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

Dietary supplementation of transient receptor potential vanilloid-1 channel agonists reduces serum total cholesterol level: a meta-analysis of controlled human trials

Abnormal cholesterol level is a major risk factor in the development of atherosclerosis, which is a fundamental derangement in cardiovascular diseases. Any efforts should be undertaken to lower blood cholesterol levels. Among dietary interventions, capsaicinoid supplementation is also considered as a novel cholesterol-lowering approach, but human studies concluded contradictory results about its effectiveness. The present meta-analysis aimed at determining the effects of capsaicinoids on serum lipid profile in humans. We searched the PubMed, EMBASE, and CENTRAL databases from inception to February 2021. We included 10 controlled studies, which involved 398 participants. We found that dietary capsaicinoid supplementation alone or in combination with other substances significantly (p = 0.004 and 0.001, respectively) reduced serum total cholesterol level compared to controls with an overall standardized mean difference of -0.52 (95% confidence interval: -0.83, -0.21). Capsaicinoids also decreased low-density lipoprotein level significantly (p = 0.035), whereas no effect was observed on serum levels of high-density lipoprotein and triglycerides. Our findings provide novel quantitative evidence for the efficacy of dietary capsaicin supplementation in lowering serum total cholesterol and low-density lipoprotein levels in humans. To validate our conclusion, further randomized controlled trials in a diverse population of adult humans receiving dietary capsaicinoid supplementation are warranted

Macrophage migration inhibitory factor as a diagnostic and predictive biomarker in sepsis: meta-analysis of clinical trials

The hunt for useful sepsis biomarkers is ongoing. Macrophage migration inhibitory factor (MIF) was implicated as a biomarker in sepsis, but its diagnostic and prognostic value has remained unclear in human studies. Here, we aimed at clarifying the value of MIF as a sepsis biomarker with the meta-analysis of clinical trials. PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched until December 2019. From the included studies, blood MIF levels and indicators of disease severity were extracted in septic and control patient groups. Twenty-one eligible studies were identified, including data from 1876 subjects (of which 1206 had sepsis). In the septic patients, blood MIF levels were significantly higher than in healthy controls with a standardized mean difference (SMD) of 1.47 (95% confidence interval, CI: 0.96-1.97; p < 0.001) and also higher than in patient groups with nonseptic systemic inflammation (SMD = 0.94; CI: 0.51-1.38; p < 0.001). Markedly greater elevation in blood MIF level was found in the more severe forms of sepsis and in nonsurvivors than in less severe forms and in survivors with SMDs of 0.84 (CI: 0.45-1.24) and 0.75 (CI: 0.40-1.11), respectively (p < 0.001 for both). In conclusion, blood MIF level is more elevated in systemic inflammation caused by infection (i.e., sepsis) compared to noninfectious causes. In more severe forms of sepsis, including fatal outcome, MIF levels are higher than in less severe forms. These results suggest that MIF can be a valuable diagnostic and prognostic biomarker in sepsis given that well-designed clinical trials validate our findings

Predictive Value of Tachycardia for Mortality in Trauma-Related Haemorrhagic Shock: A Systematic Review and Meta-Regression

OBJECTIVES: Heart rate (HR) is one of the physiological variables in the early assessment of trauma-related haemorrhagic shock, according to Advanced Trauma Life Support (ATLS). However, its efficiency as predictor of mortality is contradicted by several studies. Furthermore, the linear association between HR and the severity of shock and blood loss presented by ATLS is doubtful. This systematic review aims to update current knowledge on the role of HR in the initial haemodynamic assessment of patients who had a trauma. DESIGN: This study is a systematic review and meta-regression that follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. DATA SOURCES: EMBASE, MEDLINE, CENTRAL and Web of Science databases were systematically searched through on 1 September 2020. ELIGIBILITY CRITERIA: Papers providing early HR and mortality data on bleeding patients who had a trauma were included. Patient cohorts were considered haemorrhagic if the inclusion criteria of the studies contained transfusion and/or positive focused assessment with sonography for trauma and/or postinjury haemodynamical instability and/or abdominal gunshot injury. Studies on burns, traumatic spinal or brain injuries were excluded. Papers published before January 2010 were not considered. DATA EXTRACTION AND SYNTHESIS: Data extraction and risk of bias were assessed by two independent investigators. The association between HR and mortality of patients who had a trauma was assessed using meta-regression analysis. As subgroup analysis, meta-regression was performed on patients who received blood products. RESULTS: From a total of 2017 papers, 19 studies met our eligibility criteria. Our primary meta-regression did not find a significant relation (p=0.847) between HR and mortality in patients who had a trauma with haemorrhage. Our subgroup analysis included 10 studies, and it could not reveal a linear association between HR and mortality rate. CONCLUSIONS: In accordance with the literature demonstrating the multiphasic response of HR to bleeding, our study presents the lack of linear association between postinjury HR and mortality. Modifying the pattern of HR derangements in the ATLS shock classification may result in a more precise teaching tool for young clinicians

Role of the transient receptor potential vanilloid-1 (TRPV1) in the development of hydrogen chloride (HCl)-induced vasomotor response in isolated rodent carotid arteries.

It was shown earlier that acidic products released during anaerobic tissue metabolism are involved in the regulation of local blood flow. However, the mechanism, through which reductions of local pH evoke the change in vascular tone, is not fully elucidated. Among TRP channels located on vascular elements, TRPV1 plays an important role in sensing of environmental changes (e.g., pH, temperature, etc.). In the present study we hypothesized that TRPV1, which is abundantly expressed in the vascular wall and can be activated by acidic stimuli, plays a role in the vascular responses to low pH. Carotid arteries were isolated from Wistar rats, from mice genetically lacking TRPV1 channels (KO) and from wild-type mice. Isometric wall tension was measured with a myograph. Vessels were precontracted with 10-5 M phenylephrine (PhE), then isometric changes were measured in response to increasing concentrations of HCl (10-6–10-3 M). Functional integrity of the vessels (endothelium-dependent and -independent relaxation) was verified after each experiment. In rat carotid arteries, PhE caused a significant (~5 mN) isometric contraction, and addition of HCl caused dose-dependent relaxation, which was significant already at 10-6 M (-0.3±0.0 mN, p <0.05), and reached a maximum of -1.4±0.1 mN at 10-3 M. Capsaicin elicited significant contractions in carotid arteries isolated from wild-type mice, whereas it was ineffective in that of TRPV1 KO mice, confirming the lack of functional TRPV1 channels. Interestingly, HCl (10-6–10-3 M) caused a significantly greater arterial relaxation in TRPV1 KO mice as compared to controls (p <0.05 for each concentration). Based on these results, we can conclude that acidic environment results in arterial relaxation, the magnitude of which is limited by TRPV1 channels and that changes in local pH contributes to regulation of vasomotor tone to maintain optimal tissue blood flow. Support: SROP-4.2.2.A-11/1/KONV-2012-0024: Complex examination, SROP-4.2.2.A-11/1/KONV-2012-0017: New biomarkers, Hungarian National Scientific Research Found K108444 (AK), PD105532 (AG), Janos Bolyai Research Fellowship from Hungarian Academy of Sciences (AG)