BACKGROUND & AIMS: :Secretory granules carrying fluorescent cargo proteins are widely used to study granule biogenesis, maturation, and regulated exocytosis. We fused the soluble secretory protein peptidylglycine alpha-hydroxylating monooxygenase (PHM) to green fluorescent protein (GFP) to study granule formation. When expressed in AtT-20 or GH3 cells, the PHM-GFP fusion protein partitioned from endogenous hormone (adrenocorticotropic hormone, growth hormone) into separate secretory granule pools. Both exogenous and endogenous granule proteins were stored and released in response to secretagogue. Importantly, we found that segregation of content proteins is not an artifact of overexpression nor peculiar to GFP-tagged proteins. Neither luminal acidification nor cholesterol-rich membrane microdomains play essential roles in soluble content protein segregation. Our data suggest that intrinsic biophysical properties of cargo proteins govern their differential sorting, with segregation occurring during the process of granule maturation. Proteins that can self-aggregate are likely to partition into separate granules, which can accommodate only a few thousand copies of any content protein; proteins that lack tertiary structure are more likely to distribute homogeneously into secretory granules. Therefore, a simple "self-aggregation default" theory may explain the little acknowledged, but commonly observed, tendency for both naturally occurring and exogenous content proteins to segregate from each other into distinct secretory granules.

背景与目标： : 携带荧光货物蛋白的分泌颗粒被广泛用于研究颗粒生物发生，成熟和调节胞吐作用。我们将可溶性分泌蛋白肽基甘氨酸 α-羟化单加氧酶 (PHM) 与绿色荧光蛋白 (GFP) 融合，以研究颗粒形成。当在AtT-20或GH3细胞中表达时，PHM-GFP融合蛋白从内源性激素 (促肾上腺皮质激素，生长激素) 分配到单独的分泌颗粒池中。外源和内源颗粒蛋白均被存储并释放以响应促分泌素。重要的是，我们发现内容物蛋白质的分离不是过度表达的产物，也不是GFP标记的蛋白质所特有的。管腔酸化和富含胆固醇的膜微域在可溶性蛋白分离中均未发挥重要作用。我们的数据表明，货物蛋白的内在生物物理特性决定了它们的差异分选，在颗粒成熟过程中发生了分离。可以自我聚集的蛋白质很可能会分成单独的颗粒，只能容纳几千个拷贝的任何含量的蛋白质; 缺乏三级结构的蛋白质更有可能均匀分布成分泌颗粒。因此，一个简单的 “自聚集默认” 理论可以解释自然存在的蛋白质和外源含量蛋白质彼此分离成不同的分泌颗粒的趋势，但鲜为人知但通常观察到。

BACKGROUND & AIMS: These experiments were designed to determine whether glycogenolysis was influenced by the glycogen concentration of vascular smooth muscle. Segments of hog carotid artery smooth muscle were allowed to synthesize variable amounts of 1-[13C]glucosyl units of glycogen. Artery segments were then isometrically contracted in the presence of 2-[13C]glucose. Prior to and after isometric contraction, measurements were made of tissue glycogen content and superfusate glucose and lactate concentrations. 2-[13C]Lactate and 3-[13C]lactate peak intensities in the superfusate were measured using 13C-NMR spectroscopy. The tissue glycogen content decreased exponentially during the 4.5 h of isometric contraction (R2 = 0.990), despite more than a 3-fold range of glycogen concentration prior to contraction. The extent of glycogen utilization during a 3 h isometric contraction varied linearly with the precontraction glycogen concentration (R2 = 0.727). Lactate production specifically from glycogen breakdown increased with an increase in precontraction glycogen concentration (R2 = 0.620). During a 3 h isometric contraction neither the glucose utilization (R2 = 0.007) nor lactate production specifically produced from glucose (R2 = 0.00002) varied with the precontraction glycogen concentration. It is concluded that the rate of glycogenolysis is determined by the content of glycogen during prolonged contractions. In addition, precontraction glycogen levels influence the pathway for glycogen utilization but not the pathway for glucose utilization. Therefore, glycolysis and glycogenolysis behave independently in vascular smooth muscle.

背景与目标： 这些实验旨在确定糖原分解是否受血管平滑肌糖原浓度的影响。允许猪颈动脉平滑肌段合成可变量的1-[13C] 糖原葡萄糖单元。然后在2-[13C] 葡萄糖存在下等距收缩动脉段。在等距收缩之前和之后，测量组织糖原含量和超融合物葡萄糖和乳酸浓度。使用13C-NMR光谱测量超融合物中的2-[13C] 乳酸和3-[13C] 乳酸峰强度。组织糖原含量在等距收缩的4.5小时内呈指数下降 (R2 = 0.990)，尽管收缩前糖原浓度超过3倍。在3 h等距收缩期间糖原利用的程度随收缩前糖原浓度线性变化 (R2 = 0.727)。糖原分解产生的乳酸产量随着收缩前糖原浓度的增加而增加 (R2 = 0.620)。3小时的等距收缩葡萄糖利用率 (R2 = 0.007) 和特别由葡萄糖产生的乳酸产量 (R2 = 0.00002) 都不随收缩前糖原浓度而变化。结论是糖原分解速率由长期收缩期间糖原含量决定。此外，收缩前糖原水平会影响糖原利用的途径，但不会影响葡萄糖利用的途径。因此，糖酵解和糖原分解在血管平滑肌中独立运作。

BACKGROUND & AIMS: Shunting inhibition, a conductance increase with a reversal potential close to the resting potential of the cell, has been shown to have a divisive effect on subthreshold excitatory postsynaptic potential amplitudes. It has therefore been assumed to have the same divisive effect on firing rates. We show that shunting inhibition actually has a subtractive effect on the firing rate in most circumstances. Averaged over several interspike intervals, the spiking mechanism effectively clamps the somatic membrane potential to a value significantly above the resting potential, so that the current through the shunting conductance is approximately independent of the firing rate. This leads to a subtractive rather than a divisive effect. In addition, at distal synapses, shunting inhibition will also have an approximately subtractive effect if the excitatory conductance is not small compared to the inhibitory conductance. Therefore regulating a cell's passive membrane conductance-for instance, via massive feedback-is not an adequate mechanism for normalizing or scaling its output.

背景与目标： 分流抑制，电导增加，逆转电位接近细胞的静息电位，已显示对亚阈值兴奋性突触后电位振幅具有分裂作用。因此，人们认为它对发射速率具有相同的分裂作用。我们证明，在大多数情况下，分流抑制实际上对发射速率具有减法作用。在几个尖峰间隔内平均，尖峰机制有效地将体细胞膜电位固定到明显高于静息电位的值，因此通过分流电导的电流大致与发射速率无关。这导致减法而不是分裂效应。此外，在远端突触处，如果兴奋性电导与抑制性电导相比不小，则分流抑制也将具有近似消减作用。因此，调节细胞的被动膜电导 (例如，通过大量反馈) 并不是使其输出标准化或缩放的适当机制。

BACKGROUND & AIMS: :We review a 15-year experience with childhood idiopathic thrombocytopenic purpura (ITP) at a tertiary-care pediatric hospital in Croatia. Data confirm that ITP is typically a self-limited bleeding disorder that usually presents with mild symptoms in children between 1 and 10 years of age and affects both sexes equally. At presentation, more than half of the children had platelet counts of <10x10(9)/L. The absence of preceding viral infection and insidious onset of symptoms were significantly associated with development of chronic ITP. In our experience, observation without specific therapy seems to be the optimal approach to a child with ITP.

背景与目标： : 我们回顾了克罗地亚一家三级儿科医院对儿童特发性血小板减少性紫癜 (ITP) 的15年经验。数据证实，ITP通常是一种自限性出血性疾病，通常在1至10岁的儿童中表现为轻度症状，并且对男女影响均等。在演讲中，超过一半的儿童的血小板计数 <10x10(9)/L。先前没有病毒感染和症状的隐匿性发作与慢性ITP的发展显着相关。根据我们的经验，没有特定疗法的观察似乎是治疗ITP儿童的最佳方法。

BACKGROUND & AIMS: OBJECTIVE:To evaluate the maternal and neonatal outcomes of pregnancies complicated with isolated oligohydramnios at term, managed by induction of labor. METHODS:We conducted a retrospective case-control study. 138 women with uncomplicated oligohydramnios at term [amniotic fluid index (AFI) < or =5 cm] and a low Bishop score (< or =6) underwent induction of labor with prostaglandin E2. These women were compared to 67 women who underwent induction of labor at 42 weeks' gestation and 276 women at low-risk pregnancy and spontaneous onset of labor, matched for parity and race. RESULTS:Cesarean section (CS) rate was similar in the study and the post-date group (17.4 and 17.9%, respectively), but significantly higher than the spontaneous labor group (5.8%, OR 3.42, 95% CI 1.75-6.68). No differences were found with other outcomes. CONCLUSION:Pregnancies with isolated oligohydramnios at term apparently are not at higher risk of perinatal complications, but induction of labor is associated with increased rate of CS.

背景与目标：

BACKGROUND & AIMS: The World Bank in its document under the title 'Investing in Health' (1993) states that the health status of the population, including the working population, and working conditions in individual countries depend essentially on the value of gross national product per capita. The attitudes towards the role and objectives of occupational medicine have changed significantly over the last three decades. A high priority given to primary prevention reflects the mainstream of a new approach to preventive measures. Advancements in technology, production and services, common use of computers and flattening of work organisation structures have brought about the need for workers' active participation in planning of activities and shaping working conditions in own enterprise. At the same time, workers are required to possess much higher qualifications facilitating their participation in applying new technologies and using new information systems, which resulted in a fierce competition on the labour market. In the countries in the political, social and economic transition, the conditions for introducing a new system of sustained development, described by Gustavsen at the 25th International Congress on Occupational Health have not as yet been established. A procedure-based system involving negotiations between employers and workers' representatives failed to be successful in improving working conditions as the roles of the state, employers and trade unions had not been defined precisely. It is expected that further health promotion at the worksites in these countries will depend mainly on the economic progress and the reformed system of education.

背景与目标： 世界银行在其题为 “投资于健康” (1993) 的文件中指出，包括工作人口在内的人口的健康状况和各个国家的工作条件基本上取决于人均国民生产总值。在过去的三十年中，人们对职业医学的作用和目标的态度发生了重大变化。对初级预防的高度重视反映了预防措施新方法的主流。技术，生产和服务的进步，计算机的普遍使用以及工作组织结构的扁平化带来了工人积极参与活动计划和塑造自己企业工作条件的需求。同时，要求工人具有更高的资格，以促进他们参与应用新技术和使用新信息系统，这导致了劳动力市场的激烈竞争。在政治，社会和经济转型的国家中，古斯塔夫森在第25届国际职业健康大会上描述的引入新的可持续发展体系的条件尚未建立。涉及雇主和工人代表之间谈判的基于程序的系统未能成功改善工作条件，因为国家，雇主和工会的作用尚未得到准确定义。预计这些国家工作场所的进一步健康促进将主要取决于经济进步和教育制度的改革。

BACKGROUND & AIMS: :The aim of this study is to find out the causes of skin diseases in one-third of the staff of a perfume factory, in which 10 different perfume sprays were being manufactured. Site inspection, dermatological examination and patch testing of all 26 persons at risk with 4 perfume oils and 30 ingredients of them. The results showed 6 bottlers were found suffering from allergic contact dermatitis, 2 from irritant contact dermatitis, 12 workers showed different strong reactions to various fragrances. The main causes of allergic contact dermatitis were 2 perfume oils (12 cases) and their ingredients geraniol (12 cases), benzaldehyde(9), cinnamic aldehyde (6), linalool, neroli oil, terpenes of lemon oil and orange oil (4 each). Nobody was tested positive to balsam of Peru. Job changes for office workers, packers or printers to other rooms, where they had no longer contact with fragrances, led to a settling. To conclude, automation and replacement of glass bottles by cartridges from non-fragile materials and using gloves may minimize the risk.

背景与目标： : 这项研究的目的是找出3分之1一家香水工厂的工作人员的皮肤病的原因，该工厂生产了10种不同的香水喷雾剂。现场检查，皮肤科检查和所有26名有风险的人使用4种香料油和30种成分进行贴剂测试。结果显示，6名装瓶工人患有过敏性接触性皮炎，2名来自刺激性接触性皮炎，12名工人对各种香料表现出不同的强烈反应。过敏性接触性皮炎的主要病因为香精油2种 (12例)，其成分为香叶醇 (12例)，苯甲醛 (9例)，肉桂醛 (6例)，芳樟醇，橙花油，柠檬油和橙油的萜烯 (4例)。没有人对秘鲁的香脂测试呈阳性。办公室工作人员，包装工或打印机的工作变更到其他房间，他们不再与香水接触，导致了定居。总而言之，用非易碎材料和使用手套的墨盒自动化和更换玻璃瓶可以最大程度地降低风险。

BACKGROUND & AIMS: :Molecular biology techniques are applied for the diagnosis of meningoencephalitis due to herpesviruses, enteroviruses or polyomaviruses, for the diagnosis of human cytomegalovirus, human parvovirus B19, varicella-zoster virus and rubella virus infections occurring during pregnancy, for the diagnosis and the management of retrovirus infections (HIV and HTLV) and of hepatitis (HBV and HCV), for papillomavirus typing and to detect a link between virus and clinical manifestations (cardiomyopathy or insulinodependent diabetes with coxsackievirus B: Kaposi's sarcoma with HHV 8) or to investigate an environmental contamination with viruses. These new molecular markers which are both qualitative and quantitative represent an important advance in the field of viral diagnosis research, in the monitoring of viral load during the course of infection, in the therapy control of viral disease and in the epidemiology of virus spread. Standardization and automatization are obtained using available commercial reagents and kits.

背景与目标： : 分子生物学技术用于诊断由疱疹病毒，肠病毒或多瘤病毒引起的脑膜脑炎，用于诊断人巨细胞病毒病毒，人细小病毒B19，水痘病毒病毒和怀孕期间发生的风疹病毒病毒，用于诊断和管理复古病毒感染 (HIV和HTLV) 和肝炎 (HBV和HCV)，乳头瘤病毒分型，并检测病毒与临床表现 (心肌病或胰岛素依赖型糖尿病与柯萨奇病毒B: 卡波西氏肉瘤与HHV 8) 或调查病毒es的环境污染。这些定性和定量的新分子标记物代表了病毒诊断研究领域，感染过程中病毒载量的监测，病毒性疾病的治疗控制以及病毒传播流行病学领域的重要进展。使用可用的商业试剂和试剂盒可获得标准化和自动化。

BACKGROUND & AIMS: OBJECTIVE:To determine the degree of correlation between Farr and ELISA methods of detecting anti-dsDNA antibodies in patients with systemic lupus erythematosus (SLE), and their association with measures of disease activity. METHODS:Anti-dsDNA antibodies were assayed using the Farr and ELISA methods in patients followed between January 1, 2000, and December 31, 2002. Statistical correlations between Farr and ELISA were determined. Relationships between the 2 assays and measures of disease activity [SLE Disease Activity Index 2000 (SLEDAI-2K-DNA), renal, central nervous system (CNS), and vasculitis] were determined for the same clinic visit. RESULTS:550 patients with 2940 clinic visits met the inclusion criteria. Correlation between Farr and ELISA levels was 0.46 using the first visit for each patient. When the Farr was abnormal, the ELISA was equally likely to be normal or abnormal. Abnormal Farr results were associated with higher SLEDAI-2K scores than normal Farr results (6.2 vs 4.3, respectively; p < 0.0001). There was less of a distinction with ELISA results (5.9 vs 4.8; p = 0.04). Farr levels were significantly associated with the presence of renal disease and vasculitis, while ELISA levels were not. Neither Farr nor ELISA results correlated with the presence of active CNS involvement. CONCLUSION:Farr and ELISA techniques for the detection of anti-dsDNA antibodies in patients with SLE are poorly correlated. The Farr is superior to the ELISA in correlating with measures of global disease activity, as well as renal and vasculitis involvement. The Farr technique should continue to be used in clinical practice. The ELISA adds no additional information.

背景与目标：

BACKGROUND & AIMS: :A retrospective study of male breast cancer was undertaken at Ouagadougou University Teaching Hospital over a 3 year period (1993-1996). Authors report 5 cases representing 4.16% of all breast cancers. The patients' mean age was 61 years. The average duration of signs and symptoms before the diagnosis was 13 months. Clinically all the 5 cases presented advanced cancers (4 T4N2M0, 1 T4N2M1 according to UICC TNM System) with size ranging from 5.5, to 11.5 cm. Histology found: 2 medullary infiltrating carcinoma, 1 canalar infiltrating carcinoma, 1 colloid mucous carcinoma and 1 lobular infiltrating carcinoma. All patients had mastectomy associated with axillary clearance in 4 cases. Radiotherapy, chemotherapy and hormonotherapy were not associated because unavailable in Burkina Faso. Three patients died: the first, 10 days after surgical treatment and the 2 others respectively after 14 and 17 months. We have lost sight 1 patients. The last one is still alive. Authors find that to get better prognosis, it is important to improve medical and technical means, to increase information and to promote early detection.

背景与目标： : 在瓦加杜古大学教学医院进行了为期3年 (1993-1996年) 的男性乳腺癌回顾性研究。作者报告了5例代表所有乳腺癌4.16% 的病例。患者的平均年龄为61岁。诊断前症状和体征的平均持续时间为13个月。临床上所有5例均表现为晚期癌症 (根据UICC TNM系统，4个T4N2M0，1个T4N2M1)，大小从5.5到11.5厘米。组织学发现: 髓质浸润性癌2例，管内浸润性癌1例，胶体粘液性癌1例，小叶浸润性癌1例。所有患者均行乳房切除术伴腋窝清除4例。放疗，化疗和激素治疗不相关，因为在布基纳法索不可用。3例患者死亡: 手术治疗后第1、10天，另外2例分别在14和17个月后死亡。我们已经看不见1个病人了。最后一个还活着。作者发现，要获得更好的预后，必须改善医疗和技术手段，增加信息并促进早期发现。

BACKGROUND & AIMS: STUDY DESIGN:Clinical case series. OBJECTIVE:To describe a series of patients with progressive sagittal decompensation caused by failure at the caudal end of an instrumented lumbar fusion. SUMMARY OF BACKGROUND DATA:Lumbar kyphosis in association with global sagittal decompensation can be a disabling problem, particularly as a late complication of distraction instrumentation. Although kyphosis at the rostral end of instrumented fusions secondary to adjacent segment degeneration has been well described, substantially less has been documented about failure and kyphosis at the caudal end. METHODS:Patients who have a progressive lumbar kyphosis and sagittal decompensation requiring operative revision were retrospectively reviewed, and radiographic measurements of lumbar lordosis and sagittal balance were performed to study this problem. RESULTS:There were 13 patients identified. The most common mode of caudal junctional decompensation was related to failure of the most distal fixation. Sagittal decompensation occurred even in the presence of satisfactory lumbar lordosis. Revision surgery and improved sagittal balance were achieved typically using the technique of pedicle subtraction osteotomy and extension of the instrumentation to the sacrum. Osteoporosis, hip osteoarthritis, and substance abuse were commonly observed associations. CONCLUSIONS:Fixation failure at the caudal end of lumbar-instrumented fusion should be considered in patients with progressive sagittal decompensation. The high potential for failure of L5 pedicle screws after the index surgery warrants serious consideration of extending such fusions into the sacrum/ilium.

背景与目标：

BACKGROUND & AIMS: :The Clostridium perfringens alpha-toxin has previously been implicated as the major virulence factor in necrotic enteritis in chickens, although definitive proof has not been reported. In this study an alpha-toxin mutant was constructed in a virulent chicken isolate and shown to retain full virulence in a chicken disease model. These results demonstrated that alpha-toxin is not an essential virulence factor in the pathogenesis of necrotic enteritis in chickens.

背景与目标： : 尽管尚未报道明确的证据，但以前曾将产气荚膜梭菌 α 毒素作为鸡坏死性肠炎的主要毒力因子。在这项研究中，在强毒鸡分离株中构建了一个 α 毒素突变体，并显示在鸡疾病模型中保留了完全的毒力。这些结果表明，在鸡坏死性肠炎的发病机理中，α-毒素不是必需的毒力因子。

BACKGROUND & AIMS: :Severe preeclampsia rarely occurs prior to 20 weeks of gestation except in pregnancies with triploidy. The patient reported herein is a 29-year-old primigravida who developed severe preeclampsia at 20 weeks of gestation. Evaluation of the pregnancy demonstrated a markedly abnormal quadruple screen. Amniocentesis demonstrated a fetus with triploidy, despite a normal appearance.

背景与目标： : 除三倍体妊娠外，妊娠20周前很少发生严重的先兆子痫。本文报道的患者是一名29岁的初产妇，在妊娠20周时出现严重的先兆子痫。对妊娠的评估显示出明显异常的四重筛查。羊膜穿刺术显示胎儿具有三倍体，尽管外观正常。

BACKGROUND & AIMS: :Professional antigen-presenting cells (APC) are able to process and present exogenous antigen leading to the activation of T cells. Antigen-immunoglobulin (Ig)G complexes (IC) are much more efficiently processed and presented than soluble antigen. Dendritic cells (DC) are known for their ability to take up and process immune complex (IC) via FcgammaR, and they have been shown to play a crucial role in IC-processing onto major histocompatibility complex (MHC) class I as they contain a specialized cross-presenting transport system required for MHC class I antigen-processing. However, the MHC class II-antigen-processing pathway is distinct. Therefore various other professional APC, like macrophages and B cells, all displaying FcgammaR, are thought to present IC-delivered antigen in MHC class II. Nonetheless, the relative contribution of these APC in IC-facilitated antigen-presentation for MHC class II in vivo is not known. Here we show that, in mice, both macrophages and DC, but not B cells, efficiently capture IC. However, only DC, but not macrophages, efficiently activate antigen-specific MHC class II restricted CD4(+) T cells. These results indicate that mainly DC and not other professional APC, despite expressing FcgammaR and MHC class II, contribute significantly to IC-facilitated T cell activation in vivo under steady-state conditions.

背景与目标： : 专业抗原呈递细胞 (APC) 能够处理和呈递导致T细胞活化的外源性抗原。抗原-免疫球蛋白 (Ig)G复合物 (IC) 比可溶性抗原更有效地处理和呈现。树突状细胞 (DC) 以其通过FcgammaR吸收和处理免疫复合物 (IC) 的能力而闻名。并且它们已被证明在IC处理到主要组织相容性复合体 (MHC) I类上起着至关重要的作用，因为它们包含MHC I类抗原处理所需的专门交叉呈递转运系统。然而，MHC II类抗原处理途径是不同的。因此，其他各种专业的APC，如巨噬细胞和b细胞，都显示FcgammaR，被认为在MHC II类中呈现IC递送的抗原。尽管如此，这些APC在体内MHC II类的IC促进抗原呈递中的相对贡献尚不清楚。在这里，我们表明，在小鼠中，巨噬细胞和DC，但不是b细胞，有效地捕获IC。然而，只有DC，但不是巨噬细胞，有效激活抗原特异性MHC II类限制性CD4(+) T细胞。这些结果表明，尽管表达FcgammaR和MHC II类，但主要是DC而不是其他专业APC，在稳态条件下对IC促进的T细胞激活有显着贡献。

BACKGROUND & AIMS: :Cyproheptadine is a drug that shows high affinity for type 2 (5-HT2) receptors. We studied a series of compounds obtained by modification of the tricyclic system of Cyp (dibenzocycloheptadiene): 2f (thioxanthene), 2g (xanthene), 2h (dihydrodibenzocycloheptadiene), 2j (diphenyl), 2i (fluorene), and 3b (phenylmethyl). Their activities at the rat cerebral cortex 5-HT2A receptor were (pKi +/- S.E.M.): 8.80 +/- 0.11 (Cyp), 8.60 +/- 0.07 (2f), 8.40 +/- 0.02 (2g), 8.05 +/- 0.03 (2h), 7.87 +/- 0.12 (2j), 6.70 +/- 0.02 (2i) and 6.45 +/- 0.02 (3b); those at the rat stomach fundus 5-HT2B receptor (pA2 +/- S.E.M.) were: 9.14 +/- 0.25 (Cyp), 8.49 +/- 0.07 (2f), 7.58 +/- 0.58 (2g), 7.02 +/- 0.14 (2h), 6.07 +/- 0.20 (2j), and undetectable (2i, 3b): and those at the pig choroidal plexus 5-HT2C receptor (pKi +/- S.E.M.) were: 8.71 +/- 0.08 (Cyp), 8.68 +/- 0.01 (2f), 8.58 +/- 0.20 (2g), 7.95 +/- 0.05 (2h), 7.57 +/- 0.04 (2j), 6.98 +/- 0.04 (2i) and 6.63 +/- 0.20 (3b). The slopes did not differ significantly from unity. The compounds exhibited the same order of activities at every type of receptor, and the most active molecules presented certain steric (butterfly conformation of the tricyclic system) and electrostatic (proton affinity on the top of the central rings) patterns. It is concluded that the activity of cyproheptadine derivatives at 5-HT2 receptors is related to these molecular features, which make feasible a common disposition to interact with all three 5-HT2 subtypes.

背景与目标： : 赛庚胺是一种对2型 (5-HT2) 受体显示高亲和力的药物。我们研究了通过修饰Cyp (二苯并环庚二烯) 的三环体系获得的一系列化合物: 2f (噻吩)，2g (xanthene)，2h (二氢二苯并环庚二烯)，2j (二苯基)，2i (芴) 和3b (苯基甲基)。它们在大鼠大脑皮层5-HT2A受体上的活性为 (pKi +/-s.e.M.): 8.80 +/- 0.11 (Cyp)，8.60 +/- 0.07 (2f)，8.40 +/- 0.02 (2g)，8.05 +/- 0.03 (2h)，7.87 +/- 0.12 (2j)，6.70 +/- 0.02 (2i) 和6.45 +/- 0.02 (3b); 大鼠胃底5-HT2B受体 (pA2 +/-s.e.M.) 为: 9.14 +/- 0.25 (Cyp)，8.49 +/- 0.07 (2f)，7.58 +/- 0.58 (2g)，7.02 +/- 0.14 (2h)，6.07 +/- 0.20 (2j) 和不可检测 (2i，3b): 猪脉络丛5-HT2C受体 (pKi +/-s.e.M.) 为: 8.71 +/- 0.08 (Cyp)，8.68 +/- 0.01 (2f)，8.58 +/- 0.20 (2g)，7.95 +/- 0.05 (2h) 、7.57 +/- 0.04 (2j) 、6.98 +/- 0.04 (2i) 和6.63 +/- 0.20 (3b)。坡度与统一没有显着差异。这些化合物在每种类型的受体上都表现出相同的活性顺序，并且最具活性的分子呈现某些空间 (三环系统的蝴蝶构象) 和静电 (中心环顶部的质子亲和力) 模式。结论是，赛庚胺衍生物在5-HT2受体上的活性与这些分子特征有关，这使得与所有三种5-HT2亚型相互作用的共同处置是可行的。