N-acetyl-beta-D-glucosaminidase in acute myocardial infarction

The objective of the study was to investigate whether the lysosomal enzyme, N-Acetyl-beta-D-glucosaminidase (NAG) activity is increased in plasma of patients with acute myocardial infarction (AMI) and to determine if there is any association between plasma levels of NAG and severity of myocardial infarction (MI). NAG activity in plasma was monitored in 69 patients with AMI and 135 normal healthy subjects using a spectrofluorimetric method. A modified Aldrich ST elevation score was used to gauge the severity of MI in terms of size of the infarct. Plasma NAG levels in AMI patients and normal healthy subjects were found to be 10.92+/-7.5 U/l and 6.8+/-2.2 U/l, respectively. These two mean value when compared by Student's t-test were significantly different P = 0.0001. No statistically significant differences in NAG activity were observed in patients in terms of gender, age, location of infarct, time from onset of chest pain to blood sampling in the hospital and size of the infarct.     

Endothelial progenitor cell transplantation decreases lymphangiogenesis and adverse myocardial remodeling in a mouse model of acute myocardial infarction

Cardiac lymphatic system in the remodeling after acute myocardial infarction (AMI) has been overlooked. We wanted to investigate the role of bone marrow-derived endothelial progenitor cells (EPCs) and their contribution to lymphatic distribution in myocardial remodeling after AMI. Mouse (C57bl/6J) MI models were created by ligation of the left anterior descending coronary artery and were treated with phosphate buffered saline (PBS) or EPCs. Real-time RT-PCR with 2- to 4-week myocardial tissue samples revealed that lymphangiogenetic factors such as vascular endothelial growth factor (VEGF)-C (8.5 fold, P < 0.05), VEGF-D (6.1 fold, P < 0.05), Lyve-1 (15 fold, P < 0.05), and Prox-1 (11 fold, P < 0.05) were expressed at significantly higher levels in the PBS group than the EPC group. The PBS group also showed a significantly higher density of lymphatic vessels in the peri-infarction area. Echocardiography showed that from 2 weeks after the treatment, left ventricle (LV) dimensions at both systole and diastole were significantly smaller in the EPC group than in the PBS group (P < 0.01) and LV fractional shortening was higher in the EPC group accordingly (P < 0.01). Lymphangiogenic markers increased in a mouse MI model. EPC transplantation decreased lymphangiogenesis and adverse ventricular remodeling after AMI. These novel findings suggest that new lymphatic vessels may be formed in severely damaged myocardium, and may be involved in adverse myocardial remodeling after AMI.     

急性心肌梗死患者D-二聚体、cTnT及心肌酶谱联合检测的临床意义

为探讨急性心肌梗死患者D-二聚体、肌钙蛋白及心肌酶谱联合检测的临床意义,选择30例健康者（对照组）和100例患者（病例组）进行D-二聚体、肌钙蛋白及心肌酶谱（AST、LDH、CK、CK-MB）检测,并把100例患者（病例组）分为3组,分别为36例AMI组,34例不稳定型心绞痛（UAP）组,30例稳定型心绞痛（SAP）组。结果表明,AMI组及UAP组中D-二聚体、肌钙蛋白及心肌酶谱（AST、LDH、CK、CK—MB）的升高程度较SAP组和健康对照组显著增高（P〈0．05）;AMI组肌钙蛋白（cTnT）较UAP组明显增高（P〈0．05）;UAP组肌钙蛋白（cTnT）较对照组明显增高（P〈0．05）;D-二聚体、肌钙蛋白及心肌酶谱（AST、LDH、CK、CK—MB）的升高程度与心肌梗死的面积正相关（P〈0．01）。提示D-二聚体、肌钙蛋白及心肌酶谱（AST、LDH、CK、CK—MB）联合检测有助于急性心肌梗死诊断的提高。     

Polymorphisms in two genes, IL-1B and ACE, are associated with erythropoietin resistance in Korean patients on maintenance hemodialysis

Genetic polymorphisms may be linked to inter-individual differences in erythropoietin (EPO) resistance. We investigated the -511C/T polymorphism of the IL-1B gene and the I/D polymorphism of the ACE gene for any association with EPO resistance index (ERI) in maintenance hemodialysis patients (n=167). Because EPO responsiveness is multi-factorial, we also included other possible influences (age, sex, time on dialysis, ACE inhibitor or angiotensin receptor blocker use, ferritin, transferrin saturation, intact PTH, high sensitivity C-reactive protein, albumin, Kt/V, and presence of diabetes mellitus) on ERI in our analyses. Multiple regression analysis showed significant association of the IL-1B-511CC and ACE DD polymorphisms with ERI (P=0.038 and P=0.004 in the recessive model, respectively). The combination (C) of alleles of two loci showed that C1 (I-T) was significantly associated with ERI in the co-dominant and recessive models (P=0.005 and P=0.0001, respectively). Subjects who did not carry C1 showed significantly decreased ERI (10.10+/-5.15 IU/kg weight/g hemoglobin) compared to other study subjects (C1/C1 and C1/-; 12.97+/-4.90 and 15.12+/-7.43 IU/kg weight/g hemoglobin, respectively). Our study indicates that the IL-1B-511C/T and ACE I/D polymorphisms may be useful genetic markers of EPO requirement in hemodialysis patients. These findings might also provide a new perspective on therapeutic approaches to the treatment of end stage renal disease patients with anemia.     

An evaluation of two-dimensional electrophoresis for detection of human serum proteins in acute myocardial infarction

High resolution two-dimensional electrophoresis indicates that serum proteins previously only detected in patients with acute myocardial infarction (AMI) (Gomo et al., Electrophoresis 1983, 4, 298-302) are also present in the serum protein patterns of other patients (AMI negative or demonstrating acute phase response) and are faintly detected even in controls. Thus, these proteins are not specific to AMI and are probably acute phase reactants. However, they do demonstrate a characteristic time course response in sequential samples from AMI patients.     

Angiotensin converting enzyme I/D, angiotensinogen T174M-M235T and angiotensin II type 1 receptor A1166C gene polymorphisms in Turkish hypertensive patients

Essential hypertension is a multifactorial disease in which genetic and enviromental factors play an important role. These factors differ in each population. As there are no existing data for the Turkish population, we investigated four Renin Angiotensin System (RAS) gene polymorphisms, the angiotensin converting enzyme (ACE), angiotensinogen (AGN) M235T/T174M and angiotensin II type 1 receptor A1166C polymorphism in 109 hypertensive and 86 normotensive Turkish subjects. Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP), and agarose gel electrophoresis tecniques were used to determine these polymorphism. The frequencies of person that carry ACE D allel (DD+ID) was significantly higher in hypertensive group (99.1%) than controls (80%) (P 0.000). M235T TT genotype was also found significantly higher in hypertensives than control group (20% vs 2.7%; P 0.001). The frequency of AGN 174M allele was higher in the hypertensive group than control subjects (8.76% vs 4.81%). Frequency of ATR1 C allele (AC+CC genotypes) was found higher hypertensives than controls (39.4% vs 25.9%; P = 0.054). Our results suggest that an interaction exists between the RAS genes and hypertension in Turkish population.     

Cardiac-specific overexpression of Ndufs1 ameliorates cardiac dysfunction after myocardial infarction by alleviating mitochondrial dysfunction and apoptosis

Myocardial infarction (MI) is the leading cause of premature death among adults. Cardiomyocyte death and dysfunction of the remaining viable cardiomyocytes are the main pathological factors of heart failure after MI. Mitochondrial complexes are emerging as critical mediators for the regulation of cardiomyocyte function. However, the precise roles of mitochondrial complex subunits in heart failure after MI remain unclear. Here, we show that NADH:ubiquinone oxidoreductase core subunit S1 (Ndufs1) expression is decreased in the hearts of heart failure patients and mice with myocardial infarction. Furthermore, we found that cardiac-specific Ndufs1 overexpression alleviates cardiac dysfunction and myocardial fibrosis in the healing phase of MI. Our results demonstrated that Ndufs1 overexpression alleviates MI/hypoxia-induced ROS production and ROS-related apoptosis. Moreover, upregulation of Ndufs1 expression improved the reduced activity of complex I and impaired mitochondrial respiratory function caused by MI/hypoxia. Given that mitochondrial function and cardiomyocyte apoptosis are closely related to heart failure after MI, the results of this study suggest that targeting Ndufs1 may be a potential therapeutic strategy to improve cardiac function in patients with heart failure.Subject terms: Heart failure, Myocardial infarction, Myocardial infarction     

Evaluation of a Apo-1/Fas promoter polymorphism in Korean stroke patients

Apoptosis has been implicated in the pathogenesis of neurodegenerative diseases such as stroke and Alzheimer's disease. Apo-1/Fas gene is one of the mediators of apoptosis in stroke. Mval polymorphism is the first polymorphic marker identified in the Apo-1/Fas gene promoter, which was typed by PCR and followed by Mval digestion and gel electrophoresis. DNA isolated from peripheral blood collected from 91 stroke patients and 103 healthy blood donors was used for genotypes of GG, GA and AA by sequence specific primer PCR. Mval polymorphism was examined based on Fas gene promotor region by restriction fragment length polymorphism (RFLP). The Fas-GG genotype was the least frequent in patients with stroke and healthy controls (P = 0.57). In normal Korean controls the Mval polymorphism GA, AA and GG were 48.6%, 34.9% and 16.5%. In stroke patients were 56.2%, 29.6% and 14.2% respectively. And the allelic frequencies of Mval*2 (G) allele were less frequent than Mval*1 (A) allele in patients with stroke and healthy controls (P = 0.76). In normal Korean controls Mval*1 (A) and Mval*2 (G) alleles were 59.2% and 40.8%. In stroke patients were 57.6% and 42.4%, respectively. Our results, pending confirmation in a larger study, indicate that the Fas genotype may not appear to be a risk factor for stroke in Korean stroke patients.     

Acidity,lipophilicity, solubility,absorption, and polar surface area of some ACE inhibitors

Computational chemical methods have been used to correlate the molecular properties of the 10 ACE inhibitors (captopril, enalapril, perindopril, lisinopril, ramipril, trandolapril, quinapril, fosinopril, benazepril, and cilazapril) and some of their active metabolites (enalaprilat, perindoprilat, ramiprilat, trandolaprilat, quinaprilat, fosinoprilat, benazeprilat, and cilazaprilat). The computed pK _a values correlate well with the available experimental values. In the dicarboxylic ACE inhibitors, the carboxyalkyl carboxylate group of the ACE inhibitors studied is more acidic than the C-terminal carboxylate. However, at physiological pH = 7.4 both carboxyl groups of ACE inhibitors are completely ionized and the dicarboxyl-containing ACE inhibitors behave as strong acids. The available experimental partition coefficients of these ACE inhibitors investigated are well reproduced by the neural network-based ALOGPs and the fragment-based KoWWiN methods. All parent drugs (and prodrugs), with the exception of fosinopril, are compounds with low lipophilicity. Calculated pK _a, lipophilicity, solubility, absorption, and polar surface area of the most effective ACE inhibitors for the prevention of myocardial infarction, perindopril and ramipril, were found similar. Therefore, it is probable that the experimentally observed differences in the survival benefits in the first year after acute myocardial infarction in patients 65 years of age or older correlate closely to the physicochemical and pharmacokinetic characteristics of the specific ACE inhibitor that is used.     

The evaluation of cardiac function and the effect of therapy in acute myocardial infarction--comparison by radio nuclide method in acute and chronic phase

The cardiac function and the effect of therapy in patients with acute myocardial infarction (AMI) were assessed in over 100 patients by analysis of 201Tl-scintigraphy and 99mTc-gated pool study in our ICU. The cardiac function and 201Tl-defect ratio were compared with the results obtained in chronic phase. Sixteen of them were treated with intravenous urokinase (UK) within 6 hours from onset. The other 18 patients without UK treatment served as a control group. Significant correlation was recognized between 201Tl-defect ratio and peak-CPK levels, peak-GOT levels, peak-LDH levels. Significant correlation (r = -0.655, r = -0.713) were found between 201Tl-defect ratio and LVEF in acute and chronic phase. The UK group showed a significant increase of LVEF as compared with the control group in patients with antero-septal (A/S) AMI. In inferior (INF) AMI, no significant differences were observed UK and control group in LVEF, RVEF and 201Tl-defect ratio. In chronic phase, improvements of LVEF and 201Tl-defect ratio were observed in patients with A/S AMI. But no significant differences of LVEF, RVEF and 201Tl-defect ratio were observed in A/S AMI in acute and chronic phase. The UK group showed a significant increase of LVEF (50.1%) as compared with the control group of A/S AMI in chronic phase. We have demonstrated that a combination of 201Tl-scintigraphy and 99mTc-gated pool study are useful techniques in ICU, to evaluate the cardiac function and the effect of thrombolysis therapy and thus greatly contribute to the primary care of AMI cases.     

Myocardial infarction patients show altered lipoprotein properties and functions when compared with stable angina pectoris patients

Several parameters and risk factors were compared between Korean male myocardial infarction (MI) patients (n = 10) and angina pectoris (AP) patients (n = 17) to search unique biomarkers for myocardial infarction (MI) in lipoprotein level. Individual serum and lipoprotein fractions (VLDL, LDL, HDL₂, HDL₃) were isolated and analyzed by lipid and protein determination and enzyme assay. The MI group was found to have a 25 and 30% higher serum cholesterol and triacylglycerol (TG) level than the AP group, respectively, however, their body mass index (BMI), LDL-cholesterol (C), HDL-C, and glucose levels fell within the normal range. MI patients were found to have an approximately two-fold higher level of serum IL-6 and an 18% lower serum apoA-I level than that of the AP group. LDL and HDL₂ fraction of the MI group were more enriched with TG than those of AP group. The increased TG was correlated well with the increased level of apoC-III in the same fraction. Cholesteryl ester transfer protein (CETP) activity and protein level were greatly increased in MI patients in the LDL and HDL₃ fractions. MI patients showed more severely oxidized LDL fraction than patients in the AP group, as well as the weakest antioxidant ability of serum. Conclusively, MI patients were found to have unique serum and lipoprotein characteristics including increased IL-6 and TG in serum, with CETP and apoC-III in the LDL and HDL fractions, as well as severely impaired antioxidant ability of HDL.     

Two-dimensional electrophoresis of human serum proteins following acute myocardial infarction

Serum proteins associated with acute myocardial infarction (AMI) have been monitored by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and high resolution two-dimensional electrophoresis (2-DE) under nonreducing conditions. Proteins a, b, c (Mr 13,000; pI6.2, 6.7 and 7.5, respectively) and e(Mr27,000; pI5.2) appear simultaneously approximately 30 h after infarction, reach maximum intensity after 48 h and progressively decline thereafter. Protein d (Mr15,000; pI7-8.5; identified as hemoglobin) sometimes appears within 18 h of infarction. Proteins a-c are not detected in the 2-DE patterns of healthy myocardium, infarcted myocardium, pectoral muscle or tongue, but e is present in all and tentatively identified as myosin light chain. Other myocardial proteins which are either reduced in amount following infarction or more specifically associated with myocardium than pectoral muscle are not detected in the serum of AMI patients. Analysis of unconcentrated urine by SDS-PAGE and silver staining does not reveal proteins specific to AMI.     

Angiotensin-I converting enzyme gene polymorphism in Turkish type 2 diabetic patients

Non-insulin dependent diabetes mellitus is often associated with some complications such as nephropathy, retinopathy and neuropathy. Genes of the renin angiotensin system are potential candidate genes for diabetic complications. We investigated the relationship between angiotensin converting enzyme (ACE) gene polymorphism in type 2 diabetic patients with and without diabetic nephropathy. Seventy five patients (25 type 2 diabetic patients with nephropathy, 50 type 2 diabetic patients without nephropathy) and 37 healthy controls were studied. Gene polymorphism of ACE was determined by PCR (polymerase chain reaction) amplification using allele-spesific primers. The frequencies of ACE DD, ID and II genoypes among the patients with type 2 diabetic patients were found 48%, 42%, 10% whereas in control subjects, 27%, 60%, 13% respectively. Type 2 diabetic patients carrying DD genotype without nephropathy increased 1.77 fold than control subjects (P < 0.05). There is no significant correlation between diabetic nephropathy and ACE gene polymorphism. But we found that ACE DD genotype increased significantly in type 2 diabetic patients compared to control subjects (P <.05).     

Antioxidant Cardioprotection against Reperfusion Injury: Potential Therapeutic Roles of Resveratrol and Quercetin

Ischemia-reperfusion myocardial damage is a paradoxical tissue injury occurring during percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) patients. Although this damage could account for up to 50% of the final infarct size, there has been no available pharmacological treatment until now. Oxidative stress contributes to the underlying production mechanism, exerting the most marked injury during the early onset of reperfusion. So far, antioxidants have been shown to protect the AMI patients undergoing PCI to mitigate these detrimental effects; however, no clinical trials to date have shown any significant infarct size reduction. Therefore, it is worthwhile to consider multitarget antioxidant therapies targeting multifactorial AMI. Indeed, this clinical setting involves injurious effects derived from oxygen deprivation, intracellular pH changes and increased concentration of cytosolic Ca²⁺ and reactive oxygen species, among others. Thus, we will review a brief overview of the pathological cascades involved in ischemia-reperfusion injury and the potential therapeutic effects based on preclinical studies involving a combination of antioxidants, with particular reference to resveratrol and quercetin, which could contribute to cardioprotection against ischemia-reperfusion injury in myocardial tissue. We will also highlight the upcoming perspectives of these antioxidants for designing future studies.     

A new 3D nickel(II) framework composed of large rings: Ionothermal synthesis and crystal structure

Ionothermal reaction between Ni²⁺ and 1,3,5-benzentricarboxylic acid (H₃BTC) with [AMI]Cl (AMI=1-amyl-3-methylimidazolium) as the reaction medium produced a novel 3D mixed-ligand metal-organic framework [AMI][Ni₃(BTC)₂(OAc)(MI)₃] (1) (MI=1-methylimidazole) with [AMI]⁺ incorporated in the framework. The framework is formed by connecting 2D planes, made up of 32- and 48-membered rings, through 1D chains composed of 32-membered rings. The two BTC³⁻ ligands in 1 show the same connectivity mode with two bidentate and one μ₂ bridging carboxylic groups. This is a new connectivity mode to the already existing 17 in the Ni-BTC system. The role of MI and [AMI]Cl in the structure formation is discussed.     

Evaluation of thallium-201 myocardial emission computed tomography based on a comparison with postmortem findings

The correlative study of myocardial perfusion assessed by 201Tl myocardial ECT with the pathological finding of the heart was performed in 10 autopsied cases with mean age of 77 years old (range: 60-90 y). In 6 cases with myocardial infarction (MI) 7 perfusion defects were observed, that was, 3 in anteroseptal wall, 1 in anterolateral wall and 3 in posterior wall on the images of SPECT. Seven MIs were also found in postmortem examination. Six MIs were observed at autopsy corresponding to perfusion defect on SPECT images. In one myocardial perfusion defect at inferoposterior portion on SPECT, a non-transmural MI was found at anteroseptum. In one case with valvular disease a false positive result was obtained at posterior wall where neither myocardial necrosis nor fibrosis was observed at autopsy. This case had aortic stenosis due to bicuspid aortic valve by autopsy. The ventricle was divided into 16 segments in each of 4 short axial images to evaluate extent of MI. SPECT for extent of MI showed sensitivity of 81.9%, specificity of 96.0% and diagnostic accuracy of 92.5%. False negative segment was apt to be observed at the surrounding of non-transmural MI or basal half of left ventricle (LV) with transmural MI, while false positive segment was at posterior portion of basal half of LV. It was concluded that myocardial ECT was useful for evaluation of the site and extent of MI.     

Modulation of material properties of a decellularized myocardial matrix scaffold

Injectable materials offer the potential for minimally invasive therapy for myocardial infarction (MI), either as an acellular scaffold or as a cell delivery vehicle. A recently developed myocardial matrix hydrogel, derived from decellularized porcine ventricular tissue, has the potential to aid in cardiac repair following an MI. Herein, we set out to study the effects of cross-linking on the cardiac hydrogel stiffness, degradation properties, cellular migration, and catheter injectability in vitro. Cross-linking increased stiffness, while slowing degradation and cellular migration through the gels. Additionally, the cross-linked material was pushed through a clinically relevant catheter. These results demonstrate that the material properties of myocardial matrix can be tuned via cross-linking, while maintaining appropriate viscosity for catheter injectability.     

Common variants at the promoter region of the APOM confer a risk of rheumatoid arthritis

Although the genetic component in the etiology of rheumatoid arthritis (RA) has been consistently suggested, many novel genetic loci remain to uncover. To identify RA risk loci, we performed a genome-wide association study (GWAS) with 100 RA cases and 600 controls using Affymetrix SNP array 5.0. The candidate risk locus (APOM gene) was re-sequenced to discover novel promoter and coding variants in a group of the subjects. Replication was performed with the independent case-control set comprising of 578 RAs and 711 controls. Through GWAS, we identified a novel SNP associated with RA at the APOM gene in the MHC class III region on 6p21.33 (rs805297, odds ratio (OR) = 2.28, P = 5.20 × 10-7). Three more polymorphisms were identified at the promoter region of the APOM by the re-sequencing. For the replication, we genotyped the four SNP loci in the independent case-control set. The association of rs805297 identified by GWAS was successfully replicated (OR = 1.40, P = 6.65 × 10-5). The association became more significant in the combined analysis of discovery and replication sets (OR = 1.56, P = 2.73 × 10-10). The individuals with the rs805297 risk allele (A) at the promoter region showed a significantly lower level of APOM expression compared with those with the protective allele (C) homozygote. In the logistic regressions by the phenotype status, the homozygote risk genotype (A/A) consistently showed higher ORs than the heterozygote one (A/C) for the phenotype-positive RAs. These results indicate that APOM promoter polymorphisms are significantly associated with the susceptibility to RA.     

Development of a disposable immunosensor for the detection of human heart fatty-acid binding protein in human whole blood using screen-printed carbon electrodes

An amperometric immunosensor for the rapid detection of human heart fatty-acid binding protein (H-FABP) in whole blood was developed. Due to its rapid kinetics in plasma, H-FABP is a useful biochemical marker for the early assessment of acute myocardial infarction (AMI). A one-step direct sandwich assay in which analyte and alkaline phosphatase (AP) labelled antibody were simultaneously added to the immobilised primary antibody, was employed using two distinct monoclonal mouse anti-human H-FABP antibodies. p-Aminophenyl phosphate was converted to p-aminophenol by AP and the current generated by its subsequent oxidation at +300 mV vs. Ag/AgCl was measured. Total assay time was 50 min and the standard curve was linear between 4 and 250 ngml(-1). The intra- and inter-assay coefficients of variation were below 9%. No cross-reactivity of the antibodies was found with other early cardiac markers and endogenous substances in whole blood did not have an interfering effect. The overall performance of the sensor, wide working range, good precision and specificity demonstrate its potential usefulness for early assessment of AMI.