Fluconazole and amphotericin-B resistance are associated with increased catalase and superoxide dismutase activity in Candida albicans and Candida dubliniensis

Introduction Candida dubliniensis, a new species of Candida that has been recovered from several sites in healthy people, has been associated with recurrent episodes of oral candidiasis in AIDS and HIV-positive patients. This species is closely related to C. albicans. The enzymatic activity of C. dubliniensis in response to oxidative stress is of interest for the development of drugs to combat C. dubliniensis. Methods Fluconazole- and amphotericin B-resistant strains were generated as described by Fekete-Forgács et al. (2000). Superoxide dismutase (SOD) and catalase assays were performed as described by McCord and Fridovich (1969) and Aebi (1984), respectively. Results We demonstrated that superoxide dismutase (SOD) and catalase activities were significantly higher (p<0.05) in the fluconazole- and amphotericin B-resistant strains of C. dubliniensis and C. albicans than in the sensitive strains. The catalase and SOD activities were also significantly (p<0.01) higher in the sensitive and resistant C. albicans strains than in the respective C. dubliniensis strains. Conclusions These data suggest that C. albicans is better protected from oxidative stress than C. dubliniensis and that fluconazole, like amphotericin B, can induce oxidative stress in Candida; oxidative stress induces an adaptive response that results in a coordinated increase in catalase and SOD activities.

In vitro antimalarial activity of tigecycline against Plasmodium falciparum culture-adapted reference strains and clinical isolates from the Brazilian Amazon

Introduction: We evaluated the in vitro antimalarial activity of tigecycline as an alternative drug for the treatment of severe malaria. Methods: A chloroquine-sensitive Plasmodium falciparum reference strain, a chloroquine-resistant reference strain, and three clinical isolates were tested for in vitro susceptibility to tigecycline. A histidine-rich protein in vitro assay was used to evaluate antimalarial activity. Results: The geometric-mean 50% effective concentration (EC50%) of tigecycline was 535.5 nM (confidence interval (CI): 344.3-726.8). No significant correlation was found between the EC50% of tigecycline and that of any other tested antimalarial drug. Conclusions: Tigecycline may represent an alternative drug for the treatment of patients with severe malaria.

Proteomic analysis of a neurodegeneration cell model, treated with plant extracts with potential neuroprotective activity

Nowadays, a significant increase in chronic diseases is observed. Epidemiological studies showed a consistent relationship between the consumption of fruits and vegetables and a reduced risk of certain chronic diseases, namely neurodegenerative disorders. One factor common to these diseases is oxidative stress, which is highly related with proteins, lipids, carbohydrates and nucleic acids damage, leading to cellular dysfunction. Polyphenols, highly abundant in berries and associated products, were described as having antioxidant properties, with beneficial effect in these pathologies. The aims of this study were to evaluate by proteomic analyses the effect of oxidative insult in a neuroblastoma cell line (SK-N-MC) and understand the mechanisms involved in the neuroprotective effects of digested extracts from commercial and wild blackberry (R. vagabundus Samp.). The analysis of the total proteome by two-dimensional electrophoresis revealed that oxidative stress in SK-N-MC cells resulted in altered expression of 12 protein spots from a total of 318. Regarding some redox proteomics alterations, particularly proteins carbonylation and glutathionylation, protein carbonyl alterations during stress suggest that cells produce an early and late response; on the other hand, no glutathionylated polypeptides were detected. Relatively to the incubation of SK-N-MC cells with digested berry extracts, commercial blackberry promotes more changes in protein pattern of these cells than R. vagabundus. From 9 statistically different protein spots of cells incubated with commercial blackberry, only β-tubulin and GRP 78 were until now identified by mass spectrometry. Further studies involving the selection of sub proteomes will be necessary to have a better understanding of the mechanisms underlying the neuroprotective effects of berries.

Larvicidal activity of the methanol extract and fractions of the green fruits of Solanum lycocarpum(Solanaceae) against the vector Culex quinquefasciatus (Diptera: Culicidae)

IntroductionThe larvicidal activity of Solanum lycocarpumagainst Culex quinquefasciatus is unknown.MethodsWe evaluated the larvicidal activity of extracts of the green fruits of Solanum lycocarpum against third and fourth instar larvae of C. quinquefasciatus.ResultsDichloromethane and ethyl acetate fractions showed the greatest larvicidal effect at 200mg/L (83.3% and 86.7%, respectively). The methanol and dichloromethane, ethyl acetate, and hydromethanolic fractions demonstrated larvicidal effects against C. quinquefasciatus, with LC50 values of 126.24, 75.13, 83.15, and 207.05mg/L, respectively.ConclusionsThus, when considering new drugs with larvicidal activity from natural products, S. lycocarpum fruits may be good candidate sources.

Fabrication and characterization of transparent conductive oxide surface sensors for electrocorticography – TrECoG

Understanding how the brain works has been one of the greatest goals of mankind. This desire fuels the scientific community to pursue novel techniques able to acquire the complex information produced by the brain at any given moment. The Electrocorticography (ECoG) is one of those techniques. By placing conductive electrodes over the dura, or directly over the cortex, and measuring the electric potential variation, one can acquire information regarding the activation of those areas. In this work, transparent ECoGs, (TrECoGs) are fabricated through thin film deposition of the Transparent Conductive Oxides (TCOs) Indium-Zinc-Oxide (IZO) and Gallium-Zinc-Oxide (GZO). Five distinct devices have been fabricated via shadow masking and photolithography. The data acquired and presented in this work validates the TrECoGs fabricated as efficient devices for recording brain activity. The best results were obtained for the GZO- based TrECoG, which presented an average impedance of 36 kΩ at 1 kHz for 500 μm diameter electrodes, a transmittance close to 90% for the visible spectrum and a clear capability to detect brain signal variations. The IZO based devices also presented high transmittance levels (90%), but with higher impedances, which ranged from 40 kΩ to 100 kΩ.

Larvicidal activity of oils, fatty acids, and methyl esters from ripe and unripe fruit of Solanum lycocarpum (Solanaceae) against the vector Culex quinquefasciatus (Diptera: Culicidae)

ABSTRACTINTRODUCTION:The larvicidal activity of oils, fatty acids, and methyl esters of Solanum lycocarpum fruit against Culex quinquefasciatus is unknown.METHODS:The larvicidal activity of samples of ripe and unripe fruit from S. lycocarpum was evaluated against third and fourth instar larvae of C. quinquefasciatus .RESULTS:The oils, fatty acids, and methyl esters of S. lycocarpum showed the greatest larvicidal effect (57.1-95.0%) at a concentration of 100mg/L (LC 50values between 0.70 and 27.54mg/L).CONCLUSIONS:Solanum lycocarpum fruit may be a good source of new natural products with larvicidal activity.

Chemical composition and antifungal activity of essential oil from Eucalyptus smithii against dermatophytes

ABSTRACT INTRODUCTION: In this study, we evaluated the chemical composition of a commercial sample of essential oil from Eucalyptus smithii R.T. Baker and its antifungal activity against Microsporum canis ATCC 32903, Microsporum gypseum ATCC 14683, Trichophyton mentagrophytes ATCC 9533, T. mentagrophytes ATCC 11480, T. mentagrophytes ATCC 11481, and Trichophyton rubrum CCT 5507. METHODS: Morphological changes in these fungi after treatment with the oil were determined by scanning electron microscopy (SEM). The antifungal activity of the oil was determined on the basis of minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values. RESULTS: The compound 1,8-cineole was found to be the predominant component (72.2%) of the essential oil. The MIC values of the oil ranged from 62.5μg·mL−1 to >1,000μg·mL−1, and the MFC values of the oil ranged from 125μg·mL−1 to >1,000μg·mL−1. SEM analysis showed physical damage and morphological alterations in the fungi exposed to this oil. CONCLUSIONS: We demonstrated the potential of Eucalyptus smithii essential oil as a natural therapeutic agent for the treatment of dermatophytosis.

Sodium nitroprusside has leishmanicidal activity independent of iNOS

Abstract: INTRODUCTION: Leishmaniasis is a zoonotic disease caused by protozoa of the genus Leishmania . Cutaneous leishmaniasis is the most common form, with millions of new cases worldwide each year. Treatments are ineffective due to the toxicity of existing drugs and the resistance acquired by certain strains of the parasite. METHODS: We evaluated the activity of sodium nitroprusside in macrophages infected with Leishmania (Leishmania) amazonensis . Phagocytic and microbicidal activity were evaluated by phagocytosis assay and promastigote recovery, respectively, while cytokine production and nitrite levels were determined by ELISA and by the Griess method. Levels of iNOS and 3-nitrotyrosine were measured by immunocytochemistry. RESULTS: Sodium nitroprusside exhibited in vitro antileishmanial activity at both concentrations tested, reducing the number of amastigotes and recovered promastigotes in macrophages infected with L. amazonensis . At 1.5µg/mL, sodium nitroprusside stimulated levels of TNF-α and nitric oxide, but not IFN-γ. The compound also increased levels of 3-nitrotyrosine, but not expression of iNOS, suggesting that the drug acts as an exogenous source of nitric oxide. CONCLUSIONS: Sodium nitroprusside enhances microbicidal activity in Leishmania -infected macrophages by boosting nitric oxide and 3-nitrotyrosine.

Antimonial drugs entrapped into phosphatidylserine liposomes: physicochemical evaluation and antileishmanial activity

Abstract: INTRODUCTION: Leishmaniasis is a disease caused by the protozoan Leishmania that resides mainly in mononuclear phagocytic system tissues. Pentavalent antimonials are the main treatment option, although these drugs have toxic side effects and high resistance rates. A potentially alternative and more effective therapeutic strategy is to use liposomes as carriers of the antileishmanial agents. The aims of this study were to develop antimonial drugs entrapped into phosphatidylserine liposomes and to analyze their biological and physicochemical characteristics. METHODS: Liposomes containing meglumine antimoniate (MA) or pentavalent antimony salt (Sb) were obtained through filter extrusion (FEL) and characterized by transmission electron microscopy. Promastigotes of Leishmania infantum were incubated with the drugs and the viability was determined with a tetrazolium dye (MTT assay). The effects of these drugs against intracellular amastigotes were also evaluated by optical microscopy, and mammalian cytotoxicity was determined by an MTT assay. RESULTS: Liposomes had an average diameter of 162nm. MA-FEL showed inhibitory activity against intracellular L. infantum amastigotes, with a 50% inhibitory concentration (IC50) of 0.9μg/mL, whereas that of MA was 60μg/mL. Sb-FEL showed an IC50 value of 0.2μg/mL, whereas that of free Sb was 9μg/mL. MA-FEL and Sb-FEL had strong in vitro activity that was 63-fold and 39-fold more effective than their respective free drugs. MA-FEL tested at a ten-times higher concentration than Sb-FEL did not show cytotoxicity to mammalian cells, resulting in a higher selectivity index. CONCLUSIONS: Antimonial drug-containing liposomes are more effective against Leishmania-infected macrophages than the non-liposomal drugs.

Historic and potential technology transition paths of grid battery storage: Co-evolution of energy grid, electric mobility and batteries

Scarcity of fuels, changes in environmental policy and in society increased the interest in generating electric energy from renewable energy sources (RES) for a sustainable energy supply in the future. The main problem of RES as solar and wind energy, which represent a main pillar of this transition, is that they cannot supply constant power output. This results inter alia in an increased demand of backup technologies as batteries to assure electricity system safety. The diffusion of energy storage technologies is highly dependent on the energy system and transport transition pathways which might lead to a replacement or reconfiguration of embedded socio-technical practices and regimes (by creating new standards or dominant designs, changing regulations, infrastructure and user patterns). The success of this technology is dependent on hardly predictable future technical advances, actor preferences, development of competing technologies and designs, diverging interests of actors, future cost efficiencies, environmental performance, the evolution of market demand and design and evolution of our society.

Activity of natural killer cells during HIV-1 infection in Brazilian patients

Natural killer cells are increasingly being considered an important component of innate resistance to viruses, but their role in HIV infection is controversial. Some investigators have found that natural killer cells do not confer a protective effect during the progression of HIV disease, whereas others have shown that natural killer cells may be protective and retard the progression of the disease, either through their lytic activity or by a chemokine-related suppression of HIV replication. In this study, we analyzed functional alterations in the activity of natural killer cells during HIV-1 infection using a natural killer cells activity assay with K562 cells as targets. RESULTS: Our results show that the activity of natural killer cells decreases only in the advanced phase of HIV infection and when high (40:1) effector cell-target cell ratios were used. The depression at this stage of the disease may be related to increased levels of some viral factors, such as gp120 or gag, that interfere with the binding capacity of natural killer cells, or to the decreased production of natural killer cells -activity-stimulating cytokines, such as IFN-a and IL-12, by monocytes, a subset of cells that are also affected in the late stage of HIV infection. The data suggest that decreased natural killer cells cell activity may contribute to the severe impairment of the immune system of patients in the late stages of HIV infection.

Gastric myoelectrical activity in neonates of different gestational ages by means of electrogastrography

PURPOSE: to describe the patterns of the gastric myoelectrical activity, pre-and postprandially, in clinically stable neonates of different gestational ages, during their first two weeks of life by means of Electrogastrography. PATIENTS AND METHODS: Electrogastrography was recorded in forty-five clinically stable neonates of different gestational ages (group I: 15 neonates of > 37 weeks, group II: 15 premature neonates of 32-37 weeks; Group III: 15 premature neonates of 28-31 weeks) receiving intermittent enteral feedings during their first two weeks of life. Electrogastrography recordings were performed for 1 hour pre-and postprandially. The Electrogastrography signal was recorded using the portable MicroDigitrapper Electrogastrography recording device and after motion artifacts were deleted, the remaining Electrogastrography data were submitted to quantitative analysis based on the "Running Spectrum Analysis". RESULTS: The percentages of normogastria, pre-and postprandially were greater than the percentages of gastric dysrythmias in all three studied groups. Furthermore, all neonates had the mean values of the Electrogastrography dominant frequency predominantly within the normogastria range, in both periods analyzed. There were no significant differences in the relative change of the Electrogastrography dominant power among the groups. CONCLUSION: This study demonstrates that the Electrogastrography patterns are similar between premature and full term neonates during the pre-and postprandial periods. The results of this study also indicate that the gastric myoelectrical activity in premature and full term neonates is immature, as compared to that described for older neonates, children and adults.

Temperature influence and social interaction on the frequency of electric organ discharges in Rhamphicthys rostratus.

The frequency of electric organ discharges (EOD) of a gymnotiform fish of "pulse" frequency (40-100 Hz) from South America - Ramphicthys rostratuswas studied. The animals were settled in pairs in a aquarium and thus observed: variation in EOD frequency had at least two components: one more positively correlated with temperature, another less positively correlated due to social interaction.

Socio-demographic correlates of physical activity of European adults: A cross-sectional study from the European Social Survey

ABSTRACT - Background: From a public health perspective, the study of socio-demographic factors related to physical activity is important in order to identify subgroups for intervention programs. Purpose: This study also aimed to identify the prevalence and the socio-demographic correlates related with the achievement of recommended physical activity levels. Methods: Using data from the European Social Survey round 6, physical activity and socio-demographic characteristics were collected from 39278 European adults (18271 men, 21006 women), aged 18-64 years, from 28 countries in 2012. Meeting physical activity guidelines was assessed using World Health Organization criteria. Results: 64.50% (63.36% men, 66.49% women) attained physical activity recommended levels. The likelihood of attaining physical activity recommendations was higher in age group of 55-64 years (men: OR=1.22, p<0.05; women: OR=1.66, p<0.001), among those who had completed high school (men: OR=1.28, p<0.01; women: OR=1.26, p<0.05), among those who lived in rural areas (men: OR=1.20, p<0.001; women: OR=1.10, p<0.05), and among those who had 3 or more people living at home (men: OR=1.40, p<0.001; women: OR=1.43, p<0.001). On the other hand, attaining physical activity recommendations was negatively associated with being unemployed (men: OR=0.70, p<0.001; women: OR=0.87, p<0.05), being a student (men: OR=0.56, p<0.001; women: OR=0.64, p<0.01), being a retired person (men: OR=0.86, p<0.05) and with having a higher household income (OR=0.80, p<0.001; women: OR=0.81, p<0.01). Conclusion: This research helped clarify that, as the promotion of physical activity is critical to sustain health and prevent disease, socio-demographic factors are important to consider when planning the increase of physical activity.

Synthesis and antibiotic activity of some β-Carboline alkaloids

Nine β-carboline alkaloids were synthetized and screened for antibiotic activity. Six of the compounds testes showed inhibitory activity against one or more of the microorganisms assayed.