Időskori anorexia, sarcopenia: orexigén és anorexigén peptidek energetikai hatásainak változása az életkorral rágcsálókban = Anorexia of aging, sarcopenia: age-dependent changes in the effects of orexigenic and anorexigenic peptides on energy homeostasis in rodents

Az alpha-MSH, a melanocortin rendszer endogén agonistája intracerebroventricularisan (ICV) adva katabolikus hatású: gátolja a spontán és a 24-h éheztetéssel kiváltott táplálékfelvételt (FI-t) (anorexigén) és biotelemetriás mérések szerint fokozza az anyagcserét és a testhőmérsékletet (Tc-t). Hőszabályozási hatásai nem koordináltak, mert az anyagcserével együtt a hőleadást is fokozza, ami a Tc emelkedését limitálja, ill. az LPS-lázat csökkenti. Anorexigén hatása korfüggő: a fiatal felnőtt (3-4 hó) patkányban kimutatott erős hatás 6-12-hónapos (középkorú) állatokban fokozatosan gyengül, majd öregekben (18-24 hó) maximális lesz. A 7-napos ICV infúzió eredményei ezt megerősítik, viszont azt is igazolják, hogy a peptid metabolikus hatásai nem párhuzamosan változnak az anorexigén hatásokkal. Kimutattuk, hogy az alpha-MSH anorexigén hatása normálisan táplált, kalóriarestrikciós és high-fat-diet által elhizlalt 6-hónapos állatokban hasonló volt, tehát az előzőekben leírt érzékenység-változások valóban a kortól és nem a testösszetételtől függtek. A CRF-el eddig elért eredményeink nagymértékben hasonlítanak az alpha-MSH-val elértekhez. Az orexigén NPY 12-hónapos állatokban hatásosabb, mint a 3 hónaposakban, viszont a 24 hónaposakban sokkal kisebb FI-t indukál. Mindezek elősegíthetik a középkorúak elhízását és az öregek anorexiáját és sarcopeniáját. | The intracerebroventricular (ICV) injection of alpha-MSH, the endogenous agonist of the melanocortin system has catabolic effects: it inhibits the spontaneous and fasting-induced food intake (anorexic) and elevates metabolic rate and body temperature (Tc). Its thermoregulatory effects are uncoordinated: heat loss is enhanced together with the rise in metabolic rate, thereby limiting the rise in Tc or inhibiting LPS-fever. The anorexic effects are age-dependent: the strong effect seen in young adult (3-4 months) rats gradually decreases by the age of 6-12 months ('middle-age'), then it becomes very pronounced in old (18-24 months) rats. Results of a 7 day-long ICV infusion confirm these data, but also demonstrate that the changes in metabolic and anorexic effects are not parallel. The anorexic effect was similar in normally fed, calorie-restricted and high fat diet-induced obese 6 month-old rats, proving that the previously seen changes in the anorexic effects of the peptide are due to aging and not to body composition. Results of studies with CRF greatly resemble those gained with alpha-MSH. The orexigenic NPY is more effective in 12 than in 3 month-old rats, but its efficacy significantly decreases by the age of 24 months. All these may contribute to the development of obesity in middle-aged and anorexia/sarcopenia in old rats

Az energetika biotelemetriás vizsgálata TRPV génhiányos és vad típusú egérben: testhőmérsékleti és aktivitási ritmusok változásai különböző tápláltsági és stressz állapotokban = Biotelemetric studies of energetics in TRPV knockout and wild type mice: modifications body temperature and activity rhythms under different feeding and stress situations

C57/BL egerek maghőmérsékletét és lokomotor aktivitását vizsgáltuk biotelemetriás módszerrel különböző környezeti hőmérsékleten. Normális és zsírdús táplálás hatásait követtük a napszaki hullámzásokra táplálás, több napos teljes éheztetés és újratáplálás ideje alatt, valamint ismételt laparotomiás beavatkozást követően is. Mindezen változások energetikai hátterének megismerése céljából releváns mediátorok, gátló anyagok centrális vagy perifériás infúzióját végeztük ALZET minipumpa segítségével. Szabadon mozgó egerek napszaki hőmérsékleti és aktivitási hullámzásának nagysága fokozódik teljes éhezés során és a maghőmérséklet 30 °C-ra való csökkenése jelzi a túlélhető éhezés végét az aktivitás fokozódása mellett. Újratápláláskor, hidegben, elhízásban, CNTF infúzió alatt és laparotomia után csökken a hullámzások amplitúdója. CNTF és CCK-8 icv infúziója lázat vált ki. Eredményeink több új információval szolgáltak a szabadon mozgó egerek normális és kóros energetikájának mechanizmusáról. | Changes of core temperature and locomotor activity were monitored in C57/BL mice under different thermal conditions by using a biotelemetric method. Effects of normal or fat-rich diet were observed on daily oscillatons during feeding, total fasting, re-feeding or on repeated laparotomy. To learn the energetic background of all these stimuli relevant meditors or blocker were infused either centrally or peripherally by using ALZET minipumps. Excursions of daily changes in core temperature and activity were found to be increased during total fasting with core temperature falling to about 30 °C as a sign of threshold of survivability with locomotor activity increasing progressively. Re-feeding, cold exposure, obesity, CNTF infusion or laparotomy led to reversible decreases of daily oscillations. Icv infusion of CNTF or CCK-8 induced fever. Our results furnished new information on the mechanisms of changes in energetics observed under normal and various types of pathological conditions in freely moving mice

Meta-Analysis of the Long Term Success Rate of Different Interventions in Benign Biliary Strictures.

BACKGROUND: Benign biliary stricture is a rare condition and the majority of the cases are caused by operative trauma or chronic inflammation based on various etiology. Although the initial results of endoscopic, percutaneous and surgical treatment are impressive, no comparison about long term stricture resolution is available. AIMS: The goal of this study was to compare the long term disease free survival in benign biliary strictures with various etiology after surgery, percutaneous transhepatic-and endoscopic treatment. METHODS: PubMed, Embase, and Cochrane Library were searched by computer and manually for published studies. The investigators selected the publications according to the inclusion and exclusion criteria, processed the data and assessed the quality of the selected studies. Meta-analysis of data of 24 publications was performed to compare long term disease free survival of different treatment groups. RESULTS: Compared the subgroups surgery resulted in the highest long term stricture resolution rate, followed by the percutaneous transhepatic treatment, the multiple plastic stent insertion and covered self-expanding metal stents (SEMS), however the difference was not significant. All compared methods are significantly superior to the single plastic stent placement. Long term stricture resolution rate irrespectively of any therapy is still not more than 84%. CONCLUSIONS: In summary, the use of single plastic stent is not recommended. Further randomized studies and innovative technical development are required for improving the treatment of benign biliary strictures

Compared efficacy of preservation solutions on the outcome of liver transplantation: Meta-analysis

AIM: To compare the effects of the four most commonly used preservation solutions on the outcome of liver transplantations. METHODS: A systematic literature search was performed using MEDLINE, Scopus, EMBASE and the Cochrane Library databases up to January 31(st), 2017. The inclusion criteria were comparative, randomized controlled trials (RCTs) for deceased donor liver (DDL) allografts with adult and pediatric donors using the gold standard University of Wisconsin (UW) solution or histidine-tryptophan-ketoglutarate (HTK), Celsior (CS) and Institut Georges Lopez (IGL-1) solutions. Fifteen RCTs (1830 livers) were included; the primary outcomes were primary non-function (PNF) and one-year post-transplant graft survival (OGS-1). RESULTS: All trials were homogenous with respect to donor and recipient characteristics. There was no statistical difference in the incidence of PNF with the use of UW, HTK, CS and IGL-1 (RR = 0.02, 95%CI: 0.01-0.03, P = 0.356). Comparing OGS-1 also failed to reveal any difference between UW, HTK, CS and IGL-1 (RR = 0.80, 95%CI: 0.80-0.80, P = 0.369). Two trials demonstrated higher PNF levels for UW in comparison with the HTK group, and individual studies described higher rates of biliary complications where HTK and CS were used compared to the UW and IGL-1 solutions. However, the meta-analysis of the data did not prove a statistically significant difference: the UW, CS, HTK and IGL-1 solutions were associated with nearly equivalent outcomes. CONCLUSION: Alternative solutions for UW yield the same degree of safety and effectiveness for the preservation of DDLs, but further well-designed clinical trials are warranted

Steroid but not biological therapy elevates the risk of venous thromboembolic events in inflammatory bowel disease: a meta-analysis

Background and aim: Inflammatory bowel disease [IBD] is associated with 1.5- to 3-fold increased risk of venous thromboembolic events [VTE]. The aim of this study was to determine the risk of VTE in IBD as a complication of systemic corticosteroids and anti-tumor necrosis factor alpha [TNFalpha] therapies. Methods: A systematic review and meta-analysis was conducted, which conforms to the Preferred Reporting Items for Systematic Reviews and Meta-analyses [PRISMA] statement. PubMed, EMBASE, Cochrane Library, and Web of Science were searched for English-language studies published from inception inclusive 15 April 2017. The population-intervention-comparison-outcome [PICO] format and statistically the random-effects and fixed-effect models were used to compare VTE risk during steroid and anti-TNFalpha treatment. Quality of the included studies was assessed using the Newcastle-Ottawa scale. PROSPERO registration number is 42017070084. Results: We identified 817 records, of which eight observational studies, involving 58,518 IBD patients, were eligible for quantitative synthesis. In total, 3,260 thromboembolic events occurred. Systemic corticosteroids were associated with a significantly higher rate of VTE complication in IBD patients as compared to IBD patients without steroid medication [OR: 2.202; 95% CI: 1.698-2.856, p < 0.001]. In contrast, treatment with anti-TNFalpha agents resulted in a 5-fold decreased risk of VTE compared to steroid medication [OR: 0.267; 95% CI: 0.106-0.674, p = 0.005]. Conclusion: VTE risk should be carefully assessed and considered when deciding between anti-TNFalpha and steroids in the management of severe flare-ups. Thromboprophylaxis guidelines should be followed, no matter the therapy choice