Plasma HIV-1 RNA decline within the first two weeks of treatment is comparable for nevirapine, efavirenz, or both drugs combined and is not predictive of long-term virologic efficacy: A 2NN substudy

BACKGROUND: The initial rate of plasma HIV-1 RNA (pVL) decline has been proposed as a marker of early efficacy of antiretroviral therapy (ART) and a possible predictor of late efficacy. We compared the rate of pVL decline in patients starting ART with nevirapine (NVP), efavirenz (EFV), or both drugs combined in addition to lamivudine (3TC) and stavudine (d4T). METHODS: Analysis of the viral decay constant (VDc) during the first 2 weeks of treatment in patients enrolled in the 2NN study who remained on allocated treatment. RESULTS: The median VDc (log10 copies per day, [interquartile range]) was similar for NVP (0.30 [0.25-0.36], EFV (0.31 [0.27-0.37]), and NVP + EFV (0.30 [0.27-0.36]). Patients with a baseline pVL >100,000 copies/mL were 8.7 (95% confidence interval [CI]: 6.2-12.3) times more likely to have a VDc >75th percentile. A high VDc was not associated with plasma drug concentration or with a decreased risk of virologic failure at week 48 after the start of therapy (hazard ratio = 0.8, 95% CI: 0.6-1.2). CONCLUSION: NVP, EFV, or NVP + EFV in combination with 3TC and d4T show similar rates of pVL decline during the first 2 weeks of treatment. The VDc with these regimens is not predictive of late virologic efficacy.     

Tolerogenic dendritic cells produced by lentiviral‐mediated CD40‐ and interleukin‐23p19‐specific shRNA can ameliorate experimental autoimmune encephalomyelitis by suppressing T helper type 17 cells

Down‐regulation of soluble or membrane‐bound co‐stimulatory molecules by RNAi in dendritic cells can prevent the activation of immune responses. Therefore, this study was designed to evaluate the therapeutic efficacy of bone marrow‐derived DCs (BMDCs) transduced with lentiviral vectors to permanently expressed shRNA specific for CD40 (CD40LV‐DCs) and/or p19 subunit of interleukin (IL)‐23 (p19LV‐DCs) mRNAs in experimental autoimmune encephalomyelitis (EAE). In‐vitro studies showed that double‐transduced BMDCs (CD40⁺p19LV‐DCs) resemble tolerogenic DCs due to profound down‐regulation of CD40, lower expression of proinflammatory cytokines (IL‐6 and IL‐12), increased IL‐10 production and stronger stimulation of myelin oligodendrocyte glycoprotein (MOG)_35–55‐specific T cells for production of IL‐10 compared with CD40LV‐DCs, p19LV‐DCs and BMDCs transduced with control lentiviral vector (CoLV‐DCs). Moreover, injection of transduced CD40⁺p19LV‐ BMDCs in EAE mice resulted in more reduction in clinical score, significant reduction in IL‐17 or increased production of IL‐10 by mononuclear cells derived from the lymph nodes or spinal cord compared with CoLV‐DCs‐treated EAE mice. In conclusion, simultaneous knock‐down of CD40 and IL‐23 production by BMDCs may represent a promising therapeutic tool for the treatment of IL‐17‐dependent autoimmune diseases, including multiple sclerosis.     

干细胞移植治疗时间窗与临床疗效的荟萃分析

目的:探讨寻找干细胞移植治疗急性心肌梗死的最佳移植治疗时间,指导临床应用,提高临床疗效。方法:应用计算机检索medline2000-01/2006-05文章,检索词为:"stem cell transplantation and/or acute myocardialinfarction(AMI)and/or chronic heart failure or ischemic cardiomyopathy",限定文章语言种类为English;同时计算机检索中国期刊全文数据库,相同时间的文章,检索词:"干细胞移植治疗,干细胞移植与急性心肌梗死,干细胞移植治疗与心力衰竭或慢性缺血性心肌病",限定文章语言种类为中文。共检索到300余篇与主题有关的文献,其中12篇有价值的文章见参考文献。移植时间取平均值,并按射血分数值和P值进行列表、作图。对干细胞移植时间与射血分数值之间的关系进行分析。结果:在急性心肌梗死后2～5d和9d以后进行干细胞移植治疗疗效较24h内及6～8d为好。结论:干细胞移植治疗急性心肌梗死的移植时间与临床疗效之间可能存在一定的相关性。经冠脉注入干细胞比经静脉或经心内膜下注入可以更好地改善左室功能,但还需要进一步的临床资料证实。     

Material properties and bone marrow stromal cells response to in situ crosslinkable RGD-functionlized lactide-co-glycolide scaffolds

In situ crosslinkable biomaterials with degradation profiles that can be tailored to a particular application are indispensable for treating irregularly shaped defects and for fabrication of shape-selective scaffolds. The objective of this work was to synthesize ultra low molecular weight functionalized PLA and PLGA macromers that can be grafted with bioactive peptides and crosslinked in situ to fabricate biodegradable functional scaffolds. In situ crosslinkable lactide-co-glycolide macromer (cMLGA; "c" for crosslinkable, "M" for macromer, and "LGA" for lactide-co-glycolide) was synthesized by anionic polymerization of lactide and glycolide monomers followed by condensation polymerization with fumaryl chloride. The cMLA (100% L-lactide) and cMLGA macromers formed porous crosslinked scaffolds with NVP as the crosslinker. The mass loss of the crosslinked cMLA and cMLGA was linear with incubation time in vitro (zero-order degradation) and the degradation rate depended on the ratio of lactide to glycolide. cMLGA scaffold with 1:1 lactide to glycolide ratio completely degraded after 4 weeks while the cMLA lost less than 40% of its initial mass after 35 weeks. When cMLA scaffold was functionalized with acrylated integrin-binding Ac-GRGD amino acid sequence, bone marrow stromal (BMS) cells attached and spread on the cMLA scaffold and exhibited focal-point cell adhesion. The mRNA expression levels of collagen-1alpha, osteonectin, and osteopontin for BMS cells seeded in the scaffolds with 1 and 5% Ac-GRGD were upregulated compared with those without Ac-GRGD. cMLGA is attractive as in situ crosslinkable macromer for fabrication of functional scaffolds with degradation characteristics that can be tailored to a particular application.     

A comparative histological analysis of human pulp following direct pulp capping with Propolis, mineral trioxide aggregate and Dycal

Background:  Permanent teeth pulp exposures have traditionally been treated with calcium hydroxide pulp capping. The aim of this study was to investigate the response of human pulp tissue which were mechanically exposed to a new material, Propolis and compare it with two existing and commonly used pulp capping agents (mineral trioxide aggregate and Dycal).
Methods:  Thirty-six intact human premolars were mechanically exposed. Teeth were divided into six groups of 6 teeth each and were capped with Propolis, mineral trioxide aggregate and Dycal. Final restoration was done with posterior composite resin using light cured glass ionomer cement as a liner. The teeth were then extracted on the 15th or the 45th day and processed for histological evaluation.
Results:  Differences in inflammatory response and dentine bridge formation of the exposed pulp to the three different materials were statistically calculated using chi-square test and were found to be non-significant. There was more pulp inflammation in teeth treated with Dycal than with Propolis and MTA on the 15th as well as on the 45th day. Propolis and MTA showed bridge formation in more teeth, and the bridges were in closer proximity to pulp capping material than teeth treated with Dycal on the 45th day.
Conclusions:  The response of pulps to Propolis as a pulp capping agent was comparable to MTA and Dycal.     

Enabling a person with multiple disabilities and minimal motor behaviour to control environmental stimulation with chin movements

Purpose: To assess whether a young man with multiple disabilities and minimal motor behaviour would learn to control environmental stimulation using chin movements and a mechanical microswitch. Method: The study was carried out according to an ABAB design in which A represented baseline and B intervention phases. The chin movements controlled the stimulation only during the intervention phases. A 2-month post-intervention check was conducted. Results: The man increased the frequency of his chin movements, thus increasing the level of environmental stimulation, during the intervention phases. This performance was maintained at the post-intervention check. Conclusion: The use of chin movements is a practical strategy for enabling individuals with minimal motor movements to control environmental stimulation. Future research should examine whether similar types of movements may enable some individuals to control voice-output communication devices.     

Co-expression of CYP27B1 enzyme with the 1.5kb CYP27B1 promoter-luciferase transgene in the mouse

The renal enzyme 25-hydroxyvitamin D 1alpha-hydroxylase (CYP27B1), responsible for the synthesis of circulating. 1,25-dihydroxyvitamin D (1,25D), is also expressed in a number of non-renal tissues. The regulation of CYP27B1 expression by the short flanking promoter outside the kidney is, however, largely unknown. We have used a transgenic mice expressing the 1.5kb promoter of the human CYP27B1 gene fused to the firefly luciferase gene in order to investigate tissue-specific CYP27B1 expression. These transgenic animals demonstrated co-localised luciferase and endogenous CYP27B1 expression in kidney proximal convoluted tubular cells. Strong co-expression of luciferase and CYP27B1 also occurred in neurons and Purkinje cells of the cerebellum and in Leydig and Sertoli cells of the testes. Other tissues to exhibit CYP27B1-promoter directed luciferase activity included lung, prostate, trabecular bone and jejunum as well as the choroid epithelium. The tissue specific changes in luciferase activity were age-related. These findings demonstrate that the proximal 1.5kb 5' flanking region of the CYP27B1 gene directs the expression of CYP27B1 in a number of known and novel tissues in a specific manner.