Glutathione depletion is a major determinant of inhaled naphthalene respiratory toxicity and naphthalene metabolism in mice.

Naphthalene (NA) is metabolized to highly reactive intermediates that are primarily detoxified by conjugation to glutathione (GSH). Intraperitoneal administration of naphthalene causes substantial loss of both hepatic and respiratory GSH, yet only respiratory tissues are injured in mice. The liver supplies GSH to other organs via the circulation, making it unclear whether respiratory GSH losses reflect in situ respiratory depletion or decreased hepatic supply. To address this concern, mice were exposed to naphthalene by inhalation (1.5-15 ppm; 2-4 h), thereby bypassing first-pass hepatic involvement. GSH levels and histopathology were monitored during the first 24 h after exposure. Half of the mice were given the GSH depletor diethylmaleate (DEM) 1 hour before naphthalene exposure. Lung and nasal GSH levels rapidly decreased (50-90%) in mice exposed to 15 ppm naphthalene, with cell necrosis throughout the respiratory tract becoming evident several hours later. Conversely, 1.5 ppm naphthalene caused moderate GSH loss and only injured the nasal olfactory epithelium. Neither naphthalene concentration depleted hepatic GSH. Animals pretreated with DEM showed significant GSH loss and injury in nasal and intrapulmonary airway epithelium at both naphthalene concentrations. DEM treatment, perhaps by causing significant GSH loss, decreased water-soluble naphthalene metabolite formation by 48% yet increased NA-protein adducts 193%. We conclude that (1) GSH depletion occurs in airways independent of hepatic function; (2) sufficient GSH is not supplied by the liver to maintain respiratory GSH pools, or to prevent injury from inhaled naphthalene; and (3) GSH loss precedes injury and increases protein adduct formation.     

羧基化聚乙烯基萘纳米微球的制备和应用

以乙烯基萘(VN)为聚合单体,采用乳液聚合法制备聚乙烯基萘(PVN)纳米微球。通过对其羧基化与β2微球蛋白(β2-M)抗体偶联,制成免疫检测试剂。分别用聚苯乙烯(PS)和 PVN 检测试剂测定β2-M 含量,数据经统计学处理和分析,对自制的 PVN 纳米微球胶乳增强免疫比浊( LE-TIA)检测试剂的性能进行评价。自制的羧基化 PVN 纳米微球免疫试剂成功对标准样本进行了检测并在一定范围内有较好的线性,比 PS 检测试剂更加灵敏。利用该研究采用的方法和条件可以成功制备粒径大小可控、单分散的羧基化PVN 纳米微球,是比 PS 更优的 LETIA 新载体,具有很好的临床应用前景。     

Isolation,synthesis and characterization of ω-TRTX-Cc1a,a novel tarantula venom peptide that selectively targets L-type CaV channels

Spider venoms are replete with peptidic ion channel modulators, often with novel subtype selectivity, making them a rich source of pharmacological tools and drug leads. In a search for subtype-selective blockers of voltage-gated calcium (Ca_V) channels, we isolated and characterized a novel 39-residue peptide, ω-TRTX-Cc1a (Cc1a), from the venom of the tarantula Citharischius crawshayi (now Pelinobius muticus). Cc1a is 67% identical to the spider toxin ω-TRTX-Hg1a, an inhibitor of Ca_V2.3 channels. We assembled Cc1a using a combination of Boc solid-phase peptide synthesis and native chemical ligation. Oxidative folding yielded two stable, slowly interconverting isomers. Cc1a preferentially inhibited Ba²⁺ currents (I_Ba) mediated by L-type (Ca_V1.2 and Ca_V1.3) Ca_V channels heterologously expressed in Xenopus oocytes, with half-maximal inhibitory concentration (IC₅₀) values of 825 nM and 2.24 μM, respectively. In rat dorsal root ganglion neurons, Cc1a inhibited I_Ba mediated by high voltage-activated Ca_V channels but did not affect low voltage-activated T-type Ca_V channels. Cc1a exhibited weak activity at Na_V1.5 and Na_V1.7 voltage-gated sodium (Na_V) channels stably expressed in mammalian HEK or CHO cells, respectively. Experiments with modified Cc1a peptides, truncated at the N-terminus (ΔG1–E5) or C-terminus (ΔW35–V39), demonstrated that the N- and C-termini are important for voltage-gated ion channel modulation. We conclude that Cc1a represents a novel pharmacological tool for probing the structure and function of L-type Ca_V channels.     

Structural Effect on Thermal Cure and Property of Naphthalene‐Based Epoxies: Preparation and Characterization

Summary: Three naphthalene‐based epoxy monomers containing different size of linkages between two naphthalene rings: C? C covalent bond ( 1 ), methylene ( 2 ), cycloaliphatic hydrocarbon derived from limonene ( 3 ) were prepared, and the effect of molecular structure on thermal cure behavior and property analyzed. Judged from the combination of the dynamic DSC and isothermal FTIR results, the cure reactivities were found to increase in the order of 1 > 2 > 3 when dicyandiamide was used in the curing systems, and the situation was slightly different in the monomer/4,4′‐methylenedianiline systems. The differences in reactivity as well as in thermal and mechanical properties for the epoxies can be attributed to the differences of configuration and conformational changes during the formation of crosslinked networks. These thermosets exhibited high glass transition temperature (T_g) and had excellent thermal oxidative resistance.

DSC thermograms for epoxy/dicyandiamide systems at a heating rate of 10 °C · min^?1.     

Respiratory diseases caused by occupational exposure to 1,5-naphthalene-diisocyanate (NDI): Results of workplace-related challenge tests and antibody analyses

BACKGROUND: 1,5-naphthalene-diisocyanate (NDI) is an aromatic diisocyanate with a very low vapor pressure which is mainly used in the automotive industry. METHODS: In the present study we described five cases with workplace-related asthma and one case with extrinsic allergic alveolitis associated with pulmonary hemorrhage after NDI exposure. RESULTS: Corresponding to case histories, extrinsic alveolitis on asthmatic reactions in three subjects and a rhinitis reaction in one patient could be reproduced by inhalative challenge tests to NDI at a concentration of 10 ppb. Preliminary IgE and IgG antibody analyses in patients' sera did not produce significantly positive results. CONCLUSIONS: According to the outcome of our tests and in comparison with several other studies, we conclude that NDI should be classified as potent airway-sensitizing substance. Improved workplace conditions and decrease in threshold limit values should therefore be recommended.     

白花前胡地上部分挥发性成分对比

目的:研究白花前胡地上各部位挥发油的化学成分。方法:采用水蒸汽蒸馏法提取白花前胡新鲜地上部分各部位的挥发油,以气相色谱—质谱联用仪测定其化学组分。结果:花中含量较高的成分为氧化石竹烯(26.590%),2,6,6-三甲基双环[3.1.1]-2-烯(13.605%);果中为石竹烯(34.589%),1R-α-蒎烯(14.444%);叶柄中为(1α,4aα,8aα)-1,2,3,4,4a,5,6,8a-八氢-7-甲基-4-亚甲基-1-(1-异丙基)-萘(33.671%),[s-(E,E)]-1-甲基-5-亚甲基-8-(1-异丙基)-1,6-环己烯(22.474%%),1R-α-蒎烯(11.479%);茎中为1R-α-蒎烯(15.544%),[s-(E,E)]-1-甲基-5-亚甲基-8-(1-异丙基)-1,6-环己烯(14.212%),石竹烯(11.551%)。结论:白花前胡地上部分挥发油中,石竹烯类、1R-α-蒎烯含量较高,茎和叶柄挥发油中萘类成分含量较高,在考虑综合利用的同时,应防止人畜中毒。     

降解萘的假单胞菌ND24菌株的分离和萘污染土壤的生物修复

用富集培养法从石油工业废水中分离到高效降解萘的ND24菌株．该菌株能以萘为惟一碳源生长，在48h内将无机盐培养基中2g／L的萘降解98．4％．该菌株还能降解水杨酸、对羟基苯甲酸、邻苯二甲酸和苯乙酸．16SrRNA基因测序和同源序列比对表明，ND24菌株属于假单胞茵（Pseudomonas sp．）．将ND24菌株接种到含有0．2g／dL萘的灭菌土壤中，经过14d室温培养以后，萘的去除率为98．2％．     

Reference Values for Exposure to PAH Contaminants: Comparison of Fish from Ohio and Mid-Atlantic Streams

Reference values for background exposures of benzo[a]pyrene (BAP)- and naphthalene (NAPH)-type metabolites were calculated for white sucker, northern hog sucker, and rock bass from the mid-Atlantic region based on the 90th percentile of a probability-based sample. Preliminary findings are presented for common carp. Bile was collected from fish and assayed for polycyclic aromatic hydrocarbon metabolites using the fluorescent method of Lin et al. Exposure reference values for white sucker were 0.3 μg/mg protein for BAP-type metabolites and 40 μg/mg protein for NAPH-type metabolites. Values from the Mid-Atlantic region were similar to those previously reported for the Eastern Corn Belt Plains (ECBP) ecoregion. Exposure reference values of BAP-type metabolites for rock bass were 0.3 μg/mg protein and 0.4 μg/mg protein for northern hog sucker. Exposure reference values of NAPH-type metabolites for rock bass were 30 μg/mg protein for rock bass and 50 μg/mg protein for northern hog sucker. Provisional values for common carp based on 39 observations are 0.4 μg/mg protein for BAP-type metabolites and 120 μg/mg protein for NAPH-type metabolites. Small streams exhibited the greatest range of exposures, 0.015–0.689 μg/mg protein for BAP-type metabolites and from 5.7 to 159 μg/mg protein for NAPH-type metabolites. Larger streams had 0.11–0.859 μg/mg protein for BAP-type metabolites and 10.2–286.5 μg/mg protein for NAPH-type metabolites. Exposure reference values for BAP and NAPH-type metabolites could be used as a basis of comparison of exposure to PAH contamination.     

Naphthalene cataract in rats and rabbits: a resumé.

The effect of pigmentation on the development of naphthalene cataract in the rabbit and rat is summarized and diseussed. It is concluded that in both species 1,2-dihydroxynaphthalene is the toxic agent; in the rat its enzymic formation is probably largely by way of polyphenol oxidase, whereas in the rabbit catechol reductase probably plays a crucial role.     

Hydrocarbons and metabolites in english sole (Parophrys vetulus) exposed simultaneously to [3H]benzo[a]pyrene and [14C]naphthalene in oil-contaminated sediment

English sole (Parophrys vetulus) were exposed to $\text{[}{}^3\text{H]benzo}\text{[a]}\text{pyrene (B}\text{[a]}\text{P}\text{)}$ and [¹⁴C]naphthalene (NPH) in sediment containing 1% Prudhoe Bay crude oil (PBCO). Bioeoncentration values (pmoles of hydrocarbon equivalents in g of dry tissue/pmoles of hydrocarbon equivalents in g of sedimentassociated water (SAW)) for NPH were greater than corresponding values for B[a]P in tissues of fish exposed for 24 h. However, from 24 to 168 h of the exposure, a substamial decline (P < 0.05) in NPH-derived radioactivity and a significant (P < 0.05) increase in B[a]P-derived radioactivity occurred in most of the tissues examined. When fish were transferred for 24 h to sediment free of radioactivity and PBCO, the retention of B[a]P-derived radioactivity in the tissues of fish was considerably greater than that for NPH.Metabolites of B[a]P and NPH in sediment, SAW, liver and bile of fish were characterized by thinlayer chromatography (TLC). For liver, a two-dimensional TLC was devised to separate B[a]P and its metabolites from liver lipids. An important finding was that liver of English sole metabolized B[a]P to a far greater extent than NPH; at 24 h after the exposure, the ratio of concentrations of B[a]P to its metabolites was 1 to 49 whereas that for NPH was 6 to 1. Larger proportions of glucuronide conjugates than sulfate conjugates of both NPH and B[a]P were present in bile of English sole. Naphthalene was largely converted into a glucuronide conjugate of l,2-dihydro-l,2-dihydroxynaphthalene. A number of metabolites of B[a]P known to be toxic to mammals were detected in both liver and bile including 7,8-dihydro-7,8-dihydroxy B[a]P and its conjugates.These findings of extensive metabolism of B[a]P by fish liver very probably explain why B[a]P is usually not detected in liver of fish even when considerable concentrations of B[a]P are detected in the environment of the fish.