Východiská: Schnitzlerovej syndróm je získané autoinflamačné ochorenie so základom v poruche prirodzenej imunity. Podozrivým je proteín MyD88 – toll-like receptor zapojený do zápalovej kaskády vyúsťujúcej aj do zvýšenej sekrécie interleukínu-1 (IL-1), kľúčového cytokínu v patogenéze a klinickej manifestácii viacerých autoinflamačných stavov. Syndróm je pomenovaný po francúzskej kožnej lekárke Liliane Schnitzler, ktorá v roku 1972 opísala kazuistickú sériu pacientov s prejavmi urtikárie v spojení s monoklonálnou gamapatiou. V klinickom obraze dominujú prejavy chronickej urtikárie, pričom histologicky ide najčastejšie o neutrofilovú dermatózu. Nevyhnutným kritériom na zadefinovanie Schnitzlerovej syndrómu je monoklonálna gamapatia, pričom až v 90 % prípadov ide o monoklonálnu IgM gamapatiu. Zvyšná skupina pacientov má prítomnú gamapatiu v triede IgG. Z vedľajších kritérií potrebných na potvrdenie syndrómu podľa Strassburgskej klasifikácie je to zvýšená nešpecifická zápalová aktivita (elevácia sérového CRP, leukocytóza), morfologické zmeny na kostiach (verifikované hyperostotické či osteosklerotické zmeny skeletu na CT, scintigraficky, alebo PET/CT s použitím rádioaktívneho natrium fluoridu NaF18), bolesti kostí či artralgia. Pacienti sú vo zvýšenom riziku rozvoja lymfoproliferačného ochorenia ako Waldenströmovej makroglobulinémie alebo low-grade lymfómu (15–20 %). Rizikom je tiež rozvoj AA amyloidózy pri dlhodobej nekontrolovanej hyperinflamácii. Akútnou, život ohrozujúcou komplikáciou môže byť syndróm aktivovaných makrofágov. Vzhľadom na imunologickú podstatu ochorenia a eleváciu zápalových cytokínov je základom anticytokínová liečba. Najlepšie výsledky sú pozorované pri anakinre (antagonista receptora pre IL-1), inou možnosťou je eventuálne kanakinumab (monoklonálna protilátka proti IL-1b). Pozitívny efekt bol opisovaný aj pri inhibítoroch Brutonovej tyrozínkinázy. Kortikoidy a konvenčné imunosupresíva nie sú dostatočne efektívne. Prípad: V predkladanom texte prezentujeme formou kazuistickej série dve pacientky so Schnitzlerovej syndrómom s raritnejšími klinickými príznakmi a s diferencovanou odpoveďou na anticytokínovú liečbu. Cieľom autorov bolo informovať a zlepšiť povedomie o tomto vzácnom ochorení a jeho možnostiach liečby. Záver: Ochorenie je chronické, liečba je len symptomatická, ale vedie k ústupu klinických príznakov a dosiahnutiu kontroly nad zápalom. Riziko vzniku hematologickej malignity anticytokínová liečba pravdepodobne neovplyvňuje.

Background: Schnitzler‘s syndrome is an acquired autoinflammatory disease with a disorder in innate immune response. The suspect is the protein MyD88 – a toll-like receptor involved in the inflammatory cascade resulting in increased secretion of interleukin-1 (IL-1), a key cytokine in the pathogenesis and clinical manifestation of several autoinflammations. The syndrome is named after the French dermatologist Liliane Schnitzler, who described a case series of patients with manifestations of urticaria and monoclonal gammapathy in 1972. The clinical picture is characterized by chronic urticaria, histologically it is most often neutrophilic dermatosis. A necessary criterion for defining Schnitzler‘s syndrome is monoclonal gammapathy. In up to 90% of cases, it is monoclonal IgM gammapathy, the remaining group of patients has IgG gammapathy. Among the secondary criteria necessary to define the syndrome according to the Strasbourg classification, non-specific inflammatory activity is present in patients (elevation of CRP, leukocytosis), morphological changes on the bones (hyperostotic or osteosclerotic changes of the skeleton verified by CT, scintigraphy or PET/CT using radioactive sodium fluoride NaF18), bone pain or arthralgia. Patients are at an increased risk of developing a lymphoproliferative disease, especially Waldenström‘s macroglobulinemia or low grade lymphoma (15–20%). There is also a risk of the development of AA amyloidosis due to long-term uncontrolled hyperinflammation. Macrophage activating syndrome can be an acute life-threatening complication, as we describe in our patient. Considering the immunological nature of the disease and the elevation of inflammatory cytokines, the basis of treatment is anticytokine therapy. The best results are seen with anakinra (IL-1 receptor antagonist), possibly canakinumab (a monoclonal antibody against IL-1b). A positive effect was also described with Bruton‘s tyrosine kinase inhibitors. Corticoids and conventional immunosuppressants are not effective enough. Case: In this text, we present a case series of two patients with Schnitzler‘s syndrome with rare clinical symptoms. The authors‘ goal was to improve awareness of this rare hematoinflammatory disease and its treatment options. Conclusion: The disease is chronic, the treatment is only symptomatic, but can lead to the reduction of clinical symptoms. Anticytokine treatment probably does not affect the risk of hematological malignancy.

• MeSH
• Diagnosis, Differential MeSH
• Adult MeSH
• Immunoglobulin G immunology   MeSH
• Interleukin-1 immunology   MeSH
• Humans MeSH
• Paraproteinemias genetics   immunology   MeSH
• Aged MeSH
• Macrophage Activation Syndrome diagnosis   etiology   MeSH
• Schnitzler Syndrome * diagnosis   drug therapy   genetics   immunology   MeSH
• Urticaria diagnosis   etiology   immunology   MeSH
• Inflammation diagnosis   etiology   immunology   classification   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Familial dysautonomia is a debilitating congenital neurodegenerative disorder with no causative therapy. It is caused by a homozygous mutation in ELP1 gene, resulting in the production of the transcript lacking exon 20. The compounds studied as potential treatments include the clinical candidate kinetin, a plant hormone from the cytokinin family. We explored the relationship between the structure of a set of kinetin derivatives (N = 72) and their ability to correct aberrant splicing of the ELP1 gene. Active compounds can be obtained by the substitution of the purine ring with chlorine and fluorine at the C2 atom, with a small alkyl group at the N7 atom, or with diverse groups at the C8 atom. On the other hand, a substitution at the N3 or N9 atoms resulted in a loss of activity. We successfully tested a hypothesis inspired by the remarkable tolerance of the position C8 to substitution, postulating that the imidazole of the purine moiety is not required for the activity. We also evaluated the activity of phytohormones from other families, but none of them corrected ELP1 mRNA aberrant splicing. A panel of in vitro ADME assays, including evaluation of transport across model barriers, stability in plasma and in the presence of liver microsomal fraction as well as plasma protein binding, was used for an initial estimation of the potential bioavailability of the active compounds. Finally, a RNA-seq data suggest that 8-aminokinetin modulates expression spliceosome components.

• MeSH
• Kinetin * pharmacology   chemistry   MeSH
• Humans MeSH
• Molecular Structure MeSH
• RNA Precursors * genetics   metabolism   MeSH
• RNA Splicing * drug effects   MeSH
• Transcriptional Elongation Factors metabolism   genetics   MeSH
• Dose-Response Relationship, Drug MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Crohnova choroba a ulcerózna kolitída patria medzi heterogénnu skupinu chorôb zaradených do skupiny nešpecifických črevných zápalov (IBD – inflammatory bowel disease). Pri etiopatogenéze ochorenia sa uplatňujú multifaktoriálne príčiny, z ktorých významné zastúpenie má genetická predispozícia, zloženie mikrobiómu, abnormálna imunitná odpoveď a environmentálne faktory. Potenciálnu terapiu predstavuje cvičenie. Cvičenie vedie k zvýšeniu expresie interleukinu-6 (IL-6) a protizápalového cytokínu IL-10. Potenciálny benefit cvičenia je v ovplyvnení indukovanej črevnej bariérovej dysfunkcie a a zmiernení symptómov. Optimálna pohybová dávka znižuje viscerálny tuk a následne vedie k uvoľňovaniu prozápalových cytokínov a uvoľňovaniu myokínov, ako je IL-6. Pravidelné cvičenie je asociované s autofágiou, ktorá je spojená s intracelulárnou degradáciou s protektívnym účinkom pred vznikom ochorení. Ďalším možným mechanizmom cvičenia je ovplyvnenie tumor nekrotizujúceho faktora alfa. Cvičenie tiež môže potencovať vplyv na zlepšenie symptómov pomocou heat shock proteínu. Dôležitý vplyv cvičenia sa uplatňuje aj v prevencii pred vznikom IBD a vedie k zníženiu rizika relapsu IBD. Pravidelné cvičenie tiež prispieva k optimálnej kompozícii tela pacientov a zvyšuje kvalitu života pacientov s IBD.

Crohn’s disease and ulcerative colitis belong to a heterogeneous group of diseases classified as inflammatory bowel disease. The etiopathogenesis of the disease involves multifactorial causes of which the genetic predisposition, interstitial microbiome, abnormal immune response and environmental factors play a significant role. Physical exercise can be used as potential therapy. Exercise may increase expression of interleukin-6 (IL-6) and the anti-inflammatory cytokine IL-10. Exercise can also lead to alleviation of stress-induced intestinal barrier dysfunction and relieves symptoms of disease. Physical activity at adequate doses decreases visceral fat and results in the release of pro-inflammatory cytokines and myokines such as IL-6. Regular exercise is associated with autophagy, which is associated with intracellular degradation with a protective effect before the disease develops. Another possible mechanism induced by exercise is to affect the tumour necrosis factor alpha. Exercise can also potentiate the effect of ameliorating symptoms by means of the heat shock protein. Exercise can prevent non-specific intestinal inflammation and reduces the risk of relapse. Regular exercise also contributes to optimal patient body composition and enhances the quality of life of patients with non-specific intestinal inflammation.

• MeSH
• Crohn Disease * rehabilitation   MeSH
• Humans MeSH
• Motor Activity MeSH
• Colitis, Ulcerative * rehabilitation   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Model bronchiálnej astmy v kontexte nových poznatkov sa vyznačuje značnou heterogenitou klinického priebehu, vyvolávajúcich príčin, terapeutickou odpoveďou a pridružených komorbidít. Čoraz väčšie úsilie je vynakladané k určeniu jednotlivých subtypov, pretože rozdielnosť definovaných patomorfologických zložiek procesu je príznačná pre celé spektrum ochorenia. Súbor variabilných patologických zápalových kaskád vytvára rozličnú mieru symptomatologickej manifestácie. Súhra mnohých faktorov od predominantných cytokínov zápalu, mikrobiómu bronchov, genetickej predispozície, až po vystavenia exogénnych nox v spleti vzájomných interakcií vytvára u každého pacienta charakteristické klinické vlastnosti ochorenia – fenotypy astmy. Aj najnovšia revízia odporúčaní GINA 2021 (Global Initiative for Asthma) poukazuje na potrebu čo najskoršej detailnej fenotypizácie astmy s cieľom adekvátneho výberu liečebnej stratégie na princípe precíznej, teda personalizovanej medicíny. Začlenením konkrétneho prípadu astmy do fenotypu na základe charakteristickej klinickej symptomatologickej prezentácie v časom slede nám môže pomôcť k predikcii závažnosti a terapeutickej responzivity ochorenia.

Heterogeneity of clinical cases, causing factors and therapeutic effect and associated comorbidities determinates bronchial asthma in the context of new discoveries. Challenging task is to dissect it into subgroups because of the heterogeneity present across the spectrum of the disease. The spectrum of variable pathological inflammatory cascades creates varying degrees of symptomatologic manifestation. Combination of many factors from predominated inflammation cytokines, microbiome of bronchi, genetic predisposition and exposition to exogenous noxes creates characteristic clinical properties of disease – asthma phenotypes. Recent GINA 2021 guidelines (Global Initiative for Asthma) indicate the demand of the earliest detailed phenotypisation of asthma to make an adequate selection in the therapeutic strategy based on the accurate, thus personalized medicine. Incorporating a specific asthma case into a phenotype based on its characteristic clinical symptom presentation over time may help us to predict the severity and therapeutic responsiveness of the disease.

• MeSH
• Asthma * etiology   complications   pathology   MeSH
• Child MeSH
• Phenotype MeSH
• Humans MeSH
• Adolescent MeSH
• Disease Progression MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Autoři uvádějí přehled forem celkové zánětlivé reakce vyvolané syndromem uvolnění cytokinů a tzv. cytokinovou bouří. Mezi spouštěče nekontrolovaného uvolnění cytokinů řadíme infekce, systémová onemocnění, rozsáhlé chirurgické výkony, imunoterapii nádorů ianafylaxi. Nadměrná proliferace aktivovaných T-lymfocytů a makrofágů vyvolává cytokinovou bouři také u hemofagocytující lymfohistiocytózy a syndromu aktivovaných makrofágů. Tyto stavy se společnými klinickými znaky vyvolané systémovým zánětem vedou k hemodynamické nestabilitě a až k multiorgánovému selhání. V roce 2020 byla nejčastěji uváděným termínem spojeným s onemocněním COVID-19 cytokinová bouře. Mezi rizikové faktory jejího vzniku patří genetická predispozice, vyšší věk, obezita nad 30 BMI, kardiovaskulární onemocnění, chronická obstrukční plicní nemoc, chronické onemocnění ledvin, nádorová onemocnění. U dětí se za 2–6 týdnů po expozici SARS-CoV-2 může rozvinout systémový zánět postihující především kardiovaskulární aparát. Diferenciální diagnostika těchto klinických obrazů vyvolaných cytokinovou bouří bývá na počátku obtížná, i když patofyziologické mechanismy postižení jsou si podobné. Možností ovlivnění rozvoje cytokinové bouře je podání monoklonálních protilátek

The authors present an overview of the form of the overall inflammatory response– cytokine release syndrome and cytokine storm syndrome. Triggers starting the reaction are infection, systemic diseases, extensive surgical procedures, tumor immunotherapy and rarely anaphylaxis. Excessive proliferation of activated T-lymphocytes and macrophages causes acytokine storm in hemophagocytic lymphohistiocytosis and activated macrophage syndrome. These conditions with common clinical features induced by systemic inflammation lead to hemodynamic instability and even multiorgan failure. In 2020, at the same time as the onset of the COVID-19 pandemic, the most common term associated with disease complications was acytokine storm. Risk factors include genetic predisposition but in patients with COVID-19 already proven age, obesity above 30 BMI, cardiovascular disease, type 2 diabetes mellitus, chronic obstructive pulmonary disease, chronic kidney disease, cancer. Children may develop systemic inflammation, mainly affecting the cardiovascular system, 2–6weeks after SARS-CoV-2 exposure. Differential diagnostic of these conditions is often difficult at first, although the patho-physiological mechanisms are similar. The possibility of influencing the development of the systemic reaction and the severity of the cytokine storm is the treatment with monoclonal antibodies

• MeSH
• COVID-19 complications   MeSH
• Cyclonic Storms * classification   MeSH
• Immunomodulation MeSH
• Humans MeSH
• Receptors, Interleukin-6 antagonists & inhibitors   drug effects   MeSH
• Check Tag
• Humans MeSH

Léčba axiální spondyloartritidy (axSpA), radiografické formy (r‑axSpA) známé jako ankylozující spondylitida, ale i neradiografické formy (nr‑axSpA) zaznamenala v posledních letech významný posun. Kromě tumor nekrotizujícího faktoru (TNF) hraje v patogenezi axSpA klíčovou roli cytokinová osa interleukinu (IL) 23 a 17, což podtrhují klinické zkušenosti a účinnost biologické léčby namířené proti TNF a IL‑17. V první linii je možné podat oba přípravky, ale v současnosti se doporučuje léčbu zahájit inhibitory TNF a při jejich selhání je ve druhé linii možné nasadit inhibitory IL‑17. Ixekizumab je humanizovaná monoklonální protilátka proti IL‑17A, jejíž účinnost a bezpečnost byly studovány ve třech lékových hodnoceních u pacientů s r‑axSpA, kteří neměli dostatečnou odpověď na nesteroidní antiflogistika a dosud jim nebyla podávána biologická léčba (COAST‑V), u pacientů s r‑axSpA, u nichž léčba blokující TNF selhala (COAST‑W), a také u pacientů s nr‑axSpA (COAST‑X). V této přehledové práci budou diskutovány výsledky těchto tří klinických hodnocení, které prokázaly snížení aktivity onemocnění, zlepšení kvality života, fyzických funkčních schopností a intenzity aktivního zánětu na páteři a sakroiliakálních kloubech při léčbě ixekizumabem ve srovnání s placebem. Ixekizumab byl minimálně stejně tak účinný jako adalimumab u pacientů s r‑axSpA ve studii COAST‑V. Bezpečnostní profil ixekizumabu byl konzistentní s biologickou léčbou, v porovnání s placebem byly častější reakce v místě vpichu a mírné až středně závažné infekce, nejčastěji nazofaryngitida nebo infekce horních cest dýchacích. Ixekizumab představuje vhodnou alternativu k léčbě blokující TNF u pacientů s axSpA.

In the last few years, important advances have happened in the treatment of axial spondyloarthritis (axSpA), both radiographic (r‑axSpA) known as ankylosing spondylitis and non‑radiographic (nr‑axSpA) form. Cytokine axis of interleukin (IL) 23 and 17 plays a key role in the pathogenesis of axSpA, besides tumor necrosis factor (TNF), underlined by clinical experience and efficacy of biologic treatment against TNF and IL‑17. It is possible to administer both medicinal products in the first line but currently it is recommended to initiate the treatment with TNF inhibitors. When they fail, it is possible to administer IL‑17 inhibitors in the second line. Ixekizumab is a humanized monoclonal antibody against IL‑17A with efficacy and safety studied in three clinical trials in patients with r‑axSpA without sufficient response to non‑steroidal anti‑inflammatory drugs and no biologic treatment so far (COAST‑V), in patients with r‑axSpA where TNF inhibitors failed (COAST‑W) and in patients with nr‑axSpA (COAST‑X). This article discusses the results of these three trials that showed decreased disease activity, increased quality of life, physical functional abilities and decreased intensity of active inflammation in the spine and sacroiliac joints when treated with ixekizumab compared with placebo. Ixekizumab was at least as efficacious as adalimumab in patients with r‑axSpA in COAST‑V trial. Safety profile of ixekizumab was consistent with biologic treatment; compared with placebo, local reactions at injection site were more frequent as well as mild to moderate infections, most frequently nasopharyngitis or upper respiratory infections. Ixekizumab represents a suitable alternative to TNF inhibitors in patients with axSpA.

• MeSH
• Biological Therapy methods   MeSH
• Antibodies, Monoclonal, Humanized * pharmacology   adverse effects   therapeutic use   MeSH
• Tumor Necrosis Factor Inhibitors MeSH
• Interleukin-17 * analogs & derivatives   adverse effects   therapeutic use   MeSH
• Humans MeSH
• Arthritis, Psoriatic drug therapy   MeSH
• Spondylarthritis * drug therapy   MeSH
• Check Tag
• Humans MeSH

Cytokinins are mobile multifunctional plant hormones with roles in development and stress resilience. Although their Histidine Kinase receptors are substantially localised to the endoplasmic reticulum, cellular sites of cytokinin perception and importance of spatially heterogeneous cytokinin distribution continue to be debated. Here we show that cytokinin perception by plasma membrane receptors is an effective additional path for cytokinin response. Readout from a Two Component Signalling cytokinin-specific reporter (TCSn::GFP) closely matches intracellular cytokinin content in roots, yet we also find cytokinins in extracellular fluid, potentially enabling action at the cell surface. Cytokinins covalently linked to beads that could not pass the plasma membrane increased expression of both TCSn::GFP and Cytokinin Response Factors. Super-resolution microscopy of GFP-labelled receptors and diminished TCSn::GFP response to immobilised cytokinins in cytokinin receptor mutants, further indicate that receptors can function at the cell surface. We argue that dual intracellular and surface locations may augment flexibility of cytokinin responses.

• MeSH
• Adenine analogs & derivatives   pharmacology   MeSH
• Arabidopsis cytology   drug effects   genetics   metabolism   MeSH
• Cytokinins metabolism   MeSH
• Extracellular Fluid metabolism   MeSH
• Plants, Genetically Modified MeSH
• Histidine Kinase genetics   metabolism   MeSH
• Mutation MeSH
• Arabidopsis Proteins genetics   metabolism   MeSH
• Recombinant Proteins genetics   metabolism   MeSH
• Signal Transduction MeSH
• Green Fluorescent Proteins genetics   metabolism   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Cross-talk between exogenous salicylic acid (SA) and endogenous phytohormone pathways affects the antioxidant defense system and its response to salt stress. The study presented here investigated the effects of SA treatment before and during salt stress on the levels of endogenous plant growth regulators in three barley cultivars with different salinity tolerances: Hordeum vulgare L. cvs. Akhisar (sensitive), Erginel (moderate), and Kalaycı (tolerant). The cultivars' relative leaf water contents, growth parameters, proline contents, chlorophyll a/b ratios, and lipid peroxidation levels were measured, along with the activities of enzymes involved in detoxifying reactive oxygen species (ROS) including superoxide-dismutase, peroxidase, catalase, ascorbate-peroxidase, and glutathione-reductase. In addition, levels of several endogenous phytohormones (indole-3-acetic-acid, cytokinins, abscisic acid, jasmonic acid, and ethylene) were measured. Barley is known to be more salt tolerant than related plant species. Accordingly, none of the studied cultivars exhibited changes in membrane lipid peroxidation under salt stress. However, they responded differently to salt-stress with respect to their accumulation of phytohormones and antioxidant enzyme activity. The strongest and weakest increases in ABA and proline accumulation were observed in Kalaycı and Akhisar, respectively, suggesting that salt-stress was more effectively managed in Kalaycı. The effects of exogenous SA treatment depended on both the timing of the treatment and the cultivar to which it was applied. In general, however, where SA helped mitigate salt stress, it appeared to do so by increasing ROS scavenging capacity and antioxidant enzyme activity. SA treatment also induced changes in phytohormone levels, presumably as a consequence of SA-phytohormone salt-stress cross-talk.

• MeSH
• Antioxidants metabolism   MeSH
• Biomass MeSH
• Time Factors MeSH
• Chlorophyll A metabolism   MeSH
• Chlorophyll metabolism   MeSH
• Hordeum drug effects   growth & development   physiology   MeSH
• Salicylic Acid pharmacology   MeSH
• Thiobarbituric Acid Reactive Substances metabolism   MeSH
• Plant Leaves drug effects   physiology   MeSH
• Proline metabolism   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Plant Growth Regulators pharmacology   MeSH
• Salt Stress drug effects   MeSH
• Water MeSH
• Plant Shoots drug effects   growth & development   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Incidencia predčasných pôrodov neustále narastá, pričom stále vyšší počet novorodencov sa zachraňuje v čoraz nižších gestačných týždňoch. Aj napriek výrazným pokrokom v starostlivosti o predčasne narodeného novorodenca, prematurita aj naďalej predstavuje limitujúci faktor pre ďalší vývoj týchto detí, keďže sa spája s veľkou mierou morbidity aj mortality. Medzi najčastejšie príčiny spôsobujúce predčasný pôrod patrí chorioamnionitída. Jej problém nespočíva len v procesoch, ktoré vedú k predčasnému pôrodu, ale aj v samotnom zápale, ktorý môže spôsobiť výrazné komplikácie a signifikantne zhoršiť prognózu prematúrneho novorodenca. Negatívne účinky pritom nie sú pripísané len samotnému mikroorganizmu, ale hlavne prooxidačným a prozápalovým procesom, ktoré tieto patogény navodzujú. Keďže antibiotická liečba je zameraná len na ich usmrtenie alebo inhibíciu ďalšieho rastu a množenia, cieľom viacerých výskumov je nájsť takú terapeutickú intervenciu, ktorá by potlačila produkciu cytokínov a voľných radikálov. Najviac nádejnými sa zdajú byť melatonín, pentoxyfylín, erytropoetín a N-acetylcysteín. Tieto liečivá môžu zmierniť ničivé účinky oxidačného stresu a zápalu na rôzne orgánové systémy u novorodenca a tak znížiť komplikácie súvisiace s predčasným pôrodom vyvolaným chorioamnionitídou.

Incidence of preterm labor is progressively rising and more newborns are being saved in lower gestational ages. However, despite of advances in neonatal care are being undisputable, immaturity is still very limiting factor in normal development of a newborn because it is connected with higher incidence of perinatal and neonatal mortality as well as morbidity. One of the most frequent causes of preterm labor is chorioamnionitis. Problem of chorioamnionitis dwells not just in activation of mechanisms leading to preterm labor but inflammation may be transmitted on the fetus too, causing serious complications that significantly worsen prognosis of premature newborn. Negative effect is not linked only to a specific microorganism itself but mainly to initiation of prooxidant and proinflammatory cascade. Because antibiotics serve only for growth inhibition or killing of bacteria and are not able to intervene with cytokines or free radicals, new therapeutic strategies aimed at cytokine and free radical inhibition are in research. Melatonine, Pentoxifylline, Erythropoietine and N-acetylcysteine seem to be most promising in this indication. These drugs may attenuate deleterious effect of inflammatory process on many organ systems and thus decrease complications connected with preterm labor caused by chorioamnionitis.

• MeSH
• Chorioamnionitis * drug therapy   physiopathology   MeSH
• Humans MeSH
• Neuroprotection drug effects   MeSH
• Infant, Newborn MeSH
• Oxidative Stress * drug effects   MeSH
• Premature Birth etiology   physiopathology   MeSH
• Inflammation drug therapy   MeSH
• Check Tag
• Humans MeSH
• Infant, Newborn MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

The phytohormone cytokinin has been shown to affect many aspects of plant development ranging from the regulation of the shoot apical meristem to leaf senescence. However, some studies have reported contradictory effects of cytokinin on leaf physiology. Therefore cytokinin treatments cause both chlorosis and increased greening and both lead to decrease or increase in cell size. To elucidate this multifaceted role of cytokinin in leaf development, we have employed a system of temporal controls over the cytokinin pool and investigated the consequences of modulated cytokinin levels in the third leaf of Arabidopsis. We show that, at the cell proliferation phase, cytokinin is needed to maintain cell proliferation by blocking the transition to cell expansion and the onset of photosynthesis. Transcriptome profiling revealed regulation by cytokinin of a gene suite previously shown to affect cell proliferation and expansion and thereby a molecular mechanism by which cytokinin modulates a molecular network underlying the cellular responses. During the cell expansion phase, cytokinin stimulates cell expansion and differentiation. Consequently, a cytokinin excess at the cell expansion phase results in an increased leaf and rosette size fueled by higher cell expansion rate, yielding higher shoot biomass. Proteome profiling revealed the stimulation of primary metabolism by cytokinin, in line with an increased sugar content that is expected to increase turgor pressure, representing the driving force of cell expansion. Therefore, the developmental timing of cytokinin content fluctuations, together with a tight control of primary metabolism, is a key factor mediating transitions from cell proliferation to cell expansion in leaves.

• MeSH
• Arabidopsis genetics   growth & development   physiology   MeSH
• Cytokinins metabolism   MeSH
• Gene Ontology MeSH
• Plant Leaves genetics   growth & development   physiology   MeSH
• Cell Proliferation MeSH
• Proteome * MeSH
• Plant Growth Regulators metabolism   MeSH
• Signal Transduction * MeSH
• Transcriptome * MeSH
• Cell Enlargement MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH