In vitro antiprotozoal effects of artemisinin on Neospora caninum.

Neospora caninum is an intracellular apicomplexan parasite that infects a wide range of mammals and has been associated with abortion in cattle worldwide. Artemisinin is an effective antimalarial compound derived from a traditional Chinese herbal remedy, qinghao or Artemisia annua L. In the study reported, the cultured host cells (vero cells or mouse peritoneal macrophages) infected with N. caninum tachyzoites were incubated with alpha-MEM (minimal essential medium) 10%HS supplemented with various concentration or artemisinin (20, 10, 1, 0.1 and 0.01 microg/ml) to examine the efficacy of artemisinin against N. caninum tachyzoites intracellular multiplication. In long-term studies, at 20 or 10 microg/ml for 11 days, artemisinin reduced N. caninum and completely eliminated all microscopic foci of N. caninum. At 1 microg/ml for 14 days, artemisinin reduced N. caninum and completely achieved elimination of all microscopic foci of N. caninum. There was no apparent toxicity to host cells in long-term studies. In short-term studies, at > or = 0.1microg/ml, artemisinin reduced N. caninum tachyzoites intracellular multiplication, significantly (P < 0.05) and appeared to depend on the artemisinin concentrations. Pretreatment of host cells or N. caninum tachyzoites with artemisinin had no effect on N. caninum tachyzoites intracellular multiplication. These results demonstrate that artemisinin inhibited N. caninum tachyzoites intracellular multiplication.     

Dieckol Ameliorates Aβ Production via PI3K/Akt/GSK-3β Regulated APP Processing in SweAPP N2a Cell

The proteolytic processing of amyloid precursor protein (APP) by β-secretase (BACE1) and γ-secretase releases amyloid-β peptide (Aβ), which deposits in amyloid plaques and contributes to the initial causative events of Alzheimer’s disease (AD). In the present study, the regulatory mechanism of APP processing of three phlorotannins was elucidated in Swedish mutant APP overexpressed N2a (SweAPP N2a) cells. Among the tested compounds, dieckol exhibited the highest inhibitory effect on both intra- and extracellular Aβ accumulation. In addition, dieckol regulated the APP processing enzymes, such as α-secretase (ADAM10), β-secretase, and γ-secretase, presenilin-1 (PS1), and their proteolytic products, sAPPα and sAPPβ, implying that the compound acts on both the amyloidogenic and non-amyloidogenic pathways. In addition, dieckol increased the phosphorylation of protein kinase B (Akt) at Ser473 and GSK-3β at Ser9, suggesting dieckol induced the activation of Akt, which phosphorylated GSK-3β. The specific phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 triggered GSK-3β activation and Aβ expression. In addition, co-treatment with LY294002 noticeably blocked the effect of dieckol on Aβ production, demonstrating that dieckol promoted the PI3K/Akt signaling pathway, which in turn inactivated GSK-3β, resulting in the reduction in Aβ levels.     

Enhanced mechanical properties of silk fibroin-based composite plates for fractured bone healing

We successfully fabricated bacterial cellulose/silk fibroin (BC/SF) composite plates having similar strength to that of human cortical bone (12.8–17.7 GPa). The mechanical properties of the BC/SF composite plates were investigated at various BC nanofiber contents. The BC nanofibers acted as good reinforcements for the stress transfer produced by the interactions between the BC nanofibers and the SF matrix, as confirmed by the molecular deformation of the BC nanofibers. The BC/SF composite plates have a promising potential as a replacement material for existing metal bone plate.     

Enhanced dielectric properties of electrospun titanium dioxide/polyvinylidene fluoride nanofibrous composites

Titanium dioxide/polyvinylidene fluoride (TiO₂/PVDF) composite was prepared by electrospinning process to enhance the dielectric properties for application as a gate insulator in organic thin-film transistors (OTFTs). Scanning electron microscopy, thermogravimetric analysis, and X-ray diffraction were employed to characterize the as-prepared samples, and then their dielectric constants were investigated by impedance analysis. The impedance results show that the dielectric constant of the electrospun TiO₂/PVDF nanofibers is higher than those of other samples, demonstrating that electrospun TiO₂/PVDF composite can be a proper candidate for gate insulators in OTFTs.     

Pentacene crystal formation on the surface of silk fibroin films

Silk fibroin (SF) has attracted interest as a gate dielectric due to its electrical insulation and high mobility in pentacene based organic thin film transistors (OTFTs). In this research, the surface energy of SF is controlled by water annealing, ethanol, and methanol solution treatments in order to study the effect of pentacene morphology on SF thin films with various treatments. For different crystallization methods, the crystal structures and surface energies of SF were investigated in detail by FT-IR and contact angle. Methanol treated SF thin film has a lower surface energy than the other two thin films. Topologies of pentacene on the SF thin films with various surface energies were obtained by atomic force microscopy (AFM). The AFM results showed that the smallest grain size of pentacene was that on methanol treated SF thin film which demonstrated that methanol treated SF thin film can be a proper candidate for a gate dielectric in OTFTs.     

Anti-inflammatory response of dietary vitamin E and its effects on pain and joint structures during early stages of surgically induced osteoarthritis in dogs

There is evidence that vitamin E (VE) has anti-inflammatory and analgesic properties in human osteoarthritis (OA). This double-blinded and randomized pilot study used a broad spectrum of clinical and laboratory parameters to investigate whether such beneficial effects could be detected in a canine experimental OA model. Dogs were divided into 2 groups: control (n = 8), which received a placebo, and test group (n = 7), which received 400 IU/animal per day of VE for 55 d, starting the day after transection of the cranial cruciate ligament. Lameness and pain were assessed using a visual analogue scale (VAS), numerical rating scale (NRS), and electrodermal activity (EDA) at day 0, day 28, and day 55. Cartilage and synovial inflammation lesions were assessed. One-side comparison was conducted at an alpha-threshold of 10%. At day 56, dogs were euthanized and concentrations of prostaglandin E₂ (PGE₂), nitrogen oxides (NO_x), and interleukin-1 beta (IL-1β) were measured in synovial fluid. Concentrations of NO_x and PGE₂ in synovial fluid were lower in the test group (P < 0.0001 and P = 0.03, respectively). Values of VAS, NRS, and EDA showed a consistent trend to be lower in the test group than in the control, while statistical significance was reached for VAS at day 55 and for EDA at day 28 (adjusted P = 0.07 in both cases). Histological analyses of cartilage showed a significant reduction in the scores of lesions in the test group. This is the first time that a study in dogs with OA using a supplement with a high dose of vitamin E showed a reduction in inflammation joint markers and histological expression, as well as a trend to improving signs of pain.     

Triazole fungicides and the selection of resistance to medical triazoles in the opportunistic mould Aspergillus fumigatus

Azole resistance is an emerging problem in the opportunistic mould Aspergillus fumigatus. The triazoles are the most important agents for the management of Aspergillus diseases in humans. Selection for acquired resistance may occur in the hospital setting through exposure to high doses of azoles during azole therapy, but evidence is accumulating that A. fumigatus may become resistant to medical triazoles through environmental exposure to fungicides. The recovery of A. fumigatus isolates resistant to the medical triazoles from azole‐naive patients as well as from the environment strongly indicates an environmental route of resistance selection. Molecule alignment studies have identified five fungicides that share a very similar molecule structure with the medical triazoles, and thus may have selected for mechanisms that confer resistance to both groups of compounds. It is important to explore further the presumed fungicide‐driven route of resistance selection in order to implement effective preventive measures as the prevalence of azole resistance in A. fumigatus continues to increase and causes major challenges in the management of azole‐resistant Aspergillus diseases. Copyright © 2012 Society of Chemical Industry     

Gene expression analysis of peroxisome proliferators- and phenytoin-induced hepatotoxicity using cDNA microarray

The recent DNA microarray technology enables us to understand a large number of gene expression profiling. The technology has potential possibility to comprehend mechanism of multiple genes were related to compounds which have toxicity in biological system. So, the toxicogenomics through this technology may be very powerful for understanding the effect of unknown toxic mechanisms in biological system. We have studied that the effect of compounds related to hepatotoxin in vivo system using DNA microarray and classified chemicals which have been well characterized. We have studied three compounds; 2 peroxisome proliferators: Clofibrate (ethyl-p-chlorophenoxyisobutyrate), gemfibrozil (5-2[2,5-dimethyl-phenoxy]2-2-dimethyl-pentanonic), and an antiepileptic drug: phenytoin (5,5-diphenylhydantoin). Male Sprague-Dawely VAF(+) albino rats of 5-6 weeks old were treated with each compound for 24 hr and 2 weeks. 4.8 K cDNA microarray in house has been used for gene expression profiling. We found that the clustering of gene expression had similarity like as the toxic phenotype of compounds.     

对推行兽药GMP工作的思考

对推行实施兽药GMP工作中存在的问题进行了分析,提出了建议和对策,并指出兽药行业的规范化管理,除了要推行实施兽药GMP外,还应加快对兽药的经营、使用、研发、临床试验等各环节的立法,建立健全机构,加强队伍建设,特别是要尽快推行兽药经营质量管理规范(GSP),否则兽药GMP将很难长期坚持下去.