Biosynthesis of monacolins: conversion of monacolin L to monacolin J by a monooxygenase of Monascus ruber

The microbial metabolites monacolins J and L are specific inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase, the rate-limiting enzyme in cholesterol synthesis. The producing strain Monascus ruber M 4681 was found to convert exogenously added monacolin L to J. In this hydroxylation reaction 18O2 was incorporated into monacolin L, giving [18O]-monacolin J. The cell-free extracts of M. ruber quantitatively hydroxylated monacolin L to J, and molecular oxygen was required for the hydroxylation. The enzyme was located in the microsomal fraction and specific for NADPH. The enzyme activity was inhibited by metyrapone, carbon monoxide, sulfhydryl reagents and cytochrome c. The results indicate that monacolin L is the precursor of monacolin J, and that a monooxygenase is involved in this reaction.     

血脂康胶囊中的一个新莫纳克林类似物(英文)

血脂康胶囊(红曲醇提取物)是北京北大维信生物科技有限公司自主研究的特制红曲霉发酵制成的调脂中药。通过血脂康调整血脂的临床观察,发现血脂康可降低各种冠心病相关事件的危险性及各种死亡率。为了解释血脂康的许多临床表现,对血脂康进行系统的成分研究。通过成分分析研究,从血脂康中分离纯化了一个新的莫纳克林类化合物,命名为α,β-dehydromonacolin L(1)及两个已知的莫纳克类化合物monacolin L(2)和3-(2,6-dimethyl-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl)propanoic acid(3)。结合核磁共振和质谱分析确定了化合物的化学结构。     

Cytotoxic monacolin analogs from Monascus purpureus-fermented rice

Two new monacolin analogs, monacolins O (1) and P (2), along with three known analogs, have been isolated from the ethanolic extract of Monascus purpureus-fermented rice. Their structures and absolute configurations were elucidated by spectroscopic methods, especially 2D NMR and CD spectral analyses as well as chemical method. Both 1 and 2 were tested against five tumor cell lines, and compound 1 exhibited selective cytotoxic activity against A2780 and A549 cell lines, with IC₅₀ values of 3.7 and 8.0 μM, respectively.     

Origin of monacolin L from Aspergillus terreus cultures

In freshly harvested Aspergillus terreus cultures grown for the production of lovastatin (formerly called mevinolin), no monacolin L could be detected. However, during the isolation of lovastatin, significant quantities of monacolin L appeared. It has been discovered that a new metabolite structurally related to the members of the monacolin series is present. This metabolite is unstable and under mildly acidic conditions and elevated temperature, it converts to monacolin L. The subject metabolite is proven to be a hydroxylated derivative of dihydromonacolin L identified as 3 alpha-hydroxy-3,5-dihydromonacolin L. It seems that all monacolin L found later during various treatments of the broth and broth extracts is formed from that precursor via a dehydration reaction. The new metabolite was converted to its phenacyl ester, by means of extractive alkylation, for isolation and structure elucidation by chemical, chromatographic and spectroscopic methods. This ester, on standing, gradually formed the corresponding lactone.     

Four new monacolin analogs from Monascus purpureus-fermented rice

Four new monacolin analogs, monacolin T (1), monacolin U (2) 6a-O-methyl-4,6-dihydromonacolin L (3), and 6a-O-ethyl-4,6-dihydromonacolin L (4) were isolated from the ethanolic extract of Monascus purpureus-fermented rice. Their structures were determined by a combination of 1D, 2D NMR experiments (¹H-¹HCOSY, HSQC, HMBC, and ROESY), and mass spectrometry. In vitro cytotoxic assay, all compounds were inactive at the concentration of 10 µM.     

Microbial hydroxylation of compactin (ML-236B) and monacolin K

The Basidiomycete Schizophyllum commune was found to transform compactin (ML-236B) to 8a-hydroxycompactin. This compound was isolated by solvent extraction and column chromatography, and its structure was determined by a combination of IR, UV, 1H NMR and 13C NMR spectroscopy. Monacolin K was also converted to the corresponding hydroxylated analogue. Data on the inhibition of 3-hydroxy-3-methylglutaryl co-enzyme A reductase and sterol biosynthesis in vitro are presented for these hydroxylated compounds.     

Dihydromonacolin L and monacolin X, new metabolites which inhibit cholesterol biosynthesis

Dihydromonacolin L and monacolin X those are structurally related to monacolin K, a potent inhibitor of cholesterol biosynthesis, were isolated from cultures of a mutant of Monascus ruber. The structures of these two metabolites were determined by a combination of physical techniques. Data for dihydromonacolin L and monacolin X as inhibitors of hydroxymethylglutaryl-CoA reductase and sterol biosynthesis in vitro are also given.     

红曲菌发酵黄精渣生产monacolin K的探索性研究

目的开展以紫色红曲菌固体发酵黄精渣生产重要降血脂肪成分monacolin K的探索研究。方法系统考察了红曲菌发酵过程中黄精渣加入量、辅料黄豆粉与米粉的配比、含水量、发酵时间等因素对monacolin K产量的影响。结果在紫色红曲菌(Monascus purpureus)发酵黄精渣生产monacolin K的过程中,当含水量为40%、黄精加入量为70%,米粉与黄豆粉加入量为1∶1,在25℃下发酵30 d,monacolin K的产量可以达到16.21 mg·g~(-1)。结论这一新固体发酵方式既能充分利用黄精深加工废弃物,又能高效产生降血脂生物活性组分,是中药材深加工的一个切实可行的开发方向。     

红曲菌发酵黄精渣审查monacolin K的探索性研究

目的 开展以紫色红曲菌固体发酵黄精渣生产重要降血脂肪成分monacolin K的探索研究。方法 系统考察了红曲菌发酵过程中黄精渣加入量、辅料黄豆粉与米粉的配比、含水量、发酵时间等因素对monacolin K产量的影响。结果 在紫色红曲菌（Monascus purpureus）发酵黄精渣生产monacolin K的过程中，当含水量为40%、黄精加入量为70%，米粉与黄豆粉加入量为1:1，在25 ℃下发酵30 d，monacolin K的产量可以达到16.21 mg·g^-1。结论 这一新固体发酵方式既能充分利用黄精深加工废弃物，又能高效产生降血脂生物活性组分，是中药材深加工的一个切实可行的开发方向。     

子宫中隔切除术后预防粘连方法探讨

目的 探讨子宫中隔并不孕患者宫腔镜术后不同处理方法预防宫腔粘连的效果.方法 55例子宫中隔并不孕患者行腹腔镜监护下宫腔镜子宫中隔切除术(TCRS),术后针对不同患者采用不同术后处理措施,包括宫腔放置与不放IUD,是否进行人工周期治疗,部分患者术后使用GnRH-a类药物治疗术后第1、3个月行宫腔镜检查随访,宫内放置IUD的患者;于术后第3个月取环.结果 54例患者术后进行宫腔镜检查随访,其中40例分别于术后第1、3个月完成了术后2次宫腔镜检查,另14例只完成一次检查.宫腔术后放环与否对术后宫腔形态影响无差异(P>0.05),术后使用人工周期治疗患者较未使用者子宫内膜厚,此两者术后第3个月宫腔镜检查发现宫底创面均已有内膜覆盖.使用GnRH-a类药物患者术后官腔形态满意.结论 TCRS术后宫腔放置IUD无助于预防术后粘连的发生;术后人工周期治疗应更个体化并有针对性的使用GnRH-a类药物治疗.术后及时进行宫腔镜检查随访可防止术后宫底新粘连的形成.     

10例狂犬病误诊原因分析

狂犬病近年来发病率有逐年增加的趋势,近十二年来,我们共遇见狂大病２３例,其中１０例被误诊为其它疾病,现就其误诊原因进行分析如下。１临床资料１．１ 一般资料：男８例,女２例;年龄最大７８岁,最小４岁。发病季节为３月～１１月。首诊科室,儿科３例、内科３例、转院３例、急诊科１例。１．２ 临床表现：发热７例,恐风５例,恐水６例,怕光３例,流涎１０例,胸闷、气促、呼吸困难４例,烦躁不安１０例,多汗７例,恐惧６例,肢体麻木４例,抽搐４例,恶心、呕吐２例,昏厥１例。所有病例发病至死亡时间为２天～６天,死亡原因为…     

住院患者精神用药情况调查分析

目的：了解目前住院精神患者的药物使用情况。方法：采用一日法调查西安市精神卫生中心403例住院精神患者诊断和治疗情况，并与上海市精神卫生中心2004年调查结果相比较。结果：①传统精神药物使用显著减少，新型精神药物使用占据首位；②抗精神病药物使用趋向小剂量化；③本组联用丙戊酸盐类药物显著增多；④我院精神药物使用情况与上海精神卫生中心比较有显著差异。结论：近年来精神药物使用情况已发生了显著变化，与新型精神药物疗效好，副作用少，患者依从性高有关。     

不同方法治疗慢性宫颈炎的疗效分析

目的慢性宫颈炎是妇科最常见的疾病之一,可引起盆腔脏器炎症,并且与宫颈癌的发生关系密切。本文诣在探讨不同方法在慢性宫颈炎中的疗效。方法回顾性分析新乡市中心医院收治的210例宫颈炎患者,采用药物保妇康栓、聚焦超声治疗及宫腔镜下宫颈电切术的临床效果进行统计分析。结果宫颈电切术治疗有效率为97.9%,明显高于另外两组,差异有统计学意义。结论宫腔镜下宫颈电切术治愈慢性宫颈炎,并且切除宫颈移行带,减少宫颈癌发生。     

The effect of temperature and of cetrimide on the rate of loss of refractility of spores of Bacillus megaterium

The rate of germination of spores of Bacillus megaterium at 30° is not significantly different from the rate at 37° but the onset of germination is delayed; outgrowth is normal. At 45° germination of some spores occurs but the rate is much slower than at 37°, and there is no lag; emergence occurs from only a proportion of the germinated spores and after 3 or 4 vegetative cells have been produced, replication ceases. A single regression equation can represent the germination rate of the spores at 37° in the presence of from 0.0005 to 0.02% w/v of cetrimide and in its absence. In 0.0005% w/v of cetrimide, germ cells emerge from some of the germinated spores but many of them become swollen and disintegrate. Concentrations of 0.00125% w/v or more progressively inhibit swelling and completely inhibit emergence.     

欧洲药典适用性认证介绍

目的介绍欧洲药典适用性认证程序,为国内药品监管机构和原料药生产企业提供信息,促进我国原料药生产企业的国际化。方法通过查阅调研欧盟相关药品法规和与EDQM同行面对面的交流,详细了解欧洲药典适用性认证的组织机构和具体程序。结果与结论欧洲药典适用性认证程序在对原料药的质量控制有重要作用,加强了药典的监管力度,进一步保证了原料药的质量、安全性和有效性。     

新疆维吾尔自治区基层医院平均住院日调查分析

目的 通过对新疆维吾尔自治区14个县乡级医疗机构住院患者平均住院日及影响因素进行分析,为县乡级医疗机构进一步提高医疗管理质量提供依据.方法 将2009-2010年1504例县乡级医院住院患者平均住院天数,按性别、年龄、院别、付费方式、疾病分类进行描述性统计和秩和检验分析.结果 不同性别间及院别间平均住院日差异均有统计学意义(均P＜0.05),男性平均住院日为10.39 d,女性为8.69d,乡级医院为9.27d,县级医院为9.50 d.不同年龄间平均住院日差异有统计学意义(P＜0.05),小于15岁组、15 ～24岁组、25～44岁组、45 ～65岁组、大干65岁组平均住院日分别为8.10 d、7.66d、8.83 d、10.26 d和11.33 d.自费患者平均住院日为8.39 d,新农合组为9.10 d,商业保险组10.17 d,社会基本医疗保险患者则为11.08 d.不同疾病分类间平均住院日差异明显,妊娠类平均住院日最短,为6.73 d,而肿瘤患者则为14.26 d.结论 不同性别、不同年龄段、不同疾病分类及不同付费方式间平均住院日存在差异,县级医疗机构和乡级医疗机构住院患者平均住院日也存在差异.     

经尿道前列腺汽化电切术与经尿道前列腺电切术治疗前列腺增生症的效果对比

目的 对比分析经尿道前列腺汽化电切术与经尿道前列腺电切术治疗前列腺增生症的效果.方法 将本院2011年3月～2013年2月收治的90例前列腺增生症患者随机分为观察组（n=45）和对照组（n=45）,观察组患者采用经尿道前列腺汽化电切术治疗,对照组患者采用尿道前列腺电切术治疗,比较两组患者的疗效.结果 观察组的手术时间、术中出血量、术后冲洗时间、术后留置导尿管时间、住院时间少于对照组（P＜0.05）,残余尿量、国际前列腺症状评分和生活质量评分优于对照组（P＜0.05）,但是两组患者的并发症发生率差异无统计学意义（P＞0.05）.结论 经尿道前列腺汽化电切术治疗前列腺增生症具有疗效更确切、出血少、恢复快等优势,可以作为治疗前列腺增生症的首选方法.