An ever-increasing demand for novel antimicrobials to treat life-threatening infections caused by the global spread of multidrug-resistant bacterial pathogens stands in stark contrast to the current ...level of investment in their development, particularly in the fields of natural-product-derived and synthetic small molecules. New agents displaying innovative chemistry and modes of action are desperately needed worldwide to tackle the public health menace posed by antimicrobial resistance. Here, our consortium presents a strategic blueprint to substantially improve our ability to discover and develop new antibiotics. We propose both short-term and long-term solutions to overcome the most urgent limitations in the various sectors of research and funding, aiming to bridge the gap between academic, industrial and political stakeholders, and to unite interdisciplinary expertise in order to efficiently fuel the translational pipeline for the benefit of future generations.
•Studies varied considerably in estimating costs involved in diabetic amputation.•Inpatient care costs associated with diabetic amputation were £43.8 million.•Post-amputation care annual expenditure ...was £20.8 million.•Diabetes-related amputations create considerable public health and economic burden.
The main aim of this study was to assess the cost of diabetic amputation (both direct and indirect) to the National Health Service from the point of amputation onwards.
This systematic review involved searches of published literature between January 2007 and March 2017 mainly using the bibliographic databases, the Cochrane Library, EMBASE via Ovid®, MEDLINE via Ovid®, as well as grey literature, both in print and in electronic formats published through non-commercial publications, which reported the cost of amputation due to diabetic foot ulcers.
The studies included in this review varied considerably in estimating the cost including cost elements and how those costs were categorised. The cost estimates for inpatient care associated with amputation involving admissions or procedures on amputation stumps in people with diabetes was £43.8 million. The annual expenditure for post-amputation care involving prosthetic care, physiotherapy, transport and wheelchair use was £20.8 million.
There is a considerable public health and economic burden caused by diabetes-related amputations in England. More focussed research is needed with improved methods of estimating costs that would account for direct and indirect costs associated with diabetic amputation.
This paper presents the work performed to transition a lab-scale synthesis (1 g) to a large-scale (400 g) synthesis of the 3-5-diamino-1H-Pyrazole Disperazol, a new pharmaceutical for treatment of ...antibiotic-resistant Pseudomonas aeruginosa biofilm infections. The potentially hazardous diazotisation step in the lab-scale synthesis was transformed to a safe and easy-to-handle flow chemistry step. Additionally, the paper presents an OSHA-recommended safety assessment of active compound E, as performed by Fauske and Associates, LLC, Burr Ridge, IL, USA.
Short Total Synthesis of Ajoene Silva, Filipa; Khokhar, Shaista S.; Williams, Danielle M. ...
Angewandte Chemie (International ed.),
September 17, 2018, Letnik:
57, Številka:
38
Journal Article
Recenzirano
Odprti dostop
We describe a short total synthesis of ajoene, a major biologically active constituent of garlic. The instability of allicin as the only other known alternative starting material has led to the ...development of a reliable procedure for the synthesis of ajoene from simple building blocks that is also suitable for upscale operations.
Making garlic: An efficient total synthesis of ajoene from easily available starting materials is reported. Upscaling of the procedure enabled the synthesis of ajoene in larger amounts.
The reduction of methane emissions by ruminants is a highly desirable goal to mitigate greenhouse gas emissions. Various feed additives have already been tested for their ability to decrease methane ...production; however, practical use is often limited due to negative effects on rumen fermentation or high costs. Organosulphur compounds from garlic (
Allium sativum
) and flavonoids have been identified as promising plant-derived compounds which are able to reduce methane production. Here, we evaluated the effects of a combination of garlic powder and bitter orange (
Citrus aurantium
) extracts, Mootral, on ruminal methane production, ruminal fermentation and the community of methanogenic
Archaea
by using the rumen simulation technique as
ex vivo
model. The experiment consisted of an equilibration period of 7 days, an experimental period of 8 days and a withdrawal period of 4 days. During the experimental period three fermenters each were either treated as controls (CON), received a low dose of Mootral (LD), a high dose of Mootral (HD), or monensin (MON) as positive control. Application of Mootral strongly reduced the proportion of methane in the fermentation gas and the production rate of methane. Moreover, the experimental mixture induced a dose-dependent increase in the production rate of short chain fatty acids and in the molar proportion of butyrate. Some effects persisted during the withdrawal period. Both, single strand conformation polymorphism and Illumina MiSeq 16S rRNA amplicon sequencing indicated an archaeal community distinct from CON and MON samples in the LD and HD samples. Among archaeal families the percentage of
Methanobacteriaceae
was reduced during application of both doses of Mootral. Moreover, several significant differences were observed on OTU level among treatment groups and after withdrawal of the additives for LD and HD group. At day 14, 4 OTUs were positively correlated with methane production. In conclusion this mixture of garlic and citrus compounds appears to effectively reduce methane production by alteration of the archaeal community without exhibiting negative side effects on rumen fermentation.
Eine kurze Totalsynthese von Ajoen Silva, Filipa; Khokhar, Shaista S.; Williams, Danielle M. ...
Angewandte Chemie,
09/2018, Letnik:
130, Številka:
38
Journal Article
Recenzirano
Abstract
Wir beschreiben eine kurze Totalsynthese von Ajoen, einem wichtigen biologisch aktiven Bestandteil von Knoblauch. Die Instabilität von Allicin, dem einzigen bekannten alternativen ...Ausgangsmaterial, hat zur Entwicklung eines zuverlässigen Protokolls für die Synthese von Ajoen aus einfachen Bausteinen geführt, welches sich auch für größere Mengen eignet.
The ability to measure concentrations of a molecule underpins the building of a comprehensive knowledge of the pharmacokinetics of a pharmaceutical or nutraceutical, which is essential for the ...determination of its safety and efficacy. In this study a sensitive and selective method was developed for the analysis of a natural organic molecule, Compound X, in rat plasma. In this study, a natural organic molecule, Compound X, was investigated for its recovery from rat plasma. This molecule was purified to 99%+ levels for development of a sample preparation and bioanalysis protocol. Compound X is known to bind to haemoglobin and has high potential for protein binding. A bioanalysis method involving reverse-phase UHPLC-DAD-MS was developed to facilitate the quantitative analysis of Compound X. Compound X was spiked into the plasma alone and in combination with the internal standard, Allyl phenyl sulfone. Extraction of Compound X from plasma was achieved through protein precipitation with acetonitrile, collection and reduction of the supernatant, and reconstitution before analysis. Recovery of both Compound X and the internal standard was monitored, along with matrix effects, using the UHPLC-DAD-MS. Recovery of Compound X was achieved with minimal matrix effects allowing quantitative measurements of the molecule extracted from rat plasma. Issues including solubility, stock stability and suitable internal standard were overcome. The developed bioanalysis method was an in–house first and will underpin further development to support preclinical pharmacokinetics and toxicokinetics in efficacy and safety studies, and subsequent clinical studies.
Edible mushrooms constitute an appreciated nutritional source for humans due to their low caloric intake and their high content in carbohydrates, proteins, dietary fibre, phenolic compounds, ...polyunsaturated fatty acids, vitamins and minerals. It has been also demonstrated that mushrooms have health-promoting benefits. Cultivation of mushrooms, especially of the most common species Agaricus bisporus, represents an increasingly important food industry in Europe, but with a direct consequence in the increasing amount of by-products from their industrial production. This review focuses on collecting and critically investigating the current data on the bioactive properties of Agaricus bisporus as well as the recent research for the extraction of valuable functional molecules from this species and its by-products obtained after industrial processing. The state of the art regarding the antimicrobial, antioxidant, anti-allergenic and dietary compounds will be discussed for novel applications such as nutraceuticals, additives for food or cleaning products.
By 2030, 550 million people will have diabetes, of which 25% will go on to develop diabetic leg and foot ulcers. Characterised by persistent, polymicrobial infections and antibiotic resistance, the ...development of new antimicrobials for the treatment of diabetic ulcers is a research area of critical importance. In this study, we examined the antibacterial activity of extracts from two natural products, garlic and sandalwood, tested against a panel of five Gram-positive and Gram-negative diabetic ulcer-associated bacteria. Synergistic combinations of antimicrobials are often used as a method of combating multi-drug resistant infections due to the ability of the individual antimicrobials to exhibit different mechanisms of actions against bacteria. Here we tested the synergistic relationship of garlic and sandalwood extracts using a checkerboard titration method and subsequently completed an assessment for synergy using the fractional inhibitory concentration index (FICI). In vitro, we were able to demonstrate that the selected natural extracts successfully inhibited S. aureus, MRSA, P. aeruginosa, E. faecalis and A. baumannii – a prolific multi-drug resistant bacteria. Furthermore, a synergistic relationship between the two antimicrobials was demonstrated when tested in combination against four of the five bacteria. This includes S. aureus, which has been reported to infect up to 93.5% of diabetic ulcers. These results provide us with novel information on the synergistic antimicrobial relationship of extracts from two well-known natural products – garlic and sandalwood. Additionally, the broad-spectrum antibacterial activity exhibited by the combination of natural extracts presents a great opportunity in the future treatment of diabetic ulcers.
•Garlic bulb storage affects biotechnological quality (alliinase yield and activity).•Garlic bulb storage elicits changes in volatile organic compound (VOC) patterns.•VOC profiles from stored garlic ...are affected by temperature of storage.•Storage temperature has negative effects on bulb alliinase activity and spoilage.•Specific VOCs are identified as potential markers for garlic quality changes over time.
Garlic (Allium sativum L.) has a long history of use as a culinary seasoning and source of health-promoting compounds. In particular organosulphur compounds derived from the action of alliinase on alliin are of interest for their antimicrobial action. Due to the seasonal nature of the garlic harvest, long-term storage is required to ensure year-round supply of high-quality bulbs. However, quality is known to deteriorate throughout storage, and storage regimes are aimed at maintaining culinary, not biochemical quality, posing challenges for biotech firms extracting high value products, such as alliinase, from garlic. Storage typically involves extended periods of up to 9 months at -1.5 °C. Here, quality parameters (disease incidence and moisture content) as well as biotechnological quality parameters (alliinase yield and activity) were measured, and correlated with gene expression and volatile organic compound (VOC) profiles comparing storage at -1.5 °C and 22 °C. The aim is to develop potential molecular markers for garlic quality assessment. Alliinase activity fell in the first 6 months of storage, with garlic stored at -1.5 °C losing more activity, however 22 °C stored garlic suffered higher spoilage after 12 months storage. Alliinase activity loss was not proportional to gene transcript levels, suggesting post-translational control. A total of 150 VOCs were detected across all samples using thermal desorption gas chromatography, time of flight mass spectrometry of intact garlic bulbs, the most abundant of which were organosulphur compounds. Storage temperature significantly affected the whole VOC profile and discrete profiles were detected from garlic cold-stored for different time periods. Using weighted correlation network analysis 17 VOCs were identified that correlated with storage time, six VOCs that were indicative for storage temperature and four VOCs (azulene, octanal, o-Xylene and 4-methylhexadecane) were significantly associated with alliinase activity.
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