Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension is epidemic and currently affects 25% of the world's population and is a major cause of stroke, congestive heart failure, and end-stage renal disease. Interestingly, there is evidence that the increased frequency of hypertension is a recent event in human history and correlates with dietary changes associated with Westernization. In this article, we review the evidence that links uric acid to the cause and epidemiology of hypertension. Specifically, we review the evidence that the mutation of uricase that occurred in the Miocene that resulted in a higher serum uric acid in humans compared with most other mammals may have occurred as a means to increase blood pressure in early hominoids in response to a low-sodium and low-purine diet. We then review the evidence that the epidemic of hypertension that evolved with Westernization was associated with an increase in the intake of red meat with a marked increase in serum uric acid levels. Indeed, gout and hyperuricemia should be considered a part of the obesity, type 2 diabetes, and hypertension epidemic that is occurring worldwide. Although other mechanisms certainly contribute to the pathogenesis of hypertension, the possibility that serum uric acid level may have a major role is suggested by these studies.
 ...
PMID:Uric acid, evolution and primitive cultures. 1566 Mar 28

Gout is a condition presenting with inflammatory arthritis caused by crystallization and phagocytosis of monosodium urate in synovial fluid. It is the most common form of arthritis in men above the age of 40 years. Four clinical stages of gout have been distinguished: asymptomatic hyperuricemia, acute gouty arthritis, intercritical gout, and chronic gout. Experimental and epidemiologic studies provide growing evidence that hyperuricemia is not only the driving force behind symptoms attributed to the deposition of monosodium urate in the musculoskeletal system but also the important etiological factor in common morbidities of modern societies such as arterial hypertension, cardiovascular disease, chronic kidney disease, and type 2 diabetes mellitus. Today, the majority of gout cases demonstrate clinical features of the metabolic syndrome. Recommendations of the European League Against Rheumatism (EULAR) published in 2006 address key issues in the diagnosis of gout, as well as in the nonpharmacologic and pharmacologic management with regard to the clinical condition and comorbidities of the individual patient. Routinely used antihyperuricemic drugs include allopurinol, colchicine, and uricosuric agents. New agents have recently been introduced into clinical practice, like pegylated uricase and febuxostat, a nonpurine inhibitor analog of xanthine oxidase. Thus, novel therapeutic options are now available to combat this chronic illness which often leads to significant disability.
 ...
PMID:[Gout and comorbidities associated with hyperuricemia]. 2136 38

Hyperuricaemia (increased serum urate concentration) occurs mainly in higher primates, including in humans, because of inactivation of the gene encoding uricase during primate evolution. Individuals with hyperuricaemia might develop gout - a painful inflammatory arthritis caused by monosodium urate crystal deposition in articular structures. Hyperuricaemia is also associated with common chronic diseases, including hypertension, chronic kidney disease, type 2 diabetes and cardiovascular disease. Many mouse models have been developed to investigate the causal mechanisms for hyperuricaemia. These models are highly diverse and can be divided into two broad categories: mice with genetic modifications (genetically induced models) and mice exposed to certain environmental factors (environmentally induced models; for example, pharmaceutical or dietary induction). This Review provides an overview of the mouse models of hyperuricaemia and the relevance of these models to human hyperuricaemia, with an emphasis on those models generated through genetic modifications. The challenges in developing and comparing mouse models of hyperuricaemia and future research directions are also outlined.
 ...
PMID:Mouse models for human hyperuricaemia: a critical review. 3111 97