In vitro effect of photodynamic therapy with different lights and combined or uncombined with chlorhexidine on Candida spp.

Candidiasis is very common and complicated to treat in some cases due to increased resistance to antifungals. Antimicrobial photodynamic therapy (aPDT) is a promising alternative treatment. It is based on the principle that light of a specific wavelength activates a photosensitizer molecule resulting in the generation of reactive oxygen species that are able to kill pathogens. The aim here is the in vitro photoinactivation of three strains of Candida spp., Candida albicans ATCC 10231, Candida parapsilosis ATCC 22019 and Candida krusei ATCC 6258, using aPDT with different sources of irradiation and the photosensitizer methylene blue (MB), alone or in combination with chlorhexidine (CHX). Irradiation was carried out at a fluence of 18 J/cm2 with a light-emitting diode (LED) lamp emitting in red (625 nm) or a white metal halide lamp (WMH) that emits at broad-spectrum white light (420–700 nm). After the photodynamic treatment, the antimicrobial effect is evaluated by counting colony forming units (CFU). MB-aPDT produces a 6 log10 reduction in the number of CFU/100 μL of Candida spp., and the combination with CHX enhances the effect of photoinactivation (effect achieved with lower concentration of MB). Both lamps have similar efficiencies, but the WMH lamp is slightly more efficient. This work opens the doors to a possible clinical application of the combination for resistant or persistent forms of Candida infections

In vitro effect photodynamic therapy with differents photosensitizers on cariogenic microorganisms

Background: Antimicrobial photodynamic therapy has been proposed as an alternative to suppress subgingival species. This results from the balance among Streptococcus sanguis, Streptococcus mutans and Candida albicans in the dental biofilm. Not all the photosensitizers have the same photodynamic effect against the different microorganims. The objective of this study is to compare in vitro the photodynamic effect of methylene blue (MB), rose Bengal (RB) and curcumin (CUR) in combination with white light on the cariogenic microorganism S. mutans, S. sanguis and C. albicans. Results: Photodynamic therapy with MB, RB and CUR inhibited 6 log 10 the growth of both bacteria but at different concentrations: 0.31-0.62 µg/ml and 0.62-1.25 µg/ml RB were needed to photoinactivate S. mutans and S. sanguis, respectively//1.25-2.5 µg/ml MB for both species//whereas higher CUR concentrations (80-160 µg/ml and 160-320 µg/ml) were required to obtain the same reduction in S. mutans and S. sanguis viability respectively. The minimal fungicidal concentration of MB for 5 log10 CFU reduction (4.5 McFarland) was 80-160 µg/ml, whereas for RB it ranged between 320 and 640 µg/ml. For CUR, even the maximum studied concentration (1280 µg/ml) did not reach that inhibition. Incubation time had no effect in all experiments. Conclusions: Photodynamic therapy with RB, MB and CUR and white light is effective in killing S. mutans and S. sanguis strains, although MB and RB are more efficient than CUR. C. albicans required higher concentrations of all photosensitizers to obtain a fungicidal effect, being MB the most efficient and CUR ineffective

Comparison of Antibacterial Activity and Wound Healing in a Superficial Abrasion Mouse Model of Staphylococcus aureus Skin Infection Using Photodynamic Therapy Based on Methylene Blue or Mupirocin or Both

Background: Antibiotic resistance and impaired wound healing are major concerns in S. aureus superficial skin infections, and new therapies are needed. Antimicrobial photodynamic therapy (aPDT) is a new therapeutic approach for infections, but it also improves healing in many wound models. Objective: To compare the antimicrobial activity and the effects on wound healing of aPDT based on Methylene Blue (MB-aPDT) with mupirocin treatment, either alone or in combination, in superficial skin wounds of S. aureus-infected mice. Additionally, to evaluate the clinical, microbiological, and cosmetic effects on wound healing. Materials and Methods: A superficial skin infection model of S. aureus was established in SKH-1 mice. Infected wounds were treated with MB-aPDT, MB-aPDT with a daily topical mupirocin or only with mupirocin. No treatment was carried out in control animals. Daily clinical and microbiological examinations were performed until complete clinical wound healing. Histopathological studies and statistical analysis were performed at the end of the study. Results: MB-aPDT treatment induced the best wound healing compared to mupirocin alone or to mupirocin plus MB-aPDT. Superficial contraction at 24 h and a greater reduction in size at 48 h, quicker detachment of the crust, less scaling, and absence of scars were observed. Histopathological studies correlated with clinical and gross findings. By contrast, mupirocin showed the highest logaritmic reduction of S. aureus. Conclusions: MB-aPDT and mupirocin treatments are effective in a murine superficial skin infection model of S. aureus. One session of MB-aPDT was the best option for clinical wound healing and cosmetic results. The addition of mupirocin to MB-aPDT treatment improved antimicrobial activity; however, it did not enhance wound healing. No synergistic antibacterial effects were detected. © Copyright © 2021 Pérez, Robres, Moreno, Bolea, Verde, Pérez-Laguna, Aspiroz, Gilaberte and Rezusta

Daylight photodynamic therapy using methylene blue to treat sheep with dermatophytosis caused by Arthroderma vanbreuseghemii

Arthroderma vanbreuseghemii has been identified molecularly as the causative agent of dermatophytosis in a flock of sheep. It is necessary to explore new treatment alternatives because antifungals are not approved for use on small ruminant animals in the European Union. Antimicrobial photodynamic therapy (aPDT) has been shown to be effective for the treatment of dermatophytosis in humans. It is based on the application of a photosensitizer such as methylene blue (MB) that is activated by visible light to generate reactive oxygen species that are cytotoxic to cells. The use of daylight to perform aPDT (aDL-PDT) avoids the requirement of specific equipment because it uses sunlight to activate the photosensitizer. The aim of our study is to determine the efficacy of aDL-PDT using a 1% MB solution to treat dermatophytosis caused by A. vanbreuseghemii in ewes. Two different topical protocols (1% MB solution spray applications once or twice a week) were assayed in two groups of five infected animals. Twenty-five infected sheep were untreated. All the sheep were exposed to sunlight every day for an approximate duration of 10 h for a total of four weeks. At the end of the study, all the animals treated with aDL-PDT showed the same clinical response to both protocols. In contrast, the animals exposed only to sunlight required an additional two to four weeks before their infections resolved. Conclusion: aDL-PDT with 1% MB solution demonstrates efficacy, safety and efficiency in the treatment of dermatophytosis in sheep

Changes in the Viral Distribution Pattern after the Appearance of the Novel Influenza A H1N1 (pH1N1) Virus in Influenza-Like Illness Patients in Peru

Background: We describe the temporal variation in viral agents detected in influenza like illness (ILI) patients before and after the appearance of the ongoing pandemic influenza A (H1N1) (pH1N1) in Peru between 4-January and 13-July 2009. Methods: At the health centers, one oropharyngeal swab was obtained for viral isolation. From epidemiological week (EW) 1 to 18, at the US Naval Medical Research Center Detachment (NMRCD) in Lima, the specimens were inoculated into four cell lines for virus isolation. In addition, from EW 19 to 28, the specimens were also analyzed by real time-polymerase-chainreaction (rRT-PCR). Results: We enrolled 2,872 patients: 1,422 cases before the appearance of the pH1N1 virus, and 1,450 during the pandemic. Non-pH1N1 influenza A virus was the predominant viral strain circulating in Peru through (EW) 18, representing 57.8% of the confirmed cases; however, this predominance shifted to pH1N1 (51.5%) from EW 19–28. During this study period, most of pH1N1 cases were diagnosed in the capital city (Lima) followed by other cities including Cusco and Trujillo. In contrast, novel influenza cases were essentially absent in the tropical rain forest (jungle) cities during our study period. The city of Iquitos (Jungle) had the highest number of influenza B cases and only one pH1N1 case. Conclusions: The viral distribution in Peru changed upon the introduction of the pH1N1 virus compared to previous months. Although influenza A viruses continue to be the predominant viral pathogen, the pH1N1 virus predominated over the other influenza A viruses

Shrike predation on the lizard Mesalina adramitana in Qatar; a review of reported reptile and amphibian prey

We report, for the first time, evidence of predation by a shrike (Lanius sp.) on the lizard Mesalina adramitana. This is the first record of predation by shrikes on lizards in Qatar. Whilst we did not directly observe the event, the presence of shrikes in the area and the method of impalement indicate shrikes as the predator. The lizard was found freshly impaled on a palm tree (Phoenix dactylifera), at 150 cm above ground. Bird species of the genus Lanius are well-known predators of lizards, and in arid environments reptiles are likely common prey for these birds. We provide a review of literature concerning predatory events by shrikes on reptiles and amphibians. We suggest inspection of shrubs for animals impaled by shrikes can improve biodiversity inventories, complementing other commonly used methods

Overexpression of Dyrk1A Is Implicated in Several Cognitive, Electrophysiological and Neuromorphological Alterations Found in a Mouse Model of Down Syndrome

Down syndrome (DS) phenotypes result from the overexpression of several dosage-sensitive genes. The DYRK1A (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A) gene, which has been implicated in the behavioral and neuronal alterations that are characteristic of DS, plays a role in neuronal progenitor proliferation, neuronal differentiation and long-term potentiation (LTP) mechanisms that contribute to the cognitive deficits found in DS. The purpose of this study was to evaluate the effect of Dyrk1A overexpression on the behavioral and cognitive alterations in the Ts65Dn (TS) mouse model, which is the most commonly utilized mouse model of DS, as well as on several neuromorphological and electrophysiological properties proposed to underlie these deficits. In this study, we analyzed the phenotypic differences in the progeny obtained from crosses of TS females and heterozygous Dyrk1A (+/-) male mice. Our results revealed that normalization of the Dyrk1A copy number in TS mice improved working and reference memory based on the Morris water maze and contextual conditioning based on the fear conditioning test and rescued hippocampal LTP. Concomitant with these functional improvements, normalization of the Dyrk1A expression level in TS mice restored the proliferation and differentiation of hippocampal cells in the adult dentate gyrus (DG) and the density of GABAergic and glutamatergic synapse markers in the molecular layer of the hippocampus. However, normalization of the Dyrk1A gene dosage did not affect other structural (e.g., the density of mature hippocampal granule cells, the DG volume and the subgranular zone area) or behavioral (i.e., hyperactivity/attention) alterations found in the TS mouse. These results suggest that Dyrk1A overexpression is involved in some of the cognitive, electrophysiological and neuromorphological alterations, but not in the structural alterations found in DS, and suggest that pharmacological strategies targeting this gene may improve the treatment of DS-associated learning disabilities

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

7th Drug hypersensitivity meeting: part two

No abstract availabl