In vitro Percutaneous Absorption of (14) C-Labeled β-Lactone Promises Topical Delivery of New Bacterial Virulence Inhibitors

Bacterial infections of skin and soft tissue represent a major health threat, especially if they are caused by multidrug-resistant strains such as MRSA. Novel treatment options for topical application are urgently needed, and even if new drug candidates are identified, their properties must match the specific physical requirements of the skin in order to penetrate and reach the site of bacterial infection. β-Lactones have been shown to eliminate bacterial virulence, but knowledge about their potential in topical treatments had thus far been lacking. Herein we present the synthesis and in-depth investigations of skin permeation and skin distribution of a radioactive (14) C-labeled tool compound that was formulated with various basic ointments and applied to pig skin samples. Our results show that skin penetration depends highly on the nature of the formulation base. Vaseline is the most efficient ointment and is best suited for effecting maximal drug delivery within and through the stratum corneum, an important entrance barrier, and meets the required quantities for eliciting anti-virulence effects. We are confident that the nature of these new β-lactone virulence inhibitors confers applicability and potency for topical treatment, and will translate into a new formulation of this highly potent drug candidate for the treatment of skin and soft tissue infections.     

银杏萜内酯的提制及检测

银杏萜内酯由银杏叶，经萃取、吸附和重结晶制成纯品，它的主要成分是银杏内酯A、B、C、M、J和白果内酯。这些化学成分具有抑制血小板活化因子－PAF和对心肌缺血、脑缺血缺氧的保护作用，因而，可作成一种天然的、专一的、特效预防冠心病和脑血拴的保健食品。银杏萜内酯定性用TLC（薄层色谱）检测，定量用HPLC（高压液相色谱）检测，也可以用GC（气相色谱）定性定量分析。     

Fungal metabolism of butter and shea oils by Penicillium roquefortii in solid state cultures

Monoacylglycerols (monoglycerides, MAGs) were produced from butter oil and shea stearin fraction (shea oil) by two strains of Penicillium roquefortii, FRR 2456 (isolated from a spoilt melon) and Wisbey PJ (a commercial dairy strain), at pH 7.0 at 10 and 25 °C. The system was designed as a model of cheese using modified Czapek medium in solid state cultures. Shea oil with its unique fatty acid profile (stearic, oleic and palmitic acids) was used for comparison with butter oil. Yields of MAGs, which ranged from 3 to 14 g kg^?1 oil, were higher with butter than with shea oil and higher when the spoilage strain FRR 2456 was used. Monoacylglycerols produced by mycelium‐bound lipases from both fungal strains were mainly sn‐1(3) or α isomers (60–70 mol%). Monopalmitin was the major MAG produced from both butter and shea oils. The production and use of MAGs alone or in combination with free fatty acids (FFAs) as food preservatives are discussed. It is implied that sn‐1(3) MAGs together with free fatty acids may be part of a natural antimicrobial system in relatively high‐pH foods such as blue mould‐ripened cheese where growth of foodborne pathogens such as Listeria monocytogenes can be a problem. Copyright © 2003 Society of Chemical Industry     

Acyl Homoserine Lactone Production of Brewery Process Surface Bacteria

The aim of this study was to find out whether the first bacterial colonizers of brewery process surfaces after washing produce acyl homoserine lactone (AHL) quorum sensing signalling molecules. Microbial attachment and biofilm formation was studied by mounting sterile uncoated and coated stainless steel coupons onto critical places of the filling machines in three breweries. In the present study 26 previously deposited bacterial strains, as well as approximately 2,300 colonies from 76 process surface samples, were screened using reporter bacteria Chromobacterium violaceum CV026 and Agrobacterium tumefaciens NTLR4. AHL‐producing bacteria were detected both from process samples and among the previous isolates. From the process samples, up to 15% of the screened colonies produced AHL molecules. Production of long chain AHLs was more common than short chain AHLs. The identified AHL‐producing isolates belonged to the genera Pseudomonas, Serratia, Hafnia, Rahnella, Enterobacter and Aeromonas, which all belong to commonly found primary colonizers of brewery process surfaces. The same microbial genera producing AHL molecules were found from different breweries. Brewery filling equipment is susceptible to microbial attachment and accumulation on surfaces. In the future, inhibition of quorum sensing could be one additional way of controlling biofilm formation.     

Structural Elucidation and Biological Activity of Acyl-homoserine Lactones from the Phytopathogen Pantoea ananatis Serrano 1928

In Gram-negative bacteria, the acyl-homoserine lactones (acyl-HSLs) are the main signaling substances employed in cell-to-cell communication systems. This paper describes the chemical characterization of acyl-HSLs produced by the worldwide-spread phytopathogen Pantoea ananatis (Serrano 1928) by using gas chromatography-electron impact mass spectrometry. The absolute configuration of the major identified substance, (S)-(−)-N-hexanoyl-HSL, was determined with gas chromatography-flame ionization detection with a chiral capillary column. Biological activities of extracts, fractions, and synthetic products were evaluated with the specific reporter Agrobacterium tumefaciensNTL4(pZLR4) in β-galactosidase expression assays.     

糖类对内酯豆腐质构的影响

为研究糖类对内酯豆腐的影响,向内酯豆腐中添加不同浓度的葡萄糖、麦芽糊精、可溶性淀粉和卡拉胶,并观察其质构的变化。结果表明,糖的种类和浓度对内酯豆腐的不同质构影响显著:葡萄糖对弹性影响较大,麦芽糊精对内聚性和黏性影响较大,可溶性淀粉对硬度和咀嚼性影响较大,卡拉胶对黏着力影响较大。SPSS主成分分析法研究表明,对内酯豆腐质构综合作用强弱顺序为卡拉胶>可溶性淀粉>葡萄糖>麦芽糊精。糖分子的分子质量、分子结构和表面电荷是影响内酯豆腐质构的重要因素。     

Determination of Chlorogenic Acids with Lactones in Roasted Coffee

An HPLC method has been developed which allowed the determination of mono- and dicaffeoylquinic acids (CQA and di-CQA), corresponding lactones (CQL) and feruloylquinic acids (FQA) in roasted coffee within one chromatographic run. The elution order was verified by isolation of the individual compounds by preparative HPLC, chromatography of the fractions on the analytical HPLC system, NMR spectroscopy and thermospray LC-MS. At least 15 additional minor compounds had the spectra of hydroxycinnamic acids, some of them only occurring in roasted coffee. Caffeoyltryptophan, which has been identified some time ago by another working group could also be separated with this system. The average contents in commercial roasted coffee samples (n=12) were: 3-CQA, 5·0 g kg⁻¹; 4-CQA, 6·2 g kg⁻¹; 5-CQA, 11·4 g kg⁻¹; 4-FQA, 0·7 g kg⁻¹; 5-FQA, 1·4 g kg⁻¹; 3-CQL, 2·1 g kg⁻¹; 4-CQL, 1·0 g kg⁻¹; 3,4-di-CQA, 0·7 g kg⁻¹; 3,5-di-CQA, 0·4 g kg⁻¹ and 4,5-di-CQA, 0·8 g kg⁻¹ dry matter. There were only small differences between the different brands. Two series of samples with different degrees of roast produced from the same green coffee have also been analysed. One series was steam treated before roasting (a process which is commercially used to improve digestibility). Only in the initial stages of roasting (light roast) could a difference in the contents of the acids between both series be observed. Keeping coffee brews at an elevated temperature (4 h at 80°C) reduced the amounts of CQL to 60% of the initial value. The contents of 3-CQA and 4-CQA increased, whilst that of 5-CQA decreased. The overall contents of CQA decreased.     

Bimetallic‐Catalyzed Reduction of Carboxylic Acids and Lactones to Alcohols and Diols

The homogeneously catalyzed reduction of carboxylic acids with hydrogen was studied. Bimetallic catalysts consisting of a group 8 or 9 late transition‐metal and a second group 6 or 7 transition‐metal carbonyl showed a synergistic effect allowing the conversion in good yields under moderate conditions. Besides the effect of different catalyst precursors, the influence of temperature, hydrogen pressure, and catalyst concentration was investigated. An equimolar mixture of [Rh(acac)(CO)₂] and [Mo(CO)₆] showed the highest activity and was therefore applied to the reduction of lactones to diols. The reduction potential of the catalyst was found to be dependent on the ring size of the lactone used. Five‐membered ring lactones were hardly converted to diols whereas six‐ and seven‐ membered ring lactones reacted easily.