Linezolid and vancomycin for nosocomial infections in pediatric patients: a systematic review.

OBJECTIVE: To investigate the effectiveness of linezolid and vancomycin for the treatment of nosocomial infections in children under 12 years old. DATA SOURCES: This is a systematic review in which five randomized clinical trials about the effectiveness of linezolid and vancomycin, involving a total of 429 children with nosocomial infections, were evaluated. They were searched in scientific databases: PubMed, Bvs, and SciELO. SUMMARY OF FINDINGS: The main nosocomial infections that affected children were bacteremia, skin, and soft tissue infections followed by nosocomial pneumonia. Most infections were caused by Gram-positive bacteria, which all studies showed infections caused by Staphylococcus aureus, with methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci strains being isolated. Both linezolid and vancomycin showed high therapeutic efficacy against different types of nosocomial infections, ranging from 84.4% to 94% for linezolid and 76.9% to 90% for vancomycin. Patients receiving linezolid had lower rates of rash and red man syndrome compared to those receiving vancomycin. However, despite the adverse reactions, antimicrobials can be safely administered to children to treat nosocomial infections caused by resistant Gram-positive bacteria. CONCLUSION: Both linezolid and vancomycin showed good efficacy in the treatment of bacterial infections caused by resistant Gram-positive bacteria in hospitalized children. However, linezolid stands out regarding its pharmacological safety. Importantly, to strengthen this conclusion, further clinical trials are needed to provide additional evidence.

Participation of Oxidative Stress in the Activity of Compounds Isolated from Eleutherine plicata Herb.

From Eleutherine plicata, naphthoquinones, isoeleutherine, and eleutherol were isolated, and previous studies have reported the antioxidant activity of these metabolites. The present work evaluated the role of oxidative changes in mice infected with Plasmodium berghei and treated with E. plicata extract, fraction, and isolated compounds, as well as to verify possible oxidative changes induced by these treatments. E. plicata extracts were prepared from powder from the bulbs, which were submitted to maceration with ethanol, yielding the extract (EEEp), which was fractionated under reflux, and the dichloromethane fraction (FDMEp) was submitted for further fractionation, leading to the isolation of isoeleutherine, eleutherine, and eleutherol. The antimalarial activity was examined using the suppressive test, evaluating the following parameters of oxidative stress: trolox equivalent antioxidant capacity (TEAC), thiobarbituric acid reactive substances (TBARS), and reduced glutathione (GSH). Furthermore, the molecular docking of naphthoquinones, eleutherol, eleutherine, and isoeleutherine interactions with antioxidant defense enzymes was investigated, which was favorable for the formation of the receptor-ligand complex, according to the re-rank score values. Eleutherine and isoeleutherine are the ones with the lowest binding energy for catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPx1), showing themselves as possible targets of these molecules in the involvement of redox balance. Data from the present study showed that treatments with E. plicata stimulated an increase in antioxidant capacity and a reduction in oxidative stress in mice infected with P. berghei, with naphthoquinones being responsible for reducing oxidative changes and disease severity.

Potential Benefits of Lycopene Consumption: Rationale for Using It as an Adjuvant Treatment for Malaria Patients and in Several Diseases.

Malaria is a disease that affects thousands of people around the world every year. Its pathogenesis is associated with the production of reactive oxygen and nitrogen species (RONS) and lower levels of micronutrients and antioxidants. Patients under drug treatment have high levels of oxidative stress biomarkers in the body tissues, which limits the use of these drugs. Therefore, several studies have suggested that RONS inhibition may represent an adjuvant therapeutic strategy in the treatment of these patients by increasing the antioxidant capacity of the host. In this sense, supplementation with antioxidant compounds such as zinc, selenium, and vitamins A, C, and E has been suggested as part of the treatment. Among dietary antioxidants, lycopene is the most powerful antioxidant among the main carotenoids. This review aimed to describe the main mechanisms inducing oxidative stress during malaria, highlighting the production of RONS as a defense mechanism against the infection induced by the ischemia-reperfusion syndrome, the metabolism of the parasite, and the metabolism of antimalarial drugs. Furthermore, the effects of lycopene on several diseases in which oxidative stress is implicated as a cause are outlined, providing information about its mechanism of action, and providing an evidence-based justification for its supplementation in malaria.

Oxidative Stress in Malaria: Potential Benefits of Antioxidant Therapy.

Malaria is an infectious disease and a serious public health problem in the world, with 3.3 billion people in endemic areas in 100 countries and about 200 million new cases each year, resulting in almost 1 million deaths in 2018. Although studies look for strategies to eradicate malaria, it is necessary to know more about its pathophysiology to understand the underlying mechanisms involved, particularly the redox balance, to guarantee success in combating this disease. In this review, we addressed the involvement of oxidative stress in malaria and the potential benefits of antioxidant supplementation as an adjuvant antimalarial therapy.

Evaluation of acute and subacute toxicity of ethanolic extract and fraction of alkaloids from bark of Aspidosperma nitidum in mice.

This study investigated the acute and subacute toxicity of the ethanolic extract (EE) and alkaloid fraction (FA) from A. nitidum. The EE was obtained from trunk bark with ethanol, FA was obtained from the fractionation of EE. To test the acute toxicity, mice were divided into four groups, and the negative controls received water or aqueous solution of dimethyl sulfoxide, whereas the others received EE or FA (2000 mg/kg, orally, single dose). The same controls were used in the subacute trial. However, the animals were treated for 28 days, and the dose used was 1000 mg/kg per day of EE and FA. Daily clinical evaluations of the animals were performed. At the end of the experiment, hematological, biochemical, and histopathological assessments (liver, lung, heart, and kidney) were performed. In the acute and subacute toxicity studies, mice treated with EE and FA did not show any clinical changes, there were no changes in weight gain, hematological and biochemical parameters compared to the control groups (p > 0.05). In the histopathological examination, there was no abnormality in the organs of the treated animals. Therefore, EE and FA did not produce toxic effects in mice after acute and subacute treatment.

Dexamethasone increased the survival rate in Plasmodium berghei-infected mice.

The present study aimed to evaluate the effects of dexamethasone on the redox status, parasitemia evolution, and survival rate of Plasmodium berghei-infected mice. Two-hundred and twenty-five mice were infected with Plasmodium berghei and subjected to stimulation or inhibition of NO synthesis. The stimulation of NO synthesis was performed through the administration of L-arginine, while its inhibition was made by the administration of dexamethasone. Inducible NO synthase (iNOS) inhibition by dexamethasone promoted an increase in the survival rate of P. berghei-infected mice, and the data suggested the participation of oxidative stress in the brain as a result of plasmodial infection, as well as the inhibition of brain NO synthesis, which promoted the survival rate of almost 90% of the animals until the 15th day of infection, with possible direct interference of ischemia and reperfusion syndrome, as seen by increased levels of uric acid. Inhibition of brain iNOS by dexamethasone caused a decrease in parasitemia and increased the survival rate of infected animals, suggesting that NO synthesis may stimulate a series of compensatory redox effects that, if overstimulated, may be responsible for the onset of severe forms of malaria.

Oxidative Stress in Parkinson's Disease: Potential Benefits of Antioxidant Supplementation.

Parkinson's disease (PD) occurs in approximately 1% of the population over 65 years of age and has become increasingly more common with advances in age. The number of individuals older than 60 years has been increasing in modern societies, as well as life expectancy in developing countries; therefore, PD may pose an impact on the economic, social, and health structures of these countries. Oxidative stress is highlighted as an important factor in the genesis of PD, involving several enzymes and signaling molecules in the underlying mechanisms of the disease. This review presents updated data on the involvement of oxidative stress in the disease, as well as the use of antioxidant supplements in its therapy.

Ganoderma lucidum Ameliorates Neurobehavioral Changes and Oxidative Stress Induced by Ethanol Binge Drinking.

Ganoderma lucidum, mushroom used for centuries by Asian peoples as food supplement, has been shown interesting biological activities, including over the Central Nervous System. Besides, these mushroom bioactive compounds present antioxidant and anti-inflammatory activities. On the side, binge drinking paradigm consists of ethanol exposure that reflects the usual consumption of adolescents, which elicits deleterious effects, determined by high ethanol consumption, in a short period. In this study, we investigated whether the Aqueous Extract of G. lucidum (AEGl) reduces the behavioral disorders induced by alcohol. Male (n = 30) and female Wistar rats (n = 40), seventy-two days old, were used for behavioral/biochemical and oral toxicity test, respectively. Animals were exposed to 5 binges (beginning at 35 days old) of ethanol (3 g/kg/day) or distilled water. Twenty-four hours after the last binge administration, animals received AEGl (100 mg/kg/day) or distilled water for three consecutive days. After treatment protocol, open field, elevated plus maze, forced swim, and step-down inhibitory avoidance tests were performed. Oxidative stress parameters were measured to evaluate the REDOX balance. Our results demonstrated that AEGl elicited the recovery of spontaneous horizontal exploration capacity, anxiogenic- and depressive-profile, as well as short-term memory damage induced by binge-ethanol exposure. The behavioral effects of the extract were associated to the reequilibrium of the animals' REDOX balance. Thus, AEGl, a medicinal mushroom, ameliorates behavioral alteration on a model of motor, cognitive and psychiatric-like disorders induced by binge drinking paradigm and emerges as a useful tool as a food supplement in the management of disorders of alcoholic origin.

"Special K" Drug on Adolescent Rats: Oxidative Damage and Neurobehavioral Impairments.

Ketamine is used in clinical practice as an anesthetic that pharmacologically modulates neurotransmission in postsynaptic receptors, such as NMDA receptors. However, widespread recreational use of ketamine in "party drug" worldwide since the 1990s quickly spread to the Asian orient region. Thus, this study aimed at investigating the behavioral and oxidative effects after immediate withdrawal of intermittent administration of ketamine in adolescent female rats. For this, twenty female Wistar rats were randomly divided into two groups: control and ketamine group (n = 10/group). Animals received ketamine (10 mg/kg/day) or saline intraperitoneally for three consecutive days. Three hours after the last administration, animals were submitted to open field, elevated plus-maze, forced swim tests, and inhibitory avoidance paradigm. Twenty-four hours after behavioral tests, the blood and hippocampus were collected for the biochemical analyses. Superoxide dismutase, catalase, nitrite, and lipid peroxidation (LPO) were measured in the blood samples. Nitrite and LPO were measured in the hippocampus. The present findings demonstrate that the early hours of ketamine withdrawal induced oxidative biochemistry unbalance in the blood samples, with elevated levels of nitrite and LPO. In addition, we showed for the first time that ketamine withdrawal induced depressive- and anxiety-like profile, as well as short-term memory impairment in adolescent rodents. The neurobehavioral deficits were accompanied by the hippocampal nitrite and LPO-elevated levels.

Repeated Cycles of Binge-Like Ethanol Intake in Adolescent Female Rats Induce Motor Function Impairment and Oxidative Damage in Motor Cortex and Liver, but Not in Blood.

Moderate ethanol consumption (MEC) is increasing among women. Alcohol exposure usually starts in adolescence and tends to continue until adulthood. We aimed to investigate MEC impacts during adolescence until young adulthood of female rats. Adolescent female Wistar rats received distilled water or ethanol (3 g/kg/day), in a 3 days on-4 days off paradigm (binge drinking) for 1 and 4 consecutive weeks. We evaluate liver and brain oxidative damage, peripheral oxidative parameters by SOD, catalase, thiol contents, and MDA, and behavioral motor function by open-field, pole, beam-walking, and rotarod tests. Our results revealed that repeated episodes of binge drinking during adolescence displayed lipid peroxidation in the liver and brain. Surprisingly, such oxidative damage was not detectable on blood. Besides, harmful histological effects were observed in the liver, associated to steatosis and loss of parenchymal architecture. In addition, ethanol intake elicited motor incoordination, bradykinesia, and reduced spontaneous exploratory behavior in female rats.

Salivary Gland Extract from Aedes aegypti Improves Survival in Murine Polymicrobial Sepsis through Oxidative Mechanisms.

Sepsis is a systemic disease with life-threatening potential and is characterized by a dysregulated immune response from the host to an infection. The organic dysfunction in sepsis is associated with the production of inflammatory cascades and oxidative stress. Previous studies showed that Aedes aegypti saliva has anti-inflammatory, immunomodulatory, and antioxidant properties. Considering inflammation and the role of oxidative stress in sepsis, we investigated the effect of pretreatment with salivary gland extract (SGE) from Ae. aegypti in the induction of inflammatory and oxidative processes in a murine cecum ligation and puncture (CLP) model. Here, we evaluated animal survival for 16 days, as well as bacterial load, leukocyte migration, and oxidative parameters. We found that the SGE pretreatment improved the survival of septic mice, reduced bacterial load and neutrophil influx, and increased nitric oxide (NO) production in the peritoneal cavity. With regard to oxidative status, SGE increased antioxidant defenses as measured by Trolox equivalent antioxidant capacity (TEAC) and glutathione (GSH), while reducing levels of the oxidative stress marker malondialdehyde (MDA). Altogether, these data suggest that SGE plays a protective role in septic animals, contributing to oxidative and inflammatory balance during sepsis. Therefore, Ae. aegypti SGE is a potential source for new therapeutic molecule(s) in polymicrobial sepsis, and this effect seems to be mediated by the control of inflammation and oxidative damage.

Low doses of methylmercury intoxication solely or associated to ethanol binge drinking induce psychiatric-like disorders in adolescent female rats.

Methylmercury (MeHg) is an environmental contaminant that provokes damage to developing brain. Simultaneously, the consumption of ethanol among adolescents has increased. Evidence concerning the effects of MeHg low doses per se or associated with ethanol during adolescence are scarce. Thus, we investigate behavioral disorders resulted from exposure to MeHg low doses and co-intoxicated with ethanol in adolescent rats. Wistar rats received chronic exposure to low doses of MeHg (40 µg/kg/day for 5 weeks) and/or ethanol binge drinking (3 g/kg/day at 3 days per week for 5 weeks). Animals were submitted to behavioral assays to assess emotionality and cognitive function. Total mercury content was evaluated in the brain and hair. Oxidative parameters were analyzed in blood samples. MeHg at low doses or associated to ethanol binge drinking produced psychiatric-like disorders and cognitive impairment. Peripherally, MeHg altered oxidative parameters when associated to ethanol. Ethanol administration reduced brain mercury deposit. We proposed that ethanol reduces the necessity of mercury tissue levels to display psychiatric-like disorders/cognitive impairment.

Neurobehavioral and Antioxidant Effects of Ethanolic Extract of Yellow Propolis.

Propolis is a resin produced by bees from raw material collected from plants, salivary secretions, and beeswax. New therapeutic properties for the Central Nervous System have emerged. We explored the neurobehavioral and antioxidant effects of an ethanolic extract of yellow propolis (EEYP) rich in triterpenoids, primarily lupeol and ß-amyrin. Male Wistar rats, 3 months old, were intraperitoneally treated with Tween 5% (control), EEYP (1, 3, 10, and 30 mg/kg), or diazepam, fluoxetine, and caffeine (positive controls) 30 min before the assays. Animals were submitted to open field, elevated plus maze, forced swimming, and inhibitory avoidance tests. After behavioral tasks, blood samples were collected through intracardiac pathway, to evaluate the oxidative balance. The results obtained in the open field and in the elevated plus maze assay showed spontaneous locomotion preserved and anxiolytic-like activity. In the forced swimming test, EEYP demonstrated antidepressant-like activity. In the inhibitory avoidance test, EEYP showed mnemonic activity at 30 mg/kg. In the evaluation of oxidative biochemistry, the extract reduced the production of nitric oxide and malondialdehyde without changing level of total antioxidant, catalase, and superoxide dismutase, induced by behavioral stress. Our results highlight that EEYP emerges as a promising anxiolytic, antidepressant, mnemonic, and antioxidant natural product.

Oxidative Stress in Alzheimer's Disease: Should We Keep Trying Antioxidant Therapies?

The risk of chronic diseases such as Alzheimer's disease is growing as a result of the continuous increasing average life span of the world population, a syndrome characterized by the presence of intraneural neurofibrillary tangles and senile plaques composed mainly by beta-amyloid protein, changes that may cause a number of progressive disorders in the elderly, causing, in its most advanced stage, difficulty in performing normal daily activities, among other manifestations. Therefore, it is important to understand the underlying pathogenic mechanisms of this syndrome. Nevertheless, despite intensive effort to access the physiopathological pathways of the disease, it remains poorly understood. In that context, some hypotheses have arisen, including the recent oxidative stress hypothesis, theory supported by the involvement of oxidative stress in aging, and the vulnerability of neurons to oxidative attack. In the present revision, oxidative changes and redox mechanisms in Alzheimer's disease will be further stressed, as well as the grounds for antioxidant supplementation as adjuvant therapy for the disease will be addressed.