Comparison of radioreceptor assay and radioimmunoassay for atropine: Pharmacokinetic application

Summary A membrane suspension prepared from rat brain was able to bind the potent muscarinic antagonist quinuclidinyl benzilate (QNB). The K_D for binding was 0.48 nM and B_max was 1.42 pmol/mg protein. Atropine competitively inhibited the binding of tritiated QNB to muscarinic receptors. This new radioreceptor assay (RRA) for atropine has been compared with a radioimmunoassay (RIA) for atropine. The RRA measures only the active component of atropine, 1-hyscyamine and in this respect it differs from the RIA. As little atropine as 1.25 ng/ml (4.33 nmol/l) in a 25 µl serum sample could be reliably assayed by the RRA. Using both assay techniques the pharmacokinetics of atropine was studied after a single 0.02 mg/kg i.v. dose given to 8 anaesthetized patients. The half-life calculated by the RRA was 3.7±2.3 h (m ± SD) and by the RIA 4.3±1.7 h. Both the volume of distribution and the total clearance were higher according to the RRA than the RIA: 3.9±1.5 vs 1.7±0.71/kg and 15.4±10.3 vs 5.9±3.6 ml/min/kg, respectively. The AUC measured by the RRA and RIA was 29.8±18.9 and 103.9±110.7 µg·h/l, respectively. The differences in the pharmacokinetics according to the 2 methods are presumably due to preferential tissue uptake of the l-form.     

低浓度阿托品联合角膜塑形镜对青少年低中度近视患者治疗效果、泪膜功能及SF-36量表评分的影响

目的 探讨低浓度(0.1 g·L-1)阿托品联合角膜塑形镜对青少年低中度近视患者治疗效果、泪膜功能及健康测量量表(SF-36)评分的影响.方法 病例对照研究.选取98例青少年低中度近视患者为研究对象,按照随机数字表法分为观察组(49例)、对照组(49例);对照组患者仅使用角膜塑形镜治疗,观察组患者使用角膜塑形镜联合低浓...     

倍半萜化合物对有机磷中毒小鼠的实验治疗

通过对两种常用有机磷农药敌敌畏和乐果中毒小鼠的实验治疗,研究倍半萜化合物作为胆碱酯酶复能剂对有机磷农药中毒小鼠的治疗作用.结果 发现:倍半萜化合物与阿托品结合治疗小鼠解毒快,治愈率高.     

急性有机磷农药中毒患者抗胆碱药联合应用方法的研究

目的观察长、短效抗胆碱药不同联合治疗方法对重度急性有机磷农药中毒(AOPP)救治效果的影响。方法将80例重度AOPP患者随机分为A组(41例)及B组(39例),A组在入院后即行阿托品、戊乙奎醚联合治疗;B组应用阿托品达阿托品化后再联合应用戊乙奎醚,维持阿托品化状态,所有患者给予同样的护理干预。记录阿托品化时间、意识恢复时间、胆碱酯酶活力恢复50%以上时间、住院时间、戊乙奎醚用量、药物耐受、药物依赖、迟发性神经病、中间综合征、中毒反跳、阿托品中毒及死亡情况。结果两组阿托品化时间、意识恢复时间、戊乙奎醚用量、胆碱酯酶活力恢复50%以上时间、住院时间、药物耐受、药物依赖、中毒反跳、阿托品中毒情况比较,差异有统计学意义(P0.05,P0.01);两组迟发性神经病、中间综合征、病死率比较,差异无统计学意义(均P0.05)。结论阿托品持续泵入快速达阿托品化后,用小剂量阿托品、戊乙奎醚联合应用维持阿托品化状态治疗重度AOPP效果较好,可减少患者中毒反跳、阿托品中毒的发生,使患者平稳渡过危险期,缩短住院时间,戊乙奎醚的用量小,减少了治疗费用。     

Myopia control in Mendelian forms of myopia

Purpose

To study the effectiveness of high-dose atropine for reducing eye growth in Mendelian myopia in children and mice.

Methods

We studied the effect of high-dose atropine in children with progressive myopia with and without a monogenetic cause. Children were matched for age and axial length (AL) in their first year of treatment. We considered annual AL progression rate as the outcome and compared rates with percentile charts of an untreated general population. We treated C57BL/6J mice featuring the myopic phenotype of Donnai–Barrow syndrome by selective inactivation of Lrp2 knock out (KO) and control mice (CTRL) daily with 1% atropine in the left eye and saline in the right eye, from postnatal days 30–56. Ocular biometry was measured using spectral-domain optical coherence tomography. Retinal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured using high-performance liquid chromatography.

Results

Children with a Mendelian form of myopia had average baseline spherical equivalent (SE) –7.6 ± 2.5D and AL 25.8 ± 0.3 mm; children with non-Mendelian myopia had average SE −7.3 ± 2.9 D and AL 25.6 ± 0.9 mm. During atropine treatment, the annual AL progression rate was 0.37 ± 0.08 and 0.39 ± 0.05 mm in the Mendelian myopes and non-Mendelian myopes, respectively. Compared with progression rates of untreated general population (0.47 mm/year), atropine reduced AL progression with 27% in Mendelian myopes and 23% in non-Mendelian myopes. Atropine significantly reduced AL growth in both KO and CTRL mice (male, KO: −40 ± 15; CTRL: −42 ± 10; female, KO: −53 ± 15; CTRL: −62 ± 3 μm). The DA and DOPAC levels 2 and 24 h after atropine treatment were slightly, albeit non-significantly, elevated.

Conclusions

High-dose atropine had the same effect on AL in high myopic children with and without a known monogenetic cause. In mice featuring a severe form of Mendelian myopia, atropine reduced AL progression. This suggests that atropine can reduce myopia progression even in the presence of a strong monogenic driver.     

近视漂移与最小调节幅度之间的失衡:药物诱发的双侧急性睫状体脉络膜渗漏继发高眼压发病机制的假说

目的：报告5例药物诱发的双侧急性睫状体脉络膜渗漏(DBACE)和近视漂移，伴或不伴高眼压(OHT)的病例，总结患者的临床特点和DBACE的恢复过程，探讨其可能的病理生理机制。

方法：2017-06/2021-02期间进行的回顾性观察性病例研究。纳入患者接受以下眼部检查：1)最佳矫正视力； 2)眼压(IOP)； 3)裂隙灯显微镜； 4)眼底照相； 5)超声生物显微镜(UBM)； 6)显然验光； 7)眼轴长度和前房深度。所有患者每2d随访一次，直到屈光度完全恢复至病发前状态。

结果：本研究共招募了5名年龄在10-45岁之间的患者，其中包括3名女性和2名男性患者。所有患者均为双侧受累(5/5)，并有近视漂移(5/5)，其中3例患有OHT(3/5)。随着年龄的增长，近视漂移减少，OHT增加。根据OHT，DBACE的动态加重过程分为1期(无OHT的近视漂移)和2期(有OHT的近视漂移)。随着DBACE的恶化，当近视漂移接近或超过最小调节幅度(MAA)时，眼压逐渐升高，DBACE从1期进展到2期。随着停用可疑药物后DBACE的恢复，第2期的DBACE先恢复到1期，然后恢复正常。

结论：DBACE的病理生理机制分为2个阶段，包括1期(无OHT的近视漂移)和2期(有OHT的近视漂移)。这两个阶段之间的转换取决于近视漂移和MAA之间的失衡。     

Real-world outcomes of low-dose atropine therapy on myopia progression in an Australian cohort during the COVID-19 pandemic

Background

To report the outcomes of low-dose atropine (0.01% and 0.05%) for preventing myopia progression in a real-world Australian cohort during the COVID-19 pandemic.

Methods

Records of children presenting with myopia, from January 2016 to 2022, were retrospectively reviewed at a comprehensive ophthalmic practice. Children who discontinued treatment, ages >18, and cases with hereditary conditions were excluded. The rate of progression of myopia after treatment with atropine was compared with historical data to evaluate the effectiveness of the regime.

Results

One hundred and one children (mean baseline spherical equivalent [SphE] [−3.70 +/− 2.09 D] and axial length [AL] [24.59 +/− 1.00 mm]) were analysed. The mean age of the children was 10.4 +/− 2.89 years and 61% were females. The average follow-up time was 17.9 +/− 12.5 months. The mean rate of progression of AL and SphE on 0.01% atropine eyedrops was 0.219 +/− 0.35 mm and − 0.250 +/− 0.86 D/year, respectively. 68.1% of the children treated with 0.01% atropine were mild progressors (<0.5 D change/year). Non-responders when commenced on a higher dose of atropine (0.05%) experienced a 93% (p = 0.012) and 30% reduction in SphE and AL growth rate, respectively. Family history, higher myopia or younger age at baseline and shorter duration of treatment were associated with steeper progression (p < 0.01). Both doses were well tolerated.

Conclusions

Low-dose atropine was shown to be beneficial in a real-world clinical setting, despite interruptions to follow-ups secondary to COVID-19 pandemic. A 0.05% dose of atropine may be effective in cases where 0.01% was ineffective.     

Myopia control and prevention: From lifestyle to low-concentration atropine. The 2022 Josh Wallman Memorial Lecture

The purpose of this study was to explore the findings from the Hong Kong Children Eye Study and the Low Concentration Atropine for Myopia Progression (LAMP-1) Study. The incidence of myopia among schoolchildren in Hong Kong more than doubled during the COVID-19 pandemic, with outdoor time decreased significantly and screen time increased. The change in lifestyle during the COVID-19 pandemic aggravated myopia development. Low-concentration atropine (0.05%, 0.025% and 0.01%) is effective in reducing myopia progression with a concentration-related response. This concentration-dependent response was maintained throughout a 3-year follow-up period, and all low concentrations were well tolerated. An age-dependent effect was observed in each treatment group with 0.05%, 0.025% and 0.01% atropine. Younger age was associated with a poor treatment response to low-concentration atropine. Additionally, low-concentration atropine induced choroidal thickening along a concentration-dependent response throughout the treatment period. During the third year, continued atropine treatment achieved a better effect across all concentrations compared with the washout regimen. Stopping treatment at an older age and receiving lower concentration were associated with a smaller rebound effect. However, differences in the rebound effect were clinically small across all the three concentrations studied.     

阿托品对大鼠巩膜成纤维细胞增殖和凋亡的影响及其机制

目的 探讨不同浓度阿托品对大鼠巩膜成纤维细胞增殖和凋亡的影响及其机制。方法 取出生24 h的健康雄性SD大鼠眼巩膜组织(均为右眼)进行原代培养。取细胞进行分组：对照组(正常巩膜成纤维细胞),0.1 g·L^-1、1.0 g·L^-1及5.0 g·L^-1阿托品处理组(正常巩膜成纤维细胞分别加入三种不同浓度阿托品溶液),每组5只大鼠原代培养细胞。加药后24 h, CCK-8法检测各组巩膜成纤维细胞活力，流式细胞仪检测各组巩膜成纤维细胞凋亡率，Western blot法检测各组巩膜成纤维细胞光蛋白聚糖、基质金属蛋白酶(MMP)-2、MMP-14和MMP抑制剂(TIMP)-2蛋白表达情况。结果 CCK-8实验结果显示：与对照组相比，0.1 g·L^-1、1.0 g·L^-1及5.0 g·L^-1阿托品处理组细胞活力均增高，其中以1.0 g·L^-1阿托品处理组增高最显著，差异均有统计学意义(均为P<0.05)。流式细胞仪检测结果表明：阿托品处理组各...