Study on the Equivalent Conformation of Retinoids

具有诱导细胞分化作用及癌和皮肤病化学治疗作用的维甲类化合物，不仅要求分子一端有疏水性、另一端为极性羧基和整个分子的共轭性，而且分子的构象也起重要作用。本文合成的Ｎ（４羧基苯基）３，５双叔丁基４羟基苯甲酰胺（２）具有与全反式维甲酸（ＡＴＲＡ，１）相似性质的基团配置和构象，表现有维甲酸的生物活性。然而Ｎ甲基化合物３，由于构象的完全不同，丧失了活性。用Ｘ线晶体学、紫外和核磁共振等方法研究了化合物２、３和ＡＴＲＡ的结构异同。     

Study on the metastable state of dilution of spectinomycin

The metastable state of dilution of spectinomycin has been studied by both induction period method and direct method.The polynuclear mechanism of lsing metastability has been disclosed,The metatable zone for dilution of spectinomycin was presented .The influence ofacetone concentraion and temperature on the metastability has been investigated.The induction period elongated as acetone concentraion increased and temperature decreasd The metastable zone-with was broadened with the decreasement of solubility,High superastruation level for nucleation indicated that spectinomycfin belongs to class I system.On the basis of classical nucleation theory the fundamental nucleation parameters for dilution have also been estimated,All the results were important for the control of industrial dilution of spectinomycin.     

 Simulation Study on the Entrance of

d fund industries.The research indicates that the entrance of commercial banks into the property insurance and fund industries can increase their revenue and return per unit of risk,and significantly reduce their probability of bankruptcy.The results also indicate that appropriate proportion of nonbanking assets is indispensable for achieving the optimal effect of diversification.In addition,a comparative study shows that the simultaneous diversification into the property insurance and fund industries generates higher divers2;P<0.01)C与胰岛素水平、C反应蛋白、类风湿因子(RF)、肿胀指数、压痛指数、晨僵时间、病程、年龄、性别等无关;瘦素及瘦素受体在RA患者滑膜中的表达明显高于正常对照组。结论:瘦素可能通过在靶器官的高表达而起到调节炎症的作用;可能在炎性反应中参与急性时相蛋白的合成与调节而影响疾病的发展过程。     

Study on effects of cinobufagin on the immunologic function of mice in vitro

华蟾毒精对小鼠免疫功能影响的体外研究@宋宇$College of Animal Science and Veterinary Medicine,Jilin University!Changchun 130062,Jilin,China;National Standard Laboratory of Pharmacology for Traditional Chinese Medicine, Jilin Natural Pharmatech Co.Ltd, Chang     

Effect of The effects of Δ 9-tetrahydrocannabinol on the metabolism of norepinephrine in rat brain on the morphine-induced hyperactivity of mice

The effect of ⁹-tetrahydrocannabinol (THC) on the locomotor activity-stimulating action of morphine has been investigated in mice. THC (10 mg/kg) has been found to potentiate morphineinduced hyperactivity. On the other hand, the stimulating action of morphine on motor activity strongly diminished in mice rendered tolerant by the implantation of a morphine pellet. The pretreatment of morphine-tolerant mice with the same dose of THC did not change the effect of morphine on the motor activity. These results suggest that tolerance also developed to the potentiating action of THC on morphine-induced hyperactivity during the development of tolerance to this action of morphine.     

Do effects of propranolol on the skeletal system depend on the estrogen status?

BackgroundPropranolol, a nonselective β-adrenergic receptor antagonist, was reported to favorably affect the skeletal system in different animal models. The aim of the study was to investigate whether the effects of propranolol on the skeletal system depend on the estrogen status.MethodsThe in vivo experiments were carried out on the following groups of mature female Wistar rats: sham-operated control rats, sham-operated rats receiving propranolol, ovariectomized (OVX) control rats, OVX rats receiving propranolol, OVX rats receiving estradiol, OVX rats receiving estradiol and propranolol. Propranolol hydrochloride (10 mg/kg po) and/or estradiol (0.1 mg/kg po) were administered daily for 4 weeks. Bone mass, mineral and calcium content, macrometric and histomorphometric parameters, and mechanical properties were examined. In vitro, effects of estradiol and propranolol on the formation of mouse osteoclasts and on the mRNAexpression of genes related to osteoclastogenesis, bone formation and mineralization, as well as adrenergic and estrogen signalling in mouse osteoblasts were investigated.Results and conclusionPropranolol exerted some favorable effects on the rat skeletal system in vivo, independently of the estrogen status. However, in vitro studies indicated a possibility of some antagonistic relations between the estradiol and propranolol effects.     

Studies on the Constituents of Aerial Parts of Scutellaria planipes

首次从木根黄芩地上部分分离出１３个化合物。经理化常数和光谱分析分别鉴定为异甘草甙元（ｉｓｏｌｉｑｕｉｒｉｔｉｇｅｎｉｎ），蓟黄素（ｃｉｒｓｉｍａｒｉｔｉｎ），汉黄芩素（ｗｏｇｏｎｉｎ），芹菜素（ａｐｉｇｅｎｉｎ），粘毛黄芩素Ⅲ（ｖｉｓｃｉｄｕｌｉｎⅢ），紫丁香甙（ｓｙｒｉｎｇｉｎ），白杨素６ＣβＤ葡萄糖８ＣαＬ阿拉伯糖甙（６ＣβＤｇｌｕｃｏｓｙｌ８ＣαＬａｒａｂｉｎｏｓｙｌｃｈｒｙｓｉｎ），白杨素６ＣαＬ阿拉伯糖８ＣβＤ葡萄糖甙（６ＣαＬａｒａｂｉｎｏｓｙｌ８ＣβＤｇｌｕｃｏｓｙｌｃｈｒｙｓｉｎ），黄芩甙（ｂａｉｃａｌｉｎ），汉黄芩甙（ｗｏｇｏｎｉｎ７ＯβＤｇｌｕｃｕｒｏｎｉｄｅ），白杨素７ＯβＤ葡萄糖醛酸甙（ｃｈｒｙｓｉｎ７ＯβＤｇｌｕｃｕｒｏｎｉｄｅ）和两个苯乙醇甙（ａｃｔｅｏｓｉｄｅ和ｍａｒｔｙｎｏｓｉｄｅ）。其中异甘草甙元，蓟黄素和紫丁香甙均为首次从黄芩属植物中分离得到。     

What modulates the impacts of acid rain on the allelopathy of the two Asteraceae invasives?

Most of the allelopathic studies have focused on the independent allelopathy of one invasive plant, but have ignored the co-allelopathy of the two invasives. The variations in the type of acid rain can modulate the invasiveness of invasives via the changes in the allelopathy. Thus, it is vital to elucidate the allelopathy of invasives, particularly the co-allelopathy of the two invasives, under acid rain with different types, to illuminate the mechanisms driving the co-invasion of two invasives under diversified acid rain. However, little progress has been finished in this aspect presently. This study aimed to evaluate the co-allelopathy of two Asteraceae invasives Solidago canadensis L. and Erigeron annuus L. treated with acid rain with different nitrogen-to-sulfur ratios on seed germination and seedling growth of the horticultural Asteraceae species Lactuca sativa L. via a hydroponic experiment. Aqueous extracts of the two Asteraceae invasives generated obvious allelopathy on L. sativa. S. canadensis aqueous extracts caused stronger allelopathy. There may be an antagonistic effect for the co-allelopathy of the two Asteraceae invasives. Nitric acid at pH 5.6 weakened the allelopathy of the two Asteraceae invasives, but the other types of acid rain strengthened the allelopathy of the two Asteraceae invasives. The allelopathy of the two Asteraceae invasives increases with the increasing acidity of acid rain, but the allelopathy of the two Asteraceae invasives decreases with the increasing nitrogen-to-sulfur ratio of acid rain. Accordingly, the species number of invasives, and the acidity and type of acid rain modulated the impacts of acid rain on the allelopathy of the two Asteraceae invasives.

     

Effects of the administration of miconazole by different routes on the biomarkers of the “steroidal module” of the Athlete Biological Passport

This article reports the results obtained from the investigation of the influence of miconazole administration on the physiological fluctuation of the markers of the steroid profile included in the “steroidal module” of the Athlete Biological Passport. Urines collected from male Caucasian subjects before, during, and after either systemic (i.e., oral and buccal) or topical (i.e., dermal) treatment with miconazole were analyzed according to validated procedures based on gas chromatography coupled to tandem mass spectrometry (GC–MS/MS) (to determine the markers of the steroid profile) or liquid chromatography coupled to MS/MS (LC–MS/MS) (to determine miconazole urinary levels). The results indicate that only after systemic administration, the markers of the steroid profile were significantly altered. After oral and buccal administration, we have registered (i) a significant increase of the 5α-androstane-3α,17β-diol/5β-androstane-3α,17β-diol ratio and (ii) a significant decrease of the concentration of androsterone, etiocholanolone, 5β-androstane-3α,17β-diol, and 5α-androstane-3α,17β-diol and of the androsterone/etiocholanolone, androsterone/testosterone, and 5α-androstane-3α,17β-diol/epitestosterone ratios. Limited effects were instead measured after dermal intake. Indeed, the levels of miconazole after systemic administration were in the range of 0.1–12.5 μg/ml, whereas after dermal administration were below the limit of quantification (50 ng/ml). Significant alteration started to be registered at concentrations of miconazole higher than 0.5 μg/ml. These findings were primarily explained by the ability of miconazole in altering the kinetic/efficacy of deglucuronidation of the endogenous steroids by the enzyme β-glucuronidase during the sample preparation process. The increase of both incubation time and amount of β-glucuronidase was demonstrated to be effective countermeasures in the presence of miconazole to reduce the risk of uncorrected interpretation of the results.     

Studies on the Antitumour Activities of 8-Chloroadenosine

（Ｓｐ）－８－氯腺苷３′，５′环磷酸辛酯（ＯＣＣ）是８－氯腺苷３′，５′环磷酸的新衍生物，对人白血病细胞ＨＬ－６０有很强的抑制作用和诱导分化作用。用细胞流式光度术发现ＯＣＣ阻断ＨＬ－６０细胞周期于Ｇ１期。ＯＣＣ对ＨＬ－６０细胞ＤＮＡ合成有显著抑制作用，但不影响ＲＮＡ和蛋白质合成。ＯＣＣ能激活ＨＬ－６０细胞浆中蛋白激酶Ａ。８－氯腺苷是ＯＣＣ的活性代谢产物，能在体外和体内实验中明显抑制肿瘤的生长。８－氯腺苷也能诱导人胃癌ＭＧｃ８０－３细胞分化和人Ｔ淋巴母细胞ＭＯＴＬ－４的凋亡。本文讨论了８－氯腺苷抗肿瘤作用的机理。     

Effect of ECR on the Expression of Tau from the Brain of the Mice Induced by Overload Aluminum Salt

Aim: To study the effect of Ecdysterone (ECR) on the expression of Tau from the cerebral cortice and hippocampus and behaviors in passive avoidance reaction and spatial discrimination of the mice induced by overload aluminum salt.Methods Fourty-five NIH mice were randomly divided into five groups, the control group, the model group, the treated     

Effects of β-adrenoceptor antagonists on the firing rate of noradrenergic neurones in the locus coeruleus of the rat

Summary Acute i.v. administration of the non-selective -adrenoceptor antagonist dl-propranolol given in incremental doses (<40 mg/kg) did not affect the firing rate of locus coeruleus (LC) neurones in the rat, as revealed by single cell recording techniques. Furthermore, no effect was seen 4 h after a single i.p. dose of this -blocker (10 mg/kg). However, repeated treatment with dl-propranolol (1, 5, 10 or 20 mg/kg i.p., twice daily for 4 days) produced a significant, dose-dependent decrease of the average LC neuronal firing rate in comparison to controls. The dextro isomer of propranolol, which has negligible -blocking activity but the same local anaesthetic potency as the racemate, had no corresponding effect. The non-selective -adrenoceptor antagonist sotalol, which is one of the most hydrophilic -blockers, had much less inhibitory effect on LC neurones than dl-propranolol. The ₁-selective antagonist metoprolol did not change the firing of noradrenergic neurones in the LC after similar treatment for 4 days. However, when the rats were subjected to oral treatment for 28 days, metoprolol was found to produce a slight inhibitory effect although much less than dl-propranolol.In view of these findings we propose a stimulatory and mainly ₂-adrenoceptor-mediated control mechanism for the noradrencrgic neurones in the LC. This mechanism seems to be characterized by a delayed responsiveness.     

Studies on the Chemical Constituents of Four Species of Fritillaria Plants

The bulbs of Fritillaria spp.(Liliaceae)are used in Chinese medicine as antipyretic,anti-tussive,expectorant,etc.In order to search for the bioactive constituents from this genus,thebulbs of four species of medicinal Fritillaria plants have been investigated.Thirteen compoundswere isolated from Fritillaria thunbergii Miq.,three of them were new compounds.Fourteencompounds from Fritillaria thunbergii var.chekiangensis Hsiao et K.C.Hsia collected inDongyang of Zhejiang Province,four of them are new compounds and another one was first iso-     

The influence of azone® on the percutaneous absorption of methotrexate

The percutaneous absorption of the polar drug methotrexate has been examined in vitro. Two alcoholic gel formulations containing 1% methotrexate with or without Azone® were applied to full-thickness abdominal human skin mounted in all-glass Franz-type diffusion cells. In the absence of Azone® no percutaneous penetration of methotrexate was observed. In the presence of Azone® 190 ng/cm² permeated after 48 h. Azone® appears to be actingas an efficient penetration enhancer for this drug.     

New Aspects for the Treatment of Cardiac Diseases Based on the Diversity of Functional Controls on Cardiac Muscles: Diversity in the Excitation–Contraction Mechanisms of the Heart

The waveform of the myocardial action potential (AP) triggering contraction differs among the species, developmental stage, and pathological state. The species difference in heart rate, which inversely correlates with body size, originates in the ion-channel mechanisms responsible for diastolic depolarization of the sinoatrial node. In some cases, such as the chronically AV-blocked dog and 11- to 13-day chick embryo, the repolarization reserve is decreased making the heart useful for drug evaluation. The degree of dependence of contraction on sarcoplasmic reticulum (SR) function increases during development. The large SR dependence and short AP of the adult mouse and rat support their rapid contraction under high heart rate. The function of the Na⁺/Ca²⁺ exchanger is affected by AP waveform and ion concentrations; its major role is Ca²⁺ extrusion, but under pathological conditions such as ischemia-reperfusion, it allows Ca²⁺ influx and leads to myocardial injury, including loss of mitochondrial function. The role of mitochondria in ATP supply is less in the fetus where glycolysis plays a greater role. The pharmacological properties of the myocardium are affected by all of these factors and also by autonomic innervation and the hormonal status. Such comprehensive understanding is indispensable for the development of novel therapeutic strategies.     

Experimental Study on the Acceleration of the Hemato Immunological Reconstitution of the Lethally Irradiated Mice Following B

ＥｘｐｅｒｉｍｅｎｔａｌＳｔｕｄｙｏｎｔｈｅＡｃｃｅｌｅｒａｔｉｏｎｏｆｔｈｅＨｅｍａｔｏＩｍｍｕｎｏｌｏｇｉｃａｌＲｅｃｏｎｓｔｉｔｕｔｉｏｎｏｆｔｈｅＬｅｔｈａｌｌｙｌｒｒａｄｉａｔｅｄＭｉｃｅＦｏｌｌｏｗｉｎｇＢｏｎｅＭａｒｒｏｗＴｒａｎｓｐｌ...     

Update on the effects of the sodium pump α1 subunit on human glioblastoma: from the laboratory to the clinic

Introduction: Glioblastoma is a debilitating disease that is associated with poor prognosis and a very limited response to therapies; thus, molecularly targeted therapeutics and personalized therapy are urgently needed. The Na⁺/K⁺-ATPase sodium pump is a transmembrane protein complex that has recently been recognized as an important transducer and integrator of various signals. The sodium pump α1 subunit, which is highly expressed in most glioblastomas compared with that in normal brain tissues, is an emerging cancer target that merits further investigation.

Area covered: The purpose of this narrative review is to explore the important roles of the sodium pump α1 subunit in glioblastoma and analyze its potential therapeutic applications.

Expert opinion: Expression of the sodium pump α1 subunit in glioblastoma tissues is generally higher than that in normal tissues. Sodium pump α1 subunit-mediated pivotal antiglioblastoma signaling pathways have been reviewed, and their impact on the sensitivity of glioblastoma cells to anticancer drugs has recently been clarified. In addition, various pharmacologically optimized sodium pump inhibitors have recently reached early clinical trials, and explorations of sodium pump α1 subunit inhibitors may hold promise for the development of stratification strategies in which patients are treated based on their isoform expression status.     

An examination of the potential effect of lipids on the first‐pass metabolism of the lipophilic drug anethol trithione

In this study, an examination of the potential effect of lipids on the first‐pass metabolism of anethol trithione (ATT) was investigated. ATT is metabolized rapidly and extensively in liver into 4‐hydroxy‐anethole trithione (ATX), which was confirmed using the rat intestinal perfusion with the mesenteric cannulation model. Male Sprague–Dawley rats were orally administered of the lipid‐based formulations (prepared by medium chain triglycerides (MCT)), the cyclodextrin formulation and the suspension formulation, respectively. For 6.75 mg/kg groups, ATX/ATT area under the plasma concentration‐time curve (AUC) ratio decreased by 87% and 76% after administration of the MCT‐based formulations and the cyclodextrin formulation, when compared with the suspension formulation (p < 0.05), respectively; for 2.25 mg/kg groups, it decreased by 53% in the MCT group when compared with the cyclodextrin group (p < 0.05). The saturation of pre‐system metabolism of ATT was observed after administration of the MCT‐based formulations and the cyclodextrin formulation, likely as a result of enhanced absorption and therefore presentation of higher drug concentrations to liver, when compared with the suspension formulation. A trend toward lower systemic metabolite to parent ratios was evident after administration of the lipid formulations, when compared with the cyclodextrin formulation; however, this was not statistically significant. Further studies on the potential for lipids to inhibit hepatic metabolism are therefore warranted. © 2011 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:5048–5058, 2011