Creatine has no beneficial effect on skeletal muscle energy metabolism in patients with single mitochondrial DNA deletions: a placebo-controlled, double-blind 31P-MRS crossover study

The purpose of our randomized, double-blind, placebo-controlled crossover study in 15 patients with chronic progressive external ophthalmoplegia (CPEO) or Kearns-Sayre syndrome (KSS) because of single large-scale mitochondrial (mt) DNA deletions was to determine whether oral creatine (Cr) monohydrate can improve skeletal muscle energy metabolism in vivo. Each treatment phase with Cr in a dosage of 150 mg/kg body weight/day or placebo lasted 6 weeks. The effect of Cr was estimated by phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS), clinical and laboratory tests. (31)P-MRS analysis prior to treatment showed clear evidence of severe mitochondrial dysfunction. However, there were no relevant changes in (31)P-MRS parameters under Cr. In particular, phosphocreatine (PCr)/ATP at rest did not increase, and there was no facilitation of post-exercise PCr recovery. Clinical scores and laboratory tests did not alter significantly under Cr, which was tolerated without major side-effects in all patients. Cr supplementation did not improve skeletal muscle oxidative phosphorylation in our series of patients. However, one explanation for our negative findings may be the short study duration or the limited number of patients included.     

联合检测cTnI、MYO和CK-MB mass对病毒性心肌炎诊断的评价

目的 探讨联合检测心肌肌钙蛋白(cTnI)、肌红蛋白(MYO)和肌酸激酶同工酶MB质量(CK-MB mass)对病毒性心肌炎(VMC)的诊断价值.方法 在61例VMC和74例非病毒性心肌炎(NVMC)患儿及46例健康对照组中,用微粒子化学发光免疫分析法检测血清cTnI、MYO、CK-MB mass,并用连续监测法测定血清LDH、AST、CK和α-HBDH的活性.cTnI、MYO和CK-MB mass不同组合的诊断效率运用矩阵决策法评价.结果 入院当日VMC组cTnI(0.46±0.21μg/L)、MYO(98.7±38.2μg/L)、CK-MB(6.1±4.2μg/L)均明显高于NVMC组(分别为0.06±0.04、39.2±26.8、2.2±1.7μg/L)和对照组(分别为0.07±0.04、36.5±24.7、2.1±1.5μg/L,P＜0.01).cTnI、MYO、CK-MB mass联合检测对VMC诊断的灵敏度、特异性、阳性预报值、阴性预报值和诊断准确度分别为90.16%、85.14%、83.33%、91.30%和87.41%,其特异性、阳性预报值和诊断准确度明显比四种心肌酶联合检测法高(P＜0.05),而灵敏度和阴性预报值与后者相比差异无显著性(P＞0.05).MYO对VMC初诊的灵敏度较高,特异性欠佳,阳性持续时间短;cTnI与CK-MB对VMC诊断的特异性好,持续时间长,初诊时的灵敏度不够理想.VMC患者康复时以MYO恢复最快,CK-MB次之,cTnI最慢.结论 联合动态检测cTnI、MYO和CK-MB mass可使VMC的诊断效率进一步提高.     

磷酸肌酸钠联合果糖二磷酸钠治疗病毒性心肌炎的疗效观察

目的 探讨磷酸肌酸钠联合果糖二磷酸钠治疗病毒性心肌炎的疗效.方法 选取2010年9月至2012年8月在新疆自治区人民医院北院就诊的病毒性心肌炎患者99例,按照随机数字表法将患儿分成联合用药组（50例）和基础治疗组（49例）.两组患儿均实施常规治疗,治疗组在常规治疗的基础上加用果糖二磷酸钠,每次150剂mg/kg,每日2次,静脉滴注;联合用药组在治疗组的基础上加用磷酸肌酸钠,50 mg/kg,静脉滴注.两组疗程均为2周.结果 联合用药组治疗后的总有效率为92.0%,显著高于治疗组的67.3%（Z=2.484,P＜0.05）,联合用药组经治疗后心电图及心肌酶谱各有1例未发生变化,治疗组经治疗后心电图无变化4例,心肌酶谱无变化7例,联合用药组经治疗后心电图及心肌酶谱改变均较治疗组显著.结论 磷酸肌酸钠联合果糖二磷酸钠治疗病毒性心肌炎疗效显著,不良反应轻微,安全可行,值得临床推广.     

Increased CKMB (mass concentration) in patients without traditional evidence of acute myocardial infarction. A risk indicator of coronary death.

A study of 102 patients consecutively admitted to a coronary care unit (CCU) investigated the clinical usefulness of three different immunoenzymometrical CKMB methods: NovoClone CK-MB, ICON QSR CKMB and IMx CK-MB. Blood samples were drawn on admission and then every 6 h for 48 h. The three different methods correlated very well (r = 0.93-0.96). With discrimination levels of 10 micrograms.l-1 for NovoClone CK-MB and 5 micrograms.l-1 for the other two methods, a sensitivity of 1.0 and a still acceptable specificity (> 0.81) were achieved. In the group of patients (n = 53) with suspicion of acute myocardial infarction (AMI) but with no standard criteria for AMI, 14 patients were identified with small but significant increase of serum CKMB (mass concentration) and an increased CKMB (mass concentration)/CK ratio. During a 4 year follow-up nine out of these 14 patients died within 2 years, the majority being coronary deaths, as compared to only two out of the remaining 39 non-AMI patients with suspicion of AMI but with normal CKMB values (chi 2 = 18.47, P < 0.001). The finding of such a high mortality rate among patients with increased CKMB (mass concentration) has an important prognostic value even in patients without standard criteria for AMI.     

Casual C peptide index: Predicting the subsequent need for insulin therapy in outpatients with type 2 diabetes under primary care

BackgroundEvaluation of residual beta cell function is indispensable in patients with type 2 diabetes as it informs not only diagnoses but also appropriate treatment modalities. However, there is a lack of convenient biomarkers for residual beta cell function. Therefore, we evaluated endogenous insulin level as a biomarker in outpatients who were being treated with insulin therapy and in patients who were introduced to insulin therapy after 4 years.MethodsData of 174 outpatients with type 2 diabetes (50% male) whose glycemia was moderately controlled (glycated A1c 7.3% [5.2%–14.8%]) were reviewed. Twenty patients whose estimated glomerular filtration rate was lower than 30 ml/min/1.73 m² were excluded from the evaluation of endogenous insulin level with both casual C‐peptide index (C‐CPI) and urinary C‐peptide/creatinine ratio (determined at any time, generally 1–2 h after breakfast). Patients were stratified based on the provision of insulin therapy.ResultsC‐CPI and UCPCR were significantly lower in the insulin‐treated patients than in the insulin‐untreated patients (0.9 vs. 2.2, p < 0.0001; 24.7 vs. 75.5, p = 0.0003, respectively). Moreover, C‐CPI were significantly lower in the insulin‐requiring patients for 4 years than in the insulin‐unrequiring patients (1.0 vs. 1.7, p = 0.0184). The multivariate logistic regression analysis revealed that both indicators of insulin secretion influenced the requirement for insulin therapy, but C‐CPI could serve as the most convenient and useful biomarker for not only current insulin therapy requirements (p = 0.0002) but also the subsequent requirement for insulin therapy (p = 0.0008).ConclusionsC‐CPI could be determined easily, and it was found to be a more practical marker for outpatients; therefore, our findings would have critical implications for primary care.     

血清肌酸激酶对假肥大型肌营养不良诊断价值

肌酸激酶(cK)是一种细胞内激酶,在肌细胞能量贮存、转移中起重要作用.临床上通过CK检测,可以早期发现假肥大型肌营养不良患者.该文就CK分布、同工酶、亚型、CK检测对假肥大型肌营养不良的诊断价值及新生儿期CK筛查意义作一综述.     

Metabolic profile of the hippocampus of Zucker Diabetic Fatty rats assessed by in vivo 1H magnetic resonance spectroscopy

Localized in vivo 1H magnetic resonance spectroscopy (MRS) was used to investigate metabolite levels in the brain of adult Zucker Diabetic Fatty (ZDF) rats, an animal model for type 2 diabetes mellitus. This study focussed on the hippocampus, assumed to be one of the main brain areas affected by this disease. Together with an almost 5-fold increase in blood glucose concentration measured by glucose oxidation, significant increases were found in the hippocampal concentrations of glucose (4.93 vs 1.66 mM p < 0.001), myo-inositol (6.52 vs 4.30 mM; p < 0.05), and total creatine (12.71 vs 10.50 mM; p < 0.05) in ZDF rats (n = 5) compared with littermates (n = 5). Although no obvious alterations were detected in the hippocampal levels of other metabolites, including NAA + NAAG and choline-containing compounds in the ZDF rats, the increase in Glc and Ins levels is in line with elevated brain tissue contents of these metabolites in patients with diabetes mellitus.     

Creatine uptake in isolated soleus muscle: kinetics and dependence on sodium,but not on insulin

The increased use of creatine by athletes as a dietary supplement to improve their physical performance assumes that increased serum creatine levels will increase intracellular skeletal muscle creatine. Despite this common assumption, skeletal muscle creatine uptake awaits full characterization. Consequently, we have investigated ¹⁴C-labelled creatine uptake in isolated, incubated rat soleus (type I) muscle preparations at 37 °C. We found that the apparent K_m for creatine uptake was 73 μM and the V_max was 77 nmol h^–1 gww^–1. Creatine uptake was 82% inhibited by 2 m M β-guanidinopropionic acid, the structural analogue of creatine. In addition, a decrease in buffer Na⁺ concentration, from 145 to 25 m M , reduced the rate of ¹⁴C-labelled creatine uptake by 77%, indicating that uptake is largely Na⁺-dependent in soleus muscle. Insulin had no effect on the rate of creatine uptake in vitro. The total creatine content was 34% lower, but the rate of creatine uptake in the presence of 100 μM extracellular creatine was 45% higher, in soleus than in extensor digitorum longus (type II) muscle. However, at 1 m M extracellular creatine, the maximal rate of uptake was not significantly different for the two muscle types, implying that soleus muscle has a lower K_m for creatine uptake. We suggest that intracellular creatine levels may play a role in the regulation of skeletal muscle creatine uptake.