Terlipressin (triglycyl-lysine vasopressin TP), a "hormonogen" analogue, was introduced in gastroenterology for its low and protracted vasopressor action, reducing bleeding from gastrointestinal tract. Its antidiuretic activity, estimated originally in ethanol-anaesthetized rats (Sawyer’s method) was claimed to be equally low and protracted. We performed several series of antidiuretic tests on conscious rats (Burn’s method) with the following results. TP in low doses of 0.05-1.0 /<g/kg exhibited typical dose-dependent antidiuretic effect. In the dose of 0.2 /ig/kg, the dynamics of urine and sodium excretion did not differ from that after equivalent dose of lysine vasopressin and equipotent dose of DDAVP. The antidiuretic potency of TP (estimated by parallel line assay) was 175.0 U/rng. TP in doses of 5.0 and 20.0 /<g/kg exhibited limited diuresis and marked natriuresis. High osmolality and sodium content were present in all portions of excreted urine. The discrepancy between previous and our results concerning antidiuretic activity of TP and the role of pressure natriuresis for overall renal action of TP are discussed.
Antifosfolipidový syndrom (APS) je autoimunitně podmíněné onemocnění s celou řadou potenciálně život ohrožujících manifestací. Vyskytuje se samostatně v primární podobě nebo jako sekundární doprovázející řadu chorobných stavů (autoimunitní, nádorová onemocnění atd.). Diagnostická kritéria zahrnují jak klinickou, tak laboratorní složku. Mezi klinické manifestace patří výskyt trombóz arteriálních či žilních a dále komplikace v těhotenství. Laboratorně musí být opakovaně prokázána přítomnost antifosfolipidových protilátek v minimálním odstupu 12 týdnů. Klinická manifestace APS může být velmi pestrá a často vyžaduje multidisciplinární přístup. Obávanou, ale vzácnou komplikací je tzv. katastrofický APS spojený s vysokou morbiditou a mortalitou. Včasná diagnóza spolu s terapií výrazně ovlivňuje prognózu pacientů s APS. Klíčová slova: antifosfolipidový syndrom – systémový lupus erythematodes, Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by various potentially serious and life‑threatening manifestations. APS occurs in a primary form with no associated conditions, or in a secondary form associated with various other illnesses (autoimmune, neoplastic and others). APS is diagnosed according to clinical and laboratory criteria. It is characterized by recurrent arterial or venous thrombosis and/or pregnancy‑related complications and laboratory findings of antiphospholipid antibodies in a minimum time interval of 12 weeks between individual laboratory tests. Clinical manifestations of APS can vary and a multidisciplinary approach is needed. Catastrophic APS is a very serious and life‑threatening condition associated with high mortality and morbidity, although it is rare. An early diagnosis with proper therapy has a serious impact on the prognosis of patients with APS. Keywords: antiphospholipid syndrome – systemic lupus erythematosus, and Ciferská H.
It is known that intracellular pathogens interact and react with the cellular immune system through exosomes produced by macrophages. This study aimed to determine whether co-culture of macrophages and Talaromyces marneffei induces exosomes and leads to immune responses. T. marneffei was incubated to collect conidia, co-cultured with human macrophages, which then induced exosomes. In cellular experiments, after extraction and purification, the exosomes were then observed by electron microscopy and detected by flow cytometry and mass spectrometry. In animal experiments, flow cytometry and enzyme-linked immunosorbent assay were used to examine whether exosomes were antigenpresenting. The results showed that purified exosomes produced a pro-inflammatory response and stimulated production of TNF-α in non-fungal-treated macrophages. Protein mass spectrometry analysis of exosomes also indicated their potential ability to activate the internal immune response system and the pro-inflammatory response. Translation and ribosomes were the most abundant GO terms in proteins, and the most relevant KEGG pathway was the biosynthesis of secondary metabolites. Furthermore, in vivo experiments revealed that exosomes induced activation of lymphocytes and increased expression of TNF-α and IL-12 in the lung, mediastinum, and spleen area. In conclusion, exosomes can be released by co-culture of T. marneffei and macrophages, having antigen-presenting functions, promoting macrophage inflammation, and initiating adaptive immune responses. These processes are inextricably linked to the translation of secondary metabolites, ribosomes and biosynthesis.
Sheep scab caused by the mite Psoroptes ovis (Hering) is a highly contagious disease of sheep. As a first step in developing a mite-derived vaccine for controlling the disease, the soluble antigens in mite extracts which induce an immune response in sheep were identified by electrophoretic and immunoblotting techniques. At least 22 proteins were present in P. ovis extracts as revealed by Coomassie Blue staining. Mite-infested sheep serum recognised six antigenic bands in the extracts with approximate relative molecular weights ranging from 12 to 183 kDa. A deeply staining band at 31.2 kDa and another at 41.8 kDa are of particular diagnostic value. Immunoblotting studies showed that there was no cross reactivity between P. ovis and two other ectoparasites of sheep in the UK, the sheep louse Bovicola ovis (Schrank) and the sheep tick Ixodes ricinus L.
Na řadě konkrétních příkladů ukážeme, že se sluneční soustava i galaxie velice pozvolna rozpínají rychlostí řádově srovnatelnou s Hubbleovou konstantou. To je samozřejmé V rozporu se zákonem zachování energie. Dále ukážeme, co by mohlo být zdrojem skryté energie způsobující toto rozpínání i zrychlující se rozpínání celého vesmíru., We give several factual examples showing that the Solar System and also galaxies expand very slowly by a speed comparable with the Hubble constant. This, of course, contradicts the law of ener gy conservation. Further, we show what could be the source of dark energy causing this expansion as well as the accelerating expansion of the whole universe., Michal Křížek., and Obsahuje seznam literatury
Ve druhé části článku předložíme další argumenty, které hovoří ve prospěch hypotézy, jež tvrdí, že skrytá energie nepůsobí jenom globálně, ale i lokálně. To naznačuje, že zákon zachování energie nemusí platit. Navíc ukážeme, že skrytá energie způsobující lokální expanzi gravitačně vázaných systémů může pocházet z nepatrně malé, ale kladné hodnoty gravitační aberace, jež je důsledkem konečné rychlosti šíření gravitační interakce a principu kauzality. Předložený mechanismus může i přispívat ke zrychlujícímu se rozpínání vesmíru., In the second part of this paper we give further examples showing that dark energy acts, not only globally, but also locally. This indicates that the law of energy conservation does not hold. Moreover, we demonstrate that the dark energy needed for an accelerated expansion of the universe may come from an extremely small but positive value of gravitational aberration which would result from a finite speed of gravitational interaction and from causality., Michal Křížek., and Obsahuje seznam literatury
Sekundární prevence aterotrombotických příhod je doménou protidestičkové léčby, podle rizika jedním lékem či kombinací acetylsalicylové kyseliny s blokátory ADP receptorů. Význam kombinace duální protidestičkové léčby v kombinaci s xabany či s dabigatranem prověřovalo 6 klinických studií. Pouze jedna z nich (ATLAS ACS 2-TIMI 51) ukázala, že léčba malými dávkami rivaroxabanu (2krát 2,5 mg) může být přidána ke kombinaci kyseliny acetylsalicylové s klopidogrelem. Pro několikanásobně zvýšené riziko velkých krvácivých příhod se však čistý klinický přínos pohybuje jen kolem 0,5 % ročně. Duální léčba s kombinací kyseliny acetylsalicylové s prasugrelem či s tikagrelorem je přínosnější. V druhé části přehledu je rozebírán vyšší výskyt infarktu myokardu v kontrolovaných studiích při léčbě dabigatranem v porovnání s warfarinem. Vztah není dořešen, nicméně u nemocných s vyšším rizikem koronárních příhod je při indikaci antikoagulační léčby přímými antikoagulancii vhodnější volit ze skupiny xabanů (apixaban či rivaroxaban)., Secondary prevention of atherothrombotic events is the domain of antiplatelet therapy and according to present risk is used one drug strategy or combination of acetylsalicylic acid with ADP receptor blockers. The importance of the combination of dual antiplatelet therapy together with xabans or dabigatran was investigated in 6 clinical trials. Only one of them (ATLAS ACS 2-TIMI 51) indicated that treatment with small dose of rivaroxaban (2 × 2.5 mg) may be added to dual strategy of acetylsalicylic acid and clopidogrel. The risk of major bleeding event is increased and net clinical benefit is only about 0.5 % per year. Dual therapy with aspirin and prasugrel or tikagrelor is beneficial. In the second part of the review is discussed higher incidence of myocardial infarction in controlled group in the trial comparing treatment of dabigatran with warfarin. This relationship has not been resolved, however, in patients with higher risk of coronary events and indication of anticoagulant treatment with direct oral anticoagulants it is recommended to choose from xabans (apixaban and rivaroxaban)., and Jan Bultas
Riziko trombózy významně stoupá s věkem. U osob do 40 let se předpokládá incidence žilních tromboembolismů 1 na 10 000, u osob'nad 75 let se vyskytuje s četností 1 na 100 osob. Není zcela jasné, co nejvíce způsobuje závislost žilní trombózy a věku. Nejpravděpodobněji jde o kombinaci snížení mobility, poklesu svalového napěti, zvýšení morbidity a změn stěny cévní. K žilním tromboembolismům závislým na věku můžeme počítat i ty, které vznikly při hormonální terapii u postmenopauzálních žen. S věkem také stoupá koncentrace koagulačních faktorů, především faktoru VIII, II a IX. Vyšší věk je při antikoagulační léčbě rizikový ze dvou hledisek : a) nemocní ve vyšším věku mají významnější tendenci ke krvácení b) nemocní ve vyšším věku mají jinou toleranci antikoagulační léčby pro vyšší hladinu koagulačních faktorů a zároveň polymorbiditu (nádory, větší riziko arteriálních a žilních trombóz, kombinace kardiovaskulárních a metabolických onemocnení). Léčba musí být laboratorně kontrolována. Tzv. terapeutické rozmezí INR ohraničuje meze předpokládané terapeutické účinnosti a zároveň bezpečnosti léčby. Warfarin má dlouhý poločas účinku a není třeba ho rozdělovat do více denních dávek. Na předpokládaný antikoagulační efekt warfarinu má vliv řada vnějších a vnitřních faktorů a může působit kolísání hladiny INR. Kolísání INR může paradoxně působit protromboticky, protože antagonisté vitaminu K blokují i přirozené inhibitory koagulace (protein C a protein S)., The risk of thrombosis significantly increases with age. In people under 40 years the incidence of thromboembolism is presumed in 1 of 10 000 persons, while in people above 75 years it occurs in 1 of 100 persons. It is not quite clear what is the main cause of the relation between the venous thrombosis and the age. The most probably it is a combination of the decrease of mobility, the decline of muscular tension, the increase of morbidity and the changes of vascular wall. As the age-related venous thromboembolism can be considered also the cases of thromboembolism originated during the hormonal therapy in post-menopausal women. It is also the concentration of coagulative factors, especially the VIII, II and IX factor, which increases with ageing. There are two aspects why is the senior age at risk during the coagulative treatment-. a) there is more significant tendency to bleed in the senior patients b) the senior patients have a different tolerance of the anticoagulative treatment to the higher level of coagulative factor and to the polymorbidity at the same time (the tumours, higher risk of arterial and venous thromboses, the combination of cardiovascular and metabolic diseases) The treatment should be monitored in laboratory. So-called INR therapeutic range bounds the limits of the presumed therapeutic effectiveness and at the same time the safety of the treatment. Warfarin has a long effeaiveness half - life and it does not need to be divided into several daily doses. The presumed coagulative effect of Warfarin is influenced by the series of internal and external factors, which can cause the variance of INR level. The variance of INR can paradoxically have an antithrombotic effect since the vitamin K antagonists block the natural coagularion inhibitors (C and 5 proteins)., Jaroslav Malý, Petr Dulíček, Miroslav Pecka, Lit: 9, and Souhrn: eng
The action of two potential anticonvulsants, CM 40907 (10-50 mg/kg i.p.) and SR 41378 (1.25-20 mg/kg i.p.) against metrazol-induced seizures was studied in rats 7, 12, 18 and 25 days old. Two types of motor seizures - minimal, clonic and major, generalized tonic-clonic - were elicited by a 100-mg/kg dose of metrazol (s.c.) and their incidence and latency were evaluated. The severity of seizures was expressed as a score on a 5-point scale. Dimethylsulfoxide, an organic solvent, exhibited anticonvulsant action only in doses far exceeding those used for dissolving the two anticonvulsants. Both drugs suppressed minimal as well as major seizures in all age groups studied in a dose-dependent manner, SR 41378 being approximately four times more potent than CM 40907. The latencies could be measured only in animals given low doses of anticonvulsants. CM 40907 did not change the latencies whereas SR 41378 prolonged them. The severity of seizures was decreased again in a dose-dependent manner. There were only minor changes in the efficacy of CM 40907 among the four age groups. On the contrary, SR 41378 exhibited an extreme efficacy in 7-day-old rat pups, where even the 1.25 mg/kg dose signifcantly decreased the incidence and severity of seizures. The efficacy in the remaining three age groups was approximately at the same level as in adult rats.