History of Gout Research

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24th Nov 2017 Health Reference this


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Hyperuricemia is a biochemical defect distinguished by Serum uric acid (sUA) level greater than 6.8mg/dl (Sunkureddi et al. 2006). In majority of cases (90%), hyperuricemia arise due to reduced excretion of uric acid by kidneys, whereas in residual cases (10%), there is enlarged production of uric acid (Canella et al. 2005). .

Gout is an illness that is correlated to overload synthesis, and deposition of uric acid crystals. These crystals form secondary to hyperuricemia that is a serum urate concentration greater than 0.42 mmol/L (Eggebeen et al. 2007; Chen et al. 2008). Hyperuricemia and gout are significantly high risks for kidney or bladder stones (urolithiasis).The prevalence of gout and hyperuricemia among US adults in 2007–2008 was 3.9% (Zhu et al. 2011) while 18% observed in the German population (Mikuls et al. 2007). They are highly prevalent and have treatment preposition beyond the care of inflamed joints.

Gouty arthritis were amongst the initial disease to be documented in clinical entity, Identified by the Egyptians in 2640 BC (Nuki et al. 2006), podagra (acute gout stirring in the first metatarsophalangeal joint) was later on recognized by Hippocrates in the fifth century BC, who termed as ‘the unwalkable disease’. Some of Hippocrates’ outstanding clinical perception in relation to gout are potted in aphorisms, which are as accurate today as they were 2500 years ago (Hippocrates et al. 1886). Hippocrates also distinguished the connection between the disease and an unbalanced lifestyle referring to podagra as ‘arthritis of the rich’, as contrasting to rheumatism, an arthritis of the deprived people

There are the four differents stages that medical professionals use to classify for the gout. The Asymptomatic gout, The Acute gout ,The Chronic goutand The Interval or intercritical goutIn asymptomatic goutthere is increase in the level of uric acid with the complaint of increase in the pain in the joints and there is no more symptoms. In acute gout this patients have too much pain in their joints and there is a swelling and assiated with the redness of joints.90% of patients have attack on their big toe. Other joints involved are ankle,midfoot heel and knee but any joints can be involved. The attack with gout can be resolved within one or two days. In the interval gout stage there is acute gouty flares and the patients has no symptoms.there is increase in the number of gouty attack if the uric acid level below 6 mg/dl .the most of patients have attack but they have never exprinced another attack of gout, Chornic gout develops because of high level of uric acid in their body for many years.firm nodular swelling is called tophi.the tophi can occurs anywhere the most common location are antihelix and helix of ear,digits of feet and hands. (Hench et al.1936; Nakayama et al. 1984).

It is estimated that the incidence and prevalence of gout and hyperuricemia in the USA are over 6 and 42 million, respectively, with a progressively increasing pattern and affecting mainly men over the age of 40 years (Lawrence et al. 2008).

The rate of gout in African living in America is generally about 13% of the US population, and is double in comparison with Caucasians to develop gout. In a prospective cohort study, young men 571 Caucasian and 352 African living in America were followed for a mean duration of 29 years. The growing incidence of gout in these 2 cohorts was 5.8% and 10.9%, correspondingly. Yet, African living in America represent only 10% of the patients treated for gout.(Alvin et al2012)

All the way through history gout has been linked with rich foods and extreme alcohol consumption. Because it is evidently connected with a way of life that, at least in the past, could only be afforded bythe rich, gout has been referred to as the ‘disease of kings’. In some eras gout was apparent as publicly desirable because of its occurrence among the politically and socially influential people. In his typical monograph on the history of gout (Copeman et al. 1964), Copeman refers to a comment in the London Timesin 1900, “The common cold is well named, but the gout seems right away to lift up the patient’s social status”, and to another in Punch in 1964, “In observance with the spirit of moredemocratic times, gout is becoming less upper-class and is now open to all. It is preposterous that a man should be barred from enjoying gout because he went to the wrong school.”

In history, gout has been well thought-out to be primarily a male disease, But actuality that women can also develop gout was first documented through the reign of Nero (AD 54–68) by Seneca, who observed, in this age, women competitor men in every kind of lasciviousness. Why require we then be astonished at considering so many of the female sex afflicted with the gout (Froster et al 1979). In the current era, although gout remains first and foremost a disease of men in middle age, it has turn out to be more and more frequent in women, predominantly after the menopause.( Hench et al.1936; Nakayama et al. 1984).

The ancestral connection of gout was documented hundreds of years ago but important the exact genetic mechanisms weren’t achievable until the arrival of modern genetic tools. Gout was incorporated as an inherited disorder in the seminal work of Archibald E. Garrod in his 1931 publication on inborn errors in metabolism. Garrod well thought-out gout to be a dominantly inherited trait.(Gray et al 2012)

In earlier times, attacks of gout were also seen as a prophylactic against more serious diseases. According to the writer Horace Walpole gout “prevents other illnesses and prolongs life might I treat that gout, should not I have a fever, palsy (Lewis et al. 1873),.

In recent decades, however, the diet and lifestyle that predispose persons to hyperuricemia and gout have become all the time more common. The role of excess nutritional purines (derived from meat, seafood, and beer) in the progress of gout is illustrated by the difference between the incidence of gout in Asia and Europe. Traditional Asian diets, based on rice and vegetables, are small in dietary purines, and gout has been moderately rare in these cultures. In contrast, European and American diets, which are high in meat and definite sea foods, are linked with hyperuricemia and gout (Choi et al. 200; Zollner et al. 1973). Rising affluence has also led to an increase in the figure of people following a westernized diet and lifestyle, and this has been paralleled by an increase in the occurrence and incidence of gout throughout the world.

Purines are machinery of nucleosides, the structure blocks of DNA and RNA. Purine nucleosides are used in the formation of other metabolically significant factors as well, such asadensosinetriphosphate, S-adeneosylmethione, and nicotineadeninedinucleotide. Given the significance of purine-containing molecules for continued existence, vertebrates, including humans, have developed robust mechanism for producing enough purine nucleosides for their metabolism using willingly available materials (such as glucose, glycine, and glutamine), as well as recycling purine nucleosides from all through the body or from the diet (Richette et al; Wilson et al. 2010).

Purines can be divided into two types Endogenouspurines are manufactured within human cells. And exogenouspurines are obtained from foods. In mammals, surplus purine nucleosides are detached from the body by collapse in the liver and excretion from the kidneys. For most mammals, the purines are first transformed into the transitional uric acid, which is then metabolized by the enzymeuricaseinto the compound allantoin. Allantoin is a very soluble compound that can without difficulty pass through the bloodstream, become clean by the kidneys, and be excreted from the body. In dissimilarity to other mammals, humans and other primates lack a serviceable uricase enzyme, and can only break purines down into uric acid.

The procedure of breaking down purines results in the configuration of uric acid in the humans body is not as easy to detached, because human body lack uricase, and that can build up in body tissues.

The levels of uric acid in the blood depend on 2 factors. The first is the rate of uric acid synthesis in the liver. While uric acid consequences from purine degradation, its levels are influenced by both the amount of purines synthesized in the body, as well as the amounts of purines absorbed from the diet The second determinant of blood uric acid levels is the rate of uric acid excretion from the kidneys. The residual uric acid travels all the way through the intestines, where bacteria help break it down (Richette et al. 2010).

Excretion has the maximum effect on blood uric acid levels, with about 90% of hyperuricemia cases attributed to impaired renal excretion (Choi et al. 2005). Impaired excretion is most often due to abnormality in the kidney urate carrier or organic ion transporter, both of which control the movement of uric acid out of proximal kidney tubules and into urine (Enomoto A et al. 2002).

The treatment of gout consists of controlling the pain, Reducing the serum urate levels, changing unhealthy life styles, preventing the complications of chronic gout. (Schumacher et al 2008)

By changing the life style because unhealthy life style will result increase hypertension,hyperlipidemia and obesity,by controlling diet of purine consumption causes significant decrease in the serum urate level but the greater decrease is seen in those patients who have stop the alcohol consumption in their diet (choi et al 2005)

There are number of ways to reduced the sUA level.the best way is too control the diet,but sometime along with the drugs.sometime these drug are very effective and reduced the sUA very quickly. (choi hk et al 2008)

Following drugs are also used to lower sUA level urate levels:

  1. Uricosuric agents (ii) Allopurinol and Febuxostat:

Uricosuric agents: Two drugs that belong to this group are benzbromane and probencid.these two are weal organic acid and lower the sUA level,by inhibition of tublar rebsorptionof urate in the renal tubular system and increasing uric acid in the urine. These agents are indicated when the renal execration of urate are decreased.it is contraindicated in patient with renal calculi(Alvin et al 2012).

Two drugs that belong to xanthine oxidiase inhibitor are Allopurinol and Febuxostat. Xanthine oxidase inhibitor along with uricosuric agent are used to increase the urinary execration of urate .The two drugs Febuxostat and Allopurinolare used to lower the sUA level and their

Xanthine oxidase xanthine oxidase is the only enzyme that break down the purine bases and catalyze the conservation of hypoxanthine to xanthine and the xanthine to uric acid .then uric acid normally excerated .this enzyme deficiency is may be due to the gentic factor, sometime more consumtion of purine food and less production of enzyme.If any drug that is metabolized by xanthine oxidased,its action is increased by Allopurinol drug llike mercaptopurine

FEBUXOSTAT: Febuxostatis a urate decreasing drug and inhibitor of xanthine oxidase so that is used in the treatment of hyperuricemia and chronic gout (Grosser T et al. 2011). Febuxostat was approved by the European Medicines Agency on April 21, 2008and after one year it was approved by the U.S. Food and Drug Administration on February 16, 2009 Febuxostat lowers sUA concentrations by acting on the purine catabolism, the mechanism of action is oxidation of hypoxanthine to xanthine and xanthine to uric acid(Becker et al. 2005).

. it is structurally quite different from Allopurinol, has an different mechanism of action on enzyme inhibition, and is more potent.Unlike Allopurinol, that undergoes oxidation to the active metabolite oxypurinol and interacts chemically with the molybdenum center of xanthine oxidase, Febuxostat remains unchanged and inhibits xanthine oxidase by binding in a narrow channel leading to the molybdenum center of the enzyme. By this mechanism, Febuxostat is able to inhibit both the reduced and oxidized form of xanthine oxidase to produce sustained reductions in sUA levels. (Beckar et al 2010)

The capability of humans and primates to protect blood levels of uric acid (due to slow kidney filtration and lack of a uricase enzyme) was probably useful to our evolution, by increasing antioxidant capacity of the blood (Alvarez-Lario et al. 2011).


Humans and primates are one of the few mammals that cannot produce their own vitamin c( vit.c), and may have evolve the capability to protect uric acid to reimburse for this (Hediger MA et al. 2002). For example, blood uric acid levels in humans are in general about 6 times that of vit.c, and about ten times the levels in other mammals (Roch-Ramel F et al. 1999). Like vit.c, uric acid has a principle role in shielding high-oxygen tissues (like the brain) from spoil, and low blood uric acid levels have been linked with the succession or greater than before risk of more than a few neurological disorders, including Amyotrophic Lateral Sclerosis (Keizmann D et al. 2009), Multiple sclerosis (Rentzos M et al. 2006), and Huntington’s (Auinger P et al. 2010), Parkinson’s (Andreadou E et al. 2009), and Alzheimer’s diseases (Kim TS et al. 2006).

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