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1.
《Journal of pharmaceutical sciences》2019,108(7):2500-2504
Accurately predicting the hepatic clearance of compounds using in vitro to in vivo extrapolation (IVIVE) is crucial within the pharmaceutical industry. However, several groups have recently highlighted the serious error in the process. Although empirical or regression-based scaling factors may be used to mitigate the common underprediction, they provide unsatisfying solutions because the reasoning behind the underlying error has yet to be determined. One previously noted trend was intrinsic clearance-dependent underprediction, highlighting the limitations of current in vitro systems. When applying these generated in vitro intrinsic clearance values during drug development and making first-in-human dose predictions for new chemical entities though, hepatic clearance is the parameter that must be estimated using a model of hepatic disposition, such as the well-stirred model. Here, we examine error across hepatic clearance ranges and find a similar hepatic clearance-dependent trend, with high clearance compounds not predicted to be so, demonstrating another gap in the field. 相似文献
2.
Mohamed El-Sherbiny Mohamed Ahmed Eladl Anu Vinod Ranade Maha Guimei Hala Gabr 《Singapore medical journal》2020,61(1):39
INTRODUCTIONThis study aimed to investigate the therapeutic response to injected human umbilical cord blood mesenchymal stem cells (UCBMSCs) among albino rats with streptozotocin (STZ)-induced diabetes mellitus.METHODSControl group (GI; n = 25) rats were fed with standard rat diet. Rats with STZ-induced diabetes mellitus without (GII; n = 25) and with (GIII; n = 25) differentiated human UCBMSCs implantation were the test groups. Rats were sacrificed in Week 11 following implantation. Liver biopsies were sectioned and stained in order to highlight both the presence and function of impregnated cells in the liver tissue.RESULTSHaematoxylin and eosin-stained sections in GI and GII rats showed normal liver architecture while GIII rats showed presence of cell clusters inside the liver tissue and around the central veins. Cell clusters with blue cytoplasm were present in sections in GIII rats but absent in GI and GII rats, indicating the presence of injected differentiated human UCBMSCs. The anti-human insulin immunostaining of GIII rats showed clusters of cells within the liver parenchyma and around central veins, indicating that these cells were active and secreting insulin.CONCLUSIONUCBMSCs are proficient in differentiating into insulin-producing cells in vivo under specific conditions and, when transplanted into the liver of albino rats with STZ-induced diabetes mellitus, were able to secrete insulin and partially control the status of diabetes mellitus in rats. 相似文献
3.
肝包虫病是流行于世界畜牧业发达地区的常见人畜共患性寄生虫病。文章介绍了肝包虫病的症状体征、诊断依据,以及各种治疗方法,以期对该病的防治提供参考。 相似文献
4.
5.
目的 探讨彩超在肾移植术后并发肝脏恶性肿瘤监测中的应用价值。 方法 应用 Acuson12 8XP彩色多普勒超声诊断仪 ,对在我院行异体肾移植手术的终末期尿毒症患者 12 0 0例进行规律随访。 结果 发现 17例恶性肿瘤 ,其中肝癌 7例 ,占 4 1.17%。 5例肿块单发 ,2例多发 ;肿块最大 10 cm× 10 cm,最小 2 .3cm× 2 .1cm。其中 6例手术病理证实 ,1例肝活检证实。 结论 对移植肾术后患者 ,首选彩超随访肝脏变化 ,能早期发现肿瘤 ,为临床选择治疗方案提供时机 ,并提高换肾后发生恶性肿瘤患者的存活率 相似文献
6.
螺旋CT三期扫描对肝纤维化诊断价值研究 总被引:5,自引:1,他引:4
目的探讨螺旋CT三期扫描对肝纤维化的诊断价值。方法对66例经肝穿刺活检病理证实的慢性乙型肝炎肝纤维化患者组和42例正常对照组进行螺旋CT三期增强扫描。根据纤维化程度分期进行影像资料和相关指标的统计分析。结果肝左叶增大,肝表面形态及肝实质密度的改变,脾脏增大,门静脉增宽和侧枝循环的建立等影像学改变,随着肝纤维化严重程度的加重而有统计学差异。本研究显示57例肝纤维化患者螺旋CT三期扫描诊断肝纤维化52例,敏感性91.2%,特异性77.8%。各期肝纤维化分期准确28例,准确率49.1%;准确判断轻度纤维化(S1、S2)或重度纤维化(S3、S4)44例,准确率77.2%,诊断早期肝硬化16例,准确率84.2%。结论螺旋CT三期扫描能判断肝纤维化的程度,而且是动态观察肝纤维化的病程演进和临床随访的有效手段。 相似文献
7.
Nishida Koyo Mihara Kiyoshi Takino Toichi Nakane Sachi Takakura Yoshinobu Hashida Mitsuru Sezaki Hitoshi 《Pharmaceutical research》1991,8(4):437-444
The effect of electric charge on the hepatic disposition of macromolecules was studied in the rat. Charged derivatives of dextran (T-70) and bovine serum albumin (BSA), mitomycin C–dextran conjugates (MMC-D), and lactosaminated BSA (Lac-BSA) were employed as model macromolecules. After intravenous injection, cationic macromolecules were rapidly eliminated from plasma because of their extensive hepatic uptake, while anionic and neutral macromolecules were slowly eliminated. Cationic macromolecules were recovered from parenchymal and nonparenchymal hepatic cells at a cellular uptake (per unit cell number) ratio of 1.4–3.2, while that of Lac-BSA was 14. During liver perfusion using a single-pass constant infusion mode, cationic macromolecules were continuously extracted by the liver, with extraction ratios at steady-state (E
ss) ranging between 0.03 and 0.54, whereas anionic and neutral macromolecules were almost completely recovered in the outflow at steady state. The E
ss for cationized BSA (Cat-BSA) and cationic MMC-Dcat were concentration dependent and decreased at low temperatures and in the presence of colchicine and cytochalasin B. The possible participation of the internalization process in the uptake of cationic macromolecules by hepatocytes was suggested. 相似文献
8.
Treatment strategy for synchronous metastases of colorectal cancer: is hepatic resection after an observation interval appropriate? 总被引:1,自引:1,他引:0
Yasuhiro Shimizu Kenzo Yasui Tsuyoshi Sano Takashi Hirai Yukihide Kanemitsu Koji Komori Tomoyuki Kato 《Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie》2007,392(5):535-538
Background In cases of synchronous colorectal hepatic metastases, the primary colorectal cancer strongly influences on the metastases.
Our treatment policy has been to conduct hepatic resection for the metastases at an interval of 3 months after colorectal
resection. We examined the appropriateness of interval hepatic resection for synchronous hepatic metastasis.
Materials and methods The subjects were 164 patients who underwent resection of hepatic metastasis of colorectal cancer (synchronous, 70 patients;
metachronous, 94 patients). Background factors for hepatic metastasis and postoperative results were compared for synchronous
and metachronous cases.
Results The cumulative survival rate for 164 patients at 3, 5, and 10 years postoperatively was 71.9%, 51.8%, and 36.6%, and the post-resection
recurrence rate in remnant livers was 26.8%. Interval resection for synchronous hepatic metastases was conducted in 49 cases
after a mean interval of 131 days. No difference was seen in postoperative outcome between synchronous and metachronous cases.
Conclusion The outcome was similarly favorable in cases of synchronous hepatic metastasis and in cases of metachronous metastasis. Delaying
resection allows accurate understanding of the number and location of hepatic metastases, and is beneficial in determining
candidates for surgery and in selecting surgical procedure. 相似文献
9.
目的:观察柔肝消瘕饮对肝硬化大鼠肝组织病理形态学和血清、肝组织IL-1β、IL-6含量的影响。方法:采用复合因素造模法复制肝硬化大鼠模型,以复方鳖甲软肝片为对照,观察柔肝消瘢饮对肝硬化大鼠肝组织病理形态学、血清和肝组织IL-1β、IL-6含量的影响。结果:与正常组比较,模型组大鼠出现肝小叶损害,纤维组织增生,假小叶形成,血清IL-1β、IL-6含量和肝组织IL-6含量均明显升高(P〈0.01或P〈0.05);与模型组比较,各治疗组肝组织病理损害减轻,血清IL-1β和肝组织IL-6含量均有明显下降,差异有显著性意义(P〈0.01或P〈0.05);与对照组比较,高剂量组血清IL-6含量明显降低(P〈0.05)。结论:柔肝消瘢饮能显著下调肝硬化大鼠血清IL-1β、IL-6含量和肝组织IL-6含量,具有减轻肝硬化炎症损害,改善肝组织病理形态学作用。 相似文献
10.
血清α—L-岩藻糖苷酶(AFU)对原发性肝癌(PHC)的诊断意义 总被引:1,自引:0,他引:1
目的研究血清α-L-岩藻糖苷酶(AFU)对原发性肝癌的诊断意义。方法分别测定20例正常对照者、45例慢性乙型肝炎、40例肝硬化、50例转移性肝癌及35例原发性肝癌患者的血清AFU。结果原发性肝癌组的血清AFU浓度和阳性率显著高手其他各组。结论血清AFU对原发性肝癌的诊断有重要价值。 相似文献