Reflektujíc nedávný objev potenciálního využití beauverolidů (cyklotetradepsipeptidů produkovaných entomopatogenními houbami) v lékařství, předkládaný projekt navrhuje výzkum beauverolidů z pohledu jejich využitelnosti pro ovlivnění patologických stavů spojených s metabolickým syndromem a s deregulací buněk imunitního systému. Dopady stávající masivní aplikace beauverolidů v zemědělství a lesnictví na člověka dosud nebyly studovány. Zároveň bychom tedy v rámci předkládaného projektu rádi zjistili, zda stávající způsoby využití beauverolidů nejsou spojeny s nežádoucími účinky na člověka. Prostřednictvím modifikací v kultivačních podmínkách zdrojových organismů předpokládáme produkci širokého spektra beauverolidů navzájem odlišného chemického složení, které budou přečištěny, podrobně biochemicky charakterizovány, a následně testovány pomocí baterie biologických testů na lidských buněčných liniích a primárních buněčných izolátech. Zkoumán bude i způsob metabolizace beauverolidů.; Beauverolides represent a group of fungal cyclotetradepsipeptides, with only recently recognized potential for human medicine. Reflecting recent preclinical data, this project focuses at the use of beauverolides in modulation of pathologies associated with human metabolic syndrome and with immune system dysregulation. Current massive application of beauverolides in agriculture and forestry raises also the question on potential adverse effects of these applications on the humans, which were never addressed in detail. Thus, we would like to also focus on the association of current use of beauverolides with adverse effects on humans. Beauverolides will be produced under a spectrum of diverse cultivation conditions, which will result in a diversification of their chemical composition. Obtained fungal products will be purified and biochemically characterized in detail, and tested using the battery of biological tests, including those involving human cell lines primary cell isolates. Besides that, the exact mechanisms of metabolisation of beauverolides will be addressed as well.

• MeSH
• Beauveria izolace a purifikace   MeSH
• depsipeptidy MeSH
• imunitní systém mikrobiologie   patologie   MeSH
• kultivované buňky mikrobiologie   MeSH
• lidé MeSH
• metabolický syndrom mikrobiologie   patologie   MeSH
• Check Tag
• lidé MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• mikrobiologie, lékařská mikrobiologie
• botanika
• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

Beauverolides (beauveriolides) are abundant, biologically active cyclodepsipeptides produced by many entomopathogenic fungi, including those that are used as biopesticides. Beauverolides act as cholesterol acyltransferase inhibitors in humans; thus, their mode of action has been the subject of pharmacological and clinical research. The cost-effective analytical methods are needed for fast, routine laboratory analysis of beauverolides. We isolated beauverolides from the fungal strain Isaria fumosorosea PFR 97-Apopka and opened the rings of the isolated beauverolides using a pyridine alkaline medium. We separated fractions of cyclic and linearized beauverolides by thin-layer chromatography, and found the chloroform-acetate (9:1, v/v) and chloroform-acetonitrile-acetate (8:1:1, v/v/v) mobile phases, respectively, to be the most efficient. We examined all the fractions by liquid chromatography-mass spectrometry using ion trap and Orbitrap high resolution mass spectrometry. For rapid screening of the contents of cyclic, and, particularly, linearized beauverolides, we developed a novel analytical method that consisted of using capillary electrophoresis coupled with contactless conductivity detection. Furthermore, we improved the separation of the peptides by applying capillary micellar electrokinetic chromatography with the N-cyclohexyl-2-aminoethanesulfonic acid:SDS:NaOH buffer, pH 9.8 as the background electrolyte. The described novel methods allow fast and cost-effective separation of chemically related groups of beauverolides.

• MeSH
• anticholesteremika chemie   izolace a purifikace   MeSH
• chromatografie kapalinová MeSH
• Cordyceps chemie   MeSH
• depsipeptidy chemie   izolace a purifikace   MeSH
• hmotnostní spektrometrie MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• Klíčová slova
• beauverolidy, beauveriolidy,
• MeSH
• Alzheimerova nemoc farmakoterapie   patofyziologie   MeSH
• amyloidní beta-protein MeSH
• ateroskleróza farmakoterapie   patofyziologie   MeSH
• Beauveria metabolismus   MeSH
• cholesterolacyltransferasa antagonisté a inhibitory   fyziologie   MeSH
• cyklické peptidy terapeutické užití   MeSH
• depsipeptidy * terapeutické užití   MeSH
• fungální proteiny * biosyntéza   MeSH
• kalmodulin antagonisté a inhibitory   fyziologie   MeSH
• lidé MeSH
• makrofágy patologie   účinky léků   MeSH
• myši MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• Publikační typ
• práce podpořená grantem MeSH

BACKGROUND/AIM: Melanoma is a cancer disease with increasing incidence in the Caucasian population. It is often accompanied by spontaneous regression (SR), probably due to high immunogenicity. Understanding of this phenomenon could allow its induction in clinical practice, but detailed study in humans is impossible for ethical reasons. The aim of this study was to determine the role of fibronectin, tenascin C, and MMP-2 in the process of SR. MATERIALS AND METHODS: Time-lapse study of SR was performed in the MeLiM (Melanoma-bearing Libechov Minipig) model. Skin melanomas were taken from 3 weeks to 8 months of age and immunohistochemically processed for fibronectin, tenascin C and matrix metalloproteinase-2 (MMP-2). RESULTS: Expression of all studied proteins increased up to the 10th week of age. Two structurally different areas were distinguishable from the 3rd month of age. MPP-2 expression predominated in areas with melanoma cells, whereas fibronectin and tenascin-C prevailed in the forming fibrous tissue. CONCLUSION: Rebuilding of melanoma into the fibrous tissue during SR was connected with a general rise in fibronectin and tenascin C expression.

• MeSH
• fibronektiny metabolismus   MeSH
• matrixová metaloproteinasa 2 metabolismus   MeSH
• melanom metabolismus   patologie   MeSH
• miniaturní prasata MeSH
• modely nemocí na zvířatech MeSH
• prasata MeSH
• tenascin metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Anafylaxe je klinická náhlá událost, všichni zdravotničtí pracovníci by měli ovládat její diagnostiku, akutní a následnou terapii. V článku jsou prezentována nová doporučení pro rozeznání anafylaxe, odhad rizikových faktorů a následnou léčbu.

Anaphylaxis is a clinical emergency, all healtcare professinals should be familiar with its diagnosis and acute and ongoing management.Here, we present updated recommendations for recognition, risk factor assesment and patiens management.

• Klíčová slova
• autoinjektor,
• MeSH
• adrenalin aplikace a dávkování   terapeutické užití   MeSH
• anafylaxe * MeSH
• antagonisté histaminu H1 aplikace a dávkování   terapeutické užití   MeSH
• antagonisté histaminu H2 aplikace a dávkování   terapeutické užití   MeSH
• časná lékařská intervence metody   MeSH
• časná přecitlivělost MeSH
• imunoglobulin E MeSH
• injekce intramuskulární MeSH
• intravenózní podání MeSH
• kousnutí a bodnutí hmyzem MeSH
• kožní mastocytóza etiologie   MeSH
• léková alergie MeSH
• lidé MeSH
• mastocyty MeSH
• potravinová alergie MeSH
• samoléčba MeSH
• sekundární prevence MeSH
• systémová mastocytóza etiologie   MeSH
• vzdělávání pacientů jako téma MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

• MeSH
• anafylaxe diagnóza   chemicky indukované   MeSH
• chlorhexidin * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• dezinficiencia škodlivé účinky   terapeutické užití   MeSH
• diabetes mellitus 2. typu farmakoterapie   komplikace   MeSH
• diabetická noha farmakoterapie   komplikace   MeSH
• diferenciální diagnóza MeSH
• komorbidita MeSH
• kožní testy MeSH
• léková alergie * diagnóza   prevence a kontrola   MeSH
• lidé MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

In solid cancers, invasion and metastasis account for more than 90% of mortality. However, in the current armory of anticancer therapies, a specific category of anti-invasion and antimetastatic drugs is missing. Here, we coin the term 'migrastatics' for drugs interfering with all modes of cancer cell invasion and metastasis, to distinguish this class from conventional cytostatic drugs, which are mainly directed against cell proliferation. We define actin polymerization and contractility as target mechanisms for migrastatics, and review candidate migrastatic drugs. Critical assessment of these antimetastatic agents is warranted, because they may define new options for the treatment of solid cancers.

• MeSH
• chemorezistence MeSH
• cílená molekulární terapie MeSH
• lidé MeSH
• metastázy nádorů farmakoterapie   MeSH
• nádorové biomarkery MeSH
• nádory farmakoterapie   etiologie   metabolismus   patologie   MeSH
• objevování léků * MeSH
• pohyb buněk účinky léků   MeSH
• protinádorové látky chemie   farmakologie   terapeutické užití   MeSH
• signální transdukce účinky léků   MeSH
• synergismus léků MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Monotypic stands of common reed and the reed-gall-associated insect assemblages are distributed worldwide. However, fungi associated with these assemblages have not been characterized in detail. Here we examined 5200 individuals (12 species) of immature aculeate hymenopterans or their parasitoids collected at 34 sampling sites in Central Europe. We noticed fungal outgrowth on exoskeletons of 83 (1.60%) larvae and pupae. The most common host was eudominant Pemphredon fabricii. However, the less abundant aculeate hymenopteran reed gall inquilines were infected at higher prevalence, these included Trypoxylon deceptorium, Trypoxylon minus, Hoplitis leucomelana and Hylaeus moricei (all considered new host records). We identified three fungal species, Penicillium buchwaldii (72% of cases), Aspergillus pseudoglaucus (22%) and Penicillium quebecense (6%). When multibrooded nests were affected, only a part of individuals was infected in 62% of cases. The sampling site-specific infection rate reached up to 13%, thus fungal infections should be considered an important variable driving the abundance of gall inquilines. Infections of generalist host species were more frequent than those of reed gall specialists, suggesting that suboptimal conditions decreased the immunocompetence of non-specialized species, which only occasionally nest in reed galls and feed in reed beds.

• MeSH
• Aspergillus cytologie   genetika   fyziologie   MeSH
• DNA fungální chemie   MeSH
• fylogeneze MeSH
• Hymenoptera klasifikace   mikrobiologie   MeSH
• interakce hostitele a patogenu MeSH
• kukla mikrobiologie   MeSH
• larva mikrobiologie   MeSH
• nádory rostlin mikrobiologie   MeSH
• Penicillium cytologie   genetika   fyziologie   MeSH
• pravděpodobnostní funkce MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Growth stimuli in cancer growth resemble those exhibited in wound healing. However, the process of nemosis is absent in cancer-associated fibroblasts (CAFs), which remain constitutively active. CAFs are present in almost all solid tumors but are most abundant in breast, prostate and pancreatic cancers. TGF-β1, TGF-β2, PDGF, IL-6, bFGF, reactive oxide species and protein kinase C are considered the key players in tumor-induced transdifferentiation of surrounding fibroblasts. Full-extent transdifferentiation was obtained only when the medium contained TGF-β1 or TGF-β2 (with or without other factors), whereas PDGF, bFGF or IL-6 (each alone) induced only partial transdifferentiation. Recent evidence suggests that the fibroblasts associated with primary cancers differ from those associated with metastases. The metastases-associated fibroblasts are converted by a metastasis-specific spectrum of factors. A large portion of paracrine tumor signaling is mediated by cancer cell-derived vesicles termed exosomes and microvesicles. The cancer cell-derived exosomes contain abundant and diverse proteomes and a number of signaling factors (TGF-ß1, TGF-ß2, IL-6, MMP2 and MMP9), particularly under hypoxic conditions. In contrast to the traditional view, the clonal expansion and selection of neoplastic cells should not be viewed outside the host body context. It is vital for a neoplastic cell to achieve the ability to re-program host body cells into CAFs and by this influence to modulate its microenvironment and receive positive feedback for growth and drug resistance. Neoplastic cells, which fail to develop such capacity, do not pass critical barriers in tumorigenesis and remain dormant and benign.

• MeSH
• fibroblasty cytologie   MeSH
• lidé MeSH
• nádorové mikroprostředí fyziologie   MeSH
• nádory patologie   MeSH
• signální transdukce fyziologie   MeSH
• transdiferenciace buněk fyziologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Pimecrolimus (Elidel, SDZ ASM 981) is an anti-inflammatory and immunomodulatory 33-epichloro-derivative of macrolactam ascomycin, with low potential for affecting systemic immune responses compared with other calcineurin inhibitors, cyclosporin A and tacrolimus. Despite numerous studies focused on the mechanism of pimecrolimus action on mast cells, only the single report has addressed pimecrolimus effects on other typical FcεRI-expressing cells, the basophils. Patients allergic to birch pollen (n = 20), hymenopteran venoms (n = 23) and 10 non-allergic volunteers were examined. Primary human basophils pre-treated or not with 0.5-50 μMol pimecrolimus were exposed to various concentrations of recombinant Bet v 1a allergen, bee or wasp venom extracts and anti-IgE for 20 min, and then examined for the expression of CD45, CD193, CD203c, CD63 and CD164 using flow cytometry. The externalization of basophil activation markers (CD63 and CD164) was equally inhibited through pimecrolimus in cells activated by recombinant pollen allergen, hymenopteran venom extracts and anti-IgE. Although the individual response rate was subject to strong variation, importantly, pre-treatment with pimecrolimus lowered the number of activated basophils in response to any of the stimuli in the basophils from all patients. The inhibition was concentration-dependent; approximately half of the basophils were inhibited in the presence of 2.5 mMol pimecrolimus. Pimecrolimus is a valuable new tool for the inhibition of hyper-reactive basophils in patients with pollen allergy and a history of anaphylactic reactions to bee or wasp venoms. Further research should address short-term use of pimecrolimus in vivo in a wide spectrum of allergic diseases.

• MeSH
• alergeny imunologie   MeSH
• alergie farmakoterapie   imunologie   MeSH
• antialergika farmakologie   MeSH
• antiflogistika nesteroidní farmakologie   MeSH
• bazofily účinky léků   imunologie   MeSH
• bříza imunologie   MeSH
• dospělí MeSH
• imunoglobulin E imunologie   MeSH
• kultivované buňky MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• protilátky anti-idiotypické imunologie   MeSH
• receptory IgE imunologie   MeSH
• senioři MeSH
• sezónní alergická rýma farmakoterapie   imunologie   MeSH
• sršňovití imunologie   MeSH
• takrolimus analogy a deriváty   farmakologie   MeSH
• včely imunologie   MeSH
• vosí jedy imunologie   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• senioři MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH