Effects of the Aconitum alkaloid mesaconitine in rat hippocampal slices and the involvement of α- and β-adrenoceptors

1. The effects of mesaconitine, the main alkaloid contained in Aconiti tuber, were investigated by use of extracellular recordings of stimulus-evoked population spikes and field excitatory postsynaptic potentials (e.p.s.ps) in the CA1 region of rat hippocampal slices.
2. At a concentration of 10 nM, mesaconitine evoked excitations, which were manifested as an increase in the amplitude of the orthodromic spike and the appearance of multiple spikes following the first postsynaptic spike, without affecting the magnitude of paired-pulse facilitation. The increase in spike amplitude was persistent and was not reversed by up to 90 min of washout. At concentrations of 30 and 100 nM, the alkaloid produced a biphasic effect, that is an excitation followed by an inhibition without having any effect upon the field e.p.s.p. At concentrations above 100 nM, mesaconitine suppressed the orthodromic population spike and the field e.p.s.p.
3. The excitatory effect was also observed when electrical stimulation was stopped completely during the application of mesaconitine (10 nM) and during the first 15 min of washout.
4. The enhancement of the population spike and the appearance of multiple spikes induced by mesaconitine (10–100 nM) were blocked by pretreatment with the β-adrenoceptor antagonists propranolol (1 μM) and timolol (1 μM), whereas the inhibitory effect was blocked by the α-adrenoceptor antagonists yohimbine (1 μM) and phentolamine (10 μM). However, when the β-adrenoceptor antagonist timolol was added 10 min after the application of mesaconitine, it failed to block the long-lasting enhancement of the spike amplitude and the appearance of multiple population spikes.
5. Application of the selective β-adrenoceptor agonist isoprenaline (500 nM) to the hippocampal slices induced an increase in the amplitude of the orthodromic population spike and elicited 2–3 additional spikes. Mesaconitine (10 nM) did not further potentiate this enhancement of the spike amplitude when added after a 15 min pretreatment with isoprenaline.
6. Perfusion of forskolin, which directly activates adenylate cyclase, enhanced the population spike. Mesaconitine had no additional effect when applied after pretreatment with forskolin.
7. It is concluded that the excitatory effects evoked by lower concentrations of the plant alkaloid mesaconitine are mediated by stimulation of β-adrenoceptors and the consequent activation of intracellular processes which lead to the long-lasting changes in excitability.

     

马来酸噻吗洛尔滴眼液治疗浅表型婴幼儿血管瘤用药方法的探讨

目的：探讨使用马来酸噻吗洛尔滴眼液治疗婴幼儿血管瘤的最佳用法与用量。方法：将250例浅表型婴幼 儿血管瘤患者均分为5组;即外敷组和每日外涂2,4,6,8次组。观察不同用药方式(外敷及外涂)及不同用药频率对 疗效的影响。结果：外敷马来酸噻吗洛尔滴眼液2次/d,每次30 min组的疗效优于外涂组2 次/d(P<0.001),外涂2 次/d 或4 次/d的疗效与外涂6 次/d比较,差异有统计学意义(P<0.001),外涂6次/d的疗效与外涂8 次/d或外敷2 次/d之间比 较,差异无统计学意义(P>0.05)。结论：马来酸噻吗洛尔滴眼液治疗婴幼儿血管瘤的疗效与用药量相关,6次/d外涂 能达到最佳的疗效。     

Betaxolol

Drugs classified as beta-blockers have proved to be valuable in the treatment of patients with glaucoma. Timolol has become the most widely used ocular hypotensive agent. Actual and potential side effects associated with its non-selective beta-blockade have prevented its use in patients with reactive airways disease, and to a lesser extent, with various cardiovascular conditions. Betaxolol is a relatively selective beta-1 blocker which in most patients is almost as effective as timolol in lowering intraocular pressure, and may be partly additive with dipivefrin. It is probably safer in patients unable to tolerate non-selective beta-blockers. However, it needs to be used with caution in these patients, who are unpredictably susceptible to systemic side effects.     

An infant with localized vasoconstriction following topical propranolol exposure for infantile hemangioma

We describe a 3‐month‐old child with an infantile hemangioma on the forehead with a blanched macule provoked by topical treatment with propranolol. This observation demonstrates that topically applied (non‐selective) beta‐blockers may induce blanched macules at the site of application, a side effect due to peripheral vasoconstriction of blood vessels by non‐selective beta‐2 blockade. This side effect was linked due to overuse and was reversible. This case illustrates the importance of providing thorough instructions regarding topical propranolol application.     

曲伏前列素滴眼液治疗原发性开角型青光眼的临床效果

目的分析曲伏前列素滴眼液治疗原发性开角型青光眼的临床效果。方法将42例原发性开角型青光眼患者随机分为对照组和研究组,每组21例。对照组实施马来酸噻吗洛尔滴眼液治疗,研究组实施曲伏前列素滴眼液治疗,比较两组的临床效果。结果治疗后,研究组的眼压、视力、散光度、基础泪液分泌量、泪膜破裂时间、血浆粘度、全血粘度低切、全血粘度高切均优于对照组(P<0.05)。结论曲伏前列素滴眼液治疗原发性开角型青光眼的临床效果确切,值得临床推广应用。     

Stimuli-sensitive hydrogels: A novel ophthalmic drug delivery system

Background:

Stimuli-sensitive hydrogels are three-dimensional, hydrophilic, polymeric networks capable of imbibing large amounts of water or biological fluids on stimulation, such as pH, temperature and ionic change.

Aim:

To develop hydrogels that are sensitive to stimuli, i.e. pH, in the cul-de-sac of the eye for providing a prolonged effect and increased bioavailability with reduction in frequency of administration.

Materials and Methods:

Hydrogels were formulated by using timolol maleate as the model drug, polyacrylic acid as the gelling agents, hydroxyl ethyl cellulose as the viscolizer and sodium chloride as the isotonic agent. Stirring of ingredients in pH 4 phosphate buffer at high speed was carried out. The dynamic dialysis technique was used for drug release studies. In vivo study for reduction in intraocular pressure was carried out by using albino rabbits.

Statistical Analysis:

Drug release studies data were used for statistical analysis in first-order plots, Higuchi plots and Peppas exponential plots. Student t-test was performed for in vivo study.

Results:

Viscosity of the hydrogel increases from 3.84 cps to 9.54 cps due to change in pH 4 to pH 7.4. The slope value of the Peppas equation was found to be 0.3081, 0.3743 and 0.2964. Up to 80% of drug was released in an 8 h drug release study. Sterile hydrogels with no ocular irritation were obtained.

Conclusions:

Hydrogels show increase in viscosity due to change in pH. Hydrogels were therapeutically effacious, stable, non-irritant and showed Fickian diffusion. In vivo results clearly show a prolonged reduction in intraocular pressure, which was helpful for reduction in the frequency of administration.     

噻吗洛尔眼液治疗LASIK术后屈光回退54例疗效分析

目的:分析总结2.5g/L马来酸噻吗洛尔眼液(timolol)对准分子激光原位角膜磨镶术(laserin situkeratomileusis,LASIK)后屈光回退的治疗效果。方法:选取我院准分子中心2007-08/2008-08接受LASIK手术病例1400例2650眼,随访0.5a以上,发生屈光回退者有53例66眼,按手术时间随机分为两组,试验组使用2.5g/L马来酸噻吗洛尔眼液进行治疗,对照组使用1g/L玻璃酸钠眼液进行治疗,两组治疗时间均为2wk,治疗结束后将试验组与对照组进行分析比较(视力提高行数)。结果:试验组视力提高-1~4(平均1.45±1.09)行,对照组视力提高-2~2(平均0.61±0.86)行,行成组t检验显示,两组差异有统计学意义(t=3.500,P<0.05)。结论:马来酸噻吗洛尔眼液2.5g/L对LASIK术后屈光回退具有显著疗效。     

联合用药对高眼压型POAG患者视盘参数及视网膜神经纤维层厚度的影响

目的:研究噻吗洛尔与拉坦前列素联合应用对高眼压型原发性开角型青光眼(primary open angle glaucoma,POAG)患者视盘参数及视网膜神经纤维层厚度的影响,为临床研究提供指导.方法:将2013-11/2015-11期间于我院进行治疗的240例336眼高眼压型POAG患者按随机数字表法将患者分为两组,其中对照组120例170眼,观察组120例166眼.对照组患者仅采用拉坦前列素治疗,观察组则采用噻吗洛尔联合拉坦前列素进行治疗.观察治疗后3 mo内患者治疗效果,测量患者视盘参数和视网膜神经纤维层厚度,随访关注1a内患者不良反应发生率.结果:观察组和对照组患者治疗后的改善率分别为97.6%和80.6%,观察组疗效明显优于对照组,两组比较差异有统计学意义(P<0.05);治疗后两组患者眼部盘沿面积、盘沿容积、视盘容积和水平杯盘直径比均有所升高,差异有统计学意义(P<0.05),其中观察组显著高于对照组,差异有统计学意义(P<0.05),而两组患者的垂直杯盘直径明显下降,差异有统计学意义(P<0.05),观察组显著低于对照组,差异具有统计学意义(P<0.05);两组患者治疗期间眼睛干涩、角膜浸润、结膜充血、视觉模糊等并发症发生率比较差异无统计学意义(P>0.05),1a内随访患者也无其他不良反应发生.结论:采用噻吗洛尔与拉坦前列素联合应用治疗高眼压型POAG患者,患者病情有明显好转,视力得到提高,其视盘参数和视网膜神经纤维层厚度也有所改善.     

pH值对马来酸噻吗洛尔角膜透过性的影响

目的　研究pH值对马来酸噻吗洛尔(TM)角膜透过性的影响,为其处方设计提供理论依据。方法　测定TM的表观油水分配系数(DC_app)。用体外扩散实验考察各种pH值条件下离体兔眼角膜对TM的透过性。结果　由DC_app求得TM的分配系数和pKa分别为63.63和9.17。在生理介质中,TM的表观透过系数为1.43×10^-5cm·s^-1。随着pH值由6.65升高至9.20 ,TM透过角膜的滞后时间缩短到1/20 ,累积透过量增加1.3倍。计算得到游离型噻吗洛尔的角膜透过系数为解离型的3.3倍。结论　噻吗洛尔主要以分子状态经细胞内途径透过角膜,且角膜上皮是其扩散的主要屏障。