Heparin Anti-Xa Activity, a Readily Available Unique Test to Quantify Apixaban, Rivaroxaban, Fondaparinux, and Danaparoid Levels.

BACKGROUND: Despite their usefulness in perioperative and acute care settings, factor-Xa inhibitor-specific assays are scarcely available, contrary to heparin anti-Xa assay. We assessed whether the heparin anti-Xa assay can (1) be used as a screening test to rule out apixaban, rivaroxaban, fondaparinux, and danaparoid levels that contraindicate invasive procedures according to current guidelines (>30 ng·mL-1, >30 ng·mL-1, >0.1 µg·mL-1, and >0.1 IU·mL-1, respectively), (2) quantify the anticoagulant level if found significant, that is, if it exceeded the abovementioned threshold. METHODS: In the derivation cohort then in the validation cohort, via receiver operating characteristics (ROC) curve analysis, we evaluated the ability of heparin anti-Xa assay to detect levels of factor-Xa inhibitors above or below the abovementioned safety thresholds recommended for an invasive procedure (screening test). Among samples with relevant levels of factor-Xa inhibitor, we determined the conversion factor linking the measured level and heparin anti-Xa activity in a derivation cohort. In a validation cohort, the estimated level of each factor-Xa inhibitor was thus inferred from heparin anti-Xa activity. The agreement between measured and estimated levels of factor-Xa inhibitors was assessed. RESULTS: Among 989 (355 patients) and 756 blood samples (420 patients) in the derivation and validation cohort, there was a strong linear relationship between heparin anti-Xa activities and factor-Xa inhibitors measured level (r = 0.99 [95% confidence interval {CI}, 0.99-0.99]). In the derivation cohort, heparin anti-Xa activity ≤0.2, ≤0.3, <0.1, <0.1 IU·mL-1 reliably ruled out a relevant level of apixaban, rivaroxaban, fondaparinux, and danaparoid, respectively (area under the ROC curve ≥0.99). In the validation cohort, these cutoffs yielded excellent classification accuracy (≥96%). If this screening test indicated relevant level of factor-Xa inhibitor, estimated and measured levels closely agreed (Lin's correlation coefficient close to its maximal value: 95% CI, 0.99-0.99). More than 96% of the estimated levels fell into the predefined range of acceptability (ie, 80%-120% of the measured level). CONCLUSIONS: A unique simple test already widely used to assay heparin was also useful for quantifying these 4 other anticoagulants. Both clinical and economic impacts of these findings should be assessed in a specific study.

Association of Protein and Genetic Biomarkers With Response to Lumbar Epidural Steroid Injections in Subjects With Axial Low Back Pain.

OBJECTIVE: The purpose of this observational study was to examine the association of protein and genetic biomarkers with pain and pain-related disability in individuals with axial low back pain undergoing epidural steroid injections. DESIGN: Forty-eight adults with axial low back pain undergoing an epidural steroid injection were recruited from an academic medical center. Blood samples were assayed at baseline and follow-up for plasma proteins and functional single-nucleotide polymorphisms associated with pain. Data regarding pain and function were collected at baseline and follow-up. The characteristics of responders (defined as 50% improvement in pain score) and nonresponders were compared, and the association between response and baseline biomarkers was examined. RESULTS: Thirty-five percent of subjects were responders to injection. Responders had lower baseline plasma levels of chondroitin sulfate 846 and higher neuropeptide Y and serotonin levels than nonresponders, and baseline neuropeptide Y level correlated with change in disability levels. In addition, subjects with the variant allele for the catechol-O-methyltransferase single-nucleotide polymorphism demonstrated increased odds of responding to the injection. CONCLUSIONS: These data identify candidates who may have utility for patient selection for spinal procedures and provide support for exploration in prospective studies to assess and validate their predictive ability.

Fucosylated Chondroitin Sulfate 9-18 Oligomers Exhibit Molecular Size-Independent Antithrombotic Activity while Circulating in the Blood.

Fucosylated chondroitin sulfate (FCS) oligosaccharides extracted from sea cucumber and depolymerized exhibit potent anticoagulant activity. Knowledge of the antithrombotic activity of different size oligosaccharides and their fucose (Fuc) branch sulfation pattern should promote their development for clinical applications. We prepared highly purified FCS trisaccharide repeating units from hexasaccharide (6-mer) to octadecasaccharide (18-mer), including those with 2,4-disulfated and 3,4-disulfated Fuc branches. All 10 oligosaccharides were identified by their nuclear magnetic resonance structures and ESI-FTMS spectroscopy. In vitro anticoagulant activities and surface plasmon resonance binding tests indicated those of larger molecular sizes and 2,4-disulfated Fuc branches showed stronger anticoagulant effects with respect to anti-FXase activity, as well as stronger binding to FIXa among various clotting proteins. However, both types of FCS 9-mer to 18-mer exhibited molecular size-independent potent antithrombotic activity in vivo at the same dose. In addition, both types of the FCS 6-mer exhibited favorable antithrombotic activity in vivo, although they showed weak anticoagulant activity in vitro. Combining absorption and metabolism studies, we conclude that FCS 9-18 oligomers could remain in the circulation to interact with various clotting proteins to prevent thrombus formation, and appreciable quantities of these oligomers could be excreted through the kidneys. All FCS 9-18 oligomers also resulted in no bleeding, hypotension, or platelet aggregation risk during blood circulation. Thus, FCS 9-18 oligomers with 2,4-disulfated or 3,4-disulfated Fuc branches exhibit potent and safe antithrombotic activity needed for clinical applications.

Multivariable logistic and linear regression models for identification of clinically useful biomarkers for osteoarthritis.

Osteoarthritis (OA) is the most common chronic degenerative joint disease which causes substantial joint pain, deformity and loss of activities of daily living. Currently, there are over 500 million OA cases worldwide, and there is an urgent need to identify biomarkers for early detection, and monitoring disease progression in patients without obvious radiographic damage to the joint. We have used regression modelling to describe the association of 19 of the currently available biomarkers (predictors) with key radiographic and clinical features of OA (outcomes) in one of the largest and best characterised OA cohort (NIH Osteoarthritis Initiative). We demonstrate that of the 19 currently available biomarkers only 4 (serum Coll2-1 NO2, CS846, COMP and urinary CTXII) were consistently associated with established radiographic and/or clinical features of OA. These biomarkers are independent of one another and provide additional predictive power over, and above established predictors of OA such as age, gender, BMI and race. We also show that that urinary CTXII had the strongest and consistent associations with clinical symptoms of OA as well as radiographic evidence of joint damage. Accordingly, urinary CTXII may aid in early diagnosis of OA in symptomatic patients without radiographic evidence of OA.

Quality performance for indirect Xa inhibitor monitoring in patients using international external quality data.

Objectives Chromogenic anti-activated factor X (FXa) assays are currently the "gold standard" for monitoring indirect anticoagulants. However, anti-FXa has been shown to vary according to the choice of reagents. In the present study, the performance of anti-FXa measurement was evaluated in order to gain more insight into the clinical applications. Furthermore, the longitudinal coefficient of variation (CV) was studied to investigate whether there is improvement over time. Methods Laboratory tests results were evaluated for samples spiked with unfractionated heparin (UFH), low-molecular-weight-heparin (LMWH), fondaparinux and danaparoid sodium. External quality assessment (EQA) data from multiple years were used from more than 100 laboratories. Results Comparison of the results for all methods showed significant differences in measured values between the frequently used methods (ANOVA: p < 0.001). The largest differences were observed for LMWH and UFH measurements. These differences may be caused by differences in method composition, such as the addition of dextran sulphate. Substantial interlaboratory variation in anti-FXa monitoring was observed for all parameters, particularly at low concentrations. Our results showed that below 0.35 IU/mL, the CVs for UFH and LMWH increase dramatically and results below this limit should be used with caution. Conclusions Our study demonstrates that the choice of the anti-FXa method is particularly important for UFH and LMWH measurement. The variation in measurements may have an effect on clinical implications, such as therapeutic ranges. Furthermore, the longitudinal EQA data demonstrated a constant performance and, in at least 50% of the cases, improvement in the CV% of the anti-Xa results over time.

Serious Selenium Deficiency in the Serum of Patients with Kashin-Beck Disease and the Effect of Nano-Selenium on Their Chondrocytes.

To investigate selenium (Se) concentrations in serum of patients with rheumatoid arthritis (RA), osteoarthritis (OA), and Kashin-Beck disease (KBD), together with the effect of Se supplement (chondroitin sulfate [CS] nano-Se [SeCS]) on CS structure-modifying sulfotransferases in KBD chondrocyte. Fifty serum samples from each group with aged-matched (40-60 years), normal control (N), RA, OA, and KBD (25 males and females, respectively) were collected to determine Se concentrations. Furthermore, the KBD chondrocytes were divided into two groups following the intervention for 24 h: (a) non-treated KBD group and (b) SeCS-treated KBD group (100 ng/mL SeCS). The ultrastructural changes in chondrocytes were observed by transmission electron microscopy (TEM). Live/dead staining was used to observe cell viability. The expression of CS-modifying sulfotransferases including carbohydrate sulfotransferase 12, 13, and 15 (CHST-12, CHST-13, and CHST-15, respectively), and uronyl 2-O-sulfotransferase (UST) were examined by quantitative real-time polymerase chain reaction and western blotting analysis after SeCS intervention. The Se concentrations in serum of KBD, OA, and RA patients were lower than those in control. In OA, RA, and control, Se concentrations were higher in male than in female, while it is opposite in KBD. In the cell experiment, cell survival rate and mitochondrial density were increased in SeCS-treated KBD groups. Expressions of CHST-15, or CHST-12, and CHST-15 on the mRNA or protein level were significantly increased. Expression of UST slightly increased on the mRNA level, but no change was visible on the protein level. Se deficiency in serum of RA, OA, and KBD was observed. SeCS supplemented in KBD chondrocytes improved their survival rate, ameliorated their ultrastructure, and increased the expression of CS structure-modifying sulfotransferases.

Combined use of Serum miR-338-3p, Cartilage Oligomeric Matrix Protein and Chondroitin Sulfate-846 in the Early Diagnosis of Knee Osteoarthritis.

BACKGROUND: In this study, the serum levels of miR-338-3p, COMP, and CS-846 were detected in the patients with KOA and healthy controls, to explore the value of miR-338-3p, COMP, and CS-846 in the early diagnosis of KOA. METHODS: Real-time PCR was carried out to evaluate the level of miR-338-3p in KOA patients and healthy controls. Spearman's correlation coefficient was performed to examine the correlation between the expression of miR-338-3p, COMP, and CS-846. Receiver operating characteristic (ROC) curves were carried out to evaluate the diagnostic values of miR-338-3p, COMP, and CS-846 for KOA patients. RESULTS: In the current study, we first demonstrated that serum miR-338-3p, COMP, and CS-846 levels were increased in KOA patients compared to healthy controls. Moreover, the increase of miR-338-3p, COMP, and CS-846 levels positively correlated with VAS scores and joint space narrowing, suggesting miR-338-3p positively correlated with comprehensive disease severity. In addition, miR-338-3p, COMP, and CS-846 could be used as an independent biomarker for KOA patients. More importantly, combined use of miR-338-3p, COMP, and CS-846 demonstrates a higher diagnostic value with an AUC 0.926 for KOA patients. CONCLUSIONS: The combination of miR-338-3p, COMP, and CS-846 demonstrated higher diagnostic value for KOA patients, indicating their combination as novel and promising biomarkers for diagnosis and disease severity of KOA.

Oral Bioavailability and Pharmacokinetics of Nonanimal Chondroitin Sulfate and Its Constituents in Healthy Male Volunteers.

The pharmacokinetic profile of a new 800-mg tablet of nonanimal chondroitin sulfate (CS) (Mythocondro®, 800-mg tablets, Gnosis S.p.A., Italy) was investigated vs an animal CS in healthy volunteers for a total period of 48 hours. After a single 2400-mg dose of the test and the reference formulation, total CS, the compositional disaccharides (ΔDi6S, ΔDi4S and ΔDi0S), and the overall charge density were quantified in plasma. The safety and tolerability profile after a single dose of this new nonanimal CS tablets was excellent. After baseline-corrected concentrations, an overall greater plasma concentration was observed after 24 hours of ∼44% and after 48 hours of ∼45% from administration of nonanimal when compared to animal-derived CS. Moreover, nonanimal CS increases the specific sulfation in the 6-position of N-acetyl-galactosamine in human plasma CS and, as a consequence, the overall charge density, reaching double values (0.91), after 48 hours compared to bovine CS and to endogenous CS. In conclusion, nonanimal CS, possessing a lower molecular weight than an animal-derived sample, produces a greater CS concentration for a more prolonged period of time in plasma and an increase in charge density and specific 6-sulfation of endogenous plasma CS.

Plasma contact activation by a fucosylated chondroitin sulfate and its structure-activity relationship study.

Plasma contact system is the initial part of both the intrinsic coagulation pathway and kallikrein-kinin pathway, which mainly involves three proteins: coagulation factor XII (FXII), prekallikrein (PK) and high-molecular weight kininogen. Fucosylated chondroitin sulfate (FCS) is a unique sulfated glycosaminoglycan (GAG) composed of a chondroitin sulfate-like backbone and sulfated fucose branches. The native FCS was preliminary found to cause undesired activation of the plasma contact system. How this unusual GAG functions in this process remains to be clarified. Herein, the relationship between its structure, plasma contact activation and its effects on the PK-FXII reciprocal activation loop were studied. The recalcification time assay indicated that the FCS at high concentration could be procoagulant which may be attributed to its contact activation activity. The structure-activity relationship study indicated that its high molecular weight and distinct fucose side chains are required for contact activation by FCS, although the sulfate substitution types of its side chains have less impact. In human plasma, the native FCSs potently induced FXII-dependent contact activation. However, in purified systems FCS did not significantly activate FXII per se or induce its autoactivation, whereas FCS significantly promoted the activation of PK by factor XIIa. Polysaccharide-protein interaction assays showed that FCS bound to PK with higher affinity than other contact system proteins. These data suggested that potent contact activation by FCS requires the positive feedback loop between PK and FXII. These findings contribute to better understanding of contact activation by complex GAG.

Molecular genetics and metabolism, special edition: Diagnosis, diagnosis and prognosis of Mucopolysaccharidosis IVA.

Mucopolysaccharidosis IVA (MPS IVA, Morquio A syndrome) is an autosomal recessive disorder caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to the accumulation of specific glycosaminoglycans (GAGs), chondroitin-6-sulfate (C6S) and keratan sulfate (KS), which are mainly synthesized in the cartilage. Therefore, the substrates are stored primarily in the cartilage and its extracellular matrix (ECM), leading to a direct impact on bone development and successive systemic skeletal spondylepiphyseal dysplasia. The skeletal-related symptoms for MPS IVA include short stature with short neck and trunk, odontoid hypoplasia, spinal cord compression, tracheal obstruction, obstructive airway, pectus carinatum, restrictive lung, kyphoscoliosis, platyspondyly, coxa valga, genu valgum, waddling gait, and laxity of joints. The degree of imbalance of growth in bone and other organs and tissues largely contributes to unique skeletal dysplasia and clinical severity. Diagnosis of MPS IVA needs clinical, radiographic, and laboratory testing to make a complete conclusion. To diagnose MPS IVA, total urinary GAG analysis which has been used is problematic since the values overlap with those in age-matched controls. Currently, urinary and blood KS and C6S, the enzyme activity of GALNS, and GALNS molecular analysis are used for diagnosis and prognosis of clinical phenotype in MPS IVA. MPS IVA can be diagnosed with unique characters although this disorder relates closely to other disorders in some characteristics. In this review article, we comprehensively describe clinical, radiographic, biochemical, and molecular diagnosis and clinical assessment tests for MPS IVA. We also compare MPS IVA to other closely related disorders to differentiate MPS IVA. Overall, imbalance of growth in MPS IVA patients underlies unique skeletal manifestations leading to a critical indicator for diagnosis.

Association of Endothelial Glycocalyx and Tight and Adherens Junctions With Severity of Plasma Leakage in Dengue Infection.

Background: The role of vascular endothelial (VE) components in dengue infection with plasma leakage is unknown. Therefore, we conducted a study to determine the adjusted association of the endothelial glycocalyx layer (EGL) and tight and adherens junction markers with plasma leakage. Methods: A prospective observational study was conducted at Cipto Mangunkusumo Hospital and Persahabatan Hospital, Jakarta, Indonesia. Adult dengue patients admitted to the hospital on the third day of fever from November 2013 through August 2015 were included in the study. Multiple regression analysis was used to determine the adjusted association of the VE biomarkers with the severity of the plasma leakage. Results: A total of 103 dengue-infected patients participated in the study. In the critical phase, levels of syndecan-1 (odds ratio [OR] = 1.004; 95% confidence interval [CI] = 1.001-1.007) and chondroitin sulfate (OR = 1.157; 95% CI = 1.025-1.307) had an adjusted association with plasma leakage, whereas levels of syndecan-1 (OR = 1.004; 95% CI = 1.000-1.008) and claudin-5 (OR = 1.038; 95% CI = 1.004-1.074) had an adjusted association with severe plasma leakage. Conclusions: In dengue-infected patients, elevated levels of syndecan-1 and chondroitin sulfate are strongly associated with plasma leakage, and elevated levels of syndecan-1 and claudin-5 are strongly associated with severe plasma leakage.

Highly sensitive ratiometric detection of heparin and its oversulfated chondroitin sulfate contaminant by fluorescent peptidyl probe.

The selective and sensitive detection of heparin, an anticoagulant in clinics as well as its contaminant oversulfated chondroitin sulfate (OSCS) is of great importance. We first reported a ratiometric sensing method for heparin as well as OSCS contaminants in heparin using a fluorescent peptidyl probe (Pep1, pyrene-GSRKR) and heparin-digestive enzyme. Pep1 exhibited a highly sensitive ratiometric response to nanomolar concentration of heparin in aqueous solution over a wide pH range (2~11) and showed highly selective ratiometric response to heparin among biological competitors such as hyaluronic acid and chondroitin sulfate. Pep1 showed a linear ratiometric response to nanomolar concentrations of heparin in aqueous solutions and in human serum samples. The detection limit for heparin was calculated to be 2.46nM (R2=0.99) in aqueous solutions, 2.98nM (R2=0.98) in 1% serum samples, and 3.43nM (R2=0.99) in 5% serum samples. Pep1 was applied to detect the contaminated OSCS in heparin with heparinase I, II, and III, respectively. The ratiometric sensing method using Pep1 and heparinase II was highly sensitive, fast, and efficient for the detection of OSCS contaminant in heparin. Pep1 with heparinase II could detect as low as 0.0001% (w/w) of OSCS in heparin by a ratiometric response.

Serum levels of endothelial glycocalyx constituents in women at 20†weeks' gestation who later develop gestational diabetes mellitus compared to matched controls: a pilot study.

OBJECTIVES: The aim of this pilot study was to determine the serum concentration of heparan sulfate, hyaluronan, chondroitin sulfate and syndecan-1 and if these serum concentrations can be used to identify women at 20 weeks' gestation who later develop gestational diabetes mellitus (GDM). DESIGN: Nested case-control study from Auckland, New Zealand participants in the prospective cohort Screening for Pregnancy Endpoints study. SETTING: Auckland, New Zealand. PARTICIPANTS: 20 pregnant women (70% European, 15% Indian, 10% Asian, 5% Pacific Islander) at 20 weeks' gestation without any hypertensive complications who developed GDM by existing New Zealand criteria defined as a fasting glucose ≥5.5 mmol/L and/or 2 hours ≥9.0 mmol/L after a 75 g Oral Glucose Tolerance Test. Women not meeting these criteria were excluded from this study. The patients with GDM were matched with 20 women who had uncomplicated pregnancies and negative screening for GDM and matched for ethnicity, maternal age and BMI. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary measures were the serum concentrations of syndecan-1, heparan sulfate, hyaluronan and chondroitin sulfate determined by quantitative ELISA. There were no secondary outcome measures. RESULTS: Binary logistic regression was performed to determine if serum concentrations of endothelial glycocalyx layer constituents in women at 20 weeks' gestation would be useful in predicting the subsequent diagnosis of GDM. The model was not statistically significant χ2=12.5, df=8, p=0.13, which indicates that the model was unable to distinguish between pregnant women at 20 weeks' gestation who later developed GDM and those who did not. CONCLUSIONS: Serum concentrations of syndecan-1, heparan sulfate, hyaluronan and chondroitin sulfate in pregnant women at 20 weeks' gestation were not associated with later development of GDM. To further explore whether there is any relationship between endothelial glycocalyx constituents and GDM, the next step is to evaluate serum concentrations at the time diagnosis of GDM.

Modulating luminescence of Tb(3+) with biomolecules for sensing heparin and its contaminant OSCS.

The detection of heparin (Hep) and its contaminant oversulfated chondroitin sulfate (OSCS) is of great importance in clinics but remains challenging. Here, we report a sensitive and selective time-resolved luminescence (TRL) biosensing system for Hep by modulating the photoluminescence of Tb(3+) with guanine-rich ssDNA and Hep-specific AG73 peptide (RKRLQVQLSIRT). With the developed system, Hep including both unfractionated Hep (UFH) and the low molecular weight Hep (LMWH) has been successfully detected with a satisfactory detection limit. Owing to the highly specific interaction between Hep and AG73 peptide, major interfering substances in Hep detection, such as Hep analogs of chondrotin sulfate (Chs) and hyaluronic acid (HA), did not interfere with Hep detection. The established TRL sensing system was then successfully used for monitoring Hep metabolism in living rats by microdialysis. Moreover, the proposed TRL sensing system was further applied to analyze OSCS contaminant in Hep with heparinases treatment by exploring the inhibition effects of OSCS on the activity of heparinases. As low as 0.002% of OSCS in Hep was identified.

Laboratory Indicators of Aggrecan Turnover in Juvenile Idiopathic Arthritis.

OBJECTIVES: Evaluation of chondroitin sulfate (CS), as an early marker of aggrecan degradation, and chondroitin sulfate 846 epitope (CS846), as a biomarker of CS synthesis, is an attempt at answering the question whether the therapy used in juvenile idiopathic arthritis (JIA) patients contributes to the normalization of biochemical changes in aggrecan. METHODS AND RESULTS: Serum levels of CS and CS846 as well as catalase (CT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities in erythrocyte were assessed in patients before and after treatment. In the course of JIA, aggrecan metabolism is disturbed, which is reflected by a decrease (p < 0.001) in CS serum level and an increase (p < 0.05) in CS846 concentration. Furthermore, increased (p < 0.001) activities of CT, SOD, and GPx in untreated JIA patients were recorded. The anti-inflammatory treatment resulted in the normalization of CS846 level and SOD and GPx activities. In untreated patients, we have revealed a significant correlation between serum CS and CS846, CT, CRP, ESR, MMP-3, and ADAMTS-4, respectively, as well as between CS846 and CT, GPx, CRP, ESR, and TGF-ß1, respectively. CONCLUSION: The observed changes of CS and CS846 in JIA patients indicate a further need of the therapy continuation aimed at protecting a patient from a possible disability.

Analytical Methods for Assessing Chondroitin Sulfate in Human Plasma.

Chondroitin sulfate (CS) is a linear heteropolysaccharide of repeating disaccharide units bearing sulfate groups in various positions, commonly at C4 and/or C6 of galactosamine. CS plays important roles in various (patho)physiological processes also performing intriguing biological and therapeutical activities. Plasmatic CS is mainly composed of nonsulfated and 4-sulfated disaccharides. To obtain samples for the determination of CS amount and composition in blood/plasma, dried blood spot (DBS) could be used. DBSs have many advantages over other laboratory methods, allowing for large-scale population screening. Many analytical techniques may be used for the determination of CS. In particular, CE has proved to be a very attractive alternative separation technique for complex polysaccharide characterization. In this work, we compared CS levels between plasma and DBS samples, using CE equipped with the highly sensitive laser-induced fluorescence detector. CS from DBS differs from plasma CS owing to the high content of disaccharides sulfated in C4 and C6. This is due to the presence of the more sulfated CS derived from blood cellular fraction, in particular leukocytes. The identification and quantification of CS in blood plasma could be a useful prognostic and diagnostic tool in pathological conditions and for pharmacological applications.

Synovium and cartilage biomarkers in hemophilic arthropathy.

Some promising cartilage and synovium biomarkers are at various stages of development and awaiting further validation in larger patient populations with osteoarthritis (OA). Various reports have shown increased levels of inflammatory biomarkers, both locally (synovial fluid) and systemically (serum and plasma) in such patients. The clinical value of these parameters in combination with imaging biomarkers in order to predict early onset and the burden of OA is being investigated. This review article aims to describe the potential usefulness of synovial and cartilage biomarkers for the diagnosis and prognosis of hemophilic arthropathy (HA) by using the existing literature on OA as an applicable model. A systematic review found that serum cartilage oligomeric matrix protein (sCOMP) is elevated in patients with knee OA and is sensitive to OA disease progression.

Spectral study of interaction between chondroitin sulfate and nanoparticles and its application in quantitative analysis.

In this work, the interaction between chondroitin sulfate (CS) and gold nanoparticles (GNPs) and silver nanoparticles (SNPs) was characterized for the first time. Plasma resonance scattering (PRS) and plasma resonance absorption (PRA) were used to investigate the characteristics of their spectrum. The results suggested that the CS with negative charge could interact with metal nanoparticles with negative charge and the adsorption of CS on the surface of SNPs was more regular than that of GNPs. The resonance scattering spectra also further confirmed the interaction between CS and SNPs. A new method for detection of CS based on the interaction was developed. CS concentrations in the range of 0.02-3.5 µg/mL were proportional to the decreases of absorbance of SNPs. Compared with other reported methods, the proposed method is simple and workable without complex process, high consumption and expensive equipments. The developed method was applied to the determination of the CS contents from different biological origins and the results were compared with those obtained by the method of Chinese Pharmacopeia. The effects of matrix in plasma and other glycosaminoglycans on the determination of CS were also investigated. The results showed that a small quantity of blood plasma had no effect on the determination of CS and when the concentration ratio of CS to heparin was more than 10:1, the influence of heparin on the detection of CS could be ignored. This work gave a specific research direction for the detection of CS in the presence of metal nanoparticles.

Diet-induced hypercholesterolemia imparts structure-function changes to erythrocyte chondroitin sulphate/dermatan sulphate.

Hypercholesterolemia is one of the factors contributing to cardiovascular problems. Erythrocytes are known to contribute its cholesterol to atherosclerotic plaque. Our earlier study showed that erythrocytes overexpress chondroitin sulphate/dermatan sulphate (CS/DS), a linear co-polymer, during diabetes which resulted in increased cytoadherence to extracellular matrix (ECM) components. This study was carried out to determine whether diet-induced hypercholesterolemia had any effect on erythrocyte CS/DS and impacted cytoadherence to ECM components. Unlike in diabetes, diet-induced hypercholesterolemia did not show quantitative changes in erythrocyte CS/DS but showed difference in proportion of un-sulphated and 4-O-sulphated disaccharides. Erythrocytes from hypercholesterolemic rats showed increased adhesion to ECM components which was abrogated to various extents when subjected to chondroitinase ABC digestion. However, isolated CS/DS chains showed a different pattern of binding to ECM components indicating that orientation of CS/DS chains could be playing a role in binding.

Association between the severity of knee osteoarthritis and serum cartilage biomarker levels.

BACKGROUND: Osteoarthritis (OA) is the most common form of arthritis. However, there has been no cost-effective tool for the investigation of the severity and progression of the disease because using OA standard diagnostic methods causes cartilage damage. OBJECTIVE: To evaluate the relationship between serum chondroitinsulphate WF6 (CS-WF6) and hyaluronate (HA) and the severity of knee OA according to Kellgren-Lawrence (K/L) grades of radiographic severity and minimal joint space width (JSWV). MATERIAL AND METHOD: One-hundred and twenty-six patients with OA (knee) according to K/L grades were classified into four groups. The JSW of the tibiofemoraljoint were measured from standing PA radiographs. Serum CS-WF6 and HA were analyzed by the ELISA based technique. One-way analysis of variance, Bonferroni's method and Kendall's tau coefficient relation test were performed to evaluate the association of K/L grades and JSW with levels of CS-WF6 and HA, respectively. RESULTS: Serum CS-WF6 levels in grade 4 were significantly increased when compared with the other grades (p < 0.05). The serum HA level did not show any significant difference among the grades of severity. The serum CS-WF6 level showed a significant negative correlation with the JSW and its levels rose rapidly to the level beyond 300 ng/ml. There was no correlation found between the levels of serum HA and JSW CONCLUSION: WF6 levels may be useful in identifying patients at risk of rapid progression reflected by a point of an abruptly high WF6 level. The determination of WF6 in the serum showed increasing levels in more severe grades, so it could be useful in monitoring the effectiveness of treatment. There were some limitations because of broad distribution and overlap with the normal range. Thus, it may not be suitable as a diagnostic tool.