The switch mechanism of the cell death mode from apoptosis to necrosis in menadione-treated human osteosarcoma cell line 143B cells

Time-dependent changes in the cell death mode from apoptosis to necrosis were studied in cultured 143B cells treated with menadione, an anti-cancerous drug, excluding a possible involvement of "secondary necrosis." The population of apoptotic cells judged by FITC-Annexin V and propidium iodide (PI) double staining reached its maximum at 6 hours after 100 microM menadione treatment followed by an abrupt decrease thereafter, while that of necrotic cells continuously increased reaching 90% at 24 hours. Electron microscopically, cells attached to the culture dish at 6 hours after the treatment consisted of two different types of cells: cells with typical apoptotic features occupying the major population and those with condensed nuclei and swollen cytoplasm. Cells attached to the culture dish at 8 hours after the treatment consisted exclusively of those with condensed nuclei and swollen cytoplasm. Mitochondria in these cells showed various structural changes: those swollen to various degrees with deposition of flocculent densities, or those with highly condensed matrix. Distinct decreases both in intracellular levels of ATP and caspase-3-like activities and remarkable elevations of intracellular levels of superoxide, which were partly suppressed by NAD(P)H oxidase inhibitors, occurred at 6 hours after the treatment. These results may suggest that distinct increases of the intracellular level of superoxide derived from plasma membrane NAD(P)H oxidase besides that from mitochondria have triggered the transition of cell death mode from apoptosis to necrosis. Transition of highly condensed mitochondria to extremely swollen ones may reflect necrotic processes in menadione-treated cells. The present study strongly suggests that time-dependent study is essential using the electron microscopic technique to analyze detailed processes in the changes of the cell death mode.     

Ultrastructural basis for the transition of cell death mode from apoptosis to necrosis in menadione-treated osteosarcoma 143B cells

Time-dependent ultrastructural changes of menadione-treated human osteosarcoma 143B cells were correlated with those in their stainability to Annexin V and propidium iodide (PI). Populations of both apoptotic (Annexin V(+)/PI(-)) and necrotic (Annexin V(+)/PI(+)) cells, judged by flow cytometry, began to increase at 2 h after menadione treatment. The former reached a maximum at 6 h followed by abrupt decreases thereafter, while the latter continued to increase. Electron microscopically, cells obtained at 6 h after the menadione treatment consisted of mixed populations of cells with typical apoptotic features and those with a mixture of apoptotic and necrotic features, while cells obtained at 8-24 h consisted exclusively of cells with a mixture of apoptotic and necrotic features. Thus, necrotic cells, as judged by flow cytometry, were in a transitional state of cell death mode from apoptosis to necrosis and are thus designated as 'intermediate cells'. Lack of apoptotic bodies, judged by flow cytometric analysis on sub-G1 nuclei and by electron microscopy in menadione-treated cells, suggested that the transition of cell death mode from apoptosis to necrosis occurred before the apoptotic processes were completed. Effects of N-acetylcysteine and Z-VAD-fmk on menadione-induced ultrastructural changes were also studied.     

Low-Temperature Ammonia Oxidation Over Pt/γ-Alumina: The Influence of the Alumina Support

Deactivation of a Pt/-alumina catalyst used for low-temperature ammonia oxidation was studied using positron-emission profiling (PEP). Evidence is presented that irreversibly adsorbed nitrogen and oxygen species deactivate the catalyst. This deactivation is further accelerated by preadsorption of oxygen on the catalyst. Ammonia strongly interacts with the alumina support. A steady state of the ammonia oxidation reaction is reached after the alumina sites are saturated with ammonia. PEP experiments show that spillover of oxygen to the support is not significant during the ammonia oxidation.     

Relationships between Tg and cohesive energy: 1. Dependence of Tg on the composition of copolymers

The possibility of expressing the glass transition temperature of copolymers and homopolymers with an n-alkyl side chain as a function of two parameters (cohesive energy and steric factor) is discussed. An empirical equation representing these two factors is proposed. Calculated values are in good agreement with literature data for the investigated systems.     

Nematic-to-Isotropic Phase Transition in Poly(L-Lactide) with Addition of Cyclodextrin during Abiotic Degradation Study

Poly(L-lactide) is capable of self-assembly into a nematic mesophase under the influence of temperature and mechanical stresses. Therefore, subsequent poly(L-lactide) films were obtained and characterized, showing nematic liquid crystal properties both before and after degradation. Herein, we present that, by introducing β-cyclodextrin into the polymer matrix, it is possible to obtain a chiral nematic mesophase during pressing, regardless of temperature and time. The obtained poly(L-lactide) films exhibiting liquid crystal properties were subjected to degradation tests and the influence of degradation on these properties was determined. Thermotropic phase behavior was investigated using polarized optical microscopy, X-ray diffraction, and differential scanning calorimetry. The degradation process demonstrated an influence on the liquid crystal properties of pressed polymer films. The colored planar texture of the chiral nematic mesophase, which was not observed prior to degradation in films without the addition of β-cyclodextrin, appeared after incubation in water as a result of the entrapment of degradation products in the polymer matrix. These unusual tailor-made properties, obtained in liquid crystals in (bio)degradable polymers using a simple method, demonstrate the potential for advanced photonic applications.     

Biomedical Polyurethanes for Anti-Cancer Drug Delivery Systems: A Brief,Comprehensive Review

With the intensive development of polymeric biomaterials in recent years, research using drug delivery systems (DDSs) has become an essential strategy for cancer therapy. Various DDSs are expected to have more advantages in anti-neoplastic effects, including easy preparation, high pharmacology efficiency, low toxicity, tumor-targeting ability, and high drug-controlled release. Polyurethanes (PUs) are a very important kind of polymers widely used in medicine, pharmacy, and biomaterial engineering. Biodegradable and non-biodegradable PUs are a significant group of these biomaterials. PUs can be synthesized by adequately selecting building blocks (a polyol, a di- or multi-isocyanate, and a chain extender) with suitable physicochemical and biological properties for applications in anti-cancer DDSs technology. Currently, there are few comprehensive reports on a summary of polyurethane DDSs (PU-DDSs) applied for tumor therapy. This study reviewed state-of-the-art PUs designed for anti-cancer PU-DDSs. We studied successful applications and prospects for further development of effective methods for obtaining PUs as biomaterials for oncology.     

Scaling J2EE™ application servers with the Multi‐tasking Virtual Machine

The Java? 2 Platform, Enterprise Edition (J2EE?), is established as the standard platform for hosting enterprise applications written in the Java programming language. Similar to an operating system, a J2EE server can host multiple applications, but this is problematic due to limitations on scalability, weak inter‐application isolation and inadequate resource management facilities in the underlying Java platform. These limitations lead to a proliferation of server instances with a consequent dramatic increase in the total memory footprint and more complex system administration. The Multi‐tasking Virtual Machine (MVM) solves this problem by providing an efficient and scalable implementation of the isolate API for multiple, isolated tasks, enabling the co‐location of multiple server instances in a single MVM process. Isolates also enable the restructuring of a J2EE server implementation as a collection of isolated components, offering increased flexibility and reliability. The resulting system is a step towards a complete and scalable operating environment for enterprise applications. Copyright © 2006 John Wiley & Sons, Ltd.     

Direct T-2 Toxicity on Human Skin—Fibroblast Hs68 Cell Line—In Vitro Study

T-2 toxin is produced by different Fusarium species, and it can infect crops such as wheat, barley, and corn. It is known that the T-2 toxin induces various forms of toxicity such as hepatotoxicity, nephrotoxicity, immunotoxicity, and neurotoxicity. In addition, T-2 toxin possesses a strong dermal irritation effect and can be absorbed even through intact skin. As a dermal irritant agent, it is estimated to be 400 times more toxic than sulfur mustard. Toxic effects can include redness, blistering, and necrosis, but the molecular mechanism of these effects still remains unknown. This in vitro study focused on the direct toxicity of T-2 toxin on human skin—fibroblast Hs68 cell line. As a result, the level of toxicity of T-2 toxin and its cytotoxic mechanism of action was determined. In cytotoxicity assays, the dose and time-dependent cytotoxic effect of T-2 on a cell line was observed. Bioluminometry results showed that relative levels of ATP in treated cells were decreased. Further analysis of the toxin’s impact on the induction of apoptosis and necrosis processes showed the significant predominance of PI-stained cells, lack of caspase 3/7 activity, and increased concentration of released Human Cytokeratin 18 in treated cells, which indicates the necrosis process. In conclusion, the results of an in vitro human skin fibroblast model revealed for the first time that the T-2 toxin induces necrosis as a toxicity effect. These results provide new insight into the toxic T-2 mechanism on the skin.     

Foliar Application of Cerium Oxide-Salicylic Acid Nanoparticles (CeO2:SA Nanoparticles) Influences the Growth and Physiological Responses of Portulaca oleracea L. under Salinity

In the present study, the effects of foliar application of salicylic acid (100 μM), cerium oxide (50 mg L⁻¹), and cerium oxide:salicylic acid nanoparticles (CeO₂: SA-nanoparticles, 50 mg L⁻¹ + 100 μM) on the growth and physiological responses of purslane (Portulaca oleracea L.) were examined in non-saline and saline conditions (50 and 100 mM NaCl salinity). Foliar applications mitigated salinity-induced adverse effects, and the highest plant height and N, P, Mg, and Mn content were recorded in the variant with non-saline × foliar use of CeO₂: SA-nanoparticles. The highest values of fresh and dry weight were noted in the treatment with no-salinity × foliar use of CeO₂:SA-nanoparticles. The highest number of sub-branches was observed in the foliar treatments with CeO₂-nanoparticles and CeO₂:SA-nanoparticles without salinity stress, while the lowest number was noted in the 100 mM NaCl treatment. Moreover, the foliar application of CeO₂:SA-nanoparticles and cerium-oxide nanoparticles improved the total soluble solid content, K, Fe, Zn, Ca, chlorophyll a, and oil yield in the plants. The salinity of 0 and 50 mM increased the K content, 1000-seed weight, total soluble solid content, and chlorophyll b content. The use of 100 mM NaCl with no-foliar spray increased the malondialdehyde, Na, and H₂O₂ content and the Na⁺/K⁺ ratio. No-salinity and 50 mM NaCl × CeO₂: SA-nanoparticle interactions improved the anthocyanin content in plants. The phenolic content was influenced by NaCl₁₀₀ and the foliar use of CeO₂:SA-nanoparticles. The study revealed that the foliar treatment with CeO₂:SA-nanoparticles alleviated the side effects of salinity by improving the physiological responses and growth-related traits of purslane plants.