Implication of xanthine oxidase in muscle oxidative stress in COPD patients

Objective: The aim of this study was to determine the implication of xanthine oxidase (XO) in the exercise-induced muscle oxidative stress and muscle dysfunction of these patients.

Methods: A randomized, crossover and double-blind study was conducted in nine severe COPD patients, who performed a localized quadriceps endurance test after oral treatment with allopurinol, a XO inhibitor or placebo. Redox status was studied in arterial and venous femoral blood before and after the endurance test.

Results: In placebo condition, muscle exercise resulted in a significant increase in AOPP and isoprostanes, with a significant increase in the venoarterial difference (v-a) in isoprostanes after exercise as compared with before (p<0.05). In contrast, allopurinol treatment prevented the elevation in AOPP levels and v-a isoprostanes after exercise. However, no significant improvement in quadriceps muscle endurance was observed, but allopurinol treatment seemed to preserve muscle strength properties.

Conclusion: This study demonstrates that XO is implicated in the exercise-induced muscle oxidative stress of COPD patients. Allopurinol administration seemed to improve only some muscle properties. Therefore other sources of muscle oxidative stress should be implicated in muscle dysfunction observed in these patients.     

Transcranial magnetic stimulation as an antioxidant

In the last decades, different transcranial magnetic stimulation protocols have been developed as a therapeutic tool against neurodegenerative and psychiatric diseases, although the biochemical, molecular and cellular mechanisms underlying these effects are not well known. Recent data show that those magnetic stimulation protocols showing beneficial effects could trigger an anti-oxidant action that would favour, at least partially, their therapeutic effect. We have aimed to review the molecular effects related to oxidative damage induced by this therapeutic strategy, as well as from them addressing a broader definition of the anti-oxidant concept.     

Effects of transcranial magnetic stimulation on oxidative stress in experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) reproduces a multiple sclerosis (MS)-like experimental model. The main objective was to evaluate the effect of extremely low-frequency electromagnetic fields (EL-EMF) application, like a paradigm of transcranial magnetic stimulation (TMS) in the development of EAE. Rats were injected with a single dose of 150?μg of myelin oligodendrocyte glycoprotein (MOG, fragment 35–55) to produce experimental MS. To assess the effect of TMS application in EAE, the rats were treated with TMS (60?Hz and 0.7?mT) for 2?h in the morning, once a day, 5 days a week, during 3 weeks. TMS was applied to the head. The effect of TMS on EAE was evaluated as motor symptoms and, oxidative and cell damage. The data showed that MOG induced motor symptoms as tail paralysis and limb paresis/paralysis, oxidative stress and cell death similar to MS when compared with control animals. Importantly, TMS application attenuated motor symptoms, oxidative and cell damage, whereas it increased antioxidant system. Our findings suggest that: (i) MOG reproduces an experimental model of MS characterised by oxidative and cell damage; and (ii) TMS application decreases oxidative stress and cell death induced by MOG.     

Inspiratory muscular activation during threshold therapy in elderly healthy and patients with COPD

Inspiratory muscles training in COPD is controversial not only in relation to the load level required to produce muscular conditioning effects but also in relation to the group of patients benefiting from the training. Consequently, inspiratory muscular response assessment during Threshold^® therapy may help optimizing training strategy. The objective of this study was to evaluate the participation of the diaphragm and the sternocleidomastoid (SMM) muscle to overcome with a 30% Threshold^® load using surface electromyography (sEMG) and to analyze the correlation between SMM activation, maximum strength level of inspiratory muscles (MIP) and obstruction degree in COPD patients (FEV₁). We studied seven healthy elderly subjects, mean age of 68 ± 4 years and seven COPD patients, FEV₁ 45 ± 17% of the predicted value, with mean age 66 ± 8 years. sEMG analysis of SMM muscles and diaphragm were obtained through RMS (root-mean-square) during three stages: pre-loading, loading and post-loading.

Results

In the COPD group, the RMS of the SMM increased 28% during load (p < 0.05) while the RMS of the diaphragm remained constant. In the elderly there was a trend of a 11% increase in diaphragm activity and of 7% in SMM activity but, without reaching significance levels. SMM activity demonstrated good correlation with the obstruction level (r = −0.537).

Conclusion

To overcome the load required by Threshold^® therapy, COPD patients demonstrated an increase of accessory muscles activity, represented by SMM. For the same relative load this increase seems to be proportional to the degree of pulmonary obstruction.     

重复经颅磁刺激联合低剂量氟西汀对CUMS抑郁小鼠的影响*

目的:探讨重复经颅磁刺激(rTMS)联合低剂量氟西汀对慢性不可预知轻度压力(CUMS)抑郁小鼠的影响及其交互作用。方法:取42只雄性BALB/c小鼠随机分为正常对照组(Control,7只)和抑郁症模型组(Model,35只),Model组小鼠给予限制塑料管内、鼠笼倾斜、不筑巢、拥挤环境、明暗颠倒、白噪声等6种刺激,每种刺激随机且不同时出现2次,共刺激4周建立CUMS模型。随后35只Model组鼠随机分为CUMS组(8只)、氟西汀组(Fluoxetine,9只)、rTMS组(9只)和rTMS+Fluoxetine组(9只)。Fluoxetine组给予腹腔注射氟西汀5 mg/(kg·d),rTMS组给予10 Hz频率刺激,rTMS+Fluoxetine组给予腹腔注射氟西汀5 mg/(kg·d)和10 Hz频率刺激,Control和CUMS模型组给予相同体积生理盐水腹腔注射和伪刺激,各组均连续干预4周,随后进行行为学实验,最后运用析因设计方差分析方法分析Fluoxetine与rTMS的交互作用。结果:与Control组比,CUMS组小鼠强迫游泳实验中不动时间显著升高(P＜0.05),蔗糖实验中糖喜好程度、旷场实验中心运动次数和体重变化率均显著下降(P＜0.05)。与CUMS组比,rTMS组、Fluoxetine组和rTMS+Fluoxetine组抑郁症小鼠强迫游泳实验中不动时间显著降低(P＜0.01)、蔗糖实验中糖喜好程度和旷场实验中心运动次数显著升高(P＜0.05),其中rTMS+Fluoxetine组联合应用效果更显著(P＜0.05),但体重变化率仅rTMS+Fluoxetine组有变化(P＜0.05)。结论:重复经颅磁刺激和/或氟西汀均能不同程度的改善CUMS小鼠抑郁状态,其中联合应用的干预作用优于单独使用氟西汀或rTMS的效果,且有交互作用。     

Systemic oxygen extraction during incremental exercise in patients with severe chronic obstructive pulmonary disease

To determine if decreased systemic oxygen (O₂) extraction contributes to the exercise limit in severe chronic obstructive pulmonary disease (COPD), 40 consecutive incremental cycle ergometer exercise tests performed by such patients, from which a “log-log” lactate threshold (LT) was identified, were compared to those of 8 patients with left ventricular failure (LVF) and 10 normal controls. Pulmonary gas exchange and minute ventilation were measured continuously and arterial blood gas tensions, pH, and lactate concentrations were sampled each minute. Cardiac output (Q˙ _c) was measured by first-pass radionuclide ventriculography. The systemic O₂ extraction ratio (O₂ER) was calculated as arterial − mixed venous O₂ content difference (C _aO₂ − C _vO₂)/C _aO₂. Peak exercise O₂ uptake (V˙O_2peak) was markedly reduced in both COPD and LVF [41 (3) and 42 (3)% predicted, respectively], compared to controls [89 (2)% predicted, P < 0.0001 for each]. Similarly, the LT occurred at a low percentage of predicted maximal oxygen consumption in both COPD and LVF [25 (2) and 27 (3)%] compared to normals [46 (3)%, P < 0.0001 for each]. The systemic O₂ER at peak exercise was severely reduced in COPD [0.36 (0.02)] compared to the other groups [P < 0.0001 for each], for whom it was nearly identical [0.58 (0.03) vs 0.63 (0.04), LVF vs control, P > 0.05]. In the COPD group, an early LT correlated with reduced systemic O₂ER at peak exercise (r = 0.64, P < 0.0001), but not with any index of systemic O₂ delivery. These data suggest that lactic acidemia during exercise in patients with severe COPD is better related to abnormal systemic O₂ extraction than to its delivery and contributes to the exercise limit. Accepted: 10 March 1998     

经颅磁刺激参数与结构要件的影响分析

为了进一步探索经颅磁刺激工作机理并改进或研制出新的经颅磁刺激激励源.本文从经颅磁刺激的原理推导出了磁场、感应电流及激励源原理电路电流的表达式,利用大脑-线圈和大脑-线圈-铁芯两种经颅磁刺激模型分析影响因素与头模型各组织的磁场和感应电流分布.对比分析表明电流的性质,线圈半径,线圈激励特性与铁芯对感应电流分布与电磁场分布有着本质的影响.对经颅磁刺激参数及结构要件的研究与分析可用于指导刺激线圈参数及激励源电路参数的设置,以及探索新的激励源制作.     

重复经颅磁刺激对创伤性颅脑损伤患者脑脊液中兴奋性氨基酸含量的影响

目的：探讨重复经颅磁刺激（rTMS）对急性颅脑损伤患者脑脊液中兴奋性氨基酸（EAA）含量的影响。方法：30例创伤性颅脑损伤（TBI）病人按格拉斯哥昏迷评分分为轻型组（rTMS3）、中型组（rTMS2）、重型组（rTMS1）,每组10例,各组病人分别随机分为rTMS对照亚组（A组）及治疗亚组（B组）,每亚组5例。于TBI后第15天行腰椎穿刺采集脑脊液,采用高效液相色谱法测定脑脊液中谷氨酸（ASP）及门冬氨酸（GLU）含量。结果：脑脊液ASP和GLU水平随着脑损伤程度的加重而升高,各rTMS治疗组与相应各对照组的EAA相比,rTMS治疗组EAA的水平均低于相应对照组。结论：rTMS可通过降低TBI后脑脊液EAA水平发挥脑保护作用。脑脊液EAA的含量变化可作为TBI严重程度的生化指标。     

低频重复经颅磁刺激联合等速肌力训练模式干预对脑卒中的影响

摘要 目的：探讨等速肌力训练与低频重复经颅磁刺激对脑卒中患者下肢肌力的影响。方法：选择2020年2月到2021年8月在本院住院诊治的脑卒中患者96例作为研究对象,采用完全随机化1：1信封抽签原则把患者分为联合组与对照组各48例。对照组给予等速肌力训练,联合组在对照组治疗基础上给予低频重复经颅磁刺激治疗。两组在4周后记录下肢肌力变化情况。结果：（1）两组治疗后的美国国立卫生院神经功能缺损评分（NIHSS）低于治疗前,联合组低于对照组（P<0.05）。（2）两组治疗后的简化Fugl-Meye下肢评分高于治疗前,联合组高于对照组（P<0.05）。（3）两组治疗后的120 °/s时膝关节的伸肌与屈肌峰力矩体重比都高于治疗前,联合组高于对照组（P<0.05）。（4）两组治疗后的运动诱发电位潜伏期低于治疗前,波幅高于治疗前,联合组与对照组对比有差异（P<0.05）。结论：等速肌力训练联合低频重复经颅磁刺激在脑卒中患者的应用能促进改善神经功能与运动诱发电位,从而提高患者的下肢肌力与运动能力。     

Rhythmic arm swing enhances long latency facilitatory effect of transcranial magnetic stimulation on soleus motoneuron pool excitability

The purpose of this study was to investigate whether rhythmic arm swing modulates the long latency effect of transcranial magnetic stimulation (TMS) on soleus motoneuron pool excitability. Ten healthy humans rhythmically swung the left arm back and forth in a sitting position. The soleus H-reflex was evoked when the arm was in the backward swing phase. Conditioning TMS was delivered over the motor cortex 8?ms before the soleus H-reflex was evoked. The soleus H-reflex amplitude in both legs was depressed by the rhythmic arm swing. In contrast, rhythmic arm swing enhanced the facilitatory effect of conditioning TMS over the motor cortex contralateral to the arm swing side on the soleus H-reflex ipsilateral to the arm swing side. This finding indicates that rhythmic arm swing enhances some polysynaptic facilitatory pathways from the motor cortex contralateral to the arm swing side to the soleus motoneuron pool ipsilateral to the arm swing side.     

重复经颅磁刺激对创伤性颅脑损伤患者脑脊液中兴奋性氨基酸 含量的影响

目的:探讨重复经颅磁刺激(rTMS)对急性颅脑损伤患者脑脊液中兴奋性氨基酸(EAA)含量的影响。方法:30例创伤性颅脑损伤(TBI)病人按格拉斯哥昏迷评分分为轻型组(rTMS3)、中型组(rTMS2)、重型组(rTMS1),每组10例,各组病人分别随机分为rTMS对照亚组(A组)及治疗亚组(B组),每亚组5例。于TBI后第15天行腰椎穿刺采集脑脊液,采用高效液相色谱法测定脑脊液中谷氨酸(ASP)及门冬氨酸(GLU)含量。结果:脑脊液ASP和GLU水平随着脑损伤程度的加重而升高,各rTMS治疗组与相应各对照组的EAA相比,rTMS治疗组EAA的水平均低于相应对照组。结论:rTMS可通过降低TBI后脑脊液EAA水平发挥脑保护作用。脑脊液EAA的含量变化可作为TBI严重程度的生化指标。     

The Cu/Zn superoxide dismutase +35A/C (rs2234694) variant correlates with altered levels of protein carbonyls and glutathione and associates with severity of COPD in a Tunisian population

Chronic obstructive pulmonary disease (COPD) is a major cause of mortality that has been associated with inflammation and oxidative stress. The purpose of the present case–control study was to determine the relationships between oxidative stress-related genetic variants and the risk and severity of COPD, as well as, the influence of these variants on inflammatory and oxidative stress parameters. Genotyping of superoxide dismutase 1 (SOD1) + 35 A/C (rs2234694), catalase [A-21T (rs7943316), C-262T (rs1001179)] and glutathione peroxidase 1 (reduced glutathione (GSH)-Px1) 198Pro/Leu (rs1050450) was carried out in 143 patients with COPD and 216 healthy controls using PCR-RFLP. Serum levels of IL-6 and TNF-α were determined by enzyme-linked immunosorbent assays (ELISA), while the levels of reduced GSH, total antioxidant status (TAS), H₂O₂, lipid peroxides (TBARS) and protein carbonyls (PCs) were determined using spectrophotometric methods. We also evaluated the activities of GSH-Px, catalase, and superoxide dismutase (SOD) in both plasma and erythrocytes. We did not observe significant differences in the genotype and allele frequencies of chosen variants between COPD patients and healthy controls. A significant correlation was retrieved between the SOD1?+?35A/C variant and disease severity (odds ratios (OR) = 0.15, p?=?0.04). In addition, patients having the +35AC genotype presented increased plasma levels of GSH and a reduced level of PCs (p?=?0.03, p?=?0.04, respectively). The present data highlighted the important role of antioxidant enzymes and their genetic variants in the oxidative stress-mediated pathogenesis and progression of COPD.     

Changes in force, cross-sectional area and neural activation during strength training and detraining of the human quadriceps

Four male subjects aged 23-34 years were studied during 60 days of unilateral strength training and 40 days of detraining. Training was carried out four times a week and consisted of six series of ten maximal isokinetic knee extensions at an angular velocity of 2.09 rad.s-1. At the start and at every 20th day of training and detraining, isometric maximal voluntary contraction (MVC), integrated electromyographic activity (iEMG) and quadriceps muscle cross-sectional area (CSA) assessed at seven fractions of femur length (Lf), by nuclear magnetic resonance imaging, were measured on both trained (T) and untrained (UT) legs. Isokinetic torques at 30 degrees before full knee extension were measured before and at the end of training at: 0, 1.05, 2.09, 3.14, 4.19, 5.24 rad.s-1. After 60 days T leg CSA had increased by 8.5% +/- 1.4% (mean +/- SEM, n = 4, p less than 0.001), iEMG by 42.4% +/- 16.5% (p less than 0.01) and MVC by 20.8% +/- 5.4% (p less than 0.01). Changes during detraining had a similar time course to those of training. No changes in UT leg CSA were observed while iEMG and MVC increased by 24.8% +/- 10% (N.S.) and 8.7% +/- 4.3% (N.S.), respectively. The increase in quadriceps muscle CSA was maximal at 2/10 Lf (12.0% +/- 1.5%, p less than 0.01) and minimal, proximally to the knee, at 8/10 Lf (3.5% +/- 1.2%, N.S.). Preferential hypertrophy of the vastus medialis and intermedius muscles compared to those of the rectus femoris and lateralis muscles was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recuperating lung decoction attenuates inflammation and oxidation in cigarette smoke‐induced COPD in rats via activation of ERK and Nrf2 pathways

Oxidative/antioxidative imbalance and chronic inflammation are the main contributors to the pathogenesis of chronic obstructive pulmonary disease (COPD). This study evaluated the effect of recuperating lung decoction (RLD) on inflammation and oxidative stress in rats with COPD induced by cigarette smoke and lipopolysaccharides (LPS). We used intravenous infusion of LPS combined with cigarette smoke exposure as a COPD rat model. We observed that RLD treatment increased the protein level of GSH and the ratio of GSH/GSSG but decreased 8‐OHdG and 4‐HNE in the serum. Furthermore, RLD significantly inhibited the expressions of IL‐1β, IL‐6, TNF‐α, and TGF‐β induced by cigarette smoke exposure, reduced the number of inflammatory cells in the bronchoalveolar lavage fluid, and alleviated the severity of cigarette smoke‐induced emphysema. Mechanistically, RLD treatment prevented disease through downregulation of phosphorylated‐ERK and Nrf2 expression, which regulates the production of proinflammatory cytokines. RLD treatment exerted a dramatic therapeutic effect on COPD. This study revealed a mechanism that RLD functions on the regulation of ERK signalling to inhibit inflammation.     

Prediction of lower limb motor outcomes based on transcranial magnetic stimulation findings in patients with an infarct of the anterior cerebral artery

Abstract

The aim was to investigate the relationship between transcranial magnetic stimulation (TMS) at the early stage of stroke and 6-month motor outcome for patients with anterior cerebral artery territory infarct. Patients were classified into TMS(+) and TMS(?) groups. At the 6-month evaluation, lower limb motor function for the TMS(+) group was significantly better than those for the TMS(?) group. Thus, early TMS evaluation is useful for predicting recovery of lower limb motor function in patients experiencing this type of stroke.     

Effects of magnetic field on the antioxidant defense system of recirculation-cultured Chlorella vulgaris

Little is known about the influence of magnetic fields (MF) on growth of microalgae such as Chlorella vulgaris, which has been consumed as health food for various nutritional and pharmacological effects. This preliminary study investigated whether static MF can modulate the antioxidant system in C. vulgaris by exposing the cells to static MF generated by dual yoke electromagnets with magnetic flux density of 10-50 mT for 12 h. After exposure to 10-35 mT for 12 h, the activity of superoxide dismutases and peroxidase increased significantly compared to control cells. However, a remarkable increase of catalase activity occurred at 45 and 50 mT. The lipid peroxidation of algae cells determined by production of thiobarbituric acid-reactive substances was much increased when exposed to 35, 45, and 50 mT of MF. The scavenging ability of 2,2-diphenyl-1-picrylhydrazyl radical was decreased markedly while there was no variation of total carotenoids content in C. vulgaris cells. Assay of specific growth rate in 72 h cultivation after MF exposure was also conducted. In groups after exposure to 10-35 mT of MF, specific growth rate was significantly increased. These results suggest that 10-35 mT of static MF exposure could promote the growth of C. vulgaris and regulate its antioxidant defense system to protect cells efficiently, which could possibly enhance the growth of C. vulgaris in industrialized cultivation by MF.     

Impact of smoking on dendritic cell phenotypes in the airway lumen of patients with COPD

Background

Myeloid dendritic cells (DCs) are increased in the airway wall of patients with chronic obstructive pulmonary disease (COPD), and postulated to play a crucial role in COPD. However, DC phenotypes in COPD are poorly understood.

Methods

Function-associated surface molecules on bronchoalveolar lavage fluid (BALF) DCs were analyzed using flow cytometry in current smokers with COPD, in former smokers with COPD and in never-smoking controls.

Results

Myeloid DCs of current smokers with COPD displayed a significantly increased expression of receptors for antigen recognition such as BDCA-1 or Langerin, as compared with never-smoking controls. In contrast, former smokers with COPD displayed a significantly decreased expression of these receptors, as compared with never-smoking controls. A significantly reduced expression of the maturation marker CD83 on myeloid DCs was found in current smokers with COPD, but not in former smokers with COPD. The chemokine receptor CCR5 on myeloid DCs, which is also important for the uptake and procession of microbial antigens, was strongly reduced in all patients with COPD, independently of the smoking status.

Conclusion

COPD is characterized by a strongly reduced CCR5 expression on myeloid DCs in the airway lumen, which might hamper DC interactions with microbial antigens. Further studies are needed to better understand the role of CCR5 in the pathophysiology and microbiology of COPD.