plays a cardiovascular role within the PVN and to investigate how the actions of FKN might be altered in CHF. We show that both FKN and CX3CR1 are expressed on neurons in the PVN of rats, suggesting that they may have a physiological function in this brain nucleus. Unilateral microinjection of FKN directly into the PVN of anaesthetized rats elicited a significant dose-related decrease in blood pressure (1.0 nmol, -5 ± 3 mmHg; 2.5 nmol, -13 ± 2 mmHg; 5.0 nmol, -22 ± 3 mmHg; and 7.5 nmol, -32 ± 3 mmHg) and a concomitant increase in heart rate (1.0 nmol, 6 ± 3 beats min(-1); 2.5 nmol, 11 ± 3 beats min(-1); 5 nmol, 18 ± 4 beats min(-1); and 7.5 nmol, 27 ± 5 beats min(-1)) compared with control saline microinjections. In order to determine whether FKN signalling is altered in rats with CHF, we first performed quantitative RT-PCR and Western blot analysis and followed these experiments with functional studies in rats with CHF and sham-operated control rats. We found a significant increase in CX3CR1 mRNA and protein expression, as determined by quantitative RT-PCR and Western blot analysis, respectively, in the PVN of rats with CHF compared with sham-operated control rats. We also found that the blood pressure effects of FKN (2.5 nmol in 50 nl) were significantly attenuated in rats with CHF (change in mean arterial pressure, -6 ± 3 mmHg) compared with sham-operated control rats (change in mean arterial pressure, -16 ± 6 mmHg). These data suggest that FKN and its receptor, CX3CR1, modulate cardiovascular function at the level of the PVN and that the actions of FKN within this nucleus are altered in heart failure