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Hair follicles constitute important drug delivery targets for skin antisepsis since they contain ≈25% of the skin microbiome. Nanoparticles are known to penetrate deeply into hair follicles. By massaging the skin, the follicular penetration process is enhanced based on a ratchet effect. Subsequently, an intrafollicular drug release can be initiated by various trigger mechanisms. Here, we present novel ultraviolet A (UVA)-responsive nanocapsules (NCs) with a size between 400 and 600 nm containing hydroxyethyl starch (HES) functionalized by an o-nitrobenzyl linker. A phase transfer into phosphate-buffered saline (PBS) and ethanol was carried out, during which an aggregation of the particles was observed by means of dynamic light scattering (DLS). The highest stabilization for the target medium ethanol as well as UVA-dependent release of ethanol from the HES-NCs was achieved by adding 0.1% betaine monohydrate. Furthermore, sufficient cytocompatibility of the HES-NCs was demonstrated. On ex vivo porcine ear skin, a strong UVA-induced release of the model drug sulforhodamine 101 (SR101) could be demonstrated after application of the NCs in cyclohexane using laser scanning microscopy. In a final experiment, a microbial reduction comparable to that of an ethanol control was demonstrated on ex vivo porcine ear skin using a novel UVA-LED lamp for triggering the release of ethanol from HES-NCs. Our study provides first indications that an advanced skin antisepsis based on the eradication of intrafollicular microorganisms could be achieved by the topical application of UVA-responsive NCs.
Oral mucositis is the most common and severe non-hematological complication associated with cancer radiotherapy, chemotherapy, or their combination. Treatment of oral mucositis focuses on pain management and the use of natural anti-inflammatory, sometimes weakly antiseptic mouth rinses in combination with optimal oral cavity hygiene. To prevent negative effects of rinsing, accurate testing of oral care products is necessary. Due to their ability to mimic realistic in-vivo conditions, 3D models may be an appropriate option in compatibility testing of anti-inflammatory and antiseptically effective mouth rinses. We present a 3D model of oral mucosa based on the cell line TR-146 with a physical barrier, characterized by high transepithelial electrical resistance (TEER) and confirmed cell integrity. Histological characterization of the 3D mucosa model showed a stratified, non-keratinized multilayer of epithelial cells similar to that of human oral mucosa. By means of immuno-staining, tissue-specific expression of cytokeratin 13 and 14 was shown. Incubation of the 3D mucosa model with the rinses had no effects on cell viability, but TEER decreased 24h after incubation in all solutions except ProntOral®. Analogous to skin models, the established 3D model meets the quality control criteria of OECD guidelines and may therefore be suitable for comparing the cytocompatibility of oral rinses.
Objectives
Oral mucositis caused by intensive cancer chemotherapy or radiotherapy frequently results in pronounced damage of the oral mucosa leading to painful oral hygiene. To support oral care, antimicrobial effective mouth rinses may be used. Thus, the efficacy of a hypochlorite-based mouth rinse (Granudacyn®), assumed to be highly biocompatible because of the compounds being part of the natural pathogen defense, as possible antiseptic agent in case of oral mucositis was compared to that of an octenidine based antiseptic mouth rinse (Octenidol® md).
Materials and methods
The study was conducted as monocentric, controlled, randomized, blind cross over comparative study on 20 volunteers. As a proof of principle, we performed the study on orally healthy subjects and not cancer patients. The efficacy was determined as reduction of colony forming units (cfu) on buccal mucosa as well as in saliva. After mouth rinsing for 30 s, samples were taken after 1 min, 15 min, 30 and 60 min. The lg-reduction was calculated as difference between lg-values of cfu pre- and post-treatment.
Results
Both antiseptic mouth rinses induced a significant reduction of cfu on buccal mucosa and in saliva 1 min after mouth rinsing. The effect persisted up to 60 min. The octenidine based rinse was significantly superior to the hypochlorite-based rinse up to the last sample 60 min after rinsing. However, the known cytotoxicity of octenidine argues against its application.
Conclusion
Within the limits of this study, due to its antiseptic efficacy, the hypochlorite-based rinse Granudacyn® can be regarded appropriate to support the oral hygiene in patients with a sensitive oral mucosa during an aggressive cancer chemotherapy and radiation treatment in case of oral mucositis.
AbstractPlasma medicine refers to the application of nonequilibrium plasmas at approximately body temperature, for therapeutic purposes. Nonequilibrium plasmas are weakly ionized gases which contain charged and neutral species and electric fields, and emit radiation, particularly in the visible and ultraviolet range. Medically-relevant cold atmospheric pressure plasma (CAP) sources and devices are usually dielectric barrier discharges and nonequilibrium atmospheric pressure plasma jets. Plasma diagnostic methods and modelling approaches are used to characterize the densities and fluxes of active plasma species and their interaction with surrounding matter. In addition to the direct application of plasma onto living tissue, the treatment of liquids like water or physiological saline by a CAP source is performed in order to study specific biological activities. A basic understanding of the interaction between plasma and liquids and bio-interfaces is essential to follow biological plasma effects. Charged species, metastable species, and other atomic and molecular reactive species first produced in the main plasma ignition are transported to the discharge afterglow to finally be exposed to the biological targets. Contact with these liquid-dominated bio-interfaces generates other secondary reactive oxygen and nitrogen species (ROS, RNS). Both ROS and RNS possess strong oxidative properties and can trigger redox-related signalling pathways in cells and tissue, leading to various impacts of therapeutic relevance. Dependent on the intensity of plasma exposure, redox balance in cells can be influenced in a way that oxidative eustress leads to stimulation of cellular processes or oxidative distress leads to cell death. Currently, clinical CAP application is realized mainly in wound healing. The use of plasma in cancer treatment (i.e. plasma oncology) is a currently emerging field of research. Future perspectives and challenges in plasma medicine are mainly directed towards the control and optimization of CAP devices, to broaden and establish its medical applications, and to open up new plasma-based therapies in medicine.
Background
The approval of ethanol by the Biocidal Products Regulation has been under evaluation since 2007. This follows concern over alcohol uptake from ethanol-based hand rubs (EBHR). If ethanol is classified as carcinogenic, mutagenic, or reprotoxic by the European Chemicals Agency (ECHA), then this would affect infection prevention and control practices.
Aim
A review was performed to prove that ethanol is toxicological uncritical and indispensable for hand antisepsis because of its unique activity against non-enveloped viruses and thus the resulting lack of alternatives. Therefore, the following main points are analyzed: The effectiveness of ethanol in hand hygiene, the evidence of ethanol at blood/tissue levels through hand hygiene in healthcare, and the evidence of toxicity of different blood/tissue ethanol levels and the non-comparability with alcoholic consumption and industrial exposure.
Results
EBHR are essential for preventing infections caused by non-enveloped viruses, especially in healthcare, nursing homes, food industry and other areas. Propanols are effective against enveloped viruses as opposed to non-enveloped viruses but there are no other alternatives for virucidal hand antisepsis. Long-term ingestion of ethanol in the form of alcoholic beverages can cause tumours. However, lifetime exposure to ethanol from occupational exposure < 500 ppm does not significantly contribute to the cancer risk. Mutagenic effects were observed only at doses within the toxic range in animal studies. While reprotoxicity is linked with abuse of alcoholic beverages, there is no epidemiological evidence for this from EBHR use in healthcare facilities or from products containing ethanol in non-healthcare settings.
Conclusion
The body of evidence shows EBHRs have strong efficacy in killing non-enveloped viruses, whereas 1-propanol and 2-propanol do not kill non-enveloped viruses, that pose significant risk of infection. Ethanol absorbed through the skin during hand hygiene is similar to consumption of beverages with hidden ethanol content (< 0.5% v/v), such as apple juice or kefir. There is no risk of carcinogenicity, mutagenicity or reprotoxicity from repeated use of EBHR. Hence, the WHO Task Force strongly recommend retaining ethanol as an essential constituent in hand rubs for healthcare.
Aim
Periprosthetic joint infections are a devastating complication after arthroplasty, leading to rejection of the prosthesis. The prevention of septic loosening may be possible by an antimicrobial coating of the implant surface. Poly (hexamethylene) biguanide hydrochloride [PHMB] seems to be a suitable antiseptic agent for this purpose since previous studies revealed a low cytotoxicity and a long-lasting microbicidal effect of Ti6Al4V alloy coated with PHMB. To preclude an excessive activation of the immune system, possible inflammatory effects on macrophages upon contact with PHMB-coated surfaces alone and after killing of S. epidermidis and P. aeruginosa are analyzed.
Methods
THP-1 monocytes were differentiated to M0 macrophages by phorbol 12-myristate 13-acetate and seeded onto Ti6Al4V surfaces coated with various amounts of PHMB. Next to microscopic immunofluorescence analysis of labeled macrophages after adhesion on the coated surface, measurement of intracellular reactive oxygen species and analysis of cytokine secretion at different time points without and with previous bacterial contamination were conducted.
Results
No influence on morphology of macrophages and only slight increases in iROS generation were detected. The cytokine secretion pattern depends on the surface treatment procedure and the amount of adsorbed PHMB. The PHMB coating resulted in a high reduction of viable bacteria, resulting in no significant differences in cytokine secretion as reaction to coated surfaces with and without bacterial burden.
Conclusion
Ti6Al4V specimens after alkaline treatment followed by coating with 5–7 μg PHMB and specimens treated with H2O2 before PHMB-coating (4 μg) had the smallest influence on the macrophage phienotype and thus are considered as the surface with the best cytocompatibility to macrophages tested in the present study.
Cold physical plasmas, especially noble gas driven plasma jets, emit considerable amounts of ultraviolet radiation (UV). Given that a noble gas channel is present, even the energetic vacuum UV can reach the treated target. The relevance of UV radiation for antimicrobial effects is generally accepted. It remains to be clarified if this radiation is relevant for other biomedical application of plasmas, e.g., in wound care or cancer remediation. In this work, the role of (vacuum) ultraviolet radiation generated by the argon plasma jet kINPen for cysteine modifications was investigated in aqueous solutions and porcine skin. To differentiate the effects of photons of different wavelength and complete plasma discharge, a micro chamber equipped with a MgF2, Suprasil, or Borosilicate glass window was used. In liquid phase, plasma-derived VUV radiation was effective and led to the formation of cysteine oxidation products and molecule breakdown products, yielding sulfite, sulfate, and hydrogen sulfide. At the boundary layer, the impact of VUV photons led to water molecule photolysis and formation of hydroxyl radicals and hydrogen peroxide. In addition, photolytic cleavage of the weak carbon-sulfur bond initiated the formation of sulfur oxy ions. In the intact skin model, protein thiol modification was rare even if a VUV transparent MgF2 window was used. Presumably, the plasma-derived VUV radiation played a limited role since reactions at the boundary layer are less frequent and the dense biomolecules layers block it effectively, inhibiting significant penetration. This result further emphasizes the safety of physical plasmas in biomedical applications.
Contaminated surfaces have been discussed as a possible source of severe acute respiratory
syndrome coronavirus-2 (SARS-CoV-2). Under experimental conditions, SARS-CoV-2 can remain
infectious on surfaces for several days. However, the frequency of SARS-CoV-2 detection on surfaces
in healthcare settings and the public is currently not known. A systematic literature review was
performed. On surfaces around COVID-19 cases in healthcare settings (42 studies), the SARS-CoV2 RNA detection rates mostly were between 0% and 27% (Ct values mostly > 30). Detection of
infectious SARS-CoV-2 was only successful in one of seven studies in 9.2% of 76 samples. Most of the
positive samples were obtained next to a patient with frequent sputum spitting during sampling.
Eight studies were found with data from public surfaces and RNA detection rates between 0% and
22.1% (Ct values mostly > 30). Detection of infectious virus was not attempted. Similar results
were found in samples from surfaces around confirmed COVID-19 cases in non-healthcare settings
(7 studies) and from personal protective equipment (10 studies). Therefore, it seems plausible to
assume that inanimate surfaces are not a relevant source for transmission of SARS-CoV-2. In public
settings, the associated risks of regular surface disinfection probably outweigh the expectable health
benefit
COVID-19 Vaccinated Individuals Can Be a Source of SARS-CoV-2 Transmission—A Systematic Review
(2021)
Fundamental rights are probably given back earlier to COVID-19 vaccinated individuals
assuming that they cannot spread SARS-CoV-2 anymore. The objective of the study was to determine
if COVID-19 vaccinated individuals can still be the source of SARS-CoV-2 transmission. PubMed
was searched for studies on 4 April 2021. All studies with original data on COVID-19 cases among
vaccinated individuals (phase III RCTs) and on viral load in the upper respiratory tract of vaccinated
macaques after a SARS-CoV-2 challenge were included. Symptomatic COVID-19 cases were found
in four trials among vaccinated participants although less frequently than among control subjects.
One study revealed asymptomatic COVID-19 cases in a similar frequency among 2.168 AZD1222-
vaccinated subjects (1.0%) compared to 2.223 control subjects (1.0%). In 15 studies with vaccinated
macaques, it was found that the load of SARS-CoV-2 RNA, subgenomic RNA and infectious virus
in the upper respiratory tract is variable. Sterilizing immunity was found in none of the animal
studies. Major limitations of the animal studies are that the SARS-CoV-2 challenge took place within
a few weeks of the final or only vaccine dose, that the viral challenge was often high and, in some
studies, administered by up to four routes. Based on current knowledge it seems clear that COVID-19
vaccinated individuals can still be the source of SARS-CoV-2 transmission.
Cold physical plasma is a partially ionized gas expelling many reactive oxygen and nitrogen
species (ROS/RNS). Several plasma devices have been licensed for medical use in dermatology, and
recent experimental studies suggest their putative role in cancer treatment. In cancer therapies with
an immunological dimension, successful antigen presentation and inflammation modulation is a
key hallmark to elicit antitumor immunity. Dendritic cells (DCs) are critical for this task. However,
the inflammatory consequences of DCs following plasma exposure are unknown. To this end,
human monocyte-derived DCs (moDCs) were expanded from isolated human primary monocytes;
exposed to plasma; and their metabolic activity, surface marker expression, and cytokine profiles
were analyzed. As controls, hydrogen peroxide, hypochlorous acid, and peroxynitrite were used.
Among all types of ROS/RNS-mediated treatments, plasma exposure exerted the most notable
increase of activation markers at 24 h such as CD25, CD40, and CD83 known to be crucial for T cell
costimulation. Moreover, the treatments increased interleukin (IL)-1α, IL-6, and IL-23. Altogether,
this study suggests plasma treatment augmenting costimulatory ligand and cytokine expression in
human moDCs, which might exert beneficial effects in the tumor microenvironment.