Atomic force microscopy study of the antimicrobial activity of aqueous garlic versus ampicillin against Escherichia coli and Staphylococcus aureus

BACKGROUND: In this study the effects of ampicillin and aqueous garlic extract on Escherichia coli (ATCC 9637) and Staphylococcus aureus (ATCC 25923) were compared. Atomic force microscopy (AFM) was used to study the possible mechanisms of membrane disruption. RESULTS: Ampicillin disrupted the cell membrane of E. coli, inducing pores and cell leakage. Aqueous garlic extract also induced leakage from the cell membrane in E. coli, but no pores were observed. The trend in Young's modulus for E. coli was E_native ≈ E_age > E_amp. In contrast, S. aureus incubated with low ampicillin (≤50µg mL^?1) and garlic (≤50 mg mL^?1) concentrations showed no significant changes in surface morphology compared with the untreated bacterium. The trend in Young's modulus for S. aureus was E_native ≈ E_age ≈ E_amp. CONCLUSION: The trend E_native ≈ E_age for E. coli and S. aureus supports the hypothesis that the compounds in garlic show intracellular activity. This proof‐of‐concept study of the aqueous crude isolate of garlic points to the feasibility of further AFM investigations to compare the antimicrobial properties of various pure thiosulfinate isolates found in garlic. Copyright © 2009 Society of Chemical Industry     

In situ degradability of conventional and unconventional starch sources for ruminants,and factors determining their washable fraction: methodological implications

BACKGROUND: The in situ technique (IS) is used for characterising, screening and evaluating feedstuffs in ruminants. However, it is often not adapted to the particular characteristics of feeds (i.e. kinetics of starchy feeds with a standard framework used in forage). This may lead to potential biases in the final conclusions. In two successive experiments, we evaluated the degradative characteristics of conventional (CON) and unconventional (UNC) starchy feedstuffs (ING) and factors affecting their washable fractions (WF). The suitability of IS was then assessed. RESULTS: Two well‐defined ruminal fermentation patterns (CON and UNC) were observed. The WF and insoluble washable (ISWF) fractions were affected by ING, state of presentation [WAY, fresh (F) or pre‐dried (D)], particle size (PSI) and their interactions. The UNC and F feeds had greater WF and ISWF than CON and D, respectively. Increasing PSI linearly reduced WF and its proportion of ISWF. CONCLUSION: The PSI and WAY are critical factors to consider when designing experiments for the evaluation of starchy feedstuffs for ruminants using IS. It is still very risky to propose ‘standard’ parameters as this will always depend on the particular ING evaluated. Conducting pre‐evaluation tests before implementing each research protocol could help to refine the procedure. Copyright © 2009 Society of Chemical Industry     

Influence of dams on river water‐quality signatures at event and seasonal scales: The Sélune River (France) case study

Dams and reservoirs are known to disturb river‐water composition, among other impacts, with potential implications for downstream river ecosystems and water uses. Existing studies have emphasized the variable influence of dams on water composition according to the element, its speciation (dissolved vs. particulate), reservoir properties (residence times), reservoir functions (e.g., hydropower, irrigation), and management (water releases). A now common approach to analyzing hydrological, geochemical, and biological controls on element export from unregulated rivers is to study hydrochemical signatures such as concentration‐flow relationships. We investigated a case study to analyze hydrochemical signatures of a regulated river (Sélune River, western France) upstream and downstream of a chain of two hydropower dams, assuming that the dams disturbed the river's signatures, and that those disturbances would provide information about processes occurring in the reservoirs. Both seasonal and event‐scale signatures were analyzed over two contrasting hydrological years and a range of storm events. The dams induced a chemostatic downstream response to storm events whenever elements were diluted or concentrated upstream. Dams did not disturb the seasonality of major anions but did modify silica and phosphorus concentration‐flow relationships, especially during low flow. Such changes in dynamics of river‐water composition may affect downstream biological communities. This study presents an initial state of the hydrochemical signature of the downstream river, before the removal of the two dams.     

Direct determination of rare earth elements at the subpicogram per gram level in antarctic ice by ICP-SFMS using a desolvation system

A method, based on inductively coupled plasma sector field mass spectrometry coupled with a microflow nebulizer and a desolvation system, has been developed for the direct determination of rare earth elements (REE) (La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu) down to the subpicogram per gram level (1 pg/g = 10(-12) g g(-1)) in approximately 1 mL of molten Antarctic ice. Contamination problems were carefully taken into account by adopting ultraclean procedures during the sample pretreatment phases. The use of a desolvation system for sample introduction during the analysis greatly reduced spectral interferences from oxide formation; the residual interfering contributions were calculated and subtracted whenever necessary. A matched calibration curve method was used for the quantification of the analytes. Instrumental detection limits ranged from 0.001 pg/g for Ho, Tm, and Lu to 0.03 pg/g for Gd. The precision, in terms of relative standard deviation on 10 replicates, ranged from 2% for La, Ce, Pr, and Lu, up to 10% for Er, Tm, and Yb. This methodology allowed the direct determination of REE in a 1-mL sample of ancient Antarctic ice with concentration ranges between 0.006 and 0.4 pg/g for Tm and 0.9-60 pg/g for Ce.     

Soluble CD146 as a Potential Target for Preventing Triple Negative Breast Cancer MDA-MB-231 Cell Growth and Dissemination

Background: Triple Negative Breast Cancers (TNBC) are the most aggressive breast cancers and lead to poor prognoses. This is due to a high resistance to therapies, mainly because of the presence of Cancer Stem Cells (CSCs). Plasticity, a feature of CSCs, is acquired through the Epithelial to Mesenchymal Transition (EMT), a process that has been recently shown to be regulated by a key molecule, CD146. Of interest, CD146 is over-expressed in TNBC. Methods: The MDA-MB-231 TNBC cell line was used as a model to study the role of CD146 and its secreted soluble form (sCD146) in the development and dissemination of TNBC using in vitro and in vivo studies. Results: High expression of CD146 in a majority of MDA-MB-231 cells leads to an increased secretion of sCD146 that up-regulates the expression of EMT and CSC markers on the cells. These effects can be blocked with a specific anti-sCD146 antibody, M2J-1 mAb. M2J-1 mAb was able to reduce tumour development and dissemination in a model of cells xenografted in nude mice and an experimental model of metastasis, respectively, in part through its effects on CSC. Conclusion: We propose that M2J-1 mAb could be used as an additional therapeutic approach to fight TNBC.     

Improving the Utility of a Dynorphin Peptide Analogue Using Mannosylated Glycoliposomes

Peptide therapeutics offer numerous advantages in the treatment of diseases and disorders of the central nervous system (CNS). However, they are not without limitations, especially in terms of their pharmacokinetics where their metabolic lability and low blood–brain barrier penetration hinder their application. Targeted nanoparticle delivery systems are being tapped for their ability to improve the delivery of therapeutics into the brain non-invasively. We have developed a family of mannosylated glycoliposome delivery systems for targeted drug delivery applications. Herein, we demonstrate via in vivo distribution studies the potential of these glycoliposomes to improve the utility of CNS active therapeutics using dynantin, a potent and selective dynorphin peptide analogue antagonist of the kappa opioid receptor (KOR). Glycoliposomal entrapment protected dynantin against known rapid metabolic degradation and ultimately improved brain levels of the peptide by approximately 3–3.5-fold. Moreover, we linked this improved brain delivery with improved KOR antagonist activity by way of an approximately 30–40% positive modulation of striatal dopamine levels 20 min after intranasal administration. Overall, the results clearly highlight the potential of our glycoliposomes as a targeted delivery system for therapeutic agents of the CNS.