Tamarind seed polysaccharide: a 28-day dietary study in Sprague-Dawley rats.

Forty male and 40 female Crl:SD® CD® IGS rats were fed diets containing 0, 40,000, 80,000, or 120,000 ppm tamarind seed polysaccharide (equivalent to 3450.8, 6738.9, or 10 597.1 mg/kg bw/day and 3602.1, 7190.1, or 10,690.7 mg/kg bw/day for males and females, respectively) for 28 days. Animals were observed for adverse clinical signs, body weight, feed consumption, hematology and clinical chemistry parameters, urinalysis values were recorded, and at the end of the study the rats underwent a full necropsy. Functional Observational Battery (FOB) and Motor Activity (MA) tests were performed on all animals. There were no mortalities, no clinical or ophthalmologic signs, body weight, body weight gain, food consumption and food efficiency, FOB or MA findings associated with the administration of tamarind seed polysaccharide. Initial statistically significant decreases in body weight gain and food consumption resolved after the first week and were considered the result of reduced palatability. There were no adverse changes in hematology, coagulation, clinical chemistry or urinalysis parameters in male or female rats considered the result of test substance administration. At necropsy, there were no macroscopic, histopathological findings, estrus cycle, or organ weight changes deemed related to administration of the test substance. Under the conditions of this study and based on the toxicological endpoints evaluated, the no-observed-adverse-effect level (NOAEL) for tamarind seed polysaccharide in the diet was the highest concentration tested of 120,000 ppm (equivalent to 10,597 mg/kg bw/day and 10,691 mg/kg bw/day for male and female rats, respectively).

Subchondral cysts in dysplastic osteoarthritic hips communicate with the joint space: analysis using three-dimensional computed tomography.

INTRODUCTION: Bone cyst formation in hips increases as osteoarthritis worsens. Although bone cysts in hips have been described in many studies, their etiology remains unclear and under debate. The purpose of this study was to investigate the communication between a bone cyst and the joint space, as well as the relationship between the severity of osteoarthritis and the formation of subchondral bone cysts in dysplastic hips. METHOD: We studied bone cysts from 150 dysplastic hips in 97 patients by computed tomography (CT) and plain radiography. We investigated the distribution of the bone cysts and the presence or absence of a communication path between the cysts and the joint space by three-dimensional (3D) CT. RESULT: Of the 150 hips, 94 acetabula and 55 femoral heads were found to contain cysts. Of the 94 hips containing acetabular cysts, 89 and 5 hips showed black lines and gray lines connecting the cyst and the joint space, respectively, on 3D-CT. The rate of cyst presentation in the hip increased as the joint space became narrower. The number of hips that possessed cysts in the anterior and/or middle portion was significantly higher than that in the posterior portions. CONCLUSION: Bone cysts in dysplastic osteoarthritic hips were found to communicate with the joint space in all cases. This suggests that the formation and enlargement of the cysts in dysplastic hips may be greatly influenced by the joint fluid. Cyst formation was initially observed in the anterior acetabulum, gradually progressing to involve the entire joint, including the posterior acetabulum and the femoral head, with worsening of the osteoarthritis.

Location of intrapelvic vessels around the acetabulum assessed by three-dimensional computed tomographic angiography: prevention of vascular-related complications in total hip arthroplasty.

BACKGROUND: During total hip arthroplasty (THA), the external iliac, femoral, and obturator vessels are at risk of vascular injury when penetrating the inner cortex of the pelvis. The purpose of this study was to clarify the location of these vessels using three-dimensional computed tomographic angiography (3DCT-A). METHODS: We enrolled 100 subjects (200 hips) without hip disease and performed examinations on the following. (1) External iliac-femoral vessels: we measured the shortest distance from these vessels to the pelvis on axial CT images and investigated the factors affecting distance. The anatomical course of the iliac artery was classified as straight, curved, or tortuous, and the correlation between course and age was established. (2) Obturator vessels: we measured the shortest distance from the obturator vessels to the quadrilateral surface on axial CT images. (3) Visualization of pelvic vessels was through the pelvis by dual-phase 3DCT-A. RESULTS: (1) The external iliac vein was located significantly closer to the pelvis than the artery, especially on the left side and in aged and female subjects. The single-curved and tortuous double-curved vessel types were found in aged subjects, and external iliac vessels of these types were closer to the pelvis than vessels of the straight type. In 36 subjects, the external iliac veins lay directly on the osseous surface of the pelvis (right 16, left 36). Of these 36 subjects, only one had straight-type vessels. (2) Obturator vessels were located just behind the acetabulum near the obturator foramen. (3) Reconstructed 3DCT images enabled us to visualize the pelvic vessels and demonstrated the danger area for penetrating the inner cortex of the pelvis. CONCLUSION: Understanding the anatomical orientation of the pelvic vessels around the acetabulum using 3DCT-A could be helpful for preventing vascular injury during THA.

An anterolateral dislocated monteggia lesion with plastic lateral bowing of the ulna associated with ipsilateral epiphyseal fracture of the distal radius: a case report with 4 years of follow-up.

We encountered a rare presentation of anterolateral dislocation of the radial head with plastic lateral bowing of the ulna associated with ipsilateral epiphyseal fracture of the distal radius in a child. The patient was treated surgically and reached skeletal maturity 4 years later with no functional or growth deficiency.

A three-dimensional method for evaluating changes in acetabular osteolytic lesions in response to treatment.

UNLABELLED: The treatment of asymptomatic osteolysis among well-fixed cementless cups remains controversial. To compare the effectiveness of different treatment strategies, an objective technique for evaluating bone remodeling would be useful. By matching and comparing serial CT images with the aid of a computer-assisted imaging program, we developed a method to evaluate three-dimensional mineralization changes within osteolytic defects. Preoperative, immediate postoperative, and followup CT images were normalized based on a phantom with known densities and matched using image registration so that the same region could be analyzed on each image. New bone mineralization within the preoperative osteolytic lesion volume was quantified based on a patient-specific trabecular bone density threshold. As a pilot study, we applied this technique in 10 patients treated by polyethylene liner exchange with débridement and grafting of periacetabular osteolytic lesions using a calcium sulfate bone graft substitute. Relative to the preoperative osteolytic lesion volume, an average of 43% (range, 8%-72%) of each defect was filled with graft at revision. After resorption of the graft, an average of 24% (range, 9%-44%) of the original defect volume demonstrated evidence of new mineralization at 1-year followup. The amount of new mineralization was directly proportional (r(2) = 0.70) to the defect filling achieved at revision. CT-based image analysis offers an objective method for quantifying three-dimensional bone remodeling and can be used to evaluate the effectiveness of osteolysis treatment strategies. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Gustilo Type III Open and Comminuted Tibial Fractures Managed by Simultaneous Combination of a Free Latissimus Dorsi Muscle Flap and Ilizarov External Fixation: A Case Report.

CASE: A 70-year-old woman who sustained Gustilo type III open and comminuted tibial fractures presented with extensive soft-tissue defect. Definitive surgery was performed using a free latissimus dorsi muscle flap for the extensive soft-tissue defect and Ilizarov external fixation (IEF) to stabilize the fractures and arthrodese the ankle. Ankle arthrodesis was accomplished by the wires penetrating the implanted muscle flap. CONCLUSION: The combined free flap and IEF management protocol described in this report was effective in achieving early weight-bearing and prompt bone healing in an elderly patient with poor bone quality and extensive open and comminuted fractures.

Insufficient Postoperative Rehabilitation in Patients with Both Proximal Femoral Fracture and Antecedent Mental Illness.

INTRODUCTION: Though a combination of proximal femoral fracture and mental illness is likely, the management of this combination is not well established. The aim of this study was to clarify the current disposition of acute care and rehabilitation for patients with this combination of conditions at our institution. METHODS: We retrospectively analyzed the records of 192 patients hospitalized in the psychiatric ward who present with a proximal femoral fracture and an antecedent mental illness. We investigated walking ability prior to injury and after surgery, at discharge from our institution, using the Functional Independence Measure (FIM) score. RESULTS: Although patients in the psychiatric ward demonstrated postoperative hospital stays approximately 10 days longer than those in the orthopedic ward, more than half of the patients in the psychiatric ward were discharged from our institution with a functional level of complete dependence for walking ability. In addition, nearly 90% of the patients studied were transferred to a psychiatric hospital where no physical therapy or rehabilitation was provided to the inpatients. CONCLUSIONS: At our institution, patients with proximal femoral fracture and antecedent mental illness tended to be discharged with complete dependence in walking ability, often to a psychiatric hospital without physical therapy or rehabilitation. We hope this paper will draw attention to the need for rehabilitation in these patients.

Can the volume of pelvic osteolysis be calculated without using computed tomography?

UNLABELLED: The most common method to diagnose and monitor osteolysis is the standard anteroposterior radiograph. Unfortunately, plain radiographs underestimate the incidence and extent of osteolysis. CT scans are more sensitive and accurate but also more expensive and subject patients to more radiation. To determine whether the volume of pelvic osteolysis could be accurately estimated without a CT scan, we evaluated the relationships between CT volume measurements and other variables that may be related to the size of pelvic osteolytic lesions in 78 THAs. Only the area of pelvic osteolysis measured on radiographs, heavy patient activity level, and total volume of wear were associated with the pelvic osteolysis volume measured on CT in the context of the multivariate regression analysis. Despite a strong correlation (r = 0.93, r(2) = 0.87) between these three variables and the volume of pelvic osteolysis measured on CT, estimates of pelvic osteolysis volume deviated from the actual volume measured on CT by more than 10 cm(3) among eight of the 78 THAs in this study. CT images remain our preferred modality when accurate assessments of pelvic osteolysis volume are required. LEVEL OF EVIDENCE: Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

Computed tomography assessment of pelvic osteolysis and cup-lesion interface involvement with a press-fit porous-coated acetabular cup.

We used computed tomography to investigate the 3-dimensional pattern of expansile osteolysis that occurs with a modular cementless acetabular component incorporating a central hole. We measured pelvic osteolysis volume and evaluated how much of the porous-coated surface area was involved with osteolytic defects. Among the 34 total hip arthroplasties we studied, osteolysis almost always originated from the dome hole and typically expanded inferiorly or superiorly without involving the anterior or posterior surfaces of the cup. Larger-volume lesions generally involved greater amounts of the cup surface area, but the cup-lesion interface involvement plateaued at 40% for radiographically stable cups without clinical complications. We hypothesize that the plateauing surface area involvement may explain the absence of cup loosening among these cases despite the presence of large osteolytic lesions.

Arthroplasty using a custom-made cemented total hip prosthesis for an extensive giant cell tumor of the proximal femur: report of a patient followed up for over 30 years.

We report the case of a 26-year-old man who had a pathologic transtrochanteric fracture of the left femur due to a grade II giant cell tumor affecting the neck and the trochanteric area. This patient underwent complete resection of the tumor and arthroplasty using a custom-made cemented total hip prosthesis. The good radiologic and functional results of the surgery have been maintained for over 30 years without local recurrence or lung metastasis. Moreover, new bone formation was observed at the reattachment sites of abductors, iliopsoas tendons and vastus lateralis to the femoral component of the prosthesis although local bone resorption was detected at the upper lateral part of the femoral stem and zone I of the cup side.

Two Years of Follow-up Magnetic Resonance Imaging for Osteochondral Injury of the Lateral Femoral Condyle in an Adolescent Basketball Player.

Chondral and osteochondral injuries of the femoral condyle are rare, and relatively few cases have been reported. Therefore, the mechanism, treatment, and findings on follow-up of these injuries are not well described. Here, we report the case of an adolescent basketball player who sustained a sports-related traumatic osteochondral injury of the lateral femoral condyle. He was treated with open reduction and internal fixation with the pull-out suture technique. Two years later, he was able to resume sporting activities at his pre-injury level with no symptoms. Magnetic resonance imaging (MRI) confirmed survival of the fixed osteochondral fragment and restoration of the congruity of the articular cartilage with no sign of delamination. This report describes the clinical outcome of this osteochondral injury of the lateral femoral condyle as seen on MRI at the 2-year follow-up and discuss the mechanism and treatment of this injury. J. Med. Invest. 66 : 213-217, February, 2019.

MicroRNA-130b functions as an oncomiRNA in non-small cell lung cancer by targeting tissue inhibitor of metalloproteinase-2.

Non-small cell lung cancer (NSCLC) is the most frequent cause of cancer-related death worldwide. Although many molecular-targeted drugs for NSCLC have been developed in recent years, the 5-year survival rate of patients with NSCLC remains low. Therefore, an improved understanding of the molecular mechanisms underlying the biology of NSCLC is essential for developing novel therapeutic strategies for the treatment of NSCLC. In this study, we examined the role of miR-130b in NSCLC. Our results showed that high expression of miR-130b in clinical specimens was significantly associated with poor overall survival in patients with NSCLC. Moreover, miR-130b expression was significantly increased in NSCLC clinical specimens from patients with vascular and lymphatic invasion. Consistent with this, overexpression of miR-130b promoted invasion and matrix metalloproteinase-2 (MMP-2) activity in A549 cells. Argonaute2 immunoprecipitation and gene array analysis identified tissue inhibitor of metalloproteinase-2 (TIMP-2) as a target of miR-130b. Invasion activity promoted by miR-130b was attenuated by TIMP-2 overexpression in A549 cells. Furthermore, TIMP-2 concentrations in serum were inversely correlated with relative miR-130b expression in tumor tissues from the same patients with NSCLC. Overall, miR-130b was found to act as an oncomiR, promoting metastasis by downregulating TIMP-2 and invasion activities in NSCLC cells.

Continuous infusion of PTH1-34 delayed fracture healing in mice.

Hyperparathyroidism, which is increased parathyroid hormone (PTH) levels in the blood, could cause delayed or non-union of bone fractures. But, no study has yet demonstrated the effects of excess continuous PTH exposure, such as that seen in hyperparathyroidism, for fracture healing. Continuous human PTH1-34 (teriparatide) infusion using an osmotic pump was performed for stabilized tibial fractures in eight-week-old male mice to determine the relative bone healing process compared with saline treatment. Radiographs and micro-computed tomography showed delayed but increased calcified callus formation in the continuous PTH1-34 infusion group compared with the controls. Histology and quantitative histomorphometry confirmed that continuous PTH1-34 treatment significantly increased the bone callus area at a later time point after fracture, since delayed endochondral ossification occurred. Gene expression analyses showed that PTH1-34 resulted in sustained Col2a1 and reduced Col10a1 expression, consistent with delayed maturation of the cartilage tissue during fracture healing. In contrast, continuous PTH1-34 infusion stimulated the expression of both Bglap and Acp5 through the healing process, in accordance with bone callus formation and remodeling. Mechanical testing showed that continuously administered PTH1-34 increased the maximum load on Day 21 compared with control mice. We concluded that continuous PTH1-34 infusion resulted in a delayed fracture healing process due to delayed callus cell maturation but ultimately increased biomechanical properties.

Distinct expression of mast cell tryptase and protease activated receptor-2 in synovia of rheumatoid arthritis and osteoarthritis.

The objective of this study is to examine the differential expression of mast cell tryptase and its receptor, protease-activated receptor-2 (PAR-2), in the synovium and synovial fluid of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Biochemical and immunohistochemical analyses were performed to determine whether the trypsin-like protease in the synovium is identical to mast cell tryptase. The effects of mast cell tryptase on the proliferation of synovial fibroblast-like cells (SFCs) and the release of IL-8 thereof were evaluated by the [3H]-thymidine incorporation and ELISA, respectively. The trypsin-like protease in the synovium of RA patients was identical to human mast cell tryptase, which was composed of two subunits: 33 and 34 kDa. The 33- and 34-kDa proteins are different glycosylated forms of the 31-kDa protein, which was unglycosylated. Mast cell tryptase activity in RA synovial fluid was significantly higher than that in OA synovial fluid, while their activities and expression in the synovium were similar. Expression of PAR-2 mRNA in the synovium was higher in RA than in OA. Mast cell tryptase containing the unglycosylated 31-kDa subunit was the predominant form in synovial fluid. RA patients had higher amounts of this subunit in their synovial fluid than OA patients. Mast cell tryptase and PAR-2 activating peptide stimulated the proliferation of SFCs and release of IL-8 from these cells. Mast cell tryptase secretion into RA synovial fluid is higher than OA synovial fluid. Mast cell tryptase in synovial fluid stimulates the proliferation of SFCs and the release of pro-inflammatory cytokines via PAR-2, which may contribute to exacerbation of synovitis in RA.

Corrective Osteotomy of Malunited Diaphyseal Fractures of the Forearm Simplified Using 3-Dimensional CT Data: Proposal of Our Simple Strategy Through Case Presentation.

BACKGROUND: Reconstruction of malunited diaphyseal fractures of the forearm is one of the most difficult treatments due to its complicated structure. Widespread usage of Digital Imaging and Communications in Medicine (DICOM) data of 3-dimensional (3D) computed tomography (CT) and 3D printing can make estimating the true plane of the deformity easy. METHODS: A 21-year-old man with limited supination due to left forearm nonunion deformity initially treated by locking plate fixation was referred to our hospital. We evaluated the deformity by superimposing the mirror image bone model of the contralateral normal bone onto a model of the affected bone and 3D real full-scale bone model. RESULTS: The patient underwent a manual corrective osteotomy according to our planning. He had satisfactory improvement of his symptoms with no complications. CONCLUSIONS: We postulated that our simple preoperative simulation and manual osteotomy with the aid of 3D CT reconstruction and 3D real full-scale bone model fit in the clinical practice as a recent trend.

The alpha 2 type IX collagen gene tryptophan polymorphism is not associated with rheumatoid arthritis in the Japanese population.

The aim of this study was to investigate whether the alpha 2 type IX collagen (COL9A2) polymorphism that introduces tryptophan residue into the collagen triple-helix is a marker of susceptibility to, or severity of, rheumatoid arthritis (RA). The study included 749 Japanese patients with RA. One hundred twenty-four unrelated healthy individuals served as the control subjects. The relationship between the COL9A2 gene polymorphism and clinical manifestations of RA was evaluated. For the number of subjects positive for COL9A2 tryptophan polymorphism, there was no statistically significant difference between RA patients and normal controls. Furthermore, we did not detect any association of COL9A2 tryptophan polymorphism with disease status, least erosive subset, more erosive subset, or mutilating disease. The lack of association of COL9A2 tryptophan polymorphism with RA and the clinical findings in our study implies that the polymorphism may not function as a candidate gene marker for screening RA patients.

The miR-130 family promotes cell migration and invasion in bladder cancer through FAK and Akt phosphorylation by regulating PTEN.

Bladder cancer causes an estimated 150,000 deaths per year worldwide. Although 15% of the recurrent bladder cancer becomes an invasive type, currently used targeted therapy for malignant bladder cancer is still not efficient. We focused on the miR-130 family (miR-130b, miR-301a, and miR-301b) that was significantly upregulated in bladder cancer specimens than that of the normal urothelial specimens. We analyzed the functional significance of miR-130 family using a 5637 bladder cancer cell line and revealed that miR-130 family of inhibitors suppressed cell migration and invasion by downregulating focal adhesion kinase (FAK) and Akt phosphorylation. Mechanistic analyses indicate that the miR-130 family directly targets phosphatase and tensin homolog deleted from chromosome 10 (PTEN), resulting in the upregulation of FAK and Akt phosphorylation. In clinical bladder cancer specimens, downregulation of PTEN was found to be closely correlated with miR-130 family expression levels. Overall, the miR-130 family has a crucial role in malignant progression of bladder cancer and thus the miR-130 family could be a promising therapeutic target for invasive bladder cancer.

Outcome of an elbow check-up system for child and adolescent baseball players.

PURPOSE: Our aim was to examine the outcome of an elbow check-up system for youth baseball players. In particular, we investigated the nature of elbow injuries in youth baseball players with elbow pain and ultrasonographic findings of the capitellum. MATERIALS AND METHODS: A total of 1605 players participating in the regional summer championship in July 2013 underwent a questionnaire survey, physical examination, ultrasound imaging, and radiographic examination. RESULTS: A total of 499 (31.1%) players reported episodes of elbow pain, of whom 320 (64.1%) had abnormal findings on physical examination, and 115 (35.9%) agreed to undergo radiography. Among them, 98 (85.2%) exhibited radiographic abnormalities. On the initial ultrasonography screening, 60 (3.7%) players had an abnormal finding and 55 (91.7%) agreed to undergo radiography. Among them, 26 (47.3%) were found to have osteochondritis dissecans (OCD) of the capitellum on radiographs. CONCLUSIONS: About 30% of youth baseball players had episodes of elbow pain, and 64.1% of players with elbow pain had abnormal findings on physical examination. Furthermore, 85.2% of subjects who underwent radiographic examination exhibited radiographic abnormalities. About 4% of young baseball players had an abnormal finding on initial ultrasonography screening, and nearly 50% of them had OCD of the capitellum on radiographs. J. Med. Invest. 63: 171-174, August, 2016.

miR-629 Targets TRIM33 to Promote TGFß/Smad Signaling and Metastatic Phenotypes in ccRCC.

UNLABELLED: Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney, and clear cell RCC (ccRCC) represents its most common histological subtype. To identify a therapeutic target for ccRCC, miRNA expression signatures from ccRCC clinical specimens were analyzed. miRNA microarray and real-time PCR analyses revealed that miR-629 expression was significantly upregulated in human ccRCC compared with adjacent noncancerous renal tissue. Functional inhibition of miR-629 by a hairpin miRNA inhibitor suppressed ccRCC cell motility and invasion. Mechanistically, miR-629 directly targeted tripartite motif-containing 33 (TRIM33), which inhibits the TGFß/Smad signaling pathway. In clinical ccRCC specimens, downregulation of TRIM33 was observed with the association of both pathologic stages and grades. The miR-629 inhibitor significantly suppressed TGFß-induced Smad activation by upregulating TRIM33 expression and subsequently inhibited the association of Smad2/3 and Smad4. Moreover, a miR-629 mimic enhanced the effect of TGFß on the expression of epithelial-mesenchymal transition-related factors as well as on the motility and invasion in ccRCC cells. These findings identify miR-629 as a potent regulator of the TGFß/Smad signaling pathway via TRIM33 in ccRCC. IMPLICATIONS: This study suggests that miR-629 has biomarker potential through its ability to regulate TGFß/Smad signaling and accelerate ccRCC cell motility and invasion.

Medial patellofemoral ligament reconstruction for patellar dislocation due to rupture of the medial structures after total knee arthroplasty: a case report and review of the literature.

Patellar dislocation is a well-recognized major complication after total knee arthroplasty (TKA). Treatment of this injury is determined according to the cause of the dislocation. In particular, proximal realignment, distal realignment, and lateral retinaculum release are options if patellar instability is not caused by prosthetic malposition. Here we report a case of patellar dislocation following TKA due to rupture of the medial structures that was treated by medial patellofemoral ligament reconstruction and lateral retinacular release. In addition, we provide a brief review of the related literature.