Search

Gout is the most frequent cause of man's inflammatory arthritis after forty years of age and its prevalence is increasing. Although the physiopathology of this condition is starting to be thoroughly recognized, therapeutic approaches have not fundamentally changed during the last decades. In the absence of renal or digestive contraindications, non steroidal inflammatory drugs are the treatment of choice for acute flares of gout arthritis. If an indication for urate-lowering therapy exists, a xanthine oxydase inhibitor or an uricosurical treatment remains the treatment of choice, depending on the patient's co-morbidity. Purine restrictive diet, weight loss in case of obesity and lower alcohol intake are highly necessary co-measures.

Thesis on the endemic Cunoniaceae of New Caledonia: physiological knowledge and research of the physico-chemical and biological characteristics of their bioactive substances of interest, Thèse portant sur les Cunoniaceae endémiques de la Nouvelle-Calédonie : connaissance physiologique et recherche des caractéristiques physico-chimiques et biologiques de leurs substances bioactives d'intérêt

The great variability of slow acetylator (SA) and/or rapid acetylator (RA) frequency is mainly due to ethnic-racial origin. Using the urinary elimination ratio of three metabolites of caffeine--acetylamino formylamino methyluracil (AFMU) to AFMU + 1-methyl urate (1U) + 1-methyl xanthine (1X)--we settled the acetylation phenotype in 54 independent subjects of Khmer and 70 independent subjects of Caucasian origin. Using DNA from peripheral leucocytes, we determined by PCR, in 32 Khmer and 122 Caucasian subjects, the frequencies of wild-type alleles (NAT-2 *4) and of mutated alleles (NAT-2 *5A, *6A, *7A). The frequency of SA was respectively 28 per cent and 61 per cent in Khmer and Caucasian subjects. The antimode of the distribution of the ratio was different in the two populations: 0.07 in Khmers and 0.18 in Caucasians showing a reduced acetylation capacity in the Khmer population in spite of a higher frequency of RA. The frequencies of alleles were also different between the two populations. Between Khmers and Caucasians respectively: *4: 48.4-23.8 per cent *5A: 15.6-44.2 per cent. *6A: 29.7-32.0 per cent. *7A: 6.3-0 per cent. These differences might be taken into account to define a therapeutic strategy in the treatment of tuberculosis by isoniazide.

Hypouricemia can be observed in uncommon situations as in our two patients with hereditary xanthinuria.In the first case, hereditary xanthinuria was discovered in a 36-year-old man when routine tests revealed hypouricemia. In the second case, a 76-year-old woman, hypouricemia was also a fortuitous discovery. She had major xanthinuria and a radiotranslucid lithiasis in the right kidney.Hereditary xanthinuria is characterized by hypouricemia, low urinary urate excretion and increased concentration of xanthine and to a lesser extent hypoxanthine. The disease results from a defect in xanthine oxidase and is considered to be transmitted by autosomal recessive heredity. This rare metabolic disorder is more often asymptomatic and detected by routine chemistry. Development of xanthine lithiasis is directly related to the low solubility of xanthine and is the main complication of the disease, occurring in 30-40% of patients. There is no effective treatment and the only useful measure is to prevent xanthine urolithiasis by maintaining urinary output above 2 l/day.

Azathioprine is an immunosuppressor used with ciclosporin and corticosteroids after organ transplantation. Azathioprine is rapidly transformed into 6-mercaptopurine which in turn is metabolized by three competitive pathways: a) intracellular hypoxanthine guanine phosphoribosyl transferase leads to 6-thioguanine nucleotides which can damage chromosome DNA; b) thiopurine methyltransferase produces inactive methylated derivatives; c) xanthine oxidase produces thiouric acid. Due to inter-individual variations in the later two pathways, azathioprine dose must be adapted to each patient. A 48-year-old female patient underwent renal transplantation in 1994 and was given immunosuppressive therapy combining thymoglobulins, azathioprine and ciclosporin. Severe leukopenia (3000/mm3) occurred on day 5 requiring withdrawal of azathioprine. Known hypouricaemia (50 mumol/l) suggested xanthine oxidase deficiency. Laboratory results confirmed xanthine oxidase deficiency and also revealed reduced thiopurine methyltransferase activity (14.9 pmol/h/mg Hb). Azathioprine toxicity was confirmed by regression of the leukopenia after withdrawal and recurrence at rechallenge. Xanthine oxidase deficiency occurs in 2% of the general population. Reduced thiopurine methyltransferase activity affects 11% of the population. The combined presence of these two genetic anomalies led to early and sudden intolerance to azathioprine and emphasize the need to develop new immunosuppressor agents degraded by other metabolic pathways.

Myofibrils from rat hearts were prepared in conditions maintaining their redox state, and their sulfhydryl groups were measured using a solution of urea and sodium dodecyl sulfate (SDS) as denaturant. The sulfhydryl content was 92 n mol/mg of protein, indicating that cysteins are in reduced form. In the presence of superoxide radicals generated in vitro with purine and xanthine oxidase, the myofibrillar sulfhydryl groups were oxidized.

Xanthinuria, described in 1954 by Dent and Philpot, is a rare metabolic disorder, characterised by a deficiency in xanthine-oxidase, a key enzyme in the synthesis of uric acid. It results in hypouricaemia and hypouricuria, the urinary excretion of products of purine synthesis taking place in the form of uric acid precursors: hypoxanthine and xanthine. By virtue of the very slight solubility of xanthine, this xanthinuria may cause urinary lithiasis, in general occurring early. More often, however, the disease is asymptomatic and diagnosed following the chance discovery of hypouricaemia. We report 6 recent cases.

Seeking medical help because of an acute urinary retention, a 3-year-old child showed at intravenous urography (IVU) multiple radiotransparent lithiases. Hypouricemia suggested a diagnosis of xanthuria. The problems of this condition due to a congenital deficiency in xanthine oxydase are studied in a review of the literature. 56 xanthic lithiases have been published and since the work of Dent and Philpot, 28 xanthinurias have been reported.

Xanthine oxidase activity: O2-dependent and NAD+-dependent forms, were carried out in cytosol supernatant of Rat liver homogenat with adjuvant and hepatocytes induced arthritis and hepatitis. Both forms were increased without modification of their ratio. These results suggest that xanthine oxidase was implicated in the inflammatory reaction.

Complete lack of adenine phosphoribosyltransferase (APRT) is a not uncommon cause of urinary lithiasis in young children. The calculi are made up of a very poorly soluble substance, 2,8-dihydroxyadenine, which results from the oxidation of adenine by xanthinoxidase. A study of the 7 cases of APRT deficiency hitherto published (including 5 cases with lithiasis) shows that the diagnosis is rarely made, since the conventional methods of urinary stone analysis are unable to distinguish dihydroxyadenine from uric acid. This form of lithiasis can be prevented by inhibiting xanthinoxidase with allopurinol. The remarkable efficacy of this treatment and the frequent severity of the disease should raise the possibility of 2,8-dihydroxyadenine lithiasis in very case of alleged uric acid lithiasis in young children.

Oxygen derived free radicals are able to degrade collagen fibrils and to participate with the collagenases to collagen degradation in the inflammatory phenomena. This effect was experimentally demonstrated in vitro by the use of chemical or physical systems of oxygen free radicals production. In addition certain free radicals increase the cross-linking of collagen. The relationship between collagen degradation in inflamed areas and the subsequent fibrosis, despite its medical interest, is not yet explained.

Xanthine oxidase activity: NAD+-dependent form (D) and O2-dependent form (O) were carried out in cytosol supernatants of connective tissue growth (T.C.N.F.), skin tail, liver and plasma of carrageenan induced granuloma in the Rat. The specific activities of skin, liver and plasma were normal in animals with a granuloma. The total specific activity (D + O): 7.53 +/- 0.98 mU/mg protein, and the percentage of form O: 51.6 +/- 5.1 of the granulomatous tissue as compared to the tail are significantly increased. These results suggest the likely function of xanthine oxidase during the inflammatory response.

New drugs are proposed in an attempt to reduce the overformation of uric acid in man. The procedure is based on the inhibition of human purine nucleoside phosphorylase selectively investigated in its phosphorolytic sequence. But for technical reasons, analogous inactivation of the enzyme in its comparative guanosine arsenolysis is subject to experimentation.

Xanthinuria is a rare hereditary disorder characterized by a gross deficiency of the enzyme xanthine oxydase resulting in hypouricemia, hypouricosuria and increased serum and urinary oxypurines. Three patients with this disease are presented and the pertinent literature is reviewed. We have demonstrated in one subject the absence of xanthine oxydase activity in a renal fragment. Genetic studies were performed but we do not find any relation between this deficiency of enzyme xanthine oxydase and HLA, Pl, Gm groups.

The clinical features and biological results in a second patient with a metabolic defect of the molybdenum cofactor are described. The first case was reported in 1978 by Duran et al. Their clinical description was similar with early encephalopathy and myoclonial and dislocation of the lens. Biologically, this condition is characterised by secondary hypo-uricemia and hypo-uricuria due to xanthine oxidase deficiency and by sulphituria, resulting from sulphite oxidase deficiency. These two enzymes have a common hepatic molybdenum cofactor, the structure and metabolism of which are only partially known.

In a first part, an elementary theoretical introduction to ESR is given. In a second part, selected examples illustrate the possibilities of this method. Studies of hemoproteins, flavoproteins, model complexes and phospholipid systems are described. This review is made for biochemists who have no experience in ESR.