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101.
Thierry Simonart 《American journal of clinical dermatology》2013,14(6):429-435
There is a high unmet clinical need for new and better treatments in acne vulgaris. Propionibacterium acnes has a strong proinflammatory activity and targets molecules involved in the innate cutaneous immunity, keratinocytes and sebaceous glands of the pilosebaceous follicle. The role of P. acnes in acne confers legitimacy on the possible benefits of immunization-based approaches, which may represent a solution for limiting the development of antibiotic-resistant P. acnes. Various immunization-based approaches have been developed over the last decades, including killed pathogen-based vaccines, vaccination against cell wall-anchored sialidase, monoclonal antibodies to the Christie, Atkins, Munch-Peterson factor of P. acnes, anti-Toll-like receptors vaccines and natural antimicrobial peptides. This review summarizes the current evidence and explores the challenges to making this a realistic treatment option for the future. 相似文献
102.
Michael B. Harbut Bhumit A. Patel Bryan K. S. Yeung Case W. McNamara A. Taylor Bright Jaime Ballard Frantisek Supek Todd E. Golde Elizabeth A. Winzeler Thierry T. Diagana Doron C. Greenbaum 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(52):21486-21491
Early secretory and endoplasmic reticulum (ER)-localized proteins that are terminally misfolded or misassembled are degraded by a ubiquitin- and proteasome-mediated process known as ER-associated degradation (ERAD). Protozoan pathogens, including the causative agents of malaria, toxoplasmosis, trypanosomiasis, and leishmaniasis, contain a minimal ERAD network relative to higher eukaryotic cells, and, because of this, we observe that the malaria parasite Plasmodium falciparum is highly sensitive to the inhibition of components of this protein quality control system. Inhibitors that specifically target a putative protease component of ERAD, signal peptide peptidase (SPP), have high selectivity and potency for P. falciparum. By using a variety of methodologies, we validate that SPP inhibitors target P. falciparum SPP in parasites, disrupt the protein’s ability to facilitate degradation of unstable proteins, and inhibit its proteolytic activity. These compounds also show low nanomolar activity against liver-stage malaria parasites and are also equipotent against a panel of pathogenic protozoan parasites. Collectively, these data suggest ER quality control as a vulnerability of protozoan parasites, and that SPP inhibition may represent a suitable transmission blocking antimalarial strategy and potential pan-protozoan drug target. 相似文献
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Frédéric Gabriel Ayman Sabra Sofiane El-Kirat-Chatel Sophie Pujol Valérie Fitton-Ouhabi Daniel Brèthes Karine Dementhon Isabelle Accoceberry Thierry No?l 《Antimicrobial agents and chemotherapy》2014,58(8):4476-4485
We characterized two additional membrane transporters (Fur4p and Dal4p) of the nucleobase cation symporter 1 (NCS1) family involved in the uptake transport of pyrimidines and related molecules in the opportunistic pathogenic yeast Candida lusitaniae. Simple and multiple null mutants were constructed by gene deletion and genetic crosses. The function of each transporter was characterized by supplementation experiments, and the kinetic parameters of the uptake transport of uracil were measured using radiolabeled substrate. Fur4p specifically transports uracil and 5-fluorouracil. Dal4p is very close to Fur4p and transports allantoin (glyoxyldiureide). Deletion of the FUR4 gene confers resistance to 5-fluorouracil as well as cross-resistance to triazoles and imidazole antifungals when they are used simultaneously with 5-fluorouracil. However, the nucleobase transporters are not involved in azole uptake. Only fluorinated pyrimidines, not pyrimidines themselves, are able to promote cross-resistance to azoles by both the salvage and the de novo pathway of pyrimidine synthesis. A reinterpretation of the data previously obtained led us to show that subinhibitory doses of 5-fluorocytosine, 5-fluorouracil, and 5-fluorouridine also were able to trigger resistance to fluconazole in susceptible wild-type strains of C. lusitaniae and of different Candida species. Our results suggest that intracellular fluorinated nucleotides play a key role in azole resistance, either by preventing azoles from targeting the lanosterol 14-alpha-demethylase or its catalytic site or by acting as a molecular switch for the triggering of efflux transport. 相似文献
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The tuning of the surface morphology is crucial in the development of superhydrophobic surfaces with various wetting properties. Here, we report the synthesis and electrodeposition of poly(3,4‐ethylenedioxypyrrole) (PEDOP) derivatives containing hydrocarbon chains (ethyl to tetradecyl). Surprisingly, the alkyl chain length has a very important influence on the surface morphology and as a consequence on the water‐repellency properties. The amount of the nanoporosity and the water‐repellency properties can be controlled with alkyl chain length. Moreover, it seems the presence of surface nanoporosity is in correlation with the steric hindrances induced by the alkyl chains during the electrodeposition. This paper uses bioinspired approaches (fluorocarbon free) to reach superhydrophobic surfaces. 相似文献
109.
Thierry Bautrant Michel Grino Corinne Peloso Frédéric Schiettecatte Magali Planelles Charles Oliver Caroline Franqui 《Journal of the American Medical Directors Association》2019,20(3):377-381
Objectives
To determine whether environmental rearrangements of the long-term care nursing home can affect disruptive behavioral and psychological symptoms of dementia (BPSD) in residents with dementia.Design
Prospective 6-month study.Setting
The study was conducted before (phase 1) and after (phase 2) environmental rearrangements [skylike ceiling tiles in part of the shared premises, progressive decrease of the illuminance at night together with soothing streaming music, reinforcement of the illuminance during the day, walls painted in light beige, oversized clocks in corridors, and night team clothes color (dark blue) different from that of the day team (sky blue)].Participants
All of the patients (n = 19) of the protected unit were included in the study. They were aged 65 years or older and had an estimated life expectancy above 3 months.Measures
Number and duration of disruptive BPSD were systematically collected and analyzed over 24 hours or during late hours (6:00-12:00 pm) during each 3-month period.Results
There was no significant change in the patients' dependency, risk of fall, cognitive or depression indexes, or treatment between phase 1 and 2. Agitation/aggression and screaming were observed mainly outside the late hours as opposed to wandering episodes that were noticed essentially within the late hours. The number of patients showing wandering was significantly lower over 24 hours during phase 2. The number of agitation/physical aggression, wandering, and screaming and the mean duration of wandering episodes were significantly (P = .039, .002, .025, and .026 respectively) decreased over 24 hours following environmental rearrangements. Similarly, a significant reduction in the number and mean duration of wandering was noticed during the late hours (P = .031 and .007, respectively).Conclusions
Our study demonstrates that BPSD prevalence can be reduced following plain environmental rearrangements aimed at improving spatial and temporal orientation. 相似文献110.