Chronic immobilization stress (CIS) induces low levels of glutamate (Glu) and glutamine (Gln) and hypoactive glutamatergic signaling in the mouse prefrontal cortex (PFC), which is closely related to the Glu-Gln cycle. A Gln-supplemented diet ameliorates CIS-induced deleterious changes. Here, we investigated the effects of CIS and Gln supplementation on Glu-Gln cycle-related proteins to characterize the underlying mechanisms. Using the CIS-induced depression mouse model, we examined the expression of 11 proteins involved in the Glu-Gln cycle in the PFC. CIS decreased levels of glutamate transporter 1 (GLT1) and sodium-coupled neutral amino acid transporter (SNAT) 1, SANT2, SNAT3, and SNAT5. Gln supplementation did not affect the non-stressed group but significantly increased GLT1 and SNATs of the stressed group. By immunohistochemical analysis, we confirmed that SNAT1 and SNAT2 were decreased in neurons and GLT1, SNAT3, and SNAT5 were decreased in astrocytes in the medial PFC of the stressed group, but Gln-supplemented diet ameliorated these decrements. Collectively, these results suggest that CIS may cause depressive-like behaviors by decreasing Glu and Gln transportation in the PFC and that a Gln-supplemented diet could prevent the deleterious effects of CIS.
Amino Acid Transport System X-AG ; Amino Acid Transport Systems ; Animals ; Astrocytes ; Depression ; Depressive Disorder ; Diet ; Glutamic Acid ; Glutamine ; Immobilization ; Mice ; Neurons ; Prefrontal Cortex ; Transportation

Cross-leg flaps are a useful reconstructive option for complex lower limb defects when free flaps cannot be performed owing to vessel damage. We describe the use of the extended distally based sural artery flap in a cross-leg fashion for lower extremity coverage in three patients. To maximise the viability of these extended flaps, a delay was performed by raising them in a bipedicled fashion before gradual division of the tip over 5 to 7 days for cross-leg transfer. Rigid coupling of the lower limbs with external fixators was critical in preventing flap avulsion and to promote neovascular takeover. The pedicle was gradually divided over the ensuing 7 to 14 days before full flap inset and removal of the external fixators. In all three patients, the flaps survived with no complications and successful coverage of the critical defect was achieved. One patient developed a grade 2 pressure injury on his heel that resolved with conservative dressings. The donor sites and external fixator pin wounds healed well, with no functional morbidity. The cross-leg extended distally based sural artery flap is a reliable reconstructive option in challenging scenarios. Adequate flap delay, manoeuvres to reduce congestion, and postoperative rigid immobilization are key to a successful outcome.
Arteries ; Bandages ; Estrogens, Conjugated (USP) ; External Fixators ; Free Tissue Flaps ; Heel ; Humans ; Immobilization ; Leg Injuries ; Lower Extremity ; Perforator Flap ; Sural Nerve ; Surgical Flaps ; Tissue Donors ; Wounds and Injuries

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.
Atrophy ; Autophagy ; Calcium ; metabolism ; Caspases ; metabolism ; Connective Tissue ; metabolism ; pathology ; Contracture ; etiology ; metabolism ; pathology ; therapy ; Fibrosis ; Humans ; Immobilization ; adverse effects ; Joints ; Lysosomes ; metabolism ; Matrix Metalloproteinases ; metabolism ; Muscle, Skeletal ; metabolism ; pathology ; Proteasome Endopeptidase Complex ; metabolism ; Proteolysis ; Signal Transduction ; physiology ; Transforming Growth Factor beta1 ; metabolism ; Ubiquitin ; metabolism

immobilization. Oral administration of glucosamine and risedronate improved the degenerative changes of rat knee articular cartilage that follow immobilization. This improvement was more remarkable when both drugs were used in combination.]]>
Administration, Oral ; Adult ; Animals ; Cartilage, Articular ; Chondrocytes ; Collagen ; Collagen Type II ; Glucosamine ; Humans ; Immobilization ; Knee ; Male ; Manikins ; Models, Theoretical ; Osteoarthritis ; Proteoglycans ; Rats ; Risedronate Sodium

PURPOSE: To prevent surgical site complications, many plastic surgeons use the so-called “conventional protocol,” which immobilizes the shoulder and upper arm for 1 month after reconstruction. In an effort to improve the shoulder mobility of patients who received immediate breast reconstruction with tissue expander insertion (TEI), we introduced an early rehabilitation protocol with a short-term immobilization period of 2 weeks. This study aims to compare this early rehabilitation exercise program with the conventional protocol and to determine factors affecting shoulder mobility and quality of life of patients after immediate breast reconstruction. METHODS: A total of 115 patients with breast cancer who underwent reconstructive surgery were retrospectively reviewed. For patients who underwent reconstruction before January 2017, the conventional protocol was followed with immobilization of their shoulder for over 4 weeks. Patients who underwent reconstruction after January 2017 were educated to undergo a self-exercise program after a short-term immobilization period of 2 weeks. We compared shoulder mobility, pain, quality of life, and complications at postoperative 1 and 2 months between the groups. RESULTS: Patients who received early rehabilitation showed greater shoulder flexion and abduction range at postoperative 1 month than those who received the conventional protocol. This increased shoulder abduction range continued until postoperative 2 months. There were no significant surgical site problems in both groups during the 2 months of follow-up. CONCLUSION: To enhance the recovery of shoulder mobility, early rehabilitation with a shorter immobilization period should be recommended to patients with breast cancer undergoing reconstruction surgery with TEI. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03541161
Arm ; Breast Neoplasms ; Breast ; Case-Control Studies ; Female ; Follow-Up Studies ; Humans ; Immobilization ; Mammaplasty ; Mastectomy, Simple ; Plastics ; Quality of Life ; Range of Motion, Articular ; Reconstructive Surgical Procedures ; Rehabilitation ; Retrospective Studies ; Shoulder ; Surgeons ; Tissue Expansion Devices

PURPOSE: To compare the efficacy between cast immobilization and functional treatment using an ankle brace as a treatment for acute lateral ankle sprain. MATERIALS AND METHODS: This study reviewed the medical records of 157 acute ankle sprain patients who were treated between 2009 and 2014. A total of 101 cases were included in this study except for cases with a combined injury, and could not be followed up for eight weeks after the first visit. The patients were divided according to the treatment modality: a cast immobilization group (64 cases) and functional treatment group (37 cases). The clinical outcomes were assessed retrospectively based on the medical records of each group. The residual symptoms, such as pain, swelling, and instability, at three weeks after the primary treatment and at the last visit were compared. RESULTS: The residual pain and instability were significantly common in the functional treatment group at three weeks. Five cases (7.8%) of pain and one case (1.6%) of instability were in the cast group whereas nine cases (24.3%) of pain and six cases (16.2%) of instability in functional treatment group (p=0.021, p=0.014). On the other hand, there was no meaningful difference at the last follow-up. Residual pain, swelling, and instability at the last visit were noted in three (4.7%), six (9.4%), and four cases (6.3%) in the cast group, and three (8.1%), three (8.1%), and three (8.1%) were observed in the functional treatment group. Six patients refused cast immobilization. CONCLUSION: Although there was no significant difference at the last follow-up, cast immobilization appears to be more effective than a functional brace in terms of early pain relief and early restoration of ankle stability as a treatment for acute ankle lateral sprain in this study.
Ankle Injuries ; Ankle ; Braces ; Follow-Up Studies ; Hand ; Humans ; Immobilization ; Medical Records ; Retrospective Studies ; Sprains and Strains

BACKGROUND: Recently, a new generation of gamma knife radiosurgery (GKRS) equipped with a frameless immobilization system has encouraged the use of fractionated GKRS as an increasingly favorable treatment option. We investigated the preliminary outcome of efficacy and toxicity associated with frameless fractionated gamma knife radiosurgery (FF GKRS) for the treatment of large metastatic brain tumors. METHODS: Fifteen patients with 17 lesions were treated using FF GKRS and included in this study, because of the large tumor size of more than 10 cm3. FF GKRS was performed based on a thermoplastic mask system for 3 to 5 consecutive days. RESULTS: The mean duration of clinical follow-up was 12 months (range, 4–24), and the local control rate was 100%. Tumor volume decreased in 13 lesions (76.5%), and remained stable in 4 lesions (23.5%). One patient was classified as new lesion development because of the occurrence of leptomeningeal seeding regardless of the tumor volume change. Compared with the initial volume at the time of FF GKRS, tumor volume change at the last follow-up was 62.32% ± 29.80%. Cumulative survival rate at 12 months was 93.3% ± 6.4%. One patient died during the follow-up period because of the progression of the primary disease. No patient showed radiation necrosis on the follow-up images. CONCLUSION: Daily FF GKRS by gamma knife ICON™ revealed satisfactory tumor control rate and low morbidity, despite the short follow-up period. Further prospective studies and a longer follow-up of a large cohort of patients diagnosed with brain metastases are required to elucidate the effect of FF GKRS in brain metastases.
Brain Neoplasms ; Brain ; Cohort Studies ; Follow-Up Studies ; Humans ; Immobilization ; Masks ; Necrosis ; Neoplasm Metastasis ; Prospective Studies ; Radiosurgery ; Survival Rate ; Tumor Burden

BACKGROUND: Rhabdomyolysis is a syndrome caused by injury to skeletal muscle and characterized by myalgia and swelling of the affected muscles. Peripheral nerve injury rarely occurs in patients with rhabdomyolysis. METHODS: We reviewed the medical records of 8 consecutive patients with peripheral neuropathies associated with rhabdomyolysis. We assessed the clinical characteristics and electrodiagnostic findings of eight patients. RESULTS: In seven patients, rhabdomyolysis occurred after prolonged immobilization. In one patient, blunt trauma was a cause of rhabdomyolysis. All patients presented with weakness and paresthesia in lower extremities and electrodiagnostic tests showed peripheral nerve injury suggesting sciatic neuropathy or lumbosacral plexopathy. Although rhabdomyolysis itself recovered completely in all patients, neurologic deficits from neuropathy recovered partially and slowly. CONCLUSIONS: Sciatic nerve or lumbosacral plexus was injured in all eight patients. Among the various causes of rhabdomyolysis, prolonged immobilization is associated with development of peripheral neuropathy.
Electrodiagnosis ; Humans ; Immobilization ; Lower Extremity ; Lumbosacral Plexus ; Medical Records ; Muscle, Skeletal ; Muscles ; Myalgia ; Neurologic Manifestations ; Paresthesia ; Peripheral Nerve Injuries ; Peripheral Nervous System Diseases ; Rhabdomyolysis ; Sciatic Nerve ; Sciatic Neuropathy

In the present study, the productions of antinociception induced by acute and chronic immobilization stress were compared in several animal pain models. In the acute immobilization stress model (up to 1 hr immobilization), the antinociception was produced in writhing, tail-flick, and formalin-induced pain models. In chronic immobilization stress experiment, the mouse was enforced into immobilization for 1 hr/day for 3, 7, or 14 days, then analgesic tests were performed. The antinociceptive effect was gradually reduced after 3, 7 and 14 days of immobilization stress. To delineate the molecular mechanism involved in the antinociceptive tolerance development in the chronic stress model, the expressions of some signal molecules in dorsal root ganglia (DRG), spinal cord, hippocampus, and the hypothalamus were observed in acute and chronic immobilization models. The COX-2 in DRG, p-JNK, p-AMPKα1, and p-mTOR in the spinal cord, p-P38 in the hippocampus, and p-AMPKα1 in the hypothalamus were elevated in acute immobilization stress, but were reduced gradually after 3, 7 and 14 days of immobilization stress. Our results suggest that the chronic immobilization stress causes development of tolerance to the antinociception induced by acute immobilization stress. In addition, the COX-2 in DRG, p-JNK, p-AMPKα1, and p-mTOR in the spinal cord, p-P38 in the hippocampus, and p-AMPKα1 in the hypothalamus may play important roles in the regulation of antinociception induced by acute immobilization stress and the tolerance development induced by chronic immobilization stress.
Animals ; Diagnosis-Related Groups ; Ganglia, Spinal ; Hippocampus ; Hypothalamus ; Immobilization ; Mice ; Spinal Cord

BACKGROUND: Bone marrow oedema (BMO) in children/adolescents is a rare clinical condition without an etiologic cause. It is associated with typical increased signal intensity on T2-weighted magnetic resonance images (MRI) and an increase in bone turnover in which vitamin D plays a pivotal role. No treatment guidelines for these young patients are to date available.METHODS: We performed a retrospective study in a pediatric setting of 13 patients with diagnosis of primary BMO of the foot on the basis of clinical and radiological findings. Data collection included sex, age, patient history, symptoms at presentation, clinical examination, laboratory bone turnover markers, vitamin D levels, MRI, treatment, and outcome.RESULTS: Vitamin D deficiency or insufficiency was found in 76.9% of cases. All patients were treated with adequate vitamin D daily intake, a short course of analgesic therapy, physical therapy, avoiding detrimental feet and ankle immobilization. All fully recovered in 3-month lag period.CONCLUSIONS: Our data highlight that environmental factors, such as underestimated articular or bone microtraumatisms, as well as joint hyper mobility, in a bone turnover milieu of vitamin D deficiency could be the cause of this clinical conditions. Adequate vitamin D supplementation, associated with physical and analgesic therapy, is crucial in the management of BMO.
Adolescent ; Ankle ; Bone Marrow ; Bone Remodeling ; Child ; Data Collection ; Diagnosis ; Foot ; Humans ; Immobilization ; Joints ; Magnetic Resonance Imaging ; Retrospective Studies ; Vitamin D Deficiency ; Vitamin D ; Vitamins