Synthesis of 18F-FDG with FDG MicroLab system: basic studies for clinical application

We synthesized 18F-FDG by using an automated synthetic apparatus "FDG MicroLab" (GE Medical Systems) which produces 18F-FDG by a solid phase 18F-fluorination. Its quality and reproducibility were evaluated in order to assess feasibility of the apparatus for routine clinical production of 18F-FDG. For 5 consecutive 18F-FDG synthesis, target irradiation was carried out at 15 microA for 60 min. 18F-FDG was obtained in 50 min after EOB with an end-of-synthesis yield of 9.34 +/- 1.06 GBq. Radiochemical yield and radiochemical purity were 47 +/- 3% (decay corrected) and 98.0 +/- 0.5%, respectively. Other several quality control parameters tested conformed with "Standards of Compounds Labeled with Positron Nuclides" (RADIOISOTOPES, 44, 1995). Thus, the automated synthetic apparatus "FDG MicroLab" has proven to stably produce 18F-FDG with high yield and high purity. The apparatus is feasible for routine clinical production of 18F-FDG.     

Potential role of vacuolar H-adenosine triphosphatase in neointimal formation in cultured human saphenous vein

OBJECTIVE: Vacuolar H(+)-adenosine triphosphatase plays a pivotal role in pH regulation and molecular transport across the vacuolar membranes and is involved in cell proliferation and transformation. In the present study, possible involvement of vacuolar H(+)-adenosine triphosphatase in neointimal formation was investigated in an organ culture model of human saphenous vein. Methods and results: Cultured saphenous vein segments developed neointimal formation and marked thickening of the media within 14 days. Neointimal formation and medial thickening were completely inhibited by 10 nmol/L bafilomycin A(1), a selective inhibitor of vacuolar H(+)-adenosine triphosphatase, although structurally related macrolide antibiotics FK-506 and erythromycin were without an effect. The neointimal cells were positive for alpha-smooth muscle actin and vimentin but negative for desmin, indicative of myofibroblasts. The emergence of myofibroblasts was inhibited, and endothelial cells were preserved in the saphenous vein segments treated with bafilomycin A(1). Uptake of bromodeoxyuridine, a proliferation marker, by myofibroblasts was abrogated in the saphenous vein segments treated with 10 nmol/L bafilomycin A(1). Detection of apoptotic cells by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling concomitant with identification of desmin-expressing smooth muscle cells demonstrated that neointimal myofibroblasts, but not medial smooth muscle cells, that expressed desmin underwent apoptosis by treatment with bafilomycin A(1). CONCLUSIONS: These results suggest that vacuolar H(+)-adenosine triphosphatase may be involved in myofibroblast growth that contributes to neointimal formation and medial thickening in cultured human saphenous vein. Increased sensitivity of myofibroblasts, but not endothelial cells, and differentiated smooth muscle cells to bafilomycin A(1) may have potential therapeutic implications in the treatment for vein graft disease.     

Combination therapy with single incision laparoscopic surgery and double-balloon endoscopy for small intestinal bleeding: report of three cases

The clinical introduction of double-balloon endoscopy (DBE) has brought about a revolution in the diagnosis and the treatment of diseases of the small intestine. DBE allows not only direct observation of the entire small intestine, but also interventional therapies, tissue sampling and India ink marking (tattooing). Single incision laparoscopic surgery (SILS) was developed from conventional laparoscopic surgery to further reduce the degree of invasiveness. SILS requires only one umbilical incision, thus resulting in almost scarless surgery. This report presents three cases of small intestinal bleeding successfully treated by SILS following tattooing under DBE. The average operative time was 67 min and average blood loss was 5 ml. All patients immediately recovered without any complications. SILS, in conjunction with presurgical tattooing by DBE for small intestinal bleeding is considered to be an ideal approach in terms of minimal surgical trauma and aesthetics.     

Management of obscure gastrointestinal bleeding: Comparison of guidelines between Japan and other countries

Small-bowel bleeding accounts for the majority of obscure gastrointestinal bleeding, but it is caused by various types of small bowel disease, upper gastrointestinal disease, and colorectal disease. For the diagnosis, history taking and physical examination are required, leading to a determination of what diseases are involved. Next, cross-sectional imaging, such as computed tomography, should be carried out, followed by the latest enteroscopy such as small bowel capsule endoscopy and deep enteroscopy according to the severity of hemorrhage and patient condition. After a comprehensive diagnosis, medical, enteroscopic, or surgical treatment should be selected. This article reviews recent advances in the endoscopic diagnosis of obscure gastrointestinal bleeding and compares perspectives of the management of obscure gastrointestinal bleeding in Japan with that in other countries.     

Indigo naturalis is effective even in treatment-refractory patients with ulcerative colitis: a post hoc analysis from the INDIGO study

Background

We recently reported the efficacy of indigo naturalis (IN) in patients with active ulcerative colitis (UC) in a randomized controlled trial (INDIGO study). However, few studies have been conducted to investigate whether IN is effective even in treatment-refractory cases, such as in those with steroid dependency and anti-TNF refractoriness.

Methods

In the INDIGO study, 86 patients with active UC were randomly assigned to an IN group (0.5–2.0 g daily) or placebo group. The rate of clinical response (CR), mucosal healing (MH), and change in fecal calprotectin (FCP) levels was compared between refractory [patients with steroid-dependent disease, previous use of anti-TNF-α, and concomitant use of immunomodulators (IM)] and non-refractory patients. We also analyzed factors predicting CR and MH at week 8.

Results

The rates of CR of IN group were significantly higher than placebo group, even in patients with steroid-dependent disease (p < 0.001), previous use of anti-TNF-α (p = 0.002), and concomitant use of IM (p = 0.013). The rates of MH in IN group were significantly higher than in placebo group in patients with steroid-dependent disease (p = 0.009). In the IN group, median FCP levels, at week 8, were significantly lower than baseline in patients with steroid-dependent disease and patients with the previous use of anti-TNF-α (p < 0.001, respectively). Multivariate analysis indicated that the previous use of anti-TNF-α was not a predictive factor for CR and MH at week 8.

Conclusions

In a sub-analysis of data from a randomized placebo-controlled trial, we found that IN may be useful even in patients with steroid-dependent disease and patients with the previous use of anti-TNF-α.

     

The hypoglycemic effect of (7R*,9aS*)-7-phenyl-octahydroquinolizin-2-one in mice

(-)-Multiflorine (1), which was isolated from leguminous plants, produced a hypoglycemic effect when administered to mice with streptozotocin-induced diabetes. (-)-Multiflorine has an enaminone type conjugation on the A-ring, which is unusual in lupine alkaloids. Proceeding on the assumption that the A-B ring is responsible for the activity, several compounds bearing quinolizidin-2-one were synthesized and their hypoglycemic effects were examined. The hypoglycemic effect of (7R*,9aS*)-7-phenyl-octahydroquinolizin-2-one was approximately 4 times stronger than that of (-)-multiflorine measured by oral glucose tolerance test in normal mice. This result indicates that compounds possessing the quinolizidin-2-one ring system as the basic structure may be possible lead compounds for a new type of diabetes drug.     

Efficacy of STI571 for a patient with metastatic gastrointestinal stromal tumor

A 65-year-old man was referred to our hospital for evaluation of his huge abdominal tumor. He was diagnosed as having a gastrointestinal stromal tumor arising from the stomach. Seven months after surgery, multiple liver metastases and mesenteric dissemination occurred. He was medicated with STI571, which works by blocking proliferation of malignant cells with expression of c-kit. The tumors shrank and serum lactate dehydrogenase and alkaline phosphatase concentrations fell to below the normal limit three months later. STI571 was effective medicine for the metastatic gastrointestinal stromal tumor for six months in this case.