Improvement in Central Nervous System Functions During Treatment of Liver Failure with Albumin Dialysis MARS—A Review of Clinical,Biochemical, and Electrophysiological Data

The Molecular Adsorbent Recirculating System (MARS) is a nonbiological liver support method based on the principles of dialysis, filtration, and adsorption. It allows the safe and efficient removal of both albumin-bound and water-soluble toxic metabolites, including ammonia, aromatic amino acids, tryptophan, and related phenolic and indolic products, as well as benzodiazepines. A well-documented effect of the treatment is the improvement of the hemodynamic situation of decompensated chronic patients. Systemic vascular resistance, mean arterial pressure, cerebral blood flow, and cerebral oxygen consumption increased significantly. The degree of hepatic encephalopathy decreased significantly. Increased intracranial pressure could be normalized in both chronic and fulminant liver failure. In three randomized clinical trials significant improvement of survival could be demonstrated. In a model of murine neuronal networks cultured on multi-microelectrode array plates and incubated with plasma from liver failure patients, a normalization of the spike and burst pattern could be observed, if plasma samples from MARS-treated patients before and after treatment were compared. In conclusion, MARS significantly improves central nervous system functions. It can serve as a model for the further investigation of the role of protein-bound substances in hepatic encephalopathy and cerebral hemodynamics.     

Development and in vivo evaluation of chitosan nanoparticles for the oral delivery of albumin

Albumin is used as a plasma expander in critically ill patients and for several other clinical applications mainly via intravenous infusion. Oral administration of albumin can improve patient compliance although limited oral bioavailability of proteins is still a major challenge. Although nanomaterials have been extensively utilized for improving oral delivery of proteins, albumin has been utilized only as either a model drug or as a carrier for drug delivery. In the current study, for the first time, chitosan nanoparticles have been developed and extensively optimized to improve oral bioavailability of albumin as a therapeutic protein. Several characterizations have been performed for the albumin-loaded nanoparticles (e.g. drug encapsulation efficiency, DSC, FTIR, particle size, zeta potential, morphology, release kinetics, and enzymatic stability). Nanosized spherical particles were prepared and demonstrated high stability over three months either in a powdered form or as suspensions. Sustained release of albumin over time and high enzymatic stability as compared to the free albumin were observed. In vivo, higher serum concentrations of albumin in normal rabbits and cirrhotic rats were attained following oral and intraperitoneal administrations of the albumin-loaded nanoparticles as compared to the free albumin. The nanoparticles developed in the current study might provide efficient nanovehicles for oral administration of therapeutic albumin.     

Fluid distribution kinetics during cardiopulmonary bypass

OBJECTIVE:

The purpose of this study was to examine the isovolumetric distribution kinetics of crystalloid fluid during cardiopulmonary bypass.

METHODS:

Ten patients undergoing coronary artery bypass grafting participated in this prospective observational study. The blood hemoglobin and the serum albumin and sodium concentrations were measured repeatedly during the distribution of priming solution (Ringer''s acetate 1470 ml and mannitol 15% 200 ml) and initial cardioplegia. The rate of crystalloid fluid distribution was calculated based on 3-min Hb changes. The preoperative blood volume was extrapolated from the marked hemodilution occurring during the onset of cardiopulmonary bypass. Clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01115166","term_id":"NCT01115166"}}NCT01115166.

RESULTS:

The distribution half-time of Ringer''s acetate averaged 8 minutes, corresponding to a transcapillary escape rate of 0.38 ml/kg/min. The intravascular albumin mass increased by 5.4% according to mass balance calculations. The preoperative blood volume, as extrapolated from the drop in hemoglobin concentration by 32% (mean) at the beginning of cardiopulmonary bypass, was 0.6-1.2 L less than that estimated by anthropometric methods (p<0.02). The mass balance of sodium indicated a translocation from the intracellular to the extracellular fluid space in 8 of the 10 patients, with a median volume of 236 ml.

CONCLUSIONS:

The distribution half-time of Ringer''s solution during isovolumetric cardiopulmonary bypass was 8 minutes, which is the same as for crystalloid fluid infusions in healthy subjects. The intravascular albumin mass increased. Most patients were hypovolemic prior to the start of anesthesia. Intracellular edema did not occur.     

IMA在急性冠状动脉综合征中的诊断意义

目的：探讨ACB法检测急性冠脉综合征患者血清中IMA水平及联合检测IMA、CK、CK-MB、cTnI、LDH水平的诊断价值。方法：将80例急性冠脉综合征患者分为3组,不稳定性心绞痛组27例,ST段抬高型心肌梗死组25例,非ST段抬高型心肌梗死组28例,另选150例健康体检者为正常对照组,抽血检测其缺血修饰白蛋白（IMA）、肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）、肌钙蛋白I（cTnI）、乳酸脱氢酶（LDH）,对检测结果进行分析讨论。结果：急性冠状动脉综合征3组患者中IMA水平均明显高于正常对照组（P〈0．01）,IMA水平以不稳定性心绞痛组最高。各种心肌酶对诊断急性冠状动脉综合征的敏感性分别为：IMA88％、CK22％、CK-MB20％、cTnI32％、LDH28％;CK、CK-MB、cTnI、LDH,四者联合检测敏感性为52％;五者联合检测敏感性可达92％。结论：IMA在早期诊断急性冠脉综合征中具有临床应用价值。ACB法检测IMA对急性冠脉综合征的诊断明显优于其他传统酶类,联合检测则大大提高了急性冠脉综合征的确诊率,减少漏诊和误诊的发生。     

连续性静脉-静脉血液滤过对全身炎症反应综合征患者白蛋白代谢率的影响

目的 探讨连续性静脉-静脉血液滤过（CVVH）对全身炎症反应综合征（SIRS）患者Alb代谢率的影响.方法 回顾性分析2010年12月至2011年12月南京军区南京总医院收治的28例SIRS患者的临床资料.其中8例患者仅常规抗感染、对症治疗（对照组）;10例患者行血液滤过治疗,血液滤过置换量为2 000 mL/h（低容量组）;10例患者行血液滤过治疗,血液滤过置换量为4 000 mL/h（高容量组）.采用稳定性同位素示踪技术,向患者同时静脉输注两种稳定性同位素标记的苯丙氨酸：[1-13C]苯丙氨酸和d5-苯丙氨酸.采用气相色谱质谱联用仪的选择离子检测模式检测质荷比为192、194、197、218和219片段的峰面积.采用数学模型计算Alb合成率（FSR）和分解率（FBR）.多组比较采用单因素方差分析,组间比较采用LSD或Dunnett＇s T3检验.结果 对照组、低容量组和高容量组患者治疗前Alb FSR分别为5.8％±0.9％、5.7％±1.1％、5.7％±1.0％,3组比较,差异无统计学意义（F=0.04,P＞0.05）;治疗后Alb FSR分别为5.9％±0.8％、7.3％±0.9％、7.8％±1.1％,3组比较,差异有统计学意义（F=9.15,P＜0.05）.治疗后低容量组和高容量组患者Alb FSR均显著高于对照组患者（=3.40,3.96,P＜0.05）;低容量组和高容量组患者Alb FSR比较,差异无统计学意义（t=1.02,P＞0.05）.对照组、低容量组和高容量组患者治疗前Alb FBR分别为7.0％±1.2％、6.5％±0.9％、7.2％±1.2％,3组比较,差异无统计学意义（F =0.88,P＞0.05）;治疗后3组患者Alb FBR分别为6.9％±1.1％、6.2％±0.9％、7.4％±1.0％,3组比较,差异无统计学意义（F=2.82,P＞0.05）.结论 CVVH可调节SIRS患者蛋白代谢,能够提高Alb FSR,但不能降低Alb FBR.     

HIV/HCV重叠感染患者病情进展的相关因素研究

探讨HIV/HCV重叠感染患者病情进展的原因和影响预后的相关因素.选择HIV/HCV重叠感染患者这一特定人群,按照疾病进展分成艾滋病组(AIDS)和HIV感染组(free of AIDS),回顾性分析两组间免疫功能、HIV病毒载量、肝脏功能的差异,探讨可能影响病情进展的相关因素.艾滋病组与HIV感染组比较:艾滋病组患者的细胞免疫功能(CD 4T、CD 8T)均低于HIV感染组,差异非常显著(P＜0.001;P=0.003);HIV病毒载量在艾滋病组明显高于HIV感染组,差异显著(P=0.005);艾滋病组的肝脏功能(ALT、AST)明显高于HIV感染组(P值分别为0.043、0.002);蛋白合成指标(TP、ALB)艾滋病组较HIV感染组低下,差异非常显著(P＜0.001).以Logistic回归分析,CD 4T、感染时间和ALB是预测疾病进展的独立危险因素(P＜0.001).回归方程预测准确率为97.0%.HIV/HCV重叠感染可加快病情进展,ALB与CD 4T细胞数及感染时间是预测艾滋病病程进展的独立危险因素.     

肝纤康防治肝纤维化的实验研究

目的：观察肝纤康对小鼠实验性肝纤维化的防治作用及其机制。方法：采用四氯化碳（CCl4）复制小鼠肝纤维化模型,同时予以肝纤康灌胃治疗,观察小鼠血清丙氨酸氨基转移酶（ALT）、天门冬酸氨基转移酶（AST）、白蛋白（Alb）、肝组织羟脯氨酸（Hyp）含量及肝组织病理改变。结果：模型组小鼠ALT、AST、Hyp显升高,Alb显降低,肝纤维化病变明显;给药组ALT、AST、Hyp明显降低,Alb明显升高,与模型且比较差异有显性（P＜0．01或P＜0．05）;并能明显减轻小鼠肝细胞损害和胶原纤维增生的程度。结论：肝纤康有较好的保护肝功能和防治肝纤维化作用。     

血清胱抑素C和尿微量白蛋白/肌酐比值在原发性高血压肾损害早期诊断的临床意义*

目的探讨检测血清胱抑素C(CysC)和尿微量白蛋白/肌酐比值(m Alb/Cr,ACR)对诊断高血压早期肾损害的临床价值。方法选取原发性高血压血肌酐(Cr)正常患者290例,检测血清CysC及尿ACR,将CysC、尿ACR与CysC与尿ACR组合比较检测阳性率。结果血清CysC对高血压早期肾损害诊断高于尿ACR,血清CysC联合尿ACR组合诊断高血压早期肾损害显著高于单一检测。结论血清CysC对诊断高血压早期轻度肾损害具有较高诊断价值,联合尿ACR能进一步提高对高血压早期肾功能损害的诊断。     

Pharmacokinetics of protein and peptide conjugates

Protein and peptide conjugates have become an important component of therapeutic and diagnostic medicine. These conjugates are primarily designed to improve pharmacokinetics (PK) of those therapeutic or imaging agents, which do not possess optimal disposition characteristics. In this review we have summarized preclinical and clinical PK of diverse protein and peptide conjugates, and have showcased how different conjugation approaches are used to obtain the desired PK. We have classified the conjugates into peptide conjugates, non-targeted protein conjugates, and targeted protein conjugates, and have highlighted diagnostic and therapeutic applications of these conjugates. In general, peptide conjugates demonstrate very short half-life and rapid renal elimination, and they are mainly designed to achieve high contrast ratio for imaging agents or to deliver therapeutic agents at sites not reachable by bulky or non-targeted proteins. Conjugates made from non-targeted proteins like albumin are designed to increase the half-life of rapidly eliminating therapeutic or imaging agents, and improve their delivery to tissues like solid tumors and inflamed joints. Targeted protein conjugates are mainly developed from antibodies, antibody derivatives, or endogenous proteins, and they are designed to improve the contrast ratio of imaging agents or therapeutic index of therapeutic agents, by enhancing their delivery to the site-of-action.