Narrative review of risuteganib for the treatment of dry age-related macular degeneration (AMD)

Age-related macular degeneration(AMD)is a leading cause of blindness worldwide.AMD most commonly affects older individuals and is characterized by irreversible degeneration of the retinal pigment epithelium and neurosensory retina.Currently,there are limited treatment options for dry AMD outside of lifestyle modification and nutrient supplementation.Risuteganib[Luminate(ALG-1001),Allegro Ophthalmics,CA,USA]is an intravitreally administered inhibitor of integrin heterodimersαVβ3,αVβ5,α5β1,andαMβ2.It is currently undergoing clinical trials for the treatment of dry AMD and diabetic macular edema(DME).Preclinical studies have shown that risuteganib has an effect on the pathways for angiogenesis,inflammation,and vascular permeability.Ongoing clinical trials have had promising results showing improvements in patient best corrected visual acuity(BCVA)and reduced central macular thickness measured by optical coherence tomography(OCT).There is a pressing need for treatments for dry AMD and while risuteganib appears to have a potential benefit for patients,more data are needed before one can truly evaluate its efficacy.This narrative review provides a concise summary of the most up to date data regarding the proposed mechanism of action of risuteganib in the treatment of nonexudative AMD and DME as well as the results from recent phase 1 and phase 2 clinical trials.

薯蓣皂苷元调控Nrf2信号通道干预大鼠干性AMD氧化应激机制的研究

目的观察薯蓣皂苷元对核因子E2相关因子2(nuclear factor erythroid-2-related factor 2,Nrf2)mRNA表达及超氧化物歧化酶(Superoxide Dismutase,SOD)、谷胱甘肽过氧化物酶(Glutathione peroxidase,GSH-Px)、丙二醛(malondialdehyde,MDA)的影响,探讨其干预干性年龄相关性黄斑变性(age-related macular degeneration,AMD)氧化应激反应的机制。方法将SD系大鼠随机分为空白组、碘酸钠组、乐盯组、薯蓣皂苷元低剂量组(100 mg·kg^(-1))、薯蓣皂苷元中剂量组(200 mg·kg^(-1))、薯蓣皂苷元高剂量组(400 mg·kg^(-1)),每组20只,雌雄各半。用碘酸钠60 mg·kg^(-1)造模,乐盯组90 g·kg^(-1)乐盯灌胃,薯蓣皂苷元低、中、高剂量组分别按100 mg·kg^(-1)、200 mg·kg^(-1)、400 mg·kg^(-1)灌胃给药。连续灌胃20天和30天后分别取10只(雌雄各半)进行取材和指标检测。结果碘酸钠组大鼠视网膜组织形态学改变、Nrf2 mRNA表达及SOD值、GXH-Px值、MDA值与空白组、乐盯组有显著差异(P<0.05、P<0.01),而乐盯组与空白组之间无明显差异(P>0.05)。灌胃20天时,高中剂量组的Nrf2 mRNA表达、GSH-Px值和MDA值和高中低剂量组SOD值优于碘酸钠组(P<0.05、P<0.01),其中,高剂量组Nrf2 mRNA表达,高中剂量组SOD值、GSH-Px值和MDA值,与乐盯组、空白组无明显差异(P>0.05);灌胃30天时,高中低剂量组Nrf2mRNA表达、GSH-Px值、MDA值优于碘酸钠组(P<0.05、P<0.01),但高中剂量组优势更明显,与乐盯组、空白组无差异(P>0.05)。结论薯蓣皂苷元能够上调Nrf2mRNA表达,增加SOD、GXH-Px活性,降低MDA水平,干预干性AMD的发生。且其作用与剂量和时间具有一定相关性。

Application of Fly Ash and Organic Material as Dry Cover System in Prevention of Acid Mine Drainage Generation

The common practice in AMD prevention is a dry cover technique. In this technique, rock that is potential in producing acidity (PAF) will be placed below non-acid producing rock (NAF). Depends on NAF availability in the mine site situation, organic covers can be used to prevent diffusion of oxygen into reactive sulphide wastes and subsequently to eliminate sulphide compounds oxidation and generation of acidic waters. The utilization of additional material cover layer is proposed, by using fly ash and organic material combination. To investigate the possibility of using these materials, a column leaching test in the laboratory scale was conducted with several scenarios of simulation. By comparing between column with different thickness of fly ash and organic material, the leachate water behavior is observed in the experiment, including the measurement of water quality (pH and EC), major cations-anions. The result suggests the possible thickness of fly ash (FA) and organic material (OM) as cover layer material, especially in the case of mine with domination of PAF rock material.

Construction of Dry Cover System for Prevention of Acid Mine Drainage at Mine Waste Dump in Open Cast Coal Mines, Indonesia

Acid Mine Drainage (AMD) which occurs when sulfide minerals are exposed to water and oxygen with an excavation is one of the serious environmental problems in the world. A dry cover system is generally constructed in waste dump for the prevention of AMD in Indonesia by virtue of low cost and availability of waste rocks for a cover layer. However, the failure of the system caused by the lack of information related to the construction of cover system in mines, which leads to AMD, has been reported recently in Indonesia. In this study, the field investigation was conducted in pit and waste dump in open cast coal mine in Indonesia with the aim of obtaining the information on the construction of a cover layer and backfilling conditions of waste rocks in the waste dump. The rock samples taken in two areas of the mine were analyzed by geochemical analysis and sequential extraction with acids. The results indicated that Net Acid Producing Potential (NAPP) of the rocks in the waste dump down to 100 cm depth in both areas was from 10 to 30 kg H2SO4/ton, suggesting that Potentially Acid Forming (PAF) was backfilled in a cover layer. The backfill of PAF was contrary to the concept of cover system, which caused the failure of constructing a cover layer. The cause of the failure was likely attributed to the shortage of cover rocks which are classified as Non Acid Forming (NAF) or the failure of proper placement of them by an operational problem in the areas. Moreover, the results of the extraction with acids suggested that the form of iron and sulfur has to be taken into account to discuss the occurrence of AMD.

石灰性旱地土壤对酸性矿山废水污染的酸缓冲能力与作用

为探索酸性矿山废水(AMD)持续污染的影响程度,以贵州喀斯特岩溶区石灰性旱地土壤为研究对象,通过模拟分析AMD持续污染下石灰性旱地土壤pH、岩溶组分等特性的变化,评价石灰性旱地土壤对AMD持续污染的酸缓冲性能及其作用机理。结果表明:岩溶区石灰性旱地土壤对AMD具有较好的缓冲性能,AMD的使用量是土壤质量的10倍时,土壤对AMD的酸缓冲容量(以CaCO3计,下同),达77.266g/kg,岩溶区土壤pH仍可维持在6.65以上,风干及新鲜石灰性旱地土壤的酸缓冲容量,分别为(151.027±1.03)g/kg、(93.285±4.32)g/kg;随着AMD添加比例的增大,土壤Ca含量在低污染浓度下显著下降,在较高污染程度下稍有升高;土壤中Mg大量淋失,CO2释放量显著增加(p<0.01)。相关性分析表明,土壤pH与AMD的添加量相关关系不明显(rpH=-0.473,ppH=0.237;rCa=-0.416,pCa=0.305),而岩溶区石灰性旱地土壤Ca、Mg含量及土壤CO2释放量的变化与AMD的添加量呈极显著相关关系(rCa=-0.955**,pCa=0.000;rMg=-0.994**,pMg=0.000;rCO2=0.991**,pCO2=0.000)。表明,岩溶区石灰性旱地土壤对AMD持续污染具有较优越的缓冲性能,其中,CO32-及Ca、Mg等岩溶组分在岩溶区石灰性旱地土壤AMD酸缓冲方面发挥着重要作用。

中医治疗干性年龄相关性黄斑变性的理论探讨及机制的研究进展

年龄相关性黄斑变性(AMD)是一种老年人常见的致盲性眼底病变,可导致中心视力不可逆的丧失,发病机制复杂且病因不明,干性AMD(dAMD)在所有AMD患者中约占80%左右,以视力缓慢下降、玻璃膜疣生成和地图样萎缩为典型特征,但目前缺乏有效治疗手段。中医治疗dAMD取得了一定进展,且具有多靶点整体调节、疗效稳定等优势。本文将通过总结近年来的研究报道,探讨中医对dAMD病因病机、治法治则的理论认识,并从抑制细胞凋亡、抗氧化应激及调节免疫与炎性反应等现代研究方向综述滋阴助阳、化瘀散结类中药改善dAMD疗效机制的研究进展,以期为今后dAMD的治疗提供新思路。