Effects of Zinc on Production of Active Oxygen Species by Rat Neutrophils

Abstract: The effects of zinc on the production of active oxygen species were investigated in rat neutrophils by chemilumi-nescence and spectrophotometric assays. The luminol-dependent chemiluminescence in unstimulated neutrophils showed a single peak. Zinc at concentrations lower than 0.1 mM augmented the intensity of chemiluminescence and showed a bimodal pattern, the first peak of which was inhibited by superoxide dismutase and catalase, while the second peak disappeared in the presence of catalase, but was unaffected by superoxide dismutase. At the same concentrations of zinc, O₂^? and H₂O₂ production increased, but secretion and activity of myeloperoxidase were not affected. Zinc at 0.1 mM enhanced the second peak of luminol-dependent chemiluminescence, and concomitantly O₂^? and H₂O₂ production of neutrophils stimulated with formyl-methionyl-leucyl-phenylalanine. Homogenized neutrophils showed a bimodal pattern on induction by zinc, the second peak of which was inhibited slightly by catalase and completely by sodium azide, but was not inhibited by superoxide dismutase. Zinc-induced O₂^? production was inhibited by pertussis toxin, but was not significantly inhibited by a protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), or a calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7). These results suggest that zinc can augment luminol-dependent chemiluminescence by increasing O₂^? production through the classical signal transduction pathway, and by increasing H₂O₂ not via O₂^?.     

Two cases of Trichosporon beigelii pneumonia in immunocompromised hosts

Two cases of Trichosporon beigelli pneumonia in severely immunocompromised patients are reported. At autopsy, Trichosporon beigelii was detected in all lobes in one patient who had a small cell lung cancer. Polymycotic infection involving Trichosporon beigelii and Aspergillus was proved in the other patient who had a non-Hodgkin's lymphoma. Miconazole therapy was not effective against Trichosporon beigelii infection in both cases. Although diagnosis and management are difficult, Trichosporon beigelii must be considered as a cause of visceral opportunistic fungal infection.     

Protective effect of recombinant neutrophil elastase inhibitor (R-020) on sepsis-induced organ injury in rat

Severe inflammatory responses after major surgeries, trauma, and infection develop multiple organ dysfunction. In the mechanisms of the pathogenesis of these responses, activated neutrophils are thought to be important in terms of their ability to produce various kinds of proteinases, which can degrade various proteins constructing human tissues. Among their proteinases, neutrophil elastase is the strongest serine proteinase secreted from activated neutrophils. Thus, we examined in this study the inhibitory effect and therapeutic efficacy of newly produced recombinant human Kunitz-type proteinase inhibitor (R-020), which coded the second domain of human urinary trypsin inhibitor. R-020 was effective in significantly improving the survival rate after induction of the rat lethal peritonitis model (cecal ligation and punctureinduced septic shock model). We suggest that various serine proteinases are implicated in the pathogenesis of neutrophil-related multiple organ failure and that recombinant human Kunitz-type proteinase inhibitor might be effective in the treatment of these kinds of organ dysfunction.     

Foxl2 disruption causes mouse ovarian failure by pervasive blockage of follicle development

FOXL2 mutations cause gonadal dysgenesis or premature ovarian failure (POF) in women, as well as eyelid/forehead dysmorphology in both sexes (the 'blepharophimosis-ptosis-epicanthus inversus syndrome', BPES). Here we report that mice lacking Foxl2 recapitulate relevant features of human BPES: males and females are small and show distinctive craniofacial morphology with upper eyelids absent. Furthermore, in mice as in humans, sterility is confined to females. Features of Foxl2 null animals point toward a new mechanism of POF, with all major somatic cell lineages failing to develop around growing oocytes from the time of primordial follicle formation. Foxl2 disruption thus provides a model for histogenesis and reproductive competence of the ovary.     

Serum-manganese-superoxide dismutase: normal values and increased levels in patients with acute myocardial infarction and several malignant diseases determined by an enzyme-linked immunosorbent assay using a monoclonal antibody

An enzyme-linked immunosorbent assay (ELISA) has been developed for human manganese-superoxide dismutase (Mn-SOD), using a specific monoclonal antibody raised against the purified enzyme. The Mn-SOD molecule comprises four identical sub-units and this permitted the development of a symmetrical assay, using the same monoclonal antibody as both capture and detector. The assay offers a specific, sensitive and convenient means of measuring immunoreactive Mn-SOD in human sera. Under optimum conditions, the sensitivity of the assay permits the detection of 2-200 ng of purified Mn-SOD from human liver. The mean serum Mn-SOD levels of normal healthy males and females were 99.8 +/- 24.8 (mean +/- SD) and 88.8 +/- 20.8 (mean +/- SD), respectively. A high level of the enzyme was found in the sera of patients with acute myocardial infarction as well as malignant diseases such as acute myeloid leukemia, primary hepatoma and gastric cancer. This is the first report of an ELISA using a monoclonal antibody specific for a distinct epitope of Mn-SOD.