Monosodium Urate Monohydrate Crystals Research Articles

Hydrogel Nanoparticles Enable Nucleation Barrier Regulation and Ion Anchoring as an Alternative Pathway for Monosodium Urate Monohydrate Crystallization Control.

Gout flare-up, commonly resulting from monosodium urate monohydrate (MSUM) crystallization, has led to painful inflammatory arthritis among hundreds of millions of people. Herein, a kind of hydrogel nanoparticles (HNPs) with specific properties was developed, aimed at providing a promising pathway for MSUM crystallization control. The experimental and molecular dynamics simulation results synchronously indicate that the fabricated HNPs achieve efficient inhibition of MSUM crystallization governed by the mechanism of "host-guest interaction" even under very low-dose administration. HNPs as the host dispersed in the hyperuricemic model effectively lift the relative heterogeneous nucleation barrier of the MSUM crystal and hinder solute aggregation with strong electronegativity and hydrophobicity. The initial appearance of MSUM crystals was then delayed from 94 to 334 h. HNPs as the guest on the surface of the formed crystal can decelerate the growth rate by anchoring ions and occupying the active sites on the surface, and the terminal yield of the MSUM crystal declined to less than 1% of the control group. The good biocompatibility of HNPs (cell viability > 94%) renders it possible for future clinical applications. This study can guide the rational design of inhibitory nanomaterials and the development of their application in the control of relevant pathological crystallization.

Chronic multiarticular tophaceous gout with abnormally large tophi, case of surgical intervention: a case report from Nepal

Introduction and importance: Gout is an inflammatory disease caused by the deposition of monosodium urate monohydrate crystals around the synovial joints, affecting the first metatarsophalangeal joints followed by ankle and knees. It is found to be more prevalent among men and older women. Tophi tends to develop if the acute phase of the disease is not controlled. In contrast, our patient had an unusual presentation of multiple tophi affecting several joints accompanied by deformities. Case presentation: Here, the authors present a case of a 63 years old male with chronic multiarticular tophaceous gout with a history of more than 30 years. He presented with multiple joint deformities and prior surgical history of excision of tophi. Laboratory reports revealed elevated serum uric acid, and X-ray showed joint deformities with tophi. However, the parameters of renal function test were normal. Surgical excision of the tophi was done. Clinical discussion: Gout is one of the most common inflammatory arthritis, which if untreated can progress to tophi formation. The diagnosis can be made clinically and by several investigations including serum uric acid estimation and aspiration of the joint to reveal monosodium urate monohydrate crystals. A long standing case of multiarticular tophi causing joint deformities does require surgical intervention. Conclusion: Early treatment and diagnosis of hyperuricemia prevent the progression to gouty arthritis and tophi formation. Long history of multiple tophaceous gout is an unusual presentation, which we intend to present here as a novel case report. Nevertheless, such cases require surgical interventions.

Comparative study of Vatarakta w.s.r. to Gouty Arthritis

A healthy lifestyle isn’t just diet and exercise. Today we go over the components of leading a healthy lifestyle and how it’s important to lead a balanced life. In general, most would agree that a healthy person doesn’t smoke, is at a healthy weight, eats a balanced healthy diet, thinks positively, feels relaxed, exercises regularly, has good relationships, and benefits from a good life balance. The World Health Organization in 1946 defined health as ‘A complete state of mental, physical and social well-being not merely the absence of disease’ Vatarakta is a metabolic condition where the most common symptom is pain, which interferes with the patients' daily lives. Vatarakta is named on the basis of the Vata dosha & Rakta dosha which have their own independent derivation & are the main Samprapti Ghatak involved in the Vatarakta. Gouty arthritis is a purine metabolic condition and an inflammatory reaction to the MSUM (Monosodium Urate Monohydrate) crystals that are produced as a result of hyperuricemia.

A classical review on Guduchi Taila

Guduchi Taila is an exquisite referred to in administration of Vatarakta. Guduchi Taila is one of the efficient medicines which contain Guduchi Kwath, Guduchi Kalka, Dugdha, processed in Til Taila only used with the aid of Vaishya’s in Vatarakta. Gouty Arthritis can be well correlated to Vata-Pithadhika Vatarakta. Gout is a pathological response of joint or periarticular tissues which result from deposition of monosodium urate monohydrate crystal in joint and tissues. Vatarakta is one of the fundamental articular diseases which are characterized through severe ache, tenderness, inflammation and burning sensation in the affected joints. Due to its anti-inflammatory analgesic and arthritis properties Guduchi Taila is extensively used in Saruk, Daha, Shopha Vatarakta, these are the signs and symptoms of Vatapittasdika Vatarakta. So, the pharmacology properties and probable mode of action of Guduchi Taila has been discussed in this article.

Identification of tophi in ultrasound imaging based on transfer learning and clinical practice

Gout is a common metabolic disorder characterized by deposits of monosodium urate monohydrate crystals (tophi) in soft tissue, triggering intense and acute arthritis with intolerable pain as well as articular and periarticular inflammation. Tophi can also promote chronic inflammatory and erosive arthritis. 2015 ACR/EULAR Gout Classification criteria include clinical, laboratory, and imaging findings, where cases of gout are indicated by a threshold score of ≥ 8. Some imaging-related findings, such as a double contour sign in ultrasound, urate in dual-energy computed tomography, or radiographic gout-related erosion, generate a score of up to 4. Clearly, the diagnosis of gout is largely assisted by imaging findings; however, dual-energy computed tomography is expensive and exposes the patient to high levels of radiation. Although musculoskeletal ultrasound is non-invasive and inexpensive, the reliability of the results depends on expert experience. In the current study, we applied transfer learning to train a convolutional neural network for the identification of tophi in ultrasound images. The accuracy of predictions varied with the convolutional neural network model, as follows: InceptionV3 (0.871 ± 0.020), ResNet101 (0.913 ± 0.015), and VGG19 (0.918 ± 0.020). The sensitivity was as follows: InceptionV3 (0.507 ± 0.060), ResNet101 (0.680 ± 0.056), and VGG19 (0.747 ± 0.056). The precision was as follows: InceptionV3 (0.767 ± 0.091), ResNet101 (0.863 ± 0.098), and VGG19 (0.825 ± 0.062). Our results demonstrate that it is possible to retrain deep convolutional neural networks to identify the patterns of tophi in ultrasound images with a high degree of accuracy.

Neutrophil Extracellular Trap-Borne Elastase Prevents Inflammatory Relapse in Intercritical Gout.

Gout flares that occur during urate-lowering therapy (ULT) are typically related to the shrinkage of tophi due to aggregated neutrophil extracellular traps (NETs) that have captured monosodium urate crystals in the tissues. The present study was undertaken to analyze the blocking effect of α1 -antitrypsin on neutrophil elastase, and it was found that α1 -antitrypsin induced rapid inflammation in the presence of unstable tophi. Cell-free DNA levels in serum samples were compared between patients who experienced a varying number of gout flares. We investigated whether cell-free DNA in serum samples and α1 -antitrypsin could be altered after the initiation of ULT. In mice, an injection of monosodium urate monohydrate (MSU) crystals was used to form a mimic of tophi in the peritoneal cavity, which was then analyzed using immunofluorescence staining. Finally, we investigated the relapse of inflammation by analyzing the levels of α1 -antitrypsin in 2 kinds of artificial tophi and in tophus-bearing mice. Levels of cell-free DNA in serum samples correlated with the number of flares experienced by patients with tophaceous gout. ULT induced an increase in cell-free DNA in the serum of patients with tophi. Increases in levels of α1 -antitrypsin were seen in patients with tophi who received ULT. Chalk-like tophi removed from the peritoneal cavity of mice after MSU crystals induced inflammation showed abundant coexpression of interleukin-1β (IL-1β) and IL-6-associated NETs. A relapse in inflammation was induced by α1 -antitrypsin during the spontaneous resolution of MSU crystal-induced peritonitis. We observed that α1 -antitrypsin blocks cytokine degradation by neutrophil elastase during the resolution phase of tophi. ULT causes shrinkage of the tophi reflected by an increase in the levels of cell-free DNA in serum. In the resolution phase of tophi in mice, NET-associated neutrophil elastase degrades proinflammatory cytokines and, thus, ameliorates inflammation.

RISK FACTOR FOR GOUT AND PREVENTION : A SYSTEMATIC REVIEW

Due to the supersaturation of uric acid, monosodium urate monohydrate crystals accumulate in the tissues, causing gout. Gout is characterized by elevated serum urate levels, acute gouty arthritic episodes, the production of tophi, gouty nephropathy, and uric acid stones. Until now there is no definite percentage/number of people with gout arthritis in the world, due to differences in research sampling methods in determining the number of sufferers of this disease. However, especially in America, there has been a significant increase in cases of gouty arthritis in the last 10 years. Uric acid is a waste product created by the body when renewing cells of gout patients produce more uric acid in the body and the body is unable to eliminate uric acid through urine, causing uric acid to accumulate in the blood. Significant roles are played by genetics, gender, and diet (alcohol intake, obesity) in the development of gout. The underlying cause of hyperuricemia determines the elements that lead to the development of gout. A diet heavy in purines can precipitate gout episodes in individuals with congenital defects in purine metabolism that result in elevated uric acid generation. Many risk factors for gout have been identified via research, including alcohol risk behavior (only in males), body mass index, estimated glomerular filtration rate, triglycerides, and triglyceride levels. Gout sufferers should avoid uric acid-raising meals and beverages. The patient drinks plenty of water. Gout sufferers should exercise regularly. To maintain weight, walk 150 minutes per week or 30 minutes each day. Avoid uric acid-raising medications like hydrochlorothiazide, aspirin, and cyclosporine.

Single photon emission computed tomography/computed tomography imaging of gouty arthritis: A new voice

Abstract Gouty arthritis, often referred to simply as gout, is a disorder of purine metabolism characterized by the deposition of monosodium urate monohydrate (MSU) crystals in multiple systems and organs, especially in joints and their surrounding soft tissue. Gout is a treatable chronic disease, and the main strategy for effective management is to reverse the deposition of MSU crystals by uric acid reduction, and to prevent gout attacks, tophi deposition and complications, and thereby improve the quality of life. However, the frequent association of gout with other conditions such as hypertension, obesity, cardiovascular disease, diabetes, dyslipidemia, chronic kidney disease (CKD) and kidney stones can complicate the treatment of gout and lead to premature death. Here, we review the use of medical imaging techniques for studying gouty arthritis with special interest in the potential role of single photon emission computed tomography (SPECT)/computed tomography (CT) in the clinical management of gout and complications (e.g., chronic kidney disease and cardiovascular disease).

Ouratea spectabilis and its Biflavanone Ouratein D Exert Potent Anti-inflammatory Activity in MSU Crystal-induced Gout in Mice.

Gouty arthritis (GA) is an inflammatory arthritis triggered by the deposition of monosodium urate monohydrate (MSU) crystals, causing pain, inflammation, and joint damage. Several drugs are currently employed to manage acute flares of GA, but they either have limited effectiveness or induce severe adverse reactions. Ouratea spectabilis is traditionally used in Brazil to treat gastric ulcers and rheumatism. The ethanolic extract of O. spectabilis stems (OSpC) and four biflavanones (ouratein A - D) isolated thereof were evaluated in a murine model of GA induced by the injection of MSU crystals. The underlying mechanism of action of ouratein D was investigated in vitro in cell cultures by measurement of IL-1β levels by ELISA and Western blot analysis. The administration of OSpC (10, 30 or 100 mg/Kg, p. o.) reduced the migration of total inflammatory cells, monocytes, and neutrophils and diminished the levels of IL-1β and CXCL1 in the synovial tissue. Among the tested compounds, only ouratein D (1 mg/Kg) reduced the migration of the inflammatory cells and it was shown to be active up to 0.01 mg/Kg (equivalent to 0.34 nM/Kg, p. o.). Treatment of pre-stimulated THP-1 cells (differentiated into macrophages) or BMDMs with ouratein D reduced the release of IL-1β in both macrophage lines. This biflavanone reduced the activation of caspase-1 (showed by the increase in the cleaved form) in supernatants of cultured BMDMs, evidencing its action in modulating the inflammasome pathway. The obtained results demonstrate the anti-gout properties of O. spectabilis and point out ouratein D as the bioactive component of the assayed extract.

Particularities of Patients Dignosed with Gout in Rheumatology Departament

Gout is a chronic metabolic disease, characterized by joint inflammation caused by monosodium urate monohydrate crystals. The main objective of this study was to identify the prevalence of gout in a rheumatology department in Romania and secondary to describe the characteristics of patients diagnosed with this condition, with emphasis on the comorbidities. This is a longitudinal, retrospective study on 280 patients from the Department of Internal Medicine and Rheumatology, Dr I Cantacuzino Hospital, from January 2017 to May 2019, diagnosed with chronic or acute gout. The prevalence of gout in our hospital in 2 years period was 0.97%. Gouty attack was diagnosed in 38.2% of cases, while 61.8% were evaluated for chronic gout. Male frequency was 69.6%, alcohol consummation was observed in more than half of the cohort (53.2%) and 72.1% were retired persons. The most frequent comorbidity was hypertension (HBP) (82.1%) followed by dyslipidemia (65.3%), atherosclerotic disease(ATS) (55.0%) and chronic kidney disease (53.9%). There was a significant association between HBP, ATS and dyslipidemia with chronic gout (p=0.038, p=0.022 and p=0.009, respectively). The rate of gouty attack significantly increased with the serum level of uric acid (p<0.001). The therapeutic approach complies with international recommendations.

Restrained MSUM crystallization via hydrogel composited membrane based platform for gout prevention and control

Gout is the most common of inflammatory arthropathy caused by the crystallization and accumulation of monosodium urate monohydrate (MSUM) in joints. Herein, fabricated hydrogel composited membrane (HCM) is developed to simulate the mass transfer in joints. A facile and versatile HCM based dynamic platform is established to investigate the “triggers” mechanism of gout under alcohol and its metabolites (acetaldehyde (AH) and acetic acid (HAc) intake condition. The distinct role of EtOH on enhanced gout onset was demonstrated, which attributes to the low interaction energy (Eint) between EtOH and the main crystal surface. While, HAc and carboxyl groups exhibit potentially restrain the MSUM crystallization. This conclusion is furtherly confirmed by the different restraint performance of two kinds of fabricated HCM. PEGDA/AA (polyethylene glycol diacrylate/acrylic acid) with abundant carboxyl groups can delay the appearance time of MSUM crystals from 20 h to 82 h and reduce the crystal yield to 7.5% of the one via PEGDA/NIPAM (N-isopropylacrylamide). The excellent electronegativity of PEGDA/AA renders the adsorption of sodium ion on the HCM interface, which furtherly increases the nucleation energy barrier of MSUM crystal. The functional HCM based platform can guide the relevant biomedical research and rational drug design for gout prevention.

Clinical assessment of Mizaj (Temperament) in the patients of Niqris (Gouty arthritis)

Hippocrates (460-370BC), the father of medicine and the architect of the Unani system of medicine, was the first to propose the ideology of Mizaj (temperament). The notion of Mizaj (temperament) is unique to the Unani system of medicine, and the entire system is centered around its core principle. According to this philosophy, each person has a specific Mizaj (temperament) that is fixed and cannot be modified. Each person has their own tastes, preferences, dislikes, passions, and abilities. All of these attributes combine to form an individual's elite disposition or Mizaj (temperament). The state of a person's health and susceptibility to sicknesses are directly impacted by it. Unani physicians have described an individual's Mizaj (temperament) into four categories Damvi (sanguine), Balghami (phlegmatic), Safravi (bilious) and Saudavi (melancholic). Gout, a crystalline arthropathy is an inflammatory response to the Monosodium urate monohydrate crystals formed secondary to hyperuricemia. The objective of the study was to evaluate and analyze the Mizaj (temperament) of patients with Gout (Niqris). Based on the traditional concept of temperament, the findings of this study have the prospects to avert and manage Gouty arthritis (Niqris). The study was executed in A & U Tibbia College, Karol Bagh, New Delhi-05. 40 patients with the confirmed clinical diagnosis of Gout (Niqris) fulfilling inclusion and exclusion criteria were enrolled in the study. Mizaj of the subjects was evaluated by a standard questionnaire of temperament. In the present observational study, the higher incidence of patients was observed in Balghami (phlegmatic) followed by Damvi (sanguine) Mizaj. This study is as per classical Unani literature, so the patient's temperament (Mzaj) may be considered a key element in the origin and development of Niqris.

Long noncoding RNA SNHG8 accelerates acute gouty arthritis development by upregulating AP3D1 in mice

ABSTRACT Gout can affect the quality of life of patients due to monosodium urate monohydrate (MSU) crystals. Numerous studies have proposed that long noncoding RNAs (lncRNAs) regulate gout. We aimed to reveal the function of lncRNA small nucleolar RNA host gene 8 (SNHG8) in acute gouty arthritis (GA). A GA mouse model was established by injection of MSU into footpads. The levels of SNHG8, miR-542-3p and adaptor-related protein complex 3 subunit delta 1 (AP3D1) in footpads were detected via polymerase chain reaction analysis. Hematoxylin–eosin staining revealed the paw swelling in mice. Enzyme-linked immunosorbent assay and western blot analysis were applied to determine the concentrations of proinflammatory cytokines. SNHG8 expression was identified to be upregulated after MSU treatment. Ablation of SNHG8 decreased the MSU-induced enhancement of paw swelling and foot thickness. In addition, SNHG8 depletion decreased the protein levels of proinflammatory factors in GA mice. Mechanically, SNHG8 was verified to be a sponge of miR-542-3p, and miR-542-3p targeted AP3D1 3ʹ untranslated region. SNHG8 competitively bound with miR-542-3p to upregulate AP3D1 expression. Finally, results of rescue assays illustrated that AP3D1 upregulation offset the SNHG8-mediated inhibition on paw swelling and protein levels of proinflammatory factors in GA mice. In conclusion, SNHG8 accelerates acute GA development by upregulating AP3D1 in an miR-542-3p-dependent way in mice, providing an effective therapeutic approach to treat acute GA.

Association between genotypes of \(\textit{TLR4}\) gene rs2149356 polymorphism and serum level of il-6 in Vietnamese patients with gout

Gout is an inflammatory type of arthritis caused by the deposition of crystals of monosodium urate monohydrate (MSU) in the joints. The arthritis is mediated by the release of pro-inflammatory cytokines including IL-1β, TNF-α and IL-6 by leukocytes including macrophages. Toll-like receptor (TLR)4 is expressed in the immune cells to initiate immune response by inducing activation of signaling molecules involved in the transcription of nuclear genes. In this study, mutational analysis of TLR4 gene was examined to determine the prevalence of gene polymorphism in Vietnamese patients with gout. Molecular analysis of this gene was investigated by PCR amplification and direct DNA sequencing. Level of serum cytokines was measured by ELISA. As a result, no significant difference in frequency of TLR4 gene rs2149356 polymorphism was observed between the patient and control groups. Importantly, level of IL-6 was significantly higher in patients carrying CG genotype as compared with patients carrying TG and TT genotypes of TLR4 gene rs2149356 polymorphism and the patients carrying GG genotype exhibited higher IL-6 level than healthy individuals. The GG genotype of TLR4 gene rs2149356 polymorphism in gout patients were sensitive to IL6-induced inflammatory response. The effect is expected to affect the immune response to treatment for gout patients.

Coronary artery disease: 'gout' in the artery?

Atherosclerotic cardiovascular disease and gout through a ‘crystal lens’. We thank Prof. Zhou for the images of urate crystals (Molloy R.G.E., Sun W., Chen J., Zhou W. Structure and cleavage of monosodium urate monohydrate crystals. Chemical Communications, 2019, 5). Transmission electron micrograph (courtesy of Satu Lehti and Katariina Öörni, Helsinki, Finland) of cholesterol crystals is from an endarterectomized human carotid atherosclerotic lesion (Helsinki Carotid Endarterectomy Study 2, HeCES2). The micrograph was taken at the Electron Microscopy Unit, Institute of Biotechnology, University of Helsinki, Finland. Atherosclerotic cardiovascular disease and gout through a ‘crystal lens’. We thank Prof. Zhou for the images of urate crystals (Molloy R.G.E., Sun W., Chen J., Zhou W. Structure and cleavage of monosodium urate monohydrate crystals. Chemical Communications, 2019, 5). Transmission electron micrograph (courtesy of Satu Lehti and Katariina Öörni, Helsinki, Finland) of cholesterol crystals is from an endarterectomized human carotid atherosclerotic lesion (Helsinki Carotid Endarterectomy Study 2, HeCES2). The micrograph was taken at the Electron Microscopy Unit, Institute of Biotechnology, University of Helsinki, Finland.

Ergonomic Exercise based on Spiritual Care in the Management of Pain Levels Reduction on Elderly with Gouty Arthritis

Gouty arthritis is a metabolic disease caused by a buildup of monosodium urate monohydrate crystals in the joints. The accumulation of uric acid in the joints can form crystals such as needles that cause pain and inflammation, causing interference with the motion system and changes in daily activities. Pain management caused by the accumulation of gout is one of them with physical activities in the form of ergonomic exercise based on spiritual care. This study aims to identify the effect of ergonomic exercise based spiritual care on reducing pain levels in the elderly with gouty arthritis. The design of this study used quasy experimental with control group pre test and post test. The population in this study were all patients with arthritis gout as many as 56 elderly. Samples were taken using total sampling and divided into two groups: 28 intervention groups and 28 control groups. The intervention group was given treatment in the form of ergonomic exercise for 4 weeks with the media being given a module. Pain levels are measured by visual analog scale (VAS). Analysis of the data used was paired T test with a significance of p <0.05. The results of data analysis showed that the intervention group showed an average level of pain before intervention 6.5 and after the intervention showed an average level of pain 3.2 with a p-value of 0,000. Whereas the control group showed an average pain level of 6.2 and after 4 weeks the average pain level increased by 7.0 with a p-value of 0.008. The application of ergonomic exercise based on spiritual care can be given to people with arthritis gout in reducing pain. It is hoped that nurses can implement ergonomic exercise based spiritual care for reducing pain levels in elderly patients with gouty arthritis.

Calcium Pyrophosphate Dihydrate Crystal Deposition in Gouty Tophi.

The coexistence of calcium pyrophosphate dihydrate (CPPD) and monosodium urate monohydrate crystals in gouty tophi has rarely been reported. We undertook this study to investigate CPPD crystal deposits in a series of surgically removed gouty tophi and to identify factors associated with these deposits. Twenty-five tophi from 22 gout patients were analyzed using polarized light microscopy, field emission scanning electron microscopy (FESEM), and μ Fourier transform infrared (μFTIR) spectroscopy. Tophi consisted of multiple lobules separated by fibrous septa and surrounded by a foreign-body giant cell reaction. CPPD crystal aggregates were identified in 9 of 25 tophi from 6 patients. CPPD crystals were dispersed or highly compacted, localized at the edge or inside the tophus lobules, with some lobules completely filled with crystals. Both monoclinic and triclinic CPPD crystal phases were identified using FESEM and μFTIR. Compared to patients without CPPD, those with CPPD-containing tophi were older (mean 60.5 years versus 47.2 years; P = 0.009), and had longer-term gout duration (mean 17.0 years versus mean 9.0 years; P < 0.05) and tophi duration (mean 10.0 years versus mean 4.6 years; P < 0.01). None of the patients had radiographic chondrocalcinosis of the knee or wrist. CPPD crystal formation seems to be a late and frequent event of tophus maturation, occurring more frequently with aging, and could contribute to the speed of tophus dissolution and the apparent persistence of tophus sometimes observed even after effective, long-lasting urate-lowering therapy.

Fingolimod Phosphate (FTY720-P) Activates Protein Phosphatase 2A in Human Monocytes and Inhibits Monosodium Urate Crystal-Induced Interleukin-1β Production.

Gout is a chronic inflammatory arthritis caused by monosodium urate monohydrate (MSU) crystal deposits in joints of lower limbs. Phagocytic uptake of MSU crystals by joint-resident macrophages and recruited circulating monocytes results in IL-1β expression and production. Current acute gout treatments have serious toxicities and suffer suboptimal clinical outcomes. Protein phosphatase 2A (PP2A) plays an important role in regulating signaling pathways relevant to inflammation. We hypothesized that innate immune danger signals, e.g., lipopolysaccharide (LPS) and soluble uric acid (sUA), prime human monocytes toward MSU crystal phagocytosis and that increased IL-1β production mediated by a reduction in PP2A activity and restoring PP2A activity exerts an anti-inflammatory effect in this setting. Priming monocytes with LPS + sUA increased cytosolic pro-IL-1β and mature IL-1β and enhanced MSU crystal phagocytosis and its downstream IL-1β expression (P < 0.001). A combination of LPS + sUA priming and MSU crystals reduced PP2A activity in monocytes by 60% (P = 0.013). PP2A catalytic subunit gene knockdown reduced PP2A activity and exacerbated MSU crystal-induced IL-1β expression and secretion (P < 0.0001). Fingolimod (FTY720) and its active metabolite, fingolimod phosphate (FTY720-P), were evaluated for their ability to activate PP2A in human monocytes over 24 hours. FTY720 and FTY720-P activated PP2A to a similar extent, and maximal enzyme activity occurred at 24 hours for FTY720 and at 6 hours for FTY720-P. FTY720-P (2.5 μM) reduced pro-IL-1β production and IL-1β secretion in primed and MSU crystal-stimulated monocytes (P < 0.0001) without changing the magnitude of crystal phagocytosis. We conclude that PP2A is a promising new target in acute gout. SIGNIFICANCE STATEMENT: The activity of protein phosphatase 2A (PP2A) is implicated in the enhanced expression and production of IL-1β by human monocytes in response to priming with soluble uric acid and lipopolysaccharide and phagocytosis of monosodium urate monohydrate (MSU) crystals. Fingolimod phosphate activates PP2A in human monocytes and reduces cytosolic pro-IL-1β content and its conversion to biologically active IL-1β in human monocytes exposed to MSU crystals.

AYURVEDIC MANAGEMENT OF VATARAKTA W.S.R.TO GOUT- A CASE STUDY

The disease which is caused by aggravated Vata and vitiated Rakta is called Vatarakta. It is better correlated with ”gout” in the modern science. Vatarakta is a metabolic disorder where pain is predominant symptom, which disturbs day to day life of persons. Gouty arthritis is a disorder of Purine metabolism and is an inflammatory response to the MSUM(monosodium urate monohydrate) crystals, formed to secondary hyperuricaemia. The disease is known as ‘the King’s disease’ or ‘rich man’s disease’. In the present case study “Simhasyadi kwath mentioned in Bhaishajyaratnavali used in acute and chronic conditions. The results are significant with reduced acute attacks, decrease in the symptoms and hyperuricaemia. Further clinical trials can be conducted to prove the efficacy of the drugs statistically.

White blood cell count and total protein concentration to predict the absence of microcrystals in synovial fluid

BackgroundSynovial fluid analysis is essential for diagnosing crystal-induced arthritis. Monosodium urate monohydrate (MSU) crystals in gout and calcium pyrophosphate dihydrate (CPP) crystals in pseudogout trigger inflammatory reactions that result in white blood cell (WBC) activation. This study aimed to evaluate the predictive value of synovial fluid WBC count and total protein concentration for the absence of microcrystals. Materials and methodsThis prospective study analyzed all synovial fluid samples collected at a single center in a 6–month period. The absolute WBC count and total protein concentration were recorded for each sample. A single expert used polarized light microscopy to detect microcrystals. Mann-Whitney U-tests was used to compare mean counts and concentrations in samples with and without crystals. Diagnostic performance was assessed through the area under the receiver-operating characteristic curve (AUC). ResultsA total of 205 samples were included. The absolute WBC count was significantly higher in samples with crystals than in those without. No differences were found between MSU and CPP. The ROC curve showed an AUC 0.773, and an absolute WBC count <1650/mm3 yielded 95.7% sensitivity, 53.1% specificity, and 97.7% negative predictive value for predicting the absence of microcrystals. Total protein concentration was not significantly different between samples with and without crystals. ConclusionThe WBC count is useful for screening for the absence of microcrystals in synovial fluid; the cutoff <1650 WBC/mm3 accurately predicts the absence of crystals, obviating the need for polarized light microscopy and thus simplifying and shortening laboratory analysis of synovial fluid, leading to a reduction in laboratory turnaround time.