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51.
Federica Cruciani Elena Biagi Marco Severgnini Clarissa Consolandi Fiorella Calanni Gilbert Donders Patrizia Brigidi Beatrice Vitali 《Antimicrobial agents and chemotherapy》2015,59(5):2825-2834
The healthy vaginal microbiota is generally dominated by lactobacilli that confer antimicrobial protection and play a crucial role in health. Bacterial vaginosis (BV) is the most prevalent lower genital tract infection in women in reproductive age and is characterized by a shift in the relative abundances of Lactobacillus spp. to a greater abundance of strictly anaerobic bacteria. In this study, we designed a new phylogenetic microarray-based tool (VaginArray) that includes 17 probe sets specific for the most representative bacterial groups of the human vaginal ecosystem. This tool was implemented using the ligase detection reaction-universal array (LDR-UA) approach. The entire probe set properly recognized the specific targets and showed an overall sensitivity of 6 to 12 ng per probe. The VaginArray was applied to assess the efficacy of rifaximin vaginal tablets for the treatment of BV, analyzing the vaginal bacterial communities of 22 BV-affected women treated with rifaximin vaginal tablets at a dosage of 25 mg/day for 5 days. Our results showed the ability of rifaximin to reduce the growth of various BV-related bacteria (Atopobium vaginae, Prevotella, Megasphaera, Mobiluncus, and Sneathia spp.), with the highest antibiotic susceptibility for A. vaginae and Sneathia spp. Moreover, we observed an increase of Lactobacillus crispatus levels in the subset of women who maintained remission after 1 month of therapy, opening new perspectives for the treatment of BV. 相似文献
52.
Christopher A. Rice Beatrice L. Colon Mehmet Alp Hakan G?ker David W. Boykin Dennis E. Kyle 《Antimicrobial agents and chemotherapy》2015,59(4):2037-2044
Naegleria fowleri is a pathogenic free-living amoeba (FLA) that causes an acute fatal disease known as primary amoebic meningoencephalitis (PAM). The major problem for infections with any pathogenic FLA is a lack of effective therapeutics, since PAM has a case mortality rate approaching 99%. Clearly, new drugs that are potent and have rapid onset of action are needed to enhance the treatment regimens for PAM. Diamidines have demonstrated potency against multiple pathogens, including FLA, and are known to cross the blood-brain barrier to cure other protozoan diseases of the central nervous system. Therefore, amidino derivatives serve as an important chemotype for discovery of new drugs. In this study, we validated two new in vitro assays suitable for medium- or high-throughput drug discovery and used these for N. fowleri. We next screened over 150 amidino derivatives of multiple structural classes and identified two hit series with nM potency that are suitable for further lead optimization as new drugs for this neglected disease. These include both mono- and diamidino derivatives, with the most potent compound (DB173) having a 50% inhibitory concentration (IC50) of 177 nM. Similarly, we identified 10 additional analogues with IC50s of <1 μM, with many of these having reasonable selectivity indices. The most potent hits were >500 times more potent than pentamidine. In summary, the mono- and diamidino derivatives offer potential for lead optimization to develop new drugs to treat central nervous system infections with N. fowleri. 相似文献
53.
Paolo Spirito Camillo Autore Francesco Formisano Gabriele Egidy Assenza Elena Biagini Tammy S. Haas Sergio Bongioanni Christopher Semsarian Emmanuela Devoto Beatrice Musumeci Francesco Lai Laura Yeates Maria Rosa Conte Claudio Rapezzi Luca Boni Barry J. Maron 《The American journal of cardiology》2014
54.
Elena Biagini Iacopo Olivotto Maria Iascone Maria I. Parodi Francesca Girolami Giulia Frisso Camillo Autore Giuseppe Limongelli Massimiliano Cecconi Barry J. Maron Martin S. Maron Stefania Rosmini Francesco Formisano Beatrice Musumeci Franco Cecchi Attilio Iacovoni Tammy S. Haas Maria L. Bacchi Reggiani Paolo Ferrazzi Francesco Salvatore Paolo Spirito Claudio Rapezzi 《The American journal of cardiology》2014
55.
Recent studies on histamine receptor (HR) subtypes identified imidazolyl butyl cyanoguanidines, like UR‐PI376, as highly potent agonists at the human histamine H4 receptor (hH4R). While imidazole‐containing compounds display drawbacks in pharmacokinetics, we studied the possibility of replacing the heteroaromatic cycle by nonaromatic six‐membered heterocycles (piperidine, morpholine, thiomorpholine, and N‐methylpiperazine) as potential bioisosteres. Beyond that, this approach should give more information about the indispensability of the aromatic ring as a basic head group. Besides these changes, a variation of the spacer length (C3–C5) connecting the heterocycle and the cyanoguanidine moiety has been made to possibly trigger the selectivity towards the respective HRs. Investigations in radioligand‐binding assays exhibited only very weak activity at the hH1R and hH3R, while nearly all compounds were inactive at the hH2R and hH4R. In the case of piperidine‐containing compounds, moderate affinities at the hH3R over the single‐digit micromolar range were detected. 相似文献
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59.
Passman RS Bennett CL Purpura JM Kapur R Johnson LN Raisch DW West DP Edwards BJ Belknap SM Liebling DB Fisher MJ Samaras AT Jones LG Tulas KM McKoy JM 《The American journal of medicine》2012,125(5):447-453
Although amiodarone is the most commonly prescribed anti-arrhythmic drug, its use is limited by serious toxicities, including optic neuropathy. Current reports of amiodarone-associated optic neuropathy identified from the Food and Drug Administration's Adverse Event Reporting System and published case reports were reviewed. A total of 296 reports were identified: 214 from the Adverse Event Reporting System, 59 from published case reports, and 23 from adverse events reports for patients enrolled in clinical trials. Mean duration of amiodarone therapy before vision loss was 9 months (range 1-84 months). Insidious onset of amiodarone-associated optic neuropathy (44%) was the most common presentation, and nearly one third were asymptomatic. Optic disk edema was present in 85% of cases. Following drug cessation, 58% had improved visual acuity, 21% were unchanged, and 21% had further decreased visual acuity. Legal blindness (<20/200) was noted in at least one eye in 20% of cases. Close ophthalmologic surveillance of patients during the tenure of amiodarone administration is warranted. 相似文献
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