• MeSH
• diagnostické techniky kardiovaskulární MeSH
• echokardiografie metody   MeSH
• fibróza diagnostické zobrazování   MeSH
• kardiologické zobrazovací techniky * MeSH
• kardiomyopatie diagnostické zobrazování   MeSH
• koronární angiografie metody   MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• myokarditida diagnostické zobrazování   MeSH
• nemoci srdečních chlopní diagnostické zobrazování   MeSH
• počítačová rentgenová tomografie metody   MeSH
• SPECT/CT metody   MeSH
• srdeční selhání * diagnostické zobrazování   MeSH
• zátěžová echokardiografie metody   MeSH
• Check Tag
• lidé MeSH

I když je trombóza žilních splavů vzácná, jedná se o závažnou a často opomíjenou diagnózu. Diagnóza je častokrát těžká kvůli širokému spektru nespecifických klinických příznaků. V poslední dekádě mortalita pacientů klesá v důsledku zvýšeného povědomí o této diagnóze a pokroku v zobrazovacích metodách. V našem případu prezentujeme 70letého pacienta, u kterého se trombóza mozkových žilních splavů projevila nejdříve symptomatickým epileptickým záchvatem a byla diagnostikována na základě anamnestických dat, klinických příznaků a zobrazovacích metod. Po nasazení antikoagulační terapie a zaléčení epileptického záchvatu došlo ke stabilizaci klinického stavu a regresi bolesti hlavy. Kazuistika poukazuje na různorodost klinického obrazu trombózy mozkových splavů a dobrou prognózu pacienta, když se včasně zahájí terapie.

Although cerebral venous thrombosis is rare, it is a serious and often overlooked diagnosis. Due to the wide range of non-specific clinical symptoms, diagnosis is often difficult. In the last decade, patient mortality has been significantly reduced by improvements in treatment and diagnosis techniques and higher awareness of this diagnosis. In our case, we present a 70-year-old patient in whom cerebral venous thrombosis first manifested as a symptomatic epileptic seizure and was diagnosed thanks to anamnestic data, clinical symptoms and neuroimaging methods. The patient's conditions improved after anticoagulant therapy and treatment of the epileptic seizure. The goal of the article is to describe the diversity of the clinical picture of cerebral venous thrombosis and highlight the good prognosis of the patient if treatment is started early.

• MeSH
• bolesti hlavy etiologie   MeSH
• diferenciální diagnóza MeSH
• heparin nízkomolekulární aplikace a dávkování   MeSH
• ischemická cévní mozková příhoda * diagnostické zobrazování   etiologie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• počítačová rentgenová tomografie MeSH
• senioři MeSH
• subarachnoidální krvácení diagnostické zobrazování   etiologie   MeSH
• trombóza nitrolebních žilních splavů * diagnostické zobrazování   farmakoterapie   patologie   MeSH
• výsledek terapie MeSH
• záchvaty etiologie   farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• kazuistiky MeSH

Significance: Mitochondrial (mt) reticulum network in the cell possesses amazing ultramorphology of parallel lamellar cristae, formed by the invaginated inner mitochondrial membrane. Its non-invaginated part, the inner boundary membrane (IBM) forms a cylindrical sandwich with the outer mitochondrial membrane (OMM). Crista membranes (CMs) meet IBM at crista junctions (CJs) of mt cristae organizing system (MICOS) complexes connected to OMM sorting and assembly machinery (SAM). Cristae dimensions, shape, and CJs have characteristic patterns for different metabolic regimes, physiological and pathological situations. Recent Advances: Cristae-shaping proteins were characterized, namely rows of ATP-synthase dimers forming the crista lamella edges, MICOS subunits, optic atrophy 1 (OPA1) isoforms and mitochondrial genome maintenance 1 (MGM1) filaments, prohibitins, and others. Detailed cristae ultramorphology changes were imaged by focused-ion beam/scanning electron microscopy. Dynamics of crista lamellae and mobile CJs were demonstrated by nanoscopy in living cells. With tBID-induced apoptosis a single entirely fused cristae reticulum was observed in a mitochondrial spheroid. Critical Issues: The mobility and composition of MICOS, OPA1, and ATP-synthase dimeric rows regulated by post-translational modifications might be exclusively responsible for cristae morphology changes, but ion fluxes across CM and resulting osmotic forces might be also involved. Inevitably, cristae ultramorphology should reflect also mitochondrial redox homeostasis, but details are unknown. Disordered cristae typically reflect higher superoxide formation. Future Directions: To link redox homeostasis to cristae ultramorphology and define markers, recent progress will help in uncovering mechanisms involved in proton-coupled electron transfer via the respiratory chain and in regulation of cristae architecture, leading to structural determination of superoxide formation sites and cristae ultramorphology changes in diseases. Antioxid. Redox Signal. 39, 635-683.

• MeSH
• adenosintrifosfát metabolismus   MeSH
• homeostáza MeSH
• mitochondriální membrány * metabolismus   MeSH
• mitochondriální proteiny metabolismus   MeSH
• oxidace-redukce MeSH
• superoxidy * metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

BACKGROUND: Mitochondria and peroxisomes are the two organelles that are most affected during adaptation to microoxic or anoxic environments. Mitochondria are known to transform into anaerobic mitochondria, hydrogenosomes, mitosomes, and various transition stages in between, collectively called mitochondrion-related organelles (MROs), which vary in enzymatic capacity. Anaerobic peroxisomes were identified only recently, and their putatively most conserved function seems to be the metabolism of inositol. The group Archamoebae includes anaerobes bearing both anaerobic peroxisomes and MROs, specifically hydrogenosomes in free-living Mastigamoeba balamuthi and mitosomes in the human pathogen Entamoeba histolytica, while the organelles within the third lineage represented by Pelomyxa remain uncharacterized. RESULTS: We generated high-quality genome and transcriptome drafts from Pelomyxa schiedti using single-cell omics. These data provided clear evidence for anaerobic derivates of mitochondria and peroxisomes in this species, and corresponding vesicles were tentatively identified in electron micrographs. In silico reconstructed MRO metabolism harbors respiratory complex II, electron-transferring flavoprotein, a partial TCA cycle running presumably in the reductive direction, pyruvate:ferredoxin oxidoreductase, [FeFe]-hydrogenases, a glycine cleavage system, a sulfate activation pathway, and an expanded set of NIF enzymes for iron-sulfur cluster assembly. When expressed in the heterologous system of yeast, some of these candidates localized into mitochondria, supporting their involvement in the MRO metabolism. The putative functions of P. schiedti peroxisomes could be pyridoxal 5'-phosphate biosynthesis, amino acid and carbohydrate metabolism, and hydrolase activities. Unexpectedly, out of 67 predicted peroxisomal enzymes, only four were also reported in M. balamuthi, namely peroxisomal processing peptidase, nudix hydrolase, inositol 2-dehydrogenase, and D-lactate dehydrogenase. Localizations in yeast corroborated peroxisomal functions of the latter two. CONCLUSIONS: This study revealed the presence and partially annotated the function of anaerobic derivates of mitochondria and peroxisomes in P. schiedti using single-cell genomics, localizations in yeast heterologous systems, and transmission electron microscopy. The MRO metabolism resembles that of M. balamuthi and most likely reflects the state in the common ancestor of Archamoebae. The peroxisomal metabolism is strikingly richer in P. schiedti. The presence of myo-inositol 2-dehydrogenase in the predicted peroxisomal proteome corroborates the situation in other Archamoebae, but future experimental evidence is needed to verify additional functions of this organelle.

• MeSH
• Amoeba * genetika   metabolismus   MeSH
• anaerobióza MeSH
• Archamoebae * genetika   metabolismus   MeSH
• genomika MeSH
• lidé MeSH
• mitochondrie metabolismus   MeSH
• peroxizomy metabolismus   MeSH
• Saccharomyces cerevisiae MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

There are numerous studies supporting the contribution of oxidative stress to the pathogenesis of epilepsy. Prolonged oxidative stress is associated with the overexpression of ATP-binding cassette transporters, which results in antiepileptic drugs resistance. During our studies, three 1,2,4-triazole-3-thione derivatives were evaluated for the antioxidant activity and anticonvulsant effect in the 6 Hz model of pharmacoresistant epilepsy. The investigated compounds exhibited 2-3 times more potent anticonvulsant activity than valproic acid in 6 Hz test in mice, which is well-established preclinical model of pharmacoresistant epilepsy. The antioxidant/ROS scavenging activity was confirmed in both single-electron transfer-based methods (DPPH and CUPRAC) and during flow cytometric analysis of total ROS activity in U-87 MG cells. Based on the enzymatic studies on human carbonic anhydrases (CAs), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), one can assume that the herein investigated drug candidates will not impair the cognitive processes mediated by CAs and will have minimal off-target cholinergic effects.

• MeSH
• acetylcholinesterasa metabolismus   MeSH
• antikonvulziva chemická syntéza   chemie   farmakologie   MeSH
• antioxidancia chemická syntéza   chemie   farmakologie   MeSH
• bifenylové sloučeniny antagonisté a inhibitory   MeSH
• butyrylcholinesterasa metabolismus   MeSH
• cholinesterasové inhibitory chemická syntéza   chemie   farmakologie   MeSH
• epilepsie farmakoterapie   metabolismus   MeSH
• inhibitory karboanhydras chemická syntéza   chemie   farmakologie   MeSH
• karboanhydrasy metabolismus   MeSH
• lidé MeSH
• molekulární modely MeSH
• molekulární struktura MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• oxidační stres účinky léků   MeSH
• pikráty antagonisté a inhibitory   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• triazoly chemická syntéza   chemie   farmakologie   MeSH
• viabilita buněk účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Thylakoids are the place of the light-photosynthetic reactions. To gain maximal efficiency, these reactions are conditional to proper pigment-pigment and protein-protein interactions. In higher plants thylakoids, the interactions lead to a lateral asymmetry in localization of protein complexes (i.e. granal/stromal thylakoids) that have been defined as a domain-like structures characteristic by different biochemical composition and function (Albertsson P-Å. 2001,Trends Plant Science 6: 349-354). We explored this complex organization of thylakoid pigment-proteins at single cell level in the cyanobacterium Synechocystis sp. PCC 6803. Our 3D confocal images captured heterogeneous distribution of all main photosynthetic pigment-protein complexes (PPCs), Photosystem I (fluorescently tagged by YFP), Photosystem II and Phycobilisomes. The acquired images depicted cyanobacterial thylakoid membrane as a stable, mosaic-like structure formed by microdomains (MDs). These microcompartments are of sub-micrometer in sizes (~0.5-1.5 μm), typical by particular PPCs ratios and importantly without full segregation of observed complexes. The most prevailing MD is represented by MD with high Photosystem I content which allows also partial separation of Photosystems like in higher plants thylakoids. We assume that MDs stability (in minutes) provides optimal conditions for efficient excitation/electron transfer. The cyanobacterial MDs thus define thylakoid membrane organization as a system controlled by co-localization of three main PPCs leading to formation of thylakoid membrane mosaic. This organization might represent evolutional and functional precursor for the granal/stromal spatial heterogeneity in photosystems that is typical for higher plant thylakoids.

• MeSH
• bakteriální proteiny metabolismus   MeSH
• fotosyntéza fyziologie   MeSH
• fotosystém I (proteinový komplex) metabolismus   MeSH
• fotosystém II (proteinový komplex) metabolismus   MeSH
• fykobilizomy metabolismus   MeSH
• konfokální mikroskopie MeSH
• membránové mikrodomény metabolismus   MeSH
• Synechocystis MeSH
• tylakoidy metabolismus   MeSH
• zobrazování trojrozměrné MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Chalcones are polyphenolic secondary metabolites of plants, many of which have antioxidant activity. Herein, a set of 26 synthetic chalcone derivatives with alkyl substituted pyrazine heterocycle A and four types of the monophenolic ring B, were evaluated for the potential radical scavenging and antioxidant cellular capacity influencing the growth of cells exposed to H₂O₂. Before that, compounds were screened for cytotoxicity on THP-1 and HepG2 cell lines. Most of them were not cytotoxic in an overnight MTS assay. However, three of them, 4a, 4c and 4e showed 1,1-diphenyl-2-picrylhydrazyl (DPPH●) radical scavenging activity, through single electron transfer followed by a proton transfer (SET-PT) mechanism as revealed by density functional theory (DFT) modeling. DFT modeling of radical scavenging mechanisms was done at the SMD//(U)M052X/6-311++G** level. The in vitro effects of 4a, 4c and 4e on the growth of THP-1 cells during four days pre- or post-treatment with H₂O₂ were examined daily with the trypan blue exclusion assay. Their various cellular effects reflect differences in their radical scavenging capacity and molecular lipophilicity (clogP) and depend upon the cellular redox status. The applied simple in vitro-in silico screening cascade enables fast identification and initial characterization of potent radical scavengers.

• Publikační typ
• časopisecké články MeSH

Currently, one of the most promising treatments of lipopolysaccharides (LPS)-induced sepsis is based on hemofiltration. Nevertheless, proteins rapidly adsorbed on the artificial surface of membranes which leads to activation of coagulation impairing effective scavenging of the endotoxins. To overcome this challenge, we designed polymer-brush-coated microparticles displaying antifouling properties and functionalized them with polymyxin B (PMB) to specifically scavenge LPS the most common endotoxin. Poly[( N-(2-hydroxypropyl) methacrylamide)- co-(carboxybetaine methacrylamide)] brushes were grafted from poly(glycidyl methacrylate) microparticles using photoinduced single-electron transfer living radical polymerization (SET-LRP). Notably, only parts-per-million of copper catalyst were necessary to achieve brushes able to repel adsorption of proteins from blood plasma. The open porosity of the particles, accessible to polymerization, enabled us to immobilize sufficient PMB to selectively scavenge LPS from blood plasma.

• MeSH
• adsorpce MeSH
• akrylamidy metabolismus   MeSH
• biokompatibilní potahované materiály farmakologie   MeSH
• bioznečištění prevence a kontrola   MeSH
• epoxidové sloučeniny metabolismus   MeSH
• krevní plazma metabolismus   MeSH
• lidé MeSH
• lipopolysacharidy metabolismus   MeSH
• methakryláty metabolismus   MeSH
• polymerizace účinky léků   MeSH
• polymery chemie   MeSH
• polymyxin B farmakologie   MeSH
• povrchové vlastnosti účinky léků   MeSH
• proteiny metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Východiska: Epiteloidný angiomyolipóm (EAML) obličky na rozdiel od benígneho renálneho angiomyolipómu predstavuje zriedkavý nádor mezenchymálneho pôvodu, ktorý disponuje malígnym potenciálom. Patrí do skupiny PEComov –  tumorov vyvstávajúcich z perivaskulárnych epiteloidných buniek. Jeho dia­gnostika a terapeutický prístup zostávajú výzvou. Metódy: Autori prezentujú pacienta s malígnym EAML, ktorý bol iniciálne liečený ako renal cell karcinóm (RCC). Až neobvyklá terapeutická odpoveď vyústila k prehodnoteniu primárnej diagnózy. V príspevku je stručne sumarizovaný súčasný stav klinických a histopatologických poznatkov o renálnych PEComoch s dôrazom na ich metastatický potenciál a riziko diagnostického pochybenia. Prípad: Pacient s pôvodnou diagnózou chromofóbneho RCC so sarkomatoidnými črtami podstúpil radikálnu nefrektómiu a epinefrektómiu. Lokálna rekurencia ochorenia podnietila zahájenie prvej línie liečby sunitinibom a následné zaradenie pacienta do klinického skúšania s mTOR inhibítorom s neobvykle priaznivou odpoveďou v trvaní 30 mesiacov. Pomalá progresia ochorenia si vyžiadala extirpáciu solitárneho abdominálneho ložiska 36 mesiacov po zahájení liečby everolimom a napokon i pravostrannú hemihepatektómiu o ďalších 24 mesiacov. Imunoprofil pečeňových metastáz s pozitivitou melanómových a hladkosvalových markerov vyústil v rekvalifikáciu primárneho nálezu a metastatických ložísk na invazívny EAML obličky. Ďalšia progresia ochorenia bola napriek viacerým líniám systémovej liečby neodvratná a pacient 104 mesiacov po úvodnom stanovení diagnózy chorobe podľahol. Záver: Berúc do úvahy zriedkavosť a malígny potenciál PEComov obličiek, renálne nádory s nepriaznivými radiografickými a histopatologickými črtami sa stávajú kandidátom na imunohistochemické vyšetrenie. Neobvyklá odpoveď na liečbu upozorňuje na riziko diagnostického omylu a mala by viesť k prehodnoteniu diagnosticko-liečebného procesu u konkrétneho pacienta.

Background: Epithelioid angiomyolipoma (EAML) of the kidney, in contrast to classic benign renal angiomyolipoma, is a rare mesenchymal neoplasm with malignant potential. Representing a member of the perivascular epithelioid cells (PEComa) tumor family arising from the perivascular epithelioid cells, its accurate diagnosis and therapeutic approach remains challenging. Methods: We report a case of a patient with malignant EAML, initially treated as renal cell carcinoma (RCC) at our institution. In this paper, we briefly summarize current status of clinical and histopathological knowledge of renal PEComas with metastatic potential and reconsider the diagnostic and therapeutic approach in this particular case to highlight the risk of misdiagnosis, malignant potential of renal PEComas and to demonstrate an unexpected treatment response. Results: The patient in our case was diagnosed with chromophobe RCC with sarcomatoid features. She underwent a radical nephrectomy and epinephrectomy with a satisfactory postoperative history. Local recurrence urged chemotherapy commencement with sunitinib in the first line, and shortly afterwards, the patient was enrolled in a clinical trial with everolimus, with an extraordinary favorable treatment response for 30 months. Following the extirpation of single abdominal nodularity after 36 months of treatment with mTOR inhibitor, and proceed­ing the everolimus administration, the disease slowly progressed to the right liver lobe, resulting in right hemihepatectomy in another 24 months. The immunoprofile of liver metastases with positive staining of melanoma markers and smooth muscle markers induced the revaluation of the primary tumor and abdominal nodularity specimen to an invasive EAML of the kidney. Further disease progression was unavoidable despite several chemotherapy regimens, and the patient died 104 months after primary diagnosis. Conclusions: Renal tumors with adverse radiographic and histopathological features should become candidates for immunohistochemical staining as its omission frequently leads to a misdiagnosis, as showed in our case report. Atypical treatment response might suggest a possibility of a diagnostic mistake and should lead to reevaluation of the diagnostic and treatment process in the particular patient.

• MeSH
• diagnostické zobrazování metody   MeSH
• dospělí MeSH
• everolimus terapeutické užití   MeSH
• imunohistochemie metody   MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• nádory ledvin * diagnóza   terapie   MeSH
• nádory z perivaskulárních epiteloidních buněk * diagnóza   terapie   MeSH
• nefrektomie metody   MeSH
• počítačová rentgenová tomografie metody   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

• MeSH
• imunoglobuliny MeSH
• imunomodulační látky MeSH
• léčivé přípravky MeSH
• Publikační typ
• sborníky MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• hematologie a transfuzní lékařství
• alergologie a imunologie
• farmacie a farmakologie