Microstructure and mineral composition of dystrophic calcification associated with the idiopathic inflammatory myopathies.

INTRODUCTION: Calcified deposits (CDs) in skin and muscles are common in juvenile dermatomyositis (DM), and less frequent in adult DM. Limited information exists about the microstructure and composition of these deposits, and no information is available on their elemental composition and contents, mineral density (MD) and stiffness. We determined the microstructure, chemical composition, MD and stiffness of CDs obtained from DM patients. METHODS: Surgically-removed calcinosis specimens were analyzed with fourier transform infrared microspectroscopy in reflectance mode (FTIR-RM) to map their spatial distribution and composition, and with scanning electron microscopy/silicon drift detector energy dispersive X-ray spectrometry (SEM/SDD-EDS) to obtain elemental maps. X-ray diffraction (XRD) identified their mineral structure, X-ray micro-computed tomography (microCT) mapped their internal structure and 3D distribution, quantitative backscattered electron (qBSE) imaging assessed their morphology and MD, nanoindentation measured their stiffness, and polarized light microscopy (PLM) evaluated the organic matrix composition. RESULTS: Some specimens were composed of continuous carbonate apatite containing small amounts of proteins with a mineral to protein ratio much higher than in bone, and other specimens contained scattered agglomerates of various sizes with similar composition (FTIR-RM). Continuous or fragmented mineralization was present across the entire specimens (microCT). The apatite was much more crystallized than bone and dentin, and closer to enamel (XRD) and its calcium/phosphorous ratios were close to stoichiometric hydroxyapatite (SEM/SDD-EDS). The deposits also contained magnesium and sodium (SEM/SDD-EDS). The MD (qBSE) was closer to enamel than bone and dentin, as was the stiffness (nanoindentation) in the larger dense patches. Large mineralized areas were typically devoid of collagen; however, collagen was noted in some regions within the mineral or margins (PLM). qBSE, FTIR-RM and SEM/SDD-EDS maps suggest that the mineral is deposited first in a fragmented pattern followed by a wave of mineralization that incorporates these particles. Calcinosis masses with shorter duration appeared to have islands of mineralization, whereas longstanding deposits were solidly mineralized. CONCLUSIONS: The properties of the mineral present in the calcinosis masses are closest to that of enamel, while clearly differing from bone. Calcium and phosphate, normally present in affected tissues, may have precipitated as carbonate apatite due to local loss of mineralization inhibitors.

Controlling the fluoride dosage in a patient with compromised salivary function.

BACKGROUND: High-concentration topical fluorides are used commonly to with compromised salivary function due to irradiation and chemotherapy. CASE DESCRIPTION: The authors describe a 50-year-old man with previously treated cancer who was using tray-applied topical fluoride gel. He complained of gastric symptoms, difficulty in swallowing, leg muscle soreness and knee joint soreness. A computed tomographic scan revealed thickening of the esophageal walls. An upper endoscopy revealed abnormal motility. The motility test indicated high-amplitude peristalsis and hypertensive lower esophageal sphincter, and urine testing indicated high levels of systemic fluoride. The patient's fluoride regimen was altered, and within a short period his urinary fluoride levels returned to normal and his symptoms resolved. CLINICAL IMPLICATIONS: Clinicians prescribing home-applied high-concentration fluorides need to be cognizant of the symptoms of fluoride toxicity, carefully monitor the patient's compliance with the treatment regimen, and adjust the dosage or mode of application to control the total ingested dose of fluoride.

Triglycidylamine crosslinking of porcine aortic valve cusps or bovine pericardium results in improved biocompatibility, biomechanics, and calcification resistance: chemical and biological mechanisms.

We investigated a novel polyepoxide crosslinker that was hypothesized to confer both material stabilization and calcification resistance when used to prepare bioprosthetic heart valves. Triglycidylamine (TGA) was synthesized via reacting epichlorhydrin and NH(3). TGA was used to crosslink porcine aortic cusps, bovine pericardium, and type I collagen. Control materials were crosslinked with glutaraldehyde (Glut). TGA-pretreated materials had shrink temperatures comparable to Glut fixation. However, TGA crosslinking conferred significantly greater collagenase resistance than Glut pretreatment, and significantly improved biomechanical compliance. Sheep aortic valve interstitial cells grown on TGA-pretreated collagen did not calcify, whereas sheep aortic valve interstitial cells grown on control substrates calcified extensively. Rat subdermal implants (porcine aortic cusps/bovine pericardium) pretreated with TGA demonstrated significantly less calcification than Glut pretreated implants. Investigations of extracellular matrix proteins associated with calcification, matrix metalloproteinases (MMPs) 2 and 9, tenascin-C, and osteopontin, revealed that MMP-9 and tenascin-C demonstrated reduced expression both in vitro and in vivo with TGA crosslinking compared to controls, whereas osteopontin and MMP-2 expression were not affected. TGA pretreatment of heterograft biomaterials results in improved stability compared to Glut, confers biomechanical properties superior to Glut crosslinking, and demonstrates significant calcification resistance.