兔眼玻璃体腔注射万古霉素的视网膜毒性研究

目的探讨玻璃体腔注射万古霉素后视网膜组织结构的变化过程。方法将48只新西兰白化兔随机分为4组,每组12只(24眼)。1、2、3组玻璃体腔内分别注入0．1 mL万古霉素溶液,浓度分别为1、2、5 mg/0．1 mL;对照组注射生理盐水0．1 mL。手术后观察眼底改变,第1、4、7、14天取眼球,在光学显微镜及透射电镜下观察视网膜组织结构变化。结果对照组及1 mg组眼底检查、光镜和电镜检查未见异常;2 mg组眼底检查未见异常,第7天时光镜和电镜下可见视网膜结构改变;5 mg组1-14 d各项检查均可见明显视网膜破坏。结论玻璃体腔注射2 mg以上(含2 mg)万古霉素可引起视网膜组织结构改变,1 mg是较为安全的眼内注射剂量。     

盐酸金刚烷胺对兔急性高眼压视网膜神经节细胞损伤的保护作用

随着对青光眼发病机制的深入研究,谷氨酸对视网膜神经细胞(RGC)的毒性作用已逐步被认识。O n ley[1]证实了谷氨酸对新生小鼠RGC毒性作用并称之为“兴奋性毒性”。体外实验也证实了谷氨酸对RGC的毒性作用[2]。在青光眼发病过程中,高眼压和缺血会使眼内谷氨酸的浓度增加,并且和眼     

大鼠视网膜缺血的组织学观察

视网膜组织的缺血性病变在临床上多见 ,许多眼部疾病或全身其它组织器官的疾患常常影响视网膜血管 ,导致视网膜组织缺血。缺血的视网膜其组织学发生改变 ,视功能受损 ,近年对此有一些研究 [1～ 3 ] 。我们采用血管收缩剂对大鼠球后注射 ,使球后血管收缩 ,视网膜血液供应中断 ,建造视网膜组织急性缺血的动物模型 ,对其发生、发展过程进行组织病理学观察 ,为阐明视网膜缺血的发病机制提供实验资料。1　材料和方法1.1　动物模型及分组 :健康成年 Sprague Dawley大鼠 2 0只 ,雌雄不拘 ,体重 2 2 0～ 2 5 0 g,由第一军医大学动物室提供。随机分…     

维甲酸不良反应的新动态

作者从国内应用维甲酸治疗急性早幼粒细胞白血病（ＡＰＬ）等，论述其出现的肾功能衰竭等不良反应。     

羟基喜树碱对兔毒性作用的研究

目的 以兔为实验对象研究抗癌药羟基喜树碱的毒性作用与剂量的相关性，为进一步对羟基喜树碱毒性作用的防治研究提供科学参考资料。方法 选择新西兰兔，经耳廓静脉连续注射羟喜17天，观察不同剂量对兔免疫功能、肾脏、肝脏和心脏的毒性作用及生化指标的变化。结果 羟基喜树碱可引起兔明显腹泻及IgG、ICM、ALT、WBC、RBC等指标的异常变化。结论 羟喜可引起兔明显的肝组织、免疫功能和造血功能的损伤，明显的腹泻和轻度心脏毒性。但对其损伤机制有待进一步研究。     

维甲酸滴丸的研制

目的：研究维甲酸滴丸的制备方法。方法：采用紫外分光光度法测定滴丸中维甲酸的含量，转篮法考察其体外溶出度。结果：维甲酸平均回收率为99．32％，RSD为0．98％(n=6)，溶出参数T50=12．30min，Td=19．20min，m=0．90。结论：本品制备工艺可行，质控方法可靠。     

兔视网膜挫伤后视网膜神经上皮水通道蛋白4的表达

目的观察兔实验性视网膜挫伤后视网膜神经上皮不同时段水通道蛋白4(AQP-4)的表达特点,以期进一步了解视网膜挫伤的发病机制。方法无眼疾大白兔42只,随机分组为挫伤后1h组、3h组、1d组、3d组、7d组、14d组和正常对照组;以重击法制备兔眼视网膜挫伤模型,致伤能量约为2.87J(E=mgh);于规定时间段处死受试兔,摘除眼球并取材,通过免疫组织化学法观察AQP-4在视网膜神经上皮的表达情况。结果受试各组家兔视网膜神经上皮均有AQP-4表达;与对照组相比较,AQP-4表达在视网膜挫伤后各组均明显升高(均P<0.05);伤后1h组即高于对照组(P<0.05),3h组明显升高,24h组AQP-4表达最强,3d组AQP-4表达明显下降,挫伤后7d组表达下降更为明显,14d组AQP-4表达仍高于对照组(P<0.05);各个挫伤组AQP-4表达也存在明显差异(P<0.01)。结论兔视网膜挫伤后视网膜神经上皮AQP-4表达迅速升高;推测AQP-4是挫伤后视网膜水肿病理过程的一个重要机制。     

The negative side of retinoic acid receptors

This is a review of research that supports a hypothesis regarding early restriction of gene expression in the vertebrate embryo. We hypothesize that vertebrate retinoic acid receptors (RARs for several vertebrates but rars for zebrafish) are part of an embryonic, epigenetic switch whose default position, at the time of fertilization is "OFF". This is due to the assemblage of a rar-corepressor-histone deacetylase complex on retinoic acid response elements (RAREs) in regulatory regions of a subset of genes. In addition, selective and precise allocation of retinoic acid during early development through the interaction of Phase I enzymes throws the switch "ON" in a predictable, developmental manner. We are proposing that this is a basic, early embryonic switch that can cause the initiation of cascades of gene expression that are responsible for at least some early, diversification of cell phenotypes. Dehydrogenases and a subset of cytochrome p450 genes (cyp26a1, cyp26b1, and cyp26c1) play the major role in providing the retinoic acid and limiting its access. We also suggest that this mechanism may be playing a significant role in the repression of genes in undifferentiated stem cells.     

阿仑膦酸钠抗维甲酸骨质疏松的实验研究

目的观察和分析阿仑膦酸钠(ALN)对维甲酸所致实验性骨质疏松大鼠的防治作用。方法观察ALN(1.8、3.6 mg.kg-1.d-1)对维甲酸所致实验性骨质疏松大鼠股骨头和股骨干部位的骨矿密度、股骨头的钙磷含量以及强迫游泳时间的影响。结果与模型对照组相比,ALN可明显增加维甲酸所致实验性骨质疏松大鼠股骨头和股骨干部位的骨矿密度(P<0.05,P<0.01),钙、磷含量(P<0.05)及强迫游泳时间(P<0.01)。结论ALN可使维甲酸所致实验性骨质疏松大鼠骨钙、磷含量的提高,骨矿密度的增加,运动能力的提高,有明显的防治骨质疏松作用。     

Formation of ion pairing as an alternative to improve encapsulation and stability and to reduce skin irritation of retinoic acid loaded in solid lipid nanoparticles

This work aims to investigate the influence of the formation of ion pairing between all-trans retinoic acid (RA) and a lipophilic amine (stearylamine; STE) on the drug encapsulation efficiency (EE) and stability of solid lipid nanoparticles (SLNs). The SLNs were characterized for EE and size. The EE and particle size were significantly improved and reduced, respectively, when the surfactant or co-surfactant concentration increased. However, while the formulation without STE allowed only 13% of RA encapsulation, the EE for RA–STE-loaded SLNs was 94%. The stability studies showed a significant decrease in EE for the SLNs without STE, while, for SLNs loaded with RA and STE, the EE remained constant after 360 days. The interactions among ion pairing components and the lipid matrix were investigated through small-angle X-ray scattering (SAXS). The SAXS analysis revealed the presence of RA in the crystalline form in SLNs without ion pairing, while crystalline RA was not observed in SLNs loaded with RA/amine. Skin irritation studies showed that the SLNs loaded with the ion pairing were significantly less irritating when compared to the marketed RA-cream. This novel SLN formulation represents a promising alternative for topical treatment of acne with RA.     

维甲酸与亚砷酸双诱导结合化疗治疗急性早幼粒细胞白血病的临床效果

目的：观察维甲酸与亚砷酸双诱导结合化疗治疗急性早幼粒细胞白血病的临床效果。方法选取2011年1~10月本院收治的急性早幼粒细胞白血病患者50例,按随机数字表法将其分成实验组25例,对照组25例。实验组应用维甲酸与亚砷酸双诱导及化疗方案治疗,对照组应用维甲酸诱导结合化疗治疗,比较两组的临床效果和不良反应发生情况。结果实验组的高白细胞血症持续时间为(10.21±3.63)d,完全缓解(CR)率为96.0%,3年内死亡率为4.0%,达CR时间为(30.21±5.31)d,对照组分别为(16.21±5.32)d、88.0%、12.0%、(44.62±6.32)d,观察组的高白细胞血症持续时间短于对照组,CR率高于对照组,3年死亡率低于对照组,达CR时间短于对照组(P<0.05)。两组的高白细胞、骨髓抑制、心功能异常等不良反应发生率,差异无统计学意义(P>0.05)。结论维甲酸与亚砷酸双诱导结合化疗治疗急性早幼粒细胞白血病的效果满意,值得临床进一步推广应用。     

维A酸对实验性大鼠慢性阻塞性肺疾病MMP-9的影响

目的：利用维A酸对实验性大鼠慢性阻塞性肺疾病的干预,检测其MMP-9的变化并对其机制的探讨。方法：Wistar雄性大鼠36只,随机分为3组：正常对照组、模型组和用药组,每组12只。模型组大鼠用药后观察各组大鼠肺组织的病理改变,免疫组化方法及酶联免疫试验观察肺组织MMP-9表达情况。结果：模型MMP-9的活性和表达与正常对照组比较,差异有显著性（P〈0．01）。用药组MMP-9的活性和表达与模型组比较,差异有显著性（P〈0．01）。结论：维A酸对慢性阻塞性肺疾病防治及治疗有很好的指导意义。     

玻璃体手术中吲哚青绿对视网膜结构的影响

目的研究吲哚青绿(ICG)辅助视网膜内界膜(ILM)染色的玻璃体切割手术后,不同浓度ICG对视网膜结构的影响。方法选取健康家兔25只,体重2～2.5kg,2个月龄,雌雄不限。从中随机选取5只家兔,作为手术空白对照组(10只眼球)。根据人眼手术中实际应用ICG的浓度,实验分为0.025、0.25、2.5和25g/L4个不同浓度组,每组5只家兔(10只眼球)作为实验组。手术空白对照组与实验组均行模拟人眼的玻璃体切割手术,术中实验组行ICG染色ILM,空白对照组用平衡盐溶液做对照。所有实验动物术后14d摘取眼球制作光镜标本,低浓度组(0.025、0.25g/L)眼球制作电镜标本,观察拍片。结果ICG染色ILM玻璃体切割术后,光镜观察低浓度组,视网膜结构仅见轻微改变。高浓度组(2.5、25g/L)视网膜结构改变明显,感光细胞内外节水肿严重,空隙增大。内外核层极性紊乱,内外丛状层变薄。电镜观察0.025g/L组仅见内核层少许细胞胞质水肿,0.25g/L组可见内外核层及神经节细胞内线粒体空泡变。结论ICG染色ILM玻璃体切割术后,ICG对视网膜的结构有损伤作用。     

The relative importance of CYP26A1 in hepatic clearance of all-trans retinoic acid

All-trans retinoic acid (RA) is a critical signaling molecule and its concentration is tightly regulated. Several P450 enzymes including CYP26A1, CYP2C8, and CYP3A4 have been proposed to be responsible for RA clearance in the liver but their quantitative importance has not been demonstrated. To determine the contribution of CYP26A1 to hepatic clearance of RA, CYP26A1 protein was quantified in 37 human liver microsomes (HLMs). CYP26A1 expression ranged from not detectable to 2.80 pmol/mg microsomal protein. RA clearance by P450 enzymes abundant in human liver was measured in Supersomes^®. CYP2C8, CYP3A4, CYP3A5 and CYP3A7 metabolized RA with unbound K_m values of 3.4-7.2 μM and V_max values of 2.3-4.9 pmol/min/pmol P450, but were less efficient than CYP26A1 in clearing RA. Simulations performed for livers with varying P450 expression levels over a range of RA concentrations demonstrated that at both endogenous and therapeutic concentrations of RA, CYP26A1 is the primary enzyme responsible for 4-OH RA formation clearance. HLM incubation data showed that 4-OH RA formation velocity varied from 0.2 to 15.3 pmol/min/mg microsomal protein and velocity in HLMs was significantly correlated (p < 0.01) to CYP26A1, CYP3A4, and CYP3A5 protein content, but not to CYP2C8. When experimental data were scaled to in vivo clearances, the predicted hepatic clearance of RA (0.07 L/min using combined Supersome^® data) was similar to the published in vivo clearance of RA. These findings suggest that CYP26A1 is the P450 isoform that should be targeted when designing RA metabolism blocking agents.     

全反式维甲酸对人骨髓基质细胞分泌GM-CSF的影响

目的:探讨全反式维甲酸对骨髓基质细胞分泌GM-CSF的影响.方法:原代培养正常人和急性早幼粒细胞白血病患者的骨髓基质细胞,ELISA法检测不同浓度维甲酸对正常和急性早幼粒细胞白血病骨髓基质细胞分泌GM-CSF的差异.结果:不同浓度全反式维甲酸对正常和急性早幼粒细胞白血病骨髓基质细胞分泌GM-CSF浓度存在差异,维甲酸呈浓度依赖性调高正常和急性早幼粒细胞白血病患者骨髓基质细胞分泌GM-CSF浓度.结论:维甲酸可能通过骨髓基质细胞分泌GM-CSF而促进造血,间接诱导细胞分化治疗.