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Many diseases affecting the posterior segment of the eye require repeated intravitreal injections with corticosteroids in chronic treatments. The periocular administration is a less invasive route attracting considerable attention for long-term therapies. In the present work, dexamethasone-loaded poly(lactic- co -glycolic) acid (PLGA) microspheres (Dx-MS) were prepared using the oil-in-water (O/W) emulsion solvent evaporation technique. MS were characterized in terms of mean particle size and particle size distribution, external morphology, polymer integrity, drug content, and in vitro release profiles. MS were sterilized by gamma irradiation (25 kGy), and dexamethasone release profiles from sterilized and non-sterilized microspheres were compared by means of the similarity factor (f 2 ). The mechanism of drug release before and after irradiation exposure of Dx-MS was identified using appropriate mathematical models. Dexamethasone release was sustained in vitro for 9 weeks. The evaluation of the in vivo tolerance was carried out in rabbit eyes, which received a sub-Tenon injection of 5 mg of sterilized Dx-MS (20-53 µm size containing 165.6 ± 3.6 µg Dx/mg MS) equivalent to 828 µg of Dx. No detectable increase in intraocular pressure was reported, and clinical and histological analysis of the ocular tissues showed no adverse events up to 6 weeks after the administration. According to the data presented in this work, the sub-Tenon administration of Dx-MS could be a promising alternative to successive intravitreal injections for the treatment of chronic diseases of the back of the eye.

Retinal photoreceptor degeneration occurs frequently in several neurodegenerative retinal diseases such as age-related macular degeneration, retinitis pigmentosa, or genetic retinal diseases related to the photoreceptors. Despite the impact on daily life and the social and economic consequences, there is no cure for these diseases. Considering this, cell-based therapy may be an optimal therapeutic option. This study evaluated the neuroprotective in vitro potential of a secretome of human bone marrow mesenchymal stem cells (MSCs) for retinal photoreceptors in vitro . We analyzed the photoreceptor morphologic changes and the paracrine factors secreted by human bone marrow MSCs in a physically separated co-culture with degenerated neuroretinas, using organotypic neuroretinal cultures. The results showed that the secretome of human bone marrow MSCs had a neuroprotective effect over the neuroretinal general organization and neuropreserved the photoreceptors from degeneration probably by secretion of neuroprotective proteins. The study of the expression of 1,000 proteins showed increased paracrine factors secreted by MSCs that could be crucial in the neuroprotective effect of the stem cell secretome over in vitro retinal degeneration. The current results reinforce the hypothesis that the paracrine effect of the human bone marrow MSCs may slow photoreceptor neurodegeneration and be a therapeutic option in retinal photoreceptor degenerative diseases., (© 2020 The Author(s).)

This study compared the effects of the most frequently employed protocols of flywheel (FW) versus weight-stack (WS) resistance exercise (RE) on regional and muscle-specific adaptations of the knee extensors. Sixteen men ( n = 8) and women ( n = 8) performed 8 weeks (2-3 days/week) of knee extension RE employing FW technology on 1 leg (4 × 7 repetitions), while the contralateral leg performed regular WS training (4 × 8-12 repetitions). Maximal strength (1-repetition maximum (1RM) in WS) and peak FW power were determined before and after training for both legs. Partial muscle volume of vastus lateralis (VL), vastus medialis (VM), vastus intermedius (VI), and rectus femoris (RF) were measured using magnetic resonance imaging. Additionally, quadriceps cross-sectional area was assessed at a proximal and a distal site. There were no differences ( P > 0.05) between FW versus WS in muscle hypertrophy of the quadriceps femoris (8% vs. 9%), VL (10% vs. 11%), VM (6% vs. 8%), VI (5% vs. 5%), or RF (17% vs. 17%). Muscle hypertrophy tended ( P = 0.09) to be greater at the distal compared with the proximal site, but there was no interaction with exercise method. Increases in 1RM and FW peak power were similar across legs, yet the increase in 1RM was greater in men (31%) than in women (20%). These findings suggest that FW and WS training induces comparable muscle-specific hypertrophy of the knee extensors. Given that these robust muscular adaptations were brought about with markedly fewer repetitions in the FW compared with WS, it seems FW training can be recommended as a particularly time-efficient exercise paradigm.

Introduction: Foam roller is a device used as a massage intervention for rehabilitation and fitness performance., Objective: To examine the effects on the ankle dorsiflexion mobility of the foam roller as well as the combination of foam roller and vibration applied to the ankle plantarflexors muscles, and to observe the possible cross-effect., Methods: Thirty-eight undergraduate students participated in the study (19 males and 19 females). This study investigated. Three conditions (3 sets of 20 s) were performed in a randomized order (independent variables): 1) foam roller (Roller), 2) foam roller and vibration (Roller+VIB), and 3) no foam roller or vibration (Control). to determine whether of foam roller with or without vibration would benefit ankle dorsiflexion mobility. Ankle dorsiflexion ROM and plantar flexor were measured in both legs before and immediately after the treatment., Results: A cross-effect was found in the non-stimulated leg. There was a significant effect on ankle mobility of Roller and Roller+VIB conditions (6% and 7%, p<0.001)., Conclusion: Foam roller massage and vibration stimulus' foam roller massage increase ankle mobility producing a cross-effect.

Objectives: To evaluate the effects of whole-body vibration (WBV) on skeletal muscle activity and power performance of the upper body during decline bench press exercise at different loads., Methods: Forty-seven healthy young and active male students volunteered. Each performed dynamic decline bench press repetitions with and without WBV (50 Hz, 2.2 mm) applied through a hamstring bridge exercise at three different loads of their 1-repetition maximum (1RM): 30%, 50%, and 70% 1RM. Muscle activity of the triceps brachii (TB), biceps brachii (BB), pectoralis major (PM), and biceps femoris (BF) was measured with surface electromyography electrodes and kinetic parameters of the repetitions were measured with a rotary encoder., Results: WBV increased peak power (PP) output during the 70% 1RM condition (p<0.01). Muscle activity was increased with WBV in the TB and BF muscles at all loads (p<0.05). There were no effects of WBV on BB or PM muscles., Conclusion: WBV applied through a hamstring bridge exercise increases TB muscle activity during a decline bench press and this augmentation contributes to an increased peak power at higher loads and increased peak acceleration at lower loads., Competing Interests: The authors have no conflict of interest.

Objectives: To evaluate the effects of performing battling rope exercise with and without the addition of whole-body vibration (WBV) on muscle activity of the leg, trunk, and upper body., Methods: Twenty-eight recreationally active university students completed 20-s of battling rope undulation for 6 separate conditions: 1) alternating arm motion no WBV -Alt&#95;NoWBV; 2) alternating arm motion 30 Hz low amplitude WBV -Alt&#95;30 Hz-L; 3) alternating arm motion 50 Hz high amplitude -Alt&#95;50 Hz-H; 4) double arm motion no WBV -Double&#95;NoWBV; 5) double arm motion 30Hz low amplitude WBV -Double&#95;30Hz-L; 6) double arm motion 50 'Hz high amplitude -Double&#95;50 Hz-H. Electromyography (EMG) was measured for the gastrocnemius medialis (GM), vastus medialis oblique (VMO), vastus lateralis (VL), rectus abdominis (RA), multifidus (MF), biceps brachii (BB), and triceps brachii (TB) muscles., Results: The double arm motion during undulation resulted in greater (p<0.05) muscle activity in the VMO, VL, RA, and MF muscles while the GM was more active during the alternating arm motion. WBV at 50Hz increased EMG in all muscles measured vs NoWBV and the 30 Hz condition., Conclusion: These results are the first to demonstrate that the exercise stimulus of performing battling rope exercise can be augmented by completing the exercise while being exposed to WBV from a ground-based platform.

The first purpose of this study was to determine the effects of whole-body vibration (WBV) exercise during an isometric hand-grip exercise. The second purpose was to evaluate whether more than one vibratory focus would evoke an increase in the effects evoked by only one vibratory focus. The present study investigated whether WBV exposure during 10 repetitions of a handgrip dynamometer while standing on a WBV platform. Twenty-eight recreationally active university students completed 3 different test conditions, in random order: 1) grip dynamometer exercise with superimposed WBV and contralateral arm vibration (WBV+AV); 2) superimposed arm vibration only (AV); 3) grip dynamometer exercise without vibration (Control). The hand grip strength was slightly higher in the WBV condition as compared to the Control and AV conditions (1.1% and 3.6%, p>0.05, respectively). A main effect of the EMGrms of extensor digitorum muscle (ED) was observed indicating that the WBV+AV condition produced a lower co-activation of ED during a flexor digital task than the Control and AV (p<0.05) conditions. The application of WBV+AV may acutely increase muscle coordination and decreases the coactivation of ED. Furthermore, the muscle EMGrms showed increases in activation near the vibratory focus in both upper- and lower-body.

Objectives: To examine the post-exercise cross-transfer effects of acute whole body vibration (WBV)., Methods: Seventeen healthy male volunteers (20.8 ± 1.2 y) performed three unilateral vibration conditions in a randomized order: 1) WBV-50 Hz [high amplitude]; 2) WBV-30 Hz [low amplitude]; and 3) a control no WBV condition (Sham) applied to the dominant leg. Each condition involved maximal voluntary isometric contractions (MVC) followed by three leg press explosive repetitions (40% MVC) with non-dominant and dominant legs; which were conducted prior to and post vibration (immediately; 2 min and 5 min). Surface electromygraphy (sEMG) of the vastus lateralis (VL) and medial gastrocnemius (MG) were measured throughout each condition., Results: A condition x leg x time interaction effect was detected (p=0.001) where 50 Hz-High in the stimulated leg enhanced mean velocity at post-2 min compared to 30 Hz-Low and Sham, remaining elevated at post-5 min. Similarly, 50 Hz-High in the non-stimulated leg increased mean velocity at post-immediately and post-2 min compared to 30 Hz-Low and Sham. There were no changes in sEMG of VL and GM in the stimulated and non-stimulated post-conditions., Conclusion: WBV (50 Hz) can augment cross-transfer in neuromuscular performance. WBV could provide an alternate method of unilateral training to promote cross education explosive strength.

Proliferative vitreoretinopathy (PVR) is still the major cause of failure in retinal detachment (RD) surgery. It is believed that down-regulation in the p53 pathway could be an important key in PVR pathogenesis. The purpose was to evaluate the impact of T309G MDM2 polymorphism (rs2279744) in PVR. Distribution of T309G MDM2 genotypes among European subjects undergoing RD surgery was evaluated. Proportions of genotypes between subsamples from different countries were analyzed. Also, a genetic interaction between rs2279744 in MDM2 and rs1042522 in p53 gene was analyzed. Significant differences were observed comparing MDM2 genotype frequencies at position 309 of intron 1 between cases (GG: 21.6%, TG: 54.5%, TT: 23.8%) and controls (GG: 7.3%, TG: 43.9%, TT: 48.7%). The proportions of genotypes between sub-samples from different countries showed a significant difference. Distribution of GG genotype revealed differences in Spain (35.1-53.0)/(22.6-32.9), Portugal (39.0-74.4)/(21.4-38.9), Netherlands (40.6-66.3)/(25.3-38.8) and UK (37.5-62.4)/(23.3-34.2). The OR of G carriers in the global sample was 5.9 (95% CI: 3.2 to 11.2). The OR of G carriers from Spain and Portugal was 5.4 (95% CI: 2.2-12.7), whereas in the UK and the Netherlands was 7.3 (95% CI: 2.8-19.1). Results indicate that the G allele of rs2279744 is associated with a higher risk of developing PVR in patients undergoing a RD surgery. Further studies are necessary to understand the role of this SNP in the development of PVR.

Age-related macular degeneration is a retinal disease with important damage at the RPE layer. This layer is considered a target for therapeutical approaches. Stem cell transplantation is a promising option for retinal diseases. Adipose derived mesenchymal stem cells secret growth factors which might play a significant role in RPE maintenance. This study aimed to evaluate human AD-MSCs ability to rescue mitomycin C treated dying ARPE19 cells in co-culture condition. ARPE19 cells were treated with MMC (50 μg/ml, 100 μg/ml and 200 μg/ml) for 2 hours to induce cell death. These treated cells were co-cultured with hAD-MSCs in indirect co-culture system for 3 days and 3 weeks. Then the viability, growth and proliferation of these ARPE19 cells were evaluated by a cell viability/cytotoxicity assay kit and Alamar Blue (AB) assay. Untreated ARPE19 cells and human skin fibroblasts (HSF) were used as controls. MMC blocked ARPE19 cell proliferation significantly in 3 days and cells were almost completely dead after 3 weeks. Cell toxicity of MMC increased significantly with concentration. When these cells were co-cultured with hAD-MSCs, a significant growth difference was observed in treated cells compared to untreated cells. hAD-MSCs rescue capacity was also significantly higher than HSF for treated ARPE19 cells. This study showed that hAD-MSCs rescued MMC treated ARPE19 cells from death. It probably occurred due to undefined growth factors secreted by hAD-MSCs in the medium, shared by treated ARPE19 cells in co-culture conditions. This study supports further evaluation of the effect of hAD-MSCs subretinal transplantation over the RPE degeneration process in AMD patients.

Glucosamine (GlcN)-induced insulin resistance is associated with an increase in O-linked-N-acetylglucosaminylated modified proteins (O-GlcNAcylated proteins). The role played by O-GlcNAc-selective-N-acetyl-beta-D-glucosaminidase (O-GlcNAcase), which removes O-N-acetyl-glucosamine residues from O-GlcNAcylated proteins, has not yet been demonstrated. We investigated whether GlcN-induced whole-body insulin resistance is related to tissue O-GlcNAcase activity and mRNA expression. GlcN (30 mumol/kg/min) or physiological saline (control) was intravenously infused into Sprague-Dawley rats for 2 h. After GlcN treatment, rats were subjected to the following: intravenous glucose tolerance test, insulin tolerance test or removal of the liver, muscle and pancreas. GlcN was found to provoke hyperglycemia compared to control (8.6 +/- 0.41 vs. 4.82 +/- 0.17 mM, p < 0.001). The insulin resistance index (HOMA-IR) increased (15.76 +/- 1.47 vs. 10.14 +/- 1.41, p < 0.001) and the beta-cell function index (HOMA-beta) diminished (182.69 +/- 22.37 vs. 592.01 +/- 103, p < 0.001). Liver glucose concentration was higher in the GlcN group than in the control group (0.37 +/- 0.04 vs. 0.24 +/- 0.038 mmol/g dry weight, p < 0.001). Insulin release index (insulin/glucose) was less in the GlcN group than in the control (2.2 +/- 0.1 vs. 8 +/- 0.8 at 120 min, p < 0.001). In the GlcN group, muscle O-GlcNAcase activity diminished (0.28 +/- 0.019 vs. 0.36 +/- 0.018 nmol of p-nitrophenyl/mg protein/min, p < 0.001), and K(m) increased (1.51 +/- 0.11 vs. 1.12 +/- 0.1 mM, p < 0.001) compared to the control. In the GlcN group, O-GlcNAcase activity/mRNA expression was altered (0.6 +/- 0.07 vs. 1 +/- 0.09 of control, p < 0.05). In conclusion, O-GlcNAcase activity is posttranslationally inhibited during GlcN-induced insulin resistance., (Copyright (c) 2010 S. Karger AG, Basel.)