Effects of low-dose ketanserin on atherosclerosis in rats and rabbits

The present study was designed to test the hypothesis that a small dose of ketanserin, which enhances baroreflex activity, prevents the early lesions of atherosclerosis. In experiment 1, baroreflex sensitivity (BRS) was measured in 31 spontaneously hypertensive rats (SHRs) in a conscious state using a computerized blood pressure monitoring system. Four weeks later, the rats were administered vitamin D3 and fed a high-cholesterol diet for 8 weeks to induce atherosclerosis. Then their hearts and aortae were removed for pathological examination. A negative correlation was found between BRS and the scores of coronary (r = -0.460, P < 0.01) and aortic atherosclerosis (r = -0.448, P < 0.05) in SHR. In experiment 2, SHRs were divided into 3 groups (n = 10 in each group) and received a dose of ketanserin of 0.3, 1.0, and 3.0 mg/kg (i.g.), respectively. At the smallest dose (0.3 mg/kg), ketanserin did not lower blood pressure but enhanced BRS. In experiment 3, SHRs were administered vitamin D3, fed a high-cholesterol diet, and simultaneously treated with low-dose ketanserin. The atherosclerosis scores of the treatment group were significantly lower than those of the control group (coronary score: 0.90 ± 0.14 vs. 1.76 ± 0.27, P < 0.05; aortic scores: 1.00 ± 0.39 vs. 2.18 ± 0.41, P < 0.05). In experiment 4, male New Zealand White rabbits were fed a high-cholesterol diet and treated with low-dose ketanserin at the same time. The atherosclerosis scores of the treatment group were significantly lower than those of the control group (aortic scores: 0.26 ± 0.20 vs. 0.60 ± 0.31, P < 0.05). In conclusion, the present study demonstrated, for the first time, that low-dose ketanserin prevented the development of atherosclerosis independent of its blood pressure lowering action in SHRs and New Zealand White rabbits at least in part via enhancement of arterial baroreflex function.     

Synthesis and characterization of chitosan/ZnO nanoparticle composite membranes

Novel chitosan/ZnO nanoparticle (CS/nano-ZnO) composite membranes were prepared via the method of sol-cast transformation and studied by UV-vis absorption spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive X-ray fluorescence spectrometry (EDX). The characterization revealed that ZnO nanoparticles dispersed homogeneously within the chitosan matrix. The mechanical and antibacterial properties of the product were investigated. The results showed that the ZnO content had an effect on the mechanical properties of CS/nano-ZnO composite membranes, and that the antibacterial activities of CS membranes for Bacillus subtilis, Escherichia coli, and Staphylococcus aureus were enhanced by the incorporation of ZnO. Further, CS/nano-ZnO composite membranes with 6-10 wt % ZnO exhibited high antibacterial activities.     

Competitive study of monoclonal antibodies against the HIV-1 Gp41 core structure

Monoclonal antibodies (MAbs) 50.69, 98.6, and T26 bind specifically to the core structure of the human immunodeficiency virus type 1 (HIV-1) envelope transmembrane glycoprotein (gp41). To clarify the specificity of the anti-core structure MAbs, we performed competitive assays using the MAbs to the H9 human T cell line infected with the IIIB strain of HIV-1 (H9/IIIB). Bound MAb 50.69 inhibited MAb 98.6 binding unidirectionally. The reason for the unidirectional cross competition between MAbs 50.69 and 98.6 is not clear, but these results help to define the antigenic structure of gp41 on the surface of infected cells.     

Nuclear magnetic resonance structure-based epitope mapping and modulation of dust mite group 13 allergen as a hypoallergen

IgE-mediated allergic response involves cross-linking of IgE bound on mast cells by specific surface epitopes of allergens. Structural studies on IgE epitopes of allergens are essential in understanding the characteristics of an allergen and for development of specific allergen immunotherapy. We have determined the structure of a group 13 dust mite allergen from Dermatophagoides farinae, Der f 13, using nuclear magnetic resonance. Sequence comparison of Der f 13 with homologous human fatty acid-binding proteins revealed unique surface charged residues on Der f 13 that may be involved in IgE binding and allergenicity. Site-directed mutagenesis and IgE binding assays have confirmed four surface charged residues on opposite sides of the protein that are involved in IgE binding. A triple mutant of Der f 13 (E41A_K63A_K91A) has been generated and found to have significantly reduced IgE binding and histamine release in skin prick tests on patients allergenic to group 13 dust mite allergens. The triple mutant is also able to induce PBMC proliferation in allergic patients with indices similar to those of wild-type Der f 13 and shift the secretion of cytokines from a Th2 to a Th1 pattern. Mouse IgG serum raised using the triple mutant is capable to block the binding of IgE from allergic patients to wild-type Der f 13, indicating potential for the triple mutant as a hypoallergen for specific immunotherapy. Findings in this study imply the importance of surface charged residues on IgE binding and allergenicity of an allergen, as was also demonstrated in other major allergens studied.     

The effect of an indirect anthelmintic treatment on parasites and breeding success of free-living pheasants Phasianus colchicus

In Great Britain free-living common pheasants Phasianus colchicus are often managed at high densities owing to their popularity as a quarry species. They are prone to infection by a range of parasite species including Heterakis gallinarum, Capillaria spp. and Syngamus trachea. In 1995 the efficacy of an indirect anthelmintic technique for controlling parasitic worm burdens of pheasants was determined in a pilot study on a shooting estate in the south of England. Between 2000 and 2003 a large-scale field experiment was conducted on nine estates in eastern England to determine the effect of the technique on parasite burden and pheasant breeding success. In the absence of anthelmintic treatment worm burdens increased rapidly through March and April, whereas birds given anthelmintic-treated grain had lower worm burdens during the same period. The breeding success of pheasants was significantly higher on plots provided with anthelmintic treatment, although no long-term increases in population densities were observed. The burdens of the most common parasite H. gallinarum were significantly lower in pheasants from treatment plots six weeks after the anthelmintic treatment had ceased, but spring treatment did not influence parasite burden in the following winter.