Numerical Simulation of Bone Remodeling under Low Loading Coupled with Electrical Stimulation / 医用生物力学

Objective To study the bone disuse behavior with electric field under low load stimulation frequency. Methods A disuse model was proposed to describe the effects of mechanical and electrical stimulation on bone remodeling through the activation frequency. By establishing the finite element model of proximal femur and using the finite element method, the process of bone remodeling under low load stimulation frequency coupled with electrical stimulation was simulated, and the loss of bone density was analyzed. Results The density was significantly decreased by decreasing the frequency of daily load stimulation frequency. The electrical stimulation could resist density loss caused by the low load stimulation frequency to a certain degree, and its main influence areas were distributed in the femoral head and femoral neck. The duration of electrical stimulation significantly affected density loss of the cortical bone and cancellous bone. Conclusions The model can simulate the process of disuse caused by the decrease of daily load stimulation frequency. Meanwhile, the effect of electric field is taken into account to show the resistance to bone density loss.

Rehabilitation of a Patient with Severe COVID-19 Using Extracorporeal Membrane Oxygenation：A Case Report / The Japanese Journal of Rehabilitation Medicine

Coronavirus disease 2019 (COVID-19) has been spreading globally since 2019；however, comprehensive rehabilitation of elderly patients with COVID-19 pneumonia remains a challenge. A 76-year-old American woman with COVID-19 pneumonia was admitted to our hospital. Because her disease was complicated by acute respiratory distress syndrome (ARDS), she was treated with intensive care, including invasive ventilation and extracorporeal membrane oxygenation (ECMO). During and after intensive care, she exhibited physical symptoms such as weakness, pain, shortness of breath, and difficulty in movement and exercise. Furthermore, during approximately 3.5 months of hospitalization, she received swallowing and speech therapies along with physical therapy. These rehabilitation therapies enabled her to get home in the United States. Her rehabilitation schedule had to be carefully planned according to her symptoms and infectiousness of COVID-19. This paper highlights few important points regarding the difficulty in rehabilitation including that of physical function, mental health, and cognitive function of patients with COVID-19. Furthermore, this report provides a problem-solving approach for long-term rehabilitation in elderly patients with COVID-19 pneumonia.

Effects of traditional Chinese Songchi ointment combined with treadmill training on PI3K/Akt/mTOR signal pathway and inflammation in rats with disused muscles atrophy / 中华物理医学与康复杂志

Objective:To observe any effect of supplementing treadmill training with applications of the traditional Chinese Songchi ointment in the rehabilitation of gastrocnemius muscles atrophied through disuse.Methods:Forty-five Wistar rats were randomly divided into a normal control group ( n=8) and a model group ( n=37). The rats in the model group had their left hind limbs immobilized by the Nagai method to induce disused muscle atrophy (DMA). That group was then randomly subdivided into a model control (MC) group, a treadmill training group (the EX group), a Songchi ointment group (SC group) and a comprehensive rehabilitation group (the CR group), each of 8. The EX and SC groups were given treadmill training at 18m/min or topical application of Songchi ointment once a day, 6 days a week for 6 weeks. The CR group was given both treatments. After the 6 weeks, hematoxylin and eosin staining was used to evaluate the pathological changes in the gastrocnemius of each rat′s left hind limb. Serum levels of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-10 (IL-10) were detected using enzyme-linked immunosorbent assays. PI3K, Akt and mTOR mRNA and protein were assayed using real-time quantitative PCR and western blotting. Results:The arrangement of muscle fibers in the MC group was disordered and there was a large number of infiltrated inflammatory cells. Such conditions were significantly relieved in the CR group. After the intervention the levels of inflammatory factors TNF-α and IL-1β in the CR group were, on average, significantly lower than those observed in the MC group, the EX group or the SC group, while the level of anti-inflammatory factor IL-10 was significantly higher. The average PI3K, Akt and mTOR mRNA and protein levels of group CR were significantly higher than those of the MC and EX groups.Conclusions:The traditional Chinese Songchi ointment can usefully supplement treadmill training to relieve DMA. It upregulates IL-10, activates the PI3K Akt/mTOR signaling pathway and promotes the synthesis of muscle fiber protein while down-regulating TNF-α and IL-1β and muscle fiber inflammatory response.

Electroacupuncture promotes recovery from disuse muscular atrophy through the miR-133a/SIRT1 pathway / 中华物理医学与康复杂志

Objective:To explore the role of microRNA-133a (miR-133a) and silent mating information regulation 2 homolog 1 (SIRT1) in the effects of electroacupuncture on persons with disuse muscular atrophy.Methods:Thirty C57BL/6 mice were randomly divided into a control group, an experimental control group and an experimental group, each of 10. Disuse muscular atrophy was induced in the mice of the experimental and experimental control groups using tail suspension. The mice in the electroacupuncture group were given 15 minutes of electroacupuncture over the Yanglingquan and Zusanli points every day for 14 days. Wet weight ratio and the cross-sectional area of the gastrocnemius and soleus were tracked, and the structure of the mitochondria in the skeletal muscles was observed using a transmission electron microscope. The protein expressions of SIRT1, peroxisome proliferator-activated receptor γ coactivator-1a (PGC-1a), nicotinamide phosphoribosyl transferase (NAMPT), adenosine 5-monophosphate-activated protein kinase-a (AMPK-a) and phospho-AMPK-a (P-AMPK-a) were detected using western blotting. The expressions of the muscle atrophy F-box (Atrogin-1), muscle ring finger1 (MuRF1), miR-133a, SIRT1, paired box gene 7 (Pax7), myogenic determination (MyoD) and myogenin (MyoG) genes were detected through polymerase chain reactions. The concentration of Niacylamide adenine dinucleotide (NAD+ ) and the ratio of NAD+ to reduced nicotinamide adenine dinucleotide were also measured.Results:Compared with the experimental control group, the average wet weight increased by 21% and the cross-sectional area of the soleus increased by 30% in the experimental group. The average wet weight of the gastrocnemius increased by 5% and the area by 17%. The average expressions of Atrogin-1, MuRF1, SIRT1, PGC-1a and NAMPT, the concentration of NAD+ , as well as the average value of P-AMPK-a/AMPK-a and NAD+ /NADH were significantly lower in the experimental group than in the experimental control group, while the average expression of miR-133a in the experimental group was significantly (163%) higher. The average expressions of Pax7 and MyoD were significantly up-regulated in the experimental control group compared with the other two groups, while MyoG was highly expressed in the experimental group compared with the other 2 groups.Conclusions:The SIRT1 pathway is one of the reflexive protective mechanisms that mediate in the natural recovery of skeletal muscles. Electroacupuncture enhances myoblast differentiation, improves energy metabolism in the mitochondria, and thus promotes recovery from disuse muscular atrophy.

Bone Mineral Density and Bone Metabolic Markers for Patients with Spinal Cord Injury in Rehabilitation Wards / 中国康复理论与实践

Objective:To analyze the changes of bone mineral density (BMD), the characteristics of bone metabolic markers and related factors in patients with spinal cord injury (SCI). Methods:A total of 78 patients with SCI in our hospital from April, 2018 to May, 2020 were selected and divided into groups according to the injury courses. The people receiving physical examination in the same period were selected as control. BMD of proximal femur was measured by dual energy X-ray absorptiometry. Bone metabolic markers were detected. The correlation between BMD and clinical indicators was analyzed. Results:There was no difference in BMD between the patients within three months and the controls (P > 0.05). BMD at trochanter major, intertrochanteric and total hip in patients three to six months post injury was lower than that in the controls (|t| > 2.242, P < 0.05). The BMD at femoral neck, trochanter major, intertrochanteric and total hip in patients during six to twelve months post injury was lower than that in the controls (|t| > 2.026, P < 0.05). BMD at proximal femur in patients with twelve to 24 months post injury was lower than that in the controls (|t| > 2.189, P < 0.05). The decrease of BMD aggravated with the course of injury. There was no difference in BMD between paraplegia and quadriplegia, complete injury and incomplete injury (P > 0.05). Collagen type I C-terminal telopeptide (CTX) and N-terminal propeptide of type l precollagen (PINP) were higher than the reference range in the course of each injury, increased within three months post injury, reached the peak at three to six months post injury, and decreased to a steady state since seven months post injury. Vitamin D deficiency occurred in 87.5% of the patients. BMD at femoral neck and total hip was negatively correlated with the course of injury (|r| > 0.250, P < 0.05), and positively correlated with body mass index (r > 0.255, P < 0.05). Conclusion:The longer the duration of SCI, the more decrease of BMD. The early bone metabolism of patients with SCI is high conversion type. The rate of vitamin D deficiency in patients with SCI is quite high. It is necessary to detect and evaluate the bone metabolic markers combined with BMD at the early stage of SCI.

Effects of conservative treatment of 2-week rigorous bed rest on muscle disuse atrophy in osteoporotic vertebral fracture patients / Journal of Rural Medicine

Objective: Osteoporotic vertebral fracture (OVF) is conventionally treated with conservative management such as bed rest, but a relatively prolonged bed rest has the potential risk of muscle disuse atrophy. This study aimed to examine whether the 2-week of rigorous bed rest affects muscle disuse atrophy in OVF patients.Patients and Methods: A total of 54 OVF patients (16 males; 38 females; mean age, 80.2 ± 9.2 years) were treated with an initial 2-week rigorous bed rest by hospitalization with persistent rehabilitation. Cognitive function, swallowing function, grip strength, and lower extremity circumference were evaluated at three-time points (admission, end of bed rest, and discharge).Results: Of the 51 patients who were able to walk independently before the injury, one patient (2.0%) had to use a wheelchair after the injury. During hospitalization, cognitive function decline was observed in 33.3% of patients, but not in patients with Revised Hasegawa’s Dementia Scale score ≥25 at admission. Swallowing function decline was observed in one patient, and none of the patients developed aspiration pneumonia during hospitalization. The grip strength significantly improved both at the end of bed rest (P=0.04) and discharge (P=0.02). Although the lower extremity circumference significantly decreased at the end of bed rest (P<0.01), it was recovered afterward. The lower extremity circumference did not significantly differ between the admission and discharge (P=0.17).Conclusion: Our results suggested that conservative treatment of OVF through an initial 2-week rigorous bed rest with persistent hospital rehabilitation poses a low risk of muscle disuse atrophy. If cognitive dysfunction is observed on admission, close monitoring for exacerbation should be performed during the hospital stay.

Preventive effect and mechanism of puerarin on rat models of disuse osteoporosis / 中国中药杂志

To investigate the preventive effect and possible mechanism of puerarin(Pur) in rat model of disuse osteoporosis(DOP),thirty healthy Wistar female rats of 2 months old were randomly divided into control group(Control), hindlimb suspension group(HLS), and puerarin group(HLS+Pur) in hindlimb suspension, with 10 rats in each group. A disuse osteoporosis model was established by tail suspension method, and 15.4 mg·kg~(-1) puerarin suspension was administered to HLS+Pur group every day, and the same volume of distilled water was administered to Control group and HLS group respectively. After 28 days, the rats were sacrificed by abdominal aorta blood collection, the main organs of the rats were removed, and the bone tissues of the rats were dissected. The organ index of the rats was calculated and the histopathology of the organs was observed under microscope. Bone mineral density test and bone biomechanical experiment were performed. Bone histomorphometry results were observed after bone tissue sectioning, and serum biochemical markers of bone metabolism were determined. There was no significant difference in organ index between the groups. There was no obvious abnormality in the pathological examination of the organs. The results of bone mineral density showed that puerarin could significantly increase the bone density of the tibia and vertebrae caused by hindlimb suspension. The mechanical parameters experiments showed that puerarin could effectively increase the maximum load and elastic modulus of the tibia and vertebrae. Fluorescence labeling showed that the fluorosis interval increased and the bone formation increased during puerarin treatment. The VG staining results showed that compared with the HLS group, in the puerarin group, the number of trabecular bone increased, the thickness of the trabecular bone became thicker, and the bone separation became smaller, which greatly improved the bone microstructure after hindlinb suspension. In addition, serum biochemical indicators showed that puerarin could promote bone formation index bone calcium. The content of osteocalcin(OC) increased and inhibited the formation of tartrate-resistant acid phosphatase 5 b(TRACP 5 b). Puerarin has a preventive effect in the rat model of disuse osteoporosis and its effect is good, and its mechanism may be related to promoting bone formation and inhibiting bone resorption.

The mechanisms and treatments of muscular pathological changes in immobilization-induced joint contracture: A literature review / 中华创伤杂志(英文版)

The clinical treatment of joint contracture due to immobilization remains difficult. The pathological changes of muscle tissue caused by immobilization-induced joint contracture include disuse skeletal muscle atrophy and skeletal muscle tissue fibrosis. The proteolytic pathways involved in disuse muscle atrophy include the ubiquitin-proteasome-dependent pathway, caspase system pathway, matrix metalloproteinase pathway, Ca-dependent pathway and autophagy-lysosomal pathway. The important biological processes involved in skeletal muscle fibrosis include intermuscular connective tissue thickening caused by transforming growth factor-β1 and an anaerobic environment within the skeletal muscle leading to the induction of hypoxia-inducible factor-1α. This article reviews the progress made in understanding the pathological processes involved in immobilization-induced muscle contracture and the currently available treatments. Understanding the mechanisms involved in immobilization-induced contracture of muscle tissue should facilitate the development of more effective treatment measures for the different mechanisms in the future.

Short-term creatine supplementation changes protein metabolism signaling in hindlimb suspension

The effect of a short-term creatine supplementation on hindlimb suspension (HS)-induced muscle atrophy was investigated. Creatine monohydrate (5 g/kg b.w. per day) or placebo, divided in 2 daily doses, was given by oral gavage for 5 days. Rats were maintained in HS with dietary supplementation concomitantly for 5 days. Body weight, soleus and EDL muscle masses, and cross-sectional areas (CSA) of the muscle fibers were measured. Signaling pathways associated with skeletal muscle mass regulation (FST, MSTN, FAK, IGF-1, MGF, Akt, mTOR, atrogin-1, and MuRF1 expressions, and Akt, S6, GSK3B, and 4EBP1 proteins) were evaluated in the muscles. Soleus muscle exhibited more atrophy than the EDL muscle due to HS. Creatine supplementation attenuated the decrease of wet weight and increased p-4EBP1 protein in the EDL muscle of HS rats. Also, creatine increased mTOR and atrogin-1 expressions in the same muscle and condition. In the absence of HS, creatine supplementation increased FAK and decreased MGF expressions in the EDL muscle. Creatine attenuated the increase in FST expression due to HS in the soleus muscle. MuRF1 expression increased in the soleus muscle due to creatine supplementation in HS animals whereas atrogin-1 expression increased still further in this group compared with untreated HS rats. In conclusion, short-term creatine supplementation changed protein metabolism signaling in soleus and EDL muscles. However, creatine supplementation only slightly attenuated the mass loss of both muscles and did not prevent the CSA reduction and muscle strength decrease induced by HS for 5 days.

Sarcomere structure: the importance of desmin protein in muscle atrophy / Estructura de sarcómera: la importancia de proteína desmina en atrofia muscular

Knowing the ultrastructure of skeletal muscle is critical to understand how it works under normal situation and the disorders caused by extreme or pathological conditions. Sarcomere is the basic structural unit of striated muscle tissue. An important element of sarcomere architecture are the intermediate filaments, including the desmin protein. Desmin protein contributes to maintenance of cell integrity, efficient transmission of force and mechanochemical signaling within the myocyte. Because of this, desmin protein has constantly been a focus of research that investigates its alterations associated to damage and muscle atrophy under different conditions. The purpose of the following literature review is to describe the basic concepts of muscle ultrastructure, emphasizing the desmin protein role under conditions of muscle disuse atrophy and aging.

Conocer la ultraestructura del músculo esquelético es crítico para entender cómo trabaja bajo situaciones normales y en desórdenes causados por condiciones extremas o patológicas. La sarcómera es la unidad de estructura básica del tejido muscular estriado. Elementos importantes en la arquitectura de la sarcómera son los filamentos intermedios, incluyendo la proteína desmina. La proteína desmina contribuye en mantener la integridad celular, la transmisión eficiente de fuerza y la señalización mecanoquímica dentro del miocito. Debido a lo anterior, la proteína desmina ha sido constante foco de investigación en trabajos que estudian sus alteraciones asociadas a daño y atrofia muscular bajo diferentes condiciones. El propósito de la siguiente revisión de la literatura es describir los conceptos básicos de la ultraestructura muscular, enfatizando en el rol de la proteína desmina bajo condiciones de atrofia muscular por desuso y envejecimiento.

Electric acupuncture intervention on the effects of disuse muscular atrophy muscle fiber types of mice / 中国康复医学杂志

Objective:To study the frequency of electrical stimulation affect the atrophy recovery of mouse soleus muscle.Method:Sixty mice,30 of them were randomly divided into blank control group (Con) and atrophy model group (Atro) and validated this model after 1 week.The other 30 mice were randomly divided into three groups:the natural recovery group (Rec),the exercise intervention group (Exer),the electroacupuncture intervention group (Elec) after making them atrophy.Atrophy model group were plaster fixed one week.Natural recovery group was natural fed two weeks after removing the plaster.Exercise intervention group runs 1 hour at 16m/min speed two weeks.EA intervention group were stimulated 15min daily for 2 weeks on hind limb,with pulse duration 0.35ms,frequency 50Hz,for 2 weeks.Frozen sections and Immunofluorescence were used to measure the cross-sectional area of muscle fibers.ATPase staining was used to detect the muscle fiber type changing,and Western Blot to detect soleus muscle Troponin I-SS (TNNI1) and Troponin I-FS (TNNI2) protein expression.Result:The soleus muscle in Atro group showed significant change in cross-sectional area and wet weight compared with Con group(P＜0.01),The expression of TNNI1 and TNNI2 protein was also significantly different from that of Con group (P＜0.05).Compared with the Rec group,the cross-sectional area of slow muscle and fast muscle in the Exer and Elec groups significantly increased (P＜0.05),TNNI1 protein expression significant ly increased (P＜0.01),TNNI2 protein was no significant difference detected(P＞0.05).Conclusion:The middle low frequency electroacupuncture intervention can effectively increase the cross-sectional area of muscle fibers,in particular,increase the TNNI1 and TNNI2 protein expression of slow muscle fibers.It is as effective as exercise intervention to promote recovery of disuse muscular atrophy.

Effects of Exercises on Bone Metabolism and OPG-RANKL-RANK System of Osteoclast Differentiation in Rats with Disuse Osteoporosis / 中国运动医学杂志

Objective To explore the effect of treadmill exercises on disuse osteoporosis and the media effect of OPG-RANKL-RANK system of osteoclast differentiation in the process.Methods Forty six-week-old male Sprague-Dawley rats were randomly divided into a normal control group,a disuse model group,a normal recovery group and an exercise recovery group,each of 10.The normal control group were sacrificed 4 weeks later without receiving any special treatment.The disuse model group were sacrificed after 4 weeks of tail suspension.The normal recovery group were sacrificed after 4 weeks of tail suspension and keeping quiet for 4 weeks.The exercise recovery group were sacrificed after 4 weeks of tail suspension and another 4 weeks of treadmill exercises.The indicators of bone mineral density (BMD),bone histomorphometry,bone tissue TRACP-5b staining,bone metabolism and cytokines related to the osteoclast differentiation OPG-RANKL-RANK system were tested immediately after the rats were sacrificed.Results The BMD,trabecular bone volume percentage (TBV),trabecular bone width (Tb.Wi),concentration of serum alkaline phosphatase (ALP) and the gene expression of bone marrow oculopneumoplethysmograph (OPG) of the disuse model goup were significantly lower than those of the normal control group (P＜0.01),while the trabecular bone spacing (Tb.Sp),average positive staining area percentage (APSAP) of tartrate-resistant acid phosphatase (TRACP)-5b,concentration of serum Ca2+ and TRACP-5b and the gene expression of bone marrow cytokines including RANKL,macrophage colony-stinulating factor (M-CSF),RANK,interleukin (IL)-6 and tumor necrosis factor (TNF)-α of the disuse model goup were significantly higher than those of the normal control group (P＜0.01).The BMD,TBV,Tb.Wi,concentration of serum ALP and the gene expression of bone marrow OPG of the exercise recovery group were significantly higher than those of the normal recovery group (P＜0.05 or P＜0.01).The Tb.Sp,APSAP,concentration of serum Ca2+ and TRACP-5b and the gene expression of RANKL,M-CSF,RANK,IL-6 and TNF-α of the exercise recovery group were significantly lower than those of the normal recovery group (P＜0.05 or P＜0.01).Conclusion The 4-week tail suspension can lead to disuse osteoporosis in rats.Treadmill exercise can promote the recovery of rats with the disuse osteoporosis.The occurrence of disuse osteoporosis and the effect of exercises on disuse osteoporosis were related with the expressing of OPG-RANKL-RANK system-related cytokines of osteoclast differentiation in bone marrow microenvironment.

Micro vibration with the hand nursing methods on the disuse syndrome patients with constipation nursing effect assessment / 中国实用护理杂志

Objective To investigate the micro vibration with the hand nursing methods for disuse syndrome patients constipation curative effect. Methods During the time of March 2016 to September, 76 patients who had long term disuse syndrome with the constipation in two Elderly Care Homes in Urumqi were randomly divided into intervention group (n=37) and control group (n=39), in the experimental group, was treated by manual micro vibration nursing method which included hand micro vibration therapy, exercise therapy, health education guidance once a day, 50 minutes each time, a total of 4 weeks of intervention, while the control group received routine rehabilitation nursing. Before the intervention, intervention after 4 weeks, follow-up period after the end of 8 weeks according to the symptoms of constipation and evaluate the stool frequency. Results Preliminary experimental group and control group patients have different degrees of constipation symptoms, with the hand micro vibration method of nursing intervention, the experimental group had not constipation of symptoms, 17(43.6%) had constipation symptoms in the control group. Compared with the incidence of two groups of constipation patients. Before the intervention, intervention after 4 weeks, follow-up period after the end of 8 weeks, the experimental group patients defecation frequency was (5.33 ± 1.47), (29.70 ± 6.49) , (43.41 ± 6.15)times, The control group patients was(5.77 ± 1.39), (13.10 ± 1.27), (21.15 ± 4.23) time, comparison of the two groups, t=-1.357, 15.275, 18.458, P=0.179, 0.000, 0.000. Conclusions Hand micro vibration nursing method has remarkable effect on relieving constipation, and the treatment effect can be maintained for a long time, no recurrence occurred and adverse reactions, however, this method also economic, convenient, less time consuming and efficient.

The Effects of Inpatient Rehabilitation for Patients with Parkinson's Disease and Parkinsonian Syndrome：The Benefit of Intensive Rehabilitation / The Japanese Journal of Rehabilitation Medicine

<p>Objective：In Parkinson's disease and Parkinsonian syndrome (referred to collectively as PD), the progression of functional decline is influenced by complications such as bone fracture or pneumonia. We aimed to assess the efficiency of short-term inpatient rehabilitation therapy for patients with PD in terms of functional recovery and cost-effectiveness.</p><p>Methods：We investigated differences in outcomes of inpatient rehabilitation for 84 patients with PD, in relation to reasons for hospitalization. Patients with complications, including orthopedic diseases (n＝15), and disuse syndrome (n＝16) received therapy for 3 hours/day in Kaifukuki postacute convalescent rehabilitation wards (KRW) or 2 hours/day in other facilities. Fifty-three patients without complications and thus not eligible for admission to KWR were provided with short-term inpatient rehabilitation therapy (training for 2 hours/day, 6 days/week for 1 month).</p><p>Results：In the patients without complications, the efficiency of FIM (FIM gain/hospital stay) was significantly greater (p＝0.03) and the amount of training and the medical expenses needed to improve the FIM score by 1 point, calculated as total training units (1 unit＝20 minutes of therapy as per the Japanese medical insurance system) divided by FIM gain and total medical cost divided by FIM gain, showed a decreasing trend (p＝0.07, 0.10, respectively) in comparison with that in the patients with complications.</p><p>Conclusion：Short-term inpatient rehabilitation for PD patients without complications is beneficial in terms of rehabilitation efficiency and cost-effectiveness, and appears effective at preventing complications and reducing costs. Reconsideration of the medical insurance system may be necessary so that short-term inpatient rehabilitation can be offered in various facilities, including Kaifukuki wards.</p>

Loss of Ovarian Function Results in Increased Loss of Skeletal Muscle in Arthritic Rats / Perda da função ovariana resulta em perda de músculo esquelético aumentada em ratos artríticos

Objective We studied the effects of loss of ovarian function (ovariectomy) onmuscle mass of gastrocnemius and themRNA levels of IGF-1, atrogin-1, MuRF-1, andmyostatin in an experimental model of rheumatoid arthritis in rats. Methods We randomly allocated 24 female Wistar rats (9 weeks, 195.3±17.4 grams) into four groups: control (CT-Sham; n = 6); rheumatoid arthritis (RA; n = 6); ovariectomy without rheumatoid arthritis (OV; n = 6); ovariectomy with rheumatoid arthritis (RAOV; n = 6). We performed the ovariectomy (OV and RAOV) or Sham (CTSham or RA) procedures at the same time, fifteen days before the rheumatoid arthritis induction. The RA and RAOV groups were immunized and then were injected with Met- BSA in the tibiotarsal joint. After 15 days of intra-articular injections the animals were euthanized. We evaluated the external manifestations of rheumatoid arthritis (perimeter joint) as well as animal weight, and food intake throughout the study. We also analyzed the cross-sectional areas (CSA) of gastrocnemius muscle fibers in 200 fibers (H&E method). In the gastrocnemius muscle, we analyzed mRNA expression by quantitative real time PCR followed by the Livak method (ΔΔCT). Results The rheumatoid arthritis induced reduction in CSA of gastrocnemius muscle fibers. The RAOV group showed a lower CSA of gastrocnemius muscle fibers compared to RA and CT-Sham groups. Skeletal muscle IGF-1 mRNA increased in arthritics and ovariectomized rats. The increased IGF-1 mRNA was higher in OV groups than in the RA and RAOV groups. Antrogin-1 mRNA also increased in the gastrocnemius muscle of arthritic and ovariectomized rats. However, the increased atrogin-1 mRNA was higher in RAOV groups than in the RA and OV groups. Gastrocnemius muscle MuRF-1 mRNA increased in the OVand RAOVgroups, but not in the RA and Shamgroups. However, the RAOV group showed higher MuRF-1 mRNA than the OV group. The myostatin gene expression was similar in all groups. Conclusion Loss of ovarian function results in increased loss of skeletal musclerelated ubiquitin ligases atrogin-1 and MuRF-1 in arthritic rats.

Objetivo Foram estudados os efeitos da perda da função ovariana (ovariectomia) sobre músculo esquelético e os níveis de RNAm de IGF-1, atrogina-1, MuRF-1, e de miostatina em modelo experimental de artrite reumatóide em ratos. Métodos 24 ratos Wistar (9 semanas, 195,3±17,4 gramas) foram distribuídos aleatoriamente em quatro grupos: controle (CT-Sham, n = 6); artrite reumatóide (RA, n = 6); ovariectomia sem artrite reumatóide (OV; n = 6); ovariectomia com artrite reumatóide (RAOV; n = 6). Os procedimentos da ovariectomia (OV e RAOV) ou simulação da ovariectomia (CT-Shamou RA) foramrealizados aomesmo tempo, quinze dias antes da indução da artrite reumatóide. Os grupos RA e RAOV foramimunizados e, em seguida, foram injetados com Met-BSA na articulação tibiotársica. Após 15 dias das injeções intra-articulares, os animais foram eutanasiados. Foram avaliadas as manifestações externas da artrite reumatóide (perimetria articular), bem como o peso dos animais e a ingestão de alimentos ao longo do estudo. Além disso, as áreas de secção transversa (CSA) do músculo gastrocnêmio foram analisadas em 200 fibras (método H & E). No músculo gastrocnêmio, a expressão de RNAm foi analisada por PCR quantitativo em tempo real, seguido pelo método Livak (ΔΔCT). Resultados A artrite reumatoide reduziu a CSA das fibras do músculo gastrocnêmio. O grupo RAOV mostrou uma CSA menor nas fibras do músculo gastrocnêmio em comparação com os grupos RA e CT-Sham. O RNAm do IGF-1 do músculo esquelético aumentou nos ratos artríticos e ovariectomizados. O RNAm do IGF-1 foi maior nos grupos OV do que nos grupos RA e RAOV. A expressão de antrogina-1 também aumentou no músculo gastrocnêmio dos ratos artríticos e ovariectomizados. No entanto, o aumento do RNAm da atrogina-1 foi maior no grupo RAOV do que nos grupos RA e OV. O RNAm da MuRF-1 aumentou nos grupos OV e RAOV, mas não nos grupos RA e CT-Sham. Porém, o grupo RAOV apresentou maior expressão gênica de MuRF-1 do que o grupo OV. A expressão do gene da miostatina foi semelhante em todos os grupos. Conclusão A perda de função ovariana resulta em perda de músculo esquelético associado às ubiquitina-ligases atrogina-1 e MuRF-1 em ratos artríticos.

In Vivo Rodent Models of Skeletal Muscle Adaptation to Decreased Use

Skeletal muscle possesses plasticity and adaptability to external and internal physiological changes. Due to these characteristics, skeletal muscle shows dramatic changes depending on its response to stimuli such as physical activity, nutritional changes, disease status, and environmental changes. Modulation of the rate of protein synthesis/degradation plays an important role in atrophic responses. The purpose of this review is to describe different features of skeletal muscle adaptation with various models of deceased use. In this review, four models were addressed: immobilization, spinal cord transection, hindlimb unloading, and aging. Immobilization is a form of decreased use in which skeletal muscle shows electrical activity, tension development, and motion. These results differ by muscle group. Spinal cord transection was selected to simulate spinal cord injury. Similar to the immobilization model, dramatic atrophy occurs in addition to fiber type conversion in this model. Despite the fact that electromyography shows unremarkable changes in muscle after hindlimb unloading, decreased muscle mass and contractile force are observed. Lastly, aging significantly decreases the numbers of muscle fibers and motor units. Skeletal muscle responses to decreased use include decreased strength, decreased fiber numbers, and fiber type transformation. These four models demonstrated different changes in the skeletal muscle. This review elucidates the different skeletal muscle adaptations in these four decreased use animal models and encourages further studies.

Efeitos da terapia combinada com ácido zoledrônico e propranolol na resistência mecânica em um modelo de rato com osteoporose por desuso / Effect of combined treatment with zoledronic acid and propranolol on mechanical strength in an rat model of disuse osteoporosis

Resumo Objetivos: Investigar os efeitos aditivos do agente antirreabsorção ácido zoledrônico (ZOL), isolado e em combinação ao propranolol (PRO), em um modelo de rato com osteoporose por desuso. Métodos: Usou-se um modelo de pata traseira direita de rato privada de descarga de peso para estudar as consequências da falta de descarga de peso sobre o esqueleto durante várias condições, como missões espaciais e repouso prolongado no leito em idosos. Ratos Wistar machos de três meses de idade foram submetidos à imobilização da pata traseira direita (IPTD) por 10 semanas para induzir à osteopenia; em seguida, foram divididos aleatoriamente em quatro grupos: 1 – IPTD para controle positivo; 2 – IPTD mais ZOL (50 μg/kg, dose única intravenosa); 3 – IPTD mais PRO (0,1 mg/kg, via subcutânea, cinco dias na semana); 4 – IPTD mais PRO (0,1 mg/kg, via subcutânea, cinco dias na semana) mais ZOL (50 μg/kg, dose única intravenosa) por outras 10 semanas. Um grupo de ratos não imobilizados foi usado como controle negativo. No fim do tratamento, os fêmures foram removidos e testaram-se a porosidade do osso e suas propriedades mecânicas, além do peso seco e das cinzas do osso. Resultados: No que diz respeito à melhoria da resistência mecânica da diáfise femoral média, a terapia combinada com ZOL mais PRO foi mais eficaz do que a monoterapia com ZOL ou PRO. Além disso, a terapia combinada com ZOL mais PRO foi mais eficaz na melhoria do peso seco do osso e preservou melhor a porosidade do osso cortical do que a monoterapia com ZOL ou PRO em ratos submetidos à imobilização da pata traseira direita. Conclusões: Esses dados sugerem que a terapia combinada com ZOL mais PRO deve ser recomendada para o tratamento da osteoporose por desuso.

Abstract Objectives: A model that uses right hind-limb unloading of rats is used to study the consequences of skeletal unloading during various conditions like space flights and prolonged bed rest in elderly. This study was aimed to investigate the additive effects of antiresorptive agent zoledronic acid (ZOL), alone and in combination with propranolol (PRO) in a rat model of disuse osteoporosis. Methods: In the present study, 3-month-old male Wistar rats had their right hind-limb immobilized (RHLI) for 10 weeks to induce osteopenia, then were randomized into four groups: (1) RHLI positive control, (2) RHLI plus ZOL (50 μg/kg, i.v. single dose), (3) RHLI plus PRO (0.1 mg/kg, s.c. 5 days per week), (4) RHLI plus PRO (0.1 mg/kg, s.c. 5 days per week) plus ZOL (50 μg/kg, i.v. single dose) for another 10 weeks. One group of non-immobilized rats was used as negative control. At the end of treatment, the femurs were removed and tested for bone porosity, bone mechanical properties, and bone dry and ash weight. Results: With respect to improvement in the mechanical strength of the femoral mid-shaft, the combination treatment with ZOL plus PRO was more effective than ZOL or PRO monotherapy. Moreover, combination therapy using ZOL plus PRO was more effective in improving dry bone weight and preserved the cortical bone porosity better than monotherapy using ZOL or PRO in RHLI rats. Conclusions: These data suggest that this combined treatment with ZOL plus PRO should be recommended for the treatment of disuse osteoporosis.

Efeito combinado do ácido zoledrônico e do alfacalcidol no tratamento da osteoporose por desuso em ratos / Additive effect of zoledronic acid and alfacalcidol in the treatment of disuse osteoporosis in rats

Objetivos: O desuso pelo repouso no leito, pela imobilização de membros ou por missões espaciais provoca a perda óssea rápida. Fez-se este estudo para investigar os efeitos terapêuticos do ácido zoledrônico (ZOL), isoladamente e em combinação ao alfacalcidol (ALF), em um modelo de rato com osteoporose por desuso. Métodos: Ratos Wistar machos de três meses foram submetidos à imobilização da pata traseira direita (IPTD) por 10 semanas para induzir a osteopenia; em seguida, foram divididos em quatro grupos: 1 – IPTD para controle positivo; 2 – IPTD mais ZOL (50 µg/kg, dose única intravenosa); 3 – IPTD mais ALF (0,5 µg/kg, via oral diariamente); 4 – IPTD mais ALF (0,5 µg/kg, via oral diariamente) mais ZOL (50 µg/kg, dose única intravenosa) por outras 10 semanas. Um grupo de ratos não imobilizados foi usado como controle negativo. No fim do tratamento, os fêmures foram removidos e testaram-se a porosidade do osso e suas propriedades mecânicas, além do peso seco e das cinzas do osso. Resultados: A terapia combinada com ZOL mais ALF foi mais eficaz em reduzir a porosidade do osso do que a monoterapia com um dos fármacos administrado isoladamente em ratos submetidos à IPTD. No que diz respeito à melhoria da resistência mecânica da diáfise femoral média, o tratamento combinado com ZOL mais ALF foi mais eficaz do que a monoterapia com um dos fármacos administrado isoladamente. Além disso, a terapia combinada com ZOL mais ALF foi mais eficaz na melhoria do peso seco e das cinzas do osso do que a monoterapia com ZOL ou ALF em ratos submetidos à IPTD. Conclusões: Esses dados sugerem que a terapia combinada com ZOL mais ALF representa uma opção terapêutica potencialmente útil para o tratamento da osteoporose por desuso. .

Objectives: Disuse by bed rest, limb immobilization or space flight causes rapid bone loss. We conducted the present study to investigate the therapeutic effects of zoledronic acid (ZOL), alone and in combination with alfacalcidol (ALF) in a rat model of disuse osteoporosis. Methods: In the present study, 3-month-old male Wistar rats had their right hind-limb immobilized (RHLI) for 10 weeks to induce osteopenia, then were divided into four groups: 1 – RHLI positive control; 2 – RHLI plus ZOL (50 µg/kg, i.v. single dose); 3 – RHLI plus ALF (0.5 µg/kg, oral gauge daily); 4 – RHLI plus ALF (0.5 µg/kg, oral gauge daily) plus ZOL (50 µg/kg, i.v. single dose) for another 10 weeks. One group of non-immobilized rats was used as negative control. At the end of the treatment, the femurs were removed and tested for bone porosity, bone mechanical properties, and bone dry and ash weight. Results: Combination therapy with ZOL plus ALF was more effective in decreasing bone porosity than each drug administered as monotherapy in RHLI rats. With respect to improvement in the mechanical strength of the femoral mid-shaft, the combination treatment of ZOL plus ALF was more effective than each drug administered as a monotherapy. Moreover, combination therapy using ZOL plus ALF was more effective in improving dry bone and ash weight, than single-drug therapy using ZOL or ALF in RHLI rats. Conclusions: These data suggest that combination therapy with ZOL plus ALF represents a potentially useful therapeutic option for the treatment of disuse osteoporosis. .

Immobilization and Disuse Syndrome / The Japanese Journal of Rehabilitation Medicine

Understanding the societal and personal impact of immobilization or disuse syndrome is important in Japan with its large elderly population. The indication of disuse syndrome for rehabilitation was narrowed and the fee for disuse syndrome was set at a low level. Muscle strength decreases at a rate of 2.3 % per day in 40 % of the people. Also, the muscle fractional synthetic rate decreased with 10 days rest. Other functional or morphological changes also occur in the neuromuscular junction and the muscle internal structure. Additionally, we must consider the contribution of muscle to the limitation of joint angle after immobilization. Both elasticity and viscosity increase. Cardiac wall thickness and cardiorespiratory fitness decrease during immobilization. Gravitational dependent lung disease or deep vein thrombosis may occur. The brain is also affected by immobilization, leading to condition of learned non-use. The best solution for immobilization is to be active ; however, we must have a detailed knowledge of the pathophysiology of a patient's disease in order increase their activity level. In an acute hospital setting, prevention of immobilization is crucial. The system used in Japan, whereby therapists are assigned full-time in the ward was introduced in April 2014. Furthermore, even though 20.35% of maximal strength training is effective in atrophied muscles, it is ineffective in trained muscles. Another sticking point is that there is no evidence-based recommendation for range of motion exercise. However, rehabilitation intervention in respirator patients improves their ADL. Prophylaxis of deep vein thrombosis is also very important. And learned non-use of the brain may be diminished by the skillful application of vibrations that makes patients feel that their hand is moving even when it is not. Finally, the mechanism of hibernation may be the key to improving our rehabilitation against immobilization in the future.

An experimental model of disuse in the alveolar rat bone: A histomorphometrical study

Lack of mechanical stimulation is known to cause disuse osteopenia in bones. However, experimental models for disuse osteopenia on bones other than jawbones are not applicable to jawbones. The little available information in this field has been applied to the study of overeruption of teeth lacking antagonists. However, the absence of an antagonist in the opposite jaw means that there is no stimulation by occlusion. Our hypothesis is that the lack of stimulation due to the absence of teeth causes disuse osteopenia in the interradicular bone of the antagonist teeth. Our aim was to develop a model of disuse osteopenia due to the absence of occlusal forces. We used male Wistar rats with 215-230 g body weight, divided into 2 groups: one absolute control group (C) and one experimental group in which the three right lower molars were extracted (E). The left side of the jaw in the experimental group was used as a paired control (PC). The animals were euthanized 7 days after extraction. The jaws were placed in occlusion, fastened and fixed in 10% formalin. The heads were cut in half and radiographs made of both jaws. The upper jaws were processed histologically. After decalcification, bucco-palatine oriented sections were cut at the level of the mesial root and distal roots of the first upper molars. On the radiographs, the distance from the tip of the cusp on the first upper molar to the antagonist edentulous ridge (DA) was measured. On the microphotographs, the following parameters were measured: passive eruption degree (PED), height of periodontal ligament at the level of the furcation (HPL) and interradicular bone volume (BVI). The data were compared statistically using ANOVA and Bonferroni's post-hoc test, considering p<0.05 as statistically significant. DA in experimental animals was 0.34}0.048 mm. PED in experimental animals was significantly greater than in the control groups, both for the buccal plate and for the palatal plate. HPL showed no significant difference between groups. BVI was significantly lower in the experimental group than in the control group. The results showed that the model used produces a condition of disuse osteopenia, shown by the statistically significant reduction in interradicular bone volume. The use of this model at different experimental times will enable the evaluation of cell responses in periodontal tissues, particularly bone tissue, e.g. to compare them to known responses such as the application of orthodontic forces.

Se sabe que la falta de estimulo mecanico produce un cuadro de osteopenia por desuso en huesos de la economia. Los modelos experimentales de osteopenia por desuso utilizados en otros huesos no son aplicables a los huesos maxilares. La escasa informacion que existe en este campo se aplico al estudio de la sobreerupcion de dientes sin antagonista. Sin embargo, la ausencia de antagonista en el maxilar opuesto hace que falte el estimulo de la oclusion. Por tal razon, nuestra hipotesis es que la falta de estimulo por ausencia de piezas dentarias provoca un cuadro de osteopenia por desuso en el hueso interradicular de los dientes antagonistas. Nuestro objetivo fue poner a punto un modelo de osteopenia por desuso debido a la ausencia de fuerzas oclusales. Se emplearon ratas Wistar machos de entre 215-230 g de peso corporal divididas en 2 grupos, un grupo control absoluto (C) y un grupo experimental al que se le extrajeron los tres molares inferiores derechos (E). El lado izquierdo del maxilar del grupo experimental, fue utilizado como control apareado (CA). A los 7 dias de efectuadas las extracciones se realizo la eutanasia de los animales. Los maxilares se colocaron en oclusion, se precintaron y asi ubicados se fijaron en formol 10%. Se dividieron las hemicabezas y tomaron radiografias de ambos maxilares siendo procesados histologicamente los maxilares superiores. Luego de la descalcificacion se obtuvieron cortes orientados en sentido buco-palatino a nivel de la raiz mesial y de las raices distales de los 1o molares superiores. Sobre las radiografias se midio la distancia desde el vertice cuspideo del 1o molar superior al reborde antagonista desdentado (DA), y sobre microfotografias se midieron los siguientes parametros: grado de erupcion pasiva (GE), altura del ligamento periodontal a nivel de la furcacion (ALP) y volumen oseo interradicular (VOI). Los datos se compararon estadisticamente mediante el test ANOVA y prueba post hoc de Bonferroni, considerando una p<0,05 como estadisticamente significativa. La DA en los animales experimentales fue de 0,34}0,048 mm. La GE en los animales experimentales fue significativamente mayor que en los grupos control, tanto a nivel de la tabla vestibular como de la tabla palatina. La ALP no mostro diferencias significativas entre los grupos. El VOi fue significativamente menor en el grupo experimental con respecto a los controles. Los resultados mostraron que el modelo empleado logra una condicion de osteopenia por desuso manifestada por la disminucion del volumen oseo interradicular. La utilizacion de este modelo de desuso a diferentes tiempos experimentales permitira evaluar las respuestas celulares de los tejidos periodontales, especial - mente del tejido oseo, permitiendo por ejemplo, compararlas con respuestas conocidas como la aplicacion de fuerzas ortodoncicas.