Water soluble quinones are a group of cytotoxic anti-bacterial compounds that are secreted by many species of plants, invertebrates, fungi and bacteria. Studies in a number of species have shown the importance of quinones in response to pathogenic bacteria of the genus Pseudomonas. Two electron reduction is an important mechanism of quinone detoxification as it generates the less toxic quinol. In most organisms this reaction is carried out by a group of flavoenzymes known as NAD(P)H quinone oxidoreductases. Azoreductases have previously been separate from this group, however using azoreductases from Pseudomonas aeruginosa we show that they can rapidly reduce quinones. Azoreductases from the same organism are also shown to have distinct substrate specificity profiles allowing them to reduce a wide range of quinones. The azoreductase family is also shown to be more extensive than originally thought, due to the large sequence divergence amongst its members. As both NAD(P)H quinone oxidoreductases and azoreductases have related reaction mechanisms it is proposed that they form an enzyme superfamily. The ubiquitous and diverse nature of azoreductases alongside their broad substrate specificity, indicates they play a wide role in cellular survival under adverse conditions.

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Enteral L-arginine supplementation of 1.5 mmol/kg/d bid can be safely administered in VLBW neonates from the 3rd to the 28th day of life. Enteral L-arginine supplementation appears to reduce the incidence of stage III NEC in VLBW infants. Larger studies are needed to further evaluate the effect of L-arginine supplementation in preventing NEC in VLBW infants.

Resveratrol glucuronides inhibit cell growth by G1 arrest and cyclin D1 depletion, and our results strongly suggest a role for A3 adenosine receptors in this inhibition.

Abstract:Azoreductases are a family of diverse enzymes found in many pathogenic bacteria as well as distant homologues being present in eukarya. In addition to having azoreductase activity these enzymes are also suggested to have NAD(P)H quinone oxidoreductase activity which leads to a proposed role in plant pathogenesis. Azoreductases have also been suggested to play role in the mammalian pathogenesis of Pseudomonas aeruginosa. In view of the importance of P. aeruginosa as a pathogen, we therefore characterised recombinant enzymes following expression of a group of putative azoreductase genes from P. aeruginosa expressed in Escherichia coli. The enzymes include members of the "Arsenic resistance protein H" (ArsH), "tryptophan repressor binding protein A" (WrbA), "modulator of drug activity B" (MdaB) and YieF families. The ArsH, MdaB and YieF family members all show azoreductase and NAD(P)H quinone oxidoreductase activities. In contrast, WrbA is the first enzyme to show NAD(P)H quinone oxidoreductase activity but does not reduce any of the 11 azo compounds tested under a wide range of conditions. These studies will allow further investigation of the possible role of these enzymes in the pathogenesis of P. aeruginosa.

The major impediment to the delivery of therapeutics to the brain is the presence of the blood-brain barrier (BBB). The BBB allows for the entrance of essential nutrients while excluding harmful substances, including most therapeutic agents; hence, brain disorders, especially tumours, are very difficult to treat. Chitosan is a well-researched polymer that offers advantageous biological and chemical properties, such as mucoadhesion and the ease of functionalisation. Chitosan-based nanocarriers (CsNCs) establish ionic interactions with the endothelial cells, facilitating the crossing of drugs through the BBB by adsorptive mediated transcytosis. This process is further enhanced by modifications of the structure of chitosan, owing to the presence of reactive amino and hydroxyl groups. Finally, by permanently binding ligands or molecules, such as antibodies or lipids, CsNCs have showed a boosted passage through the BBB, in both in vivo and in vitro studies which will be discussed in this review.

The full exploration of the 'nutraceuticals' therapeutic potential in cosmetics has been hindered by their poor stratum corneum permeation. Therefore, the aim of the present study was to formulate a nutraceutical; quercetin, in novel vitamin C based nanovesicles (aspasomes), and to explore their beneficial effects in the treatment of acne. Aspasomes were characterized for their particle size, zeta potential, entrapment efficiency (EE%), 3-months storage stability, skin deposition/permeation, antioxidant potential, and morphology. Aspasomes antibacterial efficacy on Propionibacterium acnes using the zone of inhibition assay was also tested, whilst their safety on skin fibroblastic cells was assessed in vitro using 3T3 CCL92 cell lines. An exploratory clinical trial was conducted in acne patients, and the percentage reduction of inflammatory, noninflammatory and total acne lesions was taken as the evaluation criterion. Results revealed that quercetin-loaded aspasomes displayed a desirable nanometer size (125-184 nm), negative charge with good storage stability, and high skin deposition reaching 40%. Aspasomes managed to preserve the antioxidant activity of quercetin, and exhibited a significantly higher antibacterial effect (15 ± 1.53 mm) against Propionibacterium acnes than quercetin alone (8.25 ± 2.08 mm), and were safe on skin fibroblastic cells. Upon clinical examination in 20 acne patients (14 females, 6 males), quercetin aspasomes exhibited reduction percentages of 77.9%, 11.8% and 55.3% for inflammatory lesions, comedones and total lesions respectively. This opens vast applications of the presented formulation in the treatment of other oxidative skin diseases, and delineates the nutraceuticals and nanoformulations prepared from natural materials as promising dermatological treatment modes.

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