Hyperuricemia and local temperature changes in the joints of the extremities are known to be responsible, in part, for the development of gouty arthritis. No satisfactory explanation is yet available for (1) the selective deposition of monosodium urate monohydrate (MSUM) crystals in connective tissues (2) the increased incidence of gout in the later years of life and (3) the increased incidence of MSUM crystal deposition in connective tissues after trauma and in joints with preexisting disease. It is possible that the alterations in composition of the non-fibrillar matrix of cartilage and synovial fluid which are thought to occur with ageing, trauma or preexisting disease, may predispose these tissues to crystal deposition. The objectives of this study were to determine the effect of the cartilage and synovial fluid components, chondroitin sulfate, hyaluronic acid, proteoglycan monomer, proteoglycan aggregate, phospholipids and albumin on the growth of MSUM.
The degradation of MSUM solutions was studied under sterile and non-sterile conditions to determine the possible causes of degradation and to define the time span of crystal growth experiments. The rate of degradation of MSUM solutions increased with an increase in temperature. The concentration of MSUM in solution fell sharply after autoclaving and solutions stored in containers with rubber closures showed greater degradation of MSUM than autoclaved solutions stored in all-glass containers. Rubber stoppers apparently absorbed MSUM from solution. The degradation of MSUM solutions was thought to be due to both bacterial consumption and chemical decomposition in non-sterile solutions but was due only to chemical decomposition in sterile solutions.
The aqueous solubility of MSUM was determined at different temperatures and in the presence of varying concentrations of sodium chloride. Sodium chloride suppressed MSUM solubility.
The aqueous solubility of MSUM was also determined in the presence of several connective tissue components at 37°. Chondroitin sulfate (CS) decreased the saturation solubility of MSUM probably due to the sodium present in the CS samples. Proteoglycan aggregate, proteoglycan monomer, hyaluronic acid an albumin resulted in very slight increases in the solubility of MSUM.
The growth kinetics of MSUM was studied using the seeded growth technique. An equation of the general form: [formula omitted] was used to determine the overall growth rate constant, [formula omitted]. Linear plots of the integrated form of the second order growth equation gave the best fit between the points and gave reasonably constant values for [formula omitted] determined at a given initial supersaturation concentration and varying seed amounts.
An induction period or a period of slow growth was observed at both the initial supersaturation concentrations studied. The length of the induction period was inversely proportional to the added seed amount.
Differing concentrations of additives were included in the growth medium and K' determined.
Chondroitin sulfate (CS) significantly increased the growth rate constant for MSUM growth. However, the proportion of CS decreases in aged and osteoarthritic cartilage and thus a decreasing proportion of a growth accelerator is unlikely to be a factor in the deposition of MSUM in cartilage. CS has been found in the synovial fluid of arthritic joints and may act as an MSUM growth accelerator in this medium.
Hyaluronic acid (HA) and albumin caused significant inhibition of the growth of MSUM crystals. This effect may be due to the adsorption of these molecules onto the MSUM seed crystals resulting in the poisoning of the active growth sites on the crystal surface. Cartilage HA and synovial fluid albumin levels are increased in aged and/or diseased joints. Increased proportions of growth inhibitors do not offer likely explanations of crystal deposition in joint tissues. At concentrations of 0.1-1.0 mg mL⁻¹ proteoglycan monomer (PGM) and proteoglycan aggregate (PGA) slightly increased the MSUM growth rate constant but this increase was statistically insignificant.
The two phospholipids, phosphatidylcholine and phospha-tidylserine increased the growth rate constant of MSUM. Phosphatidylserine, however, did not significantly increase the growth rate constant at the concentrations studied. It is possible that the raised levels of phospholipids in aged or diseased cartilage and synovial fluid could accelerate the growth of MSUM crystals resulting in MSUM deposition in these tissues. / Pharmaceutical Sciences, Faculty of / Graduate
| Identifer | oai:union.ndltd.org:UBC/oai:circle.library.ubc.ca:2429/24633 |
| Date | January 1985 |
| Creators | Dutt, Yougesh Chander |
| Publisher | University of British Columbia |
| Source Sets | University of British Columbia |
| Language | English |
| Detected Language | English |
| Type | Text, Thesis/Dissertation |
| Rights | For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use. |
Page generated in 0.0017 seconds