Evaluation of the ability of a novel miconazole formulation to penetrate nail by using three in vitro nail models

This document is the Accepted Manuscript of the following article: Luisa Christensen, Rob Turner, Sean Weaver, Francesco Caserta, Lisa Long, Mahmoud Ghannoum, and Marc Brown, ‘Evaluation of the Ability of a Novel Miconazole Formulation To Penetrate Nail by Using Three In Vitro Nail Models’, Antimicrobial Agents and Chemotherapy, Vol. 61 (7): e02554-16, July 2017. The final, published version is available online at DOI: https://doi.org/10.1128/AAC.02554-16.In an effort to increase the efficacy of topical medications for treating onychomycosis, several new nail penetration enhancers were recently developed. In this study, the ability of 10% (wt/wt) miconazole nitrate combined with a penetration enhancer formulation to permeate the nail is demonstrated by the use of a selection of in vitro nail penetration assays. These assays included the bovine hoof, TurChub zone of inhibition, and infected-nail models.Peer reviewedFinal Accepted Versio

Principles and Operational Parameters to Optimize Poison Removal with Extracorporeal Treatments

A role for nephrologists in the management of a poisoned patient involves evaluating the indications for, and methods of, enhancing the elimination of a poison. Nephrologists are familiar with the various extracorporeal treatments ( ECTR s) used in the management of impaired kidney function, and their respective advantages and disadvantages. However, these same skills and knowledge may not always be considered, or applicable, when prescribing ECTR for the treatment of a poisoned patient. Maximizing solute elimination is a key aim of such treatments, perhaps more so than in the treatment of uremia, because ECTR has the potential to reverse clinical toxicity and shorten the duration of poisoning. This manuscript reviews the various principles that govern poison elimination by ECTR (diffusion, convection, adsorption, and centrifugation) and how components of the ECTR can be adjusted to maximize clearance. Data supporting these recommendations will be presented, whenever available.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108055/1/sdi12247.pd

Extracorporeal Treatment in Phenytoin Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup

The Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup conducted a systematic literature review using a standardized process to develop evidence-based recommendations on the use of extracorporeal treatment (ECTR) in patients with phenytoin poisoning. The authors reviewed all articles, extracted data, summarized findings, and proposed structured voting statements following a predetermined format. A 2-round modified Delphi method was used to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. 51 articles met the inclusion criteria. Only case reports, case series, and pharmacokinetic studies were identified, yielding a very low quality of evidence. Clinical data from 31 patients and toxicokinetic grading from 46 patients were abstracted. The workgroup concluded that phenytoin is moderately dialyzable (level of evidence = C) despite its high protein binding and made the following recommendations. ECTR would be reasonable in select cases of severe phenytoin poisoning (neutral recommendation, 3D). ECTR is suggested if prolonged coma is present or expected (graded 2D) and it would be reasonable if prolonged incapacitating ataxia is present or expected (graded 3D). If ECTR is used, it should be discontinued when clinical improvement is apparent (graded 1D). The preferred ECTR modality in phenytoin poisoning is intermittent hemodialysis (graded 1D), but hemoperfusion is an acceptable alternative if hemodialysis is not available (graded 1D). In summary, phenytoin appears to be amenable to extracorporeal removal. However, because of the low incidence of irreversible tissue injury or death related to phenytoin poisoning and the relatively limited effect of ECTR on phenytoin removal, the workgroup proposed the use of ECTR only in very select patients with severe phenytoin poisoning

Capric Acid Secreted by S. boulardii Inhibits C. albicans Filamentous Growth, Adhesion and Biofilm Formation

Candidiasis are life-threatening systemic fungal diseases, especially of gastro intestinal track, skin and mucous membranes lining various body cavities like the nostrils, the mouth, the lips, the eyelids, the ears or the genital area. Due to increasing resistance of candidiasis to existing drugs, it is very important to look for new strategies helping the treatment of such fungal diseases. One promising strategy is the use of the probiotic microorganisms, which when administered in adequate amounts confer a health benefit. Such a probiotic microorganism is yeast Saccharomyces boulardii, a close relative of baker yeast. Saccharomyces boulardii cells and their extract affect the virulence factors of the important human fungal pathogen C. albicans, its hyphae formation, adhesion and biofilm development. Extract prepared from S. boulardii culture filtrate was fractionated and GC-MS analysis showed that the active fraction contained, apart from 2-phenylethanol, caproic, caprylic and capric acid whose presence was confirmed by ESI-MS analysis. Biological activity was tested on C. albicans using extract and pure identified compounds. Our study demonstrated that this probiotic yeast secretes into the medium active compounds reducing candidal virulence factors. The chief compound inhibiting filamentous C. albicans growth comparably to S. boulardii extract was capric acid, which is thus responsible for inhibition of hyphae formation. It also reduced candidal adhesion and biofilm formation, though three times less than the extract, which thus contains other factors suppressing C. albicans adherence. The expression profile of selected genes associated with C. albicans virulence by real-time PCR showed a reduced expression of HWP1, INO1 and CSH1 genes in C. albicans cells treated with capric acid and S. boulardii extract. Hence capric acid secreted by S. boulardii is responsible for inhibition of C. albicans filamentation and partially also adhesion and biofilm formation

Gastrointestinal decontamination in the acutely poisoned patient

ObjectiveTo define the role of gastrointestinal (GI) decontamination of the poisoned patient.Data sourcesA computer-based PubMed/MEDLINE search of the literature on GI decontamination in the poisoned patient with cross referencing of sources.Study selection and data extractionClinical, animal and in vitro studies were reviewed for clinical relevance to GI decontamination of the poisoned patient.Data synthesisThe literature suggests that previously, widely used, aggressive approaches including the use of ipecac syrup, gastric lavage, and cathartics are now rarely recommended. Whole bowel irrigation is still often recommended for slow-release drugs, metals, and patients who "pack" or "stuff" foreign bodies filled with drugs of abuse, but with little quality data to support it. Activated charcoal (AC), single or multiple doses, was also a previous mainstay of GI decontamination, but the utility of AC is now recognized to be limited and more time dependent than previously practiced. These recommendations have resulted in several treatment guidelines that are mostly based on retrospective analysis, animal studies or small case series, and rarely based on randomized clinical trials.ConclusionsThe current literature supports limited use of GI decontamination of the poisoned patient

Case reports of extracorporeal treatments in poisoning: historical trends

There are currently limited data on the trends in case reporting of poisoned patients undergoing enhanced elimination with an extracorporeal treatment (ECTR). The present manuscript specifically reviews the longitudinal trends of reports according to technique, poison, and country of publication. To identify case reports of ECTR use in the management of poisoning, multiple databases were searched. There were no limitations on language and year of publication. All case reports describing individual patients undergoing ECTR with the intent of enhancing the elimination of a poison were included in the analysis. Since 1913, 2908 reports were identified. There were an increasing number of published reports with time except for a slight decrease during the 1990s. Hemodialysis was by far the most commonly used ECTR in poisoning, followed by hemoperfusion. The number of reported peritoneal dialyses decreased steadily since 1980s. Methanol, ethylene glycol, lithium, and salicylates remained among the most commonly reported poisons in every decade. The large majority of publications originated from either Europe or North America, and more specifically from the United States, Germany, the United Kingdom, and China. Despite the emerging apparition of new techniques, hemodialysis remains to this day the favoured ECTR in the treatment of poisoned patients

Extracorporeal blood purification for treating acute paraquat poisoning

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of extracorporeal blood purification techniques for treating paraquat poisoning.This project was supported by the UK National Institute for Health Research, through Cochrane Infrastructure funding to the Cochrane Injuries Group