Antibodies to ribosomal P proteins of Trypanosoma cruzi in Chagas disease possess functional autoreactivity with heart tissue and differ from anti-P autoantibodies in lupus

Anti-P antibodies present in sera from patients with chronic Chagas heart disease (cChHD) recognize peptide R13, EEEDDDMGFGLFD, which encompasses the C-terminal region of the Trypanosoma cruzi ribosomal P1 and P2 proteins. This peptide shares homology with the C-terminal region (peptide H13 EESDDDMGFGLFD) of the human ribosomal P proteins, which is in turn the target of anti-P autoantibodies in systemic lupus erythematosus (SLE), and with the acidic epitope, AESDE, of the second extracellular loop of the β₁-adrenergic receptor. Anti-P antibodies from chagasic patients showed a marked preference for recombinant parasite ribosomal P proteins and peptides, whereas anti-P autoantibodies from SLE reacted with human and parasite ribosomal P proteins and peptides to the same extent. A semi-quantitative estimation of the binding of cChHD anti-P antibodies to R13 and H13 using biosensor technology indicated that the average affinity constant was about 5 times higher for R13 than for H13. Competitive enzyme immunoassays demonstrated that cChHD anti-P antibodies bind to the acidic portions of peptide H13, as well as to peptide H26R, encompassing the second extracellular loop of the β₁ adrenoreceptor. Anti-P antibodies isolated from cChHD patients exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats, which resembles closely that of anti-β₁ receptor antibodies isolated from the same patient. In contrast, SLE anti-P autoantibodies have no functional effect. Our results suggest that the adrenergic-stimulating activity of anti-P antibodies may be implicated in the induction of functional myocardial impairments observed in cChHD.     

HO-1在顺铂诱导豚鼠螺旋神经元损伤中的作用

目的检测血红素加氧酶-1在豚鼠耳蜗螺旋神经节顺铂损伤后的表达变化。方法通过免疫组织化学及Western Blot技术,观察耳蜗螺旋神经元损伤后HO-1在不同组间的表达变化。将32只健康豚鼠随机分为4组,每组8只。A组对照组:按体重以0.9%生理盐水12ml/kg腹腔注射,早晚各一次,持续3天。B组顺铂组:按体重12mg/kg顺铂腹腔注射(IP),早晚各一次,持续3天。C组阿魏酸(FA)+顺铂组:先150mg/kg FA腹腔注射预处理1h,再以12mg/kg顺铂IP,早晚各一次,持续三天。D组FA+锌原卟啉Ⅸ(ZnppⅨ)+顺铂组:同时给予150mg/kg FA+ZnppⅨ15umol/kg IP预处理1h,再以12mg/kg顺铂IP,早晚各一次,持续三天。采用免疫组织化学及Wstern Blot技术检测不同组间螺旋神经元HO-1蛋白表达变化。结果在不同的分组中,HO-1在耳蜗螺旋神经节中表达量不同。空白组中,螺旋神经节组织存在微弱的HO-1表达,其蛋白表达量为0.48±0.07;A组蛋白表达量为0.81±0.07,B组蛋白表达量为0.9±0.05,C组蛋白表达量为0.61±0.07。4个组两两间差异均有统计学意义(p<0.0001)。结论 HO-1在C组中表达量最多,B组次之,D组最少,表明HO-1可能参与顺铂损伤螺旋神经元后的修复过程。     

QT Interval in Patients with Unstable Angina and Non‐Q Wave Myocardial Infarction

Background: Non‐Q wave mvocardial infarction (NQMI) and unstable angina (UAP) have similar clinical presentations and similar ST‐T changes on the electrocardiogram. The purpose of this study was to assess whether changes in QT interval might help differentiating between these entities. Methods: The QT intervals of 52 patients hospitalized with NQMI were compared to those of 52 patients hospitalized for UAP. All patients had repeated ECG for at least 4 days. Results: Maximal QTc in patients with NQMI was significantly longer than in patients with UAP (475 vs 439 ms, P < 0.0001). QTc on the admission ECG was 450 ms in patients with NQMI compared to 417 ms in UAP P < 0.005). QTc > 460 ms was present in 48% patients with NQMI and in 19% of UAP patients. Maximal QT prolongation was observed within 36 hours of admission with return to normal within 96 hours. QT dispersion was within normal range, being longer in patients with NQMI than patients with UAP (55 vs 43 ms, P < 0.003). QT prolongation was not associated with increased frequency of arrhythmia. The cause of QT prolongation in NQMI may be related to the damage of subendocardial layer exposing the M cells layer which markedly prolong action potential duration. Conclusion: Transient QT prolongation is observed in about half of patients with NQMI. These ECG changes may help differentiating between patients with NQMI and UAP already on admission. A.N.E. 2002;7(4):343–348     

MARS: a futile tool in centres without active liver transplant support.

BACKGROUND AND AIM: Studies on Molecular Adsorbent Recycling Systems (MARS) showed inconclusive survival benefits. PATIENTS AND METHOD: We evaluated the efficacy of MARS for patients with either acute liver failure (ALF) or acute-on-chronic liver failure (AoCLF) at our centre, from February 2002 till April 2006 retrospectively. RESULTS: Fifty ALF patients underwent median (range) three (1-10) sessions of MARS. Acute exacerbations of chronic hepatitis B (n=26) and drug-induced liver injury (n=12) were the commonest causes. Living donors were available in 6, 2 paediatric patients underwent left lobe and four adults underwent right lobe living donor liver transplant. Among the 44 ALF patients without a suitable living donor, one underwent deceased donor liver transplant and survived, another 19-year-old male with acute exacerbations of chronic hepatitis B recovered without transplant, and the rest died. Twenty-six had AoCLF and underwent four (1-10) MARS sessions. Sepsis (n=16) and upper gastrointestinal bleeding (n=4) were the commonest precipitating factors. None had a suitable living or deceased donor, suitable for transplantation during their hospitalization. Only one of 26 AoCLF patients survived the hospitalization, but the survivor died of sepsis 1 month later. CONCLUSION: In this non-randomized study, survival after MARS was related to the availability of transplant, and in patients where living or deceased donor transplant was unavailable, MARS was of little benefit. Randomized-controlled trials on MARS((R)) are urgently needed to clarify its clinical utility.     

Targeted delivery of adipose‐derived stem cells via acellular dermal matrix enhances wound repair in diabetic rats

Cell‐based therapeutic intervention has emerged as a new approach to accelerate wound closure. Adipose‐derived stem cells (ASCs), as a fascinating cell source, have received much attention in tissue repair and regeneration. In this study we evaluated the potential of acellular dermal matrix (ADM) scaffold serving as a carrier for the delivery of ASCs and investigated its therapeutic effects on wound healing. First, ASCs were isolated and characterized for multidifferentiation potential. ASCs–ADM grafts were then prepared, and ADM scaffold was shown to support the in vitro growth and proliferation of ASCs. Next, we analysed paracrine factors in conditioned medium and found that ASCs–ADM grafts secreted various cytokines, including VEGF, HGF, TGFβ and bFGF. Moreover, ASCs–ADM conditioned medium notably stimulated the migration and proliferation of fibroblasts. In vivo, we established an excisional wound model in diabetic rats which received phosphate‐buffered saline (PBS), ADM or ASCs–ADM grafts, respectively. Our results demonstrated that implantation of ASCs–ADM significantly enhanced tissue regeneration and increased epithelialization, resulting in accelerated wound closure. Immunofluorescence analysis further indicated that capillary density was evidently increased in the ASCs–ADM group compared with the control or ADM group. In addition, western blot analysis showed that ASCs–ADM significantly increased the expression of angiogenic factors, which was consistent with in vitro data. Taken together, our results suggest that targeted delivery of ASCs via ADM scaffold accelerate diabetic wound healing through a paracrine mechanism, with enhanced granulation tissue formation and increased re‐epithelialization and neovascularization. Copyright © 2012 John Wiley & Sons, Ltd.     

Atypical prefrontal cortical responses to joint/non-joint attention in children with autism spectrum disorder (ASD): A functional near-infrared spectroscopy study

Autism spectrum disorder (ASD) is a neuro-developmental disorder, characterized by impairments in one’s capacity for joint attention. In this study, functional near-infrared spectroscopy (fNIRS) was applied to study the differences in activation and functional connectivity in the prefrontal cortex between children with autism spectrum disorder (ASD) and typically developing (TD) children. 21 ASD and 20 TD children were recruited to perform joint and non-joint attention tasks. Compared with TD children, children with ASD showed reduced activation and atypical functional connectivity pattern in the prefrontal cortex during joint attention. The atypical development of left prefrontal cortex might play an important role in social cognition defects of children with ASD.OCIS codes: (170.2655) Functional monitoring and imaging, (170.5380) Physiology, (170.3880) Medical and biological imaging