Structure-activity relationships for inhibition of papain by peptide Michael acceptors.

Two series of peptidyl Michael acceptors, N-Ac-L-Phe-NHCH2CH = CH-E with different electron withdrawing groups (E = CO2CH3, 1a; SO2CH3, 1b; CO2H, 1c; CN, 1d; CONH2, 1e; and C6H4-p-NO2, 1f) and R-NHCH2CH = CHCOOCH3 with different recognition and binding groups (R = N-Ac-D-Phe, 2a; N-Ac-L-Leu, 3a; N-Ac-L-Met, 4a; PhCH2CH2CO, 5a; PhCO, 6a), were synthesized and evaluated as inactivators against papain. It was found that the inhibition of papain by peptidyl Michael acceptors is a general phenomenon and that the intrinsic chemical reactivity of the E group in the Michael acceptors has a direct effect on the kinetics of the inactivation process as reflected in k2/Ki. At pH 6.2, the reactivity of papain toward the Michael acceptors is about 283,000-fold higher than the reactivity of the model thiol 3-mercaptopropionate. This large increase in reactivity is attributable to at least 2 factors; one is the low apparent pKa of Cys-25 of papain, and the other is the recruitment of catalytic power by specific enzyme-substrate interactions. The unexpectedly high reactivity of 1c (E = COOH) was rationalized by proposing a direct interaction of the acid group with His-159 in the active site of papain. The unexpected inactivity of 1f (E = C6H4-p-NO2) as a Michael acceptor and its very powerful competitive inhibition of papain were rationalized by molecular graphics which showed the nitrophenyl moiety rotated out of conjugation with the olefin and interacting instead with the hydrophobic S1' region of papain. A plot of log (k2/Ki) for 1a-6a vs log (kcat/Km) for analogous R-Gly-p-NA substrates was linear (r = 0.98) with slope of 0.83, suggesting that binding energy from specific enzyme-ligand interactions can be used to drive the self-inactivation reaction to almost the same extent as it is used to drive catalysis.     

儿童阻塞性睡眠呼吸暂停低通气综合征的治疗

目的探讨儿童阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea hypopnea syndrome，OSAHS)患儿的治疗方法和疗效观察。方法经多道睡眠监测(polysomnography，PSG)确诊的4～12岁OSAHS患儿59例：扁桃体切除和(或)经口内镜(内窥镜，下同)引导下腺样体刮除54例；选择长期正压通气治疗(continue positive airway pressure，CPAP)2例；保守治疗3例。采用儿童OSAHS生活质量调查表(quality of life for children with obstructive sleep apnea 18 items，OSA-18)对患儿进行治疗前后的随访。结果围手术期无术后出血、急性呼吸道梗阻发生。随访12～18个月，手术患儿无鼻咽闭锁、咽鼓管功能障碍、腺样体残留等并发症；OSA-18调查评分显示：治疗后76．3％(45例)的患儿生活质量总体指标，88．1％(52例)的患儿睡眠呼吸障碍，67．8％(40例)的患儿身体症状得到显著改善。长期CPAP治疗的有效治疗压力在5．6～7．8cm H2O左右。3例保守治疗者略有改善。结论手术切除引起上气道阻塞的肥大的扁桃体和(或)腺样体是儿童OSAHS有效的治疗手段之一，纤维鼻咽镜检查、头颅侧位X线摄片有助于手术适应证的确定。经口内镜引导下腺样体刮除术具有直视下操作，视野清晰，切除彻底，可避免损伤周围重要结构的特点。     

前列腺癌去雄激素治疗不良反应的预防和处理

目的观察去雄激素治疗前列腺癌的不良反应,并探讨其预防和治疗。方法回顾性分析1998年7月-2006年1月112例去雄激素治疗晚期前列腺癌的临床资料。结果112例患者中,97例完成了不良反应的调查。随访3-36月,去雄激素治疗后潮热、性功能障碍、病理性骨折发生率分别为46％、75％、4％;患者潮热、精神疲乏、四肢乏力、纳差症状明显加重(P<0．05);性功能明显减退(P<0．05)。12例潮热症状严重者使用抗抑郁药博乐欣(25mg,tid)1-2周症状减轻。7例有骨转移性疼痛或严重骨质疏松患者,应用唑来膦酸4mg静脉滴注,每45d一次,骨痛症状缓解。结论去雄激素对前列腺癌患者生活质量有一定影响。博乐欣可减轻患者潮热症状,唑来膦酸可预防和治疗去雄激素相关的骨质疏松并发症。     

通瘀注射液盆腔给药法治疗外在型子宫内膜异位症的临床研究

目的　运用通瘀注射液在非直视下经输卵管盆腔给药对子宫内膜异位症 (EEMs)的治疗作用 ,探讨活血化瘀法对EEMs的作用机理及此给药法的优势。方法　将临床治疗的EEMs患者 60例随机分为治疗组 (通瘀注射液组 )和对照组 (丹那唑组 ) ,疗程各为 3个月。用药前后测定下列指标 :临床症状与体征、内分泌激素、血液流变学、癌抗原 12 5 (CA12 5)和子宫内膜抗体 (EMAb)的阳性率变化。结果　治疗组的临床症状与体征、血液粘滞度和红细胞压积、CA12 5和EMAb的阳性率均降低 ,卵泡刺激素 (FSH)、黄体生成素 (LH)、雌二醇 (E2 )和孕激素 (P)的含量均受到调节 ,与对照组相比 ,差异有显著性。而治疗组对内分泌的调节能力弱于对照组 ,但作用柔和、均衡。结论　通瘀注射液对EEMs的作用是通过清除月经时异位内膜的瘀血、水肿、改善微循环及组织供氧、调节免疫功能和内分泌紊乱而实现的 ,与丹那唑相比其副作用小、并以治本为主。盆腔给药法则可使药物直达病灶 ,见效快     

Odontoma: a clinicopathologic study of 81 cases.

BACKGROUND AND PURPOSE: Odontoma is the most common odontogenic tumor. It includes 2 types, the compound and complex odontomas. There has not been a series study of the clinical and histologic features of odontomas from Taiwan. This study evaluated the clinicopathologic features of odontoma in Taiwanese. METHODS: Cases of odontoma treated from 1998 to 2002 identified from medical records were included. The microscopic features, radiographic features, and clinical history of the patients were reviewed and analyzed. RESULTS: A total of 81 odontomas in 81 patients (36 males and 45 females) were included. There were 62 compound and 19 complex odontomas. The mean age of the patients was 18 years with the majority of odontomas occurring in the first (32%) and second decade (38%) of life. Odontomas had a marked predilection for the maxilla (70%) and for the anterior region of the jaw (83%), particularly for the anterior maxilla (62%). Sixty four (79%) of the 81 odontomas were associated with 80 impacted teeth, including 71 permanent teeth, 2 deciduous teeth, and 7 supernumerary teeth. Of the 71 impacted permanent teeth, the maxillary central incisor (27%) was most commonly affected, followed by the maxillary canine (26%) and mandibular canine (24%). Histologic examination revealed enamel matrix in 90%, dentin in 100%, cementum in 88%, pulp tissue in 96%, fibrous capsule in 93%, ghost cells in 83%, reduced enamel epithelium in 86%, and nests of odontogenic epithelium in 58% of odontomas. Dentigerous cyst was associated with 9% of odontomas. CONCLUSIONS: In this series, odontomas occurred most often in the first and second decade of life. Although complex odontomas are usually found in the posterior jaw, in this Taiwanese series they were most commonly found in the anterior maxilla. Odontoma is frequently associated with an impacted tooth and occasionally with a dentigerous cyst. No recurrence of odontomas was found after surgical excision with follow-up of 1 to 15 years.     

Changes in brain gene expression shared by scrapie and Alzheimer disease.

We have isolated two recombinant cDNAs whose corresponding RNAs have an increased abundance in scrapie-infected hamster brain. DNA sequence analysis has shown that these two recombinants represent the genes for sulfated glycoprotein 2 and transferrin. The abundance of sulfated glycoprotein 2 RNA is increased in hippocampus from patients with Alzheimer disease and Pick disease, whereas transferrin RNA is not strongly modulated in these conditions. Expression of two previously identified scrapie-modulated genes, encoding glial fibrillary acidic protein and metallothionein, is also increased in both of these neurodegenerative diseases.