聚丙烯酸改性磁性壳聚糖复合微球对药物活性物的吸附

采用化学沉淀法合成磁性壳聚糖复合微球(MCS),以MCS为核,在其表面接枝聚丙烯酸(PAA),制备了PAA改性的磁性壳聚糖复合微球(MCS/PAA)。研究了MCS/PAA对两种药物活性物双氯芬酸钠(DCF)和盐酸四环素(TC)的吸附性能,考察了吸附剂用量、溶液初始浓度和吸附温度对吸附性能的影响。结果表明,药物吸附量和去除率随着吸附剂用量的增加而减小,随溶液初始浓度的增加而增加,随温度升高,增加趋势不明显,说明温度不是影响药物吸附去除的主要因素。MCS/PAA对DCF的吸附去除效果更好,有一定的应用前景和推广价值。

Synthesis and Antibacterial Effect of New Alkylenedibiguanides

Seven new alkylenedibiguanides were synthesized and comfirmed by 1H NMR, MS and elemental analyses. The preliminary test in vitro showed that some of them had potential antibacterial activities.

A Bioactive Diterpene from the Chinese Herb Aster souliei

Aster souliei Franch, (Compositae) is a. herbaceous plant distributed innorth China. It has been used in folk medicine as antipyretic, detoxicant, expectorant andantitussive. In an effort to find biologically active components from Chinese medicinal plants ' ,we have examined the aerial parts of this herb, leading to the isolation of a clerodane-typediterpene, 18, 19-dihydroxy-5α, 10β-neo-cleroda-3, 13 (l4)-dien-16, 15-butenolide (1). In thispaper we report the structural elucidation, and the antitumor and antibacterial activities of thiscompound. It was found that 1 possesses moderate cytotoxicity against human leukemia cells (HL-60)and activity against microorganisms.

Synthesis and Antifungal Activity of 1-(1H-1,2,4-Triazole)-2-(2,4-diflurophenyl)-3-(N-methyl-N-substituted benzylamino)-2-propanols

Eleven 1-(1H-1,2,4-triazole)-2-(2,4-diflurophenyl)-3-(N-methyl-N-substituted benzylamino)-2-propanols were designed and synthesized, on the basis of the crystal structure of P450 cytochrome 14α-sterol demethylase(CYP51) and the docking results of inhibitors to the active site of the enzyme. All title compounds were first by reported. Results of preliminary biological tests showed that most of title compounds exhibited activity against the seven common pathogenic fungi. Compound 11 showed best antifungal activity with broad antifungal spectrum and proved to be more active against Cryptococcus neoformans, Candida albicans, Microsporum lanosum and Trichophyton rubrum than ketoconazole. Compounds 3, 10 and 4 also had high activities.

3D Photo-Fabrication for Tissue Engineering and Drug Delivery

The most promising strategies in tissue engineering involve the integration of a triad of biomaterials, living cells, and biologically active molecules to engineer synthetic environments that closely mimic the healing milieu present in human tissues, and that stimulate tissue repair and regeneration. To be clinically effective, these environments must replicate, as closely as possible, the main characteristics of the native extracellular matrix(ECM) on a cellular and subcellular scale. Photo-fabrication techniques have already been used to generate 3D environments with precise architectures and heterogeneous composition, through a multi-layer procedure involving the selective photocrosslinking reaction of a light-sensitive prepolymer. Cells and therapeutic molecules can be included in the initial hydrogel precursor solution, and processed into 3D constructs. Recently, photofabrication has also been explored to dynamically modulate hydrogel features in real time, providing enhanced control of cell fate and delivery of bioactive compounds. This paper focuses on the use of 3D photo-fabrication techniques to produce advanced constructs for tissue regeneration and drug delivery applications. State-of-the-art photo-fabrication techniques are described, with emphasis on the operating principles and biofabrication strategies to create spatially controlled patterns of cells and bioactive factors. Considering its fast processing, spatiotemporal control, high resolution, and accuracy, photo-fabrication is assuming a critical role in the design of sophisticated 3D constructs. This technology is capable of providing appropriate environments for tissue regeneration, and regulating the spatiotemporal delivery of therapeutics.

A nonsynonymous SNP in human cytosolic sialidase in a small Asian population results in reduced enzyme activity: potential link with severe adverse reactions to oseltamivir

The use of oseltamivir, widely stockpiled as one of the drugs for use in a possible avian influenza pandemic, has been reported to be associated with neuropsychiatric disorders and severe skin reactions, primarily in Japan. Here we identified a nonsynonymous SNP （single nucleotide polymorphism） in dbSNP database, R41Q, near the enzymatic active site of human cytosolic sialidase, a homologue of virus neuraminidase that is the target of oseltamivir. This SNP occurred in 9.29% of Asian population and none of European and African American population. Our structural analyses and Ki measurements using in vitro sialidase assays indicated that this SNP could increase the unintended binding affinity of human sialidase to oseltamivir carboxylate, the active form of oseltamivir, thus reducing sialidase activity. In addition, this SNP itself results in an enzyme with an intrinsically lower sialidase activity, as shown by its increased Km and decreased Vmax values. Theoretically administration of oseltamivir to people with this SNP might further reduce their sialidase activity. We note the similarity between the reported neuropsychiatric side effects ofoseltamivir and the known symptoms of human sialidase-related disorders. We propose that this Asian-enriched sialidase variation caused by the SNP, likely in homozygous form, may be associated with certain severe adverse reactions to oseltamivir.

Antibacterial activity of panipenem/betamipron in vitro and its pharmacokinetics and therapeutic efficacy in patients with pulmonary infection

Objective: To investigate the in vitro antimicrobial activity of panipenem/betamipron to common clinical isolates, determine its pharmacokinetics in patients with pulmonary infection and evaluate its effectiveness and safety in treatment of pulmonary infection. Methods: (1) The minimal inhibition concentrations of panipenem/betamipron were determined in 247 clinical isolates by agar dilution method. The minimal bactericidal concentrations of panipenem/betamipron for some clinical isolates were also determined. (2) Twenty cases of pulmonary infection were treated with intravenous dripping of panipenem/betamipron at 500/500 mg every 12 h for 3-7 d. Panipenem/betamipron concentration in the plasma was consecutively measured, and bacterial culture was conducted and the efficacy was evaluated. Results: (1) The in vitro antimicrobial activity of panipenem/betamipron was almost the same as that of panipenem, indicating that panipenem played the major role in antimicrobial reaction. Panipenem/betamipron had a strong antimicrobial activity against Staphylococcus aureus including methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, β-Streptococcus hemolytic, Streptococcus pneumonia, micrococcus, Escherichia coli and Klebsiea pneumonia. The drug also showed a potent effect against Haemophilus influenzae,Enterobacter cloacae, Proteus and Pseudomonas aeruginosa (2) The peak value of panipenem/betamipron in plasma was (30.25±5.43) mg/L and the level decreased to (0.66±0.34) mg/L 6 h later. The half-life of distribution and elimination of panipenem in the plasma was (0.34±0.18) h and (1.42±0.31) h, respectively. (3) The eradication rate of bacteria was 77.8% and the effective healing rate was 75%. No adverse drug reaction was found. Conclusion: Panipenem/betamipron has a strong antimicrobial activity against clinical isolates and is effective and safe for treatment of pulmonary infection.

Eggs as a Very Promising Source of Biomedical and Nutraceutical Preparations： A Review

It is generally accepted that eggs besides being a source of everyday diet, can also be used as raw material for special food, nutraceutical, pharmaceutical and cosmetic production. The biological activity of the majority of substances presented in egg matter is related to their anti-microbial and anti-cancer properties and their immunogenic features as well. Due to the use of new generation of feed additives and techniques of immunisation of hens, the chemical composition and biological features of eggs may be modified and enriched with desired components, like n-3 fatty acids （alpha-linolenic acid （ALA）, docosahexaenoic acid （DHA） phospholipids）, vitamins, microelements. Egg material may also be used for the production of new biopreparations for the prophylaxis of various civilisation diseases, such as heart and cardiovascular diseases, cancers, neurogenerative disorders, metabolic bone diseases etc.. New progress in egg science allowed to discover new bioactive substances, like monomeric and dimeric cystatin and yolkin. It is necessary to develop efficient methods of isolation of biologically active substances contained in eggs, which would make it possible to produce new generation of diet supplements and biomedical products. It seems that new generation of eggs could be the best source for production of natural, high value nutraceutical supplements of diet, and also biomedical and biocosmetic preparations.

Ethnobotany, Pharmacology and Chemistry of Medicinal Orchids from Veracruz

Orchidaceae is a large family of 1,260 species in Mexico, of which 433 grow in the state of Veracruz, Mexico. Although economically important in horticulture because of the beauty of their flowers, researches have done little work regarding their medicinal properties. This paper aimed to present the results of ethnobotanical, pharmacological and active compounds research on Veracruz medicinal orchids. The ethnobotanical information was obtained by consulting the Atlas of the Mexican Traditional Medicine Plants, Veracruz Medicinal Flora Database （CITRO-UV project） and through field work in the Nahuatl community of Cuautlajapa, Veracruz. To obtain pharmacological and active compounds information of registered species, a search was carded out through MEDLINE （USA National Library of Medicine Journal Citation database）. Twelve medicinal orchids were recorded for Veracruz, i.e., Epidendrum chlorocorymbos Schltr., Habenaria floribunda Lindl., Isochillus latibracteatus A. Rich. ＆ Galeotti, lsochillus major Schltdl. ＆ Cham., Mormodes maculata var. unicolor （Hook.） L. O. Williams, Oestlundia luteorosea （A. Rich. ＆ Galeotti） W. E. Higgins, Oncidium ascendens Lindl., Scaphyglottis fasciculata Hook., Sobralia macrantha Lindl., Spiranthes eriophora （Rob. ＆ Greenm.）, Stanhopea oculata （G. Lodd.） Lindl. and Vanilla planifolia Andrews. Only two species have been investigated in terms of their pharmacology and active compounds. Also, information for another five species closely related to already identified ones was obtained. Given the relative poverty of current information on the topic, this paper demonstrates the need to further study the ethnobotanical, pharmacological and chemical aspects of the region＇s medicinal orchids.

In Silico Screening of Potential Drug with Antileishmanial Activty and Validation of their Activity by in Vitro and in Vivo Studies

The research on discovery and development of new treatments for cutaneous leishmaniasis has been declared as priority. Using bioinformatics approaches, this study aimed to identify antileishmanial activity in drugs that are currently used as anti-inflammatory and wound healing by such anti-Leishmania activity was validated by in vitro and in vivo assays. In silico analysis identified 153 compounds from which 87 were selected by data mining of DrugBank database, 22 and 44 were detected by PASS （http：//pass.cribi.unipd.it） and BLAST （http：//blast.ncbi.nlm.nih. gov/） alignment, respectively. The majority of identified drugs are used as skin protector, anti-acne, anti-ulcerative （wound healer） or anti-inflammatory and few of them had specific antileishmanial activity. The efficacy as antileishmanial was validated in vitro in 12/23 tested compounds and in all seven compounds that were evaluated in in vivo assays. Notably, this is the first report of antileishmanial activity for adapalene. In conclusion, bioinformatics tools not only can help to reduce time and cost of the drug discovery process but also may increase the chance that candidates identified in silico which have a validated antileishmanial activity by combining different biological properties.

Current Situation of Drug Abuse and Countermeasures in Japan

Drug abuse is a common problem that all countries in the world face. The most distinguishing characteristic of drug abuse in ｜apart is that use of stimulants, mostly methamphetamine, accounts for over 80% of the arrests. Abuse of a stimulant called Philopon was widespread after the Second World War in ]apan, but the situation was dramatically improved after 1954 because the Japanese government enacted the Stimulant Control Act and restructured the police system and Japanese society recovered from post-war unrest. The situation of drug abuse in Japan has become less serious compared to the past and to the situation in many other countries, because we are taking comprehensive and nationwide measures, including proactive disclosure of the situation, control, drug abuse prevention class, and introduction of partial suspension of sentence. On the other hand, as in many countries, the rapid spread of new psychoactive substances （NPS） in recent years became a serious social issue. The situation of NPS has been rapidly improving due to comprehensive and government-wide measures, but the means of acquisition is quickly shifting to the Internet. It is necessary to strengthen cyber patrol.

Possible Mechanism of Action of Neurokinin-1 Receptors （NK1R） Antagonists

Recently, NK1R （Neurokinin-1 receptors） take attention as new and promising target in anticancer drug development area. It has been proved that non-peptide NK1R antagonists L-733,060, aprepitant and L-732,138 inhibited tumor growth in several cancer cell lines. For the development of novel NK1R antagonists as antitumor agents, heterocyclic compounds which were previously synthesized by our team, tested for their cytotoxic activities in several cancer cell lines in this study. Among the tested compounds, a benzothiazole derivative BSN-009 inhibited colon cancer cell lines growth by 57.53% by comparing the activity to the control drug aprepitant. Molecular modeling studies such as molecular docking and pharmacophore generation were performed with known NK1R antagonists and BSN-009 by using Discovery Studio 3.5 in order to explain their binding modes to NK1R. BSN-009 may be a good anticancer drug candidate as a possible NK1R antagonist and is worthy to carry on the anticancer studies.

Synthesis and antiviral bioactivities of novel chiral bis-thiourea-type derivatives containing α-aminophosphonate moiety

Starting from 1-((1R,2R)-2-aminocyclohexyl)-3-substituted thioureas (3a–c) and substituted isothiocyanates (9a–d),chiral bis-thiourea derivatives containing α-aminophosphonate moiety 10a–l were prepared and completely characterized by elemental analysis,physical and spectral (IR,1H NMR,13C NMR,31P NMR) data.The results of bioassay revealed that compounds 10a and 10e possessed appreciable curative bioactivities on cucumber mosaic virus (CMV) at 0.5 mg/mL in vivo (inhibitory rate = 60.3%,64.8% respectively) and tobacco mosaic virus (TMV) at 0.5 mg/mL in vivo (inhibitory rate = 50.3%,50.8% respectively),which were comparable to the values shown by standard reference (58.7%) and commercial product Ningnanmycin (56.3%),respectively.Chiral compound 10e displayed more potent antiviral activity (EC50 = 0.149 mg/mL) than Ningnanmycin (EC50 = 0.201mg/mL) against CMV.

Recent advances in biosynthesis of bioactive compounds in traditional Chinese medicinal plants

Plants synthesize and accumulate large amount of specialized （or secondary） metabolites also known as natural products, which provide a rich source for modem pharmacy. In China, plants have been used in traditional medicine for thousands of years. Recent development of molecular biology, genomics and functional genomics as well as high-throughput analytical chemical technologies has greatly promoted the research on medicinal plants. In this article, we review recent advances in the elucidation of biosynthesis of specialized metabolites in medicinal plants, including phenylpropanoids, terpenoids and alkaloids. Th- ese natural products may share a common upstream path- way to form a limited numbers of common precursors, but are characteristic in distinct modifications leading to highly variable structures. Although this review is focused on traditional Chinese medicine, other plants with a great medicinal interest or potential are also discussed. Under- standing of their biosynthesis processes is critical for producing these highly value molecules at large scale and low cost in microbes and will benefit to not only human health but also plant resource conservation.