scholarly journals Raman Spectroscopy Applied to the Noninvasive Detection of Monosodium Urate Crystal Deposits

2015 ◽  
Vol 8 ◽  
pp. CMAMD.S29061 ◽  
Author(s):  
Declan J. Curran ◽  
Laurence Rubin ◽  
Mark R. Towler
Keyword(s):  
Raman Spectroscopy ◽  
Signal Processing ◽  
Healthy Subject ◽  
Metatarsophalangeal Joint ◽  
Noninvasive Detection ◽  
Monosodium Urate ◽  
Raman Spectrometer ◽  
Healthy Control ◽  
Urate Crystal ◽  
Msu Crystals

An off-the-shelf Raman Spectrometer (RS) was used to noninvasively determine the presence of monosodium urate (MSU) crystals on the metatarsophalangeal joint (MTPJ) of a single gout sufferer. The spectrum sourced from the clinically diagnosed gout sufferer was compared to that sourced from an age-matched healthy subject scanned using the same protocol. Minimal signal processing was conducted on both spectra. Peaks characteristic of MSU crystals were evident on the spectrum sourced from the gout sufferer and not on the spectrum from the healthy control.

scholarly journals In vivodetection of monosodium urate crystal deposits by Raman spectroscopy—a pilot study: Table 1

Rheumatology ◽  
2015 ◽  
Vol 55 (2) ◽  
pp. 379-380 ◽  
Author(s):  
Abhishek Abhishek ◽  
Declan J. Curran ◽  
Faizan Bilwani ◽  
Adrian C. Jones ◽  
Mark R. Towler ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Pilot Study ◽  
Monosodium Urate ◽  
Urate Crystal

scholarly journals Raman spectroscopy of monosodium urate crystals: A novel tool for non-invasive gout diagnosis

2021 ◽  
Author(s):  
Faizan Bilwani
Keyword(s):  
Raman Spectroscopy ◽  
Sensitivity And Specificity ◽  
Diagnostic Tool ◽  
False Positives ◽  
Monosodium Urate ◽  
Monosodium Urate Crystals ◽  
Detection Techniques ◽  
Non Invasive ◽  
Msu Crystals ◽  
Urate Crystals

Gout is the most common form of inflammatory arthritis. It results in the deposition of monosodium urate crystals (MSU) at the surface of a joint or the articular cartilage. The gold standard for gout diagnosis is synovial fluid (SF) analysis which requires aspiration of the fluid and subsequent analysis by polarized light microscopy (PLM). This has poor reproducibility, is invasive and requires trained personal to perform the analysis. Raman spectroscopy (RS) has the potential to be a non-invasive diagnostic tool that can detect the presence of MSU crystals. The purpose of the research was to determine whether Raman spectroscopy applied onto the surface of a joint could detect MSU crystals through the skin. Two clinical studies were conducted, entitled the Pilot study (Pilot) and the sons of gout study (SOG). Pilot (n=20) considered ten clinically diagnosed gout sufferers and ten clinically diagnosed Osteoarthritis (OA) patients that acted as control. SOG (n=25) considered nine asymptomatic patients where gout was confirmed by clinicians at time of experiment by ultrasound, and 16 Non-Gouty patients, which did not show any signs of gout. An algorithm was implemented in Matlab® 2016 that removed background florescence, performed denoising and identified the presence or absence of MSU peaks. The comparisons were made against Raman peaks that are known to relate to MSU according to the literature. Three peak combinations, entitled C1, C2 and C3 were evaluated based on their resulting sensitivities and specificities for both studies. C1 was chosen as it provided the highest sensitivity for both studies. Pilot was found to have a sensitivity and specificity of 0.8 and 0.7, respectively. SOG had a sensitivity and specificity of 1 and 0.5, respectively. The results indicated that RS diagnosis is able to achieve good to high sensitivity comparable to other gout detection techniques but a moderate to good specificity. The results also show that RS is fully capable of detecting MSU crystals in-vivo, but results in a high number of false positives, 2 for Pilot and 7 for SOG. However, the false positives in Pilot may be attributed to the control subjects suffering from osteoarthritis, which can be a precursor of gout, and the false positives in the SOG study may be a result of ultrasound (US) being used as the confirmatory diagnostic technique that RS is being compared to. US is known to have sensitivity as low as 0.22 and is operator-dependent. Larger population studies are needed to confirm the ability of RS as a diagnostic tool for detecting gout.

scholarly journals Raman spectroscopy of monosodium urate crystals: A novel tool for non-invasive gout diagnosis

2021 ◽  
Author(s):  
Faizan Bilwani
Keyword(s):  
Raman Spectroscopy ◽  
Sensitivity And Specificity ◽  
Diagnostic Tool ◽  
False Positives ◽  
Monosodium Urate ◽  
Monosodium Urate Crystals ◽  
Detection Techniques ◽  
Non Invasive ◽  
Msu Crystals ◽  
Urate Crystals

Gout is the most common form of inflammatory arthritis. It results in the deposition of monosodium urate crystals (MSU) at the surface of a joint or the articular cartilage. The gold standard for gout diagnosis is synovial fluid (SF) analysis which requires aspiration of the fluid and subsequent analysis by polarized light microscopy (PLM). This has poor reproducibility, is invasive and requires trained personal to perform the analysis. Raman spectroscopy (RS) has the potential to be a non-invasive diagnostic tool that can detect the presence of MSU crystals. The purpose of the research was to determine whether Raman spectroscopy applied onto the surface of a joint could detect MSU crystals through the skin. Two clinical studies were conducted, entitled the Pilot study (Pilot) and the sons of gout study (SOG). Pilot (n=20) considered ten clinically diagnosed gout sufferers and ten clinically diagnosed Osteoarthritis (OA) patients that acted as control. SOG (n=25) considered nine asymptomatic patients where gout was confirmed by clinicians at time of experiment by ultrasound, and 16 Non-Gouty patients, which did not show any signs of gout. An algorithm was implemented in Matlab® 2016 that removed background florescence, performed denoising and identified the presence or absence of MSU peaks. The comparisons were made against Raman peaks that are known to relate to MSU according to the literature. Three peak combinations, entitled C1, C2 and C3 were evaluated based on their resulting sensitivities and specificities for both studies. C1 was chosen as it provided the highest sensitivity for both studies. Pilot was found to have a sensitivity and specificity of 0.8 and 0.7, respectively. SOG had a sensitivity and specificity of 1 and 0.5, respectively. The results indicated that RS diagnosis is able to achieve good to high sensitivity comparable to other gout detection techniques but a moderate to good specificity. The results also show that RS is fully capable of detecting MSU crystals in-vivo, but results in a high number of false positives, 2 for Pilot and 7 for SOG. However, the false positives in Pilot may be attributed to the control subjects suffering from osteoarthritis, which can be a precursor of gout, and the false positives in the SOG study may be a result of ultrasound (US) being used as the confirmatory diagnostic technique that RS is being compared to. US is known to have sensitivity as low as 0.22 and is operator-dependent. Larger population studies are needed to confirm the ability of RS as a diagnostic tool for detecting gout.

scholarly journals HSP60 regulates monosodium urate crystal-induced inflammation by activating the TLR4-NF- κ B-MyD88 signaling pathway and disrupting mitochondrial function

2020 ◽  
Author(s):  
Wei Gao ◽  
Qiushi Huang ◽  
Ting Qin ◽  
Heng Mu ◽  
Fan Long ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Mononuclear Cells ◽  
Stress Protein ◽  
Acute Gout ◽  
Monosodium Urate ◽  
Peripheral Blood Mononuclear ◽  
Hsp60 Expression ◽  
Urate Crystal ◽  
Myd88 Signaling ◽  
Msu Crystals

Abstract Background Acute gout is an inflammatory response induced by monosodium urate (MSU) crystals. HSP60 is a highly conserved stress protein that acts as a cellular “danger” signal for immune reactions. In this study, we aimed to investigate the role and molecular mechanism of HSP60 in the gout. Methods HSP60 expression was detected in peripheral blood mononuclear cells (PBMCs) and plasma of gout patients. The effect and mechanism of HSP60 in gout were studied in MSU crystals treatment macrophages and C57BL/6 mice. JC-1 probe and MitoSOX Red were used to measure the mitochondrial membrane potential (MMP) and mitochondrial reactive oxygen species (mtROS). Results HSP60 expression was significantly upregulated in the PBMCs and sera of patients with acute gout (AG) compared to those with inter-critical gout (IG) or healthy controls (HCs). MSU crystals induced expression and secretion of HSP60 in the macrophages. HSP60 knockdown or over-expression affects TLR4 and MyD88 expression, IκBα degradation and the nuclear localization of NF-κB in MSU crystal-stimulated inflammation. Further, HSP60 facilitates MMP collapse and mtROS production, and activates the NLRP3 inflammasome in MSU crystal-stimulated macrophages. In MSU crystal-induced arthritis and peritonitis mouse models pre-treated with HSP60 vivo-morpholino, paw swelling, ankle joint swelling, myeloperoxidase (MPO) activity and inflammatory cell infiltration significantly decreased. Conclusion Our study revealed that MSU crystal stimulates the expression of HSP60 which accelerates TLR4-MyD88-NF-κB signaling pathway and exacerbates mitochondrial dysfunction.

scholarly journals POS0132 IS THE INTERCRITICAL GOUT REALLY ASYMPTOMATIC? THE INFLAMMATORY ROLE OF THE SILENT URATE CRYSTAL DEPOSITION

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 277.1-278
Author(s):  
C. Diaz-Torne ◽  
M. A. Ortiz ◽  
S. Jeria Navarro ◽  
A. Garcia-Gullien ◽  
L. Sainz ◽  
...  
Keyword(s):  
Risk Factors ◽  
Whole Body ◽  
Subclinical Inflammation ◽  
Monosodium Urate ◽  
Crystal Deposition ◽  
Secretome Analysis ◽  
Healthy Donors ◽  
Cytokine Levels ◽  
Urate Crystal ◽  
Crystal Deposit

Background:Gout is the most prevalent inflammatory arthritis. Gout is chronic inflammatory deposition disease related to an increase of cardiovascular (CV) events and mortality. Subclinical chronic inflammation has been demonstrated in this patients but not its relation with the monosodium urate (MSU) crystal deposit size and the number of CV risk factors.Objectives:To study the subclinical inflammation in intercritical gout patients and its possible relation to the estimated size of the crystal deposition and the number of CV risk factors.Methods:To analyze subclinical inflammation we performed a secretome analysis and a cytokine and adiponektine plasma levels quantification (IL-1β, IL-18, IL-6, sIL-6R, TNFα, CXCL-5, RANTES, leptin, resistin and adiponectin) in a cohort of gout patients. As nowadays it is not feasible to determinate the whole body deposit of MSU crystals we created three different MSU crystal deposit size patient groups using an indirect clinical and analytical classification to estimate it. Then we compared cytokine levels between healthy donors and gout patients. We also compared cytokine levels between the different crystal size deposition groups and studied its association to the number of CV risk factors.Results:Ninety consecutive patients attending a Crystal Arthritis Unit were studied. Mean age was 68.27 (28-101) years. 81.1% were male. Clinical gout evolution was of 10.1±9.8 years. 77.5% were on urate lowering treatment. 24% had tophaceous gout. Mean uric acid was 6.3±2.1 mg/dl with 47.1% of them being on target. Hypertension was present in 68.9%, diabetes mellitus in 18.9%, dislipemia in 48.9%, BMI>30 in 32.9%, abdominal obesity in 50% and 16.1% suffered from ischemic heart disease. From the 102 molecules studied in the secretome analysis in 56 there was at least a 20% difference between donors group and any of the deposition groups. In 74% of them gout patients secreted lower levels. IL-18, sIL-6R, RANTES, leptin and adiponectin were higher in patients than in healthy donors. IL-18, sIL6-R, RANTES and CXCL5 levels were associated to the size of the crystal deposits. IL-18, sIL-6R, RANTES and leptin were higher in gout groups with CV risk factors. IL-18, sIL6-R, RANTES and leptin were higher in gout patients with no risk factors when compared to healthy donors with no risk factors. We found no differences when comparing urate lowering treated and non-treated patients.Conclusion:Our results demonstrate that some proinflammatory cytokines and metabolic proteins are raised in intercritical gout patients. Some of them are different from the flare/inflammasome expected ones. In some cytokines this elevation is related to the size of the monosodium urate crystal deposit and/or to the number of cardiovascular risk factors. This cytokine changes could help to explain the increase of the cardiovascular events in gout patients.Disclosure of Interests:Cesar Diaz-Torne Grant/research support from: Received a grant from Grünenthal, Maria Angels Ortiz: None declared, Sicylle Jeria Navarro: None declared, Andrea Garcia-Gullien: None declared, Lluis Sainz: None declared, Hector Corominas: None declared, Silvia Vidal: None declared

scholarly journals THU0406 IDENTIFICATION OF INTRACELLULAR VACUOLES IN SYNOVIAL FLUID WITH CALCIUM PYROPHOSPHATE AND MONOSODIUM URATE CRYSTALS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 440.1-441
Author(s):  
M. L. Peral ◽  
I. Calabuig ◽  
A. Martín-Carratalá ◽  
M. Andrés ◽  
E. Pascual
Keyword(s):  
Clinical Practice ◽  
Synovial Fluid ◽  
Phase Contrast ◽  
Calcium Pyrophosphate ◽  
Monosodium Urate ◽  
Fluid Analysis ◽  
Cytoplasmic Vacuoles ◽  
Contrast Microscopy ◽  
Ordinary Light ◽  
Msu Crystals

Background:Synovial fluid analysis using polarized microscopy is the gold standard for the diagnosis of crystal-related arthritis. In our experience, we have noted that, when calcium pyrophosphate (CPP) crystals are observed, they sometimes appear within intracellular vacuoles. However, this phenomenon is not seen in those samples containing monosodium urate (MSU) crystals. This finding has been scantly reported in the literature, but may be useful in clinical practice to ensure accurate crystal identification.Objectives:Our study aims to assess whether the presence of vacuoles contributes to identifying the type of crystal, and also to gauge the frequency of their presentation.Methods:We conducted an observational study in a rheumatology unit between February and June of 2019. Synovial fluids containing CPP or MSU crystals, obtained in daily clinical practice, were consecutively included for analysis. Two observers simultaneously analyzed the presence of vacuoles by ordinary light and phase contrast microscopy in less than 24 hours after their extraction, using a microscope equipped with two viewing stations. The primary study variable was to determine whether CPP and MSU crystals are seen inside intracellular vacuoles, and to calculate the frequency of this finding for each type of crystal, estimating their 95% confidence interval (95% CI) and comparing rates using Fisher’s exact test.Results:Twenty-one samples were obtained. Data is given in the Table. MSU crystals were present in 7 (33.3%) and CPP crystals in 14 (66.6%). Interestingly, none of the MSU samples showed crystal-containing vacuoles (95% CI 0-35.4%). On the contrary, cytoplasmic vacuoles containing crystals were present in all of the CPP samples (95% CI 78.5-100%). The findings were confirmed by phase-contrast microscopy. Differences were statistically significant (p<0.001).Table.SAMPLES ACCORDING TO TYPE OF MICROCRYSTAL(n=21)SAMPLES WITH VACUOLS(UNDER ORDINARY LIGHT)SAMPLES WITH VACUOLS(UNDER PHASE CONTRAST)CPP (14; 66.6%)14 (100%)(95%CI 78.5-100%)14 (100%)(95%CI 78.5-100%)MSU (7; 33.3%)0 (0%)(95%CI 0-35.4%)0 (0%)(95%CI 0-35.4%)Conclusion:The presence of vacuoles may be a useful and easy way to differentiate MSU and CPP crystals when performing synovial fluid microscopy in clinical practice, since it appears to be a distinctive feature in CPP crystal fluids.References:[1]Kohn NN, Hughes RE, McCarty DJ Jr, Faires JS. The significance of calcium phosphate crystals in the synovial fluid of arthritic patients: the «pseudogout syndrome». II. Identification of crystals. Ann InternMed. 1962 May;56:738-45.[2]Pascual E, Sivera F, Andrés M. Synovial Fluid Analysis for Crystals. CurrOpRheumatol 2011;23:161-169.[3]McCarty DJ, Koopman WJ. Arthritis and allied conditions: A textbook of rheumatology, volumen 1. Lea &amp;Febiger. 1993.[4]Pascual E, Sivera F. Synovial fluid crystal Analysis. En Gout and other crystal arthropathies. Terkeltaub R ed. Elsevier; 2012: p.20-34.[5]Hwang HS, Yang CM, Park SJ, Kim HA. Monosodium Urate Crystal-Induced Chondrocyte Death via Autophagic Process. Int J Mol Sci. 2015 Dec 8;16(12):29265-77.Image 1. Microscopy with ordinary light. Cells with cytoplasmic vacuoles are observed, as well as abundant intra and extracellular CPP crystals.Image 2. Microscopy with phase contrast technique. Cells with intracellular vacuoles are observed inside which have microcrystals with parallelepiped morphology, compatible with CPP.Disclosure of Interests: :None declared

Sampling unit for efficient signal detection and application to liquid chromatography-Raman spectroscopy

2021 ◽  
Author(s):  
Yu-Hao Lo ◽  
Shu-Chi Li ◽  
Hirotsugu Hiramatsu
Keyword(s):  
Raman Spectroscopy ◽  
Liquid Chromatography ◽  
Signal Detection ◽  
Signal Intensity ◽  
Sampling Unit ◽  
Raman Spectrometer ◽  
Unit Design

A new sampling unit design enhances the signal intensity and is available to combine Raman spectrometer with liquid chromatography.

scholarly journals Lower Temperatures Exacerbate NLRP3 Inflammasome Activation by Promoting Monosodium Urate Crystallization, Causing Gout

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1919
Author(s):  
Huijeong Ahn ◽  
Gilyoung Lee ◽  
Geun-Shik Lee
Keyword(s):  
Environmental Factor ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Optimal Temperature ◽  
Monosodium Urate ◽  
Nlrp3 Inflammasome Activation ◽  
Hyperthermia Therapy ◽  
Effects Of Temperature ◽  
Lower Temperature ◽  
Msu Crystals

Gout is a recurrent and chronic form of arthritis caused by the deposition of monosodium urate (MSU) crystals in the joints. Macrophages intake MSU crystals, the trigger for NLRP3 inflammasome activation, which leads to the release of interleukin (IL)-1β and results in the flaring of gout. The effects of temperature, an environmental factor for MSU crystallization, on IL-1β secretion have not been well studied. This study examined the effects of temperature on inflammasome activation. Specific triggers activated canonical inflammasomes (NLRP3, NLRC4, and AIM2) in murine macrophages at various temperatures (25, 33, 37, 39, and 42 °C). The maturation of IL-1β and caspase-1 was measured as an indicator for inflammasome activation. As expected, the optimal temperature of inflammasome activation was 37 °C. The MSU crystal-mediated activation of inflammasome increased at temperatures lower than 37 °C and decreased at higher temperatures. MSU crystals at lower temperatures enhanced IL-1β secretion via the NLRP3 inflammasome pathway. A lower temperature promoted the formation of MSU crystals without changing phagocytosis. Overall, lower temperatures form more MSU crystals and enhance NLRP3 inflammasome activation. In light of these findings, it is possible that hyperthermia therapy may reduce gout flaring.

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