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91.
静松灵[2-(2,4-二甲基苯胺基)-4,5-二氢噻唑,XT]是国内合成的麻醉物,经ip给药后,从大鼠尿中分离、纯化、鉴定了四个代谢产物。MB1即XT原形;MB3及MA2互为异构体,分别为2位、4位甲基氧化为羧基的产物;MA1则4位甲基氧化为羧基,二氢噻唑环中41位亚甲基氧化为羰基。初步实验表明:代谢产物MB3,MA2,MA1的药效与毒性均远低于原形药,大鼠与小鼠对XT的转化机制相近,但也存在种属的差异。 相似文献
92.
用离体大鼠肝脏灌流方法,研究了胆碱酯酶抑制剂CXN的生物转化过程。径HPLC分离纯化及光谱分析,鉴定了CXN的六个脂溶性代谢产物的化学结构。产物Ⅰ为CXN原形,其余均为氧化产物。其中产物Ⅲ尚保留部分抑酶活力,而产物Ⅱ,Ⅴ及Ⅵ对小鼠全脑胆碱酯酶的抑酶活力明显下降。另外还观察到,代谢产物Ⅱ及Ⅴ对小鼠的急性毒性也明显减小。 相似文献
93.
Hamzeh Kayhanian Emily Goode Francesco Sclafani Joo Ern Ang Marco Gerlinger David Gonzalez de Castro Scott Shepherd Clare Peckitt Sheela Rao David Watkins Ian Chau David Cunningham Naureen Starling 《Clinical colorectal cancer》2018,17(1):e69-e76
Background
Somatic v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation, present in approximately 10% of metastatic colorectal cancer (mCRC) cases, is associated with poor prognosis. Patient outcome outside of clinical trials has only been reported in small series. We report real-world data on treatment and survival for BRAF-mutated (MT) patients at a single tertiary center, compared with a matched BRAF wild type (WT) control group.Patients and Methods
All colorectal cancer patients tested for BRAF mutation, from October 2010 to November 2014 were identified. BRAF-MT mCRC cases were compared with an age and sex-matched BRAF-WT control group. Clinicopathological data were collected and survival calculated using the Kaplan–Meier method and comparisons made using Cox regression.Results
Forty-three of 503 patients (8.5%) tested had BRAF-MT mCRC and were compared with 88 BRAF-WT controls. Median overall survival (mOS) was 18.2 months for BRAF-MT and 41.1 months for BRAF-WT mCRC patients (hazard ratio, 2.74; 95% confidence interval, 1.60-4.70; P < .001). Progression-free survival for BRAF-MT and WT patients, respectively, was: 8.1 months versus 9.2 months (P = .571) first-line, 5.5 months versus 8.3 months (P = .074) second-line, and 1.8 months versus 5.6 months (P = .074) third-line. Treatment using sequential fluoropyrimidine-based doublet chemotherapy was similar between both groups. Anti-epidermal growth factor receptor (EGFR) therapy was mainly given third-line with progressive disease in 90% (n = 9 of 10) of BRAF-MT patients at first restaging.Conclusion
In this case-control study, the poor mOS of BRAF-MT mCRC was associated with reduced treatment benefit beyond first-line. Sequential doublet chemotherapy remains a reasonable option in appropriately selected patients. BRAF-MT patients did not benefit from anti-EGFR therapy in this study. Recruitment to clinical trials is recommended to improve outcomes in BRAF-MT mCRC. 相似文献94.
95.
96.
Response of Plasmodium falciparum to dihydrofolate reductase inhibitors in Malindi, Kenya 总被引:2,自引:0,他引:2
H C Spencer W W Watkins D G Sixsmith D K Koech 《Transactions of the Royal Society of Tropical Medicine and Hygiene》1986,80(2):201-203
The response of Plasmodium falciparum isolates to dihydrofolate reductase inhibitors (DHFRI) was examined in Malindi, Kenya. All 20 infected children treated with pyrimethamine/sulphadoxine responded. In contrast, after treatment with pyrimethamine, parasitaemia in 9 of 14 infections failed to clear or recrudesced during the seven-day follow-up. In a 48-hour in vitro test, five of six isolates resistant to pyrimethamine in vivo had a minimal inhibitory concentration (MIC) to pyrimethamine greater than or equal to 300 nmoles/1 compared with less than or equal to 100 nmoles/1 for the four sensitive isolates; four isolates did not grow. MIC to M-B 35769, an experimental DHFRI structurally similar to pyrimethamine were the same (six isolates) or 10-fold lower (three isolates). In the laboratory four of five isolates adapted to in vitro culture had the same MICs as in the field while one isolate became less responsive to both drugs. Cycloguanil (the active metabolite of proguanil) was more active in vitro in the laboratory than pyrimethamine or M-B 35769. 相似文献
97.
Stroke survivors’ and carers’ experiences of a systematic voiding programme to treat urinary incontinence after stroke 下载免费PDF全文
98.
Brandon L. Helfield Xucai Chen Bin Qin Simon C. Watkins Flordeliza S. Villanueva 《Ultrasound in medicine & biology》2017,43(11):2678-2689
Sonoporation is emerging as a feasible, non-viral gene delivery platform for the treatment of cardiovascular disease and cancer. Despite promising results, this approach remains less efficient than viral methods. The objective of this work is to help substantiate the merit of polymeric microbubble sonoporation as a non-viral, localized cell permeation and payload delivery strategy by taking a ground-up approach to elucidating the fundamental mechanisms at play. In this study, we apply simultaneous microscopy of polymeric microbubble sonoporation over its intrinsic biophysical timescales–with sub-microsecond resolution to examine microbubble cavitation and millisecond resolution over several minutes to examine local macromolecule uptake through enhanced endothelial cell membrane permeability–bridging over six orders of magnitude in time. We quantified microbubble behavior and resulting sonoporation thresholds at transmit frequencies of 0.5, 1 and 2 MHz, and determined that sonic cracking is a necessary but insufficient condition to induce sonoporation. Further, sonoporation propensity increases with the extent of sonic cracking, namely, from partial to complete gas escape from the polymeric encapsulation. For the subset that exhibited complete gas escape from sonic cracking, a proportional relationship between the maximum projected gas area and resulting macromolecule uptake was observed. These results have revealed one aspect of polymeric bubble activity on the microsecond time scale that is associated with eliciting sonoporation in adjacent endothelial cells, and contributes toward an understanding of the physical rationale for sonoporation with polymer-encapsulated microbubble contrast agents. 相似文献
99.
100.
Value conflicts between supervisees and supervisors can adversely affect supervisee development, service provision, and the supervision relationship. However, the role of value conflicts in supervision has been minimally considered. Building on the Farnsworth and Callahan (2013) model for addressing client-clinician value conflict, we propose a supervision-specific framework to help supervisors and supervisees navigate value conflicts that emerge during supervision. The proposed framework consists of three steps: (a) detection of value conflict in supervision; (b) identification and articulation of value conflicts; and (c) determination of appropriate recommendations for supervisees. Neither punitive nor corrective in purpose, the model is eminently exploratory and educational in nature. 相似文献