Gout

Gout continues to be a health problem around the world despite the availability of effective therapies Although the prevalence is influenced by genetic factors, the associations of alcohol consumption, obesity, and hypertension appear to be partially responsible for the increased prevalence of gout and hyperuricemia in African and Oriental countries The association between hyperuricemia and cardiovascular disease seems linked to insulin resistance This relation, in part, explains the common coexistence of hyperlipidemia and glucose intolerance in patients with gout Accordingly, it is recommended that one pay more attention to dietary manipulation in patients with gout in addition to managing hypertension, obesity, and other medical problems Although acute gout attacks can be treated, eliminating gout requires effective removal of urate from the body Allopurinol remains a dominant urate-lowering agent, however its use may be limited by allergic reactions Uricosuric agents are also effective urate-lowering agents and provide an alternative to allopurinol Strategies to treat patients who are sensitive to allopurinol continue to evolve

Gout and hyperuricemia.

As evidence emerges that complex gene alterations are involved in the onset of Parkinson's disease (PD), the role of environmental chemicals in the pathogenesis of this disease becomes intensely debated. Although it is undisputed that acute exposure to certain chemicals such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is sufficient to cause human parkinsonism, the evidence that the risk for PD increases because of environmental exposure is generally weaker. Several studies have suggested that pesticide exposure and life in rural areas are significant risks factors for PD. Among other pesticides, paraquat (PQ) has been linked to PD by epidemiological studies and experimental work in rodents, in which it causes lesions in the substantia nigra, pars compacta. However, the evidence that human exposure to the chemical results in an increased risk for PD is rather limited and based on insufficient epidemiological data. This review critically analyses the evidence that implicates PQ in parkinsonism and discusses the limitations of chemical modelling of PD.

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Paraquat and Parkinson's disease

Gout is a common and very painful inflammatory arthritis caused by hyperuricaemia. This review provides an update on the genetics of hyperuricaemia and gout, including findings from genome-wide association studies. Most of the genes that associated with serum uric acid levels or gout are involved in the renal urate-transport system. For example, the urate transporter genes SLC2A9, ABCG2 and SLC22A12 modulate serum uric acid levels and gout risk. The net balance between renal urate absorption and secretion is a major determinant of serum uric acid concentration and loss-of-function mutations in SLC2A9 and SLC22A12 cause hereditary hypouricaemia due to reduced urate absorption and unopposed urate secretion. However, the variance in serum uric acid explained by genetic variants is small and their clinical utility for gout risk prediction seems limited because serum uric acid levels effectively predict gout risk. Urate-associated genes and genetically determined serum uric acid levels were largely unassociated with cardiovascular-metabolic outcomes, challenging the hypothesis of a causal role of serum uric acid in the development of cardiovascular disease. Strong pharmacogenetic associations between HLA-B*5801 alleles and severe allopurinol-hypersensitivity reactions were shown in Asian and European populations. Genetic testing for HLA-B*5801 alleles could be used to predict these potentially fatal adverse effects.

The genetics of hyperuricaemia and gout

https://jcp.bmj.com/content/jclinpath/19/2/205.2.full.pdf

Clinical chemistry principles and technics

We measured purine degradation products of ATP in plasma after ischemic exercise in eight normal subjects, one patient with myo-phosphorylase deficiency (McArdle9s disease), and one with carnitine palmityltransferase deficiency. Normal subjects increase hypoxanthine and inosine, but not xanthine. Plasma purine levels were elevated above the normal range after ischemic exercise in McArdle9s disease and in carnitine palmityltransferase deficiency after fasting. Those changes implied abnormally accelerated ATP degradation in these two myopathies.

Vera Shively

Papers

ATP degradation products after ischemic exercise Hereditary lack of phosphorylase or carnitine palmityltransferase