Anti-inflammatory activity of myricetin-3-O-beta-D-glucuronide and related compounds

OBJECTIVE AND DESIGN: The anti-inflammatory effect of myricetinglucuronide (MGL) was investigated and structurally-related compounds were compared to examine the structure/activity-relationship in carrageenan-induced rat paw edema. MATERIALS AND SUBJECTS: In vitro studies were performed using rat basophilic leukemia (RBL-1) cells, human polymorphonuclear leukocytes (PMNL), COX-1 from ram seminal vesicle, COX-2 from sheep placenta and human venous blood. For the in vivo tests male Wistar rats were used, for the ex vivo test perfused rabbit ears. TREATMENT: 1-300 microg/kg MGL or myricetinmethylglucuronate and 0.1-5 mg/kg other related compounds administered p.o. (carrageenan edema). 5, 50 and 150 microg/kg MGL p.o. for 14 days (Freund's adjuvant arthritis), 5 and 50 microg/kg p.o. for 6 days (ulceration). METHODS: Anti-inflammatory effects were measured in carrageenan edema and in adjuvant arthritis. Incidence of gastric lesions was tested in an ulcerogenicity model in vivo. Influence on COX was determined in the perfused rabbit ear, in PMNL and in a test assay using COX-1 and COX-2. 5-LOX activity was studied using PMNL and RBL-1. The influence on platelet aggregation was evaluated measuring light transmission. RESULTS: MGL exerted a marked and dose-dependent anti-inflammatory effect in acute (carrageenan edema, ED50 15 microg/kg, indomethacin ED50 10 mg/kg) and chronic (adjuvant arthritis, inhibition at 150 microg/kg 18.1 % left paw, 20.6% right paw, indomethacin 3 mg/kg 18.0% and 19.4%)) models of inflammation. In the perfused rabbit ear 1 microg MGL inhibited the release of PGI2, PGD2 and PGE2 to the same extent as 1 microg indomethacin. The inhibition of COX-1 in the intact cell system was IC50 = 0.5 microM, that of indomethacin 0.0038 microM. In the isolated enzyme preparations of COX-1 and COX-2 the IC50 was 10 microM and 8 microM, that of indomethacin 9.2 mM and 2.4 microM. In the RBL-1 and PMNL test assay the inhibition of 5-LOX was 0.1 microM and 2.2 microM. An orally administered dose of 50 microg/kg/day induced no gastric ulcers in rats treated for 6 days. The investigations on carrageenan edema showed a close relationship between the structure of MGL and the anti-inflammatory effect. CONCLUSIONS: MGL is a COX-1, COX-2 and 5-LOX inhibitor. In view of the moderate in vitro activity and the very potent in vivo activity an additive mechanism must be involved. Small changes in the molecular structure lead to the loss or reduction of the anti-inflammatory activity.     

Differential therapy of cerebral arteriovenous malformations. An analysis with reference to personal microsurgery experiences

A total of 126 patients (63 female, 63 male) underwent microsurgical removal of their cerebral arteriovenous malformations (AVMs) by the same surgeon. The mean age at surgery was 34.7 (6-72) years. The symptoms were intracerebral hemorrhage (37.3%), seizure disorder (34.9%) or focal neurological deficits and minor symptoms. According to the Spetzler/Martin scale, 20.6% of the AVMs were grade I, 28.6% grade II, 32.5% grade III, 14.3% grade IV and 4% grade V. In all, 78 AVMs (61.9%) were located in functionally important brain regions. The series was split into three different groups: small AVMs under 3 cm in diameter (n = 62/49.2%), medium-sized AVMs (n = 58/46%) and large AVMs (n = 6/4.8%). Seventeen patients had preoperative embolization of their AVM. All patients had postoperative angiographic control and 3- and 6-month follow-up. One patient died (0.8%), and another one (0.8%), in whom the AVM was incompletely resected, suffered a secondary hemorrhage. Seventeen (27.4%) of the patients with small AVMs developed transient neurological worsening post-operatively, which remained permanently significant in 3.2%. The respective numbers for the patients with medium-sized AVMs were 48.3% and 10.3% and for the large AVMs 83.3% and 33.3%. The results of microsurgical removal of cerebral AVMs can still be considered superior to the results of stereotactic radiosurgical treatment available from the literature-even for small AVMs. This is due to immediate exclusion of the AVM under direct local control of the angioarchitecture and thereby a reduced risk of secondary hemorrhaging and a decreasing morbidity rate with increasing time after the operation. Radiosurgical treatment requires a 2-year latency period for obliteration and carries a mortality rate of up to 12.5% and a rate of unexpected side effects of up to 20%. This treatment should be reserved for small, deep, surgically inaccessible AVMs or used as part of a multimodality treatment regimen consisting of partial embolization, partial excision and consecutive radiation of the residual nidus in initially very large AVMs. Embolization therapy-such as radiosurgery-carries a significant risk of morbidity (8%) and a mortality rate of up to 6%. It should only be considered for AVMs that are expected to be fully obliterated afterwards, or for primary inoperable AVMs that are to be changed into operable ones by embolization. Size reduction of otherwise operable AVMs does not justify the additional risk of embolization. Close collaboration of the specialties involved is desirable.     

Developing competency-based perioperative orientation programs

Ensuring the competency of staff members at all levels of practice is an ongoing challenge for perioperative clinical educators. The authors developed a competency-based orientation program using AORN's perioperative nursing competency statements as a conceptual framework. The model also incorporates requirements from external regulatory agencies (e.g., the Joints Commission on Accreditation of Healthcare Organizations) that influence the direction of health care institutions seeking accreditation. The model provides the components necessary to validate the orientation of perioperative staff members and the delivery of comprehensive nursing care in perioperative settings.     

HiperLAN2: broadband wireless communications at 5 GHz

Solutions for high data rates and local coverage have been developed over a couple of years in the area of wireless local area networking. The quality of service, security, mobility, and high throughput are key components that drive the standards for broadband wireless multimedia communications presently being developed in Europe as well as in the United States and Japan for the 5 GHz band. These technologies are well suited to complement third-generation cellular networks. HiperLAN type 2 (HiperLAN2) is one of these systems, which is being specified by the ETSI project BRAN. The core parts of the specification were finalized at the end of 1999. Almost total harmonization has been achieved between the standardization bodies in Europe and Japan (ETSI and ARIB, respectively). HiperLAN2 will provide data rates up to 54 Mb/s, and is intended for local communications in indoor and outdoor environments. An overview of the HiperLAN2 standard is presented together with exemplary link and system performance results     

Analysis and optimization of pilot-channel-assisted BPSK forDS-CDMA systems

Pilot-channel-assisted binary phase-shift keying (PCA-BPSK) in direct-sequence code-division multiple-access (DS-CDMA) systems is investigated. The loss due to imperfect channel estimation is calculated, and the pilot-to-data channel power ratio is optimized analytically. The results show the effects of the various parameters and provide a suitable tool for system design     

Determination of 5-methoxypsoralen in suntan cosmetics

A method for the determination of 5-methoxypsoralene in suntan-cosmetics is described. After liquid chromatographic clean-up, the final extract is screened by twodimensional thin layer chromatography. For positive extracts 5-methoxypsoralene is analysed quantitatively by capillary gas chromatography, using 5-alpha-cholestane as an internal standard and flame ionization detection (FID). The results were confirmed by gas chromatography-mass spectrometry (GC-MS). The recoveries for suntan-cosmetics of emulsion type were 70% and for tanning oils 90%. Detection limits of the method were 0,1 to 0,5 mg/kg, depending on the sample type. By application of this method 5-methoxypsoralene was detected in 6 of the 21 cosmetic products at levels up to 28 mg/kg.     

Enzymatic transition state poise and transition state analogues

The development of kinetic isotope effect methods for enzymatic reactions has resulted in the systematic determination of enzymatic transition state structure for several distinct chemical reaction mechanisms. Although it is early in the experimental development of the method, examples of concerted nucleophilic displacements (A(N)D(N) or S(N)2), aromatic nucleophilic displacements (A(N)D(N) or S(N)Ar), and both concerted and stepwise dissociative nucleophilic displacements (D(N)A(N) and D(N)A(N); S(N)1 reactions) have been exemplified. The transition state for each reaction exhibits a characteristic extent of bond-breaking and bond-making, defined here as transition state poise. Thus, concerted nucleophilic displacements (S(N)2 or D(N)A(N)) exhibit various extents of residual bond order to the leaving group and to the attacking nucleophile at the transition state. Aromatic nucleophilic displacements reach their rate-limiting transition states before or after formation of the tetrahedral intermediate. Several concerted, symmetric nucleophilic displacements at carbon have been described. Enzymatic transition state poise is summarized in a single diagram of bond orders using the terminology of Jencks. The analysis reveals enzymatic contributions to transition state poise, provides precedent for assignment of reaction types, and summarizes the current status of the experimental characterization of enzymatic transition states. Binding strengths of transition state analogues are readily correlated with transition state poise.     

Evaluating the relationship between chemical exposure and cryptorchidism

One method for the evaluation of complex environmental and health datasets is the discrete mathematical method Hasse diagram technique based on partial orders. The introduced software program package is named PyHasse. In this paper we evaluate a possible human association between maternal exposure to organochlorine compounds used as pesticides and cryptorchidism among male children in Finland and Denmark. We identified differences in comparable and incomparable objects and quantified these differences by the software tool Similarity Analysis in the program PyHasse. Furthermore we interpreted the corresponding Hasse diagrams concerning chosen “striking objects”. We found the position of the chemicals AHCH (alpha-Hexachlorohexane), CHCE (cis-Heptachloroepoxide), DIEL (Dieldrin), and MIRE (Mirex) has some influence on the differentiation of the Hasse diagrams and hence of each two datasets analyzed. The largest disparities can be observed when we compare the Finnish and Danish datasets concerning cryptorchidism. The disparities are demonstrated in the corresponding Hasse diagrams.     

半透膜仪采集空气中多氯联苯采样速度与其结构和性质定量构效关系研究

根据MOPAC2009软件包中PM6算法得到的分子描述符研究半透膜仪(SPMDs)采集大气中多氯联苯(PCBs)采样速度(R_(air))的定量构效关系(QSPR)模型,并分析影响R_(air)的关键因素。以半经验PM6算法得到的分子量子化学描述符作为预测变量,采用偏最小二乘算法(PLS)构建了R_(air)的QSPR模型。根据交叉验证,所得到的最佳模型中PLS成分解释的因变量的累积变异(Q~2_(cum))为0.683,这表明该模型具有良好的预测能力和稳健性。通过外部验证和将实验测得的R_(air)与预测得到的R_(air)进行比较,对所构建模型的稳定性和可靠性进行了验证,结果表明无论是训练组还是预测组,其预测值与实测值间均具有较好的线性关系,线性相关系数均大于0.8376。对PCBs采样速度R_(air)的主要影响因素为PCBs与SPMDs中甘油三油酸酯分子间的相互作用大小和为将PCBs溶解在甘油三油酸酯中形成洞穴所需能量要求。