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Local release polymeric-controlled immunotherapy of cardiac transplants in rats

Systemic immunosuppression frequently results in severe side effects. To evaluate a method of limiting the adverse effects of immunosuppression, we implanted controlled release matrices containing cyclosporine-A (Cy) embedded (0.2 or 1 mg/kg/day released), steroid embedded (2%, 0.2% and 0.02% dexamethasone, Dex) or both (Cy 0.2 mg and Dex 0.2%) locally around the transplanted heart at the time of rat heterotopic (neck) heart transplants. Controls received empty (non-drug) matrix implants. To elucidate a local effect, additional groups received Cy (0.2 mg) or Dex (0.2%) matrix implanted in a subdermal distal leg pouch at the time of heart transplant, without a local neck implant. Rejection was determined by the lack of transplanted heart contractions. Recipient animals received no other form of immunosuppression. The Cy (0.2 mg) animals had whole-blood Cy levels monitored for 6 weeks following transplantation. Cy levels peaked at 7–10 days after transplant (119 ± 26 ng/ml) and decayed to <50 ng/ml by day 42. At no time did whole-blood Cy levels reach clinically significant levels. Additional animals had whole-blood, heart and kidney Cy levels measured at day 6 post-transplant. Both doses of local Cy demonstrated good survival benefit and were well absorbed locally, resulting in high Cy levels in heart tissue (>9,000 ng/mg). Furthermore, while low-dose Cy (0.2 mg) demonstrated significant survival benefit, these animals had clinically negligible blood Cy levels on day 6 (<100 ng/ml) and very low kidney Cy levels. Interestingly, the lowest dose of Dex demonstrated no survival benefit, while the mid- and high-Dex doses demonstrated good survival benefit: however, the high-Dex dose had poor wound healing. Cy and Dex combination did not increase efficacy, perhaps due to release problems from physicochemical interactions. Local immunosuppression with a controlled release matrix resulted in a significant survival advantage and was effective in delaying rejection. This approach may prove advantageous clinically, in extending transplantation and lessening immunosuppression side effects.     

Hermitian geometries in projective space

Using a Hermitian form on a vector space over GF (l), we produce a geometry on the associated projective space and prove that this geometry is characterized by its plane sections.     

Natrophosphate and kogarkoite precipitated from alkaline nuclear waste at Hanford

Journal of Radioanalytical and Nuclear Chemistry - The Hanford Site, near Richland, Washington in the U.S.A., is implementing a treatment process for liquid radioactive waste. This study determined...     

How to predict soil compaction from agricultural tires

A concept of how to predict soil compaction with regard to agricultural machinery, tires and soil is proposed. This approach should provide criteria for choosing vehicles and tires, as well as for the choice of soil testing equipment. It should be stressed that, till now, the concept has only been tested for a few kinds of soil. Therefore, its application to other soil types has to start with one of the proposed “soil calibration tests”.