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OBJECTIVE: Gastrointestinal methane generation has been demonstrated in various stress conditions, but it is not known whether nonasphyxiating amounts have any impact on the mammalian pathophysiology. We set out to characterize the effects of exogenous methane administration on the process of inflammatory events arising after reoxygenation in a large animal model of ischemia-reperfusion. DESIGN: A randomized, controlled in vivo animal study. SETTING: A university research laboratory. SUBJECTS: Inbred beagle dogs (12.7 6 2 kg). INTERVENTIONS: Sodium pentobarbital-anesthetized animals were randomly assigned to sham-operated or ischemia-reperfusion groups, where superior mesenteric artery occlusion was maintained for 1 hr and the subsequent reperfusion was monitored for 3 hrs. For 5 mins before reperfusion, the animals were mechanically ventilated with normoxic artificial air with or without 2.5% methane. Biological responses to methane-oxygen respirations were defined in pilot rat studies and assay systems were used with xanthine oxidase and activated canine granulocytes to test the in vitro bioactivity potential of different gas concentrations. MEASUREMENTS AND MAIN RESULTS: The macrohemodynamics and small intestinal pCO(2) gap changes were recorded and peripheral blood samples were taken for plasma nitrite/nitrate and myeloperoxidase analyses. Tissue superoxide and nitrotyrosine levels and myeloperoxidase activity changes were determined in intestinal biopsy samples; structural mucosal damage was measured by hematoxylin and eosin staining. Methane inhalation did not influence the macrohemodynamics but significantly reduced the magnitude of the tissue damage and the intestinal pCO(2) gap changes after reperfusion. Furthermore, the plasma and mucosal myeloperoxidase activity and the intestinal superoxide and nitrotyrosine levels were reduced, whereas the plasma nitrite/nitrate concentrations were increased. Additionally, methane effectively and specifically inhibited leukocyte activation in vitro. CONCLUSIONS: These data demonstrate the anti-inflammatory profile of methane. The study provides evidence that exogenous methane modulates leukocyte activation and affects key events of ischemia-reperfusion-induced oxidative and nitrosative stress and is therefore of potential therapeutic interest in inflammatory pathologies. [ABSTRACT FROM AUTHOR]

Background/Aims: Phosphatidylcholine (PC)-derived choline exhibits anti-inflammatory properties in stress conditions. Phosphatidylethanolamine (PE) and N-acylphosphatidylethanolamines (NAPEs) are endogenous bioactive phospholipids linked to the PC and endocannabinoid metabolisms. We hypothesized that an increased dietary input of PC, PE and NAPE may interfere with leukocyte reactions and thus decreases the inflammatory activation. Methods: CFLP mice were fed with a control diet or with a diet supplemented with 1% PC, 0.4% PE and 0.1% NAPE for 7 days before the induction of pleurisy with carrageenan. Pleural leukocyte migration, pulmonary mast cell degranulation (Alcian blue-safranin O staining), and the activities of inducible nitric oxide synthase, xanthine oxidoreductase and myeloperoxidase were determined in lung tissue biopsies. Results: The carrageenan-induced inflammatory response was characterized by pulmonary leukocyte infiltration, mast cell degranulation and significantly increased inducible nitric oxide synthase and xanthine oxidoreductase activities (by 82 and 60%, respectively). Treatment of mice with acetylsalicylic acid or with dietary PC + PE + NAPE supplementation significantly decreased the leukocyte reaction, and suppressed the activity of the pulmonary proinflammatory enzymes. Conclusion: This study confirms a potential for dietary PC + PE + NAPE supplementation to influence events crucial for the remission of acute inflammation. PC + PE + NAPE administration could possibly be a novel preventive or pharmacotherapeutic option in inflammatory pathologies. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Acetylsalicylic acid (ASA)-induced gastric injury is reduced when ASA is administered along with phosphatidylcholine. The hydrolysis of endogenous phosphatidylcholine leads to the production of betaine, which may participate in the maintenance of cellular homeostasis. The present aims were to investigate the effects of exogenous betaine and its palmitic acid complex (betaine-palmitate) in the protection of the gastric mucosa in ASA-induced subacute damage. Methods: Repeated doses of ASA were given intragastrically to male Wistar rats. Control rats were given vehicle only, while treated animals were challenged with ASA or with ASA along with betaine, palmitic acid or betaine-palmitate. The gastric mucosa was examined after 3 days and the nature of any microscopic mucosal injury was assessed by histology. The extent of macroscopic damage, changes in permeability (assessed by Evans blue method) and tissue ATP concentrations were determined in separate series. Results: ASA induced a significant fall in the ATP content of the mucosa, which was not affected by the other drugs used in the study. However, the ASA-induced mucosal permeability increase could be completely reversed by betaine-palmitate supplementation. The extent of severity of the macroscopic and microscopic lesions was 33% and 2.45, respectively, for ASA, as compared with 15% and 2.2 for betaine, 14% and 1.9 for palmitic acid and 3% and 1.4 for betaine-palmitate. Conclusions: Betaine-palmitate affords a significant protective effect against ASA-induced injury, without influencing the ATP synthesis, and this suggests that the defence is due to its ability to prevent secondary damage. [ABSTRACT FROM AUTHOR]

The in vitro effects of liposomes on HaCaT humph keratinocytes were studied with regard to their uptake, lipid fluidity and proliferation of the cells. Oligolamellar liposomes, prepared from soya bean phospholipids, had a mean size of 150 nm and consisted predominantly of phosphattdylcholine (83%) and phosphatidylethanolamine (10%) and the fatty acids comprised mainly linoleic acid (66%) or other unsaturated fatty acids. After 6 and 24 h of incubation with I and 0.1% w/v of liposomal lipids, phase-contrast microscopy revealed marked cytoplasmic vacuolization of the cells. Keratinocytes treated with the liposomes contained aggregations of multilaminated lipid material without delimiting cell membranes. The cellular lipid fluidity (reciprocal of diphenylhexatriene fluorescence polarization P-value) correlated with liposomal concentration and incubation time. A significant elevation of lipid fluidity (P < 0.05) was observed with I and 0.1% liposomes after 1 h of incubation (81.84 ± 4:7 and 95.7 ± 1.2% of control P value) and for 0.01% liposomes alter 3 h (96.24 ± 5%). Maximum fluidity occurred alter 48 h of exposure to 1% liposomes (42.1 ± 3.1%). Exposure to liposomal lipids for 24 and 48 h resulted in suppressed cell proliferation with 50% inhibition concentrations (IC50), being 0.06% for incorporation of [³H]-thymidine. 0.08% for [14C]-amino-acid corporation and > 1% for protein content per well after 24 h of exposure. The cells were able to proliferate and lipid fluidity returned to normal within 7 days following discontinuation of incubation with liposomal lipids. [ABSTRACT FROM AUTHOR]

A recent classification of alterations of midpiece and flagellum describes the phenomenon of abnormal staining behaviour of human sperm flagella during Papanicolaou and Shorr staining. In these techniques, human sperm tails normally stain red; however, if epididymal function is disturbed, the flagella appear bluish, while they are devoid of other recognizable defects. Such spermatozoa were shown to be immotile, the motility disturbance being referred to as epididymal dysfunction. To define the physiological substrates of this descriptive phenomenon, caput spermatozoa from 10 epididymides of five patients who had undergone orchiectomy because of prostatic cancer were investigated. These spermatozoa showed severe motility disturbances, and almost all their flagella stained atypically. Attempts to stimulate such spermatozoa by pentoxifylline achieved a slight improvement in motility. However, addition of seminal plasma from fertile donors resulted in a significant improvement in motility, accompanied by an increase in the number of normally stained flagella. Even better results were achieved by incubation with liposomes made from soybean lipids, mainly phosphatidylcholine. It is concluded that poor motility and atypical staining behaviour of human caput sperm tails can at least partly be related to a lack of phospholipids in the flagellar membrane. Substitution of phospholipids may be a therapeutic approach in procedures using caput spermatozoa, although in addition to the improvement of sperm motility, the enhancement of fertilizing capacity remains to be established. [ABSTRACT FROM AUTHOR]

The choline moiety of phosphatidylcholine (PC) molecules provides protection against reductive stress conditions in vitro, and PC possess remarkable antiinflammatory features by influencing intercellular adhesion and macrophage activation. During endotoxemia, PC administration may partially counteract the effects of nitric oxide overproduction by scavenging nitric oxide and enhancing its elimination. The present study also provides further support for the anti-inflammatory characteristics of PC.

The article reports that the healing and functioning of vascularized bone autografts depend mainly on the patency of the microcirculation. Mast cells (MCs) in the surrounding of the vascular network sensitively react to the redox changes of the microenvironment with release of preformed and newly synthetized mediators. Recently, researchers showed that the choline moiety of phosphatidylcholin (PC) molecules could provide electrophilic methyl groups for a defense mechanism which may operate against reductive stress conditions in vitro. The present study was designed to examine and characterize the reactive microcirculatory changes and MC reactions in the rat tibial periosteum following hindlimb ischemia and reperfusion and to evaluate the effects of systemic PC post-treatment in this condition.