Neuroactive steroids represent potential antiepileptic drugs. We tested a newly synthesized analogue of allopregnanolone 3α- hydroxy-21ξ,22-oxido-21-homo-5α-pregnan-20-on (HOHP) against two types of pentylenetetrazol-induced seizures (100 mg/kg s.c.) in 12- and 25-day-old rats. Ganaxolone, a neuroactive steroid in clinical trials, served as a reference drug. Pretreatment with either steroid suppressed generalized tonicclonic seizures in both age groups, their efficacy was comparable. HOHP as well as ganaxolone were more active in 12- than in 25-day-old rats (effective doses were 40 and 60 mg/kg, respectively). Minimal clonic seizures, which can be elicited only in 25-day-old rats, were not influenced by any drug. Very short duration of anticonvulsant action of HPOP demonstrated in 12-day-old animals indicates that this drug might be used only in acute treatment in epileptology., P. Mareš, H. Kubová, A. Kasal., and Obsahuje bibliografii a bibliografické odkazy
GABA-B receptor agonist SKF97541 exhibits age-dependent anticonvulsant and proconvulsant actions in developing rats. It suppressed tonic phase of generalized seizures induced by pentetrazol in 7-, 12- and 18-day-old rats and increased their latency in 7- and 12-day-old animals. Other results in 18-day-old animals are not so clear. SKF 97541 blocked the appearance of minimal clonic seizures, but tended to decrease latencies of both types of seizures. In addition, it significantly decreases latency of generalized seizures in adult rats. The mixed effects of SKF97541 are in agreement with those of baclofen but there are substantial differences between the actions of these two agonists in individual age groups., P. Mareš., and Obsahuje bibliografii a bibliografické odkazy
The action of progabide against motor seizures elicited by pentylenetetrazol was studied in 7-, 12-, 18-, 25-day-old and adult rats. Progabide (dissolved in dimethylsulfoxide) was injected in doses from 12.5 to 150 mg/kg i.p. 30 min before pentylenetetrazol. Minimal seizures were not affected by solvent or progabide pretreatment. The action of progabide against major, i.e. generalized tonic-clonic seizures, changed with age: adult rats exhibited a tendency to suppression of whole major seizures, whereas specific suppression of the tonic phase was observed in rat pups during the first three weeks of life. The only effect seen in 25-day-old animals was prolongation of the latency of major seizures after the highest dose of progabide.
The anticonvulsant action of SL 75 102, a metabolite of Progabide, was studied in a model of pentylenetetrazol- induced motor seizures in adult and 12-day-old rats. SL 75 102 suppressed generalized tonic-clonic seizures in adult rats and restricted the tonic phase of these seizures in rat pups. SL 75 102 was less effective than Progabide. In addition, some minor differences in anticonvulsant actions of these two drugs were observed.
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.
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