Urate Crystals (urate + crystal)

Distribution by Scientific Domains

Selected Abstracts

Role of the leucine-rich repeat domain of cryopyrin/NALP3 in monosodium urate crystal,induced inflammation in mice

Hal M. Hoffman
Objective The mechanism by which monosodium urate monohydrate (MSU) crystals intracellularly activate the cryopyrin inflammasome is unknown. The aim of this study was to use a mouse molecular genetics,based approach to test whether the leucine-rich repeat (LRR) domain of cryopyrin is required for MSU crystal,induced inflammation. Methods Cryopyrin-knockout lacZ (Cryo,Z/,Z) mice and mice with the cryopyrin LRR domain deleted and fused to the lacZ reporter (Cryo,LRR Z/,LRR Z) were generated using bacterial artificial chromosome,based targeting vectors, which allow for large genomic deletions. Bone marrow,derived macrophages from Cryo,LRR Z/,LRR Z mice, Cryo,Z/,Z mice, and congenic wild-type (WT) mice were challenged with endotoxin-free MSU crystals under serum-free conditions. Phagocytosis and cytokine expression were assessed by flow cytometry and enzyme-linked immunosorbent assay. MSU crystals also were injected into mouse synovial-like subcutaneous air pouches. The in vivo inflammatory responses were examined. Results Release of interleukin-1, (IL-1,), but not CXCL1 and tumor necrosis factor ,, was impaired in Cryo,LRR Z/,LRR Z and Cryo,Z/,Z mouse bone marrow,derived macrophages compared with WT mouse bone marrow,derived macrophages in response to not only MSU crystals but also other known stimuli that activate the cryopyrin inflammasome. In addition, a comparable percentage of MSU crystals taken up by each type of bone marrow,derived macrophage was observed. Moreover, total leukocyte infiltration in the air pouch and IL-1, production were attenuated in Cryo,Z/,Z and Cryo,LRR Z/,LRR Z mice at 6 hours postinjection of MSU crystals compared with WT mice. Conclusion MSU crystal,induced inflammatory responses were comparably attenuated both in vitro and in vivo in Cryo,LRR Z/,LRR Z and Cryo,Z/,Z mice. Hence, the LRR domain of cryopyrin plays a role in mediating MSU crystal,induced inflammation in this model. [source]

High performance liquid chromatography (HPLC) in the investigation of gout in palaeopathology

D. Swinson
Abstract Gout is a disease caused by the abnormal accumulation of uric acid in the body, which can result in sodium urate crystals forming tophi at joints, with associated erosion of bone and cartilage. Only two examples of tophi have been reported from archaeological individuals, and the diagnosis of gout based on dry bone manifestations can be difficult. This paper presents preliminary results of a new technique to aid the diagnosis of gout in palaeopathology, namely high performance liquid chromatography (HPLC). Five archaeological skeletons with suspected gout (diagnosed using visual and radiological analysis) and three controls were analysed. Two of the gouty individuals had a white powder in their erosive lesions. HPLC showed the presence of uric acid in bone in four of the five individuals with evidence of gouty arthritis and was negative for uric acid in bone from the three controls. The white powder was also positive for uric acid. With reliance on the presence of articular erosions, cases of gout will be missed in archaeological human bone. HPLC measurement of uric acid could prove useful in the differential diagnosis of erosive arthropathy in archaeology. It may also be useful in identifying individuals with an increased body pool of uric acid, linked to conditions included in the term ,metabolic syndrome'. As a result, HPLC uric acid measurement also has the potential to provide additional information on health and lifestyle in past communities. Copyright 2008 John Wiley & Sons, Ltd. [source]

Simple non-staining method to demonstrate urate crystals in formalin-fixed, paraffin-embedded skin biopsies

Joshua Weaver
Background:, Gouty tophi classically occur as nodules over joints and the helix. The ideal fixative for preservation of gout crystals has traditionally been alcohol because the crystals are formalin and water soluble. However, most biopsies are submitted in formalin fixative, which results in dissolution of urate crystals leaving behind a non-specific pale amorphous area. Although complex staining methods to show urate crystals in tissue have been described, the present study elucidates a simple non-staining method utilizing a thick unstained coverslipped microscopy slide that allows detection and confirmation of birefringence of urate crystals in formalin-fixed, paraffin-embedded tissue. Methods:, Twenty-nine cases of cutaneous gouty tophi were evaluated using a hematoxylin-eosin (H&E)-stained section, a 10-,m unstained coverslipped section and a 4-,m unstained coverslipped section. In all cases, the specimen was received and submitted in formalin. Results:, Polarizable crystals were not identified in any of the H&E sections. The use of the thicker unstained coverslipped section was more sensitive than the standard 4 ,m section by recognizing the characteristic urate crystals in 48% and 38% of the cases, respectively. Conclusions:, This inexpensive adjunctive tool can be used to document gout crystals in almost half of skin biopsies. [source]

Analgesic and anti-inflammatory actions of robenacoxib in acute joint inflammation in dog

Schmid, V. B., Spreng, D. E., Seewald, W., Jung, M., Lees, P., King, J. N. Analgesic and anti-inflammatory actions of robenacoxib in acute joint inflammation in dog. J. vet. Pharmacol. Therap. 33, 118,131. The objectives of this study were to establish dose,response and blood concentration,response relationships for robenacoxib, a novel nonsteroidal anti-inflammatory drug with selectivity for inhibition of the cyclooxygenase (COX)-2 isoenzyme, in a canine model of synovitis. Acute synovitis of the stifle joint was induced by intra-articular injection of sodium urate crystals. Robenacoxib (0.25, 0.5, 1.0, 2.0 and 4.0 mg/kg), placebo and meloxicam (0.2 mg/kg) were administered subcutaneously (s.c.) 3 h after the urate crystals. Pharmacodynamic endpoints included data from forceplate analyses, clinical orthopaedic examinations and time course of inhibition of COX-1 and COX-2 in ex vivo whole blood assays. Blood was collected for pharmacokinetics. Robenacoxib produced dose-related improvement in weight-bearing, pain and swelling as assessed objectively by forceplate analysis (estimated ED50 was 1.23 mg/kg for z peak force) and subjectively by clinical orthopaedic assessments. The analgesic and anti-inflammatory effects of robenacoxib were significantly superior to placebo (0.25,4 mg/kg robenacoxib) and were non-inferior to meloxicam (0.5,4 mg/kg robenacoxib). All dosages of robenacoxib produced significant dose-related inhibition of COX-2 (estimated ED50 was 0.52 mg/kg) but no inhibition of COX-1. At a dosage of 1,2 mg/kg administered s.c., robenacoxib should be at least as effective as 0.2 mg/kg of meloxicam in suppressing acute joint pain and inflammation in dogs. [source]

Needle-shaped crystals are not always urate crystals: Comment on the clinical image by Slobodin et al

Enrico Selvi MD
No abstract is available for this article. [source]