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1.
骨质疏松是一种全身性骨骼疾病,导致骨折风险增加。成人的骨量通过破骨细胞的骨吸收和成骨细胞的骨形成作用来维持动态平衡,治疗骨质疏松症的理想策略是抑制破骨细胞的骨吸收和/或增强成骨细胞的骨形成功能。目前针对保护成骨细胞及增强其功能的骨质疏松疗法相对较少。因此,本文针对成骨细胞相关功能蛋白、各种细胞损伤机制(内质网应激、氧化应激、机械过载、微小RNA和长链非编码RNA的影响等)及骨质疏松的治疗与预防作一综述,以期为针对增强成骨细胞功能的骨质疏松治疗策略提供新思路。 相似文献
5.
目的 研究非小细胞肺癌(NSCLC)组织中抑癌基因PTEN的表达和DNA含量与NSCLC侵袭、转移的关系.方法 采用免疫组织化学SP方法检测PTEN在78例肺癌标本中的表达,并用流式细胞术检测30例肺癌标本中DNA含量.结果:肺癌标本中PTEN蛋白总缺失率为42.3%,有淋巴结转移组和无淋巴结转移组肺癌表达缺失率分别为52.1%和26.7%(P<0.05),其表达缺失率随TNM分期增加而上升,分期越晚表达缺失率越高.PTEN缺失率高者生存时间短.DNA指数(DI)的分布范围在1.04~1.93.异倍体肿瘤24例,DI值随TNM分期增加而增加(P<0.05),与淋巴结转移呈正相关.结论 肺癌组织中PTEN的表达与肺癌淋巴结转移有显著相关性,肺癌细胞DNA含量与肺癌TNM分期及淋巴结转移密切相关.检测PTEN蛋白表达和DNA含量将有助于判断肺癌的转移及预后. 相似文献
6.
The distribution pattern of the alkaloids of A. Vasica has been studied with change of season. The study also resulted in the detection of glycosides and N-oxides of vasicine and vasicinone. 相似文献
7.
CD44是一种跨膜受体蛋白 ,属于黏附分子家族 ,可与透明质酸等配体结合 ,介导细胞与细胞、细胞与基质之间的黏附。近年来发现CD44及其变异体在许多肿瘤细胞中异常表达 ,且与肿瘤的发生发展及患者的预后存在着一定的关系 ,因此 ,可作为一个辅助性指标预测肿瘤的发展情况 相似文献
10.
The current work envisages synthesis of an ester prodrug of flurbiprofen whereby its carboxylic group was condensed with a skeletal muscle relaxant methocarbamol, with the aim of synergistic activity of two drugs, avoid flurbiprofen mediated gastro-intestinal damage and minimize the ulceration tendency of flurbiprofen. The synthesized prodrug was characterized and confirmed by physicochemical and spectroscopic studies. Solubility and partition coefficient studies indicated an increased lipophilicity and thus better suitability for oral administration than the parent drugs and the protein binding studies revealed a low protein binding capacity of the mutual prodrug. Subsequently, in-vitro hydrolysis was studied in different pH, simulated gastric fluid, simulated intestinal fluid and plasma and quantitative evaluation was performed by high performance liquid chromatography. It was found that the prodrug remained unhydrolyzed in the stomach after absorption however, underwent rapid cleavage by the esterases in blood to give the parent drug. Furthermore, the mutual ester prodrug was evaluated for its anti-inflammatory, analgesic, skeletal muscle relaxation, ulcerogenic and total acid content activity and was found to possess comparable activity with that of the parent drugs. Microscopic structures of the stomach tissues revealed significant reduction in gastric ulcer formation of mice gastric mucosa as compared to parent carboxylic acid drug. 相似文献
13.
Prasugrel and clopidogrel are antiplatelet prodrugs that are converted to their respective active metabolites through thiolactone intermediates. Prasugrel is rapidly hydrolysed by esterases to its thiolactone intermediate, while clopidogrel is oxidized by cytochrome P450 (CYP) isoforms to its thiolactone. The conversion of both thiolactones to the active metabolites is CYP mediated. This study compared the efficiency, in vivo, of the formation of prasugrel and clopidogrel thiolactones and their active metabolites. The areas under the plasma concentration versus time curve (AUC) of the thiolactone intermediates in the portal vein plasma after an oral dose of prasugrel (1 mg kg?1) and clopidogrel (0.77 mg kg?1) were 15.8 ± 15.9 ng h ml?1 and 0.113 ± 0.226 ng h ml?1, respectively, in rats, and 454 ± 104 ng h ml?1 and 23.3 ± 4.3 ng h ml?1, respectively, in dogs, indicating efficient hydrolysis of prasugrel and little metabolism of clopidogrel to their thiolactones in the intestine. The relative bioavailability of the active metabolites of prasugrel and clopidogrel calculated by the ratio of active metabolite AUC (prodrug oral administration/active metabolite intravenous administration) were 25% and 7%, respectively, in rats, and 25% and 10%, respectively, in dogs. Single intraduodenal administration of prasugrel showed complete conversion of prasugrel, resulting in high concentrations of the thiolactone and active metabolite of prasugrel in rat portal vein plasma, which demonstrates that these products are generated in the intestine during the absorption process. In conclusion, the extent of in vivo formation of the thiolactone and the active metabolite of prasugrel was greater than for clopidogrel’s thiolactone and active metabolite. 相似文献
14.
目的:评价阿立哌唑与利培酮治疗自闭症谱系障碍(ASD)与注意缺陷多动障碍(ADHD)共病患儿的疗效与安全性。方法:选取在某院精神科治疗的ASD和ADHD共病患儿68例,根据随机数字表法将患儿分为阿立哌唑组( n=34)和利培酮组( n=34)。阿立哌唑组患儿接受起始剂量为5 mg·d -1的阿立哌唑片口服治疗,最终剂量增加至15 mg·d -1。利培酮组患儿接受起始剂量为1 mg·d -1的利培酮片口服治疗,最终剂量增加至2 mg·d -1;2组患儿均治疗12周。在基线(T 0)、治疗6周(T 1)与12周(T 2)时,采用注意缺陷/多动评定量表(ADHD-RS)评价患儿总体ADHD症状变化情况;采用康纳斯行为评定量表(CRSR)教师用量表多动因子(CRSR-I)评价患儿多动症的改善情况;采用CRSR不注意缺陷-冲动因子(CRSR-H)评价患儿注意力缺陷的改善情况;采用临床整体印象-严重程度量表(CGI-S)及儿童总体评估量表(C-GAS)评分评价患儿整体功能。对患儿的相关临床指标进行常规监测,比较2组患儿药物不良事件与安全性。结果:与T 0时比较,阿立哌唑组患儿T 1与T 2时,ADHD-RS、CRSR-I、CRSR-H与CGI-S评分均显著降低(均 P<0.05),C-GAS评分显著提高(P<0.05)。利培酮组患儿T 2时,ADHD-RS、CRSR-I、CRSR-H与CGI-S评分均显著降低(均 P<0.05),C-GAS评分显著提高( P<0.05)。2组患儿的ADHD症状显著改善,多动症状与不注意缺陷-冲动症状显著改善,患儿的整体功能也显著改善。2组患儿主要的不良事件是食欲增加、体质量增加与嗜睡,但均没有发生严重的不良事件。T 2时,利培酮组患儿催乳素水平显著提高( t=9.619, P<0.001),其他临床指标没有显著性差异(均 P>0.05)。结论:阿立哌唑和利培酮能够通过减少ASD和ADHD共病患儿的注意力涣散和多动症症状来改善患儿整体功能,具有较高的疗效、安全性,值得临床推广应用。 相似文献
15.
Controlled clinical trials, usually carried out in a multicentre, randomized manner, have become fashionable and popular because they contribute to the general acceptance of the results, particularly when the difference between the treatment arms is small. The present book and the present introduction attempt to discuss when and how this form of trial is appropriate. It is recognized that the discussion may be one-sided in the sense that the undoubted and well-known merits of controlled clinical trials are not reiterated. The focus of the present discussion is on the scientific, practical and ethical problems inherent in such trials and on possibilities for improving their design. In the future clinical trials should be used with more restraint than hitherto. Phase I trials should replace inter-patient by intra-patient dose escalation in order to give each patient a chance to benefit from the treatment. Since such trials frequently cause discomfort, they should be limited to one centre at a time. The number of patients subjected to phase II trials can be appreciably reduced if reasonable statistical measures are taken, as proposed here, to optimize and minimize the trial. Phase III trials must improve the relevance of the questions asked, reporting of errors, patient information and statistical interpretation. They must be based on promising phase II studies with historical controls so that their efficacy is increased. 相似文献
16.
目的观察阿立哌唑和利培酮治疗老年痴呆精神行为症状的疗效及安全性。方法采用随机对照研究,将具有精神行为症状的痴呆患者68例完全随机分为阿立哌唑组及利培酮组,各34例。阿立哌唑组患者服用阿立哌唑,起始剂量2.5mg/d,最大剂量不超过15mg/d;利培酮组患者口服利培酮,起始剂量0.5mg/d,最大剂量不超过3mg/d。疗程均为8周。治疗前和治疗第2、4、8周末采用痴呆病理分析评定量表(BEHAVE—AD)评定疗效,用副反应量表(TESS)评定不良反应,并于入组时和治疗第8周末分别检测2组患者空腹血糖、餐后2h血糖、TC、TG、LDL—C、HDL—C及体重。结果阿立哌唑组和利培酮组患者治疗2、4、8周后BEHAVE—AD评分均明显低于治疗前[阿立哌唑组:(14.8±4.2)、(10.2±3.6)、(6.8±2.8)分比(16.4±4.6)分;利培酮组:(15.2±3.9)、(11.8±3.8)、(7.2±3.0)分比(17.2±5.O)分,P〈0.05或P〈0.01]。2组患者间治疗前及治疗后BEHAVE—AD评分比较,差异均无统计学意义(P〉0.05)。2组不良反应发生率均为8.8%(3/34),差异无统计学意义(P〉0.05)。利培酮组治疗8周末体重较治疗前增加明显[(71±6)kg比(66±6)kg,P〈0.05],TG及LDL—C升高[分别为(1.62±0.46)mmol/L比(0.96±0.29)mmol/L.(3.82±0.86)mmol/L比(3.08±0.74)mmol/L,而阿立哌唑组则改变不明显(均P〉0.05)。结论阿立哌唑治疗老年痴呆精神行为症状总体疗效、安全性与利培酮相当,但阿立哌唑对患者血糖、血脂及体重影响小于利培酮。 相似文献
18.
The distribution pattern of the alkaloids of A. VASICA has been studied with change of season. The study also resulted in the detection of glycosides and N-oxides of vasicine and vasicinone. 相似文献
19.
Distribution and retention of mercury and selenium was studied in rats exposed repeatedly to HgCl 2 injections (0.5 mg Hg/kg to the tail vein every other day) and intragastrically to Na 2SeO 3 (0.5 mg Se/kg every day), applying combined and separate administration of these metals for 2 weeks. Whole-body retention of mercury in the presence of selenium was augmented by 20% and that of selenium in the presence of mercury by 4% with respect to the administered dose. Combined administration of mercuric chloride and sodium selenite brought about damage to the epithelial cells of renal proximal convolutions and formation of protein casts in their lumen. These changes had the same pattern as those induced by administration of mercuric chloride alone, but the intensity was lower. Submicroscopic studies revealed that repeated combined administration of sodium selenite and mercuric chloride did not completely abolish the mercury-induced mitochondrial swelling and contributed to chromatin destruction in the hepatocyte nuclei.This work was supported by the Section of Medical Sciences of the Polish Academy of Sciences (Agreement 537/VI) 相似文献
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