Monosodium Urate Research Articles

Huangqin Qingrechubi Capsule alleviates inflammation and uric acid and lipid metabolism imbalance in rats with gouty arthritis by inhibiting the PTEN/PI3K/AKT signaling pathway

To investigate the effects of Huangqin Qingrechubi Capsule (HQC) on inflammation and uric acid and lipid metabolism in rats with gouty arthritis (GA) and its mechanism. SD rat models of GA established by injecting monosodium urate into the right ankle joint were treated with saline, colchicine and HQC at low, medium and high doses (n=10) by gavage for 7 days. Toe swelling of the rats was detected at 4, 8, 24, 48 and 72 h after modeling, and synovial histological changes were observed with HE staining. Serum levels of interleukin-10 (IL-10), IL-18, tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), adiponectin, leptin, resistin and visfatin were measured by ELISA, and the levels of high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), total cholesterol (TC), and uric acid (BUA) were detected. RTqPCR and Western blotting were used to detect the mRNA expressions of phosphatase and tensin homolog (PTEN), phosphatidylinositol-3-kinase (PI3K) and protein kinase B (AKT) and the protein expressions of PTEN, PI3K, p-PI3K, AKT and p-AKT. The rat models of GA showed obvious toe swelling, which reached the peak level at 48 h. HE staining revealed massive inflammatory cell infiltration and synovial tissue hyperplasia. The rat models showed significantly increased expressions of TNF-α, TGF-β1, IL-18, TC, TG, leptin, resistin and visfatin, BUA, p-PI3K, and p-AKT and lowered levels of IL-10, APN, HDL-C, and PTEN. Treatment with HQC and colchicine obviously improved these changes and alleviated synovial pathologies and toe swelling in the rat models. HQC can improve inflammation and correct the imbalance of uric acid and lipid metabolism in GA rats possibly by inhibiting the PTEN/PI3K/AKT signaling pathway.

Relationship between serum uric acid levels and complement functional activity

Uric acid (UA) is the end product of purine metabolism and a substance that promotes a chronic inflammatory process. One of the mechanisms of inflammation associated with the UA is the ability of its crystals, mainly monosodium urate, to activate NLRP3 inflammasomes, classifying UA and its salt crystals as damage-related molecular patterns (DAMPs). These crystals also activate the complement system, leading to increase in C3a, C4a, and C5a concentrations and excessive consumption of complement system proteins. It has been known for a long time that UA is able to activate complement, but the relationship between hyperuricemia and complement system functional activity, which can be assessed by complement-mediated hemolysis, remains unclear. In this study, we have made an attempt to estimate the UA concentration that does not lead to spontaneous complement system activation. The study assessed the relationships between the parameters of complement functional activity and some blood biochemical data with UA concentration ([UA]) using correlation analysis. The rate (Vlys) and time of 50% hemolysis (T50) were considered as indicators of complement functional activity, and their relationship was demonstrated using exponential functions y = a*e[x], which takes the form y = [UA]*e[C3]. Concentration of C3 is the argument of the function, base of degree is the base of the natural logarithm, and the proportionality coefficient equal to the UA concentration. Correlation analysis showed the inverse dependent between function values and the corresponding values of T50 (r = -0.83, p 0.0001) in the range of UA concentration exceeding 370 umol/L, which is near to the upper limit of the normal level for women and is within the normal range for men. Thus, the approach to assess the effect of UA on complement activation using the analysis of the complement hemolytic activity is effective to demonstrate the pathogenetic function of UA in the development of the inflammatory process without involving inflammasomes through the direct effects on complement activation processes. The relationships demonstrated suggest that the upper limits of the range of “normal” UA concentrations are arbitrary, and their revision is likely advisable.

Shirebi granules ameliorate acute gouty arthritis by inhibiting NETs-induced imbalance between immunity and inflammation

BackgroundAcute gouty arthritis (AGA) is classified as ‘arthritis’ in traditional Chinese medicine (TCM) theory. Shirebi granules (SGs), derived from the classic prescription SiMiaoWan, exerts satisfying therapeutic efficacy in ameliorating AGA clinically. However, the underlying mechanisms of SGs against AGA remain unclarified.MethodsAGA-related biological processes, signal pathways and biomarker genes were mined from the GEO database through bioinformatics. SGs components were systematically recognized using the UPLC-Q-TOF–MS/MS. A correlation network was established based on the biomarker genes and the chemical components, from which the signal pathway used for further study was selected. Finally, we established an AGA model using SD rats injected with monosodium urate (MSU) in the ankle joint for experimental validation. A combination of behavioral tests, H&E, safranin O- fast green, western blotting, and immunofluorescence were employed to reveal the mechanism of action of SGs on AGA.ResultsThe deterioration of AGA was significantly related to the imbalance between immunity and inflammation, neutrophil chemotaxis and inflammatory factor activation. HDAC5, PRKCB, NFκB1, MPO, PRKCA, PIK3CA were identified to be the candidate targets of SGs against AGA, associated with neutrophil extracellular traps (NETs) signal pathway. Animal experiments demonstrated that SGs effectively repaired cartilage damage, blocked TLR4 activation, and inhibited the expression of NETs indicators and inflammatory factors. In addition, SGs prominently alleviated joint redness and swelling, improved joint dysfunction, inhibited inflammatory infiltration of AGA rats.ConclusionOur data reveal that SGs may effectively alleviate the disease severity of AGA by suppressing NETs-promoted imbalance between immunity and inflammation.

Mechanism of Reactive Oxygen Species-Guided Immune Responses in Gouty Arthritis and Potential Therapeutic Targets.

Gouty arthritis (GA) is an inflammatory disease caused by monosodium urate (MSU) crystals deposited in the joint tissues causing severe pain. The disease can recur frequently and tends to form tophus in the joints. Current therapeutic drugs for the acute phase of GA have many side effects and limitations, are unable to prevent recurrent GA attacks and tophus formation, and overall efficacy is unsatisfactory. Therefore, we need to advance research on the microscopic mechanism of GA and seek safer and more effective drugs through relevant targets to block the GA disease process. Current research shows that the pathogenesis of GA is closely related to NLRP3 inflammation, oxidative stress, MAPK, NET, autophagy, and Ferroptosis. However, after synthesizing and sorting out the above mechanisms, it is found that the presence of ROS is throughout almost the entire spectrum of micro-mechanisms of the gout disease process, which combines multiple immune responses to form a large network diagram of complex and tight connections involved in the GA disease process. Current studies have shown that inflammation, oxidative stress, cell necrosis, and pathological signs of GA in GA joint tissues can be effectively suppressed by modulating ROS network-related targets. In this article, on the one hand, we investigated the generative mechanism of ROS network generation and its association with GA. On the other hand, we explored the potential of related targets for the treatment of gout and the prevention of tophus formation, which can provide effective reference ideas for the development of highly effective drugs for the treatment of GA.

Ameliorative impacts of Sinapic acid against monosodium urate crystal-induced gouty arthritis and inflammation through different signaling pathways.

As known, gout a metabolic disease due to the urate crystals deposition in the joints and affect human health and state. Humans are looking for safe natural remedies from plants with safe, low cost and high effect on their health. Sinapic acid (SA) is found in plants and used as phytoconstituent in human diets. SA has strong antioxidant activity, bone-regenerative, anti-cancer, anti-allergic, and antidiabetic effects. The current study was outlined to confirm the anti-gout potential of SA against monosodium urate crystals (MSU)-induced gouty arthritis in mice. Positive gouty arthritis was conducted by administration of colchicine and MSU in the hind paw. SA was orally administered to negative and positive MSU arthritic mice at 25 and 50 mg/kg, one-hour before MSU injection (100 μg/kg intra-articular). At the end of the experiment, sampling was done for serum, histopathology, oxidative stress and gene expression analysis. The results showed that SA significantly recovered the joint edema and recovered MSU crystals-showed histopathological changes. The production of cytokines, leukocyte recruitment, oxidative stress, and nucleotide-binding domain, leucinerich-containing family, pyrin domain-containing-3 (NLRP3)-inflammasome genes expressions were increased in positive arthritic mice and ameliorated significantly by SA administration. Moreover, SA showed ameliorative impacts on air pouch model of mice as reported by the down regulation in the expression of inflammation related blood cells, proinflammatory cytokines and other transcriptional genes. In conclusion, sinapic acid showed a potential therapeutic use against side effects accompanying gouty arthritis and is good as a supplement against inflammation associated disorders.

Managing Gout in Patients with Metabolic Syndrome.

Gout is characterized by monosodium urate (MSU) crystal deposition secondary to hyperuricemia. Gout is associated with metabolic syndrome (MetS) and its related comorbid conditions such as cardiovascular disease (CVD). Major advances have been made in the comprehension of the link between MetS and gout. Despite observational studies suggesting an association between MetS-related conditions and hyperuricemia, there is no proof of causality. Most studies using Mendelian randomization did not find hyperuricemia as a causal factor for MetS-related conditions. In contrast, these conditions were found associated with hyperuricemia, which suggests a reverse causality. Among patients with gout, this high CVD risk profile implies the need for systematic screening for MetS-related conditions. Most international guidelines recommend systematic screening for and care of CVD and related risk factors in patients with gout. Some anti-hypertensive agents, such as losartan and calcium channel blockers, are able to decrease serum urate (SU) levels. However, there are potential interactions between gout management therapies and the treatment of metabolic diseases. Some data suggest that anti-inflammatory drugs used for gout flare treatment, such as colchicine or canakinumab, might have benefits for CVD. Regarding the impact of urate-lowering therapies on CVD risk, recent studies found a similar CVD safety profile for allopurinol and febuxostat. Finally, sodium-glucose cotransporter-2 inhibitors are promising for gout because of their ability to decrease SU levels and risk of recurrent flares. In this review, we focus on the clinical challenge of managing MetS in patients with gout, particularly older patients with co-medications.

The pathogenesis of gout: molecular insights from genetic, epigenomic and transcriptomic studies.

The pathogenesis of gout involves a series of steps beginning with hyperuricaemia, followed by the deposition ofmonosodium urate crystal in articular structures and culminating in an innate immune response, mediated by the NLRP3 inflammasome, to the deposited crystals. Large genome-wide association studies (GWAS) of serum urate levels initially identified the genetic variants with thestrongest effects, mapping mainlyto genes that encode urate transporters in the kidney and gut. Other GWAS highlighted the importance of uncommon genetic variants. More recently, genetic and epigenetic genome-wide studies have revealed new pathways in the inflammatory process of gout, including genetic associations with epigenomic modifiers. Epigenome-wide association studies are also implicating epigenomic remodelling in gout, which perhaps regulates the responsiveness of the innate immune system to monosodium urate crystals. Notably, genes implicated in gout GWAS do not include those encodingcomponents of the NLRP3 inflammasome itself, but instead include genes encoding moleculesinvolved in its regulation. Knowledge of the molecular mechanisms underlying gout has advanced through the translation of genetic associations into specific molecular mechanisms. Notable examples include ABCG2, HNF4A, PDZK1, MAF and IL37. Current genetic studies are dominated by participants of European ancestry; however, studies focusing on other population groups are discovering informative population-specific variants associated with gout.

Ultrasound Features in Gout: An Overview.

The accurate diagnosis of gout frequently constitutes a challenge in clinical practice, as it bears a close resemblance to other rheumatologic conditions. An undelayed diagnosis and an early therapeutic intervention using uric acid lowering therapy (ULT) is of the utmost importance for preventing bone destruction, the main point of managing gout patients. Advanced and less invasive imaging techniques are employed to diagnose the pathology and ultrasonography (US) stands out as a non-invasive, widely accessible and easily reproducible method with high patient acceptability, enabling the evaluation of the full clinical spectrum in gout. The 2023 EULAR recommendations for imaging in diagnosis and management of crystal-induced arthropathies in clinical practice state that US is a fundamental imagistic modality. The guidelines underline its effectiveness in detecting crystal deposition, particularly for identifying tophi and the double contour sign (DCS). Its utility also arises in the early stages, consequent to synovitis detection. US measures of monosodium urate (MSU) deposits are valuable indicators, sensitive to change consequent to even short-term administration of ULT treatment, and can be feasibly used both in current daily practice and clinical trials. This paper aimed to provide an overview of the main US features observed in gout patients with reference to standardized imaging guidelines, as well as the clinical applicability both for diagnosis accuracy and treatment follow-up. Our research focused on summarizing the current knowledge on the topic, highlighting key data that emphasize gout as one of the few rheumatological conditions where US is recognized as a fundamental diagnostic and monitoring tool, as reflected in the most recent classification criteria.

Effects of the concentration of seeds, finite time-dependent supersaturations, and viscosity on the crystallization kinetics of monosodium urate monohydrate.

Although the crystallization of monosodium urate monohydrate (MSUM) has a crucial role in the occurrence of gout, which is an inflammatory arthritis disease, theoretical models have not been able to describe all features observed in its seeded growth kinetics. In contrast to previous modeling approaches, we show that our model can reproduce qualitative features typically observed in experiments. In particular, our results show that the higher the initial supersaturation and the lower the viscosity, the faster the crystallization kinetics, and they also indicate that there are distinct growth regimes for low and high concentrations of seeds. In this work, we introduce an alternative approach based on a master equation that allows us to incorporate hypotheses for the seeded growth crystallization of MSUM in a more transparent way. Such an approach includes not only effects that are related to the finite time-dependent supersaturation and concentration of seeds, but it can also be used to determine how the viscosity of the solution can affect the crystallization kinetics of MSUM molecules.

Magnesium-enriched deep-sea water inhibits NLRP3 inflammasome activation and dampens inflammation

The NLRP3 inflammasome is an essential component of the innate immune system, but excessive activation can lead to inflammatory diseases. Ion fluxes across the plasma membrane or from intracellular stores are known to regulate NLRP3 inflammasome activation. Deep-sea water (DSW) contains high concentrations of many mineral ions, which could potentially influence NLRP3 inflammasome activation. However, the impact of DSW on NLRP3 inflammasome activation has not been investigated. Here, we demonstrated that DSW with water hardness levels up to 500 mg/L did not affect cell viability or the expression of NLRP3 inflammasome components in macrophages derived from THP-1 cells. However, the DSW significantly inhibited IL-1β secretion and caspase-1 activation in response to NLRP3 activators such as nigericin, ATP, or monosodium urate (MSU) crystals. Mechanically, it was discovered that the presence of 5 mM magnesium ions (Mg2+), equivalent to the Mg2+ concentration found in the DSW with a water hardness of 500 mg/L, inhibits NLRP3 inflammasome activation. This indicates that Mg2+ contributes to the mechanism by which DSW mitigates NLRP3 inflammasome activation. Moreover, DSW administration effectively lessens MSU-triggered peritonitis in mice, a commonly used model for examining the impacts of NLRP3 inflammasome activation. These results show that DSW enriched with Mg2+ could potentially be beneficial in modulating NLRP3 inflammasome-associated diseases.

Effect of Xanthohumol from Humulus lupulus L. Against Gouty Bone Damage in Arthritis of Rats Induced by Mono-sodium Urate.

Xanthohumol (XAN) is an isoprenyl flavonoid from Humulus lupulus L. known for beer brewing, and an osteoprotective agent due to its active improvement in bone loss of osteoporosis. This study was first time to investigate its effects on anti-gouty bone injury in rats of gouty arthritis (GA) induced by monosodium urate (MSU). Results showed that XAN could significantly exert anti-inflammatory activity by alleviating swelling degree of joints, reducing serum level of inflammatory factors, improving inflammatory injury and degrading the Markin's score in lesion joint. Meanwhile, XAN could also fight against gouty bone damage by improving pathological changes of bone tissue and parameters of bone micro-structure. Moreover, XAN could even promote bone formation by effectively enhancing expression of Runx2 and OPG, while inhibit bone resorption with depressing matrix metalloproteinase-9 (MMP-9), MMP-13 and CTSK expression, reducing RANKL secretion, and abating the ratio of RANKL/OPG. Therefore, it was the first time to reveal the mechanism of XAN against gouty bone injury via inhibiting RANKL/OPG/RANK signaling pathway. Above all, this study provided potential strategy for the treatment of GA, and further contributed to research and resource development for hops.

Analysis of experience in the clinical use of dual-energy computed tomography in patients with undifferentiated arthritis

Dual-energy computed tomography (DECT) is a radiation diagnostic method that is used in rheumatology to verify microcrystalline arthritis, but in Russia this method is little known and the experience of its use is rather scarce.Objective of the research. To analyze the experience of using DECT in patients with undifferentiated arthritis and lesions of the axial skeleton in clinical practice.Material and Methods. The retrospective study included 20 patients (14 men and 6 women) observed at the V. A. Nasonova Research Institute of Rheumatology, who underwent DECT for diagnostic purposes. 13 patients with undifferentiated arthritis underwent DECT of peripheral joints to diagnose gout; 7 patients with an established diagnosis of gout (based on the 2015 ACR/EULAR classification criteria for gout) – to clarify the genesis of lesions to the axial joints and spine. The study was performed on a Siemens SOMATOM Definition Flash computed tomograph.Results. Using DECT in patients with undifferentiated arthritis, deposits of monosodium urate crystals (MSUc) were detected in 7 out of 13 (54 %), which made it possible to verify the diagnosis of gout. In the second sample, 6 out of 7 patients (85 %) showed signs of MSUc deposition on DECT, which explained the genesis of the existing complaints. Among these 6 patients, in 1 person, DECT revealed the presence of MSUc and calcium pyrophosphate crystals in the shoulder joint, which made it possible to make two diagnoses at once – gout and calcium pyrophosphate deposition disease.Conclusion. DECT in patients with undifferentiated arthritis makes it possible to verify the diagnosis of gout in more than half of the cases (54 %). In 85 % of patients with gout and pain in the back and axial joints of unknown origin, urate deposits are detected according to DECT. This method may be a useful tool for identifying microcrystalline arthritis of the axial joints, but further research is needed to implement the method in routine practice.

Investigating the involvement of the NLRP3/ASC/caspase-1 and NF-κb/MAPK pathways in the pathogenesis of gouty arthritis: Insights from irradiated and non-irradiated Trifolium alexandrium L. extracts and some metabolites

Ethnopharmacological relevanceTrifolium alexandrinum L. (TA), has traditionally been used in folk medicine for its anti-inflammatory properties against hyperuricemia and gout. However, the specific mechanisms of action of TA have not been thoroughly studied. Aim of the workThis study aimed to evaluate the protective effects of irradiated (TR25) and non-irradiated (TR0) Trifolium alexandrinum L. aqueous extract (TAAE), along with two isolated compounds, caffeine (CAF) and saponin (SAP), in a rat model of acute gouty arthritis (GA). Materials and methodsThe GA model was established by injecting a monosodium urate (MSU) suspension into the knee joint. Synovial tissue pathology was assessed, and levels of TNF-α, IL-6, IL-1β, NF-κB, mTOR, AKT1, PI3K, NLRP3, and ASC were measured by ELISA. mRNA expression of ERK1, JNK, and p-38 MAPK was detected using qRT-PCR, and Caspase-1 protein expression was assessed by immunohistochemical analysis. Knee swelling, uric acid levels, liver and kidney function, and oxidative stress markers were also evaluated. ResultsTAAE analysis identified 170 compounds, with 73 successfully identified using LC-HR-MS/MS, including caffeine citrate and theasapogenol B glycoside as the main constituents. The studied materials demonstrated significant protective effects against GA. TR25 administration significantly mitigated knee joint circumference compared to other treatments. It demonstrated potential in alleviating hyperuricemia, renal and hepatic impairments induced by MSU crystals. TR25 also alleviated oxidative stress and reduced levels of IL1β, IL-6, TNF-α, and NF-κB. Weak Caspase-1 immune-positive staining was observed in the TR25 group. TR25 decreased NLRP3 and ASC expression, reducing inflammatory cytokine levels in GA. It effectively inhibited the PI3K, AKT, and mTOR signaling pathways, promoting autophagy. Additionally, TR25 suppressed ERK1, JNK, and p-38 MAPK gene expression in synovial tissue. These effects were attributed to various components in TAAE, such as flavonoids, phenolic acids, tannins, alkaloids, and triterpenes. ConclusionImportantly, irradiation (25 KGy) enhanced the antioxidant effects and phtchemical contents of TAAE. Additionally, TR0, TR25, CAF, and SAP exhibited promising protective effects against GA, suggesting their therapeutic potential for managing this condition. These effects were likely mediated through modulation of the NLRP3/ASC/Caspase-1 and ERK/JNK/p-38 MAPK signaling pathways, as well as regulation of the PI3K/AKT/mTOR pathway. Further research is warranted to fully elucidate the underlying mechanisms and optimize their clinical applications.

A Conceptual Study on Vatarakta w.s.r. to Gouty Arthritis

The wellbeing of an individual depends on his/her diet and lifestyle. The rapid development and modernisation in India are causing serious health problems and Vatarakta is one of them. Vatarakta, is described under Vatavyadhis by different Acharya’s. The vitiated Vata and Rakta causes this disease, hence called Vatarakta. Gout is an inflammatory disease caused by deposition of Mono-Sodium Urate (MSU) crystals in and around synovial joints. Recent reports of prevalence and incidence of gout vary widely but ranges from prevalence of 1-2%, with greater than 5:1 male preponderance. It is imperative to comprehend complexities of Vatarakta in order to accurately diagnose and treat it, considering its increasing occurrence worldwide and the substantial influence, it has affected individuals’ quality of life. Methods: After a thorough literary review, focusing on classical Ayurvedic texts, alongside recent research articles and reviews. The gathered information was analysed to present cohesive narrative on the Niadana, Samprapti and Chikitsa of Vatarakta. Results: Vatarakta is a result of aggravated Vata Dosha and impaired Rakta Dhatu, leading to severe pain, inflammation, and joints deformity. The disease progression is influenced by dietary habits, lifestyle factors, and genetic predisposition. Its treatment involves a multi-factorial approach, including Shodhana, Shamana, dietary regulations, and lifestyle modification. Conclusion: The Ayurvedic perspective on Vatarakta offers a holistic approach in understanding and managing the disease, emphasizing the balance of bodily Doshas, detoxification, and rejuvenation. Integrating Ayurvedic principles with modern medical practices may provide a comprehensive treatment for Vatarakta.

Unraveling the pathological biomineralization of monosodium urate crystals in gout patients

Crystallization of monosodium urate monohydrate (MSU) leads to painful gouty arthritis. Despite extensive research it is still unknown how this pathological biomineralization occurs, which hampers its prevention. Here we show how inflammatory MSU crystals form after a non-inflammatory amorphous precursor (AMSU) that nucleates heterogeneously on collagen fibrils from damaged articular cartilage of gout patients. This non-classical crystallization route imprints a nanogranular structure to biogenic acicular MSU crystals, which have smaller unit cell volume, lower microstrain, and higher crystallinity than synthetic MSU. These distinctive biosignatures are consistent with the template-promoted crystallization of biotic MSU crystals after AMSU at low supersaturation, and their slow growth over long periods of time (possibly years) in hyperuricemic gout patients. Our results help to better understand gout pathophysiology, underline the role of cartilage damage in promoting MSU crystallization, and suggest that there is a time-window to treat potential gouty patients before a critical amount of MSU has slowly formed as to trigger a gout flare.

Chronic pyogenic spondylitis in patients with spinal gout: a case series and literature review

Background. Spinal gout is a rare and poorly described group of noninfectious inflammatory spinal lesions characterized by the deposition of monosodium urate crystals in the epidural space, paravertebral soft tissues, and by facet joints damage. There is no systematized data on the course of infectious spondylitis and spinal gout in the literature. The aim of the study — to present long-term outcomes of surgical treatment of chronic pyogenic spondylitis in patients with spinal gout and systematize the literature data on the issue. Methods. The clinical part of the study included 6 consecutively operated patients in the period from 2018 to 2021. The diagnosis of spinal gout and chronic pyogenic spondylitis was verified according to the results of histologic and bacteriologic studies of surgical material. Catamnesis accounted for at least 12 months. We studied the peculiarities of clinical and laboratory, radiological and histologic manifestations of the disease. Literature data systematization was carried out in the databases PubMed, Google Scholar, eLIBRARY from 2013 to 2023. Inclusion criteria: level of evidence II B-IV, catamnesis more or equal to 6 months, information on diagnostic and treatment measures. Results. The average age of the patients was 55±9 years. The duration of the diagnostic pause was 8±5 years. Multisegmented lesions of the lumbar (n = 6) spine prevailed. According to the classification of Pola E. et al. (2017) the following types of spondylitis were identified: B.3 (n = 1), C.1 (n = 1), C.3 (n = 2) and C.4 (n = 2). The clinical manifestation was dominated by chronic back pain with an intensity of 6,1±1,4 VAS scores. Neurologic disorders of the lower extremities and pelvic (ASIA scale) corresponded to types B (n = 1) and C (n = 4). The type of surgery: three-column reconstruction through combined approach in 2 cases and isolated anterior column reconstruction in 2 cases, 360° fusion in 1 case, and debridement of the epidural space and anterior column through posterior approach in 1 case. The follow-up results show the absence of recurrence of spondylitis in 4 cases, in 2 patients there were postoperative complications that required revision, after which no recurrence of spondylitis was noted. We selected 17 publications for literature review. Conclusion. The combination of chronic pyogenic spondylitis and spinal gout is a rare and poorly described pathology in the literature. Long therapeutic pause, chronic character of vertebrogenic pain syndrome in combination with increased uric acid level and formation of tophi of vertebral localization are distinctive features of the disease. Neurologic disorders with the combination of spondylitis and gout result from stenosis of the spinal canal due to two factors — epidural abscesses and tophi. Achieving local control of the combined pathology is possible with a combination of surgical intervention and long-term administration of hypouricemic drugs.

Anti-Inflammatory Effect of Atorvastatin and Rosuvastatin on Monosodium Urate-Induced Inflammation through IL-37/Smad3-Complex Activation in an In Vitro Study Using THP-1 Macrophages.

Objective: The pleiotropic effect of hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) is responsible for potent defense against inflammatory response. This study evaluated the inhibitory effects of HMG-CoA reductase inhibitors on the monosodium urate (MSU)-induced inflammatory response through the regulation of interleukin-37 (IL-37) expression. Methods: Serum was collected from patients with gout (n = 40) and from healthy controls (n = 30). The mRNA and protein expression of the target molecules IL-1β, IL-37, caspase-1, and Smad3 were measured in THP-1 macrophages stimulated with MSU, atorvastatin, or rosuvastatin using a real-time quantitative polymerase chain reaction and Western blot assay. Transfection with IL-1β or Smad3 siRNA in THP-1 macrophages was used to verify the pharmaceutical effect of statins in uric-acid-induced inflammation. Results: Serum IL-37 levels in gout patients were significantly higher than in controls (p < 0.001) and was associated with the serum uric acid level (r = 0.382, p = 0.008). THP-1 cells stimulated with MSU markedly induced IL-37 mRNA expression and the transition of IL-37 from the cytoplasm to the nucleus. Recombinant IL-37 treatment dose-dependently inhibited activation of caspase-1 and IL-1β in MSU-induced inflammation. Atorvastatin and rosuvastatin attenuated caspase-1 activation and mature IL-1β expression but augmented translocation of IL-37 from the cytoplasm to the nucleus. Atorvastatin and rosuvastatin induced phosphorylation of Smad3 in THP-1 cells treated with MSU crystals. Statins potently attenuated translocation of IL-37 from the cytoplasm to the nucleus in THP-1 macrophages transfected with Smad3 siRNA compared to cells with negative control siRNA. Conclusions: This study revealed that statins inhibit the MSU-induced inflammatory response through phosphorylated Smad3-mediated IL-37 expression in THP-1 macrophages.

Assessment of oral toxicity of Moringa oleifera Lam aqueous extract and its effect on gout induced in a murine model.

Although widely employed in traditional remedies globally, the safety and efficacy of Moringa oleifera remain inadequately documented through scientific research. This study evaluated the oral toxicity of M. oleifera leaf aqueous extract (MoAE) and its impact on gout-induced rats. 2000 mg/kg was given in a single dose during the acute oral toxicity test, while 100 mg/kg, 250 mg/kg, and 500 mg/kg were given daily for 28 days in the repeated dose toxicity test. 100 mg/kg, 250 mg/kg, and 500 mg/kg MoAE doses were administered during the assessment of its impact on gout caused by monosodium urate. In the hyperuricemia model induced by oxonic acid, serum uric acid levels were assessed and pain response was measured through acetic acid-induced writhing. In acute oral and 28-day repeated dose tests, no indications of toxicity were detected, while MoAE alleviated ankle joint swelling and reduced serum uric acid concentrations in arthritic rats, causing a significant reduction in acetic acid-induced contortions. No acute oral toxicity or toxicity in 28-day repeated doses was found for MoAE, while it exhibited antiarthritic, antihyperuricemic, and pain-relieving effects in the murine model.

The pathogenic mechanism of monosodium urate crystal-induced kidney injury in a rat model.

(MSU) crystals usually in the kidney tubules especially collecting ducts in the medulla. Previous animal models have not fully reproduced the impact of MSU on kidneys under non-hyperuricemic conditions. In the group treated with MSU, the upper pole of the rat kidney was injected intrarenally with 50 mg/kg of MSU, while the lower pole was injected with an equivalent volume of PBS solution. The body weight and kidney mass of the rats were observed and counted. H&E staining was used to observe the pathological damage of the kidney and to count the number of inflammatory cells. Masoon staining was used to observe the interstitial fibrosis in the kidneys of the rat model. Flow cytometric analysis was used for counting inflammatory cells in rats. ElISA was used to measure the concentration of serum and urine uric acid, creatinine and urea nitrogen in rats. At the MSU injection site, a significantly higher infiltration of inflammatory cells and a substantial increase in the area of interstitial fibrosis compared to the control group and the site of PBS injection were observed. The serum creatinine level was significantly increased in the MSU group. However, there were no significant differences in the rats' general conditions or blood inflammatory cell counts when compared to the control group. The injection of urate crystals into the kidney compromised renal function, caused local pathological damage, and increased inflammatory cell infiltration and interstitial fibrosis. Intrarenal injection of MSU crystals may result in urate nephropathy. The method of intrarenal injection did not induce surgical infection or systemic inflammatory response.

Hyperuricemia May Increase Risk of Achilles Tendon Rupture: A Case Control Study

It has been demonstrated in a number of studies that high levels of uric acid can cause crystal deposition in the tendons of the lower extremities, which in turn can impair the Achilles tendon. This study aimed to interpret whether hyperuricemia is relevant with Achilles tendon rupture. Patients diagnosed with Achilles tendon rupture at the same institution between 2013 and 2022 were included in the case group. Healthy subjects who had physical examinations during the same period were included in the control group. Propensity score matching was used to match in a 1:1 ratio. Demographic and clinical characteristics of patients in both groups were compared. Five hundred and fourteen patients were included in the study (ATR=257; Control group=257). The proportion of individuals with hyperuricemia varied significantly between the 2 groups (Achilles tendon rupture group=43.6%; control group=27.6%; p<0.001). The Achilles tendon rupture and hyperuricemia were linked by conditional logistic regression (p<0.001; OR=2.036; 95CI%=1.400-2.961). Compared with healthy subjects, patients with hyperuricemia have a higher risk of Achilles tendon rupture. Further studies are required to verify the effects of hyperuricemia and monosodium urate crystals on Achilles tendon structure.