In patients with hyperuricemia, gouty attacks are induced by rapid changes in serum uric acid (UA)levels. One of the cause of the rapid increase in serum UA level is a hyperpurine diet such as alcohol intake. We present here an unique experimental data showing that Kremezin, which is widely used to reduce the serum creatinine level by absorbing creatinine in the intestine to prevent the development of renal failure, is useful to reduce the serum uric acid (UA) level. First, we studied the effect of Kremezin in an animal model. We used rats with oral inosine load test after injection of the anti-uricase compound oxonic acid (OA). Kremezin was given orally just before the loading with inosine-containing food. Kremezin reduced the elevation of serum uric acid. Kremezin could absorb not only inosine but also other purine bases in vitro (e. g. inosine: 98.6%, purine: 99.3%, adenine: 96.5%, adenosine: 98.3%, guanosine: 99.1%, etc). Next, we studied the effect of Kremezin on the increase in serum UA concentration in healthy volunteers after drinking beer (1L in 10 min.). One hour after taking beer, blood samples were taken and UA concentrations were determined. Kremezin reduced the increase in serum UA levels compared with that in those who took beer without premedication (control). Based on these findings, we suggest that Kremezin might be useful to stabilize the serum UA levels by absorbing purine bases in alcoholic beverage as well as in foods. Therefore Kremezin is an alternatives trategy to reduce the increased risk of gout following alcohol intake.

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To identify gender-specific factors associating with serum uric acid concentration, we examined a healthy population composing of 337 of males and 117 of females who visited the division of medical examination in our hospital in 2002. The healthy population was defined as healthy subjects without any medical treatment for hyperlipidemia, hypertension, diabetes mellitus or hyperuricemia, whose age, sUA and serum creatinine in male and female subjects were 51+11,48+12 years old and 5.8+1.3,4.2+1.0 mg/d l, and 0.8+0.1,0.6+0.1 mg/dl, respectively. The association of all laboratory data with serum uric acid was evaluated by the linear regression analysis in male and female subjects. Serum uric acid was significantly correlated with sCr, logTG and systolic blood pressure in both gender. There was a gender-specific significant correlation between sUA and BMI in male subjects or value of Ht in female subjects. Using multiple regression analysis, sUA independently correlated with creatinine, logTG and Ht in female subjects, where 50% of total variation in sUA accounted for these independent variables. In conclusion, Ht was an independent female-specific factor associated with sUA.

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Mutation of the Hypoxanthinep hosphoribosyltransferase gene (HPRT1) cause Lesch-Nyhan (LN) syndrome, which is characterizedb y hyperuricemia, s elfmutilationa nd behavioradl ysfunctiona, nd approximately 15% of LN mutations involve large deletions and large duplications. In this study, we have identified a novel mechanism of a mutationi nvolvingt ranslocation between the HPRT1 gene and an other gene on the X chromosome. In HRT-25's cDNA obtained from a patient with LN syndrome, the upstream region of exon 3 wasa mplified, b ut thef ull-lengthr egiono f exon3 was not amplified. T he use of 3' rapida mplificationo f cDNA ends polymerase chain reaction (3' RACE-PCR) for mRNA from HRT-25 demonstrated a part of intron 3and an unknown sequence starting at the 3' end of exon 3. Analyzing genomic DNA from HRT-25 based on the data from 3'-RACE, we have clarified the breaking point in HPRT1 intron 3 and following an unknown sequence of 1007-bp. We analyzed HPRT1 genomic DNA in order to confirm the mutation with an unknown sequence in the genomic DNA. Unknown sequence compared through BLAST analysis of the human genome(NCBI; http://www.ncbi.nlm.nih.gov/BLAST/)showed that at least 0.5 to 0.6-Mb telomeric to HPRT1 on chromosome Xq wherel ocated near LOC340581. In the genomic DNA form HRT-25, a translocation between HPRT1 and the otherr egiono n the X chromosomei nvolvesa chimerag ene structureth at lost a region of downstream from intron3 of HPRT1. This study demonstratesth e molecularb asis for the involvemenot f genomici nstabilityin germc ells.

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Thirty-one hypertensive outpatients randomly and orally administered losartan (50mg, n=15) or candesaratan (8mg, n=16). Blood and urine samples were collected before and up to 3 months administration. Blood pressure was lowered relatively and significantly using either losartan or candesartan.
Losartan decreased serum uric acid concentration significantly (from6.6±1.4mg/dl to 6.0±1.2mg/dl, P<0.05), while candesartan did not (from 6.1±1.0to 6.2±15mg/dl). In 6 of 17 subjects,1.0mg/dl of uric acid reduction was achieved. Losartan also induced an increase in fractional excretion of uric acid significantly, while canderartan did not.
According to these findings, losa rtan, which has a high affinity for the urate/anion exchanger, induces a significant decrease in uric acid in hypertensive patients. The pleiotrophic effects of losartan on uric acid metabolism might contribute to cardiovascular risk reduction, according to recent world-wide clinical investigations.

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