Treatment with progesterone analogues decreases macrophage Fcgamma receptors expression.

Macrophage Fcgamma receptors (FcgammaRs) are critical for host defense against infection and have an important role in immune cytopenias. Modulation of macrophage FcgammaRs expression is a potential therapeutic approach to immune disorders. Glucocorticoids and synthetic progesterone analogues decrease macrophage FcgammaRs expression. We assessed the effect of treatment with commonly employed progestins on the expression of macrophage FcgammaRs using an experimental model in the guinea pig. Eight clinically available progesterones, medroxyprogesterone acetate (P3), megestrol acetate (P4), medrogestone (P5), alylestrenol (P6), linestrenol (P7), didrogesterone (P8), norethisterone (P9), and gestonorone caproate (P10) and two endogenous progesterones, progesterone (P1) and 17 alpha-hydroxyprogesterone (P2), were studied. Following in vivo treatment of guinea pigs, we determined the clearance of IgG-sensitized erythrocytes in vivo, the binding of IgG-sensitized erythrocytes by isolated splenic macrophages, and splenic macrophage Fcgamma receptor cell surface expression. All progesterones impaired the clearance of IgG-sensitized erythrocytes by decreasing splenic macrophage Fcgamma receptor expression. P5, P6, P7, and P8 were less effective. Flow cytometry and fluorescence microscopy with monoclonal antibodies demonstrated that progesterones decreased the cell surface expression of FcgammaR2 more than that of FcgammaR1,2. Clinically employed progestins impair the clearance of IgG-coated cells by decreasing splenic macrophage FcgammaRs expression. Thus, progesterones are candidate drugs for the treatment of immune disorders.

Female gout. Clinical spectrum and uric acid metabolism.

We reviewed the clinical features and uric acid metabolism in 37 female patients with gout. In 32 female patients (86%), gout was diagnosed after menopause. Among the five premenopausal patients, four had renal insufficiency and one had superactivity of phosphoribosylpyrophosphate synthetase. More than 50% of the female patients had osteoarthritis, hypertension, or renal insufficiency or were treated with diuretics. Comparison with 220 male patients with gout showed that female patients developed gout significantly later, more frequently had associated diseases, and more often were receiving diuretics, whereas significantly more male than female patients had alcoholism. The articular features of gout were similar in both groups. However, the prevalence of tophi was higher and its localization different in female than in male patients. Female patients with gout had a higher mean serum urate concentration and a lower mean urinary uric acid excretion than did male patients with gout. These differences were significant and independent of the effects of age, renal insufficiency, alcoholism, or previous diuretic intake. Renal underexcretion of uric acid appears to be more severe in female than in male patients with gout.

[Prevalence, physiopathology and processes associated with hypouricemia in a hospitalized population: analysis of 27,987 analytic determinations]. / Prevalencia, fisiopatología y procesos asociados a hipouricemia en una población hospitalaria: análisis de 27.987 determinaciones analíticas.

A prospective analysis of 27,987 serum samples revealed a uricemia less than 2.0 mg/dl in 172 patients (prevalence of 0.61%). One hundred and six patients were being treated with more than one drug. Amongst the 21 hypouricemic patients receiving only one drug the more frequently associated drugs were beta-lactamases, salicylates at high doses, and carbamazepine. Out of the 45 hypouricemic patients who were under no treatment, there were 12 cases of pregnancies, 6 had a neoplastic disease, 2 suffered chronic hepatopathy and one presented hereditary xanthinuria. Out of 7 non treated patients, 6 were uric acid hypersecretors and only one was hyposecretor. The results indicate that hypouricemia: a) is usually associated with an elevated renal excretion of uric acid and b) it is frequently associated with the administration of drugs although it can also be included in the context of multiple systemic disease.

Plasma oxypurinol concentration in a patient with allopurinol hypersensitivity.

Monitoring of plasma oxypurinol has been proposed to prevent allopurinol side effects. An 89-year-old man developed a severe desquamative rash, fever, eosinophilia, hepatocellular injury and renal failure after allopurinol administration. Eight hours after the last dose, plasma allopurinol was undetectable and plasma oxypurinol was 50 mumol/l. This is the first case in which severe allopurinol hypersensitivity occurred despite a simultaneous plasma oxypurinol concentration within recommended levels (below 100 mumol/l).