The effects of cichorium intybus extract on the maturation and activity of dendritic cells

Background

Cichorium intybus is a medicinal plant commonly used in traditional medicine for its benefits in immune-madiated disorders. There are several evidences showing that C. intybus can modulate immune responses. In the present study we have investigated the effects of the ethanolic root extract of this plant on the immune system by targeting dendritic cells (DCs). For this purpose, phenotypic and functional maturity of murine DCs after treatment with the extract was analyzed by flow cytometry and mixed lymphocyte reaction (MLR) assay.

Results

C. intybus did not change the expression of CD40, CD86 and MHC-II molecules as important co-stimulatory markers on DCs compared to the control, indicating that it could not promote DCs phenotypic maturation. Treatment of DCs with lower concentrations of the extract resulted in an increased production of IL-12 by these cells with no change in IL-10 release. The capacity of treated DCs to stimulate allogenic T cells proliferation and cytokines secretion was examined in the co-cuture of these cells with T cells in MLR. C. intybus at higher concentrations inhibited proliferation of allogenic T cells and in lower concentrations changed the level of cytokines such that IL-4 decreased and IFN-γ increased.

Conclusions

These results indicated that C. intybus extract at higher concentrations can inhibit T cell stimulating activity of DCs, whereas at lower concentrations can modulate cytokine secretion toward a Th1 pattern. These data may in part explain the traditional use of this plant in treatment of immune-mediated disorders.     

立体定向下经皮穿刺三叉神经半月节射频热凝术心血管反应的护理对策

目的分析立体定向及三维CT引导经皮穿刺三叉神经半月节射频热凝(PRTTG)治疗三叉神经痛(TN)时产生心血管反应的原因及护理对策。方法对138例原发性TN患者局麻下行立体定向及三维CT引导下PRTTG,术中全程监测患者的心电图、心率、呼吸、血压、血氧饱和度。结果治疗TN 138例中,有16例患者在穿刺卵圆孔过程中出现心率和血压下降,所有138例患者在行射频热凝时均出现心率及血压的升高,经积极干预,无发生心脑血管意外等重大并发症。结论立体定向导航及三维CT引导下PRTTG,密切观察患者心电及血压变化,是减轻患者心血管反应、保证手术顺利完成的关键。     

低潮气量单肺通气复合呼气末正压对肺癌手术患者肺部炎症反应的影响

目的：对比低潮气量单肺通气复合呼气末正压（PEEP）与正常潮气量单肺通气对肺癌手术患者肺部炎症反应的影响。方法40例择期肺癌手术患者随机分为低潮气量单肺通气复合PEEP组（L组）和正常潮气量单肺通气组（N组）,每组20例。两组患者分别在麻醉诱导后双肺通气时（T1）、单肺通气60 min时（T2）、单肺通气90 min时（T3）、术毕双肺通气60 min时（T4）、术后1 d（T5）采取外周静脉血,采用放射酶联免疫吸附法（ELISA）测量肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）及白细胞介素-10（IL-10）水平。结果与T1比较,两组各时点血浆TNF-α, IL-6, IL-8及IL-10水平均持续升高（P〈0.05）;L组TNF-α, IL-6, IL-8在T2、T3、T4、T5时间点均明显低于N组（P〈0.05）;L组血浆IL-10在T2、T3、T4、T5时间点明显高于N 组（P〈0.05）。结论与正常潮气量单肺通气相比,采用低潮气量单肺通气复合呼气末正压可明显减轻肺部的炎症反应,从而减轻肺部损伤。     

Role of concealed conduction and allied phenomena in the genesis,maintenance, and termination of cardiac arrhythmias

Concealed conduction is a common electrocardiographic phenomenon whereby a series of events may occur as a result of incomplete propagation of an impulse. The occurrence, maintenance, and resolution (termination) of several events such as functional block and cardiac arrhythmias are linked to concealed conduction. This phenomenon should be suspected on the surface electrocardiogram whenever an arrhythmic event occurs unexpectedly. Several electrophysiological concepts such as transseptal conduction and linking phenomenon are close allies of concealed conduction. His‐bundle electrocardiography and comprehensive electrophysiology may be needed to verify this phenomenon.     

Age-Related Differences in Intestinal Arteriolar Responses to Venous Pressure Elevation in the Rat

Objective : We previously reported differences in intestinal arteriolar responses of adult and suckling rats to three stressors (hemorrhage, hypoxia, and hypothermia) that decreased intestinal blood flow. The small, premucosal arterioles of adult rats dilated in response to all three stressors, whereas the premucosal arterioles of suckling rats constricted or remained unchanged. One explanation for this difference might be absence of myogenic responsiveness in the premucosal arterioles of the immature rat. Methods : We used in vivo videomicroscopy to observe the intestinal arteriolar responses to venous pressure elevation (a myogenic stimulus) in adult (8- to 12-week-old) and suckling (8- to 12-day-old) Sprague-Dawley rats. We increased portal venous pressure by 25 and 50% above the baseline pressure. Results : Arterioles in the adult rats displayed the expected “myogenic” response to venous pressure elevation (diameters decreased 12–19% when venous pressure was increased by 50%). In contrast to adult rats, arterioles in the suckling rats failed to constrict in response to increases in venous pressure (diameters increased 14–21% in response to a 50% increase in venous pressure). Conclusions : These results suggest diat the myogenic constrictor mechanisms for control of the microcirculation appear to be either nonfunctional or suppressed in the intestinal microcirculation of suckling rats.     

Methods for the analysis of multiple endpoints in small populations: A review

While current guidelines generally recommend single endpoints for primary analyses of confirmatory clinical trials, it is recognized that certain settings require inference on multiple endpoints for comprehensive conclusions on treatment effects. Furthermore, combining treatment effect estimates from several outcome measures can increase the statistical power of tests. Such an efficient use of resources is of special relevance for trials in small populations. This paper reviews approaches based on a combination of test statistics or measurements across endpoints as well as multiple testing procedures that allow for confirmatory conclusions on individual endpoints. We especially focus on feasibility in trials with small sample sizes and do not solely rely on asymptotic considerations. A systematic literature search in the Scopus database, supplemented by a manual search, was performed to identify research papers on analysis methods for multiple endpoints with relevance to small populations. The identified methods were grouped into approaches that combine endpoints into a single measure to increase the power of statistical tests and methods to investigate differential treatment effects in several individual endpoints by multiple testing.     

Nasal immunization of mice with AFCo1 or AFPL1 plus capsular polysaccharide Vi from Salmonella typhi induces cellular response and memory B and T cell responses

The response to infection against Salmonella involves both B and T cell mediated immunity. An effective immunization can activate an adequate immune response capable to control the primary infection and protect against a secondary infection. Mucosal vaccination, by inducing local pathogen-specific immune responses, has the potential to counter mucosally transmitted pathogens at the portal of entry, thereby increasing the efficacy of vaccines. The aim of this work was to explore the efficacy of AFCo1 or AFPL1, as mucosal adjuvants to stimulate cell immunity and memory responses against Vi polysaccharide antigen of Salmonella typhi (PsVi). Mice immunized with 3 intranasal doses exhibited high levels of PsVi-specific IgG (p < 0.05), IgG2a and IgG2c subclasses. Also, an amplified recall response after a booster immunization with a plain polysaccharide vaccine was induced. Avidities index were higher in mice immunized with adjuvanted formulations at different chaotropic concentrations. Furthermore, IL-12 and IFN-γ levels in nasally vaccinated mice with both adjuvants were induced. Moreover, priming with 3 doses followed by booster immunization with VaxTyVi^® resulted in high levels of anti-Vi specific IgG, IgG subclasses and antibody avidity. Long lived plasma cells in bone marrow, memory B cells and long-term memory T cells after booster dose were induced. The combined formulation of Vi polysaccharide with mucosal adjuvants provides an improved immunogenicity, in particular with regard to cellular responses and long lasting cells responses.     

Exploring mucosal immunization with a recombinant influenza virus carrying an HIV-polyepitope in mice with pre-existing immunity to influenza

HIV-1 vaccines based on recombinant vectors have been developed to elicit immune responses; however, the failure of the STEP HIV-1 vaccine trial has caused concern regarding the impact on vaccine efficacy of pre-existing vector seropositivity in humans. By using a mouse model of infection, we evaluated the immune responses elicited by intranasal and vaginal immunization with the recombinant influenza virus WSN/CKG carrying the PCLUS3-P18 peptide and a Gag epitope in its hemagglutinin, and the impact of pre-existing vector immunity on protection against recombinant vaccinia virus challenge. We found that despite the protective immunity induced in naïve mice by the WSN/CKG virus via either route, the vaginal immunization of mice with pre-existing influenza immunity restricted vPE16 replication more significantly in the ovaries than intranasal immunization. Thus, successful vaccination strategies under limiting conditions, such as pre-existing vector immunity, require the local induction of mucosal immunity at the site of virus infection.     

Recombinant adenoviral vector expressing HCV NS4 induces protective immune responses in a mouse model of Vaccinia-HCV virus infection: A dose and route conundrum

Hepatitis C virus (HCV) leads to chronic infection in the majority of infected patients presumably due to failure or inefficiency of the immune responses generated. Both antibody and cellular immune responses have been suggested to be important in viral clearance. Non-replicative adenoviral vectors expressing antigens of interest are considered as attractive vaccine vectors for a number of pathogens. In this study, we sought to evaluate cellular and humoral immune responses against HCV NS4 protein using recombinant adenovirus as a vaccine vector expressing NS4 antigen. We have also measured the effect of antigen doses and routes of immunization on the quality and extent of the immune responses, especially their role in viral load reduction, in a recombinant Vaccinia-HCV (Vac-HCV) infection mouse model. Our results show that an optimum dose of adenovirus vector (2 × 10⁷ pfu/mouse) administered intramuscularly (i.m.) induces high T cell proliferation, granzyme B-expressing CD8⁺ T cells, pro-inflammatory cytokines such as IFN-γ, TNF-α, IL-2 and IL-6, and antibody responses that can significantly reduce the Vac-HCV viral load in the ovaries of female C57BL/6 mice. Our results demonstrate that recombinant adenovirus vector can induce both humoral and cellular protective immunity against HCV-NS4 antigen, and that immunity is intricately controlled by route and dose of immunizing vector.     

Spectrotemporal dynamics of the EEG during working memory encoding and maintenance predicts individual behavioral capacity

We investigated the effect of memory load on encoding and maintenance of information in working memory. Electroencephalography (EEG) signals were recorded while participants performed a modified Sternberg visual memory task. Independent component analysis (ICA) was used to factorise the EEG signals into distinct temporal activations to perform spectrotemporal analysis and localisation of source activities. We found ‘encoding’ and ‘maintenance’ operations were correlated with negative and positive changes in α‐band power, respectively. Transient activities were observed during encoding of information in the bilateral cuneus, precuneus, inferior parietal gyrus and fusiform gyrus, and a sustained activity in the inferior frontal gyrus. Strong correlations were also observed between changes in α‐power and behavioral performance during both encoding and maintenance. Furthermore, it was also found that individuals with higher working memory capacity experienced stronger neural oscillatory responses during the encoding of visual objects into working memory. Our results suggest an interplay between two distinct neural pathways and different spatiotemporal operations during the encoding and maintenance of information which predict individual differences in working memory capacity observed at the behavioral level.