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Bei Menschen mit Verdacht auf eine Seltene Erkrankung ist fur die Diagnosestellung ein strukturiertes, interdisziplinares Vorgehen erforderlich. In manchen dieser Falle und bei Menschen mit einer gesicherten Diagnose einer seltenen Erkrankung, aber einem komplizierten Verlauf ist der Rat externer Experten oft sinnvoll und hilfreich, um den bestmoglichen Weg zur Diagnosestellung oder den optimalen Therapieplan zu definieren. Digitale Systeme konnen die Ablaufe in einem Zentrum fur Seltene Erkrankungen standardisieren sowie die Kommunikation zwischen Experten verschiedener medizinischer Einrichtungen erleichtern und unterstutzen. Die digitale Plattform des Bayerischen Arbeitskreises Seltene Erkrankungen, BASE-Netz, ermoglicht Betroffenen, Angehorigen und behandelnden Arzten, Informationen einzugeben und Dokumente hochzuladen, strukturiert die Ablaufe und erleichtert die Kommunikation zwischen den bayerischen Zentren fur Seltene Erkrankungen ohne Beschrankungen auf z. B. eine spezifische Krankheits- oder Expertengruppe. Das Clinical Patient Management System (CPMS) der Europaischen Referenznetzwerke (ERN) wird hingegen fur fallbezogene Konsile und Fallkonferenzen innerhalb eines der krankheitsgruppenspezifischen 24 ERN genutzt. Experten des entsprechenden ERN geben ihre Empfehlungen zu einem Fall, basierend auf pseudonymisierten Patientendaten. Sowohl BASE-Netz als auch das CPMS konnen die diagnostischen Prozesse bei Seltenen Erkrankungen unterstutzen und die Behandlung von Menschen mit einer solchen Erkrankung verbessern.

An electronic patient record offers opportunities for digital networks between medical care providers and for the digital communication between health service providers and their patients. Patients with rare diseases benefit from a diagnosis and treatment information at an early stage and receive precise treatment on the basis of multiprofessional case management. Regarding the patient care and medical research in rare diseases, electronic patient records can help to collect all data in a structured manner and to digitally map the workflows in registration, admission, diagnosis, and treatment. This can reduce costs in our healthcare system, as diagnosis and treatment can be targeted better at the patients and unnecessary medical examinations can be reduced.In two pilot projects, first experiences with electronic patient records for patients with rare diseases were gathered. In cooperation with several medical care providers, the projects BASE-Netz and TRANSLATE-NAMSE analyzed the requirements of an electronic patient record, demonstrated the technical and legal feasibility, and evaluated the practicability for medical care providers and patients. The participating centers for rare diseases see benefits in the structured registration of the patients and the simplification of cross-institutional patient management, as patients can fulfil more tasks on their own and the health professionals can easily share data. The development of the Telematikinfrastructure of the Gematik offers opportunities to ease the digital connection between doctors' offices and the center for rare diseases. In particular, constant clarification and transparency are essential in order to provide information on data protection issues. Training and support should also be provided to promote patients' digital skills.Elektronische Patientenakten (EPA) bieten zahlreiche Chancen für die digitale Vernetzung der Leistungserbringer untereinander und für die digitale Kommunikation mit den Patienten. Für Menschen mit Seltenen Erkrankungen (SE) können sich dadurch verschiedene Vorteile ergeben, wie eine frühere Diagnose und eine gezieltere Behandlung z. B. auf Grundlage eines multiprofessionellen Fallmanagements. Für die Patientenversorgung und Forschung bei Seltenen Erkrankungen kann eine EPA die Daten der Patienten strukturiert erfassen und darauf aufbauend die Arbeitsabläufe von der Anmeldung über die Aufnahme bis zu Behandlung und Monitoring digital abbilden. Für das Gesundheitswesen erhofft man sich durch EPA eine Kostenersparnis, da Diagnose- und Behandlungsprozesse zielgerichteter angeboten und unnötige Untersuchungen und Termine reduziert werden können.In 2 Pilotprojekten konnten erste Erfahrungen mit EPA für Menschen mit Seltenen Erkrankungen gesammelt werden. Die Projekte „BASE-Netz“ und „TRANSLATE-NAMSE“ haben in Zusammenarbeit mit mehreren Leistungserbringern die Anforderungen an eine EPA erfasst, die technische und rechtliche Machbarkeit aufgezeigt und die Praktikabilität für Leistungserbringer und Patienten untersucht. Während die Patienten überwiegend positive Resonanz zeigten, erwies sich die Anbindung der niedergelassenen Arztpraxen als Herausforderung. Vereinfachend könnte hierbei zukünftig der Ausbau der Telematikinfrastruktur wirken. Unerlässlich sind stetige Aufklärungen und Transparenz, um insbesondere über datenschutzrechtliche Fragen zu informieren. Auch sollten Schulungen und Unterstützung angeboten werden, um die digitalen Kompetenzen der Patienten zu fördern.

Orphanet journal of rare diseases : OJRD 17(1), 47 (2022). doi:10.1186/s13023-022-02176-1, Published by BioMed Central, London

The incidence of melanoma is steadily increasing in the Western hemisphere, and one key factor is UV exposure. Sun protection is essential, particularly in patients with diagnosed melanoma. However, data on the psychological implications of sunscreen protection in melanoma patients are lacking. This project was designed as a randomised controlled feasibility trial to explore the feasibility of the diary method and tube count to assess patient compliance in the setting of a monocentric trial, furthermore to observe any recognisable trends regarding anxiety and QoL between the intervention and control group.

Helicobacter pylori is associated with chronic gastritis, gastric or duodenal ulcers, and gastric cancer. Since the oral cavity is the entry port and the first component of the gastrointestinal system, the oral cavity has been discussed as a potential reservoir of H. pylori. Accordingly, a potential oral-oral transmission route of H. pylori raises the question concerning whether close contact such as kissing or sharing a meal can cause the transmission of H. pylori. Therefore, this topic has been investigated in many studies, applying different techniques for detection of H. pylori from oral samples, i.e. molecular techniques, immunological or biochemical methods and traditional culture techniques. While molecular, immunological or biochemical methods usually yield high detection rates, there is no definitive evidence that H. pylori has ever been isolated from the oral cavity. The specificity of those methods may be limited due to potential cross-reactivity, especially with H. pylori-like microorganisms such as Campylobacter spp. Furthermore, the influence of gastroesophageal reflux has not been investigated so far. This review aims to summarize and critically discuss previous studies investigating the potential colonization of H. pylori in the oral cavity and suggest novel research directions for targeting this critical research question.

The antimicrobial photodynamic therapy (aPDT) is a promising approach for the control of microbial and especially fungal infections such as mucosal mycosis. TMPyP [5,10,15, 20-tetrakis(1-methylpyridinium-4-yl)-porphyrin tetra p-toluenesulfonate] is an effective photosensitizer (PS) that is commonly used in aPDT. The aim of this study was to examine the localization of TMPyP in Candida albicans before and after irradiation with visible light to get information about the cellular mechanism of antifungal action of the photodynamic process using this PS. Immediately after incubation of C. albicans with TMPyP, fluorescence microscopy revealed an accumulation of the PS in the cell envelope. After irradiation with blue light the complete cell showed red fluorescence, which indicates, that aPDT is leading to a damage in the cell wall with following influx of PS into the cytosol. Incubation of C. albicans with Wheat Germ Agglutinin (WGA) could confirm the cell wall as primary binding site of TMPyP. The finding that the porphyrin accumulates in the fungal cell wall and does not enter the interior of the cell before irradiation makes it unlikely that resistances can emerge upon aPDT. The results of this study may help in further development and modification of PS in order to increase efficacy against fungal infections such as those caused by C. albicans.

Antimicrobial resistance is a serious issue for public health care all over the world. While resistance toward antibiotics has attracted strong interest among researchers and the general public over the last 2 decades, the directly related problem of resistance toward antiseptics and biocides has been somewhat left untended. In the field of dentistry, antiseptics are routinely used in professional care, but they are also included in lots of oral care products such as mouthwashes or dentifrices, which are easily available for consumers over-the-counter. Despite this fact, there is little awareness among the dental community about potential risks of the widespread, unreflected, and potentially even needless use of antiseptics in oral care. Cetylpyridinium chloride (CPC), a quaternary ammonium compound, which was first described in 1939, is one of the most commonly used antiseptics in oral care products and included in a wide range of over-the-counter products such as mouthwashes and dentifrices. The aim of the present review is to summarize the current literature on CPC, particularly focusing on its mechanism of action, its antimicrobial efficacy toward biofilms, and on potential risks of resistance toward this antiseptic as well as underlying mechanisms. Furthermore, this work aims to raise awareness among the dental community about the risk of resistance toward antiseptics in general.

Objectives The aims of this study were to investigate the antimicrobial efficacy of antiseptics in saliva-derived microcosm biofilms, and to examine phenotypic adaption of bacteria upon repeated exposure to sub-inhibitory antiseptic concentrations. Methods Saliva-derived biofilms were formed mimicking caries- or gingivitis-associated conditions, respectively. Microbial compositions were analyzed by semiconductor-based 16S rRNA sequencing. Biofilms were treated with CHX, CPC, BAC, ALX, and DQC for 1 or 10 min, and colony forming units (CFU) were evaluated. Phenotypic adaptation of six selected bacterial reference strains toward CHX, CPC, and BAC was assessed by measuring minimum inhibitory concentrations (MICs) over 10 passages of sub-inhibitory exposure. Protein expression profiles were investigated by SDS-PAGE. Results Both biofilms showed outgrowth of streptococci and Veillonella spp., while gingivitis biofilms also showed increased relative abundances of Actinomyces, Granulicatella, and Gemella spp. Antiseptic treatment for 1 min led to no relevant CFU-reductions despite for CPC. When treated for 10 min, CPC was most effective followed by BAC, ALX, CHX, and DQC. Stable adaptations with up to fourfold MIC increases were found in E. coli toward all tested antiseptics, in E. faecalis toward CHX and BAC, and in S. aureus toward CPC. Adapted E. coli strains showed different protein expression as compared with the wildtype strain. Conclusion Antiseptics showed limited antimicrobial efficacy toward mature biofilms when applied for clinically relevant treatment periods. Bacteria showed phenotypic adaptation upon repeated sub-inhibitory exposure. Clinical relevance Clinicians should be aware that wide-spread use of antiseptics may pose the risk of inducing resistances in oral bacteria.

The naturally occurring photosensitizer curcumin has excellent biocompatibility, but its antimicrobial photodynamic efficacy is limited by (i) weak adherence to Gram(-) bacteria cell walls, (ii) low (photo-)stability and (iii) limited solubility in water. In this study novel curcuminoids bearing cationic substituents were prepared by different synthetic routes. The derivatives exhibit excellent water solubility, improved photostability and low aggregation. All novel curcuminoids showed antibacterial photodynamic effects (>3 log10 reduction of CFU) against Escherichia coli and Staphylococcus aureus upon blue light illumination. In contrast to natural curcumin, effective photokilling of E. coli was possible without the addition of permeabilizing agents. Ten micromolar of the most active compound (8) achieved a 7 log10 decrease of E. coli after light activation with a fluence of 33.8 J/cm2, whereas S. aureus was inactivated by more than 4 log10 at a fluence of 5.3 J/cm2. Overall the reduction in bacterial count was at least 100-fold more effective with these new curcuminoids in comparison to natural curcumin.

Considering increasing number of pathogens resistant towards commonly used antibiotics as well as antiseptics, there is a pressing need for antimicrobial approaches that are capable of inactivating pathogens efficiently without the risk of inducing resistances. In this regard, an alternative approach is the antimicrobial photodynamic therapy (aPDT). The antimicrobial effect of aPDT is based on the principle that visible light activates a per se non-toxic molecule, the so-called photosensitizer (PS), resulting in generation of reactive oxygen species that kill bacteria unselectively via an oxidative burst. During the last 10–20 years, there has been extensive in vitro research on novel PS as well as light sources, which is now to be translated into clinics. In this review, we aim to provide an overview about the history of aPDT, its fundamental photochemical and photophysical mechanisms as well as photosensitizers and light sources that are currently applied for aPDT in vitro. Furthermore, the potential of resistances towards aPDT is extensively discussed and implications for proper comparison of in vitro studies regarding aPDT as well as for potential application fields in clinical practice are given. Overall, this review shall provide an outlook on future research directions needed for successful translation of promising in vitro results in aPDT towards clinical practice.

Cold atmospheric argon plasma is recognized as a new contact free approach for the decrease of bacterial load on chronic wounds in patients. So far very limited data are available on its toxicity and mutagenicity on eukaryotic cells. Thus, the toxic/mutagenic potential of cold atmospheric argon plasma using the MicroPlaSter β® , which has been used efficiently in humans treating chronic and acute wounds, was investigated using the XTT assay in keratinocytes and fibroblasts and the HGPRT (hypoxanthine guanine phosphoribosyl transferase) assay with V79 Chinese hamster cells. The tested clinical parameter of a 2 min cold atmospheric argon plasma treatment revealed no relevant toxicity on keratinocytes (viability: 76% ± 0.17%) and on fibroblasts (viability: 81.8 ± 0.10) after 72 hr as compared to the untreated controls. No mutagenicity was detected in the HGPRT assay with V79 cells even after repetitive CAP treatments of 2-10 min every 24 hr for up to 5 days. In contrast, UV-C irradiation of V79 cells, used as a positive control in the HGPRT test, led to DNA damage and mutagenic effects. Our findings indicate that cold atmospheric plasma using the MicroPlaSter β® shows negligible effects on keratinocytes and fibroblasts but no mutagenic potential in the HGPRT assay, indicating a new contact free safe technology. Environ. Mol. Mutagen. 58:172-177, 2017. © 2017 Wiley Periodicals, Inc.

Although conventional antimicrobial drugs have been viewed as miraculous cure-alls for the past 80 years, increasing antimicrobial drug resistance requires a major and rapid intervention. However, the development of novel but still conventional systemic antimicrobial agents, having only a single mode or site of action, will not alleviate the situation because it is probably only a matter of time until any such agents will also become ineffective. To continue to produce new agents based on this notion is unacceptable, and there is an increasing need for alternative approaches to the problem. By contrast, light-activated molecules called photoantimicrobials act locally via the in-situ production of highly reactive oxygen species, which simultaneously attack various biomolecular sites in the pathogenic target and therefore offer both multiple and variable sites of action. This non-specificity at the target circumvents conventional mechanisms of resistance and inhibits the development of resistance to the agents themselves. Photoantimicrobial therapy is safe and easy to implement and, unlike conventional agents, the activity spectrum of photoantimicrobials covers bacteria, fungi, viruses, and protozoa. However, clinical trials of these new, truly broad-spectrum, and minimally toxic agents have been few, and the funding for research and development is almost non-existent. Photoantimicrobials constitute one of the few ways forward through the morass of drug-resistant infectious disease and should be fully explored. In this Personal View, we raise awareness of the novel photoantimicrobial technologies that offer a viable alternative to conventional drugs in many relevant application fields, and could thus slow the pace of resistance development.

For caries‐active patients, antimicrobial measures may be useful in addition to mechanical biofilm removal. The aim of this study was to investigate the antimicrobial efficacy of alternative compounds for use in oral care from two main categories (i.e., preservatives and natural compounds) toward biofilms from caries‐associated bacteria as compared to oral care gold‐standards chlorhexidine digluconate (CHX), cetylpyridinium chloride (CPC), and zinc. Compounds were screened in initial Streptococcus mutans biofilms. Then, the most effective compounds were further investigated in mature S. mutans and polymicrobial biofilms comprising Actinomyces naeslundii, Actinomyces odontolyticus, and S. mutans. Here, distinct treatment periods and concentrations were evaluated. Biofilms were visualized by scanning electron microscopy and bacterial membrane damage was evaluated by means of flow cytometry and staining with SYBR Green and propidium iodide. Citrus extract was the only compound exhibiting similar antimicrobial efficacy in initial S. mutans biofilms (>5 log10) as compared to CHX and CPC, but its effect was clearly inferior in mature S. mutans and polymicrobial biofilms. Flow cytometric data suggested that the mechanism of antimicrobial action of citrus extract may be based on damage of bacterial membranes similar to CHX and CPC. From all alternative compounds investigated in this study, citrus extract exhibited the highest antimicrobial efficacy toward in vitro biofilms from caries‐associated bacteria, but still was less effective than oral care gold‐standard antiseptics CHX and CPC. Nevertheless, citrus extract may be a valuable antimicrobial compound for use in oral care for caries‐active patients.

Photodynamic antimicrobial chemotherapy (PACT) is a multi-target method to inactivate pathogenic microorganisms by exciting a photosensitizer (PS) with visible light of appropriate wavelength in the presence of molecular oxygen (3O2). There are two major pathways by which reactive oxygen species (ROS) are produced. In type I (TI)-reactions, radicals such as superoxide (O2˙−) and hydroxyl radicals (˙OH) are generated by electron transfer. In type II (TII)-reactions, highly reactive singlet oxygen (1O2) is produced by direct energy transfer. This study investigated the efficiency of PACT in Gram-negative Escherichia coli wild type (EC WT) and the mutant Escherichia coli PN134 (EC PN134) which is not able to produce SOD A and SOD B, by means of two different photosensitizers (PS) from different chemical classes with different 1O2 quantum yields: methylene blue (MB) and 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin tetra(p-toluenesulfonate) (TMPyP). Mutants, which lack antioxidant enzymes, were particularly susceptible towards TI-PACT. In the case of PACT with MB, quenching agents such as superoxide dismutase (SOD) and catalase (CAT) were sufficient for protecting both the wild type and the mutant, whereas they were not in PACT with TMPyP. The genetic levels of sodA and sodB were examined after photodynamic treatment regarding their potential resistance. This study showed that – under the photodynamic conditions presented in this study – expression of sodA and sodB was not directly influenced by PACT-generated oxidative stress, although SOD enzymes are part of the major defense machinery against oxidative stress and were thus expected to be upregulated. Overall the susceptibility of EC PN134 and EC WT differed towards photodynamic inactivation via TI-mechanism of action. Thus, already existing defense mechanisms against ROS in bacteria might influence the susceptibility against TI-PACT, while this was not the case using TII-photosensitizers.

Antibiotics have increasingly lost their impact to kill bacteria efficiently during the last 10 years. The emergence and dissemination of superbugs with resistance to multiple antibiotic classes have occurred among Gram-positive and Gram-negative strains including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter strains. These six superbugs can “escape” more or less any single kind of antibiotic treatment. That means bacteria are very good at developing resistance against antibiotics in a short time. One new approach is called photodynamic antimicrobial chemotherapy (PACT) which already has demonstrated an efficient antimicrobial efficacy among multi-resistant bacteria. Until now it has been questionable if bacteria can develop resistance against PACT. This perspective summarises the current knowledge about the susceptibility of bacteria towards oxidative stress and sheds some light on possible strategies of the development of photodynamic inactivation of bacteria (PACT)-induced oxidative stress resistance by bacteria.

Antimicrobial photodynamic therapy (aPDT) may be useful as a supportive antimicrobial measure for caries-active subjects. In this study, the antimicrobial efficacy of aPDT with a phenalen-1-one photosensitizer was evaluated in a novel in vitro biofilm model comprising Actinomyces naeslundii, Actinomyces odontolyticus, and Streptococcus mutans and was compared to chlorhexidine. The proposed biofilm model allows high-throughput screening for antimicrobial efficacy while exhibiting a differentiated response to different antimicrobial approaches. While chlorhexidine 0.2% showed a reduction of ≈4 log10 for all species, aPDT led to a more pronounced reduction of S. mutans (2.8 log10) than of Actinomyces spp. (1.2 or 1.3 log10). A similar effect was also observed in monospecies biofilms. Therefore, aPDT may be more effective against S. mutans than against Actinomyces spp. when in biofilms, and this antimicrobial approach merits further investigations.

Aim: Five photoactive compounds with variable elongated alkyl-substituents in a phenalen-1-one structure were examined in view of structural similarity to the antimicrobial agent benzalkonium chloride (BAC). Methods: All phenalen-1-ones and BAC were evaluated for their antimicrobial properties against Staphylococcus aureus, methicillin-resistant S. aureus, Escherichia coli, Pseudomonas aeruginosa and for their eukaryotic toxicity against normal human epidermal keratinocyte (NHEK) cells to narrow down the BAC-like effect and the photodynamic effect depending on the chemical structure. All compounds were investigated for effective concentration ranges, where a bacterial reduction of 5 log10 is achieved, while an NHEK survival of 80% is ensured. Results: Effective concentration ranges were found for four out of five photoactive compounds, but not for BAC and the compound with BAC-like alkyl chain length. Conclusion: Chain length size and polar area of the respective head-groups of phenalen-1-one compounds or BAC showed an influence on the incorporation inside lipid membranes and thus, head-groups may have an impact on the toxicity of antimicrobials.

Aim: Resistances to antibiotics employed for treatment of infectious diseases have increased to alarming numbers making it more and more difficult to treat diseases caused by microorganisms resistant to common antibiotics. Consequently, novel methods for successful inactivation of pathogens are required. In this instance, one alternative could be application of light for treatment of topical infections. Antimicrobial properties of UV light are well documented, but due to its DNA-damaging properties use for medical purposes is limited. In contrast, irradiation with visible light may be more promising. Methods: Literature was systematically screened for research concerning inactivation of main oral bacterial species by means of visible light. Results: Inactivation of bacterial species, especially pigmented ones, in planktonic state showed promising results. There is a lack of research examining the situation when organized as biofilms. Conclusion: More research concerning situation in a biofilm state is required.

Fluorescence imaging studies of the processes leading to photodynamic inactivation of bacteria have been limited due to the small size of microorganisms as well as by the faint fluorescence of most photosensitizers. A versatile method based on highly-sensitive fluorescence microscopy is presented which allows to study, in real time, the incorporation of photosensitizers inside S. aureus upon photodynamic action. The method takes advantage of the fluorescence enhancement of phenothiazine and porphyrin photosensitizers upon entering the bacterial cytosol after the cell wall has been compromised. In combination with typical assays, such as the addition of specific enhancers of reactive oxygen species, it is possible to extract mechanistic information about the pathway of photodynamic damage at the single-cell level. Imaging experiments in deuterated buffer strongly support a Type-I mechanism for methylene blue and a very minor role of singlet oxygen.

Two Ru(II) polypyridyl complexes, Ru(DIP)2(bdt) (1) and [Ru(dqpCO2Me)(ptpy)](2+) (2) (DIP = 4,7-diphenyl-1,10-phenanthroline, bdt = 1,2-benzenedithiolate, dqpCO2Me = 4-methylcarboxy-2,6-di(quinolin-8-yl)pyridine), ptpy = 4'-phenyl-2,2':6',2″-terpyridine) have been investigated as photosensitizers (PSs) for photodynamic therapy (PDT). In our experimental settings, the phototoxicity and phototoxic index (PI) of 2 (IC50(light): 25.3 μM, 420 nm, 6.95 J/cm(2); PI4) and particularly of 1 (IC50(light): 0.62 μM, 420 nm, 6.95 J/cm(2); PI: 80) are considerably superior compared to the two clinically approved PSs porfimer sodium and 5-aminolevulinic acid. Cellular uptake and distribution of these complexes was investigated by confocal microscopy (1) and by inductively coupled plasma mass spectrometry (1 and 2). Their phototoxicity was also determined against the Gram-(+) Staphylococcus aureus and Gram-(-) Escherichia coli for potential antimicrobial PDT (aPDT) applications. Both complexes showed significant aPDT activity (420 nm, 8 J/cm(2)) against Gram-(+) (S. aureus;6 log10 CFU reduction) and, for 2, also against Gram-(-) E. coli (4 log10 CFU reduction).

Increasing antibiotic resistances in microorganisms create serious problems in public health. This demands alternative approaches for killing pathogens to supplement standard treatment methods. Photodynamic inactivation of bacteria (PIB) uses light activated photosensitizers (PS) to generate reactive oxygen species immediately upon illumination, inducing lethal phototoxicity. Positively charged phenalen-1-one derivatives are a new generation of PS for light-mediated killing of pathogens with outstanding singlet oxygen quantum yield ΦΔ of97%. Upon irradiation with a standard photopolymerizer light (bluephase C8, 1260 ± 50 mW/cm(2)) the PS showed high activity against the oral key pathogens Enterococcus faecalis, Actinomyces naeslundii, Streptococcus mutans, and Aggregatibacter actinomycetemcomitans. At a concentration of 10 μM, a maximum efficacy of more than 6 log10 steps (≥ 99.9999%) of bacteria killing is reached in less than 1 min (light dose 50 J/cm(2)) after one single treatment. The pyridinium substituent as positively charged moiety is especially advantageous for antimicrobial action.

Surfaces can be coated with photosensitizer molecules, which generate singlet oxygen (1O2) when the surface is exposed to light. 1O2 may diffuse from the coating and has the potential to kill microorganisms present on the surface. In the present study a derivative of the meso-tetraphenylporphyrin (TPP) was immobilized onto polyurethane (PU) after being sprayed and polymerized as a thin layer onto poly-methylmethacrylate (PMMA). PU is gas permeable and thus a sufficient amount of oxygen reaches the photosensitizer in this coating. The surface generation of 1O2 and its diffusion were investigated by detecting its luminescence at 1270 nm and a tri-iodide assay. Antimicrobial photodynamic surface effects were tested on Staphylococcus aureus. The spectrally resolved detection of 1O2 luminescence yielded a clear peak at 1275 nm. The time-resolved luminescence showed multi-exponential decay, revealing rise and decay times in the range of 5–2 × 102 μs. The photodynamic inactivation of S. aureus was monitored at different photosensitizer concentrations and radiant exposures of light. A photodynamic killing of >99.9% (>3log10-steps) was achieved within an irradiation time of 30 min. The photodynamic killing on the bioactive surface confirmed the antimicrobial effect of 1O2 that was generated in the PU-coating and reached the bacteria by diffusion., Open-Access-Komponente aus der Allianzlizenz

Prevention and control of biofilm-growing microorganisms are serious problems in public health due to increasing resistances of some pathogens against antimicrobial drugs and the potential of these microorganisms to cause severe infections in patients. Therefore, alternative approaches that are capable of killing pathogens are needed to supplement standard treatment modalities. One alternative is the photodynamic inactivation of bacteria (PIB). The lethal effect of PIB is based on the principle that visible light activates a photosensitizer, leading to the formation of reactive oxygen species, e.g., singlet oxygen, which induces phototoxicity immediately during illumination. SAPYR is a new generation of photosensitizers. Based on a 7-perinaphthenone structure, it shows a singlet oxygen quantum yield ΦΔ of 99% and is water soluble and photostable. Moreover, it contains a positive charge for good adherence to cell walls of pathogens. In this study, the PIB properties of SAPYR were investigated against monospecies and polyspecies biofilms formed in vitro by oral key pathogens. SAPYR showed a dual mechanism of action against biofilms: (I) it disrupts the structure of the biofilm even without illumination; (II) when irradiated, it inactivates bacteria in a polymicrobial biofilm after one single treatment with an efficacy of ≥99.99%. These results encourage further investigation on the potential of PIB using SAPYR for the treatment of localized infectious diseases.

Aim: Cold atmospheric plasma (CAP) has already proven efficient at disinfection of microorganisms including biofilms. The objective of the present study is to assess the efficacy of CAP against the dermatophytes Trichophyton rubrum and Microsporum canis in vitro. Materials & methods:T. rubrum and M. canis were exposed to CAP for different treatment times and time intervals in vitro. Treatment with ciclopirox olamine or UVC radiation (0.120 J/cm2) served as controls. CAP was generated by the surface microdischarge technology. Fungal colony growth was measured upon CAP treatment. Results: Repeated daily CAP treatments of 10 min demonstrated an inhibition of growth during the treatment period of 9 days. Single CAP treatment sessions for 5, 8 and 10 min, as well as treatments for 5 or 8 min daily, resulted in less fungal growth inhibition. UVC radiation treatment failed, but not ciclopirox olamine. Conclusion: CAP shows promising potential for future application in the treatment of dermatophyte infections.

Cold atmospheric plasma has already been shown to decrease the bacterial load in chronic wounds. However, until now it is not yet known if plasma treatment can also improve wound healing. We aimed to assess the impact of cold atmospheric argon plasma on the process of donor site healing. Forty patients with skin graft donor sites on the upper leg were enrolled in our study. The wound sites were divided into two equally sized areas that were randomly assigned to receive either plasma treatment or placebo (argon gas) for 2 minutes. Donor site healing was evaluated independently by two blinded dermatologists, who compared the wound areas with regard to reepithelialization, blood crusts, fibrin layers, and wound surroundings. From the second treatment day onwards, donor site wound areas treated with plasma (n = 34) showed significantly improved healing compared with placebo-treated areas (day 1, p = 0.25; day 2, p = 0.011; day 3, p < 0.001; day 4, p < 0.001; day 5, p = 0.004; day 6, p = 0.008; day 7, p = 0.031). Positive effects were observed in terms of improved reepithelialization and fewer fibrin layers and blood crusts, whereas wound surroundings were always normal, independent of the type of treatment. Wound infection did not occur in any of the patients, and no relevant side effects were observed. Both types of treatment were well tolerated. The mechanisms contributing to these clinically observed effects should be further investigated.

Background: Antimicrobial photodynamic therapy is an interesting alternative for the treatment of superficial mucocutaneous mycoses. In immunodeficient patients, these infections are frequently recurrent and resistant to the most commonly used antifungal medications. Candida albicans biofilms frequently cause such infections that can even evolve to deep-seated mycoses. Materials & methods: The efficiency of a photodynamic therapy was investigated against C. albicans using a twofold positively charged porphyrin (XF-73) in comparison with the well-known fourfold positively charged porphyrin (5,10,15,20-tetrakis(1-methyl-4-pyridyl)-21H,23H-porphine, tetra-p-tosylate salt). Results: After incubation with 0.5 µM of XF-73 for 15 min and irradiation with blue light (12.1 J/cm2), the viability of C. albicans planktonic cells decreased by over 6 log10. For biofilm cells, a longer incubation time (4 h) with 1 µM of XF-73 and a light dose of 48.2 J/cm2 was necessary to achieve over 5 log10 cell killing. Cell killing was mediated by singlet oxygen that was directly detected via its luminescence at 1270 nm in XF-73-incubated C. albicans biofilms for the first time. Antimicrobial photodynamic therapy yielded better results for XF-73 compared with 5,10,15,20-tetrakis(1-methyl-4-pyridyl)-21H,23H-porphine, tetra-p-tosylate salt when using the same conditions. Conclusion: This study provides evidence that XF-73 is a highly efficient photosensitizer to kill C. albicans and it would be worthwhile to test this photosensitizer in clinical studies for both prophylaxis and treatment of infections caused by this microorganism, preventing the spread of C. albicans throughout the bloodstream.