Alpha-lipoic acid: A possible pharmacological agent for treating dry eye disease and retinopathy in diabetes

Alpha-lipoic acid (ALA) is a naturally occurring dithiol micronutrient which acts as a cofactor for mitochondrial enzyme activity. Due to its potential antioxidant activity, it is considered as “universal antioxidant”. Previous studies reported the pharmacological benefits of ALA such as glycaemic control, improved insulin sensitivity and alleviation of diabetic complications such as neuropathy and cardiovascular diseases. Dry eye disease and retinopathy are prevalent in diabetic patients. Experimental studies demonstrated the beneficial effects of ALA in dry eye and diabetic retinopathy. ALA can prevent the dry eye by down regulating the expression of matrix metalloproteinase-9 in the corneal epithelial cells and activating the antioxidant status of the ocular surface. Furthermore, its direct antioxidant effect can also prevent oxidative stress-induced corneal surface erosion and lachrymal gland damage. ALA prevents diabetic retinopathy through inhibition of O-linked β-N-acetylglucosamine transferase and nuclear factor-kappa B activity and alleviation of oxidative stress. It can activate the nuclear factor erythroid-2-related factor 2 and AMP-activated protein kinase in retinal ganglion cells. Clinical trials conducted in pre-retinopathic diabetic patients showed ALA with genistein and vitamins could protect the retinal cells and decline the inflammatory effect in diabetic patients. However, studies are scant to explore its beneficial effects in dry eye disease and diabetic retinopathy. Therefore, this review article discusses an update on the role of ALA in dry eye disease and diabetic retinopathy, two ocular diseases prevalent in diabetic patients.     

Dry powder inhalation: past,present and future

Introduction: Early dry powder inhalers (DPIs) were designed for low drug doses in asthma and COPD therapy. Nearly all concepts contained carrier-based formulations and lacked efficient dispersion principles. Therefore, particle engineering and powder processing are increasingly applied to achieve acceptable lung deposition with these poorly designed inhalers.

Areas covered: The consequences of the choices made for early DPI development with respect of efficacy, production costs and safety and the tremendous amount of energy put into understanding and controlling the dispersion performance of adhesive mixtures are discussed. Also newly developed particle manufacturing and powder formulation processes are presented as well as the challenges, objectives, and new tools available for future DPI design.

Expert opinion: Improved inhaler design is desired to make DPIs for future applications cost-effective and safe. With an increasing interest in high dose drug delivery, vaccination and systemic delivery via the lungs, innovative formulation technologies alone may not be sufficient. Safety is served by increasing patient adherence to the therapy, minimizing the use of unnecessary excipients and designing simple and self-intuitive inhalers, which give good feedback to the patient about the inhalation maneuver. For some applications, like vaccination and delivery of hygroscopic formulations, disposable inhalers may be preferred.     

含对乙酰氨基酚的感冒药及柴芩清宁胶囊对脂多糖和干酵母大鼠发热模型的解热作用研究

目的 研究含对乙酰氨基酚的西药对乙酰氨基酚片、复方氨酚烷胺片、美扑伪麻片及中成药柴芩清宁胶囊对脂多糖（LPS）及干酵母大鼠发热模型的解热作用。方法 制备大鼠100 μg/kg LPS及20%干酵母发热模型;乙酰氨基酚片、复方氨酚烷胺片、美扑伪麻片高、中、低剂量分别为205.67、102.83、51.42 mg/kg,以对乙酰氨基酚计;柴芩清宁胶囊高、中、低剂量分别为1110.60、555.30、277.65 mg/kg,以胶囊内容物质量表示,ig给药。观察大鼠体温变化,计算平均最大体温上升高度（△T）及体温反应指数（TRI）,绘制平均升温曲线。结果 对乙酰氨基酚片、复方氨酚烷胺片、美扑伪麻片及柴芩清宁胶囊各剂量组对LPS及干酵母大鼠发热模型均具有显著解热作用,且均存在一定剂量效应关系。结论 对乙酰氨基酚片、复方氨酚烷胺片、美扑伪麻片及柴芩清宁胶囊对LPS及干酵母大鼠发热模型均有一定解热作用,3种西药的解热作用起效快但是作用时间短,而柴芩清宁胶囊表现为起效慢但是作用时间长。     

Preparation and Quality Evaluation of Salvianolic Acids and Tanshinones Dry Powder Inhalation

Salvianolic acids and tanshinones both exhibit efficacy in treating idiopathic pulmonary fibrosis (IPF), but their formulation limits their clinical use. This study aimed to prepare the salvianolic acids and tanshinones dry powder for inhalation (SPI) to achieve pulmonary delivery for the treatment of IPF. The variable quantities of salvianolic acids and tanshinones composite powder were optimized using the central composite design-response surface method. Different carriers with various drug-carrier ratios were optimized to prepare SPI. The final optimized formulation of SPI was as follows: InhaLac 230^® was selected as the carrier with drug:carrier = 1:6, and the milled lactose InhaLac 400^® was added at 5%. The developed SPI characterized with an angle of repose 52.46 ± 1.04°, Carr's index of 34.00 ± 0.50% and showed high lung deposition in vitro, indicating the potential of pulmonary delivery for the treatment of IPF.     

Loteprednol etabonate for inflammatory conditions of the anterior segment of the eye: twenty years of clinical experience with a retrometabolically designed corticosteroid

Introduction: Topical corticosteroids are an important pharmacotherapy for the management of various inflammatory conditions affecting the anterior segment of the eye. However, medications in this class are associated with well-known risks including increased intraocular pressure (IOP) and development of cataracts. The topical corticosteroid loteprednol etabonate (LE) was developed with the specific intention of minimizing these side effects.

Areas covered: The focus of this review is to examine published efficacy and safety data for LE, a drug engineered to undergo rapid metabolism to inactive metabolites with the goal of improved safety. Two decades of clinical research focused on LE formulations are reviewed, including the use of LE in combination with tobramycin. The cumulative body of experience affirms the concept that the molecular design of LE confers certain safety benefits without compromising the desired anti-inflammatory efficacy of a topical corticosteroid.

Expert opinion: Loteprednol etabonate is a mainstay for topical therapy of a wide variety of commonplace and niche conditions of the ocular surface and the anterior segment, including in the healing post-operative patient. Its versatility and safety allow eye care providers to recommend both acute induction as well as chronic maintenance therapy with appropriate follow-up.     

2型糖尿病患者脂代谢异常和干眼的相关性研究

目的:探讨2型糖尿病患者脂代谢异常和干眼的相关性。方法:收集2型糖尿病患者77例（154只眼）,分为A组（脂代谢异常）40例和B组（脂代谢正常）37例,所有受试者全部进行眼表疾病指数问卷（OSDI量表）、泪膜破裂时间（ BUT）、泪液分泌试验（Schirmer Ⅰ test）、角膜荧光素钠染色、眼表分析[睑板腺缺失评分、泪河高度（TMH）、非侵入性平均泪膜破裂时间（NIBUT）]、脂质层厚度分析等干眼相关检查,对两组结果进行统计学分析,分析2型糖尿病患者合并脂代谢异常和干眼的关系。结果:A组干眼发生率为73.75%,B组为55.41%,两组间有统计学差异（χ2=5.682,P=0.017）。A组干眼OSDI量表指数（t=-8.357,P=0.000）、BUT（Z=-4.245,P=0.000）与B组有统计学差异,OSDI量表指数与总胆固醇（r=0.706,P=0.000）、低密度脂蛋白-胆固醇（r=0.653,P=0.000）以及甘油三酯（r=0.763,P=0.000）呈正相关;BUT与总胆固醇（r=-0.310,P=0.000）、低密度脂蛋白-胆固醇（r=-0.262,P=0.001）以及甘油三酯（r=-0.303,P=0.000）呈负相关;Schirmer与总胆固醇（r=-0.207,P=0.010）、低密度脂蛋白-胆固醇（r=-0.164,P=0.042）以及甘油三酯（r=-0.234,P=0.003）呈负相关。结论:脂代谢异常的2型糖尿病患者干眼发生率明显增加。     

白涩症源流浅析

本文通过对历史相关古籍文献的整理研究,梳理白涩症发展沿革,探讨历代医家对其病因病机及治疗方法的认识,以期为白涩症的研究提供理论基础,并为临床治疗开拓思路。中医对白涩症的相关记载,最早可追溯至晋代《针灸甲乙经》中有关目涩的论述,其对于自觉眼部干涩不适的症状有了初步的认识。“白涩症”之名首见于《证治准绳》,后沿用至今。其基本病因病机主要归责于津液亏少,眼目不得濡养,外感邪气、脏腑内伤、情志失常、饮食劳倦等因素均可致病,内治法治疗主要分为祛邪、泻实、补虚三个方面,外治法包括点眼法及针灸疗法,临床上当审察病因,随证治之。现代医学对该病的治疗主要以缓解症状为主,寻找有效的中医治疗手段在现代临床应用中意义重大。     

滋阴降火汤联合玻璃酸钠滴眼液治疗LASIK术后阴血不足型干眼的疗效观察

目的观察口服自拟方滋阴降火汤联合玻璃酸钠滴眼液治疗LASIK术后阴血不足型干眼的疗效。方法选取符合纳入标准的干眼患者49例(49只眼),随机分为治疗组24例(24只眼)和对照组25例(25只眼)。对照组予0.1%玻璃酸钠滴眼液治疗。治疗组在对照组的基础上予滋阴降火汤口服。2组均治疗1个月。分别于治疗前和治疗后,行泪液白介素-6(IL-6)、泪液分泌试验I(SIT)和泪膜破裂时间(BUT)检查,并记录数据。结果(1)IL-6:治疗前后比较,t_治疗组=7.018,P=0.000,t_对照组=3.391,P=0.001,差异均有统计学意义。治疗后2组比较,差异有统计学意义(t=-3.137,P=0.003);(2)SIT:治疗前后比较,t_治疗组=5.715,P=0.000;t_对照组=2.417,P=0.019,差异均有统计学意义。治疗后2组比较,差异有统计学意义(t=2.167,P=0.035);(3)BUT:治疗前后比较,t_治疗组=4.647,P=0.000;t_对照组=3.707,P=0.001,差异均有统计学意义。治疗后2组比较,差异有统计学意义(t=2.334,P=0.024);(4)临床疗效:治疗组总有效率为83.33%,对照组为56.00%,2组比较有统计学意义(c2=4.307,P=0.038)。结论滋阴降火汤联合玻璃酸钠滴眼液治疗LASIK术后阴血不足型干眼疗效显著,可能与其能降低泪液IL-6含量有关。