Szabad gyökök és a máj ischaemiás-reperfúziós károsodása

The critical importance of the ischemic-reperfusive injury is well documented with regards to numerous organs and clinical conditions. Oxygen free radicals play a central role in the mediation of the injury, which dominantly influences the prevalence of postoperative complications, (long term) organ damage, and the potential manifestation of systemic reactions. The both anatomically and pathophysiologically unique ischemic-reperfusive injury of the liver, which is expressively vulnerable to free radicals, is of utmost importance in liver surgery. Several techniques (adaptive maneuvers, chemical agents) are known to ameliorate the reperfusive injury. Based on the prior research of the workgroup of the author, the aim of the current article is to overview the set of measures capable of attenuating ischemic-reperfusive injury (ischemic preconditioning, -perconditioning, administration of adenosine, -inosine, -levosimendan, and -poly-ADP-ribose-polymerase inhibitor), with special attention to the ischemic-reperfusive injury of the liver, as well as the special pathophysiological role of free radicals in mediating hepatic damage. Orv. Hetil., 2015, 156(47), 1904-1907

Akut mesenterialis ischaemia: biomarker egyenlő diagnózis?

Acute mesenteric ischemia is an emergency condition that requires immediate therapy. Despite advances in the fields of surgery and intensive therapy, the mortality of this condition remains high. This is due to the broad variability of clinical presentations and non-specific laboratory findings, which delay the diagnosis allowing the ischemia to progress and further worsening the patients' chances of survival. Thus, there is a significant need for reliable and enhanced serological markers of intestinal ischemia. The authors review the traditionally used and novel experimental serological markers for early diagnosis of mesenteric ischemia. Orv. Hetil., 2014, 155(41), 1615-1623

Numerical analysis of the potential for mixed thermal convection in the Buda Thermal Karst, Hungary

The pilot area has high geothermal potential characterized by prominent thermal anomalies, such as thermal springs and spas which tap the Triassic carbonate aquifers. Therefore, numerical simulations were carried out to examine the temperature field and flow pattern considering three successive heat transport mechanisms: thermal conduction, forced and mixed thermal convection in order to highlight the role of different driving forces of groundwater flow in the Buda Thermal Karst. New hydrological insights for the region: Compared to thermal conduction, topography-driven heat advection increases the surface heat flux. The superimposed effect of free thermal convection facilitates the formation of time-dependent mixed thermal convection from the deep carbonate layers. The Nusselt number varied between Nu = 1.56 and 5.25, while the recharge rate (R) ranged from R = 178 mm/yr to 250 mm/yr. Radiogenic heat production and hydraulically conductive faults have only a minor influence on the basin-scale temperature field and flow pattern. Boundary conditions prescribed on the temperature and pressure can considerably affect the numerical results. In each scenario, independently of the model parameters, time-dependent mixed thermal convection evolved both in the deep and the confined parts of the karstified carbonates of the Buda Thermal Karst system

Numerical investigation of the combined effect of forced and free thermal convection in synthetic groundwater basins

The theoretical examination of the combined effect of water table configuration and heat transfer is relevant to improve understanding of deep groundwater systems, not only in siliciclastic sedimentary basins, but also in fractured rocks or karstified carbonates. Numerical model calculations have been carried out to investigate the interaction of topography-driven forced and buoyancy-driven free thermal convection in a synthetic, two-dimensional model. Effects of numerous model parameters were systematically studied in order to examine their influence on the Darcy flux, the temperature and the hydraulic head field. It was established that higher geothermal gradients and greater model depths facilitate the evolution of time-dependent free thermal convection in agreement with changes of the thermal Rayleigh number and the modified Péclet number. However, increasing water table slope and anisotropy coefficient favor the formation of stationary forced thermal convection. Free thermal convection mainly affects the deeper part of the midline and the discharge zone of the synthetic model. In the examined model basins, the position of the maximum hydraulic head is located within the bottom thermal boundary layer near the recharge zone. This divergent stagnation point underlies a local downwelling zone characterized by underpressure. These simulations draw attention to the importance of understanding the combined effect of forced and free thermal convection in sedimentary basins regarding regional groundwater flow patterns, and temperature distributions

Experimental Models of Hemorrhagic Shock: A Review

Massive blood loss leading to hypovolemic shock is still a life-threatening situation. Recently, a great number of investigations have been conducted in order to understand the pathophysiological and immunological changes taking place during shock and to develop treatment strategies. These preclinical trials are based on animal studies. Although a wide spectrum of species and experimental models are available to researchers, it is rather difficult to create an ideal animal model to study hemorrhagic shock. A major challenge for investigators is the generation of a system which is simple, easily reproducible and standardized, while being an accurate replica of the clinical situation. The goal of this review is to summarize the current experimental models of hemorrhagic shock, highlighting their advantages and disadvantages to help researchers find the most appropriate model for their own experiments on hypovolemic shock

Gépi perfúzió a vesetranszplantációban

A szervtranszplantáció területén évek óta fennálló probléma az egyre növekvő szervigény mellett az elérhető donor szervek számának stagnálása. Az ellentét feloldására tett kísérletek több irányból közelítették meg a kérdést: egyrészről a donorkritériumok kiterjesztésével, másrészt az eltávolított szervek minőségének megőrzésére kidolgozott gépi perfúzió módszerével, melynek használata bizonyítottan csökkenti a késve meginduló graftműködés előfordulását, és javítja a grafttúlélést. Ezek az előnyök különösen a kiterjesztett kritériumú donáció tekintetében kifejezettek. A vese transzplantáció során egyre szélesebb körben alkalmazzák a gépi perfúziót; jelenleg a legelterjedtebb formája a hypothermiás gépi perfúzió, azonban egyre több érv szól a normothermiás eljárás mellett is. Az alkalmazott modalitástól függően nemcsak szervkonzerválásra, de szervkondicionálásra is van lehetőség. Napjainkban számos kutatás folyik a gépi perfúzió során alkalmazható terápiás lehetőségekről, melyek a jövőben fontos szerepet játszhatnak az ischaemia reperfúziós károsodás és az immunizáció csökkentésében. Közleményünkben a kiterjesztett kritériumú donáció rövid áttekintését követően összefoglaljuk a gépi perfúzió alkalmazási módjait, aktuális eredményeit, valamint diagnosztikus és terápiás lehetőségeit a vesetranszplantáció területén

Increased circulating interleukin-17 levels in preeclampsia

Increasing evidence suggests that an exaggerated maternal systemic inflammatory response, as well as an angiogenic imbalance plays a central role in the pathogenesis of preeclampsia. In this study, we determined circulating levels of interleukin-17 (IL-17) along with those of angiogenic factors in healthy non-pregnant and pregnant women and preeclamptic patients, and examined whether serum IL-17 levels of preeclamptic patients were related to their clinical features and angiogenic factor concentrations. Fifty-nine preeclamptic patients, 60 healthy pregnant women and 56 healthy non-pregnant women were involved in this case-control study. Serum levels of IL-17A were measured by high sensitivity ELISA. Serum total soluble fms-like tyrosine kinase-1 (sFlt-1) and biologically active placental growth factor (PlGF) levels were determined by electrochemiluminescence immunoassay. For statistical analyses, non-parametric methods were applied. Serum IL-17 levels were significantly higher in preeclamptic patients than in healthy non-pregnant and pregnant women. We did not find any relationship between serum IL-17 concentrations of preeclamptic patients and their clinical features and serum sFlt-1 and PlGF levels or sFlt-1/PlGF ratios. However, elevated serum IL-17 level and sFlt-1/PlGF ratio was found to be additive for the risk of preeclampsia, as shown by the substantially higher odds ratios of their combination than of either alone. In conclusion, serum IL-17 levels are increased in preeclampsia, which might contribute to the development of the excessive systemic inflammatory response characteristic of the maternal syndrome of the disease. In addition, elevated serum IL-17 level and sFlt-1/PlGF ratio had an additive (joint) effect in the risk of preeclampsia

Alimentáris eredetű kísérletes zsírmáj és adjuváns kezelése természetes eredetű bioaktív hatóanyagokkal = Alimentary induced fatty liver and adjuvant therapy with effective natural bioactive molecules

A redox-homeosztázis változása a citokinek és szabad gyökök változásával jár és számos intracelluláris jelátviteli utat befolyásolhat különböző májbetegségekben. A liofilizált cékla+répa készítmény (GPS Powder Kft. 1361/004/ 2003BFÁÉÉÁ) bioaktív komponensei, mint például a betain, betaninok, betaxantinok, flavonoidok, polifenolok, glutamin, β-karotin, vitaminok és folsav megváltoztathatják a különböző sejtfolyamatokat. Célok: A szerzők célul tűzték ki a cékla+répa liofilizált készítmény bioaktív hatóanyagai védőhatásának vizsgálatát experimentális zsírmájban. Módszer: Hím Wistar patkányokat etettek standard és zsírdús táppal (a standard tápot kiegészítették 2% koleszterinnel, 0,5% kólsavval és 20% napraforgóolajjal) és a kezelt csoportoknak az etetéssel együtt 0,1 vagy 1 g/ttkg/nap természetes készítményt adagoltak. Az indukálható ciklooxigenáz-2 enzim, az indukált nitrogén-monoxid-szintetáz és a tumornekrózis-faktor-α mRNS-szinteket molekuláris-biológiai módszerekkel határozták meg. A szabad gyököket, a H-donor-aktivitást, a redukálóképességet és a szabad SH-csoport-koncentrációt luminometriás vagy spektrofotometriás eljárással mérték. A mobilizálható metilcsoportokat túlnyomásos folyadék-kromatográfiával tanulmányozták. Eredmények: A nagyobb dózisú természetes készítmény jobban csökkentette az indukált szabadgyök-reakciókat, az indukálható ciklooxigenáz-2 enzim, az indukált nitrogén-monoxid-szintetáz és tumornekrózis-faktor-α mRNS-szintjeit, mind egészséges májszövetben, mind zsírmájban. Bár a kezelés nem gyakorolt szignifikáns változásokat az összes globális antioxidáns-paraméterre, zsírmájban a kezelés után megnövekedett mobilizálható metilcsoport-koncentrációkat észleltek és kedvező tendenciát találtak a máj redox-homeosztázisában is. Következtetések: A vártnak megfelelően a mérsékelt dózisú cékla+répa liofilizátum „funkcionális élelmiszernek” bizonyult az élelmi zsír által indukált experimentális zsírmájban. Lehetséges, hogy e kedvező hatás a klinikumban is hasznosulást nyerhet. Orv. Hetil., 2011, 152, 1035–1042. | Changes of redox-homeostasis generate cytokines, and free radicals influence many intracellular signaling pathways in different liver diseases. Liophylised table beet and carrot powder (GPS Powder Kft. 1361/004/2003BFÁÉÉÁ) containing bioactive components such as betaine, betanins, betaxanthins, flavonoids, polyphenols, glutamine, beta carotene, vitamins and folic acid may produce changes various cellular pathways. Aim: The aim of this study was to determine the protecting effects of bioactive agents of the liophylised table beet and carrot powder on fatty liver in a “short term” experiment. Method: Male Wistar rats were fed with chow with or without high fat (2% cholesterol, 0.5% cholic acid, 20% sunflower oil) and treated with 0.1 or 1 g/bwkg/day natural product for ten days parallel with the feedings. Cyclooxygenase-2, inducible nitric oxide synthase and tumor necrosis factor-α mRNA levels were determined using molecular biologic methods. Free radicals, H-donating activity, reducing power and free SH-group concentrations were determined by luminometry and spectrophotometry. Mobilized methyl groups were assayed by over pressure liquid chromatography method in liver homogenates. Results: It was found that the higher dose of the natural product better decreased the induced free radical reactions, cyclooxygenase-2, inducible nitric oxide synthase and tumor necrosis factor-α mRNA-levels both in normal and fatty liver tissues. Although treatments failed to exert significant changes in all global antioxidant parameters, mobilized methyl group concentrations were higher after treatments in fatty liver. Favorable tendencies were also noted in the redox-homeostasis of the fatty liver after treatment. Conclusions: As expected, lyophylised table beet and carrot proved to be a “functional food” in rats with alimentary fat induced fatty liver. It cannot be ruled out that this beneficial effect may have clinical relevance. Orv. Hetil., 2011, 152, 1035–1042

Limb remote ischemic conditioning of the recipient protects the liver in a rat model of arterialized orthotopic liver transplantation

Background Ischemic-reperfusion (IR) injury still represents a major concern in clinical transplantation, especially in the era of extreme organ shortage and extended criteria donor organs. In the present study we aimed to investigate the hepatoprotective effects of remote ischemic conditioning (RIC) in a rat model of arterialized orthotopic liver transplantation (OLT). Methods Male Lewis rats were used (n = 144 / 72 OLT cases; 240-340g) as donors and recipients. Livers were flushed and stored in 4 degrees C HTK-solution for 8h before implantation. Recipients were randomly allocated into three experimental groups: RIC 1, RIC 2, Control. In RIC 1, RIC 2 groups, RIC was applied in the recipient before hepatectomy or after reperfusion (4x5-5min IR via clamping the infrarenal aorta), respectively. Animals were sacrificed at 1, 3,24,168h post-reperfusion (n = 6 recipient/group/time point). Hepatocellular injury, graft circulation, serum cytokines, tissue redox-stress and adenosine-triphosphate (ATP) levels have been assessed. Additional markers were analyzed, using Western blotting and reverse-transcription polymerase chain reaction. Results RIC 1 group showed significantly (p<0.05) improved portal venous and microcirculation flow as well as velocity. RIC has significantly reduced tissue injury according to the serum levels of transaminases and results of histopathological evaluation. Reduced TUNEL-staining (p<0.01 RIC 1-2 vs. Control) and elevated pBAD/BAD ratio was detected in the RIC groups (p<0.01 RIC 1 vs. Control). Supporting findings were obtained from measurements of serum IL-10 as well as tissue malondialdehyde and ATP levels. Hemoxygenase-1 (HO-1) mRNA-expression was significantly higher in RIC 1 compared to Control (p<0.05 RIC 1 vs. Control). Conclusion These results suggest that RIC might confer potent protection against the detrimental effects of IR injury including tissue damage, apoptosis, graft circulation, inflammation, tissue energetic status in OLT. HO-1 overexpression might play an orchestrating role in RIC mediated organ protection. An earlier intervention (RIC 1 protocol) was more effective than remote conditioning after graft reperfusion