D53 (Immucytal) is a compositive vaccine made of immunogenic ribosomes extracted from 4 bacterial species (Klebsiella pneumoniae, Haemophilus influenzae, Streptococcus pyogenes and Streptococcus pneumoniae) associated with a membrane proteoglycan from a non-encapsulated strain of Klebsiella pneumoniae (MPG-Kp). In this work we have studied the effect of the compound on human polymorphonuclear leukocyte (PMN) function "in vitro". We have demonstrated that D53 was able to significantly increase Fc- receptor dependent phagocytosis without modify the C3-receptor dependent activity. Furthermore D53 enhanced the oxidative metabolism (evaluated by chemiluminescence) both using cells in resting conditions or after stimulation with phagocytable or soluble stimuli. On the contrary D53 caused a dose-dependent inhibition of PMN migration toward different chemoattractants. Using the two constitutive fractions of the compound (ribosomes and proteoglycans) we have observed that the MPG-Kp component was mainly responsible for the modulating activity of the drug on human PMNs.

The effect in vitro of the naturally occurring flavonoid silybin on human polymorphonuclear leukocyte (PMN) functions has been studied. Preincubation of PMNs for 10 min at 37 degrees C with silybin inhibited, in a dose-dependent way, the luminol-enhanced chemiluminescence (CL) generated by stimulated cells without affecting the non-enhanced CL or superoxide anion production evaluated by the cytochrome C reduction assay. No significant effect of silybin on PMN phagocytic or chemotactic activities were found. Silybin did not absorb light at the wavelength of luminol-enhanced CL and was not toxic to PMNs at the concentrations used. Catalase, a scavenger of H2O2, inhibited luminol-enhanced CL to a similar degree as silybin; moreover, when incubated together with PMNs, silybin and catalase did not produce an additive inhibition of CL. On the contrary, the simultaneous addition of silybin and sodium azide, an inhibitor of myeloperoxidase, further increased inhibition over that seen with azide alone. These results suggest that inhibition of H2O2 may be the mechanism by which silybin inhibits the luminol-enhanced CL generated by stimulated PMNs. Such results indicate a possible anti-inflammatory activity for silybin even if their clinical relevance remains to be elucidated.

We investigated the effect of RU41740, a glycoprotein extracted from Klebsiella pneumoniae and possessing immunomodulating properties, on human neutrophil functions in vitro and ex vivo. Our in vitro results showed that RU41740 increased complement- and Fc receptor-dependent phagocytosis. Moreover, the drug enhanced the oxidative metabolism (assessed by chemiluminescence) both in resting and stimulated cells; in the latter case the RU41740-induced enhancement was observed when neutrophils were stimulated with opsonized particles of N-formyl-methionyl-leucyl-phenylalanine (FMLP) but not when phorbol myristate acetate was used. Using otherwise effective experimental conditions, RU41740 did not affect spontaneous or FMLP-induced neutrophil migration. For the ex vivo experience we tested neutrophils of ten elderly subjects with a previously demonstrated phagocytic defect. These subjects were treated orally with RU41740 at a daily dose of 2 mg for 1 week during the first month, and of 1 mg for 1 week in the second month. In this population, RU41740 was able to restore the impaired phagocytic activity and to induce a significant increase of spontaneous chemiluminescence (CL); stimulated CL was also positively influenced. These effects on neutrophils provide new explanatory bases for the immunostimulatory activity of RU41740.

We investigated the effect of RU41740, a glycoprotein extracted from Klebsiella pneumoniae and possessing immunomodulating properties, on human neutrophil functions in vitro and ex vivo.

Oxygen derived free radical release from activated neutrophils may be in part responsible of tissue damage in the acute phase of inflammation. We have shown that the methane sulfonanilide antiinflammatory agent nimesulide inhibits the respiratory burst of phagocytosing neutrophils without affecting their phagocytic or chemotactic responsiveness. In fact, chemiluminescence and superoxide anion generation by polymorphonuclear leukocytes (PMN) stimulated with zymosan particles or with the synthetic peptide FMLP are inhibited by nimesulide and its 4-OH metabolite in a dose dependent fashion without affecting cell viability. The control of the extracellular flux of radical species by phamacological compounds may affect the course of inflammation reducing tissue damage. Our data suggest that the inhibition of superoxide anion production by neutrophils is an additional mechanism of action of the antiinflammatory agent nimesulide.

The action of the new non-steroidal anti-inflammatory drug (NSAID) pirprofen on different functions of human polymorphonuclear leukocytes (PMNs) has been studied. The chemotaxis of PMNs was found to be affected by pirprofen in a dose-dependent fashion; at a concentration of 2 micrograms/ml (10 times lower than the therapeutic blood levels) it significantly inhibited PMN locomotion toward two different chemoattractants. Moreover pirprofen inhibited the chemiluminescent response in a dose- and stimulus-dependent way. In fact the drug inhibited the chemiluminescence induced by the soluble stimuli FMLP or PMA, but it was ineffective when zymosan particles were used. The phagocytosis and adhesion functions of the PMNs were not modified by pirprofen at the concentrations tested. These experimental results suggest that a reduction of the accumulation and activation of inflammatory cells in tissues may represent another way, together with cyclooxygenase inhibition, by which pirprofen realizes its antiinflammatory activity in vivo.

A 23-year-old girl with clinical and laboratory findings characteristic of chronic granulomatous disease is described. The patient was admitted to hospital because of severe disseminated aspergillosis. Studies of neutrophils showed normal phagocytosis but impaired microbicidal killing and a failure of the respiratory burst activity as measured by NBT-reduction, superoxide generation, chemiluminescence and antibody-dependent cell mediated cytotoxicity. Patient's neutrophils had normal chemotactic responsiveness but a marked impairment in the level of serum chemotactic activity was observed. Neutrophils from the parents and 2 maternal aunts showed normal values for all the determinations. The lack of evidence for a carrier state in all the family members studied together with the inability to detect a mixed population of neutrophils in our patient are in contrast with the Lyon's hypothesis of X-chromosome inactivation. Our findings suggest an autosomal recessive inheritance in this female with chronic granulomatous disease.

In order to investigate dopaminergic activity in two types of human obesity, childhood- and adult-onset, we have studied the responses of plasma TSH and prolactin to domperidone, a dopamine receptor antagonist, in 12 patients obese since early childhood, 12 patients with adult-onset obesity, and in 12 lean controls. All subjects were females. In childhood-onset obese patients the responses of plasma prolactin and TSH to antidopaminergic stimulation were lower than those of adult-onset obese patients and lean controls. Conversely, the stimulus elicited a normal response of plasma prolactin and an exaggerated response of plasma TSH in adult-onset obese patients. These data indicate the presence of differing dopaminergic tone in the two types of human obesity.

This research deals with an analysis of forms of participation in a participatory design (PD) process of a software that assesses the sustainability of agricultural cropping systems. We explore the actual forms of participation of designers and users by adapting an Actual Role Analysis in Design approach (Barcellini et al., 2013) to capture the levels of abstraction (conceptual, functional and operational) of participants' discussions. We show that: (1) the process does not only concern the design of the artifact itself, but also the design of the concept of sustainability; (2) all participants (users & designers) have a role in co-designing the concept (in our case, sustainability); (3) some roles and profiles are key to this co-design. We discuss our contributions to both the research and the practices of participatory design. These contributions deal with the production of a method and related knowledge about actual activities in participatory design situations. They may support the development of relevant training programs regarding participatory situations, or be reflexive activities that can help those who are involved in designing and leading in participatory situations, to make improvements.