BACKGROUND: The definition of minor ischemic stroke (MIS) is a topic of debate, however, the most accepted definition is a stroke with National Institutes of Health Stroke Scale (NIHSS) ≤ 5. Intravenous thrombolysis (IVT) is a crucial treatment option for acute ischemic stroke (AIS) including: alteplase, recombinant human tissue-type plasminogen activator (r-tPA), and the recently approved tenecteplase. However, there is a debate regarding its safety and efficacy. Therefore, our objective was to determine the safety and efficacy of IVT in treating minor stroke patients (NIHSS ≤ 5). METHODS: Using the search strategy assigned which was based on three keywords: "mild" or "minor", "stroke", and "intravenous thrombolysis", we searched for eligible articles on PubMed, Web of Science, Embase, and Scopus from inception till 10th January 2024. We conducted this meta-analysis using the random effect model to account for the heterogeneity among the studies. For the dichotomous variables, we calculated the odds ratio (OR) from the event and total of these variables. While for the continuous variables, we calculated the mean difference (MD) of these variables. Pooling of OR for the occurrence of events was also conducted. RESULTS: A total of 21 articles with 93,057 patients with MIS were included. The mean age of the participants ranged from 62.3 to 79.6. Most of the included patients had comorbidities such as hypertension, diabetes, previous stroke, smoking, atrial fibrillation, and hyperlipidemia. Of these, 10,850 received IVT while 82,207 did not. The use of IVT was statistically significant associated with 90-day modified Rankin score (mRs) 0-1 when compared with control with OR of 1.67 (95%CI: 1.46, 1.91, p < 0.00001) and was statistically significantly associated with improvement of NIHSS on discharge with OR of 2.19 (95%CI: 1.56, 3.08, p < 0.00001). In terms of safety outcomes, IVT has proven a safe profile, as there was no significant difference in intracranial hemorrhage (ICH) and mortality rates between the IVT and control groups with OR of 1.75 (95CI: 0.95, 3.23, p = 0.07) and 0.93 (95%CI: 0.77, 1.11, p = 0.41), respectively. CONCLUSION: Although some studies have not found any benefits of IVT in MIS patients, a substantial body of literature strongly endorses IVT as an effective and safe treatment for MIS. IVT has been shown to improve the mRs and NIHSS scores at the 90-day mark without an increased risk of ICH or mortality.

• MeSH
• cévní mozková příhoda farmakoterapie   MeSH
• fibrinolytika * aplikace a dávkování   terapeutické užití   MeSH
• intravenózní podání MeSH
• ischemická cévní mozková příhoda farmakoterapie   MeSH
• lidé MeSH
• tkáňový aktivátor plazminogenu aplikace a dávkování   terapeutické užití   škodlivé účinky   MeSH
• trombolytická terapie * metody   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH

Ischemic stroke is a common and serious condition. Timely restoration of cerebral perfusion is crucial for improving patient outcomes and reducing economic impacts. For three decades, alteplase has been the only established pharmacological treatment, often combined with endovascular therapy. Tenecteplase, a newer generation of fibrinolytic therapy, is recommended by the ESO 2023 guidelines as a suitable alternative to alteplase, particularly if treatment is initiated within 4.5 hours of symptom onset. Tenecteplase offers higher fibrin specificity, lower binding to PAI-1, and a longer plasma half-life compared to alteplase, allowing for single bolus administration. Clinical studies have shown that tenecteplase 0.25 mg/kg achieves better recanalization and clinical improvement without increased risk of bleeding. It is equally effective and safe as alteplase, with meta-analyses indicating improved recanalization and clinical outcomes at a lower risk of bleeding. Tenecteplase is a suitable alternative for treating iNCMP, especially within 4.5 hours of symptom onset. Its single bolus administration simplifies hospital management and improves the logistics of transporting patients to specialized centers.

• MeSH
• fibrinolýza účinky léků   MeSH
• ischemická cévní mozková příhoda * diagnóza   farmakoterapie   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• reperfuze klasifikace   metody   MeSH
• tenektepláza * aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• tkáňový aktivátor plazminogenu farmakologie   terapeutické užití   MeSH
• trombolytická terapie klasifikace   metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

We investigated the sex-dependent effects of inflammatory responses in visceral adipose tissue (VAT) and perivascular adipose tissue (PVAT), as well as hematological status, in relation to cardiovascular disorders associated with prediabetes. Using male and female hereditary hypertriglyceridemic (HHTg) rats-a nonobese prediabetic model featuring dyslipidemia, hepatic steatosis, and insulin resistance-we found that HHTg females exhibited more pronounced hypertriglyceridemia than males, while HHTg males had higher non-fasting glucose levels. Additionally, HHTg females had higher platelet counts, larger platelet volumes, and lower antithrombin inhibitory activity. Regarding low-grade chronic inflammation, HHTg males exhibited increased serum leptin and leukocyte levels, while females had increased serum interleukin-6 (IL-6). Both sexes had increased circulating plasminogen activator inhibitor-1 (PAI-1), higher PAI-1 gene expression in VAT and PVAT, and elevated intercellular adhesion molecule-1 (ICAM-1) gene expression in the aorta, contributing to endothelial dysfunction in the HHTg strain. However, HHTg females had lower tumor necrosis factor alpha (TNFα) gene expression in the aorta. Severe dyslipidemia in this prediabetic model was associated with hypercoagulation and low-grade chronic inflammation. The increase in PAI-1 expression in both VAT and PVAT seems to indicate a link between inflammation and vascular dysfunction. Despite the more pronounced dyslipidemia and procoagulation status in females, their milder inflammatory response may reflect an association between reduced cardiovascular damage and prediabetes.

• MeSH
• dyslipidemie * metabolismus   patologie   genetika   MeSH
• inhibitor aktivátoru plazminogenu 1 * metabolismus   genetika   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech * MeSH
• nemoci cév metabolismus   patologie   etiologie   genetika   MeSH
• nitrobřišní tuk * metabolismus   patologie   MeSH
• pohlavní dimorfismus MeSH
• zánět * metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• čas zasáhnout při rozvinutí nemoci MeSH
• cévní mozková příhoda farmakoterapie   MeSH
• fibrinolytika MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• tenektepláza * aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• tkáňový aktivátor plazminogenu aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• trombolytická terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• novinové články MeSH

Collaterals improve recanalization in acute ischemic stroke patients treated with intravenous thrombolysis, but the mechanisms are poorly understood. To investigate it, an in vitro flow model of the middle cerebral artery was developed with or without collaterals. An occlusion was achieved using human blood clots. Recanalization time, thrombolysis (clot length decrease and red blood cell (RBC) release), pressure gradient across the clot and clot compaction were measured. Results showed that with or without collateral alteplase-treated RBC dominant clots showed recanalization time 98±23 min vs 130±35 min (difference 32 min, 95% CI -6-58 min), relative clot reduction 31.8±14.9% vs 30.3±13.2% (difference 1.5%, 95% CI 10.4-13.4%) and RBC release 0.30±0.07 vs 0.27±0.09 (difference 0.03, 95% CI 0.04-0.10). Similar results were observed with fibrin-dominant clots. In RBC dominant clots, the presence vs absence of collateral caused different pressure gradients across the clot 0.41±0.09 vs 0.70±0.09 mmHg (difference 0.29 mmHg, 95% CI -0.17-0.41 mmHg), and caused the reduction of initial clot compaction by 5%. These findings align with observations in patients, where collaterals shortened recanalization time. However, collaterals did not increase thrombolysis. Instead, they decreased the pressure gradient across the clot, resulting in less clot compaction and easier distal displacement of the clot.

• MeSH
• arteria cerebri media účinky léků   patofyziologie   diagnostické zobrazování   MeSH
• erytrocyty účinky léků   MeSH
• fibrinolytika terapeutické užití   farmakologie   MeSH
• ischemická cévní mozková příhoda * farmakoterapie   patofyziologie   MeSH
• kolaterální oběh * účinky léků   MeSH
• lidé MeSH
• tkáňový aktivátor plazminogenu terapeutické užití   farmakologie   MeSH
• trombolytická terapie metody   MeSH
• trombóza farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Plasminogen activator inhibitor 1 (PAI-1) is a crucial serine protease inhibitor that prevents plasminogen activation by inhibiting tissue- and urokinase-type plasminogen activators (tPA, uPA). PAI-1 is well-known for its role in modulating hemocoagulation or extracellular matrix formation by inhibiting plasmin or matrix metalloproteinases, respectively. PAI-1 is induced by pro-inflammatory cytokines across various tissues, yet its regulation by ligand-activated transcription factors is partly disregarded. Therefore, we have attempted to summarize the current knowledge on the transcriptional regulation of PAI-1 expression by the most relevant xenobiotic and endocrine receptors implicated in modulating PAI-1 levels. This review aims to contribute to the understanding of the specific, often tissue-dependent regulation of PAI-1 and provide insights into the modulation of PAI-1 levels beyond its direct inhibition.

• MeSH
• inhibitor aktivátoru plazminogenu 1 * metabolismus   genetika   MeSH
• lidé MeSH
• ligandy MeSH
• regulace genové exprese * MeSH
• transkripční faktory metabolismus   genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Předpokládá se, že rozpustné formy Amyloidu beta (Aß) a tau proteinu narušují neuronální aktivitu u Alzheimerovy nemoci (AN) a způsobují poruchy paměti. Brain-derived neurotrophic factor (BDNF) je protein regulující neuronální aktivitu a je syntetizován z prekurzoru pro-BDNF. BDNF posiluje synaptickou aktivitu mezi neurony a tím zvyšuje dlouhodobou potenciaci. Pro-BDNF naopak synaptickou aktivitu snižuje a zvyšuje tak dlouhodobou depresi mezi neurony. Maturace BDNF je regulována tkáňovým aktivátorem plazminogenu (tPA) a inhibitorem aktivátoru plazminogenu (tPA). Z toho vyplývá, že osa tPA/PAI-1 rozhoduje o extracelulárním poměru pro-BDNF/BDNF. U pacientů a AN byly pozorovány zvýšené hladiny PAI-1 v plasmě. Nicméně není známo, zda u pacientů s AN dochází k narušení procesu zrání BDNF. Tuto hypotézy budeme testovat pomocí měření poměru hladin pro-BDNF/BDNF a tPA/PAI-1 v krevním séru a mozkomíšním moku u pacientů s AN a budeme zjišťovat, zda tyto hladiny korelují s výsledky neuropsychologických testů a neurozobrazovacích metod. Výstupem projektu bude zavedení nových biomarkerů neuronové aktivity.; It has been hypothesized that soluble forms of amyloid beta (Aß) and tau proteins in Alzheimer’s Disease (AD) interfere with neuronal activity causing memory deficits. Brain-derived neurotrophic factor (BDNF) is a protein regulating neuronal activity and is synthesized as a precursor pro-BDNF. BDNF regulates activity-dependent forms of synaptic plasticity such as long-term potentiation. Pro-BDNF downregulates synaptic activity and enhances long-term depression. Maturation of BDNF is regulated by tissue-type plasminogen activator (tPA) and by plasminogen activator inhibitor-1 (PAI-1). Thus, tPA/PAI-1 axis arbitrates the extracellular pro-BDNF/BDNF ratio. Plasma levels of PAI-1 are increased in AD patients. However, whether the process of BDNF maturation is altered in AD is not known. To verify this hypothesis, we will measure pro-BDNF/BDNF and tPA/PAI-1 ratios in serum and cerebrospinal fluid from AD patients and explore whether these changes correlate to those of neuropsychological and neuroimaging data. The outcome will be that of adding new biomarkers related to neuronal activity.

• Klíčová slova
• alzheimerova choroba, Alzheimer's disease, mírná kognitivní porucha, mild cognitive impairment, BDNF, Pro-BDNF, BDNF, pro-BDNF, PAI-1, tPA, PAI-1, tPA,

• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

Hereditární angioedém (HAE) je vzácné, geneticky podmíněné onemocnění s autozomálně dominantním přenosem a variabilním spektrem klinických projevů i život ohrožujících. V širším kontextu se jedná o imunodeficitní onemocnění, klasifikované na HAE s deficiencí C1 inhibitoru (HAE-C1-INH, dříve HAE-I a HAE-II) a HAE s normální hladinou a funkcí C1 inhibitoru (HAE nC1-INH) označovaný též jako HAE-III typu, s mutacemi jiného (mnohdy ještě neznámého) typu. Klinickým projevem jsou masivní otoky podkoží a/nebo sliznic v důsledku nekontrolované aktivace komplementového a kininového systému. V důsledku lokální nadprodukce bradykininu vznikají typické angioedémy. Vzácněji může deficit C1-inhibitoru vzniknout s vazbou na jiné patologické stavy (autoimunitní, lymfoproliferace, monoklonální gamapatie) – jedná se o získaný angioedém (AAE, acquired angioedema). Za samostatný klinický syndrom, který je nutno odlišit od získaného angioedému, je považován ACE inhibitory indukovaný angioedém (AE-ACEi). Důležitá je farmakologická anamnéza, rizikové mohou být i sartany, inhibitory mTOR, gliptiny, mezi dalšími léky je uváděn aliskiren, sakubitril, tkáňový aktivátor plasminogenu. Vznik center pro diagnostiku a péči o pacienty s HAE/AAE významně zlepšil životní osudy těchto pacientů. Do center jsou konzilárně odesíláni i pacienti s atypickými angioedémy (s převahou bradykininové etiologie).

Hereditary angioedema (HAE) is a rare, genetically determined disease with autosomal dominant transmission and a variable spectrum of clinical and life-threatening manifestations. In a broader context, it is an immunodeficiency disease, classified into HAE with a deficiency of C1 inhibitor (HAE-C1-INH, formerly HAE-I and HAE-II) and HAE with a normal level and function of C1 inhibitor (HAE nC1-INH), also referred to as HAE-III type, with mutations of another (often still unknown) type. The clinical manifestation is massive swelling of the subcutaneous tissue and/or mucous membranes due to uncontrolled activation of the complement and kinin systems. Local overproduction of bradykinin results in typical angioedema. More rarely, C1-inhibitor deficiency can arise in connection with other pathological conditions (autoimmune, lymphoproliferation, monoclonal gammopathy) – this is acquired angioedema (AAE). Angioedema induced by ACE inhibitors (AE-ACEi) is considered a separate clinical syndrome that must be distinguished from acquired angioedema. The pharmacological anamnesis is important, sartans, mTOR inhibitors, gliptins can also be risky, aliskiren, sacubitril, tissue plasminogen activator are mentioned among other drugs. The emergence of centers for the diagnosis and care of patients with HAE/AAE significantly improved the lives of these patients. Patients with atypical angioedema (predominantly of bradykinin etiology) are also sent to the centers on a consular basis.

• MeSH
• bradykinin metabolismus   škodlivé účinky   MeSH
• diferenciální diagnóza MeSH
• hereditární angioedémy * diagnóza   farmakoterapie   klasifikace   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Intravenous thrombolysis with a recombinant tissue plasminogen activator (rt-PA) is the first-line treatment of acute ischemic stroke. However, successful recanalization is relatively low and the underlying processes are not completely understood. The goal was to provide insights into clinically important factors potentially limiting rt-PA efficacy such as clot size, rt-PA concentration, clot age and also rt-PA in combination with heparin anticoagulant. We established a static in vitro thrombolytic model based on red blood cell (RBC) dominant clots prepared using spontaneous clotting from the blood of healthy donors. Thrombolysis was determined by clot mass loss and by RBC release. The rt-PA became increasingly less efficient for clots larger than 50 μl at a clinically relevant concentration of 1.3 mg/l. A tenfold decrease or increase in concentration induced only a 2-fold decrease or increase in clot degradation. Clot age did not affect rt-PA-induced thrombolysis but 2-hours-old clots were degraded more readily due to higher activity of spontaneous thrombolysis, as compared to 5-hours-old clots. Finally, heparin (50 and 100 IU/ml) did not influence the rt-PA-induced thrombolysis. Our study provided in vitro evidence for a clot size threshold: clots larger than 50 μl are hard to degrade by rt-PA. Increasing rt-PA concentration provided limited thrombolytic efficacy improvement, whereas heparin addition had no effect. However, the higher susceptibility of younger clots to thrombolysis may prompt a shortened time from the onset of stroke to rt-PA treatment.

• MeSH
• cévní mozková příhoda farmakoterapie   MeSH
• erytrocyty účinky léků   metabolismus   MeSH
• fibrinolytika terapeutické užití   MeSH
• hemokoagulace účinky léků   MeSH
• heparin * terapeutické užití   MeSH
• ischemická cévní mozková příhoda * farmakoterapie   MeSH
• lidé MeSH
• rekombinantní proteiny * terapeutické užití   MeSH
• tkáňový aktivátor plazminogenu * terapeutické užití   MeSH
• trombolytická terapie * metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Spontánna trombóza aorty v novorodeneckom veku je raritný stav s potencionálne fatálnymi následkami. Najčastejšou príčinou vzniku trombózy aorty v novorodeneckom veku je zavedenie umbilikálneho katétra do aorty. Terapia tohto ochorenia je náročná a vyžaduje si multidisciplinárny prístup. V kazuistike popisujeme prípad donoseného novorodenca prijatého na naše pracovisko so spontánnym rozvojom trombózy aorty. Pacient podstúpil úspešnú liečbu systémovou trombolýzou pomocou rekombinantného tkanivovo-špecifického aktivátora plazminogénu.

Spontaneous aortic thrombosis in the neonatal period: Case study Spontaneous aortic thrombosis in neonatal age is a rare occurence with potentially fatal consequences. The most common cause of aortic thrombosis in neonatal age, is insertion of an umbilical catheter into aorta. Therapy of this disease is difficult and requires a multidisciplinary approach. We present a case of a term neonate admitted to our unit, with spontaneous aortic thrombosis. The patient underwent a successful treatment with systemic thrombolysis with recombinant tissue plasminogen activator.