Peritoneal exudate cells from long-lived rats exhibit increased IL-10/IL-1β expression ratio and preserved NO/urea ratio following LPS-stimulation in vitro

In humans, usual aging, differently from successful aging, is associated with deregulation of proinflammatory/anti-inflammatory cytokine balance. The corresponding data from rat studies are limited. Therefore, we examined (i) cytokine messenger RNA (mRNA) profile of fresh peritoneal cells from 6- (adult), 24- (old), and 31-month-old (long-lived) AO rats and (ii) proinflammatory (IL-1β and IL-6) and anti-inflammatory (IL-10) cytokine, NO, and urea production in their LPS-stimulated cultures. Comparing with adult rats, cells from old ones expressed lower amount of TNF-α and IL-6 mRNAs, but greater amount of IL-1β mRNA. On the other hand, cells from long-lived rats exhibited a dramatic increase in IL-10 mRNA expression followed by diminished TNF-α and IL-6 mRNA expression, and comparable expression of IL-1β mRNA relative to adult rats. Consequently, IL-10/IL-1β mRNA ratio was greater in cells from long-lived rats than in adult and old rats. In LPS-stimulated peritoneal cell cultures (contained ≥95 % macrophages) from old rats, concentration of common proinflammatory cytokines was higher than in those from adult rats. Comparing with adult and old rats, in LPS-stimulated macrophage cultures from long-lived rats, TNF-α and IL-6 concentrations were lower; IL-1β concentration was comparable or greater (in respect to adult rats), whereas that of IL-10 was strikingly higher. Consistently, in macrophage cultures from long-lived rats, NO (iNOS activity marker)/urea (arginase activity marker) ratio was less and not different from that in old and adult rats, respectively. The study suggests that macrophages from long-lived rats, differently from those of old ones, have substantial ability to limit proinflammatory mediator production, which may contribute to their longevity.     

Relevancia clínica de las interacciones medicamentosas entre antiinflamatorios no esteroideos y antihipertensivos

ObjectiveTo establish the clinical relevance of drug interactions between nonsteroidal antiinflammatory drugs (NSAIDs) and antihypertensives, based on the interaction severity and probability of occurrence.DesignSystematic review.Data sourcesA PubMed/Medline search was made using the MeSH terms: NSAIDs, Antihypertensive drugs, and Drug interactions.Data extractionArticles between 2002 and 2012, human studies, in Spanish and English and full text access were included. Found articles were included and some of the references used in this works. Studies with in vitro methods, effects on ocular hypertension and those who do not consider the interaction NSAIDs, antihypertensives were excluded. For the selection of the papers included three independent reviewers were involved. We used a tool for data extraction and for assess of the interaction clinical relevance.ResultsNineteen of 50 papers found were included. There were identified 21 interactions with pharmacodynamic mechanism, classified by their clinical relevance in level-2 high risk (76.2%) and level-3 medium risk (23.8%). In addition, evidence of 16 combinations of no interaction were found.ConclusionsSome NSAIDs may attenuate the effectiveness of antihypertensive drugs when used concurrently, especially with angiotensin converting enzyme inhibitors, diuretics, beta blockers and angiotensin receptors ii blockers. There was no evidence of effect modification of calcium channel antagonists, especially dihydropyridine, by concurrent use of NSAIDs.     

选择性COX-2抑制剂和非选择性COX-1和COX-2抑制剂在预防全髋关节置换术后异位骨化的Meta分析

目的：比较选择性环加氧酶一2（COX一2）抑制剂和传统的非选择性NSAIDs药用于预防全髋关节置换（THA）术后异位骨化（H0）临床疗效。方法：通过计算机检索MEDuNE、EMBASE、CENTRAL、科学引文索引等数据库,收集选择性COX一2抑制剂和非选择性COX-1和COX-2抑制剂用于预防全髋关节置换术后异位骨化的随机临床试验。按照Cochrane协作网的标准对纳入的文献进行质量评估并提取有效数据,应用统计软件Statal0．0版本进行数据分析。比较两组在不同Brooker分期的异位骨化发生率。结果：共纳入4个符合条件的随机对照试验,808例患者。Meta分析结果表明,两组间异位骨化总发病率比较差异无统计学意义（RR=1．08,95％CI：0．71～1．64,=O．73）,重度异位骨化发病率（BrookerU,Ⅲ）（RR=0．83,95％CI：0．48～1．42,P=0．49）和任意Brooker分型的HO,两组之间比较差异无统计学意义。在整个研究中,16例接受非选择性COX抑制剂的患者（4．4％）因胃肠道反应终止治疗;而选择性COX-2抑制剂组中10例患者（2．7％）因胃肠道反应终止治疗。结论：选择性COX-2抑制剂与非选择性NSAIDs药用于预防全髋关节置换术后异位骨化同样有效。考虑到非选择性NSAIDs药的胃肠道不良反应,建议选择性COX-2抑制剂的预防全髋关节置换术后异位骨化。     

Folate receptor-targeted aminopterin therapy is highly effective and specific in experimental models of autoimmune uveitis and autoimmune encephalomyelitis

EC0746 is a rationally designed anti-inflammatory drug conjugate consisting of a modified folic acid-based ligand linked to a γ-hydrazide analog of aminopterin. In this report, EC0746's effectiveness was evaluated against experimental retinal S-antigen (PDSAg) induced autoimmune uveitis (EAU) and myelin-basic-protein induced autoimmune encephalomyelitis (EAE). In both models, functional FR-β was detected on activated macrophages in local (retinal or central-nervous-system, respectively) and systemic (peritoneal cavity) sites of inflammation. In myelin-rich regions of EAE rats, an increased uptake of ^99mTc-EC20 (etarfolatide; a FR-specific radioimaging agent) was also observed. EC0746 treatment at disease onset suppressed the clinical severity of both EAU and EAE, and it strongly attenuated progressive histopathological changes in the affected organs. In all parameters assessed, EC0746 activity was completely blocked by a benign folate competitor, suggesting that these therapeutic outcomes were specifically FR-β mediated. EC0746 may emerge as a useful macrophage-modulating agent for treating inflammatory episodes of organ-specific autoimmunity.     

三棱针刺血治疗慢性痛风对内源性肾上腺糖皮质激素水平影响的研究

目的 观察三棱针刺血治疗慢性痛风(CG)对内源性肾上腺糖皮质激素水平的影响,探讨三棱针刺血治疗CG的抗炎作用机制.方法 76例CG患者,按随机数字表法分为治疗组和对照组,每组38例.对照组采取一般治疗,治疗组在对照组治疗的基础上采用三棱针刺血治疗.比较两组患者临床疗效以及治疗前及治疗3、6个月后疼痛数字评分法(NRS)...     

归芪活血胶囊对神经根型颈椎病大鼠炎性损伤和微循环血流的影响

目的：探究归芪活血胶囊（GQ）对神经根型颈椎病（CSR）大鼠的治疗效应及机制。方法：观察CSR大鼠自发痛、热痛阈、步态评分、前肢和颈部体表微循环状态、脊髓病理结构及超微结构变化、脊髓p38磷酸化情况以及血清白细胞介素-1β（IL-1β）、IL-6以及肿瘤坏死因子-α（TNF-α）。结果：GQ高、中剂量在干预第14天时可显著升高CSR模型大鼠的热痛阈（P<0.05）,降低其步态评分和自发痛评分（P<0.05,P<0.01）;GQ各剂量均可改善CSR大鼠脊髓炎症水肿变化,显著增加尼氏（Nissl）染色阳性细胞数目（P<0.05）,恢复髓鞘和线粒体正常形态,且GQ中剂量效果较明显;GQ高、中剂量可显著升高CSR大鼠颈部和前肢皮肤血流灌注量（P<0.05）,对前肢远端血流灌注量的改善程度优于芬必得组（P<0.01）;与模型组比较,GQ中剂量可降低CSR大鼠脊髓p38磷酸化比率。结论：GQ可以缓解CSR大鼠热痛觉过敏和步态不稳的程度,改善脊髓炎症病理变化,恢复前肢和颈部体表血流灌注量,且GQ中剂量在改善CSR大鼠炎症损伤方面更有优势。     

胆碱能抗炎通路对感染性休克大鼠肺的保护作用

目的:应用盲肠结扎穿孔法(CLP)建立感染性休克模型,研究胆碱能抗炎通路对感染性休克大鼠肺的保护作用。方法:采用CLP复制感染性休克模型,取成年雄性SD大鼠40只,随机分为4组。①假CLP组(Sham);②CLP组(CLP);③迷走神经切断组(VGX);④迷走神经电刺激组(STM)。各组动物均行颈总动脉置管连续监测平均动脉压。刺激方法是将左迷走神经远端连接刺激电极,于CLP术毕即刻持续电刺激(5V、2ms和1Hz)20min。分别在各组模型制备完毕或电刺激后0,1,2,4h检测血浆TNF-α含量和4h抽动脉血行血气分析、取肺组织在透射电镜下观察肺组织超微结构变化。结果:CLP组和VGX组平均动脉血压进行性下降,STM组血压下降幅度减轻,各时间点均显著高于CLP组相应的血压值。各组动物血浆TNF-α含量均在2h出现高峰,并在4h回落。STM组1h和2h与CLP组比较,血浆TNF-α含量则显著降低。4h取颈动脉血行血气分析,CLP组和VGX组血气分析pH值、PaO2和BE显著下降(P<0.01),明显低于假CLP组和STM组(P<0.05),表明CLP组和VGX组肺功能有明显损伤,STM组肺功能有明显改善。肺组织超微结构CLP组在电镜下可见肺泡Ⅱ型上皮细胞轻度增生,肺气血屏障的中间带增厚,部分线粒体膜断裂、解体、嵴粒溶解以及线粒体空泡化。STM组病理变化明显减轻。结论:电刺激迷走神经减轻肺损伤的机制与迷走神经兴奋释放大量神经递质乙酰胆碱有关。电刺激迷走神经兴奋后,其末梢释放大量乙酰胆碱,与存在于单核巨噬细胞上的乙酰胆碱受体α7亚单位结合后,阻止单核巨噬细胞TNF-α合成,从而减轻肺脏等脏器的炎性损害。电刺激迷走神经通过胆碱能抗炎通路能缓解CLP致感染性休克大鼠的进行性血压下降,降低血清TNF-α含量,减轻急性肺功能损伤和肺组织病理损害,对肺有潜在的保护作用。     

三黄凝胶抗炎作用的实验研究

目的探讨三黄凝胶外敷的抗炎作用,为临床使用提供理论依据。方法采用二甲苯致小鼠耳肿胀,测定鸡蛋清致大鼠足跖炎症组织中PGE2和SOD含量,以小鼠气囊炎性模型观察三黄凝胶的抗炎作用。结果用三黄凝胶大、中、小剂量药后肿胀率分别下降(6.58±3.95)%,(5.50±4.42)%,(7.69±4.81)%;白细胞数分别下降(43.63±9.22,40.35±8.25,48.72±10.30)×104/mL,NO含量分别下降为13.58±3.95,12.50±4.42,14.69±4.81mg/L;PGE2含量分别下降0.217±0.0197,0.203±0.0142,0.226±0.0256;SOD含量分别提高为0.827±0.114,0.903±0.109,0.716±0.094。说明三黄凝胶能显著抑制二甲苯所致小鼠耳肿胀(P<0.01),降低气囊灌洗液中的白细胞数和炎症渗出液中NO含量(P<0.01),降低大鼠足跖炎症组织中释放的PGE2(P<0.01),提高炎症渗出液中和SOD活性(P<0.01)。结论三黄凝胶通过对小鼠耳肿胀的影响、大鼠足跖炎症组织中PGE2和SOD含量的影响及小鼠气囊炎性模型灌洗液中白细胞数及NO含量的影响,有明显的抗炎作用。     

除湿止痒软膏抗炎及止痒作用研究

目的 探讨除湿止痒软膏的抗炎及止痒作用。 方法 用2,4-二硝基氟苯（DNFB）腹部致敏和背部反复激发建立BALB/c小鼠特应性皮炎模型。实验动物分为正常对照组（未致敏也未治疗）、模型对照组（致敏但未治疗）、氢化可的松乳膏组（致敏 + 氢化可的松）、除湿止痒软膏组（致敏 + 除湿止痒软膏）。连续用药14 d,末次给药12 h后取背部皮肤,测定皮肤厚度及质量,进行HE染色和甲苯胺蓝染色,ELISA法检测皮损组织中干扰素（IFN）γ、肿瘤坏死因子（TNF）α、白细胞介素（IL）-4、IL-5含量。利用磷酸组胺诱发Hartley豚鼠局部皮肤瘙痒模型,观察除湿止痒软膏对豚鼠致痒阈的影响。 结果 用药后第15天,与模型对照组相比,氢化可的松乳膏和除湿止痒软膏均可明显减少小鼠的背部皮肤厚度和质量（P < 0.01）,减少淋巴细胞和肥大细胞浸润（P < 0.01）以及降低皮损组织中IFN-γ、TNF-α、IL-4及IL-5水平（P < 0.05或P < 0.01）。与正常对照组相比,氢化可的松乳膏组小鼠背部皮肤厚度和质量减小（P < 0.01）,除湿止痒软膏组无明显变化。此外,除湿止痒软膏也可显著提高豚鼠耐受磷酸组胺的致痒阈（P < 0.01）。 结论 除湿止痒软膏可明显抑制DNFB引起的小鼠特应性皮炎,其抗炎机制可能与恢复体内Th1/Th2型细胞因子平衡有关。除湿止痒软膏可明显减轻磷酸组胺所致豚鼠皮肤瘙痒反应。