Human liver disease decreases methacrylyl-CoA hydratase and beta-hydroxyisobutyryl-CoA hydrolase activities in valine catabolism

Oxidative modification of LDL induces immunogenic epitopes in the LDL molecule, and the presence of antibodies against oxidized LDL (anti-Ox-LDL) has been demonstrated in human sera. However, little is known about the clinical significance of anti-Ox-LDL. To elucidate a clinical relationship between the immunological response to oxidized LDL and cellular oxidative stress, we measured serum titers of anti-Ox-LDL in 45 unselected patients with hypercholesterolemia and serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), considered a biomarker of the oxidative damage to DNA. The anti-Ox-LDL titer was not correlated with the serum LDL-C concentration, but was correlated with the 8-OHdG concentration (r = 0.300, P < 0.05) in a simple linear regression. Multiple regression analysis indicated that 8-OHdG was independently correlated with anti-Ox-LDL (r = 0.429, P < 0.05), but no other variables, including LDL-C concentrations and smoking habit, were correlated with anti-Ox-LDL. In 16 subgroup patients, the concentrations of TC, TG and LDL-C decreased and the HDL-C concentration increased after cholesterol-lowering therapy with fluvastatin. In addition, both the anti-Ox LDL titer (14.0 +/- 9.5 to 11.4 +/- 6.6 AcU/ml, P < 0.05) and the 8-OHdG concentration (1.19 +/- 0.41 to 0.85 +/- 0.43 ng/ml, P < 0.05) also decreased after fluvastatin therapy. The immunological response to LDL oxidation on vascular wall tissues or cells appear to occur in association with oxidative DNA damage. The measurement of anti-Ox-LDL may be a useful indicator for lipid-lowering therapy.     

Urinary 8-OHdG: a marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis and diabetics

Reactive oxygen species (ROS) produced either endogenously or exogenously can attack lipid, protein and nucleic acid simultaneously in the living cells. In nuclear and mitochondrial DNA, 8-hydroxydeoxyguanosine (8-OHdG), an oxidized nucleoside of DNA, is the most frequently detected and studied DNA lesion. Upon DNA repair, 8-OHdG is excreted in the urine. Numerous evidences have indicated that urinary 8-OHdG not only is a biomarker of generalized, cellular oxidative stress but might also be a risk factor for cancer, atherosclerosis and diabetes. For example, elevated level of urinary 8-OHdG has been detected in patients with various cancers. In human atherosclerotic plaques, there were increased amounts of oxidatively modified DNA and 8-OHdG. Elevated urinary 8-OHdG and leukocyte DNA were also detected in diabetic patients with hyperglycemia, and the level of urinary 8-OHdG in diabetes correlated with the severity of diabetic nephropathy and retinopathy. We have discussed various methods for determining 8-OHdG in the tissue and urine, including HPLC with and without extraction, and ELISA. Using the ELISA we developed, we found that the normal range of urinary 8-OHdG for females was 43.9 +/- 42.1 ng/mg creatinine and 29.6 +/- 24.5 ng/mg creatinine for males, respectively. We found that the normal value between females and males is significantly different (p < 0.001).     

硫辛酸对2型糖尿病患者尿8-羟基脱氧鸟苷排泄的影响

目的观察α-硫辛酸(ALA)对2型糖尿病患者尿8-羟基脱氧鸟苷(8-OHdG)排泄的影响,探讨其肾脏保护的可能机制。方法选择36例2型糖尿病患者为观察组,在原抗糖尿病治疗的基础上加用ALA,并选择同期健康体检的30例作为对照组。6个月后,观察治疗前后空腹血糖(FBG)、糖化血红蛋白(HbA1c)和尿白蛋白(ALB)及尿8-OHdG水平变化。结果 (1)与对照组比较,糖尿病组尿微量白蛋白/肌酐比值(UACR)及U8CR(尿8-OHdG/Ucr)值明显升高,差异有统计学意义(P<0.01)。(2)与治疗前相比较,ALA治疗后,观察组FBG和HbA1c无明显变化,UACR及U8CR值明显降低,差异有统计学意义(P<0.01)。(3)U8CR水平与UACR显著正相关(r=0.773,P<0.01)。结论α-硫辛酸可以减少2型糖尿病患者尿8-OHdG排泄,减轻体内氧化应激,该作用可能与其肾脏保护部分有关。     

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.     

The relationship of oxidative DNA damage marker 8-hydroxydeoxyguanosine and glycoxidative damage marker pentosidine.

OBJECTIVES: 8-hydroxydeoxyguanosine (8-OHdG) is a biomarker of oxidative DNA damage. Pentosidine is a biomarker of glycoxidation reaction. In this study, we investigated relationships among 8-OHdG, pentosidine and age. DESIGN AND METHODS: We determined the urinary concentrations of 8-OHdG and pentosidine in adults with mild hypercholesterolemia or/and mild hypertension (hypercholesterolemia group, n = 31; hypertension group, n = 25; hypercholesterolemia and hypertension group, n = 7). RESULTS: The strength of the relationship between 8-OHdG and age was the same as that between pentosidine and age (the correlation coefficient between 8-OHdG and age was 0.33, pentosidine and age was 0.37). In addition, there was a positive and significant correlation between 8-OHdG and pentosidine. On the other hand, mean values of 8-OHdG and pentosidine showed no significant difference among the three groups. CONCLUSION: The results of the present study indicate that both 8-OHdG and pentosidine levels increase similarly in degenerative pathologic conditions.     

原发性肝癌患者尿8-羟基脱氧鸟苷水平的观察

目的通过测定和比较原发性肝癌患者与健康体检者尿8-羟基脱氧鸟苷水平,探讨DNA氧化损伤与肝癌发生发展的关系。方法以酶联免疫吸附法检测各100例肝癌患者（实验组）及健康体检者（对照组）尿8-OHdG水平,并进行相互比较。结果肝癌患者尿8-OHdG水平明显高于健康体检者（16．12±5．30VS12．21±4．51）ng／mgCr（P〈0．01）。结论肝癌患者尿8-OHdG水平高于健康人群,DNA氧化损伤与肝癌发生发展具有密切的关系,测定尿8-OHdG水平有助于肝癌的诊治。     

hOGG1 Genotype, Green Tea and Oxidative DNA Damage among Heavy Smokers

DNA is susceptible to damage by reactive oxygen species, and 8-hydroxydeoxyguanosine (8-OHdG) is probably one of the most abundant DNA lesions formed during oxidative stress. Several pathways exist for the removal or repair of this lesion from mammalian DNA. The most established is via the base excision repair enzyme, human 8-oxoguanine glycosylase (hOGG1). Several polymorphisms in the hOGG1 gene have been detected in human populations. We were interested in whether there were differences in increased oxidative stress susceptibility to smoking within the hOGG1 genotypes and the impact of high tea drinking on this. A phase IIb randomised, controlled, tea intervention trial was designed to study the effect of high consumption (four cups per day) of decaffeinated green or black tea on oxidative DNA damage, as measured by urinary 8-OHdG, among smokers over a 4-month period and to evaluate the role of the hOGG1 genotype as an effect modifier. A total of 120 smokers with hOGG1 data completed the 4-month intervention. The hOGG1 genotype status was determined with a polymerase chain reaction-based approach. Multiple linear regression models were used to estimate the main effects and interaction effect of green and black tea consumption on creatinine-adjusted urinary 8-OHdG, with or without adjustment for potential confounders. Finally, we studied whether the effect of treatment varied by hOGG1 status of the individual. Assessment of urinary 8-OHdG after adjustment for baseline measurements and other potential confounders revealed a highly significant decrease in urinary 8-OHdG after 4 months of drinking decaffeinated green tea (p = 0.001). No change in urinary 8-OHdG was seen among smokers assigned to the black tea group. We found the distribution of hOGG1 Ser326Cys genotypes among smokers to be 62%, 28% and 10% for Ser/Ser, Ser/Cys and Cys/Cys genotypes, respectively. Because the homozygous Cys/Cys genotype was present in only 10% of the study population, the mutant types (Ser/Cys and Cys/Cys) were combined and compared with the Ser/Ser genotype. We found no significant interaction between smoking, hOGG1 genotypes and tea intervention in terms of levels of urinary 8-OHdG. This finding suggests that green tea intervention might be effective in decreasing levels of urinary 8-OHdG among smokers regardless of their hOGG1 genotype.     

The 2003 Carl A Moyer Award: real-time metabolic monitors, ischemia-reperfusion, titration endpoints, and ultraprecise burn resuscitation

Real-time metabolic monitoring of varied vascular beds provides the raw data necessary to conduct ultraprecise burn shock resuscitation based on second-by-second assessment of regional tissue perfusion. It also illustrates shortcomings of current clinical practices. Arterial base deficit was continuously monitored during 11 clinical resuscitations of patients suffering burn shock using a Paratrend monitor. Separately, in a 30% TBSA rat burn model (N = 70), three Paratrend monitors simultaneously recorded arterial blood gas and tissue pCO2 of the burn wound and colonic mucosa during resuscitation at 0, 2, 4, 6, and 8 ml/kg/%TBSA. Paratrend data were analyzed in conjunction with previously reported laser Doppler images of actual burn wound capillary perfusion. With current clinical therapy, continuous monitoring of arterial base deficit revealed repetitive cycles of resolution/worsening/resolution during burn shock resuscitation. In the rat model, tissue pCO2 in both burn wounds and splanchnic circulation differed depending on the rate of fluid resuscitation (P <.01 between sham and 0 ml/kg/%TBSA and between 2 ml/kg/%TBSA and 4 ml/kg/%TBSA). Burn wound pCO2 values correlated well with laser Doppler determination of actual capillary perfusion (rho = -.48, P <.01). The following conclusions were reached: 1). Gratuitous and repetitive ischemia-reperfusion-ischemia cycles plague current clinical therapy as demonstrated by numerous "false starts" in the resolution of arterial base deficit; 2). in a rat model, real-time monitoring of burn wound and splanchnic pCO2 demonstrate a dose-response relationship with rate of fluid administration; and 3). burn wound and splanchnic pCO2 are highly correlated with direct measurement of burn wound capillary perfusion by laser Doppler imager. Either technique can serve as a resuscitation endpoint for real-time feedback-controlled ultraprecise resuscitation.     

Microalbuminuria in acute burn injury.

Microalbuminuria is a known finding in inflammatory states. We hypothesized that urinary albumin/creatinine ratio (ACR) would correlate with injury severity and resuscitation demands after acute burns. This pilot study evaluated 30 adults admitted within 12 hours of injury with burns > or =10% total body surface area burn injury (TBSA). The urinary ACR was calculated for each patient at 7 to 12 hours, 19 to 24 hours, and 43 to 48 hours following burn injury. Microalbuminuria was defined as a urinary ACR > or =20 mg/g. Study patients (23 males, 7 females) had a mean age of 42.9 + 14.0 years and a median TBSA burn injury of 18.8%. Inhalation injury was present in 10 of the study patients, and all patients with inhalation injury had microalbuminuria at the time of admission. One study patient died. Median time from burn injury to resuscitation was 30 hours, and the median fluid requirement was 4.2 ml/kg/%TBSA. Microalbuminuria was not uniformly present in burn-injured patients during the first 48 hours after injury. ACR values early in the hospital course correlated with higher lactate concentrations early after burn injury. However, ACR correlated with neither injury severity nor resuscitation demands after burn injury during any studied time range. Microalbuminuria does not have apparent clinical utility in burn-injured patients, and other markers of injury severity and resuscitation demands should be sought.     

卡巴胆碱对烧伤休克犬口服补液时胃排空和胃黏膜二氧化碳分压的影响

目的 研究卡巴胆碱对烧伤犬休克早期口服补液时胃排空和胃黏膜二氧化碳分压(PgCO2)的影响.方法 将24只成年雄性Beagle犬随机分为4组:35%总体表面积(TBSA)烧伤后口服葡萄糖一电解质液(GES)组及其卡巴胆碱干预组(35%TBSA GES组和35%TBSA GES/CAR组);50%TBSA烧伤后口服GES液组及其卡巴胆碱干预组(50%TBSA GES组和50%TBSA GES/CAR组),每组6只.采用凝固汽油燃烧法分别造成颈背部35%TBSA Ⅲ度烧伤和颈背部+胸腹部50%TBSA Ⅲ度烧伤.各组于烧伤后0.5 h开始按Parkland公式量和速率(4 ml·kg-1·1%TBSA-1,前8 h内补1/e量,后16 h内补另1/2量)口服补液;GES/CAR组于伤后0.5 h口服卡巴胆碱(20 μg/kg溶于GES中).烧伤后2、4、8和24 h测定胃排空率和PgCO2,并观察胃不耐受症状.结果 烧伤后各组犬胃排空率均显著低于伤前(P均＜0.05),伤后2 h 35%TBSA GES组降至51.5%.伤后4 h 50%TBSA GES组降至39.2%,之后逐渐恢复,但伤后24 h仍显著低于伤前(P均＜0.05).35%TBSA GES/CAR组伤后各时间点胃排空率均显著高于同烧伤面积GES组(P均＜0.05),平均提高15.0%,伤后8 h恢复至伤前水平;50%TBSA GES/CAR组于8 h起胃排空率显著高于同烧伤面积GES组,但伤后24 h仍低于伤前水平(P＜0.05).伤后各组犬PgCO2均较伤前显著升高(P均＜0.05),35%TBSA GES/CAR组伤后各时间点显著低于同烧伤面积GES组,50%TBSA GES/CAR组伤后4 h起显著低于同烧伤面积GES组(P均＜0.05).伤后各组犬出现呕吐等胃不耐受症状情况比较:50%TBSA GES组(83.3%,5/6)＞50%TBSA GES/CAR组(50.0%,3/6)＞35% TBSA GES组(16.7%,1/6)＞35%TBSA GES/CAR组(0,0/6).结论 卡巴胆碱能显著改善Beagle犬烧伤休克早期胃对GES的排空,降低PgCO2,提高口服液体复苏的效果.     

Oxidative stress biomarkers in four Bloom syndrome (BS) patients and in their parents suggest in vivo redox abnormalities in BS phenotype

OBJECTIVE: To evaluate an association of Bloom syndrome (BS) phenotype with an in vivo prooxidant state. METHODS: The following endpoints were measured in 4 BS patients, their 6 parents, and 78 controls: a) leukocyte and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG); b) blood glutathione (GSSG and GSH), c) plasma levels of some plasma antioxidants (uric acid, UA, ascorbic acid, AA, alpha- and gamma-tocopherol), and of glyoxal (Glx) and methylglyoxal (MGlx). RESULTS: Leukocyte 8-OHdG levels were significantly increased in the 4 BS patients vs. 40 controls (p=0.04), while the urinary 8-OHdG levels were non-significantly increased in BS patients. Glutathione disulfide levels and GSSG/GSH ratio were significantly decreased in BS patients vs. 44 controls (p=0.02). The plasma levels of UA in BS patients were significantly increased vs. 24 controls (p=0.005). No significant alterations were found in the in the plasma levels of Glx, MGlx, AA, and tocopherol. No changes in the tested parameters were found in the BS heterozygotes. CONCLUSION: This report shows a significant increase in oxidative DNA damage in leukocytes and in plasma UA levels from 4 BS patients. Should these data be confirmed in more extensive BS patient groups, an involvement of oxidative stress in the clinical BS phenotype might be suggested.     

Evaluation of urinary 8-hydroxydeoxy-guanosine as a novel biomarker of macrovascular complications in type 2 diabetes

OBJECTIVE: To evaluate urinary 8-hydroxydeoxyguanosine (8-OHdG) as a marker for the progression of diabetic macroangiopathic complications. RESEARCH DESIGN AND METHODS: The content of urinary 8-OHdG, common carotid intima-media thickness (IMT), the coronary heart disease (CHD) risk score, the severity of diabetic retinopathy, and urinary albumin excretion were examined in 96 patients with type 2 diabetes, including 32 patients who had been nominated for the Kumamoto Study [Shichiri M, et al. Diabetes Care 23 (Suppl 2):B21-B29, 2000]. In addition, the patients from the Kumamoto Study were further evaluated regarding the effect of intensive insulin therapy on urinary 8-OHdG excretion. RESULTS: The urinary 8-OHdG:creatinine ratio (U8-OHdG) was 2.5-fold higher in patients with increased HbA(1c) than in those with normal HbA(1c) (P < 0.05). In addition, U8-OHdG was 2.3-fold higher in patients with increased IMT (P < 0.005). A similar result was observed between U8-OHdG and CHD risk score (P < 0.01). U8-OHdG was significantly higher in patients with simple retinopathy (P < 0.05) and those with advanced retinopathy (P < 0.01) than in patients without retinopathy. Similarly, U8-OHdG was significantly higher in patients with albuminuria (P < 0.01). Furthermore, in the Kumamoto Study, U8-OHdG was significantly lower in the multiple insulin injection therapy group compared with the conventional insulin injection therapy group (P < 0.01). CONCLUSIONS: Hyperglycemia independently increases 8-OHdG in patients with type 2 diabetes. 8-OHdG is a useful biomarker of not only microvascular but also macrovascular complications in patients with type 2 diabetes.     

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。     

Environmental Arsenic Exposure and Urinary 8-OHdG in Arizona and Sonora

Although at high levels arsenic exposure is associated with increased cancer incidence, information on the health effects of lower exposure levels is limited. The objective of this study was to determine whether arsenic at concentrations below 40 microg/L in drinking water is associated with increased urinary 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage and repair. Urine samples were collected from 73 nonsmoking adults residing in two communities in Arizona (mean tap water arsenic (microg/L) 4.0 +/- 2.3 and 20.3 +/- 3.7), and 51 subjects in four communities in Sonora, Mexico (mean tap water arsenic (microg/L) ranging from 4.8 +/- 0.1 to 33.3 +/- 0.6). Although urinary arsenic concentration increased with higher exposure in tap water, urinary 8-OHdG concentration did not differ by community within Arizona or Sonora, and was not associated with urinary arsenic concentration. At the exposure levels evaluated in this study, drinking water arsenic was not associated with increased DNA oxidation as measured by urinary 8-OHdG.     

Urinary biomarker of oxidative stress correlating with outcome in critically septic patients

Objective To determine whether urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), an in vivo parameter of oxidative stress, is correlated with the outcome of critically septic patients. Design and setting Clinical outcome study in an adult medical ICU. Patients Eighty-five consecutive septic patients: 59 men and 26 women. Measurements and results Urinary 8-OHdG was analyzed using isotope-dilution liquid chromatography with tandem mass spectrometry (LC/MS/MS). ICU mortality in these 85 septic patients was 25.9% (n = 22) and hospital mortality 38.8% (n = 33). APACHE II scores of survivors on day 1, on day 3, and the difference between them differed significantly from those of nonsurvivors (day 1, 21.0 ± 7.1 vs. 25.9 ± 8.0; day 3, 15.0 ± 5.8 vs. 23.2 ± 8.3; difference, 6.0 ± 5.5 vs. 1.7 ± 6.6). Urinary 8-OHdG was significantly lower in survivors than in nonsurvivors on day 1 (1.8 ± 2.4 vs. 3.0 ± 2.4). The area under receiver operating characteristic curve analysis for the association between day 1 urinary 8-OHdG and ICU mortality was 0.71. The comparison performed upon discharge from hospital revealed similar results. Conclusions This is a preliminary study. The excretion of the urinary 8-OHdG, as measured using isotope-dilution LC/MS/MS, as the APACHE II score, were correlated with the outcome of critically septic patients in medical ICU. An erratum to this article can be found at     

Oxidative Stress Biomarkers and Lifestyles in Japanese Healthy People

The urinary concentrations of 8-isoprostane and 8-hydroxy-2’-deoxyguanosine (8-OHdG), which are biomarkers of oxidative stress, were measured in 677 Japanese people without any diseases, and their correlations with lifestyle facotrs, lifestyle-related blood biochemical parameters, and dietary intake of antioxidative vitamins were investigated. The mean urinary concentration of 8-isoprostane and 8-OHdG was 0.58 ng/mg creatinine and 8.43 ng/mg creatinine, respectively. Mean urinary 8-isoprostane was significantly different in terms of age, gender, smoking and alcohol consumption but not different in terms of body mass index (BMI) and exercise. By multiple regression analysis, urinary 8-isoprostane was significantly influenced by smoking and age. On the other hand, mean urinary 8-OHdG showed differences only by age group. Multiple regression analysis revealed that urinary 8-OHdG was significantly influenced by age, smoking, body weight, levels of high-sensitivity C-reactive protein (Hs-CRP) and low density lipoprotein-cholesterol in females, although it was significantly influenced by body weight in males. The present study shows that urinary 8-isoprostane is associated with lipid peroxidation related-lifestyles such as smoking, and urinary 8-OHdG is associated with arteriosclerosis related-factors such as Hs-CRP. Our findings suggest that 8-isoprostane and 8-OHdG appear to be prospective biomarkers for early prediction of lifestyle related-disease risk at the population level.     

Comparing a Single Institution's Experience With Electrical Injuries to the Data Recorded in the National Burn Repository

Electrical injuries usually represent a small proportion of a burn center's admissions. Although burn size may be small, internal tissue damage is sometimes extensive. This study reviews a single institution's experience with electrical injuries and compares it to the multi-institutional data of the National Burn Repository (NBR). The 2009 NBR and the records of a large urban burn center (single institution) were queried for adult electrical injuries over an 8-year period. Data examined included demographics, %TBSA burn, length of stay (LOS), injury circumstance, and disposition. Multiple linear regression models were created to determine factors related to LOS. One hundred ninety-one single-institution patients and 2837 multi-institution patients met the criteria. Both cohorts were mostly white males approximately 30 years of age and injuries where often work-related. Single-institution patients had a mean injury size of 4% TBSA, while multi-institution patients had 7%. The most common exposure source was domestic wiring for single-institution patients and electrical power plants/lines for multi-institution patients. Single-institution data showed that females had a shorter LOS than males (P < .0001). Single-institution data showed that independent risk factors for an increased LOS were infection, amputation, fasciotomy, and being Hispanic. Independent risk factors for multi-institution patients were being Hispanic and large %TBSA burn. There was no difference in mortality, gender, age, LOS, or intensive care unit LOS between the cohorts. In this analysis, there was no statistical difference between outcomes in the single- or multi-institutional groups. However, injuries reported in the NBR were slightly larger. In both cohorts, an increase in LOS was associated with %TBSA, as expected. Interestingly, Hispanic ethnicity correlated with an increased LOS. Future work will be aimed at understanding this correlation to determine whether it is specific to electrical injury or burns in general.     

Oxidative DNA damage in early pregnancy and risk of gestational diabetes mellitus: A pilot study

ObjectivesTo examine the association of maternal early pregnancy oxidative stress with risk of gestational diabetes mellitus (GDM).Design and methodsA pilot prospective, nested case–control study was conducted. Study participants were recruited before 20 weeks gestation. Maternal urinary 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of systemic oxidative DNA damage and repair, was measured using competitive immunoassays. Logistic regression was used to calculate odds ratio (OR) and 95% confidence intervals (95%CI).ResultsElevations in early pregnancy urinary 8-OHdG concentrations were associated with increased GDM risk. After adjusting for confounders, the OR for extreme quartiles (≥ 8.01 vs. < 4.23 ng/mg creatinine) of 8-OHdG was 3.79 (95%CI 1.03–14.00). The risk for GDM was highest for overweight women with urine 8-OHdG concentrations ≥ 8.01 ng/mg creatinine (OR = 5.36, 95%CI 1.33–21.55) when compared with lean women who had 8-OHdG concentrations < 8.01 ng/mg creatinine.ConclusionsElevated urine 8-OHdG concentrations in early pregnancy appear to be associated with increased GDM risk.     

Consequences of low birthweight on urinary excretion of DNA markers of oxidative stress in young men

OBJECTIVE: Low birthweight (LBW) has been associated with an increased risk of development of type 2 diabetes in adult life. Both type 1 and type 2 diabetes mellitus are characterized by increased oxidative stress. The purpose of this study was to investigate whether young healthy adults born with LBW showed differences in oxidative stress under normal conditions and during the added challenge of a physiological Intralipid infusion. MATERIAL AND METHODS: Urinary excretion of DNA markers of oxidative stress were analyzed by LC-MS/MS in 19 men (aged 19 years) with LBW and in 19 age matched, normal birthweight (NBW) controls pre- and post a 3-fold increase of plasma free fatty acids. RESULTS: Mean excretion rates of 8-oxo-guanine (8oxoGua), 8-oxo-guanosine (8oxoGuo), 8-oxo-2'deoxyguanosine (8oxodG), and 1,N6-ethenodeoxyadenosine (epsilon dA) did not statistically differ between subjects with LBW and NBW (66.9 versus 73.9 nmol/15 h, 17.8 versus 18.5 nmol/15 h, 11.9 versus 14.4 nmol/15 h and 44.0 versus 43.2 pmol/15 h, respectively). Furthermore, Intralipid infusion did not affect excretion of DNA adducts in LBW or NBW subjects. Statistically significant correlations were found between body mass index and urinary excretion of 8oxoGua (r = 0.64, p = 0.003) and 8oxoGuo (r = 0.64, p = 0.003) in the LBW group only. CONCLUSIONS: These findings suggest that oxidative stress may be a consequence of diabetes and is not, or at least only partly, involved in the early pathogenesis of type 2 diabetes.     

Cosmetic liposuction causes only transient elevation of acute inflammatory response and does not advance to oxidative and nitrosative stress

Cosmetic liposuction is a surgical procedure performed on normal nonobese subjects to remove unwanted fat. We are interested to know whether the impact of acute inflammatory response induced by liposuction differs from that of chronic inflammation and whether acute inflammatory response will also advance further and cause oxidative and nitrosative stress leading to various clinical complications. In our investigation we monitored 15 nonobese women prior to liposuction, and one day and one month after the surgery with multiple markers associated with chronic inflammation and oxidative stress. Our results indicate that liposuction causes only a transient elevation of acute inflammatory markers such as interleukin-6 (IL-6), high sensitive C-reactive protein (hCRP), and serum amyloid A (SAA), and a transient decrease of nitric oxide (NO). Apparently the impact of liposuction for normal subjects did not advance beyond acute inflammatory response; there was little change in the levels of markers corresponding to downstream events of chronic systemic inflammation such as adhesion molecules, urinary microalbumin (uMA), homocysteine (Hcy), uric acid (UA), and markers of oxidative stress, including urinary 8-hydroxydeoxyguanosine (8-OhdG) and 3-nitrotyrosine (3NT). It appears that the acute inflammatory response of cosmetic liposuction does not lead to impaired renal function and oxidative and nitrosative damage, which are frequently associated with chronic inflammation.