Inhibition of monosodium urate needle crystal growth

Allen, Donald J.; Milosovich, George; Mattocks, Albert M.

doi:10.1002/art.1780080611

Cited by 52 publications

(29 citation statements)

References 5 publications

(1 reference statement)

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“…An approximate heat of dissolution of 4.9(3) kcal/mol (in TMT) could be computed from these data. A similar value (5.5 kcal/mol) can be calculated from data given by Allen et al 8 for the solution of monosodium urate in water. These values may be compared with the heats of dissolution for uric acid dihydrate where a much larger difference (4.0 kcal/mol in TRIS buffer and 15.4 kcal/mol in water) was found and attributed to the exothermic acid-base reaction H 2 U+TRIS"HU -+TRISH + that occurs in the dissolution of uric acid.…”

Section: Dissolving Ability Valuessupporting

confidence: 78%

“…Another peculiarity of MSU is that its formation is clearly related to high levels of urate in the blood serum (uricemia) but, although necessary, this condition is not sufficient to provoke gout, either because crystallization in the synovial liquid may be inhibited or because the crystals are somehow blocked to develop their pathogenic actions. 6,7 Much ongoing research is concerned with these facts and it seems that surface covering of crystal faces may play a role, [8][9][10][11] but the therapy of gout is so far restricted to the symptomatic treatment of the inflammation itself and to the prevention of urate crystal formation through the control of uricemia, either reducing the urate production from purine (e.g. using xanthine oxidase inhibitors) or increasing the rate of uric acid elimination (e.g.…”

Section: Introductionmentioning

confidence: 99%

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The dissolution of monosodium urate monohydrate crystals: formulation of a biocompatible buffer solution with potential use in the treatment of gouty arthropathies

et al. 2013

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The dissolving abilities (DAs) of several aqueous media for microcrystalline monosodiumuratemonohydrate(MSU, NaC5N4O3H3·H2O) have been investigated using UV spectrophotometry for quantitative analytical determinations and X-ray diffraction, scanning electron microscopy and polarized light optical microscopy to assess structural aspects. High DAs were found for a buffer labeled TMT which contains tris(hydroxymethyl)aminomethane (TRIS), tris(hydroxymethyl)aminomethanehydrochloride (TRIS·HCl), D-mannitol (MAN) and taurine (TAU) and gave DA30=1298(5) mg/L for synthetic MSU after 30 min incubation at 37°C and pH 7.4, most of the dissolution taking place within the first 5-10 min. Semiempirical molecular modelling techniques (ZINDO/1) show a favorable energy balance for the formation of a TRIS-urate-TRIS adduct which might explain the high DA values. Buffers containing linear or dendrimeric polyamines gave DA values which suggest that complex formation toward sodium cations is less important. An ex vivo MSU sample was found to have a significantly lower DA value (DA30=1124(5) mg/L in TMT) as well as a lower crystallinity than its synthetic counterpart, possibly related to the presence of a non-crystalline impurity such as endogenous proteins. Cytotoxicity tests based on the MTT assay were used to check the biocompatibility of the TMT buffer and showed only moderate cell mortality after 24 h contact with the buffer solution

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Section: Dissolving Ability Valuessupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

The dissolution of monosodium urate monohydrate crystals: formulation of a biocompatible buffer solution with potential use in the treatment of gouty arthropathies

et al. 2013

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“…The latter two urate preparations were used in all experiments except those in which the effects ofsodium concentration and of ultrafiltration of plasma were studied. It is clear that temperature plays a significant role in urate solubility and this has been discussed previously (Wilcox and others, 1972;Allen, Milosovich, and Mattocks, 1965). Loeb (1972) suggested that the predilection of gout for the peripheral parts of the body is due to sustained lower temperatures in these areas.…”

Section: Urate Solubility In Biological Fluidsmentioning

confidence: 73%

Factors affecting urate solubility in vitro.

Kippen¹,

Klinenberg²,

Weinberger³

et al. 1974

Annals of the Rheumatic Diseases

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Acute gouty arthritis occurs when crystals of monosodium urate form and deposit in joints and connective tissue. These crystals then provoke the characteristic acute inflammatory response of gout (Seegmiller, 1965), and may accumulate chronically forming gouty tophi.Although To determine the urate solubility of each solution, three ml of the solution to be tested was added to a 16 ml glass test tube containing a small magnetic stirring bar. The test tubes were placed on a magnetic stirrer and maintained at the desired temperature. After 16 hours the solutions were centrifuged at 12,000g in a 6 ml glass centrifuge tube and the supernatant was removed. The centrifugation was repeated until no precipitate was visible. Two centrifugations were usually sufficient. The final supernatant was then assayed for urate. Using this procedure, urate crystals could not be detected in the final supernatant by light microscopy. Care was taken to maintain the desired temperature closely during all steps of the procedure including centrifugation. URATE SOLUBILITY IN BUFFER SOLUTIONSThe effect of sodium on urate solubility was determined in 0-01 mol/l. potassium phosphate buffer, pH 7 40, containing appropriate amounts of sodium chloride. The desired pH was obtained by titrating solutions of monobasic and dibasic potassium phosphate.The effect of pH on urate solubility was determined in 0-01 mol/l. sodium phosphate buffer containing 015 mol/l. sodium chloride and adjusted to the desired pH by titrating solutions of monobasic and tribasic sodium phosphate. The effect of albumin on urate solubility was determined by adding the appropriate amount of albumin to 3 ml 0 01 mol/l. sodium phosphate buffer, pH 7*40, containing 0-15 mol/l. sodium chloride and 100 mg/100 ml sodium urate. The albumin was dissolved by gentle mixing.All buffers were boiled before use. Excess sodium urate (approximately 100 mg/100 ml) was added to solutions before titration to prevent pH changes due to the urate itself. URATE SOLUBILITY IN BIOLOGICAL FLUIDSAll blood and urine samples were obtained from normal volunteers. Blood was drawn in heparinized vacutainers, separated by centrifugation for 10 minutes at 3500 r.p.m. and the plasma frozen at -20°C until the time of assay (not

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“…Uric acid is a weak organic acid (pKa, 5.75); at pH 7.40 and at 37º C, about 98% of uric acid is ionized as monosodium urate. Solubility studies have determined that at the sodium concentrations prevailing in extracellular fluids, serum is supersaturated for monosodium urate at concentrations above 6.5 mg/dL [5]. This provides a physical chemical definition of hyperuricemia.…”

Section: Definition and Causes Of Hyperuricemiamentioning

confidence: 99%

Hyperuricemia and renal function

Ruilope¹,

García-Puig²

2001

Current Science Inc

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Increased serum urate concentration is commonly seen in clinical practice. It does not represent a specific disease, nor is it an indication for therapy. Hyperuricemia can be the consequence of increased uric acid production and/or decreased renal capacity to excrete uric acid. In essential hypertension, it has been described in up to one third of patients and is directly related to an increase in renal vascular resistance and inversely correlated with renal plasma flow. In other words, abnormal renal hemodynamics, commonly seen in the initial stages of the disease, account for the increased serum urate concentration. This can be maintained if a decrease in glomerular filtration rate takes place. The increase in uric acid has been shown to be a potent predictor of the development of cardiovascular events and death. In addition, uric acid, particularly when elevated, could represent an independent risk factor. On the other hand, an altered renal function predicts in an independent manner a higher cardiovascular risk. For this reason, the predictive capacity of uric acid could be partly dependent on the fact that hyperuricemia runs in parallel with a deranged renal function.

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Inhibition of monosodium urate needle crystal growth

Cited by 52 publications

References 5 publications

The dissolution of monosodium urate monohydrate crystals: formulation of a biocompatible buffer solution with potential use in the treatment of gouty arthropathies

The dissolution of monosodium urate monohydrate crystals: formulation of a biocompatible buffer solution with potential use in the treatment of gouty arthropathies

Factors affecting urate solubility in vitro.

Hyperuricemia and renal function

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