Healing of normal and osteopenic bone with titanium implant and low-level laser therapy (GaAlAs): a histomorphometric study in rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Prostaglandin treatment at the onset of norgestomet and estradiol-based synchronization protocols did not alter the ovarian follicular dynamics or pregnancy per timed artificial insemination in cyclic Bos indicus heifers

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Safety assessment of oral photodynamic therapy in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A structure-based proposal for a comprehensive myotoxic mechanism of phospholipase A(2)-like proteins from viperid snake venoms

Envenomation via snakebites is an important public health problem in many tropical and subtropical countries that, in addition to mortality, can result in permanent sequelae as a consequence of local tissue damage, which represents a major challenge to antivenom therapy. Venom phospholipases A(2) (PLA(2)s) and PLA(2)-like proteins play a leading role in the complex pathogenesis of skeletal muscle necrosis, nevertheless their precise mechanism of action is only partially understood. Recently, detailed structural information has been obtained for more than twenty different members of the PLA(2)-like myotoxin subfamily. In this review, we integrate the available structural, biochemical and functional data on these toxins and present a comprehensive hypothesis for their myotoxic mechanism. This process involves an allosteric transition and the participation of two independent interaction sites for docking and disruption of the target membrane, respectively, leading to a five-step mechanism of action. Furthermore, recent functional and structural studies of these toxins complexed with ligands reveal diverse neutralization mechanisms that can be classified into at least three different groups. Therefore, the data summarized here for the PLA(2)-like myotoxins could provide a useful molecular basis for the search for novel neutralizing strategies to improve the treatment of envenomation by viperid snakes. (C) 2014 Elsevier B.V. All rights reserved.

Tooth Discoloration Induced by Endodontic Phenothiazine Dyes in Photodynamic Therapy

Objective: This study sought to assess if discoloration of tooth structures occurs after photodynamic therapy (PDT) and to determine the efficacy of a protocol to remove the photosensitizers. Background data: PDT has been used in root canal treatment to enhance cleaning and disinfection of the root canal system. PDT uses a low power laser in association with a dye as a photosensitizer. Photosensitizers can induce staining of the dental structures, resulting in an unaesthetic appearance. Methods: Forty teeth were randomly divided into four groups according to the photosensitizer used and pre-irradiation time: 0.01% methylene blue for 5 min (MB5); 0.01% methylene blue for 10 min (MB 10); 0.01% toluidine blue for 5 min (TB5); and 0.01% toluidine blue for 10 min (TB 10). Specimens were irradiated with a 660 nm diode laser with a 300 mu m diameter optical fiber, at 40 mW power setting for 3 min. Immediately after, the photosensitizers were removed with Endo-PTC cream +2.5% sodium hypochlorite (NaOCl). The shade was measured by a Vita Easyshade spectrophotometer based on the CIELAB color system (L*a*b* values) at three different experimental times: before PDT (T0), immediately after PDT (T1), and after removal of the photosensitizer (T2). Results: The results showed a decrease in the averages of the L*a*b* coordinate values after PDT (T1) in all the groups, when compared with the number at T0, with a significant statistical difference in group MB10. After photosensitizer removal (T2), all the values of the coordinates increased with significant statistical differences (p < 0.05) between T1 and T2 in L* and a*. Conclusions: It can be concluded that both methylene blue and toluidine blue dyes cause tooth discoloration, and that Endo-PTC cream associated with 2.5% NaOCl effectively remove these dyes, regardless of the pre-irradiation time used for PDT.

The effects of elastic tubing-based resistance training compared with conventional resistance training in patients with moderate chronic obstructive pulmonary disease: a randomized clinical trial

Objective: To investigate the effects of elastic tubing training compared with conventional resistance training on the improvement of functional exercise capacity, muscle strength, fat-free mass, and systemic inflammation in patients with chronic obstructive pulmonary disease.Design: A prospective, randomized, eight-week clinical trial.Setting: The study was conducted in a university-based, outpatient, physical therapy clinic.Subjects: A total of 49 patients with moderate chronic obstructive pulmonary disease.Interventions: Participants were randomly assigned to perform elastic tubing training or conventional resistance training three times per week for eight weeks.Main measures: The primary outcome measure was functional exercise capacity. The secondary outcome measures were peripheral muscle strength, health-related quality of life assessed by the Chronic Respiratory Disease Questionnaire (CRDQ), fat-free mass, and cytokine profile.Results: After eight weeks, the mean distance covered during six minutes increased by 73 meters (69) in the elastic tubing group and by 42 meters (+/- 59) in the conventional group (p < 0.05). The muscle strength and quality of life improved in both groups (P < 0.05), with no significant differences between the groups. There was a trend toward an improved fat-free mass in both groups (P = 0.05). After the first and last sessions, there was an increase in interleukin 1 (IL-1) and interleukin 10 (IL-10) in both groups, while tumour necrosis factor alpha (TNF-) was stimulated only in the conventional training group.Conclusion: Elastic tubing training had a greater effect on functional exercise capacity than conventional resistance training. Both interventions were equally effective in improving muscle strength and quality of life.

Effects of age on aerobic capacity in heart failure patients under beta-blocker therapy: Possible impact in clinical decision-making?

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Challenges in the therapy of visceral leishmaniasis in Brazil: a public health perspective

Over 3,000 yearly cases of Visceral Leishmaniasis (VL) are reported in Brazil. Brazilian Public Health System provides universal free access to antileishmania therapeutic options: Meglumine Antimoniate, Amphotericin B deoxycholate, and Liposomal Amphotericin B. Even though Amphotericin formulations have been advised for severe disease, this recommendation is mostly based on the opinion of experts and on analogy with studies conducted in other countries. Presently, there are two ongoing multicenter clinical trials comparing the efficacy and safety of the available therapeutic options. Some other issues require further clarification, such as severity markers and the approach to VL/AIDS coinfection. Brazil is facing the challenge of providing access to diagnosis and adequate treatment, in order to avoid VL-related deaths.

Perioperative fluid therapy: a statement from the international fluid optimization group

Perioperative fluid therapy remains a highly debated topic. Its purpose is to maintain or restore effective circulating blood volume during the immediate perioperative period. Maintaining effective circulating blood volume and pressure are key components of assuring adequate organ perfusion while avoiding the risks associated with either organ hypo- or hyperperfusion. Relative to perioperative fluid therapy, three inescapable conclusions exist: overhydration is bad, underhydration is bad, and what we assume about the fluid status of our patients may be incorrect. There is wide variability of practice, both between individuals and institutions. The aims of this paper are to clearly define the risks and benefits of fluid choices within the perioperative space, to describe current evidence-based methodologies for their administration, and ultimately to reduce the variability with which perioperative fluids are administered. Based on the abovementioned acknowledgements, a group of 72 researchers, well known within the field of fluid resuscitation, were invited, via email, to attend a meeting that was held in Chicago in 2011 to discuss perioperative fluid therapy. From the 72 invitees, 14 researchers representing 7 countries attended, and thus, the international Fluid Optimization Group (FOG) came into existence. These researches, working collaboratively, have reviewed the data from 162 different fluid resuscitation papers including both operative and intensive care unit populations. This manuscript is the result of 3 years of evidence-based, discussions, analysis, and synthesis of the currently known risks and benefits of individual fluids and the best methods for administering them. The results of this review paper provide an overview of the components of an effective perioperative fluid administration plan and address both the physiologic principles and outcomes of fluid administration. We recommend that both perioperative fluid choice and therapy be individualized. Patients should receive fluid therapy guided by predefined physiologic targets. Specifically, fluids should be administered when patients require augmentation of their perfusion and are also volume responsive. This paper provides a general approach to fluid therapy and practical recommendations.

Prescription patterns for diabetes mellitus and therapeutic implications: a population-based analysis

Objective: To analyze drug prescriptions for insulin and oral antidiabetic drugs in type 1 and type 2 diabetes mellitus patients seen in the Brazilian Public Healthcare System (Unified Health System - SUS) in Ribeirao Preto, SP, Brazil. Subjects and methods: All the patients with diabetes seen in the SUS in the western district of Ribeirao Preto, SP, Brazil between March/2006 and February/2007 were included in the study. Results: A total of 3,982 patients were identified. Mean age of the patients was 60.6 years, and 61.0% were females. Sixty percent of the patients were treated with monotherapy. Doses of oral antidiabetic drugs were lower in monotherapy than in polytherapy. Ten patients received doses of glibenclamide or metformin above the recommended maximum doses, and in elderly patients there was no reduction in drug doses. Conclusion: Monotherapy with oral antidiabetic drugs was the predominant procedure, and the doses were not individualized according to age. Arq Bras Endocrinol Metab. 2012;56(2):120-7

Tailored Therapy: Matching the Method to the Patient

Clinicians frequently have to decide when dialysis should be initiated and which modality should be used to support kidney function in critically ill patients with acute kidney injury. In most instances, these decisions are made based on the consideration of a variety of factors including patient condition, available resources and prevailing local practice experience. There is a wide variation worldwide in how these factors influence the timing of initiation and the utilization of various modalities. In this article, we review the therapeutic goals of renal support and the relative advantages and shortcomings of different dialysis techniques. We describe strategies for matching the timing of initiation to the choice of modality to individualize renal support in intensive care unit patients. Copyright (C) 2012 S. Karger AG, Basel

Endostatin gene therapy stimulates upregulation of ICAM-1 and VCAM-1 in a metastatic renal cell carcinoma model

One of the greatest challenges in urological oncology is renal cell carcinoma (RCC), which is the third leading cause of death in genitourinary cancers. RCCs are highly vascularized and respond positively to antiangiogenic therapy. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we examined the potential of ES-based antiangiogenic therapy to activate tumor-associated endothelial cells in metastatic RCC (mRCC). Balb/c-bearing Renca cells were treated with NIH/3T3-LendSN or, as a control, with NIH/3T3-LXSN cells. The T-cell subsets and lymphocyte populations of tumors, mediastinal lymph nodes and the spleen were assessed by flow cytometry. The expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was assessed by real-time PCR, flow cytometry and immunohistochemistry analysis. ES gene therapy led to an increase in the percentage of infiltrating CD4-interferon (IFN)-gamma cells (P<0.05), CD8-IFN-gamma cells (P<0.01) and CD49b-tumor necrosis factor-alpha cells (P<0.01). In addition, ES therapy caused an increase at the mRNA level of ICAM-1 (1.4-fold; P<0.01) and VCAM-1 (1.5-fold) (control vs treated group; P<0.001). Through flow cytometry, we found a significant increase in the CD34/ICAM-1 cells (8.1-fold; P<0.001) and CD34/VCAM-1 cells (1.6-fold; P<0.05). ES gene therapy induced a significant increase in both T CD4 and CD8 cells in the lymph nodes and the spleen, suggesting that ES therapy may facilitate cell survival or clonal expansion. CD49b cells were also present in increased quantities in all of these organs. In this study, we demonstrate an antitumor inflammatory effect of ES in an mRCC model, and this effect is mediated by an increase in ICAM-1 and VCAM-1 expression in tumor-associated endothelial cells.

Gray Matter Volumes in Obsessive-Compulsive Disorder Before and After Fluoxetine or Cognitive-Behavior Therapy: A Randomized Clinical Trial

Serotonin reuptake inhibitors and cognitive-behavior therapy (CBT) are considered first-line treatments for obsessive-compulsive disorder (OCD). However, little is known about their modulatory effects on regional brain morphology in OCD patients. We sought to document structural brain abnormalities in treatment-naive OCD patients and to determine the effects of pharmacological and cognitive-behavioral treatments on regional brain volumes. Treatment-naive patients with OCD (n = 38) underwent structural magnetic resonance imaging scan before and after a 12-week randomized clinical trial with either fluoxetine or group CBT. Matched-healthy controls (n = 36) were also scanned at baseline. Voxel-based morphometry was used to compare regional gray matter (GM) volumes of regions of interest (ROIs) placed in the orbitofrontal, anterior cingulate and temporolimbic cortices, striatum, and thalamus. Treatment-naive OCD patients presented smaller GM volume in the left putamen, bilateral medial orbitofrontal, and left anterior cingulate cortices than did controls (p<0.05, corrected for multiple comparisons). After treatment with either fluoxetine or CBT (n = 26), GM volume abnormalities in the left putamen were no longer detectable relative to controls. ROI-based within-group comparisons revealed that GM volume in the left putamen significantly increased (p<0.012) in fluoxetine-treated patients (n = 13), whereas no significant GM volume changes were observed in CBT-treated patients (n = 13). This study supports the involvement of orbitofronto/cingulo-striatal loops in the pathophysiology of OCD and suggests that fluoxetine and CBT may have distinct neurobiological mechanisms of action. Neuropsychopharmacology (2012) 37, 734-745; doi: 10.1038/npp.2011.250; published online 26 October 2011

Anti-Aversive Effects of Cannabidiol on Innate Fear-Induced Behaviors Evoked by an Ethological Model of Panic Attacks Based on a Prey vs the Wild Snake Epicrates cenchria crassus Confrontation Paradigm

Several pharmacological targets have been proposed as modulators of panic-like reactions. However, interest should be given to other potential therapeutic neurochemical agents. Recent attention has been given to the potential anxiolytic properties of cannabidiol, because of its complex actions on the endocannabinoid system together with its effects on other neurotransmitter systems. The aim of this study was to investigate the effects of cannabidiol on innate fear-related behaviors evoked by a prey vs predator paradigm. Male Swiss mice were submitted to habituation in an arena containing a burrow and subsequently pre-treated with intraperitoneal administrations of vehicle or cannabidiol. A constrictor snake was placed inside the arena, and defensive and non-defensive behaviors were recorded. Cannabidiol caused a clear anti-aversive effect, decreasing explosive escape and defensive immobility behaviors outside and inside the burrow. These results show that cannabidiol modulates defensive behaviors evoked by the presence of threatening stimuli, even in a potentially safe environment following a fear response, suggesting a panicolytic effect. Neuropsychopharmacology (2012) 37, 412-421; doi:10.1038/npp.2011.188; published online 14 September 2011

Effect of Nintendo Wii (TM)-based motor and cognitive training on activities of daily living in patients with Parkinson's disease: A randomised clinical trial

Objectives To investigate the effect of Nintendo Wii (TM)-based motor cognitive training versus balance exercise therapy on activities of daily living in patients with Parkinson's disease. Design Parallel, prospective, single-blind, randomised clinical trial. Setting Brazilian Parkinson Association. Participants Thirty-two patients with Parkinson's disease (Hoehn and Yahr stages 1 and 2). Interventions Fourteen training sessions consisting of 30 minutes of stretching, strengthening and axial mobility exercises, plus 30 minutes of balance training. The control group performed balance exercises without feedback or cognitive stimulation, and the experimental group performed 10 Wii Fit (TM) games. Main outcome measure Section II of the Unified Parkinson's Disease Rating Scale (UPDRS-II). Randomisation Participants were randomised into a control group (n = 16) and an experimental group (n = 16) through blinded drawing of names. Statistical analysis Repeated-measures analysis of variance (RM-ANOVA). Results Both groups showed improvement in the UPDRS-II with assessment effect (RM-ANOVA P < 0.001, observed power = 0.999). There was no difference between the control group and the experimental group before training {8.9 [standard deviation (SD) 2.9] vs 10.1 (SD 3.8)}, after training [7.6 (SD 2.9) vs 8.1 (SD 3.5)] or 60 days after training [8.1 (SD 3.2) vs 8.3 (SD 3.6)]. The mean difference of the whole group between before training and after training was -0.9 (SD 2.3, 95% confidence interval -1.7 to -0.6). Conclusion Patients with Parkinson's disease showed improved performance in activities of daily living after 14 sessions of balance training, with no additional advantages associated with the Wii-based motor and cognitive training. Registered on http://www.clinicaltrials.gov (identifier: NCT01580787). (C) 2012 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.