Affective and inflammatory responses among orchestra musicians in performance situation

A number of studies have shown that mental challenge under controlled experimental conditions is associated with elevations in inflammatory markers such as interleukin-6 (IL-6) and C-reactive protein (CRP). However, relatively little work has been done on the effects of ‘naturalistic’ stressors on acute changes in inflammatory markers. The present study examined whether perceived arousal, valence and dominance in musicians are associated with pro-inflammatory and oxidative responses to a concert situation. Blood and salivary samples obtained from 48 members of a symphony orchestra on the day of rehearsal (i.e. control situation) and on the following day of premiere concert (i.e. test situation) were used to determine changes in salivary cortisol, pro-inflammatory markers (plasma myeloperoxidase, serum CRP, plasma IL-6), oxidative stress markers (paraoxonase1 activity and malondialdehyde), and homocysteine, a risk factor for vascular disease. Results of regression analyses showed a significant trend to increased myeloperoxidase (MPO) response in individuals with low valence score. Both affective states, valence and arousal, were identified as significant predictors of cortisol response during concert. In addition, control levels of plasma malondialdehyde were positively correlated with differences in IL-6 levels between premiere and rehearsal (r = .38, p = .012), pointing to higher oxidative stress in individuals with pronounced IL-6 response. Our results indicate that stress of public performance leads to increased concentrations of plasma MPO (20%), IL-6 (27%) and salivary cortisol (44%) in musicians. The decreasing effect of pleasantness on the MPO response was highly pronounced in non-smokers (r = −.60, p < .001), suggesting a significant role of emotional valence in stress-induced secretion of MPO. Additional studies are needed to assess the generalizability of these findings to other ’naturalistic’ stress situations.     

Neutrophil activation in Alzheimer’s disease and mild cognitive impairment: A systematic review and meta-analysis of protein markers in blood and cerebrospinal fluid

Inflammation is involved in the pathophysiology of Alzheimer’s disease (AD), with multiple inflammatory processes implicated in its risk and progression. This review included original peer-reviewed studies measuring the cerebrospinal fluid or peripheral blood concentrations of protein markers specifically related to neutrophil activity in healthy controls (HC) and in patients with AD or mild cognitive impairment (MCI). A total of 35 studies (N_HC = 3095, N_AD = 2596, N_MCI = 1203) were included. Random-effects meta-analyses were used to estimate between-groups standardized mean differences (SMD) and 95 % confidence intervals. In blood, concentrations of myeloperoxidase (MPO; N_AD/N_HC = 271/209, SMD = 0.41 [0.20, 0.62]; I² = 15.7 %) and neutrophil gelatinase associated lipocalin (NGAL; N_AD/N_HC = 273/185, SMD = 0.30 [0.11, 0.49]; I² < 0.005 %) were significantly higher in AD relative to HC. Peripheral blood concentrations of NGAL were also higher in MCI compared to HC (N_MCI/N_HC = 489/145, SMD = 0.39 [0.11, 0.67]; I² = 38.6 %). None of the protein markers exhibited a significant difference between HC, MCI, or AD groups in the cerebrospinal fluid. The evidence suggests that peripheral neutrophil activation, as indicated by blood concentrations of NGAL and MPO, may be a pathological feature of cognitive impairment due to AD, evident at stages of MCI and AD dementia.     

Exogenous normal lymph reduces liver injury induced by lipopolysaccharides in rats

The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL) on lipopolysaccharide (LPS)-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg) was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg) was administered to the LPS and LPS+ENL groups, respectively, at a rate of 0.5 mL/min. Hepatocellular injury indices and hepatic histomorphology, as well as levels of P-selectin, intercellular adhesion molecule 1 (ICAM-1), myeloperoxidase (MPO), and Na⁺-K⁺-ATPase, were assessed in hepatic tissues. Liver tissue damage occurred after LPS injection. All levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in plasma as well as the wet/dry weight ratio of hepatic tissue in plasma increased. Similarly, P-selectin, ICAM-1, and MPO levels in hepatic tissues were elevated, whereas Na⁺-K⁺-ATPase activity in hepatocytes decreased. ENL treatment lessened hepatic tissue damage and decreased levels of AST, ALT, ICAM-1, and MPO. Meanwhile, the treatment increased the activity of Na⁺-K⁺-ATPase. These results indicated that ENL could alleviate LPS-induced liver injury, thereby suggesting an alternative therapeutic strategy for the treatment of liver injury accompanied by severe infection or sepsis.     

特定浓度高渗钠盐复苏液对严重烫伤大鼠早期肺损伤的影响

目的探讨特定浓度（200 mmol/L）高渗钠盐复苏液对严重烫伤大鼠早期肺损伤的影响。方法 56只SD大鼠随机分成烫伤组（48只）和对照组（8只）,其中烫伤组又分为乳酸钠林格液（LR）组（n=24）和高渗钠盐液（HS）组（n=24）。所有大鼠全部颈静脉置管,对照组大鼠不烫伤不补液,对LR组和HS组大鼠进行烫伤后复苏治疗,分别检测各组肺组织的髓过氧化物酶（MPO）与丙二醛（MDA）的含量,将所得数据进行统计学分析;采用免疫组织化学方法测定肺组织p38MAPK的活化程度,所得图片进行比较。结果 HS组复苏后肺组织的MPO含量在注射补液2、8、24 h分别为（1.48±0.45）、（1.52±0.31）、（1.46±0.15）U/g与补液2、8、24 h MDA含量（0.80±0.09）、（0.85±0.08）、（0.80±0.12）mmol/mg明显低于对应观测时间点的LR组复苏后肺组织的MPO含量（1.91±0.32）、（1.91±0.32）、（1.79±0.22）U/g与MDA含量（1.06±0.08）、（0.85±0.08）、（0.95±0.06）mmol/mg,差异有统计学意义（P〈0.05）;与对照组的MPO含量（1.49±0.22）U/g与MDA含量（0.78±0.14）mmol/mg比较,差异无统计学意义（P〉0.05）。肺组织的p38MAPK的免疫组化活性检测显示：HS组复苏后2、8、24 h的肺组织p38MAPK的表达与LR组比较明显减少,与对照组比较增加不明显,LR组与对照组比较明显增加。结论严重烫伤大鼠早期使用200 mmol/L高渗盐液进行液体复苏与乳酸钠林格液比较,通过减少肺组织的氧化应激反应与信号转导通路的活化减轻肺损伤。     

Effect of Andrographis paniculata as an Adjuvant in Combined Chemo-Radio and Whole Body Hyperthermia Treatment—A Preliminary Study

Modulation of immune responses to alleviate disease has been of interest for a long time. Intraperitoneal administration of Andrographis paniculata extract along with whole body hyperthermia (WBH) was found to enhance the total WBC count in cyclophosphamide (CTX) and radiation treated animals when compared to untreated control animals. Maximum inhibition in the solid tumor development was observed when the CTX and radiation exposed animals were treated with extract in combination with whole-body hyperthermia. Similarly myeloperoxidase activity in tumor tissue from CTX and radiation-treated animals was also significantly inhibited when they were administered with Andrographis paniculata extract along with whole body hyperthermia. Moreover the production of cytokines such as IL-2 and GM-CSF, which was reduced after combined CTX and radiation treatment was significantly increased by the simultaneous treatment of extract and whole body hyperthermia. The elevated level of serum Tumor Necrosis Factor (TNF-α) level, after CTX and radiation treatment was also lowered significantly after the administration of extract and simultaneous exposure of whole-body hyperthermia with respect to untreated tumor-bearing animals.     

Genetic Determination of TNF and Myeloperoxidase Production in Dialyzed Patients with Diabetic Nephropathy

Introduction: Diabetic nephropathy accounts for more than 20% of the cases of chronic renal failure. For many patients, the method of renal replacement therapy is chronic ambulatory peritoneal dialysis (CAPD). Diabetes, through glucose auto‐oxidation and production of free radicals, causes protein glycation. Products of protein glycation increase the concentrations of proinflammatory cytokines. The tumor necrosis factor (TNF) is one of the most important cytokines of cellular response and inflammation. Its level is increased in chronic renal failure. Numerous polymorphisms have been identified within and around the TNF gene, which is located on chromosome 6. Single nucleotide polymorphisms, such as a polymorphism at a position ? 308, probably have a direct influence on the TNF production. Myeloperoxidase (MPD) is a heme enzyme, participating in oxygen mechanisms of microorganism killing by phagocytes. Chronic renal failure patients show a significant reduction in the intracellular myeloperoxidase level. In the promoter region of myeloperoxidase gene, at position ? 463, G to A transition has been found, which causes a decreased gene expression. The aim of the present study was an analysis of genetic basis of TNF and myeloperoxidase production in dialyzed patients with diabetic nephropathy. Subjects and Methods: The study group consisted of 37 diabetic nephropathy patients treated with peritoneal dialysis. The control subjects were 58 dialyzed patients with other primary renal diseases and 115 healthy individuals. TNF and myeloperoxidase gene polymorphisms were detected by polymerase chain reaction (PCR) and amplification products were digested with the NcoI and AciI restriction enzymes respectively. ELISA determined the TNF and MPO levels in plasma. Results: We haven't found significant differences in TNF genotype and allele frequencies between the groups; however, diabetic nephropathy patients seemed to have a lower frequency of TNF1/TNF1 genotype. In diabetic nephropathy patients, the median TNF plasma level was 43.8 pg/mL, and in other renal diseases it was 36.8 pg/mL. The difference was significant (p < 0.05). The differences in TNF levels between both groups and the control group (1.7 pg/mL) were highly significant (p < 0.001). There was a statistically significant difference in MPO genotype frequencies between patients with diabetic nephropathy and patients with other renal diseases (p < 0.05). GG and AA genotypes were significantly more common in patients with diabetic nephropathy. The genotype distribution in patients with other renal diseases was similar to the distribution in the control group. Median plasma MPO level in diabetic nephropathy patients was similar to patients with other renal diseases. A significantly lower level (p < 0.05) was observed in the control group. In diabetic nephropathy, we have also observed a correlation between the MPO genotype and an earlier onset of the disease. For the TNF genotype, we haven't found such a relationship. There was also no relationship between the TNF and MPO genotypes and time to end‐stage renal disease (ESRD). There were no differences in the frequency of peritonitis between patients with diabetic nephropathy and dialyzed patients with other renal diseases. Discussion: In conclusion, we found that in diabetic nephropathy patients molecular variants of TNF are more frequent than in nondiabetic patients with chronic renal failure and these changes might be associated with altered ability to TNF synthesis. Analysis of the myeloperoxidase genotypes showed significant difference in genotype distribution in dialyzed patients with diabetic nephropathy. This, however, requires further studies to confirm the relationship with the disease.     

厄多司坦对大鼠后肢缺血再灌注所致肺损伤的影响

目的:探讨厄多司坦是否对后肢缺血再灌注所致的肺损伤具有保护作用.方法:将24只成年雄性大鼠随机分为3组:对照组、缺血再灌注组及厄多司坦组.手术后检测肺组织一氧化氮(NO)含量,髓过氧化物酶(MPO)、腺苷脱氮酶(ADA)以及黄嘌呤氧化酶(XO)的活性.同时检测支气管肺泡灌洗液NO含量、MPO活性.结果:与对照组相比,缺血再灌注组肺组织中ADA及XO活性增加(P<0.05).缺血再灌注组NO水平高于对照组(P<0.05),而厄多司坦组NO水平无改变.与对照组及厄多司坦组相比,缺血再灌注组MPO活性增加(P<0.05).与对照纽相比,缺血再灌注组支气管肺泡灌洗液MPO活性升高(P<0.05).厄多司坦组支气管肺泡灌洗液MPO活性显著低于缺血再灌注组(P<0.05).与对照组相比,缺血再灌注组及厄多司坦组支气管肺泡灌洗液NO水平升高(P<0.05).不过,相对于缺血再灌注组.厄多司坦治疗组支气管肺泡灌洗液NO水平显著降低.结论:厄多司坦可降低大鼠后肢缺血再灌注后氧化应激性损伤及中性粒细胞堆积,从而对肺损伤有一定的保护作用.     

髓过氧化物酶基因-463 G>A多态性与早发冠心病的相关性

目的 探讨髓过氧化物酶(MPO)基因-463 G＞A多态性与早发冠心病(CHD)的相关性.方法 早发CHD 134例,对照145例,采用LDR-PCR测序分型技术分析两组患者MPO基因启动子区第-463位核苷酸多态基因型分布,及其与早发CHD的关系.结果 病例组A/A基因型及A等位基因频率低于对照组,病例组G/G基因型及G等位基因频率高于对照组.杂合子G/A在两组患者中差异无统计学意义.等位基因A对早发CHD易感性的保护作用有统计学意义(P＜0.01).携带至少一个等位基因A的患者早发CHD的发病风险降低达50%(OR=0.50,95%CI:0.27～0.93),A/A基因型的患者早发CHD的发病风险降低达89%(OR=0.11,95%CI:0.03～0.40).结论 MPO-463 G＞A基因多态性与早发冠心病的发病风险相关,MPO-463 A等位基因携带者患早发冠心病的风险明显降低.     

抗髓过氧化物酶抗体阳性韦格纳肉芽肿病肺损害的临床分析

目的提高对抗髓过氧化物酶（MPO）抗体阳性的韦格纳肉芽肿（WG）病患者的肺损害的认识。方法自2002年3月至2008年1月,对确诊的8例有肺损害的韦格纳肉芽肿病患者的临床表现、实验室检查、影像学特点进行回顾性分析并结合文献进行复习。结果8例患者中,男4例、女4例,平均49.83岁。抗MPO抗体阳性4例,抗蛋白酶3（PR3）抗体阳性4例。抗MPO抗体阳性的WG患者,临床表现为发热4例,咳嗽、咳痰4例、咯血2例、呼吸困难1例、哮喘样发作1例;4例均累及上呼吸道和肾脏;胸部CT显示双肺单发或多发结节影2例、肿块影1例,双肺弥漫斑片影或磨玻璃影4例,肺实变影1例,结节性空洞1例及支气管扩张2例。误诊为肺癌、肺结核、军团菌肺炎、真菌性肺炎者各1例。结论在国人的WG患者中,抗MPO抗体阳性可能并不少见。对临床表现为发热、肺部阴影伴抗MPO抗体阳性的患者应考虑WG的可能。     

髓过氧化物酶基因-463G/A多态与中国人肺癌遗传易感性

目的 研究髓过氧化物酶（MPO）基因－463G→A单核苷酸多态与肺癌易感性的关系。方法 以PCR－单链构像多态（SSCP）技术,分析了314例肺癌患者和320例正常对照者MPO基因启动子区第－463位核苷酸多态基因型分布,及其与肺癌风险的关系。结果 正常对照组中G和A等位基因频率分别为85.0%和15.0%,而肺癌患者分别为89.0%和11.0%。携带MPO－463GG基因型的个体患肺癌风险比携带GA和AA基因型个体高1.7倍（校正的OR为1.7;95%CI为1.2-2.5）,且此种风险增高只限于肺鳞癌（OR为2.4;95%CI为1.4-3.9）,而与肺腺癌无关（OR为1.3;95%CI为0.8-2.1）。分层分析结果表明,与GA和AA基因型比较,GG基因型并不增加非吸烟者和累积吸烟量＜26包年者患肺癌的风险,但在累积吸烟量≥26包年的吸烟者中,GG基因型发生肺鳞癌的风险比GA和AA基因型高3.3倍。结论 MPO－463 A等位基因显著降低中国人发生吸烟相关性肺鳞癌的风险。