The skeletal system
Laurie K. McCorry, Martin M. Zdanowicz, Cynthia Y. Gonnella in Essentials of Human Physiology and Pathophysiology for Pharmacy and Allied Health, 2019
Gout is a condition that occurs when crystals of urate/uric acid accumulate in joint tissues and cause inflammation. Uric acid is a by-product of purine metabolism in the body. The purines adenine and guanine are derived from the breakdown of DNA and RNA. The majority of uric acid produced in the body is eliminated by the kidneys in the urine. The accumulation of uric acid can occur as a result of uric acid overproduction or a decreased elimination of uric acid by the kidneys. Uric acid crystals tend to precipitate in peripheral joint tissues because the temperature there is somewhat cooler and the synovial fluid is a poor solvent. Immune cell attack on precipitated uric acid crystals can cause marked inflammation of the joints. The accumulation of uric acid also leads to the formation of hard uric acid nodules called tophi.
The Musculoskeletal System and Its Disorders
Walter F. Stanaszek, Mary J. Stanaszek, Robert J. Holt, Steven Strauss in Understanding Medical Terms, 2020
Gout is diagnosed by its painful arthritis, most frequently in the first toe joint (the metatarsophalangeal joint between the metatarsal and phalanx), along with an elevated serum urate level (hyperuricemia) and eventually tophi deposits and kidney stones (nephrolithiasis). If the uric acid level is not elevated, analysis of synovial fluid will still show urate crystals in the white blood cells. Acute gout is treated with colchicine, nonsteroidal anti-inflammatory agents, or corticosteroids. For recurrent episodes, uricosuric agents such as probenecid and sulfinpyrazone are utilized to prevent increased serum urate levels. Allopurinol is used to decrease uric acid production. Additional terms associated with this disorder include monosodium urate, purines, and podagra.
Perioperative Metabolic Therapies in Orthopedics
Kohlstadt Ingrid, Cintron Kenneth in Metabolic Therapies in Orthopedics, Second Edition, 2018
Adequate caloric intake is essential, especially in the form of protein. It is a key macronutrient in wound healing and managing complications related to sarcopenia along with exercise,54 and is critical to help promote muscle protein synthesis and decrease inflammation-associated loss of lean body mass and function. Instruct the patient to target at least the recommended daily allowance of 0.8 g/kg body weight of protein intake, provided there is no concomitant liver, renal disease, or history of gout. Protein sources in the form of seafood and organ meats can be high in purines (some examples include: adenine, guanine, hypoxanthine, xanthine, theobromine, caffeine, uric acid, and isoguanine), usually restricted in treating gout. However, consumption of these in the presence of caffeinated or alcoholic beverages (especially beer) is more likely to precipitate a gout attack at the RDA level for protein.55 Higher dietary protein (up to 1.6 g protein/kg/day or up to 30% of total caloric intake) can enhance response to resistance exercise in the elderly.53,56 Protein intake will be metabolized best if consumed evenly throughout the day, particularly with the midday meal or for convenience in the form of protein beverages. A meta-analysis of 36 randomized controlled trials (RCT) (3790 patients) showed that the use of high‑protein supplements (>20% of calories from protein) was associated with reduced complications and readmission to hospital, improved grip strength, increased intake of protein and energy, and improvements in weight.57 Specific dietary recommendations are listed in Table 17.2.
ABCG2 as a therapeutic target candidate for gout
Published in Expert Opinion on Therapeutic Targets, 2018
Kyoko Fujita, Kimiyoshi Ichida
Uric acid is the end product of purine metabolism in humans. In the mammalian lineage, there appears to have been concerted selection toward decreased function of uricase, the enzyme that metabolizes uric acid, culminating in the complete loss of uricase function in humans and other great apes. It has been suggested that the advantage of higher serum uric acid levels stems from the antioxidant activity of this compound [1,2]. However, an abnormally high concentration of uric acid in the serum, i.e. hyperuricemia which affects 43 million Americans, is the main risk factor for the onset of gout (almost 10 million in the U.S.A) [3–5]. Clinical hyperuricemia, causes gout and urolithiasis as a direct result of the precipitation of uric acid, in the form of monosodium urate crystals, in either synovial fluid (gouty arthritis) or the kidney tubule (kidney stones). Besides gout, hyperuricemia has also been linked to hypertension, chronic kidney disease, atherosclerosis, diabetes, and metabolic syndrome [6–9]. Although hyperuricemia is largely determined by environmental factors, such as alcohol consumption, diet, and lifestyle, it is also associated with genetic influences.
Chemical composition and enzyme inhibition of Phytolacca dioica L. seeds extracts
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2019
Amalia Di Petrillo, Ana María González-Paramás, Antonella Rosa, Valeria Ruggiero, Fabio Boylan, Amit Kumar, Francesca Pintus, Celestino Santos-Buelga, Antonella Fais, Benedetta Era
An important biological source of oxygen-derived free radicals is xanthine oxidase (E.C. 1.2.3.2) (XO) that contributes to oxidative damage of living tissues that are involved in many pathological processes19,20. XO catalyses the conversion of hypoxanthine to xanthine and xanthine to uric acid with concomitant production of hydrogen peroxide and superoxide anion. The generation of excess uric acid is harmful to the human body and may lead to gout, hyperuricaemia, and other symptoms of related diseases. Several studies of plant extracts and synthetic compounds have been evaluated for their inhibitory and antioxidant activities in treatment of gout21,22. Therefore, inhibitors of XO may be potentially useful for the treatment of gout or other XO-induced diseases.
Inosine induces acute hyperuricaemia in rhesus monkey (Macaca mulatta) as a potential disease animal model
Published in Pharmaceutical Biology, 2021
Dong-hong Tang, Chen-yun Wang, Xi Huang, Hong-kun Yi, Zhe-li Li, Kai-li Ma, You-song Ye, Jian-wen Zhang
In most mammals, uric acid is degraded by hepatic uricase, i.e., urate oxidase, to allantoin, which is more soluble and more readily excreted in the urine. However, in humans and primates, the enzyme was reportedly lost during evolution (Fujiwara et al. 1987; Oda et al. 2002) for unknown reasons. Therefore, the uric acid metabolic pathway in primates is more similar to that of humans, but differs from that of rodents. Accordingly, rodents generally have limited applications as HUA animal models, but are nonetheless commonly used (Zhu et al. 2017). Purine metabolism ends at uric acid formation in chickens and in other birds, and thus, these birds have also been used as HUA animal models; however, there exists a large taxonomic distance between these birds and humans. For these reasons, a primate model of human HUA would be useful. Indeed, primates are considered as ideal, and sometimes the only suitable animal model, from which results can be directly correlated with human results because of the high similarities in the metabolic, immune and nervous systems between humans and primates. However, primates are costly and complex to manage (Zhu et al. 2017) and are rarely used, particularly as models of HUA.
Related Knowledge Centers
- Nucleotide
- Oxygen
- Purine
- Urine
- Nitrogen
- Gout
- Hyperuricemia
- Carbon
- Hydrogen
- Chemical Formula