Effects of the Anti-Tumorigenic Agent AT101 on Human Glioblastoma Cells in the Microenvironmental Glioma Stem Cell Niche

Glioblastoma (GBM) is a barely treatable disease due to its profound chemoresistance. A distinct inter- and intratumoral heterogeneity reflected by specialized microenvironmental niches and different tumor cell subpopulations allows GBMs to evade therapy regimens. Thus, there is an urgent need to develop alternative treatment strategies. A promising candidate for the treatment of GBMs is AT101, the R(-) enantiomer of gossypol. The present study evaluates the effects of AT101, alone or in combination with temozolomide (TMZ), in a microenvironmental glioma stem cell niche model of two GBM cell lines (U251MG and U87MG). AT101 was found to induce strong cytotoxic effects on U251MG and U87MG stem-like cells in comparison to the respective native cells. Moreover, a higher sensitivity against treatment with AT101 was observed upon incubation of native cells with a stem-like cell-conditioned medium. This higher sensitivity was reflected by a specific inhibitory influence on the p-p42/44 signaling pathway. Further, the expression of CXCR7 and the interleukin-6 receptor was significantly regulated upon these stimulatory conditions. Since tumor stem-like cells are known to mediate the development of tumor recurrences and were observed to strongly respond to the AT101 treatment, this might represent a promising approach to prevent the development of GBM recurrences.     

Chromium evaporation and oxidation characteristics of alumina-forming austenitic stainless steels for balance of plant applications in solid oxide fuel cells

The chromium (Cr) evaporation behavior of several different types of iron (Fe)-based AFA alloys and benchmark Cr₂O₃-forming Fe-based 310 and Ni-based 625 alloys was investigated for 500 h exposures at 800 °C to 900 °C in air with 10% H₂O. The Cr evaporation rates from alumina-forming austenitic (AFA) alloys were ~5 to 35 times lower than that of the Cr₂O₃-forming alloys depending on alloy and temperature. The Cr evaporation behavior was correlated with extensive characterization of the chemistry and microstructure of the oxide scales, which also revealed a degree of quartz tube Si contamination during the test. Long-term oxidation kinetics were also assessed at 800 to 1000 °C for up to 10,000 h in air with 10% H₂O to provide further guidance for SOFC BOP component alloy selection.     

In vivo evaluation of a mucoadhesive polymeric caplet for intravaginal anti-HIV-1 delivery and development of a molecular mechanistic model for thermochemical characterization

Context and objective: The aim of this study was to develop, characterize and evaluate a mucoadhesive caplet resulting from a polymeric blend (polymeric caplet) for intravaginal anti-HIV-1 delivery.

Materials and methods: Poly(lactic-co-glycolic) acid, ethylcellulose, poly(vinylalcohol), polyacrylic acid and modified polyamide 6, 10 polymers were blended and compressed to a caplet-shaped device, with and without two model drugs 3′-azido-3′-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Thermal analysis, infrared spectroscopy and microscopic analysis were carried out on the caplets employing temperature-modulated DSC (TMDSC), Fourier transform infra-red (FTIR) spectrometer and scanning electron microscope, respectively. In vitro and in vivo drug release analyses as well as the histopathological toxicity studies were carried out on the drug-loaded caplets. Furthermore, molecular mechanics (MM) simulations were carried out on the drug-loaded caplets to corroborate the experimental findings.

Results and discussion: There was a big deviation between the T_g of the polymeric caplet from the T_g's of the constituent polymers indicating a strong interaction between constituent polymers. FTIR spectroscopy confirmed the presence of specific ionic and non-ionic interactions within the caplet. A controlled near zero-order drug release was obtained for AZT (20 d) and PSS (28 d). In vivo results, i.e. the drug concentration in plasma ranged between 0.012–0.332?mg/mL and 0.009–0.256?mg/mL for AZT and PSS over 1–28 d.

Conclusion: The obtained results, which were corroborated by MM simulations, attested that the developed system has the potential for effective delivery of anti-HIV-agents.     

Influence of device engineering on the analog and RF performances of SOI MOSFETs

This work presents a systematic comparative study of the influence of various process options on the analog and RF properties of fully depleted (FD) silicon-on-insulator (SOI), partially depleted (PD) SOI, and bulk MOSFET's with gate lengths down to 0.08 /spl mu/m. We introduce the transconductance-over-drain current ratio and Early voltage as key figures of merits for the analog MOS performance and the gain and the transition and maximum frequencies for RF performances and link them to device engineering. Specifically, we investigate the effects of HALO implantation in FD, PD, and bulk devices, of film thickness in FD, of substrate doping in SOI, and of nonstandard channel engineering (i.e., asymmetric Graded-channel MOSFETs and gate-body contacted DTMOS).     

Foetal alcohol syndrome in Saskatchewan: unchanged incidence in a 20-year period

Ethers and thioethers of monosaccharides have been synthesised which show potent toxicity to mouse (LD50 > or = 4 g.kg-1 O.W. and 0.2 to 1.5 g.kg-1 I.P.W.). A study of calcium antagonist activity for the full series of compounds indicated that the activity was similar for both O- and S- ethers and maximum activities were observed for monoacetoneglucose ethers possessing carbon chain close to 8 carbons.     

Effects of clozapine and haloperidol on baseline levels of vacuous jaw movements in aged rats

BACKGROUND: IgE-mediated hypersensitivity to latex proteins has become a significant clinical problem over the last decade. Nursing and medical staff are at risk because of their occupational exposure to latex. AIMS: To determine the prevalence of type I hypersensitivity to latex allergens in the nursing staff of an Australian hospital. METHODS: A questionnaire which asked about symptoms associated with the use of latex gloves was completed by 140 nurses working in the Alfred Hospital (72 in general medical wards, 68 in intensive care units). Skin prick tests with eluates of five different types of latex glove as well as common aeroallergens (rye pollen and house dust mite) and banana extract were performed. RESULTS: Thirty-one nurses (22%) were skin prick test positive to at least one of the five latex glove eluates. All of these nurses were atopic, having positive skin prick tests to rye pollen or house dust mite. Symptoms of local dryness, itch and erythema associated with glove use were reported by more than half the study group, but not more frequently by those who were skin prick test positive to latex. Urticaria associated with glove use was reported more frequently by those with positive latex skin prick tests (13% vs 4%, p = 0.05). Eighty-seven per cent of the nurses who were latex skin test positive were also positive to banana extract. CONCLUSIONS: IgE-mediated hypersensitivity to latex is common in nurses working in an Australian hospital. Glove associated symptoms were frequently reported, but in most cases the symptoms were more typical of irritant or contact dermatitis rather than type I hypersensitivity reactions. However, the extent of subclinical sensitisation to latex found in this study suggests that symptomatic latex allergy is likely to emerge as an increasing problem for nursing staff in this country.     

Heat transport in dilute mixtures of3He in superfluid4He

We report new measurements of the effective thermal conductivity K_eff and relaxation time τ in dilute mixtures of³He in superfluid⁴He, with molar concentrationsX≤10⁻³. The temperature range extended fromT≈1.4 K toT _λ. Both K_cff and τ are found to agree with theoretical predictions, in contrast to previous experiments where significant differences were observed. A new thermal conductivity cell design was used which almost completely eliminates extraneous volumes and surfaces, and the earlier results are explained in relation to these design changes.