Aims Antihypertensive drugs are included in the medical therapy of vascular Ehlers–Danlos syndrome (vEDS). The β-blocker celiprolol has been suggested to prevent arterial damage in vEDS, but the underlying mechanism remains unclear. It is also unknown whether the widely used angiotensin II receptor type 1 antagonist losartan has a therapeutic effect in vEDS. Here, we evaluated the impact of celiprolol and losartan on the biomechanical integrity of the vEDS thoracic aorta. Methods and results We established a new approach to measure the maximum tensile force at rupture of uniaxially stretched murine thoracic aortic rings. In a vEDS model, which we (re-)characterized here at molecular level, heterozygous mice showed a significant reduction in the rupture force compared to wild-type mice, reflecting the increased mortality due to aortic rupture. For the assessment of treatment effects, heterozygous mice at 4 weeks of age underwent a 4-week treatment with celiprolol, losartan, and, as a proof-of-concept drug, the matrix metalloproteinase inhibitor doxycycline. Compared to age- and sex-matched untreated heterozygous mice, treatment with doxycycline or celiprolol resulted in a significant increase of rupture force, whereas no significant change was detected upon losartan treatment. Conclusions In a vEDS model, celiprolol or doxycycline, but not losartan, can improve the biomechanical integrity of the aortic wall, thereby potentially reducing the risk of dissection and rupture. As doxycycline is a broad-spectrum antibiotic with considerable side effects, celiprolol may be more suitable for a long-term therapy and thus rather indicated for the medication of patients with vEDS.
The registry data focused new light on the epidemiology of kidney diseases in Poland. These data should be used in future follow-up and prospective studies.
Background Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) currently constitutes the leading and overwhelming health issue worldwide. In comparison with adults, children present milder symptoms, with most having an asymptomatic course. We hypothesized that COVID-19 infection has a negative impact on the continuation of chemotherapy and increases nonrelapse mortality. Material and methods This study was performed to assess the course of SARS-CoV-2 among children with hematological or oncological malignancies and its impact on cancer therapy. Records of SARS-CoV-2 infection in 155 children with malignancies from 14 Polish centers for pediatric hematology and oncology were collected and analyzed. Results SARS-CoV-2 replication was observed in 155 patients. Forty-nine patients were symptomatic, with the following being the most common manifestations: fever (31 patients), gastrointestinal symptoms (10), coryza (13), cough (13) and headache (8). In children who were retested, the median time of a positive PCR result was 16 days (range 1–70 days), but 12.7% of patients were positive beyond day + 20. The length of viral PCR positivity correlated with the absolute neutrophil count at diagnosis. Seventy-six patients did not undergo further SARS-CoV-2 testing and were considered convalescents after completion of isolation. Antibiotic therapy was administered in 15 children, remdesivir in 6, convalescent plasma in 4, oxygen therapy in 3 (1—mechanical ventilation), steroids in 2, intravenous immunoglobulins in 2, and heparin in 4. Eighty patients were treated with chemotherapy within 30 days after SARS-CoV-2 infection diagnosis or were diagnosed with SARS-CoV-2 infection during 30 days of chemotherapy administration. Respiratory symptoms associated with COVID-19 and associated with oxygen therapy were present in 4 patients in the study population, and four deaths were recorded (2 due to COVID-19 and 2 due to progressive malignancy). The probability of 100-day overall survival was 97.3% (95% CI 92.9–99%). Delay in the next chemotherapy cycle occurred in 91 of 156 cases, with a median of 14 days (range 2–105 days). Conclusions For the majority of pediatric cancer patients, SARS-CoV-2 infection does not result in a severe, life-threatening course. Our data show that interruptions in therapy are common and can result in suboptimal therapy.
Amniotic fluid cells (AFCs) have been proposed as a valuable source for tissue engineering and regenerative medicine. However, before clinical implementation, rigorous evaluation of this cell source in clinically relevant animal models accepted by regulatory authorities is indispensable. Today, the ovine model represents one of the most accepted preclinical animal models, in particular for cardiovascular applications. Here, we investigate the isolation and use of autologous ovine AFCs as cell source for cardiovascular tissue engineering applications. Fetal fluids were aspirated in vivo from pregnant ewes (n = 9) and from explanted uteri post mortem at different gestational ages (n = 91). Amniotic non-allantoic fluid nature was evaluated biochemically and in vivo samples were compared with post mortem reference samples. Isolated cells revealed an immunohistochemical phenotype similar to ovine bone marrow-derived mesenchymal stem cells (MSCs) and showed expression of stem cell factors described for embryonic stem cells, such as NANOG and STAT-3. Isolated ovine amniotic fluid-derived MSCs were screened for numeric chromosomal aberrations and successfully differentiated into several mesodermal phenotypes. Myofibroblastic ovine AFC lineages were then successfully used for the in vitro fabrication of small- and large-diameter tissue-engineered vascular grafts (n = 10) and cardiovascular patches (n = 34), laying the foundation for the use of this relevant pre-clinical in vivo assessment model for future amniotic fluid cell-based therapeutic applications.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.