Aboriginal Taiwanese hepatitis B carriers have more favorable viral factors than Han Chinese carriers

Several viral factors are associated with disease progression in hepatitis B virus (HBV) carriers. Compared with Taiwanese Han Chinese, Taiwanese aborigines have a higher prevalence of chronic HBV infection and a higher standardized mortality rate of chronic liver diseases but a lower standardized mortality rate of hepatocellular carcinoma (HCC). The aim of this study was to investigate whether aboriginal Taiwanese HBV carriers have more favorable viral factors which reduce the risk for HCC than Han Chinese carriers. Blood samples from 3,488 HBV carriers (1,527 aborigines and 1,961 Han Chinese) were assayed for aminotransferases, hepatitis B e antigen (HBeAg), HBV DNA, and HBV genotype. Aboriginal HBV carriers had a lower HBeAg‐positive rate (5.3% vs. 10.2%, P < 0.0001) and a lower viral load of HBV DNA > 2,000 IU/ml (27.4% vs. 36.7%, P < 0.0001) but a higher rate of alcohol consumption (40.0% vs. 19.3%, P < 0.0001) than Han Chinese carriers. The prevalence of HBV genotype B in aboriginal carriers (92.7%) was significantly higher than that in Han Chinese carriers (72.7%) in all age groups (P < 0.05). In addition, patients with rare genotype D infections were clustered in a township in southern Taiwan. In conclusion, aboriginal Taiwanese HBV carriers have more favorable viral factors than Han Chinese carriers, which may be partly responsible for the lower standardized mortality rate of HCC in Taiwanese aborigines. J. Med. Virol. 83:1326–1331, 2011. © 2011 Wiley‐Liss, Inc.     

Encapsulation of a Fragrance via Miniemulsion Polymerization for Temperature‐Controlled Release

The encapsulation of the hydrophobic fragrance 1,2‐dimethyl‐1‐phenyl‐butyramide (DMPBA), a typical C9 amide, in poly(methyl methacrylate), polystyrene, or acrylic copolymer nanoparticles can easily be obtained using a one‐step miniemulsion process. It is shown that this hydrophobic compound directly influences the kinetics, the molecular weight, and the morphology of the nanocapsule formation. The release behavior can be tuned by the temperature in relation to the T_g of the polymer which makes these nanocapsules interesting candidates for temperature‐dependent delivery systems.

     

Hippocampal synapsin isoform levels are linked to spatial memory enhancement by SGS742

Synapsins are essential proteins for synaptic plasticity and there is no information available for their role in cognitive enhancement (CE) of spatial memory formation. It was therefore the aim of the study to link individual synapsin proteins and their isoforms to spatial memory formation enhanced by SGS742 in the mouse. Extracted hippocampal proteins from a cognitive study treating OF1 mice with the cognitive enhancer SGS742 and tested in the Morris water maze, were run on two‐dimensional gel electrophoresis. Subsequently, protein spots were unambiguously identified by qQ‐TOF mass spectrometry. Quantification of proteins from four groups (NaCl‐treated mice, SGS742‐treated mice, SGS742‐treated yoked controls, and NaCl‐treated yoked controls) was carried out according to an in‐gel stable isotope labeling method. A total of 17 protein spots representing synapsin isoforms were identified and quantified. Using quantification of individual synapsin isoforms showed that these can be clearly assigned to CE by the GABA_B antagonist SGS742. Quantitative determination of individual synapsin isoform showed an increase in SGS742‐treated mice (mean ± SD) of ratios between light and heavy stable isotope labeled synapsin protein (SGS742 vs. controls: 2.19 ± 0.41 for synapsin Ia, and 1.41 ± 0.81 for synapsin IIa). Synapsins Ib and IIb were not linked to CE. The NaCl‐treated controls and the use of yoked controls that were ruling out swimming‐ and stress‐mediated changes of synapsins, unequivocally allow to propose a role for synapsins Ia and IIa in the mechanism of CE of spatial memory formation. © 2009 Wiley‐Liss, Inc.     

Novel one-stop multidisciplinary follow-up clinic for BRCA1/2 carriers: patient satisfaction and decision making

Objective: To evaluate patient' satisfaction and cancer risk management decision making, following attendance at a novel multidisciplinary one‐stop follow‐up clinic (MDOSC) for BRCA1/2 carriers. Patients and Methods: 172 patients attended the MDOSC over a 2‐year period between 2006 and 2008. A total of 96 and 76 patients were seen in the first and second year, respectively. All patients who attended the MDOSC were sent a 17‐item Satisfaction Questionnaire (SQ) designed to examine their views about the MDOSC, using rating scales and open questions after the first year. Patients were asked to comment on the most helpful aspects of the MDOSC and on how the service might be improved. Changes were made based on this feedback. During the second year, all patients were given the SQ with three questions about cancer risk management decision making on the day of the MDOSC. Results: In total, 132 (77%) patients responded and overall satisfaction was high with a mean of 8.94 (range 1–10). BRCA1/2 carriers were pleased to see a range of health care professionals on the same day, who they viewed gave consistent information, considered every aspect of care and addressed psychosocial needs. Following improvements, based on patients' feedback, satisfaction significantly increased in year 2. Furthermore, the MDOSC also helped patients to move forward with their cancer risk management decisions. Conclusions: BRCA1/2 carriers were highly satisfied with the MDOSC, which met their needs and helped them to make informed decisions regarding their cancer risk management. Copyright © 2010 John Wiley & Sons, Ltd.     

Lipid nanocapsules: Ready-to-use nanovectors for the aerosol delivery of paclitaxel

Aerosol drug delivery permits the development of dose-intensification strategies in severe, malignant lung diseases. The aim of the study was to demonstrate that the encapsulation of paclitaxel in lipid nanocapsules (LNCs), a novel drug nanocarrier for lipophilic components, allows one to provide pulmonary drug delivery of paclitaxel by nebulisation, thereby allowing preclinical and clinical studies. LNC dispersions are made into aerosols with commercial nebulisers. The structure, drug payload and cytotoxicity of nebulised LNCs were compared to fresh LNCs. The results demonstrated that LNC dispersions could be made into aerosols by using mesh nebulisers without altering the LNC structure. Only eFlow^® rapid-produced aerosols are compatible with human use: the mean duration to nebulise 3 ml of LNC dispersion is less than 9 min, with an aerosol mass median aerodynamic diameter equal to 2.7 ± 0.1 μm and a fine-particle fraction (between 1.0 and 5.0 μm) of 81.5 ± 3.1%. No modifications of drug payload or cytotoxicity effects of paclitaxel-loaded LNC (PTX–LNC) were observed. In order to carry out preclinical studies, a scaled-up LNC formulation protocol was used. Chemical parameters, such as acidity and osmolarity, were optimised, and a storage procedure for PTX–LNC batches was set-up. Animal studies are now needed to determine the tolerance and therapeutic potential of LNC dispersion aerosols.     

In vivo acute toxicity of titanium dioxide nanoparticles to mice after intraperitioneal injection

Because of its excellent optical performance and electrical properties, TiO₂ has a wide range of applications in many fields. It is often considered to be physiologically inert to humans. However, some recent studies have reported that nano‐sized TiO₂ may generate potential harm to the environment and humans. In this paper the in vivo acute toxicity of nano‐sized TiO₂ particles to adult mice was investigated. Mice were injected with different dosages of nano‐sized TiO₂ (0, 324, 648, 972, 1296, 1944 or 2592 mg kg^–1). The effects of particles on serum biochemical levels were evaluated at various time points (24 h, 48 h, 7 days and 14 days). Tissues (spleen, heart, lung, kidney and liver) were collected for titanium content analysis and histopathological examination. Treated mice showed signs of acute toxicity such as passive behavior, loss of appetite, tremor and lethargy. Slightly elevated levels of the enzymes alanine aminotransferase and aspartate aminotransferase were found from the biochemical tests of serum whereas blood urea nitrogen was not significantly affected (P <0.05). The accumulation of TiO₂ was highest in spleen (P <0.05). TiO₂ was also deposited in liver, kidney and lung. Histopathological examinations showed that some TiO₂ particles had entered the spleen and caused the lesion of spleen. Thrombosis was found in the pulmonary vascular system, which could be induced by the blocking of blood vessels with TiO₂ particles. Moreover, hepatocellular necrosis and apoptosis, hepatic fibrosis, renal glomerulus swelling and interstitial pneumonia associated with alveolar septal thickening were also observed in high‐dose groups. Copyright © 2009 John Wiley & Sons, Ltd.     

聚乙二醇化壳聚糖制备、评价及其应用的研究进展

聚乙二醇（PEG）化壳聚糖是一类新型功能性聚合物,较未修饰的壳聚糖而言,PEG化壳聚糖在水溶液和有机溶剂中的溶解性均明显提高,同时聚合物的细胞毒性降低,生物相容性得以改善。本文将对PEG化壳聚糖的化学合成、理化性质、生物学特性以及在生物医药领域的应用作一综述。     

纳米SiO2粒子特性及其在无细胞体系中氧化能力的检测及意义

目的：检测纳米SiO₂粒子的特性及其在无细胞体系中的氧化能力,为医用纳米SiO₂粒子体内外毒性的预测提供依据。方法：用透射电镜观测2种纳米SiO₂粒子粒径、分散性、形状;用Zeta电位粒度分析仪检测纳米粒子在不同介质（纯水、生理盐水、10% Tween 80溶液、RPMI 1640培养液、含1%胎牛血清的RPMI 1640细胞培养液,超声30 s）溶液及不同时间（0、24、48和72 h）的粒径分布及团聚状态;用ＤDCFH-DA法Ｆ检测粒子在无细胞体系中自发产生自由基的能力。结果：电镜结果显示,2种纳米SiO₂粒子均呈球形,大小一致,分布均匀、分散性好,粒子平均粒径分别为（43.0±4.2）和（68.0±5.7）nm;在纯水、生理盐水、10% Tween 80溶液、RPMI 1640培养液及含1%胎牛血清的RPMI 1640细胞培养液中,Si-43 nm及Si-68 nm 粒子粒径变化很大,其中在生理盐水中的粒径最接近电镜结果,为74.0和96.7 nm。超声30 s后0、24、48和72 h时,Si-43 nm及Si-68 nm粒子粒径在生理盐水中不发生团聚;在含1%胎牛血清的RPMI 1640细胞培养液中发生团聚,形成相似大小的团聚体;在30~100 μg的质量范围内,2种粒子自发产生自由基的能力相似但很弱,相当于2.5 μmol•L^-1左右H₂O₂当量。结论：一定粒径的纳米SiO₂在细胞培养液中形成大粒径团聚体,粒子自身只有较弱的自发产生自由基的能力。     

Haemoglobin, oxygen carriers and perioperative organ perfusion

Under normal conditions, only 20-30% of the delivered oxygen is metabolised. In normovolaemic anaemia, the organism reacts with increases in cardiac output and oxygen extraction. Once these mechanisms are exceeded, allogeneic blood transfusions may be administered. However, such transfusions are associated with serious adverse effects and alternatives such as artificial oxygen carriers are being sought. The main groups of artificial oxygen carriers are extracellular haemoglobin solutions and perfluorocarbons. Preparations undergoing experimental and clinical assessment include Human Polymerized Haemoglobin (Polyheme), Polymerized Bovine Haemoglobin-based Oxygen Carrier (HBOC-201, Hemopure), Haemoglobin Raffimer (HemoLink), Diaspirin Cross-linked Haemoglobin (HemAssist), Human Recombinant Haemoglobin (rHb), Enzyme Cross-linked Poly-haemoglobin, Maleimide-activated Polyethylene-glycol Modified Haemoglobin (MP4, Hemospan), Zero-linked Haemoglobin (ZL-HbBv) and Recombinant Hybrid of Human-alpha-chains and Bovine-beta-chains and Perflubron (Oxygent). Research into some of these compounds has been discontinued, while others have advanced into clinical phase III trials, but none has achieved market approval for Europe, US or Canada so far.     

Selective attention deficits reflect increased genetic vulnerability to schizophrenia

BACKGROUND: Impairment in attention is prominent in schizophrenia and may be a valuable genetic indicator for vulnerability to this disease. AIMS: We set out to characterize the attention deficits that may be associated with genetic liability to schizophrenia. METHODS: We compared attention performance in 55 people with schizophrenia, 95 of their first-degree relatives, and 61 unrelated controls. We also segregated presumed obligate carriers of genetic risk (POCs, N=12) and compared their performance with that of controls. RESULTS: Although the relatives of people with schizophrenia did not significantly differ from the normal controls on the tasks of attention, their scores were significantly ordered such that patients>relatives>normal controls during tasks of sustained and selective attention as measured by the Jonckheere-Terpstra Test (p<.05). Additionally, POCs were significantly worse than normal controls during selective attention tasks such as the Stroop (p=.03) and Letter Cancellation Task (p=.04). CONCLUSIONS: Heterogeneity in the first-degree relatives may have diluted the attention deficits present in those who are at genetic risk for schizophrenia. On the other hand, our findings in the more homogeneous group of POCs suggest that selective attention may be an indicator of genetic liability for schizophrenia.