Thymoquinone Induces Telomere Shortening, DNA Damage and Apoptosis in Human Glioblastoma Cells

Background: A major concern of cancer chemotherapy is the side effects caused by the non-specific targeting of both normal and cancerous cells by therapeutic drugs. Much emphasis has been placed on discovering new compounds that target tumour cells more efficiently and selectively with minimal toxic effects on normal cells. Methodology/Principal Findings: The cytotoxic effect of thymoquinone, a component derived from the plant Nigella sativa, was tested on human glioblastoma and normal cells. Our findings demonstrated that glioblastoma cells were more sensitive to thymoquinone-induced antiproliferative effects. Thymoquinone induced DNA damage, cell cycle arrest and apoptosis in the glioblastoma cells. It was also observed that thymoquinone facilitated telomere attrition by inhibiting the activity of telomerase. In addition to these, we investigated the role of DNA-PKcs on thymoquinone mediated changes in telomere length. Telomeres in glioblastoma cells with DNA-PKcs were more sensitive to thymoquinone mediated effects as compared to those cells deficient in DNA-PKcs. Conclusions/Significance: Our results indicate that thymoquinone induces DNA damage, telomere attrition by inhibiting telomerase and cell death in glioblastoma cells. Telomere shortening was found to be dependent on the status of DNA-PKcs. Collectively, these data suggest that thymoquinone could be useful as a potential chemotherapeutic agent in th

Receipt for payment from Joseph H. Woodward to Dr. E. E. Worthen, Wheeling, West Virginia, January 1, 1882

A document from an extensive collection spanning four generations of the Woodward family that operated merchant pig iron companies in West Virginia and Alabama. The collection begins with Stimpson Harvey Woodward (S. H. Woodward), a native of Massachusetts, who moved from Pittsburgh to Wheeling, West Virginia in 1852. He had interests in an iron company as early as 1852 in West Virginia and began Alabama operations in 1869. The family business continued in Alabama until the death of S. H. Woodward's great-grandson in 1965

Construindo Critérios de Julgamento em Avaliação: especialistas e satisfação dos usuários com a dispensação do tratamento do HIV/Aids Building Evaluation Criteria: experts and user satisfaction with pharmaceutical delivery services for HIV/Aids

Critério é uma ferramenta típica da avaliação e pode ser definido como uma dimensão-padrão em função da qual a realidade do objeto da avaliação receberá julgamento qualitativo e/ou quantitativo. Em uma avaliação, o procedimento de elaborar, esclarecer, negociar e aplicar critérios para determinar o valor (ou mérito) do objeto avaliado faz parte de um exercício metodológico que deve ser cuidadoso. Este artigo apresenta critérios de julgamento para avaliar a satisfação dos usuários com a dispensação dos medicamentos para o tratamento do HIV/Aids e seu processo de construção por meio de consenso entre diferentes atores sociais. Para estabelecer o consenso utilizou-se técnica de Delfos, uma técnica formal utilizada para consenso de especialistas com metodologia e processos estruturados. Neste estudo, foram considerados especialistas aqueles com experiência acadêmica e em gestão, bem como ativistas informados e comprometidos com a questão. Os achados foram sistematizados sob a forma de uma nova estrutura de satisfação, sob a qual os critérios construídos são articulados hierarquicamente. Buscou-se contribuir para o desenvolvimento de uma estratégia metodológica participativa em avaliação e ampliar o conhecimento sobre a satisfação dos usuários e a dispensação dos medicamentos para HIV/Aids.<br>A criterion is a typical tool in the evaluation field that can be defined as a standard-dimension under which the object of an evaluation receives qualitative or quantitative judgments. During an evaluation, several rigorous methodological procedures are involved in development and application of suitable criteria to determine the value of the object being evaluated. This article presents a set of criteria to evaluate user satisfaction with HIV/Aids-related pharmaceutical delivery services. The criteria construction process involved consensus amongst different experts, from academia, NGOs, management, by means of the Delphi technique. This technique prescribes a series of formal steps towards a consensus of experts, based on pre-structured methodology and processes. The findings were systematically organized in a structure under which the resulting satisfaction criteria are hierarchically organized. Results suggest the importance of developing a methodological strategy in evaluation that involves participation of different actors and of enhancing knowledge on user satisfaction and pharmaceutical delivery services for HIV/Aids