沙棘(2012年9期封面植物)

【科属】胡颓子科沙棘属植物。【别名】醋柳果、醋刺柳、酸刺子、醋柳、沙枣。【采集】9、10月果实成熟时采收,除去杂质,鲜用或晒干。【性味归经】性温,味酸涩;入肝、胃、大小肠经。     

Glycine transporter-1 inhibitors: a patent review (2011–2016)

Introduction: Numerous research groups have developed GlyT-1 inhibitors in the pursuit of providing a novel antipsychotic treatment for schizophrenia. Despite multiple compounds advancing into clinical trials, a GlyT-1 inhibitor has yet to emerge to treat patients. However, the approach remains heavily investigated as it presents potential therapeutic utility for several other CNS and non-CNS-related indications.

Areas covered: This review discusses various GlyT-1 inhibitor chemotypes identified and provides an overview of patent applications filed and published during the period of 2011–2016. The review largely focuses on composition of matter patent applications, although two recently disclosed method of use patents are discussed. Clinical reports are also disseminated.

Expert opinion: Mounting clinical failures with schizophrenic patients have blunted enthusiasm for GlyT-1 inhibition as an approach to treat the disease. However, research in the area remains quite active, as therapeutic potential for several additional indications has emerged. There are numerous and diverse GlyT-1 chemotypes now available that exhibit differentiating modes of binding and ligand-target binding kinetics, and this rich diversity of chemical matter may help further elucidate the target’s pharmacological role in various indications and lead to the identification of a compound with optimal properties that may someday become a drug.     

实例(9)

1999年6月至2000年5月,我院共收治重型病毒性肝炎258例,患者年龄最小为2岁,最大80岁,高峰年龄为22～50岁,有158例(61.24％);男性226例(87.59％),女性32例(12.40％);干部31例(12.02％),工人40例(15.50％),学生23例(8.91％),农民138例(53.49％),其他26例(10.08％)。 258例中有253例做了血清学检查,其中甲型11例(4.34％),乙型230例(90.91％),丙型12例(4.74％),丁型11例(4.34％),戊型18例(7.11％),庚型1例(0.39％),其余为混合型。 并发症中自发性腹膜炎58例,肝性脑病34例,上消化道出     

养生箴言(9)

◎夫恬儋寂寞,虚无而为,此天地之平而道德之质也。故曰:圣人休休焉则平易矣。平易则恬儋矣。平易恬儋,则忧患不能人,邪气不能袭,故其德全而神不亏。     

实验诊断学(9)

8.9凝血酶原时间(PT,prothrombin time)8.9.1正常生理参考值男:11～13.7s,活动度80%～120%;女:11～14.3s,活动度80%～120%,超正常对照上限值3s以上为异常(Quick一期法)。8.9.2临床意义PT延长可见于Ⅴ、Ⅶ、Ⅹ因子缺陷、FG著减及血中抗凝物质增加时PT均可延长。重症肝病、阻塞性黄疸及其维生素K缺乏;DIC(播散性血管内凝血)和应用双香豆素治疗后等PT亦显延长,故本试验可用作抗凝药物治疗的监控方法。8.10凝血酶原消耗试验(PCT prothrombin consumption test)8.10.1正常生理参考值正常>25s;异常<20s;可疑范围:20～25s。8.10.2临床意义P…     

Acute and repeated dose (4 weeks) oral toxicity studies of two antihypertensive peptides,RYLGY and AYFYPEL,that correspond to fragments (90–94) and (143–149) from αs1-casein

The Lowpept® is a powdered casein hydrolysate containing the antihypertensive peptides RYLGY and AYFYPEL, two sequences that correspond to α_s1-casein f (90–94) (RYLGY) ¹ and α_s1-casein f (143–149) (AYFYPEL) ¹. To support the safety, Lowpept® has been examined in an acute and in a 4-week repeated dose oral toxicity studies in rats. Powdered casein hydrolysate administered in a single oral gavage dose of 2000 mg/kg resulted in no adverse events or mortality. Also, casein hydrolysate administered as a daily dose of 1000 mg/kg for 4 weeks by gavage resulted in no adverse events or mortality. No evidence or treatment-related toxicity was detected during both studies. Data analysis of body weight gain, food consumption, clinical observations, blood biochemical, haematology, organ weight ratios and histopathological findings did not show significant differences between control and treated groups. It is concluded that the casein hydrolysate containing the peptides RYLGY and AYFYPEL orally administered to rats was safe and that not treatment-related toxicity was detected even at the highest doses investigated in both acute (2000 mg/kg of body weight) and repeated dose (4 weeks) oral (1000 mg/kg of body weight) toxicity studies.     

T-type calcium channel blockers: a patent review (2012–2018)

ABSTRACT

Introduction: T-type calcium channels are attractive targets for potential treatment of epilepsy inflammatory or neuropathic pain, insomnia, Parkinson’s disease, and cancer. Three isoforms having different biophysical functions are expressed in peripheral and central nerve. Since the withdrawal of mibefradil, the first compound marketed for selective T-type calcium channel blockade, extensive efforts have been made to identify more selective T-type calcium channel blockers.

Areas covered: This review covers the 43 patents describing ‘organic small molecules as T-type calcium channel blockers’-published since 2012. The most recent similar patent review was published in 2011. Information from a recent review article and relevant research papers has been included, as well as biological data and clinical trial results where available.

Expert opinion: Triazinone derivatives, carbazole compounds, and aryl triazole/imidazole amide derivatives display potent blockade activity α1H, α1G, and pan T-type calcium channel subtypes, respectively, though the specificity of the letter is still unsatisfactory. Nonetheless, improvements seen in the efficacy of compounds targeting α1H T-type calcium channels indicate significant progress. Ongoing clinical trials are for the candidates Z944 (Phase II) and ACT-709478 (Phase II) appear promising. These studies may lead to a new generation of inhibitors with higher selectivity, improved physicochemical properties, and reduced side effects.     

RET kinase inhibitors: a review of recent patents (2012–2015)

Introduction: Tyrosine kinases are involved in the control of several biological processes and have been recognized as hot spots of oncogenic transformation, thus representing a major therapeutic target. Dysregulated activation of RET kinase, either through point mutations or gene fusions, is accountable for a significant fraction of thyroid carcinomas, as well as a minor population of lung cancers. Two drugs are currently available for the treatment of medullary thyroid carcinoma and two additional compounds have been approved for differentiated thyroid carcinoma. Several other molecules are under preclinical and clinical evaluation.

Areas covered: This review covers the most recent patent literature (2012–2015) describing compounds with activity against the RET kinase, trying to catch a view of the next generation of potential anti-RET drugs.

Expert opinion: RET has been a focus of molecularly targeted efforts for over a decade. However, none of the drugs currently on the clinical stage were specifically developed to hit RET, which was rather an off-target. Besides, only two of four drugs have activity on metastatic medullary carcinoma. Therefore, there is still a need of additional, more potent and more specific RET inhibitors, which will hopefully emerge from the new generation of compounds disclosed in most recent patents.     

腹部超声讲座(9)胆道(2)

7急性艟囊炎 急性胆囊炎是由细菌感染、胆汁淤滞和胰液反流等原因引起的胆囊急性炎症。胆囊结石、胆道寄生虫及周身感染性疾病为其常见的发病因素。主要症状为右上腹痛、发热及胆囊区压痛(墨菲征阳性),症状的轻重与病变程度不同而有较大差别。     

Imidazoline scaffold in medicinal chemistry: a patent review (2012–2015)

Introduction: Until very recently, the ‘imidazoline drugs’ were perceived as a class of central and/or peripheral sympatholytics and vasodilators acting at either the imidazoline binding sites and/or α-adrenergic receptors. However, in recent years it has become evident that the imidazoline scaffold is also contained in synthetic agents that exhibit a broad spectrum of biological activities.

Areas covered: This review provides an insight into the patents filed in the years 2012–2015, and considers 2-imidazoline-containing compounds with proven biological properties. Special attention is paid to agents for which practical applications as active ingredients of pharmaceutical compositions, diagnostic imaging agents, insecticides and herbicides, may be found.

Expert opinion: 2-Substituted imidazolines can exist in multiple tautomeric forms. The implication is that imidazolines and their imidazolidine tautomers cannot be regarded as isofunctional structures and the term ‘imidazoline scaffold’ should be treated with caution. Nevertheless, for medicinal chemists the progress made in development of both the imidazoline- and imidazolidine-containing agents useful for the treatment of neurodegenerative, inflammatory, autoimmune, cancer, and infectious diseases is of the utmost importance.     

Effekte von (-) δ9-trans-Tetrahydrocannabinol (δ9-THC) auf Psychotizismus-Tests

Zusammenfassung Die Wirkung von 250 g/kg (-)⁹-Tetrahydrocannabinol p.o. wurde in einem Doppelblindversuch an 36 freiwilligen Probanden mit solchen objektiven Tests und Leistungstests untersucht, die nach Eysenck die Persönlichkeitsdimension Psychotizismus messen. Die Hypothese der Untersuchung bestand darin, da\ sich Probanden unter ⁹-THC von solchen unter Plabeo in gleicher Richtung wie endogene Psychotiker von psychisch Gesunden unterscheiden. Die Hypothese wurde nur in 5 von 19 Variablen bestÄtigt. 4 dieser 5 Variablen können als Tests der KonzentrationsfÄhigkeit betrachtet werden.

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Effects of (-)⁹-trans-tetrahydrocannabinol (⁹-THC) on tests of psychoticism

In a double-blind study on 36 volunteers the effects of 250 g/kg (-)⁹-trans-tetrahydrocannabinol p.o. on objective and performance tests measuring psychoticism according to Eysenck were assessed. The hypothesis was tested that subjects treated with ⁹-THC differ from those receiving placebo in the same way as endogenous psychotics differ from normals. Confirmation was obtained in only 5 out of 19 variables. Four of these 5 variables may be considered as tests of concentration.

     

诊断学讲座(9) 吞咽困难

吞咽困难是指在咽下食物或饮水时感觉费力、发噎或梗阻感。这是表示食物从口腔到胃的过程中发生梗阻的一个重要症状。吞咽困难在开始时,吃固体食物感到困难,严重时连水都不能下咽。 吞咽困难发生的原因,可能是咽部或食管功能     

综合考试辅导(9)

流行性出血热病肾综合征出血热是由汉坦病毒引起的一种自然疫源性疾病,典型的临床特征有发热、出血和肾脏损害,分为发热期、低血压休克期、少尿期、多尿期和恢复期,亦称流行性出血热。1流行病学1.1传染源主要是携带本病毒的啮齿类动物,如黑线姬鼠、大林姬鼠、褐家鼠等。它们既是宿主动物,又是传染源。     

上期病案(9)分析

1 临床特点 ①老年女性,起病较急;②首发症状为头晕、恶心、呕吐、伴有说话不清;③主要体征是双眼向右侧凝视有水平震颤,右侧上下肢共济失调(+);④既往有高血压、糖尿病病史,入院时血压160/95 mmHg;⑤3个月前做三维经颅多普勒超声检查提示:椎基底动脉血流量偏低。2 进一步辅助检查,以明确诊断     

Immunochemical approach using monoclonal antibody against Δ(9)-tetrahydrocannabinolic acid (THCA) to discern cannabis plants and to investigate new drug candidates

A monoclonal antibody (MAb-4A4) against Δ9- tetrahydrocannabinolic acid (THCA) showing extensive cross-reactivity against various cannabinoids was prepared. Using this antibody, a competitive enzyme-linked immunoassay (ELISA) was developed to detect Δ9-THCA in the range of 1 to 100 mg/ml. Various cannabinoids including Δ9-THC (Δ9-tetrahydrocannabinolic acid), Δ8-THCA (Δ8-tetrahydrocannabinolic acid), Δ8-THC (Δ8-tetrahydrocannabinol), CBD (cannabidiol), and CBN (cannabinol) were recognized by MAb-4A4, and their cross-reactivities were 55-1600% compared with Δ9-THCA (100%). This novel characteristic of this MAb enabled detection of marijuana residues in biological samples by detection of residual cannabinoids. The ELISA using MAb-4A4 was found to be applicable even for withered samples which contained only trace amounts of Δ9-THCA and Δ9-THC. In addition, this method using MAb-4A4 could be useful in forensic analysis since the MAb-4A4 also shows cross-reactivities against cannabinoid metabolites in body fluids. As well as forensic applications using this MAb, an investigation of new drug candidates focusing on cannabinoid metabolites arising from biotransformation in plant tissue was performed using immunochemical screening. The resulting new drug candidates were cannabinoid glycosides biotransformed by Pinellia ternata whose bioactivity is as yet unidentified. Our results indicate the utility of the application of ELISA using MAb-4A4 for further experiments involving marijuana and cannabinoids not only in the forensic field but also in the context of drug discovery.