Novel Inflammatory Marker in Dialysis Patients: YKL‐40

YKL‐40 has been introduced as a marker of inflammation in different clinical situations. The association between YKL‐40 and inflammation in chronic renal failure patients has not been researched currently. The objectives of this study were to establish serum YKL‐40 concentrations in dialysis patients with chronic renal failure compared to healthy subjects and to explore its relationships with a proinflammatory cytokine, interleukine‐6 (IL‐6) and an acute phase mediator, high sensitivity C‐reactive protein (hs‐CRP). The study population included hemodialysis patients (N = 43; mean age of 40.9 ± 14.5), peritoneal dialysis patients (N = 38; mean age of 45.8 ± 13.7) and healthy subjects (N = 37; mean age of 45.5 ± 10.6). Serum concentrations of YKL‐40, IL‐6, hs‐CRP and routine laboratory measures were evaluated. Compared to the healthy subjects, hemodialysis and peritoneal dialysis patients had higher concentrations of YKL‐40, IL‐6, hs‐CRP, as well as lower concentrations of hemoglobin, serum albumin and high density lipoprotein‐cholesterol (P < 0.001). YKL‐40 concentrations were positively correlated with serum creatinine (P < 0.001, r = 0.495), IL‐6 (P < 0.001, r = 0.306), hs‐CRP (P = 0.001, r = 0.306) levels and inversely correlated with hemoglobin (P = 0.002, r = ?0.285), serum albumin (P < 0.001, r = ?0.355) and high density lipoprotein‐cholesterol (P = 0.001, r = ?0.306). In multivariate regression analysis YKL‐40 was associated with creatinine, serum albumin and hs‐CRP concentrations after adjustments with covariates. Dialysis patients with chronic renal failure have elevated serum YKL‐40 concentrations. Associations with standard inflammatory parameters suggest that YKL‐40 might be a novel inflammatory marker in this population.     

心房颤动与炎症和氧化应激

许多证据表明心房颤动中存在炎症和氧化应激,炎症和氧化应激可导致心房重构,包括电重构和结构重构,提示炎症和氧化应激可能在心房颤动的发生和维持中起着一定作用。抗炎和抗氧化治疗可减少心房颤动的发生和复发,这为干预心房颤动的发生和复发提供了新思路。     

炎症、氧化应激与心房颤动

许多证据表明心房颤动中存在炎症和氧化应激,炎症和氧化应激可导致心房重构,包括电重构和结构重构,提示炎症和氧化应激可能在心房颤动的发生和维持中起着一定作用。抗炎和抗氧化治疗可减少心房颤动的发生和复发,这为干预心房颤动的发生和复发提供了新思路。     

氧化应激与心房颤动关系研究进展

研究已证实氧化应激参与高血压、心力衰竭等疾病的发病过程,其与心房颤动的关系成为近年来研究热点之一。现综述氧化应激与心房颤动关系研究最新进展。     

Influence of Residual Renal Function in Carotid Modeling as a Marker of Early Atherosclerosis in Dialysis Patients

Atherosclerosis is frequently present in patients with chronic kidney disease (CKD) treated with dialysis. We evaluated the association between residual renal function (RRF), phosphate level, inflammation and other risk factors in carotid modeling as a marker of early atherosclerosis in peritoneal dialysis (PD) compared with hemodialysis (HD) patients. We studied 39 stable PD and 53 HD patients on renal replacement therapy (RRT) for 3 to 36 months duration. B‐mode ultrasonography was used to determine carotid artery intima media thickness (CIMT). We classified patients with atherosclerosis if they have CIMT >10 mm and or presence of plaque. Out of our total dialysis population studied of 92 patients, 16.3% were diabetics and 57.6% were on hemodialysis. Expectedly, PD patients had a higher RRF (P < 0.001), 24 h urine volume (P < 0.001); C‐reactive protein (P = 0.047), and a lower serum phosphate (P = 0.01), PTH (P < 0.05), alkaline phosphatase (P < 0.05), and albumin levels (P < 0.001) compared to hemodialysis patients. Atherosclerosis was found in 66.3% of patients and in 100% of a diabetic population. There was no significant difference in the presence of atherosclerosis between PD and HD patients [56.4 vs 73.6% HD, respectively]. Multiple regression analysis showed age, diabetes, HD modality, RRF, phosphate, PTH and pulse pressure as independent parameters associated with atherosclerosis. Apart from the traditional risk factors like age and diabetes, our study showed a link of atherosclerosis with metabolic abnormalities secondary to renal failure. We demonstrated a novel, independent association between RRF and atherosclerosis, underlining the importance of preservation of the RRF in dialysis patients.     

Oxidative Stress in the Dahl Salt-Sensitive Hypertensive Rat

Oxidative stress has been proposed as important in the pathogenesis of hypertension. Measurement of 8-iso prostaglandin F_2α(8-ISO) is introduced for evaluating oxidative stress in vivo. 8-ISO is the major urinary metabolite of F₂-isoprostanes and is formed nonenzymatically from the attack of superoxide radicals on arachidonic acid. We examined the oxidative stress level in the Dahl salt-sensitive (Dahl-S) rats and the Dahl salt-resistant (Dahl-R) rats. Dahl-S and Dahl-R rats were fed either a high salt diet (8% NaCl; HS) or low salt diet (0.3% NaCl; LS) for 3 weeks, and systolic blood pressure (SBP) and 24-hr urinary excretion of 8-ISO (U-8-ISO) were measured. In Dahl-S rats, the high salt diet induced hypertension (139 ± 3 mmHg in LS versus 186 ± 2 mmHg in HS, p < .05) and significantly increased the U-8-ISO (24.9 ± 3.6 ng/24 hr in LS versus 63.2 ± 14.6 ng/24 hr in HS, p < .05). No significant difference in blood pressure or U-8-ISO was observed between high-salt and low-salt treated Dahl-R rats. U-8-ISO concentration was correlated with SBP in all four experimental groups (r = 0.866). Moreover, urinary 8-hydroxy-2′-deoxyguanosine (U-8-OHdG), which is one of the most commonly used markers for evaluation of oxidative stress, was higher in Dahl-S-8% rats than in Dahl-S-0.3% rats (136.1 ± 48.4 ng/24 hr in LS versus 322.8 ± 46.7 ng/24 hr in HS, p < .05), and U-8-OHdG was correlated with SBP (r = 0.681) in Dahl-S rats. These results suggest oxygen radicals are involved in the pathogenesis of hypertension.     

氧化应激与心血管疾病

大量证据表明活性氧的慢性或急性过度产生在心血管疾病的发生发展中起重要作用。活性氧通过信号通路介导心肌细胞肥大和凋亡;通过灭活一氧化氮等机制导致内皮功能紊乱。在动脉粥样硬化、心肌缺血再灌注损伤、高血压、心力衰竭等一些主要心血管疾病的病理生理学中,氧化应激扮演关键角色。     

Effect of Doxazosin on Oxidative Stress Related Proteins in Essential Hypertensive Patients

The role of oxidative stress in the pathophysiology of hypertension has stimulated the investigation of strategies to reduce oxidative stress via antioxidant defenses. Using a molecular biology approach, we report, in essential hypertensive patients, the effect of doxazosin treatment on the mononuclear cell gene and protein expression of two major elements in the oxidative stress and vascular remodeling-related pathways: p22^phox and PAI-1. Ten essential hypertensive patients were treated with Doxazosin (4 mg/day) for two weeks (EH + D) and compared with ten untreated hypertensive patients (EH) and ten normotensive subjects (C). In EH p22^phox and PAI-1 mRNA and protein level was increased compared with C. In EH + D, doxazosin reduced p22^phox and PAI-1 gene and protein expression, which was similar to that of C. These results demonstrate for doxazosin an inhibitory effect on oxidative stress related proteins at gene and protein level, which confirms at molecular level a powerful antioxidant potential for this agent that could translate, in the long term, into a powerful antiatherosclerotic effect.     

Reactive Oxygen Metabolites (ROMs) as an Index of Oxidative Stress in Obstructive Sleep Apnea Patients

Study Objectives: Obstructive sleep apnea syndrome (OSA) is accompanied by oxygen desaturation and arousal from sleep. Free oxygen radicals are highly reactive molecules which could be produced by the OSA phenomenon of hypoxia/reoxygenation: cyclical alterations of arterial oxygen saturation with oxygen desaturation developing in response to apneas followed by resumption of oxygen saturation during hyperventilation. On the basis of these considerations, it was hypothesized that OSA may be linked to increased oxidative stress. Materials and methods: Twenty-six participants gave an interview during which a physician asked them about their age, smoking habits, and symptoms such as excessive daytime sleepiness and snoring. Physical examination and polysomnography were performed during their hospitalization. Reactive oxygen metabolites (ROMs) were measured in blood samples by the diacron reactive oxygen metabolites (D-ROM) test. Results: Twenty-one out of 26 subjects had an apnea/hypopnea index greater than 5 (OSA group). The measurement of free radicals was high in OSA patients. Furthermore, ROMs values in OSA patients were linearly correlated with the apnea/hypopnea index (R = 0.426; p = 0.042). The predictive value of a positive D-ROM test is 81%. Conclusions: ROMs were elevated in patients with OSA. When OSA was severe, similarly the value of ROMs in blood samples was enhanced, and the probable underlying mechanism for these events is the hypoxia/reoxygenation phenomenon.     

氧化应激在心房颤动发生维持中的作用

心房颤动（房颤）是临床上最常见的慢性心律失常。房颤使心房发生电重构及结构重构,然而心房重构发生的同时也加重房颤的发生及维持。有多项研究证实,氧化应激产物如活性氧能够影响房颤时心房电重构及结构重构,而房颤本身又使心房肌的氧化应激产物增加。房颤时心房氧化应激作用的机制可能与离子通道功能失调、NADPH氧化酶途径及线粒体损伤等有关。在一些近期的研究中也发现具有抗氧化作用的药物如他汀类、肾素-血管紧张素-醛固酮系统阻断剂可能通过防止心房重构,减少房颤发生。     

氧化应激与高血压研究进展

原发性高血压的发病机制目前还不完全清楚,但是大量的研究均发现氧化应激在高血压的发病机制和并发症中具有重要的作用。现从基础与临床两个方面,对高血压与氧化应激的相关性、抗高血压药物治疗与氧化应激、抗氧化应激药物与高血压的发病机制、高血压与氧化应激的因果关系等方面对高血压与氧化应激进行了较为系统的阐述,并对一些,临床研究的结果进行了初步评价。最后,对高血压与氧化应激的下一步研究方向和方法进行了展望。     

Association between Oxidative Stress Assessed by Urinary 8-Hydroxydeoxyguanosine and the Cardiac Function in Hypertensive Patients without Overt Heart Disease

Although increased oxidative stress is known to be associated with worsened cardiac function in chronic heart failure, consensus is still lacking regarding the association between oxidative stress and cardiac function in hypertensive patients without overt heart disease. This study aimed to evaluate the association between oxidative stress assessed by urinary 8-hydroxydeoxyguanosine (8-OHdG) and cardiac function in hypertensive patients without overt heart disease. We enrolled a total of 80 hypertensive patients (70 ± 11 y) who had been taking antihypertensive medications for at least 1 year. Urinary 8-OHdG levels were measured by an immunochromatographic assay (ICR-001, Selista Inc., Tokyo, Japan). Echocardiography was performed to assess the left ventricular (LV) diastolic function by measuring early diastolic mitral annular velocity (e′) and the ratio of early transmitral flow velocity (E) to e′ (E/e′). Urinary 8-OHdG was correlated with E/e′ (r = 0.346, P = .002), e′ (r = ?0.310, P = .005), and HbA1c (r = 0.276, P = .013). Multiple linear regression analysis revealed that only e′ (β = ?0.343, P = .004) was an independent determinant of urinary 8-OHdG. In conclusion, decreased e′ is independently associated with elevated urinary 8-OHdG, a marker of oxidative stress, in hypertensive patients. Therefore, an elevated urinary 8-OHdG level may be useful in detecting subclinical LV diastolic dysfunction in hypertensive patients without overt heart disease.     

The Association of Oxidative Stress with Hypertensive Retinopathy

This study was designed to answer the following questions: (i) Do levels of serum gamma-glutamyl transferase (GGT), a marker of oxidative stress, change in hypertensive retinopathy (HR)? (ii) Is there any relation between degree of HR and GGT levels? This study included 80 hypertensive patients with HR. Group 1 comprised 40 patients with grade I HR, and group 2 comprised 40 patients with grade II HR. We selected 40 healthy subjects for the control group. Level of GGT in group 2 was significantly higher than in group 1 (P = 0.005) and control group (P = 0.001); it was also higher in group 1 than in control group (P = 0.025). Our study suggests that oxidative stress, mechanisms known to be involved in vascular lesions, may promote the development of HR.     

Oxidative stress, aging and the proteasomal system

Oxygen free radicals and other oxidants are causingpotential danger for intracellular proteins during thelifetime of cells and organisms. Therefore, proteinoxidation is one of the natural consequences ofaerobic life. The degradation of non-functional,oxidized proteins is an essential part of theantioxidant defenses of cells. The major proteolyticsystem responsible for the removal of oxidizedcytosolic proteins is the proteasomal system. Thissystem consists of the 20S 'core' proteasome and amultitude of various regulators. It is known thatcertain components of this system are regulated duringoxidative stress and aging.One of the highlights of age-related changes ofcellular metabolism is the accumulation of oxidizedproteins. The question whether the accumulation ofoxidized proteins during aging is due to a malfunctionof the intracellular proteolytic machinery of the cellremains still unsolved. The information availableabout an age-related decline of the proteasomal systemis very contradictory. The current literature aboutthe proteasomal system, the regulation of this systemduring oxidative stress and the age-related changesare in the focus of this review.     

国产瑞舒伐他汀治疗低体质量女性血脂异常患者的疗效和安全性的分析研究

目的 评价国产瑞舒伐他汀(舒夫坦)治疗低体质量女性血脂异常患者的疗效和安全性.方法 40例低体质量(BMI＜19kg/m2)女性高胆固醇血症患者口服国产瑞舒伐他汀5mg/d 3个月,治疗结束后比较治疗前后患者总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)达标率及肝肾功能变化.结果 治疗后TC、LDL-C较治疗前降低,差异有统计学意义(P＜0.05).TC、LDL-C达标率分别为44.6 %和56.3 %.三酰甘油(TG)和高密度脂蛋白胆固醇(HDL-C)与治疗前比较,差异无统计学意义(P＞0.05).治疗过程中未出现严重不良事件.结论 国产瑞舒伐他汀5mg对低体质量女性血脂异常患者降低LDL-C的疗效好,安全性佳.     

Advanced Glycation End Products and Receptor–Oxidative Stress System in Diabetic Vascular Complications

Reducing sugars can react non‐enzymatically with amino groups of protein to form Amadori products. These early glycation products undergo further complex reactions, such as rearrangement, dehydration, and condensation, to become irreversibly cross‐linked, heterogeneous fluorescent derivatives, termed advanced glycation end products (AGEs). The formation and accumulation of AGEs have been known to progress at an accelerated rate in patients with diabetes mellitus, thus being involved in the development and progression of diabetic micro‐ and macroangiopathy. Indeed, there is accumulating evidence that an interaction between an AGE and its receptor (RAGE) generates oxidative stress and subsequently evokes vascular inflammation and thrombosis, thereby playing a central role in diabetic vascular complications. In this paper, we review the pathophysiological role of AGE‐RAGE–oxidative stress system and its therapeutic interventions in diabetic micro‐ and macroangiopathy.