Adaptive immunity is related to coronary artery disease severity after acute coronary syndrome in subjects with metabolic syndrome

Metabolic syndrome (MetS) is an inflammatory state associated with high coronary disease risk. Inflammation and adaptive immunity modulate atherosclerosis and plaque instability. We examined early changes in anti-oxidized lowdensity lipoprotein (LDL) (anti-oxLDL) autoantibodies (Abs) in patients with MetS after an acute coronary syndrome (ACS). Patients of both genders (n=116) with MetS were prospectively included after an acute yocardial infarction (MI) or hospitalization due to unstable angina. Anti-oxLDL Abs (IgG class) were assayed at baseline, three and six weeks after ACS. The severity of coronary disease was evaluated by the Gensini score. We observed a decrease in anti-oxLDL Abs titers (p<0.002 vs. baseline), mainly in males (p=0.01), in those under 65 y (p=0.03), and in subjects with Gensini score above median (p=0.04). In conclusion, early decrease in circulating anti-oxLDL Abs is associated with coronary disease severity among subjects with MetS.

Early Increase in Autoantibodies Against Human Oxidized Low-Density Lipoprotein in Hypertensive Patients After Blood Pressure Control

BACKGROUND Oxidized lipoproteins and antioxidized low-density lipoprotein (anti-oxLDL) antibodies (Abs) have been detected in plasma in response to blood pressure (BP) elevation, suggesting the participation of the adaptive immune system. Therefore, treatment of hypertension may act on the immune response by decreasing oxidation stimuli. However, this issue has not been addressed. Thus, we have here analyzed anti-oxLDL Abs in untreated (naive) hypertensive patients shortly after initiation of anti hypertensive therapeutic regimens. METHODS Titers of anti-oxLDL Abs were measured in subjects with recently diagnosed hypertension on stage 1 (n = 94), in primary prevention of coronary disease, with no other risk factors, and naive of anti hypertensive medication at entry. Subjects were randomly assigned to receive perindopril, hydrochlorothiazide (HCTZ), or indapamide (INDA) for 12 weeks, with additional perindopril if necessary to achieve BP control. Abs against copper-oxidized LDL were measured by enzyme-linked immunosorbent assay. RESULTS Twelve-week antihypertensive treatment reduced both office-based and 24-h ambulatory BP measurements (P < 0.0005). The decrease in BP was accompanied by reduction in thiobarbituric acid-reactive substances (TBARS) (P < 0.05), increase in anti-oxLDL Ab titers (P < 0.005), and improvement in flow-mediated dilation (FMD) (P < 0.0005), independently of treatment. Although BP was reduced, we observed favorable changes in anti-oxLDL titers and FMD. CONCLUSIONS We observed that anti-oxLDL Ab titers increase after antihypertensive therapy in primary prevention when achieving BP targets. Our results are in agreement with the concept that propensity to oxidation is increased by essential hypertension and anti-oxLDL Abs may be protective and potential biomarkers for the follow-up of hypertension treatment.

Cutting Edge: Brazilian Pemphigus Foliaceus Anti-Desmoglein 1 Autoantibodies Cross-React with Sand Fly Salivary LJM11 Antigen

The environmental factors that contribute to the development of autoimmune diseases are largely unknown. Endemic pemphigus foliaceus in humans, known as Fogo Selvagem (FS) in Brazil, is mediated by pathogenic IgG4 autoantibodies against desmoglein 1 (Dsg1). Clusters of FS overlap with those of leishmaniasis, a disease transmitted by sand fly (Lutzomyia longipalpis) bites. In this study, we show that salivary Ags from the sand fly, and specifically the LJM11 salivary protein, are recognized by FS Abs. Anti-Dsg1 monoclonal autoantibodies derived from FS patients also cross-react with LJM11. Mice immunized with LJM11 generate anti-Dsg1 Abs. Thus, insect bites may deliver salivary Ags that initiate a cross-reactive IgG4 Ab response in genetically susceptible individuals and lead to subsequent FS. Our findings establish a clear relationship between an environmental, noninfectious Ag and the development of potentially pathogenic autoantibodies in an autoimmune disease. The Journal of Immunology, 2012, 189: 1535-1539.

Juvenile neuronal ceroid lipofuscinosis; psychiatric symptoms, GAD-autoantibodies, and response to medication

Juvenile neuronal ceroid lipofuscinosis (JNCL) is one of the most common neurodegenerative diseases in childhood. Its clinical onset, with visual failure as the first sign, is between the ages of 4 to 8 years. During the disease progress, epilepsy, motor symptoms, cognitive decline, and psychiatric symptoms become apparent. It leads to premature death between ages 15 and 30. Treatment consists of symptomatic drug administration and various forms of rehabilitation, but to date, no curative treatment exists. To gain a more comprehensive picture of psychiatric problems, symptoms were evaluated by the Child Behavior Checklist, the Teacher Report Form, and the Children s Depression Inventory. The JNCL patients had a great number of severe psychiatric symptoms, with wide inter-individual variability. The most common symptoms were social, thought, attention, and sleep problems, somatic complaints, and aggressive behaviour. Patients with psychotropic treatment had more problems than did those without psychotropic treatment, and female patients had more problems than did males. Between 10 and 20% of the patients reported depressive symptoms. In a 5-year follow-up, [123I]β-CIT SPECT and MRI revealed a tendency of decreasing serotonin transporter (SERT) availability and progressive brain atrophy. The correlation between changes in midbrain SERT and total brain volume was positive; no correlation appeared between SERT or brain atrophy and depressive symptoms. Thus, it seems likely that the low SERT availability is associated with progressive brain atrophy; it may also predispose towards depression, however. An open survey of psychotropic drugs and their efficacy was performed on JNCL patients in Finland. The most commonly used psychotropic drugs were the antidepressant citalopram and the antipsychotic risperidone. Their efficacy was good or satisfactory in the majority of cases and they seemed well tolerated. Quetiapine had a marked effect on one patient with a history of severe psychotic symptoms. Glutamate decarboxylase 65 autoantibodies (GAD65ab), found in JNCL patients, indicate that an immunomediated reaction against GAD or GABAergic neurons may play a part in the underlying pathogenetic mechanism. GAD65ab s also appeared in the serum of all eight JNCL patients included and intermittent corticosteroid therapy was initiated in all cases. After one year, the GAD65ab s had disappeared in the two oldest patients, who experienced an improvement in motor symptoms and alertness associated with their prednisolone therapy. Two younger patients experienced a significant IQ increase, but no change in GADab s. A randomized study with longer follow-up time is needed, however, to clarify the effect of prednisolone on disease progression.

IgG4 Autoantibodies to DNA in Systemic Lupus erythematosus Patients

The presence of DNA-specific IgG4 antibodies was demonstrated in the sera of patients with systemic lupus erythematosus (SLE) by a microtiter solid-phase radioimmunoassay. A patient with distal inter-phalangeal swelling and extensive ulcers in the oral cavity, seronegative for anti-DNA antibodies of the IgG isotype, was found to have anti-DNA autoantibodies exclusively of the IgG4 subclass. These autoantibodies directed against the dsDNA conformation cross-reacted with chondroitin sulfate, dermatan sulfate and heparin.

Tailoring the dispersion of multiwall carbon nanotubes in co-continuous PVDF/ABS blends to design materials with enhanced electromagnetic interference shielding

Highly conducting composites were derived by selectively localizing multiwall carbon nanotubes (MWNTs) in co-continuous PVDF/ABS (50/50, wt/wt) blends. The electrical percolation threshold was obtained between 0.5 and 1 wt% MWNTs as manifested by a dramatic increase in the electrical conductivity by about six orders of magnitude with respect to the neat blends. In order to further enhance the electrical conductivity of the blends, the MWNTs were modified with amine terminated ionic liquid (IL), which, besides enhancing the interfacial interaction with PVDF, facilitated the formation of a network like structure of MWNTs. This high electrical conductivity of the blends, at a relatively low fraction (1 wt%), was further explored to design materials that can attenuate electromagnetic (EM) radiation. More specifically, to attenuate the EM radiation by absorption, a ferroelectric phase was introduced. To accomplish this, barium titanate (BT) nanoparticles chemically stitched onto graphene oxide (GO) sheets were synthesized and mixed along with MWNTs in the blends. Intriguingly, the total EM shielding effectiveness (SE) was enhanced by ca. 10 dB with respect to the blends with only MWNTs. In addition, the effect of introducing a ferromagnetic phase (Fe3O4) along with IL modified MWNTs was also investigated. This study opens new avenues in designing materials that can attenuate EM radiation by selecting either a ferroelectric (BT-GO) or a ferromagnetic phase (Fe3O4) along with intrinsically conducting nanoparticles (MWNTs).

Simultaneous enhancement in mechanical strength, electrical conductivity, and electromagnetic shielding properties in PVDF-ABS blends containing PMMA wrapped multiwall carbon nanotubes

A unique approach was adopted to drive the multiwall carbon nanotubes (MWNTs) to the interface of immiscible PVDF-ABS blends by wrapping the nanotubes with a mutually miscible homopolymer (PMMA). A tailor made interface with an improved stress transfer was achieved in the blends with PMMA wrapped MWNTs. This manifested in an impressive 108% increment in the tensile strength and 48% increment in the Young's modulus with 3 wt% PMMA wrapped MWNTs in striking contrast to the neat blends. As the PMMA wrapped MWNTs localized at the interface of PVDF-ABS blends, the electrical conductivity could be tuned with respect to only MWNTs, which were selectively localized in the PVDF phase, driven by thermodynamics. The electromagnetic shielding properties were assessed using a vector network analyser in a broad range of frequency, X-band (8-12 GHz) and Ku-band (12-18 GHz). Interestingly, enhanced EM shielding was achieved by this unique approach. The blends with only MWNTs shielded the EM waves mostly by reflection however, the blends with PMMA wrapped MWNTs (3 wt%) shielded mostly by absorption (62%). This study opens new avenues in designing materials, which show simultaneous improvement in mechanical, electrical conductivity and EM shielding properties.

ABS树脂形态结构及力学性能的研究

ABS树脂具有优良的抗冲击性、耐热性和耐化学药品性，还具有易加工性、制品尺寸稳定性等特点，广泛应用于工业领域。ABS树脂的制备方法有许多种，目前应用最为广泛的是乳液接枝ABS共聚物一本体SAN掺混法。首先采用乳液聚合方法合成聚丁二烯胶乳，然后将其作为种子进行苯乙烯和丙烯睛的接枝共聚反应生成ABS接枝共聚物；采用本体法制备SAN树脂；最后将ABS接枝共聚物（冲击改性剂）和SAN树脂共混制得ABS树脂。由此看来，ABS接枝共聚物的合成是控制ABS树脂性能的关键。目前国产ABS树脂普遍存在的问题是ABS接枝共聚物的增韧效率低。影响其增韧效率的因素包括共聚单体的组成、橡胶相的组成及结构、橡胶与树脂之间的界面结合力等。因此为提高ABS冲击改性剂的增韧效率，拓宽ABS树脂的应用领域，应合理地控制ABS冲击改性剂的合成参数。本论文采用种子乳液聚合方法在PB（聚丁二烯）橡胶粒子上接枝共聚苯乙烯和丙烯睛合成ABS接枝共聚物，将其作为冲击改性剂与SAN树脂共混制备ABS树脂，对ABS树脂形态结构及力学性能进行了研究。主要研究内容和结论如下：1、研究ABS接枝共聚物中PB／SAN组成、TDDM（叔十二碳硫醇）链转移剂和CHP（过氧化氢异丙苯）用量、单体加料方式及引发剂类型对SAN在PB橡胶粒子上接枝度的影响。sAN在PB橡胶粒子上的接枝度随PB和TDDM含量的增加而降低；随CHP用量的增加先增加后降低；随单体滴加时间的延长而增加，但过分延长时间则对接枝度影响很小；与AIBN（偶氮二异丁睛）和K25208（过硫酸钾）相比，采用氧化一还原引发体系得到的接枝度较高。2、研究ABS接枝共聚物的力学性能。DMA结果表明，随着PB含量的增加，ABS接枝共聚物的储能模量降低，橡胶相的玻璃化转变温度向低温移动，内耗峰值增加。拉伸试验结果表明，当体系中没有TDDM时，不同橡胶含量的ABS接枝共聚物均没有发生明显的应变软化；当加入适量的TDDM后，材料发生应变软化，且随着TDDM用量的增加，材料的屈服应力提高。3、研究ABS接枝共聚物对ABS树脂形态结构及力学性能的影响。ABS接枝共聚物中PB／SAN组成及TDDM链转移剂用量影响ABs树脂中橡胶粒子的内部形态及橡胶粒子在基体中的分散。在合成ABS接枝共聚物的过程中，应合理地调节PB／SAN组成及TDDM的用量以使ABS接枝共聚物达到最大的增韧效率。4、研究ABS树脂在不同应变速率下的断裂行为及形变机理。结果表明，橡胶含量及应变速率影响ABS树脂的力学性能，但没有改变ABS树脂的形变机理。ABS树脂的形变机理包括银纹、橡胶粒子的空洞化及基体的剪切屈服，其中占主导地位的是橡胶粒子的空洞化及基体的剪切屈服。