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HA Concentration (ha + concentration)

Distribution by Scientific Domains
Medical Sciences70%
Polymers and Materials Science20%

Selected Abstracts

Direct and indirect manipulation of the MEK-ERK pathway regulates the formation of a pericellular HA-dependent matrix by chick articular surface cells without modifying CD44 expresssion

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2004
Edward R. Bastow
Introduction Recent evidence suggests that hyaluronan (HA) facilitates the mechano-dependent joint cavity-forming process through the elaboration and retention of a HA-rich pericellular matrix in the developing joint interzone (IZ). The presumptive joint IZ phenotype shows a capacity to bind and synthesize HA and also exhibits elevated activated ERK, prior to synovial joint cavity formation (Lamb et al. 2001; Edwards et al. 1994; Dowthwaite et al. 1998). We have found that immobilization, which induces embryonic joint fusion with loss of the joint IZ phenotype, also reduces ERK activity levels in the IZ. As the signalling events regulating the synthesis and binding of HA have yet to be determined, we hypothesize that ERK activation plays a pivotal role in determining the presumptive joint IZ phenotype through HA synthetic and binding capacity. Materials and methods Chick articular surface (AS) cells were harvested from proximal tibiotarsal joints of embryos by collagenase digestion. Pericellular coat formation was assessed using the erythrocyte exclusion assay and cell-coat area ratios determined. ERK activity was modulated by transient transfection of GFP constructs of constitutively active (CA-) or dominant negative (DN-) forms of MEK, the direct upstream regulator of ERK or by treatment with the MEK inhibitor PD98059 (50 µm). ERK activation was monitored by immunochemistry. CD44 expression and ERK activation in PD98059-treated cells were monitored by immunoblotting and medium HA concentrations by ELISA. Results AS cells form large pericellular coats that are lost following hyaluronidase treatment and thus dependent upon HA for their construction. Treatment with PD98059 significantly reduced pericellular coat formation after 6 h. In parallel, we confirmed that PD98059 diminished active ERK expression without modifying overall levels of ERK, suggesting that the elaboration of large HA-pericellular coats is dependent upon MEK's activation of ERK. Western blot analysis of PD98059-treated cells showed that loss of pericellular coats was not, however, associated with any decreased levels of the cell surface HA receptor CD44. Although treatment with PD98059 did not change medium HA concentration after short times of exposure, at times (up to 6 h) during which coat loss was evident, prolonged treatment over 24 h significantly decreased medium HA concentration. Consistent with a role for ERK in pericellular coat formation, transfection with DN-MEK diminished, while CA-MEK increased, both active ERK expression and coat formation efficiency. We also found that, commensurate with this modification in coat forming efficiency, cells expressing DN-MEK exhibited a significant reduction in labelling of free HA on the cell surface. Discussion These studies extend our recent work to indicate that: (i) direct modulation of ERK activation by transfection with its endogenous upstream regulator modifies cell surface-associated HA (ii) PD98059-induced blockade of ERK activation restricts medium HA release and (iii) ERK-mediated changes in pericellular coat elaboration are independent of changes in cellular CD44 expression. These findings suggest an intimate relationship between ERK activation and the formation/retention of HA-rich pericellular matrices in vitro and highlight the role for ERK activation in regulating joint line-related differentiation. [source]

Measurement of serum hyaluronic acid in patients with chronic hepatitis C and its relationship to liver histology

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2000
John G McHutchison
Abstract Background and Aims: Chronic hepatitis C is a slowly progressing inflammatory disease of the liver that can lead to cirrhosis and its complications. Assessment of liver damage in hepatitis C has been primarily via histological evaluation. Liver biopsy, while useful in determining the extent of liver damage, has associated costs and places patients at a small but finite risk of bleeding. Studies in small patient populations have identified serum markers shown to correlate with liver histology, including pro-collogen III peptide and hyaluronic acid (HA). To determine whether serum HA was a reliable predictor of cirrhosis and fibrosis, we examined serum HA concentrations from 486 chronic Hepatitis C virus (HCV) patients. Methods and Results: Patients were anti-HCV and HCV RNA positive, with elevated alanine aminotransferase values and underwent a liver biopsy. Sera were obtained at the baseline for HA using radioimmunoassay methodology. Patients with cirrhosis had significantly higher serum HA concentrations compared with non-cirrhotic patients (382 ± 31 vs 110 ± 9 ,g/L respectively, P < 0.001). Patients with fibrosis had significantly higher mean serum HA concentrations (179 ± 11 ,g/L) compared with patients without fibrosis (62 ± 20 ,g/L; P < 0.001). The correlation between HA concentration and the components of the Knodell histological activity index score revealed no strong associations with the exception of fibrosis, which showed moderate correlation (R = 0.5421, P < 0.001). The clinical value of HA measurement appears to be its ability to exclude cirrhosis. A HA value of < 60 ,g/L excluded the presence of cirrhosis or significant fibrosis with a predictive value of 99 and 93%, respectively. Conclusions: Serum HA measurement may be clinically useful to non-invasively assess the degree of fibrosis and cirrhosis. Further prospective studies are warranted to determine the clinical utility of HA as a non-invasive marker of liver fibrosis. [source]

Noninvasive serum markers in the diagnosis of structural liver damage in chronic hepatitis C virus infection

LIVER INTERNATIONAL, Issue 9 2006
Edison R. Parise
Abstract: Aim: Several noninvasive markers are being used to assess the structural liver damage in patients with chronic hepatitis C (CHC). We evaluated the capacity of serum hyaluronic acid (HA), aspartate aminotransferase (AST)/ALT ratio, the AST to platelet ratio index (APRI) and ,-glutamyltransferase (GGT) levels to predict the intensity of hepatic fibrosis in patients with CHC. Patients and methods: In a total of 206 hepatitis C virus RNA-positive biopsied patients, AST, ALT, GGT levels, platelet count and serum HA concentration were determined. The APRI was calculated as the ratio of AST to platelets. Results: HA levels were best correlated with disease stage (r=,0.694; P<0.001). In the diagnosis of significant fibrosis (F2,F4), HA levels [AUC=0.879, 95% CI (0.832,0.927)] and APRI [AUC=0.824 (0.772,0.903)] were the markers with the best diagnostic accuracy. These parameters also best identified the presence of cirrhosis (F4), with an AUC of 0.908 (0.868,0.949) for HA and of 0.837 (0.772,0.903) for APRI. Conclusion: Serum HA was the parameter that alone presented the best diagnostic accuracy in the assessment of hepatic fibrosis in CHC. The APRI showed a better diagnostic sensitivity than GGT levels or the AST/ALT ratio. Its simple determination and low cost make this index a valid alternative for the noninvasive staging of CHC. [source]

Synthesis of Guanidinium-Modified Hyaluronic Acid Hydrogel

MACROMOLECULAR RAPID COMMUNICATIONS, Issue 13 2010
Oommen P. Varghese
Abstract In this report, a new guanidinylating reagent is presented, which was developed without any protection/deprotection strategy and was successfully employed for linking to hyaluronan in aqueous solution. The dually functionalised HA biopolymer bearing guanidinium and hydrazide groups was synthesised to form hydrogel in less than a minute when mixed with aldehyde-modified HA. This hydrogel exhibited higher storage modulus with enhanced stability in PBS when compared to the non-guanidine-containing gel. The gel shift assay showed that this biopolymer formed a stable complex with DNA as well as efficient gene transfection to cells that express HA-receptor CD44. The toxicity studies of this polymer with fibroblast cells revealed that the cells were almost 80% viable after 4,d of incubation at high HA concentration (2.5,×,10,3,M). [source]

Catalytic effect of dissolved humic acids on the chemical degradation of phenylurea herbicides

PEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 7 2008
Stefano Salvestrini
Abstract BACKGROUND: Although biodegradation seems to be the main cause of herbicide degradation, abiotic degradation can also be important for chemicals such as phenylureas, which are subject to catalysed soil reactions. The aim of this work is to investigate the effect of dissolved humic acids (HAs), normally present in natural waters, on the hydrolysis of phenylurea herbicides, and it presents a kinetic model that takes into account the role of adsorption. RESULTS: The linearity of the adsorption isotherms indicates that phenylurea,humic acid interaction can be considered in terms of a repartition-like equilibrium of phenylurea between water and HAs. Kinetic experiments show that the degradation rates of phenylureas increase with HA concentration. CONCLUSION: The kinetic equation adopted adequately describes the experimental data trend, allowing the evaluation of the catalytic effect of HAs on the chemical degradation of phenylureas. Carboxyl groups of HAs seem to play a leading role in the catalysis. The kinetic equation derived in this work could be helpful in predicting the persistence of phenylureas and of related compounds in natural water. Copyright © 2008 Society of Chemical Industry [source]

The effects of age and sex on chondroitin sulfates in normal synovial fluid

ARTHRITIS & RHEUMATISM, Issue 8 2002
Yoshihito Nakayama
Objective To examine how age and sex influence chondroitin sulfates (CS) in normal synovial fluid, we measured the concentrations of chondroitin 6-sulfate (C6S), chondroitin 4-sulfate (C4S), and hyaluronic acid (HA) in healthy subjects of different ages. Methods Synovial fluid samples were obtained from 82 healthy volunteers, ages 20,79 years. Results The concentrations of CS and HA and the C6S:C4S ratio varied with age. Their values were highest between 20 and 30 years of age, and thereafter they showed a tendency to decrease. Statistically, the C6S concentration and the C6S:C4S ratio at ages 60,70 years were significantly lower than those at 20,30 years of age. There was also a clear between-sex difference, in which the CS concentrations and the C6S:C4S ratio in women were significantly lower than those in men (P = 0.0003 for C6S, P = 0.02 for C4S, P = 0.002 for C6S:C4S ratio). In sharp contrast, little between-sex difference was found in the HA concentration. In multiple regression analysis, age correlated strongly with the C6S concentration and the C6S:C4S ratio (r = ,0.521 and r = ,0.617, respectively), weakly with the C4S concentration (r = ,0.202), and moderately with the HA concentration (r = ,0.483). Sex showed a weak correlation with the concentrations of C6S and C4S and the C6S:C4S ratio (r = 0.307, r = 0.225, and r = 0.237, respectively), and little correlation was seen between sex and the HA concentration. Conclusion The CS concentrations and the sulfation patterns in normal synovial fluid vary with age and sex, and these physiologic variations need to be taken into account when using synovial fluid CS as markers for arthritic conditions. [source]

Direct and indirect manipulation of the MEK-ERK pathway regulates the formation of a pericellular HA-dependent matrix by chick articular surface cells without modifying CD44 expresssion

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2004
Edward R. Bastow
Introduction Recent evidence suggests that hyaluronan (HA) facilitates the mechano-dependent joint cavity-forming process through the elaboration and retention of a HA-rich pericellular matrix in the developing joint interzone (IZ). The presumptive joint IZ phenotype shows a capacity to bind and synthesize HA and also exhibits elevated activated ERK, prior to synovial joint cavity formation (Lamb et al. 2001; Edwards et al. 1994; Dowthwaite et al. 1998). We have found that immobilization, which induces embryonic joint fusion with loss of the joint IZ phenotype, also reduces ERK activity levels in the IZ. As the signalling events regulating the synthesis and binding of HA have yet to be determined, we hypothesize that ERK activation plays a pivotal role in determining the presumptive joint IZ phenotype through HA synthetic and binding capacity. Materials and methods Chick articular surface (AS) cells were harvested from proximal tibiotarsal joints of embryos by collagenase digestion. Pericellular coat formation was assessed using the erythrocyte exclusion assay and cell-coat area ratios determined. ERK activity was modulated by transient transfection of GFP constructs of constitutively active (CA-) or dominant negative (DN-) forms of MEK, the direct upstream regulator of ERK or by treatment with the MEK inhibitor PD98059 (50 µm). ERK activation was monitored by immunochemistry. CD44 expression and ERK activation in PD98059-treated cells were monitored by immunoblotting and medium HA concentrations by ELISA. Results AS cells form large pericellular coats that are lost following hyaluronidase treatment and thus dependent upon HA for their construction. Treatment with PD98059 significantly reduced pericellular coat formation after 6 h. In parallel, we confirmed that PD98059 diminished active ERK expression without modifying overall levels of ERK, suggesting that the elaboration of large HA-pericellular coats is dependent upon MEK's activation of ERK. Western blot analysis of PD98059-treated cells showed that loss of pericellular coats was not, however, associated with any decreased levels of the cell surface HA receptor CD44. Although treatment with PD98059 did not change medium HA concentration after short times of exposure, at times (up to 6 h) during which coat loss was evident, prolonged treatment over 24 h significantly decreased medium HA concentration. Consistent with a role for ERK in pericellular coat formation, transfection with DN-MEK diminished, while CA-MEK increased, both active ERK expression and coat formation efficiency. We also found that, commensurate with this modification in coat forming efficiency, cells expressing DN-MEK exhibited a significant reduction in labelling of free HA on the cell surface. Discussion These studies extend our recent work to indicate that: (i) direct modulation of ERK activation by transfection with its endogenous upstream regulator modifies cell surface-associated HA (ii) PD98059-induced blockade of ERK activation restricts medium HA release and (iii) ERK-mediated changes in pericellular coat elaboration are independent of changes in cellular CD44 expression. These findings suggest an intimate relationship between ERK activation and the formation/retention of HA-rich pericellular matrices in vitro and highlight the role for ERK activation in regulating joint line-related differentiation. [source]

Potentiometric studies on the interaction between superoxide dismutase and hyaluronic acid

JOURNAL OF APPLIED POLYMER SCIENCE, Issue 4 2009
Yaofeng Fan
Abstract The formation process of soluble complexes and insoluble aggregates between superoxide dismutase (SOD) and hyaluronic acid (HA) was studied using quasielastic light scattering and turbidimetric titration. The electrostatic binding between them was investigated in detail through potentiometric titration and turbidimetric titration carried out from high to low pH. Turbidimetric titration was used to determine the specific pH values at which soluble complex formation was initiated (pHc) and phase separation occurred (pH,). An increase of the ionic strength causes a decrease of pHc and pH,. With the increase of HA concentrations, pH, increases but pHc does not vary. The formed "salt bridges" between (SOD) and COO, (HA) result in the formation of stable SOD-HA complexes and even aggregates. The necessary condition of electrostatic binding was also given for protein-acidic polyelectrolyte systems. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009 [source]

Measurement of serum hyaluronic acid in patients with chronic hepatitis C and its relationship to liver histology

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2000
John G McHutchison
Abstract Background and Aims: Chronic hepatitis C is a slowly progressing inflammatory disease of the liver that can lead to cirrhosis and its complications. Assessment of liver damage in hepatitis C has been primarily via histological evaluation. Liver biopsy, while useful in determining the extent of liver damage, has associated costs and places patients at a small but finite risk of bleeding. Studies in small patient populations have identified serum markers shown to correlate with liver histology, including pro-collogen III peptide and hyaluronic acid (HA). To determine whether serum HA was a reliable predictor of cirrhosis and fibrosis, we examined serum HA concentrations from 486 chronic Hepatitis C virus (HCV) patients. Methods and Results: Patients were anti-HCV and HCV RNA positive, with elevated alanine aminotransferase values and underwent a liver biopsy. Sera were obtained at the baseline for HA using radioimmunoassay methodology. Patients with cirrhosis had significantly higher serum HA concentrations compared with non-cirrhotic patients (382 ± 31 vs 110 ± 9 ,g/L respectively, P < 0.001). Patients with fibrosis had significantly higher mean serum HA concentrations (179 ± 11 ,g/L) compared with patients without fibrosis (62 ± 20 ,g/L; P < 0.001). The correlation between HA concentration and the components of the Knodell histological activity index score revealed no strong associations with the exception of fibrosis, which showed moderate correlation (R = 0.5421, P < 0.001). The clinical value of HA measurement appears to be its ability to exclude cirrhosis. A HA value of < 60 ,g/L excluded the presence of cirrhosis or significant fibrosis with a predictive value of 99 and 93%, respectively. Conclusions: Serum HA measurement may be clinically useful to non-invasively assess the degree of fibrosis and cirrhosis. Further prospective studies are warranted to determine the clinical utility of HA as a non-invasive marker of liver fibrosis. [source]

Diurnal variation of serum and urine biomarkers in patients with radiographic knee osteoarthritis

ARTHRITIS & RHEUMATISM, Issue 8 2006
S. Y. Kong
Objective To evaluate diurnal variation of biomarkers in subjects with osteoarthritis (OA) of the knee. Methods Twenty subjects with radiographic knee OA were admitted to the General Clinical Research Center of Duke University for an overnight stay to undergo serial blood and urine sampling. Biomarkers measured included serum hyaluronan (HA), cartilage oligomeric matrix protein (COMP), keratan sulfate (KS-5D4), aggrecan neoepitope (CS846), high-sensitivity C-reactive protein (hsCRP), osteocalcin, transforming growth factor ,1 (TGF,1), and type II collagen (CII),related epitopes (neoepitope from cleavage of CII [C2C], carboxy-terminus of three-quarter peptide from cleavage of CI and CII [C1,2C], and type II procollagen carboxy-propeptide [CPII] in serum, and C-terminal telopeptides of CII [CTX-II] and C2C in urine). Results Levels of serum HA, COMP, KS-5D4, and TGF,1 increased significantly from T0 (before arising from bed) to T1 (1 hour after arising). More diurnal variation in HA was observed in patients with higher daily mean HA concentrations. CPII increased significantly from T0 to T2 (4 hours after arising). Urinary concentrations of CTX-II were also found to vary with morning activity, decreasing significantly from T0 to T2. Urinary C2C concentrations increased significantly from T0 until T3 (early evening). No diurnal variations in CS846, hsCRP, osteocalcin, serum C2C, or C1,2C were observed. Six biomarkers (serum C2C, C1,2C, COMP, KS-5D4, TGF,1, and urinary CTX-II) were associated with radiographic knee OA (expressed as the sum of Kellgren/Lawrence radiographic severity grades), with the strongest correlations observed with measurements obtained at later time points (either T2 or T3). Conclusion Our study results suggest that serum and urine sampling for HA, COMP, KS-5D4, TGF,1, CPII, urinary CTX-II, and urinary C2C should be standardized in future OA clinical trials. Serum and urine sampling at late midday time points may be the optimal approach for OA studies, although this result should be validated in a larger cohort. [source]