E. Capodicasa

Activity Inhibition of Cytolytic Lymphocytes by Omeprazole

This study examined the in vitro effect of omeprazole (OM) on various types of murine cytocidal lymphocytes. The results show that OM caused a strong inhibition of basal natural killer (NK) activity in spleen cells (SC) from untreated CD2F1 mice; in peritoneal exudate cells and SC activated in vivo by injection of maleic anhydride divinyl ether 1,2‐copolymer (MVE‐2) or inactivated Candida albicans (CA); in lymphokine‐activated killer (LAK) activity generated in vitro from splenocytes cultured with rhIL‐2 and in allo‐specific cytotoxic lymphocyte‐mediated lysis generated in vitro. A significant inhibition of cytotoxic activity of all types of effector cells after 30u2003min incubation was already induced by OM at 1u2003×u200310−3u2003m concentration, after 1u2003h incubation at 5u2003×u200310−4u2003m and after 4u2003h incubation at 1u2003×u200310−4u2003m OM. Complete inhibition of lytic activity was obtained after 4u2003h incubation of effector cells with 1u2003×u200310−3u2003m OM. No inhibitory effect was observed at 5u2003×u200310−5u2003m OM concentration. Indomethacin did not abrogate the OM inhibitory effect on NK/LAK activity, suggesting that prostaglandins are not involved in the process leading to suppression of cytocidal activity. When effector cells were incubated with OM in presence of rhIL‐2 (500u2003U/ml), the cytokine failed to antagonize the inhibitory effect of the drug. On the contrary, if OM pretreated cells were incubated with rhIL‐2 for a further 18u2003h after drug removal, this cytokine was able to restore NK activity, but only when NK inhibition was incomplete. These results demonstrate for the first time that in vitro OM causes a rapid, strong effect on various types of cytotoxic lymphocytes ranging from cytotoxicity inhibition to irreversible cell damage.

Effect of Lansoprazole on Human Leukocyte Function

Recent findings on the capacity of omeprazole to influence various leukocyte functions, in vitro, raises the question on the potential use of protonic pump inhibitors, commonly used in the treatment of acid-secretion-related disorders, as immunomodulators. The aim of this study was to evaluate the in vitro effect of lansoprazole on human natural killer (NK) cell cytotoxix activity, chemotaxis and superoxide anion (O2*-) generation exerted by polymorphonucleated cells (PMNs). NK cytotoxicity activity was assessed by a 51Cr release assay, PMN chemotaxis was determined by an under agarose method and O2*- generation was analyzed on the basis of reduced cytochrome C. Incubation times with lansoprazole was 30 min for PMNs and 1-4.5 hours for NK cells, respectively. Lansoprazole induced significant dose dependent inhibition of NK cell activity and PMN functions at concentrations ranging from 100 to 1,000 microM. This study demonstrate that lansoprazole, like omeprazole, inhibits several leukocyte functions, in vitro, then suggesting that protonic pump inhibitors are able to provoke these effects, at least at certain doses.

Neutrophil peripheral count and human leukocyte elastase during chronic lithium carbonate therapy.

Abstract Plasma levels of human polymorphonuclear elastase (PMN-E) are considered a marker of granulocyte activation and can potentially complement the peripheral neutrophil count in laboratory and pathophysiological settings. Neutrophilic leukocytosis is a well known effect of lithium therapy, but there is no information about the concomitant behaviour of PMN-E in these patients. The aim of this study was to evaluate both polymorphonuclear leukocyte count and plasma PMN-E levels in depression patients undergoing chronic lithium therapy. Absolute and differential leukocyte count in venous peripheral blood was determined by an automated method, and PMN-E evaluated by enzyme immunoassay. 39 patients (11 males, 28 females; mean age 43. ± 6 02) with depression disorders were studied, during lithium carbonate therapy. Neutrophilia (neutrophil count > 7.500±109 cells per liter) was found in 7 (18 %) patients and an increase in plasma PMN-E levels (PMN-E > 56μg per liter) in 6 (15 %), No correlations were found between neutrophil count, plasma concentration of PMN-E, plasma level of lithium and duration of therapy. The results show that in these patients, not only the PMN count but also elastase levels can exceed the normal range. The absence of correlation between these two parameters suggests that the state of PMN activation is not linked to their number in peripheral blood.

Changes in plasma level of human leukocyte elastase during leukocytosis from physical effort

Abstract Physical exercise is known to induce immunological changes, mainly leukocytosis and neutrophil activation. However, it is not known to what extent the leukocytosis, observed after exertion, is associated with an increase in plasma neutrophil elastase, an early marker of inflammatory response and neutrophil degranulation. In the present study changes in circulating leukocyte and neutrophil counts and human neutrophil elastase plasma levels were evaluated in volley‐ball players before and after 2 h and 12 h prolonged training, during a competition season. For comparison, the same parameters were evaluated in untrained subjects before and after a jogging session. Basal white blood cell WBC, polymorpho nuclear PMN, and human polymorpho nuclear‐elastase PMN‐ELA values were within the normal healthy reference range and no significant differences were found between the two groups studied. Venous blood samples of nine volley‐ball players showed a statistically significant increase in blood WBCs after 2 h exercise. This effect was paralleled by a statistically significant increase in PMN‐ELA concentration compared to the values observed in the same individuals at rest. The exercise did not significantly change the basal correlation parameters between PMN level and PMN‐ELA concentration. More pronounced WBC, PMN, and PMN‐ELA increases were observed in the seven inactive subjects after 2 h jogging. There was no linear correlation between increased PMN counts and increased PMN‐ELA concentrations in untrained subjects after exercise. The results show that not only the leukocyte count but also PMN‐ELA plasma levels can be higher after physical effort. This has a practical significance as regards differential diagnosis demonstrating that determination of these two laboratory parameters can give abnormally high values even in the absence of an existing inflammatory process. Besides, lack of correlation between PMN count and PMN‐ELA plasma levels in the untrained group suggest a state in which activation of the neutrophils is not connected with their number in peripheral blood.

Study of Ethane Level in Exhaled Breath in Patients with Age-Related Macular Degeneration: Preliminary Study

Purpose: A variety of factors have been implicated in the pathogenesis of age-related macular degeneration (ARMD), and oxidative stress plays an important role in the onset and progression of the disease. Breath ethane is now considered a specific and non-invasive test for determining and monitoring the trend of lipid peroxidation and free radical-induced damage in vivo. This test provides an index of the patients’ overall oxidative stress level. We evaluated the breath ethane concentration in exhaled air in patients with advanced ARMD. Methods: In this study, we enrolled 13 patients with advanced ARMD and a control group, and a breath analysis was carried out by gas chromatography. Results: The mean ethane level in the ARMD patients was 0.82 ± 0.93 nmol/l (range: 0.01–2.7 nmol/l) and the mean ethane value in the control group was 0.12 ± 0.02 nmol/l (range: 0.08–0.16 nmol/l). The difference between the values of the 2 groups was statistically significant (p < 0.005). Receiver operating characteristic analysis showed an elevated area under the curve (0.831; 95% CI: 0.634–0.948), with a significance level of p < 0.0014 (area = 0.5). Conclusions: These preliminary results seem to indicate that breath ethane levels are higher in most patients with ARMD. The breath ethane test could thus be a useful method for evaluating the level of oxidative stress in patients with ARMD. To our knowledge, there are no data on this type of analysis applied to ARMD.

Plasma Levels of Elastase-Alfa 1-Proteinase Inhibitor in Dependent Legs of Patients with Venous Disease: A Preliminary Report

Polymorphonuclear leukocyte elastase (PMN-elastase) is a potent serine protease stored in azurophilic granules of neutrophils. During activation or lysis of polymorphonuclear cells, PMN-elastase, primarly responsable for intracellular protein breakdown, is liberated in intercellular compartments.

Study of Morphoquantitative Leukocytic District Behaviour in Chronic Venous Disease: Relationship Between Haematic Values and Leukocytic Integrin

In the last few years numerous and detailed publications have indicated the leukocyte as potentially beging in a position to play a pathogenous rather than a defensive role in many circumstances. Nowadays particular interest is being paid to the pathogenous role thatwhite blood cells can have in the cardiovascularfield, and particulary at a microcirculatory level.