An evaluation of chemical photoreactivity and the relationship to phototoxicity

The existing regulatory guidance for photosafety testing of new drug products states that studies are warranted for those chemicals that both absorb light in the range of 290–700 nm, and that are either applied locally/topically, or “reach” (EMEA)/“significantly partition” (FDA) to the skin or eyes. The initial in vitro study recommended for the assessment of phototoxic potential is the 3T3 Neutral Red Uptake (NRU) Assay. The current study was undertaken to establish superior triggers for the initiation of biological photosafety testing. In this study, photophysical and photochemical parameters for 40 drug or drug-like molecules were studied. Principal Component Analysis (PCA), Partial Least Squares-Discriminant Analysis (PLS-DA), and a fivefold cross-validation PLS algorithm were used to evaluate the relationship between subsets of photophysical and photochemical parameters with the 3T3 NRU PIF/MPE (Photo Irritation Factor/Mean Photo Effect) results. The parameters most indicative of a 3T3 NRU positive PIF or MPE score were the extent of degradation in solution, the quantum yield of formation of singlet oxygen and the relative formation of superoxide anion. The results demonstrate that while absorption of light is critical to the induction of a light-induced process, it is the resultant events that may be used to predict the 3T3 NRU assay result. It is therefore proposed that the trigger for photosafety testing be revised to include a molecular basis for photoreactivity. From this limited investigation, estimated thresholds leading to 3T3 NRU positive results due to photodegradation, formation of singlet oxygen quantum yield or a relative superoxide anion formation value are proposed.     

大豆异黄酮对初老大鼠卵巢Bcl-2基因和Caspase-3基因mRNA表达的影响

目的观察大豆异黄酮(soy isoflavones,SI)对初老大鼠卵巢Bcl-2、Caspas e-3 mRNA表达及氧自由基含量的影响。方法利用自然衰老的雌性大鼠建立初老动物模型,连续灌胃给药8周后,采用逆转录-聚合酶链反应(RT-PCR)检测卵巢Bcl-2和Caspase-3 mRNA表达,采用硫代巴比妥酸和黄嘌呤氧化法分别检测卵巢丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性。结果与初老组相比,各SI处理组卵巢Bcl-2 mRNA表达量和SOD的活性均明显增高、Caspase-3表达量明显下降,中剂量(158 mg.kg-1)和高剂量(500 mg.kg-1)SI处理组MDA含量也显著降低(P<0.05或P<0.01)。结论大豆异黄酮上调卵巢Bcl-2、下调Caspase-3表达、抑制氧自由基生成并增强SOD活性,可能是其改善衰老卵巢功能的机制之一。     

先天性感音性聋患者大脑皮层静息态功能磁共振研究

目的：应用血氧水平依赖功能磁共振成像（blood oxygenation level dependent functional magnetic resonance imag ing ,BOLD－ fM RI）技术观察先天性感音神经性聋患者静息态双侧大脑半球皮层功能活动。方法对23例行人工耳蜗植入术的双侧先天性感音性聋患者（实验组）和10例听力正常者（对照组）行静息态BOLD—fMRI检查,采用fMRI低频震荡振幅（ALFF）方法比较实验组和对照组双侧大脑皮层功能活动情况,并进行定量分析。结果实验组大脑皮层左侧颞下回、左侧梭状回、右侧扣带回及左侧中央后回静息态激活强度明显大于对照组相应皮层的激活强度（P＜0．01）。结论先天性感音性聋患者感觉系统相关皮层可能发生了功能重塑,其大脑皮层存在知觉补偿现象。     

Protective effects of Terminalia arjuna against Doxorubicin-induced cardiotoxicity

Terminalia arjuna has been marked as a potential cardioprotective agent since vedic period. The present study was aimed to investigate the effects of butanolic fraction of Terminalia arjuna bark (TA-05) on Doxorubicin (Dox)-induced cardiotoxicity. Male wistar rats were used as in vivo model for the study. TA-05 was administered orally to Wistar rats at different doses (0.42 mg/kg, 0.85 mg/kg, 1.7 mg/kg, 3.4 mg/kg and 6.8 mg/kg) for 6 days/week for 4 weeks. Thereafter, all the animals except saline and TA-05-treated controls were administered 20 mg/kg Dox intraperitonially. There was a significant decrease in myocardial superoxide dismutase (38.94%) and reduced glutathione (23.84%) in animals treated with Dox. Concurrently marked increase in serum creatine kinase-MB (CKMB) activity (48.11%) as well as increase in extent of lipid peroxidation (2.55-fold) was reported. Co-treatment of TA-05 and Dox resulted in an increase in the cardiac antioxidant enzymes, decrease in serum CKMB levels and reduction in lipid peroxidation as compared to Dox-treated animals. Electron microscopic studies in Dox-treated animals revealed mitochondrial swelling, Z-band disarray, focal dilatation of smooth endoplasmic reticulum (SER) and lipid inclusions, whereas the concurrent administration of TA-05 led to a lesser degree of Dox-induced histological alterations. These findings suggest that butanolic fraction of Terminalia arjuna bark has protective effects against Dox-induced cardiotoxicity and may have potential as a cardioprotective agent.     

Temporal effect of Guanxin No. 2 on cardiac function, blood viscosity and angiogenesis in rats after long-term occlusion of the left anterior descending coronary artery

AIM: Cardiac infarction is one of the main causes of death in both developing and developed countries over past decades. Currently available approaches for treating patients with this disease are not satisfactory. Traditional Chinese medicines have been increasingly paid attention to. The aim of this study was to characterize the dynamic protective effects of Guanxin No. 2 decoction (GX II) on cardiac dysfunction combined with the blood viscosity and myocardial hypertrophy parameters in myocardial infarction (MI) rats. METHODS: Male Sprague-Dawley rats (180-200 g) were randomly divided into three groups: sham-operated, coronary artery ligation (CAL), and CAL plus GX II (GX II, 10.0 g raw materials/kg/d, bid, p.o.). The experiment was carried out at 4 time points as the 3rd, 7th, 14th, and 28th day after ligation. RESULT: It was found that on the one hand, GX II could significantly improve the heart function, and remarkably decrease infarct size and inhibit ventricular remodeling. On the other hand, GX II showed some unique effects such as angiogenesis which was induced in the left ventricular tissue. This result was consistent with the finding of an augmented vascular endothelial growth factor (VEGF) expression in this area. CONCLUSIONS: The studies demonstrated that GX II exerted extensively beneficial cardioprotective effect on CAL rats, it might stimulate angiogenesis of ischemic region to compensate blood supply to the heart via upregulated VEGF expression.     

泛素蛋白酶体途径在高氧肺损伤发病机制中的研究进展

泛素蛋白酶体途径是生物中特异的蛋白质降解系统之一。它参与体内许多重要的生理过程,临床中许多疾病的发生都与该途径的激活有关。高氧将产生氧自由基,引起细胞损伤、凋亡、坏死,同时引起炎性介质产生、炎性细胞浸润,从而产生肺部炎性反应、组织损伤和异常修复发生。本文将探讨泛素蛋白酶体途径的组成、功能及其在高氧肺损伤发病机制的作用。     

养肺消积分期疗法治疗晚期非小细胞肺癌的疗效观察

目的 观察养肺消积分期疗法对晚期(Ⅲb-Ⅳ期)非小细胞肺癌患者的临床疗效及生存的影响.方法 采用队列研究,选取符合入组标准非小细胞肺癌患者156例,其中综合治疗组82例,单纯西医组74例,综合治疗组在西医规范化疗的基础上采用养肺消积分期疗法按阶段治疗,以中位无疾病进展时间(M-PFS)、中位生存期(MST)为主要观察指标,中医临床症状积分变化、肿瘤控制率(DCR)、不良反应等为次要观察指标.结果 综合治疗组第1年、第2年总生存率分别较单纯西医组提高了23.9%、14.6%(P<0.05);与单纯西医组比较,综合治疗组无疾病进展时间、中位生存期均提高了3个月(P<0.01);综合治疗组瘤体控制率比单纯西医组提高13.2%(P<0.05).结论 养肺消积分期疗法联合西医治疗能够提高晚期非小细胞肺癌患者的总生存期,延长中位无疾病进展时间、中位生存期;同时,可以改善患者中医临床症状积分,增加肿瘤控制率,不良反应小,具有增效减毒作用.     

Motor Mapping with Functional Magnetic Resonance Imaging: Comparison with Electrical Cortical Stimulation

The aim of the present study was to evaluate motor area mapping using functional magnetic resonance imaging (fMRI) compared with electrical cortical stimulation (ECS). Motor mapping with fMRI and ECS were retrospectively compared in seven patients with refractory epilepsy in which the primary motor (M1) areas were identified by fMRI and ECS mapping between 2012 and 2019. A right finger tapping task was used for fMRI motor mapping. Blood oxygen level-dependent activation was detected in the left precentral gyrus (PreCG)/postcentral gyrus (PostCG) along the “hand knob” of the central sulcus in all seven patients. Bilateral supplementary motor areas (SMAs) were also activated (n = 6), and the cerebellar hemisphere showed activation on the right side (n = 3) and bilateral side (n = 4). Furthermore, the premotor area (PM) and posterior parietal cortex (PPC) were also activated on the left side (n = 1) and bilateral sides (n = 2). The M1 and sensory area (S1) detected by ECS included fMRI-activated PreCG/PostCG areas with broader extent. This study showed that fMRI motor mapping was locationally well correlated to the activation of M1/S1 by ECS, but the spatial extent was not concordant. In addition, the involvement of SMA, PM/PPC, and the cerebellum in simple voluntary movement was also suggested. Combination analysis of fMRI and ECS motor mapping contributes to precise localization of M1/S1.