SHORT-TERM SOCIAL ISOLATION DOES NOT REDUCE ELEVATED PLUS-MAZE EXPLORATION IN EARLY PROTEIN MALNOURISHED RATS

An increased number of visits and time spent in the open arms of the elevated plus-maze by malnourished rats has been used as indicative of lower anxiety or impulsiveness. In order to study how this behavior profile responds to an anxiogenic procedure (short-term social isolation), control (16% protein) and malnourished (6% protein) rats were socially isolated prior to the test in the maze. Litters (dam plus 6 male 2 female pups) were fed the diets from birth to 49 days of age. From 50 days on, all rats were fed a lab chow diet. Social isolation consists in removing the rats from the group and placing in individual cages for 2h before the test. During the test each rat was individually placed on the center of the maze and allowed to explore for 5 min. The results showed higher open arms exploration and lower attempts to enter open arms by the malnourished rats than by the controls. Social isolation decreased open arm exploration and increased time spent on the central platform in control animals, but had no effect on the malnourished rats. The results reinforce the lower anxiety or higher impulsiveness of malnourished rats, as well as the anxiogenic effect of social isolation in control rats. However, the malnourished rats were unresponsive to the anxiogenic effects of social isolation, indicating that protein deficiency early in life not only induces lower anxiety or higher impulsiveness in the maze, but also changes the behavior of these animals in response to another environmentally-induced procedure of anxiety (social isolation). Keywords: Early protein malnutrition, Social isolation, Anxiety, Impulsiveness, Stress, Rats.

Rhinovirus C and Respiratory Exacerbations in Children with Cystic Fibrosis

To investigate a possible role for human rhinovirus C in respiratory exacerbations of children with cystic fibrosis, we conducted microbiologic testing on respiratory specimens from 103 such patients in São Paulo, Brazil, during 2006–2007. A significant association was found between the presence of human rhinovirus C and respiratory exacerbations

Monitoring fungal burden and viability of Sporothrix spp. in skin lesions of cats for predicting antifungal treatment response

Skin lesions in feline sporotrichosis usually present a high fungal burden, making cats an important source of infection. This study evaluated the fungal burden and isolation in skin lesions of feline sporotrichosis during treatment with itraconazole (ITZ), combined with or without potassium iodide (KI). Treatment-naïve cats with culture-confirmed sporotrichosis and presenting skin ulcers were treated for up to 40 weeks with oral ITZ alone (n = 74) or combined with KI (n = 56). These cats were submitted to monthly sampling of the same lesion for mycological culture and cytopathology until healing of lesion or up to twelve weeks. The fungal burden was expressed as the mean yeast cell count in three microscopic fields from imprint smears. The fungal burden before treatment was significantly higher in cats in which the lesion persisted and in cases of treatment failure when using ITZ alone. After twelve weeks, the median fungal burden decreased to zero in both treatment protocols, suggesting a potential decrease in the risk of transmission of Sporothrix spp. from cats. These findings encourage the early treatment of feline sporotrichosis as a control measure. Moreover, the fungal burden in feline sporotrichosis lesions can be a prognostic indicator and a parameter for choosing appropriate therapeutic regimen

Histoplasmose crônica disseminada com lesões exclusivas na boca: relato de caso

We report a rare case of chronic disseminated histoplasmosis with several ulcerated lesions in the oral cavity in an alcoholic patient without human immunodeficiency virus infection, with no detectable signs and symptoms of systemic disease or extraoral manifestations. Histopathological analysis revealed chronic inflammatory process with granulomas containing Histoplasma-like organisms. The isolation of Histoplasma capsulatum provided the definitive diagnosis. Treatment with itraconazole resulted in complete remission of oral lesions. As far we aware, this is the second case report of oral histoplasmosis in an HIV negative patient described in Brazil.Reportamos um caso raro de histoplasmose crônica disseminada com diversas lesões ulceradas na cavidade oral de um paciente alcoólatra, sem o vírus da imunodeficiência humana, com nenhum outro sinal detectável ou sintomas de doença sistêmica ou manifestações extra-orais. Análise histopatológica revelou processo inflamatório crônico com granulomas contendo organismos fúngicos. O isolamento do Histoplasma capsulatum forneceu o diagnóstico definitivo. Tratamento com itraconazol resultou numa remissão completa das lesões orais. De acordo com nosso conhecimento, este é o segundo caso reportado de histoplasmose oral em um paciente HIV negativo descrito no Brasil

Towards a genome-wide transcriptogram: the Saccharomyces cerevisiae case

A genome modular classification that associates cellular processes to modules could lead to a method to quantify the differences in gene expression levels in different cellular stages or conditions: the transcriptogram, a powerful tool for assessing cell performance, would be at hand. Here we present a computational method to order genes on a line that clusters strongly interacting genes, defining functional modules associated with gene ontology terms. The starting point is a list of genes and a matrix specifying their interactions, available at large gene interaction databases. Considering the Saccharomyces cerevisiae genome we produced a succession of plots of gene transcription levels for a fermentation process. These plots discriminate the fermentation stage the cell is going through and may be regarded as the first versions of a transcriptogram. This method is useful for extracting information from cell stimuli/responses experiments, and may be applied with diagnostic purposes to different organisms

Unveiling the mechanism of action of 7α-acetoxy-6β-hydroxyroyleanone on an mrsa/visa strain: Membrane and cell wall interactions

UIDB/00100/2020 PTDC/MED-QUI/29036/2017 CEECIND/03414/2018 UIDB/04378/2020 PTDC/BIA-MIC/31645/2017 UID/DTP/04138/2019 UID/DTP/04567/2019 CBIOS/PRUID/BI1/2017 UIDB/04567/2020 UID/AMB/50017 UIDP/50017/2020 UIDB/50017/2020The number of cases of failure in the treatment of infections associated with resistant bacteria is on the rise, due to the decreasing efficacy of current antibiotics. Notably, 7α-Acetoxy-6β-hydroxyroyleanone (AHR), a diterpene isolated from different Plectranthus species, showed antibacterial activity, namely against Methicillin-resistant Staphylococcus aureus (MRSA) strains. The high antibacterial activity and low cytotoxicity render this natural compound an interesting alternative against resistant bacteria. The aim of this study is to understand the mechanism of action of AHR on MRSA, using the MRSA/Vancomycin-intermediate S. aureus (VISA) strain CIP 106760, and to study the AHR effect on lipid bilayers and on the cell wall. Although AHR interacted with lipid bilayers, it did not have a significant effect on membrane passive permeability. Alternatively, bacteria treated with this royleanone displayed cell wall disruption, without revealing cell lysis. In conclusion, the results gathered so far point to a yet undescribed mode of action that needs further investigation.publishersversionpublishe

Identification by MALDI-TOF MS of Sporothrix brasiliensis isolated from a subconjunctival infiltrative lesion in an immunocompetent patient

Sporotrichosis is a globally distributed subcutaneous fungal infection caused by dimorphic fungi belonging to the Sporothrix species complex that affects the skin of limbs predominantly, but not exclusively. A rare case of ocular sporotrichosis in an immunocompetent Brazilian patient from the countryside of Rio de Janeiro State is reported. A 68-year-old woman presented with a subconjunctival infiltrative lesion in the right eye with pre-auricular lymphadenopathy of onset 4 months ago that evolved to suppurative nodular lesions on the eyelids. Conjunctival secretion was evaluated by histopathological examination and inoculated on Sabouraud Dextrose Agar (SDA). Histopathology showed oval bodies within giant cells and other mononucleated histiocytes. Fungus grown on SDA was identified as Sporothrix sp. by morphological observations. The isolated strain was finally identified by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) associated with an in-house database enriched with reference Sporothrix complex spectra. The strain presented a MALDI spectrum with the ion peaks of the molecular mass profile of S. brasiliensis. The patient was adequately treated with amphotericin B subsequently replaced by itraconazole. Due to scars left by the suppurative process, the patient presented poor final visual acuity. The present work presents an overview of ocular sporotrichosis and discusses the diagnostic difficulty that can lead to visual sequelae in these cases.Financial support for this work by Fundação de Amparo à Pesquisa do Rio de Janeiro [FAPERJ] (Grants: INST E-26/010.001784/2016; JCNE E-26/203.301/2017), by Conselho Nacional de Desenvolvimento Científico e Tecnológico [CNPq] (Grant Proc. 409227/2016-1). This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES). MALDI-TOF MS analyses were partially developed using equipment funded by CONICYT/Chile through the project Fondequip EQM160054 2016. The Universidad de La Frontera (Temuco, Chile) partially funded this work through the Project DIUFRO PIA19-0001. Furthermore, this study was also supported by FCT under the scope of the strategic funding of UID/BIO/04469/2019 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte.info:eu-repo/semantics/publishedVersio

Superpulsed low-level laser therapy protects skeletal muscle of mdx mice against damage, inflammation and morphological changes delaying dystrophy progression.

Aim: To evaluate the effects of preventive treatment with low-level laser therapy (LLLT) on progression of dystrophy in mdx mice. Methods: Ten animals were randomly divided into 2 experimental groups treated with superpulsed LLLT (904 nm, 15 mW, 700 Hz, 1 J) or placebo-LLLT at one point overlying the tibialis anterior muscle (bilaterally) 5 times per week for 14 weeks (from 6th to 20th week of age). Morphological changes, creatine kinase (CK) activity and mRNA gene expression were assessed in animals at 20th week of age. Results: Animals treated with LLLT showed very few morphological changes in skeletal muscle, with less atrophy and fibrosis than animals treated with placebo-LLLT. CK was significantly lower (p = 0.0203) in animals treated with LLLT (864.70 U.l−1, SEM 226.10) than placebo (1708.00 U.l−1, SEM 184.60). mRNA gene expression of inflammatory markers was significantly decreased by treatment with LLLT (p<0.05): TNF-α (placebo-control = 0.51 µg/µl [SEM 0.12], - LLLT = 0.048 µg/µl [SEM 0.01]), IL-1β (placebo-control = 2.292 µg/µl [SEM 0.74], - LLLT = 0.12 µg/µl [SEM 0.03]), IL-6 (placebo-control = 3.946 µg/µl [SEM 0.98], - LLLT = 0.854 µg/µl [SEM 0.33]), IL-10 (placebo-control = 1.116 µg/µl [SEM 0.22], - LLLT = 0.352 µg/µl [SEM 0.15]), and COX-2 (placebo-control = 4.984 µg/µl [SEM 1.18], LLLT = 1.470 µg/µl [SEM 0.73]). Conclusion: Irradiation of superpulsed LLLT on successive days five times per week for 14 weeks decreased morphological changes, skeletal muscle damage and inflammation in mdx mice. This indicates that LLLT has potential to decrease progression of Duchenne muscular dystrophy

Studies on the mechanism of action of anti-tumor bis(aminophenolate) ruthenium(III) complexes

Two recently published Ru(III) comp lexes bearing ( N 2 O 2 ) tetradentate bis(aminophenolate) ligands, 20 formulated as [Ru(III)( s alan )(PPh 3 )Cl] ( where s alan is the tetradentate ligand 6,6' - (1S,2S) - 21 cyclohexane - 1,2 - diylbis(azanediyl)bis(met hylene)bis(3 - methoxyphenol) in c omplex 1 , or 2,2' - (1S,2S) - 22 cyclohexane - 1,2 - diylbis(azanediyl)bis(meth ylene)bis(4 - methoxyphenol) in c omplex 2 , and PPh 3 is 23 triphenylphosphane ) were studied herein to outline their antitumor mode of action. Previously, it was 24 found that they were very active against human ovar ian and bre a st adenocarcinoma cells (on a 72 h 25 challenge ) . In this work, the human cisplatin - sensitive o varian adeno carcinoma line A2780 was used 26 as the cell model for further studies a t a 24 h challenge . B oth complexes are active , their cytotoxicity 27 being c omparable to that of c isplatin in the same conditions. 28 A s a possible target in the cell for their action, the int eraction of 1 and 2 with DNA was assessed 29 through displacement of well - established DNA fluorescent probes ( ethidium bromide , EB, and 4',6 - 30 d iamidino - 2 - p henylindole, DAPI ) through s teady - state and time - resolved fluorescence spectroscopy . 31 The complete emission spectra were analysed globally for the binary DNA ‒ p robe and ternary DNA ‒ 32 p robe ‒ Ru(III) complex systems . B oth Ru(III) complexes can displace EB and bind to DNA with 33 similar and moderate strong affinity with conditional stability constants of log K’ = ( 5.05 ± 0.01 ) for 1 34 and log K’= ( 4.79 ± 0.01 ) for 2 . The analysis of time - domain fluorescence intensity decays confirmed 35 both qualitatively and quantitatively the model used to describe the binding and competition processes. 36 Cell studies indicated that apoptosis is t he major mechanism of cell death for both complexes , with 2 37 (the mo re active complex ) promoting that process more efficiently than 1 . Transmission electron 38 micro graphs revealed clear a lteration s on intracellular organization consistent with the induction of 39 programmed cell death processes

Liquid-Ordered Phase Formation by Mammalian and Yeast Sterols: A Common Feature With Organizational Differences

Here, biophysical properties of membranes enriched in three metabolically related sterols are analyzed both in vitro and in vivo. Unlike cholesterol and ergosterol, the common metabolic precursor zymosterol is unable to induce the formation of a liquid ordered (lo) phase in model lipid membranes and can easily accommodate in a gel phase. As a result, Zym has a marginal ability to modulate the passive membrane permeability of lipid vesicles with different compositions, contrary to cholesterol and ergosterol. Using fluorescence-lifetime imaging microscopy of an aminostyryl dye in living mammalian and yeast cells we established a close parallel between sterol-dependent membrane biophysical properties in vivo and in vitro. This approach unraveled fundamental differences in yeast and mammalian plasma membrane organization. It is often suggested that, in eukaryotes, areas that are sterol-enriched are also rich in sphingolipids, constituting highly ordered membrane regions. Our results support that while cholesterol is able to interact with saturated lipids, ergosterol seems to interact preferentially with monounsaturated phosphatidylcholines. Taken together, we show that different eukaryotic kingdoms developed unique solutions for the formation of a sterol-rich plasma membrane, a common evolutionary trait that accounts for sterol structural diversity.Peer Reviewe