Effects of Nrf2 deficiency on bone microarchitecture in an experimental model of osteoporosis

Objective. Redox imbalance contributes to bone fragility. We have evaluated the in vivo role of nuclear factor erythroid derived 2-related factor-2 (Nrf2), an important regulator of cellular responses to oxidative stress, in bone metabolism using a model of postmenopausal osteoporosis. Methods. Ovariectomy was performed in both wild-type and mice deficient in Nrf2 (Nrf2-/-). Bone microarchitecture was analyzed by CT. Serum markers of bone metabolism were also measured. Reactive oxygen species production was determined using dihydrorhodamine 123. Results. Sham-operated or ovariectomized Nrf2 -/- mice exhibit a loss in trabecular bone mineral density in femur, accompanied by a reduction in cortical area in vertebrae. Nrf2 deficiency tended to increase osteoblastic markers and significantly enhanced osteoclastic markers in sham-operated animals indicating an increased bone turnover with a main effect on bone resorption. We have also shown an increased production of oxidative stress in bone marrow-derived cells from sham-operated or ovariectomized Nrf2-/- mice and a higher responsiveness of bone marrow-derived cells to osteoclastogenic stimuli in vitro. Conclusion. We have demonstrated in vivo a key role of Nrf2 in the maintenance of bone microarchitectureThis work was supported by grants SAF2010-22048, SAF2010-17822, RD12/0043/0013 (Ministerio de Economía y Competitividad, ISCIII, FEDER), and Prometeo2010-047 (Generalitat Valenciana). Lidia Ibáñez thanks Spanish Ministerio de Economía y Competitividad for a fellowship (FPI

Effects of diacerein on cartilage and subchondral bone in early stages of osteoarthritis in a rabbit model

Background: Osteoarthritis is thought to be the most prevalent chronic and disabling joint disease in animals and humans. At present, there is no ideal treatment option. The aim of this study was to assess the effects of the treatment with oral diacerein on articular cartilage, synovial membrane and subchondral bone in an experimental rabbit model of osteoarthritis by micro-CT evaluation and histological analysis. To this purpose, osteoarthritis was surgically induced on one knee of 16 rabbits using the contralateral knee as healthy controls. Treatment was started three weeks later and lasted eight weeks. Animals were divided into two groups for treatment: Placebo (treated daily with oral saline) and diacerein (treated orally with 1.5 mg/kg/day of diacerein). Results: Sample analysis revealed that this model induced osteoarthritis in the operated knee joint. Osteoarthritis placebo group showed a significant increase in non-calcified cartilage thickness and volume with respect to the control placebo group and important changes in the synovial membrane; whereas the parameters measured in subchondral bone remained unchanged. In the osteoarthritis diacerein-treated group the results showed an improvement with respect to the OA placebo group in all parameters, although the results were not statistically significant. Conclusion: The results of this animal study suggested that the diacerein treatment for OA may be able to ameliorate the swelling and surface alterations of the cartilage and exert an anti-inflammatory effect on the synovial membrane, which might contribute to OA improvement, as well as an anabolic effect on subchondral trabecular bone.The authors are grateful to the Directorate-General of Research, Development and Innovation, Ministry of Economy and Industry, Xunta de Galicia for funding this work through research project 09CSA008E, co-financed by the European Regional and Social Funds (FEDER and FSE) and by a grant from the Fundación Salud 2000S

Effects of glucosamine and risedronate alone or in combination in an experimental rabbit model of osteoarthritis

Background: The osteoarthritis (OA) treatment in humans and in animals is a major orthopaedic challenge because there is not an ideal drug for preserving the joint structure and function. The aim of this study was to assess the effects of the treatment with oral glucosamine and risedronate alone or in combination on articular cartilage, synovial membrane and subchondral bone in an experimental rabbit model of OA. Osteoarthritis was surgically induced on one knee of 32 New Zealand White rabbits using the contralateral as healthy controls. Three weeks later treatments were started and lasted 8 weeks. Animal were divided in four groups of oral treatment: the first group received only saline, the second 21.5 mg/kg/day of glucosamine sulfate, the third 0.07 mg/kg/day of risedronate; and the fourth group both drugs simultaneously at the same dosages. Following sacrifice femurs were removed and osteochondral cylinders and synovial membrane were obtained for its histological and micro-CT evaluation. Results: Sample analysis revealed that the model induced osteoarthritic changes in operated knees. OA placebo group showed a significant increase in cartilage thickness respect to the control and inflammatory changes in synovial membrane; whereas subchondral bone structure and volumetric bone mineral density remained unchanged. All the treated animals showed an improvement of the cartilage swelling independent of the drug used. Treatment with glucosamine alone seemed to have no effect in the progression of cartilage pathology while risedronate treatment had better results in superficial fibrillation and in resolving the inflammatory changes of the tissues, as well as modifying the orientation of trabecular lattice. The combination of both compounds seemed to have additive effects showing better results than those treated with only one drug. Conclusions: The results of this animal study suggested that glucosamine sulfate and risedronate treatment alone or in combination may be able to stop cartilage swelling. The risedronate treatment could partially stop the fibrillation and the inflammation of synovial membrane as well as modify the orientation of trabeculae in healthy and in osteoarthritic kneesThe authors thank the Dirección Xeral de I + D + i, Consellería de Economía e Industria, Xunta de Galicia for funding this work through research project 09CSA008E, cofinanced by European regional and social funds (FEDER and FSE) from European Union and by a grant of Fundación Salud 2000S

INFLUENCE OF MITRAGYNA CILIATA (MYTA) ON THE MICROSOMAL ACTIVITY of ATPase Na+/K+ DEPENDENT EXTRACT ON A RABBIT HEART

Mitragyna ciliata (MYTA) (Rubiaceae) inhibits plasmodia activity. MYTA induces a cardiotonicity of the digitalic type on rat’s isolated heart. In this work we studied the effect of MYTA on microsomal Na+/K+ -dependant ATPase (Na+, K+ ATPase) extracted from the heart of a rabbit since digitalics inhibit Na+, K+ ATPase. Our results revealed that the Na+/K+ ATPase has an optimum pH of 7.4 and temperature of 37oC respectively. There is a linear relationship between the organic phosphate formed and the incubation time over 25 mins incubation period. The ATP hydrolysis rate in the presence of MYTA was 0.775 µM/min. LINEWEAVER and BURK plots showed that MYTA did not alter KM (1.31 mM) but decreased VMAX. This study shows that MYTA exerts a non-competitive inhibition on the microsomal Na+/K+ ATPase extracted from rabbit heart with a Ci50 of 48 µg / ml. We conclude that the mechanism of action of MYTA is linked to the inhibition of the Na+/K+ ATPase like cardiotonics of the digitalic type

Comparison of various SYSADOA for the osteoarthritis treatment: an experimental study in rabbits

Background: Osteoarthritis is thought to be the most prevalent chronic and disabling joint disease in animals and humans and its treatment is a major orthopaedic challenge because there is no ideal drug treatment to preserve joint structure and function, as well as to ameliorate the symptomatology of the disease. The aim of the present study was to assess, using histology, histomorphometry and micro-CT, the effects of the treatment with several drugs of the SYSADOA group and a bisphosphonate in a model of early osteoarthritis, comparing all the results obtained. Methods: Osteoarthritis was surgically induced by anterior cruciate ligament transection and partial meniscectomy on one knee of 56 rabbits; treatment was started three weeks after surgery and lasted 8 weeks; at the end of this period, the animals were sacrificed. Animals were divided into seven groups (8 animals each), one for each regimen of treatment (glucosamine sulfate, chondroitin sulfate, hyaluronic acid, diacerein, risedronate and a combination of risedronate and glucosamine) and one for the control (placebo-treated) group. Following sacrifice, femoral osteochondral cylinders and synovial membrane samples were obtained for their evaluation by qualitative and quantitative histology and micro-CT. Results: The model induced osteoarthritic changes in the knee joints and none of the treatments showed a significantly better efficacy over the others. Regarding cartilage thickness and volume, all the treatments achieved scores halfway between control groups, without statistical differences. Regarding the synovial membrane, diacerein and risedronate showed the best anti-inflammatory profile, whereas glucosamine and chondroitin did not present any effect standing the hyaluronic acid results between the others. Regarding the subchondral bone, there were no differences in thickness or volume, but risedronate, diacerein and hyaluronic acid seemed to have considerably modified the orientation of the trabecular lattice. Conclusions: Out of the different drugs evaluated in the study for OA treatment, diacerein and risedronate showed, in all the parameters measured, a better profile of effectiveness; hyaluronic acid ameliorated cartilage swelling and promoted bone formation, but with a poor synovial effect; and finally, chondroitin and glucosamine sulfate prevented cartilage swelling in a similar way to the others, but had no effect on cartilage surface, synovial membrane or subchondral bone.The authors thank the Dirección Xeral de I + D + i, Consellería de Economía e Industria, Xunta de Galicia for funding this work through research project 09CSA008E, cofinanced by European regional and social funds (FEDER and FSE) from European Union and by a grant of Fundación Salud 2000S

Effectiveness of Exergames on Functional Physical Performance in Older Adults with Knee/Hip Osteoarthritis: A Randomized Controlled Trial

Background/Objectives: Osteoarthritis (OA) is a leading cause of mobility impairment in older adults, yet few studies have explored exergames (EXGs) as a complementary therapy for knee and/or hip OA (KOA/HOA). This study evaluated the effects of integrating EXGs into conventional therapy (CT) on functional mobility. Methods: Sixty participants were randomized into an EXG/CT group or a CT-only group. The interventions lasted 10 weeks (3 sessions/week), and the EXGs were selected from the interactive game Ring Fit Adventure (Nintendo Switch®, Kyoto, Japan). Results: Functional mobility (Timed Up and Go test) significantly improved in the EXG/CT group but not in the CT group. Additionally, lower-limb strength and aerobic endurance increased in the EXG/CT group. No adverse events were reported, and the adherence was high. Conclusions: These findings support EXG-based interventions as a viable complement to CT. Future studies should design OA-specific EXGs and include patient subgroups to expand the impact of interventions using virtual systems

Effects of Non-Immersive Virtual Reality Exercise on Self-Reported Pain and Mechanical Hyperalgesia in Older Adults with Knee and Hip Osteoarthritis: A Secondary Analysis of a Randomized Controlled Trial

Background and Objectives: Osteoarthritis (OA) of the knee and hip is a major cause of pain and functional impairment. This study evaluated the effects of non-immersive virtual reality (NIVR) combined with conventional physical therapy (CPT) on pain intensity, mechanical hyperalgesia, and perceived recovery in older adults with OA. Materials and Methods: Sixty older adults with mild-to-moderate knee or hip OA were randomly assigned to a NIVR group (NIVR-G; n = 30) or a CPT group (CPT-G; n = 30). Both groups completed 30 sessions over 10 weeks (3 sessions/week). The NIVR-G performed 20 minutes of exergames integrated into CPT. Pain intensity was assessed using the Visual Analog Scale (VAS), and mechanical hyperalgesia was evaluated through pressure pain thresholds (PPTs). Secondary outcomes included the Global Rating of Change (GRoC) and the minimal clinically important difference (MCID) for the VAS. This study is a secondary analysis of a randomized controlled trial registered at ClinicalTrials.gov (ID: NCT05839262). Results: The NIVR-G demonstrated significant reductions in pain intensity after 30 sessions (p < 0.05, d = 1.50), with greater improvements compared to the CPT-G (p < 0.05, d = 1.17). The MCID for the VAS was established at 9.2 mm, with a higher proportion of responders in the NIVR-G (p < 0.05). The NIVR-G also reported superior recovery perception on the GRoC scale (p < 0.05). No significant changes in PPTs were observed in either group. However, the improvements in the NIVR-G diminished four weeks post-intervention. Conclusions: NIVR exergames combined with CPT significantly reduced pain intensity, improved perceived recovery, and resulted in a higher proportion of responders compared to CPT alone. These findings support the use of NIVR as an effective adjunct to CPT in older adults with OA; however, further research is needed to optimize its long-term benefits

Effects of different tonic, isometric and isometric/vibratory strength training programs on motor symptomatology in people with Parkinson’s disease: Study protocol for a randomized trial

Background: The Chilean population has experienced increased longevity in recent decades, leading to an increased incidence of and mortality from neurodegenerative diseases such as Parkinson’s disease (PD). PD is a chronic degenerative condition that affects the central nervous system. The main objective of this research is to evaluate the effect of 12-week programs of tonic, isometric, and isometric/vibratory muscular strength training while controlling the manipulation of the intensity variable on motor and non-motor symptomatology in PD patients. The secondary objective is to assess the levels of muscular strength in PD patients and their relationship with motor and non-motor symptomatology. Methods: A parallel-group, randomized trial will randomly assign (n = 34) people of both sexes with Parkinson’s disease between stages I–III Hoehn and Yahr (H&Y), aged between 50 and 70 years to one of the experimental groups, in which they will undergo a total of 24 strength training sessions during 12 weeks. During the intervention period, the participants will be advised not to undertake additional exercise programs, to avoid substances that may disrupt metabolism and circadian cycles, and to maintain their medication regimen. The primary or motor evaluation of rest tremor will be performed with an accelerometer (Actigraphy), balance with the Mini-BESTest balance test, gait speed with the Ten Meters Walk Test, and non-motor symptomatology through anxiety, depression (MDS-UPDRS), and quality of life (PDQ-39) questionnaires. The Secondary evaluation of muscle strength will be performed with a functional electromechanical dynamometer. Discussion: Established as a hypothesis is that manipulating intensity variables in 12-week tonic, isometric, and isometric/vibratory muscle strength training programs has an effect on motor and non-motor symptomatology in people with Parkinson’s disease. The research will establish the extent to which controlled muscular strength training has an effect on relevant factors related to motor and non-motor symptomatology

Effects of High-Intensity Interval Training on Blood Pressure Levels in Hypertensive Patients: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Objective: This systematic review and meta-analysis aimed to (I) evaluate the evidence on the effects of high-intensity interval training (HIIT) on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in hypertensive patients; (II) determine whether HIIT impacts SBP and DBP differently; and (III) assess the clinical relevance of these effects. Methods: A comprehensive search was conducted across multiple electronic databases, resulting in the inclusion of seven randomized clinical trials in the meta-analysis. The outcomes were analyzed using random-effects models to compute mean differences (MD) and standardized mean differences (SMD) for SBP and DBP. Results: A small reduction in SBP was observed with HIIT interventions (MD −3.00; 95% CI −4.61 to −1.39; p < 0.0001; SMD −0.28; 95% CI −0.42 to −0.13; p = 0.0003). However, no statistically significant reductions were detected for DBP (MD −0.70; 95% CI −1.80 to 0.39; p = 0.21; SMD −0.07; 95% CI −0.22 to 0.08; p = 0.35). Despite demonstrating statistical significance for SBP, the effects did not reach clinical relevance. Conclusions: HIIT interventions yield small reductions in SBP, with minimal impact on DBP. These findings suggest limited clinical relevance in the management of hypertension. Further randomized controlled trials are necessary to standardize HIIT protocols, with specific emphasis on intensity control and manipulation, to better understand their potential role in hypertensive populations

Effect of muscle strength at different intensities on resting energy expenditure

Introduction: the regular practice of physical exercise is an important modulator of resting energy expenditure (REE), which depending on the intensity, duration, and type of exercise can increase the REE in an acute manner as well as long term. The effects of dynamic muscular strength exercises on the REE have been treated very little in literature. Objective: compare the effect of muscle strength exercise (MSE) at different intensities on the REE in young males. Methods: Intra-group design. Fourteen subjects aged 22,5±1,5 0,05) after the exercise at 40%RM. The REEpost 24h was maintained according to the REEpre when the intensity was 80%RM. Conclusion: The REEpost exercise is independent of the intensity of the exercise and only is maintained after 24 hours when the MSE is at a high intensity