Insulin and the Brain: A Sweet Relationship With Intensive Care.

BACKGROUND: Insulin receptors (IRs) in the brain have unique molecular features and a characteristic pattern of distribution. Their possible functions extend beyond glucose utilization. In this systematic review, we explore the interactions between insulin and the brain and its implications for anesthesiologists, critical care physicians, and other medical disciplines. METHODS: A literature search of published preclinical and clinical studies between 1978 and 2014 was conducted, yielding 5996 articles. After applying inclusion and exclusion criteria, 92 studies were selected for this systematic review. RESULTS: The IRs have unique molecular features, pattern of distribution, and mechanism of action. It has effects on neuronal function, metabolism, and neurotransmission. The IRs are involved in neuronal apoptosis and neurodegenerative processes. CONCLUSION: In this systematic review, we present a close relationship between insulin and the brain, with discernible effects on memory, learning abilities, and motor functions. The potential therapeutic effects extend from acute brain insults such as traumatic brain injury, brain ischemia, and hemorrhage, to chronic neurodegenerative diseases such as Alzheimer and Parkinson disease. An understanding of the wider effects of insulin conveyed in this review will prompt anaesthesiologists and critical care physicians to consider its therapeutic potential and guide future studies.

The long-term effectiveness of the Family Check-Up on school-age conduct problems: Moderation by neighborhood deprivation.

Several studies suggest that neighborhood deprivation is a unique risk factor in child and adolescent development of problem behavior. We sought to examine whether previously established intervention effects of the Family Check-Up (FCU) on child conduct problems at age 7.5 would persist through age 9.5, and whether neighborhood deprivation would moderate these effects. In addition, we examined whether improvements in parent-child interaction during early childhood associated with the FCU would be related to later reductions in child aggression among families living in the highest risk neighborhoods. Using a multisite cohort of at-risk children identified on the basis of family, child, and socioeconomic risk and randomly assigned to the FCU, intervention effects were found to be moderated by neighborhood deprivation, such that they were only directly present for those living at moderate versus extreme levels of neighborhood deprivation. In addition, improvements in child aggression were evident for children living in extreme neighborhood deprivation when parents improved the quality of their parent-child interaction during the toddler period (i.e., moderated mediation). Implications of the findings are discussed in relation to the possibilities and possible limitations in prevention of early problem behavior for those children living in extreme and moderate levels of poverty.

A family-based intervention for improving children's emotional problems through effects on maternal depressive symptoms.

OBJECTIVE: This study focused on whether a brief family-based intervention for toddlers, the Family Check-Up (FCU), designed to address parent management skills and prevent early conduct problems, would have collateral effects on maternal depressive symptoms and subsequent child emotional problems. METHOD: Parents with toddlers were recruited from the Women, Infants, and Children Nutritional Supplement Program based on the presence of socioeconomic, family, and child risk (N = 731). Families were randomly assigned to the FCU intervention or control group with yearly assessments beginning at child age 2. Maternal depressive symptoms were measured using the Center for Epidemiological Studies Depression Scale at child ages 2 and 3. Child internalizing problems were collected from primary caregivers, alternative caregivers, and teachers using the Child Behavior Checklist at ages 7.5 and 8.5. RESULTS: Structural equation models revealed that mothers in families randomly assigned to the FCU showed lower levels of depressive symptoms at child age 3, which in turn were related to lower levels of child depressed/withdrawal symptoms as reported by primary caregivers, alternative caregivers, and teacher at ages 7.5-8.5. CONCLUSIONS: Findings suggest that a brief, preventive intervention improving maternal depressive symptoms can have enduring effects on child emotional problems that are generalizable across contexts. As there is a growing emphasis for the use of evidence-based and cost-efficient interventions that can be delivered in multiple delivery settings serving low-income families and their children, clinicians and researchers welcome evidence that interventions can promote change in multiple problem areas. The FCU appears to hold such promise.

Protective factors in the development of early child conduct problems.

The present study utilized a resilience model to investigate child, family, and community protective factors in toddlerhood as they relate to low levels of conduct problems at age 5 in a sample of low income children at risk for early disruptive problem behavior. Child, family, and community factors were associated with lower levels of conduct problems at age 5. Child, family, and community protective factors also distinguished between children who remained below and above a clinical threshold for aggressive problems between age 2 and 5. Finally, each domain of protective factors made small but significant unique contributions to lower aggression at age 5. These results emphasize the importance of multivariate analysis of the ecology of development predicting child outcome, and suggest potential areas for intervention with children at high risk for conduct problems.

Maternal depression in childhood and aggression in young adulthood: evidence for mediation by offspring amygdala-hippocampal volume ratio.

BACKGROUND: There is abundant evidence that offspring of depressed mothers are at increased risk for persistent behavior problems related to emotion regulation, but the mechanisms by which offspring incur this risk are not entirely clear. Early adverse caregiving experiences have been associated with structural alterations in the amygdala and hippocampus, which parallel findings of cortical regions altered in adults with behavior problems related to emotion regulation. This study examined whether exposure to maternal depression during childhood might predict increased aggression and/or depression in early adulthood, and whether offspring amygdala:hippocampal volume ratio might mediate this relationship. METHODS: Participants were 258 mothers and sons at socioeconomic risk for behavior problems. Sons' trajectories of exposure to maternal depression were generated from eight reports collected prospectively from offspring ages 18 months to 10 years. Offspring brain structure, aggression, and depression were assessed at age 20 (n = 170). RESULTS: Persistent, moderately high trajectories of maternal depression during childhood predicted increased aggression in adult offspring. In contrast, stable and very elevated trajectories of maternal depression during childhood predicted depression in adult offspring. Increased amygdala: hippocampal volume ratios at age 20 were significantly associated with concurrently increased aggression, but not depression, in adult offspring. Offspring amygdala: hippocampal volume ratio mediated the relationship found between trajectories of moderately elevated maternal depression during childhood and aggression in adult offspring. CONCLUSIONS: Alterations in the relative size of brain structures implicated in emotion regulation may be one mechanism by which offspring of depressed mothers incur increased risk for the development of aggression.

The Predictive Utility of Early Childhood Disruptive Behaviors for School-Age Social Functioning.

Research suggests that school-age children with disruptive behavior (DB) problems frequently demonstrate impaired social skills and experience rejection from peers, which plays a crucial role in the pathway to more serious antisocial behavior. A critical question is which DB problems in early childhood are prognostic of impaired social functioning in school-age children. This study examines the hypothesis that aggression in early childhood will be the more consistent predictor of compromised social functioning than inattentive, hyperactive-impulsive, or oppositional behavior. Participants included an ethnically diverse sample of 725 high-risk children from 3 geographically distinct areas followed from ages 2 to 8.5. Four latent growth models of DB from child ages 2 to 5, and potential interactions between dimensions, were used to predict latent parent and teacher ratings of school-age social dysfunction. Analyses were conducted in a multi-group format to examine potential differences between intervention and control group participants. Results showed that age 2 aggression was the DB problem most consistently associated with both parent- and teacher-rated social dysfunction for both groups. Early starting aggressive behavior may be particularly important for the early identification of children at risk for school-age social difficulties.

Inhibitory control as a mediator of bidirectional effects between early oppositional behavior and maternal depression.

Maternal depression is an established risk factor for child conduct problems, but relatively few studies have tested whether children's behavioral problems exacerbate mothers' depression or whether other child behavioral characteristics (e.g., self-regulation) may mediate bidirectional effects between maternal depression and child disruptive behavior. This longitudinal study examined the parallel growth of maternal depressive symptoms and child oppositional behavior from ages 2 to 5; the magnitude and timing of their bidirectional effects; and whether child inhibitory control, a temperament-based self-regulatory mechanism, mediated effects between maternal depression and child oppositionality. A randomized control trial of 731 at-risk families assessed children annually from ages 2 to 5. Transactional models demonstrated positive and bidirectional associations between mothers' depressive symptoms and children's oppositional behavior from ages 2 to 3, with a less consistent pattern of reciprocal relations up to age 5. Mediation of indirect mother-child effects and child evocative effects depended on the rater of children's inhibitory control. Findings are discussed in regard to how child evocative effects and self-regulatory mechanisms may clarify the transmission of psychopathology within families.

Developmental pathways to sexual risk behavior in high-risk adolescent boys.

OBJECTIVE: Adolescent boys' involvement in pregnancy and sexual risk behavior is a public health concern. Although research has identified predictors of sexual risk behavior during adolescence, few studies have investigated precursors to boys' sexual risk behavior beginning in early childhood, the identification of which could serve to inform interventions and help reduce involvement in pregnancy. Our goal was to identify early developmental pathways associated with sexual risk behavior in a sample of low-income adolescent boys. METHODS: Data from a prospective longitudinal study in 310 at-risk boys were used to examine externalizing problems, mothers' depressive symptoms, and low-nurturant parenting in early childhood (1.5, 2, and 3.5 years old) and daring, externalizing, parental monitoring, and deviant peer affiliation during emerging adolescence (11 and 12 years old) as precursors of sexual risk behavior between the ages 15 and 20 years. Structural equation modeling was used to explore pathways associated with later high-risk sexual behavior (HRSB). RESULTS: In multivariate analyses, adolescent daring and deviant peer affiliation at age 12 were associated with later HRSB. Furthermore, deviant peer affiliation during emerging adolescence mediated the relationship between mothers' depressive symptoms and nurturant parenting during early childhood and later adolescent HRSB. CONCLUSIONS: Family-based risk factors in early childhood are predictive of HRSB in adolescence but are also influenced, and in some cases mediated, by relationships with peers and child characteristics during emerging adolescence.

Prevention of problem behavior through annual family check-ups in early childhood: intervention effects from home to early elementary school.

This randomized intervention trial examined the effects of yearly Family Check-Ups (FCUs) and tailored parent management training on parent report of problem behavior from age 2 to 5 years and teacher report of oppositional behavior at age 7.5. A multiethnic risk sample of 731 families in 3 distinct geographical settings who were receiving assistance from the Women, Infants, and Children Nutritional Supplement (WIC) program were randomly assigned to a yearly FCU. Intention to treat (ITT) analyses were used to examine overall intervention effects, and complier average causal effect (CACE) modeling was used to examine the effects of annual intervention engagement in the FCU on parent reports of child problem behavior from age 2 to 5 and teacher reports of problem behavior at age 7.5. ITT intervention effects were found regarding parent report at ages 2 to 5 and teacher report at age 7.5, indicating less growth in problem behavior for children in the intervention group than for those in the control group. CACE modeling of intervention engagement revealed that the effect sizes on parent- and teacher-reported problem behavior increased as a function of the number of yearly FCUs caregivers participated in. Findings suggest that embedding yearly FCU services within the context of social, health, and educational services in early childhood can potentially prevent early-onset trajectories of antisocial behavior. The increases in effect size with successive FCU engagement underscores the importance of a motivational approach to parenting support among high-risk families.

Indirect Effects of the Family Check-Up on School-Age Academic Achievement Through Improvements in Parenting in Early Childhood.

This project examined the hypothesis that the impact of the Family Check-Up on parent use of positive behavior support would indirectly improve academic achievement scores at school age. The study included a sample of 731 high-risk families recruited from Women, Infant, and Children Supplemental Nutrition Program settings in 3 geographically distinct areas. The results demonstrated that changes in positive parenting between the child ages of 2 and 3 were associated with higher scores on children's school-age academic achievement, as measured by the Woodcock-Johnson III (W-J) Academic Skills composite. Moreover, structural equation modeling revealed that random assignment to the intervention was associated with higher levels of children's academic achievement at age 5 and age 7.5 indirectly, through greater increases in parents' use of positive behavior support in intervention families than in control families. Results are discussed with respect to the potential of a brief parenting intervention for improving parenting practices that promote academic achievement up to 5 years later. The results have promising implications for efforts to promote child adaptation in the school environment.

Postoperative delirium: risk factors, diagnosis and perioperative care.

UNLABELLED: Postoperative delirium (PD) relates to increased morbidity -associated with prolonged hospital stay, institutionalization and persistent functional and cognitive decline- poor long term outcome and higher perioperative mortality. Aim of this literature review is to identify established risk factors for PD and to categorize them according timing of occurrence (pre, intra and post operative), and clinical impact (Odds ratio [OR], % increase in incidence of PD). SOURCE OF INFORMATION: medical literature databases (medline and embase) were searched for published manuscripts on "postoperative delirium". Predictors and preoperative risk factors for PD were categorized into 4 groups: demographics; co morbidities; surgery and anesthesia-related (age, education, laboratory anomalies, smoking habits, benzodiazepines premedication, cardiac and thoracic surgery, etc). Intra operative risk factors for PD were categorized into 2 groups: surgery and anesthesia-related (anemia, duration and type of surgery, selected opioid, intraoperative hypotension, etc). Post operative risk factors and precipitating factors include various pathophysiological and environmental conditions, (i.e., ICU admission, low cardiac output requiring inotropes infusion; new onset atrial fibrillation; persistent hypoxia or hypercarbia; use of narcotic analgesics, delayed ambulation, inadequate nutritional status; sensory deprivation, etc). In conclusion, the effective identification, prevention and treatment of pre, intra and postoperative risk factors are the cornerstones for the prevention of PD. A dedicated perioperative care path that encompasses a tailored selection of drugs used perioperatively, the appropriate anesthesia strategy, qualified nursing surveillance, systematic use of diagnostic tools and accurate staff communication reduces the incidence and clinical impact of PD.

Revisiting data related to the age of onset and developmental course of female conduct problems.

Children who exhibit persistently elevated levels of conduct problems (CP) from early childhood, so-called early-starters, are known to be at increased risk for continued CP throughout middle childhood, adolescence, and adulthood. Theoretical and empirical work has focused on this subgroup of children characterized by similar risk factors, an early age of onset, and a persistent developmental course of CP. However, females were historically neglected from this literature. Although research on female CP has increased, conclusions drawn from limited prior work continue to predominate. The primary aim of this review was to evaluate the updated literature to determine the percentage of females who show the early-starter CP pattern relative to two other trajectories often theorized to be more characteristic of females: early-starting desisting and adolescent-onset CP. The findings suggest that a subgroup of females exhibits an early-starting and persistent CP pattern, while a separate group of females demonstrates an onset of CP in adolescence. In addition, although it has been argued that females with childhood CP are not likely to show CP into adolescence and adulthood, evidence for early-starting desisting CP was inconsistent. The results are discussed with respect to implications for developmental taxonomy theory and future basic research in the area of CP development, as well as intervention efforts.

Assessment of NGAL as an early biomarker of acute kidney injury in adult cardiac surgery patients.

Early and predictive acute kidney injury (AKI) markers may be decisive for the clinical outcome of heart surgery. Hence, this study set out to evaluate the biological variability of urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels in adult cardiac surgery patients, to test their feasibility as a biomarker of early AKI in a routine laboratory setting. uNGAL levels were measured with an automated immunoassay in urine samples from patients undergoing cardiac surgery using cardiopulmonary bypass, at the time of admission (T0) and 4 hours (T1) and 24 hours (T2) after surgery. Patients without post-operative AKI did not show significant differences in urine NGAL levels after surgery. In contrast, patients developing AKI displayed a significant increase (P=0.011) in uNGAL levels compared to T0. This increase was detectable at an earlier time point (T1, 4 hours) with respect to serum creatinine (T2, 24 hours). Confirming its utility as a biomarker, at T1 the uNGAL levels were significantly higher in AKI patients than in non-AKI patients (P=0.021). A receiver operating characteristic curve analysis of the uNGAL assay gave a sensitivity of 55.3 (95percent confidence interval, 26.59-78.73), a specificity of 72.9 (95 percent CI, 55.88-86.21), and a cut-off value for AKI prediction of 55.2. These results support the notion that urinary NGAL is an earlier marker of AKI than serum creatinine. However, the cut-off value of the assay was too low to consider it as a positive or negative diagnostic marker in AKI patients with moderate degree of severity. Likewise, its sensitivity and specificity were not high enough for it to be considered better than the others currently in use.

Early predictors of boys' antisocial trajectories.

Despite the large number of studies tracing patterns of youth antisocial behavior (AB) during adolescence, few have prospective data on the developmental precursors of AB beginning during infancy. Using a cohort of 268 low-income boys first assessed at 18 months, the current study examined predictors of early- and late-starting trajectories of AB assessed during early childhood and early adolescence. Four trajectory groups were identified, including early- and late-starting groups, a low stable group, and a high decreasing group, characterized by multiple risk factors during early childhood and early adolescence. During early childhood, parenting and maternal depression discriminated two AB trajectory groups, an early-starting and a high decreasing group, who would go on to demonstrate a high preponderance of juvenile court involvement (60% to 79%) and elevated rates of clinical depression 13 to 15 years later. The results were discussed in reference to targeting malleable family risk factors during early childhood associated with patterns of AB and mental health disorders during adolescence.

Longitudinal predictors of school-age academic achievement: unique contributions of toddler-age aggression, oppositionality, inattention, and hyperactivity.

This project examined the unique predictive validity of parent ratings of toddler-age aggression, oppositionality, inattention, and hyperactivity-impulsivity to academic achievement at school-age in a sample of 566 high-risk children and families. The study also investigated potential indirect effects of the Family Check-Up on school-age academic achievement through changes in child behavior problems. The results demonstrated that toddler-age aggression was most consistently associated with school-age academic achievement, albeit modestly. Moreover, findings showed that the intervention predicted greater decreases in aggression from ages 2-3 to 4-5 compared to controls. The results suggest that in high-risk toddler-aged children, aggression may be a more consistent predictor of school-age academic achievement than other externalizing dimensions, which has implications for early identification and efforts to promote children's adaptation.

P-glycoprotein potentiates CYP3A4-mediated drug disappearance during Caco-2 intestinal secretory detoxification.

Human intestinal Caco-2 cell monolayers grown in the presence of 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) were used to test the hypothesis that drugs which interact with the apical efflux pump P-glycoprotein (Pgp) may enhance CYP3A4-mediated disappearance of substrates. 6beta-hydroxytestosterone production, a marker of CYP3A4 activity, was approximately 3- and 7-fold greater in 1,25(OH)2D3-treated cells compared to untreated cells when incubated with 50 and 500 microM testosterone, respectively, and was unaffected by the addition of digoxin to reduce Pgp activity. In the presence of digoxin, secretory transport of vinblastine and erythromycin, substrates for both Pgp and cytochrome P450 3A4 (CYP3A4), was significantly reduced, whereas absorptive transport was unaffected. In contrast, no directional transport of testosterone, a substrate for CYP3A4 only, was observed, either in the presence or absence of digoxin. Over 2 h, disappearance of erythromycin and vinblastine from the incubation medium was significantly greater from the basolateral than from the apical compartments. In the presence of digoxin, disappearance of both compounds from the basolateral, but not from the apical compartments, was significantly reduced. In contrast, disappearance of testosterone was unaffected by the addition of digoxin, demonstrating that the effect of digoxin on erythromycin and vinblastine disappearance was via inhibition of Pgp function, rather than on CYP3A4 activity. Thus, evidence is provided for Pgp/CYP3A4 co-substrates, Pgp potentiates CYP3A4-mediated drug disappearance during intestinal secretory detoxification.

The ABCs of drug transport in intestine and liver: efflux proteins limiting drug absorption and bioavailability.

Many orally administered drugs must overcome several barriers before reaching their target site. The first major obstacle to cross is the intestinal epithelium. Although lipophilic compounds may readily diffuse across the apical plasma membrane, their subsequent passage across the basolateral membrane and into blood is by no means guaranteed. Efflux proteins located at the apical membrane, which include P-glycoprotein (Pgp; MDR1) and MRP2, may drive compounds from inside the cell back into the intestinal lumen, preventing their absorption into blood. Drugs may also be modified by intracellular phase I and phase II metabolising enzymes. This process may not only render the drug ineffective, but it may also produce metabolites that are themselves substrates for Pgp and/or MRP2. Drugs that reach the blood are then passed to the liver, where they are subject to further metabolism and biliary excretion, often by a similar system of ATP-binding cassette (ABC) transporters and enzymes to that present in the intestine. Thus a synergistic relationship exists between intestinal drug metabolising enzymes and apical efflux transporters, a partnership that proves to be a critical determinant of oral bioavailability. The effectiveness of this system is optimised through dynamic regulation of transporter and enzyme expression; tissues have a remarkable capacity to regulate the amounts of protein both at transcriptional and post-transcriptional levels in order to maintain homeostasis. This review addresses the progress to date on what is known about the role and regulation of drug efflux mechanisms in the intestine and liver.

Organic anion transporter 3 (Slc22a8) is a dicarboxylate exchanger indirectly coupled to the Na+ gradient.

Basolateral uptake of organic anions in renal proximal tubule cells is indirectly coupled to the Na(+) gradient through Na(+)-dicarboxylate cotransport and organic anion/dicarboxylate exchange. One member of the organic anion transporter (OAT) family, Oat1, is expressed in the proximal tubule and is an organic anion/dicarboxylate exchanger. However, a second organic anion carrier, Oat3, is also highly expressed in the renal proximal tubule, but its mechanism is unclear. Thus we have assessed Oat3 function in Xenopus laevis oocytes and rat renal cortical slices. Probenecid-sensitive uptake of p-aminohippurate (PAH, an Oat1 and Oat3 substrate) and estrone sulfate (ES, an Oat3 substrate) in rat Oat3-expressing oocytes was significantly trans-stimulated by preloading the oocytes with the dicarboxylate glutarate (GA). GA stimulation of ES transport by oocytes coexpressing rabbit Na(+)-dicarboxylate cotransporter 1 and rat Oat3 was significantly inhibited when the preloading medium contained Li(+) or methylsuccinate (MS) or when Na(+) was absent. All these treatments inhibit the Na(+)-dicarboxylate cotransporter, but not rat Oat3. Li(+), MS, and Na(+) removal had no effect when applied during the ES uptake step, rather than during the GA preloading step. Concentrative ES uptake in rat renal cortical slices was also demonstrated to be probenecid and Na(+) sensitive. Accumulation of ES was stimulated by GA, and this stimulation was completely blocked by probenecid, Li(+), MS, taurocholate, and removal of Na(+). Thus Oat3 functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the Na(+) gradient.

[Antioxidant therapeutic efficiency after the use of carnitine in infertile patients with bacterial or non bacterial prostato-vesiculo-epididymitis]. / Vantaggi terapeutici antiossidanti dopo carnitine in pazienti infertili con prostato-vesciculo-epididimite batterica o abatterica.

OBJECTIVE: In the male genital tract, reactive oxygen species (ROS) overproduction generated by infiltrating WBC or spermatozoa is one of the major causes of defective sperm function. Recently, we demonstrated that prostato-vesiculo-epididymitis (PVE) is the male accessory gland infection more crucial for the establishment of this cellular (sperm and/or WBC oxidative) response. This biochemical stress is due to an imbalance of pro and antioxidants factors and persists even after treatment with antimicrobials. Thus, the antioxidative properties of Carnitines (in terms of combined "Carnitine-Acetil-Carnitine" system) have currently found more attention as part of antimicrobial therapies. In this study, we compared which antioxidative strategy was more beneficial for the treatment of PVE. MATERIALS AND METHODS: We selected two groups of infertile patients. One group consisted of 55 abacterial PVE patients (mean age 34 yrs, range 27-40) (group A); the other included other 35 bacterial PVE patients (mean age 35 yrs, range 28-38) (group B). Each group was randomly subdivided into the following treatment subsets: 1) A1 (n = 14) and B1 (n = 23) subsets received respectively a combined antibiotic and/or antiphlogistic regimen (x 14 days/ monthly x 3 months) (first step) followed by L-Carnitine 1 g x 2 day + acetyl-Carnitine 0.5 g x 2/day x other 3 months (second step) and finally no drug x other 3 months (third step). 2) A2 (n = 8) and B2 (n = 16) subsets received, for a 3 month period, in the meantime the combined antibiotic and/or antiphlogistic regimen (x 14 days/monthly) and L-Carnitine 1 g x 2/day + acetyl-Carnitine 0.5 g x 2/day (first step) and finally no drug x other 3 months (second step). 3) A3 (n = 8) and B3 (n = 12) subsets received for a 3-month period L-Carnitine 1 g x 2/day + acetyl-Carnitine 0.5 g x 2 day (first step) and finally no drug x other 3 months (second step). Before and after each step of the therapeutical design, all patients underwent semen and quantitative bacteriological analyses and 60/90 semen specimens were also investigated about ROS production analysis by chemiluminescence in their 45% and 90% Percoll-generated fractions. RESULTS: The antioxidative response either in terms of significant decrease in the ROS production and increase in some semen parameters (sperm motility and viability) were highest in the patients of A1/B1 subsets, followed by A2/B2 subsets and lowest in the A3/B3 subsets. CONCLUSION: These results indicate that in PVE patients antimicrobials and/or antiphlogistic drugs get a full positive antimicrobial response but a partial antioxidative response, which seems to be potentiated by the addition of antioxidative agents (Carnitines). Furthermore, it is important to underline that the antioxidative treatment with Carnitines administered in the meantime with antiinfectious agents is less effective, and finally this treatment is unsuccessful without the eradication of the pro-oxidant (germs and WBC) agents.