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1.
Angiogenesis in gynecological cancers and the options for anti-angiogenesis therapy
Bahar Yetkin-Arik, Arnoud W. Kastelein, Ingeborg Klaassen, Charlotte H. J. R. Jansen, Yani P. Latul, Miloš Vittori, Aydan Biri, Korhan Kahraman, Arjan W. Griffioen, Frederic Amant, Christianne A. R. Lok, Reinier O. Schlingemann, Cornelis J. F. van Noorden, 2021, pregledni znanstveni članek

Povzetek: Angiogenesis is required in cancer, including gynecological cancers, for the growth of primary tumors and secondary metastases. Development of anti-angiogenesis therapy in gynecological cancers and improvement of its efficacy have been a major focus of fundamental and clinical research. However, survival benefits of current anti-angiogenic agents, such as bevacizumab, in patients with gynecological cancer, are modest. Therefore, a better understanding of angiogenesis and the tumor microenvironment in gynecological cancers is urgently needed to develop more effective anti-angiogenic therapies, either or not in combination with other therapeutic approaches. We describe the molecular aspects of (tumor) blood vessel formation and the tumor microenvironment and provide an extensive clinical overview of current anti-angiogenic therapies for gynecological cancers. We discuss the different phenotypes of angiogenic endothelial cells as potential therapeutic targets, strategies aimed at intervention in their metabolism, and approaches targeting their (inflammatory) tumor microenvironment.
Ključne besede: angiogenesis, anti-angiogenic therapy, endothelial cells, endothelial cell metabolism, gynecological cancer, non-tip cells, tip cells, tumor microenvironment, vascular disrupting agents
Objavljeno v DiRROS: 05.08.2024; Ogledov: 187; Prenosov: 158
.pdf Celotno besedilo (5,60 MB)
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2.
Endothelial tip cells in ocular angiogenesis : potential target for anti-angiogenesis therapy
Martin J. Siemerink, Ingeborg Klaassen, Cornelis J. F. van Noorden, Reinier O. Schlingemann, 2013, izvirni znanstveni članek

Povzetek: Endothelial tip cells are leading cells at the tips of vascular sprouts coordinating multiple processes during angiogenesis. In the developing retina, tip cells play a tightly controlled, timely role in angiogenesis. In contrast, excessive numbers of tip cells are a characteristic of the chaotic pathological blood vessels in proliferative retinopathies. Tip cells control adjacent endothelial cells in a hierarchical manner to form the stalk of the sprouting vessel, using, among others, the VEGF-DLL-Notch signaling pathway, and recruit pericytes. Tip cells are guided toward avascular areas by signals from the local extracellular matrix that are released by cells from the neuroretina such as astrocytes. Recently, tip cells were identified in endothelial cell cultures, enabling identification of novel molecular markers and mechanisms involved in tip cell biology. These mechanisms are relevant for understanding proliferative retinopathies. Agents that primarily target tip cells can block pathological angiogenesis in the retina efficiently and safely without adverse effects. A striking example is platelet-derived growth factor, which was recently shown to be an efficacious additional target in the treatment of retinal neovascularization. Here we discuss these and other tip cell-based strategies with respect to their potential to treat patients with ocular diseases dominated by neovascularization.
Ključne besede: angiogenesis, endothelial tip cell, proliferative retinopathy, anti-angiogenesis therapy, retinal neovascularization, vascular sprouts, endothelial stalk cell, molecular mediators of angiogenesis, pericytes
Objavljeno v DiRROS: 02.08.2024; Ogledov: 220; Prenosov: 134
.pdf Celotno besedilo (816,40 KB)
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3.
Polysaccharide-based bilayer coatings for biofilm-inhibiting surfaces of medical devices
Urban Ajdnik, Thomas Luxbacher, Alenka Vesel, Alja Štern, Bojana Žegura, Janja Trček, Lidija Fras Zemljič, 2021, izvirni znanstveni članek

Povzetek: Chitosan (Chi) and 77KS, a lysine-derived surfactant, form polyelectrolyte complexes that reverse their charge from positive to negative at higher 77KS concentrations, forming aggregates that have been embedded with amoxicillin (AMOX). Dispersion of this complex was used to coat polydimethylsiloxane (PDMS) films, with an additional layer of anionic and hydrophilic hyaluronic acid (HA) as an outer adsorbate layer to enhance protein repulsion in addition to antimicrobial activity by forming a highly hydrated layer in combination with steric hindrance. The formed polysaccharide-based bilayer on PDMS was analyzed by water contact angle measurements, X-ray photoelectron spectroscopy (XPS), and surface zeta (ζ)-potential. All measurements show the existence and adhesion of the two layers on the PDMS surface. Part of this study was devoted to understanding the underlying protein adsorption phenomena and identifying the mechanisms associated with biofouling. Thus, the adsorption of a mixed-protein solution (bovine serum albumin, fibrinogen, γ-globulin) on PDMS surfaces was studied to test the antifouling properties. The adsorption experiments were performed using a quartz crystal microbalance with dissipation monitoring (QCM-D) and showed improved antifouling properties by these polysaccharide-based bilayer coatings compared to a reference or for only one layer, i.e., the complex. This proves the benefit of a second hyaluronic acid layer. Microbiological and biocompatibility tests were also performed on real samples, i.e., silicone discs, showing the perspective of the prepared bilayer coating for medical devices such as prostheses, catheters (balloon angioplasty, intravascular), delivery systems (sheaths, implants), and stents.
Ključne besede: polysaccharides, chitosan, hyaluronic acid, anti-biofilm, silicone
Objavljeno v DiRROS: 19.07.2024; Ogledov: 182; Prenosov: 143
.pdf Celotno besedilo (6,81 MB)
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4.
TXM peptides inhibit SARS-CoV-2 infection, syncytia formation, and lower inflamatory consequences
Tea Govednik, Duško Lainšček, Urška Kuhar, Marva Lachish, Sandra Janežič, Malan Štrbenc, Uroš Krapež, Roman Jerala, Daphne Atlas, Mateja Manček Keber, 2024, izvirni znanstveni članek

Povzetek: After three years of the SARS-CoV-2 pandemic, the search and availability of relatively low-cost benchtop therapeutics for people not at high risk for a severe disease are still ongoing. Although vaccines and new SARS-CoV-2 variants reduce the death toll, the long COVID-19 along with neurologic symptoms can develop and persist even after a mild initial infection. Reinfections, which further increase the risk of sequelae in multiple organ systems as well as the risk of death, continue to require caution. The spike protein of SARS-CoV-2 is an important target for both vaccines and therapeutics. The presence of disulfide bonds in the receptor binding domain (RBD) of the spike protein is essential for its binding to the human ACE2 receptor and cell entry. Here, we demonstrate that thiol-reducing peptides based on the active site of oxidoreductase thioredoxin 1, called thioredoxin mimetic (TXM) peptides, can prevent syncytia formation, SARS-CoV-2 entry into cells, and infection in a mouse model. We also show that TXM peptides inhibit the redox-sensitive HIV pseudotyped viral cell entry. These results support disulfide targeting as a common therapeutic strategy for treating infections caused by viruses using redox-sensitive fusion. Furthermore, TXM peptides exert anti-inflammatory properties by lowering the activation of NF-κB and IRF signaling pathways, mitogen-activated protein kinases (MAPKs) and lipopolysaccharide (LPS)-induced cytokines in mice. The antioxidant and anti-inflammatory effects of the TXM peptides, which also cross the blood-brain barrier, in combination with prevention of viral infections, may provide a beneficial clinical strategy to lower viral infections and mitigate severe consequences of COVID-19.
Ključne besede: SARS-CoV-2, Disulfides, Thiol-reacting compound, Spike, Anti-inflammatory activity
Objavljeno v DiRROS: 06.02.2024; Ogledov: 564; Prenosov: 229
.pdf Celotno besedilo (7,11 MB)
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The effects of topical antibiotics on eradication and acquisition of third-generation cephalosporin and carbapenem-resistant Gram-negative bacteria in ICU patients : ǂa ǂpost hoc analysis from a multicentre cluster-randomized trial
Nienke L. Plantinga, Bastiaan H. Wittekamp, Christian Brun-Buisson, Marc J. M. Bonten, 2020, izvirni znanstveni članek

Povzetek: Objectives: The aim was to quantify the effects of selective digestive tract decontamination (SDD) consisting of a mouth paste and gastro-enteral suspension, selective oropharyngeal decontamination with a mouth paste (SOD) and 1-2% chlorhexidine (CHX) mouthwash on eradication and acquisition of carriage of third-generation cephalosporin-resistant Enterobacterales (3GCR-E) and carbapenem-resistant Gram-negative bacteria (CR-GNB) in Intensive Care Unit (ICU) patients. Methods: This was a nested cohort study within a cluster-randomized cross-over trial in six European countries and 13 ICUs with 8665 patients. Eradication and acquisition during ICU stay of 3GCR-E and CRGNB were investigated separately in the rectum and respiratory tract for the three interventions and compared with standard care (SC) using Cox-regression competing events analyses. Results: Adjusted cause specific hazard ratios (CSHR) for eradication of rectal carriage for SDD were 1.76 (95% CI 1.31-2.36) for 3GCR-E and 3.17 (95% CI 1.60-6.29) for CR-GNB compared with SC. For the respiratory tract, adjusted CSHR for eradication of 3GCR-E were 1.47 (0.98-2.20) for SDD and 1.38 (0.92-2.06) for SOD compared with SC, and for eradication of CR-GNB these were 0.77 (0.41-1.45) for SDD and 0.81 (0.44-1.51) for SOD, compared with SC. Adjusted CSHRs for acquisition of rectal carriage during SDD (compared with SC) were 0.51 (0.40-0.64) for 3GCR-E and of 0.56 (0.40-0.78) for CR-GNB. Adjusted CSHRs for acquiring respiratory tract carriage with 3GCR-E compared with SC were 0.38 (0.28-0.50) for SDD and 0.55 (0.42-0.71) for SOD, and for CR-GNB 0.46 (0.33-0.64) during SDD and 0.60 (0.44-0.81) during SOD, respectively. SOD was not associated with eradication or acquisition of 3GCR-E and CR-GNB in the rectum. Conclusions: Among mechanically ventilated ICU patients, SDD was associated with more eradication and less acquisition of 3GCR-E and CR-GNB in the rectum than SC. SDD and SOD were associated with less acquisition of both 3GCR-E and CR-GNB than SC in the respiratory tract.
Ključne besede: intensive care units -- analysis -- epidemiology, bacterial drug resistance, anti-infective agents -- therapeutic use decontamination, beta-lactamases, Gram-negative bacteria, gastrointestinal tract -- microbiology -- drug therapy, cohort studies, colonization, ESBL, digestive tract
Objavljeno v DiRROS: 27.05.2022; Ogledov: 796; Prenosov: 289
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7.
The efficacy, safety and tolerability of canakinumab in the treatment of familial Mediterranean fever : a systematic review of the literature
Mark Kačar, Sinisa Savic, Jeroen CH van der Hilst, 2020, pregledni znanstveni članek

Povzetek: Familial Mediterranean Fever (FMF) is the most prevalent genetic autoinflammatory disorder. In most patients, treatment with colchicine can prevent attacks of fever and inflammation. However, 5%-10% of patients are resistant to colchicine treatment, while a similar percentage cannot tolerate colchicine in doses needed to prevent attacks. For these patients, Canakinumab, a full human antibody against IL-1[beta], has been approved recently by the FDA and EMA. In this article, we present a systematic review of the long-term efficacy, safety, and tolerability of Canakinumab in FMF patients who cannot tolerate colchicine or who are resistant to colchicine treatment.
Ključne besede: familial Mediterranean fever -- therapy -- review, monoclonal antibodies, canakinumab, anti-IL1 therapy
Objavljeno v DiRROS: 08.04.2021; Ogledov: 1553; Prenosov: 875
.pdf Celotno besedilo (463,72 KB)
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8.
Decontamination strategies and bloodstream infections with antibiotic-resistant microorganisms in ventilated patients : a randomized clinical trial
Bastiaan H. Wittekamp, Nienke L. Plantinga, Ben S. Cooper, Joaquin Lopez-Contreras, Pere Coll, Jordi Mancebo, Matt P. Wise, Matt P. G. Morgan, Pieter Depuydt, Jerina Boelens, Viktorija Tomič, Franc Šifrer, 2018, izvirni znanstveni članek

Povzetek: Importance: The effects of chlorhexidine (CHX) mouthwash, selective oropharyngeal decontamination (SOD), and selective digestive tract decontamination (SDD) on patient outcomes in ICUs with moderate to high levels of antibiotic resistance are unknown. Objective: To determine associations between CHX 2%, SOD, and SDD and the occurrence of ICU-acquired bloodstream infections with multidrug-resistant gram-negative bacteria (MDRGNB) and 28-day mortality in ICUs with moderate to high levels of antibiotic resistance. Design, setting, and participants: Randomized trial conducted from December 1, 2013, to May 31, 2017, in 13 European ICUs where at least 5% of bloodstream infections are caused by extended-spectrum [beta]-lactamase-producing Enterobacteriaceae. Patients with anticipated mechanical ventilation of more than 24 hours were eligible. The final date of follow-up was September 20, 2017. Interventions: Standard care was daily CHX 2% body washings and a hand hygiene improvement program. Following a baseline period from 6 to 14 months, each ICU was assigned in random order to 3 separate 6-month intervention periods with either CHX 2% mouthwash, SOD (mouthpaste with colistin, tobramycin, and nystatin), or SDD (the same mouthpaste and gastrointestinal suspension with the same antibiotics), all applied 4 times daily. Main outcomes and measures: The occurrence of ICU-acquired bloodstream infection with MDRGNB (primary outcome) and 28-day mortality (secondary outcome) during each intervention period compared with the baseline period. Results: A total of 8665 patients (median age, 64.1 years; 5561 men [64.2%]) were included in the study (2251, 2108, 2224, and 2082 in the baseline, CHX, SOD, and SDD periods, respectively). ICU-acquired bloodstream infection with MDRGNB occurred among 144 patients (154 episodes) in 2.1%, 1.8%, 1.5%, and 1.2% of included patients during the baseline, CHX, SOD, and SDD periods, respectively. Absolute risk reductions were 0.3% (95% CI, -0.6% to 1.1%), 0.6% (95% CI, -0.2% to 1.4%), and 0.8% (95% CI, 0.1% to 1.6%) for CHX, SOD, and SDD, respectively, compared with baseline. Adjusted hazard ratios were 1.13 (95% CI, 0.68-1.88), 0.89 (95% CI, 0.55-1.45), and 0.70 (95% CI, 0.43-1.14) during the CHX, SOD, and SDD periods, respectively, vs baseline. Crude mortality risks on day 28 were 31.9%, 32.9%, 32.4%, and 34.1% during the baseline, CHX, SOD, and SDD periods, respectively. Adjusted odds ratios for 28-day mortality were 1.07 (95% CI, 0.86-1.32), 1.05 (95% CI, 0.85-1.29), and 1.03 (95% CI, 0.80-1.32) for CHX, SOD, and SDD, respectively, vs baseline. Conclusions and relevance: Among patients receiving mechanical ventilation in ICUs with moderate to high antibiotic resistance prevalence, use of CHX mouthwash, SOD, or SDD was not associated with reductions in ICU-acquired bloodstream infections caused by MDRGNB compared with standard care.
Ključne besede: anti-infective agents -- therapeutic use, bacteremia -- prevention and control, chlorhexidine -- therapeutic use, cross infection -- prevention and control, disinfection -- methods, bacterial drug resistance, gastrointestinal tract -- microbiology, Gram-negative bacterial infections -- prevention and control, hospital mortality, intensive care units, mouthwashes -- therapeutic use, oropharynx -- microbiology, artificial respiration, multicenter study, randomized controlled trial
Objavljeno v DiRROS: 09.11.2020; Ogledov: 1483; Prenosov: 520
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9.
An EAACI position paper on the investigation of perioperative immediate hypersensitivity reactions
Lene Heise Garvey, Didier G. Ebo, Paul Michel Mertes, Pascale Dewachter, Tomaz Garcez, Peter Kopač, Jose Julio Laguna, Anca Chiriac, Ingrid Terreehorst, Susanna Voltolini, K Scherer, 2019, pregledni znanstveni članek

Povzetek: Perioperative immediate hypersensitivity reactions are rare. Subsequent allergy investigation is complicated by multiple simultaneous drug exposures, the use of drugs with potent effects and the many differential diagnoses to hypersensitivity in the perioperative setting. The approach to the investigation of these complex reactions is not standardized and it is becoming increasingly apparent that collaboration between experts in the field of allergy/immunology/dermatology and anaesthesiology is needed to provide the best possible care for these patients. The EAACI task force behind this position paper has therefore combined the expertise of allergists, immunologists and anaesthesiologists. The aims of this position paper are to provide recommendations for the investigation of immediate type perioperative hypersensitivity reactions and to provide practical information that can assist clinicians in planning and carrying out investigations.
Ključne besede: allergy and immunology -- diagnosis, drug hypersensitivity -- diagnosis, anaphylaxis, anesthesia, anesthetics, opioid analgesics, anti-bacterial agents, anti-inflammatory agents, non-steroidal opioids, antibiotics
Objavljeno v DiRROS: 16.10.2020; Ogledov: 1847; Prenosov: 474
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10.
Comparative epidemiology of suspected perioperative hypersensitivity reactions
Paul Michel Mertes, Didier G. Ebo, Tomaz Garcez, Michael Rose, Vito Sabato, Tomonori Takazawa, Peter J. Cooke, Russel C. Clarke, Pascale Dewachter, Lene Heise Garvey, Anne Berit Guttormsen, David L. Hepner, Philip M. Hopkins, David A. Khan, Peter Kopač, Peter R. Platt, Louise C. Savic, 2019, pregledni znanstveni članek

Povzetek: Suspected perioperative hypersensitivity reactions are rare but contribute significantly to the morbidity and mortality of surgical procedures. Recent publications have highlighted the differences between countries concerning the respective risk of different drugs, and changes in patterns of causal agents and the emergence of new allergens. This review summarises recent information on the epidemiology of perioperative hypersensitivity reactions, with specific consideration of differences between geographic areas for the most frequently involved offending agents.
Ključne besede: anaphylaxis, anti-bacterial agents, blood, chlorhexidine, latex, neuromuscular blocking agents, hypersensitivity, drug hypersensitivity, sugammadex, antibiotics, blood products, perioperative anaphylaxis, perioperative hypersensitivity
Objavljeno v DiRROS: 16.10.2020; Ogledov: 1694; Prenosov: 463
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