Milbemycin derivatives: epoxidation of milbemycins

Epoxidation reactions (MCPBA epoxidation and Sharpless epoxidation) were examined as a means of chemically modifying milbemycins as part of our program for discovering anthelmintics. 8,9-Epoxy-, 14,15-epoxy-, 8,9-14,15-diepoxy-, and 3,4-8,9-14,15-triepoxymilbemycin A4 were selectively obtained from milbemycin A4 and its derivatives, in which either the C-5 and C-7 hydroxyl groups or C-5 alone were protected as appropriate by a silyl ether (in the former case) or a carbonyl group. Further silylation or epoxidation on these epoxidized compounds indicated that the configuration of each epoxide moiety of the mono- and diepoxides is in accord with that of the corresponding epoxide moiety of the triepoxide. Furthermore, in order to confirm the absolute configurations of these epoxide functionalities, an X-ray analysis of a carbamate derivative from the triepoxymilbemycin was conducted.     

Anabolic agents in trauma and sepsis: repleting body mass and function

Both growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are potent anabolic agents. Exogenous GH improves nitrogen metabolism in patients undergoing surgery; however, the anabolic effects of GH in cases of multiple injury, burn, and sepsis are equivocal. Moreover, few data are available concerning the effects of GH in organ failures. Exogenous IGF-1 attenuates catabolism in animal trauma models. A clinical trial, however, did not confirm the anabolic actions of IGF-1. Further knowledge of the interaction between the GH/IGF-1 axis in critical illness is essential for GH and IGF-1 therapy. Theoretically, the improved nitrogen metabolism achieved with exogenous anabolic agents may provide functional benefits. However, only a few studies have confirmed the beneficial effects of GH on body function in trauma and sepsis. GH treatment decreases the postoperative depression of hand grip strength. GH also stimulates wound healing. Both GH and IGF-1 exert their effects on immune system, suggesting that these anabolic agents are potentially beneficial for the prevention and treatment of sepsis. On the contrary, inhibition of polymorphonuclear neutrophil apoptosis and the potentiation of PMNs by GH may have harmful effects on the systemic responses. Further studies are required to determine the safety and clinical benefits of GH administration in critical illness.     

Suppression of HIV-1 replication in peripheral blood mononuclear cells by fasudil

Fasudil is a potent inhibitor for various protein kinases such as myosin light chain kinase and protein kinase C. It has been used as a drug for improvement of intracranial vasospasm and following ischaemic diseases. In this report, we demonstrate that fasudil suppressed the replication of human immunodeficiency virus type 1 (HIV-1) in mitogen-activated peripheral blood mononuclear cells. Our finding shows that fasudil may be useful as a new and distinct chemotherapeutic agent against HIV-1 infection.     

Curve implicitization using moving lines

It is a classical result that two corresponding pencils of lines intersect in a conic section, and likewise any conic section can be expressed as the intersection of two pencils of lines. We here extend the idea of pencils to higher degree families lines, and show that any planar rational curve can be expressed as the intersection of two families of lines. This extension leads to a more efficient implicitization algorithm for curves, in which, for example, the implicit equation of a degree four rational curve can generally be expressed as the determinant of a 2 × 2 matrix (Bezout's resultant produces a 4 × 4 matrix and Sylvester's resultant an 8 × 8 matrix).     

Ex vivo evidence for asymmetric tyrosine phosphorylation of ZAP-70 on double-positive thymocytes in the positive selection process

Antigen stimulation via TCR in mature T cells provides rapid induction of tyrosine phosphorylation of intracellular substrates including ZAP-70. To study the potential involvement of tyrosine phosphorylation in CD4+CD8+ [double-positive (DP)] thymocytes in the positive selection process in vivo, we isolated and analyzed them in the presence of phosphatase inhibitor. DP thymocytes were obtained from TCR transgenic mice (TCR-Tg) expressing MHC class I- or class II-restricted TCR in selecting and non-selecting MHC backgrounds respectively. The phosphorylation of ZAP-70 in DP thymocytes of class I-restricted TCR-Tg was significantly higher in the positively selecting background than in the non-selecting one. However, such a phosphorylation difference between selecting and non-selecting TCR-Tg was found to be considerably less in class II-restricted TCR-Tg. A similar bias for ZAP-70 phosphorylation was also observed on selecting DP thymocytes when I-A(beta) deficient- and beta2-microglobulin-deficient mice were compared. These ex vivo studies suggest that TCR-mediated signaling on DP thymocytes induces ZAP-70 phosphorylation under a different manner of engagement of TCR to class I and class II molecules in the positive selection process.     

Nickel dioxide polymorphs as lithium insertion electrodes

Five kinds of nickel dioxide polymorphs, Li_xNiO₂ with x≈0, were prepared by treating LiNiO₂ with sulfuric acid solutions, occasionally followed by low-temperature heating. Here we report their structure and properties as lithium insertion electrodes. Acid-treated Li_0.10NiO₂ with two layered phases turned into a single-layered compound at 160 °C and then to a spinel-related compound at 170 °C. Acid-treated Li_0.04NiO₂ contained a phase with a cadmium iodide structure, which was not observed with Li_0.10NiO₂. Heating this Li_0.04NiO₂ yielded a spinel-related compound on heating. The NiO distances in these compounds suggested that the nickel oxidation state was kept approximately +4. These ‘nickel dioxide’ polymorphs exhibited varied characteristics as lithium insertion electrodes. We discuss the electrode behavior together with the structural changes that occur during lithium insertion. We also examined the effect of the electrode drying condition on the cycling performance.