CT造影剂碘海醇注射液的制备及动物实验

本文报道了非离子型Ｘ－ＣＴ造影剂碘海醇注射液的制备及动物实验结果。磺海醇的最大吸收波长λ＿（ｍａｘ）为２４４ｎｍ。讨论了温度、浓度对磺海醇溶液粘度的影响：粘度随温度的升高而下降，呈负线型相关；粘度随浓度（Ｃ）升高而激剧升高，与浓度的四次方呈线性相关：Ｖ＿（３７℃）＝４７２．５８９［Ｃ］￣４＋１．１２１（ｒ＝０．９９７７）Ｖ＿（３０℃）＝６６３．８１３［Ｃ］￣４＋１．１５２（ｒ＝０．９９９６）Ｖ＿（２０℃）＝１０８２．９５３［Ｃ］￣４＋１．４３３（ｒ＝０．９９８２）使用该注射液进行狗的造影实验，获得了清晰的造影图像。     

Comparative genomic hybridization provides new insights into the molecular taxonomy of the Saccharomyces sensu stricto complex

The science of taxonomy is constantly improving as new techniques are developed. Current practice is to construct phylogenetic trees based on the analysis of the DNA sequence of single genes, or parts of single genes. However, this approach has recently been brought into question as several tree topologies may be produced for the same clade when the sequences for various different genes are used. The availability of complete genome sequences for several organisms has seen the adoption of microarray technology to construct molecular phylogenies of bacteria, based on all of the genes. Similar techniques have been used to reveal the relationships between different strains of the yeast Saccharomyces cerevisiae. We have exploited microarray technology to construct a molecular phylogeny for the Saccharomyces sensu stricto complex of yeast species, which is based on all of the protein-encoding genes revealed by the complete genome sequence of the paradigmatic species, S. cerevisiae. We also analyze different strains of S. cerevisiae itself, as well as the putative species S. boulardii. We show that in addition to the phylogeny produced, we can identify and analyze individual ORF traits and interpret the results to give a detailed explanation of evolutionary events underlying the phylogeny.     

FK317, a novel substituted dihydrobenzoxazine, exhibits potent antitumor activity against human tumor xenografts in nude mice.

The antitumor effects of FK317, a novel substituted dihydrobenzoxazine, were evaluated using human tumor xenografts (small cell lung cancer, non-small cell lung cancer, stomach cancer, colon cancer, pancreatic cancer, breast cancer, cervical cancer and ovarian cancer). Tumor growth-inhibitory effects and the effective dose-range of FK317 were much stronger and broader, respectively, than those of reference drugs such as mitomycin C, adriamycin, cisplatin, taxol and irinotecan. Furthermore, the body weight decrease and myelosuppression in FK317-treated mice were less than in the animals given any of the reference drugs. To explain this tumor selectivity, the distribution of FK317 was investigated after dosing tumor-bearing mice with the 14C-labelled compound. The concentration of FK317 in tumor tissues was relatively low, and long tumor retention was not observed. However, thin-layer chromatographic separation revealed that the radioactivity in the tumor resided mainly in strongly cytotoxic metabolites, while that in other tissues resided mainly in non-cytotoxic metabolites. These results suggest that FK317 shows strong antitumor activity without side effects, and one reason for this is its specific metabolite pattern. FK317 is now undergoing phase I clinical trials.     

Anti-cachectic effect of FK317, a novel anti-cancer agent, in colon26 and LX-1 models in mice.

The effects of FK317 (11-acetyl-8-carbamoyloxymethyl-4-formyl-6- methoxy-14-oxa-1,11-diazatetracyclo[7.4.1.0(2, 7). 0(10, 2] tetradeca-2,4,6-trien-9-yl acetate), a novel anti-cancer agent, on murine adenocarcinoma colon26- and human lung carcinoma LX-1-induced cachexia were investigated in mice. Mice bearing colon26 or LX-1 s.c. lost weight and became cachectic, associated with tumor growth. FK317 and mitomycin C (MMC) inhibited the growth of both tumors. FK317 ameliorated the weight loss induced by the presence of colon26 or LX-1, while MMC enhanced it. An attenuation of the reduction in the weights of epididymal fat, gastrocnemius muscle and carcass was observed in FK317-treated tumor-bearing mice in both cachexia models, but not in MMC-treated mice. The decreases in the circulating levels of triglyceride, glucose and non-esterified fatty acid, which were induced by the presence of colon26, was partially inhibited by treatment with FK317. Overall, this study revealed that FK317 is a potent anti-cancer drug with anti-cachectic activity, suggesting that FK317 has potential utility for the treatment of cancer.     

Cytotoxic Mechanisms of FK317, a New Class of Bioreductive Agent with Potent Antitumor Activity

FK317 is a member of a new class of bioreductive agents that exhibit strong cytotoxicity against various human cancer cells. The effect of FK317 was found to be stronger than that of mitomycin C (MMC), adriamycin (ADR) or cisplatin (CDDP). Alkaline elution analysis indicated that FK317 formed interstrand DNA-DNA and DNA-protein cross-links in cells. On the other hand, no DNA single-strand breaks were observed in the cells treated with FK317. In a cell-free system the deacetylated metabolites produced cross-linked DNA under reductive conditions, though FK317 itself did not form DNA-DNA cross-links. In order to elucidate the metabolic activation mechanisms, we established an FK317-resistant subline from human non-small cell lung cancer cells (Lu99) by stepwise and brief exposure (1 h) to FK317. The resistant subline (Lu99/317) showed cross-resistance to MMC and carboquone (CQ), but not to ADR or CDDP. DT-diaphorase, which is one of the activation enzymes of MMC and CQ, was deficient in Lu99/317 cells as determined by enzyme activity assay. However, the levels of NADPH:cytochrome P450 reductase, which is another activation enzyme for MMC and CQ, were comparable in resistant and parent cell lines. Treatment of the cells with dicumarol, an inhibitor of DT-diaphorase, reduced the cytotoxicity of FK317 to Lu99 cells, but not to Lu99/317 cells. These results indicate that deacetylation of FK317 is necessary for its reductive activation, and deacetylated FK317 is reduced by DT-diaphorase to form an active metabolite, which produces DNA-DNA interstrand and DNA-protein cross-links that lead to cell death.     

New method of neck surface electromyography for the evaluation of tongue‐lifting activity

Elevation of the posterior part of the tongue is important for normal deglutition and speech. The purpose of this study was to develop a new surface electromyography (EMG) method to non‐invasively and objectively evaluate activity in the muscles that control lifting movement in the posterior tongue. Neck surface EMG (N‐EMG) was recorded using differential surface electrodes placed on the neck, 1 cm posterior to the posterior border of the mylohyoid muscle on a line orthogonal to the lower border of the mandible. Experiment 1: Three healthy volunteers (three men, mean age 37·7 years) participated in an evaluation of detection method of the posterior tongue lifting up movement. EMG recordings from the masseter, temporalis and submental muscles and N‐EMG revealed that i) N‐EMG was not affected by masseter muscle EMG and ii) N‐EMG activity was not observed during simple jaw opening and tongue protrusion, revealing the functional difference between submental surface EMG and N‐EMG. Experiment 2: Seven healthy volunteers (six men and one woman, mean age 27·9 years) participated in a quantitative evaluation of muscle activity. Tongue‐lifting tasks were perfor‐med, exerting a prescribed force of 20, 50, 100 and 150 gf with visual feedback. For all subjects, a significant linear relationship was observed bet‐ween the tongue‐lifting force and N‐EMG activity (P < 0·01). These findings indicate that N‐EMG can be used to quantify the force of posterior tongue lifting and could be useful to evaluate the effect of tongue rehabilitation in future studies.     

Influence of Fermentation and Drying Materials on the Contamination of Cocoa Beans by Ochratoxin A

Ochratoxin A (OTA) is a mycotoxin produced mainly by species of Aspergillus and Penicillium. Contamination of food with OTA is a major consumer health hazard. In Côte d’Ivoire, preventing OTA contamination has been the subject of extensive study. The current study was conducted to evaluate the influence of fermentation and drying materials on the OTA content in cocoa. For each test, 7000 intact cocoa pods were collected, split open to remove the beans, fermented using 1 of 3 different materials, sun-dried on 1 of 3 different platform types and stored for 30 days. A total of 22 samples were collected at each stage of post-harvesting operations. The OTA content in the extracted samples was then quantified by high-performance liquid chromatography. OTA was detected in beans at all stages of post-harvesting operations at varying levels: pod-opening (0.025 ± 0.02 mg/kg), fermentation (0.275 ± 0.2 mg/kg), drying (0.569 ± 0.015 mg/kg), and storage (0.558 ± 0.04 mg/kg). No significant relationships between the detected OTA level and the materials used in the fermentation and drying of cocoa were observed.     

A novel automated detection system for swallowing sounds during eating and speech under everyday conditions

The wave analysis of swallowing sounds has been receiving attention because the recording process is easy and non‐invasive. However, up until now, an expert has been needed to visually examine the entire recorded wave to distinguish swallowing from other sounds. The purpose of this study was to establish a methodology to automatically distinguish the sound of swallowing from sound data recorded during a meal in the presence of everyday ambient sound. Seven healthy participants (mean age: 26·7 ± 1·3 years) participated in this study. A laryngeal microphone and a condenser microphone attached to the nostril were used for simultaneous recording. Recoding took place while participants were taking a meal and talking with a conversational partner. Participants were instructed to step on a foot pedal trigger switch when they swallowed, representing self‐enumeration of swallowing, and also to achieve six additional noise‐making tasks during the meal in a randomised manner. The automated analysis system correctly detected 342 out of the 352 self‐enumerated swallowing events (sensitivity: 97·2%) and 479 out of the 503 semblable wave periods of swallowing (specificity: 95·2%). In this study, the automated detection system for swallowing sounds using a nostril microphone was able to detect the swallowing event with high sensitivity and specificity even under the conditions of daily life, thus showing potential utility in the diagnosis or screening of dysphagic patients in future studies.