48 research outputs found

    Teaching women’s health skills: Confidence, attitudes, and practice patterns of academic generalist physicians

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    This study assesses the readiness of academic general internists to perform and precept a commonly utilized women's health examination, and procedural and management skills

    Complication rates for a telephone-based anticoagulation service

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    Antimicrobial Peptides and Acanthamoeba: Peptide expression and anti-amoebicidal activity via time-lapse imaging

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    Purpose: A prototype of an atmospheric pressure cold plasma (APCP) source has been developed for the treatment of corneal infections and for ocular surface sterilization. Two minutes of APCP treatment was previously found effective against various microorganisms but caused, in corneal fibroblast cultures, transitory ROS formation, expression of the ogg1 marker of oxidative damage and increase of apoptosis. In the present study we investigated the transcriptome changes of whole human cornea (HC) ex vivo exposed to the disinfectant dose of APCP. Methods: The effects of exposure to APCP for 2 min on HC, in the absence or presence of the antioxidant N-acetyl L-cysteine (NAC) and related to unexposed controls were assessed at 6 h post-treatment by histological and immunohistochemical analysis, Western blotting and Illlumina RNA sequencing (RNA-seq). Additional HC were subsequently exposed to APCP in the same conditions to measure the expression

    Esc1-21 a Novel Antimicrobial Peptide for Microbial Keratitis

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    Purpose: To investigate the antimicrobial efficacy of a novel amphibian antimicrobial peptide, Esculentin1-21 (Esc1-21), in vitro and in a murine model of Pseudomonas aeruginosa (PA) keratitis. Methods: Standard cfu assays were used to determine the MIC of Esc1-21 against PA strains ATCC 27853 and 19660. The effects of physiological salt concentrations and tears (basal and reflex) on antipseudomonal activity were also tested. MTT assays were performed to determine if Esc1-21 was toxic to a human corneal epithelial cell line (HCEC). For in vivo studies corneas of C57BL/6 mice were scratched; then 105-106 cfu PA ATCC19660 applied topically. Esc1-21 (40 μM) or PBS was applied topically three times/day for up to 5 days (pi) post-infection. At 1, 3 and 5 days pi, severity of infection was graded by slit-lamp, neutrophil infiltration was assessed by MPO assay and viable bacterial counts were determined. Results: The MIC for Esc1-21 was 4 μM and 32 μM for ATCC 27853 and 19660 (n=3) respectiv

    A frog skin-derived antimicrobial peptide against Pseudomonas aeruginosa-induced infections

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    P. aeruginosa is the most prevalent bacterium causing mucosal surface infections such as those found in the lungs of cystic fibrosis sufferers or associated with contact lens wear resulting in bacterial keratitis [1]. The growing emergence of multidrug-resistant strains calls for the discovery of new antibiotics with new modes of action. Naturally occurring antimicrobial peptides (AMPs) hold promise as new therapeutics [2]. They are produced by almost all forms of life as key components of the innate immune response [3]. Unlike conventional antibiotics, most AMPs interact with and increase the permeability of the microbial membrane as part of their killing mechanism [4]. Amphibian skin secretions are one of the richest sources for AMPs, which are synthesized and stored within granules of holocrine-type serous glands and released upon stimulation [6-8]. Here we investigated the anti-Pseudomonal efficacy of a frog skin-derived AMP, Esculentin(1-21) [Esc(1-21)], in vitro and in mouse models of lung/ocular Pseudomonas infections [5]. Our results revealed that Esc(1-21) has (i) a rapid anti-Pseudomonal activity against both free-living and biofilm forms of this pathogen, with a membrane-perturbing activity as a plausible mode of action. This limits the emergence of resistance; (ii) the capability to preserve its bactericidal activity under physiological conditions that better mimic the lung/ocular surface milieu (i.e. in the presence of high salt concentration and/or tears); (iii) the ability to neutralize the toxic effect of bacterial lipopolysaccharide and (iv) the ability to induce migration of epithelial cells in a wound healing assay. Regarding in vivo studies, Esc(1-21) has been found to promote survival in mouse models of P. aeruginosa-induced pulmonary infections by reducing the number of colony counts within the lungs, after a single intratracheal administration. In addition, it has been shown to significantly reduce the level of ocular infection in murine models of P. aeruginosa keratitis, upon topical treatment, three times/day for up to 5 days post-infection and to reduce the amount of viable bacterial cells and neutrophil infiltration within the cornea, compared to PBS treated animals. Overall, Esc(1-21) has great potential for development as a novel pharmaceutical for the treatment of Pseudomonas-induced pneumonia or keratitis upon local application to the site of infection. 1. Kolar SS and McDermott AM. Cell Mol Life Sci (2011); 68:2201-13 2. Mookherjee, N., and Hancock, R. E. Cell Mol Life Sci(2007); 64, 922-933 3. Boman H.G. Annu. Rev. Immunol. (1995); 13:61-92. 4.Shai, Y. Biochim. Biophys. Acta(1999); 1462, 55–70 5. Luca V et al. Cell Mol Life Sci(2013); 70:2773-8
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