Der Einfluss von Hydrogensulfid auf die Aktivität humaner Thrombozyten und die mikrovaskuläre Thrombogenese im Modell der dorsalen Rückenhautkammer

Das Gas Hydrogensulfid (H2S) ist als endogener, pleiotroper Mediator bekannt. Die Arbeit untersucht den Einfluss des H2S Donors GYY4137 (GYY) auf Thrombozyten und auf die mikrovaskuläre Thrombogenese. GYY-behandelte Thrombozyten wurden durchflusszytometrisch und mittels Biotin Switch Essay untersucht. Die In-vivo-Versuche erfolgen in der dorsalen Rückenhautkammerpräparation. Die Exposition humaner Thrombozyten mit GYY reduzierte dosisabhängig die Expression aller untersuchten Adhäsionsmoleküle und steigerte die S-Sulfhydrierung. GYY verlängert die Thrombogenese und wirkt somit antithrombogen

Multimodal imaging techniques to evaluate the anticancer effect of cold atmospheric pressure plasma

Background: Skin cancer is the most frequent cancer worldwide and is divided into non-melanoma skin cancer, including basal cell carcinoma, as well as squamous cell carcinoma (SCC) and malignant melanoma (MM). Methods: This study evaluates the effects of cold atmospheric pressure plasma (CAP) on SCC and MM in vivo, employing a comprehensive approach using multi-modal imaging techniques. Longitudinal MR and PET/CT imaging were performed to determine the anatomic and metabolic tumour volume over three‐weeks in vivo. Additionally, the formation of reactive species after CAP treatment was assessed by non‐invasive chemiluminescence imaging of L‐012. Histological analysis and immunohistochemical staining for Ki‐67, ApopTag®, F4/80, CAE, and CD31, as well as protein expression of PCNA, caspase‐3 and cleaved‐caspase‐3, were performed to study proliferation, apoptosis, inflammation, and angiogenesis in CAP‐treated tumours. Results: As the main result, multimodal in vivo imaging revealed a substantial reduction in tumour growth and an increase in reactive species after CAP treatment, in comparison to untreated tu-mours. In contrast, neither the markers for apoptosis, nor the metabolic activity of both tumour entities was affected by CAP. Conclusions: These findings propose CAP as a potential adjuvant therapy option to established standard therapies of skin cancer

Molecular Mechanisms of the Efficacy of Cold Atmospheric Pressure Plasma (CAP) in Cancer Treatment

Recently, the potential use of cold atmospheric pressure plasma (CAP) in cancer treatment has gained increasing interest. Especially the enhanced selective killing of tumor cells compared to normal cells has prompted researchers to elucidate the molecular mechanisms for the efficacy of CAP in cancer treatment. This review summarizes the current understanding of how CAP triggers intracellular pathways that induce growth inhibition or cell death. We discuss what factors may contribute to the potential selectivity of CAP towards cancer cells compared to their non-malignant counterparts. Furthermore, the potential of CAP to trigger an immune response is briefly discussed. Finally, this overview demonstrates how these concepts bear first fruits in clinical applications applying CAP treatment in head and neck squamous cell cancer as well as actinic keratosis. Although significant progress towards understanding the underlying mechanisms regarding the efficacy of CAP in cancer treatment has been made, much still needs to be done with respect to different treatment conditions and comparison of malignant and non-malignant cells of the same cell type and same donor. Furthermore, clinical pilot studies and the assessment of systemic effects will be of tremendous importance towards bringing this innovative technology into clinical practice. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Molecular mechanisms of the efficacy of cold atmospheric pressure plasma (CAP) in cancer treatment

Recently, the potential use of cold atmospheric pressure plasma (CAP) in cancer treatment has gained increasing interest. Especially the enhanced selective killing of tumor cells compared to normal cells has prompted researchers to elucidate the molecular mechanisms for the efficacy of CAP in cancer treatment. This review summarizes the current understanding of how CAP triggers intracellular pathways that induce growth inhibition or cell death. We discuss what factors may contribute to the potential selectivity of CAP towards cancer cells compared to their non-malignant counterparts. Furthermore, the potential of CAP to trigger an immune response is briefly discussed. Finally, this overview demonstrates how these concepts bear first fruits in clinical applications applying CAP treatment in head and neck squamous cell cancer as well as actinic keratosis. Although significant progress towards understanding the underlying mechanisms regarding the efficacy of CAP in cancer treatment has been made, much still needs to be done with respect to different treatment conditions and comparison of malignant and non-malignant cells of the same cell type and same donor. Furthermore, clinical pilot studies and the assessment of systemic effects will be of tremendous importance towards bringing this innovative technology into clinical practice. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Oxytocin effects on experimental skin wound healing

Oxytocin (OXY) has significant effects on mammalian behavior. Next to its role in lactation and social interactions, it is described to support better wound healing as well. However, direct OXY effects on wound healing and the regeneration of the microvascular network are still not clarified. We therefore examined the effects of OXY and an OXY receptor antagonist [atosiban (ATO)] on skin wound healing, focusing on epithelialization and neovascularization

Experimental Models to Study Skin Wound Healing with a Focus on Angiogenesis

A large number of models are now available for the investigation of skin wound healing. These can be used to study the processes that take place in a phase-specific manner under both physiological and pathological conditions. Most models focus on wound closure, which is a crucial parameter for wound healing. However, vascular supply plays an equally important role and corresponding models for selective or parallel investigation of microcirculation regeneration and angiogenesis are also described. In this review article, we therefore focus on the different levels of investigation of skin wound healing (in vivo to in virtuo) and the investigation of angiogenesis and its parameters

The effects of hydrogen sulfide on platelet–leukocyte aggregation and microvascular thrombolysis

The volatile transmitter hydrogen sulfide (H2S) is known for its various functions in vascular biology. This study evaluates the effect of the H2S-donor GYY4137 (GYY) on thrombus stability and microvascular thrombolysis. Human whole blood served for all in vitro studies and was analyzed in a resting state, after stimulation with thrombin-receptor activating peptide (TRAP) and after incubation with 10 or 30 mM GYY or its vehicle DMSO following TRAP-activation, respectively. As a marker for thrombus stability, platelet–leukocyte aggregation was assessed using flow cytometry after staining of human whole blood against CD62P and CD45, respectively. Furthermore, morphology and quantity of platelet–leukocyte aggregation were studied by means of scanning electron microscopy (scanning EM). Therefore, platelets were stained for CD62P followed by immuno gold labeling. In vivo, the dorsal skinfold chamber preparation was performed for light/dye induction of thrombi in arterioles and venules using intravital fluorescence microscopy. Thrombolysis was assessed 10 and 22 h after thrombus induction and treatment with the vehicle, GYY, or recombinant tissue plasminogen activator (rtPA). Flow cytometry revealed an increase of CD62P/CD45 positive aggregates after TRAP stimulation of human whole blood, which was significantly reduced by preincubation with 30 mM GYY. Scanning EM additionally showed a reduced platelet–leukocyte aggregation and a decreased leukocyte count within the aggregates after preincubation with GYY compared to TRAP stimulation alone. Further on, morphological signs of platelet activation were found markedly reduced upon treatment with GYY. In mice, both GYY and rtPA significantly accelerated arteriolar and venular thrombolysis compared to the vehicle control. In conclusion, GYY impairs thrombus stability by reducing platelet–leukocyte aggregation and thereby facilitates endogenous thrombolysis

Assessment of Quality of Life after Endovascular and Open Abdominal Aortic Aneurysm Repair: A Retrospective Single-Center Study

Postoperative quality of life is an important outcome parameter after treatment of abdominal aortic aneurysms. The aim of this retrospective single-center study was to assess and compare the health-related quality of life (HRQoL) of patients after open repair (OR) or endovascular treatment (EVAR), and furthermore to investigate the effect of incisional hernia (IH) formation on HRQoL. Patients who underwent OR or EVAR for treatment of an abdominal aortic aneurysm between 2008 and 2016 at a University Medical Center were included. HRQoL was assessed using the SF-36 questionnaire. The incidence of IH was recorded from patient files and by telephone contact. SF-36 scores of 83 patients (OR: n = 36; EVAR: n = 47) were obtained. The mean follow-up period was 7.1 years. When comparing HRQoL between OR and EVAR, patients in both groups scored higher in one of the eight categories of the SF36 questionnaires. The incidence of IH after OR was 30.6%. In patients with postoperative IH, HRQoL was significantly reduced in the dimensions “physical functioning”, “role physical” and “role emotional” of the SF-36. Based on this data, it can be concluded that neither OR nor EVAR supply a significant advantage regarding HRQoL. In contrast, the occurrence of IH has a relevant impact on the HRQoL of patients after OR

Evaluation of Hyperspectral Imaging for Follow-Up Assessment after Revascularization in Peripheral Artery Disease

Background: Assessment of tissue oxygenation is an important aspect of detection and monitoring of patients with peripheral artery disease (PAD). Hyperspectral imaging (HSI) is a non-contact technology for assessing microcirculatory function by quantifying tissue oxygen saturation (StO2). This study investigated whether HSI can be used to monitor skin oxygenation in patients with PAD after appropriate treatment of the lower extremities. Methods: For this purpose, 37 patients with PAD were studied by means of ankle–brachial index (ABI) and HSI before and after surgical or endovascular therapy. Thereby, the oxygenation parameter StO2 and near infrared (NIR) perfusion index were quantified in seven angiosomes on the diseased lower leg and foot. In addition, the effects of skin temperature and physical activity on StO2 and the NIR perfusion index and the respective inter-operator variability of these parameters were investigated in 25 healthy volunteers. Results: In all patients, the ABI significantly increased after surgical and endovascular therapy. In parallel, HSI revealed significant changes in both StO2 and NIR perfusion index in almost all studied angiosomes depending on the performed treatment. The increase in tissue oxygenation saturation was especially pronounced after surgical treatment. Neither heat nor cold, nor physical activity, nor repeated assessments of HSI parameters by independent investigators significantly affected the results on StO2 and the NIR perfusion index. Conclusions: Tissue oxygen saturation data obtained with HSI are robust to external confounders, such as temperature and physical activity, and do not show inter-operator variability; therefore, can be used as an additional technique to established methods, such as the ABI, to monitor peripheral perfusion in patients with PAD

Bacteriophages for the Treatment of Graft Infections in Cardiovascular Medicine

Bacterial infections of vascular grafts represent a major burden in cardiovascular medicine, which is related to an increase in morbidity and mortality. Different factors that are associated with this medical field such as patient frailty, biofilm formation, or immunosuppression negatively influence antibiotic treatment, inhibiting therapy success. Thus, further treatment strategies are required. Bacteriophage antibacterial properties were discovered 100 years ago, but the focus on antibiotics in Western medicine since the mid-20th century slowed the further development of bacteriophage therapy. Therefore, the experience and knowledge gained until then in bacteriophage mechanisms of action, handling, clinical uses, and limitations were largely lost. However, the parallel emergence of antimicrobial resistance and individualized medicine has provoked a radical reassessment of this approach and cardiovascular surgery is one area in which phages may play an important role to cope with this new scenario. In this context, bacteriophages might be applicable for both prophylactic and therapeutic use, serving as a stand-alone therapy or in combination with antibiotics. From another perspective, standardization of phage application is also required. The ideal surgical bacteriophage application method should be less invasive, enabling highly localized concentrations, and limiting bacteriophage distribution to the infection site during a prolonged time lapse. This review describes the latest reports of phage therapy in cardiovascular surgery and discusses options for their use in implant and vascular graft infections