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Gout
Published in Charles Theisler, Adjuvant Medical Care, 2023
Gout, or acute gouty arthritis, typically presents as an excruciating attack of pain, usually in a single joint of the foot or ankle. Gout is the most common inflammatory arthritis of men and is increasing in prevalence.1 Gout is associated with an overproduction (10% of patients) or decreased renal excretion (90% of patients) of purines. Because the end product of purine metabolism is uric acid, gout is characterized by elevated blood uric acid levels.2 Needle-like uric acid crystals form in joint spaces resulting in episodes of sudden excruciating pain, swelling, redness, warmth, and tenderness. Chronic inflammation and clumps of crystals (tophi) can lead to permanent joint damage, deformity, and stiffness. Tophi can also form in white chalky nodules on the helix of the ear. These tophi typically become painful before or during gout attacks.
Rheumatology
Published in Kristen Davies, Shadaba Ahmed, Core Conditions for Medical and Surgical Finals, 2020
Uric acid is produced as a breakdown product of purine metabolism and produced by the enzyme xanthine oxidase. Excess purine ingestion from diets contain large amounts of saturated fat and fructose, which contribute to increased levels. Purines are also released during cell death.
Micronutrient Supplementation and Ergogenesis — Metabolic Intermediates
Published in Luke Bucci, Nutrients as Ergogenic Aids for Sports and Exercise, 2020
Adenine, however, is well absorbed from the diet and incorporated into nucleotides in vivo.589 Adenine is also commonly used to preserve stored erythrocytes,590 and was named vitamin B4 until its nonessentiality was proven.553 Sublingual and parenteral administration of adenosine and adenosine phosphates by German clinicians have been reported to lower serum cholesterol,591 improve angina and atherosclerotic senility,591 and prevent recurrence of secondary myocardial infarcts.592 However, no reports of oral adenine or adenosine supplementation on athletic performance have been found. In addition, adenine supplementation may lead to renal tubular damage caused by formation of the insoluble metabolite 2,8-dihydroxyadenine, as has been seen in dogs.593 In conclusion, the mechanism of action of purine supplements as ergogenic aids may deserve further study in animals, but potential toxicities may render human testing and use hazardous. At this time, no guidelines for use of inosine or other nucleotides as ergogenic aids are apparent.
Clinical significance of a novel uric-acid-based biomarker in the prediction of disease activity and response to infliximab therapy in Crohn’s disease
Published in Scandinavian Journal of Gastroenterology, 2023
Yan Pan, Xijing Huang, Zhou Zhou, Xue Yang, Liangping Li, Caiping Gao, Yan Zhang, Yinghui Zhang
It is well known that neutrophils are important components of the active inflammatory response [33]. They contribute to tissue destruction by secreting cytokines (including interleukin-1, interleukin-6, and TNF-α) [34] and producing reactive oxygen species, the latter of which results in oxidative damage [34], one of the major contributors to CD pathology [34,35]. Uric acid, produced endogenously by purine, is a major antioxidant in the human body that clears free radicals in the blood [36]. Low UA levels occur with various autoimmune and neurodegenerative disorders, such as multiple sclerosis [20,37] and acute ischemic stroke [38,39]. Recently, the role of UA levels in IBD have attracted attention. It was found that CD patients had lower UA than healthy controls, and this was associated with increased mucosal inflammation. Consistent with previous studies [17,18,25], our study found elevated neutrophil percentages and lower UA levels in active CD patients. The neutrophil percentage divided by the UA level is regarded as the NUR. Our study suggested that CD patients have elevated NUR, which is positively correlated with both clinical activity and endoscopic inflammation. Even if only one of these two factors is useful to predict disease activity, combining the two inversely correlated indicators improves the practical value. The lack of significant difference between the moderate and severe disease group may be due to the relatively small sample size. More notably, NUR serves as a reliable biomarker of endoscopic activity and mucosal healing in CD.
Genetic and Epigenetic Regulation of the Innate Immune Response to Gout
Published in Immunological Investigations, 2023
Jordana Dinorá de Lima, André Guilherme Portela de Paula, Bruna Sadae Yuasa, Caio Cesar de Souza Smanioto, Maria Clara da Cruz Silva, Priscila Ianzen dos Santos, Karin Braun Prado, Angelica Beate Winter Boldt, Tárcio Teodoro Braga
Hyperuricemia is the main clinical parameter in gout diagnosis. There are three main causes of hyperuricemia. The first is disorders at purine synthesis through de novo and salvage pathways (essential for replacing damaged nitrogen bases and producing ATP and cyclic AMP (cAMP)), which ultimately leads to urate crystallization and accumulation (Huang et al. 2021). The second is high purine ingestion, mainly through meat, and seafood, which adds excessive purine from external dietary sources (Choi et al. 2005). Similarly, fructose and alcohol-rich diets lead to an AMP excess, which causes inosine monophosphate (IMP) accumulation, one of the uric acid precursors (Huang et al. 2021). Third, purine excretion defects may increase UA. Despite being converted by uricase into allantoin in most animals, UA excretion is hampered in humans, which lost this enzyme during the evolutionary process (Zhu et al. 2018).
Effects of allopurinol on renal function in patients with diabetes: a systematic review and meta-analysis
Published in Renal Failure, 2022
Qian Luo, Yuzi Cai, Qihan Zhao, Lei Tian, Yuning Liu, Wei jing Liu
Allopurinol, which belongs to xanthine oxidase inhibitors, is one of the first-line urate-lowering agents used in patients with gout. Allopurinol inhibits purine synthesis and decreases uric acid formation [8,9]. The 2020 ACR guideline strongly recommends allopurinol as the first-line therapy, especially for patients with moderate-to-severe CKD (CKD stage 3 or worse). In contrast to the 2012 ACR guidelines, the preference for allopurinol in the 2020 guidelines is based in part on the cost of each medication [8]. Moreover, some studies have shown that allopurinol has potentially greater cardiovascular safety than febuxostat [8]. Therefore, it is necessary to conduct a meta-analysis to evaluate the efficacy and safety of allopurinol on renal function in patients with diabetes mellitus. Last year, there was a retrospective analysis on the topic [10], which was limited to older adults (>65 years old) and had a small sample size and limited generalizability. Here, we conducted a meta-analysis of randomized controlled trials (RCTs) with the aim to clarify the role of allopurinol in decreasing blood pressure, maintaining blood glucose levels, and improving renal function in patients with diabetes.