艺术嗓音歌声客观评价初探

目的探讨客观评价艺术嗓音歌声的方法。方法对48名声乐专业青年大学生录制专业训练歌声信号,提取歌声平均能量、频率误差、音域误差作为评价参数,使用神经网络方法和多元线性回归方法客观评价歌声质量,并与资深专业教师的主观评价进行比较。结果客观评价歌声质量的方法中,神经网络方法误差在4%之内,而线性回归方法误差在6%之内,前者较优。结论神经网络方法利用评价参数能正确客观评价歌声质量,有助于科学地指导选拔和训练艺术嗓音人才。     

Caffeic acid improves the bioavailability of l‐dopa in rabbit plasma

The impacts of caffeic acid (3,4‐dihydroxycinnamic acid, CA) on the pharmacokinetics of levodopa (L‐dopa) were studied in rabbits. A single dose of 5/1.25 mg·kg^?1 l ‐dopa/carbidopa was administered alone or was co‐administered with three different doses of caffeic acid (2.5, 5, and 10 mg·kg^?1), or a single dose of 5 mg·kg^?1 caffeic acid was administered alone via an intramuscular route to six rabbits each in a crossover treatment protocol. Plasma levels of l ‐dopa, 3‐O‐methyldopa (3‐OMD), caffeic acid, and ferulic acid were determined and subsequently used to calculate their pharmacokinetic parameters. The results indicated that caffeic acid administered at a dose of 10 mg·kg^?1 decreased about 22% of the peripheral formation of 3‐OMD and about 31% of the C_max of 3‐OMD. In addition, the metabolic ratios (MR, AUC of 3‐OMD/AUC of L‐dopa) decreased by about 22%. Results also indicated that caffeic acid significantly decreased the proportion of 3‐OMD (p < 0.05). In contrast, the parameters of neither caffeic acid nor ferulic acid were significantly affected by l ‐dopa/carbidopa. In conclusion, caffeic acid at a dose of 10 mg·kg^?1 can significantly affect the COMT metabolic pathway of L‐dopa. Copyright © 2009 John Wiley & Sons, Ltd.     

穿透性角膜移植治疗高危真菌性角膜溃疡36例:同期非对照随访

背景:单纯药物治疗高危真菌性角膜溃疡效果不佳,目前穿透性角膜移植已是挽救眼球和视力的主要手段.目的:观察穿透性角膜移植治疗高危真菌性角膜溃疡的随访结果.设计、时间及地点:回顾性病例分析,于2000-01/2005-01在青岛大学医学院附属医院眼科完成.对象:选择在青岛大学医学院附属医院行穿透性角膜移植的高危真菌性角膜溃疡患者36例(36眼),其中9例穿孔,前房积脓25例.术前合并白内障6例,合并青光眼3例.方法:移植前给予抗真菌联合抗细菌治疗,36例患者均在入院4 d内完成了穿透性角膜移植,术后局部和全身给予抗炎和抗真菌药物治疗,随访6～24个月.主要观察指标:观察移植后视力变化和真菌复发、植片排斥、继发性青光眼、并发性白内障等并发症的发生情况.结果:①36例患者中13例随访6～12个月,17例随访13～18个月,6例随访19～24个月.②35例患者(97%)成功地保存了眼球.34例(94%)患者视力有不同程度提高.③移植后4例患者(11%)真菌复发,其中3例药物治疗后治愈,1例摘除眼球:13例患者(36%)植片发生排斥,其中10例经抗排斥治疗植片转为透明,3例因药物治疗无效而行二次穿透性角膜移植术;3例患者(8%)植片发生溃疡,其中2例治愈,1例因合并角膜内皮功能失代偿而行再次穿透性角膜移植;5例患者(14%)继发青光眼,眼压均得到成功控制:4例患者(11%)发生并发性白内障,其中2例行白内障摘除.其余患者移植后随访期间眼部情况稳定,植片保持透明.最终随访时,32例患者(89%)角膜植片透明.结论:对于保守治疗无效的高危真菌性角膜溃疡患者,穿透性角膜移植是挽救眼球和视力的有效方法.     

Association of CYP2E1, GST and mEH genetic polymorphisms with urinary acrylamide metabolites in workers exposed to acrylamide

This study elucidates the association of acrylamide metabolites, N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA), N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-cysteine (GAMA2), and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-cysteine (GAMA3) in urine with genetic polymorphisms of the metabolic enzymes cytochrome P450 2E1 (CYP2E1), microsomal epoxide hydrolase (mEH) in exon 3 and exon 4, glutathione transferase theta (GSTT1) and mu (GSTM1), involved in the activation and detoxification of acrylamide (AA) in humans. Eighty-five workers were recruited, including 51 AA-exposed workers and 34 administrative staffs serve as controls. Personal air sampling was performed for the exposed workers. Each subject provided pre- and post-shift urine samples and blood samples. Urinary AAMA, GAMA2 and GAMA3 levels were simultaneously quantified using liquid chromatography-electronspray ionization/tandem mass spectrometry (LC-ESI-MS/MS). CYP2E1, mEH (in exon 3 and exon 4), GSTT1, and GSTM1 were analyzed using polymerase chain reaction (PCR). Our results reveal that AA personal exposures ranged from 4.37 × 10⁻³ to 113.61 μg/m³ with a mean at 15.36 μg/m³. The AAMA, GAMA2, and GAMA3 levels in the exposed group significantly exceeded those in controls. The GAMAs (the sum of GAMA2 and GAMA3)/AAMA ratios, potentially reflecting the proportion of AA metabolized to glycidamide (GA), varied from 0.003 to 0.456, and indicate high inter-individual variability in the metabolism of AA to GA in this study population. Multivariate regression analysis demonstrates that GSTM1 genotypes significantly modify the excretion of urinary AAMA and the GAMAs/AAMA ratio, exon 4 of mEH was significantly associated with the urinary GAMAs levels after adjustment for AA exposures. These results suggest that mEH and/or GSTM1 may be associated with the formation of urinary AAMA and GAMAs. Further study may be needed to shed light on the role of both enzymes in AA metabolism.     

Pharmacokinetic– pharmacodynamic analysis of the role of CYP2C19 genotypes in short-term rabeprazole-based triple therapy against Helicobacter pylori

AIMS

The aim was to explore the role of CYP2C19 polymorphism in short-term rabeprazole-based triple therapy against Helicobacter pylori infection.

METHODS

Patients with H. pylori infection were tested for CYP2C19 genotype as poor metabolizers (PMs) or extensive metabolizers (EMs, homozygous EM or heterozygous EM) and given rabeprazole for 7 days. Antibiotics (clarithromycin and amoxicillin) were given on days 1–4, days 4–7, or days 1–7. A direct link model with an effect compartment was used in the population pharmacokinetic–pharmacodynamic analysis. The status of H. pylori infection was evaluated.

RESULTS

Rabeprazole clearance was lower in CYP2C19 PMs than in EMs (with average values of 10.7 vs. 16.8 l h⁻¹ in PMs and EMs, respectively), resulting in higher plasma levels in the former group. The values of EC₅₀ and k_eo of gastrin response increased with multiple doses of rabeprazole. The k_eo values were lower in CYP2C19 PMs than in EMs on day 1 (0.012 vs. 0.017 × 10⁻⁴ l min⁻¹), and higher than in EMs on day 4 (0.804 vs. 0.169 × 10⁻⁴ l min⁻¹) of rabeprazole treatment. The predicted gastrin-time profile showed a higher response in CYP2C19 PMs than in EMs on days 4 and 7. Helicobacter pylori was eradicated in all CYP2C19 PMs except in one patient infected by a resistant strain. In contrast, in CYP2C19 EMs the eradication rates ranged from 58 to 85%.

CONCLUSIONS

CYP2C19 genotypes play a role in H. pylori eradication therapy. Rabeprazole-based short-term triple therapy may be applicable in CYP2C19 PMs for H. pylori eradication.     

羟基磷灰石／左旋聚乳酸对人骨髓有核细胞毒性的实验

目的：评价不同浓度羟基磷灰石／左旋聚乳酸与人体骨髓有核细胞复合体体外培养时的细胞毒性及生物相容性。 方法：实验于2003-03／05在南方医科大学珠江医院神经外科实验室完成。将自行制备的羟基磷灰石／左旋聚乳酸配制成不同浓度（4,2，1，0．5，0．1g／L）与来自临床志愿者骨髓的人体骨髓有核细胞进行复合体外培养，对照组单纯接种细胞。采用相差显微镜逐日观察细胞生长及与生物材料的附着情况。并采用四甲基偶氮唑盐微量酶反应比色法于不同培养时间（2，4，6，8d）测定细胞增值率（以酶联仪上570nm处测吸光度值表示），以反映羟基磷灰石／左旋聚乳酸复合材料对骨髓有核细胞的毒性作用。 结果：④对照组及不同浓度（4，2，1，0．5，0．1g／L）羟基磷灰石／左旋聚乳酸细胞培养溶液在培养2，4，6，8d时所测得光密度值均比较接近，差异无显著性（F=0．070-0．255，P=O．929-0．996）。②相差显微镜观察细胞增殖形态学变化见骨髓基质细胞与羟基磷灰石／左旋聚乳酸材料复合培养组早期可见培养板内细胞增多，少量细胞向材料移行贴附于材料周边，部分细胞直接贴附于材料表面，随复合培养时间延长，附着的细胞增多，无细胞衰老及异常分裂现象。 结论：从形态学观察羟基磷灰石／左旋聚乳酸对人体骨髓有核细胞增殖无明显影响，未见明显细胞毒性。     

A dose-dependent pharmacokinetic study on caffeic acid in rabbits after intravenous administration

The dose-dependent pharmacokinetics of caffeic acid (CA) were studied in rabbits. Three different doses (5, 10, and 25 mg kg⁻¹) were administered intravenously to six rabbits each. The concentration–time profiles for CA could be fitted by a two-compartment model for each dose. The results showed that total-body clearance and elimination rate constant from the central compartment (k₁₀) after a 5 mg kg⁻¹ dose were greater than those after the other two doses. Furthermore, the terminal elimination half-life (β half-life) and mean residence time (MRT) after a 5 mg kg⁻¹ dose were less than after the other doses. The AUC value increased linearly with dose within the range of 10–25 mg kg⁻¹. Most of the unchanged caffeic acid was excreted in the urine within 2 h. The percentage of unchanged caffeic acid excreted in the urine was 63·4, 60·0, and 55·4% after doses of 5, 10, and 25 mg kg⁻¹, respectively, which was not significantly different. However, significant differences in the renal clearances and renal excretion rate constants were observed with a 5 mg kg⁻¹ dose compared to the other doses. On the other hand, nonrenal clearances and nonrenal excretion rate constants showed no dose-related differences. The differences observed in total-body clearance, k₁₀, β half-life, and MRT between a 5 mg kg⁻¹ dose and the other doses can be explained on the basis of the differences in renal clearance and renal excretion rate constants. ©1997 John Wiley & Sons, Ltd.     

表面活性剂对蔗糖结晶MA、CV及CRI影响的研究

本文对制糖工业常用的几种表面活性剂在影响蔗糖结晶平均孔径(MA),变异系数(CV)及晶体规一性指数(CRI)方面作了系统的研究。参考国内外资料,我们自行设计按装了一套性能良好的实验室模拟煮糖装置,它充分满足试验要求。试验结果表明:在糖膏煮炼过程中,应该选用降粘和降表面张力作用强,受糖液性质影响小的非离子型表面活性剂,这不仅可降低废蜜纯度,缩短煮糖时间,而且可改善蔗糖晶体外形和均匀度,提高成品白砂糖的感观质量。