Operative costs associated with arthroscopic assisted open reduction and internal fixation of acute ankle fractures.

BACKGROUND: Ankle fractures are a common orthopedic injury that frequently involves associated cartilage lesions, soft tissue damage, and a significant inflammatory burden. Despite studies revealing intra-articular pathology in up to 79% of ankle fractures, only 1% of open reduction and internal fixation (ORIF) procedures undergo arthroscopic evaluation. The primary purpose of this study was to determine the cost effectiveness of ankle arthroscopy performed at time of ORIF for ankle fracture. METHODS: An IRB approved retrospective review of patients who sustained ankle fractures and underwent ORIF with and without concomitant arthroscopic surgery between 2015 and 2020 were investigated. Patient demographics, fracture characteristics, outcomes, and cost data were collected and analyzed. RESULTS: There were 567 total ORIF and 28 ORIF and scope included for cost analysis purposes. Total surgical costs averaged $6,537.62 and $6,886.46 for the ORIF only and ORIF and scope procedures respectively. Total direct costs, including operating room time, for the same procedures were found to average $6,212.34 and $7,312.10 for the ORIF only and ORIF and scope procedures respectively. The cost difference between the ORIF only and with arthroscopy was not statistically significant (p = 0.1174). Twelve of the 28 arthroscopic patients (42.86%) had grade 3 or full thickness chondral lesions, and 11/28 (39.28%) arthroscopic patients were found to have grade 1-2 cartilage changes. CONCLUSION: In the acute treatment of ankle fractures, concurrent arthroscopic evaluation does not add a significant cost to the procedure and may result in improved short and long term benefits for the patient. With improved arthroscopic efficiency, the cost differential can be further reduced. LOE: IV.

Relationship between Blood Acetaldehyde Concentration and Psychomotor Function of Individuals with Different ALDH2 Genotypes after Alcohol Consumption.

ABSTRACT: Objective To explore the change rules of blood ethanol and blood acetaldehyde concentration, the impairment of psychomotor functions of different acetaldehyde dehydrogenase （ALDH） 2 genotype individuals after alcohol consumption and the relationship among them. Methods The ALDH2 genotypes in seventy-nine healthy volunteers were obtained by SNaPshotTM method, then divided into ALDH2*1/*1 （wild type） and ALDH2*1/*2 （mutant type） group. After volunteers consumed 1.0 g/kg of alcohol, blood ethanol concentration and blood acetaldehyde concentration at a series of time points before and after alcohol consumption and psychomotor functions, such as, visual selective response time, auditory simple response time and tracking experiment were detected. Biphasic alcohol response questionnaires were collected. Results After alcohol consumption, ALDH2*1/*2 group's blood ethanol and blood acetaldehyde concentration reached the peak earlier than ALDH2*1/*1 group. Its blood acetaldehyde concentration was higher than that of ALDH2*1/*1 group, 1-6 h after alcohol consumption. The psychomotor functions, such as visual selective response time and auditory simple response time in ALDH2*1/*2 group were more significantly impaired than those in ALDH2*1/*1 group after alcohol consumption. There was no statistical significance between the two groups in excitement or sedation reactions （P>0.05）. Pearson correlation coefficient test showed that blood acetaldehyde concentration was related with psychomotor function. Conclusion There are significant differences between the psychomotor function of ALDH2 wild type and mutant type individuals after alcohol consumption estimated to be related to the difference in blood acetaldehyde concentration after alcohol consumption.

[A Study on the establishment of immune thrombocytopenia model induced by anti-platelet GPâ bα antibodies].

Objective: To establish primary immune thrombocytopenia (ITP) animal model induced by anti-platelet membrane glycoprotein GPⅠbα antibodies AN51 and R300. Methods: Twenty guinea pigs (6-8 week) were divided into 4 groups. Five guinea pigs in each group were intravenously injected with different doses of AN51 (0.05, 0.1, 0.2 µg/g) and 0.2 µg/g IgG as control. The whole blood was collected from inner angular venous plexus. Platelets number was determined by an automated cell counter and Swiss-Jim method. Then, the similar protocol was used to establish ITP nude mice model by intraperitoneal injection of different concentrations of anti-platelet GPⅠbα antibody R300, respectively. Results: ①Five minutes after intravenous injection of AN51 at 0.05, 0.1 and 0.2 µg/g, the platelet counts of guinea pigs reduced about 0-5%, 50%-60% and 70%-80% compared to the control group, respectively. The difference was statistically significant (P<0.01) . ②Six hours after intraperitoneal injection of R300 at 0.05, 0.1, 0.2 µg/g, the platelet counts of nude mice decreased about 20%-30%, 60%-70% and 80%-90% compared to the control group, respectively. The difference was statistically significant (P<0.01) . The nude mice, injected 0.2 µg/g R300 once a day for 2 weeks, showed typical ITP clinical manifestations including large number of petechiaes or ecchymoses on limbs, head and abdomen. Conclusion: AN51 at 0.2 µg/g and R300 at 0.2 µg/g could establish stable ITP model in guinea pigs and nude mice respectively.

A global database of nitrogen and phosphorus excretion rates of aquatic animals.

Animals can be important in modulating ecosystem-level nutrient cycling, although their importance varies greatly among species and ecosystems. Nutrient cycling rates of individual animals represent valuable data for testing the predictions of important frameworks such as the Metabolic Theory of Ecology (MTE) and ecological stoichiometry (ES). They also represent an important set of functional traits that may reflect both environmental and phylogenetic influences. Over the past two decades, studies of animal-mediated nutrient cycling have increased dramatically, especially in aquatic ecosystems. Here we present a global compilation of aquatic animal nutrient excretion rates. The dataset includes 10,534 observations from freshwater and marine animals of N and/or P excretion rates. These observations represent 491 species, including most aquatic phyla. Coverage varies greatly among phyla and other taxonomic levels. The dataset includes information on animal body size, ambient temperature, taxonomic affiliations, and animal body N:P. This data set was used to test predictions of MTE and ES, as described in Vanni and McIntyre (2016; Ecology DOI: 10.1002/ecy.1582).

Zoledronic acid suppresses callus remodeling but enhances callus strength in an osteoporotic rat model of fracture healing.

MINI-ABSTRACT: In this study, we demonstrated that the use of zoledronic acid does not impair fracture healing, but results in superior callus size and resistance at the fracture site, which could be the consequence of a lower rate of bone turnover due to its anti-catabolic effect. OBJECTIVE: To investigate the effect of inhibition of bone remodeling by the bisphosphonate, zoledronic acid, on callus properties in an osteoporotic rat model of fracture healing. METHODS: Ovariectomized (OVX) rats were randomly divided into four treatment groups (n=24 per group): saline control (CNT); and three systemic zoledronic acid-injected groups (0.1mg/kg), administered 1 day (ZOLD1), 1 week (ZOLW1), and 2 weeks (ZOLW2) after fracture. Rats were killed at either 6 or 12 weeks postoperatively. Postmortem analyses included radiography, microcomputed tomography, histology, histomorphometry, biomechanical tests, and nanoindentation tests. RESULTS: Treatment with zoledronic acid led to a significant increase in trabecular bone volume within the callus, as well as in callus resistance, compared to those in the saline control rats; delayed administration (ZOLW2) reduced intrinsic material properties, including ultimate stress and elastic modulus, and microarchitecture parameters, including bone volume/total volume (BV/TV), trabecular thickness (Tb.Th), and connectivity density (Conn.D), compared with ZOLD1 at 12 weeks after surgery. OVX had a negative effect on the progression of endochondral ossification at 6 weeks. Zoledronic acid administration at an early stage following fracture may bind to early callus, and thus not affect subsequent callus formation and endochondral ossification, while delayed administration (ZOLW2) mildly suppresses bony callus remodeling. CONCLUSION: The superior results obtained with zoledronic acid (ZOLD1, ZOLW1, and ZOLW2) compared to CNT in terms of callus size and resistance could be the consequence of a lower rate of bone turnover at the fracture site due to the anti-catabolic effect of zoledronic acid. Mild suppression of callus remodeling by delayed administration did not impair the initial phase of the fracture healing process.

Safety of voriconazole and sirolimus coadministration after allogeneic hematopoietic SCT.

Antifungal prophylaxis with azoles is considered standard in allogeneic hematopoietic SCT (allo-HSCT). Although sirolimus is being used increasingly for the prevention of GVHD, it is a substrate of CYP3A4, which is inhibited by voriconazole, and concurrent administration can lead to significantly increased exposure to sirolimus. We identified 67 patients with hematologic malignancies who underwent allo-HSCT with sirolimus, tacrolimus and low-dose MTX and received concomitant voriconazole prophylaxis from April 2008 to June 2011. All patients underwent a non-myeloablative or reduced-intensity conditioned allo-HSCT. Patients received sirolimus and voriconazole concurrently for a median of 113 days. The median daily dose reduction of sirolimus at the start of coadministration was 90%. The median serum sirolimus trough levels before and at steady state of coadministration were 5.8 ng/mL (range: 0-47.6) and 6.1 ng/mL (range: 1-14.2) (P=0.45), respectively. One patient with an average sirolimus level of 6 ng/mL developed sirolimus-related thrombotic microangiopathy that resolved after sirolimus discontinuation. No sinusoidal obstructive syndrome was reported. Seventeen patients (25%) prematurely discontinued voriconazole because of the adverse events. Only two patients (3%) presented with possible invasive fungal infections at day 100. We demonstrate that sirolimus and voriconazole coadministration with an empiric 90% sirolimus dose reduction and close monitoring of sirolimus trough levels is safe and well tolerated.

Coffee, tea, and the risk of hip fracture: a meta-analysis.

UNLABELLED: The present meta-analysis shows no clear association between coffee consumption and the risk of hip fractures. There was a nonlinear association between tea consumption and the risk of hip fracture. Compared to no tea consumption, drinking 1-4 cups of tea daily was associated with a lower risk of hip fracture. INTRODUCTION: Prospective cohort and case-control studies have suggested that coffee and tea consumption may be associated with the risk of hip fracture; the results have, however, been inconsistent. We conducted a meta-analysis to assess the association between coffee and tea consumption and the risk of hip fracture. METHODS: We performed systematic searches using MEDLINE, EMBASE, and OVID until February 20, 2013, without limits of language or publication year. Relative risks (RRs) with 95% confidence intervals (CI) were derived using random-effects models throughout all analyses. We conducted categorical, dose-response, heterogeneity, publication bias, and subgroup analyses. RESULTS: Our study was based on 195,992 individuals with 9,958 cases of hip fractures from 14 studies, including six cohort and eight case-control studies. The pooled RRs of hip fractures for the highest vs. the lowest categories of coffee and tea consumption were 0.94 (95% CI 0.71-1.17) and 0.84 (95% CI 0.66-1.02), respectively. For the dose-response analysis, we found evidence of a nonlinear association between tea consumption and the risk of hip fracture (p(nonlinearity) < 0.01). Compared to no tea consumption, 1-4 cups of tea per day may reduce the risk of hip fracture by 28% (0.72; 95% CI 0.56-0.88 for 1-2 cups/day), 37% (0.63; 95% CI 0.32-0.94 for 2-3 cups/day), and 21% (0.79; 95% CI 0.62-0.96 for 3-4 cups/day). CONCLUSIONS: We found no significant association between coffee consumption and the risk of hip fracture. A nonlinear association emerged between tea consumption and the risk of hip fracture; individuals drinking 1-4 cups of tea per day exhibited a lower risk of hip fractures than those who drank no tea. The association between 5 daily cups of tea, or more, and hip fracture risk should be investigated.

OA-4 inhibits osteoclast formation and bone resorption via suppressing RANKL induced P38 signaling pathway.

Osteoclasts are one of the key therapeutic targets for a variety of orthopedic diseases such as osteoporosis and osteoarthritis. In this study, we synthesized a novel compound N-(3-(cyclohexylcarbamoyl) phenyl)-1H-indole-2- carboxamide (termed as OA-4) and investigated the effects of OA-4 on the differentiation and function of osteoclasts. OA-4 markedly diminished osteoclast differentiation and osteoclast specific gene expression in a dose-dependent manner. In addition, OA-4 dose-dependently suppressed osteoclastic bone resorption. Furthermore, we found OA-4 attenuated RANKL-induced p38 phosphorylation without affecting JNK or NF-κB signaling pathways. Collectively, we synthesized a novel compound OA-4 which can inhibit osteoclast formation and functions via the suppression of p38 signaling pathway.

Production and repair of implant-induced microdamage in the cortical bone of goats after long-term estrogen deficiency.

SUMMARY: By using an ovariectomized goat model, we found that estrogen depletion decreases bone quality and makes it susceptible to screw-induced mechanical microdamage. Both diffuse microdamage and linear cracks accumulated up to 3 weeks after screw implantation, and the microdamage was repaired gradually after 4-8 months. INTRODUCTION: The aim of this study was to observe the effect of long-term estrogen deficiency on the creation and repair of microdamage in cortical bone adjacent to bone screw. METHODS: Cortical bone screws were placed in the tibial diaphyses 28 months after ovariectomy (OVX) or sham operation (Sham-Op) in female goats. The goats were euthanized at 0 day, 21 days, 4 months, and 8 months after screw implantation. Microdamage morphology and repair were examined in peri-screw bone using histomorphometric method, and the nanomechanical properties of peri-screw bone were examined with nanoindentation testing. RESULTS: Tibiae from ovariectomized goats in which screws had been placed had significantly higher levels of diffuse microdamage and significantly more linear cracks than those from sham goats, and the diffuse microdamage was more obvious than linear cracks in the region adjacent to the implant. Both diffuse microdamage and linear cracks accumulated up to day 21 and then gradually repaired at 4 and 8 months after surgery. The trend for bone remodeling in each group was consistent with changes in the level of microdamage. Nanoindentation testing showed that both elastic modulus and hardness in peri-screw bone were significantly decreased in OVX group compared to Sham-Op group. The hardness and elastic modulus also showed a downward trend up to 4 months after screw implantation and then exhibited some recovery after 8 months. CONCLUSIONS: Estrogen depletion decreases bone quality and makes it vulnerable to screw-induced mechanical damage, which may compromise the initial stability of an orthopedic implant.

Andrographolide suppresses RANKL-induced osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo.

BACKGROUND AND PURPOSE: Osteoclasts play a pivotal role in diseases such as osteoporosis, rheumatoid arthritis and tumour bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. Here, we examined changes in osteoclastogenesis and LPS-induced osteolysis in response to andrographolide (AP), a diterpenoid lactone isolated from the traditional Chinese and Indian medicinal plant Andrographis paniculata. EXPERIMENTAL APPROACH: Effects of AP on osteoclast differentiation and bone resorption were measured in vitro. Western blots and RT-PCR techniques were used to examine the underlying molecular mechanisms. The bone protective activity of AP in vivo was assessed in a mouse model of osteolysis. KEY RESULTS: AP concentration-dependently suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro and reduced the expression of osteoclast-specific markers, including tartrate-resistant acid phosphatase, calcitonin receptors and cathepsin K. Further molecular analysis revealed that AP impaired RANKL-induced NF-κB signalling by inhibiting the phosphorylation of TGF-ß-activated kinase 1, suppressing the phosphorylation and degradation of IκBα, and subsequently preventing the nuclear translocation of the NF-κB p65 subunit. AP also inhibited the ERK/MAPK signalling pathway without affecting p38 or JNK signalling. CONCLUSIONS AND IMPLICATIONS: AP suppressed RANKL-induced osteoclastogenesis through attenuating NF-κB and ERK/MAPK signalling pathways in vitro, thus preventing bone loss in vivo. These data indicated that AP is a promising natural compound for the treatment of osteoclast-related bone diseases.

OA10 is a novel p38alpha mitogen-activated protein kinase inhibitor that suppresses osteoclast differentiation and bone resorption.

In search of anti-bone resorbing agents for the potential treatment of osteoporosis, we synthesized a novel compound Tert-butyl 4-(3-[1H-indole-2-carboxamido]benzoyl)piperazine-1-carboxylate (OA10) and found that OA10 is capable of inhibiting RANKL-mediated osteoclast formation and osteoclastic bone resorption in a dose-dependent manner. This biological effect is further supported by the fact that OA10 suppressed osteoclastic-specific gene expression, including tartrate-resistant acid phosphatase, cathepsin K receptor, and calcitonin receptor. Further molecular mechanism investigation revealed OA10 inhibited p38 phosphorylation, suppressed c-fos and NFATc1 expression without affecting NF-κB or JNK signaling pathways. Taken together, this study suggested that OA10 can inhibit osteoclastogenesis by suppressing p38-c-Fos-NFATc1 cascade. OA10 may be developed as a therapeutic drug for osteoclast-related osteolytic diseases.

Dexamethasone shifts bone marrow stromal cells from osteoblasts to adipocytes by C/EBPalpha promoter methylation.

Dexamethasone (Dex)-induced osteoporosis has been described as the most severe side effect in long-term glucocorticoid therapy. The decreased bone mass and the increased marrow fat suggest that Dex possibly shifts the differentiation of bone marrow stromal cells (BMSCs) to favor adipocyte over osteoblast, but the underlying mechanisms are still unknown. In this paper, we established a Dex-induced osteoporotic mouse model, and found that BMSCs from Dex-treated mice are more likely to differentiate into adipocyte than those from control mice, even under the induction of bone morphogenetic protein-2 (BMP2). We also discovered both in vitro and in vivo that the expression level of adipocyte regulator CCAAT/enhancer-binding protein alpha (C/EBPalpha) is significantly upregulated in Dex-induced osteoporotic BMSCs during osteoblastogenesis by a mechanism that involves inhibited DNA hypermethylation of its promoter. Knockdown of C/EBPalpha in Dex-induced osteoporotic cells rescues their differentiation potential, suggesting that Dex shifts BMSC differentiation by inhibiting C/EBPalpha promoter methylation and upregulating its expression level. We further found that the Wnt/beta-catenin pathway is involved in Dex-induced osteoporosis and C/EBPalpha promoter methylation, and its activation by LiCl rescues the effect of Dex on C/EBPalpha promoter methylation and osteoblast/adipocyte balance. This study revealed the C/EBPalpha promoter methylation mechanism and evaluated the function of Wnt/beta-catenin pathway in Dex-induced osteoporosis, providing a useful therapeutic target for this type of osteoporosis.

Total hip replacement for developmental dysplasia of the hip with more than 30% lateral uncoverage of uncemented acetabular components.

In developmental dysplasia of the hip (DDH), a bone defect is often observed superior to the acetabulum after the reconstruction at the level of the true acetabulum during total hip replacement (THR). However, the essential amount of uncemented acetabular component coverage required for a satisfactory outcome remains controversial. The purpose of this study was to assess the stability and function of acetabular components with a lack of coverage > 30% (31% to 50%). A total of 760 DDH patients underwent THR with acetabular reconstruction at the level of the true floor. Lack of coverage above the acetabular component of > 30% occurred in 56 patients. Intra-operatively, autogenous morcellised bone grafts were used to fill the uncovered portion. Other than two screws inserted through the acetabular shell, no additional structural supports were used in these hips. In all, four patients were lost to follow-up. Therefore, 52 patients (52 hips, 41 women and 11 men) with a mean age of 60.1 years (42 to 78) were available for this study at a mean of 4.8 years (3 to 7). There were no instances of prosthesis revision or marked loosening during the follow-up. The Harris hip score improved from a mean of 40.7 points (sd 12.2) pre-operatively to 91.1 (sd 5.0) at the last follow-up. Radiological analysis with medical imaging software allowed us to calculate the extent of the uncoverage in terms of the uncovered arc of the implant as viewed on the anteroposterior pelvic radiograph. From this we propose that up to 17 mm of lateral undercoverage in the presence of a stable initial implantation in the presence of bone autografting, with an inclination angle of the acetabular component between 40° and 55°, is acceptable. This represents undercoverage of ≤ 50%.

V-ATPases in osteoclasts: structure, function and potential inhibitors of bone resorption.

The vacuolar-type H(+)-ATPase (V-ATPase) proton pump is a macromolecular complex composed of at least 14 subunits organized into two functional domains, V(1) and V(0). The complex is located on the ruffled border plasma membrane of bone-resorbing osteoclasts, mediating extracellular acidification for bone demineralization during bone resorption. Genetic studies from mice to man implicate a critical role for V-ATPase subunits in osteoclast-related diseases including osteopetrosis and osteoporosis. Thus, the V-ATPase complex is a potential molecular target for the development of novel anti-resorptive agents useful for the treatment of osteolytic diseases. Here, we review the current structure and function of V-ATPase subunits, emphasizing their exquisite roles in osteoclastic function. In addition, we compare several distinct classes of V-ATPase inhibitors with specific inhibitory effects on osteoclasts. Understanding the structure-function relationship of the osteoclast V-ATPase may lead to the development of osteoclast-specific V-ATPase inhibitors that may serve as alternative therapies for the treatment of osteolytic diseases.

Osteoblastogenesis regulation signals in bone remodeling.

Bone remodeling is essential for adult bone homeostasis. The failure of this process often leads to the development of osteoporosis, a present major global health concern. The most important factor that affects normal bone remodeling is the tightly controlled and orchestrated regulation of osteoblasts and osteoclasts. The present review summarized the recent discoveries related to osteoblast regulation from several signals, including transforming growth factor-ß, bone morphogenetic proteins, Wnt signal, Notch, Eph-Ephrin interaction, parathyroid hormone/parathyroid hormone-related peptide, and the leptin-serotonin-sympathetic nervous systemic pathway. The awareness of these mechanisms will facilitate further research that explores bone remodeling and osteoporosis. Future investigations on the endogenous regulation of osteoblastogenesis will increase the current knowledge required for the development of potential drug targets in the treatment of osteoporosis.

The first multicenter and randomized clinical trial of herbal Fufang for treatment of postmenopausal osteoporosis.

UNLABELLED: This multicenter and randomized clinical trial showed that daily oral herbal formula Xian Ling Gu Bao (XLGB) was safe in postmenopausal women over a 1-year treatment. Those patients (n ∼ 50) treated with XLGB at the conventional dose demonstrated a statistically significant increase in dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) at lumbar spine at 6 months and a numerically increased BMD at 12 months. INTRODUCTION: The aim of this study was to examine the safety and efficacy of a herbal formula XLGB in postmenopausal women (ChiCTR-TRC-00000347). METHODS: One hundred eighty healthy postmenopausal women (≥60 years old) with BMD T-score ≤ -2.0 (lumbar spine or femoral neck) were recruited from four clinical centers to receive low-dose (conventional dose) XLGB (L-XLGB group, 3 g/day, n = 61) or high-dose XLGB (H-XLGB group, 6 g/day, n = 58) or placebo (CON group, n = 61). Women received daily calcium (500 mg) and vitamin D (200 IU) supplementation. Primary endpoints were lumbar spine BMD and safety; secondary endpoints were femoral neck BMD and bone turnover markers measured at baseline and at 6 and 12 months. RESULTS: Of 180 women recruited, 148 completed the study. The compliance in each group was comparable. Prominent adverse events were not observed in either group. In the L-XLGB group at 6 months, lumbar spine BMD by DXA increased significantly from baseline (+2.11% versus CON +0.58%, p < 0.05), but femoral neck BMD did not; at 12 months, BMD in the L-XLGB group decreased from 6-month levels yet remained higher than baseline, but without difference from the CON group. There was no dose-dependent response. Bone turnover marker levels declined during the first 6 months after XLGB treatment. There was no significant difference in the overall incidence of side effects among treatment and control groups. CONCLUSION: XLGB over 1-year treatment at the conventional dose demonstrated safe and only a statistically significant increase in BMD at lumbar spine at 6 months in postmenopausal women.

Association of single-nucleotide polymorphisms in HLA class II/III region with knee osteoarthritis.

OBJECTIVE: A genome-wide association study and a replication using Japanese, Spanish and Greek Caucasian populations have recently indicated two single-nucleotide polymorphisms (SNPs) (rs7775228 and rs10947262) associated with knee Osteoarthritis (OA) susceptibility. We have further evaluated the association in knee OA subjects from Han Chinese and Australian Caucasian origin. METHODS: Two independent case-control association studies were performed using Han Chinese and Australian Caucasian populations. The two SNPs were genotyped in patients who had primary symptomatic knee OA with radiographic confirmation and/or received total knee replacement surgery as well as in matched controls. They were subjected to statistic analyses. RESULTS: A total of 991 OA patients and 1536 controls were genotyped. No significant difference was detected in genotype or allele frequencies of the two SNPs between knee OA and control groups in the two populations (all P>0.05). The association was also negative even after stratification by sex, body mass index (BMI) and Kellgren/Lawrence scores. The significant heterogeneity was detected between Chinese and Japanese (both P<0.05). In the Caucasian samples, no significant heterogeneity was detected (both P>0.05). The result of meta-analysis showed significant association between knee OA and rs10947262 in total subjects [summary OR=1.26, 95%confidence intervals (CI)=1.07-1.27, P=3 × 10(-8)] and in Caucasian samples (summary OR=1.28, 95%CI=1.04-1.57, P=0.02). CONCLUSION: We demonstrated no association between the two SNPs in human leukocyte antigen (HLA) class II/III region and knee OA in Han Chinese population. A significant association was detected between SNP rs10947262 and knee OA in Caucasian subjects. Further replication studies are required to identify the impact of controversial association.

The glycoprotein Ibalpha-von Willebrand factor interaction induces platelet apoptosis.

BACKGROUND: The interaction of glycoprotein (GP) Ibalpha with von Willebrand factor (VWF) initiates platelet adhesion, and simultaneously triggers intracellular signaling cascades leading to platelet aggregation and thrombus formation. Some of the signaling events are similar to those occurring during apoptosis, however, it is still unclear whether platelet apoptosis is induced by the GPIbalpha-VWF interaction. OBJECTIVES: To investigate whether the GPIbalpha-VWF interaction induces platelet apoptosis and the role of 14-3-3zeta in apoptotic signaling. METHODS: Apoptotic events were assessed in platelets or Chinese hamster ovary (CHO) cells expressing wild-type (1b9) or mutant GPIb-IX interacting with VWF by flow cytometry or western blotting. RESULTS: Ristocetin-induced GPIbalpha-VWF interaction elicited apoptotic events in platelets, including phosphatidylserine exposure, elevations of Bax and Bak, gelsolin cleavage, and depolarization of mitochondrial inner transmembrane potential. Apoptotic events were also elicited in platelets exposed to pathologic shear stresses in the presence of VWF; however, the shear-induced apoptosis was eliminated by the anti-GPIbalpha antibody AK2. Furthermore, apoptotic events occurred in 1b9 cells stimulated with VWF and ristocetin, but were significantly diminished in two CHO cell lines expressing mutant GPIb-IX with GPIbalpha truncated at residue 551 or a serine-to-alanine mutation at the 14-3-3zeta-binding site in GPIbalpha. CONCLUSIONS: This study demonstrates that the GPIbalpha-VWF interaction induces apoptotic events in platelets, and that the association of 14-3-3zeta with the cytoplasmic domain of GPIbalpha is essential for apoptotic signaling. This finding may suggest a novel mechanism for platelet clearance or some thrombocytopenic diseases.

Hypergravity results in human platelet hyperactivity.

Thrombotic diseases or fatalities have been reported to occasionally occur under conditions of hypergravity although the mechanism is still unclear. To investigate the effect of hypergravity on platelets that are the primary players in thrombus formation, platelet rich plasma (PRP) or washed platelets were exposed to hypergravity at 8 G for 15 minutes. No platelet aggregation was induced by 8 G alone, whereas ristocetin or collagen-induced platelet aggregation was significantly increased. The number of platelets adherent to immobilized fibrinogen and the area of platelets spreading on von Willbrand factor (VWF) matrix were increased simultaneously. Flow cytometry assay indicated that integrin alphaIIbbeta3 was partially activated in 8 G-exposed platelets, but there was no significant difference in P-selectin surface expression between platelets treated with 8 G and 1 G control. The results indicate that hypergravity leads to human platelet hyperactivity, but fails to incur essential platelet activation events, suggesting a novel mechanism for thrombotic diseases occurring under hypergravitional conditions.

Hypergravity results in human platelet hyperactivity

Thrombotic diseases or fatalities have been reported to occasionally occur underconditions of hypergravity although the mechanism is still unclear. To investigate theeffect of hypergravity on platelets that are the primary players in thrombus formation,platelet rich plasma (PRP) or washed platelets were exposed to hypergravity at8 G for 15 minutes. No platelet aggregation was induced by 8 G alone, whereas ristocetinor collagen-induced platelet aggregation was significantly increased. Thenumber of platelets adherent to immobilized fibrinogen and the area of plateletsspreading on von Willbrand factor (VWF) matrix were increased simultaneously.Flow cytometry assay indicated that integrin áIIbâ3 was partially activated in 8 Gexposedplatelets, but there was no significant difference in P-selectin surface expressionbetween platelets treated with 8 G and 1 G control. The results indicate thathypergravity leads to human platelet hyperactivity, but fails to incur essential plateletactivation events, suggesting a novel mechanism for thrombotic diseases occurringunder hypergravitional conditions(AU)