Claes Friman

A placebo-controlled trial of primary biliary cirrhosis treatment with colchicine and ursodeoxycholic acid

BACKGROUND/AIMSnUrsodeoxycholic acid (UDCA) and colchicine have beneficial effects in primary biliary cirrhosis (PBC). The efficacy of colchicine and UDCA in PBC was compared in a 2-year placebo-controlled study (n = 90).nnnMETHODSnClinical events, laboratory test results, and liver histology were recorded at the beginning and end of the trial.nnnRESULTSnThere were significantly fewer dropouts for hepatic reasons with UDCA than with placebo. Pruritus was reduced by both active drugs. Colchicine improved liver function test results only modestly, whereas UDCA significantly decreased the serum activities of aminotransferases, alkaline phosphatase, and gamma-glutamyltransferase compared with colchicine and placebo. Serum total bilirubin levels were decreased only by UDCA. Both colchicine and UDCA reduced serum cholesterol levels, and UDCA also reduced high-density lipoprotein cholesterol levels. Furthermore, UDCA reduced the serum levels of immunoglobulin (Ig) M and IgG, and colchicine reduced IgG levels compared with placebo. The elevated serum level of aminoterminal propeptide of type III procollagen remained unchanged by colchicine or UDCA, whereas the serum level of carboxyterminal propeptide of type I procollagen was significantly decreased by UDCA. UDCA significantly decreased ductular proliferation compared with colchicine or placebo.nnnCONCLUSIONSnThese data suggest that UDCA frequently is superior to colchicine and especially to placebo in the treatment of PBC.

Differential effects of reactive oxygen species on native synovial fluid and purified human umbilical cord hyaluronate

The ability of reactive oxygen species produced by triggered neutrophilic leukocytes, hypoxanthine/xanthine oxidase (HX/XAO), hydrogen peroxide, and hypochlorous acid/mycloperoxidase (HOC1/MPO) systems to degrade hyaluronate (HA) in human synovial fluid (SF) and purified umbilical cord HA was compared by measuring the molecular weight distribution of HA using high-performance liquid chromatography with a size-exclusion column. The exposure of noninflammatory SF to phorbol myristic acetate (PMA) -activated neutrophils or to hydrogen peroxide (H2O2) caused depolymerization of SF HA to the degree corresponding to that found in rheumatoid SFs. When HX/XAO was used as radical generator, the molecular weight of SF HA decreased from 3.42×106 to 1.40 × 104 daltons with concomitant decrease of SF viscosity to 36% from the original value. The HOC1/MPO system caused no depolymerisation of SF HA, even at very high unphysiological HOC1 concentrations that induced the precipitation of SF HA together with SF proteins. This effect was found to be comparable to conventional mucin clot formation in SF. However, purified human umbilical cord HA was easily depolymerized with HOC1/ MPO or with H2O2, but these effects were sensitive to the hydroxyl radical scavenger mannitol and iron chelator desferrioxamine, indicating that the formation of reactive hydroxyl radical (OH) is likely to participate in these reactions. Thus we conclude that in inflammatory SF HA is mainly depolymerized by OH produced by decomposition of H2O2 catalyzed by iron, free or locally bound to HA itself. In contrast to what has been reported earlier, HOC1/MPO only depolymerizes purified umbilical cord HA (in a hydroxyl radical-dependent manner) but does not depolymerize HA in SF. As a matter of fact, HOC1/MPO has a scavenging action on SF HA by consuming H2O2 and thus preventing the formation of reactive hydroxyl radicals.

Isolation and characterization of undersulphated chondroitin-4-sulphate from normal human plasma

The present study was undertaken in order to characterize further the glycosaminoglycans of normal human plasma. Coagulation factor IX concentrate prepared from undiluted plasma by DEAE-Sephadex chromatography was used as the starting material. The concentrate was subjected to proteolytic treatment with papain and pronase, deproteinised with trichloroacetic acid, dialysed and passed through an AG 1 X 2 anion-exchange column. Glycosaminoglycans were eluted stepwise from the column with NaC1. The sole glycosaminoglycan obtained was an undersulphated chondroitin-4-sulphate which was identified by chemical analyses, digestibility with testicular hyaluronidase, electrophoretic behaviour and infrared spectrum. Gel-exclusion chromatography indicated a molecular weight of 17 000 for the compound. The undersulphated chondroitin-4-sulphate was calculated to represent at least 80% of the macromolecular glycosaminoglycans present in normal human plasma and to occur in a concentration of approx. 3 mg hexuronate per 1 of plasma.