Fallopian tube stem cell medium of porcine and bovine: In vitro regenerative effect on maturation and parthenogenesis of porcine oocytes.

Assisted reproductive technology (ART) has been widely developed over the decades. This advanced technology has shown efficacy in the conception and breeding of an animal. However, several issues such as polyspermy, low maturation rate, and low development rate in vitro remain unresolved. Fallopian tube derived cells are proposed to promote the maturation and development of oocyte. This study aims to characterize porcine (PFTSC) and bovine fallopian tube stem cell (BFTSC) while comparing allogeneic and xenogeneic paracrine effects on porcine oocyte. FTSC of Taiwan yellow cattle (B. indicus) and porcine (Landrace x Yorkshire dam x Duroc) were isolated and identified. Conditioned media (Medium 199 or PZM-3) from porcine and bovine was collected and added to porcine cells during in vitro maturation (IVM) and in vitro culture (IVC). Both PFTSC and BFTSC expressed little CD44, CD105, and CD4. Both cells were induced to transform into chondrocytes, very few cells gave rise to osteocytes and adipocytes. IVM test showed a significant elevation of maturation rate in both groups (Porcine: 66.5 ± 3.5% > 55.9 ± 1.7%, p < .05; Bovine: 68.9 ± 2.3% > 55.9 ± 1.7%, p < .05). IVC test demonstrated markedly reduction of blastocyst in both groups. In a diluted conditioned medium with different concentration, 25% and 50% PFTSC showed a decrease in blastocyst rate which is significantly different, but BFTSC demonstrated no significant difference. PFTSC and BFTSC possessed properties of stem cells. Conditioned media from both PFTSC and BFTSC could improve maturation rate but not blastocyst rate in vitro.

Increased COUP-TFII Expression Mediates the Differentiation Imbalance of Bone Marrow-Derived Mesenchymal Stem Cells in Femoral Head Osteonecrosis.

OBJECTIVE: Bone marrow-derived mesenchymal stem cells (BMSCs) have multilineage differentiation potential, which allows them to progress to osteogenesis, adipogenesis, and chondrogenesis. An imbalance of differentiation between osteogenesis and adipogenesis will result in pathologic conditions inside the bone. This type of imbalance is also one of the pathological findings in osteonecrosis of the femoral head (ONFH). Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) was previously reported to mediate the differentiation of mesenchymal stem cells. This study investigated the expression of the osteogenesis regulator Runx2, osteocalcin, the adipogenesis regulator PPARγ, and COUP-TFII in the femoral head tissue harvested from ONFH patients, and characterized the effect of COUP-TFII on the differentiation of primary BMSCs. METHODS: Thirty patients with ONFH were recruited and separated into 3 groups: the trauma-, steroid- and alcohol-induced ONFH groups (10 patients each). Bone specimens were harvested from patients who underwent hip arthroplasty, and another 10 specimens were harvested from femoral neck fracture patients as the control group. Expression of the osteogenesis regulator Runx2, osteocalcin, the adipogenesis regulator PPARγ, C/EBP-α, and COUP-TFII was analyzed by Western blotting. Primary bone marrow mesenchymal cells were harvested from ONFH cells treated with COUP-TFII RNA interference to evaluate the effect of COUP-TFII on MSCs. RESULTS: ONFH patients had significantly increased expression of the adipogenesis regulator PPARγ and C/EBP-α and decreased expression of the osteogenesis regulator osteocalcin. ONFH bone tissue also revealed higher COUP-TFII expression. Immunohistochemical staining displayed strong COUP-TFII immunoreactivity adjacent to osteonecrotic trabecular bone. Increased COUP-TFII expression in the bone tissue correlated with increased PPARγ and decreased osteocalcin expression. Knockdown of COUP-TFII with siRNA in BMSCs reduced adipogenesis and increased osteogenesis in mesenchymal cells. CONCLUSION: Increased COUP-TFII expression mediates the imbalance of BMSC differentiation and progression to ONFH in patients. This study might reveal a new target in the treatment of ONFH.

Anti-inflammatory and anti-osteoarthritis effects of Cm-02 and Ck-02.

Osteoarthritis (OA) is a common degenerative joint disease characterized by progressive deterioration of articular cartilage. There have been reports that small molecule inhibitors have anti-osteoarthritis effects; however, the effects of 3-(4-chloro-2-fluorophenyl)-6-(2,4-difluorophenyl)-2H-benzo[e] [1,3]oxazine-2,4(3H)-dione (Cm-02) and 6-(2,4-difluorophenyl)-3-(3,4-difluorophenyl)-2H-benzo[e] [1,3]oxazine-2,4(3H)-dione (Ck-02), small molecule inhibitors which share many structural similarities with quercetin (a potent anti-inflammatory flavonoid), remain unclear. In this study, TNF-α-stimulated porcine and human chondrocyte models were used to investigate the inhibitory effects of Cm-02 and Ck-02 on the molecular mechanisms underlying the anti-OA effects. TNF-α was used to stimulate porcine and human chondrocytes to mimic immunomodulatory potency in-vitro. Anti-osteoarthritic effects were characterized in terms of protein and mRNA levels associated with the pathogenesis of OA. We also examined (1) the inducible nitric oxide synthase (iNOS)-nitric oxide (NO) system in cultured chondrocytes, (2) matrix metalloproteinases (MMPs) in cultured chondrocytes, and (3) aggrecan degradation in cartilage explants. Finally, we tested the activation of nuclear factor-kappaB (NF-κB), interferon regulatory factor-1 (IRF-1), and activate the protein-1 (AP-1), and we tested the signal transduction and activation of transcription-3 (STAT-3). Our results indicate that, in chondrocytes, Cm-02 and Ck-02 inhibit TNF-α induced NO production, iNOS, MMP, the expression of disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), and the enzyme activity of MMP-13. Furthermore, both Cm-02 and Ck-02 were found to stimulate TNF-α, which has been shown to suppress the activation of several transcription factors, including NF-κB, STAT-3, and IRF-1 in porcine and human chondrocytes. Cm-02 and Ck-02 were also found to help prevent the release of proteoglycans from cartilage explants. Our findings demonstrate that both Cm-02 and Ck-02 have potent anti-inflammatory activities and the ability to protect cartilage in an OA cell model. These findings indicate that Cm-02 and Ck-02 have the potential to be further developed for the therapeutic treatment of OA.

Outcomes of distal femoral fractures treated with minimally invasive plate osteosynthesis versus open reduction internal fixation with combined locking plate and interfragmentary screws.

PURPOSE: Fractures of the distal femur remain challenging to treat, and numerous fixation methods are designed to promote stability and fracture healing. Locking plate constructs have recently become the mainstream fixation method, but debate exists on whether to use locking plates alone or to augment them with interfragmentary screws. This article compares outcomes of distal femur fractures treated with a single locking plate alone versus those treated with a locking plate and interfragmentary screws. METHODS: We retrospectively reviewed 57 patients treated for distal femur fractures from 2010 to 2013. Patients were divided into two groups: Those treated with a locking plate alone utilizing the minimally invasive plate osteosynthesis (MIPO) technique and those treated with combination of a locking plate and interfragmentary screws using an open technique. Postoperative outcomes were obtained via a manual chart review. Fracture healing and callus indices were evaluated from radiographs. RESULTS: 9 patients required revision surgery in the locking plate alone group (6 for persistent nonunion and 3 for varus deformity). Only two patients in the combination group required revisions (both for nonunion). Average time to full weight bearing was 19.54 weeks in the locking plate group versus 14.57 weeks in the combination group (p = 0.004). At the time of full weight bearing, frontal (1.15 versus 1.11, p = 0.004) and sagittal (1.22 versus 1.15, P = 0.008) callus indices were both significantly greater in the locking plate group. CONCLUSIONS: In this study, the combination of a locking plate and interfragmentary screws achieved suitable stability and a faster time to full weight bearing than using a locking plate alone. Surgeons should consider combining a locking plate with interfragmentary screws as an effective method for fixation of distal femur fractures, particularly in cases when plate fixation alone fails to provide adequate fracture stability.

Long-term results of posterior cruciate ligament tear with or without reconstruction: A nationwide, population-based cohort study.

BACKGROUND: There is increasing interest in the long-term outcomes of patients with posterior cruciate ligament (PCL) tears following conservative treatment or reconstruction. However, limited information is available regarding these results because of the relative rarity of cases and lack of long-term follow-up. PURPOSE: The goals of this study are to (1) compare the occurrence of secondary meniscal tears, osteoarthritis (OA) or subsequent total knee replacement (TKR) in patients with or without PCL injury, and (2) evaluate the potential protective effect of PCL reconstruction against long-term sequela in patients with PCL deficiency. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This retrospective cohort study evaluated the long-term results of PCL deficiency with or without reconstruction in Taiwan based on data from the National Health Insurance Research Database (NHIRD) from 2000 to 2015. The cumulative incidence rates of meniscus tear, OA and TKR were analyzed using the Kaplan-Meier estimator. Cox proportional hazards models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: A total of 4,169 patients diagnosed with PCL tear from 2000 to 2015 in Taiwan were included in the study. There was a higher cumulative incidence of meniscus tear (1.13%), OA (2.71%) and subsequent TKR (0.91%) among patients with a PCL tear than among patients without one (0.22%, 1.90%, 0.62%; all p < 0.05). PCL reconstruction patients had a decreased cumulative incidence of meniscus tear (0.41%), OA (2.30%) and subsequent TKR (0.48%) compared with non-reconstructed patients (2.44%, 3.46%, 1.69%; all p < 0.05). After adjusting for covariates, PCL-injured patients who underwent reconstruction within one year after PCL injury showed a significantly lower risk of subsequent sequelae than those who never underwent reconstruction (within 1 month: adjusted HR = 0.390, 95% CI = 0.284-0.535; 1 month to 1 year: adjusted HR = 0.546, 95% CI = 0.398-0.748). CONCLUSIONS: Patients with PCL tears have a significantly higher risk of meniscus tear, OA and subsequent TKR than patients without PCL tears. PCL reconstruction could decrease the cumulative incidence of these outcomes. The results suggest that PCL-injured patients should undergo reconstruction as early as possible (within one year) to reduce the risk of further degeneration.

Arthroprotective Effects of Cf-02 Sharing Structural Similarity with Quercetin.

In this study, we synthesized hundreds of analogues based on the structure of small-molecule inhibitors (SMIs) that were previously identified in our laboratory with the aim of identifying potent yet safe compounds for arthritis therapeutics. One of the analogues was shown to share structural similarity with quercetin, a potent anti-inflammatory flavonoid present in many different fruits and vegetables. We investigated the immunomodulatory effects of this compound, namely 6-(2,4-difluorophenyl)-3-(3-(trifluoromethyl)phenyl)-2H-benzo[e][1,3]oxazine-2,4(3H)-dione (Cf-02), in a side-by-side comparison with quercetin. Chondrocytes were isolated from pig joints or the joints of patients with osteoarthritis that had undergone total knee replacement surgery. Several measures were used to assess the immunomodulatory potency of these compounds in tumor necrosis factor (TNF-α)-stimulated chondrocytes. Characterization included the protein and mRNA levels of molecules associated with arthritis pathogenesis as well as the inducible nitric oxide synthase (iNOS)⁻nitric oxide (NO) system and matrix metalloproteinases (MMPs) in cultured chondrocytes and proteoglycan, and aggrecan degradation in cartilage explants. We also examined the activation of several important transcription factors, including nuclear factor-kappaB (NF-κB), interferon regulatory factor-1 (IRF-1), signal transducer and activator of transcription-3 (STAT-3), and activator protein-1 (AP-1). Our overall results indicate that the immunomodulatory potency of Cf-02 is fifty-fold more efficient than that of quercetin without any indication of cytotoxicity. When tested in vivo using the induced edema method, Cf-02 was shown to suppress inflammation and cartilage damage. The proposed method shows considerable promise for the identification of candidate disease-modifying immunomodulatory drugs and leads compounds for arthritis therapeutics.

Chondroprotective Effects and Mechanisms of Dextromethorphan: Repurposing Antitussive Medication for Osteoarthritis Treatment.

Osteoarthritis (OA) is the most common joint disorder and primarily affects older people. The ideal anti-OA drug should have a modest anti-inflammatory effect and only limited or no toxicity for long-term use. Because the antitussive medication dextromethorphan (DXM) is protective in atherosclerosis and neurological diseases, two common disorders in aged people, we examined whether DXM can be protective in pro-inflammatory cytokine-stimulated chondrocytes and in a collagen-induced arthritis (CIA) animal model in this study. Chondrocytes were prepared from cartilage specimens taken from pigs or OA patients. Western blotting, quantitative PCR, and immunohistochemistry were adopted to measure the expression of collagen II (Col II) and matrix metalloproteinases (MMP). DXM significantly restored tumor necrosis factor-alpha (TNF-α)-mediated reduction of collagen II and decreased TNF-α-induced MMP-13 production. To inhibit the synthesis of MMP-13, DXM blocked TNF-α downstream signaling, including I kappa B kinase (IKK)α/ß-IκBα-nuclear factor-kappaB (NF-κB) and c-Jun N-terminal kinase (JNK)-activator protein-1 (AP-1) activation. Besides this, DXM protected the CIA mice from severe inflammation and cartilage destruction. DXM seemed to protect cartilage from inflammation-mediated matrix degradation, which is an irreversible status in the disease progression of osteoarthritis. The results suggested that testing DXM as an osteoarthritis therapeutic should be a focus in further research.

No difference in the functional improvements between unilateral and bilateral total knee replacements.

BACKGROUND: Differences between staged bilateral total knee replacement (TKR) and simultaneous bilateral TKR have been investigated, but few studies have investigated differences in the functional improvements resulting from these methods. Therefore, this study investigates the different functional improvements between staged bilateral total knee TKR and simultaneous bilateral TKR. METHODS: Among 144 potential bilateral TKR patients who were included in this study, 93 (64.6%) patients selected unilateral TKR and 51 (35.4%) selected bilateral TKR. Functional improvements were assessed using the Western Ontario and McMaster University osteoarthritis index (WOMAC) and the Medical Outcomes Trust Short Form-36 (SF-36), and patients were interviewed pre-operatively and after 6 months. A generalized equation was used to test for differences in functional improvements. RESULTS: After TKR, pain, stiffness, function and total WOMAC scores were significantly reduced in both groups, with mean changes from - 26.6 to - 41.4 and from - 27.5 to - 42.2.The mean health change of SF-36 scores, physical component and mental component scores changed to 45.2 ± 18.2, 74.0 ± 15.4 and 77.0 ± 9.6, respectively, in Group 1 and 47.1 ± 17.1, 74.0 ± 15.2 and 75.5 ± 12.1, respectively, in Group 2. Unilateral and simultaneous bilateral TKR produce similar functional improvements, although current work status may be a novel impact factor. CONCLUSION: No differences in functional improvements were identified between patients who selected unilateral versus bilateral TKR, indicating no recommendation for one procedure over the other.

Infusion of Porcine-Derived Amniotic Fluid Stem Cells for Treatment of Experimental Colitis in Mice.

Recently, stem cells have offered an alternative treatment for inflammatory bowel disease (IBD) or colitis to overcome the poor outcomes associated with current therapies. Amniotic fluid-derived stem cells (AFSCs) have the potential for the regeneration of impaired organs and the recovery of normal physiologic functions of damaged tissues without ethical concerns or risk of tumor formation. In this work, we aimed to examine the therapeutic effects of infusion of porcine AFSCs (pAFSCs) in dextran sulfate sodium (DSS)-induced colitis in mice. Treatment with pAFSCs was shown to inhibit the shortening of the colon after induction of colitis and dramatically ameliorated the body weightloss induced by the DSS treatment. In addition, pAFSCs could also reduce the extent of the inflamed area represented by epithelial mesenchymal transformation in the colitis mice. The levels of the inflammatory cytokines interleukin 6 (IL-6) and interferon gamma (IFN-γ) were also reduced in colitis mice transplanted with pAFSCs. In conclusion, pAFSCs can ameliorate experimental colitis in mice, suggesting that they may be a potential treatment for IBD or colitis.

Comparison of arthroplasty vs. osteosynthesis for displaced femoral neck fractures: a meta-analysis.

BACKGROUND: This meta-analysis compared clinical outcomes of arthroplasty vs. osteosynthesis for displaced femoral neck fractures. METHODS: Meta-analysis was performed on the difference in revision rate and overall mortality between participants undergoing osteosynthesis vs. total hip arthroplasty (THA), osteosynthesis vs. hemiarthroplasty (HA), or THA vs. HA. RESULTS: Pooled direct and indirect results indicated no significant difference in mortality between THA and HA (pooled OR = 0.87, 95% CI 0.55 to 1.38; P = 0.556), between THA and osteosynthesis (pooled OR = 1.17, 95% CI 0.69 to 1.99; P = 0.553), and between HA and osteosynthesis (pooled OR = 1.21, 95% CI 0.84 to 1.74; P = 0.304). Pooled direct and indirect results indicated no significant difference in revision rates between THA and HA (pooled OR = 0.90, 95% CI 0.26 to 3.19; P = 0.874). But, fewer revisions (OR = 0.19, 95% CI 0.10 to 0.34; P = 0.000) were seen in patients treated with THA than osteosynthesis and also in those treated with HA than osteosynthesis (OR = 0.12, 95% CI 0.07 to 0.20; P = 0.000). After excluding studies without showing normal cognition in inclusion criteria, pooled direct and indirect results also indicated no significant difference in mortality between THA, HA, and osteosynthesis. Similarly, there was no significant difference in revision rates between THA and HA, but HA and THA had significantly lower revision rates compared with osteosynthesis. CONCLUSIONS: There was no significant difference in overall mortality among osteosynthesis, HA, and THA. However, HA and THA had significantly lower revision rates compared with osteosynthesis. Results of the present study provide support for the use of hip arthroplasty to treat displaced fractures of the femoral neck.

Physiological concentrations of soluble uric acid are chondroprotective and anti-inflammatory.

High uric acid levels are a risk factor for cardiovascular disorders and gout; however, the role of physiological concentrations of soluble uric acid (sUA) is poorly understood. This study aimed to clarify the effects of sUA in joint inflammation. Both cell cultures of primary porcine chondrocytes and mice with collagen-induced arthritis (CIA) were examined. We showed that sUA inhibited TNF-α- and interleukin (IL)-1ß-induced inducible nitric oxide synthase, cyclooxygenase-2 and matrix metalloproteinase (MMP)-13 expression. Examination of the mRNA expression of several MMPs and aggrecanases confirmed that sUA exerts chondroprotective effects by inhibiting the activity of many chondro-destructive enzymes. These effects attenuated collagen II loss in chondrocytes and reduced proteoglycan degradation in cartilage explants. These results were reproduced in chondrocytes cultured in three-dimensional (3-D) alginate beads. Molecular studies revealed that sUA inhibited the ERK/AP-1 signalling pathway, but not the IκBα-NF-κB signalling pathway. Increases in plasma uric acid levels facilitated by the provision of oxonic acid, a uricase inhibitor, to CIA mice exerted both anti-inflammatory and arthroprotective effects in these animals, as demonstrated by their arthritis severity scores and immunohistochemical analysis results. Our study demonstrated that physiological concentrations of sUA displayed anti-inflammatory and chondroprotective effects both in vitro and in vivo.

Characteristics of Intratendinous Microcirculation Shortly After an Achilles Rupture and Subsequent Treatment Outcomes.

BACKGROUND: Early microcirculatory responses after experimental tenotomy are critical to the healing of tendons and their ultimate tensile strength. The effects of changes in microcirculation on the outcomes of tendon healing, however, have not been determined. OBJECTIVES: To assess microcirculation values in injured Achilles tendons in the first 3 months after surgical repair and to correlate the inter-limb microcirculatory changes with functional outcomes at 3 and 6 months after surgery. DESIGN: Case-control study. SETTING: A university sports physiotherapy laboratory. PARTICIPANTS: Thirteen subjects (median age: 45 years; range: 34.8-51.9 years) with a repaired Achilles tendon were recruited. METHODS OR INTERVENTION: Surgical repair. MAIN OUTCOME MEASUREMENTS: Measurements were obtained at 1, 2, 3, and 6 months after surgery. Bilateral measurements of tendon microcirculation (total hemoglobin [THb] and oxygen saturation [StO2]) were recorded at the first 3 time points, whereas outcome measures of a Taiwan Chinese version of the Victorian Institute of Sport Assessment Scale-Achilles questionnaire, one-leg hopping distance, the star excursion balance test, and the heel raise index were conducted at the third and fourth time points. Correlations between the inter-limb microcirculatory changes, eg, between the measurements at 2 months and 1 month (2-1) after surgery, at 3 months and 2 months (3-2) after surgery, and at 3 months and 1 month (3-1) after surgery, and the outcome measures were investigated. RESULTS: Compared with the noninjured tendons, the repaired Achilles demonstrated greater THb (at 1, 2, and 3 months; P = .017, .008, and .012 respectively) and StO2 (at 3 months; P = .017). Furthermore, the THb2-1 and THb3-2, StO2 2-1, and StO2 3-2 showed correlations with the heel raise index, differences in the star excursion balance test and one-leg hopping distance between the noninjured leg and injured leg, and Taiwan Chinese version of the Victorian Institute of Sport Assessment Scale-Achilles questionnaire scores (rho -0.921 to 0.855). CONCLUSIONS: Changes in the inter-limb microcirculation shortly after Achilles repair were correlated with subsequent symptoms and functional symmetry. LEVEL OF EVIDENCE: III.

Combined Innovative Portal Arthroscopy and Fluoroscopy-Assisted Reduction and Fixation in Subtle Injury of the Lisfranc Joint Complex: Analysis of 10 Cases.

Subtle injuries of the Lisfranc joint complex are uncommon and difficult to diagnose clinically and thus are easily missed even by experienced orthopedic doctors. Misdiagnosed injuries can lead to chronic disability until eventual fusion surgery. We describe 10 cases diagnosed with subtle injury of the Lisfranc joint that were treated with combined innovative portal arthroscopy and fluoroscopy-assisted reduction and percutaneous screw fixation in an interfragmentary fashion. The distance between the first and second metatarsals (the Lisfranc distance) and that between the medial cuneiform and fifth metatarsal base (foot arch height) was measured before and after surgery. The American Orthopaedic Foot and Ankle Society function score was evaluated perioperatively. The average preoperative and postoperative Lisfranc distance was 4.38 ± 0.39 mm and 2.68 ± 0.9 mm, the foot arch height was 12.63 ± 2.75 mm and 21.80 ± 3.50 mm, and the American Orthopaedic Foot and Ankle Society score was 59.1 ± 5.69 and 86.8 ± 10.1, respectively. Of the 10 patients, 3 had excellent outcomes, 6 had good outcomes, and 1 had a fair outcome. In conclusion, we report a useful and minimally invasive surgery for acute, subacute, and even chronic subtle injury of the Lisfranc joint. The Lisfranc distance, foot arch height, and function of the foot were restored clinically, and all measurements showed statistically significant differences.

Effects of Collagen Crosslink Augmentation on Mechanism of Compressive Load Sharing in Intervertebral Discs.

Exogenous crosslinking has been shown to have potential for treating disc degeneration and back pain due to its ability to increase the strength and toughness of the annulus fibrosus, increase intervertebral joint stability, decrease intradiscal pressure, and increase fluid flow through the disc. Some results imply that crosslink augmentation may also lead to changes in the compressive load sharing properties of the disc. The objective of the present study was to evaluate directional stress distribution changes of the disc following genipin crosslinking treatment. Bovine lumbar motion segments were randomly divided into control and crosslinked groups. Annular strains were determined from simultaneous deformation measurements at various time points during compressive creep testing. Four stress components of the annulus were then calculated according to the previously measured modulus data. Immediately after the application of a 750-N compressive load, mean axial and radial compressive stresses in the crosslinked group were twofold higher than control means. Conversely, mean lamellae-aligned and circumferential tensile stresses of the crosslinked discs were 8- and threefold lower, respectively, compared to control means. After 1-h creep loading, the two compressive mean stresses in both the control and genipin-crosslinked specimens increased approximately threefold from their initial 750-N-loaded values. The two tensile mean stresses in the crosslinked group remained lower than the respective levels of the control means after creep loading. A greater proportion of annular compressive load support under compressive creep loading, with a commensurate decrease in both tensile stresses and strains, was seen in the discs following exogenous crosslink augmentation.

A New Application of Parallel Synthesis Strategy for Discovery of Amide-Linked Small Molecules as Potent Chondroprotective Agents in TNF-α-Stimulated Chondrocytes.

As part of an effort to profile potential therapeutics for the treatment of inflammation-related diseases, a diversity of amide-linked small molecules was synthesized by using parallel synthesis strategy. Moreover, these new compounds were also evaluated for their inhibitory effects on nitric oxide (NO) by using tumor necrosis factor alpha (TNF-α)-induced inflammatory responses in chondrocytes. Among the tested compounds, N-(3-chloro-4-fluorophenyl)-2-hydroxybenzamide (HS-Ck) was the most potent inhibitor of NO production and inducible nitric oxide synthase (iNOS) expression in TNF-α-stimulated chondrocytes. In addition, our biological results indicated that HS-Ck might suppress the expression levels of iNOS and matrix metalloproteinases-13 (MMP-13) activities through downregulating the activation of nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT-3) transcriptional factors. Therefore, the parallel synthesis was successful used to develop a new class of potential anti-inflammatory agents as chondroprotective candidates for the treatment of osteoarthritis.

Effects of Therapeutic Physical Agents on Achilles Tendon Microcirculation.

STUDY DESIGN: Controlled laboratory study. OBJECTIVES: To measure Achilles tendon microcirculation (total hemoglobin [THb] and oxygen saturation [StO2]) before and after the application of a physical agent in asymptomatic participants, and to compare differences between application location and physical agent dosage. BACKGROUND: Tendon microcirculation can be altered by superficial heating or cryotherapy. METHODS: Fifty-one healthy adults (median age, 22 years; range, 20-34 years) were recruited and randomly assigned into 1 of 4 groups. Participants in each group received an intervention consisting of 1 of the following 4 physical agents: ultrasound (n = 12), interferential current (n = 14), low-level laser (n = 11), or vibration massage (n = 14). In each group, the selected intervention was applied at 2 different doses (ultrasound, 0.8 or 1.2 W/cm(2); laser, 5.4 or 18 J) or target locations (vibration and electrostimulation, calf muscle or Achilles tendon). For each participant, each dose or target location was randomly applied to 1 randomly selected lower leg (each leg receiving only 1 of the 2 options). RESULTS: The StO2 values significantly increased after ultrasound at both doses (P<.008), and the THb value significantly increased for the higher dose only (P<.008). Both THb and StO2 values also significantly increased in response to vibration massage targeting the Achilles tendon (P<.008), and these values were greater than those resulting from the vibration massage applied to the calf muscle (P = .003 and .002, respectively). No significant THb and StO2 differences were found after the application of interferential current or low-level laser. CONCLUSION: Tendon microcirculation increases after ultrasound and vibration massage intervention concentrated on the Achilles tendon. These modalities may be considered for the purpose of temporarily increasing microcirculation in the tendon.

Using a modified Pauwels method to predict the outcome of femoral neck fracture in relatively young patients.

BACKGROUND: Pauwels classification has long been used in femoral neck fracture to measure the inclination of the fracture line and is still widely used. In recent years, however, some studies have contested the reliability of this measurement method. This study investigates modified measurement method to assess the inclination angle with assisted parameters to evaluate the correlation between the different angles and the incidences of loss of reduction, nonunion and avascular necrosis. PATIENTS AND METHODS: A retrospective study was conducted to analyse the clinical data of 209 relatively young patients (between 20 and 60 years old) with intracapsular femoral neck fracture fixed by inverted triangular screws between January 2004 and December 2010, including 111 males and 98 females, with an average age of 47.08±9.93 years. Using the modified measurement method, the pre-operative inclination angles of patients with intracapsular femoral neck fracture were analyzed. The measured angles were classified into three types: type I, <30 degrees; type II, 30-50 degrees; and type III, >50 degrees. RESULTS: With regard to loss of reduction, nonunion and avascular necrosis, there were no significant differences with respect to age, sex and fracture side. However, there were significant differences with respect to fracture type, reduction quality and different modified Pauwels types. In the multiple regression analysis, the factors associated with loss of reduction were the fracture type (odds ratio [OR]=7.22), reduction quality (anatomic vs unacceptable reduction, OR=0.11; acceptable vs unacceptable reduction, OR=0.23), and modified Pauwels type (type II vs type III, OR=0.36). The factors associated with fracture nonunion were the fracture type (OR=9.43), reduction quality (acceptable vs unacceptable reduction, OR=0.17) and modified Pauwels type (type II vs type III, OR=0.22). And the factors associated with avascular necrosis were the modified Pauwels type (type I vs type III, OR=0.15; type II vs type III, OR=0.36). CONCLUSIONS: A displaced fracture, poor reduction quality and high modified Pauwels type are noted risk factors for loss of reduction and fracture nonunion in the post-operative follow up of intracapsular femoral neck fracture. The modified Pauwels type is also noted a risk factor for avascular necrosis. Thus, this modified method is a useful tool for correcting the deficiencies of traditional Pauwels classification and predicting the outcome of femoral neck fractures.

Exogenous Crosslinking Restores Intradiscal Pressure of Injured Porcine Intervertebral Discs: An In Vivo Examination Using Quantitative Discomanometry.

STUDY DESIGN: In vivo examination of intradiscal pressure by quantitative discomanometry (QD). OBJECTIVE: To determine whether an injectable, exogenous crosslinking could acutely restore intradiscal pressure of stab-injured discs in vivo by short-term treatment. SUMMARY OF BACKGROUND DATA: Disc biomechanical performance depends on its integrity associated with the intradiscal pressure and mechanical properties. Genipin crosslink augmentation has demonstrated the in vitro biomechanical capability to improve intervertebral joint stability and increase mechanical properties of the annulus fibrosus. METHODS: 4 lumbar discs on each of 8 swine were randomly assigned to 4 groups: intact, injured, untreated, and crosslinked. A 16G needle was stabbed into the annulus fibrosus to create the disc injury model. An injection of 0.33% genipin solution was delivered into the annulus to treat the injury. QD technique was performed to examine the intradiscal pressure for the intact and injured discs at the time of surgery, while untreated and crosslinked discs were measured 1-week postsurgery. 4 QD parameters were analyzed and compared across the 4 groups: leakage pressure and volume, and saturation pressure and volume. RESULTS: The leakage and saturation pressures of the injured group were significantly lower than those of the intact group (P = 0.004 and P = 0.01, respectively). The leakage and saturation pressures of untreated discs were statistically equivalent to the injured levels, but with a 2-times higher saturation volume. Relative to the untreated group, the leakage pressure and saturation pressure of genipin-crosslinked discs had a 617% (P = 0.008) and a 473% increase (P = 0.007), respectively. CONCLUSION: A large disc injury produced by annular puncture immediately lowered intradiscal pressure when left untreated. Genipin crosslinking can restore intradiscal pressure acutely in vivo without any obvious morbidity associated with the injection.

The thickness of the anterior compartment does not indicate compartment syndrome in acutely traumatised legs?

BACKGROUND: The study was conducted to achieve early detection of increased compartment pressure by comparing the changes between the thickness and pressure within the musculofascial compartments after lower leg injury. METHODS: We included cases of a lower-leg fracture between January and December 2007. Bilateral lower leg compartment pressure and thickness were measured before the surgery and post-anaesthesia, and the surgery was performed within 12 h after the initial trauma. The intracompartment pressure (ICP) was measured with a Wick catheter pressure monitor. The thickness (width) of the anterior compartment of lower leg was measured using ultrasound. RESULTS: All data were measured within 4-6h of the injury. The average thickness in injured legs versus uninjured was 30 mm (15-46 mm) versus 20.4 mm (13-30 mm), P<0.001. The average intracompartment pressure (ICP) in injured leg versus uninjured was 45.3 mmHg (26-80 mmHg) versus 17.5 mmHg (15-20 mmHg), P<0.001. The thickness and ICP were significantly increased for injured lower legs compared to the uninjured legs, but the increase in ICP did not show a significant relationship with the change in thickness of the injured lower leg. CONCLUSION: In this study, the results of ICP and thickness changes of injury lower leg compared with uninjured leg revealed no statistically significant correlation. Some injuries showed a high ICP with only mild changes in thickness, while some showed a high ICP with significant changes. Although ultrasound has many advantages for the evaluation of soft tissue changes after trauma, this study revealed that thickness changes are not a predicable parameter for determining pressure on the acute fracture of lower leg.

Bilateral passive leg raising attenuates and delays tourniquet deflation-induced hypotension and tachycardia under spinal anaesthesia: a randomised controlled trial.

BACKGROUND: The pneumatic tourniquet is frequently used in total knee arthroplasty. Tourniquet deflation may result in hypotension and tachycardia caused by the rapid shift of blood volume back to the ischaemic limb and a decrease in cardiac preload. Passive leg raising (PLR) represents a 'self-volume challenge' that can result in an increase in preload. Such a PLR-induced increase in preload was hypothesised to attenuate the decrease in preload resulting from tourniquet deflation. OBJECTIVE: To evaluate the effect of PLR on hypotension and tachycardia following tourniquet deflation. DESIGN: A randomised controlled trial. SETTING: Single medical centre. PATIENTS: Seventy patients who underwent unilateral total knee arthroplasty were randomised into two groups: tourniquet deflation with PLR (n = 35) or without PLR (control group, n = 35). INTERVENTION(S): Patients in both groups were administered a single dose of plain bupivacaine for spinal anaesthesia. The pneumatic tourniquet was inflated on the thigh and the surgery was performed. The study composed of four steps: for the PLR group, step 1 - inflation of the tourniquet while the patient was supine; step 2 - the patient's legs were raised to a 45° angle; step 3 - the tourniquet was deflated while the patient's legs were still raised; and step 4 - the legs were returned to the supine position. In the control group, the same perioperative procedure was used, but PLR was not conducted. MAIN OUTCOME MEASURES: The patients' blood pressure and heart rate were measured before, during and after tourniquet deflation. RESULTS: After tourniquet deflation, the magnitude of the changes in blood pressure and heart rate was less in the PLR group than that in the control group. In addition, the blood pressure nadir also occurred later in the PLR group than in the controls. CONCLUSION: Bilateral PLR is a simple, reversible manoeuvre that mimics rapid fluid loading. Bilateral PLR attenuates the severity of, and delays the time to, hypotension and tachycardia following deflation of a lower limb tourniquet. TRIAL REGISTRATION: ClinicalTrials.gov number NCT01592669.