进展性缺血性卒中

进展性卒中在缺血性脑血管病中的发生率较高。研究发现，某些因素与其发生有关，可预测卒中进展的发生，因此干预这些因素可阻止其发生和发展。这些危险因素包括高血糖、高纤维蛋白原、发热、糖尿病史、早期CT局灶性低密度影、大脑中动脉高密度征、临床-DWI不匹配，以及兴奋性氨基酸(如谷氨酸)、一些细胞因子(如促炎因子IL-6和抗炎因子IL-10、IL-4)水平异常等。目前一些针对性治疗已进行了临床试验，有望在不久将来可用于临床。     

进展性卒中的神经影像学预测因素

进展性卒中在缺血性脑血管病中的比例较高,预后较差,有关其预测因素的研究也较多.早期神经影像学表现,如弥散加权成像(diffusion- weighted imaging,DWI)显示的梗死部位与大小、卒中类型、出血性转化、大血管病变、灌注加权成像(perfusion-weighted imaging,PWI)-DWI不匹配以及临床-DWI不匹配对进展性卒中的发生有一定的预测价值.     

核因子-κB反义寡核苷酸对系膜细胞炎症因子基因表达的影响

目的 :探讨NF κB反义寡核苷酸 (oligodeoxynucleotide ,ODN)对人肾小球系膜细胞炎症因子表达的影响 ,为利用NF κB反义ODN治疗肾小球炎性病变奠定基础。　 方法 :人工合成p65反义、正义及错配ODN并行全程硫代磷酸化修饰。应用核酸酶保护法观察阳离子脂质体介导的不同浓度的反义ODN(0 0 0 1、0 0 1、0 1、1、1 0μmol/L)对系膜细胞TNF α、IL 1α、IL 1 β、MCP 1、IL 8、TGF β1mRNA表达的影响 ,以正义ODN(1 0 μmol/L)及错配ODN(1 0 μmol/L)作为对照组。　 结果 :正常培养状态下 ,系膜细胞可组成型表达TNF α、IL 1 β、IL 8和TGF β1mRNA ,而不表达IL 1α和MCP 1mRNA。细菌脂多糖 (lipopolysaccharide,LPS)刺激后上述 6种炎症因子表达显著上调。p65反义ODN可呈剂量依赖性地抑制LPS诱导的系膜细胞炎性细胞因子TNF α ,IL α,IL 1 β,MCP 1和IL 8的基因表达 ,而对TGF β1无显著抑制作用 ;p65正义及错配ODN均不能抑制炎性细胞因子的表达。　 结论 :p65反义ODN可明显抑制LPS诱导的肾小球系膜细胞炎性细胞因子的表达 ,提示NF κB在肾小球疾病进展中起关键性调控作用 ,其反义ODN有可能应用于肾脏病变的实验性治疗之中     

肺炎衣原体和动脉粥样硬化

1999年Ross提出了“动脉粥样硬化—慢性炎症学说”[1,2 ] ,Ross认为 :AS是发生在大中动脉血管壁的内皮细胞损伤后 ,有细胞免疫介导的慢性炎症反应。有研究表明在AS患者中 ,不仅有炎性因子的表达如C反应蛋白 (CRP)、肿瘤坏死因子 (TNF a)、白介素 6 (IL 6 )、白介素 8(IL 8)、白介素 12 (IL 12 ) ,也有抗炎因子如白介素 10 (IL 10 )合成释放增加 ,而且有CD4 0 ,CD4 0L重要的炎症信号通道的激活 ,这条通道的激活又进一步促进了炎症介质如血管粘附因子和细胞因子、组织因子等物质的释放[3,4 ,9] 。这无疑给Ross的“动脉…     

促炎细胞因子与卒中复发性风险的相关性

有关促炎细胞因子与首发性或复发性卒中风险的报告为数不多.在一项来自培哚普利预防复发性卒中研究(Perindopril Protection Against Recurrent Stroke Study,PROGRESS)的巢式病例对照研究中,英国格拉斯哥大学皇家医院的Welsh等对白细胞介素(interleukin,IL)-6、IL-18和肿瘤坏死因子(tumor necrosis factor,TNF)-α与复发性卒中的相关性进行了研究.     

新型脂肪因子与动脉粥样硬化性脑梗死关系的研究进展

动脉粥样硬化性脑梗死(ASCI)的多个危险因素涉及代谢综合征(MS)的组分,而脂肪因子作为炎性反应介质在MS及ASCI发生、发展中发挥重要作用.随着研究的不断探索,一些新型脂肪因子逐渐被认识,其可通过参与胰岛素抵抗及炎性反应直接或间接与动脉粥样硬化及ASCI密切相关.充分理解新型脂肪因子在ASCI中的病理生理作用机制,...     

胰岛素抗炎作用研究进展

近年研究发现胰岛素(INS)具有一定的抗炎作用。INS可通过抑制核因子(NF)-κB的活性、增强抗炎因子的活性以及间接途径来发挥抗炎效应,且各种途径之间存在协同作用。在INS的作用下多种炎症因子,如C反应蛋白、粘附分子、纤溶酶原激活物抑制因子(PAI)-1、白介素(IL)-1水平明显降低,抗炎因子如内皮型一氧化氮(eNO)、IL-4、IL-10生成与释放增加。另外,INS对炎症性疾病如动脉粥样硬化具有潜在的对抗作用。     

胰岛素抗炎作用研究进展

近年研究发现胰岛素(INS)具有一定的抗炎作用。INS可通过抑制核因子(NF)-κB的活性、增强抗炎因子的活性以及间接途径来发挥抗炎效应，且各种途径之间存在协同作用。在INS的作用下多种炎症因子，如C反应蛋白、粘附分子、纤溶酶原激活物抑制因子(PAI)-1、白介素(IL)-1水平明显降低，抗炎因子如内皮型一氧化氮(eNO)、IL-4、IL-10生成与释放增加。另外，INS对炎症性疾病如动脉粥样硬化具有潜在的对抗作用。     

进展性卒中相关危险因素临床分析

目前进展性卒中发病率逐渐增多，进展性卒中的致死率及致残率较非进展性卒中高，进展性卒中与多种因素有关。现回顾分析72例进展性卒中病人的高血压、高血糖、高血脂、脑血管狭窄程度、心房纤颤及短暂性脑缺血发作等因素，探讨发生进展性卒中的危险因素，以期为预防发生进展性卒中提供依据。     

牛津郡社区卒中项目分型对进展性脑梗死的预测作用

目的探讨英国牛津郡社区卒中项目(OCSP)分型对进展性脑梗死的预测作用。方法收集2010年1月—2014年6月在合肥市第三人民医院神经内科住院的脑梗死病人,OCSP分型分为:完全前循环梗死(TACI)、部分前循环梗死(PACI)、后循环梗死(POCI)、腔隙性梗死(LACI);再根据病情有无进展分为非进展性和进展性脑梗死。比较各临床亚型脑梗死在非进展性和进展性脑梗死组间的分布差异,并分析梗死临床亚型与是否进展的相关性分析,然后进一步回归分析进展性脑梗死的危险因素。结果共150例病人入选,其中非进展性脑梗死99例,进展性脑梗死51例;其临床亚型分型中,发生在TACI为7例,PACI 45例,LACI64例,POCI 34例。不同临床亚型梗死在非进展性和进展性脑梗死组间分布差异有统计学意义(χ2=13.33,P=0.004),其中进展性脑梗死发生TACI、PACI的几率显著高于非进展性脑梗死。梗死临床亚型与是否进展的相关性分析表明:进展性脑梗死更易发生于TACI和PACI(r=0.18,P=0.03;r=0.21,P=0.01);进展性脑梗死危险因素的Logistic回归分析显示:梗死的临床亚型与其有关(P=0.007),表现为TACI、PACI发生梗死进展的可能性较其他亚型显著增加,但经年龄、血糖等相关因素校正后,此种趋势消失(P=0.09)。结论梗死临床亚型与其是否进展密切相关,发生在TACI、PACI的病人更容易出现病情进展,但年龄、血糖等相关因素更决定了脑梗死病情的进展。     

进展性卒中相关危险因素的预测价值

进展性卒中的病理生理学机制目前尚不清楚,难以准确预测哪些患者会出现神经功能恶化.卒中早期的血压水平、C-反应蛋白浓度、脑动脉狭窄程度、高血糖和卒中部位等因素与进展性卒中密切相关,对其发生有一定预测价值.     

进展性缺血性脑卒中患者血清IL-6和C-反应蛋白水平的变化及临床意义

目的探讨白细胞介素6(IL-6)、C-反应蛋白(CRP)在进展性缺血性脑卒中发病中的作用。方法分别采用双抗体夹心酶联免疫法和透射比浊法测定80例急性脑梗死患者不同时期血清IL-6、CRP水平变化,并根据临床神经功能缺损程度量表(NDS)评分判断是否发展为进展性脑卒中。另选40名健康体检者作为对照组。结果 80例急性脑梗死患者中有27例(33.75%)于7d内发展为进展性脑卒中,其发病后第1、3、7、14天外周血IL-6、CRP水平明显高于无进展的脑梗死患者(P0.05),第14天与正常对照组比较差异无统计学意义(P0.05)。发病当天IL-6、CRP水平与人院时体温、血白细胞数、血浆纤维蛋白原呈正相关(相关系数r=0.87、0.66、0.51,P均0.01),IL-6、CRP是进展性脑卒中危险因素。结论急性脑梗死患者血清IL-6、CRP增高与进展性缺血性脑卒中密切相关,可能在进展性缺血性脑卒中的发病过程中具有重要作用,监测血清IL-6、CRP水平对于监测疾病活动情况及严重程度等具有重要意义。     

Role of protein Z in stroke

Opinion statement Protein Z (PZ) is a vitamin K-dependent plasma glycoprotein that acts as a cofactor for PZ-dependent protease inhibitor to inhibit coagulation factor X_a. Studies in mice suggest that that decreased blood PZ levels lead to reduced inhibition of blood coagulation, thereby predisposing to thrombosis; however, clinical studies in humans have yielded conflicting results. Among patients with stroke, some epidemiologic studies have reported that reduced PZ levels increase the risk of stroke, whereas others have reported no association between PZ levels and stroke, or that elevated PZ levels increase stroke risk. Polymorphisms involving the gene for PZ can influence the PZ concentration and some polymorphisms (eg, intron G79A AA allele) may be protective against stroke, particularly among younger individuals. Although the association between PZ levels and stroke appears to be stronger in younger patients and in patients who do not have conventional vascular risk factors, it remains unclear whether the link between PZ levels and stroke is confounded or causal or whether blood levels of PZ are altered as a consequence of the acute stroke event.     

The Emerging Role of Biomarkers in Atrial Fibrillation

Improved diagnostic techniques have identified various biomarkers that might play an important role in prediction of atrial fibrillation (AF) and related outcomes (cardio- and cerebrovascular events, and mortality and rhythm outcomes). Biomarkers can include blood markers (eg, von Willebrand factor, D-dimer, natriuretic peptides, etc), urine (eg, proteinuria, estimated glomerular filtration rate, or creatinine clearance), cardiac imaging (echocardiography; transthoracic or transoesophageal), or cerebral imaging (eg, computed tomography or magnetic resonance imaging), which can provide additional refinement to clinical stroke risk stratification for identification of “high risk” subjects. Although inclusion of some blood-based biomarkers (eg, von Willebrand factor, D-dimer) in existing clinical stroke risk stratification schemes might improve their predictive value for identifying “high risk” patients, this concept might be outdated and overtaken by new developments in thromboprophylaxis (which now focus on initial identification of “low risk” patients who do not need any antithrombotic therapy, followed by patients with 1 or more stroke risk factors, to whom anticoagulation can be offered), and additional questionable practicality in “everyday” practice. Biomarkers could be applied as a “rule out” approach or as surrogates of anticoagulation efficacy in trials of new antithrombotic strategies. The present review aims to provide an update of the role of biomarkers in AF, with particular focus on AF outcomes.     

A putative immunotherapy with biological response modifiers (BRM) against intractable pulmonary tuberculosis]

The problem of tuberculosis is emerging again with increase in the population of aged people and immunocompromised patients in Japan. It has been well documented that cell-mediated immunity play a central role in host resistance to infection with Mycobacterium tuberculosis. Many recent studies have provided evidences suggesting that the Th1-Th2 cytokine balance may determine the outcome of some diseases: predominant production of Th1 cytokines may prevent the occurrence of infectious diseases caused by intracellularly growing pathogens and Th2 cytokines may be involved in the exacerbation of allergic diseases. On the other hand, IL-12 plays an essential role in the differentiation of Th1 cells from naive T cells, and IL-18 potentiates this effect although it does not show such effect by itself. In previous investigations using gene-disrupted mice, the essential roles for IFN-gamma, IL-12 and IL-18 have been demonstrated. There are several host factors which determines the outcome of mycobacterial infection. Among them, steroid treatment and AIDS are important factors. In this lecture, I addressed the effect of these pathological conditions on Th1-Th2 cytokine balance and outcome of mycobacterial infection using murine models. In both conditions, the exacerbated infection was well correlated with the reduced production of IFN-gamma. Furthermore, I also talked about the relationship between other host factors and balance in the production of Th1 and Th2 cytokines. Using a murine model of fatal infection with M. tuberculosis, we demonstrated the therapeutic effect of Th1-type cytokines against this infection and suggested that immunotherapy with these cytokines may be clinically effective in the intractable infection. We tried a combined therapy with anti-tuberculous agents and IFN-gamma in intractable pulmonary tuberculosis caused by multidrug-resistant pathogen in a patient with insulin-dependent diabetes mellitus. Although no report showing the clinical use of IL-12 in infectious diseases has been seen, clinical trials already commenced for the therapy of malignant neoplastic diseases. It may not be in far future that this cytokine is clinically used for the treatment of infectious diseases. IL-18 has not yet been under the clinical trials.     

Inflammatory cytokines in the pathophysiology of hypertension during preeclampsia

Reduced uterine perfusion pressure during pregnancy is an important initiating event in preeclampsia. Inflammatory cytokines are thought to link placental ischemia with cardiovascular and renal dysfunction. Supporting a role for cytokines are findings of elevated tumor necrosis factor (TNF)-α and interleukin (IL)-6 plasma levels in preeclamptic women. Blood pressure regulatory systems (eg, renin-angiotensin system [RAS] and sympathetic nervous system) interact with proinflammatory cytokines, which affect angiogenic and endothelium-derived factors regulating endothelial function. Chronic reductions in placental perfusion in pregnant rats are associated with enhanced TNF-α and IL-6 production. Chronic infusion of TNF-α or IL-6 into normal pregnant rats significantly increases arterial pressure and impairs renal hemodynamics. TNF-α activates the endothelin system in placental, renal, and vascular tissues, and IL-6 stimulates the RAS. These findings suggest that inflammatory cytokines elevate blood pressure during pregnancy by activating multiple neurohumoral and endothelial factors.     

Plasma cell myeloma--new biological insights and advances in therapy

Plasma cell myeloma is a more complex neoplasm than suggested by the relative uniformity of its dominant plasma cells, which represent the terminal stage of normal B-cell differentiation. Phenotypic, molecular, and cellular genetic data favor the presence of a myeloma stem cell early in hematopoietic development so that, as in chronic myelogenous leukemia (CML), a far distance exists between the primordial malignant cell that was the target of malignant transformation and the dominant clinical phenotype. Traces of pre-B, myeloid, and T cells are coexpressed with the mature B-cell phenotype, an occurrence unknown in normal B-cell differentiation. Analogous to CML, disease progression is marked by disease dedifferentiation, occasionally with cessation of myeloma protein production and development instead of extramedullary lymphomalike features with high LDH or myelodysplasia/acute myelogenous leukemia (AML) syndromes. The prognostic importance of serum LDH levels even in newly diagnosed myeloma suggests the early presence of tumor cells with "LDH phenotype," which, as a result of drug resistance and proliferative advantage, expand preferentially during disease progression. Further characterization of these cells may provide important clues about the ontogeny of multiple myeloma. Myeloma cells express many receptors for different biological signals that might be exploitable for therapy with immunotoxins or radioisotopes. Plasma cells and their precursors also produce a variety of cytokines, some of which have putatively autostimulatory functions (eg, IL-1, IL-5, IL-6) and/or are related to disease manifestations (eg, IL-1 and TNF-beta as OAF). The wealth of cellular expression by plasma cells provides clues for understanding the mechanisms of gene activation and the nature of abnormal growth and differentiation. The accuracy of prognostically relevant staging systems has been refined with the use of new quantitative parameters that reflect tumor mass (ie, serum B2M levels) and biology. Further studies of cellular and molecular biology (ie, CAL-LA, H-ras) may reveal those tumor cell features that define clinical entities, response to therapy, and long-term prognosis. The lack of a major advance in prognosis despite the use of more drugs and more intensive regimens justifies the continued use of standard melphalan-prednisone for patients with a highly favorable prognosis, for the very aged, and for those with a short life expectancy due to other major medical problems. However, a radical departure from standard practice is required to improve the prognosis for younger patients with poor risk features.(ABSTRACT TRUNCATED AT 400 WORDS)     

Predicting and preventing Post-ERCP pancreatitis

Pancreatitis is rightly the most feared complication of endoscopic retrograde cholangiopancreatography (ERCP). Ten percent to 15% of cases of post-ERCP pancreatitis (PEP) are severe by clinical and radiologic criteria. Such cases carry significant morbidity and mortality and are responsible for the vast majority of ERCP-related deaths. The prediction and prevention of PEP have been of great interest to endoscopists since the introduction of ERCP 30 years ago. Prediction and diagnosis of PEP have become more accurate with the widespread availability of serum amylase estimation. A variety of cytokines (eg, interleukin [IL]-1, IL-6, and IL-8) and acute phase reactants (eg, C-reactive protein) are also elevated in the serum in acute pancreatitis, and these form the basis of evolving tests for PEP. Urine testing (for amylase) in acute pancreatitis is obsolete, but it may soon undergo a revival in the form of a rapid (3-minute) dipstick test for trypsinogen-2, a sensitive and specific test for this disease. The prevention of PEP takes multiple forms. The following steps are recommended for clinicians: 1) avoid ERCP when other, less invasive or noninvasive imaging tests can do the job (eg, CT or magnetic resonance imaging); 2) avoid highrisk (of PEP) procedures, such as needle-knife papillotomy, balloon dilation of the biliary sphincter, and pancreatic sphincterotomy, and take steps to reduce risk when these procedures are unavoidable; 3) ensure that those who perform ERCP have adequate training and experience; and 4) consider pharmacologic intervention. Despite a depressing catalog of drug interventions that have failed over the years (eg, antihistamines, anticholinergics, and corticosteroids), three agents have recently shown promise: somatostatin; its octapeptide analogue, octreotide; and gabexate mesylate, a protease inhibitor.     

Th1 cytokine-based immunotherapy for cancer

Cytokine-based immunotherapy is executed by harnessing cytokines to activate the immune system to suppress tumors. Thl-type cytokines including IL-1, IL-2, IL-12 and granulocyte-macrophage colony-stimulating factor are potent stimulators of Thl differentiation and Thl-based antitumor response. Many preclinical studies demonstrated the antitumor effects of Thl cytokines but their clinical efficacy is limited. Multiple factors influence the efficacy of immunotherapy for tumors. For instance immunosuppressive cells in the tumor microenvironment can produce inhibitory cytokines which suppress antitumor immune response. Most studies on cytokine immunotherapy focused on how to boost Thl response; many studies combined cytokine-based therapy with other treatments to reverse immunosuppression in tumor microenvironment. In addition, cytokines have pleiotropic functions and some cytokines show paradoxical activities under different settings. Better understanding the physiological and pathological functions of cytokines helps clinicians to design Thl-based cancer therapy in clinical practice.     

Chronic heart failure and skeletal muscle catabolism: effects of exercise training

Although the clinical picture of cardiac cachexia is well-known in patients with advanced chronic heart failure (CHF) the factors that determine who is at risk for this progressive catabolic syndrome and who is not remain unclear. Different endocrine systems have been accused of being involved in this process: an imbalance between catabolic and anabolic steroids with an elevated cortisol/dihydroepiandrosterone ratio, an increased resting metabolic rate due to high levels of circulating catecholamines, various cytokines are activated in CHF (i.e. TNF-alpha, IL-6, IL-1beta and others), and elevated levels of growth hormone (GH) with inappropriately normal or low serum levels of insulin-like growth factor-I (IGF-I) have been described in cardiac cachexia. These catabolic factors contribute to peripheral muscle atrophy, augment the expression of the inducible nitric oxide synthase (iNOS), which in turn inhibits the aerobic cellular metabolism. The present review examines whether the catabolic factors can be influenced by a classical anabolic intervention: regular physical exercise training. Long-term training programs increase skeletal muscle cytochrome c oxidase activity and are associated with reduced local expression of pro-inflammatory cytokines as well as iNOS, and augment local IGF-I production. In concert, these beneficial effects of exercise training may help to retard the catabolic process in CHF finally leading to cardiac cachexia and death.