Some antidepressant drugs, especially tricyclic ones - (TCA), have cardiovascular side effects. To compare the effects of antidepressant drugs, the electrocardiogram (ECG), vectorcardiogram (VCG), and body surface maps (BSM) were recorded in psychiatric patients without cardiovascular diseases treated by a) TCA amitriptyline or dosulepin (daily dose 50-200 mg, 22 patients), b) lithium (serum level 0.66±0.08 meq/1, 21 patients), c) selective serotonine reuptake inhibitor citalopram (daily doses 20-60 mg, 30 patients), and in 23 control patients. In the TCA-treated patients, the heart rate was increased, QT and RR intervals shortened (p<0.01, antimuscarinic effect). This was not observed in lithium- and citalopram-treated patients. All antidepressants decreased the absolute maximum values of depolarization isointegral maps, lithium and TCA reduced the initial and citalopram the later phase of depolarization. Citalopram slightly diminished the amplitude of the R wave. The results confirm the antimuscarinic effects of TCA in therapeutic doses and specify the intraventricular effects of antidepressants.
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