Promoted water transport across graphene oxide-poly(amide) thin film composite membranes and their antibacterial activity

Hybrid composite membranes have great potential for desalination applications since water transport can be favorably promoted by selective diffusion at the interface between matrix and reinforcement materials. In this paper, graphene oxide nano-sheets were successfully incorporated across 200nm thick poly(amide) films by interfacial polymerization to form novel thin-film composite membranes. The impact of the graphene oxide on the morphology, chemistry, and surface charge of the ultra-thin poly(amide) layer, and the ability to desalinate seawater was investigated. The graphene oxide nano-sheets were found to be well dispersed across the composite membranes, leading to a lower membrane surface energy and an enhanced hydrophilicity. The iso-electric point of the samples, key to surface charge repulsion during desalination, was found to be consistently shifted to higher pH values with an increasing graphene oxide content. Compared to a pristine poly(amide) membrane, the pure water flux across the composite membranes with 0.12wt.% of graphene oxide was also found to increase by up to 80% from 0.122 to 0.219L·μm·m-2·h-1·bar-1 without significantly affecting salt selectivity. Furthermore, the inhibitory effects of the composite membrane on microbial growth were evaluated and the novel composite membranes exhibited superior anti-microbial activity and may act as a potential anti-fouling membrane material.

Synthesis and evaluation of cationic norbornanes as peptidomimetic antibacterial agents

A series of structurally amphiphilic biscationic norbornanes have been synthesised as rigidified, low molecular weight peptidomimetics of cationic antimicrobial peptides. A variety of charged hydrophilic functionalities were attached to the norbornane scaffold including aminium, guanidinium, imidazolium and pyridinium moieties. Additionally, a range of hydrophobic groups of differing sizes were incorporated through an acetal linkage. The compounds were evaluated for antibacterial activity against both Gram-negative and Gram-positive bacteria. Activity was observed across the series; the most potent of which exhibited an MIC's ≤ 1 μg mL(-1) against Streptococcus pneumoniae, Enterococcus faecalis and several strains of Staphylococcus aureus, including multi-resistant methicillin resistant (mMRSA), glycopeptide-intermediate (GISA) and vancomycin-intermediate (VISA) S. aureus.

Norbornane-based peptidomimetics as antibacterial agents

 A library of norbornane-based peptide mimetics have been synthesised and shown to exhibit antibacterial activity against a range of troublesome Gram-positive and Gram-negative bacterial pathogens.

Novel feature of nano-titanium dioxide on textiles: antifelting and antibacterial wool

In this study, the antifelting and antibacterial features of wool samples treated with nanoparticles of titanium dioxide (TiO2) were evaluated. To examine the antifelting properties of the treated samples, the fabric shrinkage after washing was determined. The antimicrobial activity was assessed through the calculation of bacterial reduction against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) bacteria. TiO 2 was stabilized on the wool fabric surface by means of carboxylic acids, including citric acid (CA) and butane tetracarboxylic acid (BTCA). Both oxidized samples with potassium permanganate and nonoxidized wool fabrics were used in this study. The relations between both the TiO2 and carboxylic acid concentrations in the impregnated bath and the antifelting and antibacterial properties are discussed. With increasing concentration in the impregnated bath, the amount of TiO2 nanoparticles on the surface of the wool increased; subsequently, lower shrinkage and higher antibacterial properties were obtained. The existence of TiO2 nanoparticles on the surface of the treated samples was proven with scanning electron microscopy images and energy-dispersive spectrometry.

Antibacterial activity of the venom of Heterometrus xanthopus

Heterometrus xanthopus (Scorpion) is one of the most venomous and ancient arthropods. Its venom contains anti-microbial peptides like hadrurin, scorpine, Pandinin 1, and Pandinin 2 that are able to effectively kill multidrug-resistant pathogens. The present study was conducted to evaluate the anti-bacterial activity of H. xanthopus venom. Six Gram-positive and Gram-negative bacterial strains were tested against 1/100, 1/10, and 1/1 fractions of distilled water diluted and crude venom. 1/100 and 1/10 dilutions were not successful in any of the six bacterial strains studied while the 1/1 dilution was effective on Bacillus subtilis ATCC 6633, Salmonella typhimurium ATCC 14028, and Pseudomonas aeruginosa ATCC 27853 with highest zone of inhibition were obtained on B. subtilis. Crude venom was effective against Enterococcus faecalis ATCC 14506, B. subtilis, S. typhimurium, and P. aeruginosa. The most effective results were observed on B. subtilis.

Use of in vitro critical inhibitory concentration, a novel approach to predict in vivo synergistic bactericidal effect of combined amikacin and piperacillin against pseudomonas aeruginosa in a systemic rat infection model

PURPOSE: This study was undertaken to explore the use of in vitro critical inhibitory concentration (CIC) as a surrogate marker relating the pharmacokinetic (PK) parameters to in vivo bactericidal synergistic effect [pharmacodynamic (PD)] of amikacin + piperacillin combination against Pseudomonas aeruginosa in a systemic rat infection model. METHODS: The in vitro antibacterial activities of amikacin and piperacillin, alone and in combinations at various ratios of the concentrations, were tested against a standard [5 x 10(5) colony-forming units (CFU)/ml] and a large (1.5 x 10(8) CFU/ml) inoculum of P. aeruginosa ATCC 9027 using a modified survival-time method. The CIC of each individual antibiotic for the different combinations was determined using a cup-plate method. In vivo studies were performed on Sprague-Dawley rats using a systemic model of infection with P. aeruginosa ATCC 9027. PK profiles and in vivo killing effects of the combination at different dosing ratios were studied. RESULTS: An inoculum effect was observed with the antibiotics studied. Synergy was seen against both the inocula at the following concentration ratios: 70% C(ami) + 30% C(pip) and 75% C(ami) + 25% C(pip), where C(ami) and C(pip) are the concentrations of amikacin and piperacillin to produce a 1000-fold decrease in bacterial population over 5 h, respectively. The CIC values determined corroborated with the order of in vitro bacterial killing observed for the antibiotic combinations. The dosing ratio of 12.6 mg/kg amikacin + 36 mg/kg piperacillin (a 70:30 ratio of the individual doses) exhibited the greatest killing in vivo when compared to the other ratios. The PK-PD relationships were described by simple, linear regression equations using the area under the in vivo killing curve as a PD marker and the AUCIC(ami)/CIC(ami) + AUCIC(pip)/CIC(pip), AUC(ami)/CIC(ami) + AUC(pip)/CIC(pip), C(max,ami)/CIC(ami) + C(max,pip)/CIC(pip), and AUCIC(ami)/MIC(ami) + AUCIC(pip)/MIC(pip) as PK markers for the amikacin + piperacillin combination. CONCLUSION: The combination of amikacin and piperacillin exhibited synergistic killing effect on P. aeruginosa that could be modeled using CIC as a surrogate marker relating the PK parameters to in vivo bactericidal effect.

Drug bioactivation, covalent binding to target proteins and toxicity relevance

A number of therapeutic drugs with different structures and mechanisms of action have been reported to undergo metabolic activation by Phase I or Phase II drug-metabolizing enzymes. The bioactivation gives rise to reactive metabolites/intermediates, which readily confer covalent binding to various target proteins by nucleophilic substitution and/or Schiff's base mechanism. These drugs include analgesics (e.g., acetaminophen), antibacterial agents (e.g., sulfonamides and macrolide antibiotics), anticancer drugs (e.g., irinotecan), antiepileptic drugs (e.g., carbamazepine), anti-HIV agents (e.g., ritonavir), antipsychotics (e.g., clozapine), cardiovascular drugs (e.g., procainamide and hydralazine), immunosupressants (e.g., cyclosporine A), inhalational anesthetics (e.g., halothane), nonsteroidal anti-inflammatory drugs (NSAIDSs) (e.g., diclofenac), and steroids and their receptor modulators (e.g., estrogens and tamoxifen). Some herbal and dietary constituents are also bioactivated to reactive metabolites capable of binding covalently and inactivating cytochrome P450s (CYPs). A number of important target proteins of drugs have been identified by mass spectrometric techniques and proteomic approaches. The covalent binding and formation of drug-protein adducts are generally considered to be related to drug toxicity, and selective protein covalent binding by drug metabolites may lead to selective organ toxicity. However, the mechanisms involved in the protein adduct-induced toxicity are largely undefined, although it has been suggested that drug-protein adducts may cause toxicity either through impairing physiological functions of the modified proteins or through immune-mediated mechanisms. In addition, mechanism-based inhibition of CYPs may result in toxic drug-drug interactions. The clinical consequences of drug bioactivation and covalent binding to proteins are unpredictable, depending on many factors that are associated with the administered drugs and patients. Further studies using proteomic and genomic approaches with high throughput capacity are needed to identify the protein targetsof reactive drug metabolites, and to elucidate the structure-activity relationships of drug's covalent binding to proteins and their clinical outcomes.

Two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for Crohn's disease

Background & Aims: Mycobacterium avium subspecies paratuberculosis has been proposed as a cause of Crohn’s disease. We report a prospective, parallel, placebo-controlled, double-blind, randomized trial of 2 years of clarithromycin, rifabutin, and clofazimine in active Crohn’s disease, with a further year of follow-up. Methods: Two hundred thirteen patients were randomized to clarithromycin 750 mg/day, rifabutin 450 mg/day, clofazimine 50 mg/day or placebo, in addition to a 16-week tapering course of prednisolone. Those in remission (Crohn’s Disease Activity Index ≤150) at week 16 continued their study medications in the maintenance phase of the trial. Primary end points were the proportion of patients experiencing at least 1 relapse at 12, 24, and 36 months. Results: At week 16, there were significantly more subjects in remission in the antibiotic arm (66%) than the placebo arm (50%; P = .02). Of 122 subjects entering the maintenance phase, 39% taking antibiotics experienced at least 1 relapse between weeks 16 and 52, compared with 56% taking placebo (P = .054). At week 104, the figures were 26% and 43%, respectively (P = .14). During the following year, 59% of the antibiotic group and 50% of the placebo group relapsed (P = .54). Conclusions: Using combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for up to 2 years, we did not find evidence of a sustained benefit. This finding does not support a significant role for Mycobacterium avium subspecies paratuberculosis in the pathogenesis of Crohn’s disease in the majority of patients. Short-term improvement was seen when this combination was added to corticosteroids, most likely because of nonspecific antibacterial effects.

Bamboo fibres and their unique properties

This paper collates the different properties of bamboo fibres as claimed by bamboo fibre and product manufacturers. The available information suggests that bamboo fibres have unique properties such as excellent appearance and feel, natural antibacterial, UV-shielding and moisture-controlling characteristics. Hence bamboo fibres provide a very promising alternative to other natural fibres by virtue of their novel properties. However, those properties may largely depend on the manufacturing process, which is not widely disclosed. Moreover, common manufacturing process may require the use of a large amount of chemicals and hence further process development may be required in order to make the product truly eco-friendly. It is identified that the data of those unique properties rarely appear in scientific journals and the validity of those claims can be speculative. Therefore, there is a strong need for non-biased scientific research and evaluation on the unique properties of bamboo fibres.

Lactoferrin and cancer in different cancer models

Lactoferrin (Lf) is a multifunctional protein and an essential element of innate immunity. Cancer is a major killer in today's world accounting for around 13% of all deaths according to the World Health Organisation (W.H.O.). The five most common forms of cancer include lung, colorectal, stomach, liver and breast cancer. Lactoferrin is a natural forming iron-binding glycoprotein with antibacterial, antioxidant and anti-carcinogenic effects. It is produced in exocrine glands and is secreted in many external fluids as a first line of defence. Lactoferrin also has the capacity to induce apoptosis and inhibit proliferation in cancer cells as well as restore white and red blood cell levels after chemotherapy. This review focuses on the therapeutic effect bovine sourced lactoferrin has on various forms of cancer in various models. It also focuses on the benefits of 3D in vitro cell culture. 3D cell culture has vast advantages over 2D models including demonstration of realistic therapeutic results and heightened resistance that 2D models fail to display.

Inter-bonded fibrous matrices for 3D tissue engineering scaffolds

The thesis established a stable three-dimensional fibrous tissue scaffold that has controlled pore structure and inter-bonded fibrous structure, and also examined the effects of the 3D fibrous matrices and functional surfaces including nano-scale topography, bioactive CaP coating and antibacterial treatment on the cell growth behavior for tissue engineering application.

Inter-bonded fibrous matrics for 3D tissue engineering scaffolds

This thesis established a stable three-dimensional fibrous tissue scaffold that has controlled pore structure and inter-bonded fibrous structure, and also examined the effects of the 3D fibrous matrices and functional surfaces including nano-scale topography, bioactive CaP coating and antibacterial treatment on the cell growth begaviour for tissue engineering application.

Drug release rate and anti-microbial effect of controlled-diffusion biopolymer membranes

In this study, a series of fibrous membranes made from cellulose acetate (CA) and polyester urethane (PEU) by co-electrospining or blend-electrospining were evaluated for drug release kinetics, in vitro anti-microbial activity and in vivo would healing performance when used as wound dressings. To stop common clinical infections, an antibacterial agent, Polyhexamethylene Biguanide (PHMB) was incorporated into e-spun fibres. The presence of CA in the wound healing membrane was found to improve hydrophilicity and permeability to air and moisture. The in vivo tests indicated that the addition of PHMB and CA considerably improved the wound healing efficiency. CA fibres became slightly swollen upon contacting with the wound exudates. It can not only speed up the liquid evaporation but also create a moisture environment for wound recovery. The drug release dynamics of membranes was controlled by the structure of membranes and component rations within membranes. The lower ration of CA:PEU retained the sound mechanical properties of membranes, and also reduced the boost release effectively and slowed down diffusion of antibacterial agent during in vitro tests. The controlled-diffusion membranes exert long-term anti-infective effect.

Silkworm silk cocoon structure-property relationship

A collection of images examining the microstructure of raw cocoons. The research investigates how the microstructure varies from one layer to another in the same cocoon and also from one cocoon variety to another. The research is being undertaken to study the structure and property relationships, specifically the antibacterial properties, photodegradability and mechanical strength of different cocoon components - fibre, sericin, and crystals. The aim is to understand the role of different cocoon components and their mechanism of protecting the pupa from extremes of climatic conditions, microorganisms, and other pathogens and predators. Scanning electron microscopy (SEM) and Energy Dispersive Spectroscopy (EDS) were used to analyse the structure of the cocoons, fibre, and sericin.