FV3-like ranavirus infection outbreak in black-spotted pond frogs (Rana nigromaculata) in China.

In April 2016, an outbreak emerged in a cultured population of black-spotted pond frog tadpoles in Shuangliu County, China, whereas tadpoles were suffering from substantial mortality (90%). Principal clinical signs of diseased tadpoles were comprised haemorrhage on their body surface, swollen abdomen with yellow ascites, congestion and swelling of the liver. The diseased tadpole's homogenates tissue were inoculated into epithelioma papulosum cyprini (EPC) cells at 25 °C for 4 days which caused typical cytopathic effect, and the viral titer TCID50 reached 107/0.1 mL. In pathogenicity tests, tadpoles were immersed in 2‰ virus fluid for 8 h, the clinical signs were observed similar to those recognized in naturally infected tadpoles and mortality rate were reached up to 80%, which affirms that the virus was the main cause for this disease. In addition, transmission electron microscopy of EPC cells infected with isolated virus reflected that the virus was in a regular hexagon way (shape) with capsule like structure. The diagonal diameter was recorded 135 ±â€¯8 nm, wherever virus particles were arrayed in crystalline manner in the cytoplasm. The electrophoresis of MCP gene PCR-product showed that the samples of diseased tadpoles, aquaculture water source and isolated virus were all positive. The sequence of the isolate revealed more than 99% similarities to ranavirus based on homology and genetic evolution analysis of the whole MCP gene, and the isolate belongs to FV3-like virus group. This study confirmed that ranavirus was the causative agent of this outbreak, and named the virus as Rana nigromaculata ranavirus (RNRV).

Chronic peritoneal dialysis in Chinese infants and children younger than two years.

OBJECTIVE: To review the outcome for Chinese infants and young children on chronic peritoneal dialysis. METHODS: The Paediatric Nephrology Centre of Princess Margaret Hospital is the designated site offering chronic dialysis to children in Hong Kong. Medical records of children who started chronic peritoneal dialysis before the age of 2 years, from 1 July 1995 to 31 December 2013, were retrieved and retrospectively reviewed. RESULTS: Nine Chinese patients (male-to-female ratio, 3:6) were identified. They were commenced on automated peritoneal dialysis at a median age of 4.7 (interquartile range, 1.1-13.3) months. The median duration of chronic peritoneal dialysis was 40.9 (interquartile range, 22.9-76.2) months. The underlying aetiologies were renal dysplasia (n=3), pneumococcal-associated haemolytic uraemic syndrome (n=3), ischaemic nephropathy (n=2), and primary hyperoxaluria I (n=1). Peritonitis and exit-site infection rate was 1 episode per 46.5 patient-months and 1 episode per 28.6 patient-months, respectively. Dialysis adequacy (Kt/Vurea>1.8) was achieved in 87.5% of patients. Weight gain was achieved in our patients although three required gastrostomy. Four patients were delayed in development. All patients survived except one patient with primary hyperoxaluria I who died of acute portal vein thrombosis following liver transplantation. One patient with pneumococcal-associated haemolytic uraemic syndrome had sufficient renal function to be weaned off dialysis. Four patients received deceased donor renal transplantation after a mean waiting time of 76.7 months. Three patients remained on chronic peritoneal dialysis at the end of the study. CONCLUSIONS: Chronic peritoneal dialysis is technically difficult in infants. Nonetheless, low peritonitis rate, low exit-site infection rate, and no chronic peritoneal dialysis-related mortality can be achieved. Chronic peritoneal dialysis offers a promising strategy to bridge the way to renal transplantation.

Placing the maxilla in the most aesthetic sagittal position: validation of several reference lines in relation to the forehead shape.

The ideal sagittal position of the maxilla is highly subjective in orthognathic surgical treatment planning. There is no consensus on an analysis to predict the ideal sagittal position of the maxilla. The objective of this study was to determine the preferred maxillary position in relation to the forehead shape, in the Southern Chinese population. The maxilla position of eight patients was simulated based on Steiner's analysis (SA), glabella vertical (GV), Andrews' Element II (AE2), and the Barcelona reference (BR). The simulations were then used in an electronic survey, where respondents ranked the images for each patient from to 1-4 (most to least attractive). A total of 128 responses were collected from dental professionals and laypersons. The most preferred to the least preferred simulation was as follows (mean rank scores for the male and female patients in parenthesis): BR (males 2.06; females 1.98), GV (males 2.11; females 2.21), SA (males 2.59; females 2.40), and AE2 (males 3.24; females 3.41). There was no significant difference in the results according to the sex, age group, or profession of the respondents. The Barcelona reference and glabella vertical are useful in predicting the ideal maxillary position in patients with a flat forehead, and the Barcelona reference is the most preferred in patients with a rounded forehead.

Detection and characterisation of extended-spectrum beta-lactamases among blood stream isolates of Enterobacter species in Hong Kong.

1. Extended-spectrum beta-lactamase(ESBL) resistance in Enterobacter spp may be under-recognised. 2. Detection methods for ESBL resistance in Enterobacter spp may need to be modified.

Ten-year review of disease pattern from percutaneous renal biopsy: an experience from a paediatric tertiary renal centre in Hong Kong.

OBJECTIVE: To study the childhood renal disease pattern based on the renal biopsy histology in a local paediatric tertiary renal centre. DESIGN: Retrospective study. SETTING: Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong. PATIENTS: All patients who underwent real-time ultrasound-guided closed renal biopsy from 1 April 1997 to 31 March 2007 were included. RESULTS: A total of 209 renal biopsies were performed, 162 on native kidneys and 47 on grafts. In the native group, major indications were renal manifestations secondary to systemic diseases (34%), followed by idiopathic nephrotic syndrome (28%) and haematuria (27%). In 94% the histopathology revealed glomerular diseases. Among the primary glomerular diseases, thin glomerular basement membrane disease, immunoglobulin A nephropathy, minimal change disease, and focal segmental glomerulosclerosis accounted for most. In all, 37% of patients with steroid-resistant nephrotic syndrome had focal segmental glomerulosclerosis and its relative incidence was increased when compared to previous studies. Minimal change disease and minimal change disease with mesangial immunoglobulin M deposits accounted for the majority of steroid dependent and frequent relapsers. Among patients with isolated microscopic haematuria, 73% had thin glomerular basement membrane disease, while patients with concomitant haematuria and proteinuria had a wide variety of pathology. In the kidney graft group, acute graft dysfunction was due to acute rejection in 38% of the patients, followed by calcineurin inhibitor toxicity in 14%. Chronic allograft nephropathy caused chronic allograft dysfunction in the majority of cases. Post-transplant proteinuria was caused by recurrence of the primary renal disease in all of our patients. CONCLUSION: This study provides updated epidemiological information for childhood renal disease and a change in the pattern of disease was observed.

The influence of link protein stabilization on the viscometric properties of proteoglycan aggregate solutions.

The dynamic, steady-shear and transient shear flow properties of precisely prepared link-stable (s0 136, 66% aggregate) and link-free (s0 93, 59% aggregate) proteoglycan aggregate solutions at concentrations ranging from 10 to 50 mg/ml were determined using a cone-on-plate viscometer in a mechanical spectrometer. All proteoglycan solutions tested possessed: (1) linear viscoelastic properties - as measured by the dynamic complex modulus under small amplitude steady oscillatory conditions (1 less than or equal to omega less than or equal to 100 rad/s) - and (2) nonlinear shear-rate dependent apparent viscosities and primary normal stress difference under steady shearing conditions (0.25 less than or equal to gamma less than or equal to 250 s-1). Our transient flow data show that all proteoglycan aggregate solutions exhibited transient stress overshoot effects in shear stress and normal stress. From these steady and transient flow data, we conclude that link protein stabilized aggregates have significant effects on their dynamic and steady-shear properties as well as transient flow properties. The transient stress overshoot data provide a measure of the energy per unit volume of fluid required to overcome the proteoglycan networks in solution from a resting state. Thus we found that link-stable aggregates form much stronger networks than link-free aggregates. This is corroborated by the fact that link-stable aggregates form more elastic (lower than delta) and stiffer (higher [G*]) networks than link-free aggregates. The complete spectrum of viscometric flow data is entirely compatible with the proposed role of link protein in adding structural stability to the proteoglycan-hyaluronate bond. In cartilage, the enhanced strength of the networks formed by link-stable aggregates may play an important role in determining the material properties of the tissue and thereby contribute to the functional capacity of cartilage in diarthrodial joints.

Viscoelastic properties of proteoglycan solutions with varying proportions present as aggregates.

Monomer and aggregated proteoglycans were prepared from pig laryngeal cartilage. Vascoelastic flow properties, comprising linear complex dynamic shear modulus, nonlinear steady-state shear-rate dependent viscosity, and primary normal stress difference, were measured in proteoglycan solutions containing varying proportions of aggregate (0-80%) and at different concentrations (10-50 mg/ml). Results were analyzed using the simple Oldroyd four-parameter nonlinear rate-type rheological equation. All solution properties were strongly dependent on proteoglycan concentration and on the proportion of aggregates present. Aggregation was found to have a great effect on the zero shear-rate viscosity at 50 mg/ml, which increased fivefold from 0-100% aggregate. The results showed that network formation in proteoglycan solutions increased with concentration from 10-50 mg/ml and also increased with aggregation. All proteoglycan solutions showed shear thinning, which was most marked with aggregated proteoglycan at high concentration (50 mg/ml), where the viscosity decreased tenfold from the zero shear-rate limit to the infinite shear-rate limit. The intermolecular interactions in the network were therefore increasingly disrupted by increasing shear rate, but repeated measurements showed that these were reversible changes and that testing did not induce disaggregation or degradation of proteoglycan. These rheological properties show that aggregation is likely to immobilize proteoglycan at high concentration within cartilage and to contribute to the material properties of the porous solid matrix of articular cartilage that are important for its load-bearing function.

The density and strength of proteoglycan-proteoglycan interaction sites in concentrated solutions.

Rheological flow properties of link-stable and link-free proteoglycan (PG) aggregates in concentrated solutions were measured using a cone-on-plate viscometer. A second-order constitutive model, based upon the statistical-network theories of Lodge, [Rheol. Acta 7, 379-392 (1968)] and De Kee and Carreau [J. Non-Newtonian Fluid Mech. 6, 127-143 (1979)], was developed to describe the measured steady and transient flow responses exhibited by the PG solutions. Our measurements confirmed previous experimental findings that the complex shear modulus of PG solutions depends on the frequency of the imposed small-amplitude oscillatory shear, and the apparent viscosity and primary normal-stress difference depend nonlinearly on the shear rate under steady-shear flow conditions [Mow et al., J. Biomechanics 17, 325-338 (1984b); Hardingham et al., J. orthop. Res. 5, 36-46 (1987)]. In the present study, we found that PG solutions exhibit pronounced stress overshoot responses and large hysteresis loop effects. These transient responses were shown to be sensitive to acceleration strain (i.e. the second rate of strain) as well as PG structure (i.e. link-protein stabilization). The model parameters were determined by curvefitting of the second-order constitutive model and experimental data from steady, oscillatory and transient shear flow measurements. Using this network model, we calculated the density of the idealized interaction sites existing in the PG network, and the average strength of these interaction sites. The results indicate that link-protein stabilization of PG aggregates does not change the density of interaction sites formed in the PG network, rather, it increases the average strength of these interaction sites.

Transport of fluid and ions through a porous-permeable charged-hydrated tissue, and streaming potential data on normal bovine articular cartilage.

Using the triphasic mechano-electrochemical theory [Lai et al., J. biomech. Engng 113, 245-258 (1991)], we analyzed the transport of water and ions through a finite-thickness layer of charged, hydrated soft tissue (e.g. articular cartilage) in a one-dimensional steady permeation experiment. For this problem, we obtained numerically the concentrations of the ions, the strain field and the fluid and ion velocities inside when the specimen is subject to an applied mechanical pressure and/or osmotic pressure across the layer. The relationships giving the dependence of streaming potential and permeability on the negative fixed charge density (FCD) of the tissue were derived analytically for the linear case, and calculated for the nonlinear case. Among the results obtained were: (1) at a fluid pressure difference of 0.1 MPa across the specimen layer, there is a 10% flow-induced compaction at the downstream boundary; (2) the flow-induced compaction causes the FCD to increase and the neutral salt concentration to decrease in the downstream direction; (3) while both ions move downstream, relative to the solvent (water), the anions (Cl-) move with the flow whereas cations (Na+) move against the flow. The difference in ion velocities depends on the FCD, and this difference attained a maximum at a physiological FCD of around 0.2 meq ml-1; (4) the apparent permeability decreases nonlinearly with FCD, and the apparent stiffness of the tissue increases with FCD; and (5) the streaming potential is not a monotonic function of the FCD but rather it has a maximum value within the physiological range of FCD for articular cartilage. Finally, experimental data on streaming potential were obtained from bovine femoral cartilage. These data support the triphasic theoretical prediction of non-monotonicity of streaming potential as a function of the FCD.

Biphasic indentation of articular cartilage--I. Theoretical analysis.

A mathematical solution has been obtained for the indentation creep and stress-relaxation behavior of articular cartilage where the tissue is modeled as a layer of linear KLM biphasic material of thickness h bonded to an impervious, rigid bony substrate. The circular (radius = a), plane-ended indenter is assumed to be rigid, porous, free-draining, and frictionless. Double Laplace and Hankel transform techniques were used to solve the partial differential equations. The transformed equations and boundary conditions yielded an integral equation of the Fredholm type which was analyzed asymptotically and solved numerically. Our asymptotic analyses showed that the linear KLM biphasic material behaves like an incompressible (v = 0.5) single-phase elastic solid at t = 0+; the instantaneous response of the material is governed by the shear modulus (mu s) of the solid matrix. The linear KLM biphasic material behaves like a compressible elastic solid with material properties defined by those of the solid matrix, i.e. (lambda s, mu s) or (mu s, v s) as t----infinity. The transient viscoelastic creep and stress-relaxation behavior, 0 less than t less than infinity, of this material is controlled by the frictional drag (which is inversely proportional to the permeability k) associated with the flow of the interstitial fluid through the porous-permeable solid matrix. For given values of the Poisson's ratio of the solid matrix v s and the aspect ratio a/h, where a is the radius of the indenter and h is the thickness of the layer, the creep behavior with respect to the dimensionless time H Akt/a2 is completely controlled by the load parameter P/2 mu sa2 and the stress relaxation behavior is completely controlled by the rate of compression parameter R0 = kH A/V0h where H A = lambda s + 2 mu s and the equilibrium strain u0/h. This mathematical solution may now be used to describe an indentation experiment on articular cartilage to determine the intrinsic material properties of the tissue, i.e. permeability k, and the elastic coefficients of the solid phase (lambda s, mu s) or (mu s, v s).

A triphasic analysis of negative osmotic flows through charged hydrated soft tissues.

Osmotic flow and ion transport in a one-dimensional steady diffusion process through charged hydrated soft tissues such as articular cartilage were analysed using the triphasic theory (Lai et al., 1991, J. biomech. Engng 113, 245-258). It was found that solvent would flow from the high NaCl concentration side to the low concentration side (i.e. negative osmosis) when the fixed charge density within the tissue (or membrane) separating the two electrolyte (NaCl) solutions was lower than a critical value. The condition for negative osmosis was derived based on a linear version of the triphasic theory. Distributions of ion concentration and strain field within the tissue were calculated numerically. Quantitative results of osmotic flow rates (ordinary and negative osmosis), ion flux and electric potential across the tissue during this diffusion process suggest that the negative osmosis phenomenon is due to the friction between ions and water since they could flow through the tissues at different rates and different directions.

Fluid transport and mechanical properties of articular cartilage: a review.

This review is aimed at unifying our understanding of cartilage viscoelastic properties in compression, in particular the role of compression-dependent permeability in controlling interstitial fluid flow and its contribution to the observed viscoelastic effects. During the previous decade, it was shown that compression causes the permeability of cartilage to drop in a functional manner described by k = ko exp (epsilon M) where ko and M were defined as intrinsic permeability parameters and epsilon is the dilatation of the solid matrix (epsilon = tr delta u). Since permeability is inversely related to the diffusive drag coefficient of relative fluid motion with respect to the porous solid matrix, the measured load-deformation response of the tissue must therefore also depend on the non-linearly permeable nature of the tissue. We have summarized in this review our understanding of this non-linear phenomenon. This understanding of these flow-dependent viscoelastic effects are put into the historical perspective of a comprehensive literature review of earlier attempts to model the compressive viscoelastic properties of articular cartilage.

On the conditional equivalence of chemical loading and mechanical loading on articular cartilage.

Osmotic pressure loading of articular cartilage has been customarily invoked to be equivalent to mechanical loading. In the literature, this equivalence is defined by the amount of water squeezed from the tissue, i.e. if the amount of water content lost by these two modes of loading are the same, it has been generally regarded that the two loadings are equivalent. This assumption has never been proven. Using the water content lost concept, in this paper, we derived the exact conditions under which an osmotic pressure loading of cartilage can be considered to be equivalent to a mechanical loading. However, the mechanical loading condition satisfying this equivalency criterion, i.e. an isotropic loading delivered via a porous permeable rigid platen uniformly applied all around the specimen, is not practically achievable. Moreover, even if this were achieved experimentally, the interstitial fluid pressure caused by the two loading conditions are not the same. This result has important ramifications for interpretation of experimental data from mechanical stimulations of cartilage explant studies.

A finite deformation theory for cartilage and other soft hydrated connective tissues--I. Equilibrium results.

The determination of valid stress-strain relations for articular cartilage under finite deformation conditions is a prerequisite for constructing models for synovial joint lubrication. Under physiological conditions of high strain rates and/or high stresses in the joint, large strains occur in cartilage. A finite deformation theory valid for describing cartilage, as well as other soft hydrated connective tissues under large loads, has been developed. This theory is based on the choice of a specific Helmholtz energy function which satisfies the generalized Coleman-Noll (GCN0) condition and the Baker-Ericksen (B-E) inequalities established in finite elasticity theory. In addition, the finite deformation biphasic theory includes the effects of strain-dependent porosity and permeability. These nonlinear effects are essential for properly describing the biomechanical behavior of articular cartilage, even when strain rates are low and strains are infinitesimal. The finite deformation theory describes the large strain behavior of cartilage observed in one-dimensional confined compression experiments at equilibrium, and it reduces to the linear biphasic theory under infinitesimal strain and slow strain rate conditions. Using this theory, we have determined the material coefficients of both human and bovine articular cartilages under large strain conditions at equilibrium. The theory compares very well with experimental results.

An asymptotic solution for the contact of two biphasic cartilage layers.

This study addresses the hypothesis that interstitial fluid plays a major role in the load support mechanism of articular cartilage. An asymptotic solution is presented for two contacting biphasic cartilage layers under compression. This solution is valid for identical thin (i.e. epsilon = h'/a'0 << 1), frictionless cartilage layers, and for the 'early' time response (i.e. t' << (h')2/HAk) after the application of a step load. An equilibrium asymptotic solution is also presented (i.e.t'-->infinity). Here h' is the thickness, a'0 is a characteristic contact radius, HA is the aggregate modulus and k is the permeability of the cartilage layer. A main conclusion from this analysis is that the fluid phase of cartilage plays a major role in providing load support during the first 100-200 s after contact loading. Further, the largest component of stress in cartilage is the hydrostatic pressure developed in the interstitial fluid. For tissue fluid volume fraction (porosity) in the range 0.6 < or = phi f < or = 0.8, k = O(10(-15) m4/Ns) and HA = O(1 MPa), the peak magnitude of the principal effective (or elastic) stress may be as low as 14% of the peak hydrostatic pressure within the tissue, or the contact stress at the surface. In effect, the interstitial fluid shields the solid matrix from high normal stresses and strains. The asymptotic solution also shows that pressure-sensitive film measurements of intra-articular contact stress do not measure the elastic stress at the surface, but they rather provide a measure of the interstitial fluid pressure. Finally, this analysis provides strong support for the hypothesis that, if sudden loading causes shear failure within the cartilage-bone layer structure, this failure would take place at the cartilage-bone interface, and the plane of failure would be either parallel or perpendicular to this interface.

An analysis of the squeeze-film lubrication mechanism for articular cartilage.

An asymptotic analysis of a lubrication problem is presented for a model of articular cartilage and synovial fluid under the squeeze-film condition. This model is based upon the following constitutive assumptions: (1) articular cartilage is a linear porous-permeable biphasic material filled with a linearly viscous fluid (i.e. Newtonian fluid); (2) synovial fluid is also a linearly viscous fluid. The geometry of the problem is defined by assuming that (1) cartilage is a uniform layer of thickness H; (2) synovial fluid is a very thin layer compared to H; (3) the radius R of the load-supporting area (or the effective radius of curvature of joint surface, Ri) is large compared to H. Squeeze-film action is generated in the lubricant by a step loading function applied onto the two bearing surfaces. The model assumptions and the material properties yield two small parameters in the mathematical formulation. Based on these two small parameters, two coupled nonlinear partial differential equations were derived from an asymptotic analysis of the problem: one for the lubricant (analogous to the Reynolds equation) and one for the cartilage. For known properties of normal cartilage, our calculations show: (1) the cartilage layer deforms to enlarge the load-supporting area; (2) cartilage deformation acts to reduce the lateral fluid speed in the lubricant, thus prolonging the squeeze-film time which ranges from 1 to 10 s; (3) lubricant fluid in the gap is forced from the central high-pressure region into cartilage, and expelled from the tissue at the low-pressure periphery of the load-bearing region; and (4) tensile hoop stress exists at the cartilage surface despite the compressive squeeze-film loading condition. This hoop stress results directly from the radial flow of the interstitial fluid in the cartilage layer.

Biphasic indentation of articular cartilage--II. A numerical algorithm and an experimental study.

Part I (Mak et al., 1987, J. Biomechanics 20, 703-714) presented the theoretical solutions for the biphasic indentation of articular cartilage under creep and stress-relaxation conditions. In this study, using the creep solution, we developed an efficient numerical algorithm to compute all three material coefficients of cartilage in situ on the joint surface from the indentation creep experiment. With this method we determined the average values of the aggregate modulus. Poisson's ratio and permeability for young bovine femoral condylar cartilage in situ to be HA = 0.90 MPa, vs = 0.39 and k = 0.44 x 10(-15) m4/Ns respectively, and those for patellar groove cartilage to be HA = 0.47 MPa, vs = 0.24, k = 1.42 x 10(-15) m4/Ns. One surprising finding from this study is that the in situ Poisson's ratio of cartilage (0.13-0.45) may be much less than those determined from measurements performed on excised osteochondral plugs (0.40-0.49) reported in the literature. We also found the permeability of patellar groove cartilage to be several times higher than femoral condyle cartilage. These findings may have important implications on understanding the functional behavior of cartilage in situ and on methods used to determine the elastic moduli of cartilage using the indentation experiments.

Changes in proteoglycan synthesis of chondrocytes in articular cartilage are associated with the time-dependent changes in their mechanical environment.

Explant loading experiments were conducted to investigate the effect of load duration on proteoglycan synthesis. A compressive load of 0.1 MPa applied for 10 min was found to stimulate proteoglycan synthesis, while the same load applied for 20 h suppressed synthesis. This bimodal response suggests that the cells are responding to different mechanical stimuli as time progresses. A theoretical model has therefore been developed to describe the mechanical environment perceived by cells within soft hydrated tissues (e.g. articular cartilage) while the tissue is being loaded. The cells are modeled, using the biphasic theory, as fluid-solid inclusions embedded in and attached to a biphasic extracellular matrix of distinct material properties. A method of solution is developed which is valid for any axisymmetric loading configuration, provided that the cell radius, a, is small relative to the tissue height, h (i.e. h/a >> 1). A closed-form analytical solution for this inclusion problem is then presented for the confined compression configuration. Results from this model show that the mechanical environment in and around the cells is time dependent and inhomogeneous, and can be significantly influenced by differences in properties between the cell and the extracellular matrix.

Viscoelastic properties of proteoglycan subunits and aggregates in varying solution concentrations.

Using a cone-on-plate mechanical spectrometer, we have measured the linear and non-linear rheological properties of cartilage proteoglycan solutions at concentrations similar to those found in situ. Solutions of bovine nasal cartilage proteoglycan subunits (22S) and aggregates (79S) were studied at concentrations ranging from 10 to 50 mg ml-1. We determined: (1) the complex viscoelastic shear modulus G (omega) under small amplitude (0.02 radians) oscillatory excitation at frequencies (omega) ranging from 1.0 to 20.0 Hz, (2) the non-linear shear rate (gamma) dependent apparent viscosity napp (gamma) in continuous shear, and (3) the non-linear shear rate dependent primary normal stress difference sigma 1 (gamma) in continuous shear. Both the apparent viscosity and normal stress difference were measured over four decades of shear rates ranging from 0.25 to 250 s-1. Analysis of the experimental results were performed using a variety of materially objective non-linear viscoelastic constitutive laws. We found that the non-linear, four-coefficient Oldroyd rate-type model was most effective for describing the measured flow characteristics of proteoglycan subunit and aggregate solutions. Values of the relaxation time lambda 1, retardation time lambda 2, zero shear viscosity no, and nonlinear viscosity parameter muo were computed for the aggregate and subunit solutions at all of the solute concentrations used. The four independent material coefficients showed marked dependence on the two different molecular conformations, i.e. aggregate or subunit, of proteoglycans in solution.