Publications by authors named "Juliana Rosa"

44 Publications

TLR4-pathway impairs synaptic number and cerebrovascular functions through astrocyte activation following traumatic brain injury.

Br J Pharmacol 2021 Apr 8. Epub 2021 Apr 8.

InstitutoTeófilo Hernando, Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.

Background And Purpose: Activation of astrocytes contributes to synaptic remodelling, tissue repair and neuronal survival following traumatic brain injury (TBI). However, the mechanisms by which these cells interact to resident/infiltrated inflammatory cells to rewire neuronal networks and repair brain functions remain poorly understood. Here, we explored how TLR4-induced astrocyte activation modified synapses and cerebrovascular integrity following TBI.

Experimental Approach: We used pharmacological and genetic approaches to determine how functional astrocyte alterations induced by activation of TLR4-pathway in inflammatory cells regulate synapses and neurovascular unit after TBI. For that, we used calcium imaging, immunofluorescence, flow cytometry, blood-brain barrier (BBB) integrity assessment and molecular and behavioural tools.

Key Results: Shortly after a TBI there is a recruitment of excitable and reactive astrocytes mediated by TLR4-pathway activation with detrimental effects on PSD-95/VGlut1 synaptic puncta, BBB integrity and neurological outcome. Pharmacological blockage of the TLR4-pathway with TAK242 partially reverted many of the observed effects. Synapses and BBB recovery after TAK242 administration were not observed in IP R2 mice, indicating that effects of TLR4-inhibition depend on the subsequent astrocyte activation. In addition, TBI increased the astrocytic-protein thrombospondin-1 necessary to induce a synaptic recovery in a sub-acute phase.

Conclusions And Implications: Our data demonstrate that TLR4-mediated signalling, most probably through microglia and/or infiltrated monocyte-astrocyte communication, plays a crucial role in the TBI pathophysiology and that its inhibition prevents synaptic loss and BBB damage accelerating tissue recovery/repair, which might represent a therapeutic potential in CNS injuries and disorders.
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http://dx.doi.org/10.1111/bph.15488DOI Listing
April 2021

Multiple cellular targets involved in the antidepressant-like effect of glutathione.

Chem Biol Interact 2020 Sep 22;328:109195. Epub 2020 Jul 22.

Department of Biochemistry, Federal University of Santa Catarina, 88040-900, Florianópolis, SC, Brazil. Electronic address:

A previous study demonstrated that glutathione (GSH) produces specific antidepressant-like effect in the forced swimming test (FST), a predictive test of antidepressant activity. The present study investigated the involvement of multiple cellular targets implicated in the antidepressant-like effect of GSH in the FST. The antidepressant-like effect of GSH (300 nmol/site, icv) lasted up to 3 h when mice were submitted to FST. The central administration of oxidized GSH (GSSG, 3-300 nmol/site) did not alter the behavior of mice submitted to the FST. Furthermore, the combined treatment of sub-effective doses of GSH (100 nmol/site, icv) with a sub-effective dose of classical antidepressants (fluoxetine 10 mg/kg, and imipramine 5 mg/kg, ip) presented synergistic effect by decreasing the immobility time in the FST. The antidepressant-like effect of GSH was abolished by prazosin (1 mg/kg, ip, α-adrenoceptor antagonist), baclofen (1 mg/kg, ip, GABAB receptor agonist), bicuculline (1 mg/kg, ip, GABAA receptor antagonist), l-arginine (750 mg/kg, ip, NO precursor), SNAP (25 μg/site, icv, NO donor), but not by yohimbine (1 mg/kg, ip, α-adrenoceptor antagonist). The NMDA receptor antagonists, MK-801(0.001 mg/kg, ip) or GMP (0.5 mg/kg, ip), potentiated the effect of a sub-effective dose of GSH in the FST. These results suggest that the antidepressant-like effect induced by GSH is connected to the activation of α1 adrenergic and GABAA receptors, as well as the inhibition of GABAB and NMDA receptors and NO biosyntesis. We speculate that redox-mediated signaling on the extracelular portion of cell membrane receptors would be a common mechanism of action of GSH.
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http://dx.doi.org/10.1016/j.cbi.2020.109195DOI Listing
September 2020

Early toll-like receptor 4 blockade reduces ROS and inflammation triggered by microglial pro-inflammatory phenotype in rodent and human brain ischaemia models.

Br J Pharmacol 2019 08 17;176(15):2764-2779. Epub 2019 Jun 17.

Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria-Hospital Universitario de la Princesa, Madrid, Spain.

Background And Purpose: Ischaemic stroke is a leading cause of death, disability, and a high unmet medical need. Post-reperfusion inflammation and an up-regulation of toll-like receptor 4 (TLR4), an upstream sensor of innate immunity, are associated with poor outcome in stroke patients. Here, we identified the therapeutic effect of targeting the LPS/TLR4 signal transduction pathway.

Experimental Approach: We tested the effect of the TLR4 inhibitor, eritoran (E5564) in different in vitro ischaemia-related models: human organotypic cortex culture, rat organotypic hippocampal cultures, and primary mixed glia cultures. We explored the therapeutic window of E5564 in the transient middle cerebral artery occlusion model of cerebral ischaemia in mice.

Key Results: In vivo, administration of E5564 1 and 4 hr post-ischaemia reduced the expression of different pro-inflammatory chemokines and cytokines, infarct volume, blood-brain barrier breakdown, and improved neuromotor function, an important clinically relevant outcome. In the human organotypic cortex culture, E5564 reduced the activation of microglia and ROS production evoked by LPS.

Conclusion And Implications: TLR4 signalling has a causal role in the inflammation associated with a poor post-stroke outcome. Importantly, its inhibition by eritoran (E5564) provides neuroprotection both in vitro and in vivo, including in human tissue, suggesting a promising new therapeutic approach for ischaemic stroke.
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http://dx.doi.org/10.1111/bph.14703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609554PMC
August 2019

The effect of group exercises on balance, mobility, and depressive symptoms in older adults with mild cognitive impairment: a randomized controlled trial.

Clin Rehabil 2019 Mar 4;33(3):439-449. Epub 2018 Dec 4.

1 Institute of Geriatrics and Gerontology, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil.

Objective:: To determine the effects of group exercises on balance, mobility, and depressive symptoms in community-dwelling older adults with mild cognitive impairment.

Design:: Single blinded, randomized, matched pairs clinical trial.

Setting:: Four primary healthcare units.

Subjects:: Fifty-two sedentary subjects with mild cognitive impairment were paired (age, sex, body mass index, and Addenbrooke's Cognitive Examination Revised score), tested, and then randomized into an intervention group ( n = 26) and a control group ( n = 26).

Intervention:: The intervention group performed strength (ankle weights, elastic bands, and dumbbells) and aerobic exercises (walking) in their communities' public spaces, twice a week (60 minutes each), during 24 weeks. The control group maintained its usual routine.

Main Measures:: Balance (Berg Balance Scale (BBS)), mobility (Timed Up and Go Test (TUG)), and depressive symptoms (Geriatric Depression Scale-15) were assessed before and after the intervention.

Results:: Before the intervention, the two groups did not differ statistically. After, the intervention group showed significant improvement ( P < 0.05) in balance (before: 53 ± 3; after: 55.1 ± 1.1 points), mobility (before: 10.7 ± 2.9 seconds; after: 8.3 ± 2 seconds), and depressive symptoms (median punctuation (interquartile range) before: 4 (1.8-6); after: 2.5 (1-4)). The control group presented a significant increase in their depressive symptoms (median before: 3.5 (2-7.3); after: 4 (2-5.3)), while their balance and mobility showed no significant modification. Small effect sizes were observed in the intervention group and control group depressive symptoms, as well as in the control group's mobility and balance. Large effect sizes were observed the intervention group's mobility and balance.

Conclusion:: Group exercises improved balance, mobility, and depressive symptoms in community-dwelling older adults with mild cognitive impairment.
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http://dx.doi.org/10.1177/0269215518815218DOI Listing
March 2019

Current Non-viral siRNA Delivery Systems as a Promising Treatment of Skin Diseases.

Curr Pharm Des 2018 ;24(23):2644-2663

School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Avenida do Cafe, s/n, 14040903, Ribeirao Preto, SP, Brazil.

Background: Gene therapy is a new approach to discover and treat many diseases. It has attracted considerable attention from researchers in the last decades. The gene therapy through RNA interference has been considered one of the most recent and revolutionary approaches used in individualized therapy. In the last years, we have witnessed the rapid development in the field of the gene silencing and knockdown by topical siRNA. Its application in gene therapy has become an attractive alternative for drug development.

Methods: This article will address topical delivery of siRNA as a promising treatment for skin disorders. An update on the advances in siRNA-based nanocarriers as a powerful therapeutic strategy for several skin diseases will be discussed giving emphasis on in vitro evaluations.

Results: Through the in-depth review of the literature on the use of siRNAs for skin diseases we realize how widespread this use is. We have also realized that nanoparticles as non-viral vectors are increasingly being explored. Skin diseases where the use of siRNA has been explored most are skin cancer (melanoma and nonmelanoma), psoriasis, vitiligo, dermatitis and leprosy. But we also report here other diseases where the use of siRNA has been growing as acne, alopecia areata, cutaneous leishmaniasis, mycoses, herpes, epidermolysis bullosa and oculocutaneous albinism. Also highlighted, the first clinical trial of siRNA for cutaneous diseases, aimed at Pathyounychia Congenita.

Conclusion: The treatment of skin diseases based on topical delivery of siRNA, which act by inhibiting the expression of target transcripts, offers many potential therapeutic advantages for suppressing genes into the skin.
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http://dx.doi.org/10.2174/1381612824666180807120017DOI Listing
October 2019

Multidrug-resistant Stenotrophomonas maltophilia: Description of new MLST profiles and resistance and virulence genes using whole-genome sequencing.

J Glob Antimicrob Resist 2018 12 20;15:212-214. Epub 2018 Jul 20.

LIM-54, Tropical Medicine Institute, Department of Infectious Diseases, University of São Paulo, Laboratory of Medical Investigation 54, Hospital Das Clínicas FMUSP, São Paulo, SP, Brazil. Electronic address:

Objectives: Stenotrophomonas maltophilia is an opportunistic pathogen that has high intrinsic and acquired antimicrobial resistance, with great genetic diversity. The aim of this study was to characterise four S. maltophilia clinical isolates displaying different susceptibility profiles using whole-genome sequencing.

Methods: The whole genomes of four clinical isolates of S. maltophilia from three patients were sequenced using Ion Torrent™ PGM technology. The isolates presented different susceptibilities to trimethoprim/sulfamethoxazole (SXT) and levofloxacin.

Results: Three new multilocus sequence typing (MLST) profiles were identified (ST144, ST172 and ST173), differing in virulence and resistance genes. The ST172 isolate had more genes related to toxins than related to motility or adhesion and had different types of efflux pumps than the other isolates. The SXT-resistant strains belonged to ST172 or ST144 and did not harbour the sul1, sul2 or dfrA resistance genes. Strains I and II, from the same patient and belonging to the same ST but differing in resistance to SXT, had all of the resistance genes searched for in common, except for the SmeABC efflux pump complex genes that were only found in the SXT-resistant strain. All strains, including the strain susceptible to levofloxacin, harboured the qnrB gene, which may question the importance of this gene in determining levofloxacin resistance in S. maltophilia.

Conclusion: Here we describe three new MLST profiles. Resistance to SXT in these strains appears to be associated with efflux pumps.
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http://dx.doi.org/10.1016/j.jgar.2018.07.009DOI Listing
December 2018

Cocrystallization as a novel approach to enhance the transdermal administration of meloxicam.

Eur J Pharm Sci 2018 Oct 20;123:184-190. Epub 2018 Jul 20.

Programa de Pós-Graduação em Farmácia, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-970, Brazil. Electronic address:

Despite its large effectiveness, the long-term oral administration of high doses of meloxicam (MLX) may lead to gastrointestinal events such as abdominal pain, diarrhea, dyspepsia, ulceration, hemorrhage, and gastrointestinal perforation. Moreover, the pH-dependent solubility of MLX makes the development of new oral formulations even more challenging. As an alternative to overcome these limitations, the transdermal delivery of this drug has been purposed. Although various physical and chemical approaches to enhance the absorption of MLX may be found in literature, the use of cocrystallization has not been reported so far. Cutaneous permeation of MLX and 1:1 meloxicam-salicylic acid cocrystal (MLX-SLC) were evaluated using Franz diffusion cells. Cocrystal was suspended in an aqueous solution and in a gel to evaluate the vehicle effect on permeation parameters. In aqueous medium, the cocrystallization showed to enhance the drug permeation coefficient from 1.38 to 2.15 × 10 cm/h. MLX-SLC generated supersaturation with respect to the drug during dissolution studies simulating the conditions in the Franz cell donor chamber. This greater amount of free drug in the solution could contribute to explain the higher transdermal absorption and shorter lag time of this system. In addition, the acidic coformer ionization led to a pH reduction from 7.4 to 5.8, which, in turn, provided an increase in the unionized species of the drug, enhancing its permeation rate. The gel containing cocrystals reduced MLX permeation rate significantly (P = 0.42 × 10 cm/h), which was attributed to its higher viscosity.
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http://dx.doi.org/10.1016/j.ejps.2018.07.038DOI Listing
October 2018

Effect of Exercise on Cognition, Conditioning, Muscle Endurance, and Balance in Older Adults With Mild Cognitive Impairment: A Randomized Controlled Trial.

J Geriatr Phys Ther 2019 Apr/Jun;42(2):E15-E22

School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil.

Background And Purpose: Mild cognitive impairment (MCI) may be a precursor to dementia; however, its progression may be prevented or slowed with exercise. This study aimed at determining the effects of group aerobic and strength training on cognition, conditioning, muscle endurance, and balance in underprivileged community-dwelling older adults with MCI.

Methods: This was a single-blind, randomized, and matched-pair controlled (gender, age, body mass index, and Addenbrooke's Cognitive Examination-Revised for MCI diagnosis) clinical trial. It was developed in 4 community centers. Fifty-two sedentary, functionally independent individuals, aged 60 years or more, with MCI were randomized into intervention group (n = 26) and control group (n = 26). Participants were tested before and after a 24-week exercise program. Sociodemographic characteristics, cognition (Mini-Mental State Examination), conditioning (2-minute stationary walk test), lower-limb endurance (30-second sit/stand test), and balance data (Functional Reach test) were collected. The intervention group walked and exercised twice weekly (60 minutes each) using ankle weights, latex resistance bands, and dumbbells. The exercise load and intensity were regularly increased on the basis of a preestablished incremental number of sets and repetitions and on the basis of the participants' correct movement execution with a given load. Data were analyzed with Pearson χ test, Fisher exact test, Student t test, Mann-Whitney U test, 2-way repeated measures analysis of variance, and the Cohen d.

Results And Discussion: Before the intervention, no significant differences were found between groups for any of the variables. Postintervention, significant differences were observed in cognition, conditioning, muscle endurance, and balance. Significant time-by-group interactions were detected in all the intergroup analyses. The improvements observed in the intervention group had medium to large effect sizes (0.35-1.15). The control group's decrease in cognition (13.9%) had a large effect size, while its Functional Reach test decrease (11.4%) had a medium effect size, with no significant change in conditioning or muscle endurance.

Conclusion: The training program improved cognitive function, muscle endurance, aerobic conditioning, and balance in older adults with MCI.
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http://dx.doi.org/10.1519/JPT.0000000000000191DOI Listing
March 2020

In Vitro and In Vivo Antitumoral Activity of Exobiopolymers from the Royal Sun Culinary-Medicinal Mushroom Agaricus brasiliensis (Agaricomycetes).

Int J Med Mushrooms 2017 ;19(9):767-775

Department of Biology, Universidade Estadual do Centro-Oeste, Guarapuava, Paraná, Brazil.

We studied antitumor activity in vitro and in vivo and partial chemical characterization of exobiopolymers (EBPs) of Agaricus brasiliensis produced by submerged cultivation. The EBPs comprised 61.2% total sugar and 22.3% total protein, and the chromatographic profile mainly identified mannose (65.5%), galactose (17.5%), and glucose (13.1%). In vitro analysis revealed a dose with antitumor effectiveness, time-dependent treatment, and 46% inhibition of solid Walker 256 tumors in rats. Metabolic changes were significant in the spleens of the animals; this is possibly related to higher immune activity triggered by the presence of EBPs in the treated group. The increase of nitric oxide production by peritoneal macrophages from animals may be related to the tumor reduction observed, because nitric oxide acts as an important effector pathway in the defense of the organism.
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http://dx.doi.org/10.1615/IntJMedMushrooms.2017024492DOI Listing
July 2018

Mapping QTLs for drought tolerance in a SEA 5 x AND 277 common bean cross with SSRs and SNP markers.

Genet Mol Biol 2017 Oct-Dec;40(4):813-823. Epub 2017 Oct 23.

Centro de Recursos Genéticos Vegetais, Instituto Agronômico (IAC), Campinas, SP, Brazil.

The common bean is characterized by high sensitivity to drought and low productivity. Breeding for drought resistance in this species involves genes of different genetic groups. In this work, we used a SEA 5 x AND 277 cross to map quantitative trait loci associated with drought tolerance in order to assess the factors that determine the magnitude of drought response in common beans. A total of 438 polymorphic markers were used to genotype the F8 mapping population. Phenotyping was done in two greenhouses, one used to simulate drought and the other to simulate irrigated conditions. Fourteen traits associated with drought tolerance were measured to identify the quantitative trait loci (QTLs). The map was constructed with 331 markers that covered all 11 chromosomes and had a total length of 1515 cM. Twenty-two QTLs were discovered for chlorophyll, leaf and stem fresh biomass, leaf biomass dry weight, leaf temperature, number of pods per plant, number of seeds per plant, seed weight, days to flowering, dry pod weight and total yield under well-watered and drought (stress) conditions. All the QTLs detected under drought conditions showed positive effects of the SEA 5 allele. This study provides a better understanding of the genetic inheritance of drought tolerance in common bean.
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http://dx.doi.org/10.1590/1678-4685-GMB-2016-0222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738610PMC
October 2017

Variability and population genetic structure in Achyrocline flaccida (Weinm.) DC., a species with high value in folk medicine in South America.

PLoS One 2017 22;12(8):e0183533. Epub 2017 Aug 22.

Department of Biological Sciences, Plant Genetics and Molecular Biology Laboratory, Universidade Estadual do Centro-Oeste, UNICENTRO, Guarapuava, Paraná, Brazil.

Better knowledge of medicinal plant species and their conservation is an urgent need worldwide. Decision making for conservation strategies can be based on the knowledge of the variability and population genetic structure of the species and on the events that may influence these genetic parameters. Achyrocline flaccida (Weinm.) DC. is a native plant from the grassy fields of South America with high value in folk medicine. In spite of its importance, no genetic and conservation studies are available for the species. In this work, microsatellite and ISSR (inter-simple sequence repeat) markers were used to estimate the genetic variability and structure of seven populations of A. flaccida from southern Brazil. The microsatellite markers were inefficient in A. flaccida owing to a high number of null alleles. After the evaluation of 42 ISSR primers on one population, 10 were selected for further analysis of seven A. flaccida populations. The results of ISSR showed that the high number of exclusive absence of loci might contribute to the inter-population differentiation. Genetic variability of the species was high (Nei's diversity of 0.23 and Shannon diversity of 0.37). AMOVA indicated higher genetic variability within (64.7%) than among (33.96%) populations, and the variability was unevenly distributed (FST 0.33). Gene flow among populations ranged from 1.68 to 5.2 migrants per generation, with an average of 1.39. The results of PCoA and Bayesian analyses corroborated and indicated that the populations are structured. The observed genetic variability and population structure of A. flaccida are discussed in the context of the vegetation formation history in southern Brazil, as well as the possible anthropogenic effects. Additionally, we discuss the implications of the results in the conservation of the species.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183533PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568751PMC
October 2017

Molecular characterization of carbapenem-resistant Klebsiella pneumoniae isolates from a university hospital in Brazil.

J Infect Dev Ctries 2017 Jun 1;11(5):379-386. Epub 2017 Jun 1.

Londrina State University, Londrina, Brazil.

Introduction: The emergence of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kpn) isolates is attracting significant attention in nosocomial infection settings. K. pneumoniae is the main pathogen that harbours blaKPC genes.

Methodology: This study evaluated 54 K. pneumoniae carbapenem-resistant isolates from patients hospitalized at the University Hospital of Londrina, between July 2009 and July 2010. The isolates were phenotypically screened for carbapenemase production and submitted for genotypic confirmation by polymerase chain reaction (PCR) for KPC, metallo-β-lactamases, OXA-48, and extended-spectrum beta-lactamase genes. The absence of outer membrane proteins (OMP) was investigated by SDS-PAGE. The susceptibility profile was determined by broth microdilution, according to Clinical and Laboratory Standards Institute protocol.

Results: All isolates were phenotypically positive for class A carbapenemase production, but negative for metallo-β-lactamase activity. PCR analysis demonstrated that all isolates carried blaKPC genes and sequencing showed that all strains belonged to KPC-2 subtype. Four strains did not show porin expression, and all isolates were resistant to ertapenem, meropenem, and imipenem. Susceptibility rates reached 35.2% for gentamicin, 85.2% for polymixyn B, 87% for colistin, and 98.1% for both tigecycline and fosfomycin. Pulsed-field gel electrophoresis showed six clones, and three of them predominated among the isolates.

Conclusions: KPC-2-producing K. pneumoniae is becoming predominant among carbapenem-resistant K. pneumoniae isolates at the hospital. The association of the enzyme KPC with other resistance determinants, such as loss of porins, may increase the severity of the situation of nosocomial infections. There is an urgent need to develop strategies for infection control and prevention.
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http://dx.doi.org/10.3855/jidc.8614DOI Listing
June 2017

Entomopathogenic nematodes in agricultural areas in Brazil.

Sci Rep 2017 04 6;7:45254. Epub 2017 Apr 6.

Departamento de Proteção Vegetal, Universidade Estadual Paulista (UNESP/FCA), Rua José Barbosa de Barros, 1780, CEP 18610-307, Botucatu, São Paulo, Brasil.

Entomopathogenic nematodes (EPNs) (Steinernematidae and Heterorhabditidae) can control pests due to the mutualistic association with bacteria that kill the host by septicemia and make the environment favorable for EPNs development and reproduction. The diversity of EPNs in Brazilian soils requires further study. The identification of EPNs, adapted to environmental and climatic conditions of cultivated areas is important for sustainable pest suppression in integrated management programs in agricultural areas of Brazil. The objective was to identify EPNs isolated from agricultural soils with annual, fruit and forest crops in Brazil. Soil samples were collected and stored in 250 ml glass vials. The nematodes were isolated from these samples with live bait traps ([Galleria mellonella L. (Lepidoptera: Pyralidae) larvae]. Infective juveniles were collected with White traps and identified by DNA barcoding procedures by sequencing the D2/D3 expansion of the 28S rDNA region by PCR. EPNs identified in agricultural areas in Brazil were Heterorhabditis amazonensis, Metarhabditis rainai, Oscheios tipulae and Steinernema rarum. These species should be considered pest biocontrol agents in Brazilian agricultural areas.
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http://dx.doi.org/10.1038/srep45254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382772PMC
April 2017

Clonality, outer-membrane proteins profile and efflux pump in KPC- producing Enterobacter sp. in Brazil.

BMC Microbiol 2017 03 17;17(1):69. Epub 2017 Mar 17.

LIM-54, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

Background: Carbapenems resistance in Enterobacter spp. has increased in the last decade, few studies, however, described the mechanisms of resistance in this bacterium. This study evaluated clonality and mechanisms of carbapenems resistance in clinical isolates of Enterobacter spp. identified in three hospitals in Brazil (Hospital A, B and C) over 7-year.

Methods: Antibiotics sensitivity, pulsed-field gel electrophoresis (PFGE), PCR for carbapenemase and efflux pump genes were performed for all carbapenems-resistant isolates. Outer-membrane protein (OMP) was evaluated based on PFGE profile.

Results: A total of 130 isolates of Enterobacter spp were analyzed, 44/105 (41, 9%) E. aerogenes and 8/25 (32,0%) E. cloacae were resistant to carbapenems. All isolates were susceptible to fosfomycin, polymyxin B and tigecycline. KPC was present in 88.6% of E. aerogenes and in all E. cloacae resistant to carbapenems. The carbapenems-resistant E. aerogenes identified in hospital A belonged to six clones, however, a predominant clone was identified in this hospital over the study period. There is a predominant clone in Hospital B and Hospital C as well. The mechanisms of resistance to carbapenems differ among subtypes. Most of the isolates co-harbored blaKPC, blaTEM and /or blaCTX associated with decreased or lost of 35-36KDa and or 39 KDa OMP. The efflux pump AcrAB-TolC gene was only identified in carbapenems-resistant E. cloacae.

Conclusions: There was a predominant clone in each hospital suggesting that cross-transmission of carbapenems-resistant Enterobacter spp. was frequent. The isolates presented multiple mechanisms of resistance to carbapenems including OMP alteration.
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http://dx.doi.org/10.1186/s12866-017-0970-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356252PMC
March 2017

Linkage and mapping of quantitative trait loci associated with angular leaf spot and powdery mildew resistance in common beans.

Genet Mol Biol 2017 Jan-Mar;40(1):109-122. Epub 2017 Feb 20.

Centro de Recursos Genéticos Vegetais, Instituto Agronômico de Campinas (IAC), Campinas, SP, Brazil.

Angular leaf spot (ALS) and powdery mildew (PWM) are two important fungi diseases causing significant yield losses in common beans. In this study, a new genetic linkage map was constructed using single sequence repeats (SSRs) and single nucleotide polymorphisms (SNPs), in a segregating population derived from the AND 277 x SEA 5 cross, with 105 recombinant inbred lines. Phenotypic evaluations were performed in the greenhouse to identify quantitative trait loci (QTLs) associated with resistance by means of the composite interval mapping analysis. Four QTLs were identified for ALS resistance. The QTL ALS11AS, linked on the SNP BAR 5054, mapped on chromosome Pv11, showed the greatest effect (R2 = 26.5%) on ALS phenotypic variance. For PWM resistance, two QTLs were detected, PWM2AS and PWM11AS, on Pv2 and Pv11, explaining 7% and 66% of the phenotypic variation, respectively. Both QTLs on Pv11 were mapped on the same genomic region, suggesting that it is a pleiotropic region. The present study resulted in the identification of new markers closely linked to ALS and PWM QTLs, which can be used for marker-assisted selection, fine mapping and positional cloning.
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http://dx.doi.org/10.1590/1678-4685-GMB-2015-0314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409766PMC
February 2017

Contributions of Rod and Cone Pathways to Retinal Direction Selectivity Through Development.

J Neurosci 2016 09;36(37):9683-95

Department of Molecular and Cell Biology and Helen Wills Neurosciences Institute, University of California, Berkeley, California 94720

Unlabelled: Direction selectivity is a robust computation across a broad stimulus space that is mediated by activity of both rod and cone photoreceptors through the ON and OFF pathways. However, rods, S-cones, and M-cones activate the ON and OFF circuits via distinct pathways and the relative contribution of each to direction selectivity is unknown. Using a variety of stimulation paradigms, pharmacological agents, and knockout mice that lack rod transduction, we found that inputs from the ON pathway were critical for strong direction-selective (DS) tuning in the OFF pathway. For UV light stimulation, the ON pathway inputs to the OFF pathway originated with rod signaling, whereas for visible stimulation, the ON pathway inputs to the OFF pathway originated with both rod and M-cone signaling. Whole-cell voltage-clamp recordings revealed that blocking the ON pathway reduced directional tuning in the OFF pathway via a reduction in null-side inhibition, which is provided by OFF starburst amacrine cells (SACs). Consistent with this, our recordings from OFF SACs confirmed that signals originating in the ON pathway contribute to their excitation. Finally, we observed that, for UV stimulation, ON contributions to OFF DS tuning matured earlier than direct signaling via the OFF pathway. These data indicate that the retina uses multiple strategies for computing DS responses across different colors and stages of development.

Significance Statement: The retina uses parallel pathways to encode different features of the visual scene. In some cases, these distinct pathways converge on circuits that mediate a distinct computation. For example, rod and cone pathways enable direction-selective (DS) ganglion cells to encode motion over a wide range of light intensities. Here, we show that although direction selectivity is robust across light intensities, motion discrimination for OFF signals is dependent upon ON signaling. At eye opening, ON directional tuning is mature, whereas OFF DS tuning is significantly reduced due to a delayed maturation of S-cone to OFF cone bipolar signaling. These results provide evidence that the retina uses multiple strategies for computing DS responses across different stimulus conditions.
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http://dx.doi.org/10.1523/JNEUROSCI.3824-15.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039248PMC
September 2016

Streptomyces lunalinharesii 235 prevents the formation of a sulfate-reducing bacterial biofilm.

Braz J Microbiol 2016 Jul-Sep;47(3):603-9. Epub 2016 Apr 19.

Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

Streptomyces lunalinharesii strain 235 produces an antimicrobial substance that is active against sulfate reducing bacteria, the major bacterial group responsible for biofilm formation and biocorrosion in petroleum reservoirs. The use of this antimicrobial substance for sulfate reducing bacteria control is therefore a promising alternative to chemical biocides. In this study the antimicrobial substance did not interfere with the biofilm stability, but the sulfate reducing bacteria biofilm formation was six-fold smaller in carbon steel coupons treated with the antimicrobial substance when compared to the untreated control. A reduction in the most probable number counts of planktonic cells of sulfate reducing bacteria was observed after treatments with the sub-minimal inhibitory concentration, minimal inhibitory concentration, and supra-minimal inhibitory concentration of the antimicrobial substance. Additionally, when the treated coupons were analyzed by scanning electron microscopy, the biofilm formation was found to be substantially reduced when the supra-minimal inhibitory concentration of the antimicrobial substance was used. The coupons used for the biofilm formation had a small weight loss after antimicrobial substance treatment, but corrosion damage was not observed by scanning electron microscopy. The absence of the dsrA gene fragment in the scraped cell suspension after treatment with the supra-minimal inhibitory concentration of the antimicrobial substance suggests that Desulfovibrio alaskensis was not able to adhere to the coupons. This is the first report on an antimicrobial substance produced by Streptomyces active against sulfate reducing bacteria biofilm formation. The application of antimicrobial substance as a potential biocide for sulfate reducing bacteria growth control could be of great interest to the petroleum industry.
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http://dx.doi.org/10.1016/j.bjm.2016.04.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927686PMC
January 2017

Descriptive analysis of the type and design of contact lenses fitted according to keratoconus severity and morphology.

Arq Bras Oftalmol 2016 Apr;79(2):82-4

Setor de Lentes de Contato e Refração, Universidade Federal de São Paulo, São Paulo, SP, Brazil.

Purpose: Keratoconus is characterized by bilateral asymmetrical corneal ectasia that leads to inferior stromal thinning and corneal protrusion. There is currently a lack of consensus regarding the most efficacious method for fitting contact lenses in patients with keratoconus, given the various topographical patterns and evolution grades observed in affected populations. The purpose of the present study was to evaluate the association between keratoconus evolution grade and topography pattern and the type and design of fitted contact lens.

Methods: We performed a retrospective analysis of contact lenses fitted in a total of 185 patients with keratoconus (325 eyes). Keratoconus was classified as either grade I, II, III, or IV based on keratometry and cone morphology (nipple, oval, globus, or indeterminate) results.

Results: A total of 325 eyes were evaluated in the present study. Of the 62 eyes classified as grade I, 66.1% were fitted with monocurve contact lenses. Of the 162 eyes classified as grade I and II, 51%, 30%, and 19% were fitted with adapted monocurve rigid gas-permeable contact lenses (RGPCL), bicurve lenses, and others lens types, respectively. Bicurve lenses were fitted in 52.1% and 62.2% of eyes classified as grade III and IV, respectively. Of the eyes classified as grade III and IV, monocurve and bicurve RGPCL were fitted in 26% and 55%, respectively. In eyes with oval keratoconus, 45%, 35%, and 20% were fitted with monocurve lenses, bicurve lenses, and other lens types, respectively. In eyes with round cones (nipple morphology), 55%, 30%, and 15% were fitted with bicurve lenses, monocurve lenses, and other lens types, respectively.

Conclusion: Monocurve RGPCL were most frequently fitted in patients with mild to moderate keratoconus and oval cones morphology, while bicurve lenses were more frequently fitted in patients with severe and advanced keratoconus. This was probably because bicurve lenses are more appropriate for round cones due to increased corneal asphericity.
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http://dx.doi.org/10.5935/0004-2749.20160025DOI Listing
April 2016

Crossover Inhibition Generates Sustained Visual Responses in the Inner Retina.

Neuron 2016 04 7;90(2):308-19. Epub 2016 Apr 7.

MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK; School of Life Sciences, University of Sussex, Brighton, BN1 9QG, UK. Electronic address:

In daylight, the input to the retinal circuit is provided primarily by cone photoreceptors acting as band-pass filters, but the retinal output also contains neuronal populations transmitting sustained signals. Using in vivo imaging of genetically encoded calcium reporters, we investigated the circuits that generate these sustained channels within the inner retina of zebrafish. In OFF bipolar cells, sustained transmission was found to depend on crossover inhibition from the ON pathway through GABAergic amacrine cells. In ON bipolar cells, the amplitude of low-frequency signals was regulated by glycinergic amacrine cells, while GABAergic inhibition regulated the gain of band-pass signals. We also provide the first functional description of a subset of sustained ON bipolar cells in which synaptic activity was suppressed by fluctuations at frequencies above ∼0.2 Hz. These results map out the basic circuitry by which the inner retina generates sustained visual signals and describes a new function of crossover inhibition.
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http://dx.doi.org/10.1016/j.neuron.2016.03.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848346PMC
April 2016

Determining Proportion of Exfoliative Vaginal Cell during Various Stages of Estrus Cycle Using Vaginal Cytology Techniques in Aceh Cattle.

Vet Med Int 2016 10;2016:3976125. Epub 2016 Feb 10.

Faculty of Veterinary Medicine, Syiah Kuala University, Banda Aceh 23111, Indonesia.

The aim of this study was to investigate the period of estrus cycle in aceh cattle, Indonesia, based on vaginal cytology techniques. Four healthy females of aceh cattle with average weight of 250-300 kg, age of 5-7 years, and body condition score of 3-4 were used. All cattle were subjected to ultrasonography analysis for the occurrence of corpus luteum before being synchronized using intramuscular injections of PGF2 alpha 25 mg. A vaginal swab was collected from aceh cattle, stained with Giemsa 10%, and observed microscopically. Period of estrus cycle was predicted from day 1 to day 24 after estrus synchronization was confirmed using ultrasonography analysis at the same day. The result showed that parabasal, intermediary, and superficial epithelium were found in the vaginal swabs collected from proestrus, metestrus, and diestrus aceh cattle. Proportions of these cells in the particular period of estrus cycle were 36.22, 32.62, and 31.16 (proestrus); 21.33, 32.58, and 46.09 (estrus); 40.75, 37.58, and 21.67 (metestrus); and 41.07, 37.38, and 21.67 (diestrus), respectively. In conclusion, dominant proportion of superficial cell that occurred in estrus period might be used as the base for determining optimal time for insemination.
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http://dx.doi.org/10.1155/2016/3976125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4764765PMC
March 2016

Contact lens fitting in a patient with Alport syndrome and posterior polymorphous corneal dystrophy: a case report.

Arq Bras Oftalmol 2016 Feb;79(1):42-3

Setor de Lentes de Contato e Refração, Universidade Federal de São Paulo, São Paulo, SP, Brazil.

Alport Syndrome is a hereditary disease that is caused by a gene mutation and affects the production of collagen in basement membranes; this condition causes hemorrhagic nephritis associated with deafness and ocular changes. The X-linked form of this disease is the most common and mainly affects males. Typical ocular findings are dot-and-fleck retinopathy, anterior lenticonus, and posterior polymorphous corneal dystrophy. Some cases involving polymorphous corneal dystrophy and corneal ectasia have been previously described. Here we present a case report of a 33-year-old female with Alport syndrome, posterior polymorphous corneal dystrophy, and irregular astigmatism, whose visual acuity improved with a rigid gas permeable contact lens.
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http://dx.doi.org/10.5935/0004-2749.20160012DOI Listing
February 2016

A Qualitative Study of Smoker Identity Among College Student Smokers.

Subst Use Misuse 2015 19;50(12):1510-7. Epub 2015 Nov 19.

a Department of Psychology , Colorado State University , Fort Collins , Colorado , USA.

Background: This research was motivated by findings that college students who smoke cigarettes often self-categorize as nonsmokers, that is, they reject the social identity of "smoker."

Objectives: The goal of the present study was to shed light on college students' smoker identities beyond the smoker/nonsmoker dichotomy.

Methods: Focus groups were conducted to investigate how college students categorize their own smoking patterns and to identify what behaviors and attitudes are associated with these different categories of smoker identities. Forty-one students from a western university participated in this study in November 2011.

Results: The focus group results indicated that there were five distinct smoker identities on campus. Light and regular smokers were the daily smoker identities present, while stress, social, and drunk smokers were the occasional smoker identities. Moreover, each of these smoker identities was defined by a unique pattern of smoking behavior, attitudes, and motives.

Conclusions/importance: These findings support the notion that there are different types of smokers, both daily and occasional, in the college population. We suggest that researchers, healthcare providers, and prevention/intervention programs may all benefit from distinguishing between these different types of smokers.
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http://dx.doi.org/10.3109/10826084.2015.1018549DOI Listing
September 2016

Molecular identification and phylogenetic analysis of Metarhabditis blumi (Nematoda: Rhabditida).

Vet Parasitol 2015 Nov 20;214(1-2):184-6. Epub 2015 Jun 20.

Biological Institute, Campinas, São Paulo, Brazil.

The species Metarhabditis blumi was diagnosed for the first time in Brazil using a molecular assay. Parasites isolated from two cattle herds from the state of Minas Gerais, southeastern Brazil, were classified as M. blumi according to their D2/D3 expansion fragments of the 28S rDNA sequence, which had a high degree of homology (100% similarity) with a M. blumi sequence deposited in GenBank (EU195965.1). The phylogenetic tree comparison also confirmed grouping of the populations evaluated in the current study as M. blumi.
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http://dx.doi.org/10.1016/j.vetpar.2015.06.014DOI Listing
November 2015

Neuron-glia signaling in developing retina mediated by neurotransmitter spillover.

Elife 2015 Aug 14;4. Epub 2015 Aug 14.

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.

Neuron-glia interactions play a critical role in the maturation of neural circuits; however, little is known about the pathways that mediate their communication in the developing CNS. We investigated neuron-glia signaling in the developing retina, where we demonstrate that retinal waves reliably induce calcium transients in Müller glial cells (MCs). During cholinergic waves, MC calcium transients were blocked by muscarinic acetylcholine receptor antagonists, whereas during glutamatergic waves, MC calcium transients were inhibited by ionotropic glutamate receptor antagonists, indicating that the responsiveness of MCs changes to match the neurotransmitter used to support retinal waves. Using an optical glutamate sensor we show that the decline in MC calcium transients is caused by a reduction in the amount of glutamate reaching MCs. Together, these studies indicate that neurons and MCs exhibit correlated activity during a critical period of retinal maturation that is enabled by neurotransmitter spillover from retinal synapses.
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http://dx.doi.org/10.7554/eLife.09590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566075PMC
August 2015

CaV3.2 KO mice have altered retinal waves but normal direction selectivity.

Vis Neurosci 2015 Jan;32:E003

Department of Molecular and Cell Biology,University of California,Berkeley,Berkeley,California.

Early in development, before the onset of vision, the retina establishes direction-selective responses. During this time period, the retina spontaneously generates bursts of action potentials that propagate across its extent. The precise spatial and temporal properties of these "retinal waves" have been implicated in the formation of retinal projections to the brain. However, their role in the development of direction selective circuits within the retina has not yet been determined. We addressed this issue by combining multielectrode array and cell-attached recordings to examine mice that lack the CaV3.2 subunit of T-type Ca2+ channels (CaV3.2 KO) because these mice exhibit disrupted waves during the period that direction selective circuits are established. We found that the spontaneous activity of these mice displays wave-associated bursts of action potentials that are altered from that of control mice: the frequency of these bursts is significantly decreased and the firing rate within each burst is reduced. Moreover, the projection patterns of the retina demonstrate decreased eye-specific segregation in the dorsal lateral geniculate nucleus (dLGN). However, after eye-opening, the direction selective responses of CaV3.2 KO direction selective ganglion cells (DSGCs) are indistinguishable from those of wild-type DSGCs. Our data indicate that although the temporal properties of the action potential bursts associated with retinal waves are important for activity-dependent refining of retinal projections to central targets, they are not critical for establishing direction selectivity in the retina.
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http://dx.doi.org/10.1017/S0952523814000364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4547621PMC
January 2015

Using motives for smoking to distinguish between different college student smoker typologies.

Psychol Addict Behav 2014 Dec;28(4):1297-304

Department of Psychology, Colorado State University.

Relatively little is known about how to categorize different types of smokers, especially occasional smokers. Because of the prevalence of occasional smoking among college students, the current study aimed to gain an understanding of the different typologies of smokers on campus. To accomplish this, a latent class analysis (LCA) was conducted using 17 motives for smoking items (N = 327). The LCA revealed that four smoker groups were present: (1) addicted smokers who endorsed smoking due to pleasure and habit/addiction; (2) stress smokers, who endorsed smoking to relax, to reduce levels of stress, and to regulate mood; (3) social smokers, who endorsed smoking because of social factors such as to fit in or because friends smoke; and (4) nonendorsing smokers, who had a low endorsement for all the items. An additional LCA with covariates revealed that age of initiation, current smoking patterns, smoker self-classification, and quit likelihood differentiated these groups of smokers whereas current age and alcohol use did not. These typologies should be considered when designing interventions for occasional smokers.
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http://dx.doi.org/10.1037/a0038355DOI Listing
December 2014

Neurodevelopment: a novel role for activity in shaping retinal circuits.

Curr Biol 2014 Oct;24(19):R964-6

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, California 94720, USA. Electronic address:

The number of synaptic inputs onto retinal bipolar cells is influenced by transmitter release from neighboring bipolar cells, implicating a new form of population-based retrograde plasticity in the development of these neural circuits.
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http://dx.doi.org/10.1016/j.cub.2014.09.002DOI Listing
October 2014

Non-multidrug-resistant, methicillin-resistant Staphylococcus aureus in a neonatal unit.

Pediatr Infect Dis J 2014 Oct;33(10):e252-9

From the *Department of Infectious Diseases and LIM-54; †Department of Infection Control, Hospital das Clínicas; ‡Department of Pediatrics; §Faculty of Public Health; ¶Department of Obstetrics; and ‖Instituto de Medicina Tropical de São Paulo, University of São Paulo, São Paulo, Brazil.

Background: In the last decade, non-multiresistant methicillin-resistant Staphylococcus aureus (NM-MRSA) has been described as an important agent in bloodstream infections in our hospital.

Methods: This prospective cohort study, conducted from February 2009 through January 2010 in the neonatal unit, evaluated 403 newborns (NB), their 382 mothers and 148 health care workers (HCW).

Results: Approximately 217 NB (54%), 187 mothers (48%) and 87 HCW (59%) were colonized by S. aureus (SA). MRSA colonization was greater among NB (15%) than mothers (4.7%) and HCW (3.4%). Although mother-to-NB transmission occurred, in most cases mothers were not responsible for NB colonization. There were 2 predominant PFGE patterns among the NB and some mothers and HCW became colonized by them. Factors significantly associated with MRSA carriage by NB were lower level of maternal schooling (risk factor: odds ratio: 2.99; 95% confidence interval: 1.10-8.07) and maternal rhinosinusitis (protective factor: odds ratio: 0.33; 95% confidence interval:0.12-0.88). Among NB who remained hospitalized for more than 72 hours, breast feeding was protective (odds ratio: 0.22; 95% confidence interval: 0.05-0.98). All the isolates were NM-MRSA, carried few virulence factors and SCCmec types IVa and type IVd predominated.

Conclusions: Although there were no cases of infection, nosocomial transmission of MRSA clearly occurred in the neonatal unit, and this highlights the need for infection control practices such as hand hygiene to prevent cross-dissemination. Other healthcare practices, which are very basic but also ample in scope, may play a role, such as general education of women and breast feeding.
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http://dx.doi.org/10.1097/INF.0000000000000435DOI Listing
October 2014

Polyclonal outbreak of bloodstream infections caused by Burkholderia cepacia complex in hematology and bone marrow transplant outpatient units.

Rev Inst Med Trop Sao Paulo 2014 Jan-Feb;56(1):71-6

Infection Control Department, Hospital das Clinicas, Universidade de São Paulo, SP, Brazil, Infection Control Department, Hospital das Clinicas, Universidade de São Paulo, SP, Brazil.

Aim: The objective was to describe an outbreak of bloodstream infections by Burkholderia cepacia complex (Bcc) in bone marrow transplant and hematology outpatients.

Methods: On February 15, 2008 a Bcc outbreak was suspected. 24 cases were identified. Demographic and clinical data were evaluated. Environment and healthcare workers' (HCW) hands were cultured. Species were determined and typed. Reinforcement of hand hygiene, central venous catheter (CVC) care, infusion therapy, and maintenance of laminar flow cabinet were undertaken. 16 different HCWs had cared for the CVCs. Multi-dose heparin and saline were prepared on counter common to both units.

Findings: 14 patients had B. multivorans (one patient had also B. cenopacia), six non-multivorans Bcc and one did not belong to Bcc. Clone A B. multivorans occurred in 12 patients (from Hematology); in 10 their CVC had been used on February 11/12. Environmental and HCW cultures were negative. All patients were treated with meropenem, and ceftazidime lock-therapy. Eight patients (30%) were hospitalized. No deaths occurred. After control measures (multidose vial for single patient; CVC lock with ceftazidime; cleaning of laminar flow cabinet; hand hygiene improvement; use of cabinet to store prepared medication), no new cases occurred.

Conclusions: This polyclonal outbreak may be explained by a common source containing multiple species of Bcc, maybe the laminar flow cabinet common to both units. There may have been contamination by B. multivorans (clone A) of multi-dose vials.
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http://dx.doi.org/10.1590/S0036-46652014000100011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4085834PMC
April 2014

Antidepressant-like responses in the forced swimming test elicited by glutathione and redox modulation.

Behav Brain Res 2013 Sep 11;253:165-72. Epub 2013 Jul 11.

Department of Biochemistry, Biological Sciences Centre, Federal University of Santa Catarina, 88040-900 Florianópolis, SC, Brazil.

Glutathione (GSH) displays a broad range of functions, among them a role as a neuromodulator with some neuroprotective properties. Taking into account that oxidative stress has been associated with depressive disorders, this study investigated the possibility that GSH, a major cell antioxidant, elicits an antidepressant-like effect in mice. Thus, GSH was administered by i.c.v. route to mice that were tested in the forced swimming test and in the tail suspension test, two predictive tests for antidepressant drug activity. In addition, GSH metabolism and the redox environment were modulated in order to study the possible mechanisms underlying the effects of GSH in the forced swimming test. The administration of GSH decreased the immobility time in the forced swimming test (300-3000nmol/site) and tail suspension test (100-1000nmol/site), consistent with an antidepressant-like effect. GSH depletion elicited by l-buthionine sulfoximine (3.2μmol/site, i.c.v.) did not alter the antidepressant-like effect of GSH, whereas the inhibition of extracellular GSH catabolism by acivicin (100nmol/site, i.c.v.) prevented the antidepressant-like effect of GSH. Moreover, a sub-effective dose (0.01nmol/site, i.c.v.) of the oxidizing agent DTNB (5,5'-dithiobis(2-nitrobenzoic acid)) potentiated the effect of GSH (100nmol/site, i.c.v.), while the pretreatment (25-100mg/kg, i.p.) with the reducing agent DTT (dl-dithiothreitol) prevented the antidepressant-like effect of GSH (300nmol/site, i.c.v.). DTNB (0.1nmol/site, i.c.v.), produced an antidepressant-like effect, per se, which was abolished by DTT (25mg/kg, i.p.). The results show, for the first time, that centrally administered GSH produces an antidepressant-like effect in mice, which can be modulated by the GSH metabolism and the thiol/disulfide reagents. The redox environment may constitute a new venue for future antidepressant-drug development.
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http://dx.doi.org/10.1016/j.bbr.2013.07.009DOI Listing
September 2013