The effect of two additive solutions on the postthaw storage of RBCs

BACKGROUND: Sterile systems for freezing and for washing thawed blood will allow the storage of RBCs for more than 24 hours after removal of the cryoprotectant glycerol. This study assessed the effect of two ASs in maintaining deglycerolized RBCs. STUDY DESIGN AND METHODS: Twenty-four RBC units were stored for 6 days, pooled in groups of 4, realiquoted, sterilely glycerolized, and frozen. One month later, the units were thawed, sterilely deglycerolized by using an automated system (H215; Haemonetics), and stored for 5 weeks in either 100 or 200 mL of AS-3 or an experimental AS (EAS-61). Sterile samples were taken weekly for chemical and morphometric analysis. RESULTS: The glycerolization and deglycerolization process produced highly comparable RBC units, but it caused a marked reduction of RBC pH, to about 6.4 at the beginning of storage. The addition of acidic AS-3 further reduced the pH, which in turn reduced glucose consumption, lactate formation, and RBC ATP concentrations. Alkaline EAS-61 increased these measures. Hypotonic EAS-61 caused increased cell swelling and hemolysis, despite better RBC morphology. CONCLUSIONS: Automation of sterile glycerolization and deglycerolization with the H215 works well, but the solutions should be reformulated for extended postthaw storage. This would best be accomplished by raising the pH of the wash solutions by the addition of disodium phosphate or sodium bicarbonate or both, by using alkaline ASs, and by matching the osmolality of the wash solution and ASs.     

Extrapolation: Experience gained from original biologics

Biologicals undergo modifications throughout their commercial lifecycle. Major changes can unintentionally magnify their inherent physicochemical variability. Although trials comparing the pre- and the post-change versions have been requested occasionally, analytical comparison is the most sensitive approach to anticipating clinical equivalence. Therefore, it may be concluded, by means of ‘extrapolation’, that non-identical versions of a given biologic will behave equally in all indications. Despite the lessons learned with original biologics, there are still controversies around the approval of biosimilars through extrapolation. Here, a comprehensive analysis of scattered information allows for an account of cases of original biologic versions approved in some indications with no patient trials involved. Healthcare professionals can be reassured that inasmuch as extrapolation has proven valid for new versions of original biologics, the same holds for biosimilars.     

Tissue-specific activating mutations of Ha- and Ki-ras oncogenes in skin, lung, and liver tumors induced in mice following transplacental exposure to DMBA

Transplacental carcinogenesis represents a good model in which to study the involvement of tissue-specific oncogene activation in carcinogenesis because a single exposure to a carcinogen induces tumors at various sites. We tested tumors of the skin, liver, and lung produced in mice after transplacental 7,12-dimethylbenz[a]-anthracene (DMBA) exposure for possible activation of ras genes. XbaI restriction fragment-length polymorphism analysis has shown that exposure to DMBA in utero may result in appearance of A----T transversion at the second position of codon 61 of Ha-ras oncogene in skin and liver tumors but not in lung tumors. Moreover, DNA samples isolated from spontaneous and DMBA-induced lung and liver tumors were analyzed for mutations at the same position of Ki-ras oncogene using differential hybridization with specific oligonucleotides. Among five spontaneous lung tumors, three cases of A----G transition, and one case of A----T transversion were found, whereas four of ten lung tumors of DMBA-treated animals were positive for A----T mutation. No Ki-ras mutation was detected in one spontaneous and four DMBA-induced hepatomas. In two cases, we revealed Ki-ras A----T mutation in the lung tumor and Ha-ras mutation in the liver tumor taken from the same animal. These results indicate first that DMBA treatment may induce A----T mutation at the second position of codon 61 both in Ha-ras and in Ki-ras and, second, that the role of different activated oncogenes in carcinogenesis may differ, depending on the tissue in which the tumor develops.     

急性冠脉综合征患者血小板表面活化标志的研究

目的通过与血管内皮损伤标志物进行对比分析,探讨流式细胞术(FCM)测定血小板表面活化标志物在急性冠脉综合征(ACS)患者中的意义。方法应用FCM测定36例ACS患者药物治疗前后外周血中血小板糖蛋白(CD62p)和血小板质膜蛋白(CD61)的表达水平,用酶联免疫吸附试验(ELISA)测定血浆假性血友病因子(vWF),并对两者在ACS时的变化作对比分析。20例健康体检者作对照组。结果CD62p在ACS患者的表达明显高于正常人(P<0·05),药物干预治疗后明显下降(P<0·05),其水平的变化与vWF、心绞痛和心电图缺血ST-T的改善相一致。CD61在ACS患者的表达与正常人的表达无显著性差异(P>0·05),药物干预治疗后变化不明显(P>0·05)。结论CD62p是血小板活化的敏感指标,并与vWF、临床疗效有很好的相关性;FCM是检测血小板活化功能准确可靠的方法。     

清热利湿通络法对痛风性关节炎模型大鼠Cyr61、IL-1β表达的影响

目的:探讨Cyr61在痛风炎性微环境中的作用同时观察清热利湿通络法对痛风性关节炎模型大鼠Cyr61及IL-1β表达的影响。方法:将经典痛风性关节炎模型大鼠造模后采用随机数表法分为空白组、模型组、虎杖组、清热利湿组、通络组、秋水仙碱组和慢病毒组。造模72h后取材,随后运用RT-PCR技术检测大鼠滑膜组织中Cyr61、IL-1βmRNA变化;Western blot法检测大鼠滑膜组织中Cyr61蛋白表达变化;ELISA法检测大鼠血清中IL-1β含量。结果:与正常组比较,模型组Cyr61 mRNA和蛋白及IL-1βmRNA表达均显著升高(P<0.05,P<0.01),干扰Cyr61表达后,慢病毒组IL-1βmRNA表达显著降低(P<0.05);与模型组比较,虎杖组Cyr61mRNA和蛋白表达、血清IL-1β含量显著降低(P<0.05,P<0.01);清热利湿组Cyr61蛋白表达水平、血清IL-1β含量显著降低(P<0.01,P<0.05),通络组Cyr61蛋白表达显著降低(P<0.01)。结论:Cyr61作为一种重要的促炎症因子参与GA的炎症过程,清热利湿通络法可通过下调Cyr61及IL-1β的表达水平,拮抗急性痛风炎症。     

Posttransplant Lymphoproliferative Disorder in Kidney and Liver Transplant Recipients: A Single-Center Experience

Introduction

Posttransplant lymphoproliferative disorder (PTLD) is a heterogeneous group of lymphoid malignant neoplasms arising after solid organ transplantation or hematopoietic stem cell transplantation. The current World Health Organization classification identified 4 basic histologic types of PTLD: early, polymorphic variant, monomorphic variant, and classical Hodgkin lymphoma-type lesions.

24-hour Arterial Stiffness Monitoring in Kidney Transplant Recipients in the Early Postoperative Period

Introduction

Laboratory tests and anthropometric assessments are essential in determining the risk for cardiovascular disease in patients after kidney transplantation (KTx). Patients with hypertension and elevated pulse wave velocity (PWV) are at a higher risk of cardiovascular mortality. The purpose of this study was to determine the role of blood pressure, arterial stiffness, and selected laboratory and anthropometric parameters in estimating the risk of cardiovascular disease in KTx patients.

Risk factors for metabolic syndrome after liver transplantation: A systematic review and meta-analysis

Introduction

Metabolic syndrome is associated with increased risk of cardiovascular events, which contributes to the elevated mortality rate among liver transplant recipients. The objective of this systematic review and meta-analysis was to assess the prevalence and risk factors for metabolic syndrome after liver transplantation.