Devices to fight catheter-related infections

Healthcare-Associated Infections (HAI) affect ~1.7 M people in the USA and 4.1 M in Europe, contributing to 99,000 and 37,000 deaths/year, respectively. Catheter-related infections are the most frequent cause of HAI, leading to life-threatening complications and colossal medical costs. Current prevention/treatment options – sterilization protocols, lock solutions, systemic antibiotic administration – are inefficient and lead to bacterial resistance, a huge threat to public health. This review addresses the existing solutions in the market – mostly catheter caps –, and emerging alternatives, to fight catheter-related infections. Graphene-based biomaterials arise as interesting weapons against these infections, particularly in combination with light: their photothermal and photodynamic properties boost their own antimicrobial action, allowing them to kill bacteria without contributing to bacterial resistance.Healthcare-Associated Infections (HAI) affect ~1.7 M people in the USA and 4.1 M in Europe, contributing to 99,000 and 37,000 deaths/year, respectively. Catheter-related infections are the most frequent cause of HAI, leading to life-threatening complications and colossal medical costs. Current prevention/treatment options – sterilization protocols, lock solutions, systemic antibiotic administration – are inefficient and lead to bacterial resistance, a huge threat to public health. This review addresses the existing solutions in the market – mostly catheter caps –, and emerging alternatives, to fight catheter-related infections. Graphene-based biomaterials arise as interesting weapons against these infections, particularly in combination with light: their photothermal and photodynamic properties boost their own antimicrobial action, allowing them to kill bacteria without contributing to bacterial resistance.Peer Reviewe

Candida tropicalis biofilm and human epithelium invasion is highly influenced by environmental pH

Objective: The main goal of this study was to investigate the role of pH on Candida tropicalis virulence determinants, namely the ability to form biofilms and to colonize/invade reconstituted human vaginal epithelia. Methods: Biofilm formation was evaluated by enumeration of cultivable cells, total biomass quantification and structural analysis by scanning electron microscopy and confocal laser scanning microscopy. Candida tropicalis human vaginal epithelium colonization and invasiveness were examined qualitatively by epifluorescence microscopy and quantitatively by a novel quantitative real-time PCR protocol for Candida quantification in tissues. Results: The results revealed that environmental pH influences C. tropicalis biofilm formation as well as the colonization and potential to invade human epithelium with intensification at neutral and alkaline conditions compared to acidic conditions. Conclusions: For the first time, we have demonstrated that C. tropicalis biofilm formation and invasion is highly influenced by environmental pH.We would like to thank Mrs Lucília Goreti Pinto for processing and sectioning tissue samples. The authors acknowledge Fundação para a Ciência e Tecnologia (FCT), Portugal, for supporting Sonia Silva (SFRH/BPDT/111645/2015). This study was also supported by the Programa Operacional, Fatores de competitividade– COMPETE and by national funds through FCT –Fundação para a Ciência e a Tecnologia on the scope of the projects FCT PTDC/EBB-EBI/120495/2010 and RECI/EBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462).info:eu-repo/semantics/publishedVersio

Screening of the antibacterial activity of phenolic extracts from Portuguese north-eastern plants

Thermal injury, trauma, chronic ulcerations, pressure or venous stasis result in lost of skin integrity allowing the deposition and colonisation of the injury tissue by a wide range of bacteria. Skin and soft tissues infection are typically colonized by staphylococci or streptococci, but virtually any microorganism may induce tissue inflammation and immune response. The severity of the infection may range from self-limit superficial infections to life-threatening diseases. However, the most common treatment for skin and soft tissue infections is antibiotics. However the indiscriminate use of this kind of drugs affects the normal skin flora and may result in multi-resistant strains. In order to overcome this issue it is critical to identify new antimicrobial agents. Nowadays, the synthetic antimicrobial agents have been replaced by natural ones, since these are more friendlly to the user and are more available. Plants are, virtually, inexhaustible sources of biologically-active compounds, responsible for defence mechanisms against microorganisms, insects and herbivores. Therefore, bioactive compounds from plants have been widely used in the food, cosmetic and pharmaceutical industries. Such molecules include polyphenolics, alkaloids and polysaccharides, and they, all, have pharmacological properties, such as anti-inflammatory, antimicrobial and antioxidant properties. Several ethonobotanical surveys conducted in the north-eastern region of Portugal by Ana M. Carvalho sellected some wild plants used on folk pharmacopeia and tradicional cusine as potential antimicrobials. In the present work, a screening of the antibacterial activity against Staphylococcus epidermidis, Staphylococcus aureus and Klebsiella pneumoniae, usually associated with skin infections, was performed using nine phenolic extracts of wild plants and eight coumpounds from selected extracts. The phenolic extracts were characterized by HPLC–DAD-ESI/MS. The antibacterial activity of the extracts and the compounds was assed by the disk difussion assay described on National Committee for Clinical Laboratory Standards (NCCLS), M27-A2 document (NCCLS, 2002), with some modifications and the minimal inhibition concentration (MIC) was obtained by the method described by Wiegand et al, 2008a. The results obtained from the disk diffusion assay allowed the selection of the phenolic extracts with higher activity against the three bacteria strains. The phenolic extracts from the Cistus ladanifer, Castanea sativa, Filipendula ulmaria and Rosa micrantha showed halo formation for all bacteria. Hence, the MIC of these four phenolic extracts was evaluated, the values ranged between 0.313 mg.mL-1of extract (Cistus ladanifer/K. pneumoniae) and 2.5 mg.mL-1 (Filipendula ulmaria/S. epidermidis, K. pneumoniae; Rosa micrantha/ S. epidermidis, K. pneumoniae). Antimicrobial activity of the most important compounds present on the selected extracts was measured by the disk diffusion method. Gallic acid was the compound with the highest activity for all bacteria. Thus, it was used in combination with other compounds in order to predict synergism/antagonism among them. The results showed that the activity of gallic acid was reduced or even annulled by the other compounds used. Moreover, ellagic acid, caffeic acid, gallic acid, kaempferol, rutin, quercetin and chrysin exhibited halo formation at least for one of the bacteria used, thus their MIC was assessed. Gallic acid was the one with the lowest MIC value (9.75, 39 and 19 µg.mL-1 for S.aureus, S. epidermidis and K. pneumoniae, respectively), while ellagic acid had the highest values (>5 mg.mL-1 for all bacteria strains). Overall, the phenolic extract of C. ladanifer, C. sativa, F. ulmaria and R. micrantha inhibit the growth of the most common bacteria found on skin infections and gallic acid was the phenolic compound present in the extracts with higher activity

Development of a new chitosan hydrogel for wound dressing

Wound healing is a complex process involving an integrated response by many different cell types and growth factors in order to achieve rapid restoration of skin architecture and function. The present study evaluated the applicability of a chitosan hydrogel (CH) as a wound dressing. Scanning electron microscopy analysis was used to characterize CH morphology. Fibroblast cells isolated from rat skin were used to assess the cytotoxicity of the hydrogel. CH was able to promote cell adhesion and proliferation. Cell viability studies showed that the hydrogel and its degradation by-products are noncytotoxic. The evaluation of the applicability of CH in the treatment of dermal burns in Wistar rats was performed by induction of full-thickness transcutaneous dermal wounds. Wound healing was monitored through macroscopic and histological analysis. From macroscopic analysis, the wound beds of the animals treated with CH were considerably smaller than those of the controls. Histological analysis revealed lack of a reactive or a granulomatous inflammatory reaction in skin lesions with CH and the absence of pathological abnormalities in the organs obtained by necropsy, which supported the local and systemic histocompatibility of the biomaterial. The present results suggest that this biomaterial may aid the re-establishment of skin architecture

A Pyranoxanthone as a potent antimitotic and sensitizer of cancer cells to low doses of Paclitaxel

Microtubule-targeting agents (MTAs) remain a gold standard for the treatment of several cancer types. By interfering with microtubules dynamic, MTAs induce a mitotic arrest followed by cell death. This antimitotic activity of MTAs is dependent on the spindle assembly checkpoint (SAC), which monitors the integrity of the mitotic spindle and proper chromosome attachments to microtubules in order to ensure accurate chromosome segregation and timely anaphase onset. However, the cytotoxic activity of MTAs is restrained by drug resistance and/or toxicities, and had motivated the search for new compounds and/or alternative therapeutic strategies. Here, we describe the synthesis and mechanism of action of the xanthone derivative pyranoxanthone 2 that exhibits a potent anti-growth activity against cancer cells. We found that cancer cells treated with the pyranoxanthone 2 exhibited persistent defects in chromosome congression during mitosis that were not corrected over time, which induced a prolonged SAC-dependent mitotic arrest followed by massive apoptosis. Importantly, pyranoxanthone 2 was able to potentiate apoptosis of cancer cells treated with nanomolar concentrations of paclitaxel. Our data identified the potential of the pyranoxanthone 2 as a new potent antimitotic with promising antitumor potential, either alone or in combination regimens.Portugal 2020: PTDC/SAU-PUB/28736/2017 (POCI-01-0145-FEDER-028736; FCT: SFRH/BD/116167/2016/ SFRH/BD/140844/2018/ PD/00016/2012info:eu-repo/semantics/publishedVersio

In Vitro

Stryphnodendron species, popularly named “barbatimão,” are traditionally used in Brazil as anti-inflammatory agents. This study aimed to investigate the effect of barbatimão and 11 other species on the production of tumor necrosis factor-alpha (TNF-α) in lipopolysaccharide- (LPS-) stimulated THP-1 cells, as well as their anti-arthritis activity. The extracts of Stryphnodendron adstringens, Stryphnodendron obovatum, Campomanesia lineatifolia, and Terminalia glabrescens promoted a concentration-dependent inhibition of TNF-α. Mice injected with LPS in the knee joint were treated per os with fractions from the selected extracts. Both the organic (SAO) and the aqueous (SAA) fractions of S. adstringens promoted a dose-dependent reduction of leukocyte migration and neutrophil accumulation into the joint, but none of them reduced CXCL1 concentration in the periarticular tissue. In contrast, treatment with C. lineatifolia and T. glabrescens fractions did not ameliorate the inflammatory parameters. Analyses of SAO by Ultra Performance Liquid Chromatography (UPLC) coupled to electrospray ionization mass spectrometry (ESI-MS) led to the identification of gallic acid along with 11 prodelphinidins, characterized as monomers and dimers of the B-type. Our findings contribute to some extent to corroborating the traditional use of S. adstringens as an anti-inflammatory agent. This activity is probably related to a decrease of leukocyte migration into the inflammatory site. Polyphenols like gallic acid and prodelphinidins, identified in the active fraction, may contribute to the observed activity

SARS-CoV-2 introductions and early dynamics of the epidemic in Portugal

Genomic surveillance of SARS-CoV-2 in Portugal was rapidly implemented by the National Institute of Health in the early stages of the COVID-19 epidemic, in collaboration with more than 50 laboratories distributed nationwide. Methods By applying recent phylodynamic models that allow integration of individual-based travel history, we reconstructed and characterized the spatio-temporal dynamics of SARSCoV-2 introductions and early dissemination in Portugal. Results We detected at least 277 independent SARS-CoV-2 introductions, mostly from European countries (namely the United Kingdom, Spain, France, Italy, and Switzerland), which were consistent with the countries with the highest connectivity with Portugal. Although most introductions were estimated to have occurred during early March 2020, it is likely that SARS-CoV-2 was silently circulating in Portugal throughout February, before the first cases were confirmed. Conclusions Here we conclude that the earlier implementation of measures could have minimized the number of introductions and subsequent virus expansion in Portugal. This study lays the foundation for genomic epidemiology of SARS-CoV-2 in Portugal, and highlights the need for systematic and geographically-representative genomic surveillance.We gratefully acknowledge to Sara Hill and Nuno Faria (University of Oxford) and Joshua Quick and Nick Loman (University of Birmingham) for kindly providing us with the initial sets of Artic Network primers for NGS; Rafael Mamede (MRamirez team, IMM, Lisbon) for developing and sharing a bioinformatics script for sequence curation (https://github.com/rfm-targa/BioinfUtils); Philippe Lemey (KU Leuven) for providing guidance on the implementation of the phylodynamic models; Joshua L. Cherry (National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health) for providing guidance with the subsampling strategies; and all authors, originating and submitting laboratories who have contributed genome data on GISAID (https://www.gisaid.org/) on which part of this research is based. The opinions expressed in this article are those of the authors and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. This study is co-funded by Fundação para a Ciência e Tecnologia and Agência de Investigação Clínica e Inovação Biomédica (234_596874175) on behalf of the Research 4 COVID-19 call. Some infrastructural resources used in this study come from the GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by Fundação para a Ciência e a Tecnologia (FCT).info:eu-repo/semantics/publishedVersio