Cigarette smoke toxicants alter growth and survival of cultured mammalian cells.

Our purpose was to determine the effects of six cigarette toxicants (pyridine, nicotine, 2-ethylpyridine, 3-ethylpyridine, p-cresol, and pyrazine) on three types of cultured mammalian cells (human umbilical vein endothelial cells [HUVECs], human microvascular endothelial cells [HMVECs], and NIH 3T3 cells) using a cell proliferation/survival assay. Synchronized cells were cultured in proliferation or survival medium containing various doses (10(-18)M-10(-2)M) of the tested chemicals. After 48 h, cells were counted using a hemacytometer. The no observable adverse effect level (NOAEL), lowest observable adverse effect level (LOAEL), and the efficacy were determined for each compound in the cell proliferation and survival assays. Pyridine and p-cresol did not show significant effects with any cell types, except at high doses. Derivitization of the pyridine ring altered its potency, especially when an ethyl group or nitrogen was added. In survival medium, nicotine stimulated proliferation of all three cell types at doses found in smoker's serum (10(-8)M-10(-7)M). For HUVEC and HMVEC, 2-ethylpyridine, 3-ethylpyridine, and pyrazine inhibited proliferation in proliferation medium and induced cell death in survival medium at attomolar and femtomolar doses. All chemicals, except pyridine and pyrazine, stimulated NIH 3T3 cell proliferation at low doses and induced cell death at high doses. LOAELs and efficacies revealed that endothelial cells from a developing organ (umbilical cord) were more sensitive to these chemicals than endothelial cells from an adult organ (lung). 3-Ethylpyridine and pyrazine, which induced cell death at low doses, are added to consumer products and should be subjected to further toxicological testing.     

Syntheses,Cholinesterases Inhibition,and Molecular Docking Studies of Pyrido[2,3‐b]pyrazine Derivatives

Cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), have a role in cholinergic deficit which evidently leads to Alzheimer's disease (AD). Inhibition of cholinesterases with small molecules is an attractive strategy in AD therapy. This study demonstrates synthesis of pyrido[2,3‐b]pyrazines ( 6a ‐ 6q ) series, their inhibitory activities against both cholinesterases, AChE and BChE, and molecular docking studies. The bioactivities data of pyrido[2,3‐b]pyrazines showed 3‐(3′‐nitrophenyl)pyrido[2,3‐b]pyrazine 6n a potent dual inhibitor among the series against both AChE and BChE with IC₅₀ values of 0.466 ± 0.121 and 1.89 ± 0.05 μm , respectively. The analogues 3‐(3′‐methylphenyl)pyrido[2,3‐b]pyrazine 6c and 3‐(3′‐fluorophenyl)pyrido[2,3‐b]pyrazine 6f were found to be selective inhibition for BChE with IC₅₀ values of 0.583 ± 0.052 μm and AChE with IC₅₀ value of 0.899 ± 0.10 μm , respectively. Molecular docking studies of the active compounds suggested the putative binding modes with cholinesterases. The potent compounds among the series could potentially serves as good leads for the development of new cholinesterase inhibitors.     

Investigating a persistent odor at an aircraft seat manufacturer

An aircraft seat manufacturing company requested a NIOSH health hazard evaluation to help identify a strong odor that had persisted throughout the facility for over a year. Employees reported experiencing health effects thought to be related to the odor.

We collected and analyzed area air samples for volatile organic compounds, endotoxin, bacterial and fungal metagenome, and metalworking fluid aerosol. Bulk metalworking fluid samples were analyzed for endotoxin, bacterial and fungal metagenome, and viable bacteria and fungus. We also evaluated the building ventilation systems and water diversion systems. Employees underwent confidential medical interviews about work practices, medical history, and health concerns.

Based on our analyses, the odor was likely 2-methoxy-3,5-dimethylpyrazine. This pyrazine was found in air samples across the facility and originated from bacteria in the metalworking fluid. We did not identify bacteria known to produce the compound but bacteria from the same Proteobacteria order were found as well as bacteria from orders known to produce other pyrazines. Chemical and biological contaminants and odors could have contributed to health symptoms reported by employees, but it is likely that the symptoms were caused by several factors.

We provided several recommendations to eliminate the odor including washing and disinfecting the metalworking machines and metalworking fluid recycling equipment, discarding all used metalworking fluid, instituting a metalworking fluid maintenance program at the site, and physically isolating the metalworking department from other departments.     

四甲基吡嗪对内毒素血症小鼠的保护作用及其与血小板活化因子的关系(英文)

研究四甲基吡嗪（ＴＭＰ）对内毒素血症小鼠的保护作用及其与血小板活化因子（ＰＭ）的关系．方法：给 ＴＭＰ处理的小鼠 ｉｖ　 ＬＰＳ,观察其存活率及血清ＰＡＦ水平．体外用ＬＰＳ刺激小鼠ＰＭφ,测定 ＰＭ及 ＰＬＡ２和乙酰辅酶 Ａ乙酰基转移酶的活性．结果：ＴＭＰ明显提高小鼠存活率和降低血清ＰＡＦ水平．体外,ＴＭＰ（０．０５－５０μｍｏｌ· Ｌ－１）剂量依赖性减少ＰＭφ释放ＰＡＦ［１２．７±１．６）,（８．９±１．２）,（６．９±０．８）,（５．５±１．０）μｇ·Ｌ－１,Ｐ＜０．０１］,降低ＰＬＡ２活性肝（１４９．９±２．８）（１１７．５±２．０）,（８９．６±２．０）,（７５．０±２．８） Ｕ,Ｐ＜０．０１］和乙酰辅酶Ａ乙酰基转移酶活性［ＰＡＦ（９．５±０．７）,（５．２± ０．７）,（２．９±０． ３）,（２．５±０． ３）μｇ· ｇ－１（ｐｒｏｔｅｉｎ）·ｍｉｎ－１, Ｐ＜０．０１］．结论： ＴＭＰ对内毒血症小鼠有保护作用,其机制是通过抑制 ＰＬＡ２和乙酰辅酶Ａ乙酰基转移酶的活性而抑制ＰＡＦ的合成。     

四甲基吡嗪对低密度脂蛋白损伤内皮细胞的保护作用(英文)

观察了四甲基吡嗪(TMP)对LDL损伤内皮细胞(EC)的保护作用。LDL(1.5 mgprotein·ml~(-1))显著增高EC的MDA含量,抑制SOD活性,降低cGMP和epoprostenol含量。LDL的毒性作用可被TMP(20mg和150mg·L~(-1)所消除。结果提示,TMP可通过促进epoprostenol的生成和/或释放保护EC。     

Pyrazine derivatives: a patent review (2008 – present)

Introduction: Pyrazines derivatives are well-known and important two-nitrogen-containing six-membered ring aromatic heterocyclic compounds and can carry substituents at one or more of the four ring carbon atoms. Pyrazines are a class of compounds that occur in nature and various methods have been worked out for their synthesis. A large number of pyrazine derivatives have been found to possess diverse pharmacological properties, which has caused an increasing interest by researchers in this core.

Area covered: This review provides a comprehensive review of the pyrazines derivatives patented between the years 2008 to 2012 as potential active compounds. The patent databases SciFinder and esp@cenet were used to locate patent applications that were published between 2008 to present. Information from articles published was also included.

Expert opinion: The diversity of pyrazines derivatives found in organisms in nature with different applications began to arouse the interest of research in this nucleus. The pyrazines derivatives have numerous prominent pharmacological effects, such as antibacterial, antifungal, antimycobacterial, anti-inflammatory, analgesic, anticancer for different types, antidiabetic, treatment for arteriosclerosis, antiviral. It's the time to conduct further studies aimed at rationalizing the biological activities found in order to develop more effective and clinically interesting compounds.     

基于气相-离子迁移谱的不同干燥方式下金银花挥发性成分分析

目的 通过分析不同干燥方式（晒干、阴干、低温烘干、蒸制杀青-烘干）对金银花Lonicerae Japonicae Flos挥发性成分的影响,发现金银花保留挥发性成分的最佳干燥方式。方法 采用气相离子迁移谱（GC-IMS）技术分析不同干燥方式下金银花中挥发性成分并对其进行差异分析。结果 4种干燥方式下,金银花中共鉴定出48个挥发性成分,包括醛类（14个）、醇类（10个）、酮类（5个）、吡嗪类（6个）、吡咯类（1个）、呋喃类（2个）、酯类（5个）、酸类（2个）、其他类（3个）。经过显著性差异检验,发现了34个差异性挥发性成分。晒干法中挥发性成分种类更为丰富,总体含量更高;蒸制杀青-烘干法中挥发性成分种类最少,总体含量较低。阴干与低温烘干法之间差异较小,这2种方法保留挥发性成分的能力优于蒸制杀青-烘干法,但次于晒干法。结论 不同干燥方式下挥发性成分存在明显差异,综合对比后得出晒干是金银花保留挥发性成分和风味的最佳干燥方式,为金银花干燥方式的优化、芳香健康功效及风味品质的研究提供科学理论指导。     

四甲吡嗪对活性氧自由基的清除作用(英文)

用电子自旋共振技术和化学发光法研究了四甲吡嗪(川芎嗪,Lig)对活性氧自由基的清除作用,Lig 25 mg·ml~(-1)对两种水溶液体系产生的O_2和OH的清除率分别为100％和44％。该作用被化学发光法证实。Lig 25mg·ml~(-1)对一种脂溶液体系产生的LOO的清除达80％。提示两性药物Lig能直接清除具细胞毒性作用的自由基(O_2,LOO,OH)。     

Preparation of labelled 2‐methoxy‐3‐alkylpyrazines: synthesis and characterization of deuterated 2‐methoxy‐3‐isopropylyrazine and 2‐methoxy‐3‐isobutylpyrazine

Efficient synthetic routes for a number of deuterated analogues of 2‐methoxy‐3‐isopropylpyrazines and 2‐methoxy‐3‐isobutylpyrazines have been developed involving the condensation of glyoxal with an α‐amino acid amide followed by methylation with iodomethane. In this way [²H₃]2‐methoxy‐3‐isopropylpyrazine, 2‐methoxy‐3‐isopropyl‐[²H₂]pyrazine, [²H₃]2‐methoxy‐3‐isopropyl‐[²H₂]pyrazine, [²H₃]2‐methoxy‐3‐isobutylpyrazine; 2‐methoxy‐3‐isobutyl‐[²H₂]pyrazine and [²H₃]2‐methoxy‐3‐isobutyl‐[²H₂]pyrazine were prepared and characterized by NMR and MS. Copyright © 2002 John Wiley & Sons, Ltd.     

四甲吡嗪对人类白细胞呼吸爆发氧代谢的影响

目的研究四甲吡嗪(川芎嗪,Lig)对白细胞呼吸爆发期间氧消耗和过氧化物的影响。方法采用电子自旋共振自旋捕集技术,自旋探针氧测定法和化学发光法检测白细胞呼吸爆发期间氧消耗和活性氧自由基。结果Lig对白细胞呼吸爆发期间的氧消耗无明显影响(P＞0.05),但能明显抑制其产生的化学发光(P＜0.01),这是Lig清除O2和OH·的结果。结论Lig可以不抑制白细胞氧化代谢的功能而通过清除氧自由基防止白细胞对组织的损伤。