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INTRODUCTION: Osteosynthesis of posterior pelvic segment injuries with iliosacral screws is one of the most commonly used methods today. The most accurate method of checking these types of operations is the CT navigation. The aim of this study was to evaluate the use of computer-assisted CT navigation during osteosynthesis of posterior pelvic segment in a case report. METHODS AND RESULTS: A 58-year-old patient with pelvic injury underwent osteosynthesis of the left sacroiliac joint disjunction using a cannulated screw. This operation was performed under the control of computer- assisted CT navigation. The time of individual parts of the surgery as well as the dose of perioperative X-ray irradiation were monitored. DISCUSSION: Currently, computer-assisted CT navigation is not commonly used in pelvic trauma; there is more experience with CT-guided pelvic surgery. In the world literature, there are papers on smaller cohorts of patients where its benefit over standard methods is demonstrated. CONCLUSION: The use of computer-assisted CT navigation in posterior pelvic segment osteosynthesis allows better orientation in the sacroiliac region. Precise targeting of screws to the sacrum in segments S1, S2 is possible.
- MeSH
- chirurgie s pomocí počítače MeSH
- kostní šrouby MeSH
- lidé středního věku MeSH
- lidé MeSH
- pánev * chirurgie zranění MeSH
- PET/CT MeSH
- polytrauma MeSH
- vnitřní fixace fraktury metody MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
BACKGROUND: The length of hospital stay in patients with acute myocardial infarction and ST-segment elevation (STEMI) has been shortened in recent years with corresponding savings in costs, but there is limited available data on its implementation in clinical practice. The aim of this trial was to determine whether early discharge in selected patients after STEMI is feasible and safe. METHODS: 151 patients with STEMI successfully treated with primary percutaneous coronary intervention (PCI) who fulfilled the inclusion criteria of low risk were randomly assigned to two groups on a 1:1 ratio: early (within 48-72 h of admission) and standard (after 72 h) discharge. The primary end point was the composite of death, myocardial infarction (MI), unstable angina, stroke, unplanned rehospitalization, repeated target vessel revascularization and stent thrombosis at 90 days after discharge. The study is registered with ClinicalTrials.gov (identifier NCT02023983). RESULTS: The primary end point occurred in 5 patients in the early group and 6 in the standard group (6.6% vs. 8.0%, P=0.765). There were no significant differences in the incidence of individual components of the primary end point at 90 days. The length of hospital stay was significantly shorter in the intervention group (60.8 ± 8.5 vs. 92.1 ± 12.1 h, P<0.0001). CONCLUSION: This study confirms that early discharge within 48-72 h in selected low risk patients after STEMI treated with successful primary PCI is feasible and safe, with outcomes comparable to the later discharge. This strategy applies to more than a quarter of all STEMI patients.
- MeSH
- časové faktory MeSH
- délka pobytu statistika a číselné údaje MeSH
- infarkt myokardu s elevacemi ST úseků patofyziologie chirurgie MeSH
- kontinuita péče o pacienty normy MeSH
- koronární angioplastika * MeSH
- lidé MeSH
- monitorování fyziologických funkcí MeSH
- propuštění pacienta normy MeSH
- prospektivní studie MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
The Bordetella adenylate cyclase toxin-hemolysin (CyaA) and the α-hemolysin (HlyA) of Escherichia coli belong to the family of cytolytic pore-forming Repeats in ToXin (RTX) cytotoxins. HlyA preferentially binds the αLβ2 integrin LFA-1 (CD11a/CD18) of leukocytes and can promiscuously bind and also permeabilize many other cells. CyaA bears an N-terminal adenylyl cyclase (AC) domain linked to a pore-forming RTX cytolysin (Hly) moiety, binds the complement receptor 3 (CR3, αMβ2, CD11b/CD18, or Mac-1) of myeloid phagocytes, penetrates their plasma membrane, and delivers the AC enzyme into the cytosol. We constructed a set of CyaA/HlyA chimeras and show that the CyaC-acylated segment and the CR3-binding RTX domain of CyaA can be functionally replaced by the HlyC-acylated segment and the much shorter RTX domain of HlyA. Instead of binding CR3, a CyaA1-710/HlyA411-1024 chimera bound the LFA-1 receptor and effectively delivered AC into Jurkat T cells. At high chimera concentrations (25 nm), the interaction with LFA-1 was not required for CyaA1-710/HlyA411-1024 binding to CHO cells. However, interaction with the LFA-1 receptor strongly enhanced the specific capacity of the bound CyaA1-710/HlyA411-1024 chimera to penetrate cells and deliver the AC enzyme into their cytosol. Hence, interaction of the acylated segment and/or the RTX domain of HlyA with LFA-1 promoted a productive membrane interaction of the chimera. These results help delimit residues 400-710 of CyaA as an "AC translocon" sufficient for translocation of the AC polypeptide across the plasma membrane of target cells.
- MeSH
- adenylátcyklasový toxin metabolismus MeSH
- antigen-1 spojený s lymfocytární funkcí metabolismus MeSH
- Bordetella * MeSH
- CHO buňky MeSH
- Cricetulus MeSH
- cytosol metabolismus MeSH
- Jurkat buňky MeSH
- lidé MeSH
- makrofágový antigen 1 metabolismus MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- THP-1 buňky MeSH
- transport proteinů MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The whooping cough agent, Bordetella pertussis, secretes an adenylate cyclase toxin-hemolysin (CyaA) that plays a crucial role in host respiratory tract colonization. CyaA targets CR3-expressing cells and disrupts their bactericidal functions by delivering into their cytosol an adenylate cyclase enzyme that converts intracellular ATP to cAMP. In parallel, the hydrophobic domain of CyaA forms cation-selective pores that permeabilize cell membrane. The invasive AC and pore-forming domains of CyaA are linked by a segment that is unique in the RTX cytolysin family. We used mass spectrometry and circular dichroism to show that the linker segment forms α-helical structures that penetrate into lipid bilayer. Replacement of the positively charged arginine residues, proposed to be involved in target membrane destabilization by the linker segment, reduced the capacity of the toxin to translocate the AC domain across cell membrane. Substitutions of negatively charged residues then revealed that two clusters of negative charges within the linker segment control the size and the propensity of CyaA pore formation, thereby restricting the cell-permeabilizing capacity of CyaA. The 'AC to Hly-linking segment' thus appears to account for the smaller size and modest cell-permeabilizing capacity of CyaA pores, as compared to typical RTX hemolysins.
- MeSH
- adenylátcyklasový toxin chemie genetika metabolismus MeSH
- adenylátcyklasy chemie genetika MeSH
- AMP cyklický metabolismus MeSH
- Bordetella pertussis chemie patogenita MeSH
- hemolyziny genetika MeSH
- lidé MeSH
- lipidové dvojvrstvy chemie metabolismus MeSH
- perforin chemie MeSH
- permeabilita buněčné membrány účinky léků MeSH
- pertuse genetika mikrobiologie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVES: The aim of this study was to compare eptifibatide and abciximab as adjuncts to primary percutaneous coronary intervention (PCI). BACKGROUND: The glycoprotein (GP) IIb/IIIa receptor inhibitor abciximab as adjunct to primary PCI in patients with ST-segment elevation myocardial infarctions has been shown to reduce ischemic complications and improve clinical outcomes. So far, no trial has been performed to compare the efficacy of another GP IIb/IIIa receptor inhibitor, eptifibatide, and abciximab in primary PCI. METHODS: A total of 427 patients with ST-segment elevation myocardial infarctions <12 h and planned primary PCI were randomized to double-bolus eptifibatide (n = 226) followed by a 24-h infusion or single-bolus abciximab (n = 201) followed by a 12-h infusion. In this noninferiority trial, the primary end point was the incidence of complete (> or =70%) ST-segment resolution (STR) 60 min after PCI, a measure of myocardial reperfusion. The assumption was a 60% complete STR rate in the abciximab group. The noninferiority margin was set to 15%. RESULTS: The incidence of complete STR at 60 min after PCI in the intention-to-treat analysis was 62.6% after eptifibatide and 56.3% after abciximab (adjusted difference: 7.1%; 95% confidence interval: 2.7% to 17.0%). All-cause mortality 6.2% versus 4.5% (p = 0.50); reinfarction 0.4% versus 3.5% (p = 0.03); target vessel revascularization 4.4% versus 6.5% (p = 0.40); the combined end point of death, nonfatal reinfarction, and target vessel revascularization 10.6% versus 10.9% (p = 0.90); stroke 0.5% versus 0.5% (p = 1.00) after 6 months; and Thrombolysis In Myocardial Infarction major bleeding complications 4.0% versus 2.0% (p = 0.20) after 30 days were observed after eptifibatide and abciximab, respectively. CONCLUSIONS: Eptifibatide as an adjunct to primary PCI is equally as effective as abciximab with respect to STR. (Efficacy of Eptifibatide Compared to Abciximab in Primary Percutaneous Coronary Intervention [PCI] for Acute ST Elevation Myocardial Infarction [STEMI]; NCT00426751). Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
- MeSH
- balónková koronární angioplastika metody MeSH
- dvojitá slepá metoda MeSH
- elektrokardiografie MeSH
- financování organizované MeSH
- imunoglobuliny - Fab fragmenty aplikace a dávkování MeSH
- infarkt myokardu diagnóza patofyziologie terapie MeSH
- inhibitory agregace trombocytů aplikace a dávkování MeSH
- intravenózní infuze MeSH
- koronární angiografie MeSH
- lidé středního věku MeSH
- lidé MeSH
- monoklonální protilátky aplikace a dávkování MeSH
- následné studie MeSH
- peptidy aplikace a dávkování MeSH
- prospektivní studie MeSH
- randomizované kontrolované studie jako téma MeSH
- trombocytový glykoproteinový komplex IIb-IIIa antagonisté a inhibitory MeSH
- výsledek terapie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- multicentrická studie MeSH
- srovnávací studie MeSH
AIMS: Bioresorbable vascular scaffolds (BVSs) have been studied in chronic coronary artery disease, but not in acute ST-segment elevation myocardial infarction (STEMI). This prospective multicentre study analysed the feasibility and safety of BVS implantation during primary percutaneous coronary intervention (p-PCI) in STEMI. METHODS AND RESULTS: Bioresorbable vascular scaffold implantation became the default strategy for all consecutive STEMI patients between 15 December 2012 and 30 August 2013. A total of 142 patients underwent p-PCI; 41 of them (28.9%) fulfilled the inclusion/exclusion criteria for BVS implantation. The BVS device success was 98%, thrombolysis in myocardial infarction 3 flow was restored in 95% of patients, and acute scaffold recoil was 9.7%. An optical coherence tomography (OCT) substudy (21 patients) demonstrated excellent procedural results with only a 1.1% rate of scaffold strut malapposition. Edge dissections were present in a 38% of patients, but were small and clinically silent. Reference vessel diameter measured by quantitative coronary angiography was significantly lower than that measured by OCT by 0.29 (±0.56) mm, P = 0.028. Clinical outcomes were compared between BVS group and Control group; the latter was formed by patients who had implanted metallic stent and were in Killip Class I or II. Combined clinical endpoint was defined as death, myocardial infarction, or target vessel revascularization. Event-free survival was the same in both groups; 95% for BVS and 93% for Control group, P = 0.674. CONCLUSION: Bioresorbable vascular scaffold implantation in acute STEMI is feasible and safe. The procedural results evaluated by angiography and OCT are excellent. The early clinical results are encouraging.
- MeSH
- infarkt myokardu terapie MeSH
- inhibitory agregace trombocytů aplikace a dávkování MeSH
- koronární angiografie MeSH
- lidé MeSH
- optická koherentní tomografie MeSH
- prospektivní studie MeSH
- senioři MeSH
- stenty uvolňující léky * MeSH
- studie proveditelnosti MeSH
- tkáňové podpůrné struktury * MeSH
- vstřebatelné implantáty MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky kontrolované MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
Two distinct conformers of the adenylate cyclase toxin (CyaA) appear to accomplish its two parallel activities within target cell membrane. The translocating conformer would deliver the N-terminal adenylyl cyclase (AC) enzyme domain across plasma membrane into cytosol of cells, while the pore precursor conformer would assemble into oligomeric cation-selective pores and permeabilize cellular membrane. Both toxin activities then involve a membrane-interacting 'AC-to-Hly-linking segment' (residues 400 to 500). Here, we report the NMR structure of the corresponding CyaA411-490 polypeptide in dodecylphosphocholine micelles and show that it consists of two α-helices linked by an unrestrained loop. The N-terminal α-helix (Gly418 to His439) remained solvent accessible, while the C-terminal α-helix (His457 to Phe485) was fully enclosed within detergent micelles. CyaA411-490 weakly bound Ca2+ ions (apparent KD 2.6 mM) and permeabilized negatively charged lipid vesicles. At high concentrations (10 μM) the CyaA411-490 polypeptide formed stable conductance units in artificial lipid bilayers with applied voltage, suggesting its possible transmembrane orientation in the membrane-inserted toxin. Mutagenesis revealed that two clusters of negatively charged residues within the 'AC-to-Hly-linking segment' (Glu419 to Glu432 and Asp445 to Glu448) regulate the balance between the AC domain translocating and pore-forming capacities of CyaA in function of calcium concentration.
- MeSH
- adenylátcyklasový toxin chemie metabolismus MeSH
- AMP cyklický metabolismus MeSH
- biologický transport genetika MeSH
- Bordetella pertussis chemie metabolismus MeSH
- buněčná membrána chemie metabolismus MeSH
- hemolýza genetika MeSH
- konformace proteinů, alfa-helix genetika MeSH
- lidé MeSH
- lipidové dvojvrstvy chemie metabolismus MeSH
- permeabilita buněčné membrány genetika MeSH
- vápník metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: The objective of our study was to assess whether optical coherence tomography (OCT) guidance could guide intervention to avoid balloon angioplasty and stenting during primary percutaneous coronary intervention. METHODS: One hundred patients with ST-segment elevation myocardial infarction and thrombus-containing lesion were enrolled in this study. Thrombus aspiration was performed in all cases followed by an OCT study. After thrombectomy, no stent was implanted in residual significant stenosis (> 50%) if examination using OCT suggested that the occlusion was mostly thrombotic, provided that the patient was symptom-free and the Thrombolysis in Myocardial Infarction (TIMI) flow was ≥ 2. All patients managed only using thrombectomy underwent 1-week and 9-month angiography and OCT. Patients with significant lesion or those in whom thrombectomy failed to re-establish flow underwent standard treatment. RESULTS: Based on the OCT information, 20 patients (20%) were treated only with aspiration even in the presence of angiographically detected "high-grade stenosis." Angiogram and OCT performed at 1 week and 9 months showed a "normal vessel" without significant stenosis in all 20 cases. There were no cases of major adverse cardiovascular event (including death, myocardial infarction, and target lesion revascularization) during the in-hospital period or at the 12-month follow-up. CONCLUSIONS: The results of our pilot study suggest that ST segment elevation myocardial infarction patients with TIMI 2/3 flow in the angiogram and without significant coronary narrowing using OCT examination (even in the presence of angiographically detected "high-grade stenosis"), in whom thrombus aspiration is performed in addition to optimal medical therapy might benefit only from thrombus aspiration without plain old balloon angioplasty/stenting during primary percutaneous coronary intervention. Validation of these preliminary data in larger randomized studies is warranted.
- MeSH
- aterosklerotický plát radiografie MeSH
- balónková koronární angioplastika využití MeSH
- dospělí MeSH
- infarkt myokardu terapie MeSH
- koronární angiografie MeSH
- koronární okluze radiografie terapie MeSH
- koronární stenóza radiografie terapie MeSH
- koronární trombóza klasifikace radiografie terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- optická koherentní tomografie * MeSH
- pilotní projekty MeSH
- prospektivní studie MeSH
- rychlost toku krve MeSH
- stenty využití MeSH
- trombektomie * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
AIMS: To present a new method of dynamic Purkinje-metry and to verify it by comparison with a commercially available anterior segment optical coherence tomography CASIA2. PATIENTS AND METHODS: A dynamic Purkinje-meter with a movable fixation target was assembled. A coaxial circular pattern formed by infrared LEDs was projected onto the eye and evoked Purkinje images (1st, 3rd, 4th = P1, P3, P4). The measurement was performed on 29 eyes with an implanted toric IOL (intraocular lens), under mydriatic conditions, with reference to the visual axis. The IOL tilt was calculated from the position of a fixation target at the moment of P3 and P4 superposition. The IOL decentration was determined based on the relative position of P1 during on-axis fixation and of P3 and P4 superposition during off-axis fixation. A custom-developed software was used for distance measurements. Using CASIA2, the IOL position was fully calculated by the device. RESULTS: The mean absolute difference between CASIA2 and Purkinje-meter values was 0.6° ± 0.4° for the tilt magnitude and 10° ± 10° for the tilt direction, and 0.11 mm ± 0.08 mm for the decentration magnitude and 16° ± 14° for the decentration direction. There was no statistically significant difference between the values determined by the two methods for the tilt and decentration direction. The differences were statistically significant for the tilt and decentration magnitude. CONCLUSION: The values of IOL tilt and decentration direction are similar for both devices. The values of IOL tilt and decentration magnitude measured by Purkinje-meter are higher than those from CASIA2, but overall, they correspond to the values presented in other published studies.
- MeSH
- algoritmy MeSH
- lidé středního věku MeSH
- lidé MeSH
- nitrooční čočky * MeSH
- optická koherentní tomografie MeSH
- optické zobrazování * přístrojové vybavení metody MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- srovnávací studie MeSH
VDAC1, an outer mitochondrial membrane protein overexpressed in cancers, regulates apoptosis by interacting with antiapoptotic proteins and releasing apoptotic factors. We investigate novel multiblock cationic peptide amphiphiles targeting the VDAC1-Hexokinase-II complex in the mitochondria of cervical carcinoma cells. Amphiphilic peptide variants were designed by modifying the C-terminus of VDAC1 fragment LP1 with a cationic hydrophilic segment and the N-terminus with a hydrophobic domain, enabling self-assembly into nanofiber-like structures at elevated concentrations. In HeLa cells, these peptides triggered mitochondrial-mediated apoptosis through a decrease of the mitochondrial membrane potential, cytochrome C release, and caspase activation, suggesting a disrupted VDAC1-HK-II interaction. The mitochondria-targeting peptides showed notable selective cytotoxicity to cancer cells, with minimal effects on normal 3T3 cells. Our findings demonstrate that amphiphilic peptides for VDAC1-HK-II-targeting represent a promising mitochondria-focused therapeutic strategy for cervical cancer inhibition, combining structural self-assembly properties with enhanced apoptotic efficacy in malignant cells.
- MeSH
- apoptóza * účinky léků MeSH
- HeLa buňky MeSH
- hexokinasa * metabolismus antagonisté a inhibitory MeSH
- lidé MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- mitochondrie účinky léků metabolismus MeSH
- myši MeSH
- nádory děložního čípku * patologie metabolismus farmakoterapie MeSH
- napětím ovládaný aniontový kanál 1 * metabolismus MeSH
- peptidy * farmakologie chemie chemická syntéza MeSH
- protinádorové látky * farmakologie chemie chemická syntéza MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH