Imaging of acute pancreatitis--the role of US, CT and MRI

Imaging of the pancreas with US and CT plays a major role in the diagnosis and evaluations of patients with acute pancreatitis. In severe acute pancreatitis, dynamic CT is essential to assess the severity of the disease and evaluate the complications. MRI is comparable to CT in its capacity to provide precise information about the severity of acute pancreatitis. MRI has some advantages over CT in being free from ionizing radiation and lower toxity of gadolinium which is used for contrast medium intravenously. The disadvantages of MRI, however, include cost, longer exam duration, limited availability and the practical difficulties of scanning a patient with ICU equipment.     

Lymph node metastasis of gastric cancer: comparison of Union International Contra Cancer and Japanese systems

BACKGROUND: The pN classification of gastric cancer (GC) in the Japanese system (Japanese Gastric Cancer Association; JGCA) is based on the site and distance of metastatic nodes from the primary tumour. Union International Contra Cancer (UICC) has recently proposed a classification system based on the number of nodes involved (TNM-1997). The aim of the present study is to assess which classification system is more suitable for providing a prognosis in advanced GC with lymph node metastasis. METHODS: A total of 224 patients who underwent curative gastrectomy (R0: UICC-TNM and Resection A and B: JGCA) and D2 lymphadenectomy between 1990 and 1999, and diagnosed as pT2, pT3 and pT4 GC were enrolled. Patients were followed until the end of 2002. The disease-free survival rates of patients were compared between the two-stage systems (UICC-TNM and JGCA). RESULTS: Using the JGCA system, there was a significant difference between the two survival curves (pN0 and pN1, P = 0.025; pN1 and pN2, P < 0.001; pN2 and pN3, P = 0.031), but the 5-year survival rate of 27 pN2 patients (32.7%) was not significantly different from that of 14 pN3 patients (34.3%, P = 0.994) using the UICC-TNM. In 47 patients with JGCA pN2, the 5-year survival rate of 18 patients with UICC-TNM pN1 (42.9%) was not significantly different from that of 18 patients with UICC-TNM pN2 (25.2%, P = 0.422) or from that of 11 patients with UICC-TNM pN3 (24.2%; P = 0.383). CONCLUSIONS: The JGCA system is more suitable for estimating the prognosis of Japanese patients with advanced GC than the UICC-TNM.     

Osteopontin is a negative regulator of proliferation and differentiation in MC3T3-E1 pre-osteoblastic cells

Osteopontin (OPN) is an important mediator of bone remodeling. However, the role of OPN in the process of bone formation is not fully understood. In previous studies, we have shown that MC3T3-E1 pre-osteoblastic cells at higher passage number exhibited weakened osteogenic capacity and elevated OPN mRNA expression. In this work, we investigated the role of OPN on proliferation and differentiation of low-passage MC3T3-E1 cells by studying stable cell lines overexpressing either OPN mRNA or its antisense RNA. Overexpression was verified by both Northern and Western blot analyses. Overexpression of OPN markedly inhibited proliferation as determined by daily cell counts, while overexpression of antisense RNA stimulated cellular proliferation. We also examined the effect of OPN level on BMP-2-induced alkaline phosphatase activity. Overexpression of OPN inhibited BMP-2 responsiveness while overexpression of antisense RNA enhanced the effect of BMP-2 on alkaline phosphatase activity. Increased OPN expression also caused decreases in expression of osteocalcin and bone sialoproteins while a reduction of OPN level caused the opposite. Furthermore, endogenous OPN expression in response to BMP-2 exhibited a biphasic pattern, that is, it was initially inhibited and then enhanced by the treatment of BMP-2, indicating that OPN might function as a negative feedback regulator for osteoblastic differentiation. Finally, overexpression of OPN inhibited mineral deposition. In contrast, overexpression of antisense RNA enhanced mineral deposition. These results indicate that OPN is a negative regulator of proliferation and differentiation in MC3T3-E1 cells.     

Reduction of allergic airway eosinophilia by dietary raffinose in Brown Norway rats

Oral administration of raffinose, a naturally occurring indigestible oligosaccharide, has reportedly ameliorated atopic dermatitis in human subjects although the mechanism is unknown. The present study investigated the effect of dietary raffinose on allergen-induced airway eosinophilia in ovalbumin-sensitised Brown Norway rats as an atopic disease model. Brown Norway rats were immunised by subcutaneous injection with ovalbumin on day 0 and fed either a control diet or the diet supplemented with raffinose (50 g/kg diet). The rats were exposed to aerosolised ovalbumin on day 20, and broncho-alveolar lavage fluid was obtained on the next day. The number of eosinophils in the fluid was significantly lower in the rats fed the raffinose diet than in those fed the control diet. Dietary raffinose significantly reduced IL-4 and IL-5 mRNA levels in lung tissue and tended to lower ovalbumin-specific Ig E levels. Suppression of eosinophilia by dietary raffinose was still observed in caecectomised and neomycin-administered rats, suggesting little contribution by the colonic bacteria to the effect of raffinose. Intraperitoneal administration of raffinose also suppressed eosinophilia. Significant concentrations of raffinose were detected in portal venous and abdominal arterial plasma after the intragastric administration of raffinose. Overall, the findings suggest that dietary raffinose ameliorates allergic airway eosinophilia at least partly via post-absorptive mechanisms in Brown Norway rats.     

Regulatory effects of macrolides on bacterial virulence: potential role as quorum-sensing inhibitors

Pseudomonas aeruginosa is an opportunistic pathogen, and this organism is a major cause of pulmonary damage and mortality in patients with cystic fibrosis (CF), diffuse panbronchiolitis (DPB) and other forms of bronchiectasis. A break-through in the treatment of DPB and associated chronic P. aeruginosa pulmonary infection was realized when a patient with DPB improved dramatically after treatment with erythromycin for years. Now, long-term macrolide therapy has become a first line of treatment in DPB patients, and the immunomodulatory properties have now been extended to other clinical settings, including CF. An important factor in the pathogenesis of chronic P. aeruginosa infection is a bacterial cell-to-cell signaling mechanism, referred to as "quorum sensing", which enables bacteria to coordinately turn on and off specific virulence genes through the production of autoinducer molecules. Interference or blocking of quorum-sensing systems has been considered an attractive therapeutic strategy. Clinical and basic science data suggests the potential of macrolides as relevant inhibitors of the Pseudomonas quorum-sensing system. In fact, certain macrolides strongly suppressed quorum-sensing associated genes and autoinducer production, in addition to inhibition of a variety of virulence factors. In this review, clinical efficacy of macrolides on DPB and CF patients will be briefly summarized. Additionally, the mechanisms of action of macrolides will be discussed from the standpoint of sub-MIC macrolide effects on P. aeruginosa, particularly the ability of this antibiotic to suppress quorum-sensing systems, which may be crucial in the pathogenesis of chronic P. aeruginosa infection.     

Liposomal surface-loading of water-soluble cationic iron(III) porphyrins as anticancer drugs

A novel design of anticancer drug delivery system, based on an electrostatic binding of negatively charged liposomes and cationic metalloporphyrins under physiological conditions, is reported. A lack of cytotoxicity of the iron(III) porphyrin-loaded liposomes and an efficient generation of a toxic hydroxyl radical (OH*) from a superoxide anion radical (O2-*) through the iron(III)-catalyzed dismutation and the Fenton-like reaction allow for a targeted necrosis of tumor cells where the concentration of O2-* is locally increased as a result of the reduced activity of superoxide dismutase and catalase in these cells.