Use of quantitative real-time PCR to determine the local inflammatory response in the intestinal mucosa and muscularis of horses undergoing small intestinal resection.
- 作者列表："Lisowski ZM","Lefevre L","Mair TS","Clark EL","Hudson NPH","Hume DA","Pirie RS
BACKGROUND:Studies in rodents and humans have demonstrated that intestinal manipulation or surgical trauma initiates an inflammatory response in the intestine which results in leucocyte recruitment to the muscularis externa causing smooth muscle dysfunction. OBJECTIVES:To examine the intestinal inflammatory response in horses undergoing colic surgery by measuring relative differential gene expression in intestinal tissues harvested from surgical colic cases and control horses. STUDY DESIGN:Prospective case-control study. METHODS:Mucosa and muscularis externa were harvested from healthy margins of resected small intestine from horses undergoing colic surgery (n = 12) and from intestine derived from control horses euthanised for reasons unrelated to the gastrointestinal tract (n = 6). Tissue was analysed for genes encoding proteins involved in the inflammatory response: interleukin (IL) 6 and IL1β, C-C motif chemokine ligand 2 (CCL2), tumour necrosis factor (TNF), prostaglandin-endoperoxide synthase 2 (PTGS2) and indoleamine 2,3-dioxygenase (IDO1). Relative expression of these genes was compared between the two groups. Further analysis was applied to the colic cases to determine whether the magnitude of relative gene expression was associated with the subsequent development of post-operative reflux (POR). RESULTS:Samples obtained from colic cases had increased relative expression of IL1β, IL6, CCL2 and TNF in the mucosa and muscularis externa when compared with the control group. There was no difference in relative gene expression between proximal and distal resection margins and no association between duration of colic, age, resection length, short-term survival and the presence of pre-operative reflux and the relative expression of the genes of interest. Horses that developed POR had significantly greater relative gene expression of TNF in the mucosa compared with horses that did not develop POR. MAIN LIMITATIONS:Small sample size per group and variation within the colic cases. CONCLUSIONS:These preliminary data support an upregulation of inflammatory genes in the intestine of horses undergoing colic surgery.
背景: 对啮齿类动物和人类的研究表明，肠道操作或手术创伤在肠道中引发炎症反应，导致白细胞募集到外肌，引起平滑肌功能障碍。 目的: 通过测量从外科绞痛病例和对照马收获的肠组织中的相对差异基因表达，检查接受绞痛手术的马的肠道炎症反应。 研究设计: 前瞻性病例对照研究。 方法: 从接受结肠手术的马 (n = 12) 切除的小肠的健康边缘和出于与胃肠道无关的原因实施安乐死的对照马 (n = 6) 的肠中收获粘膜和外肌。分析组织中编码参与炎症反应的蛋白质的基因: 白细胞介素 (IL) 6和IL1β 、c-c基序趋化因子配体2 (CCL2) 、肿瘤坏死因子 (TNF) 、前列腺素内过氧化物合酶2 (PTGS2) 和吲哚胺2,3-双加氧酶 (IDO1)。比较两组之间这些基因的相对表达。对结肠病例进行进一步分析，以确定相对基因表达的大小是否与术后反流 (POR) 的后续发展相关。 结果: 与对照组相比，从结肠病例获得的样本在粘膜和外肌中IL1β 、IL6、CCL2和TNF的相对表达增加。近端和远端切缘之间的相对基因表达没有差异，绞痛持续时间、年龄、切除长度、短期存活和术前反流的存在与目的基因的相对表达之间没有关联。与未发生POR的马相比，发生POR的马在粘膜中具有显著更大的TNF相对基因表达。 主要局限性: 每组样本量小，结肠病例内变异。 结论: 这些初步数据支持在接受结肠手术的马的肠道中炎症基因的上调。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.