Aminophylline, a bronchodilator mainly used to treat severe asthma attacks, may induce arrhythmias. Unfortunately, the underlying mechanism is not well understood. We have recently described a significant, on average inhibitory effect of aminophylline on inward rectifier potassium current IK1, known to substantially contribute to arrhythmogenesis, in rat ventricular myocytes at room temperature. This study was aimed to examine whether a similar effect may be observed under clinically relevant conditions. Experiments were performed using the whole cell patch clamp technique at 37°C on enzymatically isolated healthy porcine and failing human ventricular myocytes. The effect of clinically relevant concentrations of aminophylline (10-100 μM) on IK1 did not significantly differ in healthy porcine and failing human ventricular myocytes. IK1 was reversibly inhibited by ∼20 and 30 % in the presence of 30 and 100 μM aminophylline, respectively, at -110 mV; an analogical effect was observed at -50 mV. To separate the impact of IK1 changes on AP configuration, potentially interfering ionic currents were blocked (L-type calcium and delayed rectifier potassium currents). A significant prolongation of AP duration was observed in the presence of 100 μM aminophylline in porcine cardiomyocytes which well agreed with the effect of a specific IK1 inhibitor Ba2+ (10 μM) and with the result of simulations using a porcine ventricular cell model. We conclude that the observed effect of aminophylline on healthy porcine and failing human IK1 might be involved in its proarrhythmic action. To fully understand the underlying mechanism, potential aminophylline impact on other ionic currents should be explored.
- MeSH
- akční potenciály účinky léků MeSH
- aminofylin * farmakologie MeSH
- draslíkové kanály dovnitř usměrňující * metabolismus MeSH
- kardiomyocyty * účinky léků metabolismus MeSH
- lidé MeSH
- metoda terčíkového zámku MeSH
- prasata MeSH
- srdeční komory účinky léků metabolismus MeSH
- srdeční selhání metabolismus farmakoterapie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Úvod: Staphylococcus aures (S. aureus) je grampozitívny fakultatívne anaeróbny kok, ktorý je schopný vyvolať infekčné ochorenie zvierat aj ľudí. Zvlášť nebezpečné sú multirezistentné formy s nižšou, alebo aj žiadnou odpoveďou na dostupnú liečbu. Ciele: Cieľom práce je overiť vplyv enzybiotík v hojení S. aureus infikovaných kožných rán na exprimentálnom modeli prasiat. Metodika: Do pokusu boli zaradené dve prasatá, ktorým boli na chrbtovej oblasti vyrezané rany (10x/1prasa) o veľkosti 5x5 cm s 2 cm odstupmi. Rany boli infikované methicilin (Oxacilin) a amoxicilin resistentným kmeňom S. aureus baktérie (MRSA). Experimentálne skupiny pozostávali z jednotlivých rán, ktoré boli infikované jedným sekvenčným typom baktérie S. aureus v koncentrácii 2x10 9 CFU/ml. Dve rany ostali neliečené (N), štyri rany boli liečené hydrogélom doplneným lyzostatínom (L) a štyri boli liečené hydrogélom doplneným lyzostatínom a endolyzínom (LE). Následne boli na štvrtý, siedmy, jedenásty a štrnásty deň odoberané vzorky z jednotlivých rán. Materiál bol spracovaný štandardnou histologickou technikou formou parafinových bločkov a rezy boli farbené hematoxylínom-eozínom. Výsledky: Z výsledkov vyplýva, že ide o defekty s celým spektrom reparačných zmien s reepitelizáciou so striedaním úsekov nekróz a novovytvoreného granulačného tkaniva s doprevádzajúcim guľatobunečným zápalovým infiltrátom na podklade edematózneho tkaniva a povrchovými chrastami. Na povrchu rán a tiež v menších skupinkách v novovytvorenom granulačnom tkanive sú viditeľné kokovitné útvary charakteru S. aureus. V hydrogélových krytoch, ktoré obsahujú lyzostafín, alebo kombináciu lyzostafínu s endolyzínom sa porovnaním s neliečenými ranami zachytávajú väčšie množstvá kolónie S. aureus kokov, ktoré tu vo veľkej miere následne odumierajú. Záver: Enzybiotiká môžu mať potenciál v topickej terapii MRSA infikovaných kožných rán.
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Pseudomonas aeruginosa poses a significant threat to both immunocompetent and immunocompromised individuals, often resulting in life-threatening infections. With increasing antimicrobial resistance, novel therapeutic strategies are urgently needed. Although animal models are crucial for preclinical studies, limited data are available for porcine models, more specifically for P. aeruginosa complicated skin and soft tissue infections (cSSTIs). This study presents a novel porcine model inducing and sustaining cSSTI for 14 days. Six pigs (120 wounds) were used for the development of infections, and within this group, two pigs (40 wounds) were used to evaluate the progression of the cSSTI infection. The model demonstrated bacterial loads of more than 107 CFU/gram of tissue or higher. The cSSTI fully developed within three days and remained well above these levels until day 14 post-infection. Due to the immunocompetence of this model, all the immunological processes associated with the response to the presence of infection and the wound healing process are preserved.
Kokcidióza patří mezi nejčastější onemocnění králíků v době odstavu a je jedním z limitujících faktorů odchovu králíků. Mezi patogenní kokcidie řadíme u králíků druhy parazitující ve střevech (E. magna, E. irresidua, E. intestinalis, E. flavescens, E. piriformis, a E. media) a jaterní kokcidie (E. stiedae). Stupeň infekce je závislý na druhu Eimerie, množství pozřených oocyst, věku a imunitním stavu hostitele. Diagnostika je založena na flotačním vyšetření, případně na přesném určení druhu pomocí molekulárněbiologických metod. Terapie spočívá v aplikaci antikokcidik (sulfonamidů, toltrazurilu) ve vodě nebo podaných přímo do dutiny ústní. Prevence onemocnění spočívá v dobrých zoohygienických podmínkách, správně provedeném odstavu, krmné dávce a jejím složení (v obsahu vlákniny, škrobů a bílkovin), snížení stresových faktorů a v případě velkochovů nebo malochovů v podání peletovaného krmiva s obsahem kokcidiostatik.
Coccidiosis is one of the most common diseases of rabbits at the time of weaning and is one of the limiting factors in rabbit breeding. Pathogenic coccidia in rabbits includes species parasitizing in the intestines (E. magna, E. irresidua, E. intestinalis, E. flavescens, E. piriformis, and E. media) and liver (E. stiedae). The severity of infection depends on the species of Eimeria, the number of ingested oocysts, age, and immune status of the host. Diagnostics is based on a flotation examination, or the exact determination of the species using molecular biological methods. Therapy consists of the oral administration of anticoccidials (sulphonamides, toltrazuril) in water or directly into the oral cavity. Disease prevention consists of optimal zoohygiene, properly performed weaning, feed ration and its composition (fiber, starch, and protein content), reduction of stress factors, and, in the case of large-scale or small-scale farms, in the form of pelleted diets containing coccidiostatics.
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
Encephalitozoonosis is a common infectious disease widely spread among rabbits. Encephalitozoon cuniculi, is considered as a zoonotic and emerging pathogen capable of infecting both immunocompetent and immunocompromised hosts. The aim of the study was to describe in detail the spread of the E. cuniculi in a rabbit organism after experimental infection and the host humoral and cellular immune response including cytokine production. For that purpose, healthy immunocompetent rabbits were infected orally in order to simulate the natural route of infection and euthanised at 2, 4, 6 and 8-weeks post-infection. Dissemination of E. cuniculi in the body of the rabbit was more rapid than previously reported. As early as 2 weeks post-infection, E. cuniculi was detected using immunohistochemistry not only in the intestine, mesenteric lymph nodes, spleen, liver, kidneys, lungs and heart, but also in nervous tissues, especially in medulla oblongata, cerebellum, and leptomeninges. Based on flow cytometry, no conspicuous changes in lymphocyte subpopulations were detected in the examined lymphoid organs of infected rabbits. Cell-mediated immunity was characterized by ability of both CD4+ and CD8+ T cells to proliferate after stimulation with specific antigens. Th1 polarization of immune response with a predominance of IFN-γ expression was detected in spleen, mesenteric lymph nodes and Peyer's patches. The increased expression of IL-4 and IL-10 mRNA in mixed samples from the small intestine is indicative of balanced control of IFN-γ, which prevents tissue damage. On the other hand, it can enable E. cuniculi to survive and persist in the host organism in a balanced host-parasite relationship. The Th17 immunity lineage seems to play only a minor role in E. cuniculi infection in rabbits.
- MeSH
- buněčná imunita * MeSH
- Encephalitozoon cuniculi fyziologie MeSH
- encephalitozoonóza imunologie parazitologie veterinární MeSH
- humorální imunita * MeSH
- imunokompetence MeSH
- králíci * MeSH
- zvířata MeSH
- Check Tag
- králíci * MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Biological experiments involving isolated organs and tissues demand precise temperature monitoring and regulation. An automatic temperature control system was proposed and optimised on real isolated swine hearts and the prototype is described in this work. The traditional Langendorff apparatus consists of a heart holder, a reservoir of perfusion solution flowing to aortic cannula and a heating bath allowing passive heat transfer to the reservoir of perfusion solution. The commercial infrared camera FLIR T62101 was added to this basic set-up and used for very precise monitoring of the temperature kinetic of the organ and connected with an electronic feedback loop, which allowed real-time and precise regulation of heat transfer from the heating bath to the perfusion solution and in turn indirectly to the heart tissue. This provides real time control and active regulation of the myocardial tissue temperature. The infrared camera was tested in several modes and several variants of detection were optimised for ideal measurement of the region of interest of the ex vivo organ. The kinetics of the temperature changes and temperature stability of the tissue were recorded and calibrated by external electronic thermometers (type Pt100, inserted in tissue). The time lapse from the hang-up of the hypo termed organ (30 °C) until optimal warming (37 °C) was less than eight minutes in the final instrument prototype. The final stability of the 37 °C tissue temperature was approved; the temperature fluctuation of left ventricle tissue was characterised as 36.8 ± 0.5 °C. This upgraded traditional instrument could be used in specific preclinical and clinical transplantation and analytical projects in future.
- MeSH
- infračervené záření MeSH
- lidé MeSH
- preparace izolovaného srdce * metody MeSH
- termoregulace MeSH
- zahřívání metody přístrojové vybavení MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
