Estimated Glomerular Filtration Rate —A More Stable Indicator than Creatinine Clearance in Peritoneal Dialysis Practice

Objective: The usefulness of estimated glomerular filtration rate may not be restricted to pre-dialysis patients, since we reported that estimated glomerular filtration rate was well correlated with measured total creatinine clearance in peritoneal dialysis patients. To clarify the clinical usefulness of estimated glomerular filtration rate as a parameter for peritoneal dialysis adequacy, we retrospectively surveyed estimated glomerular filtration rate and total creatinine clearance in peritoneal dialysis patients treated at JA Toride Medical Center.Patients and Methods: A total of 114 data sets of estimated glomerular filtration rate and total creatinine clearance from 21 PD patients treated at JA Toride Medical Center were collected from November 2010 to October 2011. The patients consisted of 15 men and six women with an average age of 66.6 ± 12.6 years (46–95 years old). The average number of samples was 5.4 ± 1.5 (2 to 7) per patient.Results: The collected data showed less correlation of estimated glomerular filtration rate and total creatinine clearance (r. = 0.435) than that of a previous cross-sectional study (r. = 0.836). As reported in pre-dialysis patients, the differences between estimated glomerular filtration rate and total creatinine clearance were correlated with total creatinine excretion in urine and PD effluent (r. = 0.821). The differences were also correlated with normalized protein catabolic rate, which was one of the main determinant factors for total creatinine excretion (r. = 0.636). A similar tendency was apparently observed in one patient with poor compliance to diet therapy and fluctuating dietary intake. From the analysis of these data, serum creatinine seemed to fluctuate less possibly due to compensatory capacity of the residual renal function in small solute clearance.Conclusions: Consequently, estimated glomerular filtration rate was turned out to be a more stable parameter than total creatinine clearance, which might be a desirable feature in long-term follow-up of peritoneal dialysis patients.     

围产期子痫前期B型钠尿肽与肌酸激酶MB同工酶的对照分析

目的研究B型钠尿肽(BNP)与肌酸激酶MB同工酶(CK-MB)在围产期子痫前期病情评估中的作用。方法回顾性分析82例孕妇临床资料,其中健康孕妇25例(A组)、轻度子痫前期患者18例(B组),未并发肺水肿的重度子痫前期患者22例(C组),并发心力衰竭肺水肿重度子痫前期患者17例(D组),检测产前6h内(T0)及产后6h内(T1)、产后24～36h内(T2)所测BNP、CK-MB浓度,并进行统计学分析。结果在T1时C组患者的BNP、CK-MB均高于A组和B组,差异均有统计学意义(t分别=6.50、6.54、3.73、2.46,P均<0.05);而D组患者较C组更高,差异均有统计学意义(t分别=7.38、3.69,P均<0.05)。线性相关性分析显示:C、D组T1时的CK-MB与BNP之间呈正相关(r分别=0.70、0.85、P均<0.05)。在T0时,D组患者的BNP、CK-MB均高于C组,差异均有统计学意义(t分别=11.61、3.43,P均<0.05),C组患者的BNP均高于A组和B组,差异均有统计学意义(t分别=6.99、6.60,P均<0.05),但A、B、C组间的CK-MB比较,差异均无统计学意义(t分别=0.47、1.30、0.74,P均>0.05)。结论 BNP及CK-MB可用于围产期子痫前期患者的病情评估,BNP的敏感性更优于CK-MB。     

Inositol hexakisphosphate kinase-2 determines cellular energy dynamics by regulating creatine kinase-B

Inositol hexakisphosphate kinases (IP6Ks) regulate various biological processes. IP6Ks convert IP6 to pyrophosphates such as diphosphoinositol pentakisphosphate (IP7) and bis-diphosphoinositol tetrakisphosphate (IP8). IP7 is produced in mammals by a family of inositol hexakisphosphate kinases, IP6K1, IP6K2, and IP6K3, which have distinct biological functions. The inositol hexakisphosphate kinase 2 (IP6K2) controls cellular apoptosis. To explore roles for IP6K2 in brain function, we elucidated its protein interactome in mouse brain revealing a robust association of IP6K2 with creatine kinase-B (CK-B), a key enzyme in energy homeostasis. Cerebella of IP6K2-deleted mice (IP6K2-knockout [KO]) produced less phosphocreatine and ATP and generated higher levels of reactive oxygen species and protein oxidative damage. In IP6K2-KO mice, mitochondrial dysfunction was associated with impaired expression of the cytochrome-c1 subunit of complex III of the electron transport chain. We reversed some of these effects by combined treatment with N-acetylcysteine and phosphocreatine. These findings establish a role for IP6K2–CK-B interaction in energy homeostasis associated with neuroprotection.

Inositol pyrophosphates are versatile messenger molecules that mediate a variety of cellular functions, including cell growth, apoptosis, endocytosis, and cell differentiation. The most extensively studied inositol pyrophosphate, diphosphoinositol pentakisphosphate (IP7), displays a 5′-diphosphate (1, 2). IP7 is generated in mammals by a family of inositol hexakisphosphate kinases (IP6Ks) (3, 4). IP6Ks exists in three isoforms: IP6K1, IP6K2, and IP6K3. Inositol hexakisphosphate kinase-2 (IP6K2) sensitizes cells to apoptosis (5, 6). Mice with targeted deletion of IP6K2 display an increased incidence of aero-digestive tract carcinoma (7). Cell survival associated with heat shock protein 90 also involves IP6K2 (8, 9).We previously reported a major role for IP6K2 in the disposition of cerebellar granule cells as well as Purkinje cell morphology and motor coordination. The influence of IP6K2 upon cerebellar disposition involved protein 4.1N, both of which were highly expressed in cerebellar granule cells (10).To further assess the functions of IP6K2 in the brain, we explored its binding partners using coimmunoprecipitation and tandem liquid chromatography mass spectrometry (LC-MS/MS). Here, we report that IP6K2 robustly interacts with creatine kinase-B (CK-B), which regulates energy homeostasis of cells and exists in two forms, brain type (CK-B) and muscle type (CK-M). CK catalyzes the reversible transfer of the phosphate group of phosphocreatine to ADP to yield ATP (11, 12). A functional interplay between mitochondrial and cytosolic isoforms of CK regulates cellular energy homeostasis. Cytosolic CK rephosphorylates locally produced free ADP and increases creatine globally, while the mitochondrial enzyme catalyzes the conversion of creatine to phosphocreatine utilizing mitochondrial ATP (13–15).Here, we show that IP6K2 loss leads to decreased CK-B expression, reduced ATP levels, and diminished mitochondrial activity associated with increased oxidative stress. About 80 to 90% of ATP is generated in the mitochondria by oxidative phosphorylation, and diminished ATP levels are the immediate effect of mitochondrial dysfunction. Loss of IP6K2 and CK-B reflects the suppression of the mitochondrial cytochrome c1 expression, a component of complex III of the mitochondrial electron transport chain. In the present study, we report a physiologic association of CK-B and IP6K2, whose disruption impacts mitochondrial functions.Dendritic morphogenesis was reduced in IP6K2-deficient neurons and was rescued by restoring normal levels of ATP. These observations reveal an essential role of IP6K2 in the energy production of the brain. Our findings indicate that IP6K2 is a key regulator of mitochondrial homeostasis which promotes neuroprotection.     

非体外循环冠状动脉旁路移植术围术期cTnI、CK及CK-MB的变化

目的 :通过对非体外循环冠状动脉旁路移植术 （OPCABG）患者 ,围手术期血清心肌肌钙蛋白 I（c Tn I）、肌酸磷酸激酶 （CK）、肌酸磷酸激酶同工酶 MB（CK- MB）变化的观察 ,探讨 OPCABG围手术期心肌损伤的情况。方法 :选择 2 0例全麻常温下进行 OPCABG患者及 2 0例同期行肺叶切除术患者 （对照组 ） ,麻醉诱导气管插管后以微量输液泵持续输注异丙酚、利多卡因复合液 ,并间断静脉注射芬太尼和哌库溴铵维持麻醉。在麻醉诱导前、术后 1h、2 4h、4 8h4个时间点抽取血样测定 c Tn I、CK、CK- MB值。结果 :所有患者手术经过及术后恢复顺利 ,OPCABG组无一例转为体外循环。两组患者术前 CK、CK- MB均在正常范围 ,术后 1h开始升高 ,术后 2 4 h达峰值 ,与麻醉前比较 ,均 P<0 .0 1;术后 4 8h明显下降 ,但仍高于麻醉前水平 （P<0 .0 1）。 4个时间点两组 CK、CK- MB值相比 ,差异无显著性。OPCABG组 c Tn I值与术前比较 ,术后 1h开始升高 （P<0 .0 1） ,2 4 h达峰值 （P<0 .0 1） ,术后 4 8h有所下降 ,但仍高于麻醉前水平 （P<0 .0 1） ;而肺叶切除组术后 c Tn I值始终不高。术前、术后 1h两组 c Tn I值差异无显著性 ,但 OPCABG组术后 2 4 h、4 8h值均明显高于肺叶切除组 （P<0 .0 1）。手术全程及术后 4 8h动态心电图未发现心肌梗死 ,血?     

Myoglobin and creatine kinase rates of release during acute myocardial infarction

The release of cardiac enzymes as an index of infarct size (IS) development was studied in patients with acute myocardial infarction (AMI) treated at a coronary care unit. Serial determinations of serum myoglobin (MG) and creatine kinase (CK) were made on 34 consecutive patients with duration of symptoms less than 6 h at admission and with initial CK values below the upper reference limit. Computer-calculated CK-IS was determined on the basis of the log-normal algorithm. This was compared to discretely calculated CK and MG release. The correlation between computer- and discretely calculated cumulated CK release was 0.995 with a regression close to the line of equivalence. Computer-calculated CK rates of release showed a one-peak development, while, when discretely calculated, mostly three or four peaks were observed, as found also for MG rates of release. The occurrence of MG and CK peaks was related as indicated by a correlation coefficient of 0.75. The initial CK rate of release was slower when computer-calculated. In the group studied, CK release began about 3 h post onset of symptoms, at which time 56% had an MG value above the upper reference limit. The CK and MG releases were finished about 31 and 36 h post onset of symptoms, respectively, with MG peaks at 6, 11, 19, and 22 h with corresponding CK peaks delayed 2, 3, 3, and 9 h. The first MG and CK peaks represented between 30 and 40% of the total release while the following three peaks represented between 20 and 30% each. Cumulative MG release was correlated to the time of AMI development. No such correlation was found for CK. The results indicate that the development of AMI is a wavelike process not sufficiently described by the log-normal algorithm, on the basis of which, however, an index of total release might be obtained.     

不同剂量磷酸肌酸钠对病毒性心肌炎患儿T淋巴细胞亚群及炎症因子的影响

目的：探讨不同剂量磷酸肌酸钠对儿童病毒性心肌炎T淋巴细胞亚群及血清炎症因子的影响。方法：选取我院2016年5月至2017年4月收治的90例病毒性心肌炎患儿,随机分为高剂量组、中剂量组和低剂量组各30例;选取30例同期在我院体检健康儿童作为对照组。高剂量组、中剂量组和低剂量组分别采用1.5 g、1.3 g和1.0 g磷酸肌酸钠静脉滴注,每日1次,疗程2~3周,治疗14 d后比较三组患儿的临床疗效、T淋巴细胞亚群及血清炎症因子水平。结果：高剂量组总有效率为96.67%,中剂量组的总有效率为90.00%,高于低剂量组的76.67％（P<0.05）;高、中、低三个剂量组患儿治疗后的T淋巴细胞亚群及血清炎症因子水平改善情况均高于治疗前（P<0.05）。治疗后,三组患儿CD4+、CD8+、IL-6、IL-8、TNF-α水平比较差异有统计学意义（P均<0.05）。高剂量组、中剂量组患儿的T淋巴细胞亚群水平高于低剂量组（P<0.05）;高剂量组、中剂量组患儿的IL-6、IL-8和TNF-α等血清炎症因子水平高于低剂量组（P<0.05）。结论：磷酸肌酸钠对病毒性心肌炎患儿T淋巴细胞亚群及血清炎症因子水平的影响与治疗剂量呈正相关关系且具有良好的安全性。     

肌酸化学交换饱和转移加权成像评估大鼠胶质瘤模型肌酸浓度变化

目的 观察肌酸化学交换饱和转移（Cr-CEST）成像评估大鼠胶质瘤Cr浓度的价值。方法 对浓度10 mmol/L的单一Cr试管模型及浓度20、40、60、80、100 mmol/L的混合Cr试管模型（pH均为7.0）行CEST扫描,以优化Cr-CEST成像参数,并计算Cr试管的Cr-CESTR值,观察Cr-CEST效应。将C6胶质瘤细胞接种至8只SD大鼠右侧基底节区,制备脑胶质大鼠模型。于造模后2~3周以优化参数采集Cr-CEST图像,比较肿瘤区域与对侧正常脑组织Cr-CESTR值差异。结果 于单一Cr试管模型Z谱频率2.0 ppm处见明显波谷,提示存在Cr-CEST效应,且B1值为0.5~3.0 μT时,Cr-CEST效应随B1值升高而升高,而B1值增高至5.0 μT后Cr-CEST效应减弱。混合Cr试管模型Z谱显示Cr-CEST效应随Cr浓度升高而增强。大鼠胶质瘤病灶区域Cr-CESTR值[0.098（0.012,0.393）%]低于对侧正常脑组织[3.499（3.072,3.656）%,Z=-3.361,P<0.001]。结论 Cr-CEST成像有助于评估大鼠脑胶质瘤模型Cr浓度变化,有望为活体检测脑内Cr代谢提供新方法。