Background: Progesterone is the source of the steroid general anesthetic Alfaxalone, which became commercially available in the 1970s when combined with alfadolone, another steroid anesthetic.Objective: the goal of the present research was to discover and assess the sub-anesthetic effects of Alfaxalone: the antinociceptive and anti-inflammatory properties in broiler chicks. Methods: One hundred and three Ross broiler chicks (80-100 g, 7-8 days old) were used. The electric stimulation test, hot water test (HWT), and formalin test were performed on broiler chicks to assess the antinociceptive and anti-inflammatory properties of Alfaxalone. The up-and-down method that described by Dixon was used to determine the median effective antinociceptive dose.Results: The median effective antinociceptive doses (ED50s) of Alfaxalone by electric stimulation test and hot water test were 0.94 and 0.65 mg/kg intraperitoneally, respectively. Alfaxalone, at doses of 1, 2, and 4 mg/kg intraperitoneally, induced an antinociceptive effect in the electric stimulation test and HWT as well as antinociceptive and anti-inflammatory effects during the formalin test in the chicks. The antinociceptive effect was displayed 15 min after treatment and the maximum effect was observed 30 min after injection.Conclusion: The results showed that Alfaxalone had antinociceptive and anti-inflammatory effects, with a stronger antinociceptive effect in the electric stimulation test than in the thermal stimulation test, which was illustrated by shorter antinociceptive time.

• Klíčová slova
• alfaxalon,
• MeSH
• analgetika aplikace a dávkování   farmakologie   MeSH
• antiflogistika aplikace a dávkování   farmakologie   MeSH
• elektrická stimulace MeSH
• fyzikální stimulace metody   MeSH
• injekce intraperitoneální MeSH
• kur domácí MeSH
• modely u zvířat MeSH
• pregnandiony * aplikace a dávkování   farmakologie   MeSH
• Publikační typ
• práce podpořená grantem MeSH

Novel aminonaphthylcysteine (ANC) adducts, formed via naphthylnitrenium ions and/or their metabolic precursors in the biotransformation of naphthylamines (NA) and nitronaphthalenes (NN), were identified and quantified in globin of rats dosed intraperitoneally with 0.16 mmol/kg b.w. of 1-NA, 1-NN, 2-NA and 2-NN. Using HPLC-ESI-MS2 analysis of the globin hydrolysates, S-(1-amino-2-naphthyl)cysteine (1A2NC) together with S-(4-amino-1-naphthyl)cysteine (4A1NC) were found in rats given 1-NA or 1-NN, and S-(2-amino-1-naphthyl)cysteine (2A1NC) in those given 2-NA or 2-NN. The highest level of ANC was produced by the most mutagenic and carcinogenic isomer 2-NA (35.8 ± 5.4 nmol/g globin). The ratio of ANC adduct levels for 1-NA, 1-NN, 2-NA and 2-NN was 1:2:100:3, respectively. Notably, the ratio of 1A2NC:4A1NC in globin of rats dosed with 1-NA and 1-NN differed significantly (2:98 versus 16:84 respectively), indicating differences in mechanism of the adduct formation. Moreover, aminonaphthylmercapturic acids, formed via conjugation of naphthylnitrenium ions and/or their metabolic precursors with glutathione, were identified in the rat urine. Their amounts excreted after dosing rats with 1-NA, 1-NN, 2-NA and 2-NN were in the ratio 1:100:40:2, respectively. For all four compounds tested, haemoglobin binding index for ANC was several-fold higher than that for the sulphinamide adducts, generated via nitrosoarene metabolites. Due to involvement of electrophilic intermediates in their formation, ANC adducts in globin may become toxicologically more relevant biomarkers of cumulative exposure to carcinogenic or non-carcinogenic arylamines and nitroarenes than the currently used sulphinamide adducts.

• MeSH
• 1-naftylamin aplikace a dávkování   metabolismus   toxicita   MeSH
• 2-naftylamin aplikace a dávkování   metabolismus   toxicita   MeSH
• acetylcystein analogy a deriváty   moč   MeSH
• biologické markery krev   moč   MeSH
• cystein MeSH
• globiny metabolismus   MeSH
• injekce intraperitoneální MeSH
• naftaleny aplikace a dávkování   krev   toxicita   MeSH
• potkani Wistar MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Prolactin-releasing peptide (PrRP) has been proposed to mediate the central satiating effects of cholecystokinin (CCK) through the vagal CCK1 receptor. PrRP acts as an endogenous ligand of G protein-coupled receptor 10 (GPR10), which is expressed at the highest levels in brain areas related to food intake regulation, e.g., the paraventricular hypothalamic nucleus (PVN) and nucleus of the solitary tract (NTS). The NTS and PVN are also significantly activated after peripheral CCK administration. The aim of this study was to determine whether the endogenous PrRP neuronal system in the brain is involved in the central anorexigenic effect of the peripherally administered CCK agonist JMV236 or the CCK1 antagonist devazepide and whether the CCK system is involved in the central anorexigenic effect of the peripherally applied lipidized PrRP analog palm-PrRP31 in fasted lean mice. The effect of devazepide and JMV236 on the anorexigenic effects of palm-PrRP31 as well as devazepide combined with JMV236 and palm-PrRP31 on food intake and Fos cell activation in the PVN and caudal NTS was examined. Our results suggest that the anorexigenic effect of JMV236 is accompanied by activation of PrRP neurons of the NTS in a CCK1 receptor-dependent manner. Moreover, while the anorexigenic effect of palm-PrRP31 was not affected by JMV236, it was partially attenuated by devazepide in fasted mice. The present findings indicate that the exogenously influenced CCK system may be involved in the central anorexigenic effect of peripherally applied palm-PrRP31, which possibly indicates some interaction between the CCK and PrRP neuronal systems.

• MeSH
• anorektika aplikace a dávkování   MeSH
• antagonisté hormonů aplikace a dávkování   MeSH
• chemokiny CC účinky léků   metabolismus   MeSH
• cholecystokinin metabolismus   MeSH
• devazepid aplikace a dávkování   MeSH
• hormon uvolňující prolaktin aplikace a dávkování   analogy a deriváty   MeSH
• injekce intraperitoneální MeSH
• injekce subkutánní MeSH
• myši inbrední C57BL MeSH
• nucleus paraventricularis hypothalami účinky léků   metabolismus   MeSH
• nucleus solitarius účinky léků   metabolismus   MeSH
• omezení příjmu potravy MeSH
• peptidové fragmenty aplikace a dávkování   MeSH
• přijímání potravy účinky léků   MeSH
• protoonkogenní proteiny c-fos metabolismus   MeSH
• signální transdukce MeSH
• sinkalid aplikace a dávkování   analogy a deriváty   MeSH
• stravovací zvyklosti účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The effectiveness of cell transplantation can be improved by optimization of the transplantation site. For some types of cells that form highly oxygen-demanding tissue, e.g., pancreatic islets, a successful engraftment depends on immediate and sufficient blood supply. This critical point can be avoided when cells are transplanted into a bioengineered pre-vascularized cavity which can be formed using a polymer scaffold. In our study, we tested surface-modified poly(lactide-co-caprolactone) (PLCL) capsular scaffolds containing the pro-angiogenic factor VEGF. After each modification step (i.e., amination and heparinization), the surface properties and morphology of scaffolds were characterized by ATR-FTIR and XPS spectroscopy, and by SEM and AFM. All modifications preserved the gross capsule morphology and maintained the open pore structure. Optimized aminolysis conditions decreased the Mw of PLCL only up to 10% while generating a sufficient number of NH2 groups required for the covalent immobilization of heparin. The heparin layer served as a VEGF reservoir with an in vitro VEGF release for at least four weeks. In vivo studies revealed that to obtain highly vascularized PLCL capsules (a) the optimal VEGF dose for the capsule was 50 μg and (b) the implantation time was four weeks when implanted into the greater omentum of Lewis rats; dense fibrous tissue accompanied by vessels completely infiltrated the scaffold and created sparse granulation tissue within the internal cavity of the capsule. The prepared pre-vascularized pouch enabled the islet graft survival and functioning for at least 50 days after islet transplantation. The proposed construct can be used to create a reliable pre-vascularized pouch for cell transplantation.

• MeSH
• bioinženýrství * MeSH
• experimentální diabetes mellitus chemicky indukované   metabolismus   patologie   MeSH
• fyziologická neovaskularizace * MeSH
• injekce intraperitoneální MeSH
• krevní glukóza analýza   MeSH
• krysa rodu rattus MeSH
• molekulární struktura MeSH
• polyestery chemie   metabolismus   MeSH
• potkani inbrední LEW MeSH
• streptozocin aplikace a dávkování   MeSH
• tobolky chemie   metabolismus   MeSH
• transplantace Langerhansových ostrůvků * MeSH
• vaskulární endoteliální růstové faktory chemie   metabolismus   MeSH
• velikost částic MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Beta-hydroxy-beta-methyl butyrate (HMB) is a unique product of leucine catabolism with positive effects on protein balance. We have examined the effects of HMB (200 mg/kg/day via osmotic pump for 7 days) on rats with diabetes induced by streptozotocin (STZ, 100 mg/kg intraperitoneally). STZ induced severe diabetes associated with muscle wasting, decreased ATP in the liver, and increased α-ketoglutarate in muscles. In plasma, liver, and muscles increased branched-chain amino acids (BCAAs; valine, isoleucine, and leucine) and decreased serine. The decreases in mass and protein content of muscles and increases in BCAA concentration were more pronounced in extensor digitorum longus (fast-twitch muscle) than in soleus muscle (slow-twitch muscle). HMB infusion to STZ-treated animals increased glycemia and serine in the liver, decreased BCAAs in plasma and muscles, and decreased ATP in the liver and muscles. The effects of HMB on the weight and protein content of tissues were nonsignificant. We concluded that fast-twitch muscles are more sensitive to STZ than slow-twitch muscles and that HMB administration to STZ-treated rats has dual effects. Adjustments of BCAA concentrations in plasma and muscles and serine in the liver can be considered beneficial, whereas the increased glycemia and decreased ATP concentrations in the liver and muscles are detrimental.

• MeSH
• aminokyseliny aplikace a dávkování   farmakologie   MeSH
• diabetes mellitus 1. typu chemicky indukované   farmakoterapie   metabolismus   MeSH
• injekce intraperitoneální MeSH
• injekce subkutánní MeSH
• játra účinky léků   metabolismus   MeSH
• kosterní svaly účinky léků   metabolismus   MeSH
• krysa rodu rattus MeSH
• potkani Wistar MeSH
• streptozocin aplikace a dávkování   MeSH
• valeráty aplikace a dávkování   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The plant extract aristolochic acid (AA), containing aristolochic acid I (AAI) and II (AAII) as major components, causes aristolochic acid nephropathy and Balkan endemic nephropathy, unique renal diseases associated with upper urothelial cancer. Differences in the metabolic activation and detoxification of AAI and AAII and their effects on the metabolism of AAI/AAII mixture in the plant extract might be of great importance for an individual's susceptibility in the development of AA-mediated nephropathies and malignancies. Here, we investigated in vivo metabolism of AAI and AAII after ip administration to Wistar rats as individual compounds and as AAI/AAII mixture using high performance liquid chromatography/electrospray ionization mass spectrometry. Experimental findings were supported by theoretical calculations using density functional theory. We found that exposure to AAI/AAII mixture affected the generation of their oxidative and reductive metabolites formed during Phase I biotransformation and excreted in rat urine. Several Phase II metabolites of AAI and AAII found in the urine of exposed rats were also analyzed. Our results indicate that AAI is more efficiently metabolized in rats in vivo than AAII. Whereas AAI is predominantly oxidized during in vivo metabolism, its reduction is the minor metabolic pathway. In contrast, AAII is mainly metabolized by reduction. The oxidative reaction only occurs if aristolactam II, the major reductive metabolite of AAII, is enzymatically hydroxylated, forming aristolactam Ia. In AAI/AAII mixture, the metabolism of AAI and AAII is influenced by the presence of both AAs. For instance, the reductive metabolism of AAI is increased in the presence of AAII while the presence of AAI decreased the reductive metabolism of AAII. These results suggest that increased bioactivation of AAI in the presence of AAII also leads to increased AAI genotoxicity, which may critically impact AAI-mediated carcinogenesis. Future studies are needed to explain the underlying mechanism(s) for this phenomenon.

• MeSH
• hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
• injekce intraperitoneální MeSH
• krysa rodu rattus MeSH
• kyseliny aristolochové aplikace a dávkování   metabolismus   moč   MeSH
• potkani Wistar MeSH
• teorie funkcionálu hustoty MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment modality for peritoneal surface malignancies with efficacy reported in many trials. Discrepancies, however, in the indication criteria, the extent of the surgical procedure, HIPEC regimens and toxicity evaluation represent a problem when comparing this method with other therapeutic modalities. METHODS: We describe the initial experience with CRS/HIPEC using different chemotherapy regimens (oxaliplatin, cisplatin, mitomycin C and doxorubicin) at the Comprehensive Oncology Centre Olomouc. RESULTS: A perioperative mortality of 2% and perioperative morbidity of 11%, according to Clavien-Dindo were observed. Interestingly, all these patients underwent HIPEC with oxaliplatin 460 mg/m2. The median duration of admission to hospital was 6 days in the intensive care unit (range 2-28 days) and 7 days in the surgical ward (range 1-21 days). Hospital admission did not exceed 2 weeks in 75% of patients. These results are consistent with the published results of large centres performing this treatment modality mainly due to pre-operative preparation of patients and pre-treatment and post-treatment management of HIPEC/CRS toxicity. Evaluation of the efficacy in terms of time to progression and overall survival (OS) is limited by the short follow up period. CONCLUSION: CRS/HIPEC performed is a safe method with low perioperative mortality.

• MeSH
• cisplatina terapeutické užití   MeSH
• cytoredukční chirurgie metody   MeSH
• dospělí MeSH
• doxorubicin terapeutické užití   MeSH
• injekce intraperitoneální MeSH
• kombinovaná terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mitomycin terapeutické užití   MeSH
• oxaliplatin terapeutické užití   MeSH
• peritoneální nádory farmakoterapie   chirurgie   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

• Klíčová slova
• hypertermická intraperitoneální chemoterapie,
• MeSH
• cytoredukční chirurgie * metody   škodlivé účinky   MeSH
• indukovaná hypertermie metody   MeSH
• injekce intraperitoneální metody   MeSH
• karcinom chirurgie   terapie   MeSH
• kolorektální nádory * chirurgie   komplikace   terapie   MeSH
• kombinovaná terapie MeSH
• lidé MeSH
• peritoneální nádory chirurgie   sekundární   MeSH
• peritoneum chirurgie   patologie   účinky léků   MeSH
• tlusté střevo chirurgie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

Hypertermická intraperitoneální chemoterapie (HIPEC) je metoda využívaná k léčbě pacientů s peritoneální karcinomatózou. Mezi cytostatika, která se k terapii využívají, patří, mimo jiné, platinové deriváty - cisplatina a oxaliplatina. Tato alkylační antineoplastika napadají DNA nádorových buněk a indukují apoptózu. Protože ale působí na všechny rychle proliferující buňky, mají také řadu nežádoucích účinků. Kromě typické trombocytopenie a neutropenie se můžeme setkat i s akutním renálním selháním u cisplatiny (36 % pacientů), nebo neuropatií u oxaliplatiny (19 % pacientů). Dále se objevují respirační nemoci, infekce ran nebo hemoperitoneum. Jelikož při HIPEC přichází personál přímo do styku s cytostatikem, které je navíc většinou více koncentrované než při intravenóz-ním podání, je potřeba se zaměřit i na bezpečnost pracovníků přítomných při zákroku. Základem je dodržení všech bezpečnost-ních zásad včetně pravidelné kontroly vzorků moči a krve. Studie ukazují, že koncentrace platinových derivátu ve zmiňovaných vzorcích jsou pod hranicí detekovatelnosti a že by tedy metoda HIPEC měla být bezpečná. Ovšem studie prokazující bezpečnost z dlouhodobého hlediska zatím chybí.

Hyperthermic intraperitoneal chemotherapy (HIPEC) is a method used to treat patients with peritoneum carcinomatosis. Cytostatics used in therapy include platinum derivatives - cisplatin and oxaliplatin. These alkylating chemotherapeutics attack the tumor cell DNA and induce apoptosis. They have a lot of side effects because they affect all of the proliferating cells. Besides typical thrombocytopenia and neutropenia, acute renal failure in cisplatin (36% of patients) or neuropathy in oxaliplatin (19% of patients) may occur. Others include respiratory diseases, wound infections, or hemoperitoneum. During HIPEC, the staff comes directly into contact with a cytostatic agent, which is usually more concentrated than when administered intravenously. It is essential to comply with the safety principles, including the control of sample of urine and blood. Studies show, that platinum derivatives in samples are below the detection limit and that the HIPEC method could be safe. However, studies showing safety in the long term are missing.

• MeSH
• cisplatina škodlivé účinky   terapeutické užití   MeSH
• cytoredukční chirurgie MeSH
• indukovaná hypertermie MeSH
• injekce intraperitoneální MeSH
• lidé MeSH
• personál nemocniční MeSH
• protokoly protinádorové léčby MeSH
• sloučeniny platiny * škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• lidé MeSH

A series of 2-aryl-2-(pyridin-2-yl)acetamides were synthesized and screened for their anticonvulsant activity in animal models of epilepsy. The compounds were broadly active in the 'classical' maximal electroshock seizure (MES) and subcutaneous Metrazol (scMET) tests as well as in the 6 Hz and kindling models of pharmacoresistant seizures. Furthermore, the compounds showed good therapeutic indices between anticonvulsant activity and motor impairment. Structure-activity relationship (SAR) trends clearly showed the highest activity resides in unsubstituted phenyl derivatives or compounds having ortho- and meta- substituents on the phenyl ring. The 2-aryl-2-(pyridin-2-yl)acetamides were derived by redesign of the cardiotoxic sodium channel blocker Disopyramide (DISO). Our results show that the compounds preserve the capability of the parent compound to inhibit voltage gated sodium currents in patch-clamp experiments; however, in contrast to DISO, a representative compound from the series 1 displays high levels of cardiac safety in a panel of in vitro and in vivo experiments.

• MeSH
• acetamidy aplikace a dávkování   chemie   terapeutické užití   MeSH
• antikonvulziva aplikace a dávkování   chemie   terapeutické užití   MeSH
• disopyramid aplikace a dávkování   chemie   terapeutické užití   MeSH
• elektrický šok MeSH
• injekce intraperitoneální MeSH
• injekce subkutánní MeSH
• krysa rodu rattus MeSH
• molekulární struktura MeSH
• myši MeSH
• pentylentetrazol aplikace a dávkování   MeSH
• potkani Wistar MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• záchvaty chemicky indukované   farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH