Interaction between poly(A)-binding protein PABPC4 and nuclear receptor corepressor NCoR1 modulates a metabolic stress response.

Mitochondria are organelles known primarily for generating ATP via the oxidative phosphorylation process. Environmental signals are sensed by whole organisms or cells and markedly affect this process, leading to alterations in gene transcription and, consequently, changes in mitochondrial function and biogenesis. The expression of mitochondrial genes is finely regulated by nuclear transcription factors, including nuclear receptors and their coregulators. Among the best-known coregulators is the nuclear receptor corepressor 1 (NCoR1). Muscle-specific knockout of NCoR1 in mice induces an oxidative phenotype, improving glucose and fatty acid metabolism. However, the mechanism by which NCoR1 is regulated remains elusive. In this work, we identified the poly(A)-binding protein 4 (PABPC4) as a new NCoR1 interactor. Unexpectedly, we found that silencing of PABPC4 induced an oxidative phenotype in both C2C12 and MEF cells, as indicated by increased oxygen consumption, mitochondria content, and reduced lactate production. Mechanistically, we demonstrated that PABPC4 silencing increased the ubiquitination and consequent degradation of NCoR1, leading to the derepression of PPAR-regulated genes. As a consequence, cells with PABPC4 silencing had a greater capacity to metabolize lipids, reduced intracellular lipid droplets, and reduced cell death. Interestingly, in conditions known to induce mitochondrial function and biogenesis, both mRNA expression and PABPC4 protein content were markedly reduced. Our study, therefore, suggests that the lowering of PABPC4 expression may represent an adaptive event required to induce mitochondrial activity in response to metabolic stress in skeletal muscle cells. As such, the NCoR1-PABPC4 interface might be a new road to the treatment of metabolic diseases.

Coleoborers in Bambusa sp. in the Southern Amazon / Coleobrocas em Bambusa sp. na Amazonia Meridional

Bamboo (Bambusa sp.) is a grass species with high potential for exploitation, however, this raw material is easily attacked by xylophagous agents such as Coleoptera. The objective of this study is thus to analyse the presence of wood-boring beetles associated with Bambusa sp. in Alta Floresta, Mato Grosso, Brazil. The study was carried out in a bamboo plantation, from August 2016 to July 2017. Two models of ethanolic traps were used, PET Santa Maria and ESALQ-84. Three families of wood-boring beetles were observed in this study: Bostrichidae, Cerambycidae and Curculionidae. 2,144 individuals were identified, belonging to 19 species, in four subfamilies and 11 tribes, and the species Xyleborus affinis was the most frequently collected. Thus, this study constitutes an important contribution to the knowledge of coleoborers associated with bamboo plantations, with the registration of the occurrence of species, as well as contributing to the knowledge of the entomofauna associated with species cultivated in the Southern Amazon.(AU)

O bambu (Bambusa sp.) é uma espécie de gramínea com alto potencial de exploração de fibras, no entanto, essa matéria-prima é facilmente atacada por agentes xilófagos, como os coleópteros. O objetivo deste estudo foi analisar a presença de besouros associados a Bambusa sp. em Alta Floresta, Mato Grosso, Brasil. O estudo foi realizado em um plantio de bambu, no período de agosto de 2016 a julho de 2017. Foram utilizados dois modelos de armadilhas etanólicas, o PET Santa Maria e ESALQ-84. Três famílias de coleobrocas foram observadas neste estudo: Bostrichidae, Cerambycidae e Curculionidae. Foram identificados 2,144 indivíduos, pertencentes a 19 espécies, em quatro subfamílias e 11 tribos, e Xyleborus affinis foi a espécie com maior número de indivíduos coletados. Assim, este estudo constitui-se em uma importante contribuição para o conhecimento de coleobrocas associadas a plantios de bamboo, com o registro de ocorrência de espécies, bem como contribui para o conhecimento da entomofauna associada a espécies cultivadas na Amazônia Meridional.(AU)

Coleoborers in Bambusa sp. in the Southern Amazon / Coleobrocas em Bambusa sp. na Amazonia Meridional

Bamboo (Bambusa sp.) is a grass species with high potential for exploitation, however, this raw material is easily attacked by xylophagous agents such as Coleoptera. The objective of this study is thus to analyse the presence of wood-boring beetles associated with Bambusa sp. in Alta Floresta, Mato Grosso, Brazil. The study was carried out in a bamboo plantation, from August 2016 to July 2017. Two models of ethanolic traps were used, PET Santa Maria and ESALQ-84. Three families of wood-boring beetles were observed in this study: Bostrichidae, Cerambycidae and Curculionidae. 2,144 individuals were identified, belonging to 19 species, in four subfamilies and 11 tribes, and the species Xyleborus affinis was the most frequently collected. Thus, this study constitutes an important contribution to the knowledge of coleoborers associated with bamboo plantations, with the registration of the occurrence of species, as well as contributing to the knowledge of the entomofauna associated with species cultivated in the Southern Amazon.

O bambu (Bambusa sp.) é uma espécie de gramínea com alto potencial de exploração de fibras, no entanto, essa matéria-prima é facilmente atacada por agentes xilófagos, como os coleópteros. O objetivo deste estudo foi analisar a presença de besouros associados a Bambusa sp. em Alta Floresta, Mato Grosso, Brasil. O estudo foi realizado em um plantio de bambu, no período de agosto de 2016 a julho de 2017. Foram utilizados dois modelos de armadilhas etanólicas, o PET Santa Maria e ESALQ-84. Três famílias de coleobrocas foram observadas neste estudo: Bostrichidae, Cerambycidae e Curculionidae. Foram identificados 2,144 indivíduos, pertencentes a 19 espécies, em quatro subfamílias e 11 tribos, e Xyleborus affinis foi a espécie com maior número de indivíduos coletados. Assim, este estudo constitui-se em uma importante contribuição para o conhecimento de coleobrocas associadas a plantios de bamboo, com o registro de ocorrência de espécies, bem como contribui para o conhecimento da entomofauna associada a espécies cultivadas na Amazônia Meridional.

Coleoborers in Bambusa sp. in the Southern Amazon / Coleobrocas em Bambusa sp. na Amazonia Meridional

Abstract Bamboo (Bambusa sp.) is a grass species with high potential for exploitation, however, this raw material is easily attacked by xylophagous agents such as Coleoptera. The objective of this study is thus to analyse the presence of wood-boring beetles associated with Bambusa sp. in Alta Floresta, Mato Grosso, Brazil. The study was carried out in a bamboo plantation, from August 2016 to July 2017. Two models of ethanolic traps were used, PET Santa Maria and ESALQ-84. Three families of wood-boring beetles were observed in this study: Bostrichidae, Cerambycidae and Curculionidae. 2,144 individuals were identified, belonging to 19 species, in four subfamilies and 11 tribes, and the species Xyleborus affinis was the most frequently collected. Thus, this study constitutes an important contribution to the knowledge of coleoborers associated with bamboo plantations, with the registration of the occurrence of species, as well as contributing to the knowledge of the entomofauna associated with species cultivated in the Southern Amazon.

Resumo O bambu (Bambusa sp.) é uma espécie de gramínea com alto potencial de exploração de fibras, no entanto, essa matéria-prima é facilmente atacada por agentes xilófagos, como os coleópteros. O objetivo deste estudo foi analisar a presença de besouros associados a Bambusa sp. em Alta Floresta, Mato Grosso, Brasil. O estudo foi realizado em um plantio de bambu, no período de agosto de 2016 a julho de 2017. Foram utilizados dois modelos de armadilhas etanólicas, o PET Santa Maria e ESALQ-84. Três famílias de coleobrocas foram observadas neste estudo: Bostrichidae, Cerambycidae e Curculionidae. Foram identificados 2,144 indivíduos, pertencentes a 19 espécies, em quatro subfamílias e 11 tribos, e Xyleborus affinis foi a espécie com maior número de indivíduos coletados. Assim, este estudo constitui-se em uma importante contribuição para o conhecimento de coleobrocas associadas a plantios de bamboo, com o registro de ocorrência de espécies, bem como contribui para o conhecimento da entomofauna associada a espécies cultivadas na Amazônia Meridional.

Coleoborers in Bambusa sp. in the Southern Amazon

Abstract Bamboo (Bambusa sp.) is a grass species with high potential for exploitation, however, this raw material is easily attacked by xylophagous agents such as Coleoptera. The objective of this study is thus to analyse the presence of wood-boring beetles associated with Bambusa sp. in Alta Floresta, Mato Grosso, Brazil. The study was carried out in a bamboo plantation, from August 2016 to July 2017. Two models of ethanolic traps were used, PET Santa Maria and ESALQ-84. Three families of wood-boring beetles were observed in this study: Bostrichidae, Cerambycidae and Curculionidae. 2,144 individuals were identified, belonging to 19 species, in four subfamilies and 11 tribes, and the species Xyleborus affinis was the most frequently collected. Thus, this study constitutes an important contribution to the knowledge of coleoborers associated with bamboo plantations, with the registration of the occurrence of species, as well as contributing to the knowledge of the entomofauna associated with species cultivated in the Southern Amazon.

Resumo O bambu (Bambusa sp.) é uma espécie de gramínea com alto potencial de exploração de fibras, no entanto, essa matéria-prima é facilmente atacada por agentes xilófagos, como os coleópteros. O objetivo deste estudo foi analisar a presença de besouros associados a Bambusa sp. em Alta Floresta, Mato Grosso, Brasil. O estudo foi realizado em um plantio de bambu, no período de agosto de 2016 a julho de 2017. Foram utilizados dois modelos de armadilhas etanólicas, o PET Santa Maria e ESALQ-84. Três famílias de coleobrocas foram observadas neste estudo: Bostrichidae, Cerambycidae e Curculionidae. Foram identificados 2,144 indivíduos, pertencentes a 19 espécies, em quatro subfamílias e 11 tribos, e Xyleborus affinis foi a espécie com maior número de indivíduos coletados. Assim, este estudo constitui-se em uma importante contribuição para o conhecimento de coleobrocas associadas a plantios de bamboo, com o registro de ocorrência de espécies, bem como contribui para o conhecimento da entomofauna associada a espécies cultivadas na Amazônia Meridional.

Matteucinol combined with temozolomide inhibits glioblastoma proliferation, invasion, and progression: an in vitro, in silico, and in vivo study.

Glioblastoma is the most prevalent and malignant brain tumor identified in adults. Surgical resection followed by radiotherapy and chemotherapy, mainly with temozolomide (TMZ), is the chosen treatment for this type of tumor. However, the average survival of patients is around 15 months. Novel approaches to glioblastoma treatment are greatly needed. Here, we aimed to investigate the anti-glioblastoma effect of the combination of matteucinol (Mat) (dihydroxyflavanone derived from Miconia chamissois Naudin) with the chemotherapeutic TMZ in vitro using tumor (U-251MG) and normal astrocyte (NHA) cell lines and in vivo using the chick embryo chorioallantoic membrane (CAM) assay. The combination was cytotoxic and selective for tumor cells (28 µg/mL Mat and 9.71 µg/mL TMZ). Additionally, the combination did not alter cell adhesion but caused morphological changes characteristic of apoptosis in vitro. Notably, the combination was also able to reduce tumor growth in the chick embryo model (CAM assay). The docking results showed that Mat was the best ligand to the cell death membrane receptor TNFR1 and to TNFR1/TMZ complex, suggesting that these two molecules may be working together increasing their potential. In conclusion, Mat-TMZ can be a good candidate for pharmacokinetic studies in view of clinical use for the treatment of glioblastoma.

Matteucinol combined with temozolomide inhibits glioblastoma proliferation, invasion, and progression: an in vitro, in silico, and in vivo study

Glioblastoma is the most prevalent and malignant brain tumor identified in adults. Surgical resection followed by radiotherapy and chemotherapy, mainly with temozolomide (TMZ), is the chosen treatment for this type of tumor. However, the average survival of patients is around 15 months. Novel approaches to glioblastoma treatment are greatly needed. Here, we aimed to investigate the anti-glioblastoma effect of the combination of matteucinol (Mat) (dihydroxyflavanone derived from Miconia chamissois Naudin) with the chemotherapeutic TMZ in vitro using tumor (U-251MG) and normal astrocyte (NHA) cell lines and in vivo using the chick embryo chorioallantoic membrane (CAM) assay. The combination was cytotoxic and selective for tumor cells (28 μg/mL Mat and 9.71 μg/mL TMZ). Additionally, the combination did not alter cell adhesion but caused morphological changes characteristic of apoptosis in vitro. Notably, the combination was also able to reduce tumor growth in the chick embryo model (CAM assay). The docking results showed that Mat was the best ligand to the cell death membrane receptor TNFR1 and to TNFR1/TMZ complex, suggesting that these two molecules may be working together increasing their potential. In conclusion, Mat-TMZ can be a good candidate for pharmacokinetic studies in view of clinical use for the treatment of glioblastoma.

Coleoborers in Bambusa sp. in the Southern Amazon.

Bamboo (Bambusa sp.) is a grass species with high potential for exploitation, however, this raw material is easily attacked by xylophagous agents such as Coleoptera. The objective of this study is thus to analyse the presence of wood-boring beetles associated with Bambusa sp. in Alta Floresta, Mato Grosso, Brazil. The study was carried out in a bamboo plantation, from August 2016 to July 2017. Two models of ethanolic traps were used, PET Santa Maria and ESALQ-84. Three families of wood-boring beetles were observed in this study: Bostrichidae, Cerambycidae and Curculionidae. 2,144 individuals were identified, belonging to 19 species, in four subfamilies and 11 tribes, and the species Xyleborus affinis was the most frequently collected. Thus, this study constitutes an important contribution to the knowledge of coleoborers associated with bamboo plantations, with the registration of the occurrence of species, as well as contributing to the knowledge of the entomofauna associated with species cultivated in the Southern Amazon.

Microemulsion systems: from the design and architecture to the building of a new delivery system for multiple-route drug delivery.

Poorly soluble active pharmaceutical ingredients (APIs) create major problems in drug dosage form formulation resulting in significant delays in drug pharmaceutical screening, impairing the drug dosage form production. Aiming to minimize the use of excipients for increasing drug apparent solubility and, as a result, its bioavailability, exploration of innovative approaches is an earnest need. Microemulsion is an alternative drug delivery system that emerged as a valuable tool to achieve safe formulations for insoluble compounds and to improve their biopharmaceutical properties and pharmacokinetics. This review aims to present the state of the art of microemulsion systems, bringing an overview about their origin and how they can be properly produced and thoroughly characterized by different approaches. Furthermore, comments on regulatory issues regarding stability assessment and toxicity evaluation are discussed. The review concludes with a current opinion on microemulsion systems. The overall objective of this work was to describe all the potentialities of microemulsion systems as a drug carrier for therapeutic purposes, highlighting the unique features of this nanotechnological platform. Display Image.

Evaluation of Heat Stress Through Temperature and Pupillary Dilatation of the Guinea Fowl (Numida Meleagris) in a Controlled Environment

The commercial exploitation of guinea fowl (Numidia meleagris) is a viable alternative for small rural properties in arid and semi-arid regions, as they are rustic birds and capable of withstanding the climatic adversities of these regions. The objective of this study was to evaluate the pupillary temperature, smaller pupillary diameter, larger pupillary diameter and pupil area of guinea fowl housed in a controlled environment, under two air temperatures: 26 ºC (thermal comfort zone) and 32 ºC (above the thermal comfort zone). The birds were distributed in a completely randomized design, with two treatments (air temperatures) and four replications (experimental box), with twelve birds each. The increase in air temperature resulted in a significant average increase (P < 0.05) of 6.0, 17.9, 18.6 and 38.4%, respectively, in pupillary temperature, smaller pupillary diameter, larger pupillary diameter and pupillary area of birds, being these measurements accurate in evaluation of thermal stress in homeothermic animals.(AU)

Evaluation of Heat Stress Through Temperature and Pupillary Dilatation of the Guinea Fowl (Numida Meleagris) in a Controlled Environment

The commercial exploitation of guinea fowl (Numidia meleagris) is a viable alternative for small rural properties in arid and semi-arid regions, as they are rustic birds and capable of withstanding the climatic adversities of these regions. The objective of this study was to evaluate the pupillary temperature, smaller pupillary diameter, larger pupillary diameter and pupil area of guinea fowl housed in a controlled environment, under two air temperatures: 26 ºC (thermal comfort zone) and 32 ºC (above the thermal comfort zone). The birds were distributed in a completely randomized design, with two treatments (air temperatures) and four replications (experimental box), with twelve birds each. The increase in air temperature resulted in a significant average increase (P < 0.05) of 6.0, 17.9, 18.6 and 38.4%, respectively, in pupillary temperature, smaller pupillary diameter, larger pupillary diameter and pupillary area of birds, being these measurements accurate in evaluation of thermal stress in homeothermic animals.

New Approach For Simvastatin As An Antibacterial: Synergistic Effect With Bio-Synthesized Silver Nanoparticles Against Multidrug-Resistant Bacteria.

BACKGROUND: Multidrug-resistant bacteria such as extended-spectrum beta-lactamase (ESBL), Enterobacteriaceae, and methicillin-resistant Staphylococcus aureus (MRSA) pose a challenge to the human health care system. MRSA is among the major causes of hospital-acquired and community infections. METHODS: Therefore, in the present study, we evaluated the antibacterial activity of silver nanoparticles synthesized by Fusarium oxysporum (AgNPbio) in combination with simvastatin against reference and multidrug-resistant bacterial strains. RESULTS: Simvastatin showed a minimal inhibitory concentration (MIC) ranging from 0.062 to 0.25 mg mL-1 against MRSA. AgNPbio with a size of 77.68± 33.95 nm and zeta potential -34.6 ± 12.7 mV showed an MIC of 0.212 mg mL-1 against S. aureus including MRSA strains. The checkerboard assay and time-kill curves exhibited a synergistic effect of the simvastatin-AgNPbio combination on antibacterial activity against MRSA strains. The combination of simvastatin and AgNPbio demonstrated antibacterial activity against Escherichia coli producing ESBL. Scanning electron microscopy showed the formation of cell surface protrusions after treatment with AgNPbio and the formation of a large amorphous mass after treatment with simvastatin, both in MRSA. CONCLUSION: Our results indicate that the combination of AgNPbio and simvastatin could be a great future alternative in the control of bacterial infections, where, when combined with simvastatin, smaller doses of AgNPbio are required, with the same antibacterial activity.

Nycthemeral Rhythm of Phlebotominae (Diptera: Psychodidae) in a Craggy Region, Transitioning Between the Wetland and the Plateau, Brazil.

Recording the nycthemeral rhythm of sand flies allows the evaluation of the daily activity in different ecotypes, the period of greatest activity, and their degree of anthropophily. We investigated the fauna and the rhythm of sand fly activity in an ecotourism region in Mato Grosso do Sul (MS) state, Brazil. Sand flies were captured monthly, using a Shannon trap for 24 h periods between July 2012 and June 2014. We collected 1,815 sand flies, in which Lutzomyia whitmani (=Nyssomyia whitmani, sensu Galati) and Lutzomyia longipalpis were the most abundant species during the dry season, with activity from 5 p.m.-7 a.m. and 6 p.m.-5 a.m., respectively. Both species require particular attention as vectors of Leishmania (Viannia) braziliensis and Leishmania (Leishmania) infantum in several regions of Brazil, including MS. However, Lutzomyia dispar was more anthropophilic, and was most active between January and March, from 5 p.m. to 5 a.m. Lutzomyia misionensis (=Pintomyia misionensis, sensu Galati) was present throughout both years, active from 4 p.m. to 5 a.m. Other species were active from 5 p.m. to 6 a.m. Due to intense tourism in the months that coincide with a high number of vectors for leishmaniases in Piraputanga, it is essential to determine vector-monitoring strategies in the area by investigating sand fly rhythm while not neglecting other periods of the year when the insects are present.

Electrical observation of sub-band formation in SnO2 nanobelts.

The electrical observation of energy sub-band formation in the electronic structure, that gives rise to the phenomenon of quantized transport is reported in tin oxide (SnO2) nanobelt back-gate field-effect transistors, at low temperatures. Sub-band formation was observed as current oscillations in the drain current vs. gate voltage characteristics, and was analyzed considering the nanobelt as a "quantum wire" with a rectangular cross-section and hard walls. The lateral quantum confinement in the nanowires created conditions for the successive filling of the first twelve electron energy sub-bands, as the gate voltage increases. When the source-drain voltage is changed, the oscillations are not dislocated with respect to the gate voltage indicating flat-band energies, and that the observations are incompatible with the phenomena of Coulomb blockade and tunnelling oscillations. The separation of the energy sub-bands was found to be in good agreement with the measured cross-section dimensions of the nanobelt and with the threshold temperature, since for T > 60 K the oscillations tend to vanish.

Behavioral aspects of Lutzomyia longipalpis (Diptera: Psychodidae) in urban area endemic for visceral leishmaniasis.

The study of some of the behavioral aspects of the main vector of Leishmania infantum chagasi Cunha & Chagas in the Americas, Lutzomyia longipalpis (Lutz & Neiva), such as dispersion, population size, and vector survival rates, is important for the elucidation of the mechanisms of visceral leishmaniasis transmission. These parameters were studied by means of capture-mark-release-recapture experiments in an urban area of Campo Grande municipality, an endemic area of visceral leishmaniasis, situated in Mato Grosso do Sul state, Brazil. Six capture-mark-release-recapture experiments were undertaken between November 2009 and November 2010 and once in January 2012 with a view to assessing the population size and survival rate of Lu. longipalpis. The insects were released in a peridomicile surrounded by 13 residences. The recaptures were undertaken with automatic light traps for four consecutive weeks after release in the surrounding area. In total, 3,354 sand flies were captured, marked, and released. The overall recapture rate during the capture-mark-release-recapture experiments was 4.23%, of which 92.45% were recaptured at the release site, indicating limited dispersal. The greatest distance recorded from the release site was 165 m for males and 241 m for females. The male daily survival rate, calculated on the basis of regressions from the numbers of marked recaptured insects during the 15 successive days after release was 0.897. The estimated male population size measured by the Lincoln Index was 10,947.127. Though Lu. longipalpis presented a limited dispersion the physical barriers typical of urban environments did not prevent the sand flies from flying long distances.

Anatomic variations of paranasal sinuses-clinical case report.

This article describes the clinical case of an 86-year-old female patient with an asymptomatic clinical condition, without presenting a history of previous traumatisms. When routine radiographic exam-panoramic radiograph-was performed, the following extensions of the paranasal sinuses were found: maxillary sinus (palate), sphenoid sinus (pterygoid process, major wing, and anterior clinoid process), and supraorbital portion of the frontal sinus. Thus computerized tomography was performed to confirm the diagnosis.

Biocompatibilidade e biodegradabilidade de micropartículas de poli-lactato-co-glicolato na ceratite infecciosa em coelhos / Biocompatibility and biodegradability of poly-latic-co-glycolatic microparticles in the infectious keratitis in rabbits

Avaliaram-se a biocompatibilidade e a biodegradabilidade do sistema de liberação controlada de poli-lactato-co-glicolato (PLGA) no tratamento com ciprofloxacina das ceratites por Staphylococcus aureus em coelhos. Foram utilizados 20 coelhos, distribuídos em quatro grupos (G). Os animais dos G1, G3 e G4 foram inoculados com 2,5µL da bactéria - 108UFC, no estroma corneano. Os do G2 não receberam a aplicação do inóculo. O tratamento foi realizado com solução salina básica para os animais do G1, micropartículas de PLGA contendo ciprofloxacina nos animais dos G2 e G4 e colírio de ciprofloxacina naqueles do G3. Suabe e biópsia da superfície ocular foram coletados para cultura. Apenas um animal do G1 apresentou cultura positiva para S. aureus. Exame histológico revelou a presença bacteriana em todos os animais do G1 e em dois animais do G3. Também foi constatada reação inflamatória no local da aplicação do sistema de liberação controlada. O tratamento com micropartículas de PLGA foi eficiente no tratamento de ceratites bacterianas, ao eliminar por completo a presença do S. aureus, mas entretanto não foi completamente biocompatível e biodegradável após cinco dias.

The biocompatibility and biodegradability of the controlled delivery system of Poly-Latic-Co-Glucolatic (PLGA) in the treatment of Staphylococcus aureus keratitis with ciprofloxacin in rabbits were evaluated. Twenty rabbits divided into four groups (G) were used. G1, G3 and G4 animals were inoculated with bacterial 2.5µL (108CFU) in the corneal stroma, and G2 animals did not receive the application of inoculum. The treatment was performed with basic saline solution in G1 rabbits, micro particles of PLGA containing ciprofloxacin in G2 and G4 animals, and ciprofloxacin eye drops in G3 rabbits. Swab and biopsy of the ocular surface were collected for culture. Only one animal in G1 had positive culture for S. aureus in the processed material. Histological examination showed a bacterial presence in all animals in G1 and two animals in G3. Inflammatory reaction was noted at the application site of the controlled release. Data analysis showed that treatment with micro particles of PLGA was effective in treating bacterial keratitis, completely eliminating the presence of S. aureus, but it was not being completely biocompatible and biodegradable after five days.

Double-stranded RNA-activated protein kinase is a key modulator of insulin sensitivity in physiological conditions and in obesity in mice.

The molecular integration of nutrient- and pathogen-sensing pathways has become of great interest in understanding the mechanisms of insulin resistance in obesity. The double-stranded RNA-dependent protein kinase (PKR) is one candidate molecule that may provide cross talk between inflammatory and metabolic signaling. The present study was performed to determine, first, the role of PKR in modulating insulin action and glucose metabolism in physiological situations, and second, the role of PKR in insulin resistance in obese mice. We used Pkr(-/-) and Pkr(+/+) mice to investigate the role of PKR in modulating insulin sensitivity, glucose metabolism, and insulin signaling in liver, muscle, and adipose tissue in response to a high-fat diet. Our data show that in lean Pkr(-/-) mice, there is an improvement in insulin sensitivity, and in glucose tolerance, and a reduction in fasting blood glucose, probably related to a decrease in protein phosphatase 2A activity and a parallel increase in insulin-induced thymoma viral oncogene-1 (Akt) phosphorylation. PKR is activated in tissues of obese mice and can induce insulin resistance by directly binding to and inducing insulin receptor substrate (IRS)-1 serine307 phosphorylation or indirectly through modulation of c-Jun N-terminal kinase and inhibitor of κB kinase ß. Pkr(-/-) mice were protected from high-fat diet-induced insulin resistance and glucose intolerance and showed improved insulin signaling associated with a reduction in c-Jun N-terminal kinase and inhibitor of κB kinase ß phosphorylation in insulin-sensitive tissues. PKR may have a role in insulin sensitivity under normal physiological conditions, probably by modulating protein phosphatase 2A activity and serine-threonine kinase phosphorylation, and certainly, this kinase may represent a central mechanism for the integration of pathogen response and innate immunity with insulin action and metabolic pathways that are critical in obesity.

Emergence of clonal complex 5 (CC5) methicillin-resistant Staphylococcus aureus (MRSA) isolates susceptible to trimethoprim-sulfamethoxazole in a Brazilian hospital

In this study, genotyping techniques including staphylococcal chromosomal cassette mec (SCCmec) typing, pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and restriction-modification tests were used to compare the molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered at two times within a 10-year interval (1998 and 2008) from a tertiary Brazilian hospital. In addition, the antimicrobial susceptibility profiles were analyzed. All 48 MRSA isolates from 1998 and 85.7% from 2008 (48/56 isolates) displayed multidrug-resistance phenotypes and SCCmec III. All but one of the 13 representative SCCmec III isolates belonged to CC8 and had PFGE patterns similar to that of the BMB9393 strain (Brazilian epidemic clone of MRSA; BEC). In 2008, we found an increased susceptibility to rifampicin and chloramphenicol among the SCCmec III isolates. In addition, we detected the entrance of diverse international MRSA lineages susceptible to trimethoprim-sulfamethoxazole (SXT), almost all belonging to CC5. These non-SCCmec III isolates were related to the USA 300 (ST8-SCCmec IV; PFGE-type B), USA 800 (ST5-SCCmec IV; subtype D1), USA 100 (ST5-SCCmec II; subtype D2), and EMRSA-3/Cordobes (ST5-SCCmec I, type C) clones. To the best of our knowledge, this is the first report of the emergence of isolates genetically related to the EMRSA-3/Cordobes clone in southeast Brazil. In this regard, these isolates were the most common non-SCCmec III MRSA in our institution, accounting for 8.9% of all isolates recovered in 2008. Thus, despite the supremacy of BEC isolates in our country, significant changes may occur in local MRSA epidemiology, with possible consequences for the rationality of MRSA empiric therapy.