Amyloid-P-component-like immunoreactivity in β/A4-immunoreactive deposits in Alzheimer-type dementia brains

An immunohistochemical study using the mirror-image technique was performed in order to establish whether amyloid P component is involved in the mechanism of deposition of amyloid fibrils in senile plaques (SPs) in Alzheimer-type dementia (ATD). Ninety percent of /A4 protein-immunoreactive SPs were also stained by the anti-amyloid P component immunchistochemistry, and this applied to all of the diffuse, primitive and classical types of /A4 deposits. These findings may suggest an involvement of amyloid P component in the formation of amyloid fibrils in senile plaques in ATD brains.     

Polyclonal 111In-IgG, 125I-LDL and 125I-endothelin-1 accumulation in experimental arterial wall injury

To test iodine-125 labelled low-density lipoprotein (¹²⁵I-LDL), polyclonal indium-111 labelled immunoglobulin G (¹¹¹In-IgG) and iodine-125 labelled endothelin-1 uptake in metabolically active atheromatous plaques after arterial wall injury, we performed balloon de-endothelialization of carotid arteries or abdominal aortas in 24 New Zealand male rabbits which were fed with a normal diet (n=14) or a hypercholesterolaemic diet (n=10) after surgery. Six weeks later the animals were injected with 200 Ci of (¹²⁵I-LDL), and/or with 100 Ci of ¹¹¹In-IgG or with 9 Ci of ¹²⁵I-endothelin-1. Forty-eight hours later the animals were sacrificed. Carotid arteries and aortas were removed, counted and fixed for autoradiography and light microscopy examination. Contralateral carotid arteries and thoracic aortas served as controls.Significant ¹¹¹In-IgG uptake was observed in the injured arteries at autoradiography, with localization mainly in the healing edges, and at well counting. The percentage of the injected dose per gram (%D.inj/g) was 0.0188±0.06 versus 0.0059±0.003 in controls (P< 0.05). There was no difference in ¹¹¹In-IgG uptake between arteries with injury alone and those with active atheroma formation at the site of the injury. Significant (¹²⁵I-LDL), uptake was observed only when lipid deposition was present at light microscopy (%D.inj/g of 0.0024±0.0005 vs 0.0010±0.0003 in controls, P < 0.05). ¹²⁵I-endothelin-1 accumulation was observed in four of five injured aortas both at autoradiography, with diffuse localization, and at well counting (%D.inj/g of 0.0012±0.0004 in the abdominal aortas vs 0.0008±0.0003 in the thoracic aortas).Polyclonal IgG may accumulate in injured arteries without active atheroma formation. Inflammatory reaction at the site of the injury may cause ¹¹¹In-IgG uptake independently of atheromatous plaque formation. LDL accumulation takes place only with active atheroma formation at the site of the injury. Use of labelled peptides such as endothelin-1 may provide further insight into the mechanisms of atheromatous plaque formation.     

Increased senile plaques without microglia in Alzheimer's disease

Summary To clarify the association of microglia with senile plaques, the brains from 13 patients with Alzheimer's disease (AD) and 23 nondemented aged controls were investigated immunohistochemically by a double-labeling method using anti--protein antiserum and anti-ferritin antibody, which is a recently reported microglia marker. In addition, a quantitative analysis was performed. The senile plaques which appeared initially in the nondemented aged controls consisted of a diffuse type without any amyloid cores and these were found in the group aged 50–59 years. The great majority of them were found to contain no ferritin-positive microglia. The number and proportion (percentage) of microglia-containing diffuse plaques increased with age. Classical and compact plaques began to appear in the brains of the group aged 70 years and over, and practically all of them contained microglia. These results suggest that microglia are not associated with initial plaque formation, but correlate with amyloid core formation. In AD, the most prominent feature was that the diffuse plaques, which contained either no or only a few ferritin-positive microglia, increased markedly.Supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan     

颈动脉斑块与心脑血管阻塞性疾病关系的临床探讨

目的 探讨颈动脉斑块与心脑阻塞性疾病及视网膜中央动脉阻塞(CRAO)的关系。方法 1995年10月至2002年7月采用彩色多普勒超声对我院心脑血管疾病患者149例行颈动脉检查。结果 检出颈动脉斑块者74例，未检出斑块者75例。有斑块者较无斑块者颈动脉内膜中层厚度明显增加(P＜0．01)。结论 颈动脉斑块严重程度的增加，其内膜中层厚度亦呈增厚趋势。前者是造成脏器梗死的重要原因之一。颈动脉斑块的检测和治疗可作为心脑血管及CRAO疾病的重要预防措施。     

Increased carotid intima–media thickness in the absence of atherosclerotic plaques in an adult population with Fabry disease

Aim: Fabry disease is considered primarily as a progressive small vessel disease, with ischaemic degenerative lesions involving the kidneys, brain and heart. Macrovascular involvement in male patients includes an accelerated wall hypertrophy of the radial artery and a thickening of the intima–media of the common carotid artery. The aim of this study is to evaluate the prevalence and severity of carotid artery atherosclerosis in hemizygous and heterozygous patients with Fabry disease, compared with a matched control population.
Methods: The common carotid artery intima–media thickness (IMT) of 53 patients with Fabry disease (24 men, 29 women) was measured by high-definition ultrasonography, and the presence or absence of atherosclerotic plaques reported. Results were compared with those of 120 age-matched healthy individuals (83 men, 37 women).
Results: The common carotid artery IMT was increased to the same extent in male and female patients with Fabry disease (706±211 µm and 749±395 µm, respectively) compared with that of the control population (614±113 µm). In the Fabry population, IMT did not correlate with either systolic blood pressure or with renal function (plasma creatinine). In the control population, only systolic blood pressure was positively and significantly correlated with IMT. Atherosclerotic plaques in the common carotid artery were not observed in any patient with Fabry disease, whereas 34% of the control population had carotid artery plaques, as evidenced by focal non-homogeneous intima–media thickening greater than 1.2 mm.
Conclusion: This study presents evidence of a major increase in common carotid artery IMT, both in hemizygous and heterozygous patients with Fabry disease, in the absence of focal atherosclerotic plaques. These results suggest that the conduit arteries may be protected from atherosclerosis in Fabry disease.     

牙周基础治疗对龈下菌斑中螺旋体及牙周状态影响的研究

目的：动态观测牙周基础治疗对龈下菌斑中螺旋体百分组成及牙周临床指标的影响。方法：对26例牙周病患者78个牙位的龈下菌斑用刚果红染色，计数螺旋体的百分比，记录牙周探诊深度，探诊出血指数和牙齿动度，分析治疗前后的变化。结果：龈上洁治及龈下刮治后1周，龈下菌斑中螺旋体百分比显著下降且牙周临床指数明显改善；刮治后2周，龈下菌斑中螺旋体百分比继续下降，但不具有显著性；刮治后3周，龈下菌斑中螺旋体百分比出现回升趋势。结论：牙周基础治疗是慢性牙周病有效治疗手段；牙周维护治疗对防止牙周再感染和牙周病的复发具有重要意义。     

COX基因多态性与缺血性卒中的相关性研究

【摘要】 目的 探讨环氧合酶(COX)代谢通路基因多态性及其与缺血性卒中发病率的关系。方法 将2013年2月~2015年11月在德阳市人民医院和温州医科大学第三附属医院神经内科住院经头颅CT和MRI检查确诊的299例急性缺血性卒中患者,根据彩超结果分为颈动脉易损斑块组（VP）94例、稳定斑块组（SP）74例和无斑块组（NP）131例;同时再分为颈动脉内膜增厚组（IT）108例和非内膜增厚组（NT）191例。使用聚合酶链反应和质谱分析测定基因多态性,包括前列腺素合酶1(PTGS1 rs1236913)、前列腺素H合酶2(PTGS2 rs689466)、血栓素A2合酶(TBXAS1 rs2267679、rs41708、rs194149)、前列腺素E合酶(PTGES2 rs6478818)、环前列腺素合成酶(PTGIS rs5602、rs5629)。结果 在易损斑块组和无斑块组之间TBXAS1 rs194149 GG基因型(P=00281),PTGIS rs5602 CT基因型(P=00319)存在显著差异。内膜增厚组和非内膜增厚组之间PTGS2 rs689466 GG基因型(P=00216)显示显著差异。多元回归分析显示,PTGIS的AA基因型(P=00308,OR:0275,95%CI:0079～0955)和PTGS2的AG+ GG基因型(P=00065,OR:2162,95%CI:1232～3795)是内膜增厚的破坏性因素。结论 COX的单核苷酸多态性(SNP)与脑梗死的发病率存在相关性,PTGIS和PTGS2基因多态性与内膜增厚脑卒中患者相关。     

Application of targeted therapy strategies with nanomedicine delivery for atherosclerosis

Atherosclerosis(AS)is the main pathological cause of coronary heart disease(CHD).Current clinical interventions including statin drugs can effectively reduce acute myocardial infarction and stroke to some extent,but residual risk remains high.The current clinical treatment regimens are relatively effective for early atherosclerotic plaques and can even reverse their progression.However,the effectiveness of these treatments for advanced AS is not ideal,and advanced atherosclerotic plaques—the pathological basis of residual risk—can still cause a recurrence of acute cardiovascular and cerebrovascular events.Recently,nanomedicine-based treatment strategies have been extensively used in antitumor therapy,and also shown great potential in anti-AS therapy.There are many microstructures in late-stage atherosclerotic plaques,such as neovascularization,micro-calcification,and cholesterol crystals,and these have become important foci for targeted nanomedicine delivery.The use of targeted nanoparticles has become an important strategy for the treatment of advanced AS to further reduce the residual risk of cardiovascular events.Furthermore,the feasibility and safety of nanotechnology in clinical treatment have been preliminarily confirmed.In this review,we summarize the application of nanomedicine delivery in the treatment of advanced AS and the clinical value of several promising nanodrugs.     

缬沙坦对颈动脉不稳定斑块患者血清炎症介质及缺血性脑卒中复发的影响

目的探讨缬沙坦对颈动脉不稳定斑块患者血清C-反应蛋白(CRP)、可溶性血管内皮细胞黏附分子-1(sVCAM-1)、白细胞介素-6(IL-6)的影响及对缺血性脑卒中复发干预的临床研究。方法不稳定斑块65例,缬沙坦治疗组33例,缬沙坦胶囊,80 mg,每日1次,口服,其他治疗措施与对照组基本相同。对照组32例,利尿降压药,口服。治疗前、1个月、2个月、38个月抽空腹静脉血共计5 ml,检测CRP、sVCAM-1、IL-6、血糖,同时监测血压。38个月时统计两组脑梗死复发和死亡情况,以CT或磁共振成像(MRI)出现新的梗塞灶为准。结果在1、2、38个月后治疗组血清CRP、sVCAM-1I、L-6浓度逐渐降低,组内相比差异有统计学意义(P<0.05),对照组除转变为硬斑者外其余变化不大。治疗组和对照组组间相比变化较大,差异有统计学意义(P<0.05)。终点38个月时,治疗组、对照组经CT或MRI证实脑梗死复发为7例(21.2%)和15例(46.9%)例,死亡为2例(6.1%)和5例(15.6%)例,治疗组复发率和病死率明显低于对照组(P<0.05)。结论缬沙坦稳定颈动脉斑块与血清中CRP、sVCAM-1I、L-6炎症介质的降低密切相关,降低不稳定斑块的破裂,从而减少了缺血性脑卒中的复发和死亡。     

Inactivation Methods for Experimental Nipah Virus Infection

Nipah virus (NiV) is an emerging zoonotic paramyxovirus that causes severe disease in humans and livestock. Due to its high pathogenicity in humans and the lack of available vaccines and therapeutics, NiV needs to be handled in biosafety level 4 (BSL-4) laboratories. Safe inactivation of samples containing NiV is thus necessary to allow further processing in lower containment areas. To date, there is only limited information available on NiV inactivation methods validated by BSL-4 facilities that can be used as a reference. Here, we compare some of the most common inactivation methods in order to evaluate their efficacy at inactivating NiV in infected cells, supernatants and organs. Thus, several physical and chemical inactivation methods, and combinations thereof, were assessed. Viral replication was monitored for 3 weeks and NiV presence was assessed by RT-qPCR, plaque assay and indirect immunofluorescence. A total of nineteen methods were shown to reduce NiV infectious particles in cells, supernatants and organs to undetectable levels. Therefore, we provide a list of methods for the safe and efficient inactivation of NiV.