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101.
CVLM咪唑啉-I和α_2-肾上腺素受体共同参与可乐定的降压效应 总被引:4,自引:1,他引:4
目的 探讨大鼠尾端延髓腹外侧区 (CVLM)咪唑啉 I受体 (I1R)和α2 肾上腺素受体 (α2 AR)在介导可乐定中枢降压机制中的作用。方法 在氨基甲酸乙酯麻醉SD大鼠中 ,观察CVLM内局部给予I1R和α2 AR阻断剂后对基础血压(BP)、心率 (HR)以及外周给予可乐定导致降压效应的变化。结果 双侧CVLM分别微量注射选择性α2 AR阻断剂育亨宾 (单侧剂量 5 0 0 pmol·L-1,10 0nl,n =8)或I1R和α2 AR混合性阻断剂idazoxan(单侧剂量 2nmol·L-1,10 0nl,n =10 )后不仅明显降低BP和HR(P <0 0 1) ,而且能明显减弱静脉给予可乐定 (5 μg·kg-1)导致的降压效应 (P <0 0 1) ,此外 ,idazoxan对可乐定降压效应的减弱作用高于育亨宾 (P <0 0 1)。结论 CVLM内I1R和α2 AR共同参与维持紧张性心血管活动和介导可乐定的降压效应 相似文献
102.
拓扑替康在临床应用的研究进展 总被引:4,自引:0,他引:4
拓扑替康 (topotecan ,TPT)是新的喜树碱衍生物。TPT是DNA拓扑异构酶Ⅰ抑制剂。 1996年FDA批准治疗小细胞肺癌 (SCLC)和卵巢癌(OVC)。临床试验表明 ,TPT与顺铂和紫杉醇无交叉耐药性。TPT单药治疗SCLC的效果与目前的一线治疗方案相当。TPT单药治疗OVC的效果相同或好于紫杉醇 ,TPT单药或结合治疗作为一线药物 ,治疗SCLC和OVC进行了很多研究并得到肯定的结果。TPT是少有的能进入血脑屏障的药物之一 ,口服TPT与静脉注射效果相同 ,但有低的骨髓抑制毒性。TPT单药或结合治疗也对白血病、非何杰金病、骨髓异常增生症、选择性胰腺癌有效 相似文献
103.
腺苷对模拟缺血再灌注豚鼠心室肌细胞动作电位的影响及其离子机制 总被引:3,自引:3,他引:3
目的 研究腺苷 (Ado)在模拟缺血缺氧时对豚鼠心室肌细胞动作电位 (AP)、L 型钙电流 (ICa.L)和ATP敏感性钾电流 (IK .ATP)的影响。方法 在离体豚鼠心室肌和酶解法分离的单个豚鼠心室肌细胞上 ,分别应用细胞内微电极和全细胞膜片钳技术记录动作电位和电流。结果 在模拟缺血缺氧状态下 ,Ado剂量依赖性的增大动作电位时程 (APD)的缩短 (P <0 0 5 ) ;抑制再灌注后APD恢复 ,而表现出迟后恢复。在缺血缺氧状态下 ,ICa.L受到抑制 ,Ado并不加重心肌细胞缺血缺氧时ICa.L的减小 ,而再灌注后ICa .L的恢复比较缓慢 ,但同对照组比较无差异。Ado可加速缺血缺氧时IK .ATP的激活 ,Ado(10 0 μmol·L-1)组在缺血缺氧时和再灌注后IK .ATP较对照组均明显增大。结论 在缺血缺氧状态下 ,Ado可增大APD的缩短 ,抑制再灌注后APD的恢复 ,其机制主要在于在缺血缺氧状态下Ado增大了IK .ATP。 相似文献
104.
升麻地上部分化学成分研究升麻地上部分化学成分研究 总被引:3,自引:0,他引:3
目的 为开发中药升麻(Cimicifuga foetida L.)的地上部分资源,从中寻找新的天然活性成分。方法 利用多种色谱技术进行分离纯化,根据理化性质和现代波谱技术并辅以化学方法进行结构鉴定。结果 从升麻地上部分80%乙醇提取物的乙酸乙酯部分分得5个9,19-环菠萝蜜烷型三萜皂苷和1个甾醇苷。分别鉴定为:西麻苷I(1),西麻苷II(2),升麻醇半乳糖苷(3),12β-羟基升麻醇木糖苷(4),12β-羟基升麻醇阿拉伯糖苷(5),胡萝卜苷(6)。结论 1和2为新化合物,4及5为首次从该植物中分得。 相似文献
105.
《Journal of labelled compounds & radiopharmaceuticals》2003,46(6):499-510
Arg34Lys26(Nε‐(γ‐L ‐glutamyl(Nα‐palmitoyl)))‐GLP‐1(7‐37) (NN2211) is currently in development as a diabetes type 2 drug. The fatty acid attached to the GLP‐1(7‐37) ensures a long and controlled duration of action. The synthesis of [125I]NN2211, [127I]NN2211 and [14C]NN2211 used for preclinical ADME studies are described. NN2211 was iodinated using the lactoperoxidase/hydrogen peroxide method, and [14C]NN2211 was synthesized in 4 steps by two routes both starting from an α‐protected [U‐14C]glutamic acid. Copyright © 2003 John Wiley & Sons, Ltd. 相似文献
106.
Abstract: New analogues of deltorphin I (DT I), in which the Phe residue in position 3, and the Val residue in position 5 or 6 are replaced with respective amphiphilic α‐hydroxymethylamino acid residues (HmAA), were synthesized and tested for receptor affinity and selectivity to μ and δ opioid receptors. The analogue with (R)‐HmPhe at position 3 lost receptor selectivity, as a result of a partial decrease of affinity to δ and a significant increase of affinity to μ receptors. In contrast, an analogue with (S)‐HmPhe in the same position, was very potent and more specific to δ receptors than parent DT I. The analogue with (R)‐HmVal at position 5 expressed higher δ affinity and selectivity than parent DT I. The analogue with other possible isomer (S)‐HmVal was less selective for δ opioid receptors, as a result of decreasing affinity to δ and increasing affinity to μ receptors. The analogues with (R)‐ or (S)‐HmVal in position 6 expressed equally low receptor affinity and selectivity. The data obtained support a previously proposed model of active conformation of deltorphins. 相似文献
107.
K Nakagawa T Tamura S Negoro S Kudoh N Yamamoto N Yamamoto K Takeda H Swaisland I Nakatani M Hirose R-P Dong M Fukuoka 《Annals of oncology》2003,14(6):922-930
BACKGROUND: This phase I dose-escalating study investigated the tolerability and toxicity of the selective epidermal growth factor receptor tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839) in Japanese patients with solid tumors. Thirty-one patients were included. PATIENTS AND METHODS: Patients initially received a single oral dose of gefitinib followed by 10-14 days of observation. Oral gefitinib was subsequently administered on 14 consecutive days, every 28 days. Dose escalation was from 50 mg/day to a maximum of 925 mg/day or dose-limiting toxicity (DLT). RESULTS: Most adverse events were mild (grade 1/2); the most frequent were an acne-like rash and gastrointestinal effects. Two of six patients at 700 mg/day had DLT; no further dose escalation occurred. C(max) was reached within 3-7 h and exposure to gefitinib increased with dose. Mean terminal half-life following multiple dosing was 50.1 h (range 27.8-79.7 h). A partial response (duration 35-361 days) was observed in five of the 23 patients with non-small-cell lung cancer over a range of doses (225-700 mg/day), and seven patients with a range of tumors had disease stabilization (duration 40-127 days). CONCLUSIONS: In conclusion, gefitinib showed a favorable tolerability profile in Japanese patients. The safety profile, pharmacokinetic parameters and antitumor activity observed in our study are comparable to those observed in patients from the USA and Europe. 相似文献
108.
A phase I dose-escalation study of docetaxel with granulocyte colony-stimulating factor support in patients with solid tumours. 总被引:1,自引:0,他引:1
P L R Mitchell R Basser M Chipman A Grigg J Cebon I D Davis J Zalcberg S Ng F Appia M Green 《Annals of oncology》2003,14(5):788-794
BACKGROUND: Docetaxel is a widely active cytotoxic agent. The principal dose-limiting toxicities (DLTs) of the 3-weekly regimen are neutropenia and febrile neutropenia. Use of prophylactic granulocyte colony-stimulating factor (G-CSF) may allow higher doses of docetaxel to be administered with potentially greater anticancer efficacy. The objectives of this study were to determine the maximum tolerated dose (MTD) and toxicity profile of docetaxel given with G-CSF support. PATIENTS AND METHODS: Eligible patients had solid tumours and were aged 18-75 years with a WHO performance status of up to 2. Strict criteria for liver function were followed. Patients may have received one previous regimen of chemotherapy in addition to adjuvant chemotherapy. Cohorts of three to six patients received docetaxel over 60-90 min every 3 weeks, commencing at 110 mg/m(2) and escalating at 10 mg/m(2) increments. Patients also received G-CSF 5 micro g/kg/day until neutrophil recovery. A 3-day corticosteroid prophylaxis was given. RESULTS: Twenty-nine patients with median age 55 years (range 29-75) were included. Fourteen (48%) had previously received chemotherapy. At the 170 mg/m(2) dose level (the MTD), two of three patients had DLTs and 160 mg/m(2) was determined to be the recommended dose. The principal DLTs were skin and neurosensory toxicity. Asthenia was frequent, especially at dose levels >/=140 mg/m(2). Grade 4 neutropenia occurred in only 10 patients (35%) and was not dose related, with febrile neutropenia in three patients (10%). CONCLUSIONS: Docetaxel may be escalated considerably above standard doses when administered with G-CSF support. The recommended dose for phase II studies is 160 mg/m(2). With escalated-dose docetaxel, DLTs were non-haematological and qualitatively similar to the toxicity profile at standard doses. 相似文献
109.
EIJI TAKEDA HIRONORI YAMAMOTO YUTAKA TAKETANI KEN-ICHI MIYAMOTO 《Pediatrics international》1997,39(4):508-513
Two distinct hereditary defects, vitamin D-dependent rickets type I (VDDR I) and type II (VDDR II), have been recognized in vitamin D metabolism. VDDR I is suggested to be a deficiency of the renal 25-hydroxyvitamin D (25(OH)D)-1α-hydroxylase. Muscle weakness and rickets are the prominent clinical findings. A normal physiologic dose of 1α-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 is sufficient to maintain remission of rickets in this disorder. VDDR II consists of a spectrum of intracellular vitamin D receptor (VDR) defects and is characterized by the early onset of severe rickets and associated alopecia. This can be attributed to mutations in the VDR gene. Massive doses of vitamin D analogs and calcium supplementation is usually required for the treatment; however, the response to therapy is sometimes variable. 相似文献
110.
Takashi Sekiguchi Makoto Noguchi Kenji Nakamori Gen-iku Kohama 《International journal of clinical oncology / Japan Society of Clinical Oncology》1997,2(1):21-28
Background Changes in interstitial collagen in human oral cancer have not yet been fully studied. We examined the relationship between
the degree of interstitial collagen deposition at the invading edge of the tumor, and the clinical and pathologic findings
in oral squamous cell carcinoma. We also investigated the therapeutic implication of the changes in distribution patterns
of collagen deposition by comparing biopsy specimens and surgical specimens.
Methods Immunohistochemical staining was performed by the streptavidin-biotin method using antibody against human type I collagen
for visualizing interstitial collagen in 50 biopsy and 45 surgical specimens.
Results Carcinomas with scanty interstitial collagen in biopsy specimens tended to have highly malignant characteristics. Large carcinomas
with scanty deposition both in biopsy and surgical specimens were likely to have positive resection margins in spite of radical
surgery.
Conclusion Immunostaining patterns for type I collagen of oral squamous cell carcinomas can provide information of importance in determining
safe resection margins. 相似文献