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991.
Cytotoxic activities of new jadomycin derivatives 总被引:1,自引:0,他引:1
Zheng JT Rix U Zhao L Mattingly C Adams V Chen Q Rohr J Yang KQ 《The Journal of antibiotics》2005,58(6):405-408
Cytotoxic activities of jadomycin B and five new jadomycin derivatives against four cancer cell lines (HepG2, IM-9, IM-9/Bcl-2 and H460) were evaluated. Jadomycin S was most potent against HepG2, IM-9 and IM-9/Bcl-2 while jadomycin F was most potent against H460. Their potencies correlated with the degrees of apoptosis induced. Structure-activity-relationship analyses clearly demonstrate that the side chains of the oxazolone ring derived from the incorporated amino acids make a significant impact on biological activity. Therefore, jadomycin offers an ideal scaffold to manipulate structure and could be exploited to make many novel bioactive compounds with altered activities. 相似文献
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Fehsel K Loeffler S Krieger K Henning U Agelink M Kolb-Bachofen V Klimke A 《Journal of clinical psychopharmacology》2005,25(5):419-426
The present study examined cellular effects of the atypical antipsychotic drug clozapine on blood cells of treated patients with and without clozapine-induced agranulocytosis (CA). Blood from one patient who commenced clozapine treatment was examined at weekly intervals for 128 days. Olanzapine-treated (n = 5) and polymedicated (n = 14) schizophrenic patients, as well as healthy subjects (n = 19) and septic shock patients (n = 8), were studied for comparison. We observed dramatically increased numbers of native neutrophils stained for superoxide anion production (P < or = 0.005, n = 10) and significantly elevated expression levels of the proapoptotic genes p53 (P < or = 0.020), bax alpha (P < or = 0.001), and bik (P < or = 0.002) in all tested non-CA patients (n = 19) and CA patients (n = 4). In non-CA patients, the expression of these genes did not correlate to the percentage of apoptotic neutrophils (2.0% +/- 1.3%), but in CA patients about 37% of the neutrophils show morphologic signs of apoptosis (P < or = 0.001). Under G-CSF therapy of CA, the number of apoptotic neutrophils and the expression of the proapoptotic genes decreased significantly. In conclusion, high production of reactive oxygen species in neutrophils of clozapine-treated patients, together with increased expression of proapoptotic genes, suggests that neutrophils are predisposed to apoptosis in schizophrenic patients under clozapine therapy. The correlation between drug and proapoptotic markers was highest for clozapine and bax alpha as well as superoxide anion radicals. This indicates oxidative mitochondrial stress in neutrophils of clozapine-treated patients which probably contributes to the induction of apoptosis and sudden loss of neutrophils and their precursors in CA patients. 相似文献
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Susilo R Korting HC Strauss UP Menke G Schuster O Menke A 《Arzneimittel-Forschung》2005,55(6):338-342
The purpose of this open study was to evaluate the rate and extent of the penetration of sertaconazole nitrate (CAS 99592-32-2, Zala?n) penetration into the stratum corneum/lucidum of the human skin. Selected areas of 9 cm2 each of the back skin of 12 healthy volunteers were exposed over 8 different time intervals (between 0 and 48 h) to 100 mg of a 2% cream preparation of the compound or to placebo. Using a HPLC-assay the relative amounts of the applied dose of sertaconazole nitrate were determined in the residual cream of the skin surface as well as in 3 layers of the epidermis obtained by the stripping technique. Sertaconazole nitrate was shown to penetrate into the stratum corneum shortly after application, disappearing from the application areas with a mean apparent half-life of approximately 60 h. Immediately after topical application the residual amount of the applied mean dose of 2103 +/- 146.3 microg on the skin's surface was 88.9 +/- 2.3%, decreasing steadily to 52.4 +/- 8.5% after 48 h. A relevant amount of the applied dose (5.3 +/- 3.0%) was recovered from the stratum corneum already 30 min after application, and 3 h after administration a plateau was reached (6.9 +/- 3.2) which could be maintained until 48 h. A gradient from the site of application to the epidermis was apparent since the amounts recovered in The estimated average level of sertaconazole nitrate for a volume of 1 mL of stratum corneum after application of 100 mg cream was 1409 microg immediately after application and reached a plateau at 3 h with 9029 microg. Although not directly measured, the results also gave information about the mean amount of sertaconazole nitrate that penetrated through the stratum corneum and deeper layers allowing an estimate of the total mean amount of compound penetrating into the skin. The relative portion of this amount steadily increased from 1.1% of the applied dose at 0 h to 24.1% at 12 h, 34.2% at 24 h and finally to 37.6% of dose after 48 h of exposure. In view of the high target organ levels of the compound maintained over days, its rapid appearance in the stratum corneum after application and the earlier finding that Sertaconazole nitrate is not distributed into blood in substantial quantities the pharmacokinetic properties of this antifungal preparation therapy can be regarded as favourable. 相似文献
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Staat M Trenz E Lohmann P Frotscher R Klinge U Tabaza R Kirschner-Hermanns R 《Journal of biomedical materials research. Part B, Applied biomaterials》2012,100(4):924-933
Suburethral slings as well as different meshes are widely used treating stress urinary incontinence and prolaps in women. With the development of MiniSlings and special meshes using less alloplastic material anchorage systems become more important to keep devices in place and to put some tension especially on the MiniSlings. To date, there are many different systems of MiniSlings of different companies on the market which differ in the structure of the used meshes and anchors. A new objective measurement method to compare different properties of MiniSling systems (mesh and anchor) is presented in this article. Ballistic gelatine acts as soft tissue surrogate. Significant differences in parameters like pull-out strength of anchors or shrinkage of meshes under loading conditions have been determined. The form and size of the anchors as well as the structural stability of the meshes are decisive for a proper integration. The tested anchorings sytems showed markedly different mechanical function at their respective load bearing capacity. As the stable fixation of the device in tissue is a prerequisite for a permanet reinforcement, the proposed test system permits further optimisation of anchor and mesh devices to improve the success of the surgical treatment. 相似文献