北野菊黄酮类成分研究

从北野菊(Dendranthema lavandulifolium)全草中分得四个黄酮类化合物。经光谱(UV,IR,氢谱,碳谱,质谱等)方法鉴定其结构,分别为木樨草素(I),洋芹素(I),金合欢素-7-O-α-L-鼠李糖基(1→6)-β-D-葡萄糖甙(II)和金合欢素-7-O-α-L-鼠李糖基(1→6)-[2-O-乙酰基-β-D-葡萄糖基(1→2)]-β-D-葡萄糖甙(IV)。其中,I和I为首次从该植物中得到,IV为一个新化合物。     

毛白杨化学成分的研究

从毛白杨(Populus tomentosa Carr.)的叶中分得一个新的黄酮类化合物,鉴定为洋芹素-7-O-(6″-O-p-羟基肉桂酰)-B-D-吡喃葡萄糖甙(Ⅰ),同时还分得四个已知成分分别鉴定为水杨甙(salicin,Ⅱ)、2″-苯甲酰水杨甙(tremulodin,Ⅲ)、特里杨甙(tremulacin,Ⅳ)和胡萝卜甙(dauvasterol,Ⅴ)。     

金不换山酮成分的研究Ⅲ一个新山酮甙的结构测定

从民族药金不换(Veratrilla baillonii Franch)根中分离到多种酮化合物,经化学及光谱法测定,其中之一为2,3,4,7-四甲氧基酮-1-O-β-D-木糖基(1→6)-β-D-葡萄糖甙(Ⅰ),是新的酮甙。     

茜草中蒽醌类成分的研究

从茜草Rubia cordifolia L.根的乙醇提取物中分得七个蒽醌类化合物,经理化性质及光谱分析,分别鉴定为1,3,6-三羟基-2-甲基蒽醌(Ⅰ),1-羟基蒽醌(Ⅱ),1,2,4-三羟基蒽醌(Ⅲ),1,3,6-三羟基-2-甲基蒽醌-3-O-β-D-吡喃葡萄糖甙(Ⅳ),1,2-二羟基蒽醌-2-O-β-D-吡喃木糖(1→6)-β-D-吡喃葡萄糖甙(Ⅴ),1,3-二羟基-2-羟甲基蒽醌-3-O-β-D-吡喃木糖(1→6)-β-D-吡喃葡萄糖甙(Ⅵ)及1,3,6-三羟基-2-甲基蒽醌-3-O-β-D-吡喃木糖(1→2)-β-D-(6'-O-乙酰基)吡喃葡萄糖甙(Ⅶ).其中Ⅶ为一新化合物。     

伊贝母中伊贝碱甙C的分离和结构鉴定

自吉林栽培的伊贝母(Fritillaria pallidiflora Schrenk)中分得一种新的甾体生物碱甙,命名为伊贝碱甙C(yibeinosideC)。根据红外、质谱、氢谱、碳谱、¹H-¹HCOSY和¹H-¹³CCOSY谱确定其结构为22,26-环亚胺胆甾-6-酮-3-O-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃半乳糖甙(1)。     

长瓣金莲花茎叶化学成分的研究

从长瓣金莲花(Trollius macropetalus Fr.Schmidt)的干燥茎叶中分离到五个单体,经理化常数测定和光谱分析,确定化合物Ⅰ为牡荆素-2″-O-β-D-吡喃木糖甙(vitexin-2″-O-β-D-pyranxyloside),Ⅱ为荭草素-2″-O-β-D-吡喃木糖甙(orientin-2″-O-β-D-pyranxyloside),Ⅲ为牡荆甙(vitexin),Ⅳ为荭草甙(orientin)Ⅴ为3-甲氧基-4-羟基-5-(3′-甲基-2′-)西烯基甲酸(3-methoxy-4-hydroxyl-5-(3′-methyl-2′-)butylenyl benzoic acid)。其中Ⅰ和Ⅱ系首次从金莲花属植物中获得。Ⅴ为新化合物,命名为原金莲酸(proglobeflowery acid)。     

巫山淫羊藿的化学研究

从小檗科Berberidaceae淫羊藿属Epimedium植物巫山淫羊藿Epimedium wushanense T.S.Ying的地上部分中分得两种黄酮甙单体,经理化性质鉴定及紫外、红外、质谱、氢谱、碳谱等光谱分析,确定甙Ⅰ是新化合物,命名为巫山淫羊藿甙(wushanicariin)。甙Ⅱ是已知化合物淫羊藿甙(icariin),系首次从该种植物中分离。     

通光散藤茎的C21甾体成分

为了研究通光散藤茎中的C₂₁甾体类成分，采用不同的色谱方法对通光散藤茎乙醇提取物进行分离纯化，并用波谱学的方法鉴定化合物的结构。从氯仿部位共分离得到8个C₂₁甾体类化合物，其结构分别被鉴定为11α-O-tigloyl-17β-tenacigenin B (1)、 17β-tenacigenin B (2)、 tenacigenoside A (3)、 11α-O-2-methylbutyryl-12β-O-acetyl tenacigenin B (4)、 tenacissoside H (5)、 marsdenoside A (6)、 tenacissoside G (7)和tenacissoside I (8)。其中化合物1为新化合物。     

穿心莲中两种新的二萜内酯甙的分离和结构测定

本文报道了自穿心莲(Andrographis paniculata Nees)醇提取物中分得两种新的二萜内酯甙:14-去氧穿心莲内酯甙(14-deoxyandrographoside)[Ⅴ]及穿心莲内酯甙(andrographoside)[Ⅶ]。经紫外光谱、红外光谱、质谱及核磁共振氢谱分析,水解及衍生物的制备证明[Ⅴ]为14-去氧穿心莲内酯-19-β-葡萄糖甙,[Ⅶ]为穿心莲内酯-19-β-葡萄糖甙。     

白水茶中二种新黄酮甙的结构

从广西野生的白水茶(Camellia sinensis L.)中分得三种黄酮类成分:Ⅰ,Ⅱ和Ⅲ。经理化常数测定、光谱分析和化学反应鉴定:Ⅰ为已知成分芹菜素(apigenin),Ⅱ为芹菜素-5-O-α-L-吡喃鼠李糖基(1→4)-6″-O-乙酰基β-D-吡喃葡萄糖甙,Ⅲ为芹菜素-5-O-α-L-吡嘀鼠李糖基(1→4)-β-D-吡喃葡萄糖甙。Ⅱ和Ⅲ为首次报道的新黄酮甙,暂分别命名为山茶甙A(camellianin A)和山茶甙B(camcllianin B)。     

Kinetik der Elimination von 2-Propanol und seines Metaboliten Aceton bei Hund und Ratte

Zusammenfassung Die Eliminationskinetik von 2-Propanol und dessen Metaboliten Aceton wird in Versuchen an Hund und Ratte nach Gabe von 1,0 g/kg 2-Propanol i.v. bzw. i.p. festgelegt. Die Elimination von 2-Propanol und Aceton folgt einem einfachen Exponentialgesetz. Der Acetonplasmaspiegel in der Zeit nach 2-Propanolgabe kann durch die Bateman-Funktion mit hinreichender Genauigkeit beschrieben werden. Ein Vergleich mit der Eliminationscharakteristik von Methanol und Äthanol zeigt, daß jeder dieser drei Alkohole bei seiner Elimination einer anderen Kinetik folgt.

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Elimination of 2-propanol in dogs and rats

Summary The kinetics of elimination of 2-propanol and its metabolite acetone were determined in experiments on dogs and rats after administration of 1,0 g/kg 2-propanol i.v. and i.p. respectively. 2-propanol and acetone are eliminated according to a simple exponential function. The concentration of acetone in plasma following administration of 2-propanol can be described satisfactorily by the Bateman-function. Comparing the characteristics of elimination of methanol and ethanol to those of 2-propanol it becomes evident that each of these alcohols follows a different pattern in its elimination.

Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

HPLC法测定不同产地地龙中尿嘧啶、次黄嘌呤、尿苷、肌苷的含量

目的:测定不同产地、品种的地龙药材中尿嘧啶、次黄嘌呤、尿苷、肌苷的含量,建立地龙质量控制的客观指标。方法:用0.9%生理盐水超声提取地龙药材,采用反相高效液相色谱法,Waters Symmetry C₁₈色谱柱（150mm×4.6mm,5μm）,以0.01mol·L^-1磷酸二氢钾溶液和50%甲醇为流动相,流速为0.8ml·min^-1,梯度洗脱,检测波长254nm,柱温27℃,同时测定尿嘧啶、次黄嘌呤、尿苷、肌苷等4种成分的含量。结果:尿嘧啶的线性范围为0.75～24.00μg·ml^-1（r=0.9993）,平均回收率99.82%,RSD=2.34%（n=6）;次黄嘌呤的线性范围2.50～80.00μg·ml^-1（r=0.9992）,平均回收率101.93%,RSD=1.45%（n=6）;尿苷的线性范围1.25～40.00μg·ml^-1（r=0.9992）,平均回收率97.53%,RSD=1.73%（n=6）;肌苷的线性范围5.00～160.00μg·ml^-1（r=0.9991）,平均回收率102.06%,RSD=2.44%（n=6）。结论:该方法重复性,回收率好,可用于地龙药材中尿嘧啶等4种成分的含量测定。     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Drug education: myth and reality

Recently there has been an increase in Australian public funds for drug education. The accompanying rhetoric asserts that it is to enable abstinence among young people. This contradicts some State Government education guidelines endorsing harm minimization. A literature search of the key electronic databases, drug agency libraries, the Internet and reference lists identified evaluation research in school‐based drug education. There is little evidence to support the new public rhetoric. The predictors of adolescent drug use are social and personal; schools can have little effect on these. Four models of drug education are described. Schools, however, mix‐and‐match activities from different models, and exposure is too slight for major effects on behaviours. Although methodological difficulties affect findings, none of the drug education models show consistent behavioural effects over time. There is a mismatch between the new public rhetoric and the evaluation research literature. Reasons for this are explored, including that there are two stakeholder groups, one with exaggerated ideological anti‐drug messages and the other with more realistic perspectives about what schools can reasonably achieve. The paradox is that the rhetoric is needed for continued funding, yet this same rhetoric sets up criteria which doom drug education to failure.     

Metabolism and excretion of (S)-6-(3-cyclopentyl-2-(4-trifluoromethyl)-1H-imidazol-1-yl)propanamido)nicotinic acid (PF-04991532), a hepatoselective glucokinase activator,in humans: confirmation of the MIST potential noted in first-in-Human metabolite scouting studies

1. The absorption, metabolism, and excretion of a single oral 450-mg dose of [¹⁴C]-(S)-6-(3-cyclopentyl-2-(4-trifluoromethyl)-1H-imidazol-1-yl)propanamido)nicotinic acid (PF-04991532), a hepatoselective glucokinase activator, was investigated in humans. Mass balance was achieved with ～94.6% of the administered dose recovered in urine and feces. The total administered radioactivity excreted in feces and urine was 70.6% and 24.1%, respectively. Unchanged PF-04991532 collectively accounted for ～47.2% of the dose excreted in feces and urine, suggestive of moderate metabolic elimination in humans.

2. The biotransformation pathways involved acyl glucuronidation (M1), amide bond hydrolysis (M3), and CYP3A4-mediated oxidative metabolism on the cyclopentyl ring in PF-04991532 yielding monohydroxylated isomers (M2a–d). Unchanged PF-04991532 was the major circulating component (64.4% of total radioactivity) whereas M2a–d collectively represented 28.9% of the total plasma radioactivity.

3. Metabolites M2a–d were not detected systemically in rats and dogs, the preclinical species for the toxicological evaluation of PF-04991532. In contrast, cynomologus monkeys dosed orally with unlabeled PF-04991532 revealed M2a–d in circulation, whose UV abundance was comparable to the profile in humans. This observation suggested that monkeys could potentially serve as a non-rodent alternative for studying the toxicity of PF-04991532 and its metabolites M2a–d.

4. The present results are in excellent agreement with our previously generated metabolite scouting data, which provided preliminary evidence for the disproportionate metabolism of PF-04991532 in humans.     

The safety of second-line treatment options for non-small cell lung cancer

Introduction: Non-small-cell lung cancer (NSCLC) patients after first-line therapy ultimately suffer progression. At this time, many patients still have a good performance status and can be considered for further active treatment. Two chemotherapeutic agents, docetaxel and pemetrexed (only in non-squamous histology), and the biological drug anti-epidermal growth factor receptor (EGFR) erlotinib, were approved for clinical use in the second-line treatment of NSCLC patients. In the last few years further new second-line therapies have become available in the clinical practice.

Areas covered: This review will discuss the adverse events of the pivotal trials ledding to the approval of second-line therapies for the treatment of not oncogene-addicted NSCLC patients.

Expert opinion: In recent years, new second-line options for NSCLC are: the anti-EGFR, afatinib (only in squamous NSCLC); the anti-angiogenics, nintedanib (only in lung adenocarcinoma) and ramucirumab, in combination with docetaxel; the immunotherapeutics, nivolumab, pembrolizumab, and atezolizumab. In the second-line approach, the main endpoint of treatment should always be survival, but with great respect for symptoms palliation and preserving patients’ quality of life. Therefore, differing toxicity profiles of the available therapeutic options are often a deciding factor in second-line setting for NSCLC.     

Drug-induced uveitis

Introduction: Drug-induced uveitis is a well described but often overlooked and/or misdiagnosed adverse reaction to medication. There are an increasing number of medications that have been related to the onset of intraocular inflammation. Identification of these inciting agents may decisively help the diagnostic algorithm involving new cases of uveitis.

Areas covered: This review intends to be an updated comprehensive, practical guide for practitioners regarding the main drugs that have been associated with uveitis. A classification proposed by Naranjo et al. in 1981 for establishing potential causality is applied examining possible mechanisms of action. A guide for clinicians about the rationale of these observations when dealing with patients with uveitis is provided.

Expert opinion: Several agents with different routes of administration (systemic, topical and/or intraocular) may cause intraocular inflammation. The mechanism behind ocular inflammation is frequently unknown. Clinicians should be aware of the potential drug effect to optimize diagnosis and management of such patients.     

Validated chromatographic method for the simultaneous determination of eight drugs (morphine,ropivacaine, bupivacaine,baclofen, clonidine,sufentanil, fentanyl and ziconotide) for intrathecal analgesia

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Self-injection of barbiturates and benzodiazepines in baboons

Self-injection of three barbiturates, six benzodiazepines, and chlorpromazine was examined in baboons. Intravenous injections of drug were dependent upon completion of 160 lever presses (a 160-response fixed-ratio schedule). A 3-h time-out period followed each injection, permitting a maximum of eight injections per day. Prior to testing each dose of drug, self-injection performance was established with cocaine. Subsequently, a test dose was substituted for cocaine. Amobarbital, pentobarbital, and secobarbital maintained the highest levels of self-injection, which were similar to those maintained by cocaine. Clonazepam, clorazepate, diazepam, flurazepam, medazepam, and midazolam maintained relatively modest levels of self-injection, while chlorpromazine maintained only low levels, which were in the range of vehicle control. Of the six benzodiazepines, midazolam produced the highest levels of self-injection. At the highest self-injected doses, the barbiturates produced anesthesia in contrast to the benzodiazepines, which produced only sedation. None of the drugs affected food intake except for chlorpromazine, which produced dose-related decreases. The differences among the drug classes (i.e., barbiturate, benzodiazepine, phenothiazine) with respect to the maintenance of self-injection correspond well with the results of previous animal and human drug self-administration studies.