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21.
Andries S. Koster 《Pharmacy World & Science》1991,13(3):123-126
Quinones can be metabolized by various routes: substitution or reductive addition with nucleophilic compounds (mainly glutathione and protein thiol groups), one-electron reduction (mainly by NADPH: cytochrome P-450 reductase) and two-electron reduction (by D,T-diaphorase). During reduction semiquinone radicals and hydroquinones are formed, which can transfer electrons to molecular oxygen, resulting in the formation of reactive oxygen intermediates and back-formation of the parent quinone (redox cycling). Reaction of semiquinones and reactive oxygen intermediates with DNA and other macromolecules can lead to acute cytotoxicity and/or to mutagenicity and carcinogenicity. The enhanced DNA-alkylating properties of certain hydroquinones are exploited in the bioreductive alkylating quinones. Acute cytotoxicity of quinones appears to be related to glutathione depletion and to interaction with mitochondria and subsequent disturbance of cellular energy homoeostasis and calcium homoeostasis. These effects can to a certain extent be predicted from the electron-withdrawing and electron-donating effects of the substituents on the quinone nucleus of the molecule. Prediction of cytostatic potential remains much more complicated, because reduction of the quinones and the reactivity of the reduction products with DNA are modulated by the prevailing oxygen tension and by the prevalence of reducing enzymes in tumour cells.This article is based on a lecture given at the 16th LOF Symposium, 27 October 1989, Utrecht, the Netherlands. 相似文献
22.
Alemtuzumab (CAMPATH 1H) Induction Therapy in Cadaveric Kidney Transplantation—Efficacy and Safety at Five Years 总被引:2,自引:0,他引:2
Christopher J. E. Watson J. Andrew Bradley Peter J. Friend John Firth Craig J. Taylor John R. Bradley Kenneth G. C. Smith Sathia Thiru Neville V. Jamieson Geoff Hale Herman Waldmann Roy Calne 《American journal of transplantation》2005,5(6):1347-1353
Alemtuzumab is a powerful lymphocyte depleting antibody currently being evaluated in solid organ transplantation. This paper describes 5-year results of a single center study of alemtuzumab as induction in renal transplantation. Thirty-three renal transplant recipients received 20 mg alemtuzumab on day 0 and 1, followed by half-dose cyclosporin monotherapy (trough concentration 75-125 ng/mL) from day 3. They were compared in a retrospective contemporaneous-controlled manner with 66 kidney transplant recipients transplanted in the same period and center who received conventional immunosuppression with cyclosporin, azathioprine and prednisolone. In the alemtuzumab group 12% of recipients died compared to 17% in the control group (p = 0.48); likewise graft loss was similar in both groups (21% vs. 26%, respectively, p = 0.58). Incidence of acute rejection was also comparable at 5 years (31.5% vs. 33.6%), although the pattern of rejection was different with 14% patients in the alemtuzumab group experiencing rejection over 1 year post-transplant compared to none in the control group. There was no significant difference between groups in terms of infection or serious adverse events. While acknowledging the limitations of a relatively small single-center study, results suggest that alemtuzumab induction allowed satisfactory long-term patient and graft survival equivalent to that seen with standard triple immunosuppression, while avoiding steroid therapy. 相似文献
23.
黄震华 《中国新药与临床杂志》2005,24(10):829-832
心肌钠钙交换在调节心肌细胞内外钠、钙平衡中发挥重要作用。钠钙交换分为前向型和逆向型2种。在心力衰竭、心肌缺血、心肌再灌注等病理情况下,通过钠钙交换器的离子交换可产生致心律失常性的一过性内向电子流,引起延迟后除极和非折返激动型的室性心动过速。钠钙交换器抑制药在预防这些病理情况下的心律失常具有潜在的作用。 相似文献
24.
Overactive bladder (OAB) is a prevalent and costly condition that can affect any age group. Typical symptoms include urinary urgency, frequency, incontinence and nocturia. OAB occurs as a result of abnormal contractions of the bladder detrusor muscle caused by the stimulation of certain muscarinic receptors. Therefore, antimuscarinic agents have long been considered the mainstay of pharmacologic treatment for OAB. Currently, there are five such agents approved for the management of OAB in the United States: oxybutynin, tolterodine, trospium, solifenacin and darifenacin. This article summarizes the efficacy, contraindications, precautions, dosing and common side effects of these agents. All available clinical trials on trospium, solifenacin and darifenacin were reviewed to determine its place in therapy. 相似文献
25.
Summary The objective of this study was to evaluate the effect of two non-steroid anti-inflammatory drugs, indomethacin and metamizole, on ureteral peristalsis during acute occlusion similar to the situation in renal colic. In 12 pentobarbital anesthetized sheep, both ureters were cannulated and the frequency of ureteral contractions, urine flow, mean ureteral pressure and blood pressure were recorded during 10-min control and i.v. drug administration periods. Both indomethacin (1–2 mg/kg) and metamizole (60–120 mg/kg) showed a dose dependent reduction in peristaltic frequency without reduction of the mean pressure. In addition, the pressure amplitude of the peristaltic waves was also lowered, particularly with indomethacin. Only indomethacin reduced the urine flow. Arterial blood pressure was elevated by both drugs, particularly after the first dose of indomethacin. It can be concluded that indomethacin and metamizole reduce ureteral peristaltic frequency, probably blocking the impulse transmission at the ureteropelvic junction.For the partial fulfillment of a Master's degree in Pharmacology 相似文献
26.
氟西汀与阿米替林治疗105例抑郁障碍病人的双盲对照试验 总被引:6,自引:4,他引:2
目的:评价国产氟西汀的抗抑郁作用及安全性。方法:采用随机、双盲对照、多中心研究,分为国产氟西汀组57例(男性22例,女性35例;年龄40±s13a),口服氟西汀20mg,qd,阿米替林57例(男性27例,女性30例;年龄40±14a),口服阿米替林75mg,bid,疗程6wk。结果:氟西汀治疗抑郁障碍的疗效与阿米替林相当,总有效率分别为85%及92%(P>0.05);氟西汀组的主要副作用有口干、便秘、恶心、心动过速等,但较之阿米替林程度轻且发生率低。结论:氟西汀的抗抑郁作用与阿米替林相当,副作用少,服用方便。 相似文献
27.
人癌干细胞集落形成测定常用双层琼脂平皿法。新法系采用园形玻璃毛细管法培养!可
以减少细胞用量及药物消耗。管内径为1.3mm,管长9.75cm,内盛15.000有核细胞/50μl,培养7~
14天。50例肿瘤活检标本生长成功率为88%,并可供化疗药物敏感性试验用。这种微量化检测具有
独特的优点,便于推广应用。 相似文献
28.
In rabbit platelet rich plasma (PRP), 5-hydroxytraptamine (5-HT,0.03~3μmol/L) induced decrease in light transmission (DLT) dose-de pendently with centralization, as revealed by electron microscopy. However, 5-HT did not induced platelet aggregation and release reaction. 5-HT-induced DLT was inhibited by methysergide (0.3~30μmol/L), indomethacin (0.3~10μmol/L) and PGE_1 (0.01~0.3μmol/L) in a dose-dependent manner, but not EGTA(0.3~3mmol/L). Collagen(Coll), arachidonic acid (AA), adenosine diphosphate (ADP) and a stable thromboxane A2 analoge(STA_2) also induced DLT before aggregation by themselves, which was also inhibited by PGE_1, but not inhibited by EGTA except for Coll However,Coll-, AA-, STA_2-and ADP-induced DLT were reduced by pretreatment of PRP with 5-HT dose-depen-dently. The duration of DLT by Coll and AA were decreased from 151.4±5.93 sec and 15(?)38±0.60sec to 45.44±4.04 sec and 9.00±1.25 sec respectively ((?)±s(?) P<0.01), but not by ADP and STA_2, 3μmol/L of ADP-and 0.3μmol/L of STA_2-induced aggregation which was not accompanied with release reaction were enhanced by 5-HT pretreatment, but in those (Coil 5μg/ml, AA 100~200μmol/L and STA_2 1~3 μmol/L) with release reaction, the amount of adenosine triphosphate(ATP)were suppressed significantly (P<0.001) by 5-HT pretreatment without the effect on the magnitude of aggregation, The mobilization of cytosolic free calcium concentration ([Ca~(2+)]i) was observed after 5-HT treatment in single washed platelet, the results indicated that the basic level of [Ca~(2+)] i was 64.78±3.24nmol/L and this level was increased dose-dependently and significantly at 30 sec after administration of 5-HT and the time of peak value of [Ca~(2+)] i was at 90~100 sec.The similar time courses of suppression of ATP released during aggregation, in cases of Coll(5μg/ml), AA (200μmol/L) and STA_2(3μmol/L), by 5-HT were also found in the present experiment. 相似文献
29.
杨兴旺 《眼外伤职业眼病杂志》1994,16(3):202-204
采用综合治疗,抗炎,散瞳,局部治疗与全身应用免疫抑制疗法,治疗319例352眼外伤获得了满意的疗效,眼球挫伤104例,眼球穿孔伤93例,化学烧伤71例,眼炸伤46例。眼热烧伤5例,治疗包括及时清创胶粘或缝合,清除前房出血合理用皮质类固醇和免疫抑制剂等。眼球挫伤治愈率97.12%,穿透伤93.18%,热烧伤66.67%。319例眼外伤治愈率94.67%好转5.33%,并对各种治疗方法进行了讨论。 相似文献
30.
杨世海 《华中科技大学学报(医学版)》1994,(4)
应用足叶乙甙与阿糖胞苷联合化疗方案治疗13例急性单核细胞白血病取得较好疗效,13例中完全缓解8例(61.5%),部分缓解3例(23.1%),总有效率达84.6%。文中对用药剂量及疗效进行了讨论。 相似文献