Developmental Programming of Cardiovascular Disease Following Intrauterine Growth Restriction: Findings Utilising A Rat Model of Maternal Protein Restriction

Over recent years, studies have demonstrated links between risk of cardiovascular disease in adulthood and adverse events that occurred very early in life during fetal development. The concept that there are embryonic and fetal adaptive responses to a sub-optimal intrauterine environment often brought about by poor maternal diet that result in permanent adverse consequences to life-long health is consistent with the definition of “programming”. The purpose of this review is to provide an overview of the current knowledge of the effects of intrauterine growth restriction (IUGR) on long-term cardiac structure and function, with particular emphasis on the effects of maternal protein restriction. Much of our recent knowledge has been derived from animal models. We review the current literature of one of the most commonly used models of IUGR (maternal protein restriction in rats), in relation to birth weight and postnatal growth, blood pressure and cardiac structure and function. In doing so, we highlight the complexity of developmental programming, with regards to timing, degree of severity of the insult, genotype and the subsequent postnatal phenotype.     

孟根乌森乌日乐对小鼠的急性毒性研究

目的：了解孟根乌森乌日乐的急性毒性作用剂量及给药后的急性毒性反应和死亡分布情况,确定孟根乌森乌日乐的半数致死量（ LD50）。方法用孔氏综合法（改进寇氏法）分为14．30,9．28,6．04,3．92,2．55,1．66 g? kg－16个剂量组,以0．4 mL／10 g的量灌胃给药1次。实验后观察14 d,记录体重变化及不良反应情况。结果孟根乌森乌日乐小鼠半数致死量为5．1597 g? kg－1（95％CI：3．6652～7．2637 g? kg－1）。14 d内未出现明显不良反应症状且体重有增长趋势。结论孟根乌森乌日乐的急性毒性实验的半数致死量为临床用药量的100倍,提示单次口服较为安全。     

五种布鲁氏菌核酸检测试剂盒检测性能的评价北大核心CSCD

目的比较5种布鲁氏菌核酸实时荧光PCR检测试剂盒的一致性和检出能力,为临床实验室选择检测方法和布鲁氏菌的诊断提供参考依据。方法选用经病原学检测确定为布鲁氏菌阳性的血液样本38份,健康人的血液样本24份,潘氏变形杆菌、溶藻弧菌、河弧菌、铜绿假单胞菌、肺炎克雷伯菌DNA各1份,使用5种试剂盒(编号A-E)分别进行核酸检测,比较5种试剂盒临床样本检测的一致性;选择1份阳性样本核酸用无RNA酶水梯度稀释得到5个浓度(浓度1:4453.13 fg/μL,浓度2:1113.28 fg/μL,浓度3:278.32 fg/μL,浓度4:69.58 fg/μL,浓度5:17.40 fg/μL),每个浓度使用5种试剂盒(编号A-E)分别进行3次检测,比较5种试剂盒的阳性检出率及批内重复性。结果5种试剂盒检测67份DNA样品的符合率稍有不同,试剂盒ABDE的符合率均为100%,试剂盒C的符合率为98.51%。批内重复性显示5种试剂盒在浓度1、浓度2、浓度3水平重复检测DNA的Ct值变异系数均<5%;在浓度1与浓度4梯度区间,试剂盒的阳性检出能力比较显示试剂盒A、B、D较高,为11/12,试剂盒C和E较低,为8/12。结论5种试剂盒的真实性和可靠性较好,灵敏度和符合率稍有差别,特异度均为100%;重复性较好,检测性能良好。部分试剂盒对弱阳性样本的检出能力不强,该类样本可使用多种试剂盒复核,以保障结果的准确性。     

Hospitalisation costs associated with heart failure with preserved ejection fraction (HFpEF): a systematic review

Heart Failure Reviews - Heart failure with preserved ejection fraction (HFpEF) is problematic to treat, with guidelines for HFpEF management concentrated on treating prevalent comorbidities. The...     

The in vitro effects of stem cell factor, interleukin 3 and granulocyte-macrophage colony stimulating factor on haemopoietic progenitor cells from premature infants

Summary. Circulating haemopoietic progenitor cells from premature infants were assessed for their ability to respond to interleukin 3, granulocyte-macrophage colony stimulating factor and stem cell factor (SCF) in vitro. All three cytokines increased the number of colonies derived from burst forming units erythroid (BFU-E), colony forming units granulocyte-macrophage (CFU-GM) and multi-lineage progenitors (CFU-Mix) grown in the presence of erythropoietin (Epo). The size and haemoglobin content of BFU-E derived colonies also increased in the presence of the cytokines. Of those tested, SCF was found to be the most potent additive to Epo for the enhanced growth of BFU-E and CFU-Mix. In short-term liquid cultures without Epo, SCF alone induced globin synthesizing cells. Progenitors from premature infants were at least as responsive to all three cytokines as those from healthy adults. The use of SCF in combination with Epo in the prevention or treatment of anaemia in premature infants warrants further investigation.     

Renin messenger RNA localization in congenital mesoblastic nephroma using in situ hybridization

Renin messenger (m) RNA distribution was studied in congenital mesoblastic nephroma, a usually benign renal tumour of early infancy which may be associated with excess renin production and hypertension. Using in situ hybridization with synthetic radiolabelled oligonucleotide probes combined with immunohistochemical studies, renin expression was found in areas of tumours containing recognizable cortical structures including glomeruli and tubules. Renin mRNA was also detected in vessels and larger vascular spaces within the tumour not associated with cortical structures. Cells in the tumour vessel walls and sinusoids which expressed renin also stained positively for vascular smooth muscle-specific alpha actin.     

Effects of pharmacologic coronary hyperemia on echocardiographic left ventricular function in patients with single vessel coronary artery disease

To assess whether pharmacologic coronary vasodilation could provoke new left ventricular wall motion abnormalities in patients with single vessel coronary artery disease, systemic hemodynamics, coronary blood flow velocity and left ventricular wall motion were measured by two-dimensional echocardiography during administration of 10 mg of intracoronary papaverine in 14 patients before and again immediately after left coronary angioplasty (group 1). As a comparison with an intravenous method, left ventricular wall motion was analyzed after 0.56 mg/kg body weight of intravenous dipyridamole in a separate group of 13 patients with single vessel coronary disease (group 2). Heart rate-blood pressure product increased 3% to 6% in papaverine-treated patients and 14 +/- 11% (p = NS) in dipyridamole-treated patients. No angiographic collateral vessels were present in either group. Although intracoronary mean flow velocity measured in the 14 group 1 patients and in 5 normal control subjects during papaverine treatment increased from 125% to 400% of basal flow velocity, papaverine induced new left ventricular wall motion abnormalities in only 5 of the 14 patients before coronary angioplasty. In three of five patients, left ventricular wall motion abnormalities persisted after successful coronary angioplasty. Four of the 14 patients demonstrated augmentation of left ventricular wall motion with papaverine. After intravenous dipyridamole, only 3 of the 13 group 2 patients developed new left ventricular regional asynergy. These data suggest that selective (papaverine) and, most likely, global (dipyridamole) augmentation of coronary flow alone does not reliably identify potential ischemic left ventricular regions affected by critical single vessel coronary artery disease.     

Epstein-Barr virus (EBV)-associated lymphoproliferations in severe combined immunodeficient mice transplanted with Hodgkin's disease lymph nodes: implications of EBV-positive bystander B lymphocytes rather than EBV-infected Reed-Sternberg cells

To establish an in vivo model for the study of Hodgkin's disease and Reed-Sternberg (RS) cells, 25 lymph node tissue samples involved by Hodgkin's disease were grafted into severe combined immunodeficiency (SCID) mice. Ten Epstein-Barr virus (EBV)-associated tumors were obtained in SCID mice. EBV-positive tumors growing in SCID mice were correlated with the presence of EBV-positive nonneoplastic B cells in patient tumors (90% v 26.6%; P<.01) and was independent of the EBV status of RS cells. Our results suggested that EBV-positive tumors growing in SCID mice originated from normal EBV-positive small lymphocytes (bystander B lymphocytes). We also compared the characteristics of these tumors with those obtained after transplantation of 15 non-Hodgkin's lymphoma and four reactive lymph nodes. The latent period to observe a growing tumor in SCID mice was similar between the two groups (12.86 +/- 5.59 weeks for Hodgkin's disease v 13.6 +/- 5.36 weeks for non-Hodgkin's lymphoma and reactive lymph nodes). The relatively high number of EBV-positive small lymphocytes detected in Hodgkin's disease and T-cell lymphoma compared with B-cell lymphoma may account for the greater percentage of EBV- positive tumors obtained in SCID mice. Our results show that SCID mice do not provide the growth conditions that are required for in vivo growth of RS cells. We noted in some SCID tumors, the presence of binucleated and/or multinucleated giant cells resembling RS cells. However, the presence of such cells was not restricted to mice grafted with lymph nodes involved by Hodgkin's disease. We postulate that in previous reports, cells resembling RS cells were just binucleated EBV- positive lymphoma blastoid cells rather than actual RS cells.