Down-regulation of muscarinic receptors in the striatum of organophosphate-treated swine

Subacute (daily) administration of diisopropylfluorophosphate (DFP) to male swine (Yorkshire white) resulted in a 97% inhibition of cholinesterase and a decrease of [3H]quinuclidinyl benzilate [( 3H]QNB) binding sites in homogenates of striata by approximately 50% after 14 days. The maximal density of receptors (Bmax) decreased from 2.1 +/- 0.3 to 1.0 +/- 0.2 pmole/mg protein. There was no significant change in the dissociation constant (Kd) for [3H]QNB binding (control: 52.6 +/- 10.7 pM; 7-day: 57 +/- 2.8 pM). Carbachol displacement of [3H]QNB binding yielded data best fit by a two-binding site model. The dissociation constants were KiL = 115 +/- 62 microM (55 +/- 3%) and KiH = 1.8 +/- 0.7 microM (45 +/- 3%), respectively, for the low- and high-affinity states. Seven-Day treatment with DFP reduced the percentage of high-affinity receptors to 22 +/- 8.6%, but affected neither the low- nor the high-affinity Kd (100 +/- 20 and 2 +/- 0.6 microM). With the addition of Mg2+, striatal homogenates had low- and high-affinity receptors in the proportion of approximately 1 to 1. In the presence of Gpp(NH)p + Mg2+ the ratio of high- to low-affinity receptors was 3:1 in homogenates of control tissue (to 26 +/- 5%). This treatment had no effect on this ratio in homogenates of tissue from 7-day DFP-treated swine (3:1) since it was already 3:1. Pirenzepine displacement of [3H]QNB binding was best described by a two-binding site model, with Ki values of 38 +/- 14 and 201 +/- 78 nM, which represent 74 and 26% of the binding sites, respectively. The high affinity Kd value was unchanged following 7 days of DFP treatment (24 +/- 5 nM). There appears to be little change in the displacement curves for pirenzepine inhibition of [3H]QNB binding. This suggests that about 75% of the receptors are of the M1 subtype. Thus, subacute administration of DFP causes not only a decrease in the number of receptors, but also a change in the proportion of agonist affinity states which is related to the interaction of the guanine nucleotide binding protein and the muscarinic receptor.     

Efficacy of radical neck dissection for the control of cervical metastasis after radiotherapy for nasopharyngeal carcinoma

Fifty-one patients who had persistent or recurrent neck disease from nasopharyngeal carcinoma after radiotherapy underwent radical neck dissection. The follow-up period ranged from 0.5 to 9 years (median: 2 years). Multiple cervical lymph node involvement was present in 51% of the patients (26 of 51). Malignant cells were detected in 88% of the resected specimens (45 of 51). The clinical sign of fixation of lymph node is the only factor that affects the successful control of neck disease (p = 0.04). Extracapsular extension of the nodal disease was present, and 35% of the lymph nodes were adherent to surrounding structures at operation (18 of 51). There was one hospital mortality and the overall morbidity was minimal. The actuarial survival at 5 years was 38%, and the probability of control of neck disease was 66%. Radical neck dissection is effective in controlling post-irradiation cervical metastasis from nasopharyngeal carcinoma.     

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喘息是儿童时期常见的症状之一,支气管扩张药物在年幼儿童中使用的有效性是多年来颇有争议的一个临床问题。争论的焦点在于,以往认为婴儿支气管平滑肌发育不成熟,喘息时气道动态闭合度增高和相对显著的黏膜水肿使其对支气管扩张剂的反应较弱。而近年的研究显示,虽然婴幼儿对支气管扩张剂的治疗反应弱于年长儿童和成年人,但在婴儿时期气道就存在对支气管扩张剂的反应[1],合理使用支气管扩张剂有利于改善喘息儿童的临床症状。1临床常用的支气管扩张剂1.1β2肾上腺素受体激动剂选择性β2受体激动剂是强效支气管扩张剂,支气管扩张作用是氨茶碱的…     

101例尿毒症相关性肺水肿的特殊护理措施

目的 探讨尿毒症相关性肺水肿的特殊护理措施。方法 对尿毒症相关性肺水肿的护理除常规护理措施外，应做到以下几点特殊护理：①密切观察血压、血氧饱和度、近期尿量变化；②有效控制血压；③采取不同的透析方式适时适量透析超滤、加强透析中的护理；④改善全身营养状况，防止肺部感染；⑤牢记护理程序体位-吸氧-血管扩张药-血液透析；⑥严格控制入量。结果 101例病人中抢救成功84例，死亡13例，自动出院3例。结论 采取治疗和特殊护理对抢救尿毒症相关性肺水肿患者有较好效果。     

重组促红细胞生成素对腹膜透析患者心功能的影响

目的　了解基因重组人促红细胞生成素 (r HuEPO)对持续性非卧床腹膜透析 (CAPD)患者心室结构及功能的影响。方法　 32例CAPD伴高血压患者 ,其中 1 6例应用降压药物控制血压 ,同时应用r HuEPO纠正贫血 ,1 6例单用降压药物 ,随访 6个月。结果　两组治疗前后差值比较 ,治疗组的LVPWT、E/A与对照组比较有显著差异(P <0 .0 5 )。结论　长期纠正贫血和控制血压有利于透析患者左室结构及功能异常的逆转     

药物洗脱支架直接置入治疗A型和B_1型病变的临床观察

目的　评价直接置入药物洗脱支架 (CYPHERTM,codis)在A或B1 型病变的冠心病患者治疗中的安全性、可行性。方法　 6 2例接受CYPHERTM 支架直接置入的患者 (直接支架组 )和一般情况匹配的 5 1例球囊扩张后行冠脉支架术的患者 (常规支架组 ) ,比较两组的一般情况 ,冠脉造影及介入治疗即刻和临床随访结果。结果　直接支架组介入操作时间明显短于常规支架组 [(17.2± 8.6 )比 (2 6 .3± 7.1)min ,P <0 .0 1],直接支架组平均扩张压明显高于常规支架组 [(14± 3)比 (12± 1.9)atm ,P<0 .0 1],两组无一例发生介入治疗相关的严重心脏事件。随访期间两组严重心脏不良事件发生率无显著差异。结论　A或B1 型病变的冠心病患者CYPHERTM 支架直接置入术可缩短介入操作时间 ,即刻效果、并发症及中期临床随访与常规支架组差异无显著性意义     

82例创伤性脑膜炎患者的治疗及护理

目的 :为了提高创伤性脑膜炎的治愈率及护理满意度。方法 :对收治的 82例患者在治疗上应用足量有效的抗生素 ,及时处理原发伤 ,反复腰穿以控制感染。在护理上密切观察病情 ,保持气道通畅 ,加强头痛、高热及脑脊液耳、鼻漏的护理 ,保持创口清洁 ,注重健康宣教。结果 :77例治愈 ,5例死亡。结论 :早期诊断、有效处理原发伤及对症护理可促进创伤性脑膜炎的康复     

Vectorization of morpholino oligomers by the (R-Ahx-R)4 peptide allows efficient splicing correction in the absence of endosomolytic agents.

The efficient and non-toxic nuclear delivery of steric-block oligonucleotides (ON) is a prerequisite for therapeutic strategies involving splice correction or exon skipping. Cationic cell penetrating peptides (CPPs) have given rise to much interest for the intracellular delivery of biomolecules, but their efficiency in promoting cytoplasmic or nuclear delivery of oligonucleotides has been hampered by endocytic sequestration and subsequent degradation of most internalized material in endocytic compartments. In the present study, we compared the splice correction activity of three different CPPs conjugated to PMO(705), a steric-block ON targeted against the mutated splicing site of human beta-globin pre-mRNA in the HeLa pLuc705 splice correction model. In contrast to Tat48-60 (Tat) and oligoarginine (R(9)F(2)) PMO(705) conjugates, the 6-aminohexanoic-spaced oligoarginine (R-Ahx-R)(4)-PMO(705) conjugate was able to promote an efficient splice correction in the absence of endosomolytic agents. Our mechanistic investigations about its uptake mechanisms lead to the conclusion that these three vectors are internalized using the same endocytic route involving proteoglycans, but that the (R-Ahx-R)(4)-PMO(705) conjugate has the unique ability to escape from lysosomial fate and to access to the nuclear compartment. This vector, which has displays an extremely low cytotoxicity, the ability to function without chloroquine adjunction and in the presence of serum proteins. It thus offers a promising lead for the development of vectors able to enhance the delivery of therapeutic steric-block ON in clinically relevant models.