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131.
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
132.
《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
133.
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
134.
The effects of mechanical loading on the osteoblast phenotype remain unclear because of many variables inherent to the current
experimental models. This study reports on utilization of a mouse tooth movement model and a semiquantitative video image
analysis of in situ hybridization to determine the effect of mechanical loading on cell-specific expression of type I collagen (collagen I) and
alkaline phosphatase (ALP) genes in periodontal osteoblasts, using nonosseous cells as an internal standard. The histomorphometric
analysis showed intense osteoid deposition after 3 days of treatment, confirming the osteoinductive nature of the mechanical
signal. The results of in situ hybridization showed that in control periodontal sites both collagen I and ALP mRNAs were expressed uniformly across the
periodontium. Treatment for 24 hours enhanced the ALP mRNA level about twofold over controls and maintained that level of
stimulation after 6 days. In contrast, collagen I mRNA level was not affected after 24 hours of treatment, but it was stimulated
2.8-fold at day 6. This increase reflected enhanced gene expression in individual osteoblasts, since the increase in osteoblast
number was small. These results indicate that (1) the mouse model and a semiquantitative video image analysis are suitable
for detecting osteoblast-specific gene regulation by mechanical loading; (2) osteogenic mechanical stress induces deposition
of bone matrix primarily by stimulating differentiation of osteoblasts, and, to a lesser extent, by an increase in number
of these cells; (3) ALP is an early marker of mechanically-induced differentiation of osteoblasts. (4) osteogenic mechanical
stimulation in vivo produces a cell-specific 2.8-fold increase in collagen gene expression in mature, matrix-depositing osteoblasts located on
the bone surface and within the osteoid layer.
Received: 9 August 1999 / Accepted: 4 February 2000 相似文献
135.
Elin Lindhagen Pernille‐Julia Vig Hjarnaa Lena E. Friberg Scilla Latini Rolf Larsson 《Drug development research》2004,61(4):218-226
When a candidate drug enters clinical trials, decisions regarding dosing are mainly based on animal data. Occasionally, toxicity problems are faced in the clinic because of unexpected species differences in pharmacokinetics or pharmacodynamics between humans and preclinical species. Fludarabine and topotecan are examples of such drugs. In the first clinical trials of the new agent CHS 828, the maximum tolerated dose was reached earlier than expected from animal data. This paper discusses the issue of species differences in the development of anticancer drugs, and preclinical models for detection and quantification of such differences. Pharmacokinetic and hematological toxicity data of CHS 828 from studies in rats and humans are presented. In vitro sensitivity to CHS 828 and some established cytotoxic agents was measured in lymphocytes from humans and rats and in a panel of human and rodent cell‐lines. 10–100 times higher CHS 828 exposure was tolerated by rats than by patients. In both in vitro cell systems, CHS 828 showed higher potency in human cells compared to rodent cells. A species difference was evident also for fludarabine, but not for doxorubicin and cisplatin. CHS 828 pharmacokinetics were similar across species. In conclusion, the lower tolerance of CHS 828 in humans than in rats could be detected in vitro in cultures of peripheral lymphocytes. Preclinical studies of species differences could help the interpretation of in vivo effect studies as well as the choice of starting dose for clinical trials. We suggest peripheral lymphocytes from different species as a potential model system for such studies. Drug Dev. Res. 61:218–226, 2004. © 2004 Wiley‐Liss, Inc. 相似文献
136.
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
137.
牛角地黄冲剂对大鼠免疫性血小板减少模型血浆血栓素A2、前列环素I2的实验研究 总被引:2,自引:0,他引:2
观察牛角地黄冲剂对大鼠免疫性血小板减少模型血栓素A2(TXA2)、前列环素I2(PGI2)的影响.将100只SD大鼠随机分成正常对照组、模型对照组、强的松对照组、牛角地黄冲剂高剂量组、牛角地黄冲剂低剂量组.除正常组外,各组均以注射免抗大鼠血小板血清(APS)造模,分别灌药和蒸馏水,每日1次,连续11天,分别在第7天和第11天各测一半大鼠血浆血栓素B2(TXB2)、6-酮-前列腺素F1α(6-keto-PGF1α)值,并作骨髓涂片检查.结果显示强的松组6-keto-PGF1α水平明显高于正常组水平(P<0.05)而牛角地黄冲剂高剂量组6-keto-PGF1α浓度明显高于模型组,且接近正常组水平.而各组TXB2水平改变均不显著.说明牛黄地黄冲剂有改善ITP出凝血功能低下的作用,且不改变机体生理平衡. 相似文献
138.
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
139.
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
140.
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