Maria Laura Ciompi

Uric acid metabolism in two patients with coexistent Down's syndrome and gout

SummaryTwo patients with coexistent Downs syndrome and gout are described. Although increased serum urate levels are frequently reported in Downs syndrome, only a few such patients have been described with concomitant gout. In our patients no significant alterations of the purine salvage pathway were found, and the turnover parameters of uric acid, determined by means of a14C-labeled uric acid study, were consistent with the metabolic findings observed in normoexcretor gouty patients.

Behaviour of Von Willebrand Factor Antigen in Follow-up of Polymyalgia Rheumatica/Giant Cell Arteritis

The von Willebrand Factor Antigen (vWF: Ag) is a high molecular weight glycoprotein synthesized by endothelial cells and megakaryocytes. It is present inside the endothelium cells in Welbel-Palade bodies (1) and is also present in the alpha granules of platelets (2). Elevated levels of vWF: Ag have been reported in several diseases characterized by vessel injury, such as scleroderma (3), glomerulonephritis (4), diabetes mellitus (5), Behcets syndrome (6), Systemic Lupus Erythematosus, Rheumatoid Arthritis and vasculitis in general (7). Increased vWF: Ag plasma levels have also been described in patients with Giant Cell Arteritis (GCA) and/or Polymyalgia Rheumatic (PMR) (8, 9). In both these diseases an apparent or clinically hidden vasculitis is or may be present and vWF: Ag is reported to be most helpful in discriminating between PMR and GCA, since its levels seem to be higher in patients affected by GCA (8, 9).

D-penicillamine and gold salt treatments were complicated by myasthenia and pemphigus, respectively, in the same patient with rheumatoid arthritis

A 53-year-old woman with rheumatoid arthritis developed myasthenia gravis after 6 months of therapy with D-penicillamine. Nineteen months after D-penicillamine was discontinued and 12 months after the beginning of gold therapy, she developed pemphigus vulgaris. This is the first reported case of gold-induced pemphigus in rheumatoid arthritis. This study further underlines the complex interactions between the effects of treatment with sulfhydryl-disulfide exchange drugs and the altered immunological system of patients affected by rheumatoid arthritis.

A2 Adenosine Receptors in Neutrophils from Health Volunteers and Patients with Rheumatic Disease

Inflammation is the primary response to tissue injury or microbial invasion and is characterized by the local accumulation of neutrophils. While neutrophils are essential for limiting the spread of infection, stimulated neutrophyls are capable of damaging injured tissues while en route to sites of infection or inflammation. It has been recently discovered that release of adenosine is one mechanism by which normal cells may protect themselves from activated neutrophils (Cronstein et al., 1986). Extracellular adenosine and its analogues diminish generation of toxic oxygen product (e. g. O2− or H2O2) by activated neutrophils, yet promote neutropil chemiotaxis (Cronstein et al., 1985; Roberts et al., 1985; Rose et al., 1988). There are two types of cell surface adenosine receptors, A1 and A2 which are differentiated by their affinity for adenosine, the order of potency of adenosine analogues and opposing effects on cellular cAMP metabolism (van Calker et al., 1979). Recently it has been possible to label adenosine receptors by adenosine analogues such as 3H-N6-cyclohexyl adenosine (CHA) for A1 adenosine receptors and 3H-5’N-ethylcarboxamido adenosine (NECA) for A2 receptors in cells from synovial fluid from rheumatic patients (Martini et al., 1989). In the present report we described the presence of A2 adenosine receptors in neutrophils from health volunteers and from rheumatic patients. Initially, the sites were labeled by 3H-NECA but the binding properties of this ligand did not agree with the pharmacology of A2 receptors and indicated the presence of A2 -like binding protein. Then, the characterization of A2 adenosine binding sites in human neutrophils was carried out using 3H- (2 [p- (2- carboxyethyl)-phen ethylamido]-5’ -N- ethylcarboxamido adenosine (CGS 21680), a novel high affinity and selectivity ligand for striatal A2 receptors ( Jarvis et al., 1989).

Acute Renal Failure During Adenine Therapy in Lesch-Nyhan Syndrome

Additional adenine and folic acid are required for optimal growth of hypoxanthine-guaine phosphoribosyltransferase (HGPRT) deficient fibroblasts in tissue culture(1). On this ground adenine therapy was advised in Lesch-Nyhan (LN) syndrome and resulted in a prompt correction of megaloblastic anemia in two cases(2). In mammalian tissue adenine is easily converted into adenosine monophosphat by adenine phosphoribosyltransferase, utilizing 5-phosphoribosylpyrophosphate (PRPP). “Inappropriate” purine biosynthesis “de novo” in ln syndrome can be just accounted for an increased availability of PRPP due to missing competition between HGPRT and glutamine-PRPP-amidotransferase for this substrate(3–5). Consequently PRPP consumption from adenine is likely to result in a decreased purine biosynthesis, as proved by lesser incorporation of 14C-glycine in urinary uric acid (ua)(2). Nevertheless adenine therapy showed conflicting evidence of inhibiting purine biosynthesis, since a decrease of urinary ua was not evidenced in two cases in spite of a reduction of erythrocyte PRPP(6). Therefore we think that any further contribution on this topic is of some interest.

Isolation of an urate-binding protein by affinity chromatography

This paper describes an affinity chromatography procedure to purify an urate binding protein from human serum. The specific ligand was 8-amino-2,6-dihydroxypurine bound to Sepharose through the amino group. The specific elution was obtained with an uric acid or allopurinol solution. Electrophoretic analysis of the eluted protein shows a single sharp band with an α2-globulin mobility. Molecular weight, determined by gel filtration, is approximately 70,000 daltons.

Urate-Binding Proteins in Plasma Studied by Affinity Chromatography

The existence in humans of one or more plasma proteins, which specifically bind uric acid (UA) is still discussed. There is no agreement on the nature of the binding protein, identified as the serum albumin1, or as a specific α1-α2-globulin2, nor on the extent of the bound quote. Most investigations have been till now performed by ultrafiltration1 or column chromatography2, but the specificity and the sensitivity of both are rather unsatisfactory; for example, recovery is lesser than 30% in the later technique3. On the other hand, the existence itself of a significant urate binding to human plasma proteins has been denied even recently, by means of continuous ultrafiltration and equilibrium dialysis4.

Plasma levels of fibronectin in polymyalgia rheumatica giant cell arteritis

SummaryIn order to verify whether measurement of plasma fibronectin (Fn) could represent a useful tool in acute-phase-response assessment, Fn was measured in 16 previously untreated patients (group A) affected by polymyalgia rheumatica giant cell arteritis (PMR-GCA), both before, during, and after 45 days of steroid therapy, and its course was compared with the behavior of some acute-phase reactants such as erythrocyte sedimentation rate (ESR), fibrinogen (Fng), and prealbumin (Preal). No difference was detected between the baseline Fn levels found in patients and those registered in a control group composed of 15 sex- and age-matched healthy subjects; no correlation was found with the other acute-phase parameters considered, and no significant variation of plasma Fn levels was registered as a result of the steroid therapy administered. On the contrary, all the other parameters revealed a good degree of correlation and tended progressively and homogeneously towards normalization as a result of the therapy administered.Plasma Fn was also measured in another group of 16 PMR-GCA patients (group B), all of whom had pathological retinal fluoroangiographic findings, and its levels were compared with those of the von Willebrand factor antigen (vWfAg), a biochemical index of vascular damage. While the levels of Fn continued to be the same as those detected in the control group, the values of vWfAg registered in group B proved to be significantly different from those found in another homogeneous control group of 25 healthy subjects. Finally, no correlation could be detected between Fn and vWfAg, and neither of them showed any significant correlation with the ESR. These results indicate that plasma Fn may not be considered to be an acute-phase reactant in PMR-GCA, and that it is not useful for revealing the vascular involvement in PMR-GCA.

Behavioural Changes During Adenine Therapy in Lesch-Nyhan Syndrome

It seems useful to us to report here the changes observed in a child affected by the Lesch-Nyhan syndrome when given adenine treatment for 15 months.

A2 Adenosine Receptors in Neutrophils from Healthy Volunteers and Patients with Rheumatoid Arthritis

At physiological concentrations, adenosine can modulate a variety of biological activities by engaging specific cells surface receptors, termed A1 and A2, with different affinity for adenosine and adenosine analogues 1. Engagement of A2 adenosine receptors induces an increase in cAMP levels in several cells types, in contrast stimulation of A1 receptors causes opposite effects 2. It has been shown that adenosine and its analogues inhibit O2 generation 3, 4, phagocytosis and adherence by occupancy of specific adenosine A2 receptors, while the occupancy of A1 adenosine receptors enhance chemiotaxis 5, phagocytosis and adherence 6. In general, activation of adenosine receptors on leukocytes reduces immune and inflammatory responses7. Therefore, it may be suggested that release of adenosine is one mechanism by which normal cells protect themselves from activated neutrophils. Since it is possible that a decreased adenosine receptor functions are implicated in diseases like rheumatic pathologies characterised by an excess of inflammation. In the present report we described characteristics of adenosine binding sites on human neutrophils from healthy volunteers and rheumatic patients afflicted with rheumatoid arthritis by using [3 H]N ethylcarboxamidoadenosine (NECA) and [3 H] 2-p-(2-carboxyethyl) phenethylamino 5’ N-ethylcarboxamidoadenosine (CGS 21680) as ligands.