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
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.
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
The main characteristics of the Antimüllerian hormone from the points of view of biochemistry, molecular genetics, physiological functions and importance for diagnostics in reproductive endocrinology and related biomedical fields are reviewed. The role of the hormone in male and female development, its participation in oocyte maturation including selection of a dominant follicle are summarized, as well as its changes under various pathological situations in both sexes. The physiological changes of serum AMH leves in the life span in both sexes and their alterations under various pathological conditions are provided, too., R. Hampl, M. Šnajderová, T. Mardešić., and Obsahuje bibliografii a bibliografické odkazy
Research on brown adipose tissue and its hallmark protein, mitochondrial uncoupling protei n UCP1, has been conducted for half a century and has been traditionally studied in the Institute of Physiology (AS CR, Prague), likewise UCP2 residing in multiple tissues for the last two decades. Our group has significantly contributed to the elucidation of UCP uncoupling mechanism, fully dependent on free fatty acids (FFAs) within the inner mitochondrial membrane. Now we review UCP2 physiological roles emphasizing its roles in pancreatic β-cells, such as antioxidant role, possible tuning of redox homeostasis (consequently UCP2 participation in redox regulations), and fine regulation of glucose-stimulated insulin secretion (GSIS). For example, NADPH has been firmly established as being a modulator of GSIS and since UCP2 may influence redox homeostasis, it likely affects NADPH levels. We also point out the role of phospholipase iPLA2 isoform γ in providing FFAs for the UCP2 antioxidant function. Such initiation of mild uncoupling hypothetically precedes lipotoxicity in pancreatic β-cells until it reaches the pathological threshold, after which the antioxidant role of UCP2 can be no more cell-protective, for example due to oxidative stress-accumulated mutations in mtDNA. These mechanisms, together with impaired autocrine insulin function belong to important causes of Type 2 diabetes etiology., P. Ježek ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Diabetes mellitus is characterized by oxidative stress, which in turn determines endothelial dysfunction. Gliclazide is a sulphonylurea antidiabetic drug with antioxidant effects due to its azabicyclo-octyl ring. It has been reported to potentially protect the vasculature through improvements in plasma lipid levels and platelet function. We hypothesized that gliclazide has a beneficial effect on endothelial function in Goto-Kakizaki rats (GK), an animal model of type 2 diabetes fed an atherogenic diet for 4 months. We evaluated the influence of gliclazide on both metabolic and oxidative status and NO-mediated vasodilation. GKAD rats showed increased oxidative stress and impaired endothelium-dependent vasodilation. GKAD rats treated with gliclazide showed increased sensitivity to NO-mediated vasodilation, a significant decrease in fasting glycemia and insulinemia, and a significant decrease in systemic oxidative stress. In conclusion, our results suggest that gliclazide treatment improves NO-mediated vasodilation in diabetic GK rats with dyslipidemia probably due to its antioxidant effects, although we cannot rule out substantial benefits due to a reduction in fasting blood glucose. The availability of a compound that simultaneously decreases hyperglycemia, hyperinsulinemia, and inhibits oxidative stress is a promising therapeutic candidate for the prevention of vascular complications of diabetes., C. M. Sena ... [et al.]., and Obsahuje seznam literatury