海南粗榧新碱衍生物HH07A经大鼠肝微粒体的代谢转化研究

用大鼠肝微粒体体外代谢法对HH07A进行了代谢转化研究。用HPLC结合二极管阵列检测器对体外代谢体系进行了分析,判断在体外代谢体系中HH07A有二个代谢产物,并用减压柱色谱、薄层色谱及高效液相色谱法分离制备了其中一个代谢物的纯品,经核磁共振、质谱、红外、紫外光谱确定了结构。     

Genetic variation in the IGSF6 gene and lack of association with inflammatory bowel disease.

The immunoglobulin superfamily 6 gene (IGSF6) on chromosome 16p11-p12 has been investigated as a positional and functional candidate for inflammatory bowel disease (IBD) susceptibility. Screening of the six exons of IGSF6 for single nucleotide polymorphisms (SNPs) detected four novel SNPs, and validated three of six SNPs listed in the international SNP database (dbSNP). The seven SNPs in IGSF6 formed five distinct linkage disequilibrium groups. There was no evidence for association of the common SNPs with disease in a large cohort of patients with IBD. The novel SNPs and the linkage disequilibrium map will be a useful resource for the analysis of IGSF6 in other immune disorders.     

(D-Phe12) bombesin and substance P analogues function as central bombesin receptor antagonists

The potency of synthetic bombesin (BN) analogues with D-Phe12 substitutions and substance P analogues was investigated in the rat CNS. (D-Phe12,Leu14)BN, (D-Phe12)BN and (Tyr4,D-Phe12)BN inhibited binding to rat brain slices with IC50 values of approximately 2 microM. Similarly, spantide inhibited binding to rat brain slices with an IC50 value of 1.5 microM. Spantide inhibited specific (125I-Tyr4)BN binding as a result of decreased rate of association, whereas the rate of dissociation was unaffected. Neither the (D-Phe12)BN analogues nor the substance P analogues inhibited specific binding of 125I-VIP to rat brain slices. Central administration of BN (0.5 micrograms) induced grooming and suppressed feeding and resting. (Tyr4, D-Phe12)BN (5 micrograms) antagonized the behavioral effects of BN. Although spantide (2 micrograms) also antagonized many of the BN effects, it had intrinsic effects and hence the behavioral antagonism was not specific. These data suggest that although both (D-Phe12)BN and substance P analogues may function as central BN receptor antagonists, the (D-Phe12)BN analogues may be functionally the more useful class of antagonists.     

Effects of outer hair cell loss on the frequency selectivity of the patas monkey auditory system

This report describes a study that took advantage of the unique reactivity of the patas monkey (Erythrocebus patas) to dihydrostreptomycin-sulfate (DHSM) to investigate the effects of selective outer hair cell (OHC) lesions on psychophysical tuning curves (PTC). Four patas monkeys were trained using operant reinforcement techniques to perform forward masking PTCs at frequencies of 500 Hz, 2, 4, and 8 kHz, at 10 dB SL. Steady and pulsed-tone thresholds were also measured from 63 Hz to 40 kHz in half-octave steps. The animals were given daily i.m. injections of DHSM at 20 mg/kg per day until shifts in absolute threshold at 16 kHz exceeded 10 dB, at which time the drug was discontinued. Initial changes in PTC shape included elevations in the tip region associated with the increase in threshold and no elevation or a hypersensitivity of the low-frequency tail region. In general, threshold and therefore PTC tip elevations of at least 40 dB were required before any increase in the low-frequency tail became evident. Following completion of psychophysical testing, animals were sacrificed and cytochochleograms were determined. At frequencies corresponding to regions of complete OHC loss and complete IHC retention a lack of selectivity was evident and PTCs closely resemble low-pass filters. This residual low-pass tuning is similar to that seen in VIIIth nerve fibers in ears devoid of OHCs and in basilar membrane transfer functions from traumatized ears. PTCs taken at frequencies corresponding to areas with no loss of receptors showed no systematic changes in sensitivity or selectivity. Because loss of normal OHC function results in greater than a 50-dB loss in sensitivity, as well as a detuned PTC, these findings strongly support the suggestion that the role of the OHC system is to increase the sensitivity and selectivity of the auditory system.     

Four-week arc radiotherapy for B2-Cprostate cancer: The need for prospective evaluation of short fractionation schemes

A retrospective review of 173 men with clinical stage B2-C prostate cancer treated by small-volume arc radiotherapy to 5200 cGy in 16 fractions over 4 weeks was undertaken. At 5 years, clinical local failure rates were 14% for stage B2 and 18% for stage C. Five-year survival rates were 81 and 61 %, respectively. No discernible differences were detected between a policy of encompassing the planning target volume by the 90% or 95% isodose. The limitations of this retrospective evidence and that of the literature are discussed. In the context of resource limitations affecting radiation oncology, prospective assessment of this technique is required to determine the true outcome.