Copolymerization of ethylene oxide and propylene oxide by asymmetric catalysts

In order to determine whether asymmetric selection polymerization of alkylene oxide occurs by a polymer chain-end controlled mechanism or by a catalyst controlled mechanism, copolymerizations of ethylene oxide and propylene oxide are carried out in the presence of asymmetric catalyst. The results show that the stereoselective propagation is catalyst controlled.     

Effect of the admixture of tetracycline and nadifloxacin ointments on their stability and their antibacterial activity

Impetigo contagiosa staphylogenes is commonly treated by administering a combination of nadifloxacin and tetracycline ointments. However, it is not clear whether nadifloxacin and tetracycline are stable after mixing. The purpose of this study was to evaluate the stability of these agents in combination. We also evaluated changes in antibacterial activity after mixing. Mixing the two ointments caused tetracycline to change from yellow to brown in the admixture. Furthermore, the tetracycline content in the ointment decreased in a time-dependent manner, to about 40% at 288 h after mixing. In addition, the nadifloxacin content in the ointment did not change 288 h after mixing. In an alkaline environment (pH 9.0 and 11.0), the tetracycline content decreased and the color of tetracycline changed to brown. These results suggest that sodium hydroxide, which is an additive in nadifloxacin ointment, influences the content of tetracycline. We evaluated the chemical sensitivity of Staphylococcus aureus using disk tests. Nadifloxacin and tetracycline ointment showed the largest radius of inhibition circle, followed by the admixture 0 h after mixing and the admixture 72 h after mixing. These results suggest that the antibacterial activity is inhibited by the admixture. We propose that pharmacists should avoid mixing nadifloxacin with tetracycline ointment in the treatment of impetigo contagiosa staphylogenes and should take care to avoid interactions caused by additives in the ointments.     

Glutathione reductase activity in serum and liver tissue of human and rat with hepatic damage.

Glutathione reductase activity of both serum and liver tissue homogenates was measured in normal controls and in cases of hepatic parenchymatous diseases, and the results were compared with those from animal experiments in which hepatic damage was produced by CCl4 injection. Glutathione reductase showed a different attitude from those of transaminases and alkaline phosphatases under these clinical and experimental conditions. Glutathione reductase activity increased in both serum and liver in patients with hepatic damage, and this increase occurred earlier than the changes in alkaline phosphatase activity.     

Detection of matrix metalloproteinases in canine mammary tumours: analysis by immunohistochemistry and zymography

Expression of matrix metalloproteinases (MMPs) was examined immunohistochemically (MMP-9 and -2) and by gelatin zymography (MMP-9) in 12 benign and 12 malignant canine mammary tumours. In nine of 12 benign tumours, weak expression of MMP-9 was demonstrated immunohistochemically in the cytoplasm of neoplastic cells. In the remaining three benign tumours (mixed or complex) MMP-9 expression was observed in the neoplastic luminal epithelial cells and myoepithelial cells in some areas. The neoplastic luminal epithelial cells in 12 malignant tumours reacted strongly for MMP-9. MMP-2 immunolabelling was observed in both benign and malignant tumour tissues, but was stronger in the latter. Zymography and densitometry showed that expression of MMP-9 was higher in the benign mammary tumours than in normal canine mammary tissues, but highest in the malignant mammary tumours. In benign and malignant canine mammary tumours, the zymography and densitometry results for MMP-9 accorded well with the immunohistochemical results obtained with anti-human MMP-9 monoclonal antibody.     

Synthesis and evaluation of novel carbon-11 labeled oxopurine analogues for positron emission tomography imaging of translocator protein (18 kDa) in peripheral organs

To develop a PET ligand for imaging TSPO in peripheral organs, we designed three novel oxopurine analogues [(11)C]3a-c (LogD: 1.81-2.17) by introducing a pyridine ring in place of a benzene ring in the lead compound [(11)C]2 (LogD: 3.48). The desmethyl precursors 10 for radiosynthesis were synthesized by reacting glycine 7 with picolylamines 4, followed by hydrolysis and by Curtius rearrangement with diphenylphosphoryl azide. Methylation of 10a-c with methyl iodide produced unlabeled compounds 3a-c. The radiosynthesis of [(11)C]3a-c was performed by reacting 10a-c with [(11)C]methyl iodide. Compounds 3a-c displayed high or moderate in vitro binding affinities (K(i): 5-40 nM) for TSPO. PET with [(11)C]3a-c in rats showed high uptake in the lung, heart, and kidney, which are organs with high TSPO expression. Metabolite analysis with [(11)C]3a showed that radioactivity in these organs mainly corresponded with unchanged [(11)C]3a. PET with [(11)C]3a using a rat model of lung inflammation showed a significant signal in the lipopolysaccharide-treated lung.     

[11C]Gefitinib ([11C]Iressa): Radiosynthesis, In Vitro Uptake, and In Vivo Imaging of Intact Murine Fibrosarcoma

Objective

Gefitinib (N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(morpholin-4-yl)propoxy]quinazolin-4-amine, Iressa) is an approved anticancer drug. In this study, we labeled gefitinib with carbon-11 and evaluated [¹¹C]gefitinib to explore its specific binding in intact fibrosarcoma (NFSa)-bearing mice.

Methods

[¹¹C]Gefitinib was synthesized by the reaction of desmethyl precursor (1) with [¹¹C]CH₃I. In vitro uptake of [¹¹C]gefitinib into NFSa, human-A431 epidermoid carcinoma, and Jurkat T cells was determined. Positron emission tomography (PET) imaging using [¹¹C]gefitinib was performed for NFSa-bearing mice.

Results

[¹¹C]Gefitinib accumulated into NFSa cells with 2.1 uptake ratio (UR)/mg protein in cells. Addition of nonradioactive gefitinib decreased uptake in a concentration-dependent manner. [¹¹C]Gefitinib also had high uptake (2.6 UR/mg protein) into epidermal growth factor receptor/tyrosine kinase (EGFR/TK)-rich A431 cells but low uptake (0.2 UR/mg protein) into EGFR/TK-poor Jurkat cells. In vivo distribution study on NFSa-bearing mice by the dissection method revealed that [¹¹C]gefitinib specifically accumulated into the tumor. The ratio of radioactivity in tumors to that in blood and muscle as two comparative regions increased from 0.4 to 6.0 and from 0.6 to 5.0 during this experiment (0–60 min), respectively. PET for NFSa-bearing mice produced a clear tumor image, although high radioactivity was distributed throughout the body. Treatment with nonradioactive gefitinib (100 mg/kg) decreased uptake in the tumor. In vivo metabolite analysis demonstrated that [¹¹C]gefitinib was stable in the tumor, liver, kidney, and blood.

Conclusion

These results demonstrated the promising potential of [¹¹C]gefitinib to serve as a PET ligand for in vivo imaging of NFSa-bearing mice.     

Imaging of peripheral-type benzodiazepine receptor in tumor: in vitro binding and in vivo biodistribution of N-benzyl-N-[C]methyl-2-(7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide

IntroductionThe aim of this study was to evaluate N-benzyl-N-[¹¹C]methyl-2-(7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide ([¹¹C]DAC) as a novel peripheral-type benzodiazepine receptor (PBR) ligand for tumor imaging.Methods[¹¹C]DAC was synthesized by the reaction of a desmethyl precursor with [¹¹C]CH₃I. In vitro uptake of [¹¹C]DAC was examined in PBR-expressing C6 glioma and intact murine fibrosarcoma (NFSa) cells. In vivo distribution of [¹¹C]DAC was determined using NFSa-bearing mice and small-animal positron emission tomography (PET).Results[¹¹C]DAC showed specific binding to PBR in C6 glioma cells, a standard cell line with high PBR expression. Specific binding of [¹¹C]DAC was also confirmed in NFSa cells, a target tumor cell line in this study. Results of PET experiments using NFSa-bearing mice, showed that [¹¹C]DAC was taken up specifically into the tumor, and pretreatment with PK11195 abolished the uptake.Conclusions[¹¹C]DAC was taken up into PBR-expressing NFSa. [¹¹C]DAC is a promising PET ligand that can be used for imaging PBR in tumor-bearing mice.     

Prostate cancer in patients with Hansen''s disease

Hansen's disease causes testicular failure secondarily, and because of this, it has been considered that prostate cancer would not be found in association. Three of 14 patients with chronic leprosy in Suruga National Sanatorium Hansen's Disease Hospital were found to have prostate cancer. A 72-year-old with lepromatous leprosy was diagnosed with stage T3a prostate cancer and treated with radical prostatectomy after hormonal therapy, plus irradiation. An 80-year-old with lepromatous leprosy was diagnosed with stage T2 prostate cancer and treated with irradiation and follow up only without hormone therapy and surgery because of his low testosterone level and old age. An 82-year-old with borderline leprosy was diagnosed with stage T1c prostate cancer and because of the pathological finding of low Gleason score and his old age, he was treated with hormonal therapy only. Two of the three cases had elevated concentrations of follicle-stimulating hormone and luteinizing hormone, which suggests that their prostatic cancers might have been equivalent to be under the influence of hormone therapy. Therefore, in aged male patients with Hansen's disease, the follicle-stimulating hormone, luteinizing hormone and testosterone concentrations should be measured, as well as that of prostate-specific antigen, and a prostate biopsy should be also considered if the prostate-specific antigen concentration is increased, even with hypogonadism.     

Epidermoid cyst of the testis: a case of testis preservation]

A 19-year-old man complained of an asymptomatic right testicular mass. Physical examination revealed a firm, small-finger sized, mass lesion with a smooth surface in the right testis. The ultrasonographic appearance was hypoechoic and well-demarcated intratesticular lesion. All laboratory investigations, including tumor markers, were normal. The testis was explored through an inguinal incision. The mass was excised locally and the biopsy of the adjacent testicular tissue was done with gentle code clamping. The histological diagnosis was epidermoid cyst of the testis and the testicular tissue obtained was normal. About 90 cases of testicular epidermoid cyst have been reported in the Japanese literature, and are reviewed briefly here.