Induction of forward mutations at the thymidine kinase locus of mouse lymphoma cells: evidence for electrophilic and non-electrophilic mechanisms

A database of 209 chemicals tested for induction of forward mutations at the heterozygous thymidine kinase (TK +/-) locus in L5178Y mouse lymphoma cells was analyzed for structure-activity relationships using the MultiCASE expert system. Consistent with evidence of several contributing biological mechanisms, these studies suggest that such mutations may occur by more than one mechanism. As might be expected, there was evidence for a component involving direct electrophilic attack on the cellular DNA, in a manner previously established as causative in the induction of mutations in Salmonella. In addition, however, there was also strong evidence for another mechanism or mechanisms involving chromosome missegregation, cellular toxicity or an alternate site of action, such as the microtubules.     

A Holistic Evolutionary and 3D Pharmacophore Modelling Study Provides Insights into the Metabolism,Function, and Substrate Selectivity of the Human Monocarboxylate Transporter 4 (hMCT4)

Monocarboxylate transporters (MCTs) are of great research interest for their role in cancer cell metabolism and their potential ability to transport pharmacologically relevant compounds across the membrane. Each member of the MCT family could potentially provide novel therapeutic approaches to various diseases. The major differences among MCTs are related to each of their specific metabolic roles, their relative substrate and inhibitor affinities, the regulation of their expression, their intracellular localization, and their tissue distribution. MCT4 is the main mediator for the efflux of L-lactate produced in the cell. Thus, MCT4 maintains the glycolytic phenotype of the cancer cell by supplying the molecular resources for tumor cell proliferation and promotes the acidification of the extracellular microenvironment from the co-transport of protons. A promising therapeutic strategy in anti-cancer drug design is the selective inhibition of MCT4 for the glycolytic suppression of solid tumors. A small number of studies indicate molecules for dual inhibition of MCT1 and MCT4; however, no selective inhibitor with high-affinity for MCT4 has been identified. In this study, we attempt to approach the structural characteristics of MCT4 through an in silico pipeline for molecular modelling and pharmacophore elucidation towards the identification of specific inhibitors as a novel anti-cancer strategy.     

Nanogoldpharmaceutics (i) The use of colloidal gold to treat experimentally-induced arthritis in rat models; (ii) Characterization of the gold in Swarna bhasma, a microparticulate used in traditional Indian medicine

Nanosized gold particles (27 +/− 3 nm) have been proven to be effective in ameliorating the symptoms of mycobacterial-, collagen- and pristane-induced arthritis in rat models. This contrasts with the drug sodium aurothiomalate that was only effective against mycobacterial-induced arthritis but not to the same extent as Au⁰. Gold in the traditional Indian Ayurvedic medicine,Swarna bhasma (gold ash), has been characterized as globular particles of gold with an average size of 56–57 nm.     

High resolution XPS characterization of chemical functionalised MWCNTs and SWCNTs

High resolution XPS analysis of chemical functionalised multi-wall carbon nanotubes (MWCNTs) and single wall carbon nanotubes (SWCNT) was done with ESCA300 (overall instrument resolution of 0.35 eV). Information to the degree of functionalisation was ascertained by argon ion bombardment of the samples followed by XPS analysis to detect the functional groups, the percentage atomic concentration of various elements present and whether or not the detected functional groups imposed a chemical shift on the CNT atoms. The results show that true chemical functionalisation was achieved and by argon ion bombardment these functional groups can be altered relative to the C 1s carbon atoms of the CNT. The choice of chemicals used for functionalisation, the techniques employed and the types of nanotubes treated are important factors in chemical characterisation. The carbon atom on the nanotube ring to which the functional group (atom) is bonded, the chirality of the CNT, the electronegativity of the functional group, the bond type and whether the CNT is single-wall or multi-wall, or cut (short) could play a role in determining the chemical shift on the CNTs atoms. These investigations are relevant to chemical functionalisation of carbon nanotubes for various applications for example DNA sensors and other biomedical sensors.     

Oxidative functionalization of carbon nanotubes in atmospheric pressure filamentary dielectric barrier discharge (APDBD)

The surface compositional and any structural changes that occur on carbon nanotubes using air-atmospheric pressure dielectric barrier discharge (APDBD) for functionalization are investigated employing Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), thermal gravimetric analysis (TGA), X-ray diffraction (XRD), and neutron diffraction techniques. Atmospheric pressure plasmas (APP) are suggested to be particularly suitable for functionalization of aligned nanotubes, where wet chemical manipulation could damage or even destroy the highly desirable vertical alignment. In this work a detailed experimental study elucidating the effects of APDBD plasma treatment parameters (e.g. power density, discharge composition, inter-electrode gap and treatment time) on the electronic structure, physical, and chemical behaviour of carbon nanotubes has been conducted. In an atmospheric air we find an optimal oxidative functionalization of CNTs in our DBD system within few seconds (<5 s) at a discharge power of ∼0.5 kW. This investigation may find useful application as functionalization technique for CNT engineered devices and sensors.     

Enhancing self-scheduling algorithms via synchronization and weighting

Existing dynamic self-scheduling algorithms, used to schedule independent tasks on heterogeneous clusters, cannot handle tasks with dependencies because they lack the support for internode communication. To compensate for this deficiency we introduce a synchronization mechanism that provides inter-processor communication, thus, enabling self-scheduling algorithms to handle efficiently nested loops with dependencies. We also present a weighting mechanism that significantly improves the performance of dynamic self-scheduling algorithms. These algorithms divide the total number of tasks into chunks and assign them to processors. The weighting mechanism adapts the chunk sizes to the computing power and current run-queue state of the processors. The synchronization and weighting mechanisms are orthogonal, in the sense that they can simultaneously be applied to loops with dependencies. Thus, they broaden the application spectrum of dynamic self-scheduling algorithms and improve their performance. Extensive testing confirms the efficiency of the synchronization and weighting mechanisms and the significant improvement of the synchronized–weighted versions of the algorithms over the synchronized-only versions.     

Gingival recession and exposure of barrier membrane: effect on guided tissue regeneration of Class II furcation defects

The purpose of the present study was to evaluate the effect of barrier membrane exposure on the success of guided tissue regeneration in Class II furcation defects. Twenty-six subjects with mandibular Class II furcation defects received initial periodontal therapy followed by guided tissue regeneration surgery. The membrane was placed and the flaps were repositioned so that the membrane was totally submerged. Membranes were removed 4 to 6 weeks later, at which time the extent of their exposure was recorded. An overall improvement in all clinical parameters was observed for all subjects 1 year after surgery. Half of the patients had experienced no membrane exposure, while the other 13 subjects had experienced mild to pronounced exposure; both groups showed similar improvement in all clinical and surgical parameters. In light of the comparable results obtained in exposed sites, and the anatomic difficulties sometimes encountered in covering a membrane completely, in some of these cases the membrane may be left only partially submerged. This approach will allow for tighter occlusal "seal" of the tooth-membrane interface and preservation of the keratinized gingiva.     

Stabilization of optical characteristics of DNA cholesteric liquid-crystalline dispersions

Abnormal optical properties of liquid-crystalline dispersions (phases) formed as a result of phase exclusion of double-stranded DNA and RNA from water-salt poly(ethylene glycol) solutions and X-ray parameters of these phases are compared. It is shown that the cholesteric packing of nucleic acid molecules is realized at the certain osmotic pressure of a solvent only. A comparison of the optical properties of liquid-crystalline phases (dispersions) to their X-ray parameters allows one to put forward a suggestion on various hydratation (fluctuation) regimes of the nucleic acid behaviour under the condensed phases formation and factors, influencing the mode of packing of these molecules in phases formed. It is shown as well, that immobilization of DNA cholesteric liquid-crystalline particles in the content of polymeric matrix is accompanied by the stabilization of these particles and, hence, their specific abnormal optical activity as well as by formation of particles having a structure, which corresponds to the "optically isotropic ordered liquid" without abnormal optical activity. Data on stabilization of the cholesteric structure of liquid-crystalline DNA dispersions by creation of polymeric chelate bridges between the neighbouring DNA molecules, fixed in the structure of liquid-crystalline dispersions, are shown.     

Refining the level for anticipated hepatotoxicity in acetaminophen poisoning

Treatment of an acetaminophen overdose with N-acetyl cysteine usually is based on the position of the 4-h acetaminophen (APAP) level on the Rumack-Matthew nomogram; however, there is disagreement on the level at which clinically relevant hepatotoxicity occurs. A retrospective review of all acute adult formulation APAP exposures reported to our poison center between 1986 and 1993 was performed and cases corresponding to the "possible risk or toxicity" range on the nomogram were identified. Our current poison center protocol for APAP poisoning does not recommend treatment with N-acetylcysteine (NAC) in low-risk patients if the 4-h serum APAP level or the extrapolated equivalent falls within the possible toxicity range on the nomogram. Seventeen cases met the inclusion criteria for the study and received no NAC; six additional patients met inclusion criteria but received one or two doses of NAC before therapy was discontinued. No patients in either group demonstrated clinical evidence of hepatotoxicity. This pilot study suggests that patients with no risk factors and APAP levels in the "possible risk" range may not require NAC therapy.     

Experimental and clinical validation of auto- and allodermoplasty using transverse dermal micrografts in deep burns

A new method of autoallodermoplasty is proposed which is as follows: a patient's skin band is cut out 40 times less than the total area of the wound surface. The wound in the donor area is sutured tightly. The skin flap is dissected to thin transverse rectangular pieces with a special microdermatome or with a razor and then they are laid with their lateral side onto the wound and covered with the allo-skin. Experimental and clinical observations have shown that at remote terms both the anatomical and functional restitution of the integument occurred. The method is indicated for huge dermal defects of the "functionally passive" areas in patients with restricted, not big resources of the donor sites, especially in patients with high operative risk.