Meropenem may be an important drug in the treatment of open tibial fractures and chronic osteomyelitis. Therefore, the objective of this study was to describe meropenem pharmacokinetics in plasma, subcutaneous adipose tissue (SCT), and cancellous bone using microdialysis in a porcine model. Six female pigs were assigned to receive 1000 mg of meropenem intravenously over five minutes. Measurements of meropenem were obtained from plasma, SCT, and cancellous bone for eight hours thereafter. Microdialysis was applied for sampling in solid tissues. The meropenem concentrations were determined using ultra-high-performance liquid chromatography.Objectives
Methods
Osteoporosis is a systemic bone metabolic disease, which often occurs among the elderly. Angelica polysaccharide (AP) is the main component of angelica sinensis, and is widely used for treating various diseases. However, the effects of AP on osteoporosis have not been investigated. This study aimed to uncover the functions of AP in mesenchymal stem cell (MSC) proliferation and osteoblast differentiation. MSCs were treated with different concentrations of AP, and then cell viability, Cyclin D1 protein level, and the osteogenic markers of runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP-2) were examined by Cell Counting Kit-8 (CCK-8) and western blot assays, respectively. The effect of AP on the main signalling pathways of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Wnt/β-catenin was determined by western blot. Following this, si-H19#1 and si-H19#2 were transfected into MSCs, and the effects of H19 on cell proliferation and osteoblast differentiation in MSCs were studied. Finally, Objectives
Methods
During the last decades, several research groups have used bisphosphonates for local application to counteract secondary bone resorption after bone grafting, to improve implant fixation or to control bone resorption caused by bone morphogenetic proteins (BMPs). We focused on zoledronate (a bisphosphonate) due to its greater antiresorptive potential over other bisphosphonates. Recently, it has become obvious that the carrier is of importance to modulate the concentration and elution profile of the zoledronic acid locally. Incorporating one fifth of the recommended systemic dose of zoledronate with different apatite matrices and types of bone defects has been shown to enhance bone regeneration significantly
The aim of this study was to provide a comprehensive understanding of alterations in messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in cartilage affected by osteoarthritis (OA). The expression profiles of mRNAs, lncRNAs, and circRNAs in OA cartilage were assessed using whole-transcriptome sequencing. Bioinformatics analyses included prediction and reannotation of novel lncRNAs and circRNAs, their classification, and their placement into subgroups. Gene ontology and pathway analysis were performed to identify differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs), and differentially expressed circRNAs (DECs). We focused on the overlap of DEGs and targets of DELs previously identified in seven high-throughput studies. The top ten DELs were verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in articular chondrocytes, both Objectives
Methods
Bioresorbable orthopaedic devices with calcium phosphate (CaP) fillers are commercially available on the assumption that increased calcium (Ca) locally drives new bone formation, but the clinical benefits are unknown. Electron beam (EB) irradiation of polymer devices has been shown to enhance the release of Ca. The aims of this study were to: 1) establish the biological safety of EB surface-modified bioresorbable devices; 2) test the release kinetics of CaP from a polymer device; and 3) establish any subsequent beneficial effects on bone repair ActivaScrew Interference (Bioretec Ltd, Tampere, Finland) and poly(L-lactide-co-glycolide) (PLGA) orthopaedic screws containing 10 wt% β-tricalcium phosphate (β-TCP) underwent EB treatment. Objectives
Methods
The aim of this study was to identify key pathological genes in osteoarthritis (OA). We searched and downloaded mRNA expression data from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) of joint synovial tissues from OA and normal individuals. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses were used to assess the function of identified DEGs. The protein-protein interaction (PPI) network and transcriptional factors (TFs) regulatory network were used to further explore the function of identified DEGs. The quantitative real-time polymerase chain reaction (qRT-PCR) was applied to validate the result of bioinformatics analysis. Electronic validation was performed to verify the expression of selected DEGs. The diagnosis value of identified DEGs was accessed by receiver operating characteristic (ROC) analysis.Objectives
Methods
The diagnosis of periprosthetic joint infection can be difficult
due to the high rate of culture-negative infections. The aim of
this study was to assess the use of next-generation sequencing for
detecting organisms in synovial fluid. In this prospective, single-blinded study, 86 anonymized samples
of synovial fluid were obtained from patients undergoing aspiration
of the hip or knee as part of the investigation of a periprosthetic
infection. A panel of synovial fluid tests, including levels of
C-reactive protein, human neutrophil elastase, total neutrophil
count, alpha-defensin, and culture were performed prior to next-generation
sequencing.Aims
Materials and Methods
Recently, the field of tissue engineering has made numerous advances towards achieving artificial tendon substitutes with excellent mechanical and histological properties, and has had some promising experimental results. The purpose of this systematic review is to assess the efficacy of tissue engineering in the treatment of tendon injuries. We searched MEDLINE, Embase, and the Cochrane Library for the time period 1999 to 2016 for trials investigating tissue engineering used to improve tendon healing in animal models. The studies were screened for inclusion based on randomization, controls, and reported measurable outcomes. The RevMan software package was used for the meta-analysis.Objectives
Methods
The aim of this study was to review the impact of smoking tobacco on the musculoskeletal system, and on bone fractures in particular. English-language publications of human and animal studies categorizing subjects into smokers and nonsmokers were sourced from MEDLINE, The Cochrane Library, and SCOPUS. This review specifically focused on the risk, surgical treatment, and prevention of fracture complications in smokers.Objectives
Methods
Stem cells are defined by their potential for self-renewal and the ability to differentiate into numerous cell types, including cartilage and bone cells. Although basic laboratory studies demonstrate that cell therapies have strong potential for improvement in tissue healing and regeneration, there is little evidence in the scientific literature for many of the available cell formulations that are currently offered to patients. Numerous commercial entities and ‘regenerative medicine centres’ have aggressively marketed unproven cell therapies for a wide range of medical conditions, leading to sometimes indiscriminate use of these treatments, which has added to the confusion and unpredictable outcomes. The significant variability and heterogeneity in cell formulations between different individuals makes it difficult to draw conclusions about efficacy. The ‘minimally manipulated’ preparations derived from bone marrow and adipose tissue that are currently used differ substantially from cells that are processed and prepared under defined laboratory protocols. The term ‘stem cells’ should be reserved for laboratory-purified, culture-expanded cells. The number of cells in uncultured preparations that meet these defined criteria is estimated to be approximately one in 10 000 to 20 000 (0.005% to 0.01%) in native bone marrow and 1 in 2000 in adipose tissue. It is clear that more refined definitions of stem cells are required, as the lumping together of widely diverse progenitor cell types under the umbrella term ‘mesenchymal stem cells’ has created confusion among scientists, clinicians, regulators, and our patients. Validated methods need to be developed to measure and characterize the ‘critical quality attributes’ and biological activity of a specific cell formulation. It is certain that ‘one size does not fit all’ – different cell formulations, dosing schedules, and culturing parameters will likely be required based on the tissue being treated and the desired biological target. As an alternative to the use of exogenous cells, in the future we may be able to stimulate the intrinsic vascular stem cell niche that is known to exist in many tissues. The tremendous potential of cell therapy will only be realized with further basic, translational, and clinical research. Cite this article:
The aim of this study was to evaluate the surface damage, the density of crosslinking, and oxidation in retrieved antioxidant-stabilized highly crosslinked polyethylene (A-XLPE) tibial inserts from total knee arthroplasty (TKA), and to compare the results with a matched cohort of standard remelted highly crosslinked polyethylene (XLPE) inserts. A total of 19 A-XLPE tibial inserts were retrieved during revision TKA and matched to 18 retrieved XLPE inserts according to the demographics of the patients, with a mean length of implantation of 15 months (1 to 42). The percentage areas of PE damage on the articular surfaces and the modes of damage were measured. The density of crosslinking of the PE and oxidation were measured at loaded and unloaded regions on these surfaces.Aims
Materials and Methods
Many Specific keywords were used to search electronic databases (EMBASE, PubMed, and Web of Science) for English-language literature published between 1995 and 2017.Objectives
Methods
Osteoarthritis (OA) is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control the expression of genes and are likely to regulate the OA transcriptome. We performed integrative genomic analyses to define methylation-gene expression relationships in osteoarthritic cartilage. Genome-wide DNA methylation profiling of articular cartilage from five patients with OA of the knee and five healthy controls was conducted using the Illumina Infinium HumanMethylation450 BeadChip (Illumina, San Diego, California). Other independent genome-wide mRNA expression profiles of articular cartilage from three patients with OA and three healthy controls were obtained from the Gene Expression Omnibus (GEO) database. Integrative pathway enrichment analysis of DNA methylation and mRNA expression profiles was performed using integrated analysis of cross-platform microarray and pathway software. Gene ontology (GO) analysis was conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID).Aim
Patients and Methods
This study aimed to assess the performance of an automated multiplex polymerase chain reaction (mPCR) technique for rapid diagnosis of native joint septic arthritis Consecutive patients with suspected septic arthritis undergoing aseptic diagnostic joint aspiration were included. The aspirate was used for analysis by mPCR and conventional microbiological analysis. A joint was classed as septic according to modified Newman criteria. Based on receiver operating characteristic (ROC) analysis, the area under the ROC curve (AUC) values of the mPCR and the synovial fluid culture were compared using the z-test. A total of 72 out of 76 consecutive patients (33 women, 39 men; mean age 64 years (22 to 92)) with suspected septic arthritis were included in this study.Aims
Patients and Methods
Charcot neuroarthropathy is a rare but serious complication of diabetes, causing progressive destruction of the bones and joints of the foot leading to deformity, altered biomechanics and an increased risk of ulceration. Management is complicated by a lack of consensus on diagnostic criteria and an incomplete understanding of the pathogenesis. In this review, we consider recent insights into the development of Charcot neuroarthropathy. It is likely to be dependent on several interrelated factors which may include a genetic pre-disposition in combination with diabetic neuropathy. This leads to decreased neuropeptides (nitric oxide and calcitonin gene-related peptide), which may affect the normal coupling of bone formation and resorption, and increased levels of Receptor activator of nuclear factor kappa-B ligand, potentiating osteoclastogenesis. Repetitive unrecognized trauma due to neuropathy increases levels of pro-inflammatory cytokines (interleukin-1β, interleukin-6, tumour necrosis factor α) which could also contribute to increased bone resorption, in combination with a pre-inflammatory state, with increased autoimmune reactivity and a profile of monocytes primed to transform into osteoclasts - cluster of differentiation 14 (CD14). Increased blood glucose and loss of circulating Receptor for Advanced Glycation End-Products (AGLEPs), leading to increased non-enzymatic glycation of collagen and accumulation of AGLEPs in the tissues of the foot, may also contribute to the pathological process. An understanding of the relative contributions of each of these mechanisms and a final common pathway for the development of Charcot neuroarthropathy are still lacking.
Tuberculosis (TB) infection of bones and joints accounts for
6.7% of TB cases in England, and is associated with significant
morbidity and disability. Public Health England reports that patients
with TB experience delays in diagnosis and treatment. Our aims were
to determine the demographics, presentation and investigation of
patients with a TB infection of bones and joints, to help doctors
assessing potential cases and to identify avoidable delays. This was a retrospective observational study of all adults with
positive TB cultures on specimens taken at a tertiary orthopaedic
centre between June 2012 and May 2014. A laboratory information
system search identified the patients. The demographics, clinical presentation,
radiology, histopathology and key clinical dates were obtained from
medical records.Aims
Patients and Methods
The aim of this study was to determine the prevalence and characteristics of C-reactive protein (CRP)-negative prosthetic joint infection (PJI) and evaluate the influence of the type of infecting organism on the CRP level. A retrospective analysis of all PJIs affecting the hip or knee that were diagnosed in our institution between March 2013 and December 2016 was performed. A total of 215 patients were included. Their mean age was 71 years (Aims
Patients and Methods
The aim of this study was to investigate the effect of hyperglycaemia on oxidative stress markers and inflammatory and matrix gene expression within tendons of normal and diabetic rats and to give insights into the processes involved in tendinopathy. Using tenocytes from normal Sprague-Dawley rats, cultured both in control and high glucose conditions, reactive oxygen species (ROS) production, cell proliferation, messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, interleukin-6 (IL-6), matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-1 and -2 and type I and III collagens were determined after 48 and 72 hours Objectives
Methods
Osteoporosis is a chronic disease. The aim of this study was to identify key genes in osteoporosis. Microarray data sets GSE56815 and GSE56814, comprising 67 osteoporosis blood samples and 62 control blood samples, were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified in osteoporosis using Limma package (3.2.1) and Meta-MA packages. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify biological functions. Furthermore, the transcriptional regulatory network was established between the top 20 DEGs and transcriptional factors using the UCSC ENCODE Genome Browser. Receiver operating characteristic (ROC) analysis was applied to investigate the diagnostic value of several DEGs.Objectives
Methods
