生理模型同时预报普鲁卡因胺及其代谢物乙酰普鲁卡因胺在大鼠体内处置动力学

用生理模型同时对iv普鲁卡因胺(PA)后,PA及其代谢产物乙酰普鲁卡因胺(NAPA)在大鼠体内处置动力学进行预报。测定了所需的有关PA参数.结果PA在大鼠血液、肝和肾脏清除率分别为47.28,13.56和33.71 ml·kg^-1·min^-1。估算的组织/血液药物浓度比表明,心、肝、肾、肌肉和小畅对PA的亲和力大于血液成分。对大鼠iv PA后,PA及其NAPA在组织中浓度进行预报,并与实验结果比较。结果大多数组织中浓度预报值与观察值基本—致。同时对PA及其NAPA在人血浆中浓度进行了预报。     

紫杉醇药物涂层支架植入术后患者外周血单核细胞中热休克蛋白70的变化：生物材料临床应用近期效果随访

目的:植入材料、靶血管病变特征、术前状态、炎症因子及急性期蛋白均对急性冠状动脉综合征接受支架材料介入治疗后的效果有影响,为验证紫杉醇涂层支架临床应用后材料及宿主的相关反应,实验观察了接受紫杉醇涂层支架介入治疗的急性冠状动脉综合征患者的外周血热休克蛋白70水平变化,并分析其临床意义。方法:①连续性入选2004-12/2006-03在江苏大学附属人民医院行经皮冠状动脉介入治疗的78例急性冠状动脉综合征患者,全部病例均置入紫杉醇药物涂层支架。采用流式细胞仪测定症状发作平均(34.1±16.2)h的外周血单核细胞热休克蛋白70阳性表达水平。②所有患者随访至术后6个月,出现心源性死亡、再次心肌梗死、再发心绞痛、再次血运重建术和继发心衰等主要心脏不良事件者为近期预后不良组,无上述情况者判定为近期预后良好组,用logistic多元回归法分析术前状态、靶血管病变特征、植入支架的各项参数及外周血热休克蛋白70水平与主要心脏不良事件发生率的关系,并以同期健康体检者20例为正常对照组。结果:68例患者完成随访进入结果分析。①外周血热休克蛋白70水平:急性心肌梗死患者和不稳定型心绞痛患者比较差异无统计学意义(P>0.05),但均显著高于正常对照组(P<0.05)。②在多变量的logistic回归分析中,外周血热休克蛋白70独立于其危险因素,能预测急性冠状动脉综合征患者经皮冠状动脉介入治疗后近期主要心脏不良事件发生率(OR值为0.904,P<0.05)。结论:回归分析结果提示,应用紫杉醇涂层支架临床治疗近期效果评估中,外周血热休克蛋白70水平高的急性冠状动脉综合征患者近期心脏事件发生率较高,说明外周血热休克蛋白70可能成为判断紫杉醇涂层支架介入治疗后不良事件发生率的独立因素之一。     

Characteristics of a donor population in western Venezuela

To determine the characteristics of blood donors in western Venezuela, we collected data from 1983 to 1985 on 31,320 volunteer donors at the Blood Bank of the State of Zulia in Maracaibo. Fifty-nine percent of the donors were blood group O, 30 percent were group A, 9 percent were group B, and 2 percent were group AB. Most of the donors (93%) were Rh positive. One percent of donors had positive reactions to hepatitis B surface antigen, 3.15 percent for syphilis, 1.43 percent for antibodies to Trypanosoma cruzi, and 0.32 percent to human immunodeficiency virus antibodies. About one-half of the donors were between 18 and 30 years old, and only 10 percent were women. To determine if iron deficiency anemia was a cause for the small size of the female donor pool, we measured serum ferritin in 50 first-time female donors. Ten of these (20%) had serum ferritin values below normal, and the distribution of serum ferritin levels of all 50 was very similar to that reported for frequent donors in Europe and the United States, with a clustering of ferritin values between 10 and 70 ng per ml. The data indicate that blood donors in western Venezuela are markedly different from those in the United States and that iron supplementation may be indicated for female Venezuelan donors.     

Attitude of the Omani population toward organ transplantation

Transplantation from deceased donors is still scarce in Oman, mainly due to family refusal. We conducted a survey to learn the attitudes of the Omani population regarding transplantation. SUBJECTS AND METHODS: Among 500 individuals who were distributed, a questionnaire 304 responded including 247 (81%) Omani and 57 (19%) foreign residents. There were 213 (70%) male respondents of the 304 subjects, 256 individuals (84%) were between 18 and 50 years of age, and 270 (89%) had at least a high school education. RESULTS: Thirty-eight percent and 32% of Omani individuals had a family member or a friend with kidney disease or a renal transplantation, respectively. Only 42% of respondents knew that renal transplantation is performed in Oman. It was encouraging to note that 65% of Omanis knew that commercial transplantations are against Islamic and international standards. Sixty-four percent of the respondents stated that they would donate a kidney to a relative with renal failure. Nevertheless, only 49% knew that donation after death is permitted by Islam; 42% respondents would accept a kidney from a deceased person. Only 35% would donate a kidney or an organ after death. We concluded that the awareness of the Omani people toward donation after death is low, with a great need for public education and awareness programs, particularly for high school and university students.     

Differential toxicity profile of ricin isoforms correlates with their glycosylation levels

Ricin is one of the most potent and deadly plant toxins from the seeds of Ricinus communis. In view of its high toxicity, ricin is being used as an immunotoxin in cancer therapy. Ricin also has several isoforms with differential glycosylation depending on the seed variety. Our study shows three isoforms designated 1, 2 and 3, which differed in their surface charge, resulting in a different behavior on cation exchange chromatography, two dimensional (pI 5.5-8.7) and native PAGE. The molecular masses of isoform-1, 2 and 3 were measured as 63.55 kDa, 64.03 kDa and 62.8 kDa, respectively, by MALDI-TOF/MS. In vitro studies with monkey kidney (Vero) cells showed a time dependent increase in cytotoxicity of the isoforms evaluated by extracellular lactate dehydrogenase activity and mitochondrial dehydrogenase assay. These isoforms also induce oxidative stress and DNA damage. Among the isoforms, isoform-3 was quick to generate reactive oxygen species (ROS), (in 90 min) and exhibited maximum cytotoxicity. Morphological changes, catalase activity and DNA fragmentation were significantly higher with isoform-3 treatment compared to others. The glycosylation studies by MALDI-TOF/MS showed that isoform-3 is highly glycosylated with high sugar levels containing more of hybrid/complex type glycopeptides with mannose as hexose units. These experimental evidences clearly suggest that isoform-3 is superior in its early ROS generation, potency to induce oxidative stress and cytotoxicity, that could be due to it's higher glycosylation levels which make isoform-3 as an ideal candidate for immunotoxin studies.     

Preparation and biological evaluation of 111In-, 177Lu- and 90Y-labeled DOTA analogues conjugated to B72.3

Three 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA) analogues were evaluated for relative in vivo stability when radiolabeled with (111)In, (90)Y and (177)Lu and conjugated to the monoclonal antibody B72.3. The DOTA analogues evaluated were "NHS-DOTA" [N-hydroxysuccinimdyl (NHS) group activating one carboxylate], "Arm-DOTA" (also known as MeO-DOTA; with a p-NCS, o-MeO-benzyl moiety on the methylene group of one acetic acid arm) and "Back-DOTA" (with a p-NCS-benzyl moiety on a backbone methylene group of the macrocycle). The B72.3 was conjugated to the DOTA analogues to increase the retention time of the radioloabeled conjugates in vivo in mice. The serum stability of the various radiometalated DOTA conjugates showed them to have good stability out to 168 h (all >95% except (111)In-NHS-DOTA-B72.3, which was 91% stable). Hydroxyapatite stability for the (111)In and (177)Lu DOTA-conjugates was >95% at 168 h, while the (90)Y DOTA-conjugates were somewhat less stable (between 90% and 95% at 168 h). The biodistribution studies of the radiometalated DOTA-conjugates showed that no significant differences were observed for the (111)In and (177)Lu analogues; however, the (90)Y analogues showed lower stabilities, as evidenced by their increased bone uptake relative to the other two [2-20% injected dose per gram (% ID/g) for (90)Y and 2-8% ID/g for (111)In and (177)Lu]. The lower stability of the (90)Y analogues could be due to the higher beta energy of (90)Y and/or to the larger ionic radius of Y(3+). Based on the bone uptake observed, the (177)Lu-NHS-DOTA-B72.3 had slightly lower stability than the (177)Lu-Arm-DOTA-B72.3 and (177)Lu-Back-DOTA-B72.3, but not significantly at all time points. For (90)Y, the analogue showing the lowest stability based on bone uptake was (90)Y-Arm-DOTA-B72.3, perhaps because of the metal's larger ionic radius and potential steric interactions minimizing effective complexation. The (111)In analogues all showed similar biological distributions at the various time points. This study suggests that care must be taken when evaluating (90)Y-labeled antibodies and in using NHS-DOTA-antibody conjugates with (177)Lu. All evaluations should be extended to time points relevant to the half-life of the radiometal and the therapy applications.     

Donor gender balance in a living-related kidney transplantation program in Oman

It has been observed in several Eastern and Western countries that there is a gender imbalance among kidney donors. In the international experience, approximately 65% of live kidney donors have been women. We retrospectively studied the distribution of female and male donors or recipients among living kidney transplantations performed from 1980 to 2005, namely 198 Omani recipients of living-related kidney transplantations. To examine cultural influences, transplantations performed or expatriates were excluded from the study. For the whole period, 98 out of 198 donors (49.5%) were women. The number of female recipients 75 of 198 (38%) versus males were 123 (62%) recipients. We then subdivided the period into three intervals: 1980 to 1990, 1991 to 2000, and 2001 to 2005. The numbers of female donors for these three periods were 29 of 64 (45%), 42 of 89 (47%), and 27 of 45 (60%), respectively. There was a persistent preponderance of male recipients ranging from 58% to 66% during these periods. We concluded that there was no gender imbalance for kidney donors. Nevertheless, there was a male preponderance in the recipient group.