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991.
曲马多(奇曼丁)治疗肌肉骨骼系统慢性疼痛的I临床疗效评价 总被引:3,自引:0,他引:3
目的 :评价盐酸曲马多缓释片 (奇曼丁 )治疗中度以上肌肉骨骼系统慢性持续性疼痛的临床疗效与耐受性。方法 :在骨科门诊选择中度以上慢性非癌症性疼痛 ,应用NASIDs疼痛缓解不满意的成人病例共 4 0例 ,服用奇曼丁 ,根据疼痛控制程度和副反应调整剂量。总观察时间为 4周 ,受试者记录疼痛治疗手册 ,每周门诊随访 1次 ,医师检查后填写临床观察表。结果 :全部病例均完成试验 ,无失访和因不能耐受而退出者。服药前VSA值平均为 ( 6 8± 1 84 )分 ,服药后VSA值平均为 ( 1 0± 1 4 6 )分 ,两者经t检验 ,差异有显著性意义 (P <0 0 0 1)。平均疼痛缓解度为 ( 85 5± 5 35 ) % ,其中完全缓解和明显缓解占 77 5 %。不良反应 9例 ,总发生率为 2 2 5 % ,结论 :奇曼丁作为盐酸曲马多的缓释片 ,是一种长效中枢性镇痛剂 ,使用方便。在治疗肌肉骨骼系统的慢性疼痛方面具有优良的镇痛效果 ,副反应程度轻 ,有良好的耐受性 ,为骨科慢性疼痛的药物治疗提供了一种新的选择。 相似文献
992.
S. Vichier‐Guerre R. Lo‐Man L. BenMohamed E. Driaud S. Kovats C. Leclerc S. Bay 《Chemical biology & drug design》2003,62(3):117-124
Abstract: Over the last few years, anticancer immunotherapy has emerged as a new exciting area for controlling tumors. In particular, vaccination using synthetic tumor‐associated antigens (TAA), such as carbohydrate antigens hold promise for generating a specific antitumor response by targeting the immune system to cancer cells. However, development of synthetic vaccines for human use is hampered by the extreme polymorphism of human leukocyte‐associated antigens (HLA). In order to stimulate a T‐cell dependent anticarbohydrate response, and to bypass the HLA polymorphism of the human population, we designed and synthesized a glycopeptide vaccine containing a cluster of a carbohydrate TAA B‐cell epitope (Tn antigen: α‐GalNAc‐Ser) covalently linked to peptides corresponding to the Pan DR ‘universal’ T‐helper epitope (PADRE) and to a cytotoxic T lymphocyte (CTL) epitope from the carcinoembryonic antigen (CEA). The immunogenicity of the construct was evaluated in outbred mice as well as in HLA transgenic mice (HLA‐DR1, and HLA‐DR4). A strong T‐cell dependent antibody response specific for the Tn antigen was elicited in both outbred and HLA transgenic mice. The antibodies induced by the glycopeptide construct efficiently recognized a human tumor cell line underlying the biological relevance of the response. The rational design and synthesis of the glycopeptide construct presented herein, together with its efficacy to induce antibodies specific for native tumor carbohydrate antigens, demonstrate the potential of a such synthetic molecule as an anticancer vaccine candidate for human use. 相似文献
993.
Bruce D. Uhal Rongqi Wang Jeremy Laukka Jiaju Zhuang Valerie Soledad‐Conrad Gerasimos Filippatos 《Basic & clinical pharmacology & toxicology》2003,92(2):81-87
Abstract: Earlier work in this laboratory showed that amiodarone induces apoptosis in alveolar epithelial cells by a mechanism inhibitable by angiotensin system antagonists. A variety of recent studies suggests a critical role for alveolar epithelial cell apoptosis in the pathogenesis of lung fibrosis. On this basis we hypothesized that amiodarone‐induced alveolar epithelial cell apoptosis and lung fibrosis in vivo might be inhibitable by the angiotensin converting enzyme inhibitor captopril or the angiotensin receptor antagonist losartan. Amiodarone‐induced lung fibrosis was induced in male Wistar rats by oral adminstration over six months. Replicate groups of rats received captopril or losartan in addition to amiodarone. Apoptosis was detected by increased total lung activity of caspase 3 and in situ end labeling (ISEL) of fragmented DNA. Collagen was localized and quantitated by the picrosirius red technique. Alveolar epithelial cell apoptosis was detected in amiodarone‐treated animals as early as three weeks after the start of amiodarone administration; by six months exposure, the incidence of alveolar epithelial cell apoptosis was significantly reduced by coadministration of captopril or losartan. Alveolar wall collagen accumulation also was significantly attenuated by captopril (100%) or losartan (74%), but neither agent blunted the accumulation of alveolar macrophages evoked by amiodarone (5.3‐fold at 6 months). Lung neutrophil content was unchanged by amiodarone treatment for three weeks or six months. These results indicate that amiodarone induces alveolar epithelial cell apoptosis in vivo that is inhibitable by angiotensin antagonists. They also support the hypothesis that blockade of angiotensin formation or function attenuates amiodarone‐induced lung fibrosis irrespective of the severity of alveolitis. 相似文献
994.
Carlos M. Villaln Eduardo Ramírez‐San Juan Araceli Snchez‐Lpez Guadalupe Bravo Edwin W. Willems Pramod R. Saxena David Centurin 《Basic & clinical pharmacology & toxicology》2003,92(4):165-172
Abstract: The present study investigated the effects of dopamine on the canine external carotid circulation. One min. intracarotid artery (i.c.) infusions of dopamine (10–310 μg min.?1) produced dose‐dependent decreases in the canine external carotid conductance without affecting blood pressure or heart rate. This effect was mimicked by the D1/2‐like receptor agonist apomorphine (1–310 μg min?1), but not by the D2‐like receptor agonist, bromocriptine (31–310 μg min.?1). In contrast, fenoldopam (1–310 μg min.?1, intracarotid), a D1‐like receptor agonist, produced dose‐dependent increases in external carotid conductance. The vasoconstrictor response to dopamine was abolished after intravenous administration of the antagonists, phentolamine (α1/2; 2000 μg kg?1) or rauwolscine (α2; 100 μg kg?1), but remained unaffected after prazosin (α1; 100 μg kg?1) or haloperidol (D2‐like; 1000 μg kg?1). Interestingly, after phentolamine not only were the vasoconstrictor responses to dopamine abolished, but even a dose‐dependent vasodilator component was unmasked. These vasodilator responses to dopamine remained unchanged after intravenous haloperidol or propranolol (1000 μg kg?1 each). On the other hand, the vasodilator responses to fenoldopam, which remained unchanged after intravenous saline (0.1 ml kg?1), propranolol (1000 μg kg?1) or vagosympathectomy, were abolished by the D1‐like receptor antagonist, SCH‐23390 (10 μg kg?1). Lastly, the responses to dopamine and fenoldopam were not significantly altered after intraperitoneal pretreatment with reserpine (5 mg kg?1; ?24 hr). The above results suggest that the canine external carotid vasoconstrictor responses to dopamine: (i) are mainly mediated by α2‐adrenoceptors; and (ii) overshadow a vasodilator component, which involves vascular D1‐like receptors. 相似文献
995.
Christel M. Olsen Elise T. M. Meussen‐Elholm Mari Samuelsen Jrn A. Holme Jan K. Hongslo 《Basic & clinical pharmacology & toxicology》2003,92(4):180-188
Abstract: Bisphenol A is extensively used in the manufacturing of epoxy resins and polycarbonate plastics, whereas several brominated and chlorinated analogues are used as flame retardants and intermediates in the plastic industry. Due to the structural relationship between these chemicals and the high production volumes, we wanted to characterize and compare their potential oestrogen‐like potency using several end‐points in MCF‐7 cells: induction of pS2 protein and progesterone receptor, reduction of oestrogen receptor level, and stimulation of cell growth. Bisphenol A, tetrachloro‐ and tetrabromo‐bisphenol A, 4‐hydroxybiphenyl and 4,4′‐dihydroxybiphenyl all showed oestrogen‐like properties in MCF‐7 cells. The chemicals tested had affinity to the oestrogen receptor isolated from MCF‐7 cells, although their EC50s were 1,000 to 80,000 times higher than the EC50 of 17β‐oestradiol. Bisphenol A and 4‐hydroxybiphenyl induced cell growth in MCF‐7 cells, and the highest test concentrations induced responses, apparently exceeding the cell growth induced by 17β‐oestradiol. The other chemicals tested induced less than 50% of the maximum 17β‐oestradiol‐stimulated cell growth. Bisphenol A, 4‐hydroxybiphenyl, tetrabromobisphenol A and tetrachlorobisphenol A all increased the level of the oestrogen‐regulated proteins, progesterone receptor and pS2, whereas 4,4′‐dihydroxybiphenyl showed no such effect. Bisphenol A was the only chemical tested that clearly mimicked 17β‐oestradiol in its ability to reduce the level of cytosolic oestrogen receptors in MCF‐7 cells. By measuring several oestrogen‐dependent endpoints it seems that some xeno‐oestrogens cause an imbalanced oestrogen‐response. Their ability and potency in mimicking 17β‐oestrogen in one parameter is not necessarily accompanied by a similar effect in another oestrogen‐linked parameter. 相似文献
996.
Henrik Gren Kourosh Lotfi Anna‐Lena Zackrisson Curt Peterson 《Basic & clinical pharmacology & toxicology》2003,93(6):297-304
Abstract: Increased expression of P‐glycoprotein encoded by the mdr‐1 gene is a well‐characterised mechanism for resistance to cancer chemotherapeutic drugs in cell lines. However, the P‐glycoprotein expression after removal of the selection pressure has not fully been elucidated. The stability of P‐glycoprotein expression in the presence (+) and absence (?) of vincristine (30 or 150 nM) was studied in multidrug resistant K562 cell lines (VCR30+, VCR150+, VCR30? and VCR150?) for 11 months. The P‐glycoprotein protein and mdr‐1 mRNA levels were determined at regular intervals using flow cytometry and real‐time PCR, respectively. Chemosensitivity to a panel of antineoplastic drugs was measured using an MTT assay. The presence of vincristine (VCR30+ and VCR150+) resulted in high and stable levels of P‐glycoprotein and mdr‐1 mRNA during the whole period compared to wild type. As for the VCR30? and VCR150? subcultures, the expressions of P‐glycoprotein and mdr‐1 mRNA were stable for five months, and then the levels decreased rapidly. Concomitantly, the sensitivity to drugs known as P‐glycoprotein substrates was restored. In conclusion, resistant cells growing in the presence of the inducing drug have a stable P‐glycoprotein expression and resistance level, but removing the inducing drug may result in a sudden and rapid lowering of P‐glycoprotein and mdr‐1 mRNA levels as long as five months after drug withdrawal. 相似文献
997.
Prostatic neoplasia in transgenic mice with prostate-directed overexpression of the c-myc oncoprotein 总被引:3,自引:0,他引:3
BACKGROUND: Promoter elements within the 5' DNA region of the rat C(3)1 gene have been shown to direct prostate-specific expression of gene products when they are fused through recombinant DNA procedures and used to produce transgenic mice. In order to test the in vivo effects of chronic overexpression of the mouse c-myc protooncogene on the prostate glands of transgenic mice, we created several lines of C(3)1-c-myc transgenic mice and then examined the phenotype of males with this genetic alteration. METHODS: The modified promoter and 5' region of the rat C(3)1 gene was fused to the coding region of the mouse c-myc gene using recombinant DNA techniques. This DNA was used to create three different founder lines of transgenic mice. Tissues from males and females heterozygous for the transgene were examined for expression of the recombinant mouse c-myc mRNA by an RNase protection assay. Prostates from males were examined for expression of recombinant c-myc mRNA by in situ hybridization. Thin sections of fixed ventral prostates from males were analyzed by microscopy for histological abnormalities. RESULTS: Three different lines of transgenic mice were obtained from these procedures. These mice demonstrated expression of recombinant mouse c-myc mRNA in the testis and ventral prostates of males and in the uterus of females. In situ hybridization demonstrated that the epithelial cells were the source of recombinant c-myc expression in the ventral prostates of the transgenic lines. Microscopic analysis of the ventral prostates from these mice demonstrated abnormalities in epithelial cell morphology seemingly typical of an intraepithelial neoplasia-like phenotype. However, none of the males of any of the lines developed overt prostatic adenocarcinoma over their lifetimes. CONCLUSIONS: Chronic overexpression of c-myc in the ventral prostate epithelial cells of C3(1)-c-myc transgenic mice leads to the development of epithelial cell abnormalities similar to those seen in low-grade prostatic intraepithelial neoplasia in humans. These abnormalities were not found to progress to adenocarcinoma over the lifetimes of the transgenic mice, suggesting the need for additional oncogenic changes in the pathway to prostatic adenocarcinomas. Furthermore, our cumulative experience with the use of the C3(1) gene promoter in the generation of transgenic mice suggests that the probasin promoter element provides a much more specific and effective means to target transgenes to the prostate glands of mice. 相似文献
998.
目的 探讨实施院内规范化围手术期预防用药方案的可行性和效果。方法 选择外科Ⅰ、Ⅱ类切口择期手术病例,以2003年10月~2004年3月出院者210例作为实验组,按规范方案用药,以2002年10月~2003年3月出院者212例作为对照组,按习惯方法用药,考察预防手术部位感染的效果及费用指标。结果 实验组与对照组手术部位感染的发生率没有显著性差异,抗菌药物费用、药品费用、住院费用显著降低。结论 在院内制定和实施规范化的围手术期预防用药方案的做法切实可行,可以促进合理用药,降低医疗费用,节约卫生资源,值得推广。 相似文献
999.
武当道药治疗风湿性关节炎100例初探 总被引:5,自引:0,他引:5
目的 :观察武当道药熏洗液熏蒸冲浪浴治疗风湿性关节炎的临床疗效。方法 :将 2 0 0例风湿性关节炎患者随机分为 3组 ,治疗组用武当道药熏蒸冲浪浴治疗 ,对照 1组用普通水熏蒸冲浪浴治疗 ,对照 2组用武当道药熏洗液浸浴治疗。结果 :总有效率治疗组 91% ,对照组 1组 6 8% ,对照组 2组 78% ,治疗组与对照 1组比较有非常显著性差异 (P<0 .0 1) ,与对照组 2组比较有显著性差异 (P<0 .0 5 ) ,且治疗组的 4项理化检查治疗后转阴率也明显优于两对照组 (P<0 .0 5~ 0 .0 1)。结论 :武当道药熏蒸冲浪浴治疗风湿性关节炎效果明显。 相似文献
1000.
T.W.‐M. Fan A.N. Lane E. Chekmenev R.J. Wittebort R.M. Higashi 《Chemical biology & drug design》2004,63(3):253-264
Abstract: Soil humic substances (HS) are heterologous, polydispersive, and multi‐functional organometallic macromolecules ubiquitous in soils and sediments. They are key players in the maintenance of the belowground ecosystems and in the bioavailability of both organic and inorganic contaminants. It is widely assumed that the peptidic substructures of HS are readily degraded and therefore do not contribute significantly to interactions with contaminants such as toxic metals. To investigate the turnover of humified peptides, laboratory soil aging experiments were conducted with 13C‐glucose or 15N‐nitrate for 8.5 months. Evidence for random‐coil peptidic structures in the labeled HS was obtained from 2‐D nuclear magnetic resonance (NMR), pyrolysis gas chromatography‐mass spectrometry (pyro‐GC‐MS), and circular dichroism data. Interaction of metals with the peptidic carbonyls of labeled HS was rationalized from the solid‐state NMR data. Detailed 13C and 15N labeling patterns of amino acid residues in the acid hydrolysates of HS acquired from NMR and GC‐MS revealed two pools of peptides, i.e. one extant (unlabeled) and the other, newly humified with little isotopic scrambling (fully labeled). The persistence of pre‐existing peptidic structures indicates their resistance to degradation while the presence of fully labeled peptidic amino acids suggests wholesale incorporation of newly synthesized peptides into HS. These findings are contrary to the general notion that humified peptides are readily degraded. 相似文献