The effect of nutritional intervention on the lipid profile and dietary intake of adolescents with juvenile systemic lupus erythematosus: a randomized, controlled trial.

Objective This study sought to evaluate the effects of a nutritional intervention on the lipid metabolism biomarkers associated with cardiovascular risk, and their variation over time, in juvenile systemic lupus erythematosus (JSLE) patients. This study also investigated the relationships between these biomarkers and dietary intake, nutritional status, disease variables, and medication used. Methods A total of 31 10- to 19-year-old female adolescents with JSLE for at least six months were analyzed. The participants were randomly allocated to two groups: nutritional intervention or control. The intervention group received verbal and printed nutritional instructions once per month over nine months. Before and after the intervention, the participants underwent assessments of anthropometry; dietary intake; physical activity; socioeconomic status; total cholesterol and fractions; triglycerides; apolipoprotein A (Apo A-I); apolipoprotein B (Apo B); paraoxonase (PON) activity (a) and amount (q); myeloperoxidase (MPO); and small, dense LDL-c (sdLDL) particles. Results After nine months, we found significant reductions in the calorie, carbohydrate, total fat, saturated fat, and trans fat intakes in the intervention compared with the control group over time. The PONa/HDL-c ratio increased by 3.18 U/ml/mg/dl in the intervention group and by 0.63 U/ml/mg/dl in the control group ( p = 0.037). Unlike the intervention group, the sdLDL levels of the control group worsened over time ( p = 0.018). Conclusion The present study detected a reduction in calorie and fat intake, which indicates an improvement of HDL-c function and possible protection against cardiovascular risk for the intervention group.

Sleep deprivation alters gene expression and antioxidant enzyme activity in mice splenocytes.

Cellular defence against the formation of reactive oxygen species (ROS) involves a number of mechanisms in which antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD) play an important role. The relation between sleep deprivation and oxidative stress has not yet been completely elucidated. Although some authors did not find evidence of this relationship, others found alterations in some oxidative stress markers in response to sleep deprivation. Thus, the objective of this study was to identify changes induced by sleep deprivation in the activity and gene expression of antioxidant enzymes in mice splenocytes, ideally corroborating a better understanding of the observed effects related to sleep deprivation, which could be triggered by oxidative imbalance. Splenocytes from mice sleep deprived for 72 h showed no significant difference in CAT and CuZnSOD gene expression compared with normal sleep mice. However, sleep-deprived mice did show higher MnSOD gene expression than the control group. Concerning enzymatic activity, CuZnSOD and MnSOD significantly increased after sleep deprivation, despite the expression in CuZnSOD remained unchanged. Moreover, CAT activity was significantly lower after sleep deprivation. The data suggest that the antioxidant system is triggered by sleep deprivation, which in turn could influence the splenocytes homoeostasis, thus interfering in physiological responses.

Extracorporeal membrane oxygenation in children after repair of congenital cardiac lesions.

BACKGROUND: The purpose of this study was to review our experience in the early application of extracorporeal membrane oxygenation (ECMO) in patients requiring mechanical assistance after cardiac surgical procedures. METHODS: The hospital records of all children requiring ECMO after cardiac operation were retrospectively reviewed, and an analysis of variables affecting survival was performed. RESULTS: Fifty pediatric patients between May 1997 and October 2000 required ECMO for cardiopulmonary support after cardiac operation. Patients ranged in age from 1 day to 11 years (median age, 40 days). Forty-eight patients underwent repair of congenital cardiac lesions and 2 were included after receiving a heart transplant. Twenty-two children could not be weaned from cardiopulmonary bypass and were placed on ECMO in the operating room for circulatory support. Of the 28 children who required ECMO in the intensive care unit, 10 had ECMO instituted after cardiopulmonary arrest (mean cardiopulmonary resuscitation time 42 minutes; range, 5 to 110 minutes). In infants with single-ventricle physiology, survival to discharge was 61% (11 of 18 patients) as compared with 43% (14 of 32 patients) in those with biventricular physiology. Thirty of the 50 patients (60%) were successfully weaned from ECMO, of which 25 (83%) were discharged home. Overall survival to discharge in the entire cohort was 50%. Extracorporeal membrane oxygenation support greater than 72 hours was a grave prognostic indicator. Overall survival in this group was 36% (9 of 25 patients) compared with 56% (14 of 25 patients) in those with ECMO support less than 72 hours (p < 0.05). Univariate analysis revealed the presence of renal failure, extended periods of circulatory support, and a prolonged period of cardiopulmonary resuscitation as risk factors for mortality. The presence of shunt-dependent flow, operative procedure, and institution of ECMO in the intensive care unit did not alter survival. CONCLUSIONS: Extracorporeal membrane oxygenation provides effective support for postoperative cardiac and pulmonary failure refractory to medical management. Early institution of ECMO may decrease the incidence of cardiac arrest and end-organ damage, thus increasing survival in these critically ill patients.

In vivo metabolism of tert-butyl hydroperoxide to methyl radicals. EPR spin-trapping and DNA methylation studies.

Metabolic activation of peroxides and hydroperoxides to free radicals is associated with the tumor promoting activity of these compounds. tert-Butyl hydroperoxide (t-BOOH) metabolism has been extensively studied as a model of peroxide biotransformation. In vivo studies are limited, and the hemoglobin-thiyl radical was the only species thus far identified in the blood of treated rats. Here we further examine t-BOOH metabolism in vivo with regard to free radical and DNA adduct production. Spin-trapping experiments with phenyl-N-tert-butylnitrone (PBN) led to the detection of EPR signals in the blood, bile, and organic extracts of the liver and stomach of rats treated with t-BOOH. Analysis of these signals demonstrated that t-BOOH metabolism in vivo produces alkyl radicals, detected in the bile and organic extracts of liver and stomach, in addition to the previously identified hemoglobin-thiyl radical. To characterize the produced alkyl radicals, experiments were performed with (13)C-labeled t-BOOH and two spin traps, PBN and alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN). The latter was used because the EPR signals obtained with PBN were too weak to be unambiguous. Nevertheless, the EPR signals present in the bile of animals treated with (13)C-labeled t-BOOH and PBN or POBN were consistent with adducts of (13)C-labeled methyl radical and an unidentified alkyl radical. The latter is probably derived from lipids oxidized by the metabolically produced primary radicals, methyl and its precursor, tert-butoxyl. The presence of 8-methylguanine and 7-methylguanine in hydrolysates of DNA from liver and stomach of rats treated with t-BOOH was also examined. 8-Methylguanine, a typical product of methyl radical attack on DNA, was detectable in both the liver and stomach of treated rats. The results may be relevant to the understanding of the genotoxic properties of other peroxides, particularly of cumene hydroperoxide.

DNA methylation by tert-butyl hydroperoxide-iron (II): a role for the transition metal ion in the production of DNA base adducts.

Metabolic degradation of both endogenous and exogenous peroxides is associated with the etiology of several diseases including cancer. Tert-butyl hydroperoxide (TBHP) has been widely employed as a model compound to study the cytotoxicity and promoting effects of organic peroxides. Recently, we reported that incubations of TBHP with iron (II) and calf thymus DNA led to generation of high yields of methyl radicals and to DNA methylation. Interestingly, DNA was methylated to products expected from both free radical and ionic mechanisms such as 8-methylguanine (C8-MeGua) and 7-methylguanine (N7-MeGua), respectively. To elucidate the mechanisms by which methyl radicals can produce different types of DNA adducts, we examined the effects of transition metal ions (iron (II), iron (III) and copper (I)) and metal ion chelators (ethylenediamine-N,N,N",N"-tetraacetate (EDTA) and desferal) on the nature and the yields of the DNA adducts produced during TBHP decomposition. The results led us to propose that a direct methyl radical attack on DNA guanine residues produces C8-MeGua whereas N7-MeGua and 3-methyladenine (N3-MeAde) are likely to be produced by attack of nucleophilic DNA centers on methyl radical generated in situ by the assistance of transition metal ions bound to DNA.

DNA methylation by tert-butyl hydroperoxide-iron (II).

Reduction of tert-butyl hydroperoxide (TBHP) by iron (II) at pH 4.0 or pH 7.0 in the presence of calf thymus DNA led to generation of high yields of methyl radicals and to DNA methylation. Methyl radicals were identified by spin-trapping experiments with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN). The methylated DNA-base adducts were identified in treated DNA hydrolysates by high pressure liquid chromatography (HPLC) and photodiode array UV spectroscopy. In the case of DNA several methylated adducts were identified, namely N7-methylguanine, C8-methylguanine, N3-methyladenine, and O6-methylguanine. By contrast, 2'-deoxyguanosine is alkylated almost exclusively to C8-methyl-2'-deoxyguanosine. These results constitute the first evidence that TBHP is able to alkylate DNA.