血浆对氧磷酯酶1活性与肝硬化Child-Pugh分级的关系

目的对肝硬化患者血浆对氧磷酯酶1（PON1）活性进行检测，探讨肝硬化患者PON1活性与Child-Pugh分级的相关性。方法肝硬化患者108例，Child-Pugh分级A级35例，B级38例，C级35例。健康对照组66例。用对氧磷为底物的酶速率比色法测定肝硬化患者血浆PON1活性，同时测定清蛋白（Alb）、前清蛋白（PAB）和胆碱酯酶（ChE）活性，分析PON—1活性与Alb、PAB、ChE之间的关系。结果肝硬化患者PON1活性较健康对照组显著降低[分别为（93．4±33．1）U／mL及（168．3±28．4）U／mL，P〈0．013，且肝硬化Child—PughA、Child-PughB、Child—PughC相比，PON1活性依次显著降低（分别为（115．1±36．1）U／mL）、（92．3±32．4）U／mL、（69．1±31．4）U／mL]。肝硬化患者血浆PON-1活性与Alb、PAB、ChE呈正相关（分别为r=0．622，P〈0．01；r=0．699，P〈0．01；r=0．702，P〈0．01）。结论血浆PON1活性与肝硬化患者肝脏实质损害有关，可反映肝细胞损害的严重程度，对肝硬化的诊断和预后判断有重要参考意义。     

The relationship between paraoxonase1-192 polymorphism and activity with coronary artery disease

ObjectiveWe tested the association between PON1 polymorphism, PON1 activity, oxidative susceptibility of LDL and coronary artery disease in Egyptians.MethodsPON1 polymorphism, serum PON1 activity, lipoprotein oxidation susceptibility and lipid profile were measured.ResultsLevels of HDL and paraoxonase activity were significantly decreased in CAD patients compared to control group, and in patients with three vessels compared to those of single or two vessels disease. High-activity allele (R) has a more atherogenic lipid profile than for the low activity allele (Q). PON1 RR genotype has nine fold risks to develop CAD in Egyptians while those with PON1 QR genotype have four fold risks.ConclusionThe PON1 activity is lower in subject with CAD and there is a significant relationship between activity of PON1 and the severity of coronary atherosclerosis. Also, we provide evidence of a significant association between R allele of the PON1 polymorphism and the development of coronary artery disease.     

1型糖尿病患者对氧磷酶1活性和氧化低密度脂蛋白水平变化

目的观察1型糖尿病(type 1diabetes mellitus,T1DM)患者血清对氧磷酶1(paraoxonase 1,PON1)活性和氧化低密度脂蛋白(oxidative low-density lipoprotein,ox-LDL)水平的变化。方法 51例T1DM患者(T1DM组)分为有并发症组36例和无并发症组15例,45例体检健康者对照组,测定各组血清PON1活性、ox-LDL及血生化水平,并分析其相关性。结果 T1DM组血清PON1活性低于对照组(P<0.01),ox-LDL水平高于对照组(P<0.01);有并发症组血清PON1活性低于无并发症组(P<0.01),ox-LDL和三酰甘油水平高于无并发症组(P<0.05);血清PON1活性和ox-LDL水平呈负相关(r=-0.3660,P<0.01)。结论血清PON1活性和ox-LDL水平变化对阐述T1DM的发病机制,预防T1DM并发症的发生有重要意义。     

Age- and sun exposure-dependent differences in 8-hydroxy-2'-deoxyguanosine and N-(carboxymethyl)lysine in human epidermis

Aging and exposure to sunlight are two major factors in the deterioration of skin function. In this study, thirty-six fixed human skin samples from sun-exposed and unexposed areas from young and old individuals were used to evaluate the localization of oxidative stress according to levels and distribution of 8-hydroxy-2'-deoxyguanosine and N(ε)-(carboxymethyl)lysine in samples using immunohistochemistry. In the epidermis of the young, negligible amounts of 8-hydroxy-2'-deoxyguanosine and N(ε)-(carboxymethyl)lysine were detected in unexposed areas, whereas nuclear 8-hydroxy-2'-deoxyguanosine and cytoplasmic N(ε)-(carboxymethyl)lysine were increased in the lower epidermis in sun-exposed areas. In contrast, the aged presented prominent nuclear 8-hydroxy-2'-deoxyguanosine and nuclear N(ε)-(carboxymethyl)lysine in the epidermis of unexposed areas, concomitant with dermal increase in N(ε)-(carboxymethyl)lysine. However, the immunostaining of 8-hydroxy-2'-deoxyguanosine and N(ε)-(carboxymethyl)lysine revealed a decrease in the epidermis of sun-exposed areas in the aged. These results suggest an age-dependent difference in the adaptation and protective mechanisms of the epidermis against sunlight-associated oxidative stress, thus necessitating distinct standards for evaluation in each age group. Further investigation is warranted to elucidate underlying molecular mechanisms.     

Urinary levels of interleukin-8 (IL-8) and disease activity in patients with IgA nephropathy

Using quantitative sandwich ELISA, we studied 27 patients with IgA nephropathy to determine whether the levels of urinary IL-8 might reflect the disease activity. The levels of urinary IL-8 in patients with advanced stage IgA nephropathy were significantly higher than those in the patients with the mild stage of this disease, or in the healthy controls. The results showed a positive significant correlation between the levels of IL-8 and disease activity, i.e., between levels of urinary protein and urinary casts. A significant correlation between levels of urinary IL-8 and tubular function damage was also found. It was thus suggested that measurement of urinary IL-8 might be useful in evaluating the degree of renal injuries and/or prognosis in patients with IgA nephropathy.     

Exercise and activity level in Alzheimer's disease: a potential treatment focus

This article provides information on the baseline health and physical function of 30 individuals with Alzheimer's disease (AD); describes a community-based program designed to increase balance, flexibility, strength, and endurance in these persons by the training of caregivers to facilitate and supervise exercise activity; and documents the adherence of these subjects and their caregivers to this intervention. Subjects were recruited from an ongoing, community-based Alzheimer's Disease Patient Registry, and met NINCDS-ADRDA criteria for probable or possible AD. Caregivers were family members living with the demented individuals in the community. Physical performance was measured using walking speed, functional reach, and standing balance. Health status was measured with the Medical Outcomes Study Short Form, the Sickness Impact Profile, and caregiver reports of subject's restricted activity days, bed disability days, falls, and exercise participation. Baseline data indicated that persons with AD were impaired on measures of physical performance and function, compared to published data on nondemented older adults. During a 12-wk treatment period, caregivers were taught to guide their demented charges in an individualized program of endurance activities (primarily walking), strength training, and balance and flexibility exercises. Adherence data indicated that 100% of the subjects were compliant with some exercise recommendations, and one-third completed all assigned exercises during the training period. Caregivers were able to learn and direct subjects during scheduled exercise activities. These findings indicate that the integration of exercise training into the care of persons with AD is both needed and feasible. Further research is currently underway to determine the efficacy of this approach for reducing additional physical disability in these individuals.     

终末期肾病中DNA氧化损伤标志物8-OHdG水平的研究

目的通过检测终末期肾病（ESRD）患者血清中的DNA氧化损伤标志物8-羟基脱氧鸟苷（8-OHdG）含量,探讨ESRD患者中DNA氧化损伤的程度及其影响因素。方法选取年龄及性别匹配的研究对象40例,分为3组：对照组、CRF（慢性肾功能不全）组和HD（血液透析）组。采用ELISA法检测血清8-OHdG水平,改良镀铜镉颗粒还原法检测一氧化氮（NO）水平,硫代巴比妥酸产物比色法检测丙二醛（MDA）水平。结果与对照组相比,CRF组、HD组透析前、后血清8-OHdG水平均显著增高（P〈0.01）,且HD组透析后8-OHdG水平较透析前显著增高（P〈0.05）。CRF组、HD组透析前和透析后NO、MDA水平较对照组明显增高（P〈0.05）。血清8-OHdG和Scr、NO水平呈显著正相关（P〈0.05）。结论在ESRD患者血清中8-OHdG水平明显增高,提示DNA氧化损伤增强。8-OHdG作为一种DNA氧化损伤产物,可被认为是评价ESRD氧化损伤水平的可靠观测指标。     

Arylesterase and paraoxonase activity of paraoxonase (PON1) affected by ischemia in the plasma of patients with arterial occlusion of the lower limbs

ObjectivesThe aim of the study was to evaluate the effect of different degrees of chronic ischemia of the lower limbs on PON1 activity in plasma, in relation to different substrates.Design and methodsThe studied group consisted of patients with chronic arterial occlusion of the lower limbs due to atherosclerosis. The paraoxonase and arylesterase activities of PON1 were measured according to the Karen Gan method.ResultsPON1 arylesterase activity was affected by ischemia of the lower limbs depending on its degree. In the group with critical ischemia decreased PON1 activity was observed in comparison with that in the moderate ischemia group and the control group (50.05 ± 21.40 U/mL and 82.59 ± 29.27 U/mL, 85.30 ± 35.05 U/mL, respectively).ConclusionsThe results revealed a reverse relationship between PON1 activity and the progress of atherosclerosis to the ischemic level. The present study demonstrates, for the first time, that the arylesterase activity of PON1 is affected by critical ischemia of the lower limbs.     

血清对氧磷酶1活性与2型糖尿病患者颈动脉粥样硬化的关系

目的：探讨血清对氧磷酶1（paraoxonase 1,PON1）活性与2型糖尿病患者颈动脉粥样硬化的关系。方法2型糖尿病患者117例,根据颈动脉彩色多普勒超声测定结果,分为无动脉粥样硬化（AS）组38例,AS组79例;选择同期健康体检者75例（对照组）,测量血压、体质量指数（BMI）、腰臀比、空腹血糖、餐后2小时血糖、糖化血红蛋白、总胆固醇、甘油三酯（TG）、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、血尿酸等各项指标,同时测定血清 PON1活性。分析血清PON1活性与颈动脉粥样硬化的关系。结果与对照组比较,糖尿病组血清 PON1（240．0±15．6） kU／L vs （229．5±19．6）kU／L、AS发生率（44．0％ vs 67．5％）、BMI（24．3±3．6）kg／m2 vs （25．8±3．2）kg／m2、腰臀比（0．89±0．05）vs （0．93±0．06）、收缩压（131．0±8．3）mmHg（1 mmHg＝0．133 kPa）vs （134．0±8．8）mmHg、TG （1．8±0．8）mmol／L vs （2．1±1．3）mmol／L等比较差异有统计学意义（P＜0．05）;AS组血清 PON1活性明显低于非AS组（235．5±19．9）kU／L vs （226．7±18．9）kU／L（P＜0．05）;糖尿病患者血清PON1活性与年龄呈负相关（r＝－0．382,P＜0．01）,与血清TG水平呈正相关（r＝0．223,P＜0．05）。结论2型糖尿病患者血清PON1活性显著下降,PON1活性降低与颈动脉粥样硬化发生密切相关。     

Hyperhomocysteinemia, paraoxonase activity and risk of coronary artery disease

OBJECTIVES: Paraoxonase-1 (PON1) detoxifies homocysteine thiolactone (HcyT) in human blood and could thus delay the development of atherosclerosis. We investigated (a) PON1 activity and polymorphisms, and (b) the relationship between PON1 activity, homocysteine (Hcy) and the severity of CAD patients in Tunisian population. DESIGN AND METHODS: We used PCR-RFLP analysis to detect the Q192R and L55M variants of the PON1 gene in 100 patients with CAD and in 120 healthy controls. Paraoxonase activity was measured spectrophotometrically using phenylacetate as a substrate. Total plasma homocysteine concentrations were determined by direct chemiluminescence assay. RESULTS: We found an increased Hcy level in CAD patients compared to the control group (15.86+/-8.63 vs. 11.9+/-3.25 micromol/L respectively, P<0.001), and a decrease in PON1 activity in CAD patients as compared to the control group (117+/-56 vs. 181+/-73 U/mL respectively, P<0.001). PON1 Q192R and L55M polymorphisms were not associated with the presence of CAD (P=0.592, P=0.294, respectively). However, we found that PON1 activity is lower with the PON1 192RR than with PON1 192QQ genotypes in the study population. Furthermore, there were no association between PON1 L55M polymorphism and PON1 activity. We showed a significant decrease in PON1 activity in CAD patients presenting 0- to 3-vessel stenosis (155+/-39; 135+/-36; 103+/-22; 77+/-24 U/mL, respectively; P<0.001). CONCLUSION: In this study, we showed that low PON1 activity is associated with the PON1 192RR genotypes and associated with the severity of CAD in the Tunisian population. We hypothesize that high level of Hcy together with low PON1 activity results in an increased plasma HcyT plasma concentration leading to protein N-homocysteinylation and the development and progression of atherosclerosis.     

慢性胰腺炎患者血清对氧磷酶1活性变化

目的探讨血清对氧磷酶1活性与慢性胰腺炎发病的关系。方法152例慢性胰腺炎患者（观察组）和128例体检健康者（对照组），采用分光光度法检测血清对氧磷酶1活性，并进行2组间比较。结果观察组血清对氧磷酶1活性（（412．56±135．86）u／mL）明显低于对照组（（582．74±176．37）u／mL）（P〈O．01）；多因素logistic回归分析结果显示，血清对氧磷酶1活性降低是慢性胰腺炎发病的独立危险因子。结论血清对氧磷酶1可作为预测慢性胰腺炎发病的一项血清学标志物。     

Assessment of paraoxonase 1 activity and malondialdehyde levels in patients with rheumatoid arthritis

OBJECTIVES: We aimed to evaluate antioxidant paraoxonase 1 activity together with malondialdehyde (MDA) (an oxidative stress parameter) levels in patients with rheumatoid arthritis. DESIGN AND METHODS: Fifty-seven rheumatoid arthritis patients were included in the study and subgrouped according to disease activity (active, n = 31; inactive, n = 26) and compared with healthy controls (n = 25). Serum paraoxonase 1 activity and MDA levels were measured according to an enzymatic spectrophotometric method. RESULTS: Serum MDA level was higher (P = 0.001) whereas paraoxonase 1 activity was lower (P = 0.001) in the patient group than the controls. When active and inactive subgroups were compared with the control group, there was a statistically significant difference between each parameter. Serum MDA levels were significantly higher, while paraoxonase 1 activity was lower in the active and inactive rheumatoid arthritis groups than the control group. But there was not any difference between active and inactive patients with RA. There was a negative correlation between MDA levels and paraoxonase 1 activity. CONCLUSIONS: Increased reactive oxygen species levels in rheumatoid arthritis may result in a pro-oxidation environment, which in turn could result in decreased antioxidant paraoxonase 1 activity and increased MDA levels.     

Increased oxidative DNA damage, as assessed by urinary 8-hydroxy-2'-deoxyguanosine concentrations, and serum redox status in persons exposed to mercury

BACKGROUND: Mercury is a ubiquitous and highly toxic environmental pollutant. In this study, we evaluated the relationship between mercury exposure and oxidative stress, serum and urinary mercury concentrations, oxidative DNA damage, and serum redox status in chronically mercury-exposed persons compared with healthy controls. METHODS: We measured urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), which we used as a biomarker of oxidative DNA damage in the mercury-exposed persons, by HPLC with electrochemical detection (ECD). We evaluated antioxidant status by measuring the activities of superoxide dismutase and glutathione peroxidase and the concentrations of total reduced glutathione and protein-bound thiols in serum. RESULTS: The significant increase in 8-OHdG concentrations in urine indicated that mercury-induced oxidative damage to DNA occurred in vivo. Differences in body mercury burden and antioxidant enzyme activities were statistically significant between the mercury-exposed persons and controls. Serum and urinary mercury concentrations in the mercury-exposed persons were more than 40-fold higher than in controls. CONCLUSIONS: Mercury exposure can induce oxidative DNA damage, whereas the antioxidative repair systems can be expected to minimize DNA lesions caused by mercury. Measurement of urinary 8-OHdG could be useful for evaluating in vivo oxidative DNA damage in mercury-exposed populations.     

Functional independence level and cognitive deficit in elderly individuals with Alzheimer's disease

This study investigated the influence of the functional independence level of elderly individuals with Alzheimer's disease, according to cognitive assessment scores. Participants were 67 elderly individuals who received care in the Behavioral Neurology Outpatient Clinic of Hospital das Clinicas in Ribeir?o Preto. Participants were evaluated in 2008 through a questionnaire for sociodemographic data, Functional Independence Measure (FIM) and the mini-mental state examination (MMSE). The cognitive deficit influenced the performance in carrying out activities of daily living. The average FIM for elderly people without cognitive deficit was 107.7 and for individuals with deficit, 63.2 (p < 0.001). Average FIM motor scores were 81.7 and 49.4 (p < 0.001), and FIM cognitive scores were 25.7 and 13.8 (p < 0.001), respectively. Knowing the reduction of independence and cognitive capacity is essential to maintain the provision of the basic needs of daily life. The study can support nurses' practice, improving elderly individuals and their families' living conditions.     

8-Oxo-7,8-dihydro-2'-deoxyguanosine Forms a Relatively Unstable Tetrameric Structure Compared with 2'-Deoxyguanosine

The hydrogen-bonded guanine tetrad, or G-quartet has been implicated in a variety of biological roles, including the function of chromosome telomeres. Here effect of the hydroxylation of guanosine at the 8 position on the G-quartet formation was examined. Electrospray inonization mass (ESI-MS) spectra of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 2'-deoxyguanosine (dG) were measured in order to know whether or not 8-oxodG forms a tetrameric structure as 2'-deoxyguanosine forms in teromeres. The ESI-MS spectra of dG shows prominent peaks at m/z 290, m/z 557, and m/z 1092, corresponding to [dG + Na]⁺, [dG2 + Na]⁺, and [dG₄ + Na]⁺ in the presence of 0.1 mM NaCl. On the other hand, the ESI-MS spectra of 8-oxodG in the presence of 0.1 mM NaCl shows prominent peaks at m/z 306 and m/z 589, corresponding to [8-oxodG + Na]⁺ and [8-oxodG₂ + Na]⁺. The results showed that 8-oxodG forms a relatively unstable tetrameric structure compared with dG.     

Severe systemic immune response syndrome, low plasma paraoxonase activity, and a new albumin species in a traumatized patient with Gaucher's disease

INTRODUCTION: Gaucher's disease (GD) is an inborn error, autosomal recessive lysosomal lipid storage disorder characterized by the lack of the enzyme glucocerebrosidase. We observed some abnormalities in the plasma of a traumatized patient with GD. CASE REPORT: We report of a traumatized patient with GD that developed a severe systemic immune response during the course of an extended hospital stay. Plasma paraoxonase (PON) activity was assayed and found to be extremely low possibly due to the existence of GD in this particular patient. Also, a potentially novel post-translational modification (PTM) of albumin was noticed in the patient's plasma that coincided with enzyme replacement therapy (ERT) with Cerezyme. CONCLUSIONS: The decreased plasma PON activity measured might be a contributive factor in the development of an accentuated systemic immune response in a traumatized patient with GD. A modified albumin species could serve as a biomarker for ERT in Gaucher patients.     

Serum paraoxonase activity in patients with type 1 diabetes compared to healthy controls

BACKGROUND: The oxidation of low-density lipoprotein (LDL) is central to current theories on the initiation and progression of atherosclerosis. Type 1 diabetes is associated with an increase in oxidative stress, which may be responsible for the increased susceptibility to coronary heart disease seen in type 1 diabetes. High-density lipoprotein (HDL) associated paraoxonase (PON1) can retard the oxidation of LDL. DESIGN: Paraoxonase activity, concentration and genotype were therefore investigated in 152 people with type 1 diabetes and 282 healthy controls. These parameters were also investigated in the group with type 1 diabetes in relation to the presence of diabetic complications. RESULTS: Both PON1 activity and concentration were significantly lower by 16.7% and 19.2% (both P < 0.05) in the type 1 diabetes group. These differences were independent of the PON1 coding region polymorphisms. The distribution of PON1 activity and mass were the same in both populations, i.e. for the PON1-192 polymorphism RR > RQ > QQ and for the PON1-55 polymorphism LL > LM > MM. There were no differences in either the PON1 polymorphisms, PON1 activity and concentration in people with type 1 diabetes in the presence or absence of micro and macro vascular complications of diabetes. CONCLUSIONS: Low PON1 activity may contribute to the increased atherosclerosis found in type 1 diabetes by reducing the ability of HDL to retard LDL oxidation despite the frequently-found increased HDL in type 1 diabetes when good glycaemic control is established.     

Activity of paraoxonase 1 (PON1) on HDL2 and HDL3 subclasses in renal disease

IntroductionCardiovascular complications, as the main cause of mortality in renal patients, are followed with altered lipoproteins composition. Considering that paraoxonase-1 (PON1) is an anti-oxidative enzyme located mainly on HDL particles, the current study has aim to investigate whether failure of kidney function leads to changes in the distribution of PON1 activity between different HDL subclasses.Materials and methodsIn 77 renal patients (21 chronic kidney disease (CKD) and 56 end stage renal disease (ESRD) patients on dialysis) and 20 healthy subjects PON1 activity on HDL₂ and HDL₃ subclasses was determined by zymogram method that combines gradient gel electrophoresis separation of HDL subclasses and measurement of PON1 activity in the same gel.ResultsSerum paraoxonase (p<0.01) and arylesterase activity (p<0.001) of PON1 as well as its concentration (p<0.01) were significantly lower in CKD and ESRD patients compared to controls. Relative proportion of HDL₃ subclasses was higher in ESRD patients than in healthy participants, while HDL₂ subclasses was significantly decreased in CKD (p<0.05) and ESRD (p<0.001) patients, as compared to controls. Furthermore, control subjects had higher PON1 activity on HDL₂ (CKD and ESRD patients p<0.001) and HDL₃ (CKD p<0.05; ESRD patients p<0.001) subclasses in comparison with the both patients groups. Also, significant negative correlation was found between paraoxonase activity of PON1 in serum and creatinine concentration (ρ=‐0.373, p<0.01).ConclusionsThis study showed that altered HDL subclasses distribution, changed PON1 activities on different HDL subclasses as well as diminished anti-oxidative protection could be important factors in atherosclerosis development in CKD and ESRD patients.     

Alpha2-macroglobulin deletion polymorphism and plasma levels in late onset Alzheimer's disease.

The acute-phase "panproteinase" inhibitor alpha2-macroglobulin (alpha2M), a protein involved in inflammatory reactions, has been identified in amyloid plaques in Alzheimer's disease (AD). In addition, alpha2M is involved in AD susceptibility at the genetic level, and a deletion polymorphism at the a2M gene has been found to be associated with sporadic AD. We analyzed the deletion polymorphism and alpha2M plasma levels in 93 ultraoctuagenarian patients with late-onset sporadic AD and in controls (n=157). alpha2M allele frequencies did not differ between AD patients (alpha2M*2=0.169) and controls (alpha2M*2=0.146). The mean plasma concentrations of alpha2M were similar in patients (271.8+/-79 mg/dl) and controls (269.5+/-81.2 mg/dl). No difference was found in the alpha2M mean plasma levels associated with the three alpha2M genotypes, indicating that the deletion has no effect on alpha2M protein level. However, in AD patients alpha2M mean plasma values differed significantly according to apolipoprotein E genotypes (p=0.03), with E3/E3 homozygotes showing the highest levels. Since in a previous work E3/E3 were found to be associated with the highest plasma levels of alpha1-antichymotrypsin, another acute-phase protein, the present findings seem to support the hypothesis that inflammation may be a relevant factor in AD pathogenesis peculiar to E3/E3 subjects.