β3-肾上腺素受体激动剂的研究进展

摘要β     

Effects of cannabidiol and of diphenylhydantoin on the hippocampus and on learning

Cannabidiol (3.5 mg/kg, i.p.) depressed hippocampal facilitation and posttetanic potentiation of evoked responses in rats, such, as had been reported before for diphenylhydantoin. Both diphenylhydantoin (80 mg/kg, i.p.) and cannabidiol blocked the increase of hippocampal RNA concentration caused by afferent stimulation, and depressed the acquisition of a conditioned avoidance response in rats. Neither drug affected the retention of such response when given by posttrial injection, nor the spontaneous locomotor activity of mice. The effects of both agents may be explained by the interference they have been previously shown to produce with the release of K⁺ from the hippocampus during stimulation. In fact, hippocampal facilitation and posttetanic potentiation and the RNA response to stimulation have been shown to be phenomena which depend on this K⁺ release, and have been attributed a role in learning.     

朱砂及含朱砂制剂的肝肾毒性研究

目的 探讨朱砂、含朱砂制剂（柏子养心片）及甲基汞对大鼠的体内外毒性,为其临床安全用药提供科学依据。方法 ①对比甲基汞、朱砂及柏子养心片体外对人肝HL-7702细胞和人肾近曲小管上皮HK2细胞的毒性,计算半数抑制浓度（IC₅₀）。②SD大鼠随机分为对照组,朱砂组0.1 g/kg,柏子养心片0.2、0.4、0.8 g/kg组,甲基汞组0.001 g/kg,每天ig 1次,连续给药90 d后,取血及肝、肾组织;试剂盒法检测血清中丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、肌酐（CREA）、尿素氮（BUN）水平,测汞仪固体直接进样法检测肝、肾组织中汞蓄积量,并对大鼠肝脏和肾脏做组织病理学检查。结果 体外试验表明,朱砂、柏子养心片及甲基汞对HL-7702细胞的IC₅₀分别为7.852、6.035、0.009 5 g/L;对HK2细胞的IC₅₀分别为6.297、4.484、0.008 9 g/L。亚慢性毒性试验表明,甲基汞组大鼠肝、肾组织中汞蓄积量及血清中ALT、AST、CREA、BUN值均显著高于对照组,而朱砂及柏子养心片（高、中、低剂量）组与对照组比较均没有显著性差异;甲基汞组大鼠肝脏呈现肝细胞变性,肾脏可见明显肾小管损伤,而朱砂及柏子养心片（高、中、低剂量）组与对照比较没有明显差异。结论 朱砂及柏子养心片的体内外毒性均显著低于甲基汞,在目前药典规定的临床用量下使用安全性较好。     

左乙拉西坦与托吡酯治疗儿童原发性癫痫的效果及其对免疫功能的影响

目的:观察左乙拉西坦与托吡酯治疗原发性癫痫的疗效及安全性,并探讨其对患儿免疫功能的影响。方法:选择我院2013年3月至2015年6月收治的原发性癫痫患儿60例,随机分为左乙拉西坦组和托吡酯组各30例,另选同期体检的健康儿童30例作为对照组。三组儿童均采集晨起空腹静脉血(患儿分别于治疗前和治疗3个月时各采集1次),采用免疫比浊法检测血清免疫球蛋白IgG、IgA、IgM 水平,采用流式细胞技术检测T 淋巴细胞亚群CD3+、CD4+、CD8+水平。观察治疗前后各组患儿免疫功能指标变化、临床疗效及不良反应。结果:治疗前两组患儿IgA、IgG、IgM、CD3+、CD4+及CD8+水平与对照组比较,差异均有统计学意义(P均<0.05);治疗后两组患儿IgA、IgG、CD8+和(或)CD4+水平较治疗前明显改善(P均<0.05),且与对照组比较差异无统计学意义(P均>0.05),两组患儿之间比较差异也无统计学意义(P均>0.05)。治疗3个月后,左乙拉西坦组总有效率为93.33%,托吡酯组为86.67%,两组比较差异无统计学意义(P>0.05)。两组患儿治疗过程中均无明显电解质紊乱、血尿常规及肝肾功能检查异常,不良反应轻微,无停药病例。结论:癫痫患儿存在免疫功能异常,应用左乙拉西坦和托吡酯均能改善其免疫功能,且二者疗效相当,安全性较高,均具有较高的临床应用价值。     

东南沿海南日岛部队驻地恙虫病自然疫源地调查及防治研究

为查明东南沿海财日岛驻地恙虫病疫源地及流行病学特征，对该岛恙 虫病患者４５例进行分析和流行病学研究。结果表明该岛存在恙 虫病流行，属夏季型，临床症状典型，并出现多脏器功能损害。     

丹参多酚酸盐治疗不稳定型心绞痛的疗效及其对一氧化氮和内皮素的影响

目的观察丹参多酚酸盐治疗不稳定型心绞痛（UA）的疗效及其对血清一氧化氮（NO）和内皮素（ET）水平的影响。方法 60例患者随机分为治疗组和对照组各30例。对照组给予常规抗心绞痛治疗,治疗组在对照组治疗的基础上加用丹参多酚酸盐注射液。观察比较2组临床疗效、血清NO和ET水平及心电图改善和药物不良反应情况。结果 治疗组临床疗效、血清NO和ET水平及心电图改善情况均优于对照组,差异有统计学意义（P〈0.05）。2组均未发生药物不良反应。结论丹参多酚酸盐可明显改善UA患者的临床症状和心电图ST-T改变,要提高血清NO水平的同时降低ET水平。     

Influence of streptozotocin-induced diabetes on blood pressure and on renin formation and release

Summary I.v. injection of 40 mg/kg or 65 mg/kg streptozotocin reliably induced diabetes in female Sprague-Dawley rats, but failed to induce hypertension within the following 42 days. In most animals injected with the higher dose and in some animals injected with the lower dose, the tail blood flow was permanently impaired so that no blood pressure signals could be obtained by tail plethysmography. This phenomenon occurred also when the drug was injected into the jugular vein and thus was not due to a local effect of streptozotocin. 15 days after 65 mg/kg streptozotocin, the mean arterial pressure of the rats was similar to that of controls, when measured in the awake state (carotid cannula) or under ether anaesthesia. 42 days after streptozotocin, under pentobarbital anaesthesia, the blood pressure was again normal in the animals given 40 mg/kg of the drug and depressed in the animals given 65 mg/kg of the drug 42 days previously. The increase of blood pressure induced by 1 g/kg (–)-noradrenaline i.v. was similar in the latter group of animals and in controls.The renal cortical renin concentration was much lower than in controls 42 days after either dose of streptozotocin, while the plasma renin activity was normal (40 mg/kg) or increased (65 mg/kg). The low renal renin content may have been due to the diabetic state, rather than to the drug itself. Adrenal medullary dopamine-beta-hydroxylase activity was increased 42 days after the higher dose of streptozotocin.Supported by the Swiss National Science Foundation, grant Nr. 3.410.078     

妊娠合并子宫肌瘤对母儿影响的分析

目的 探讨妊娠合并子宫肌瘤对母儿的影响。方法 对1999年1月～2004年12月73例在剖宫产术中发现的子宫肌瘤进行分析。结果 妊娠合并肌瘤的胎位异常（臂位）率、产后出血率分别为17．8％、20．54％,而对照组分别为3．18％和8．97％;低体重儿发生率12、33％,而对照组为6．07％,有显著差异。结论 子宫肌瘤增加了母儿并发症的可能性;合并黏膜下肌瘤也有望使妊娠过程成功。     

Effect of endothelin on total and regional coronary resistance and on myocardial contractility

Endothelin is a 21-amino acid peptide produced by the endothelium and has a potent vasoconstrictor effect. Because of the importance of the endothelium on vasomotor regulation, we studied the effect of endothelin on total and regional coronary vascular resistance and on myocardial contractility in the intact heart of anesthetized dogs. Intracoronary administration of 2 to 80 pmol/kg of endothelin produced a dose-dependent increase in coronary resistance, ischaemic decrease in myocardial contractility and atrium-ventricular blockade. The increase in resistance was greater towards the outer layer of the left ventricular wall. When the coronaries were perfused at a constant rate and vasoconstriction was prevented with adenosine or nitroglycerine, endothelin did not produce inotropic changes. These results show that endothelin is a potent vasoconstrictor of the resistance coronary vessels, producing a redistribution of transmural blood flow and a decrease in myocardial contractility secondary to ischaemia.     

Effect of ranitidine on ileal myenteric plexus preparation and on acetyl- and butyrylcholinesterase

Ranitidine at concentrations from 1 microM to 0.1 mM brought about a dose-dependent potentiation of the twitch responses elicited by electrical stimulation of the ileal myenteric preparation. At higher concentrations (0.3-3 mM) ranitidine also caused irregular slow contractions of the unstimulated ileal preparation which were potentiated by eserine and blocked by atropine and tetrodotoxin. In order to identify the mechanism of these apparently cholinomimetic actions, the effects of ranitidine on AChE and BuChE were studied. Ranitidine showed an instantaneous and promptly reversible inhibitory action at concentrations between 0.5 and 30 microM. Double reciprocal plots were prepared and equilibrium dissociation constants calculated. It appears that ranitidine exerts an inhibition of the "mixed" type on both AChE and BuChE, but the dissociation constants for BuChE were markedly higher than those for AChE. Since AChE inhibition occurs in the same concentration range potentiating the twitch responses on the ileal myenteric preparation, it may explain the cholinomimetic effect of ranitidine.     

Enniatin B and Deoxynivalenol Activity on Bread Wheat and on Fusarium Species Development

Fusarium head blight (FHB) is a devastating wheat disease, mainly caused by Fusarium graminearum (FG)—a deoxynivalenol (DON)-producing species. However, Fusarium avenaceum (FA), able to biosynthesize enniatins (ENNs), has recently increased its relevance worldwide, often in co-occurrence with FG. While DON is a well-known mycotoxin, ENN activity, also in association with DON, is poorly understood. This study aims to explore enniatin B (ENB) activity, alone or combined with DON, on bread wheat and on Fusarium development. Pure ENB, DON, and ENB+DON (10 mg kg⁻¹) were used to assess the impacts on seed germination, seedling growth, cell death induction (trypan blue staining), chlorophyll content, and oxidative stress induction (malondialdehyde quantification). The effect on FG and FA growth was tested using ENB, DON, and ENB+DON (10, 50, and 100 mg kg⁻¹). Synergistic activity in the reduction of seed germination, growth, and chlorophyll degradation was observed. Conversely, antagonistic interaction in cell death and oxidative stress induction was found, with DON counteracting cellular stress produced by ENB. Fusarium species responded to mycotoxins in opposite directions. ENB inhibited FG development, while DON promoted FA growth. These results highlight the potential role of ENB in cell death control, as well as in fungal competition.     

Warnings on alcohol containers and advertisements: International experience and evidence on effects

Issues. In light of possible introduction of alcohol warning labels in Australia and New Zealand, this paper discusses the international experience with and evidence of effects of alcohol warning labels. Approach. The report describes international experience with providing information and warnings concerning the promotion or sale of alcoholic beverages, and considers the evidence on the effects of such information and warnings. The experience with and evaluations of the effects of tobacco warning labels are also considered. Key Findings. The most methodologically sound evaluations of alcohol warning labels are based on the US experience. Although these evaluations find little evidence that the introduction of the warning label in the USA had an impact on drinking behaviour, there is evidence that they led to an increase in awareness of the message they contained. In contrast, evaluations of tobacco warning labels find clear evidence of effects on behaviour. Implications. There is a need and opportunity for a rigorous evaluation of the impacts of introducing alcohol warning labels to add to the published work on their effectiveness. The experience with tobacco labels might guide the way for more effective alcohol warning labels. Conclusion. Alcohol warning labels are an increasingly popular alcohol policy initiative. It is clear that warning labels can be ineffective, but the tobacco experience suggests that effective warning labels are possible. Any introduction of alcohol warning labels should be evaluated in terms of effects on attitudes and behaviour.[Wilkinson C, Room R. Warnings on alcohol containers and advertisements: International experience and evidence on effects. Drug Alcohol Rev 2009;28:426–435]     

猴头多糖抗肿瘤及对免疫功能的影响

目的　研究猴头多糖 ( HEPS)对小鼠 S1 80 肉瘤及免疫功能的影响。方法　 H EPS按 10 0、2 0 0、40 0m g/ kg体重连续灌胃 15 d,测定荷瘤小鼠瘤重 ,通过检测小鼠抗体生成细胞、迟发性变态反应、NK细胞活性 ,荷瘤小鼠免疫器官分别检测 HEPS对体液免疫、细胞免疫、非特异免疫及异常免疫的调节作用。结果　 HEPS可显著抑制 S1 80 肉瘤的生长 ,提高荷瘤小鼠胸腺和脾重 ,增强正常小鼠抗体形成细胞溶解绵羊红细胞能力、迟发型变态反应能力、NK细胞活性。结论　 HEPS具有抗肿瘤及免疫调节作用     

The effects of d-fenfluramine on saccharin intake and preference, and on food and water intake

The effects of d-fenfluramine on saccharin intake and preference were examined to investigate whether the reduced rate of eating induced by this compound reflects a reduction in the palatability of foods. In two separate experiments, water deprived rats were offered a choice between a 0.05% solution of saccharin and water, or a 0.2% saccharin solution and water. Injection of d-fenfluramine at doses which reliably decreased food intake resulted in dose dependent reductions in total fluid intake and saccharin intake. A trend towards reduced water intake was observed also, and this together with the reduced saccharin intake resulted in no overall change in saccharin preference. In a further experiment, d-fenfluramine reduced the water intake of water deprived rats to the same extent as it reduced total fluid intake in the choice tests. Since d-fenfluramine failed to alter saccharin preference, it is unlikely that the slowed eating rate induced by this compound indicates a reduction in food palatability. Instead, it is likely that this behaviour results from a subtle motor deficit, such that fenfluramine treated animals are unable to maintain ingestion at the same rate as non-drugged animals. This explanation could account for the reduction in the consumption of non-nutritive saccharin solutions and water in water deprived animals. The relevance of this action to the anorectic effect of fenfluramine is discussed.     

Changes in crystallinity and solubility on comminution of digoxin and observations on spironolactone and oestradiol.

Using infrared spectroscopy, X-ray diffractometry, differential thermal analysis, scanning electron microscopy, solubility and dissolution rate measurements, it was demonstrated that the comminution of digoxin results in the appearance of an amorphous phase. The examination of spironolactone and 17 beta-oestradiol by infrared spectroscopy and differential thermal analysis showed that these compounds also undergo changes in their crystallinity on grinding. Since the dissolution characteristics of poorly soluble drugs may be complex functions of surface area and crystallinity, it is concluded that the most pertinent method for standardizing a sample of a polymorphic drug of low solubility is by means of a powder dissolution test, as the results embrace the influences of particle size, aggregation and polymorphism.     

Effects of arsenic and UVB on normal human cultured keratinocytes: impact on apoptosis and implication on photocarcinogenesis

Inorganic arsenic is an environmental toxin and a human carcinogen. Being a co-mutagen, arsenic enhances carcinogenesis of ultraviolet irradiation on the mouse skin. Apoptosis, a well-regulated cell death process, is essential for cell development and tissue homeostasis. Dysregulation of apoptosis will lead to various kinds of pathological conditions, such as cancers. The purpose of this study is to investigate the apoptotic effect induced by the interactions of arsenic and UVB on cultured human keratinocytes. Cultured keratinocytes were treated with sodium arsenite (1 microM) and/or UVB 50 mJ/cm2 irradiation in different combinations, including arsenic alone (As group), UVB alone (UVB group), arsenic followed by UVB (As/UVB group), and UVB followed by As (UVB/As group) treatments. Our results revealed that a low concentration of sodium arsenite did not induce keratinocytes apoptosis. The UVB group showed obvious elevation of caspase-8, -9, and -3 activities in addition to strong induction of apoptosis as determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine nick-end labeling (TUNEL) assay. Similar pro-apoptotic effects were observed in the UVB/As group. In contrast, only subtle changes of cell morphology and survival rate were noticed in the As/UVB group. In addition, the results of Western blot and activity assay of caspase-8, -9, and -3 revealed that neither the receptor nor the mitochondrial apoptotic signaling pathway was activated in the As/UVB group. Therefore, we conclude that the pretreatment of keratinocytes with sodium arsenite decreased the pro-apoptotic effects induced by UVB. This finding corroborated with the animal model studying the effects of arsenic and UVB on carcinogenesis. The molecular mechanisms by which arsenic decreased UVB-induced apoptosis remain to be elucidated.     

An update on anesthetics and impact on the brain

Introduction: While anesthetics are indispensable clinical tools and generally considered safe and effective, a growing concern over the potential neurotoxicity of anesthesia or specific anesthetic agents has called into question the safety of general anesthetics, especially when administered at extremes of age.

Areas covered: This article reviews and updates research findings on the safety of anesthesia and anesthetics in terms of long-term neurotoxicity, with particular focus on postoperative cognitive dysfunctions, Alzheimer’s disease and dementias, developing brain, post-operative depression and autism spectrum disorder.

Expert opinion: Exposure to general anesthetics is potentially harmful to the human brain, and the consequent long-term cognitive deficits should be classified as an iatrogenic pathology, and considered a public health problem. The fact that in laboratory and clinical research only certain anesthetic agents and techniques, but not others, appear to be involved, raises the problem on what is the safest and the least safe anesthetic to maximize anesthesia efficiency, avoid occurrence of adverse events, and ensure patient safety. New trends in research are moving toward the theory that neuroinflammation could be the hallmark of, or could have a pivotal role in, several neurological disorders.