2-Naphthol levels and genotoxicity in rubber workers

Urinary bladder cancer is a historical disease of rubber workers often been associated with exposure to aromatic amines such as 2-naphthylamine. While exposure to these compounds has decreased markedly over time, the bladder cancer risk has not decreased in direct proportion. Polycyclic aromatic compounds (PAC) are candidates for urinary bladder cancer causation. We determined pre- and post-exposure urinary levels of 2-napthol (2NAP), the major metabolite of a model volatile PAC, in a group of non-smoking rubber workers. Pre- and post-exposure urine samples were collected from 43 non-smoking workers. Overall mean post-shift 2-naphthol levels were increased (13.95 ± 28.4 μg/l), but non-significantly compared to samples collected pre-exposure (7.97 ± 22.1 μg/l; p=0.29). The greatest difference was observed in the curing department where post-exposure samples were 4.5 fold higher, post shift samples were significantly higher in production workers as compared to non-production workers (p=0.02). Levels of 2NAP were not correlated with levels of carcinogen-DNA adducts in exfoliated urothelial cells nor with other estimates of exposure or effect. These data suggest that post-shift urinary 2NAP levels are increased, particularly in the curing department. However, the differences were not significantly different overall and urinary 2NAP levels did not predict the level of carcinogen DNA adducts in exfoliated urothelial cells.     

Crystal Structures of a New Polymorphic Form of Gabapentin Monohydrate and the E and Z Isomers of 4‐Tertiarybutylgabapentin

Gabapentin, a widely used antiepileptic drug, crystallizes in multiple polymorphic forms. A new crystal form of gabapentin monohydrate in the space group Pbca is reported and the packing arrangement compared with that of a previously reported polymorph in the space group P2₁/c [Ibers, J.A. (2001) Acta Crystallogr; C57:641]. Gabapentin polymorphs can also occur from a selection of one of the two distinct chair forms of the 1,1‐disubstituted cyclohexane. Crystal structures of the E and Z isomers of 4‐tert‐butylgabapentin provide models for analyzing anticipated packing modes in the conformational isomers of gabapentin. The E isomer crystallized in the space group Pca2₁, while the Z isomer crystallized in the space group P2₁/c. The crystal structure of E‐4‐tert‐butylgabapentin provides the only example of a structure in a non‐centrosymmetric space group. Crystal structures of the hydrochloride and hydrobromide salts of 4‐tert‐butyl derivatives are reported. The results suggest that for gabapentin, a large ‘polymorph‐space’ may be anticipated, in view of the multiple conformational states that are accessible to the molecule.     

气固顶空GC法测定难溶性植入剂中环己烷残留

目的 测定难溶性植入剂中环己烷残留量。方法 研碎供试品，置针管中于60℃保温作气固顶空平衡，顶空气以气相色谱法测定，氢焰检测器测定，SE—30固定相，柱温80℃。结果 精密度RSD为2．8％，回收率101．4％，10～110μg／L范围内线性良好，检出限3．4Pg／L。结论 气固顶空CG法是检测难溶性固体药物的有机溶剂残留量可靠的方法。     

维生素A胶丸含量测定方法的研究

目的：改进维生素A胶丸的含量测定方法。方法；用盐酸溶解维生素A胶丸的胶壳后，以环己烷萃取内容物，采用紫外分光光度法测定含量。结果：该方法与药典方法的测定结果无显著性差异，RSD为1．6％(n=8)。结论：方法操作简便，重现性好，可作为维生素A胶丸的含量测定方法。     

Branched Versus Linear Polyisoprene: Flory–Huggins Interaction Parameters for their Solutions in Cyclohexane

Flory‐Huggins interaction parameters were determined as a function of composition for solutions of linear and of branched polyisoprene in cyclohexane (CH) at 25, 45, and 65 °C by means of vapor pressure measurements (moderate to concentrated solutions) and by vapor pressure osmometry (dilute solutions). The results demonstrate that CH is a considerably worse solvent for branched polyisoprene than for the linear analog at all temperatures and at all compositions. This observation corroborates the expectation based on a recent phenomenological approach, which accounts explicitly for the incapability of the segments of an individual polymer molecule to spread out over the entire volume of the system and for its ability to adjust its chain conformation to an altering molecular environment.

     

环己烷氧化过程的模拟与分析

建立了适用于工业反应器的环己烷无催化氧化动力学模型和反应器数学模型,根据无催化氧化工艺的指导思想,把环己基过氧化氢的选择率和总的选择率作为氧化反应主要的工艺指标,对温度、压力、气相进口氧气含量、气液流量、反应器个数等因素进行模拟分析,从而为工业反应器的优化设计和操作提供依据。     

顶空气相色谱法测定一次性使用输液器中环己烷残留量

目的 采用顶空气相色谱法对一次性使用输液器中黏合剂环己烷的残留进行检测.方法 色谱柱为HP-5石英毛细管柱(30m×0.32 mm×0.25 μm),柱温采用程序升温,检测器为氢火焰离子化检测器,检测器温度为250℃,进样口温度为130℃,分流比为20∶1,以15％乙醇为溶解介质.结果 该方法的检测限可达12 ng/mL,检测浓度的线性范围为0.10～50.57 μg/mL (r=0.999 5),平均回收率为93.6％.结论 本方法简单、快速、准确性高、重复性好,能够满足一次性使用输液器中环己烷残留量检测的需要.     

Identification,Synthesis, and Characterization of a Major Circulating Human Metabolite of TRPV4 Antagonist GSK2798745

GSK2798745, an antagonist of the transient receptor potential vanilloid 4 (TRPV4) ion channel, was recently investigated in clinical trials for the treatment of cardiac and respiratory diseases. Human plasma and urine samples collected from healthy volunteers following oral administration were analyzed to identify circulating and excreted metabolites of the parent drug. One major circulating metabolite (1) was found in pooled human plasma samples, accounting for approximately half of the observed drug-related material. Isolation of metabolite 1 from urine samples followed by MS and NMR studies led to a putative structural assignment of 1 where hydroxylation of GSK2798745 occurred on the central ring, producing a penta-substituted cyclohexane structure containing three stereocenters. Two unique chemical syntheses of the proposed structure were developed to confirm the identity of metabolite 1 and provide access to gram quantities for biological characterization.     

Microencapsulation of hydroxyzine HCl by thermal phase separation: in vitro release enhancement and in vivo pharmacodynamic evaluation

The systemic effect of hydroxyzine hydrochloride following its oral administration or topical application is associated with non compliant anticholinergic effect. Subsequently, the present study aims to prepare microcapsules loaded with hydroxyzine hydrochloride enabling its controlled release into the skin and reducing the side effect of its systemic absorption. The microcapsules were prepared by thermal phase separation method using ethyl cellulose/cyclohexane. Optimization of the formulation parameters was carried out by: (1) varying the type and the concentration of the coacervation inducer with microcapsules prepared with three different core: wall ratios, (2) by using ethyl cellulose with two different viscosities, (3) and by the addition of pore inducers such as pregelatinized starch and sucrose in order to enhance the drug release. Microcapsules of 99% encapsulation efficiency were prepared using 1% w/v polyisobutylene, and 1:0.1 core: wall ratio. The highest percent of drug is released after 9 h from microcapsules prepared using 1:0.1 core :wall ratio. Almost 100% drug was released after 3 h, from the same microcapsules prepared with pregelatinized starch that acts as a core coated with the drug. The pharmacodynamic effect of the chosen preparation was tested on the shaved back of histamine sensitized rabbits. Histopathological studies were driven for the detection of the healing of inflamed tissues.     

Study of the conformational profile of the cyclohexane analogs of l‐phenylalanine

Abstract: The conformational profile of the conformationally constrained cyclohexane analogs of phenylalanine (1‐amino‐2‐phenylcyclohexanecarboxylic acids, c₆Phe) was assessed using computational methods. For this purpose, the conformational space of the N‐acetyl methylamide derivatives of the stereoisomers (2S,3R)c₆Phe and (2S,3S)c₆Phe was explored by computing their respective Ramachandran maps, and low‐energy minima were characterized at molecular mechanics level by means of the amber program, using the parm94 force field set of parameters. In order to assess the performance of the molecular mechanics calculations, each of the low‐energy conformations was also investigated further at the ab initio level. Accordingly, the molecular mechanics geometries were used as starting conformations to perform full geometry optimizations at the Hartree‐Fock level, using a 6‐31G(d) basis set. Analysis of the results revealed that the cyclohexane structure directly induces some restrictions on the backbone, and constrains the orientation of the aromatic side‐chain to two narrow regions for each stereoisomer. The conformational profile of these amino acids is then explained on the grounds of the interaction between the rigidly held phenyl ring and the main chain NH and CO groups. The results obtained are in good accordance with the experimental observations.