Evaluation of the efficacy of radiation-modifying compounds using γH2AX as a molecular marker of DNA double-strand breaks

Radiation therapy is a widely used therapeutic approach for cancer. To improve the efficacy of radiotherapy there is an intense interest in combining this modality with two broad classes of compounds, radiosensitizers and radioprotectors. These either enhance tumour-killing efficacy or mitigate damage to surrounding non-malignant tissue, respectively. Radiation exposure often results in the formation of DNA double-strand breaks, which are marked by the induction of H2AX phosphorylation to generate γH2AX. In addition to its essential role in DDR signalling and coordination of double-strand break repair, the ability to visualize and quantitate γH2AX foci using immunofluorescence microscopy techniques enables it to be exploited as an indicator of therapeutic efficacy in a range of cell types and tissues. This review will explore the emerging applicability of γH2AX as a marker for monitoring the effectiveness of radiation-modifying compounds.

Unmodified silver nanoparticles for rapid analysis of the organophosphorus pesticide, dipterex, often found in different waters

A novel, uncomplicated and rapid method of analysis for organophosphorus (OP) pesticides was researched and developed using the important, common OP, dipterex, as a typical example. The basis of the method involved the citrate-capped silver nanoparticles (citrate-capped AgNPs) and Acetylthiocholine (ATCh). The latter compound can be catalyzed by Acetylcholinesterase (AChE) to form thiocholine (TCh), which induces the aggregation of AgNPs. Correspondingly, the color of AgNPs in solution changes from bright yellow to pink, and the UV–vis characteristic absorption peak of AgNPs at about 400 nm decreases; simultaneously, a new absorption band appears at about 520 nm. Irreversible inhibition of AChE activity caused by dipterex, prevents the aggregation of AgNPs. Thus, a UV–vis spectrophotometric method was developed for the analysis of dipterex. The absorbance ratio A396 nm/A520 nm was found to be linearly related to the concentration of dipterex in the range of 0.25–37.5 ng mL−1 with a detection limit of 0.18 ng mL−1. This method was used successfully to analyse dipterex in spiked, different water samples.

Assessment of volatile organic compounds in urban schools

There is an increased concern about airborne particles not only because of their environmental effects, but also due to their potential adverse health effects on humans, especially children. Despite the growing evidence of airborne particles having an impact on children’s health, there have been limited studies investigating the long term health effects as well as the chemical composition of ambient air which further helps in determining their toxicity. Therefore, a systematic study on the chemical composition of air in school environment has been carried out in Brisbane, which is known as “Ultrafine Particles from Traffic Emissions on Children’s Health” (UPTECH). This study is also a part of the larger project focusing on analysis of the chemical composition of ambient air, as well as source apportionment and the quantification of ambient concentrations of organic pollutants in the vicinity of schools. However, this particular paper presents some of the results on concentration of different Volatile Organic Compounds in both indoor and outdoor location from different schools. The database consisted of 750 samples (500 outdoor and 250 indoor) collected for VOCs at 25 different schools. The sampling and analysis were conducted following the standard methods. A total of 90 individual VOCs were identified from the schools studied. Compounds such as toluene, acetic acid, nonanal, benzaldehyde, 2- ethyl 1- hexanol, limonene were the most common in indoors whereas isopentane, toluene, hexane, heptane were dominant in outdoors. The indoor/ outdoor ratio of average sum of VOCs were found to be more than one in most of the schools indicating that there might be additional indoor sources along with the outdoor air in those schools. However, further expansion of the study in relation to source apportionment, correlating with traffic and meteorological data is in progress.

Volatile organic compounds: Characteristics, distribution and sources in urban schools

Long term exposure to organic pollutants, both inside and outside school buildings may affect children’s health and influence their learning performance. Since children spend significant amount of time in school, air quality, especially in classrooms plays a key role in determining the health risks associated with exposure at schools. Within this context, the present study investigated the ambient concentrations of Volatile Organic Compounds (VOCs) in 25 primary schools in Brisbane with the aim to quantify the indoor and outdoor VOCs concentrations, identify VOCs sources and their contribution, and based on these; propose mitigation measures to reduce VOCs exposure in schools. One of the most important findings is the occurrence of indoor sources, indicated by the I/O ratio >1 in 19 schools. Principal Component Analysis with Varimax rotation was used to identify common sources of VOCs and source contribution was calculated using an Absolute Principal Component Scores technique. The result showed that outdoor 47% of VOCs were contributed by petrol vehicle exhaust but the overall cleaning products had the highest contribution of 41% indoors followed by air fresheners and art and craft activities. These findings point to the need for a range of basic precautions during the selection, use and storage of cleaning products and materials to reduce the risk from these sources.

Planar silver nanowire, carbon nanotube and PEDOT:PSS nanocomposite transparent electrodes

Highly conductive, transparent and flexible planar electrodes were fabricated using interwoven silver nanowires and single-walled carbon nanotubes (AgNW:SWCNT) in a PEDOT:PSS matrix via an epoxy transfer method from a silicon template. The planar electrodes achieved a sheet resistance of 6.6 ± 0.0 Ω/squ and an average transmission of 86% between 400 and 800 nm. A high figure of merit of 367 Ω−1 is reported for the electrodes, which is much higher than that measured for indium tin oxide and reported for other AgNW composites. The AgNW:SWCNT:PEDOT:PSS electrode was used to fabricate low temperature (annealing free) devices demonstrating their potential to function with a range of organic semiconducting polymer:fullerene bulk heterojunction blend systems.

Stable organic photovoltaics using Ag thin film anodes

The interaction at the interface between a metal electrode and photoactive polymer is crucial for overall performance and stability of organic photovoltaics (OPVs). In this article, we report a comparative study of the stability of thin film Ag and indium tin oxide (ITO) as electrodes when used in conjunction with an interfacial PEDOT:PSS layer for P3HT:PCBM blend OPV devices. XPS measurements were taken for Ag and ITO/PEDOT:PSS layered samples with different exposure times to ambient conditions (∼25 °C, ∼50% relative humidity) to investigate the migration of Ag and In into the PEDOT:PSS layer. The change in efficiency of OPVs with a longer exposure time and degree of migration is explained by the analysis of XPS results. We propose the mechanism behind the interactions occurring at the interfaces. The efficiency of the ITO electrode OPVs continuously decreased to below 10% of the initial efficiency. However, the Ag devices displayed a slower degradation and maintained 50% of the initial efficiency for the same period of time.

Synthesis and luminescent properties of star-burst D-Pi-A compounds based on 1,3,5-triazine core and carbazole end-capped phenylene ethynylene arms

Two new star-burst compounds based on 1,3,5-triazine core and carbazole end-capped phenylene ethynylene arms (1a and 1b) were synthesized and characterized. Their photophysical properties were investigated systematically via spectroscopic and theoretical methods. Both compounds exhibit strong 1π–π⁎ transitions in the UV region and intense 1π–π⁎/intramolecular charge transfer (1ICT) absorption bands in the UV–vis region. Introducing the carbazole end-capped phenylene ethynylene arm on the 1,3,5-triazine core causes a slight bathochromic shift and enhanced molar extinction coefficient of the 1π–π⁎/1ICT transition band. Both compounds are emissive in solution at room temperature and 77 K, which exhibit pronounced positive solvatochromic effect. The emitting state could be ascribed to 1ICT state in more polar solvent, and 1π–π⁎ state in low-polarity solvent. The high emission quantum yields (Φem=0.90~1.0) of 1a and 1b (in hexane and toluene) make them potential candidates as efficient light-emitting materials. The spectroscopic studies and theoretical calculations indicate that the photophysical properties of these compounds can be tuned by the carbazole end-capped phenylene ethynylene arm, which would also be useful for rational design of photofunctional materials.

Spontaneous generation of optical activity in urea inclusion compounds vis-a-vis current theories

A novel test of recent theories of the origin of optical activity has been designed based on the inclusion of certain alkyl 2-methylhexanoates into urea channels.

Fabrication and evaluation of 1 Ah silver/metal hydride cells

Silver/metal hydride (Ag/MH) cells of about 1 Ah capacity have been fabricated and their discharge characteristics at different rates of discharge, faradaic efficiency, cycle life and a.c. impedance have been evaluated. These cells comprise metal-hydride electrodes prepared by employing similar to 60 mu m powder of an AB(2)-Laves phase alloy of nominal composition Zr0.5Ti0.5V0.6Cr0.2Ni1.2 with PTFE binder on a nickel-mesh substrate as the negative plates and commercial-grade silver electrodes as the positive plates. The cells are positive limited and exhibit two distinct voltage plateaus characteristic of two-step reduction of AgO to Ag during their low rates of discharge between C/20 and C/10. This feature is, however, absent when the cells are discharged at C/5 rate. On charging the cells to 100% of their capacity, the faradaic efficiency is found to be 100%. The impedance of the Ag/MH cell is essentially due to the impedance of the silver electrodes, since MH electrodes offer negligible impedance. The cells may be subjected to a large number of charge-discharge cycles with little deterioration.

Antibacterial Applications of Silver Nanoparticles Synthesized by Aqueous Extract of Azadirachta Indica (Neem) Leaves

Silver nanoparticles are known to have bactericidal effects. A new generation of dressings incorporating antimicrobial agents like silver nanoparticles is being formulated to reduce or prevent infections. The particles can be incorporated in materials and cloth rendering them sterile. Recently, it was found that aqueous silver ions can be reduced by aqueous extract of plant parts to generate extremely stable silver nanoparticles in water. Apart from being environmentally friendly process, use of Neem leaves extract might add synergistic antibacterial effect of Neem leaves to the biosynthesized nanoparticles. With this hypothesis the biosynthetic production of silver nanoparticles by aqueous extract of Neem leaves and its bactericidal effect in cotton cloth against E. Coli were studied in this work. Silver nanoparticles were synthesized by short term (1 day) and long term (21 days) interaction of Neem extract (20% w/v) and 0.01 M AgNO3 solution in 1:4 mixing ratio. The synthesized particles were characterized by UV visible spectroscopy, transmission electron microscopy, and incorporated into cotton disks by (i) centrifuging the disks with liquid broth containing nanoparticles, (ii) in-situ coating process during synthesis, and (iii) coating with dried and purified nanoparticles. The antibacterial property of the nanoparticles coated cotton disks was studied by disk diffusion method. The effect of consecutive washing of the coated disks with distilled water on antibacterial property was also investigated. This work demonstrates the possible use of biologically synthesized silver nanoparticles by its incorporation in cloths leading them to sterilization.

A Synthetic Model for the Inhibition of Glutathione Peroxidase by Antiarthritic Gold Compounds

In this paper, inhibition of the glutathione peroxidase activity of two synthetic organoselenium compounds, bis[2-(N,N-dimethylamino)benzyl]diselenide (5) and bis[2-(N,N-dimethylamino)benzyl]selenide (9), by gold(I) thioglucose (1), chloro(triethylphosphine)gold(I), chloro(trimethylphosphine)gold(I), and chloro(triphenylphosphine)gold(I) is described. The inhibition is found to be competitive with respect to a peroxide (H2O2) substrate and noncompetitive with respect to a thiol (PhSH) cosubstrate. The diselenide 5 reacts with PhSH to produce the corresponding selenol (6), which upon treatment with 1 equiv of gold(I) chlorides produces the corresponding gold selenolate complexes 11−13. However, the addition of 1 equiv of selenol 6 to complexes 11−13 leads to the formation of bis-selenolate complex 14 by ligand displacement reactions involving the elimination of phosphine ligands. The phosphine ligands eliminated from these reactions are further converted to the corresponding phosphine oxides (R3PO) and selenides (R3PSe). In addition to the replacement of the phosphine ligand by selenol 6, an interchange between two different phosphine ligands is also observed. For example, the reaction of complex 11 having a trimethylphosphine ligand with triphenylphosphine produces complex 13 by phosphine interchange reactions via the formation of intermediates 15 and 16. The reactivity of selenol 6 toward gold(I) phosphines is found to be similar to that of selenocysteine.

XANES and EXAFS of copper compounds: Studies of copper carboxylates with metal-metal bonds and of the complex formed byPseudomonas aeruginosa

X-ray absorpion near edge structure (xanes) of copper compounds with copper in 1+, 2+ and 3+ states has been studied. Extended x-ray absorption fine structure (exafs) has been employed to determine bond distances and coordination numbers in several model copper compounds. Employing bothxanes andexafs, the structure of the copper complex formed by the micro-organismPseudomonas aeruginosa has been shown to be square-planar with the Cu-O distance close to that in cupric glucuronates and cupric acetylacetonate.exafs has been shown to be useful for studying metal-metal bonds in copper carboxylates.

Purification of pharmaceuticals and nutraceutical compounds by sub- and supercritical extraction and chromatography

This thesis discusses the use of sub- and supercritical fluids as the medium in extraction and chromatography. Super- and subcritical extraction was used to separate essential oils from herbal plant Angelica archangelica. The effect of extraction parameters was studied and sensory analyses of the extracts were done by an expert panel. The results of the sensory analyses were compared to the analytically determined contents of the extracts. Sub- and supercritical fluid chromatography (SFC) was used to separate and purify high-value pharmaceuticals. Chiral SFC was used to separate the enantiomers of racemic mixtures of pharmaceutical compounds. Very low (cryogenic) temperatures were applied to substantially enhance the separation efficiency of chiral SFC. The thermodynamic aspects affecting the resolving ability of chiral stationary phases are briefly reviewed. The process production rate which is a key factor in industrial chromatography was optimized by empirical multivariate methods. General linear model was used to optimize the separation of omega-3 fatty acid ethyl esters from esterized fish oil by using reversed-phase SFC. Chiral separation of racemic mixtures of guaifenesin and ferulic acid dimer ethyl ester was optimized by using response surface method with three variables per time. It was found that by optimizing four variables (temperature, load, flowate and modifier content) the production rate of the chiral resolution of racemic guaifenesin by cryogenic SFC could be increased severalfold compared to published results of similar application. A novel pressure-compensated design of industrial high pressure chromatographic column was introduced, using the technology developed in building the deep-sea submersibles (Mir 1 and 2). A demonstration SFC plant was built and the immunosuppressant drug cyclosporine A was purified to meet the requirements of US Pharmacopoeia. A smaller semi-pilot size column with similar design was used for cryogenic chiral separation of aromatase inhibitor Finrozole for use in its development phase 2.

Lebanese Plants and Plant-Derived Compounds Against Colon Cancer

Colorectal cancer (CRC) is a major health concern and demands long-term efforts in developing strategies for screening and prevention. CRC has become a preventable disease as a consequence of a better understanding of colorectal carcinogenesis. However, current therapy is unsatisfactory and necessitates the exploration of other approaches for the prevention and treatment of cancer. Plant based products have been recognized as preventive with regard to the development of colon cancer. Therefore, the potential chemopreventive use and mechanism of action of Lebanese natural product were evaluated. Towards this aim the antitumor activity of Onopordum cynarocephalum and Centaurea ainetensis has been studied using in vitro and in vivo models. In vitro, both crude extracts were non cytotoxic to normal intestinal cells and inhibited the proliferation of colon cancer cells in a dose-dependent manner. In vivo, both crude extracts reduced the number of tumors by an average of 65% at weeks 20 (adenomas stage) and 30 (adenocarcinomas stage). The activity of the C. ainetensis extract was attributed to Salograviolide A, a guaianolide-type sesquiterpene lactone, which was isolated and identified through bio-guided fractionation. The mechanism of action of thymoquinone (TQ), the active component of Nigella sativa, was established in colon cancer cells using in vitro models. By the use of N-acetyl cysteine, a radical scavenger, the direct involvement of reactive oxygen species in TQ-induced apoptotic cells was established. The analytical detection of TQ from spiked serum and its protein binding were evaluated. The average recovery of TQ from spiked serum subjected to several extraction procedures was 2.5% proving the inability of conventional methods to analyze TQ from serum. This has been explained by the extensive binding (>98%) of TQ to serum and major serum components such as bovine serum albumin (BSA) and alpha-1-acid glycoprotein (AGP). Using mass spectrometry analysis, TQ was confirmed to bind covalently to the free cysteine in position 34 and 147 of the amino acid sequence of BSA and AGP, respectively. The results of this work put at the disposal for future development new plants with anti-cancer activities and enhance the understanding of the pharmaceutical properties of TQ, a prerequisite for its future clinical development.