基于“同气相求”理论的激痛点疗法治疗顽固性偏头痛15例

笔者基于同气相求理论,遵循经络辨证,以求同气、通经络为治则,针刺患侧或双侧手足少阳经远端激痛点及井穴,同时按揉近端激痛点,治疗顽固性偏头痛15例,现报道如下。1临床资料15例患者均为2018年1月至2018年6月包头医学院第二附属医院针灸科门诊就诊的顽固性偏头痛患者,其中男6例,女9例;单侧头痛9例,双侧6例;年龄15~65岁,平均46岁;病程0.5~15年,平均2年。均表现为单侧或双侧颞部反复发作的搏动性疼痛,伴失眠、健忘,痛甚者恶心,行头颅CT或MRI检查未见异常。     

Preclinical to Clinical Translation of CNS Transporter Occupancy of TD-9855, a Novel Norepinephrine and Serotonin Reuptake Inhibitor

Background:

Monoamine reuptake inhibitors exhibit unique clinical profiles that reflect distinct engagement of the central nervous system (CNS) transporters.

Methods:

We used a translational strategy, including rodent pharmacokinetic/pharmacodynamic modeling and positron emission tomography (PET) imaging in humans, to establish the transporter profile of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor.

Results:

TD-9855 was a potent inhibitor of norepinephrine (NE) and serotonin 5-HT uptake in vitro with an inhibitory selectivity of 4- to 10-fold for NE at human and rat transporters. TD-9855 engaged norepinephrine transporters (NET) and serotonin transporters (SERT) in rat spinal cord, with a plasma EC₅₀ of 11.7ng/mL and 50.8ng/mL, respectively, consistent with modest selectivity for NET in vivo.Accounting for species differences in protein binding, the projected human NET and SERT plasma EC₅₀ values were 5.5ng/mL and 23.9ng/mL, respectively. A single-dose, open-label PET study (4–20mg TD-9855, oral) was conducted in eight healthy males using the radiotracers [¹¹C]-3-amino-4- [2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile for SERT and [¹¹C]-(S,S)-methylreboxetine for NET. The long pharmacokinetic half-life (30–40h) of TD-9855 allowed for sequential assessment of SERT and NET occupancy in the same subject. The plasma EC₅₀ for NET was estimated to be 1.21ng/mL, and at doses of greater than 4mg the projected steady-state NET occupancy is high (>75%). After a single oral dose of 20mg, SERT occupancy was 25 (±8)% at a plasma level of 6.35ng/mL.

Conclusions:

These data establish the CNS penetration and transporter profile of TD-9855 and inform the selection of potential doses for future clinical evaluation.     

Clinical pharmacokinetics of intranasal sumatriptan

A substantial proportion of migraine patients have gastric stasis and suffer severe nausea and/or vomiting during their migraine attack. This may lead to erratic absorption from the gastrointestinal tract and make oral treatment unsatisfactory. For such patients, an intranasal formulation may be advantageous. Sumatriptan is a potent serotonin 5HT(1B/1D) agonist widely used in the treatment of migraine; the effectiveness of the intranasal formulation (20mg) has been well established in several clinical studies. This article reviews the pharmacokinetics of intranasal sumatriptan and includes comparisons with oral and subcutaneous administration. After intranasal administration, sumatriptan is directly and rapidly absorbed, with 60% of the maximum plasma concentration (C(max)) occurring at 30 minutes after administration of a single 20mg dose. Following intranasal administration, approximately 10% more sumatriptan is absorbed probably via the nasal mucosa when compared with oral administration. Mean C(max) after a 20mg intranasal dose is approximately 13.1 to 14.4 ng/mL, with median time to C(max) approximately 1 to 1.75 hours. When given as a single dose, intranasal sumatriptan displays dose proportionality in its extent of absorption and C(max) over the dose range 5 to 10mg, but not between 5 and 20mg for C(max). The elimination phase half-life is approximately 2 hours, consistent with administration by other routes. Sumatriptan is metabolised by monoamine oxidase (MAO; predominantly the A isozyme, MAO-A) to an inactive metabolite. Coadministration with a MAO-A inhibitor, moclobemide, leads to a significant increase in sumatriptan plasma concentrations and is contraindicated. Single-dose pharmacokinetics in paediatric and adolescent patients following intranasal sumatriptan were studied to determine the effect of changes in nasal morphology during growth, and of body size, on pharmacokinetic parameters. The pharmacokinetic profile observed in adults was maintained in the adolescent population; generally, factors such as age, bodyweight or height did not significantly affect the pharmacokinetics. In children below 12 years, C(max) is comparable to that seen in adolescents and adults, but total exposure (area under the concentration-time curve from zero to infinity) was lower in children compared with older patients, especially in younger children treated with 5mg. Clinical experience suggests that intranasal sumatriptan has some advantages over the tablet (more rapid onset of effect and use in patients with gastrointestinal complaints) or subcutaneous (noninvasive and fewer adverse events) formulations.     

Enoxaparin: an update of its clinical use in the management of acute coronary syndromes

Enoxaparin (enoxaparin sodium) is a low molecular weight heparin (LMWH) indicated for use in the treatment of ischaemic complications of unstable angina and non-Q wave myocardial infarction (MI). Unfractionated heparin (UFH) has for many years represented the standard in anticoagulant therapy for patients with acute coronary syndromes; however, recent studies suggest that enoxaparin is also a viable option for anticoagulant therapy in these patients. The ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events) and the TIMI 11B (Thrombolysis in Myocardial Infarction) studies reported that twice daily enoxaparin was significantly more effective than a continuous infusion of UFH in reducing the composite triple endpoint of death, MI, or recurrent angina or urgent revascularisation. Follow-up of both patient populations showed continued benefit associated with enoxaparin. Enoxaparin has been compared with tinzaparin in the treatment of unstable coronary artery disease using a nonblind study design. There was no difference between treatment groups in the therapeutic endpoints. Three nonblind studies have also compared the effects of enoxaparin and UFH in patients receiving thrombolytic therapy following acute MI. The HART II (Heparin and Aspirin Reperfusion Therapy), the ASSENT 3 (Assessment of the Safety and Efficacy of a New Thrombolytic Regimen) and the ENTIRE-TIMI 23 (Enoxaparin and Tenecteplase with or without glycoprotein IIb/IIIa Inhibitor as Reperfusion strategy in ST Elevation MI - Thrombolysis in Myocardial Infarction) studies have revealed that enoxaparin in combination with alteplase or tenecteplase is at least equivalent (HART II and ENTIRE-TIMI 23), and possibly superior (ASSENT 3) to UFH. Enoxaparin is administered as a twice-daily subcutaneous injection. In contrast, UFH is administered as an intravenous infusion which requires routine monitoring of the activated partial thromboplastin time to ensure adequate levels of anticoagulation are maintained. During the acute phase of the the ESSENCE and TIMI 11B studies, the incidence of major bleeding was similar in patients receiving enoxaparin to that in patients receiving UFH. In contrast, the rates of minor bleeding were higher in patients receiving enoxaparin than in those receiving UFH throughout these studies. Conclusions: Data from the ESSENCE, TIMI 11B and ASSENT 3 studies have prompted calls for those LMWHs which have been shown to be superior to UFH, to be considered as first choice treatment for anticoagulation in unstable coronary syndromes. To date, these suggestions are not reflected in current guidelines which consider UFH and LMWHs equally. Irrespective, the clinical data reported in this review support the use of enoxaparin in the treatment of acute coronary syndromes. These data suggest that enoxaparin shows certain clinical and practical advantages over standard treatment with UFH and represents an important development in the treatment of acute coronary syndromes.     

四川省自贡市儿童1型糖尿病发病率研究

为摸清我省儿童１型糖尿病的发病情况,按ＷＨＯ儿童糖尿病多国研究计划方案,我们在自贡市（四区,两县）对１９８９～１９９６年儿童１型糖尿病发病率进行了调查研究。１　材料与方法１．１　病例来源　第一来源：自贡市３０个县区级有１型糖尿病诊断能力的医院。第二来...     

唐古特大黄提取物不同成分泻下作用的比较研究

目的：研究唐古特大黄提取物不同成分的泻下作用。方法：采用炭末推进方法、酚红排空方法进行肠推进实验,观察大黄提取物各成分(15 g·kg^-1)对小鼠小肠推进和肠水分吸收、大鼠大肠运动的影响。结果：唐古特大黄提取物不同成分与对照组相比,对小鼠小肠推进和肠水分吸收、大肠推进作用均有显著性差异(P<0.01)；与大黄水煎液、醇提液相比,泻下活性存在一些差异。结论：唐古特大黄提取物不同成分均有显著的泻下作用,但与大黄水煎液和醇提液相比有一些差异。     

电感耦合等离子体原子发射光谱法分析珍宝类藏药七十味珍珠丸中汞的5种形态和分布

目的:研究藏药七十味珍珠丸中汞的5种存在形态和分布.方法:将七十味珍珠丸中汞的形态分为水溶态汞、溶于盐酸的无机汞和有机汞、络合汞、单质汞和残渣态汞,通过电感耦合等离子体原子发射光谱(ICP-AES)法分析5种形态汞的含量和分布.结果:藏药七十味珍珠丸中总汞的93.8％是以惰性汞形式存在的硫化汞,6.18％是与锌、铝、钙...     

Decellularized dermis in combination with cultivated keratinocytes in a short- and long-term animal experimental investigation

Decellularized human dermis as a potentially ideal scaffold for dermal substitution in severe burns was examined in a two‐staged animal experiment. In an initial step, an in vitro generated composite graft consisting of human keratinocytes and decellularized dermis (AlloDerm®) was transplanted onto nude mice in a short‐term trial (n = 20, 14 days). Subsequently, a combined one‐step grafting of full thickness wounds with both decellularized dermis (in part preincubated with fibroblasts) and cultivated autologous keratinocytes as a cell suspension in fibrin glue was done in a long‐term porcine animal model (n = 10, 6 months). In both series, macroscopic wound healing was evaluated by planimetry. Histological investigations included morphological as well as immunohistochemical parameters. The short‐term study showed both successful integration of the composite grafts and reduction of wound contraction compared with the control group (epithelial grafts). The long‐term porcine study displayed reduced myofibroblast formation and contraction in the wounds that had been treated with fibroblast‐preincubated dermis. After 4 weeks, a decline of the structural integrity of the dermal matrix could be noticed. The utility of decellularized dermis as template for both dermal reconstitution and keratinocyte delivery vehicle was shown. The closure of full thickness wounds by a single‐step combination of an autologous keratinocyte fibrin sealant suspension and acellular dermis in a pig animal model could be shown. Incorporation of fibroblasts led to reduced wound contraction but could not prevent the loss of dermal integrity. The engineered ‘skin’ remained viable and stable over a period of 6 months.     

Does the perception of downloading speed influence the evaluation of web-based lectures?

Medical schools put little emphasis upon education on public health, even though public health has played an important role in this century. One way to harness its benefit in order to improve global health in the 21st century is to globally share lectures on public health through the Internet. We have developed the Supercourse comprising of web-based learning modules on epidemiology in a standardized format with the size of each web page less than 10 kilobytes. A cross-sectional observational study was conducted to investigate the association of the perception of the access speed to Web-based lectures by teachers with their perception of lecture quality. There were 223 teachers who rated the lectures: 72% were from North America or Western Europe, 40% had taught epidemiology, and 14% reported that the speed of access was slow. Odds ratio of above-average rating among those who reported that the speed of access was fast relative to those who reported that the speed of access was slow was 4.25 (2.03-8.91; P = 0.001). The odds ratios were similar and significant after taking into account several other factors, including the variation of rating across lectures, region, and experiences in teaching epidemiology. The results indicate that the perception of the quality of Web-based lectures is related to the speed of access to a web page. The speed of access may be as important, if not more important, as the content itself. This suggests that, to share educational materials on the Web globally for teachers, one must consider not only the content, but also how people at local sites gain access to the Internet.