抗真菌剂三氮唑含硫化合物的合成

合成了１３个三氮唑含硫化合物，均为未见文献报道的新化合物，对所合成的化合物，选择三种常见真菌进行体外最低抑菌浓度（ＭＩＣ）的测定，结果表明它们均有较好的抗真菌活性，有些化合物抑菌活性极高，有进一步研究和开发前景。     

提高H2O2/甲酸体系选择性氧化抽提脱硫效率的研究

为了降低焦化蜡油(CGO)-甲酸／H2O2选择性氧化体系中H2O2的无效分解速度，屏蔽重金属离子对H2O2分解的催化效应，考察了造纸行业中常用的硅酸钠、硅酸镁和乙二胺四乙酸(EDTA)等稳定剂和螯合剂的加入对有机溶剂抽提后CGO中含硫量的影响。实验结果表明，EDTA可以很好地和重金属离子螯合，氧化后CGO抽余油中硫含量大幅降低。     

环氧乙烷对大鼠DNA损伤机理的研究

为探讨环氧乙烷（ＥｔＯ）对ＤＮＡ分子水平的损伤作用，采用血红蛋白基因特异性的单引物，对用ＥｔＯ染毒不同时间的Ｗｉｓｔａｒ雄鼠和对照个体的肝、肾、睾丸等组织的ＤＮＡ进行半随机ＰＣＲ扩增。结果显示：在吸入染毒（８００ｍｇ／ｍ３）６～９周条件下，ＥｔＯ可引起肝、肾、睾丸等组织不同程度的ＤＮＡ损伤，其中睾丸组织ＤＮＡ损伤最为严重。     

Identification of N-(deoxyguanosin-8-yl)-4-azobiphenyl by (32)P-postlabeling analyses of DNA in human uroepithelial cells exposed to proximate metabolites of the environmental carcinogen 4-aminobiphenyl

DNA adducts formed in human uroepithelial cells (HUC) following exposure to N-hydroxy-4-aminobiphenyl (N-OH-ABP), the proximate metabolite of the human bladder carcinogen 4-aminobiphenyl (ABP), were analyzed by the (32)P-postlabeling method. Two adducts detected by (32)P-postlabeling were previously identified as the 3',5'-bisphospho derivatives of N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP) and N-(deoxyadenosin-8-yl)-4-aminobiphenyl (dA-C8-ABP) (Frederickson S et al. [1992] Carcinogenesis 13: 955-961; Hatcher and Swaminathan [1995b] Carcinogenesis 16: 295-301). In contrast to the dG-C8-ABP adduct, which was 3'-dephosphorylated by nuclease P1, dA-C8-ABP was resistant to nuclease P1, thus providing an enrichment step before postlabeling. Autoradiography of the two-dimensional thin-layer chromatogram of the postlabeled products obtained following nuclease P1 digestion revealed several minor adducts, one of which has been identified in the present study. Postlabeling analyses following nuclease P1 digestion of the products obtained from the reaction of N-acetoxy-4-aminobiphenyl with deoxyguanosine-3'-monophosphate (dGp) demonstrated the presence of this minor adduct. The 3'-monophosphate derivative of the adduct was subsequently chromatographically purified and subjected to spectroscopic analyses. Based on proton NMR and mass spectroscopic analyses of the synthetic product, the chemical structure of the adduct has been identified as N-(deoxyguanosin-N(2)-yl)-4-azobiphenyl (dG-N==N-ABP). (32)P-Postlabeling analysis of the nuclease P1-enriched DNA hydrolysate of HUCs treated with N-OH-ABP or N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP) showed the presence of the dG-N==N-ABP adduct. It was also detected in calf thymus DNA incubated with HUC cytosol and N-OH-ABP in the presence of acetyl-CoA, or incubated with HUC microsomes and N-OH-AABP. These results demonstrate that in the target cells for ABP carcinogenesis in vivo, N-OH-ABP and N-OH-AABP are bioactivated by acyltransferases to reactive arylnitrenium ions that covalently interact at the N2 position of deoxyguanosine in DNA.     

Dissociation of hepatitis A virus antigen-anti-HAV antibody complexes by 2-mercaptoethanol and dithiothreitol

Intravenous inoculation of two marmosets and one chimpanzee with hepatitis A virus (HAV) resulted in the replication of virus in liver, excretion of HAV particles in stool, and the appearance of circulating antibodies specific for hepatitis A. The development of an early antibody response in the chimpanzee and in one of the two infected marmosets was shown to interfere with the serologic detection of HAV antigen (HAV Ag) in homogenates of acute phase liver tissue obtained from these animals. Treatment of HAV Ag-positive and IgM anti-HAV-positive liver homogenates with thiol reducing compounds was shown to release HAV Ag from in vitro formed immune complexes. The increased RIA response for HAV Ag in homogenates treated with 2-mercaptoethanol (2-ME) or dithiothreitol (DTT) was further shown not to be due to activation of HAV Ag itself or to a nonspecific effect on the RIA coating antibody, radiolabeled probe, or homogenized liver tissue. IgG and IgM double-antibody sandwich RIAs for HAV Ag were also compared for their ability to detect HAV Ag under reducing and nonreducing conditions. Application of the 2-ME or DTT treatment procedure to the serologic detection of other viral antigens or viruses whose presence in blood, stool, tissue macerate, or other milieu may be masked by specific antibody appears to be feasible.     

Polyphenolic compounds from propolis modulate immune responses and increase host resistance to tumour cells

Propolis contains a variety of polyphenolic compounds. We investigated the effect of a water-soluble derivatives of propolis (WSDP) and polyphenolic compounds, components of propolis, on growth of Ehrlich ascites tumour (EAT) in mice. Tumour in peritoneal cavity was produced by 2×10⁶ EAT cells. WSDP and polyphenolic compounds (caffeic acid-CA, caffeic acid phenethyl ester-CAPE and quercetin-QU) were given to mice perorally (po). It was found that the volume of ascitic fluid induced by EAT cells and total number of cells present in the peritoneal cavity was markedly reduced in EAT-bearing mice treated with test components and the survival time of treated mice was prolonged. Inhibition of EAT growth was due to their effect on the immune system of mice. When innate and acquired immune responses were evaluated, a dose-related increase of cytotoxic T-cell, NK and B cells activity was observed in test components-treated mice. Furthermore, exposure of animals to test components increased functional activity of macrophages to produce factors regulating the function of B-, T-, and NK- cells respectively. In conclusion, these findings imply that the antitumour activity of WSDP and polyphenolic compounds of propolis enhanced host resistance in the EAT tumour model, increasing the activities of macrophages, cytotoxic T cells, B cells and NK cells.     

Contraluminal transport of organic cations in the proximal tubule of the rat kidney

In order to study the quantitative structure/activity relationship of organic cation transport across the contraluminal side of the proximal renal tubule cell, the stopped-flow capillary microperfusion method was applied and the inhibitory potency (apparent K _i values) of different homologous series of substrates against N ¹-[³H]methylnicotinamide (NMeN⁺) transport was evaluated. Aniline and its ring- or N-substituted analogues as well as the aminonaphthalines do not interact with the contraluminal NMeN⁺ transporter except for the quaternary trimethylphenylammonium and pararosaniline, which bear a permanent positive charge, and for 1,8-bis-(dimethylamino)naphthaline, which forms an intramolecular hydrogen bond. If, however, one or more than one methylene group is interposed between the benzene ring and the amino group, the compounds interact with the contraluminal NMeN⁺ transporter in proportion to their hydrophobicity parameter, i.e. the octanol/water partition coefficient (log octanol). The catecholamines and other hydroxyl-substituted phenylethyl analogues also follow this rule. In addition, the N-heterocyclic pyridine, quinoline, isoquinoline and acridine analogues also interact with the contraluminal NMeN⁺ transporter, when their pK _a values are higher than 5.0, and, an inverse correlation between pK _a and log K _{i, NMeN} was observed. An exception to this rule are those hydroxy compounds of pyridine, quinoline and isoquinoline that show tautomerism. These compounds slightly inhibit NMeN⁺ transport despite low pK _a values. The quaternary nitrogen compounds of aniline and the N-heterocyclic analogues, as far as tested, all interact with the contraluminal NMeN⁺ transporter in relation to their hydrophobicity. The data indicate that the contraluminal NMeN⁺ transporter interacts with N-compounds according to their hydrophobicity and/or according to their basicity (affinity to protons). The reason for deviation of the aniline analogues and the OH-tautomeric heterocyclic N-compounds from this behaviour is discussed.     

Effects of a feed additive blend on broilers challenged with heat stress

ABSTRACT

We evaluated a blend of medium-chain fatty acids (MCFA), organic acids, and a polyphenol antioxidant on gut integrity. Eighty Ross Broilers were exposed to 20–22°C (control – normothermic) or to 35–39.5°C (heat stress) for eight hours a day for a period of 1 or 5 days. Birds were fed a standard diet, or a diet supplemented with the test blend. Thereafter, birds were euthanized, and intestinal sections were excised for morphological, morphometric and gene expression analyses. Blood samples were collected for glucose-6-phosphate dehydrogenase (G6PD), glutathione peroxidase (GSH-Px) activity and trolox equivalent antioxidant capacity (TEAC) determination. Heart and liver tissues were used to quantify the expression of heat shock proteins 60 and 70 (HSP60 and HSP70, respectively) and inhibitor of kappa light chain gene enhancer in B cells alpha (IKBA). The jejunum was the most sensitive intestinal section, where heat stress modulated the expression of HSP70, of the inflammatory markers IKBA, interleukin 8 (IL-8), interferon gamma (IFNγ), and toll-like receptor 4 (TLR4). Moreover, expression of tight junctions (CLDN1, ZO1 and ZO2) and nutrient transporters (PEPT1 and EAAT3) was modulated especially in the jejunum. In conclusion, the feed additive blend protected intestines during heat stress from the decrease in villus height and crypt depth, and from the increase in villus width. Especially in the jejunum, heat stress played an important role by modulating oxidative stress and inflammation, impairing gut integrity and nutrient transport, and such deleterious effects were alleviated by the feed additive blend.

RESEARCH HIGHLIGHTS

• Jejunum is the most sensitive intestinal segment during heat stress.

• Heat stress affects the expression of tight junctions and nutrient transporters.

• Feed management helps to alleviate the disturbances caused by heat stress.

• A blend of MCFA, organic acids and a polyphenol protects broilers under heat stress.

     

Evaluation of the Chemical Composition of Dacryodes Edulis and Raphia Hookeri Mann and Wendl Exudates used in Herbal Medicine in South Eastern Nigeria

The phytochemical contents and medicinal values of Dacroydes edulis and Raphia hookeri exudates were investigated. Phytochemical screening of the plant showed that they contain the presence of bioactive compounds comprising saponins (2.08–3.98mg 100g⁻¹), alkaloids (0.28–0.49 mg 100g⁻¹), tannins (0.47–0.72 mg 100g⁻¹), flavonoids (0.26–0.39 mg 100g⁻¹), and phenolic compounds (0.01–0.05 mg 100g⁻¹). The carbohydrates, lipids and protein content were 77.42–78.90%, 2.02–4.185% and 16.63–18.38% respectively. The exudates are a good source of water soluble vitamins; ascorbic acid (7.04–26.40 mg 100g⁻¹), niacin (3.12–4.00 mg 100g⁻¹), riboflavin (0.14–0.54 mg 100g⁻¹) and thiamine (0.15–0.22 mg 100g⁻¹),). Both plants exudates are good sources of minerals such as Ca, Mg, P, Fe, Zn, Cu and Mn while Cr and Co were trace. These results indicate that exudates can be potential sources of feedstock for the pharmaceutical industry.