Circulating Myeloperoxidase May Cause False Negative Findings in the Analysis of Myeloperoxidase Antibodies in Systemic Vasculitis

In systemic vasculitis reliable detection of myeloperoxidase antibodies (MPO-Abs) is of great clinical importance in the diagnosis and follow-up of patients. We have studied whether circulating myeloperoxidase (MPO) could have an effect on MPO-Ab findings. Serum MPO and MPO-Abs were measured in 50 healthy individuals, 35 patients and in the follow-up samples from two patients with Wegener's granulomatosis.
Heating the sera at 56°C for 30min reduced the concentration of immunoreactive MPO both in control and patient sera. In 71% of the patient sera heating made initially negative MPO-Abs detectable. In a few cases with severe vasculitis the antibody findings remained totally negative. These results, together with the data from the follow-up samples from two patients with Wegener's granulomatosis, revealed that the serological diagnosis of vasculitis may be considerably delayed if only native samples are analysed for MPO-Abs. These findings are of considerable clinical significance for the interpretation of MPO-Ab results.
Circulating myeloperoxidase affects MPO-Ab measurements, causing false negative findings in MPO-Ab assays. Therefore, it is recommended to denaturate circulating MPO by heating the sera before the analysis of MPO-Abs and to re-evaluate the cut off-values.     

Role of extracellular calcium in in vitro uptake and intraphagocytic location of macrolides.

We compared the uptakes and intracellular locations of four 14-membered-ring macrolides (roxithromycin, dirithromycin, erythromycin, and erythromycylamine) in human polymorphonuclear neutrophils (PMNs) in vitro. Intracellular location was assessed by cell fractionation and uptake kinetics in cytoplasts (granule-poor PMNs). Trapping of dirithromycin within PMN granules (up to 80% at 30 min) was significantly more marked than the intracellular trapping of the other drugs (erythromycylamine, 45% +/- 5.1%; erythromycin, 42% +/- 3.7%; roxithromycin, 35% +/- 3.0%). A new finding was that, in the absence of extracellular calcium, the uptakes of all of the macrolides by PMNs and cytoplasts were significantly impaired, by about 50% (PMN) and 90% (cytoplasts). Furthermore, inorganic Ca2+ channel blockers inhibited macrolide uptake in a concentration-dependent manner, with 50% inhibitory concentrations of 1.6 to 2.0 mM and 29 to 35 microM, respectively, for Ni2+ and La3+. The intracellular distributions of the drugs were unchanged in the presence of Ni2+ and La3+ and in Ca(2+)-free medium supplemented with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. The organic Ca2+ channel blocker nifedipine had no effect on macrolide uptake, whereas verapamil inhibited it in a time- and concentration-dependent manner. These data show the importance of extracellular Ca2+ in macrolide uptake by phagocytes and suggest a link with Ca2+ channels or a Ca2+ channel-operated mechanism.     

Epigenetic change in e-cardherin and COX-2 to predict chronic periodontitis

Background  

DNA methylation of certain genes frequently occurs in neoplastic cells. Although the cause remains unknown, many genes have been identified with such atypical methylation in neoplastic cells. The hypermethylation of E-Cadherin and Cyclooxygenase 2 (COX-2) in chronic inflammation such as chronic periodontitis may demonstrate mild lesion/mutation epigenetic level. This study compares the hypermethylation status of E-Cadherin and COX-2 genes which are often found in breast cancer patients with that in chronic periodontitis.     

The current state of diabetes management in Taiwan

Antidisialosyl antibodies have been previously associated to chronic and acute ataxic neuropathies. We studied the presence of these antibodies in nine patients with acute self-limiting ataxic neuropathy (ASLAN) using ELISA and TLC immunodetection. One patient showed serum IgG immunoreactivity against gangliosides GD3 and GQlb. The patient's IgG was able to bind to the nodes of Ranvier on frozen human dorsal root. Our studies confirmed that antidisialosyl reactivity is associated to ataxic neuropathy and its specific binding to the dorsal root could explain the predominant sensory involvement. Nevertheless, the low incidence of this reactivity indicates that a different pathogenic mechanism should be involved in most ASLAN patients.     

Early immunological prediction of renal allograft rejection

Reliable predictors of impending renal allograft rejection would be valuable for better patient management. To date, no available test has been shown to be consistently predictive and results have often been conflicting. We evaluated an effector of cell-mediated immunity, antibody-dependent cell-mediated cytotoxicity (ADCC) as well as the response of these cells to different biological response modifiers (BRM) in patients following renal allograft transplantation. The in vitro test used assayed monocytes as ADCC effector cells against antibody-sensitized chicken red blood cells. The effects of BRM were studied by preincubating the monocytes with lymphoblastoid IFN, recombinant alpha 2-interferon or gamma-interferon. A follow-up study was performed on 47 patients with end-stage renal disease treated with renal allograft transplantation. ADCC activity and its response to BRM were assayed prior to transplantation, 2, 4, and 9 weeks post transplantation. In the case of rejection, ADCC was then studied prior to initiation of antirejection therapy and for 2 months following treatment of rejection episode. We noted that in patients with stable grafts, the ADCC activity as well as its response to BRM declined gradually during the first 2 weeks post grafting and remained decreased up to 3 months after transplantation. In contrast, in recipients who experienced rejection episodes there was a sustained and significant increase in ADCC response to BRM during the first 3 weeks post grafting. By the time the diagnosis of rejection had been established the baseline ADCC activity had also increased. Following treatment and stabilization of the graft, ADCC activity and its response to BRM was decreased, similar to that in patients with stable grafts.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cell-mediated immunity and biological response modifiers in insulin-dependent diabetes mellitus complicated by end-stage renal disease

Previous studies have shown several immunoregulatory abnormalities in insulin-dependent diabetes mellitus (IDDM). In this report we compared peripheral blood mononuclear cells (PBMC) from patients with IDDM complicated by end-stage renal disease (ESRD) to those from normal subjects and from patients with ESRD of different etiologies for their: natural killer (NK) and antibody-dependent cell-mediated cytotoxic (ADCC) activities; modulation of NK and ADCC activities by biological response modifiers (BRM) including purified human lymphoblastoid interferon, human recombinant alpha-2 interferon, human gamma interferon and human recombinant interleukin 2; proliferative response of T and B lymphocytes to concanavalin A (Con A), phytohemagglutinin and pokeweed mitogen, and ability to produce T-cell growth factor (interleukin 2; IL-2). PBMC of diabetic patients demonstrated significantly lower NK activity than normal and ESRD subjects. Upon treatment with BRM, NK activity was augmented and achieved normal levels. ADCC activity was not different from that of normal controls and exhibited similar increases when stimulated by BRM. The proliferative responses to Con A, phytohemagglutinin and pokeweed mitogen as well as IL-2 production in response to Con A stimulation were significantly lower in the IDDM group. Our results indicated that NK cells from patients with IDDM can respond to IL-2 with enhanced cytotoxicity, and, because activation of resting T cells by mitogenic stimuli depends on the production of IL-2 as well as the appearance of a receptor for IL-2, our finding of low levels of in vitro IL-2 production by PBMC from patients with IDDM may explain the depressed NK activity and the observed poor response to T-cell mitogens.     

Immunological monitoring and early prediction of rejection in renal allograft recipients

Graft rejection remains the major problem complicating renal allograft transplantation. A reliable posttransplant predictor of impending rejection will be valuable to help maintain better graft function. We monitored 47 patients with end-stage renal disease treated by renal allograft starting 1 day pretransplantation and continuing for up to 90 days postgrafting. Peripheral blood mononuclear cells (PBMC) from both patients and 71 healthy subjects were compared for: (1) DNA synthesis in T and B lymphocytes in response to mitogens; (2) interleukin-2 (IL-2) production; (3) natural killer (NK) and antibody-dependent cell-mediated cytotoxic (ADCC) activities; (4) induced augmentation of NK and ADCC activities by the biological response modifiers (BRM), lymphoblastoid interferon, recombinant alpha-2-interferon, gamma-interferon and recombinant IL-2. During the 2 weeks preceding rejection we found lower than normal levels of IL-2 production (p less than 0.0005) and DNA synthesis (p less than 0.01) in concanavalin A-stimulated PBMC. IL-2 yield reached its lowest level on the day of rejection and increased sharply the following week after antirejection therapy was started. Mitogen-stimulated DNA synthesis rose in parallel with increasing levels of IL-2 production. Both NK and ADCC activities increased during rejection (p less than 0.05). The ADCC response to BRM activation measured during the first 2 weeks postgrafting was found to correlate with the stability of the graft. Recipients whose graft function remained stable had a minimal ADCC response to BRM.(ABSTRACT TRUNCATED AT 250 WORDS)     

糖尿病患者消化间期胃肠运动障碍

目的:观察糖尿病患者消化间期胃肠运动的特征。方法:于1998-06/2003-06选择首都医科大学附属北京同仁医院消化内科收治2型糖尿病患者243例,为糖尿病组。同期选择健康志愿者20例,为对照组。使用胃肠测压法进行消化间期胃肠运动功能的检测,6个测压孔分别置于胃窦、十二指肠和近端空肠的位置。根据测压管顶端的3个金属标记物在X射线透视下定位或根据移行性复合运动压力波的频率特征定位,一般胃窦收缩频率约3次/min,十二指肠和近端空肠为8～12次/min,测定时间为240～360min。结果:在两组全部受检测人群中发现3种胃肠运动类型:类型1:发生于胃和小肠发生的移行性复合运动,在糖尿病组占23.05%(56/243),对照组占70.00%(14/20),两组比较差异有显著性意义(χ2=20.86,P<0.01);类型2:单纯发生于小肠的移行性复合运动,胃窦缺乏Ⅲ期收缩活动,在糖尿病组占13.58%(33/243),对照组占15.00%(3/20),两组比较差异无显著性意义;类型3:表现为周期性不规则收缩活动,在胃窦和小肠均缺乏Ⅲ期收缩活动,在糖尿病组占57.20%(139/243),在对照组占15.00%(3/20),两组比较差异有显著性意义(χ2=13.24,P<0.01);连续4h的胃肠动力检测中未出现胃、小肠的收缩活动者,在糖尿病组占6.17%(15/243),在对照组0例,两组比较差异无显著性意义(χ2=1.30,P>0.05)。结论:糖尿病患者消化间期胃肠运动功能障碍的主要特征是周期性不规则收缩活动取代了移行性复合运动,其结果可能会延长食物在小肠停留的时间,加重糖尿病的代谢紊乱和并发症。有效地改善和恢复糖尿病患者的胃肠功能是治疗糖尿病及其并发症的一个重要方面。     

益气生骨颗粒对大鼠骨折愈合骨痂中无机质及钙含量的影响

目的:中药黄芪有补气固表作用,当归、川芎、红花、有补血活血散瘀止痛功效。观察由黄芪、党参、当归、川芎、红花等组成的新药制剂益气生骨颗粒对骨折大鼠骨痂无机物和钙含量的影响,探讨其促进骨折愈合的机制。方法:实验于2006-04/09在河南省正骨研究院生物医学工程研究室完成。实验分组:选择SD雄性大鼠36只,随机分为空白组、模型组、对照组和益气生骨颗粒剂组,每组9只。实验材料:益气生骨颗粒(自行研制,由黄芪、党参、当归、川芎、红花等组成)。实验过程:①除空白组外其余3组动物称质量后,以30g/L戊巴比妥钠(40mg/kg)腹腔注射麻醉,用手术剪剪断左侧桡骨,造成左侧桡骨骨折模型,缝合切口,不包扎。②造模后第2天开始灌胃给药,模型组动物给予颗粒剂辅料9.6g/(kg·d),每日分2次灌胃;对照组给予恒古骨伤愈合剂2.5mL/(kg·d),每2日1次灌胃;益气生骨颗粒组给予益气生骨颗粒12g/(kg·d),每日分2次灌胃;空白组正常喂养。实验评估:6周后动物麻醉后处死。取骨痂,用焚烧法测定骨痂无机质和有机物含量,利用原子吸收分光光度法测定骨痂钙含量。结果:空白组因麻醉死亡2只大鼠,共34只进入结果分析。①骨痂无机质和有机质含量:益气生骨颗粒剂组和阳性药物对照组无机质含量都高于空白组和模型组[(29.039±3.082)%,(27.761±2.885)%比(24.450±3.620)%,(25.989±3.749)%,P<0.05],而有机质含量均低于空白组和模型组(P<0.05)。②骨痂钙含量:益气生骨颗粒剂组骨痂钙含量高于空白组[(4.365±0.435)%,(3.743±0.239)%,P<0.05]。结论:益气生骨颗粒通过提高骨痂无机质含量和促进钙的沉积促进骨折愈合。     

Adolescents,parents and teachers’ perceptions of risk and protective factors of substance use in Moroccan adolescents: a qualitative study

Background

Substance use in adolescents is a global public health concern that continues to draw attention from academics, policy experts, and government officials. In Morocco, few studies have investigated the influencing factors of substance use in adolescents. Here, we aimed to fill this gap and to better understand factors that protect or influence substance use in adolescents.

Methods

We conducted a qualitative study using focus group discussions. The semi-structured interview guides were based on the socio-ecological model as a theoretical framework to explore perceptions of students, parents, and teachers regarding substance use risks and protective factors in adolescents. Data from each group were audio-recorded, transcribed, and analyzed using thematic analysis.

Results

From May to July 2016, 17 focus group discussions were conducted at two middle schools in Taza city, Morocco, which included 8 groups of 7 adolescents (28 boys and 28 girls) aged 14 to 16 years, 5 groups of parents (5 females and 21 males), and 4 groups of teachers (13 males and 5 females). Thematic analysis resulted in six common themes that represented the most salient perceived risk and protective factors regarding substance use among adolescents: perceived benefits of substance use, awareness and beliefs, family influence, peer influence, easy accessibility of substances, and social norms.

Conclusions

Our results demonstrate that multilevel prevention programs in adolescents should address influencing factors from the individual to the societal level, including social norms and the government’s policy toward substance use. Health education programs included as part of the school curriculum can contribute to promoting awareness and reducing risky behaviors of Moroccan adolescents.