人参Ｒb组皂苷对犬实验性心肌梗死的保护作用

目的：研究人参Ｒb组皂苷对犬实验性心肌缺血的保护作用。方法：通过结工冠状动脉前降支（ＬＤＡ）产生急性心肌梗死模型,从心肌梗死面积（ＭＩＳ）及血清酶学变化观察人参Ｒb组皂苷的抗心肌缺血作用,并从心肌代谢及自由基损伤等角度分析其可能的作用机制。结果人参Ｒb组皂苷２５,５０mg/kg经十二指肠给药,对ＬＡＤ急悸阻断６h犬,能明显缩小ＭＩＳ,降低血清肌酸磷酸激酶（ＣＫ）及乳酸脱氢酶（ＬＤＨ）活性,亦能明显降低血清游离脂肪酸（ＦＦＡ）及过氧化脂质（ＬＰＯ）含量,提高超氧化物歧化酶（ＳＯＤ）活性。结论：人参Ｒb组皂苷对急性缺血心肌产生明显保护作用,作用机制可能与其纠正心肌缺血时ＦＦＡ代谢紊乱及对抗氧自由基引发的脂质过氧化反应,增强体内抗氧化酶活性等有关。     

间断温血灌注对供心代谢及酶的影响

在１２次猪的心脏移植实验中，供心的保护分两组，Ⅰ组供心用冷晶体停搏液灌注，Ⅱ组用温血灌注，在供心取出前及主动脉开放１５ｍｉｎ后对心肌代谢及酶学的有关指标进行监测。Ⅰ组心肌氧耗率明显低于正常，而Ⅱ组与正常无明显差异。心肌氧耗率下降程度Ⅰ组明显高于Ⅱ组。心肌糖耗率及冠状动静脉ｐＨ、磷酸肌酸激酶同功酶差值两组均与正常无明显差异。本实验结果提示间断温血停搏对心肌的保护作用与冷晶体停搏相似，但对于心肌代谢功能的恢复则优于后者。     

心肌肌钙蛋白I检测在重症肺炎儿童心肌损害中价值探讨

目的：探讨小儿重症肺炎并发心肌损害中心肌钙蛋白I（cardiac troponin I,cTnI）的测定及其意义。方法选取重症肺炎患儿200例为观察组,轻症肺炎患儿180例为轻症组,正常儿童200例为对照组,对比3组儿童cTnI水平、肌酸激酶同工酶（creatine kinase MB,CK-MB）水平。结果观察组 cTnI、CK-MB、肌酸激酶（creatine kinase,CK）、乳酸脱氢酶（lactate dehydrogenase,LDH）及天冬氨酸转氨酶（aspartate amino-transferase,AST）水平高于轻症组（P＜0．05）,观察组和轻症组 cTnI、CK-MB、LDH、AST水平高于对照组（P＜0．05）。观察组 cTnI阳性率高于轻症组（P＜0．05）。观察组与轻症组CK-MB阳性率差异无统计学意义（P＞0．05）。结论重症肺炎患儿多伴有不同程度的心肌损害,cTnI可作为监测心肌损伤的重要标志物。早期检测 cTnI有利于重症肺炎并发心急损害患儿的早期诊疗,从而预防心肌衰竭发生。     

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 berestricted to pre-dialysis patients, since we reported that estimated glomerularfiltration rate was well correlated with measured total creatinine clearance in peritonealdialysis patients. To clarify the clinical usefulness of estimated glomerular filtrationrate as a parameter for peritoneal dialysis adequacy, we retrospectively surveyedestimated glomerular filtration rate and total creatinine clearance in peritoneal dialysispatients treated at JA Toride Medical Center.Patients and Methods: A total of 114 data sets of estimated glomerularfiltration rate and total creatinine clearance from 21 PD patients treated at JA TorideMedical Center were collected from November 2010 to October 2011. The patients consistedof 15 men and six women with an average age of 66.6 ± 12.6 years (46–95 years old). Theaverage number of samples was 5.4 ± 1.5 (2 to 7) per patient.Results: The collected data showed less correlation of estimated glomerularfiltration rate and total creatinine clearance (r. = 0.435) than that of a previouscross-sectional study (r. = 0.836). As reported in pre-dialysis patients, the differencesbetween estimated glomerular filtration rate and total creatinine clearance werecorrelated with total creatinine excretion in urine and PD effluent (r. = 0.821). Thedifferences were also correlated with normalized protein catabolic rate, which was one ofthe main determinant factors for total creatinine excretion (r. = 0.636). A similartendency was apparently observed in one patient with poor compliance to diet therapy andfluctuating dietary intake. From the analysis of these data, serum creatinine seemed tofluctuate less possibly due to compensatory capacity of the residual renal function insmall solute clearance.Conclusions: Consequently, estimated glomerular filtration rate was turnedout to be a more stable parameter than total creatinine clearance, which might be adesirable feature in long-term follow-up of peritoneal dialysis patients.     

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.     

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。     

血清电解质、CKBB及血乳酸水平与新生儿缺氧缺血性脑病严重程度的相关性分析

分析血清电解质、肌酸激酶同工酶(CKBB)及血乳酸水平与新生儿缺氧缺血性脑病严重程度的相关性。80例缺氧缺血性脑病患儿中轻度患儿27例、中度患儿26例、重度患儿27例。以本院同期健康的足月新生儿60例为对照组。结果显示与对照组新生儿比较,观察组新生儿氯离子及钙离子水平明显降低(P<0.05),CKBB和血乳酸水平明显升高(P<0.05);重度患儿的氯离子及钙离子水平明显低于中度患儿和轻度患儿(P<0.05),CKBB和血乳酸水平明显高于中度患儿和轻度患儿(P<0.05);血清中氯离子和钙离子与缺氧缺血性脑病严重程度呈现负相关性(P<0.05),但CKBB和血乳酸与缺氧缺血性脑病严重程度呈明显的正相关性(P<0.05)。结果说明血清氯离子和钙离子、CKBB及血乳酸水平与新生儿缺氧缺血性脑病严重程度呈明显的相关性。     

Creatine transporter expression after antidepressant therapy in rats bred for learned helplessness

In cells and tissues with a high demand of energy such as neurons the major pool of energy is supplied by phosphocreatine. The necessary supply with creatine is directly related to the expression level of the creatine transporter (CRT). To study possible interactions between this transporter and depressive like behavior we have used a congenitally learned helplessness (cLH) model. Because uptake via CRT is the only means to supply neurons with creatine, we hypothesized a rise in CRT expression following antidepressive treatment strategies. The hippocampus of the cLH animals exhibited a significantly lower CRT expression as compared to wild type (WT) animals. Treatment with escitalopram and ECS induced an elevation of CRT levels in the hippocampus and the prefrontal cortex. In WT animals there was no treatment effect. In summary, our data presented here suggest an association between depressive behavior and cellular energy metabolism in defined brain areas.