One of the major neuropeptide groups in insects is adipokinetic hormone/red pigment-concentrating hormone (AKH/RPCH) family of peptides. AKH had improving effects on depression and anxiety in animal models and it may be a new treatment choice in these disorders. Aim of this study was to investigate effects of Anax imperator AKH (Ani-AKH), Libellula auripennis AKH (Lia-AKH) and Phormia-Terra hypertrehalosemic hormone (Pht-HrTH) on animal behavior in olfactory bulbectomy (OBX) model and in posttraumatic stress disorder (PTSD) model of Wistar-albino rats. Lia-AKH and Pht-HrTH significantly increased time spent in escape platform's quadrant compared to sham control while Lia-AKH significantly increased time spent in escape platform's quadrant compared to OBX controls in probe trial of Morris water maze (MWM). Ani-AKH, Lia-AKH and Pht-HrTH significantly decreased immobility time compared to OBX controls in forced swimming test (FST). Pht-HrTH significantly increased %open arm time compared to OBX controls in elevated plus maze (EPM) test. Ani-AKH significantly increased %open arm entry compared to sham control while Ani-AKH and Pht-HrTH significantly increased %open arm entry compared to OBX controls in EPM. In PTSD study Ani-AKH and Lia-AKH significantly decreased immobility time compared to traumatized controls in FST. In acoustic startle reflex test, Ani-AKH, Lia-AKH and Pht-HrTH significantly decreased average startle amplitude compared to non-traumatized controls in PTSD study. Metabolomic studies showed that AKH may affect glutamatergic and dopaminergic system and neurochemistry. In conclusion, AKH peptides had wide ranging effects on behavior and improved performance in OBX and PTSD models in rats.

• MeSH
• bulbus olfactorius chirurgie   MeSH
• chování zvířat MeSH
• hmyzí hormony farmakologie   MeSH
• krysa rodu rattus MeSH
• kyselina pyrrolidonkarboxylová analogy a deriváty   farmakologie   MeSH
• modely nemocí na zvířatech MeSH
• neuropeptidy farmakologie   MeSH
• oligopeptidy farmakologie   MeSH
• posttraumatická stresová porucha farmakoterapie   metabolismus   patologie   MeSH
• potkani Wistar MeSH
• úzkost farmakoterapie   metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Publikační typ
• abstrakt z konference MeSH

Cíl studie: Endoteliální glykokalyx (EG) hraje ústřední roli v udržení vaskulární integrity a správné funkce mikrocirkulace. Poškození EG u pacientů po úspěšné kardiopulmonální resuscitaci bylo popsáno měřením hladin rozpadových produktů EG (syndekan-1, heparan sulfát). Poměrně novou metodou k hodnocení stavu EG je parametr perfundované hraniční zóny (PBR), který udává v µm boční rozptyl červených krvinek směrem k EG. Cílem této studie bylo zhodnotit změny PBR na zvířecím modelu srdeční zástavy u prasete domácího a zhodnotit použitelnost PBR jako indikátoru poškození EG. Typ studie: Experimentální na zvířecím modelu srdeční zástavy u prasete domácího. Materiál a metody: Srdeční zástava byla indukována nitrosrdeční elektrodou navozením fibrilace komor, která byla léčena defibrilací dle doporučení ERC 2015 po 15 minutách. Sublingvální mikrocirkulace byla vyšetřena ručním mikroskopem fungujícím na principu ortogonálně polarizované spektroskopie. Pořízené nahrávky byly hodnoceny automaticky programem, který poskytl hodnotu PBR. Hodnocení bylo ve třech časových bodech: základní měření (PBR_B), po návratu spontánní cirkulace (PBR_ROSC) a 20 minut poté (PBR_ROSC_20). Výsledky: Hodnoty PBR byly získány od 11 prasat. Hodnoty PBR po ROSC nebyly statisticky signifikantně zvýšeny (p = 0,47). PBR_B bylo 2,129 (± 0,21) µm, PBR_ROSC bylo 2,206 (± 0,27) µm and PBR_ROSC_20 bylo 2,18 (± 0,19) µm. Výsledky jsou ve tvaru průměr (směrodatná odchylka). Závěr: Naše data udávají nevýznamné zvýšení parametru PBR v sublingvální oblasti po srdeční zástavě u prasete. Parametr PBR vyžaduje další testování, než by mohl být zaveden jako neinvazivní parametr udávající míru poškození EG na modelu srdeční zástavy u prasete.

Objective: Endothelial glycocalyx (EG) plays key role in maintaining vascular integrity. Perturbation of the EG in patients after cardiac arrest has been described by measuring syndecan-1 and heparan sulphate levels. Non-invasive method of evaluating EG thickness by using Perfused Boundary Region (PBR) has been introduced recently. PBR represents the amount of lateral deviation of red blood cells towards the EG in µm. The aim of the study was to evaluate changes in PBR on porcine model of cardiac arrest in order to assess the usefulness of PBR as an indicator of glycocalyx damage. Design: Experimental study on a porcine model of cardiac arrest. Material and Methods: Cardiac arrest was induced by intracardiac electrode triggering ventricular fibrillation and treated by defibrillation after 15 minutes in accordance with 2015 ERC guidelines. Sublingual microcirculation was measured by hand-held microscope working on the principle of orthogonal spectral imaging and PBR was computed automatically with specialized software in three timepoints. At baseline (PBR_B), after return of spontaneous circulation (PBR_ROSC) and 20 minutes after ROSC (PBR_ROSC_20). Results: PBR data was obtained from 11 pigs. There was insignificant increase of PBR after ROSC (p = 0.47). The PBR_B was 2.129 (± 0.21), PBR_ROSC was 2.206 (± 0.27) and PBR_ROSC_20 was 2.18 (± 0.19), data are presented as mean and standard deviation. Conclusions: Our data demonstrate insignificant increase of PBR after cardiac arrest in pig. The value of PBR as an indicator of EG shedding requires further study before introducing this parameter as a routine non-invasive tool in pig model of cardiac arrest.

• Klíčová slova
• endoteliální glykokalyx,
• MeSH
• cévní endotel MeSH
• glykokalyx * MeSH
• kardiopulmonální resuscitace MeSH
• modely nemocí na zvířatech MeSH
• náhlá srdeční smrt * MeSH
• prasata MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

The adipokinetic and red pigment-concentrating hormone (AKH/RPCH) family of peptides controls fat, carbohydrate, and protein metabolism in insects. In our previous study, we showed that AKH possesses antidepressant, anxiolytic, and analgesic effects, causes hyperlocomotion, and exerts neuroprotective effects and increased brain neurotrophic factors in mice. The aim of this study was to investigate the effects of Anax imperator AKH (Ani-AKH), Libellula auripennis AKH (Lia-AKH), and Phormia-Terra hypertrehalosemic hormone (Pht-HrTH) on MK-801-induced memory deterioration in the active allothetic place avoidance test (AAPA) and MK-801-induced sensorimotor gating deficit in the prepulse inhibition test (PPI). In the AAPA task, Long-Evans rats were treated with Ani-AKH (2 mg/kg), Lia-AKH (2 mg/kg), Pht-HrTH (2 mg/kg), MK-801 (0.15 mg/kg), and the combination of MK-801 with the hormones subchronically. In the prepulse inhibition test, Wistar albino rats were treated with Ani-AKH (1 mg/kg), Lia-AKH (1 mg/kg), Pht-HrTH (1 mg/kg), MK-801 (0.1 mg/kg), or the combination of MK-801 with hormones acutely before the test. In our study, Ani-AKH (2 mg/kg), Lia-AKH (2 mg/kg), and Pht-HrTH (2 mg/kg) reversed MK-801 (0.15 mg/kg)-induced cognitive memory impairment effects in the AAPA task. Lia-AKH (1 mg/kg) significantly potentiated the MK-801-induced PPI disruption, while Ani-AKH (1 mg/kg) partially potentiated the impairment caused by MK-801, and Pht-HrTH did not modify the effect of MK-801. In conclusion, AKH had no effect in sensorimotor gating deficits in the PPI test in schizophrenia model while AKH improved memory in the schizophrenia model of MK-801.

• MeSH
• anxiolytika farmakologie   MeSH
• dizocilpinmaleát farmakologie   MeSH
• hmyzí hormony farmakologie   MeSH
• krysa rodu rattus MeSH
• kyselina pyrrolidonkarboxylová analogy a deriváty   farmakologie   MeSH
• modely nemocí na zvířatech MeSH
• neuropeptidy farmakologie   MeSH
• neuroprotektivní látky MeSH
• oligopeptidy farmakologie   MeSH
• paměť účinky léků   MeSH
• peptidy farmakologie   MeSH
• poruchy paměti chemicky indukované   farmakoterapie   MeSH
• potkani Long-Evans MeSH
• potkani Wistar MeSH
• schizofrenie chemicky indukované   farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Cíl studie: Přestože je adrenalin pevnou součástí protokolu pro rozšířenou neodkladnou resuscitaci, jeho úloha je v poslední době zpochybňována. Proto jsme realizovali experiment s cílem posoudit vliv podávání adrenalinu na hemodynamiku během experimentální srdeční zástavy (SZ). Typ studie: Randomizovaná nezaslepená experimentální studie. Typ pracoviště: Experimentální laboratoř v univerzitní nemocnici. Materiál a metoda: U 14 samic prasete domácího byla navozena SZ s fibrilací komor trvající 15 minut (dvě minuty bez resuscitačních pokusů, tři minuty pouze srdeční masáž, deset minut srdeční masáž a umělá plicní ventilace) s následnou defibrilací a sledováním po dobu 20 minut. Před indukcí SZ byla experimentální zvířata randomizována k nitrožilnímu bolusovému podání 15 μg/kg adrenalinu pátou a desátou minutu SZ (skupina A), nebo ke kardiopulmonální resuscitaci bez podávání adrenalinu (skupina B). Protokol byl realizován za kontinuálního monitorování hemodynamických parametrů včetně kalkulace koronárního (CoPP) a cerebrálního perfuzního tlaku (CPP). Výsledky: Ve skupině A byl dosažen návrat spontánní cirkulace u všech 7 zvířat, ve skupině B pouze u 5 zvířat (p = 0,462). Sledované parametry kromě tělesné teploty byly před indukcí SZ v obou skupinách srovnatelné. Podání adrenalinu ve skupině A vedlo k významnému nárůstu CoPP v první minutě po obou podáních ve srovnání se skupinou B (6. minuta: 30,6 ± 6,4 vs. 14,3 ± 3,2 mm Hg; 11. minuta: 29,4 ± 8,5 vs. 12,3 ± 2,4 mm Hg, p < 0,05) s postupným poklesem na původní hodnoty. Ve skupině A jsme pozorovali podobný nárůst CPP bez nežádoucího vzestupu nitrolebního tlaku. Závěr: V našem experimentálním modelu SZ vedlo pravidelné podávání adrenalinu k výraznému dočasnému nárůstu CoPP i CPP bez nežádoucího vzestupu nitrolebního tlaku.

Objective: Although adrenaline administration is a part of the advanced life support algorithm, its role has been questioned recently. Therefore, we conducted a study to investigate the effect of adrenaline administration on the haemodynamics during experimental cardiac arrest (CA). Design: Randomized, unblinded, experimental study. Setting: Experimental laboratory in a university hospital. Materials and methods: Ventricular fibrillation was induced for 15 minutes (two minutes without resuscitation attempts, three minutes of chest compressions, ten minutes of chest compressions and mechanical ventilation) in 14 anaesthetized domestic pigs. After spontaneous circulation was restored, the animals were observed for 20 minutes. Prior to CA induction, the experimental animals were randomized to receive a bolus of 15 μg/kg of adrenaline intravenously (IV) in the 5th and 10th minute of CA (group A) or to undergo cardiopulmonary resuscitation without adrenaline administration (group B). Haemodynamic variables including coronary (CoPP) and cerebral perfusion pressure (CPP) were continuously monitored throughout the protocol. Results: While return of spontaneous circulation was reached in all 7 group A animals, in group B it was achieved in 5 animals only (p=0.462). The observed variables except body temperature were comparable in both the groups prior to the cardiac arrest induction. Administration of adrenaline in group A resulted in a significant increase in CoPP in the first minute after both administrations compared to group B, where adrenaline was not administered (6th minute: 30.6±6.4 vs. 14.3±3.2 mm Hg, 11th minute: 29.4±8.5 vs. 12.3±2.4 mm Hg, p < 0.05) with a gradual decrease to the baseline levels. A similar increase in CPP without undesirable elevation of the intracranial pressure was identified in group A. Conclusion: In our experimental model of CA, regular adrenaline administration resulted in a significant temporary increase in CoPP and CPP without an unfavourable increase of the intracranial pressure.

• Klíčová slova
• experimentální srdeční zástava, cerebrální perfuzní tlak, koronární perfuzní tlak,
• MeSH
• adrenalin * aplikace a dávkování   farmakologie   škodlivé účinky   MeSH
• fibrilace komor MeSH
• hemodynamika * účinky léků   MeSH
• intrakraniální tlak účinky léků   MeSH
• kardiopulmonální resuscitace MeSH
• koronární cirkulace účinky léků   MeSH
• krevní tlak MeSH
• modely u zvířat MeSH
• mozkový krevní oběh účinky léků   MeSH
• prasata MeSH
• prognóza MeSH
• randomizované kontrolované studie jako téma MeSH
• rozšířená kardiopulmonální recuscitace * metody   MeSH
• srdeční zástava * farmakoterapie   terapie   MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Mephedrone (MEPH) is a synthetic cathinone derivative with effects that mimic MDMA and/or cocaine. Our study in male Wistar rats provides detailed investigations of MEPH's and its primary metabolite nor-mephedrone's (nor-MEPH) pharmacokinetics and bio-distribution to four different substrates (serum, brain, lungs, and liver), as well as comparative analysis of their effects on locomotion [open field test (OFT)] and sensorimotor gating [prepulse inhibition of acoustic startle reaction (PPI ASR)]. Furthermore, in order to mimic the crowded condition where MEPH is typically taken (e.g., clubs), the acute effect of MEPH on thermoregulation in singly- and group-housed rats was evaluated. Pharmacokinetics of MEPH and nor-MEPH after MEPH (5 mg/kg, sc.) were analyzed over 8 h using liquid chromatography with mass spectrometry. MEPH (2.5, 5, or 20 mg/kg, sc.) and nor-MEPH (5 mg/kg, sc.) were administered 5 or 40 min before the behavioral testing in the OFT and PPI ASR; locomotion and its spatial distribution, ASR, habituation and PPI itself were quantified. The effect of MEPH on rectal temperature was measured after 5 and 20 mg/kg, sc. Both MEPH and nor-MEPH were detected in all substrates, with the highest levels detected in lungs. Mean brain: serum ratios were 1:1.19 (MEPH) and 1:1.91 (nor-MEPH), maximum concentrations were observed at 30 min; at 2 and 4 h after administration, nor-MEPH concentrations were higher compared to the parent drug. While neither of the drugs disrupted PPI, both increased locomotion and affected its spatial distribution. The effects of MEPH were dose dependent, rapid, and short-lasting, and the intensity of locomotor stimulant effects was comparable between MEPH and nor-MEPH. Despite the disappearance of behavioral effects within 40 min after administration, MEPH induced rectal temperature elevations that persisted for 3 h even in singly housed rats. To conclude, we observed a robust, short-lasting, and most likely synergistic stimulatory effect of both drugs which corresponded to brain pharmacokinetics. The dissociation between the duration of behavioral and hyperthermic effects is indicative of the possible contribution of nor-MEPH or other biologically active metabolites. This temporal dissociation may be related to the risk of prolonged somatic toxicity when stimulatory effects are no longer present.

• Publikační typ
• časopisecké články MeSH

We conducted an experimental study to evaluate the presence of coordinated left ventricular mechanical myocardial activity (LVMA) in two types of experimentally induced cardiac arrest: ventricular fibrillation (VF) and pulseless electrical activity (PEA). Twenty anesthetized domestic pigs were randomized 1:1 either to induction of VF or PEA. They were left in nonresuscitated cardiac arrest until the cessation of LVMA and microcirculation. Surface ECG, presence of LVMA by transthoracic echocardiography and sublingual microcirculation were recorded. One minute after induction of cardiac arrest, LVMA was identified in all experimental animals. In the PEA group, rate of LVMA was of 106+/-12/min. In the VF group, we identified two patterns of LVMA. Six animals exhibited contractions of high frequency (VFhigh group), four of low frequency (VFlow group) (334+/-12 vs. 125+/-32/min, p<0.001). A time from cardiac arrest induction to asystole (19.2+/-7.2 vs. 7.3+/-2.2 vs. 8.3+/-5.5 min, p=0.003), cessation of LVMA (11.3+/-5.6 vs. 4.4+/-0.4 vs. 7.4+/-2.9 min, p=0.027) and cessation of microcirculation (25.3+/-12.6 vs. 13.4+/-2.4 vs. 23.2+/-8.7 min, p=0.050) was significantly longer in VFlow group than in VFhigh and PEA group, respectively. Thus, LVMA is present in both VF and PEA type of induced cardiac arrest and moreover, VF may exhibit various patterns of LVMA.

• MeSH
• fibrilace komor patofyziologie   MeSH
• prasata MeSH
• srdeční komory patofyziologie   MeSH
• srdeční zástava patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Methylone (3,4-methylenedioxy-N-methylcathinone) is a synthetic cathinone analog of the recreational drug ecstasy. Although it is marketed to recreational users as relatively safe, fatalities due to hyperthermia, serotonin syndrome, and multi-organ system failure have been reported. Since psychopharmacological data remain scarce, we have focused our research on pharmacokinetics, and on a detailed evaluation of temporal effects of methylone and its metabolite nor-methylone on behavior and body temperature in rats. Methylone [5, 10, 20, and 40 mg/kg subcutaneously (s.c.)] and nor-methylone (10 mg/kg s.c.) were used in adolescent male Wistar rats across three behavioral/physiological procedures and in two temporal windows from administration (15 and 60 min) in order to test: locomotor effects in the open field, sensorimotor gating in the test of prepulse inhibition (PPI), and effects on rectal temperature in individually and group-housed rats. Serum and brain pharmacokinetics after 10 mg/kg s.c. over 8 h were analyzed using liquid chromatography mass spectrometry. Serum and brain levels of methylone and nor-methylone peaked at 30 min after administration, both drugs readily penetrated the brain with serum: brain ratio 1:7.97. Methylone dose-dependently increased overall locomotion. It also decrease the amount of time spent in the center of open field arena in dose 20 mg/kg and additionally this dose induced stereotyped circling around the arena walls. The maximum of effects corresponded to the peak of its brain concentrations. Nor-methylone had approximately the same behavioral potency. Methylone also has weak potency to disturb PPI. Behavioral testing was not performed with 40 mg/kg, because it was surprisingly lethal to some animals. Methylone 10 and 20 mg/kg s.c. induced hyperthermic reaction which was more pronounced in group-housed condition relative to individually housed rats. To conclude, methylone increased exploration and/or decreased anxiety in the open field arena and with nor-methylone had short duration of action with effects typical for mixed indirect dopamine-serotonin agonists such as 3,4-metyhlenedioxymethamphetamine (MDMA) or amphetamine. Given the fact that the toxicity was even higher than the known for MDMA and that it can cause hyperthermia it possess a threat to users with the risk for serotonin syndrome especially when used in crowded conditions.

• Publikační typ
• časopisecké články MeSH

Objectives: Aminoindanes ("bath salts," a class of novel psychoactive substances, NPSs) increased rapidly in popularity on the recreational drug market, particularly after mephedrone and other synthetic cathinones were banned in the UK in 2010. Novel aminoindanes continue to emerge, but relatively little is known about their effects and risks. Their history, chemistry, pharmacology, behavioral effects, pharmacokinetics, and toxicity are reviewed in this paper. Methods: Scientific literature was searched on ISI Web of Knowledge: Web of Science (WoS) during June and July 2017, using English language terms: aminoindanes such as 5,6-methylenedioxy-2-aminoindane (MDAI), 5-iodo-2-aminoindane (5-IAI), 2-aminoindane (2-AI), 5,6-methylenedioxy-N-methyl-2-aminoindane (MDMAI), and 5-methoxy-6-methyl-2-aminoindane (MMAI). WoS was selected as it searches several databases simultaneously and has quality criteria for inclusion. For typical use and effects, Erowid, PsychonautWiki, Bluelight, and Drugs-Forum were searched; for legal status and epidemiology, the European Information System and Database on New Drugs (EDND) was used. Results: Aminoindanes were first synthesized for medical use, e.g., as anti-Parkinsonian drugs and later as a potential compound facilitating psychotherapy; however, they are now widely substituted for ecstasy. Their mechanisms of action (primarily via serotonin) mean that they may pose a significant risk of serotonin syndrome at high doses or when combined with other drugs. Fatally toxic effects have been observed both in the laboratory in animal studies and in clinic, where deaths related with aminoindanes have been reported. Conclusion: Greater knowledge about aminoindanes is urgently required to decrease risks of fatal intoxication, and appropriate legislation is needed to protect public health without impeding research.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH