4－氨基吡啶诱发组胺释放及某些药物的拮抗作用

４－氨基吡啶（４－ＡＰ）有组胺释放作用。小鼠ｉｐ４－ＡＰ５ｍｇ·ｋｇ－１后，肺中组胺含量明显减低，血中组胺含量显著增高。钙拮抗剂硝苯啶、ＴＭＢ－８及钾通道开放剂米诺地尔均能明显抑制４－ＡＰ诱发的小鼠ＰＭＣ释放组胺。结果提示，ＭＣ可能存在钾通道，４－ＡＰ诱发ＭＣ释放组胺可能与它阻滞钾通道，从而使钙通道开放，增加Ｃａ２＋内流有关。     

刺蒺藜果中一种新桂皮酰胺类成分的分离和鉴定

从刺蒺藜(Tribulus terrestris L)果实中分得两个化合物,经理化常数测定和光谱(UV,IR,¹HNMR,¹³CNMR,¹H-¹³CCOSY和MS)解析。化合物I鉴定为N-对羟基苯乙酮基-3-甲氧基-4-羟基取代桂皮酰胺,为一新化合物,命名为蒺藜酰胺(terrestriamide)。化合物II为8-甲基氢化茚酮-1,首次从该植物中获得。     

商陆多糖Ⅰ联合白细胞介素2对小鼠脾细胞杀瘤活性的影响

商陆多糖Ⅰ(PAP-I),0.3～3μg·ml^-1和小鼠脾细胞培养3～5d可显著增强其杀伤P815肿瘤细胞活性及IL-2(250～500IU·ml^-1)诱导的LAK细胞活性,最适浓度为1μg·ml^-1。PAP-I及IL-2和脾细胞培养的上清液对P815肿瘤细胞无细胞毒作用,但能增强脾细胞及LAK细胞杀瘤活性。PAP-I,5,10及50mg·kg-1,ip可增强脾细胞杀伤P₈₁₅和L₉₂₉细胞的活性及IL-2诱导的LAK细胞活性。     

Biodegradable microspheres: polyacryl starch microparticles as a delivery system for the antileishmanial drug, sodium stibogluconate

Liver parasite burdens of Leishmania donovani in the mouse have been determined after treatment with intravenous administration of sodium stibogluconate in the free or carrier form. The carrier form, in which the drug was covalently bound to polyacryl starch microparticles, was up to 100x more effective than the free form in this murine model of visceral leishmaniasis. Empty microparticles had no effect on liver parasite burdens and the enhanced in-vivo antileishmanial activity of the carrier form of the drug was apparently due to passive drug delivery to the infected liver.     

柴胡皂甙q及其甙元的结构鉴定

从小叶黑柴胡(Bupleurum smithii Wolffvar;parvifolium ShanetY.Li)的根中得到3个化合物,柴胡皂甙元A和Q及柴胡皂甙q。柴胡皂甙元Q和柴胡皂甙q为新化合物,根据理化性质和波谱分析,确定其结构分别为齐墩果烷-11,13(18)-二烯-3β,16β,23,28,30-五醇和3β,16β,23,28,3O-五羟基齐墩果烷-11,13(18)-二烯-3-O-β-D-吡喃葡萄糖基(1→6)-[α-L-吡喃鼠李糖基(1→4)]-β-D-吡喃葡萄糖甙。     

Rapid liquid chromatography with tandem mass spectrometry-based screening procedures for studies on the biotransformation of drug candidates.

The accelerated pace of contemporary drug discovery and development in the pharmaceutical industry has generated increasing demands for early information on the metabolic fate of candidate drugs to guide the selection of new compounds for clinical evaluation. In response to these demands, we have developed a procedure for the rapid analysis of complex biological mixtures for the presence of drug-related materials and have embarked on the development of novel computer-based approaches whereby such procedures can be automated. The goal of this work was to rapidly identify drug metabolites (derived either from a single substrate or from a mixture of substrates) formed in vivo or in vitro. The approach that we have developed relies on the use of generic chromatographic and mass spectrometric methods for analysis of mixtures of drugs and metabolites and on correlation analysis of tandem mass spectrometry spectra to distinguish drug-related components from endogenous materials. Cross-correlation of the spectra also is used to identify the relationship between each metabolite and its respective parent drug in the mixture. In this manner, metabolites of a mixture of several drugs may be analyzed in the time it normally would take to analyze the products from a single substrate. We show that this rapid analytical approach can, with only minor sacrifices in the completeness of the data, significantly increase the number of compounds whose metabolic fate can be elucidated in a given time.     

Analysis of peptide mimotopes of Burkholderia pseudomallei exopolysaccharide

Previously two capsule-specific monoclonal antibodies (4VA5 and 3VIE5) were identified as protective against Burkholderia pseudomallei in passive transfer experiments. Panning these antibodies against evolutionary phage libraries identified reactive peptides capable of inhibiting its parent monoclonal from binding to B. pseudomallei. Mice immunized with peptide conjugated to thyroglobulin developed serum antibodies capable of recognizing the immunizing peptide of which a subset recognized exopolysaccharide in the context of whole B. pseudomallei cells. These serum antibodies recognized protease treated B. pseudomallei but not B. thailandensis suggesting that these peptides are mimotopes of the B. pseudomallei capsular exopolysaccharide. In a murine model of acute melioidosis, immunization with the mimotope of the 4VA5 binding site extended the mean time to death to 8.00 days over the 2.18 days afforded by immunization with thyroglobulin alone. This mimotope may be of use in developing an antibody response against B. pseudomallei exopolysaccharide.     

Comparison of the efficacies of various formulations of amphotericin B against murine visceral leishmaniasis.

The antileishmanial efficacies of four proprietary amphotericin B (AmB) formulations (Fungizone, AmBisome, Abelcet, and Amphocil) and an experimental nonionic surfactant vesicle (NIV) formulation were compared in a murine model of acute visceral leishmaniasis. By a multiple-dosing regimen, groups of Leishmania donovani-infected BALB/c mice were treated (2.5 mg of AmB per kg of body weight) on days 7 to 11 postinfection with one of the AmB formulations, and parasite burdens were determined on day 18 postinfection. All of the formulations caused significant suppression parasite burdens in spleens (P < 0.01 to 0.0005) and livers (P < 0.0005) compared with those in the spleens and livers of the controls. In addition, a significant suppression of parasite burdens in bone marrow (P < 0.0005) compared to the burdens in the bone marrow of the controls was obtained for all the formulations except Abelcet, which was inactive at this site. On the basis of their overall efficacies (activity against liver, spleen, and bone marrow parasites), the formulations could be ranked as follows: Amphocil = AmBisome > AmB-NIV > Abelcet >> Fungizone. On the basis of spectrophotometric measurements, AmB was shown to exist in a predominantly aggregated state in all of the formulations. Although incubation in 50% serum altered the degree of aggregation, the AmB remained predominantly aggregated, indicating that the AMB-lipid complex in all of the formulations was physically stable. The results of the study showed that antiparasitic efficacy is associated positively with the degree of AmB aggregation in the presence of serum.