Serum adenosine deaminase activity in HIV positive subjects. A hypothesis on the significance of ADA2.

Adenosine deaminase activity (ADA) was assayed in the serum of 137 HIV positive subjects: 131 intravenous drug abusers, 3 female partners of HIV positive abusers, 1 son of HIV positive abuser and 2 blood-transfused patients, subdivided into the following groups: 73 asymptomatic, 15 with ARC, 37 with LAS, 5 with L-AIDS and 7 with AIDS. Results show an increase of ADA activity in 100% of L-AIDS group, in 64% of AIDS group, in 62% and 42% of LAS and ARC groups, respectively, and in 36% of the asymptomatic groups. These findings must be confirmed with wider series in order to be further and better evaluated. According to relative substrate specificities, optimal pH and Km, enzymatic activity can be attributed principally to the ADA2 isoenzyme. The probability that ADA2 originates exclusively from the Monocyte-Macrophage cell system (MoMaCS) which actively releases this enzyme in the presence of live parasites in the cells' interior, is discussed. Moreover, it was hypothesized that in the MoMaCS the enzyme constitutes a microbicidal mechanism independent of the respiratory burst.

Acute respiratory distress syndrome due to influenza virus A/H1N1v in a patient with HIV/HCV co-infection.

The clinical severity of human infection with the novel influenza virus A/H1N1v has not been completely defined, especially in HIV/hepatitis C virus (HCV) infected patients. Although most patients develop mild to moderate symptoms, severe disease may occur in a limited proportion of cases. We report the case of a 44-year-old man infected with HIV and HCV with a high CD4 cell count who developed acute respiratory distress syndrome associated with influenza virus A/H1N1v infection. The patient recovered completely after oseltamivir therapy and mechanical ventilation.

Increased red cell calcium, decreased calcium adenosine triphosphatase, and altered membrane proteins during fava bean hemolysis in glucose-6-phosphate dehydrogenase-deficient (Mediterranean variant) individuals.

RBCs from four glucose-6-phosphate dehydrogenase (G6PD)-deficient (Mediterranean variant) subjects were studied during fava bean hemolysis. In the density-fractionated RBC calcium level, Ca2+-ATPase activity, reduced glutathione level, and ghost protein pattern were studied. In the bottom fraction, containing most heavily damaged RBCs, calcium level ranged from 143 to 244 mumol/L RBCs (healthy G6PD-deficient controls: 17 +/- 5 mumol/L RBCs). The Ca2+-ATPase activity ranged from 0.87 to 1.84 mumol ATP consumed/g Hb/min (healthy G6PD-deficient controls: 2.27 +/- 0.4). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of ghosts showed: (1) the presence of high mol wt aggregates (in three cases they were reduced by dithioerythritol; in one case, only partial reduction was possible); (2) the presence of multiple, scattered new bands; and (3) the reduction of band 3. Oxidant-mediated damage to active calcium extrusion, hypothetically associated with increased calcium permeability, may explain the large increase in calcium levels. They, in turn, could activate calcium-dependent protease activity, giving rise to the profound changes in the ghost protein pattern.

Mechanisms of red cell clearance in favism.

Divicine (2,6-diamino-4,5-dihydroxypyrimidine) is a quinoid compound contained in high amounts in all fava bean strains. It elicits a number of metabolic and rheological modifications in G6PD-deficient RBC. Besides this, it stimulates erythrophagocytosis by mouse peritoneal macrophages and formation of crossbonded red cells. The latter are intracellularly membrane-bonded red cells, which form during hypertonic incubation and subsequent swelling. All effects observed in vitro were also observed in vivo in the early phases of fabic hemolysis. In particular, phagocytosis and crossbonding offer a basis for understanding extravasal hemolysis.

Red cell G6PD decay in circulating cells: a possible marker for variants identification.

The age dependent decay of G6PD activity was studied in G6PD deficient red cells free of leukocytes and platelets and separated on a density gradient. The pattern of decay can be a useful additional parameter to characterize enzyme variants.

Effect of divicine and isouramil on red cell metabolism in normal and G6PD-deficient (Mediterranean variant) subjects. Possible role in the genesis of favism.

Fava beans contain high amounts (up to 6.7 g/100 g dry weight) vicine and convicine. Their active aglycones divicine and isouramil have equivalent metabolic effects. They rapidly oxidize GSH to GSSG in normal and G6PD-deficient red cells. No regeneration of GSH occurs in deficient cells. The stoichiometry of the divicine oxidation of GSH is 1:1. Ascorbic acid is quickly oxidized by isouramil in both normal and deficient cells but regenerates only in normal cells. Isouramil oxidizes NADH at a much lesser extent than NADPH. Glycolysis is activated at the glyceraldehyde 3-phosphate dehydrogenase step. Divicine strongly stimulates hexone monophosphate shunt only in normal red cells. Divicine alone or associated with ascorbic acid has almost no effect in deficient red cells. Malonyl dialdehyde production is slight and virtually the same in normal and deficient cells treated with 5 mM isouramil. Large polypeptide aggregates are formed after 12 and 24 hours incubation with 1 mM divicine in deficient cells only. Divicine (0.25 mM) markedly decreases the filterability of deficient cells. The results are consistent with a causal role of divicine/isouramil in the genesis of the hemolytic crisis occurring in G6PD-deficient subjects after fava bean ingestion.