Recommendations for antibiotic selection for severe nosocomial infections.

Severe infection and its evolution to sepsis are becoming more prevalent every day and are among the leading causes of critical illness and mortality. Proper management is crucial to improve prognosis. This document addresses three essential points that have a significant impact on this objective: a) early recognition of patients with sepsis criteria, b) identification of those patients who suffer from an infection and have a high risk of progressing to sepsis, and c) adequate selection and optimization of the initial antimicrobial treatment.

Effect of taurine associated gold nanoparticles on oxidative stress in muscle of mice exposed to overuse model.

Muscle overuse and its consequent muscle damage has no cure. Therefore, the present study aimed to investigate the regulatory role of tau-AuNPs on muscle recovery of muscle overuse model. The animals (Male Swiss mice) were randomly divided into four groups: Control (Ctr; n=6); tau-AuNPs (n=6); overuse (n=6); and overuse plus tau-AuNPs (n=6). Exercise sessions were performed for 21 consecutive days, and one exercise model was applied daily in the following sequence: low intensity, moderate intensity, and high intensity. The mice were then sacrificed. The quadriceps muscles were surgically removed for subsequent biochemical analysis (oxidative stress parameters, DNA damage markers and muscle differentiation protein). The overuse group significantly increased the oxidative stress parameters and DNA damage markers, whereas tau-AuNPs significantly decreased the oxidative stress parameters in the overuse animal model. However, there were no significant differences observed between overuse group and overuse plus tau-AuNPs administrated group in relation to DNA damage markers including DNA damage frequency and index levels when compared to control and tau-AuNPs groups. Muscle differentiation protein Myf-5 was increased in the overuse plus tau-AuNPs administration group when compared to control group. In conclusion, tau-AuNPs had significant effect on reducing oxidative stress parameters and increasing myogenic regulatory protein Myf-5 in the overuse group. However, it did not have significant effect on reducing DNA damage.

Neuroinflammatory Regulation of Gold Nanoparticles Conjugated to Ethylene Dicysteine Diethyl Ester in Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis (MS) is a demyelinating chronic autoimmune inflammatory disease of the central nervous system (CNS). A large amount of proinflammatory cytokines is released in the CNS from the self-reactive T cells infiltrate, leading to the destruction of the myelin sheath and contributing to the development of MS. Several drugs have emerged in recent years to treat MS, and studies have shown that gold nanoparticles (GNPs) have anti-inflammatory properties in autoimmune diseases. Thus, the effects of GNP conjugation to ethylene dicysteine diethyl ester (ECD) were evaluated in C57BL/6 female mice exposed to experimental MS. Animals were exposed to experimental autoimmune encephalitis (EAE) induced by myelin oligodendrocyte glycoprotein (MOG35-55) in complete Freund's adjuvant supplemented with Mycobacterium tuberculosis. The clinical and cerebral effects of the different doses of ECD-GNPs (0.3, 0.6, and 1.0 mg/kg) were first studied, and the results showed that the group treated with 0.6 mg/kg ECD-GNPs improved clinical symptoms, inflammatory infiltrate, and myelin integrity. In the following step, GNPs and ECD-GNPs (0.6 mg/kg) showed improvements in the clinical signs of the disease. Moreover, there was a reduction in the levels of proinflammatory cytokines in both groups compared to EAE, and only the isolated use of GNPs increased IL-4 expression. Both NF-κB and TGFß immunoexpression were significantly reduced following EAE + GNPs and EAE + ECD-GNPs treatment. In conclusion, GNPs and ECD-GNPs at 0.6 mg/kg attenuate the neurological signs of EAE likely due to inhibition of neuroinflammation induced by EAE.

Fish-processing effluent discharges influenced physicochemical properties and prokaryotic community structure in arid soils from Patagonia.

Along the Patagonian coast, there are processing factories of marine products in land that produce fish-processing effluents. The aim of the present study was to assess the physicochemical properties and the prokaryotic community composition of soils receiving fish-processing effluent discharges (effluent site-ES), and to compare them with those of unaltered soils (control site-CS) in the arid Patagonian steppe. We analyzed soil prokaryotic communities (using amplicon-based sequencing of 16S rRNA genes), soil physicochemical properties and fish-processing effluent characteristics. Soil moisture, electrical conductivity (EC), total and inorganic C were significantly higher in ES than in CS (p < .05). Effluent discharges induced a decrease in the total number of operational taxonomic units (OTUs) and in the Shannon diversity index (p = .0009 and .01, respectively) of soil prokaryotic community. Proteobacteria, Actinobacteria and Acidobacteria were the dominant phyla in CS, while ES soil showed a more heterogeneous composition of phyla. Linear discriminant analysis (LDA) effect size (LEfSe) analysis showed that fish-processing effluent discharges promoted an enrichment of Firmicutes and Bacteroidetes, which are active contributors to organic matter mineralization, along with a decrease of oligotrophic phyla such as Acidobacteria, Chloroflexi, Armatimonadetes and Nitrospirae, commonly found in nutrient-poor arid soils. The concentrations of inorganic C and ammonium, the EC and the soil moisture explained 73% of the total variation within the community composition. Due to its salinity and nutrients, fish-processing effluents have potential mainly for native salt-tolerant plant irrigation, however the impacts of soil prokaryotic community shifts over plant growth remain to be determined.

Gold nanoparticles prevent cognitive deficits, oxidative stress and inflammation in a rat model of sporadic dementia of Alzheimer's type.

Alzheimer's disease (AD) is the most common form of neurodegenerative dementia in the aged brain. Even though its etiology is unknown, factors such as neuroinflammation, mitochondrial dysfunction, formation of reactive oxygen species (ROS), and impaired insulin signaling may play a role. We used a sporadic AD model in rats generated by intracerebroventricular-streptozotocin (i.c.v.-STZ) injection to test the therapeutic effect of gold nanoparticles (GNPs). We tested the null hypothesis that there would be no difference between the STZ+GNPs group and the STZ group in the analyzed markers. We observed that STZ-induced impairment in mitochondrial ATP production, neuroinflammation, and oxidative stress were all prevented by GNP treatment. Moreover, while STZ induced deficits in both spatial and recognition memory, GNPs prevented this effect. These results suggest that GNPs may be considered as a potential treatment for dementias.

Metagenomics reveals the high polycyclic aromatic hydrocarbon-degradation potential of abundant uncultured bacteria from chronically polluted subantarctic and temperate coastal marine environments.

AIMS: To investigate the potential to degrade polycyclic aromatic hydrocarbons (PAHs) of yet-to-be-cultured bacterial populations from chronically polluted intertidal sediments. METHODS AND RESULTS: A gene variant encoding the alpha subunit of the catalytic component of an aromatic-ring-hydroxylating oxygenase (RHO) was abundant in intertidal sediments from chronically polluted subantarctic and temperate coastal environments, and its abundance increased after PAH amendment. Conversely, this marker gene was not detected in sediments from a nonimpacted site, even after a short-term PAH exposure. A metagenomic fragment carrying this gene variant was identified in a fosmid library of subantarctic sediments. This fragment contained five pairs of alpha and beta subunit genes and a lone alpha subunit gene of oxygenases, classified as belonging to three different RHO functional classes. In silico structural analysis suggested that two of these oxygenases contain large substrate-binding pockets, capable of accepting high molecular weight PAHs. CONCLUSIONS: The identified uncultured micro-organism presents the potential to degrade aromatic hydrocarbons with various chemical structures, and could represent an important member of the PAH-degrading community in these polluted coastal environments. SIGNIFICANCE AND IMPACT OF THE STUDY: This work provides valuable information for the design of environmental molecular diagnostic tools and for the biotechnological application of RHO enzymes.

Gold nanoparticles and/or N-acetylcysteine mediate carrageenan-induced inflammation and oxidative stress in a concentration-dependent manner.

We report the effect of gold nanoparticles (AuNP) in an acute inflammation model induced by carrageenan (CG) and compared this effect with those induced by the antioxidant N-acetylcysteine (NAC) alone and by the synergistic effect of NAC and AuNP together. Male Wistar rats received saline or saline containing CG administered into the pleural cavity, and some rats also received NAC (20 mg/kg) subcutaneously and/or AuNP administered into the pleural cavity immediately after surgery. Four hours later, the rats were sacrificed and pleural exudates obtained for evaluation of cytokine levels and myeloperoxidase activities. Oxidative stress parameters were also evaluated in the lungs. The results demonstrated that the inflammatory process caused by the administration of CG into the pleural cavity resulted in a substantial increase in the levels of tumor necrosis factor-α, interleukin-1ß, and myeloperoxidase and a reduction in interleukin-10 levels. These levels seem to be reversed after different treatments in animals. Antioxidant enzymes exhibited positive responses after treatment of NAC + AuNP, and all treatments were effective at reducing lipid peroxidation and oxidation of thiol groups induced by CG. These findings suggest that small compounds, such as NAC plus AuNP, may be useful in the treatment of conditions associated with local inflammation.

Inflammatory cytokines content in Achilles tendinopathy after phonophoresis treatment combined with gold nanoparticles and diclophenac diethylammonium in rats.

Tendinitis is a painful condition that occurs in tendons in response to repetitive use or direct trauma. The therapeutic approaches commonly employed to modulate inflammation have not achieved complete success in chronic cases of tendinitis. In this scenario, considering the anti-inflammatory properties of pulsed therapeutic ultrasound and gold nanoparticles (GNPs), this study assesses the possible therapeutic effects of phonophoresis in association with diclophenac diethylammonium and GNPs by measuring the inflammatory parameters interleukin 1ß and tumor necrosis factor alpha in acute tendinous injury. Wistar rats were randomly divided into three groups and were treated with phonophoresis and diclophenac diethylammonium, GNP gel, and a combination thereof. A significant decrease in interleukin 1ß and tumor necrosis factor alpha occurred in tendons treated with phonophoresis+diclophenac+GNPs. The content of both cytokines were similar after combined treatment with phonophoresis+diclophenac+GNPs. Apart from the anti-inflammatory effect, GNPs transported and enhanced drug action when used with phonophoresis.

Effects of phonophoresis and gold nanoparticles in experimental model of muscle overuse: role of oxidative stress.

The aim of the study described here was to investigate the effects of pulsed ultrasound and gold nanoparticles (AuNPs) on behavioral, inflammatory and oxidative stress parameters in an experimental model of overuse. Wistar rats performed 21 d of exercise on a treadmill at different intensities and were exposed to ultrasound in the presence or absence of AuNPs. The overuse model promoted behavioral changes and increased creatine kinase, superoxide dismutase and glutathione peroxidase activity, as well as the levels of superoxide, nitrotyrosine, nitric oxide, thiobarbituric acid reactive substance, carbonyl, tumor necrosis factor α and interleukin-6. These values were significantly decreased by AuNPs and by AuNPs plus ultrasound. Catalase activity remained unchanged and the glutathione level increased significantly after exposure to AuNPs plus ultrasound. These results suggest a susceptibility to anxiety as well as elevated levels of oxidative stress. However, therapeutic interventions with AuNPs plus ultrasound reduced the production of oxidants and oxidative damage and improved the anti-oxidant defense system.

Iontophoresis with gold nanoparticles improves mitochondrial activity and oxidative stress markers of burn wounds.

The aim of this study was to analyse the effects of microcurrent and gold nanoparticles on oxidative stress parameters and the mitochondrial respiratory chain in the healing of skin wounds. Thirty 60-day old male Wistar rats (250-300 g) were divided into five groups (N=6): Control; Burn wounds; Microcurrent (MIC); Gold nanoparticle gel (GNP gel) and Microcurrent+Gold nanoparticle gel (MIC+GNP gel). The microcurrent treatment was applied for five consecutive days at a dose of 300 µA. The results demonstrate a significant decrease in the activity of complexes I, II-III and IV in the Burn Wounds group compared to the control, and the MIC+GNP gel group was able to reverse this inhibition in complexes I, III and IV. Furthermore, a significant reduction in oxidative damage parameters and a significant increase in the levels of antioxidant defence enzymes were induced in the MIC+GNP gel group compared to the Burn Wounds group. The data strongly indicate that the group receiving treatment with MIC+GNP gel had improved mitochondrial functioning and oxidative stress parameters, which contributed to tissue repair.

Gold nanoparticles and diclofenac diethylammonium administered by iontophoresis reduce inflammatory cytokines expression in Achilles tendinitis.

INTRODUCTION: Tendinitis affects a substantial number of people in several occupations involving repetitive work or direct trauma. Iontophoresis is a therapeutic alternative used in the treatment of injury during the inflammatory phase. In recent years, gold nanoparticles (GNP) have been studied due to their therapeutic anti-inflammatory capacity and as an alternative to the transport of several proteins. PURPOSE: This study evaluates the therapeutic effects of iontophoresis using GNPs and diclofenac diethylammonium on inflammatory parameters in rats challenged with traumatic tendinitis. METHODS: Wistar rats were divided in three treatment groups (n = 15): (1) iontophoresis + diclofenac diethylammonium; (2) iontophoresis + GNP; and (3) iontophoresis + diclofenac diethylammonium + GNP. External control was formed by challenged tendons without treatment (n = 15). Iontophoresis was administered using 0.3 mA direct current on 1.5 cm(2) electrodes. RESULTS: The levels of both inflammatory cytokines were significantly higher in untreated challenged rats, when compared with the control (5.398 ± 234 for interleukin 1 beta and 6.411 ± 432 for tumor necrosis factor alpha), which confirms the occurrence of an inflammatory stage in injury (P < 0.05). A significant decrease was observed in expression of cytokines interleukin 1 beta in the three treatment groups, in comparison with untreated challenged tendons, although, in the group treated with diclofenac and GNP, results were similar to the control (1.732 ± 239) (P < 0.05). Concerning tumor necrosis factor alpha, only the group treated with the association diclofenac and GNPs presented decreased levels, compared with the control (3.221 ± 369) (P < 0.05). CONCLUSION: The results show the efficacy of drug administration using direct current to treat tendinitis in an animal model, and the potential anti-inflammatory, carrier, and enhancing effects of GNPs in iontophoresis.

Pulsed ultrasound associated with gold nanoparticle gel reduces oxidative stress parameters and expression of pro-inflammatory molecules in an animal model of muscle injury.

BACKGROUND: Nanogold has been investigated in a wide variety of biomedical applications because of the anti-inflammatory properties. The purpose of this study was to evaluate the effects of TPU (Therapeutic Pulsed Ultrasound) with gold nanoparticles (GNP) on oxidative stress parameters and the expression of pro-inflammatory molecules after traumatic muscle injury. MATERIALS AND METHODS: Animals were divided in nine groups: sham (uninjured muscle); muscle injury without treatment; muscle injury + DMSO; muscle injury + GNP; muscle injury + DMSO + GNP; muscle injury + TPU; muscle injury + TPU + DMSO; muscle injury + TPU + GNP; muscle injury + TPU + DMSO + GNP. The ROS production was determined by concentration of superoxide anion, modulation of antioxidant defenses was determined by the activity of superoxide dismutase, catalase and glutathione peroxidase enzymes, oxidative damage determined by formation of thiobarbituric acid-reactive substance and protein carbonyls. The levels of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) were measured as inflammatory parameters. RESULTS: Compared to muscle injury without treatment group, the muscle injury + TPU + DMSO + GNP gel group promoted a significant decrease in superoxide anion production and lipid peroxidation levels (p < 0.050). It also showed a significant decrease in TNF-α and IL-1ß levels (p < 0.050) when compared to muscle injury without treatment group. CONCLUSIONS: Our results suggest that TPU + DMSO + GNP gel presents beneficial effects on the muscular healing process, inducing a reduction in the production of ROS and also the expression of pro-inflammatory molecules.

Aromatic hydrocarbon degradation genes from chronically polluted Subantarctic marine sediments.

AIM: The goal of this study was to identify functional targets to detect polycyclic aromatic hydrocarbon (PAH)-degrading bacterial populations in cold marine ecosystems. METHODS AND RESULTS: We designed a degenerate primer set targeting genes encoding the alpha subunit of PAH-dioxygenases from Gram-positive bacteria. This primer set was used to amplify gene fragments from metagenomic DNA isolated from Subantarctic marine sediments (Ushuaia Bay, Argentina). These gene fragments were cloned and sequenced. We identified 14 distinct groups of genes, most of them showing significant relatedness with dioxygenases from Gram-positive bacteria of the genera Rhodococcus, Mycobacterium, Nocardioides, Terrabacter and Bacillus. The level of identity with these genes, however, was low to moderate (33-62% at the amino acid level). CONCLUSION: These results indicate the presence of a high diversity of hitherto unidentified dioxygenase genes in this cold polluted environment. SIGNIFICANCE AND IMPACT OF THE STUDY: Subantarctic marine ecosystems are particularly vulnerable to hydrocarbon pollution, and the development of environmental restoration strategies for these environments is pressing. The information obtained in this work will be the starting point for the design of quantitative molecular tools to analyse the abundance and dynamics of these aromatic hydrocarbon-degrading bacterial populations in the marine environment.

DNA damage after acute and chronic treatment with malathion in rats.

Malathion is an insecticide widely used in agriculture and in public health programs that when used indiscriminately in large amounts can cause environmental pollution and risk to human health. However, it is possible that during the metabolism of malathion, reactive oxygen species can be generated, and malathion may produce oxidative stress in intoxicated rats that can be responsible for alterations in DNA molecules related in some studies. As a result, the present study aimed to investigate the DNA damage of cerebral tissue and peripheral blood in rats after acute and chronic malathion exposure. We used single cell gel electrophoresis (Comet assay) to measure early damage in hippocampus and peripheral blood and the Micronucleus test in total erythrocytes samples. Malathion was administered intraperitoneally once a day for one day (acute) or for 28 days (chronic) protocols (in both protocols, malathion was administered at 25, 50, 100, and 150 mg/kg). Our results showed that malathion (100 and 150 mg/kg) increased the DNA damage index in the peripheral blood and in the hippocampus after both chronic and acute treatment. Malathion increased the frequency of micronuclei only in chronic treatment at 150 mg/kg dose, and induced a cytotoxic dose-dependent decrease in the frequency of polychromatic erythrocytes in the peripheral blood of rats. In conclusion, since malathion increased both the peripheral blood and hippocampus DNA damage index using the Comet assay and increased the frequency of micronuclei in the total peripheral blood, it can be regarded as a potential mutagen/carcinogenic agent.

Effect of ruthenium complexes on the activities of succinate dehydrogenase and cytochrome oxidase.

In this article, we report the effects of acute administration of ruthenium complexes, trans-[RuCl(2)(nic)(4)] (nic=3-pyridinecarboxylic acid) 180.7 micromol/kg (complex I), trans-[RuCl(2)(i-nic)(4)] (i-nic=4-pyridinecarboxylic acid) 13.6 micromol/kg (complex II), trans-[RuCl(2)(dinic)(4)] (dinic=3,5-pyridinedicarboxylic acid) 180.7 micromol/kg (complex III) and trans-[RuCl(2)(i-dinic)(4)]Cl (i-dinic=3,4-pyridinedicarboxylic acid) 180.7 micromol/kg (complex IV) on succinate dehydrogenase (SDH) and cytochrome oxidase (COX) activities in brain (hippocampus, striatum and cerebral cortex), heart, skeletal muscle, liver and kidney of rats. Our results showed that complex I inhibited SDH activity in hippocampus, cerebral cortex, heart and liver; and inhibited COX in heart and kidney. Complex II inhibited SDH in heart and hippocampus; COX was inhibited in hippocampus, heart, liver and kidney. SDH activity was inhibited by complex III in heart, muscle, liver and kidney. However, COX activity was increased in hippocampus, striatum, cerebral cortex and kidney. Complex IV inhibited SDH activity in muscle and liver; COX activity was inhibited in kidney and increased in hippocampus, striatum and cerebral cortex. In a general manner, the complexes tested in this work decrease the activities of SDH and COX in heart, skeletal muscle, liver and kidney. In brain, complexes I and II were shown to be inhibitors and complexes III and IV activators of these enzymes. In vitro studies showed that the ruthenium complexes III and IV did not alter COX activity in kidney, but activated the enzyme in hippocampus, striatum and cerebral cortex, suggesting that these complexes present a direct action on COX in brain.

Modulation of creatine kinase activity by ruthenium complexes.

Creatine kinase is a crucial enzyme for brain, heart and skeletal muscle energy homeostasis, and a decrease of its activity has been associated with cell death. Many biological properties have been attributed to ruthenium complexes. In this context, this work was performed in order to evaluate creatine kinase activity from rat brain, heart and skeletal muscle (quadriceps) after administration of ruthenium complexes, trans-[RuCl(2)(nic)(4)] (nic=3-pyridinecarboxylic acid) 180.7 micromol/kg (complex I), trans-[RuCl(2)(i-nic)(4)] (i-nic=4-pyridinecarboxylic acid) 13.6 micromol/kg (complex II), trans-[RuCl(2)(dinic)(4)] (dinic=3,5-pyridinedicarboxylic acid) 180.7 micromol/kg (complex III) and trans-[RuCl(2)(i-dinic)(4)] (i-dinic=3,4-pyridinedicarboxylic acid) 180.7 micromol/kg (complex IV). Our results showed that complex I caused inhibition of creatine kinase activity in hippocampus, striatum, cerebral cortex, heart and skeletal muscle. Besides, complex II did not affect the enzyme activity. complexes III and IV increased creatine kinase activity in hippocampus, striatum, cerebral cortex and heart, but not in skeletal muscle. Besides, none of the complexes in vitro altered creatine kinase activity, suggesting that enzymatic activity is indirectly affected by complexes I, III and IV. It is believed that diminution of creatine kinase in brain of rats caused by complex I may be related to results from other study reporting memory impairment caused by the same complex. Further research is necessary in order to elucidate the effects of ruthenium complexes in other important metabolic enzymes.

Trombosis de las venas porta y mesentérica superior asociada a déficit de proteína S / Portal and mesenteric thrombosis and protein "S" deficiency

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