Galactosylated chitosan-graft-polyethylenimine as a gene carrier for hepatocyte targeting

Chitosans have been proposed as alternative, biocompatible cationic polymers for nonviral gene delivery. However, the low transfection efficiency and low specificity of chitosan need to be addressed before clinical application. We prepared galactosylated chitosan-graft-polyethylenimine (GC-g-PEI) copolymer by an imine reaction between periodate-oxidized GC and low-molecular-weight PEI. The molecular weight and composition were characterized using gel permeation chromatography column with multi-angle laser scattering and (1)H nuclear magnetic resonance, respectively. The copolymer was complexed with plasmid DNA in various copolymer/DNA (N/P) charge ratios, and the complexes were characterized. GC-g-PEI showed good DNA-binding ability and superior protection of DNA from nuclease attack and had low cytotoxicity compared to PEI 25K. GC-g-PEI/DNA complexes showed higher transfection efficiency than PEI 25K in both HepG2 and HeLa cell lines. Transfection efficiency into HepG2, which has asialoglycoprotein receptors, was higher than that into HeLa, which does not. GC-g-PEI/DNA complexes also transfected liver cells in vivo after intraperitoneal (i.p.) administration more effectively than PEI 25K. These results suggest that GC-g-PEI can be used in gene therapy to improve transfection efficiency and hepatocyte specificity in vitro and in vivo.     

Hepatocellular carcinoma presenting with bone metastasis: clinical characteristics and prognostic factors

Purpose  The survival of patients with hepatocellular carcinoma (HCC) has been prolonged with improvements in various diagnostic tools and treatment modalities. Consequently, bone metastases from HCC are diagnosed more frequently. We investigated the clinical features, prognosis, treatment outcomes, and prognostic factors of HCC presenting with bone metastasis. Methods  Between June 2000 and April 2007, we recruited 37 consecutive HCC patients presenting with bone metastasis. These patients were divided into an untreated control group (n = 16) and a treated group (n = 21). Results  The mean age of the patients was 61.1 years (male:female, 31:6). The most common cause of HCC was hepatitis B virus infection (56.8%). Twenty-two patients (59.5%) were of Child-Pugh class A and 15 (40.5%) were of Child-Pugh class B. Spinal metastasis was most common and noted in 21 patients (56.7%). The treatment modalities in the treated group included intra-arterial chemotherapy in nine patients (42.8%), systemic chemotherapy in five (23.8%), and both intra-arterial and systemic chemotherapy in seven (33.4%). The median survival of all patients was 6.2 months (range 0.7–46.6); that of untreated control group and the treated group was 2.9 (range 0.7–42.2) and 9.7 (range 0.9–46.6) months, respectively, with no significant difference (log-rank test, P = 0.081). Cox regression analysis revealed that the presence of ascites at the initial presentation was the only prognostic factor (P = 0.016). Conclusion  Although our study showed that locoregional and/or systemic chemotherapy did not provide significant survival prolongation compared to supportive care in patients with HCC initially accompanied by bone metastasis, a more large-scaled randomized study might be required. S. U. Kim and D. Y. Kim have equally contributed to this work.     

Long-term outcomes of minor dissection at the edge of stents detected with intravascular ultrasound

We evaluated the influences of minor edge dissections on late angiographic in-stent restenosis in 327 patients with 348 lesions (281 lesions without edge dissection and 67 lesions [19.3%] with edge dissection); the angiographic restenosis rate was 29.9% in the lesions with edge dissections versus 25.3% without edge dissections (p = 0.540). The minor non-flow-limiting dissections at the edge of stents may not be associated with the development of late angiographic in-stent restenosis.     

Right-sided myxomas with extramedullary hematopoiesis and ossification in Carney complex

The authors report the case of multiple right-sided myxomas in a 42-year-old man with Carney complex. He had previously been diagnosed as Cushing's syndrome and undergone resection of pituitary adenoma at the age of 21. After 10 years, bilateral adrenalectomy had been performed with recurrence of Cushing's syndrome. Recently, he complained of palpitation and intracardiac masses were detected. On physical examination, he had nevi on the lips and in the oral cavity. A tiny eyelid nodule was noted and histopathological analysis confirmed the diagnosis of skin myxoma. Thyroid ultrasonography revealed multiple hypoechoic nodules, which were confirmed pathologically as follicular adenomas. Scrotal ultrasonography also revealed small multiple testicular tumors. Echocardiography demonstrated intracardiac masses in right atrium and right ventricle. Right atriotomy revealed a right atrial mass attached to the annulus of the tricuspid valve and another mass arising from the interatrial septum. In right ventricle, a polypoid mass arose from the anterior leaflet of the tricuspid valve. Also, there were multiple tiny to small masses on the interatrial septum. The masses were completely excised and the tricuspid valve was repaired with annuloplasty. Histopathological analysis confirmed myxomas with foci of extramedullary hematopoiesis and ossification.     

A case of spontaneous biloma complicated with choledocholithiasis and chronic cholecystitis]

A biloma is an encapsulated bile collection outside the biliary tree. Most cases of biloma are caused by iatrogenic injury or trauma. Intrahepatic rupture of the biliary tree due to nontraumatic cause is a rare event. A 68- year-old man was admitted because of abdominal pain and fever. He had no past history of abdominal surgery, instrumentation or trauma. Computed tomography (CT) scan and magnetic resonance cholangiopancreatography (MRCP) demonstrated a large subcapsular fluid collection in the right liver associated with choledocholithiasis and cholecystitis. Biloma was confirmed by sono-guided percutaneous needle aspiration and was drained through a pigtail catheter. After the successful treatment by percutaneous drainage and endoscopic sphincterotomy, the patient recovered. Here, we report an uncommon case of spontaneous biloma formation in association with choledocholithiasis with a review of literatures.     

Butyl paraben-induced changes in DNA methylation in rat epididymal spermatozoa

Parabens have been shown to affect male rodent reproductive parameters, including testosterone levels and sperm production. In this study, we examined the effect of long-term exposure to butyl paraben (BP) on rat epididymal sperm DNA methylation. Adult male rats were exposed to BP (0, 10, 100 and 1000 mg kg(-1) per day) according to OECD TG407 for a repeated 28-day oral toxicity study. Sperm DNA methylation was examined by differential display random amplification of polymorphic DNA (RAPD) following methylation-specific restriction digestion of DNA. Among the 57 RAPD amplicons, six were methylation specific. Of these, five amplicons increased by 1.4- to 3.8-fold in epididymal sperm DNA at testing dose of BP. This indicates that BP can cause DNA hypermethylation in germ cells from the mitotic through post-meiotic stage in adult rat testes. To our knowledge, this is the first report on the epigenetic modification of sperm DNA by parabens.     

假细锥香茶菜新二萜成分——假细锥甲素的结构

从假细锥香茶菜(Rabdosia coetsoides C.Y.Wu)叶分离得到新二萜成分,根据紫外光谱、红外光谱、质谱、核磁共振氢谱及碳谱等分析,推定了化学结构,并经X-射线衍射确证,命名为假细锥甲素。     

间硝苯地平对血管紧张素Ⅱ促进血管平滑肌细胞增殖和蛋白质合成的影响

以培养血管平滑肌细胞（ｖａｓｃｕｌａｒｓｍｃｏｔｈｍｕｓｃｌｅｃｅｌｌ，ＶＳＭＣ）为模型，观察了间硝苯地平（ｍ－ｎｉｆｅｄｉｐｉｎｅ，ｍ－Ｎｉｆ）对血管紧张素Ⅱ（ａｎｇｉｏｔｅｎｓｉｎⅡ，ＡＮＧⅡ）促进ＶＳＭＣ增殖和蛋白质合成的影响。结果表明，ｍ－Ｎｉｆ抑制ＡＮＧⅡ（１００ｎｍｏｌ·Ｌ￣（－１））引起ＶＳＭＣ［￣３Ｈ］ｔｈｙｍｉｄｉｎｅ和［￣３Ｈ］ｌｅｕｃｉｎｅ参入，并呈剂量依赖性。ｍ－Ｎｉｆ（２×１０￣（－６）ｍｏｌ·Ｌ￣（－１））可抑制ＡＮＧⅡ对ＶＳＭＣ的刺激、ＤＮＡ及蛋白质合成速率，分别降低了４６％，５８％，５３％。提示ｍ－Ｎｉｆ可抑制ＡＮＧⅡ对ＶＳＭＣ增殖和蛋白合成的促进作用