8 research outputs found

    Analysis of the Ex Vivo and In Vivo Antiretroviral Activity of Gemcitabine

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    Replication of retroviral and host genomes requires ribonucleotide reductase to convert rNTPs to dNTPs, which are then used as substrates for DNA synthesis. Inhibition of ribonucleotide reductase by hydroxyurea (HU) has been previously used to treat cancers as well as HIV. However, the use of HU as an antiretroviral is limited by its associated toxicities such as myelosuppression and hepatotoxicity. In this study, we examined the ribonucleotide reductase inhibitor, gemcitabine, both in cell culture and in C57Bl/6 mice infected with LP-BM5 murine leukemia virus (LP-BM5 MuLV, a murine AIDS model). Gemcitabine decreased infectivity of MuLV in cell culture with an EC50 in the low nanomolar range with no detectable cytotoxicity. Similarly, gemcitabine significantly decreased disease progression in mice infected with LP-BM5. Specifically, gemcitabine treatment decreased spleen size, plasma IgM, and provirus levels compared to LP-BM5 MuLV infected, untreated mice. Gemcitabine efficacy was observed at doses as low as 1 mg/kg/day in the absence of toxicity. Higher doses of gemcitabine (3 mg/kg/day and higher) were associated with toxicity as determined by a loss in body mass. In summary, our findings demonstrate that gemcitabine has antiretroviral activity ex vivo and in vivo in the LP-BM5 MuLV model. These observations together with a recent ex vivo study with HIV-1[1], suggest that gemcitabine has broad antiretroviral activity and could be particularly useful in vivo when used in combination drug therapy

    Family planning in conflict: results of cross-sectional baseline surveys in three African countries

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    Abstract Background Despite the serious consequences of conflict for reproductive health, populations affected by conflict and its aftermath face tremendous barriers to accessing reproductive health services, due to insecurity, inadequate numbers of trained personnel and lack of supplies. Family planning is often particularly neglected. Methods In six conflict-affected areas in Sudan, northern Uganda and the Democratic Republic of Congo, household surveys of married or in-union women of reproductive age were conducted to determine baseline measures of family planning knowledge, attitudes and behaviors regarding contraception. Health facility assessments were carried out to assess baseline measures of family planning services availability. Data were double-entered into CSPro 3.2 and exported to SAS 9.2, which was used to calculate descriptive statistics. The studies' purposes were to guide program activities and to serve as a baseline against which program accomplishments could be measured. Results Knowledge of modern contraceptive methods was low relative to other sub-Saharan African countries, and use of modern methods was under 4% in four sites; in two sites with prior family planning services it was 12% and 16.2%. From 30% to 40% of women reported they did not want a child within two years, however, and an additional 12% to 35% wanted no additional children, suggesting a clear need for family planning services. The health facilities assessment showed that at most only one-third of the facilities mandated to provide family planning had the necessary staff, equipment and supplies to do so adequately; in some areas, none of the facilities were prepared to offer such services. Conclusions Family planning services are desired by women living in crisis situations when offered in a manner appropriate to their needs, yet services are rarely adequate to meet these needs. Refugee and internally displaced women must be included in national and donors' plans to improve family planning in Africa.</p

    Characterization and Combustion of Aluminum Nanopowders in Energetic Systems

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    Following a comprehensive literature survey about use of Al nanopowders in a range of HEM applications — including rocket propulsion, pyrotechnics, and explosives - a through treatment is offered of the ideal and delivered thermochemical performance of the most interesting metallic ingredients to augment solid and hybrid rocket propulsion. The particular but fundamental class of nAl powders is then investigated in detail: critical issues such as coating and characterization of the powders, rheological and mechanical properties, combustion and ballistic behavior are all examined under a variety of operating conditions. Although attractive for fundamental studies and much used in laboratory experiments, no rocket propulsion operational systems are yet reported in use for nAl powders. Loss of active metal, cold cohesion, and poor propellant castability globally overcome advantages such as increased burning rate (easily achievable by other ways) and reduced specific impulse losses associated with 2P flow (thanks to less agglomeration with respect to the corresponding micrometric powders). Use of dual metallic fuels, by properly blending μAl and nAl, and/or modification of the natural properties of nAl particles, by suitable coatings, represent two possible ways to exploit the potential of nanopowders. Several approaches are also discussed so as to improve dispersion and mechanical properties of solid propellants or solid fuels containing nAl. Overall, a good control of particle size, metal content, and dispersion is a crucial requirement for successful applications of nanoingredients in propulsion
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