Application of target repositioning and in silico screening to exploit fatty acid binding proteins (FABPs) from Echinococcus multilocularis as possible drug targets.

Fatty acid binding proteins (FABPs) are small intracellular proteins that reversibly bind fatty acids and other hydrophobic ligands. In cestodes, due to their inability to synthesise fatty acids and cholesterol de novo, FABPs, together with other lipid binding proteins, have been proposed as essential, involved in the trafficking and delivery of such lipophilic metabolites. Pharmacological agents that modify specific parasite FABP function may provide control of lipid signalling pathways, inflammatory responses and metabolic regulation that could be of crucial importance for the parasite development and survival. Echinococcus multilocularis and Echinococcus granulosus are, respectively, the causative agents of alveolar and cystic echinococcosis (or hydatidosis). These diseases are included in the World Health Organization's list of priority neglected tropical diseases. Here, we explore the potential of FABPs from cestodes as drug targets. To this end, we have applied a target repurposing approach to identify novel inhibitors of Echinococcus spp. FABPs. An ensemble of computational models was developed and applied in a virtual screening campaign of DrugBank library. 21 hits belonging to the applicability domain of the ensemble models were identified, and 3 of the hits were assayed against purified E. multilocularis FABP, experimentally confirming the model's predictions. Noteworthy, this is to our best knowledge the first report on isolation and purification of such four FABP, for which initial structural and functional characterization is reported here.

Effects of Warm-Up and Fatigue on Knee Joint Position Sense and Jump Performance.

The purpose of this study was to evaluate the effects of a warm-up and fatigue protocol on the vertical jump and knee joint position sense of sprinters. Thirty-two sprinters were randomly allocated to either a control group (CONT) or a plyometric group (PLYO) that performed a warm-up, followed by a high-intensity plyometric protocol. Absolute (AAE), relative (RAE), and variable (VAE) angular errors and vertical jump were evaluated before and after the warm-up, as well as after the plyometric protocol and again 5 min later. After the warm-up, athletes improved RAE and jump performance. After the plyometric protocol, scores on the RAE, VAE, and the vertical jump performance worsened compared to the control group and to the values obtained after the warm-up. Five minutes later, RAE and vertical jump continued to be impaired. AAE did not show significant differences. The vertical jump is improved after the warm-up, although it is deteriorated after high-intensity plyometry. Regarding knee proprioception, the lack of impairments in the AAE make unclear the effects of the plyometric exercises on knee proprioception.

Low power laser stimulation of the bone consolidation in tibial fractures of rats: a radiologic and histopathological analysis.

The objective of this study is to analyze the effectiveness of low power laser irradiation in the bone consolidation of tibial fractures in rats. An experimental, comparative, prospective study with control group was designed. Twenty Wistar rats were grouped into control (n = 10) and experimental groups (n = 10). A tibial fracture, with a mechanical drill, was inflicted in all rats. The experimental group received ten days of low power arsenide-gallium laser irradiation of 850 nm (KLD, Sao Paulo, Brasil)-100 mW, 8 J/cm(2), 64 s. Before and after the laser treatment, a radiologic analysis was carried out in both groups, in which the rats were graded from 0 to IV according the Montoya scale of bone consolidation. Also, we histopathologically analyzed the bone to estimate the proliferation of fibroblasts, bone matrix, and angiogénesis with a microscopy, which were graded as I (thin layer of fibroblasts and osteoid matrix), II (thick layer of fibroblasts and osteoid matrix), or III (thick layer of fibroblasts and osteoid matrix and new blood vessels). Radiologic data showed that the experimental group had a higher bone consolidation of Montoya scale after ten days of laser irradiation compared to control group (P < 0.004). Histopathologic data showed more fibroblasts and angiogenesis presence in the group receiving laser irradiation, compared to control group (P < .002). The low power laser radiation therapy may expedite the bone repair after tibial fractures in rats, according to radiologic and histopathologic analysis.

Effects of an anaerobic lactic training session on the postural stability of athletes.

AIM: The aim of this study was to analyze the short-term effects of a lactate-accumulation training session on postural stability. METHODS: Fifteen athletes performed two trainings sessions (warm-up and lactic-training session). Before training (Pre), immediately after (Post(0min)), thirty minutes later (Post(30min)) and after 24 hours (Post(24h)), athletes were subject to a bipodal and a monopodal stabilometries and a lactate blood analysis to ensure a high stress level. RESULTS: Variance analysis (α=0.05) showed that, in lactic training, athletes experienced an increase of length and velocity in post(0min), a decrease at post(30min) and a new decrease at post(24h), which was lower than basal values. In monopodal stability, left-leg support showed a decrease at post(0min) in anteroposterior plane of athletes after lactic training. Also, in both monopodal supports, athletes displayed higher values of length and velocity in post(0min) after lactic training, with a progressive decrease which was significant at Post(24h), when they reached baseline. CONCLUSION: Right after anaerobic lactic training, center-of-pressure dispersion variables in bipodal stabilometry are worsened. Thirty minutes later, stabilometric variables are still deteriorated. At 24 hours, stabilometry is better than baseline. In monopodal support, dispersion values are worsened after lactic training and anteroposterior stability is impaired in left monopodal support, although the deterioration is less evident as time passes.