Comparative Pharmacokinetics and Preliminary Pharmacodynamics Evaluation of Piscidin 1 Against PRV and PEDV in Rats.

Antimicrobial peptide (Piscidin-1) is an effective natural polypeptide, which has great influence and potential on porcine epidemic diarrhea virus (PEDV) and pseudorabies virus (PRV). As an alternative antibiotic substitute, Piscidin-1 was subjected for pharmacokinetics study with three administration routes (i.v, i.m, and p.o) after a single dose of 2 mg/kg in rats and preliminary pharmacodynamics including antiviral activity in cell against PEDV and PRV. Based on 50 percent tissue culture infective dose (TCID50), there were about 2 and 10% virus survived ratios for Piscidin-1 against PRV and PEDV, respectively. The plaque test showed 1 and 2 µg/ml Piscidin-1 could eliminate 95% PRV and 85% PEDV, respectively. The main pharmacokinetics parameters of Cmax, AUC0-∞, Ke, t1/2, Tmax, MRT, and Clb in plasma were not applicable value, 25.9 µg*h/ml, 0.041 h-1, 16.97 h, not available value, 22.77 h, 0.067 L/h*kg after i.v administration, 2.37 µg/ml, 18.95 µg*h/ml, 0.029 h-1, 23.50 h, 0.33 h, 30.12 h, 0.095 L/h*kg after i.m administration and 0.73 µg/ml, 9.63 µg*h/ml, 0.036 h-1, 19.46 h, 0.50 h, 26.76 h, 0.171 L/h*kg after p.o administration. The bioavailability values after i.m and p.o administrations were calculated as 73.17 and 37.18%, respectively. The i.m administration was selected for pharmacokinetics study in ileum content against PEDV. The main pharmacokinetic parameters of Cmax, AUC0-∞, Ke, t1/2, Tmax, MRT, and Clb in ileum content were 1.67 µg/ml, 78.40 µg*h/ml, 0.034 h-1, 20.16 h, 8.12 h, 36.45 h, 0.026 L/h*kg. The Cmax values in plasma (2.37 µg/ml) and ileum content (1.67 µg/ml) were higher than the effective inhibitory concentration determined in the plaque test, and this indicates that Piscidin-1 might have effective inhibition effect against PRV and PEDV after administration of 2 mg/kg i.m. The results of this study represent the first investigations toward the pharmacokinetic characteristics of piscidin-1 in plasma upon three different administration routes, among which i.m. resulted in the highest bioavailability (73.17%). Furthermore, the pharmacokinetics study of ileum content indicated Piscidin-1 might have good effect against PEDV and could be regarded as an alternative antibiotic in clinical veterinary in the future study.

Design and Synthesis of Chlorinated and Fluorinated 7-Azaindenoisoquinolines as Potent Cytotoxic Anticancer Agents That Inhibit Topoisomerase I.

The 7-azaindenoisoquinolines are cytotoxic topoisomerase I (Top1) inhibitors. Previously reported representatives bear a 3-nitro group. The present report documents the replacement of the potentially genotoxic 3-nitro group by 3-chloro and 3-fluoro substituents, resulting in compounds with high Top1 inhibitory activities and potent cytotoxicities in human cancer cell cultures and reduced lethality in an animal model. Some of the new Top1 inhibitors also possess moderate inhibitory activities against tyrosyl-DNA phosphodiesterase 1 (TDP1) and tyrosyl-DNA phosphodiesterase 2 (TDP2), two enzymes that are involved in DNA damage repair resulting from Top1 inhibitors, and they produce significantly more DNA damage in cancer cells than in normal cells. Eighteen of the new compounds had cytotoxicity mean-graph midpoint (MGM) GI50 values in the submicromolar (0.033-0.630 µM) range. Compounds 16b and 17b are the most potent in human cancer cell cultures with MGM GI50 values of 0.063 and 0.033 µM, respectively. Possible binding modes to Top1 and TDP1were investigated by molecular modeling.

A three-stage approach to shadow field estimation from partial boundary information.

In this paper, we present a system for estimating the shadow field from a single natural image. Unlike previous works that require extensive user assistance, our system only needs the user to roughly specify the shadow boundary with a broad brush. As the user finishes drawing a stroke, the system starts to estimate the shadow field around the stroke and generates pretty accurate result even if the underlying surface is highly textured. We also propose an optimization scheme to propagate the estimated shadow field to the entire image, achieving a further reduction of user effort required for the system. The shadow field estimated by our system can be used to seamlessly remove the shadow from the image. It is also useful for many shadow editing tasks such as pasting an object's shadow from one image to another. Experimental results on a variety of photos are provided to show the effectiveness of the proposed system.