Bioactivity of Inhaled Methane and Interactions With Other Biological Gases

A number of studies have demonstrated explicit bioactivity for exogenous methane (CH4), even though it is conventionally considered as physiologically inert. Other reports cited in this review have demonstrated that inhaled, normoxic air-CH4 mixtures can modulate the in vivo pathways involved in oxidative and nitrosative stress responses and key events of mitochondrial respiration and apoptosis. The overview is divided into two parts, the first being devoted to a brief review of the effects of biologically important gases in the context of hypoxia, while the second part deals with CH4 bioactivity. Finally, the consequence of exogenous, normoxic CH4 administration is discussed under experimental hypoxia- or ischaemia-linked conditions and in interactions between CH4 and other biological gases, with a special emphasis on its versatile effects demonstrated in pulmonary pathologies

Dietary phosphatidylcholine supplementation attenuates inflammatory mucosal damage in a rat model of experimental colitis

This study was designed to follow the time course of inflammatory activation in a rodent model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. We hypothesized that oral phosphatidylcholine (PC) pretreatment regimens may influence leukocyte-mediated microcirculatory reactions in this condition. In series I, Wistar rats were monitored 1 day after colitis induction (n = 24), and in series II (n = 24) on day 6 following a TNBS enema. The PC-pretreated animals received a 2% PC-enriched diet for 6 days before the TNBS enema (series I), or for 3 days before and 3 days after TNBS treatment (series II). The macrohemodynamics, serosal microcirculation (visualized by intravital videomicroscopy), colonic xanthine oxidoreductase, myeloperoxidase and nitric oxide end products, and changes in proinflammatory cytokine levels in plasma were measured. The mucosal structural injury was monitored in vivo by means of confocal laser scanning endomicroscopy. The TNBS enema induced a systemic hyperdynamic circulatory reaction with increased serosal capillary blood flow and significantly elevated colonic inflammatory enzyme activities, levels of nitric oxide production, and cytokine concentrations. Acute colitis caused disruption of the capillary network, whereas the morphologic damage was less severe in series II. The PC pretreatment protocols led to significant decreases in the serosal hyperemic reaction, the cytokine levels, and the inflammatory enzyme activities. The objective signs of tissue damage were reduced in both series, and the number of mucus-producing goblet cells in the resolving phase of colitis was increased. Dietary PC efficiently decreases the cytokine-mediated progression of inflammatory events and preserves the microvascular structure in the large intestine. © 2012 by the Shock Society

A pericardialis tamponád kórélettana, klinikuma és állatkísérletes vizsgálati lehetőségei = Pathophysiology, clinical and experimental possibilities of pericardial tamponade

Absztrakt: A pericardialis tamponád a szívsebészeti ellátás egyik fontos sürgősségi kórképe, amelynek hátterében számos kóroki tényező állhat. A pericardialis folyadékfelszaporodás diagnosztikája és terápiája a klinikai gyakorlatban ma már sikeres, ugyanakkor a kialakuló kardiogén sokk következményeinek eredményes kezelése még sok esetben kihívást jelent. Az akut pericardialis tamponád és a krónikus pericardialis folyadékgyülem hatékony kezelési tervéhez a kórélettani folyamat megértése szükséges. A jelen közlemény célja, hogy a pericardialis tamponád jelenségéről és jelentőségéről is összefoglaló képet nyújtson, az orvostörténeti háttér és a fontosabb kórélettani tényezők ismertetésén át egészen az állatkísérletes modellalkotás szerepéig. Orv Hetil. 2018; 159(5): 163–167. | Abstract: Acute pericardial tamponade is one of the most emergent clinical scenarios in cardiac surgery. With numerous causes in the background, pericardial tamponade can lead to cardiogenic shock and death. In modern diagnostic era, the recognition of pericardial tamponade is simple, but its management and the long-term effects can still be challenging. Without the detailed understanding of the pathophysiological pathways diagnostic and therapeutic management plans of pericardial tamponade is very difficult. The aim of this review was to give a complex picture of pericardial tamponade, from its role in medical history to pathophysiology and its significance in surgical experimental models. Orv Hetil. 2018; 159(5): 163–167

Foszfolipidek szerepe a gyulladásban és a szeptikus szövődmények kialakulásában = Modulatory role of phospholipid metabolites in the inflammatory response and septic complications

A membránalkotó foszfatidilkolin (PC) és származékai gyulladáscsökkentő hatását bizonyítottuk számos szerv, köztük a pleura, a térdízület és a gasztrointesztinális nyálkahártya mikrokeringés funkcionális és strukturális károsodásával járó gyulladásos kórfolyamataiban. Elsőként közöltünk adatokat a központi idegrendszerben neuroprotektív hatású NMDA receptor antagonisták terápiás hatékonyságáról az enterális idegrendszerben akut és krónikus colitis modellekben. A mikrokeringési gyulladásos reakció jellemzésére standardizálható intravitális mikroszkópos eljárásokat dolgoztunk ki; karakterizáltuk a nyálkahártya károsodás jellegzetes paramétereit in vivo körülmények között, valamint a fokozott PC bevitel hatását: a mucin termelő kehelysejtek számának fokozódását. A PC előkezelés mérsékelte az endotoxin által kiváltott perifériás gyulladás miatt bekövetkező neurogenezis csökkenést a központi idegrendszerben is. Igazoltuk, hogy az ischaemia-reperfúziót kísérő antigén-független gyulladásos reakció alatt fokozódik az endogén metánképződés, és hogy PC-t tartalmazó speciális táppal befolyásolható. Meghatároztuk a PC deacilált származék GPC hatását a kémiai hipoxia által kiváltott szisztémás gyulladásos reakció fontosabb elemeire. A krónikus Na-azid kezelés is szignifikáns metán felszabadulást okoz, a metanogén bélflórától függetlenül. Mivel normoxiás metán inhaláció mérsékli a nyálkahártya strukturális károsodását, a képződő metán hozzájárulhat a mucosa homeosztázis normalizálásához. | We have characterized the anti-inflammatory action of a phosphatidylcholine (PC) and its metabolites in animal models of pleurisy, arthritis and gastrointestinal inflammatory damage. The microcirculatory consequences were evaluated by novel methods developed for direct intravital microscopic observations, and we have shown that the therapeutic potential of PC could be linked to the reduction of neutrophil leukocyte-mediated reactions. Dietary PC efficiently preserved the microvascular structure and the number of mucus-producing goblet cells in the large intestine. We have shown protective effects for the PC-enriched diet in endotoxin-induced experimental neuroinflammation in the central nervous system as well. We demonstrated that blockade of peripheral NMDA-sensitive glutamate receptors also provides therapeutic option to influence intestinal hypermotility, microcirculatory changes and inflammatory activation simultaneously. Further, we have provided evidence that exogenous PC modulated ischaemia-reperfusion-induced methane generation. Sodium azide-induced chemical hypoxia also increased endogenous methane production independently of the methanogenic flora. The inflammatory activities were reduced by treatment with GPC, a deacylated PC derivative. Since exogenous, normoxic methane inhalation was found to be protective against structural damage and inflammatory consequences, the results suggest that endogenous methane may normalize mucosal homeostasis after hypoxic events

Complement C5a inhibition improves late hemodynamic and inflammatory changes in a rat model of nonocclusive mesenteric ischemia

BACKGROUND: Nonocclusive mesenteric ischemia (NOMI) can evolve in a variety of low-flow states. Although the mechanisms leading to NOMI-related intestinal necrosis are largely unknown, circumstantial evidence suggests that excessive vasoconstriction and complement activation both play important roles in this process. Because targeting of the circulatory malfunction of the splanchnic area could be of therapeutic relevance, we set out to investigate the long-term effects of treatment with a complement C5a antagonist in a rat model of partial aortic occlusion (PAO)-induced transient mesenteric hypoperfusion. METHODS: The mean arterial pressure of the splanchnic area was kept between 30 and 40 mm Hg by 60 minutes of PAO in anesthetized male Sprague-Dawley rats. C5a inhibitor acetyl-peptide-A (AcPepA; 4 mg kg-1 intravenously) or vehicle administration was initiated at the 45th minute of PAO. After 24 hours, the animals were reanesthetized to record the macrohemodynamics and ileal microcirculation, and plasma and tissue samples were taken for determination of high-mobility group box protein-1 (HMGB-1), endothelin-1, tumor necrosis factor (TNF)-alpha levels, and small intestinal leukocyte infiltration. Epithelial structural changes were visualized by in vivo confocal laser scanning endomicroscopy. RESULTS: At 24 hours after PAO, mean arterial pressure, heart rate, and cardiac output were significantly greater, the intestinal intramural microcirculation was significantly impaired, and plasma HMGB-1, endothelin-1, TNF-alpha levels, the degree of epithelial damage and leukocyte infiltration was increased. The AcPepA treatment moderated the hemodynamic and microcirculatory changes, and decreased inflammatory activation and histologic signs of mucosal damage. CONCLUSION: C5a inhibition ameliorated the potentially harmful local mesenteric hypoperfusion and global long-term inflammatory consequences of PAO. This approach is of promise for use in NOMI-associated situations

Conjugation with Tris Decreases the Risk of Ketoprofen-Induced Mucosal Damage and Reduces Inflammation-Associated Methane Production in a Rat Model of Colitis

We have designed a new compound from the non-steroidal anti-inflammatory drug (NSAID) ketoprofen (Ket) and 2-amino-2-(hydroxymethyl)-1,3-propanediol (Tris) precursors, with the aim to reduce the gastrointestinal (GI) side effects of NSAID therapies. We investigated mucosal reactions in a standard rat model of colitis together with methane generation as a possible indicator of pro-inflammatory activation under this condition (approval number: V./148/2013). Whole-body methane production (photoacoustic spectroscopy) and serosal microcirculation (intravital videomicroscopy) were measured, and mucosal damage was assessed (conventional histology; in vivo laser-scanning endomicroscopy). Inflammatory markers were measured from tissue and blood samples. Colitis induced an inflammatory response, morphological colonic damage and increased methane output. Ket treatment lowered inflammatory activation and colonic mucosal injury, but macroscopic gastric bleeding and increased methane output were present. Ket-Tris reduced inflammatory activation, methane emission and colonic mucosal damage, without inducing gastric injury. Conjugation with Tris reduces the GI side effects of Ket and still decreases the inflammatory response in experimental colitis. Methane output correlates with the mucosal inflammatory response and non-invasively demonstrates the effects of anti-inflammatory treatments