Development of inclusion complex of brinzolamide with hydroxypropyl-β-cyclodextrin

Glaucoma is an accumulative optic neuropathy resulted from increasing intraocular pressure. Brinzolamide (BRZ) is a kind of carbonic anhydrase inhibitors for glaucoma treatment. In this study, brinzolamide-hydroxypropyl-β-cyclodextrin (BRZ-HP-β-CD) inclusion complex was prepared by solvent evaporation method to improve the solubility of BRZ and enhance the therapeutic effect of BRZ. The formation of the inclusion complex was confirmed by Fourier transform infrared spectroscopy, differential scanning calorimeter and nuclear magnetic resonance spectroscopy. The solubility of BRZ increased about 10-fold after the formation of the BRZ-HP-β-CD inclusion complex. The in vitro corneal accumulative permeability of the inclusion complex increased 2.91-fold compared to the commercial available formulation (AZOPT^®). In addition, BRZ-HP-β-CD inclusion complex (0.5% BRZ) had an equivalent efficiency of lowering intraocular pressure with AZOPT^® (1% BRZ) in vivo. These results identified the BRZ-HP-β-CD inclusion complex might have a promising future as a novel formulation of BRZ for glaucoma treatment.     

Diurnal and circadian variations in intraocular pressure in goats exposed to different lighting conditions

ABSTRACT

The effect of constant light and constant darkness on intraocular pressure (IOP) in goats has not been investigated. We hypothesized that IOP variations would differ between goats kept under a cycle of 12 hours of light and 12 hours of darkness (LD), constant darkness (DD), and constant light (LL). To test this hypothesis, goats were exposed to these conditions for five days (LD, 30 goats; DD, 10 goats; LL, 10 goats). IOP was measured by applanation tonometry at 9 a.m. (beginning of photophase in LD) and 9 p.m. (beginning of scotophase in LD) on the fourth and fifth days of exposure. We found that changes in mean IOP from 9 a.m. to 9 p.m. differed significantly between groups (χ²(2) = 23.04, p < .0001). Most goats in LD showed a regular pattern of higher IOP in the morning and lower IOP in the evening, whereas those in DD and LL did not follow this pattern. In LD conditions, mean IOP was 2.4 mm Hg lower at 9 p.m. than at 9 a.m. (95% confidence interval for the difference (CI): ?2.8 to ?1.9 mm Hg, p < .0001). In DD conditions, mean IOP did not differ between 9 p.m. and 9 a.m. (CI: ?0.9 to 0.8 mm Hg, p = .90). In LL conditions, it was 0.6 mm Hg lower at 9 p.m. (CI: ?1.5 to 0.2 mm Hg, p = .12). Our results indicate that IOP in goats kept in LD is higher in the morning than in the evening, and that IOP variations are reduced in goats kept in DD and LL. These results suggest that exposure to alternating periods of light and darkness is important for maintaining rhythmic variations in IOP in this species.     

Brain tissue transplanted to the anterior chamber of the eye: 2. Fluorescence histochemistry of immature catecholamine and 5-hydroxytryptamine neurons innervating the rat vas deferens

Summary Small pieces of the wall of the rat vas deferens were homologously transplanted to the anterior chamber of the eye together with small pieces of embryonic brain stem containing either developing noradrenaline (NA) cells of the locus coeruleus or 5-hydroxytryptamine (5-HT) neurons of the developing raphe system. The eyes of the recipients were sympathetically denervated. The double transplants became rapidly vascularized from the host iris. After 31/2 months the irides, together with their two transplants were analyzed by Falck-Hillarp fluorescence microscopy. Both the NA and the 5-HT neurons had survived and matured in the eye. Fluorescent varicose nerve terminals of the NA and 5-HT type respectively were found in all three potential receptor areas, i.e. within the CNS transplants, in the host irides and in the vas deferens transplants. In the latter, the newly formed monoamine nerve terminals arborized mainly within a well developed smooth muscle layer. The density of such new fibres was higher than or similar to that of the normally present sympathetic plexus in areas of the transplant close to the CNS transplant and lower in areas at a distance from the CNS transplant. It is concluded that immature central NA and 5-HT fibres are able to grow simultaneously into different types of sympathetically denervated smooth muscle tissues to form networks of fibres in the receptor organs resembling the normal sympathetic innervation.Supported by the Swedish Medical Research Council (04X-3185), and by grants from Magnus Bergvalls Stiftelse, Tidningen Expressens Prenatalforskningsfond and Karolinska Institutets fonder. We thank miss Ingrid Strömberg for skilful technical assistance. Nialamide^® was generously donated by Swedish Pfizer AB.     

曲伏前列腺素滴眼液对原发性开角型青光眼患者眼压、血流动力学及ET-1、TIMP-2的影响

目的:探讨曲伏前列腺素滴眼液对原发性开角型青光眼(POAG)患者眼压、血流动力学及内皮素-1(ET-1)、基质金属蛋白酶-2抑制因子(TIMP-2)的影响。方法:选取2015年2月至2017年2月我院眼科收治的70例患者,按照随机数字表法分为对照组和观察组,每组各35例,对照组和观察组患者分别给予马来酸噻吗洛尔滴眼液和曲伏前列腺素滴眼液治疗,治疗周期为3个月。对比分析治疗前、治疗4周、8周及12周后两组患者的平均眼压(IOP)、昼夜IOP差,并对比治疗前、治疗12周后的睫状后动脉(PCA)、视网膜中央动脉(CRA)、收缩期峰值血流速度(PSV)、舒张末期血流速度(EDV)、血管阻力指数(RI)、血浆ET-1及房水TIMP-2的改善情况。结果:治疗前两组患者平均IOP、昼夜IOP差、PCA和CRA血流动力学、血浆ET-1及房水TIMP-2差异无统计学意义(P0.05);治疗4周、8周、12周后,两组平均IOP、昼夜IOP差明显低于治疗前,且治疗12周后观察组平均IOP、昼夜IOP差低于对照组,差异均有统计学意义(P0.05);治疗12周后,观察组PCA和CRA的PSV、EDV高于治疗前,RI低于治疗前,差异均有统计学意义(P0.05),且观察组PCA和CRA的PSV、EDV高于对照组,RI低于对照组,差异均有统计学意义(P0.05);治疗12周后,两组患者血浆ET-1和房水TIMP-2较治疗前显著下降,且观察组血浆ET-1和房水TIMP-2含量低于对照组,差异均有统计学意义(P0.05)。结论:曲伏前列腺素滴眼液治疗POAG患者,能够有效降低患者的眼压、血浆ET-1、房水TIMP-2水平,并改善患者PCA、CRA的血流动力学。     

Highly hydrophilic 1,3-oxazol-5-yl benzenesulfonamide inhibitors of carbonic anhydrase II for reduction of glaucoma-related intraocular pressure

Four inhibitors of human carbonic anhydrase II (hCA II) were designed based on the previously reported subnanomolar 1,3-oxazole-based sulfonamide inhibitors of the enzyme to incorporate primary and secondary amine functionality in the carboxamide side chain. The new hydrophilic compounds were found to inhibit the target isoform in sub-nanomolar to low nanomolar range with a good degree of selectivity to several other hCA isoforms. The hydrophilic character of these compounds is advantageous for intraocular residence time but not for corneal permeability which generally requires that a drug be sufficiently lipophilic. Two of the four compounds investigated, however, were found to exert comparable efficacy as 1% eye drops in PBS to that of the clinically used 2% dorzolamide (Trusopt®) eye drops. This indicated that the absorption of the compounds may occur via alternative route across conjunctiva and sclera.     

超声乳化吸除联合人工晶体植入术治疗白内障的疗效及术后前房渗出的影响因素分析

摘要 目的：观察超声乳化吸除（PE）联合人工晶体植入术（IOL）治疗白内障的疗效,并分析术后前房渗出的影响因素。方法：回顾性分析我院2018年1月~2021年2月收治的行PE联合IOL治疗的白内障患者406例（482眼）的临床资料,观察其视力变化情况及术后并发症发生情况。通过单因素及多因素Logistic回归分析术后前房渗出的影响因素。结果：白内障患者术后视力0.6~0.9、≥1.0眼数占比高于术前（P<0.05）。白内障患者术后发生并发症46眼,分别为晶状体色素沉着、后囊浑浊、角膜水肿各3眼,纤维性渗出膜2眼,术后前房渗出35眼,并发症发生率为9.54%（46/482）。单因素分析结果显示：PE联合IOL术后前房渗出与高血压病史、高度近视、合并青光眼、术前眼内压＞21 mmHg、术中晶状体后囊膜破裂、葡萄膜炎、术中瞳孔直径<3 mm、晶状体核分级≥IV级有关（P<0.05）。多因素Logistic回归分析结果显示：术前眼内压＞21 mmHg、合并青光眼、高度近视、术中晶状体后囊膜破裂、葡萄膜炎、晶状体核分级≥IV级是术后前房渗出的影响因素（P<0.05）。结论：PE联合IOL治疗白内障,疗效较好,可有效改善患者视力,且并发症发生率较低。患者术后前房渗出受多种因素影响,临床工作中应根据相关因素制定干预、治疗措施以降低术后前房渗出风险。     

布林佐胺与噻吗洛尔滴眼液对新生血管性青光眼患者眼压及血清和房水IL-6、PEDF和VEGF水平的影响

目的:探讨布林佐胺联合噻吗洛尔滴眼液对新生血管性青光眼(NVG)患者眼压及血清和房水中白细胞介素-6(IL-6)、色素上皮衍生因子(PEDF)、血管内皮生长因子(VEGF)水平的影响。方法:选取我院2014年6月～2016年12月择期行手术治疗的86例NVG患者,按照随机数字表法均分为两组。对照组术后采取噻吗洛尔滴眼液治疗,观察组在此基础上加用布林佐胺滴眼液治疗。记录比较两组临床疗效,治疗前后眼压及血清和房水中IL-6、PEDF和VEGF水平的变化及不良反应的发生情况。结果:术后6个月,观察组总有效率为95.3%,较对照组明显升高(79.1%,P0.05)。与术前对比,两组术后7天、6个月时24 h眼压峰值、平均眼压、眼压波动值、血清和房水中IL-6、VEGF水平均显著下降(P0.01),血清和房水中PEDF水平均显著上升(P0.01),且观察组以上眼压指标较对照组同期改善更为明显(P0.01)。对照组和观察组不良反应的发生率对比差异无统计学意义(7.0%vs 11.6%,P0.05)。结论:术后应用布林佐胺联合噻吗洛尔滴眼液治疗NVG患者更能有效降低眼压和控制其波动,调节机体血管生成促进/抑制因子平衡,提高治疗效果,且安全性高。     

Basis of Chloride Transport in Ciliary Epithelium

The aqueous humor is formed by the bilayered ciliary epithelium. The pigmented ciliary epithelium (PE) faces the stroma and the nonpigmented ciliary epithelium (NPE) contacts the aqueous humor. Cl⁻ secretion likely limits the rate of aqueous humor formation. Many transport components underlying Cl⁻ secretion are known. Cl⁻ is taken up from the stroma into PE cells by electroneutral transporters, diffuses to the NPE cells through gap junctions and is released largely through Cl⁻ channels. Recent work suggests that significant Cl⁻ recycling occurs at both surfaces of the ciliary epithelium, providing the basis for modulation of net secretion. The PE-NPE cell couplet likely forms the fundamental unit of secretion; gap junctions within the PE and NPE cell layers are inadequate to maintain constancy of ionic composition throughout the epithelium under certain conditions. Although many hormones, drugs and signaling cascades are known to have effects, a persuasive model of the regulation of aqueous humor formation has not yet been developed. cAMP likely plays a central role, potentially both enhancing and reducing secretion by actions at both surfaces of the ciliary epithelium. Among other hormone receptors, A₃ adenosine receptors likely alter intraocular pressure by regulating NPE-cell Cl⁻ channel activity. Recently, functional evidence for the regional variation in ciliary epithelial secretion has been demonstrated; the physiologic and pathophysiologic implications of this regional variation remain to be addressed.This revised version was published online in June 2005 with a corrected cover date.     

Intraocular pressure (IOP) in relation to four levels of daily geomagnetic and extreme yearly solar activity

The link between geomagnetic field activity (GMA), solar activity and intraocular pressure (IOP) in healthy individuals was investigated. The IOP of 485 patients (970 eyes) was recorded over three nonconsecutive years (1979, 1986, 1989) which were characterized by maximal solar activity (1979, 1989) or minimal solar activity (1986). The measurements were also correlated with four categories of GMA activity: quiet (level I⁰), unsettled (II⁰), active (III⁰), and stormy (IV⁰). Participants were also differentiated by age and sex. We found that IOP was lowest on days of level IV⁰ (stormy) GMA. The drop in IOP concomitant with a decrease in GMA level was more significant during periods of low solar activity and in persons over 65 years of age. There was a trend towards higher IOP values on days of levels II⁰ and IV⁰ GMA in years of high solar activity. Differences between the sexes and among individuals younger than 65 years were not significant. Our results show an interesting aspect of environmental influence on the healthy population.     

折叠式人工晶状体临床应用观察

目的:探讨白内障超声乳化摘除联合折叠式人工晶状体植入术的临床应用效果。方法:对109例(147只眼)白内障行超声乳化吸除术联合折叠式人工晶状体植入术,分别植入人工晶状体CANON STAARAQ-110NV型53眼、AMO S140NB型43眼、Pharmacia Ceeon 911型32眼、Alcon Acrysof型20眼。对术后视力、术前术后角膜散光、术后前房反应、人工晶状体位置、手术并发症进行观察。结果:术后6个月。矫正视力≥0.5眼数分别为94.3％、93.0％、90.6％、90.0％;术后6个月,AQ-110NV型和S140NB型、CeeOn 911型和Alcon Actysof型间角膜平均散光度数无显著差异,AQ-110NV型和S140NB型与Ceeon 911型和Alcon Acrysof型有显著差异(P<0.05);术后前房反应轻微;角膜水肿、后囊破裂、后囊混浊、人工晶状体破损,发生率分别为6.1％、4.1％、10.9％、3.9％;未发现人工晶体状体明显移位者。结论:各种材料的折叠式人工晶状体在临床上的应用都是有效的,推注式人工晶状体(AQ-110NV、S140NB型)植入术无须扩大切口,容易掌握,术后反应轻,并发症少,手术疗效满意。