痛风清颗粒治疗慢性尿酸性肾病临床研究

[目的]观察痛风清颗粒治疗慢性尿酸性肾病的疗效机理。[方法]15例以湿浊内蕴为主证的慢性尿酸性肾病患者,予痛风清颗粒为主治疗3周,与服药前后观察症状、体征、各项实验室检查,并系统观察患者治疗前后在实验室检查和症状改善等方面的差别和安全性。[结果]治疗后总有效率为80%。相关症状、体征及实验室检查均较治疗前有显著改善,统计学有显著意义,安全性较好。[结论]痛风清颗粒治疗慢性尿酸性肾病疗效佳好,值得进一步研究。     

The Effective Control of Hyperuricemia in Cancer Patients: A New Recombinant Conjugated Variant of Urate Oxidase

Objective: Management of hyperuricemia is crucial to controlling tumor lysis syndrome (TLS) during cancer therapy. Urate oxidase (UOX) that catalyzes the enzymatic oxidation of uric acid into allantoin, is effective in lowering plasma uric acid levels and controlling hyperuricemia. Recently, we developed a new recombinant conjugate variant of UOX therapeutic drug using PASylation technology. This study was designed to evaluate the stability, plasma half-life and immunogencity of PASylated UOX. Methods: A recombinant variant of PASylated UOX from the Aspergillus flavus was manufactured using bioinformatics and experimental techniques. Ex vivo evaluation of stability of PASylated UOX was done in 50% human serum. For half-life test, recombinant PASylated UOX and rasburicase were administered at 1.5 mg/kg to 10 rats in two different groups and samples were collected after injection Production of antibodies against PASylated drug was also assayed. Results: Residual activity of PASylated UOX in 50% human serum was higher than rasburicase and native UOX. Stability of PASylated UOX at 25°C and 37°C was also higher than rasburicase and native UOX. The PASylated half-life was ~32.1 hours, whereas half-life for rasburicase and native UOX was ~25.1 and ~22.8 hours, respectively. In immunogenicity examination, there is 33% and 36% decrease in the absorbance of native UOX and rasburicase, respectively when compared with that of PASylated UOX. Conclusion: Our data confirmed the efficacy and stability of PASylated UOX in comparison to the rasburicase. In summary, the results indicated that PASylated UOX drug is effective at lowering plasma uric acid levels with prolonged plasma half-life and decreased cost.     

Birefringent crystals deposition and inflammasome expression in human atheroma plaques by levels of uricemia

ObjectiveTo verify the monosodium urate (MSU) crystal deposition in artery walls following a structure assessment and to assess NLRP3 inflammasome expression in human atheroma plaques by levels of uricemia.MethodsPatients with peripheral arterial disease who were candidates for amputation were recruited and classified as normouricemic or hyperuricemic. During surgery, an artery segment from the amputated limb was sampled, divided and fixed separately by cryo-embedding, 100% ethanol or Glyo-fixx. Samples were assessed by compensated polarized-light microscopy to identify MSU crystals on the artery walls. Afterwards, macrophages, neutrophils and NLRP3 inflammasome components at the plaque were categorized by immunostaining and compared between normouricemics and hyperuricemics.ResultsThirty artery samples from 27 patients were studied; 10 (37.0%) participants were hyperuricemic. Birefringent needle-shaped crystals were found in three samples (10.0%), all processed by frozen sectioning. Other methods showed no crystals. No accompanying inflammatory process was noted, and the presence of crystals was equally distributed across ranges of uricemia, making it unlikely they were MSU crystals. Regarding immunostaining, 28 artery samples were available for analysis, with similar infiltration of macrophages and neutrophils. NLRP3 and gasdermin-D expression were significantly greater in hyperuricemics compared to normouricemics (P = 0.044 and P = 0.017, respectively). ASC content was numerically larger in hyperuricemics as well, while caspase-1 and IL-1beta expression were similar between groups.ConclusionsThe presence of MSU crystals on artery walls was not confirmed. Hyperuricemia was associated with greater NLRP3 and gasdermin-D expression on human atheroma plaques in patients with peripheral artery disease.     

UltraSound evaluation in follow-up of urate-lowering therapy in gout phase 2 (USEFUL-2): Duration of flare prophylaxis

ObjectivesTo determine whether changes in ultrasonography (US) features of monosodium urate crystal deposition is associated with the number of gouty flares after stopping gout flare prophylaxis.MethodsWe performed a 1-year multicentre prospective study including patients with proven gout and US features of gout. The first phase of the study was a 6-month US follow-up after starting urate-lowering therapy (ULT) with gout flare prophylaxis. After 6 months of ULT, gout flare prophylaxis was stopped, followed by a clinical follow-up (M6 to 12) and ULT was maintained. Outcomes were the proportion of relapsing patients between M6 and M12 according to changes of US features of gout and determining a threshold decrease in tophus size according to the probability of relapse.ResultsWe included 79 gouty patients [mean (± SD) age 61.8 ± 14 years, 91% males, median disease duration 4 (IQR 1.5;10) years]. Among the 49 completers at M12, 23 (47%) experienced relapse. Decrease in tophus size ≥ 50% at M6 was more frequent without than with relapse (54% vs. 26%, P = 0.049). On ROC curve analysis, a threshold decrease of 50.8% in tophus size had the best sensitivity/specificity ratio to predict relapse [AUC 0.649 (95% confidence interval 0.488; 0.809)]. Probability of relapse was increased for patients with a decrease in tophus size < 50% between M0 and M6 [OR 3.35 (95% confidence interval 0.98; 11.44)].ConclusionA high reduction in US tophus size is associated with lower probability of relapse after stopping gout prophylaxis. US follow-up may be useful for managing ULT and gout flare prophylaxis.     

2020 recommendations from the French Society of Rheumatology for the management of gout: Urate-lowering therapy

ObjectiveTo develop French Society of Rheumatology-endorsed recommendations for the management of urate-lowering therapy (ULT).MethodsEvidence-based recommendations were developed by 9 rheumatologists (academic or community-based), 3 general practitioners, 1 cardiologist, 1 nephrologist and 1 patient, using a systematic literature search, one physical meeting to draft recommendations and two Delphi rounds to finalize them.ResultsA set of 3 overarching principles and 5 recommendations was elaborated. The overarching principles emphasize the importance of patient education, especially the need for explaining the objective of lowering serum urate (SU) level to obtain crystal dissolution, clinical symptoms disappearance and avoidance of complications. ULT is indicated as soon as the diagnosis of gout is established. SU level must be decreased below 300 μmol/l (50 mg/l) in all gout patients or at least below 360 μmol/l (60 ml/l) when the 300 μmol/l target cannot be reached, and must be maintained at these targets and monitored life-long. The choice of the ULT primarily relies on renal function: in patients whose estimated glomerular filtration rate (eGFR) is above 60 ml/min/1.73 m², first-line ULT is allopurinol; in those with eGFR between 30 and 60 ml/min/1.73 m², allopurinol use must be cautious and febuxostat can be considered as an alternative; and in those whose eGFR is below 30 ml/min/1.73 m², allopurinol must be avoided and febuxostat should be preferred. Prophylaxis of ULT-induced gout flares involves progressive increase of ULT dosage and low-dose colchicine for at least 6 months. Cardiovascular risk factors and diseases, the metabolic syndrome and chronic kidney disease must be screened and managed.ConclusionThese recommendations aim to provide simple and clear guidance for the management of ULT in France.     

Treatment advances in gout

The purpose of gout treatment is to alleviate symptoms of flares, prevent flares from recurring by lowering serum urate, and minimize structural joint damage and functional impairment. In recent years, several new medications to treat gout have been developed, and novel agents continue to be investigated, in addition to several long-established treatments. Although a number of effective therapies are available, optimal management and outcomes are frequently not achieved due to physician under prescribing of urate-lowering therapy (ULT) and poor adherence with therapy when it is prescribed. This article reviews recent developments in the management of gout with reference to recently published clinical guidelines, outlines some important questions regarding the safety and efficacy of particular agents, and remaining gaps in our knowledge about the most effective strategies for using currently available treatments.     

尿酸盐结晶在手足部位的沉积规律

目的：了解尿酸盐结晶在人体手足的沉积部位,探索其分布规律。方法：128例痛风患者均在双源CT（DECT）上行手足部位的尿酸盐结晶扫描,利用痛风识别软件处理,记录绿色尿酸盐结晶沉积部位并统计分析。结果：尿酸盐结晶在手足沉积部位依次为跖趾关节、腕骨韧带、跖趾骨肌腱、掌指关节、胫腓骨肌腱、指浅屈肌腱、踝关节、跗关节、腕关节。结论：尿酸盐结晶在痛风患者手足多部位均有沉积,除关节外,周围组织也存在大量尿酸盐结晶沉积现象。     

调整空气距离与骨距离参数减少足部双能量CT痛风石成像指甲伪影

目的 探讨通过调整空气距离与骨距离参数减少足部双能量CT(DECT)痛风石成像指甲伪影的可行性。方法 收集20例痛风患者进行足部DECT扫描,分别采用标准空气距离与骨距离参数、调整后空气距离与骨距离参数对图像进行重建,应用自动体积计算软件测量痛风石体积及指甲伪影体积,并进行统计学分析。结果 20例患者均存在痛风石及指甲伪影。采用标准参数检测到66个痛风石,63个指甲伪影。调整参数后共检测到66个痛风石,31个指甲伪影。调整参数后痛风石体积[0.07(0.03~0.12)cm³]与标准参数下[0.07(0.03~0.16)cm³]的差异无统计学意义(Z=-0.2,P=0.84),指甲伪影体积[(0.02±0.02)cm³]较标准参数下[(0.07±0.06)cm³]明显减小(t=4.56,P<0.01)。结论 通过调整空气距离与骨距离参数可以明显减少DECT痛风石成像中的指甲伪影,且不影响痛风石的观察。     

The antinociceptive and anti-inflammatory effects of the crude extract of Jatropha isabellei in a rat gout model

Ethnopharmacological relevance: Jatropha isabellei Müll Arg. (Euphorbiaceae) is a medicinal plant that has been used in South American folk medicine for the treatment of arthritic diseases, particularly gout.