Antioxidant protection of statins in acute kidney injury induced by sepsis

Objective Evaluating the effect of preconditioning with simvastatin in acute kidney injury induced by sepsis. Method Male adult Wistar rats were divided into the following groups: SHAM (control); SHAM+Statin (0.5 mg/kg simvastatin, orally); Sepsis (cecal puncture ligation – CPL); Sepsis+Statin. Physiological parameters, peritoneal fluid culture, renal function, oxidative metabolites, severity of acute kidney injury and animal survival were evaluated. Results The treatment with simvastatin in induced sepsis showed elevation of creatinine clearance with attenuation of generation of oxidative metabolites, lower severity of acute kidney injury and reduced mortality. Conclusion This investigation confirmed the renoprotection with antioxidant principle of the simvastatin in acute kidney injury induced by sepsis in an experimental model.

Nrf2 links epidermal barrier function with antioxidant defense.

The skin provides an efficient permeability barrier and protects from microbial invasion and oxidative stress. Here, we show that these essential functions are linked through the Nrf2 transcription factor. To test the hypothesis that activation of Nrf2 provides skin protection under stress conditions, we determined the consequences of pharmacological or genetic activation of Nrf2 in keratinocytes. Surprisingly, mice with enhanced Nrf2 activity in keratinocytes developed epidermal thickening, hyperkeratosis and inflammation resembling lamellar ichthyosis. This resulted from upregulation of the cornified envelope proteins small proline-rich proteins (Sprr) 2d and 2h and of secretory leukocyte peptidase inhibitor (Slpi), which we identified as novel Nrf2 targets in keratinocytes. Since Sprrs are potent scavengers of reactive oxygen species and since Slpi has antimicrobial activities, their upregulation contributes to Nrf2's protective function. However, it also caused corneocyte fragility and impaired desquamation, followed by alterations in the epidermal lipid barrier, inflammation and overexpression of mitogens that induced keratinocyte hyperproliferation. These results identify an unexpected role of Nrf2 in epidermal barrier function, which needs to be considered for pharmacological use of Nrf2 activators.

Juvenile antioxidant treatment prevents adult deficits in a developmental model of schizophrenia.

Abnormal development can lead to deficits in adult brain function, a trajectory likely underlying adolescent-onset psychiatric conditions such as schizophrenia. Developmental manipulations yielding adult deficits in rodents provide an opportunity to explore mechanisms involved in a delayed emergence of anomalies driven by developmental alterations. Here we assessed whether oxidative stress during presymptomatic stages causes adult anomalies in rats with a neonatal ventral hippocampal lesion, a developmental rodent model useful for schizophrenia research. Juvenile and adolescent treatment with the antioxidant N-acetyl cysteine prevented the reduction of prefrontal parvalbumin interneuron activity observed in this model, as well as electrophysiological and behavioral deficits relevant to schizophrenia. Adolescent treatment with the glutathione peroxidase mimic ebselen also reversed behavioral deficits in this animal model. These findings suggest that presymptomatic oxidative stress yields abnormal adult brain function in a developmentally compromised brain, and highlight redox modulation as a potential target for early intervention.

Communication skills training and clinicians' defenses in oncology: an exploratory, controlled study.

Objective: The underlying mechanisms modifying clinician's communication skills by means of communication skills training (CST) remain unknown. Defense mechanisms, defined as psychological processes protecting the individual against emotional stress, may be a mediating factor of skills improvement.Methods: Using an adapted version of the Defense Mechanism Rating Scale-Clinician, this study evaluated clinicians' defense mechanisms and their possible modification after CST. Interviews with simulated patients of oncology clinicians (N=57) participating in CST (pre-/post-CST with a 6-month interval) were compared WITH interviews with the same simulated patients of oncology clinicians (N=56) who did not undergo training (T1 and T2 with a 6-month interval).Results: Results showed (i) a high number (mean=16, SD=6) and variety of defenses triggered by the 15-min interviews, (ii) no evolution difference between groups, and (iii) an increase in mature defenses after CST for clinicians with an initial higher level of defensive functioning.Conclusions: This is the first study describing clinicians' defensive functioning; results indicate a possible mediating role of defenses in clinician-patient communication.

Influence of early antioxidant supplements on clinical evolution and organ function in critically ill cardiac surgery, major trauma, and subarachnoid hemorrhage patients.

INTRODUCTION: Oxidative stress is involved in the development of secondary tissue damage and organ failure. Micronutrients contributing to the antioxidant (AOX) defense exhibit low plasma levels during critical illness. The aim of this study was to investigate the impact of early AOX micronutrients on clinical outcome in intensive care unit (ICU) patients with conditions characterized by oxidative stress. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled, single-center trial in patients admitted to a university hospital ICU with organ failure after complicated cardiac surgery, major trauma, or subarachnoid hemorrhage. Stratification by diagnosis was performed before randomization. The intervention was intravenous supplements for 5 days (selenium 270 microg, zinc 30 mg, vitamin C 1.1 g, and vitamin B1 100 mg) with a double-loading dose on days 1 and 2 or placebo. RESULTS: Two hundred patients were included (102 AOX and 98 placebo). While age and gender did not differ, brain injury was more severe in the AOX trauma group (P = 0.019). Organ function endpoints did not differ: incidence of acute kidney failure and sequential organ failure assessment score decrease were similar (-3.2 +/- 3.2 versus -4.2 +/- 2.3 over the course of 5 days). Plasma concentrations of selenium, zinc, and glutathione peroxidase, low on admission, increased significantly to within normal values in the AOX group. C-reactive protein decreased faster in the AOX group (P = 0.039). Infectious complications did not differ. Length of hospital stay did not differ (16.5 versus 20 days), being shorter only in surviving AOX trauma patients (-10 days; P = 0.045). CONCLUSION: The AOX intervention did not reduce early organ dysfunction but significantly reduced the inflammatory response in cardiac surgery and trauma patients, which may prove beneficial in conditions with an intense inflammation. TRIALS REGISTRATION: Clinical Trials.gov RCT Register: NCT00515736.

Identifying psychotic defenses in a clinical interview.

The Defense Mechanisms Rating Scales (DMRS), one of the most widely used and validated instruments in the study of defense mechanisms, does not include psychotic defenses. The Psychotic-DMRS (P-DMRS) has been developed to include 6 psychotic defense mechanisms: psychotic denial, autistic withdrawal, distortion, delusional projection, fragmentation, and concretization. We discuss psychotic defenses, including the difference between psychotic defenses and psychotic symptoms. Six clinical illustrations demonstrate how the 6 P-DMRS defenses can be identified in patients' narratives selected from the transcripts of dynamic interviews. Implications with respect to patient evaluation and treatment are discussed.

Effect of potassium sources on the antioxidant activity of eggplant¹

Potassium participates in the essential processes in plant physiology, however, the effects of K sources on plant metabolism have been little studied. Also, in certain cases, K sources and concentrations may cause undesirable effects, e.g., soil salinization. The objective was to evaluate the effect of K sources and levels on the enzyme activity of the antioxidant system and protein content in eggplant (Solanum melongena L.) leaves and to determine the most suitable K sources for these physiological characteristics. The experiment was conducted in randomized blocks, in a 2 × 4 factorial design, consisting of two K sources (KCl and K2SO4) and rates (250, 500, 750, and 1000 kg ha-1 K2O), with four replications. The following variables were evaluated: plant height, number of leaves per plant, superoxide dismutase (SOD), catalase (CAT), and leaf protein content. There was an increase in CAT activity with increasing K levels until 30 days after transplanting (DAT), when K2SO4 was applied and until 60 DAT, when KCl was used; after this period, the enzyme activity decreased under both sources. The activity of SOD increased in the presence of KCl, but was reduced with the application of K2SO4. For both K sources, increasing rates reduced the protein content and number of leaves per plant, and this reduction was greater under KCl application. Thus it was concluded that KCl tends more strongly to salinize the soil than K2SO4. Both for KCl and for K2SO4, the increasing rates adversely affected the activities of CAT and SOD and the levels of leaf protein in eggplant. The potential of KCl to reduce the enzyme activity of SOD and CAT, leaf protein content and plant growth of eggplant was stronger than that of K2SO4.

Monitoring the clinical introduction of a glutamine and antioxidant solution in critically ill trauma and burn patients

OBJECTIVE: Enteral glutamine supplementation and antioxidants have been shown to be beneficial in some categories of critically ill patients. This study investigated the impact on organ function and clinical outcome of an enteral solution enriched with glutamine and antioxidant micronutrients in patients with trauma and with burns. METHODS: This was a prospective study of a historical control group including critically ill, burned and major trauma patients (n = 86, 40 patients with burns and 46 with trauma, 43 in each group) on admission to an intensive care unit in a university hospital (matching for severity, age, and sex). The intervention aimed to deliver a 500-mL enteral solution containing 30 g of glutamine per day, selenium, zinc, and vitamin E (Gln-AOX) for a maximum of 10 d, in addition to control treatment consisting of enteral nutrition in all patients and intravenous trace elements in all burn patients. RESULTS: Patients were comparable at baseline, except for more inhalation injuries in the burn-Gln-AOX group (P = 0.10) and greater neurologic impairment in the trauma-Gln-AOX group (P = 0.022). Intestinal tolerance was good. The full 500-mL dose was rarely delivered, resulting in a low mean glutamine daily dose (22 g for burn patients and 16 g for trauma patients). In burn patients intravenous trace element delivery was superior to the enteral dose. The evolution of the Sequential Organ Failure Assessment score and other outcome variables did not differ significantly between groups. C-reactive protein decreased faster in the Gln-AOX group. CONCLUSION: The Gln-AOX supplement was well tolerated in critically ill, injured patients, but did not improve outcome significantly. The delivery of glutamine below the 0.5-g/kg recommended dose in association with high intravenous trace element substitution doses in burn patients are likely to have blunted the impact by not reaching an efficient treatment dose. Further trials testing higher doses of Gln are required.

Histone deacetylase inhibitors impair antibacterial defenses of macrophages.

Histone deacetylases (HDACs) control gene expression by deacetylating histones and nonhistone proteins. HDAC inhibitors (HDACi) are powerful anticancer drugs that exert anti-inflammatory and immunomodulatory activities. We recently reported a proof-of-concept study demonstrating that HDACi increase susceptibility to bacterial infections in vivo. Yet, still little is known about the effects of HDACi on antimicrobial innate immune defenses. Here we show that HDACi belonging to different chemical classes inhibit at multiple levels the response of macrophages to bacterial infection. HDACi reduce the phagocytosis and the killing of Escherichia coli and Staphylococcus aureus by macrophages. In line with these findings, HDACi decrease the expression of phagocytic receptors and inhibit bacteria-induced production of reactive oxygen and nitrogen species by macrophages. Consistently, HDACi impair the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits and inducible nitric oxide synthase. These data indicate that HDACi have a strong impact on critical antimicrobial defense mechanisms in macrophages.

Chemical defenses in Sacoglossan Opisthobranchs: Taxonomic trends and evolutionary implications

Sacoglossan sea slugs (Mollusca: Opisthobranchia) are one of the few groups of specialist herbivores in the marine environment. Sacoglossans feed suctorially on the cell sap of macroalgae, from which they 'steal' chloroplasts (kleptoplasty) and deterrent substances (kleptochemistry), retaining intracellularly both host plastids and chemicals. The ingested chloroplasts continue to photosynthesize for periods ranging from a few hours or days up to 3 months in some species. Shelled, more primitive sacoglossans feed only on the siphonalean green algal genus Caulerpa, and they do not have functional kleptoplasty. The diet of sacoglossans has radiated out from this ancestral food. Among the shell-less Plakobranchidae (=Elysiidae), the more primitive species feed on other siphonales (families Derbesiaceae, Caulerpaceae, Bryopsidaceae and Codiaceae) and fix carbon, while the more 'advanced' species within the Plakobranchidae and Limapontioidae have a more broad dietary range. Most of these 'advanced' species are unable to fix carbon because the chloroplasts of their food algae are mechanically disrupted during ingestion. Mesoherbivores are likely to be eaten if they live on palatable seaweeds, their cryptic coloration and form not always keeping them safe from predators. Sacoglossans prefer to live on and eat chemically defended seaweeds, and they use ingested algal chemicals as deterrents of potential predators. The most ancestral shelled sacoglossans (Oxynoidae) and some Plakobranchidae such as Elysia translucens, Thuridilla hopei and Bosellia mimetica have developed a diet-derived chemical defense mechanism. Oxynoids and Thuridilla hopei are able to biomodify the algal metabolites. However, the Plakobranchidae Elysia timida and E. viridis, together with Limapontioidea species, are characterized by their ability to de novo synthesize polypropionate metabolites. A whole analysis of kleptoplasty and chemical defenses in sacoglossans may offer a better understanding of the ecology and evolution of these specialized opisthobranchs. In this paper we summarize some of the latest findings, related mainly to Mediterranean species, and offer a plausible evolutionary scenario based on the biological and chemical trends we can distinguish in them.

How Does Addressing Patient's Defenses Help to Repair Alliance Ruptures in Psychodynamic Psychotherapy?: An Exploratory Study.

Interpreting or addressing defenses is an important aspect of psychoanalytic technique. Previous research has shown that therapist addressing defenses (TADs) can produce a positive effect on alliance. The potential value of TADs during the process of alliance rupture and resolution has not yet been documented. We selected patients (n = 17) undertaking a short-term dynamic psychotherapy in which the therapeutic alliance, measured with the Helping Alliance Questionnaire and monitored after each session, showed a pattern of rupture and resolution. Two control sessions (5 and 15) were also selected. Presence of TADs was examined in each therapist interpretation. Compared with control sessions, rupture sessions were characterized by fewer TADs and especially fewer TADs addressing specifically intermediate-essentially neurotic-defenses. Resolution sessions were characterized by more TADs addressing specifically intermediate defenses. This confirms the link between therapist technique and alliance process in psychodynamic psychotherapy.

The Utilization of Agriculturally Derived Lignin as an Antioxidant in Asphalt Binder, TR-557, 2008

Oxidation is the primary cause of long-term aging in asphalt pavements. As a pavement oxidizes, it stiffens and can eventually crack. The use of an antioxidant as a performance enhancer in an asphalt binder could delay aging, thus increasing the life of an asphalt pavement. Lignin is a highly available and well-studied antioxidant. A wet-mill ethanol plant produces several co-products, some of which contain lignin. The use of lignin from ethanol production could provide a benefit to asphalt pavements and also give more value to the co-products. The following research examined the effects of lignin on asphalt pavements. Three lignin-containing co-products were separately combined with four asphalt binders in varying amounts to determine the optimum amount of co-product that would provide the greatest benefit to the asphalt binders. The asphalt binder and co-product blends were evaluated according to Superpave specifications and performance graded on a continuous scale. The data indicated a stiffening effect on the binder caused by the addition of the co-products. The more a co-product was added, the more a binder stiffened. Binder stiffening benefited the high temperature properties and the low temperature binder properties were negatively affected. However, the low temperature stiffening effects were small and in many cases not significant. The co-products had an overall effect of widening the temperature range of the binders. This result suggests some antioxidant activity between the binder and the lignin. Testing with a fourth co-product with no lignin supported the idea that lignin acts as an antioxidant. The samples with no lignin aged significantly more than the samples with lignin. Infrared spectrometry also supported the idea that lignin acts as an antioxidant by observing decreases in some oxidative aging products.

Effect of an 8-weeks aerobic training program in elderly on oxidative stress and HSP72 expression in leukocytes during antioxidant supplementation.

OBJECTIVE: To investigate the effect of aerobic training in the context of antioxidant supplementation on systemic oxidative stress and leukocytes heat shock protein (Hsp)72 expression in the elderly. DESIGN: Sixteen septuagenarians (8 males and 8 females, mean age 74.6) were supplemented with Vitamin C and E (respectively 500 and 100mg per day) and randomly assigned either to sedentary (AS) or individualized aerobically trained (AT) group for 8 weeks. METHODS: Plasma Vitamin C and E concentrations and aerobic fitness, as well as resting and post graded exercise (GXT) Hsp72 expression in leukocytes, plasma levels of thiobarbituric acid reactive substances (TBARS) and advanced oxidation protein product (AOPP) were measured pre and post training / supplementation. RESULTS: At the end of the intervention, the two groups showed a significant increase in resting plasma vitamin C and E (approximately 50 and 20% increase respectively) and a significant decrease in both resting and post GXT plasma TBARS and AOPP (approximately 25 and 20% decrease respectively). These changes were of similar magnitude in the two groups. The reduced oxidative stress was concomitant with a 15% decreased expression of Hsp72 in monocytes and granulocytes in both groups. CONCLUSION: This study provides evidence that in elderly, increased concentration of antioxidant vitamins C and E is associated with a reduction in oxidative stress and leukocytes Hsp72. In this context, 8 weeks of aerobic training has no impact on oxidative stress or leukocytes Hsp72 expression in elderly people.