PHARMACEUTICAL NANOTECHNOLOGY: A Novel Composite Hydrogel Based on Chitosan and Inorganic Phosphate for Local Drug Delivery of Camptothecin Nanocolloids

In attempt to overcome the problem of low water solubility and severe toxicity of camptothecin (CPT) after intravenous administration, a novel drug carrier system based on chitosan (CS) and dibasic sodium phosphate (DSP) has been developed in this paper to encapsulate CPT intending for local administration. Nanocolloids of CPT with size about 500 nm were first prepared, followed by encapsulation in the chitosan/dibasic sodium phosphate (CS/DSP) formulation. The formulation was sol state below 37°C and transformed to nonflowing gel state at 37°C. Encapsulation of CPT nanocolloids had greatly effect on the gelling time as well as the micro-structure of hydrogel. In vitro and in vivo degradation studies revealed that the developed CS/DSP hydrogel was biodegradable and biocompatible. In vitro release study revealed that CPT released from CS/DSP hydrogel in an extended period with about 70% of total CPT released from hydrogel after 18 days. Furthermore, nearly 90% of CPT in the chitosan hydrogels could be preserved in the lactone form (active form) even after 7 days's storage at 37°C. Furthermore, in vitro cytotoxicity of CPT nanocolloids on SKOV3 human ovarian cancer cells suggested the well anti-tumor cell efficiency could be gained at a lower concentration.     

Klotho is a genetic risk factor for ischemic stroke caused by cardioembolism in Korean females

An aging-suppressor gene, klotho, is a candidate factor for vascular disease because its deficiency leads to impaired endothelium-dependent vasodilation and impaired angiogenesis. We investigated the association of polymorphisms in klotho with ischemic stroke. We searched for sequence variants in promoter and exons of klotho gene. For the association study, selected variants were genotyped in control subjects and in patients with ischemic stroke and vascular dementia. The association with ischemic stroke was further investigated with its subtypes classified based on Trial of Org 10172 in Acute Stroke Treatment (TOAST). No significant association was observed for both G-395A and C1818T with ischemic stroke and vascular dementia (P > 0.05). The analysis with subtypes of ischemic stroke revealed the associations that the A allele of G-395A increased the risk of cardioembolic stroke (CE, OR = 2.60; P = 0.006), and subjects carrying the A allele were susceptible to CE in both of dominant (AA + GA versus GG; OR = 2.50; P = 0.046) and recessive (AA versus GA + GG; OR = 6.52; P = 0.007) models. Further analysis of data partitioned by gender showed that the associations of G-395A with CE only existed in women (A versus G; OR = 4.33; P = 0.002), AA + GA versus GG; OR = 5.68; P = 0.014, and AA versus GA + GG; OR = 9.07; P = 0.012), but the significance disappeared in men (P > 0.05). The sequence variant of G-395A in klotho might be a genetic risk factor for CE in females.     

电化学治疗昆明小鼠肉瘤及其机理分析

研究了电化学治疗昆明小鼠肉瘤的疗效,并分析其机理。在体外将S-180细胞用不同参数的电场处理,研究适合电化学治疗的电场条件。通过复制肉瘤模型,将肉瘤小鼠随机分成4组:对照组、电疗组、化疗组、电化疗组。研究了不同处理组的肿瘤抑瘤率、治愈率以及小鼠的自由基代谢水平。结果电化疗组的抑瘤率、治愈率都显著高于化疗组和电疗组(P<0.05),电化疗组小鼠受到氧自由基的攻击显著降低,免疫力提高。分析机理发现,电化学治疗肿瘤的机理可能至少涉及细胞膜通透性提高、细胞的耐药性降低、机体的免疫力提高三个方面。     

CD44 antibody-targeted liposomal nanoparticles for molecular imaging and therapy of hepatocellular carcinoma

Most hepatocellular carcinoma (HCC) therapies fail to target cancer stem cells (CSCs) and monitor cancer progression or regression. The purpose of this study was to evaluate the possibility of cancer imaging and simultaneously monitoring targeted therapy in a single animal by anti-CD44 antibody-mediated liposomal nanoparticle. In this study, an in situ liver tumor model was applied for therapy by injecting 1.0 × 10(6) HepG2 cells carrying a reporter system encoding a double fusion (DF) reporter gene consisting of firefly luciferase (Fluc) and green fluorescent protein (GFP) into the liver of NOD/SCID mice. A strategy was developed which specifically targeted HCC via anti-CD44 antibody-mediated liposomal nanoparticle delivery, loaded of either doxorubicin (Dox) or a triple fusion (TF) gene containing the herpes simplex virus truncated thymidine kinase (HSV-ttk) and renilla luciferase (Rluc) and red fluorescent protein (RFP). The NOD/SCID mice were subsequently treated with ganciclovir (GCV) and the growth status of tumor was monitored by optical bioluminescence imaging (BLI) of Fluc and specific targeting of the liposomal nanoparticle was tracked by Rluc imaging. CD44 antibody-mediated liposomal nanoparticle, loaded of TF plasmids, were shown to be useful for monitoring and evaluating targeting efficacy and gene therapy by non-invasive molecular imaging. Here, we demonstrate the time intensive preclinical steps involved in molecular target identification, validation, and characterization by dual molecular imaging. This targeted and traceable therapeutic strategy has potential advantages to overcome the problems of conventional tumor therapy and may open a new application for the treatment of HCC by targeting CSCs.     

Cyclooxygenase-2 mRNA expression is associated with c-fos mRNA expression and transient water ADC reduction detected with diffusion MRI during acute focal ischemia in rats

Cyclooxygenase-2 (COX-2) plays an important role in the development of injury during cerebral ischemia and inhibition of its activity can reduce infarct size. COX-2 expression during acute ischemia is caused by activation of post-synaptic glutamate receptors, which occurs during spreading depression and ischemic depolarization. Both of these phenomena cause a reduction in the apparent diffusion coefficient of water (ADC), which can be detected with diffusion-weighted magnetic resonance imaging. The reduction is believed to be caused by cellular swelling that occurs as cells depolarize. The goal of this work was to determine the spatial relationship between cyclooxygenase-2 mRNA (cox-2) expression, c-fos mRNA expression and ADC reduction during acute focal cerebral ischemia. Adult rats were subjected to either 30- or 60-min permanent occlusion of the middle cerebral artery. A 2-Tesla scanner was used to acquire diffusion-weighted echo-planar images throughout the ischemic period, which were used to calculate ADC maps. Cox-2 and c-fos mRNA were detected with (35)S in situ hybridization. The results indicate that, for rats subjected to 60-min ischemia, cox-2 was observed in superficial layers of cortex, where transient ADC reduction and c-fos expression were observed. The same was true for most rats subjected to 30-min ischemia. However, in a small number of rats of the 30-min group, cox-2 mRNA expression was observed in regions exhibiting transient and persistent ADC reduction with no c-fos expression. The results suggest that cox-2 mRNA expression during acute MCA occlusion is caused by either or both spreading depression and transient ischemic depolarization.     

氟化物与ＤＮＡ结合作用的研究

本文应用紫外吸收光谱法、ＤＮＡ融点（Ｔm)测定法及高压液相ＬＣ－ＶＰ离子谱色分析法分别对氟化物与ＤＮＡ的结合作用进行了检测,从不同角度均证实氟化钠（ＮaF)与ＤＮＡ不能发生稳定结合,提示氟化物直接作用ＤＮＡ而造成遗传性损伤的可能性较小,但不能否认对ＤＮＡ聚合酶抑制作用而造成的损伤。     

库欣病经蝶手术复发的影响因素

目的探讨可能影响库欣病经蝶手术后复发的因素。方法回顾性分析了1992~2002年在我科接受经蝶手术治疗的182例库欣病患者的临床资料。结果接受经蝶手术后库欣病患者的复发率与术前MRI发现肿瘤与否(P=0·001)、肿瘤切除方式(P=0·001)、肿瘤病理类型(P=0·04)及术后激素下降水平(P=0·02)有关,而与肿瘤大小无关(P=0·43)。结论术前MRI发现肿瘤与否、肿瘤切除方式、肿瘤病理类型及术后激素下降水平是库欣病手术复发的影响因素。     

Sleep position and infant care practices in an urban community in Kuala Lumpur

Several modifiable risk factors for sudden infant death syndrome (SIDS) have been identified such as sleeping prone or on the side, sleeping on a soft surface, bed-sharing, no prenatal care and maternal ante-natal smoking. A cross-sectional survey of infant sleep and care practices was conducted among parents of babies aged below 8 months to determine the prevalence and predictors of non-supine sleep position and the prevalence of other high-risk infant care practices for SIDS. Of 263 infants, 24.7% were placed to sleep in the non-supine position and age of infants was a factor positively associated with this (adjusted odds ratio 1.275, 95% CI=1.085, 1.499). The most common modifiable risk factor was the presence of soft toys or bedding in the infants' bed or cot (89.4%). Results from this study indicate that although the predominant sleep position of Malaysian infants in this population is supine, the majority of infants were exposed to other care practices which have been shown to be associated with SIDS.