R M Pertusi

The metabolism of poly(ADP-ribose) in peripheral blood mononuclear (PBM) cells was studied in 13 patients with systemic lupus erythematosus (SLE) and in 12 age and sex matched controls. Poly(ADP-ribose) polymerase activity was measured as the net accumulation of ADP-ribose polymers during the conversion of 32P-NAD to poly(ADP-ribose) in PBM cells in vitro. The control population showed a mean activity of 418 +/- 91(s.d.)pmol ADP-ribose/10 min/10(6) cells. The SLE population was more heterogeneous and showed a lower mean of 225 +/- 147(s.d.)pmol ADP-ribose/10 min/10(6) cells. The mechanism of decreased ADP-ribose polymer accumulation was investigated. Measurements of turnover of the ADP-ribose polymers and its substrate, NAD+, showed that diminished ADP-ribose polymer accumulation in SLE subjects resulted from decreased poly(ADP-ribose) synthesis and not from altered rates of polymer turnover or NAD utilization. Western blot analyses of enzyme protein levels, kinetic studies of poly(ADP-ribose) polymerase activity and analyses of polymer size distribution suggested that the mechanisms of poly(ADP-ribose) synthesis in SLE cells is not altered but that the number of active poly(ADP-ribose) polymerase molecules is reduced.

CS1 (CRACC, CD319) and 2B4 (CD244), members of the signalling lymphocyte activation molecule (SLAM) family receptors, regulate various immune functions. Genes encoding SLAM family receptors are located at 1q23, implicated in systemic lupus erythematosus (SLE). In this study, we have investigated the expression and alternative splicing of CS1 and 2B4 in immune cells from SLE patients. The surface expression of CS1 and 2B4 on total peripheral blood mononuclear cells (PBMCs), T, B, natural killer (NK) cells and monocytes in 45 patients with SLE and 30 healthy individuals was analysed by flow cytometry. CS1-positive B cell population was increased significantly in SLE patients. Because CS1 is a self-ligand and homophilic interaction of CS1 induces B cell proliferation and autocrine cytokine secretion, this could account for autoreactive B cell proliferation in SLE. The proportion of NK cells and monocytes expressing 2B4 on their surface was significantly lower in patients with SLE compared to healthy controls. Our study demonstrated altered expression of splice variants of CS1 and 2B4 that mediate differential signalling in PBMC from patients with SLE.

The use of anabolic steroids among competitive athletes, particularly bodybuilders, is widespread. Numerous reports have noted "hepatic" dysfunction secondary to anabolic steroid use based on elevated serum aminotransferase levels. The authors' objective was to assess whether primary care physicians accurately distinguish between anabolic steroid-induced hepatotoxicity and serum aminotransferase elevations that are secondary to acute rhabdomyolysis resulting from intense resistance training. Surveys were sent to physicians listed as practicing family medicine or sports medicine in the yellow pages of seven metropolitan areas. Physicians were asked to provide a differential diagnosis for a 28-year-old, anabolic steroid-using male bodybuilder with an abnormal serum chemistry profile. The blood chemistries showed elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine kinase (CK) levels, and normal gamma-glutamyltransferase (GGT) levels. In the physician survey (n = 84 responses), 56% failed to mention muscle damage or muscle disease as a potential diagnosis, despite the markedly elevated CK level of the patient. Sixty-three percent indicated liver disease as their primary diagnosis despite normal GGT levels. Prior reports of anabolic steroid-induced hepatotoxicity that were based on aminotransferase elevations may have overstated the role of anabolic steroids. Correspondingly, the medical community may have been led to emphasize anabolic steroid-induced hepatotoxicity and disregard muscle damage when interpreting elevated aminotransferase levels. Therefore, when evaluating enzyme elevations in patients who use anabolic steroids, physicians should consider the CK and GGT levels as essential elements in distinguishing muscle damage from liver damage.

Many patients with arthritis are using alternative modes of therapy, including nutritional supplements, to treat their arthritis. Most patients never tell their doctors that they are taking alternative medications, and few doctors even ask about such activities. Over-the-counter supplements are expensive and consume large amounts of patients' healthcare dollars. Glucosamine has been widely touted as being an effective arthritis treatment. The authors designed and undertook a study to test the efficacy of a polymer of N-acetyl-D-glucosamine (NAG), or POLY-Nag, in a double-blind, placebo-controlled study in patients with osteoarthritis. Results indicate that POLY-Nag may be useful in treating patients with osteoarthritis.