A vázizom, valamint az artériás és a vénás kiserek iszkémiás és iszkémia-reperfúziós károsodása. Az oxidatív stressz szerepe = Ischemic and ischemia-reperfusion injury of skeletal muscle and that of small arteries and veins . The role of oxidative stress

Kísérleteinkben a végtag ereiben lezajló érfali reperfúziós károsodást és az ebben a folyamatban esetleg szerepet játszó szabadgyökök szerepét vizsgáltuk. A méréseket patkányokból vett végtag artéria és véna gyűrűkön végeztük miográf segítségével. Immun hisztokémiával megmértük a szabadgyök képződést. Eredmények: 1. 30 percig tartó oxigénhiány nem befolyásolta az erek reakciókészségét vazoaktív szerekre (noradrenalin, Na-niropruszid, angiotenzin, acetilkolin, adenozin). 2. Kénhidrogén (egyfajta újabb természetes antioxidáns szer) a szuperoxid diszmutázhoz hasonlítva sokkal kevésbé hatékony antioxidánsnak mutatkozott mind az érpreparátumokon, mind mesterséges vizes oldatban. 3. Két óra iszkémia majd az ezt követő egyórás reperfúzió az endotélium értágító hatását csökkenti és, különösen a vénákban, a símaizom kontraktilitását fokozza. Ezzel vénák külön is hozzájárulnak a reperfúziós károsodás kialakulásához. 4. A szabadgyök képződés sem az artériákban, sem a vénákban a reperfúzió adott állapotában jelentősen nem fokozódott a símaizom sejtekben. | Reperfusion injury and the possible role of free radicals in this process were studied within the vascular wall of the lower extremity. Arterial and venous segments of the rat were used for the measurements. Contraction force of the rings was measured. Free radical production was followed by immuno cytochemistry. Main results: 1. 30 min anoxia had no effect on vascular contractions elicited by vasoactive substances (norepinephrine, Na-nitroprusid, angiotensine, adenosine). 2. Hydrogen sulphide (a novel naturally occurring antioxidant agent) was less effective as an antioxidant compared to superoxide dismutase both on vessel preparations and in in vitro watery solutions. 3. Vasodylating effect of the endothelium was reduced after two hours of ischemia followed by one hour reperfusion. Smooth muscle contractions, particularly in the veins, were increased in reperfusion injury. 4. There was no substantial increase of free radical production in the smooth muscle cells either of the arteries or the veins

Menthol can be safely applied to improve thermal perception during physical exercise : a meta-analysis of randomized controlled trials

Menthol is often used as a cold-mimicking substance to allegedly enhance performance during physical activity, however menthol-induced activation of cold-defence responses during exercise can intensify heat accumulation in the body. This meta-analysis aimed at studying the effects of menthol on thermal perception and thermophysiological homeostasis during exercise. PubMed, EMBASE, Cochrane Library, and Google Scholar databases were searched until May 2020. Menthol caused cooler thermal sensation by weighted mean difference (WMD) of - 1.65 (95% CI, - 2.96 to - 0.33) and tended to improve thermal comfort (WMD = 1.42; 95% CI, - 0.13 to 2.96) during physical exercise. However, there was no meaningful difference in sweat production (WMD = - 24.10 ml; 95% CI, - 139.59 to 91.39 ml), deep body temperature (WMD = 0.02 °C; 95% CI, - 0.11 to 0.15 °C), and heart rate (WMD = 2.67 bpm; 95% CI - 0.74 to 6.09 bpm) between the treatment groups. Menthol improved the performance time in certain subgroups, which are discussed. Our findings suggest that different factors, viz., external application, warmer environment, and higher body mass index can improve menthol's effects on endurance performance, however menthol does not compromise warmth-defence responses during exercise, thus it can be safely applied by athletes from the thermoregulation point of view

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

Maternal overnutrition impairs offspring's insulin sensitivity: A systematic review and meta-analysis

This systematic review and meta-analysis aimed to investigate the association between maternal overnutrition and offspring's insulin sensitivity-following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Studies published in English before April 22, 2019, were identified through searches of four medical databases. After selection, 15 studies aiming to explore the association between prepregnancy body mass index (ppBMI) or gestational weight gain (GWG) of non-diabetic mothers and their offspring's insulin sensitivity (fasting insulin or glucose level and Homeostatic Measurement Assessment for Insulin Resistance [HOMA-IR]) were included in the meta-analysis. Associations of ppBMI and GWG with offspring's insulin sensitivity were analysed by pooling regression coefficients or standardized differences in means with 95% confidence intervals (CIs). Maternal ppBMI showed significant positive correlations with the level of both fasting insulin and HOMA-IR in offspring (standardized regression coefficient for fasting insulin: 0.107, CI [0.053, 0.160], p < 0.001 and that for HOMA-IR: 0.063, CI [0.006, 0.121], p = 0.031). However, the result of the analysis on coefficients adjusted for offspring's actual anthropometry (BMI and adiposity) was not significant. Independent from ppBMI, GWG tended to show a positive correlation with insulin level, but not after adjustment for offspring's anthropometry. Offspring of mothers with excessive GWG showed significantly higher HOMA-IR than those of mothers with optimal GWG (p = 0.004). Our results demonstrate that both higher ppBMI and GWG increase the risk of offspring's insulin resistance, but the effect of ppBMI on insulin sensitivity in offspring may develop as consequence of their adiposity

Probiotics have beneficial metabolic effects in patients with type 2 diabetes mellitus : a meta-analysis of randomized clinical trials

Probiotics have been reported to have a positive impact on the metabolic control of patients with type 2 diabetes. We aimed to systematically evaluate the effects of probiotics on cardiometabolic parameters in type 2 diabetes based on randomized controlled studies. MEDLINE, Embase, and CENTRAL databases were reviewed to search for randomized controlled trials that examined the effects of probiotic supplementation on cardiometabolic parameters in patients with type 2 diabetes. 32 trials provided results suitable to be included in the analysis. The effects of probiotics were calculated for the following parameters: BMI, total cholesterol levels, LDL, triglycerides, HDL, CRP, HbA1c levels, fasting plasma glucose, fasting insulin levels, systolic and diastolic blood pressure values. Data analysis showed a significant effect of probiotics on reducing total cholesterol, triglyceride levels, CRP, HbA1c, fasting plasma glucose, fasting insulin levels, and both systolic and diastolic blood pressure values. Supplementation with probiotics increased HDL levels however did not have a significant effect on BMI or LDL levels. Our data clearly suggest that probiotics could be a supplementary therapeutic approach in type 2 diabetes mellitus patients to improve dyslipidemia and to promote better metabolic control. According to our analysis, probiotic supplementation is beneficial in type 2 diabetes mellitus

Hyperthermia induced by transient receptor potential vanilloid-1 (TRPV1) antagonists in human clinical trials: Insights from mathematical modeling and meta-analysis

Antagonists of the transient receptor potential vanilloid-1 (TRPV1) channel alter body temperature (Tb) in laboratory animals and humans: most cause hyperthermia; some produce hypothermia; and yet others have no effect. TRPV1 can be activated by capsaicin (CAP), protons (low pH), and heat. First-generation (polymodal) TRPV1 antagonists potently block all three TRPV1 activation modes. Second-generation (mode-selective) TRPV1 antagonists potently block channel activation by CAP, but exert different effects (e.g., potentiation, no effect, or low-potency inhibition) in the proton mode, heat mode, or both. Based on our earlier studies in rats, only one mode of TRPV1 activation - by protons - is involved in thermoregulatory responses to TRPV1 antagonists. In rats, compounds that potently block, potentiate, or have no effect on proton activation cause hyperthermia, hypothermia, or no effect on Tb, respectively. A Tb response occurs when a TRPV1 antagonist blocks (in case of hyperthermia) or potentiates (hypothermia) the tonic TRPV1 activation by protons somewhere in the trunk, perhaps in muscles, and - via the acido-antithermogenic and acido-antivasoconstrictor reflexes - modulates thermogenesis and skin vasoconstriction. In this work, we used a mathematical model to analyze Tb data from human clinical trials of TRPV1 antagonists. The analysis suggests that, in humans, the hyperthermic effect depends on the antagonist's potency to block TRPV1 activation not only by protons, but also by heat, while the CAP activation mode is uninvolved. Whereas in rats TRPV1 drives thermoeffectors by mediating pH signals from the trunk, but not Tb signals, our analysis suggests that TRPV1 mediates both pH and thermal signals driving thermoregulation in humans. Hence, in humans (but not in rats), TRPV1 is likely to serve as a thermosensor of the thermoregulation system. We also conducted a meta-analysis of Tb data from human trials and found that polymodal TRPV1 antagonists (ABT-102, AZD1386, and V116517) increase Tb, whereas the mode-selective blocker NEO6860 does not. Several strategies of harnessing the thermoregulatory effects of TRPV1 antagonists in humans are discussed

Predictive Performance of Serum S100B Versus LDH in Melanoma Patients: a Systematic Review and Meta-Analysis

Currently, no consensus on the use of blood tests for monitoring disease recurrence in patients with resected melanoma exists. The only meta-analysis conducted in 2008 found that elevated serum S100B levels were associated with significantly worse survival in melanoma patients. Serum LDH is an established prognostic factor in patients with advanced melanoma.To compare the discriminative and prognostic ability of serum S100B with that of serum LDH in patients with melanoma.This systematic review and meta-analysis were reported in accordance with the PRISMA Statement. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42019137138).A quantitative analysis of data from 6 eligible studies included 1,033 patients with cutaneous melanoma. The discriminative ability of serum S100B at identifying disease relapse [pooled Area Under the ROC (AUROC) 78.64 (95% CI 70.28; 87.01)] was significantly greater than the discriminative ability of serum LDH [AUROC 64.41 (95% CI 56.05; 7278)] (p=0.013). Ten eligible studies with 1,987 patients were included in the risk of death analysis. The prognostic performance of serum S100B [pooled estimate of adjusted hazard ratio (HR) 1.78 (95% CI 1.38; 2.29)] was independent but not superior to that of serum LDH [HR 1.60 (95% CI 1.36; 2.29)].A relatively small number of articles were eligible and there was considerable heterogeneity across the included studies.Serum biomarkers may provide relevant information on melanoma patient status and should be further researched. Serum S100B is a valid marker for diagnosis of melanoma recurrence.The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42019137138)

Restoration of energy level in the early phase of acute pediatric pancreatitis

Acute pancreatitis (AP) is a serious inflammatory disease with rising incidence both in the adult and pediatric populations. It has been shown that mitochondrial injury and energy depletion are the earliest intracellular events in the early phase of AP. Moreover, it has been revealed that restoration of intracellular ATP level restores cellular functions and defends the cells from death. We have recently shown in a systematic review and meta-analysis that early enteral feeding is beneficial in adults; however, no reviews are available concerning the effect of early enteral feeding in pediatric AP. In this minireview, our aim was to systematically analyse the literature on the treatment of acute pediatric pancreatitis. The preferred reporting items for systematic review (PRISMA-P) were followed, and the question was drafted based on participants, intervention, comparison and outcomes: P: patients under the age of twenty-one suffering from acute pancreatitis; I: early enteral nutrition (per os and nasogastric- or nasojejunal tube started within 48 h); C: nil per os therapy; O: length of hospitalization, need for treatment at an intensive care unit, development of severe AP, lung injury (including lung oedema and pleural effusion), white blood cell count and pain score on admission. Altogether, 632 articles (PubMed: 131; EMBASE: 501) were found. After detailed screening of eligible papers, five of them met inclusion criteria. Only retrospective clinical trials were available. Due to insufficient information from the authors, it was only possible to address length of hospitalization as an outcome of the study. Our mini-meta-analysis showed that early enteral nutrition significantly (SD = 0.806, P = 0.034) decreases length of hospitalization compared with nil per os diet in acute pediatric pancreatitis. In this minireview, we clearly show that early enteral nutrition, started within 24-48 h, is beneficial in acute pediatric pancreatitis. Prospective studies and better presentation of research are crucially needed to achieve a higher level of evidence

Vénás mikroerek vazomotor funkciója hiperhomociszteinémiában = Vasomotor function of venous microvessels in hyperhomocysteinemia

Kutatásaink kiderítették a konstriktor prosztaglandinok döntő szerepét mind a vénás erek mind az agyi erek vasomotor működésében, egészséges és kóros körülmények között. Ez idáig úgy gondolták, hogy a konstriktor prosztaglandinoknak csak kóros szerepe van. A homocystein magas szintje csökkenti a vaszkuláris működést és thrombotikus irányban tereli az endothelium működését, ami felelős lehet a vénás thromboembolitikus elváltozások kialakulásában. Ugyanakkor kimutattuk, hogy a konstriktor prosztaglandinoknak fontos szerepe van az agyi autóreguláció kialakulásában. Feltehető, hogy ezen eredmények elméleti alapot szolgáltatnak új gyógyszertermékek kidolgozásához. | These investigations revealed the important role of constrictor prostaglandins, not only in diseased conditions, but in normal conditions, as well. These results draw the attention again the utmost importance of constrictor prostaglandins in the maintenance of normal and diseased vascular functions, especially to their role in antithrombotic events. In addition, we have shown that constrictor prostaglandins are importantly involved in the modulation of and autoregulation of cerebral circulation, which have not been known previously. These new pathways provide the theoretical basis for the development of new drugs