The Relationship Between Serum Mannose-Binding Lectin Levels and Acute Ischemic Stroke Risk

Complement activation and inflammation have been suggested in the pathogenesis of stroke, mannose-binding lectin (MBL) were found to have roles during the process. The aim of this study was to investigate the relationship between acute ischemic stroke (AIS) and serum MBL levels in Chinese population. From January 1 to June 30 2013, all patients with first-ever AIS were recruited to participate in the study. Serum MBL levels and routine test were examined. The National Institutes of Health Stroke Scale (NIHSS) score was assessed on admission blinded to MBL levels. During the inclusion period, 148 patients with AIS were registered and completed study. The results indicated that the serum MBL levels were significantly (p < 0.0001) higher in acutely ischemic stroke patients as compared to normal controls [1,332; interquartile range (IQR) 996–2,134 μg/L and 897; IQR 678–1,100 μg/L, respectively]. There was a correlation between serum levels of MBL and NIHSS score [r (spearman) = 0.608, p < 0.0001). In multivariate analysis, serum MBL as a continuous variable was associated with an increased risk of AIS, after adjustment for above possible confounders (OR 1.002, 95 % CI 1.001–1.008; p < 0.0001). These results indicated that elevated MBL levels could be considered as an independent stroke risk factor in Chinese population, suggesting a role of MBL and the lectin pathway of complement activation in the pathogenesis of stroke.     

The Insulin-Like Growth Factor System

The insulin-like growth factor (IGF) system in ubiquitous and plays a role in every tissue of the body. It is comprised of ligands, receptors and binding proteins, each with specific functions. While it plays an essential role in embryonic and post-natal development, the IGF system is also important in normal adult physiology. There are now numerous examples of diseases such as diabetes, cancer, and malnutrition in which the IGF system is a major player and, not surprisingly, there are attempts to affect these disorders by manipulating the system.     

Demonstration of Type I Insulin-Like Growth Factor Receptors on Human Platelets

Abstract

Human platelets, freshly isolated from healthy human adults, express receptors for insulin-like growth factor I. The IC₅₀ for displacement of ¹²⁵I-IGF-I binding by unlabeled IGF-I was 0.2 nM, by IGF-II 32 nM and by insulin 160 nM. Scatchard analysis of IGF-I binding demonstrates dissociation constants of 0.14 ± 0.08 nM for high affinity binding site and 54 ± 18 nM for low affinty binding site. The presence of the α-subunit of type I IGF receptor, as high affinity binding site, was verified by affinity crosslinking of ¹²⁵I-IGF-I to platelet surface membranes. Under reducing con-conditions a M_r= 135,000 band was preferentially labeled. The complete type I IGF receptor complex, which revealed under nonreducing conditions, has an approximately molecular mass of M_r > 400,000. The immunoprecipitation of the ¹²⁵I-IGF-I cross-linked type I receptor with αIR-3 confirmed the results achieved by affinity crosslinking.     

Insulin-Like Growth Factor I Receptor Expression and Function in Nerve Growth Factor-Differentiated PC12 Cells

Abstract: Receptors for insulin-like growth factor I (IGF-I) were studied on PC12EY cells, a subclone of PC12. Differentiation of PC12EY cells with nerve growth factor (NGF) did not alter either the number of IGF-I receptors nor their affinity for IGF-I. IGF-I receptors remained fully functional during differentiation, promoting increases in thymidine incorporation, glucose uptake, amino acid uptake, and the phosphorylation of the S6 protein of the ribosomes. IGF-I also increased the proportion of differentiated cells found in S-phase. But although the addition of IGF-I to naive cells caused an increase in cell number, there was no comparable increase when IGF-I was added to differentiated cells. Thus, although the receptor for IGF-I continues to be present and functional, IGF-I fails to induce cell proliferation in differentiated PC12 cells.     

The Insulin-Like Growth Factor System and Neurological Complications in Diabetes

The IGF system plays vital roles in neuronal development, metabolism, regeneration and survival. It consists of IGF-I, IGF-II, insulin, IGF-I-receptor, and those of IGF-II and insulin as well as IGF-binding proteins. In the last decades it has become clear that perturbations of the IGF system play important roles in the pathogenesis of diabetic neurological complications. In the peripheral nervous system IGF-I, insulin, and C-peptide particularly in type 1 diabetes participate in the development of axonal degenerative changes and contributes to impaired regenerative capacities. These abnormalities of the IGF system appear to be less pronounced in type 2 diabetes, which may in part account for the relatively milder neurological complications in this type of diabetes. The members of the IGF system also provide anti-apoptotic effects on both peripheral and central nervous system neurons. Furthermore, both insulin and C-peptide and probably IGF-I possess gene regulatory capacities on myelin constituents and axonal cytoskeletal proteins. Therefore, replenishment of various members of the IGF system provides a reasonable rational for prevention and treatment of diabetic neurological complications.     

Myostatin and Insulin-Like Growth Factor I: Potential Therapeutic Biomarkers for Pompe Disease

Objective

Myostatin and insulin-like growth factor 1 (IGF-1) are serum markers for muscle growth and regeneration. However, their value in the clinical monitoring of Pompe disease – a muscle glycogen storage disease – is not known. In order to evaluate their possible utility for disease monitoring, we assessed the levels of these serum markers in Pompe disease patients receiving enzyme replacement therapy (ERT).

Design

A case-control study that included 10 patients with Pompe disease and 10 gender- and age-matched non-Pompe disease control subjects was performed in a referral medical center. Average follow-up duration after ERT for Pompe disease patients was 11.7 months (range: 6–23 months). Measurements of serum myostatin, IGF-1, and creatine kinase levels were obtained, and examinations of muscle pathology were undertaken before and after ERT in the patient group.

Results

Compared with control subjects, Pompe disease patients prior to undergoing ERT had significantly lower serum IGF-1 levels (98.6 ng/ml vs. 307.9 ng/ml, p = 0.010) and lower myostatin levels that bordered on significance (1.38 ng/ml vs. 3.32 ng/ml, p = 0.075). After ERT, respective myostatin and IGF-1 levels in Pompe disease patients increased significantly by 129% (from 1.38 ng/ml to 3.16 ng/ml, p = 0.047) and 74% (from 98.6 ng/ml to 171.1 ng/ml, p = 0.013); these values fall within age-matched normal ranges. In contrast, myostatin and IGF-1 serum markers did not increase in age-matched controls. Follistatin, a control marker unrelated to muscle, increased in both Pompe disease patients and control subjects. At the same time, the percentage of muscle fibers containing intracytoplasmic vacuoles decreased from 80.0±26.4% to 31.6±45.3%.

Conclusion

The increase in myostatin and IGF-1 levels in Pompe disease patients may reflect muscle regeneration after ERT. The role of these molecules as potential therapeutic biomarkers in Pompe disease and other neuromuscular diseases warrants further study.     

Insulin-Like Growth Factor I Receptor Binding in Brains of Alzheimer''s and Alcoholic Patients

Patients with chronic alcoholism and/or Alzheimer's disease show degenerative changes in the cerebral cortex and hippocampus. To investigate possible changes in insulin-like growth factor I receptor binding sites in brain tissue of patients with these pathological conditions, the number of 125I-insulin-like growth factor I binding sites was determined in tissues obtained from control patients and those with Alzheimer's and/or with a history of alcoholism. The four experimental groups examined consisted of patients from similar age groups. Postmortem histology and a clinical history were used for the diagnosis of Alzheimer's disease and alcoholism, respectively. Careful clinical records were kept concerning other variables such as immediate cause of death and medications administered before death. Specific binding of 125I-insulin-like growth factor I to homogenates prepared from cerebral cortex of Alzheimer's, alcoholic, alcoholic Alzheimer's, and age-matched control patients was similar, although Alzheimer's patients tended to have slightly higher binding values. No significant differences in insulin-like growth factor I binding in cerebral cortex were found with regard to age of patients, the interval between death and autopsy, and CNS-active medications. No statistical differences in 125I-insulin-like growth factor I binding were noted in hippocampal tissue from the four patient groups. Thus, human insulin-like growth factor I binding sites in cerebral cortex and hippocampus appear unaffected by several variables.     

Insulin-Like Growth Factor Binding Proteins Increase Intracellular Calcium Levels in Two Different Cell Lines

Background

Insulin-like growth factor binding proteins (IGFBPs) are six related secreted proteins that share IGF-dependent and -independent functions. If the former functions begin to be well described, the latter are somewhat more difficult to investigate and to characterize. At the cellular level, IGFBPs were shown to modulate numerous processes including cell growth, differentiation and apoptosis. However, the molecular mechanisms implicated remain largely unknown. We previously demonstrated that IGFBP-3, but not IGFBP-1 or IGFBP-5, increase intracellular calcium concentration in MCF-7 cells (Ricort J-M et al. (2002) FEBS lett 527: 293–297).

Methodology/Principal Findings

We perform a global analysis in which we studied, by two different approaches, the binding of each IGFBP isoform (i.e., IGFBP-1 to -6) to the surface of two different cellular models, MCF-7 breast adenocarcinoma cells and C2 myoblast proliferative cells, as well as the IGFBP-induced increase of intracellular calcium concentration. Using both confocal fluorescence microscopy and flow cytometry analysis, we showed that all IGFBPs bind to MCF-7 cell surface. By contrast, only four IGFBPs can bind to C2 cell surface since neither IGFBP-2 nor IGFBP-4 were detected. Among the six IGFBPs tested, only IGFBP-1 did not increased intracellular calcium concentration whatever the cellular model studied. By contrast, IGFBP-2, -3, -4 and -6, in MCF-7 cells, and IGFBP-3, -5 and -6, in C2 proliferative cells, induce a rapid and transient increase in intracellular free calcium concentration. Moreover, IGFBP-2 and -3 (in MCF-7 cells) and IGFBP-5 (in C2 cells) increase intracellular free calcium concentration by a pertussis toxin sensitive signaling pathway.

Conclusions

Our results demonstrate that IGFBPs are able to bind to cell surface and increase intracellular calcium concentration. By characterizing the IGFBPs-induced cell responses and intracellular couplings, we highlight the cellular specificity and complexity of the IGF-independent actions of these IGF binding proteins.     

血清胆红素水平与缺血性卒中的相关性研究

目的：脑卒中是威胁人类健康三大疾病之一,是我国成人致残的首要原因,其中80％是缺血性卒中。本文意在研究血清胆红素水平与缺血性卒中严重程度、发病机理以及颈动脉粥样硬化斑块的关系,以进一步为防治缺血性卒中的发生、发展提供新的途径。方法：选择缺血性脑卒中患者（观察组）150例和同期健康体检者（对照组）150例,分别测定两组的血清总胆红素水平（TBIL）、间接胆红素（DBIL）、直接胆红素（IBIL）,并对病例组进行TOAST分型、NIHSS评分及颈部血管超声检查。比较两组间血清胆红素,及观察组内不同分型组间血清胆红素的差异。结果：缺血性卒中患者TBIL、DBIL水平显著高于正常对照组,差异具有统计学意义（P〈0．05）。缺血性卒中患者按TOAST分型各亚型间血清TBIL、DBIL、IBIL水平差异无统计学意义（P〉0．05）。中重型脑梗死组与轻型脑梗死组比较,血清TBIL、DBIL、IBIL浓度均明显升高,差别具有统计学意义（P〈0．05）。缺血性卒中患者中有动脉粥样硬化斑块形成组血清TBIL、DBIL水平低于颈部动脉内膜光滑、完整者组,差别有统计学意义（P〉0．05）。结论：缺血性卒中患者血清胆红素升高,参与急性应激反应,可能作为衡量缺血性卒中严重程度的指标之一;高水平血清胆红素可能预防颈动脉粥样硬化斑块的形成,从而预防缺血性卒中的发生。     

Relationship between High Serum Cystatin C Levels and the Risk of Gestational Diabetes Mellitus

Aims

Serum cystatin C (CysC) has recently been shown to be associated with the incidence of type 2 diabetes mellitus (T2DM) and progression to the pre-diabetic state. The aim of this study was to explore the relationship between serum CysC and the risk of gestational diabetes mellitus (GDM) in Chinese pregnant women.

Methods

This cross-sectional study consisted of 400 pregnant women including111 with GDM and 289 with normal glucose tolerance at 24–28 weeks of gestation. The subjects were further divided into four groups according to the CysC quartiles, and their clinical characteristics were compared. The serum CysC concentration was measured using immunoturbidimetry and the degree of insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR).

Results

Serum CysC levels were significantly higher in pregnant women with GDM than in the healthy pregnant women[1.0(0.8–1.8) vs 0.7(0.6–1.0), P<0.01). The Spearman’s correlation analysis showed that serum CysC was positively associated with HOMA-IR(r = 0.118, P<0.05) and the occurrence of GDM(r = 0.348, P<0.01). The pregnant women were divided into quartiles according to their serum CysC concentrations. Compared to the first quartile, pregnant women in Q2 (OR, 2.441; P = 0.025), Q3 (OR, 3.383; P = 0.001) and Q4 (OR, 5.516; P<0.001) had higher risk of GDM after adjusted for age, BMI, HbA1c and HOMA-IR. Further, with a rise in the serum CysC, there was an increasing trend in the HOMA-IR levels (P<0.05). A binary logistic regression analysis after adjusting for other confounding variables revealed a significant and independent association between serum CysC and GDM [OR = 14.269; 95% confidence interval, 4.977–40.908, P<0.01].The receiver operating characteristic curve analysis revealed that the optimal cutoff point for serum CysC to indicate GDM was 0.95mg/L.

Conclusions

Serum CysC is significantly and independently associated with insulin resistance and GDM. It may be a helpful biomarker to identify the risk of GDM in Chinese pregnant women.     

Insulin-Like Growth Factor I/Somatomedin-C: A Rapid Isolation Procedure with FPLC

Insulin-like growth factor I (IGF l)/somatomedin-C (SM-C) was purified from lyophilized human serum by acid-ethanol extraction. The extract was precipitated with acetone-ethanol. The precipitate was purified by Sephadex G-50 chromatography. The protein peak within a molecular weight range of 5000 – 10 000 was further purified with FPLC-reversed phase chromatography using a Pep RPC HR 5/5 column (Pharmacia) with a solvent system of acetonitrile (CH₃ CN) and 0.1% trifluoroacetic acid (TFA) in water. The purification of IGF I was monitored by radioimmunoassay for SM-C. Purity was established by analytical isoelectric focusing and by SDS poly-acrylamide gel electrophoresis. Analytical isoelectric focusing showed one single protein band with an apparent pi of 8.3 0.1. SDS polyacryl-amide gel electrophoresis showed also one single protein band with an apparent molecular weight of 7000. Biological activity was demonstrated by measureing the (³H)thymidine incorporation into DNA of cultured arterial smooth muscle cells.     

首发缺血性脑卒中患者血清Hcy和EPO水平的变化及临床意义

目的:探究首发缺血性脑卒中患者血清同型半胱氨酸(Hcy)和红细胞生成素(EPO)水平的变化和意义。方法:于2013年10月-2015年4月我科收治的首发缺血性脑卒中患者中随机选取98例作为观察组,另选取同期健康体检者98例作为对照组,检测患者的血小板、血浆纤维蛋白原(Fib)以及血白细胞水平,比较两组血清Hcy、EPO、血小板、Fib及血白细胞水平,使用Logistic回归分析法评价缺血性脑卒中病发的危险因素,采用Spearman法对血清Hcy与EPO间相关性进行分析。结果:观察组的Hcy(23.52±12.15)m IU/L与EPO(34.61±11.25)m IU/L水平显著高于对照组的(10.57±2.18)m IU/L、(17.54±5.83)m IU/L;观察组血小板、血浆纤维蛋白原(fibrinogen,Fib)及血白细胞水平均高于对照组;差异均有统计学意义(均P0.05)。经Logistic回归分析法分析可知,Hcy为缺血性脑卒中病发的独立因素,经Spearman相关性分析显示,首发缺血性脑卒中患者EPO水平与Hcy呈正相关。结论:缺血性脑卒中病发与血清Hcy和EPO水平升高密切相关,且Hcy是导致缺血性脑卒中病发的高危因素。     

Divergent Effects of Short-Term,Very-Low-Calorie Diet on Insulin-Like Growth Factor-I and Insulin-Like Growth Factor Binding Protein-3 Serum Concentrations in Premenopausal Women with Obesity

DE PERGOLA, GIOVANNI, MAURO ZAMBONI, NICOLA PANNACCIULLI, EMANUELA TURCATO, FRANCESCO GIORGINO, FABIO ARMELLINI, FRANCESCO LOGOLUSO, MARCELLO SCIARAFFIA, OTTAVIO BOSELLO, RICCARDO GIORGINO. Divergent effects of short-term, very-low-calorie diet on insulinlike growth factor-I and insulin-like growth factor binding protein-3 serum concentrations in premenopausal women with obesity. Obes Res. 1998;6:408–415. Objective : Insulin-like growth factor-I (IGF-I) and insulinlike growth factor binding protein-3 (IGFBP-3) serum concentrations provide a good measure of the biological effects of growth, hormone. The aims of the present study were to: (1) investigate the associations of IGF-I and IGFBP-3 with body fat mass and distribution, and (2) evaluate the effects of 3 weeks of very-low-calorie diet (VLCD) (318 kcal/day, with 40 g protein, 35 g carbohydrate, and 2 g fat) on IGF-I and IGFBP-3 serum concentrations. Research Methods and Procedures : The study was performed in 21 nondiabetic premenopausal women with obesity (body mass index <27.0 kg/m²; age: ranging from 18 to 48 years). Body fat mass and distribution were measured by computed tomography. Results : Before dietary treatment, IGF-I and IGFBP-3 serum concentrations were inversely associated with visceral adipose tissue (VAT) area (p<0.005 and p<0.05, respectively), but not with either total body fat or subcutaneous adipose tissue area. VLCD produced a significant decrease of body mass index (p<0.001), total body fat (p<0.001), VAT (p<0.005), subcutaneous adipose tissue (p<0.001), IGF-I concentrations (p<0.05), and an increase of IGFBP-3 serum levels (p<0.001). The association of VAT with either IGF-I or IGFBP-3 serum concentrations was not maintained following VLCD. Discussion : Our study suggests that visceral adipose tissue, rather than adiposity per se, accounts for IGF-I and IGFBP-3 serum concentrations, and that rapid weight loss, possibly due to nutritional changes, results in lower IGF-I concentrations, higher IGFBP-3 concentrations, and abrogation of the inverse associations of VAT with IGF-I and IGFBP-3.     

胰岛素样生长因子IGF系统与鱼类性腺的研究进展

IGFs系统包含3个配体(IGF-1、IGF-2、IGF-3)、2个受体(IGF-1R、IGF-2R)和6个IGF结合蛋白(IGFBP).生殖和生长是生物体最基本的特征,两者既密切相关又相互区别,胰岛素样生长因子(IGFs)是生长轴和生殖轴相交联的关键因子.最近研究表明:鱼类性腺的发育及成熟伴随着细胞分化和组织生长,传统的生长因子IGF-1、IGF-2和最近发现的IGF-3,对鱼类性腺发挥着重要作用.本文重点介绍鱼类特有的配体IGF-3的结构,鱼类IGFs系统的信号通路及其与鱼类性腺的相关性研究进展.     

血清超敏C-反应蛋白水平与急性缺血性脑卒中预后的关系

目的:探讨急性缺血性脑卒中患者血清超敏C-反应蛋白(hs-CRP)的水平对卒中后功能障碍的预测价值.方法:分别在发病后第1和7天,采用颗粒增强免疫透射比浊法对92例急性缺血性脑卒中患者检测血清hs-CRP水平,并选取40例健康受试者作为对照.随访并记录患者1月、3月和6月mRS评分.结果:①急性缺血性脑卒中患者血清hs-CRP水平较对照组显著升高.②急性缺血性卒中患者入院1d和7d血清hs-CRP水平与1月、3月和6月mRS评分,均有明显的相关性.与入院1d血清hs-CRP水平相比,入院7d血清hs-CRP水平与mRS评分相关性更好.③与无颈动脉粥样硬化危险因素的缺血性卒中患者相比,有颈动脉粥样硬化危险因素的缺血性卒中患者入院7d血清hs-CRP水平明显升高.结论:与入院1d血清hs-CRP水平相比,入院7d血清hs-CRP水平对卒中后功能障碍的预测价值更好.