“Detoxication,a most Stimulating Concept of Toxicology”

1. Large, independent variations occur among New Zealand White rabbits in the 21-and 6β-hydroxylation of progesterone as catalysed by liver microsomes.

2. These reactions are catalysed respectively by two electrophoretically distinct types of rabbit-liver microsomal cytochrome P-450, 1 and 3b, as judged by their catalytic efficiency and the capacity of specific monoclonal antibodies to extensively inhibit the respective microsomal hydroxylases.

3. The relatively large variations in progesterone 6β-hydroxylase activity do not appear to be associated with differences in microsomal content of cytochrome P-450 3b, whereas differences in the microsomal concentration of cytochrome P-450 1 may underlie variations in 21-hydroxylase activity.

4. Preparations of cytochrome P-450 3b contain at least two catalytically distinct subforms, one of which catalyses both 6β- and 16α-hydroxylation of progesterone with a low K_m while the other subform catalyses predominantly 16α-hydroxylation with a significantly greater K_m.

5. The two catalytic subforms of cytochrome P-450 3b can be independently modulated in vitro by positive and negative effectors that can arise in vivo from the metabolism of progesterone.

6. The 6β-hydroxylase subform of cytochrome P-450 3b is not expressed in a genetically defined strain of rabbits, IIIVO/J, indicating a heritable basis for the differential expression of the two subforms of cytochrome P-450 3b.

7. These results indicate that the extent of cytochrome P-450 multiplicity may be greater than is evident from the isolation of electrophoretically distinct forms of cytochrome P-450, and that small differences in structure may underlie large differences in catalytic properties.

8. It is not known whether the differences among outbred New Zealand White rabbits in the expression of either cytochrome P-450 1 or the subforms of cytochrome P-450 3b reflect regulatory phenomena or genetic polymorphism.     

Cardiovascular effects of agmatine,a “clonidine-displacing substance”, in conscious rabbits

Agmatine has been identified as a clonidine-displacing substance in extracts from bovine brain. We studied its effect on cardiovascular regulation and the role played in this effect by ₂-adrenoceptors.In conscious rabbits, agmatine 10 g kg^–1 injected intracisternally (i.e.) caused no change, whereas agmatine 30, 100 and 300 g kg^–1 i.e. increased renal sympathetic nerve firing, the plasma concentration of noradrenaline and adrenaline and arterial blood pressure. Heart rate tended to be decreased. Yohimbine 1.5 g kg^–1 i.e. caused no change, whereas yohimbine 5, 15 and 50 g kg^–1 increased renal sympathetic nerve activity, the plasma concentration of noradrenaline and adrenaline, blood pressure and heart rate. In rabbit brain cortex slices preincubated with [³H]-noradrenaline, agmatine 1 to 100 M did not modify the electrically evoked overflow of tritium (either 4 pulses at 100 Hz or 36 pulses at 3 Hz). The evoked overflow was reduced by 5-bromo-6-(2-imidazolin-2-ylamino)quinoxaline (UK 14304) 0.03 to 30 nM (4 pulses at 100 Hz), and this inhibition was not affected by agmatine 10 and 100 M. Agmatine did not change the basal efflux of tritium.The results show that agmatine, like yohimbine, causes central sympathoexcitation when given i.e., but agmatine differs from yohimbine in that it does not increase heart rate. Agmatine acts neither as an agonist nor as an antagonist at the ₂-autoreceptors in rabbit brain cortex. ₂-Adrenoceptors, therefore, are probably not involved in its cardiovascular effects. An action at imidazoline receptors in the medulla oblongata or some other hitherto unknown mechanism may be responsible for the sympathoexcitation.     

“Medicamentation” of society, non-diseases and non-medications: a point of view from social pharmacology

This review presents the definition and goals of social pharmacology, a new branch of clinical pharmacology, investigating relationships between drugs and society through the example of medicamentation, defined as the use of drugs for social problems previously not requiring drug utilisation (ageing, smoking cessation, vigilance troubles, sleep synchronisation, loss of libido, etc.). The involvement of the different actors from our society (patients, physicians, pharmaceutical industries, clinical pharmacologists, regulatory agencies, etc.) in this phenomenon is also discussed.     

Pilot study,in a rental retirement village,of an “AdherenceCheck” on the management of medicines by the older-aged

Background The older-aged living in a low socioeconomic, rental, retirement village have a low adherence to medicines and a poor understanding of their illnesses. MedsChecks are commonly used in Australian pharmacies in an attempt to improve the management of medicines. There is no published evidence that MedsChecks, or similar brief/single, interventions improve the management of medicines in the older-aged. Objective The objective of our study was to determine the effect of an AdherenceCheck, which is similar to a MedsCheck, but is performed in the home of the older-aged, had on the ongoing management of medicines by the older-aged living independently. Both a MedsCheck and an AdherenceCheck involves forming an individual Action Plan. Setting Rental retirement village. Method After interviewing the older-aged in the village about their management of medicines, they were given an AdherenceCheck and an Action Plan. Six months later their management of medicines and the Action Plan were (re-)evaluated. Main outcome measure Present and ongoing adherence to medicines. Results Only 15 of the original 23 participants completed the study. The AdherenceCheck with Action Plan did not significantly change the adherence to medicines of these older-aged living in the rental retirement village. Pre- to post-AdherenceCheck, there was a reduction in the percentage of participants with a good knowledge of their illnesses, and thus a corresponding significant increase in the percentage with no knowledge of their illnesses, and this may have been age related. Only 11 of the 15 participants remembered receiving an Action Plan, as part of the AdherenceCheck, and 7 of these considered that the Action Plan helped them manage their medicines. Conclusion An AdherenceCheck may not improve the management of medicines by the older-aged living in a rental retirement village. As there are no peer-reviewed publications as to whether the commonly used MedsChecks, which have some similarities to the AdherenceCheck, improve the management of medicines, it is suggested that these MedsChecks should also be formally evaluated.     

A Review of: “Excipient Development for Pharmaceutical,Biotechnology, and Drug Delivery Systems”

The feasibility of delivering hydromorphone by transdermal iontophoresis to obtain therapeutically effective analgesic concentrations for the management of cancer-related pain was evaluated. Anodal iontophoresis was performed, and the effect of current strength, current duration, solution pH, presence of buffer ions, and drug concentration on the transdermal permeation of hydromorphone was investigated in vitro. Freshly excised full‐thickness hairless rat skin and side-by-side permeation cells connected to the Phoresor II^TM with Ag/AgCl electrodes was used. The flux of hydromorphone was observed to significantly increase (P < 0.05) from 72.04–280.30 μg/cm²/h with increase in current strength from 0.10–0.50 mA. A linear relationship was obtained between hydromorphone flux and current strength. Furthermore, the flux of hydromorphone was influenced by solution pH and presence of buffer ions. Also, the in vitro permeation flux of hydromorphone was observed to significantly increase (P < 0.05) with a 10-fold increase in hydromorphone hydrochloride concentration from 0.01–0.10 M. However, with further increase to 0.50 M, there was no significant difference in flux. These results show that by manipulating electronic and formulation variables, the transdermal iontophoretic delivery of hydromorphone can be controlled, and therapeutically effective concentrations of hydromorphone for the management of cancer-related pain can be obtained.     

“厥”,“脱”概念辨析

以往所称“厥脱证（或病）”实质包括厥病类、脱病类两类性质不同的病变，“国标”已将其分化成３０余种具体疾病。厥多因邪所致，病性偏实，以昏厥为主症；脱为脏气衰绝，精血亡脱，以面白、气微、脉绝等为主要表现。厥病与脱病可以兼并存在，厥、脱且为辨证基本内容之一。     

Development of the Technology of the Complex Antipyretic Drug “Antigripp,” which Is Stable on Storage

Pharmaceutical Chemistry Journal -     

Search of anti-allodynic compounds from Plantaginis Semen,a crude drug ingredient of Kampo formula “Goshajinkigan”

Journal of Natural Medicines - Chemotherapy-induced peripheral neuropathy (CIPN) is one of the dose-limiting side effects of cancer chemotherapy. Although the control of CIPN is important, it is...     

Synthesis and Antibacterial Activity of a Novel Class of 15-Membered Macrolide Antibiotics, “11a-Azalides”

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Discriminative stimulus properties of the “atypical” antidepressant, mirtazapine, in rats: a pharmacological characterization

Rationale  Though interoceptive properties of antidepressants have been described, discriminative stimulus (DS) properties of mirtazapine, which does not affect monoamine reuptake, remain uncharacterized. Objectives  The objectives of the study are to train rats to recognize a mirtazapine DS, then perform substitution studies with other antidepressants and drugs acting at sites occupied by mirtazapine. Materials and methods  Using a two-lever, fixed-ratio 10 schedule, rats were trained to discriminate mirtazapine (2.5 mg/kg, i.p.) from saline. Results  Sessions, 63 ± 8, were necessary to reach the criterion for 14 rats that all subsequently recognized (100%) mirtazapine at the training dose. Mirtazapine blocks serotonin (5-HT)_2C receptors, and the 5-HT_2C antagonists, SB242,084, SB243,213 and S32006, revealed dose-dependent and full (≥80%) substitution at doses of 2.5, 2.5, and 0.63 mg/kg, respectively. By contrast, the 5-HT_2A antagonists, MDL100,907 and SR46349-B, the 5-HT_2B antagonist, SB204,741, and the 5-HT₃ antagonist, ondansetron, showed no significant substitution. Though mirtazapine indirectly recruits 5-HT_1A receptors, the 5-HT_1A agonists, buspirone and 8-OH-DPAT, did not substitute. Mirtazapine blocks α₂-adrenoceptors, but several α₂-adrenoceptor antagonists (yohimbine, RX821,002 and atipamezole) failed to substitute. Despite blockade by mirtazapine of histamine H₁ receptors, no substitution was seen with the selective H₁ antagonist, pyrilamine. Finally, the selective noradrenaline reuptake inhibitor, reboxetine (0.16), fully substituted for mirtazapine, whereas the 5-HT/noradrenaline reuptake inhibitors, duloxetine and S33005, several 5-HT reuptake inhibitors (citalopram, fluvoxamine, and paroxetine) and the dopamine reuptake inhibitors, bupropion and GBR12,935, did not substitute. Conclusion  Mirtazapine elicits a DS in rats for which selective antagonists at 5-HT_2C receptors display dose-dependent substitution, whereas drugs acting at other sites recognized by mirtazapine are ineffective.     

雌黄,能“杀毒”的“修正液”

现在是农历蛇年了。提到蛇,我们很容易想到它传说中的克星——雄黄,进而想到端午雄黄酒、急救用的安宫牛黄丸,甚至联想到著名的白娘子。不过,今天我们要谈的不是雄黄,而是它的"兄弟"——雌黄。关于雌黄,大家可能就陌生多了,也许也就知道一个成语——信口雌黄。魏晋时期有一位名士王衍,生得风流倜傥,清明俊秀。有一次他去拜访当时的名士山涛,他走     

名医,从“相轻”到“相亲”

清朝初年,江苏有叶天士、薛雪两位名医,同在一条街行医。叶天士(1667-1746年),本名叶桂、字香岩,吴县人,承家学行医,集众人之才,只要知某人有治病奇招,就会前去学习,历经17位老师的指导而最终自成一家,创立了温病学说,著有《温热论》、《医案存真》等。薛雪(1681-1770年),字生白,号一瓢,苏州人,原学文后从医,选辑《内经》,著《温热病》、《一瓢诗话》等。     

“糖友”们,请对“表”

大家都知道,糖尿病并发症很多,发生心血管疾病的几率大大增加,但如何判定一直没有定论,直到去年年底,中华医学会推出大众版《糖尿病患者心血管疾病风险评估表》,这才为患者提供了简单易行的评判标准。     

“医托”落网,自曝行骗“心得”

近日，两名受到公安部通缉的女“医托”在重庆落网。出乎人们意料的是，两名文化程度不高的中年妇女，竟在不到4年时间里使400多人上当受骗，诈骗金额高达200多万元。 是什么原因让这么多受害者将自己的救命钱、养命钱拱手交给“医托”？这其中真有什么高明的骗术吗？     

冠心病治疗,“保心”重于“救心”

冠心病是老年人易发的慢性病。随着年龄增加,冠状动脉会逐步出现纤维化斑块和粥样硬化斑块,导致血管管腔狭窄。当血管腔狭窄超过70%,人在运动量增加、情绪激动等情况下,就可能出现胸闷、胸痛,严重时血管壁上的斑块还会破裂、脱落,形成血栓,造成急性心肌缺血,甚至心肌梗死。     

肾结石,既“伤肾”又“伤心”

<正>日前,意大利和美国学者联合进行的前瞻性研究表明,在无冠心病(CHD)病史的女性中,肾结石病史与CHD危险存在独立且显著的相关性;但在无CHD病史的男性中,二者不相关。研究概述肾结石是一种常见病,其发病率随着年龄和性别而不同。据全国健康与营养检测调查——美国人口的一个具有代表性的样本——近来做的一次的估计报告,肾结石病史的发生率在男性中为10.6%,女性     

防暑,用“正气水”还是“十滴水”

藿香正气水和十滴水都是家庭常备的防暑药，均能缓解胃肠不适、腹痛、恶心等症状。很多人据此认为，这两种可相互替代使用。实际上，藿香正气水和十滴水在组成、功效和用法上都不相同，稀里糊涂混淆使用，不但治不了病，还可能引起不良后果。那么，藿香正气水和十滴水到底有什么区别，怎样才能做到科学选用呢？     

迈向“2030”,迈向“健康中国”

正新中国成立以来,特别是改革开放以来,我国健康领域改革发展取得显著成就。但同时,工业化、城镇化、人口老龄化、疾病谱变化、生态环境及生活方式的改变等,都给维护和促进健康带来一系列新的挑战,需要从国家战略层面统筹解决关系健康的重大和长远问题。在这个背景下,2016年10月25日,中共中央、国务院印发《"健康中国2030"规划纲要》,这是建国以来首次在国家层面提出健康领域中的长期战略规划。根据《纲要》,未来十余年中国的健康指数将发生哪些变化?这些变化     

The systematic review of randomized controlled trials of PCSK9 antibodies challenges their “efficacy breakthrough” and the “lower,the better” theory

Background: A Cochrane review with meta-analysis showed controversial results about the efficacy of PCSK9 antibodies in the prevention of cardiovascular diseases. This review gives the opportunity to test the relationship between LDL-C levels and cardiovascular events.

Methods: The authors analyzed the relationship between the calculated LDL-C lowering and the risk of all-cause mortality, fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, any adverse event, cardiovascular events and cardiovascular disease mortality.

Results: No beneficial relationship was found between LDL-C lowering and cardiovascular events explored by meta-regression; instead, there was a trend toward harm. For any of the other outcomes there was no significant association between LDL-C lowering and risk. Furthermore, the authors calculated the efficacy that would be expected through the LDL-C lowering showed in the meta-analysis, considering widely accepted predictions. These were respected only for stroke, while the observed efficacy on other cardiovascular events was significantly lower than the expected, and no significant result was observed at all for fatal outcomes. A separate meta-analysis of trials recruiting familial hypercholesterolemia patients have showed a tendency to harm for almost all outcomes.

Conclusions: The relationship between LDL-C lowering and cardiovascular events has not showed any significant association (and even a tendency toward harm), challenging the “lower the better” theory. A separate meta-analysis of trials recruiting familial hypercholesterolemia patients has showed a tendency to harm for all outcomes with PCSK9 antibodies. Therefore, at the moment, the data available from randomized trials does not clearly support the use of these antibodies.