Effects of Total Saponins from Dioscorea Nipponica Makino on Monosodium Urate-Induced M1-Polarized Macrophages through Arachidonic Acid Signaling Pathway: An in vitro Study / 中国结合医学杂志

OBJECTIVE@#To investigate and reveal the underlying mechanism of the effect of total saponins from Dioscoreae nipponica Makino (TSDN) on the arachidonic acid pathway in monosodium urate (MSU) crystal-induced M1-polarized macrophages.@*METHODS@#M1 polarization of RAW264.7 cells were induced by 1 µ g/mL lipopolysaccharide (LPS). The methylthiazolyldiphenyl-tetrazolium bromide method was then used to screen the concentration of TSDN. MSU (500 µ g/mL) was used to induce the gouty arthritis model. Afterwards, 10 µ g/L TSDN and 8 µ mol/L celecoxib, which was used as a positive control, were added to the above LPS and MSU-induced cells for 24 h. The mRNA and protein expressions of cyclooxygenase (COX) 2, 5-lipoxygenase (5-LOX), microsomal prostaglandin E synthase derived eicosanoids (mPGES)-1, leukotriene B (LTB)4, cytochrome P450 (CYP) 4A, and prostaglandin E2 (PGE2) were tested by real-time polymerase chain reaction and Western blotting, respectively. The enzyme-linked immunosorbent assay was used to test the contents of M1 markers, including inducible nitric oxid synthase (NOS) 2, CD80, and CD86.@*RESULTS@#TSDN inhibited the proliferation of M1 macrophages and decreased both the mRNA and protein expressions of COX2, 5-LOX, CYP4A, LTB4, and PGE2 (P<0.01) while increased the mRNA and protein expression of mPGES-1 (P<0.05 or P<0.01). TSDN could also significantly decrease the contents of NOS2, CD80, and CD86 (P<0.01).@*CONCLUSION@#TSDN has an anti-inflammation effect on gouty arthritis in an in vitro model by regulating arachidonic acid signaling pathway.

Immediate analgesic effect of electroacupuncture combined with diclofenac sodium on acute gouty arthritis: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the immediate analgesic effect of electroacupuncture (EA) combined with diclofenac sodium on acute gouty arthritis (AGA).@*METHODS@#A total of 90 patients with AGA were randomly divided into a low-dose medication (LM) group (30 cases, 1 case was eliminated, 1 case dropped off), a conventional medication (CM) group (30 cases, 1 case dropped off) and a combination of acupuncture and medication (AM) group (30 cases ). The LM group was given oral administration of 50 mg diclofenac sodium sustained-release capsule; the CM group was given oral administration of 100 mg diclofenac sodium sustained-release capsule; on the basis of the treatment of LM group, the AM group was treated with electroacupuncture at ashi points, Dadu (SP 2), Taichong (LR 3), Taibai (SP 3), Neiting (ST 44), Sanyinjiao (SP 6), Zusanli (ST 36) and Yinlingquan (SP 9) on the affected side, and Taichong (LR 3) and Zusanli (ST 36), Sanyinjiao (SP 6) and Yinlingquan (SP 9) were connected to electroacupuncture respectively, continuous wave, 2 Hz in frequency. The visual analogue scale (VAS) scores of pain before treatment and after 10 min, 2 h, 4 h and 6 h of treatment completion, joint tenderness and swelling scores before treatment and after 10 min and 6 h of treatment completion were compared, and the rate of diclofenac sodium addition within 24 h after treatment completion was recorded among the three groups.@*RESULTS@#After 10 min of treatment completion, the scores of VAS, joint tenderness and joint swelling in the AM group were lower than those before treatment (P<0.05), and the VAS score in the AM group was lower than that in the other two groups (P<0.05). After 2, 4 and 6 h of treatment completion, the VAS scores of the three groups were lower than those before treatment (P<0.05), and the scores in the AM group were lower than those in the LM group (P<0.05). After 6 h of treatment completion, the joint tenderness scores of the three groups and the joint swelling scores of the AM group and the CM group were lower than those before treatment (P<0.05), and the joint tenderness and swelling scores of the AM group were lower than those of the LM group (P<0.05). The rate of diclofenac sodium addition was 3.3 % (1/30) and 3.4 % (1/29) in the AM group and the CM group, respectively, which were lower than 17.9% (5/28) in the LM group (P<0.05).@*CONCLUSION@#Electroacupuncture combined with diclofenac sodium have a good immediate analgesic effect in the treatment of AGA, and have the advantages of small dosage of analgesic drugs and less adverse reactions.

Comprehensive chemical profiling and quantitative analysis of ethnicYi medicine Miao-Fu-Zhi-Tong granules using UHPLC-MS/MS / 中国天然药物

Developing analytical methods for the chemical components of natural medicines remains a challenge due to its diversity and complexity. Miao-Fu-Zhi-Tong (MFZT) granules, an ethnic Yi herbal prescription, comprises 10 herbs and has been clinically applied for gouty arthritis (GA) therapy. Herein, a series of chemical profiling strategies including in-house library matching, molecular networking and MS/MS fragmentation behavior validation based on ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) were developed for qualitative analysis of MFZT granules. A total of 207 compounds were identified or characterized in which several rare guanidines were discovered and profiled into alkyl substituted or cyclic subtypes. Moreover, network pharmacology analysis indicated that MFZT's anti-gout mechanism was mostly associated with the nuclear factor kappa-B (NF-κB) signaling, nucleotide oligomerization domain (NOD)-like signaling and rheumatoid arthritis pathways, along with the synergistic effect of 84 potential active compounds. In addition, a quantitative analytical method was developed to simultaneously determine the 29 potential effective components. Among them, berberine, pellodendrine, 3-feruloylquinic acid, neoastilbin, isoacteoside and chlorogenic acid derivatives at higher concentrations were considered as the chemical markers for quality control. These findings provide a holistic chemical basis for MFZT granules and will support the development of effective analytical methods for the herbal formulas of natural medicines.

Mechanism and experimental verification of "Polygoni Cuspidati Rhizoma et Radix-Ligustri Lucidi Fructus" combination in treatment of acute gouty arthritis based on network pharmacology / 中国中药杂志

Based on network pharmacology, the mechanism of Polygoni Cuspidati Rhizoma et Radix-Ligustri Lucidi Fructus(PL) combination against acute gouty arthritis(AGA) was explored and preliminarily verified by animal experiment. The chemical components and corresponding targets of PL were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The active components with oral bioavailability(OB)≥30% and drug-likeness(DL)≥0.18 were screened based on literature, and the related protein targets were collected. Then the protein targets were standardized with the help of UniProt database. The AGA-related targets were searched from GeneCards, NCBI, and DrugBank. The common targets of the disease and the medicinals were yielded by FunRich V3, and the protein-protein interaction(PPI) network was constructed to screen the key targets, followed by Gene Ontology(GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the key targets. Afterwards, some of the key targets were verified by sodium urate crystal-induced AGA mouse model. A total of 25 active components and 287 targets of PL, 811 targets of AGA, and 88 common targets were screened out. PPI network analysis showed that tumor necrosis factor(TNF), interleukin-6(IL-6), and interleukin-1β(IL-1β) may be the core targets of PL in the treatment of AGA. The key targets were mainly involved in 566 GO terms(P<0.05), including multiple biological processes such as inflammatory response and immune response. Moreover, they were related to 116 KEGG pathways and these pathways were involved in inflammation and immunity, mainly including NOD-like receptor signaling pathway and TNF signaling pathway. Animal experiment confirmed that PL can alleviate ankle swelling, improve abnormal gait, and down-regulate the protein expression of TNF-α, IL-6, and IL-1β in AGA mice, indicating that PL can treat AGA through TNF-α, IL-6, and IL-1β and the feasibility of network pharmacology to predict drug targets. This study preliminarily discussed the key targets and biological signaling pathways involved in the treatment of AGA with PL combination, which reflected the multi-pathway and multi-target action characteristics of Chinese medicine. Moreover, this study laid a scientific basis for research on the treatment of AGA with PL combination, as well as the mechanism of action.

Research progress on anti-hyperuricemia effects and mechanisms of Chinese medicines based on regulation of intestinal flora and metabolites / 中国中药杂志

Chronical hyperuricemia, a severe metabolic disease characterized by increased serum uric acid, urea nitrogen, and creatinine, has a positive correlation with the risks of gouty arthritis, diabetes, hypertension, and kidney damage. Abnormal purine metabolism and reduced uric acid excretion are the major causes of hyperuricemia, which, thus, points to a potential strategy of preventing from or delaying the progress of hyperuricemia-related diseases and its complications by effectively controlling the serum uric acid level. Increasing evidence has revealed that Chinese medicines alleviate hyperuricemia through regulating intestinal flora, which plays a pivotal role in regulating metabolites, including uric acid level. The disease treatment with traditional Chinese medicine is based on syndrome differentiation, and Chinese medicines often have multiple effects and a wide range of targets. In this review, we summarized the anti-hyperuricemia effects and mechanisms of active compounds in Chinese medicines, single Chinese medicinal herbs, and Chinese medicinal prescriptions in regulating the uric acid level via intestinal flora and metabolites, which will be helpful for further study and application of Chinese medicines in hyperuricemia treatment.

Effect of rebamipide on the acute gouty arthritis in rats induced by monosodium urate crystals / 北京大学学报(医学版)

OBJECTIVE@#To investigate the role of rebamipide in the treatment of acute gout arthritis rats induced by monosodium urate (MSU) crystal.@*METHODS@#Forty-two male rats were randomly divided into three groups (n=14). Group A was treated with oral rebamipide, group B with oral colchicine, and group C with oral placebo. The rats were monitored for the induction of arthritis with clinical manifestations and pathological changes, and the levels of interleukin (IL)-1β、IL-6、IL-10, and tumor necrosis factor (TNF)-α in serum were measured.@*RESULTS@#In group C, the clinical score and swelling index reached the maximum in 24 h, and then gradually decreased to 72 h. After 24 h of model induced, the clinical scores in group C were significantly higher than those in group A and group B [2 (1-3) vs. 0 (0-1) vs. 1 (0-2), P < 0.01], the swelling indexes in group C were significantly higher than those in group A and group B [0.36 (0.16-0.52) vs. 0.11 (0-0.20) vs. 0.12 (0-0.16), P < 0.01]. Histologically, after 24 h of model induced, there was a large number of neutrophil infiltration in the synovium of group C [scale score: 4 (2-4)], and there was no significant inflammatory cell infiltration in group A [1 (0-2)] and group B [1 (0-2)], the difference was statistically significant (P < 0.001). After 24 h of model induced, the levels of IL-1β, IL-6, IL-10, and TNF-α in serum of group C were significantly higher than those in group A and B [IL-1β: (41.86±5.72) vs. (27.35±7.47) vs. (27.76±5.28) ng/L, IL-6: (1 575.55±167.11) vs. (963.53±90.22) vs. (964.08±99.31) ng/L, IL-10: (37.96±3.76) vs. (21.68±4.83) vs. (16.20±2.49) ng/L, TNF-α: (21.32±1.34) vs. (15.82±2.54) vs. (17.35±7.47) μg/L, P < 0.001].@*CONCLUSION@#Rebamipide has a protective effect on acute gout arthritis rats induced by MUS crystals.

Differentially expressed inflammatory proteins in acute gouty arthritis based on protein chip / 浙江大学学报·医学版

OBJECTIVE@#To detect the differentially expressed inflammatory proteins in acute gouty arthritis (AGA) with protein chip.@*METHODS@#The Raybiotech cytokine antibody chip was used to screen the proteomic expression in serum samples of 10 AGA patients and 10 healthy individuals. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were applied to determine the biological function annotation of differentially expressed proteins and the enrichment of signal pathways. ELISA method was used to verify the differential protein expression in 60 AGA patients and 60 healthy subjects. The ROC curve was employed to evaluate the diagnostic value of differential proteins in AGA patients.@*RESULTS@#According to|log@*CONCLUSIONS@#Proteomics can be applied to identify the biomarkers of AGA, which may be used for risk prediction and diagnosis of AGA patients.

Analysis of risk factors influencing the detection rate of urate crystal by dual energy computed tomography / 北京大学学报(医学版)

OBJECTIVE@#To explore the risk factors of detection of uric acid crystals by dual energy CT (DECT) in patients with gout diagnosed by gold standard.@*METHODS@#From June 2011 to December 2018, clinical data of 29 patients were collected who were diagnosed with acute or chronic gout by positive polarized light analysis of joint synovial fluid in First Hospital of Peking University. Chi-square test, Logistic regression and t-test were used. The relationship between DECT and the clinical data, laboratory examination and drug treatment were analyzed.@*RESULTS@#In this study, 29 patients were included, of whom, 22 patients were detected with uric acid crystals by DECT, and 7 patients were not. According to whether the uric acid crystals were detected or not by DECT, the patients were divided into two groups. Compared with the negative group, the patients were older in positive group [(47±12) vs. (39±11) years, P=0.15], had higher body bass index (BMI) [(27.9±3.7) vs. (22.8±2.1) kg/m2, P=0.002], longer gout disease duration [(135±102) vs.(45±53) months, P=0.035], higher in the highest serum uric acid in history [(643±121) vs. (543±103) μmol/L, P=0.043]. Although uric acid near DECT in positive group was higher than in negative group, there was no statistical difference [(558±150) vs. (513±89) μmol/L, P=0.497]. Comparing positive group with negative group, the percentage of the patients in acute phase was higher than in chronic phase [18(81.8%) vs. 4(57%), P=0.311];the percentage of the patients taking uric-acid-lowering drugs was higher than the other group [22(100%) vs. 5 (71%), P=0.052];the percentage of the patients with recurrent typical attacks was higher than that of those without typical attacks [22 (100%) vs.6 (85%), P=0.241]. The consistency of symptoms and the finding of uric acid crystals by DECT had been compared between the joints. The right knee joint had the highest consistency (Kappa=0.627), followed by the left MTP1 (Kappa=0.58), the right metatarsophalangeal 1(MTP1, Kappa=0.551) and the left knee (Kappa=0.494), all of which had statistical significance. The consistency of the ankle joint was lower (the right ankle joint: Kappa=0.19, the left ankle joint: Kappa=0.256), showing no statistical significance. BMI (kg/m2) [2.307 (1.139-4.670), P=0.02], gout duration (years) [0.306 (0.906-4.881), P=0.186], and the highest uric acid level in history (mg/dL) [0.023 (0.981-2.764), P=0.137] had relationship to the positive result of urate crystals in DECT.@*CONCLUSION@#Gout patients with larger BMI, higher previous highest uric acid value and longer gout duration had higher sensitivity of the positive result in DECT.

Artritis Gotosa. 10 años de Seguimiento / Artritis Gotosa. 10 años de Seguimiento

Introduction: gouty arthritis is a persistent metabolic disease that produces an increase of the circulating uric acid, with the resulting deposit of monosodic urate crystals in the tissues. Objective: to characterize patients with gouty arthritis clinically and epidemiologically. Methods: a descriptive investigation of 72 patients with a diagnosis of gouty arthritis, assisted at Arnaldo Milián Castro Clinical Surgical University Hospital was carried out from January 2008 to December 2017. Results: patients between 40 and 49 years of age were the most representative group with a highest incidence in not white patients and the male sex. Obesity and hypertension prevailed as previous personal antecedents. Alcohol intake was the most represented toxic habit. A crisis of inflammation of the big toe was the more frequent starting manifestation. Swelling of soft tissues was the main radiologic alteration. Conclusion: gouty arthritis is present with a highest frequency in the male sex with a peak of incidence in the fourth decade of life. It is associated to bad diet habits and alcohol intake that could cause joint damage(AU)

Introducción: la artritis gotosa es una enfermedad metabólica persistente, que produce un aumento del ácido úrico circulante, con el consiguiente depósito de cristales de uratos monosódicos en los tejidos. Objetivo: caracterizar clínica y epidemiológicamente a los pacientes con artritis gotosa. Método: se realizó una investigación descriptiva de 72 pacientes con diagnóstico de artritis gotosa, atendidos en el Hospital Universitario Clínico Quirúrgico Arnaldo Milián Castro, entre enero del 2008 y diciembre del 2017. Resultados: los pacientes entre 40 y 49 años de edad fueron los más representativos, con mayor incidencia en no blancos y del sexo masculino. Predominó la obesidad y la hipertensión arterial como antecedentes patológicos personales. El alcohol fue el hábito tóxico mayoritariamente representado. La crisis de podagra resulto ser la manifestación inicial más usual. El aumento de partes blandas fue la principal alteración radiológica. Conclusiones: La gota se presenta con mayor frecuencia en el sexo masculino con un pico de incidencia en la cuarta década de la vida. Está asociada a malos hábitos dietéticos y al consumo de bebidas alcohólicas pudiendo ocasionar daño articular(AU)

Gota tofácea crónica en un adulto / Chronic tophaceous gout in an adult

Se presenta el caso clínico de un paciente de 57 años de edad, mestizo, con antecedentes de artritis reumatoidea y gota, quien acude a la consulta especializada de Dermatología del Hospital Clinicoquirúrgico Docente Celia Sánchez Manduley de Manzanillo, provincia de Granma, por presentar lesiones nodulares dolorosas diseminadas. Se realizaron estudios complementarios y biopsia de piel, cuyos resultados permitieron diagnosticar una gota tofácea crónica. El paciente llevaba tratamiento medicamentoso con prednisona, colchicina y metrotexate, pero luego de discutir el caso con los especialistas en medicina interna y reumatología se decidió sustituir la colchicina por el alopurinol.

The case report of a 57 year-old mestizo patient, is presented with a history of rheumatoid arthritis and gout who visited the specialized Dermatology department of Celia Sánchez Manduley Teaching Clinical-Surgical Hospital in Manzanillo, Granma province, for presenting disseminated painful nodular lesions. Complementary studies and skin biopsy were carried out which results allowed to diagnose a chronic . The patient was under drugs treatment with prednisona, colchicina and metrotexate, but after discussing the case with the specialists in internal medicine and rheumatology it was decided to sustitute colchicina by alopurinol.

Prominent Inflammatory Features of Monocytes/Macrophages in Acute Calcium Pyrophosphate Crystal Arthritis: a Comparison with Acute Gouty Arthritis

Calcium pyrophosphate (CPP) crystals can present as acute inflammatory arthritis which is known as an acute CPP crystal arthritis. Although monocytes/macrophages have been shown to play a role in the initiation of crystal-mediated inflammatory responses, differences in their phenotypes between acute CPP crystal arthritis and acute gouty arthritis have not yet been investigated. We examined the immunological characteristics of synovial monocytes/macrophages in patients with acute CPP crystal and acute gouty arthritis. CD14⁺CD3⁻CD19⁻CD56⁻ cell frequencies in synovial fluid mononuclear cells (SFMCs) were measured. Expression of pro- and anti-inflammatory cytokines and markers was determined. The SFMCs were dominated by a population of monocytes/macrophages in acute CPP crystal arthritis similar to that in acute gout. Synovial monocytes/macrophages showed the phenotypes of infiltrated monocytes as shown by expression of CD88, C-C chemokine receptor type 2, myeloid-related protein (MRP)8 and MRP14 but not proto-oncogene tyrosine-protein kinase MER. Comparatively, the CD14⁺ cells from patients with acute CPP crystal arthritis had similar high levels of IL-1β and TNF-α production but significantly lower expression of IL-10 and M2 marker (CD163). The monocytes/macrophages had the capacity to produce IL-8 in response to CPP crystals. Proinflammatory features were more dominant in monocytes/macrophages during acute CPP crystal arthritis than those during acute gouty arthritis.

Effect of ethanolic extract of Polygonum cuspidatum on acute gouty arthritis in mice through NLRP3/ASC/caspase-1 axis / 中国中药杂志

The aim of this paper was to study the effect and mechanism of alcohol extract from Polygonum cuspidatum(PCE) on acute gouty arthritis in C57 BL/6 mice through NLRP3/ASC/caspase-1 axis. The model mice which injected with ankle joint injection of sodium urate crystals(MSU) were orally administrated with three different concentration of PCE, with colchicine as positive control. HE staining was used for observing the morphological changes of synovial tissue; concentration of IL-1β, IL-6 and TNF-α secreted by synovial tissue of the ankle joint were detected by ELISA; mRNA and protein expression of NLRP3, ASC and caspase-1 in synovial tissue were detected by RT-PCR and Western blot respectively. The results showed that the swelling degree of ankle joint in model mice were significantly elevated; expression of IL-1β, IL-6 and TNF-α were significantly increased; mRNA and protein expression of NLRP3, ASC and caspase-1 also significant increase, compared with normal control group. The swelling degree of ankle joint significantly relief; expression of IL-1β, IL-6 and TNF-α in joint synovium significantly decrease; mRNA and protein expression of NLRP3, ASC and caspase-1 were significantly decrease in PCE treatment group compared with model group. Our research implied that alcohol extract from P. cuspidatum had positive effect on acute gouty arthritis in mice, and the regulation of NLRP3/ASC/caspase-1 axis may be its mechanism.

The Relationship between Hyperuricemia and Triglyceride Glucose Index: Based on 2016 Korean National Health and Nutrition Examination Survey

BACKGROUND: Hyperuricemia refers to an excess of uric acid in the blood and is associated with gouty arthritis, hypertension, metabolic syndrome, atrial fibrillation, kidney stones, insulin resistance (IR), and type 2 diabetes mellitus. Previous studies have used the homeostatic model assessment of IR (HOMA-IR), a well-known index of IR, to investigation the correlation between serum uric acid levels and IR. However, difficulty with measuring insulin levels limits the clinical applicability of the HOMA-IR index. This study investigated the correlation between hyperuricemia and the triglyceride glucose (TyG) index.METHODS: We used data from the Seventh Korea National Health and Nutrition Examination Survey, 2016. The study population included adults without diabetes aged >19 years. The TyG index, which serves as an indicator of IR, was calculated using fasting serum glucose and triglyceride levels to investigate the correlation between the TyG index and hyperuricemia. Pearson's correlation coefficient and analysis of covariance were used for statistical analysis, which was performed using IBM SPSS software.RESULTS: A statistically significant correlation was observed between serum uric acid levels and the TyG index. After adjustment for factors that may affect IR (age, body mass index, waist circumference, and systolic and diastolic blood pressures), we observed that the TyG index was significantly higher in the hyperuricemia than in the non-hyperuricemia group (8.96 vs. 8.54, P < 0.001).CONCLUSION: Serum uric acid levels were significantly correlated with IR assessed using the TyG index in adults without diabetes aged >19 years.

Pancreatitis, Panniculitis, and Polyarthritis Syndrome Simulating Cellulitis and Gouty Arthritis / 대한소화기학회지

Pancreatitis, panniculitis, and polyarthritis (PPP) syndrome is a rare but critical disease with a high mortality rate. The diagnostic dilemma of PPP syndrome is the fact that symptoms occur unexpectedly. A 48-year-old man presented with fever and painful swelling of the left foot that was initially mistaken for cellulitis and gouty arthritis. The diagnosis of PPP syndrome was made based on the abdominal CT findings and elevated pancreatic enzyme levels, lobular panniculitis with ghost cells on a skin biopsy, and polyarthritis on a bone scan. The pancreatitis and panniculitis disappeared spontaneously over time, but the polyarthritis followed its own course despite the use of anti-inflammatory agents. In addition to this case, 30 cases of PPP syndrome in the English literature were reviewed. Most of the patients had initial symptoms other than abdominal pain, leading to misdiagnosis. About one-third of them were finally diagnosed with a pancreatic tumor, of which pancreatic acinar cell carcinoma was the most dominant. They showed a mortality rate of 32.3%, associated mainly with the pancreatic malignancy. Therefore, PPP syndrome should be considered when cutaneous or osteoarticular manifestations occur in patients with pancreatitis. Active investigation and continued observations are needed for patients suspected of PPP syndrome.

Insulin resistance is an independent predictor of erectile dysfunction in patients with gout

BACKGROUND/AIMS: Gout is associated with metabolic disorders that are important risk factors for cardiovascular disease and erectile dysfunction (ED). We aimed to identify independent predictors of ED in patients with gout. METHODS: From August 2014 to August 2015, male outpatients who were being treated for gout in our rheumatology clinic and healthy males without any history of inflammatory disease (control group) were studied. ED was assessed in participants using the five-item version of the International Index of Erectile Function questionnaire. Insulin resistance (IR) was estimated using the homeostatic model assessment (HOMA-IR). Logistic regression analysis was performed to determine the effect of variables on ED risk in all of the study subjects and in patients with gout. RESULTS: We analyzed 80 patients with gout and 70 healthy controls. The median age of patients with gout was 52 years and median disease duration was 120 months. Gout patients were more likely to have ED than controls (55.3% vs. 41.4%, p < 0.047). After adjustment for confounding factors, only HOMA-IR was significantly associated with ED (odds ratio [OR], 1.82; 95% confidence interval [CI], 1.05 to 3.15). Gout patients with ED were more likely to be older (p < 0.001), have higher HOMA-IR (p = 0.048), and have lower glomerular filtration rate (p = 0.038) than those without ED. Multivariate logistic regression analysis showed that HOMA-IR was an independent predictor for ED (OR, 1.62; 95% CI, 1.03 to 2.82) in gout patients. CONCLUSIONS: IR is an independent predictor of ED in patients with gout.

Pancreatitis, Panniculitis, and Polyarthritis Syndrome Simulating Cellulitis and Gouty Arthritis / 대한소화기병학회잡지

Pancreatitis, panniculitis, and polyarthritis (PPP) syndrome is a rare but critical disease with a high mortality rate. The diagnostic dilemma of PPP syndrome is the fact that symptoms occur unexpectedly. A 48-year-old man presented with fever and painful swelling of the left foot that was initially mistaken for cellulitis and gouty arthritis. The diagnosis of PPP syndrome was made based on the abdominal CT findings and elevated pancreatic enzyme levels, lobular panniculitis with ghost cells on a skin biopsy, and polyarthritis on a bone scan. The pancreatitis and panniculitis disappeared spontaneously over time, but the polyarthritis followed its own course despite the use of anti-inflammatory agents. In addition to this case, 30 cases of PPP syndrome in the English literature were reviewed. Most of the patients had initial symptoms other than abdominal pain, leading to misdiagnosis. About one-third of them were finally diagnosed with a pancreatic tumor, of which pancreatic acinar cell carcinoma was the most dominant. They showed a mortality rate of 32.3%, associated mainly with the pancreatic malignancy. Therefore, PPP syndrome should be considered when cutaneous or osteoarticular manifestations occur in patients with pancreatitis. Active investigation and continued observations are needed for patients suspected of PPP syndrome.

Chronic Multiple Gouty Arthritis Diagnosed during Anti-Tuberculosis Treatment of Recurrent Tuberculous Arthritis: A Case Report / 대한족부족관절학회지

Gout occurs mainly in monoarthritis and is found in more than 50% of cases in hallux of the foot. In addition, symptoms sometimes begin in the hand, wrist, and elbow, but they are rarely observed in the spine. The patient was referred for tuberculous polyarthritis due to antituberculosis drug failure. Inflammatory findings were observed in the lumbar, elbow, wrist, hand and foot areas. Surgery was performed on the foot area and a pathology diagnosis revealed gouty arthritis. We report this case with a review of the relevant literature.

A case of gout secondary to primary myelofibrosis / 北京大学学报(医学版)

A 52-year-old man was referred to our department with a 2-year history of polyarthritis. He was diagnosed as gout due to acute arthritis of bilateral feet dorsum 2 years ago,but he didn't receive any standard treatment. 1 year ago,there were more and more joints evolved during the gout attack, and many subcutaneous nodules occurred. When he presented to our clinic 1 month ago,the urate acid level was as high as 715 μmol/L. Moreover, we could find bone erosion in the X rays of his hand and foot,as well as synovitis,double contour sign and tophus on the ultrasound examination. The diagnosis of gout was clearly and definitely. However, he had leukocytosis and thrombocytosis for 4 years in the past history, and the urate acid level was only 400 μmol/L at that time. He also had well-controlled hypertension. The family history was unremarkable. Furthermore, we found megalosplenia on his physical examination. The bone marrow examination showed myelofibrosis and JAK2 V617F gene was positive. He was diagnosed as primary myelofibrosis and treated with interferon-α, together with urate acid-lowing therapy (febuxostat 60 mg once daily). Following-up for 1 year,the dosage of febuxostat decreased to 40 mg once daily, and the patient didn't have gout attack again, some of the tophus diminished, and the urate acid level ranged from 400 to 500 μmol/L. Gout is a common disease in clinical practice,usually combined with metabolic syndrome,chronic renal failure and specific drugs using (diuretic and calcineurin inhibitors). However,it is relatively rare to see gout associated with myeloproliferative diseases, including polycythemia vera, primary thrombocythemia, primary myelofibrosis and chronic myelocytic leukemia. In these diseases, the turnover of nucleic acids is greatly augmented, and an excess of purine metabolites, including uric acid, is released. In the natural course of gout, the appearance of tophus from the first onset of arthritis usually takes several years. This patient only had one traditional risk factor, but his urate acid level was remarkably high and he developed tophus in a short term. After treatment of primary myelofibrosis, the symptom of gout partially alleviated. Careful physical examination and medical history taking lead to the diagnosis of secondary gout, which should be reminded in the daily practice.

Anti-inflammatory effects of traditional mixed extract of medicinal herbs (MEMH) on monosodium urate crystal-induced gouty arthritis / 中国天然药物

Korean oriental medicine prescription is widely used for the treatment of gouty diseases. In the present study, we investigated anti-inflammatory effects of modified Korean herbal formulation, mixed extract of medicinal herbs (MEMH), and its modulatory effects on inflammatory mediators associated with gouty arthritis. Both in vitro and in vivo studies were carried out to assess the anti-inflammatory efficacy of MEMH on monosodium urate (MSU) crystals-induced gouty inflammation. MSU crystals stimulated human chondrosarcoma cell line, SW1353, and human primary chondrocytes were treated with MEMH in vitro. The expression levels of pro-inflammatory mediators and metalloproteases were analyzed. The effect of MEMH on NFκB signaling pathway in SW1353 cells was examined. Effect of MEMH on the mRNA expression level of pro-inflammatory mediators and chemotactic factor from human monocytic cell line, THP-1, was also analyzed. The probable role of MEMH in the differentiation process of osteoblast like cells, SaOS-2, after MSU treatment was also observed. To investigate the effects of MEMH in vivo, MSU crystals-induced ankle arthritic model was established. Histopathological changes in affected joints and plasma levels of pro-inflammatory mediators (IL-1β and TNFα) were recorded. MEMH inhibited NFκB signaling pathway and COX-2 protein expression in chondrocytes. MSU-induced mRNA expressions of pro-inflammatory mediators and chemotactic cytokines were suppressed by MEMH. In MSU crystals-induced ankle arthritic mouse model, administration of MEMH relieved inflammatory symptoms and decreased the plasma levels of IL-1β and TNFα. The results indicated that MEMH can effectively inhibit the expression of inflammatory mediators in gouty arthritis, demonstrating its potential for treating gouty arthritis.

Tophaceous Gout in the Lumbar Spinal Canal Mimicking Epidural Spinal Tumor

Gout is an inflammatory arthritis characterized by deposition of monosodium urate crystals in joints. Though gout frequently involves the big toe or other extremities, it rarely occurs in the spinal canal. A 35-year-old man presented with left L5 radiculopathy. He had leg pain for 8 months and received several epidural steroid injections. Magnetic resonance imaging revealed a 1.7×1.1-cm ovoid contrast-enhancing mass, causing pressure erosion of the left L5 pedicle. Microscopic laminotomy was performed at the left L5 lamina. White chalky materials, identified at the left lateral recess of the spinal canal, were removed in a piecemeal manner. The histopathologic diagnosis was tophaceous gout. Although the patient's radiating pain did not resolve postoperatively, it was dramatically relieved with uric acid-lowering medications. If a mass effect is suspected, surgical removal of gouty tophi might aid in symptom release and definite diagnosis. Medical treatment after rheumatology consultation is crucial.