Protein macromonomers containing reduction-sensitive linkers for covalent immobilization and glutathione triggered release from dextran hydrogels

We report an efficient strategy to conjugate methacrylamide moieties to the lysine units of lysozyme for co-polymerization and subsequent triggered release from hydrogels. Two novel linker molecules, containing an ester bond and/or a disulfide bond for temporary immobilization, were synthesized and conjugated to lysozyme. Lysozyme was successfully modified with on average 2.5 linker molecules per protein molecule, as evidenced by MALDI-TOF and by titration of the free amine groups, while spectral analysis verified the preservation of the protein structure. Next, methacrylated dextran (Dex-MA) was polymerized in presence of native or modified lysozyme to yield hydrogels. The release of native and modified lysozyme from Dex-MA hydrogels was studied in acetate buffer (pH 5, in absence of any trigger) and only a minor fraction (~ 15%) of the modified lysozyme was released, whereas ~ 74% of the native lysozyme was released. This indicates successful immobilization of the majority of the modified lysozyme in the hydrogel network. Upon hydrolysis of the ester bonds or incubation with glutathione to reduce disulfide bonds of the linker molecules that conjugate the lysozyme to the gel network, the modified lysozyme was mobilized and released from the hydrogel to the same extent as native lysozyme. These data were confirmed by fluorescence recovery after photobleaching experiments. This approach appeared to be highly interesting for temporary immobilization and subsequent glutathione triggered intracellular delivery of proteins from hydrogels.     

Serum hepatitis B surface antigen correlates with fibrosis and necroinflammation: A multicentre perspective in China

The kinetics of serum hepatitis B surface antigen (HBsAg) during the natural history of hepatitis B virus (HBV) infection has been studied, but the factors affecting them remain unclear. We aimed to investigate the factors affecting HBsAg titres, using data from multicentre, large‐sized clinical trials in China. The baseline data of 1795 patients in 3 multicentre trials were studied, and the patients were classified into 3 groups: hepatitis B early antigen (HBeAg)‐positive chronic HBV infection (n = 588), HBeAg‐positive chronic hepatitis B (n = 596), and HBeAg‐negative chronic hepatitis B (n = 611). HBsAg titres in the different phases were compared, and multiple linear progression analyses were performed to investigate the implicated factors. HBsAg titres varied significantly in different phases (P = .000), with the highest (4.60 log10 IU/mL [10%‐90% confidence interval: 3.52 log10 IU/mL‐4.99 log10 IU/mL]) in patients with HBeAg‐positive chronic HBV infection. In all phases, age and HBV DNA were correlated with serum HBsAg level. In HBeAg‐positive chronic hepatitis B patients, a negative correlation between HBsAg titres and fibrosis stage was observed. Alanine amonitransferase or necroinflammatory activity was also correlated with HBsAg titres in HBeAg‐negative chronic hepatitis B patients. In conclusion, decreased HBsAg titres may be associated with advancing fibrosis in HBeAg‐positive chronic hepatitis B patients or increased necroinflammation in those with HBeAg‐negative chronic hepatitis B. Our findings may help clinicians better understand the kinetics of HBsAg and provide useful insights into the management of this disease.     

Pulmonary resection of colorectal metastases in patients with or without a history of hepatic metastases

Introduction

In selected patients with isolated colorectal lung or liver metastases resection can provide an increase in overall survival and even cure. Here, we evaluate whether also patients with combined or sequential metastatic disease to liver and lung may still be candidates for surgical resection.

Methods

From 1997 till 2006 39 patients underwent pulmonary metastasectomy. Two subgroups were identified: resection of pulmonary metastases only (PM) and resection of hepatic and later pulmonary metastases (LPM).

Results

Patient characteristics were identical in both groups. Median follow-up in group PM was 35 months and 38 months in group LPM. Two-year survival in group PM was 61%, and in group LPM 81% (p = NS). Five-year survival was 30% and 20% in PM and LPM groups, respectively (p = NS). The median disease free survival was 12 months in the PM group and 13 months in the LPM group.The extent of pulmonary resection had no impact on survival. Complications occurred in seven patients in the PM group and two patients in the LPM group. Complication rate and severity were related to the extent of pulmonary resection. A small group of patients underwent repeated pulmonary resection without serious complications.

Conclusion

Resection of pulmonary colorectal metastases may improve survival, even in patients who underwent hepatic resection for colorectal liver metastases at an earlier stage.     

Autopsy analysis in surgical patients: a basis for clinical audit.

An autopsy study was performed to quantify diagnostic fallibility in clinical surgery. Autopsy results in 312 surgical patients were compared with clinical findings. The primary clinical diagnosis was correct in 93 per cent of patients; complications had been correctly diagnosed in 60 per cent and error in treatment was found in 16 per cent. Error in treatment had an adverse impact on the course of disease in 11 per cent of patients. Infective complications such as abdominal sepsis and bronchopneumonia were encountered most often. Sensitivity was low for the clinical diagnosis of pulmonary embolism, bronchopneumonia, myocardial infarction and terminal haemorrhage. Statistical analysis showed that sudden unexpected death is the most obvious condition in which a high yield is expected from a post-mortem examination. Autopsy remains a valuable means of quality control in clinical surgery and could be a basis for surgical audit.     

乌拉尔甘草中新香豆素的化学研究

甘草是一味重要的传统中药,为临床广泛使用。多年来国内外学者对其化学成分的研究颇为重视。近来,用不同溶剂对甘草进行分步提取,以酶和受体生物学指标进行监测,发现乌拉尔甘草(Glycyrrhiza uralensis Fisch)的二氯甲烷提取物对安定受体,胆囊收缩素受体以及二氢还原酶具有明显的抑制作用。为了寻找其中的有效成分,我们对该部分进行了化     

Development after prenatal exposure to cocaine, heroin and methadone

In Amsterdam a longitudinal, prospective and multidisciplinary study on the development of infants of drug-dependent mothers (IDDM) was started in 1983: 35 IDDM and 35 reference infants were originally enrolled. The drug-dependent women had used combinations of methadone, heroin, cocaine and other drugs during pregnancy. Of the IDDM, 80% had to be treated pharmaceutically for neonatal abstinence symptoms (NAS). Physical, neurological, cognitive and the socio–emotional development of the children were studied regularly from birth until 5.5 years of age. Differences between the reference group and the IDDM were found most clearly in cognitive development. The IDDM also had more behavioural problems at some of the ages studied. No group differences were seen in motor development. So far the results of the study show that IDDM and their caregivers need extra support in order to improve early communication and the children's cognitive development.