Does the catalepsy phenomenon reflect the functional dopaminergic activity in pharmacological investigations?

The dynamics of spontaneous and haloperidol-induced catalepsy in mice has been studied. It is established that the degree of manifestation of the spontaneous catalepsy is directly related to the number of manipulations (mice standings in the "lector position"). At the same time, the intensity of catalepsy (both spontaneous and haloperidol-induced) was not related to the mice response to apomorphine injections. It is concluded that spontaneous catalepsy rather insignificantly influences the results of pharmacological tests, but this factor has to be taken into account in the study of physiological mechanisms. The absence of correlations between catalepsy manifestations and the apomorphine test results is indicative of complexity of the mechanism of this disorder and cannot be attributed entirely to the violation of dopaminergic processes in CNS.     

EQ-5D量表在出院患者自我健康状况评价的应用

随着我国医学科学发展的进步,一些一直被用来衡量健康的指标(如死亡率等)日趋稳定,失去了原有的灵敏度,不足以反映健康的发生发展变化。欧洲生命质量(EQ-5D)量表作为一种有效测量生命质量的量表,具有良好的效度、信度,获得了广泛的应用。EQ-5D量表是由欧洲生命质量组织(EuroQoL Group)于1990年发布的一个标准化的生命质量测量工具[1],主要由两个部分构成,第一部分是五维度     

基于EQ-5D量表的高血压患者生命质量评价及其用药现状

目的调查分析高血压患者基本用药情况与生命质量现状及其影响因素,为促进临床合理用药,提高患者生命质量提供参考。方法采用嵌合欧洲五维健康(EQ-5D)量表的自编问卷,纳入意识清楚、自愿参与的非继发性18周岁以上高血压患者,于2016年7月5日至2016年8月30日对成都市部分"三甲"综合医疗机构心血管内科门诊高血压患者的用药情况及生命质量状况进行调查。结果共纳入符合标准的高血压患者562例;问卷统计分析结果表明,被调查高血压患者健康效用值为0.84±0.13,健康效用值视觉模拟(EQ-VAS)评分为(73.42±13.93)分。患者用药类别以二氢吡啶类钙通道阻滞药(CCB)降压药物使用比例最高;二联用药以血管紧张素受体拮抗药(ARB)联合二氢吡啶类CCB比例最高(42.9%),三联用药以二氢吡啶类CCB+ARB+β受体阻滞药占比最高(34.5%);8.0%的二联用药患者联用了同一类药物,1.8%的二联用药患者联合使用了血管紧张素转化酶抑制药和ARB;与男性患者相比,女性患者的EQ-5D指数相对更低。结论临床上应高度关注降压药物的联合应用,尽量避免两种同类降压药物联合应用等不合理用药情况;鉴于抽样的局限,本研究相关结果尚有待大规模临床研究予以证实。     

欧洲五维健康量表EQ-5D-3L和EQ-5D-5L中文版比较的实证研究

目的:从各个方面分析比较EQ-5D-3L和EQ-5D-5L,从而验证EQ-5D-5L比EQ-5D-3L能够更好地区分不同的健康水平。方法:对324名受访者进行问卷调查,每名受访者首先回答一些自身基本情况的问题和EQ-5D-3L问卷,半小时之后填写EQ-5D-5L问卷。根据EQ-5D-3L和EQ-5D-5L在各水平的重新分布来确定不同版本性能的差异,也可以使用Shannon指数和天花板效应来评价其各自的信息性或者使用EQ-5D指数得分对健康状况进行衡量等。结果:通过调查发现,EQ-5D-3L问卷的各水平大致被分给相应的EQ-5D-5L的各水平,EQ-5D的两个版本的平均不一致率为0.8%。EQ-5D-5L的辨别能力高于EQ-5D-3L,但是它们信息的有效性基本上是一致的。相比EQ-5D-3L的70.1%的完全健康状态,EQ-5D-5L下降到52.8%,而且EQ-5D-5L能够证明和EQ-VAS有更好的相关关系。结论:与EQ-5D-3L相比,EQ-5D-5L有更好的辨别力和较低的天花板效应。此外,EQ-5D-5L还表现出了良好的有效性。因此,EQ-5D-5L比EQ-5D-3L更具优越性,它能够更好地区分不同的健康水平,但是EQ-5D-5L的天花板效应依然存在。     

Does the urinary concentration of an inhaled beta‐2 agonist always reflect the inhaled dose and method of administration?

The urinary threshold of 1000 ng/mL for salbutamol was established by the International Olympic Committee (IOC) in 2001 following a study that was not undertaken for that purpose. At least 25 athletes have exceeded this concentration and some after inhaling no more than the permitted daily maximum dose of 1600 μg. However, there is concern that some providing expert evidence and tribunal members hearing such cases are unaware of the occasional unpredictability of the pharmacokinetics of beta‐2 agonists. The World Anti‐Doping Agency's (WADA's) change from 1 March 2018 to allow correction of urinary specific gravity (SG) down to 1.020 for prohibited substances with a urinary threshold is a major advance and will assist in some instances. However, future cases are anticipated to occur when athletes unexpectedly exceed the urinary threshold for salbutamol after inhaling no more than the allowable dose and within WADA's stated time frame. They will then be required to appear before doping tribunals. The rapidity by which salbutamol is inhaled can influence the resultant urinary concentration and is yet to be addressed adequately in WADA's 2019 Prohibited List. The list's recommended pharmacokinetic study fails to replicate the circumstances that prevailed when the athlete was competing and the adverse analytical finding (AAF) occurred. Tribunals, and experts who advise them, need to be cognizant that the urinary concentration of salbutamol does not invariably reflect the inhaled dose and that a high urinary salbutamol concentration is not always ipso facto evidence of super‐dosing with inhaled salbutamol.     

Does serotonin relax the rat anococcygeus muscle via 5-HT7 receptors?

The mechanisms of serotonin (5-HT)-induced contraction and relaxation were studied in the rat anococcygeus muscle. In the presence of prazosin (1 nM) and ketanserin (10 nM), concentration/response curves to 5-HT were shifted to the right and the maximum effects were not affected (pKB values 9.09+/-0.29 and 8.66+/-0.06 for prazosin and ketanserin, respectively). On contrary, guanethidine (10 microM) antagonised the 5-HT-induced contractions non-competitively. In the presence of guanethidine, prazosin or ketanserin further inhibited the responses to 5-HT at lower concentrations. The serotonergic receptor agonists 5-carboxamidotrypamine, metoclopramide and sumatriptan did not produce any effect in tissues under baseline conditions. 5-HT caused concentration-dependent relaxation in phenylephrine (1 microM) -precontracted preparations in the presence of guanethidine (10 microM). Tetrodotoxin (1 microM), N(G)-nitro-L-arginine (100 microM) and capsaicin (1 microM) were ineffective in antagonising the relaxation induced by 5-HT. The serotonergic receptor antagonists: ketanserin (0.1 microM), ICS 205930 (10 microM), GR 113808 (10 microM), GR 55562 (10 microM), methiothepin (10 nM), mesulergine (10 microM), ritanserin (0.1 microM) and spiperon (0.1 microM) did not antagonise 5-HT-induced relaxation. On the other hand, clozapine (0.01-0.1 microM) and metergoline (0.1-1 microM) attenuated the relaxation induced by 5-HT. These results demonstrate that 5-HT contracts rat anococcygeus muscle directly by an action on alpha1-adrenergic receptors and indirectly by releasing noradrenaline from adrenergic nerve endings. None of the 5-HT receptors plays a role in the 5-HT-induced contractions. Moreover 5-HT induces concentration-dependent relaxation in the precontracted preparations which apparently are not mediated through known 5-HT receptor types.     

Does the patient or pathology exist?

For a long time, the guidelines of medical conduct represented a useful, but not binding, model for adapting in order to avoid professional liability. In this sense, the idea of relying solely on these guidelines raises serious concerns, as very often there is no real “evidence” to scientifically support the recommendations. The authors have conducted a review of the literature to draw the attention of the scientific community to the highlights and shadows of this dangerous Italian prospect.     

Does the homeopathic remedy alleviate insomnia?

Naudé DF, Couchman IMS, Maharaj A. Chronic primary insomnia: efficacy of homeopathic simillimum. Homeopathy 2010; 99: 63–8.     

Does Breast Cancer Start in the Womb?

Perturbations in the foetal environment predispose individuals to diseases that become apparent in adulthood. These findings prompted researchers to hypothesize that foetal exposure to environmental oestrogens may play a role in the increased incidence of breast cancer observed in European and US populations over the last 50 years. There is widespread human exposure to bisphenol A, an oestrogenic compound that leaches from dental materials and consumer products. In CD-1 mice, perinatal exposure to environmentally relevant bisphenol A levels induced alterations of the mammary gland architecture. Bisphenol A increased the number of terminal end buds at puberty and terminal ends at 6 months of age and increased ductal lateral branching at 4 months of age. Exposed mice also showed an enhanced sensitivity to oestradiol when ovariectomized prior to puberty. All these parameters are associated in human beings with an increased risk for developing breast cancer. To assess whether bisphenol A induces mammary gland neoplasia, we chose a rat model because it more closely mimics the human disease than mouse models. Examination of the mammary glands of Wistar/Furth rats during early adulthood revealed that gestational exposure to bisphenol A induced the development of pre-neoplastic lesions and carcinoma in situ in the absence of any additional treatment aimed at increasing tumour development. Emerging epidemiological data reveal an increased incidence of breast cancer in women exposed to diethylstilboestrol during gestation. Hence, both animal experiments and epidemiological data strengthen the hypothesis that foetal exposure to xenooestrogens may be an underlying cause of the increased incidence of breast cancer observed over the last 50 years.