Gout
Charles Theisler in Adjuvant Medical Care, 2023
Diet: Losing weight reduces the number of gout attacks. A gout diet may help decrease uric acid levels in the blood to help lower the risk of recurring gout attacks and slow the progression of joint damage.12 Patients with gout should limit their intake of purine rich animal protein (e.g., organ meats, anchovies, sardines, tuna, beef, lamb, pork, shellfish).14,15 Saturated fats from red meat, fatty poultry, and high-fat dairy products should be avoided and replaced by lean meats and poultry, low-fat and non-fat dairy products, vegetables, and lentils as sources of protein. Reducing or avoiding beer and distilled liquors decreases the risk of gout and recurring attacks, as does limiting or avoiding sugar-sweetened foods such as sweetened cereals, baked goods, and candies.15,16 Consumption of vegetables and low-fat dairy products is encouraged.5
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.
Limbs
Keith Hopcroft, Vincent Forte in Symptom Sorter, 2020
SMALL PRINT: blood screen for underlying causes in peripheral neuropathy or Raynaud’s syndrome, if clinically indicated. X-ray: may show a fracture in trauma, joint erosions in RA, the typical features of OA, and sclerosis or collapse of the lunate in Kienböck’s disease.FBC: Hb may be reduced in inflammatory arthritis; WCC raised in infection.ESR/CRP: raised in infective and inflammatory conditions.Rheumatoid factor: may support a clinical diagnosis of RA.Uric acid: an elevated level (post episode) supports a diagnosis of gout.
Inosine supplements only reach the CNS in molybdenum deficient humans and may cause astrocyte degeneration and bulbar–respiratory disease
Published in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2022
A 12-week pilot trial of oral inosine in ALS patients was published after the ALS untangled review (5). The rationale for the trial was that oxidative stress is implicated in the pathogenesis of ALS and inosine is metabolized to urate, and urate is a potent antioxidant. The 25 participants had a baseline serum urate level of 4.1 mg/dL. Oral inosine loading, up to 3000 mg per day, lifted this to 7–8 mg/dL over 6 weeks. These figures are consistent with only partial metabolization of inosine to urate, the remaining inosine would have reached the CNS. Three biomarkers of oxidative stress were measured, 3-nitrotyrosine, ferric-reducing antioxidant power, and glutathione. Plasma levels for the first two changed in a predictable manner in response to the urate increase, CSF levels were not determined. More significantly, urate did not trigger an increase in plasma or brain glutathione, almost as though some other factor was preventing this, for example, concurrent sulfite oxidase deficiency. SO is a Mo-dependent enzyme.
In vitro enzyme inhibition and in vivo anti-hyperuricemic potential of eugenol: an experimental approach
Published in Drug Development and Industrial Pharmacy, 2021
V. Vijeesh, A. Vysakh, Ninan Jisha, M. S. Latha
Hyperuricemia is characterized by the accumulation of excess amount of uric acid in the blood. Imbalance in the rate of production and excretion of uric acid results in the occurrence of numerous associated diseases such as gout, cardiovascular complications, diabetes, chronic kidney diseases, etc. [1,2]. Uric acid is the end product of purine degradation pathway, which is produced by the oxidation of hypoxanthine to xanthine and subsequently into uric acid [3]. Xanthine oxidase (XO) is the key enzyme accountable for the catalysis of uric acid production. Mitigation of hyperuricemic condition may gain a reasonable therapeutic significance in the treatment of hyperuricemia and its associated diseases. This can be achieved through inhibiting the activity of XO [4]. Allopurinol and febuxostat are the common medications used to alleviate the hyperuricemia. Unfortunately, these XO inhibitors exert severe side effects such as gastrointestinal intolerance, nausea, rash, hypersensitivity, undesirable liver, and cardiovascular function [5,6]. Hence, the search for a novel XO inhibitor with respectable efficacy and least side effect will get a great acceptance.
Metabolism and disposition of lesinurad, a uric acid reabsorption inhibitor, in humans
Published in Xenobiotica, 2019
Vishal Shah, Chun Yang, Zancong Shen, Bradley M. Kerr, Kathy Tieu, David M. Wilson, Jesse Hall, Michael Gillen, Caroline A. Lee
Gout is a metabolic disorder resulting from insufficient renal excretion of uric acid that can lead to hyperuricemia. As urate serum uric acid (sUA) levels rise and exceed its solubility limit in the blood, urate crystals can deposit in joints, soft tissues, and organs. These crystals that form in and around the joints often lead to recurrent attacks of gout and deposition of crystals in the kidney vasculature resulting in decreased kidney function and the formation of kidney stones. An estimated 14.3 million people are diagnosed with chronic gout in the United States, European Union, and Japan with its prevalence increasing to 17.7 million by 2021 (Heap & Sosa, 2012). Among the population, gout occurred three times more frequently in men than in women under the age of 60 (Zhu et al., 2011); however, gender disparity is greatly reduced as women reach post-menopausal age (Bhole et al., 2010; Mikuls et al., 2005). The therapeutic goal in managing gout is to lower sUA levels below 6 mg/dL [360 µM]; which improves the signs and symptoms of gout (Grayson et al., 2011; Nakagawa et al., 2006). However, for many patients, the resolution of deposits of crystalline uric acid (tophus) is achieved when sUA levels are further reduced to 5 mg/dL or less, which facilitates reduction of crystal deposition as well as dissolution of urate crystal deposits in the joints (Khanna et al., 2012; Richette et al., 2017).