Methylene blue prevents osteoarthritis progression and relieves pain in rats via upregulation of Nrf2/PRDX1.

Oxidative stress-related cartilage degeneration, synovitis, and joint pain play vital roles in the progress of osteoarthritis (OA). Anti-oxidative stress agents not only prevent structural damage progression but also relieve OA-related pain. In this study, we investigated the therapeutic effect of methylene blue (MB), a classical and important anti-oxidant with strong neural affinity. Experimental OA was established in rats by radial transection of medial collateral ligament and medial meniscus (MCLT + MMT) of the right knee joint. The OA rats received intra-articular injection of MB (1 mg/kg) every week starting one week after surgery. We showed that MB administration exerted significant cartilage protection, synovitis inhibition as well as pain relief in OA rats. In human chondrocytes and fibroblast-like synoviocytes, MB significantly attenuated tert-butyl hydroperoxide (TBHP)-induced inflammatory response and oxidative stress. We demonstrated that these effects of MB resulted from dual targets of important antioxidant enzymes, Nrf2 and PRDX1, which also mutually reinforcing and participated in an interaction. Furthermore, we found that calcitonin gene-related peptide (CGRP), a neural inflammatory mediator, was accumulated around the vessel in synovium and subchondral bone in OA rats and in TBHP-treated primary cortical neurons; MB administration significantly inhibited CGRP expression through upregulation of Nrf2 and PRDX1. Taken together, these results suggest that MB ameliorates oxidative stress via Nrf2/PRDX1 regulation to prevent progression and relieve pain of OA.

A Safe and Efficient Strategy for the Rapid Elimination of Blood Lead In†Vivo Based on a Capture-Fix-Separate Mechanism.

Lead poisoning is an important problem because of its serious effects on human health. Yet a solution is not available due to an incomplete understanding of the state of lead ions in blood. Since most blood lead binds to hemoglobin (Hb) in red blood cells, identifying and capturing lead-contaminated Hb in RBCs is important. Herein, a magnetic blood lead remover with hyperbranched poly(amidoamine)s (HPAM) as template/co-adsorbent and core-shell mesoporous structure was synthesized. Lead-containing Hb was selectively captured and then fixed by mesoporous channels. The magnetic separation technology was used to separate the magnetic remover from blood. A related blood lead clean-up apparatus was used to remove lead from the blood of a pig in vivo. Results of physical/chemical characterizations, biocompatibility experiments, animal tests, and theoretical simulation verify the safety and efficiency of this removal strategy and the high efficiency of the blood lead clean-up apparatus.

[Revision total hip arthroplasty using a cementless prosthesis].

OBJECTIVE: To assess the operative technique and results with the usage of cementless prosthesis in hip revision. METHODS: Retrospective study was done on revision of total hip arthroplasty with cementless prosthesis in 72 patients (41 males and 31 females) with an average age of 65.7 years (28-82 years) from January 2004 to December 2009. The reason for revision was 2 infection, 54 aseptic loosening, 4 periprosthetic fractures, 5 fracture of femoral stems and 7 cases of acetabular abrasion after hemi-arthroplasty. The operation time, bleeding loss, complications of infection, dislocation, periprosthetic fractures and loosening were evaluated. The Harris score were used for hip function evaluation. RESULTS: The average operation time was (146±47) minutes (70-280 minutes) and bleeding loss during the operation was (970±540) ml (200-2500 ml). Bacterium cultivation during operation demonstrated infection in 2 patients. Bone windows at the lateral femoral were opened in 4 patients and extend trochanteric osteotomy was done in 7 patients. Fracture of the proximal femur occurred in 8 cases. Twenty-nine patients were treated with bone graft including 18 autografts and 11 allografts. Sixty-seven patients were followed up for an average time of 66 months (20-92 months). Additional revisions were performed in 3 cases including 2 dislocations and 1 infection. There were no death, no damage of major blood vessels and nerves. The bone graft healed during 3-5 months. The survival rates of the femoral prosthesis and the acetabulum prostheses were 95.5% and 98.4%. The mean Harris score was 86±8 (55-95 points). Osteolysis were seen in 13 hips but migration was seen in only 1 patient. CONCLUSIONS: The cementless prosthesis is useful in revision total hip arthroplasty and the perfect clinical results are related to the reliable primary fixation.

Extracorporeal shock wave treatment in nonunions of long bone fractures.

We reviewed the clinical results of the past 7 years in order to investigate the effect of extracorporeal shock wave therapy (ESWT) in nonunions of long bone fracture. Sixty-nine patients with 69 nonunions (22 femora, 28 tibiae, 13 humeri, 5 radii, and 1 ulna) were treated with extracorporeal shock waves. The technical parameters were 6,000 to 10,000 impulses at 28 kV (0.62 mJ/mm(2) energy flux density) for the femur and tibia, 4,000 impulses at 24 kV for the humerus (0.56 mJ/mm(2) energy flux density), and 3,000 impulses at 24 kV (0.56 mJ/mm(2) energy flux density) for the radius and ulna. Sixty-six patients were followed up. The total successful rate of bony union was 75.4%. ESWT was successful in hypertrophic nonunions and seemed to have no evident effect in atrophic nonunions. We believe that extracorporeal shock wave therapy may be a good choice for nonunions of long bone fracture especially in hypertrophic nonunions.

VEGF C-634G polymorphism is associated with protection from isolated ventricular septal defect: case-control and TDT studies.

The ventricular septal defect (VSD) is the most common congenital heart defect and no candidate susceptibility gene has been identified. Endocardial cushion and outflow septal morphogenesis, malalignment of which induces VSD, have been suggested to be mediated by the vascular endothelial growth factor (VEGF). Three single-nucleotide polymorphism (SNP) variants in promoter and 5'-UTR region of the VEGF gene, C-2578A (rs699947), G-1154A (rs1570360) and G-634C (rs2010963), were reported to alter its expression. We assessed the association in a Chinese population between these SNPs and VSD using a double approach: case-control and TDT designs. Among the three SNPs, only -634C allele was less frequently present in 222 patients compared to 352 controls (odds ratio: 0.76, 95% CI: 0.59-0.97, X(2)=5.06, P=0.024, not significant after a Bonferroni correction). This was significantly less transmitted to VSD patients (trios: 142) (odds ratio: 0.39, 95% CI: 0.25-0.62, X(2)=8.11, df=1, P=0.004, corrected P=0.024). A similar result was observed for haplotype -2578C/-1154G/-634C allele in both studies (in TDT: X(2)=7.51, df=1, P=0.006, corrected P=0.048). All these associations for the first time demonstrated that -634C allele was in a significant protective association against VSD, suggesting that VEGF dysregulation was involved in the pathological processes of VSD.

Association of estrogen receptor alpha gene polymorphisms with bone mineral density: a meta-analysis.

BACKGROUND: A number of studies have examined the association between estrogen receptor alpha (ESR-α) gene polymorphisms and bone mineral density (BMD), but previous studies of ESR-α gene XbaI (rs9340799) and PvuII (rs2234693) polymorphisms have been hampered by small sample size, regional restrictions and inconclusive results. Thus a meta-analysis is needed to assess their pooled effects. METHODS: This study reviewed all published articles indexed in Pubmed using the keywords in the title or abstract. All data were extracted independently by two reviewers using a standard form, the studies were meta-analyzed and minor discrepancies were resolved by authors' discussion. RESULTS: Twenty seven eligible studies involving 8467 women and 2032 men were identified. The XbaI and PvuII polymorphisms were significantly associated with BMD of the lumbar spine. XX and PP homozygotes had a protective effect in comparison with carriers of the x and p alleles, the effects were more significant in premenopausal women or Western women. At the femoral neck, the results were different. XX served as a protective factor in postmenopausal women, Western women, Western postmenopausal women, and men, while PP was likely to serve as a risk factor in Eastern women, Eastern postmenopausal women, and men. CONCLUSIONS: The XbaI polymorphism is correlated to BMD at diverse skeletal sites. PP had a protective role for the lumbar spine but might be a risk factor for the femoral neck.

[Clinical analysis and prevention from coating shedding of uncemented hip prosthesis].

OBJECTIVE: The long-term biological effects of HA-coated prostheses remain uncertain. The purpose of the study is to analyze the reasons of coating shedding of uncemented hip prothesis, so as to provide evidences for the preventions and treatment. METHODS: From 2002.10 to 2009.2, 5 patients with coating shedding of uncemented hip prosthesis were treated with kip revision operation. Among the patients, 3 patients were male and 2 patients were female, ranging in age from 55 to 68 years. The hip prosthesis were taken out in the operation and the cause of coating shedding was analyzed. Another ten normal prosthesis taken out from the revision operation were used as the control group. The histomorphology and microarchitecture of hip prosthesis were observed. The micrometer caliper and vickers hardness test were used to measure the thickness and hardness. The interface shearing force was measured by push-out test. The function of hip joint was evaluated by Harris score. RESULTS: There were difference between control and experience groups in his tomorphology observation. In the 2 patients with HA-coated shedding, the thickness of coating were 112 microm and 138 microm respectively; Vickers hardness were 5,843 Hv and 4,524 Hv respectively; and the shear strength were 12.4 MPa and 11.6 MPa respectively. In the 3 patients with Ti-coated shedding, the Harris scores were 82, 88 and 87 respectively. CONCLUSION: There are many reasons of coating shedding of uncemented hip prosthesis. But most reasons have relationship with the quality of hip prosthesis. Nowadays, there are many methods to enhance the binding strength between the coating and prosthesis, and to prevent the early coating shedding.