Uric Acid Crystallization Interrupted with Competing Binding Agents (original) (raw)
Related papers
Journal of Crystal Growth, 1993
Crystals of uric acid have been grown in tetra methoxy silane and silica gel medium. Small winged, transparent, platy crystals of uric acid of about 0.5 X 0.5 X 0.1 mm were grown and were found to be hydrated uric acid.
Frontiers in Medicine
Gout is the most common inflammatory arthropathy caused by the deposition of monosodium urate (MSU) crystals. The burden of gout is substantial with increasing prevalence of gout globally. The prevalence of Gout in the United States has increased by over 7% in the last two decades. Initially, it was believed that MSU crystal deposits occur only in the joints with the involvement of the periarticular soft tissues, but recent studies have shown the presence of MSU crystal deposition in extra-articular sites as well. Human plasma becomes supersaturated with uric acid at 6.8 mg/dl, a state called hyperuricemia. Beyond this level, uric acid crystals precipitate out of the plasma and deposit in soft tissues, joints, kidneys, etc. If left untreated, hyperuricemia leads to chronic gout characterized by the deposition of tophi in soft tissues such as the joints, tendons, and bursae. With the advent of newer imaging techniques such as DECT, MSU crystals can be visualized in various extra-arti...
A Review of Uric Acid, Crystal Deposition Disease, and Gout
Advances in Therapy, 2014
There has been increased interest in gout in both academic and clinical practice settings. Several reasons may explain this. The prevalence of both hyperuricemia and gout has risen in the last decades in developed countries and therefore the burden of gout has
Uric acid crystal binding to renal inner medullary collecting duct cells in primary culture
Journal of the American Society of Nephrology : JASN, 1990
Attachment of microcrystals to cellular membranes may be an important component in the pathophysiology of urolithiasis. This study characterizes the concentration-dependent binding of uric acid crystals to rat renal inner medullary collecting duct cells in primary culture. Collecting duct cell cultures grew as monolayers with interspersed aggregates of rounded cells. Cultures were incubated with 14C-uric acid crystals, and the crystals that bound were quantitated by adherent radioactivity. Uric acid crystal adherence demonstrated concentration dependent saturation with a 1/alpha value (maximum micrograms of crystals adhering to 1 cm2 of binding area) of 645 micrograms/cm2. The beta values (fraction of cross-sectional area which bound crystals) of uric acid (mean = 0.15) and calcium oxalate monohydrate (mean = 0.13) crystals did not differ significantly. Uric acid crystal binding was inhibited by pre-bound calcium oxalate monohydrate crystals in a concentration dependent manner. Thes...
Both gout and osteoarthritis (OA) are common forms of arthritis that inflict a huge burden to an aging population with the increasing prevalence of obesity. Clinicians have long observed the link between these two conditions. In this review, we summarize the evidence from epidemiologic and immunological studies that described the possible relationship between the two conditions. The recent new understanding on monosodium uric acid crystal-induced inflammation has given insight into probable shared pathogenesis pathways for both conditions. We describe the potential therapeutic implications, particularly regarding the possibility of repurposing traditional gout medications for use in OA.
ROLE OF URINARY INHIBITORS AND PROMOTERS IN CALCIUM OXALATE CRYSTALLISATION
Urine of most people is supersaturated with stone forming constituents, including calcium,oxalate, phosphate and uric acid. Crystals or foreign bodies can act as nidi, upon which ions from the supersaturated urine form microscopic crystalline structures. The majority of urinary calculi contain calcium. Calcium stones occur when urine becomes supersaturated with calcium oxalate and phosphate. They form crystals that bind into hardened mineral deposits known as renal stones. The process of stone formation includes crystal nucleation, growth, aggregation and retention. Various substances in our urine modify these stone forming processes, thereby influencing a person’s ability to promote or inhibit stone formation. Promoters of stone formation facilitate stone formation while inhibitors prevent it. Low urine volume, low urine pH, calcium, sodium, oxalate, and urate are known to promote stone formation. Many inorganic (eg. Citrate, magnesium, pyrophosphate etc.) and organic (eg. Tamm-Horsfall protein, glycosaminoglycans, uropontin, nephrocalcin, renal lithostathine etc.) Substances, high urine volume are known to inhibit stone formation. This paper presents role of urinary inhibitors and promoters in calcium oxalate crystallization.
Defective urinary crystallization inhibition and urinary stone formation
International braz j urol, 2006
Introduction: Nephrocalcin (NC) is a glycoprotein produced in the kidney and inhibits calcium oxalate crystal formation. It has been separated into 4 isoforms (A, B, C, and D) and found that (A + B) are more abundant than (C + D) in urine of healthy subjects, but the reverse is seen in human urine of kidney stone patients. To further examine the role of this protein in inhibition of urinary crystallization, nephrocalcin isoforms were purified from 2 genetically pure dog species. Materials and Methods: We studied healthy Beagles, known to be non-stone forming dogs, and Mini-Schnauzers, known to be calcium oxalate stone formers. NC was isolated and purified from each group. Urinary biochemistry and calcium oxalate crystal growth inhibition were measured. Results: Specific crystal growth inhibition activity was significantly higher in non-stone forming dogs (9.79 ± 2.25 in Beagles vs. 2.75 ± 1.34 of Mini-Schnauzers, p < 0.005). Dissociation constants toward calcium oxalate monohydrate were 10-fold different, with Beagles' isoforms being 10 times stronger inhibitors compare to those of Mini-Schnauzers'. Isoforms C + D of NC were the main isoforms isolated in stone-forming dogs. Conclusion: NC of these two species of dogs differently affects calcium oxalate crystallization and might have a role in determining ulterior urinary stone formation.
Urease activity in the crystalline state
Protein Science, 1995
Crystalline Klebsiella aerogenes urease was found to have less than 0.05% of the activity observed for the soluble enzyme under standard assay conditions. Li2S04, present in the crystal storage buffer at 2 M concentration, was shown to inhibit soluble urease by a mixed inhibition mechanism (Ki's of 0.38 f 0.05 M for the free enzyme and 0.13 k 0.02 M for the enzyme-urea complex). However, the activity of crystals was less than 0.5% of the expected value, suggesting that salt inhibition does not account for the near absence of crystalline activity. Dissolution of crystals resulted in-43% recovery of the soluble enzyme activity, demonstrating that protein denaturation during crystal growth does not cause the dramatic diminishment in the catalytic rate. Finally, crushed crystals exhibited only a threefold increase in activity over that of intact crystals, indicating that the rate of substrate diffusion into the crystals does not significantly limit the enzyme activity. We conclude that urease is effectively inactive in this crystal form, possibly due to conformational restrictions associated with a lid covering the active site, and propose that the small amounts of activity observed arise from limited enzyme activity at the crystal surfaces or trace levels of enzyme dissolution into the crystal storage buffer.