Single bout of vibration-induced hamstrings fatigue reduces quadriceps inhibition and coactivation of knee muscles after anterior cruciate ligament (ACL) reconstruction

Persistent quadriceps strength deficits in individuals with anterior cruciate ligament reconstruction (ACLr) have been attributed to arthrogenic muscle inhibition (AMI). The purpose of the present study was to investigate the effect of vibration-induced hamstrings fatigue on AMI in patients with ACLr. Eight participants with unilateral ACLr (post-surgery time: M = 46.5, SD = 23.5 months; age: M = 21.4, SD = 1.4 years) and eight individuals with no previous history of knee injury (age: M = 22.5, SD = 2.5 years) were recruited. A fatigue protocol, consisting of 10 min of prolonged local hamstrings vibration, was applied to both the ACLr and control groups. The central activation ratio (CAR) of the quadriceps was measured with a superimposed burst of electrical stimulation, and hamstrings/quadriceps coactivation was assessed using electromyography (EMG) during isometric knee extension exercises, both before and after prolonged local vibration. For the ACLr group, the hamstrings strength, measured by a load cell on a purpose-built chair, was significantly (P = 0.016) reduced about 14.5%, indicating fatigue was actually induced in the hamstrings. At baseline, the ACLr group showed a trend (P = 0.051) toward a lower quadriceps CAR (M = 93.2%, SD = 6.2% versus M = 98.1%, SD = 1.1%) and significantly (P = 0.001) higher hamstrings/quadriceps coactivation (M = 15.1%, SD = 6.2% versus M = 7.5%, SD = 4.0%) during knee extension compared to the control group. The fatigue protocol significantly (P = 0.001) increased quadriceps CAR (from M = 93.2%, SD = 6.2% to M = 97.9%, SD = 2.8%) and significantly (P = 0.006) decreased hamstrings/quadriceps coactivation during knee extension (from M = 15.1%, SD = 6.2% to M = 9.5%, SD = 4.5%) in the ACLr group. In conclusion, vibration-induced hamstrings fatigue can alleviate AMI of the quadriceps in patients with ACLr. This finding has clinical implications in the management of recovery for ACLr patients with quadriceps strength deficits and dysfunction.     

研究miR-219下调TGFBR2影响ENDMT途径抑制急性心肌梗死

目的: 主要是miR-219通过对TGFBR2调控机制,介导ENDMT途径缓解急性心肌梗死的发展。方法: qRT-PCR检测AMI患者及AMI小鼠血清中miR-219的表达量;过microRNA靶基因数据库TargetScan进行筛选预测;萤光素酶报告基因法及qRT-PCR分析TGFBR2与miR-219的调控机制;通过心脏超声心动图检测AMI小鼠心肌注射miR-219慢病毒4周后的血分数(LVEF);采用qRT-PCR检测心肌注射miR-219慢病毒的AMI小鼠中Nppa 的mRNA的表达量;通过Masson’s trichrome染色法检测小鼠4周后左心室纤维化变化;使用α平滑肌肌动蛋白(α-SMA)对小鼠左室切片进行免疫组化分析;通过Western blot检测P-smad2、P-smad3及TGFBR2缺氧诱导蛋白磷酸化的表达水平。结果: miR-219对AMI有调控作用;miR-219可抑制TGFBR2的mRNA表达,而miR-219 inhibitor可以抑制这种下调效果,miR-219对TGFBR2具有抑制调控性;miR-219可抑制急性心肌梗死的进程,促进梗死心肌功能的恢复;miR-219能促进AMI小鼠心肌组织血管的新生和成熟,最终心脏收缩能力上升,心功能恢复;miR-219能抑制TGFBR2抑制EndMT途径,导致缓解AMI的病理进程。结论: miR-219能通过抑制TGFBR2影响EndMT途径,心肌纤维化减少,促进血管的新生和成熟,心功能恢复,抑制AMI的病理发展。     

AMI 患者血浆NT-proBNP 水平与心肌缺血及预后关系的研究

目的:探讨急性心肌梗死(AMI)患者血浆N末端B型尿钠肽前体(NT-proBNP)的水平与心肌缺血及预后的关系。方法:98例急性心肌梗死患者根据患者是否行直接PCI手术治疗,分为PCI手术治疗组和非PCI治疗组,观察缺血改善情况与NT-proBNP水平的关系,同时根据治疗后NT-proBNP的水平分为三组,A组NT-proBNP<125pg/ml、B组125pg/ml≤NT-proBNP<450pg/ml、C组NT-proBNP≥450pg/ml,观察NT-proBNP的水平与预后的关系。结果:行PCI组NT-proBNP的水平下降程度(438.3±134.5)明显高于未行PCI组者(158.6±146.1,P<0.05),MACE的发生情况C组明显高于A组(P=0.006<0.01),也高于B组(P=0.028<0.05),A组与B组相比,B组的MACE发生率有上升的趋势,但是无统计学意义(P=0.432>0.05)。结论:急性心肌梗死患者早期血浆NT-proBNP的水平在一定程度上可以反应心肌的缺血程度,且与患者的预后成明显的负相关。     

Hymenolepis diminuta: Effect of infection on ion transport in colon and blood picture of rats

The aim of this study was to examine the effect of an infection with Hymenolepis diminuta on ion transport in an isolated colon and blood picture of rats. Fifty rats were orally infected with five cysticercoids of H. diminuta. The experimental groups of rats were assigned to four groups: group I - 8 days post-infection (dpi), group II - 16 dpi, group III - 40 dpi and group IV- 60 dpi. The control group comprised non-infected rats. The experiments consisted of measuring the transepithelial electrical potential difference (PD) and the transepithelial electrical resistance (R) of the rat colon under controlled conditions as well as during mechanical stimulation (MS) using a modified Ussing chamber. Ion transport was modified using inhibitors of the epithelial sodium channel (amiloride - AMI) and the epithelial chloride channel (bumetanide - BUME), and also using capsaicin (CAPSA), a substance which activates C-fibres. The experimental data presented in this study indicates that experimental hymenolepidosis inhibits sodium and chloride ion transport in the epithelium of the rat colon, with preserved tight junction continuity (except at 40 dpi) and a decreased mechanical sensitivity. The effect of capsaicin on ion transport in the rat colon was varied. In control rats it increased ionic current, and in H. diminuta-infected rats it did not cause any changes in PD.Blood picture in this study showed a statistically significantly lower red blood cells (RBC) count and haemoglobin (HGB) concentration in infected rats in comparison to non-infected. Red cell distribution width (RDW) values and platelet (PLT) count were negatively correlated with the duration of infection, whereas mean corpuscular volume (MCV) value was positively correlated. We did not observe leukocytosis during infection, and amongst the differential leukocyte counts eosinophils and basophils showed statistically significant lower values in infected rats in comparison to non-infected.Our results indicate that hymenolepidosis is associated with the activation of inflammatory mediators and stimulation of nervous fibres, which significantly affects the function of ion channels in the epithelium of the colon in the host. At the same time, a significant decrease in eosinophil count during infection suggests that such an infection did not trigger a strong immunological reaction in rats.     

Chitinase 3-like 1 gene-329G/A polymorphism, plasma concentration and risk of coronary heart disease in a Chinese population

Background

The chitinase-like 1 protein, YKL-40, is involved in inflammation and tissue remodeling. Patients with coronary heart disease (CHD) and acute myocardial infarction have elevated levels of serum YKL-40. The goal of the present study was to investigate whether the chitinase-like 1 gene-329G/A variant (rs10399931) confers susceptibility to CHD, and whether it is associated with the clinical phenotype and severity of disease.

Methods

We performed a case-control study of 410 unrelated CHD patients (coronary stenosis ≥ 50% or documented myocardial infarction) and 442 controls from China. A ligase detection reaction was used to determine a single-nucleotide polymorphism in rs10399931. The genotypic and allelic associations of this single-nucleotide polymorphism with CHD, phenotypes and severity were also evaluated. Plasma levels of YKL-40 were measured using ELISA assays.

Results

Three genotypes, CC, CT, and TT, existed in rs10399931 and there were no significant differences found in either the genotypic or allelic frequencies between the CHD cases and controls. Patients with CHD had higher YKL-40 levels compared to controls and those with acute myocardial infarction had the highest levels of YKL-40 compared to patients with either stable or unstable angina pectoris (all p < 0.01). Rs10399931 affected neither the main anthropometric or metabolic characteristics, nor did there exists any association between rs10399931 and the severity of coronary lesions assessed by Gensini scores (all p > 0.05).

Conclusions

Our results do not support that rs10399931 is associated with clinical phenotypes of CHD and the extent of coronary lesions; however, YKL-40 levels are higher in CHD patients and associated with its clinical phenotypes.     

Human circulating microRNA-1 and microRNA-126 as potential novel indicators for acute myocardial infarction

Circulating miRNAs have been shown as promising biomarkers for various pathologic conditions. The aim of this study was to clarify that circulating miR-1 and miR-126 in human plasma might be useful as biomarkers in acute myocardial infarction (AMI). In our study, after pre-test, two candidate miRNAs were detected by using real-time RT-PCR. Cardiac troponin I (cTnI) concentrations were measured by ELISA assay in plasma from patients with AMI (n=17) and healthy subjects (n=25), simultaneously. Increased miR-1 and decreased miR-126 in plasma from patients with AMI after the onset of symptoms compared with healthy subjects were found. A remarkable finding in this study is that miR-1, miR-126 and cTnI expression levels exhibited the same trend. Our results suggest that the plasma concentrations of miR-1 and miR-126 may be useful indicators for AMI.     

通心络对急性心肌梗死保守治疗患者疗效观察

目的:观察通心络胶囊对急性心肌梗死(AMI)未接受经皮冠状动脉介入治疗(PCI)或溶栓治疗后患者的疗效。方法:对我院收治的ST段抬高未实施PCI或溶栓治疗的AMI患者,随机分为常规药物治疗作为对照组(20例)和同时加服用通心络胶囊的治疗组(20例)。于发病后一月内观察再发心绞痛、急性心血管事件、左室射血分数(LVEF)改变。结果:通心络组心功能改善较对照组明显,通心络组再发心绞痛及急性心血管事件较对照组明显减少。结论:通心络对急性心肌梗死保守治疗患者不仅减少心绞痛发作及急性心血管事件的发生而且可改善心功能。     

Crosstalk of mesenchymal stem cells and macrophages promotes cardiac muscle repair

Transplantation of bone-marrow derived mesenchymal stem cells (MSCs) has potential therapeutic effects on cardiac muscle repair. However, the underlying mechanism remains not completely clarified. Here we show that transplantation of MSCs significantly increased local recruitment of macrophages to facilitate cardiac muscle repair. MSCs-induced recovery of cardiac function and attenuation of fibrosis after injury were all abolished by either impaired macrophage infiltration, or by MSCs depletion after macrophage recruitment. However, angiogenesis seemed to be only affected by depletion of macrophages, but not by depletion of MSCs, suggesting that macrophages are responsible for the augmented angiogenesis after MSCs transplantation, while MSCs do not directly contribute to angiogenesis in the functional cardiac repair. Moreover, high level of transforming growth factor β 1 (TGFβ1) was detected in macrophages and high level of BMP7 was detected in MSCs, suggesting that MSCs not only may recruit macrophages to enhance angiogenesis to promote regeneration, but also may secrete BMP7 to contradict the fibrogenic effect of TGFβ1 by macrophages. Our study thus sheds new insight on the interaction of MSCs and macrophages in a functional cardiac repair triggered by MSCs transplantation.     

人心脏型脂肪酸结合蛋白检测试剂盒的临床评价

目的评价人心脏型脂肪酸结合蛋白(H-FABP)检测试剂盒(胶体金法)在急性心肌梗死(AMI)诊断中的价值。方法采用平行、盲法、对照的对比试验设计,比较其试验产品和对比产品对诊断AMI的敏感性、特异性、准确性。结果共测定240份临床血液标本。试验产品和对比产品的阳性符合率为100%,阴性符合率为96.15%,总符合率为97.92%。对比产品和试验产品结果不一致的5例标本以临床诊断结果为标准进行验证后,试验产品与临床诊断结果的阳性符合率为100%,总符合率为100%。采用Kappa检验考核两种产品测定结果的一致性,Kappa指数为0.958。经McNamara's test分析,两产品之间无差异,χ2=3.20,P>0.05。结论试验产品显示出较好的诊断价值,可以作为AMI早期诊断标志物,试验产品与对比产品等效。     

Selective binding interactions of deramciclane to the genetic variants of human α1-acid glycoprotein

Background

α₁-Acid glycoprotein (AGP) plays a decisive role in the serum protein binding of several drugs.Genetic variants of AGP have different ligand binding properties. The binding of deramciclane (DER), a chiral anxiolytic agent, has been studied on A and F1/S genetic variants of AGP.

Methods

The effects of DER and reference drugs on the binding of specific fluorescent and circular dichroism (CD) probes of AGP were determined. Dicumarol (DIC) binding was measured by CD and equilibrium dialysis.

Results

DER effectively displaced probes bound to variant A, while it was less effective at displacing probes bound to variant F1/S. DER increased the binding and inverted the induced CD spectrum of DIC in the solution of variant F1/S. This phenomenon could not be brought about by the enantiomer of DER.

Conclusion

DER has high-affinity binding (K_a ≥ 2×10⁶ M^-1) to variant A, while its binding to the variant F1/S is about thirty times weaker. During simultaneous binding of DER and DIC to variant F1/S a ternary complex having about four times higher affinity is formed, in which the opposite chiral conformation of DIC is favored.

General significance

The binding interactions found prove that AGP can simultaneously accommodate different ligand molecules. Even weakly bound ligands can provoke unexpected allosteric protein binding interactions.