Effect of saccharin on antibacterial activity of chlorhexidine gel

Although chlorhexidine is the most effective agent against dental plaque it is extremely bitter. To prepare formulations, it is necessary to use flavoring and sweetening, which can inhibit the antibacterial effect of chlorhexidine. Saccharin has been considered a compatible substance to use in chlorhexidine rinse or gel preparations; however, the effect of a range of concentrations has not been studied. To evaluate the effect of different concentrations of saccharin on the antibacterial activity of chlorhexidine gel, hydroxy-ethyl-cellulose gels containing 1.0% chlorhexidine digluconate and 0.0 to 1.0% sodium saccharin were prepared. Activity against Streptococcus mutans was evaluated using the agar diffusion method and determination of MIC values. The inhibitory zones of growth were 7.83 +/- 0.54 mm when no saccharin was added to the chlorhexidine gel and 7.75 +/- 0.50, 7.63 +/- 0.48, 6.21 +/- 0.40, 4.13 +/- 0.38, when the concentrations of saccharin in the gels were 0.02, 0.10, 0.5, and 1.0%, respectively. The range of MIC values was 1-2 micrograms/ml, with saccharin concentrations of 0%, 0.02, and 0.1%. In contrast, the MIC values were 4-8 and 8-16 micrograms/ml with saccharin concentrations of 0.5% and 1.0%, respectively. The paired "t" test showed that 0.5 and 1.0% sodium saccharin inhibit the antibacterial activity of 1% digluconate chlorhexidine gel. These in vitro results suggest that saccharin may inhibit the efficacy of chlorhexidine against mutans streptococci, depending on the concentration.Although chlorhexidine is the most effective agent against dental plaque it is extremely bitter. To prepare formulations, it is necessary to use flavoring and sweetening, which can inhibit the antibacterial effect of chlorhexidine. Saccharin has been considered a compatible substance to use in chlorhexidine rinse or gel preparations; however, the effect of a range of concentrations has not been studied. To evaluate the effect of different concentrations of saccharin on the antibacterial activity of chlorhexidine gel, hydroxy-ethyl-cellulose gels containing 1.0% chlorhexidine digluconate and 0.0 to 1.0% sodium saccharin were prepared. Activity against Streptococcus mutans was evaluated using the agar diffusion method and determination of MIC values. The inhibitory zones of growth were 7.83 +/- 0.54 mm when no saccharin was added to the chlorhexidine gel and 7.75 +/- 0.50, 7.63 +/- 0.48, 6.21 +/- 0.40, 4.13 +/- 0.38, when the concentrations of saccharin in the gels were 0.02, 0.10, 0.5, and 1.0%, respectively. The range of MIC values was 1-2 micrograms/ml, with saccharin concentrations of 0%, 0.02, and 0.1%. In contrast, the MIC values were 4-8 and 8-16 micrograms/ml with saccharin concentrations of 0.5% and 1.0%, respectively. The paired "t" test showed that 0.5 and 1.0% sodium saccharin inhibit the antibacterial activity of 1% digluconate chlorhexidine gel. These in vitro results suggest that saccharin may inhibit the efficacy of chlorhexidine against mutans streptococci, depending on the concentration1112934Embora clorexidina seja reconhecida como o agente antimicrobiano mais eficiente contra placa dental, seu gosto extremamente amargo é uma limitação nos preparos farmacêuticos. Substâncias adoçantes e flavorizantes usadas para preparar formulações podem inibir a atividade antibacteriana da clorexidina. Sacarina tem sido considerada uma substância compatível para ser usada em enxaguatórios bucais ou géis, entretanto o efeito da concentração deste adoçante não tem sido estudado. A atividade antibacteriana de géis de clorexidina a 1%, contendo sacarina de 0,0 a 1,0%, foi avaliada a partir de preparações farmacêuticas formuladas. Atividade contra Streptococcus mutans foi avaliada através da inibição do crescimento em ágar e determinação da concentração inibitória mínima (CIM). Os halos de inibição de crescimento foram de 7,83 ± 0,54 mm, na ausência de sacarina, e de 7,75 ± 0,50, 7,63 ± 0,48, 6,21 ± 0,40 e 4,13 ± 0,38 quando da presença de sacarina a 0,02, 0,10, 0,5 e 1%, respectivamente, nos géis de clorexidina a 1%. A faixa de CIM foi de 1-2 µg/ml quando da presença de 0,0, 0,02 e 0,1% de sacarina nos géis. Quando o gel de clorexidina a 1% continha sacarina a 0,5 e 1% a CIM foi de 4-8 e 8-16 µg/ml, respectivamente. Teste "t" pareado mostrou que sacarina sódica nas concentrações de 0,5 e 1% inibiu a atividade anti mutans de digluconato de clorexidina a 1% em gel. Estes resultados in vitro sugerem que sacarina pode inibir a eficácia de clorexidina contra streptococcus do grupo mutans, dependendo da concentração usad

3-200 keV spectral states and variability of the INTEGRAL Black Hole binary IGR J17464-3213

On March 2003, IBIS, the gamma-ray imager on board the INTEGRAL satellite, detected an outburst from a new source, IGR J17464-3213, that turned out to be a HEAO-1 transient, H1743-322. In this paper we report on the high energy behaviour of this BHC studied with the three main instruments onboard INTEGRAL. The data, collected with unprecedented sensitivity in the hard X-Ray range, show a quite hard Comptonised emission from 3 keV up to 150 keV during the rising part of the source outburst, with no thermal emission detectable. A few days later, a prominent soft disk multicolour component appears, with the hard tail luminosity almost unchanged: 10-9 erg*cm-2*s-1. Two months later, during a second monitoring campaign near the end of the outburst, the observed disk component was unchanged. Conversely, the Comptonised emission from the central-hot part of the disk reduced by a factor of 10. We present here its long term behaviour in different energy ranges and the combined JEM-X, SPI and IBIS wide band spectral evolution of this source.Comment: 12 pages, 4 figures, accepted for pubblication in AP

Evolutionarily conserved heterogeneous nuclear ribonucleoprotein (hnRNP) A/B proteins functionally interact with human and drosophila tar DNA-binding protein 43 (TDP-43)

Background: TDP-43 and hnRNPA1/A2 factors are implicated in neurodegeneration. Results: The human and fruit fly TDP-43 and hnRNPA1/A2 orthologs show physical, genetic, and functional interplays. Conclusion: The functional cooperation between TBPH/Hrp38 and TDP-43/hnRNP A/B is conserved throughout evolution. Significance: TBPH/Hrp38 interplay can be critical for neurodegeneration, and Drosophila is a model suitable to study the impact of this interaction. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc

Participação dos professores na escola

Na proximidade do século XXI, a Escola Portuguesa vive momentos de incerteza, de preocupação e desafio face ao futuro. Estamos perante uma sociedade que não se compadece com uma escola parada no tempo, mas, sim, exige uma escola activa, dinâmica e aberta ao meio. Pretende-se uma escola que desenvolva uma cultura de participação1, que saiba partilhar a educação com a família (principal entidade, responsável pela educação), com os trabalhadores não docentes, com a comunidade envolvente e assim todos possam contribuir para o desenvolvimento pleno e harmonioso da personalidade dos indivíduos, tornando-os cidadãos mais responsáveis e livres na sociedade. É este tipo de escola que é preconizada pela Lei de Bases (Lei nº46 / 86, de 14 de Outubro) e que exige uma mudança do Sistema Tradicional de Ensino. Por isso, a escola de hoje exige novas posturas, novas responsabilidades de todos os que nela intervêm e contribuem para uma melhoria do ensino, quer sejam professores, pais ou outros. Mas, o papel do professor, como principal impulsionador e dinamizador, é e será determinante para o sucesso de qualquer reforma do sistema educativo. O professor assume o papel primordial de dinamizador de participação e de mobilização de todos os outros intervenientes, no sentido de os levar a darem o seu contributo e a assumirem a sua cota parte de responsabilidade na educação, para que a escola possa realizar os seus objectivos. A escola é um local onde se trocam experiências, onde todos os que aí participam vivem um pouco ou grande parte da sua vida. Por isso, é imprescindível que cada um se sinta parte integrante dela. Assim, abordaremos a escola como um espaço de interacção, bem como as formas de participação dos seus intervenientes. Porque compreender a acção dos que fazem a escola leva-nos a conhecer os estatutos de cada membro e os papéis a eles associados, as normas organizacionais que orientam a interacção e o contributo de cada um para a prossecução das actividades. É na conjugação destes factores que se definem as formas de cada um estar na escola

Characterization and functional analysis of seven flagellin genes in Rhizobium leguminosarum bv. viciae. Characterization of R. leguminosarum flagellins

<p>Abstract</p> <p>Background</p> <p><it>Rhizobium leguminosarum </it>bv. <it>viciae </it>establishes symbiotic nitrogen fixing partnerships with plant species belonging to the Tribe Vicieae, which includes the genera <it>Vicia, Lathyrus, Pisum </it>and <it>Lens</it>. Motility and chemotaxis are important in the ecology of <it>R. leguminosarum </it>to provide a competitive advantage during the early steps of nodulation, but the mechanisms of motility and flagellar assembly remain poorly studied. This paper addresses the role of the seven flagellin genes in producing a functional flagellum.</p> <p>Results</p> <p><it>R. leguminosarum </it>strains 3841 and VF39SM have seven flagellin genes (<it>flaA</it>, <it>flaB, flaC, flaD, flaE, flaH</it>, and <it>flaG</it>), which are transcribed separately. The predicted flagellins of 3841 are highly similar or identical to the corresponding flagellins in VF39SM. <it>flaA, flaB, flaC</it>, and <it>flaD </it>are in tandem array and are located in the main flagellar gene cluster. <it>flaH </it>and <it>flaG </it>are located outside of the flagellar/motility region while <it>flaE </it>is plasmid-borne. Five flagellin subunits (FlaA, FlaB, FlaC, FlaE, and FlaG) are highly similar to each other, whereas FlaD and FlaH are more distantly related. All flagellins exhibit conserved amino acid residues at the N- and C-terminal ends and are variable in the central regions. Strain 3841 has 1-3 plain subpolar flagella while strain VF39SM exhibits 4-7 plain peritrichous flagella. Three flagellins (FlaA/B/C) and five flagellins (FlaA/B/C/E/G) were detected by mass spectrometry in the flagellar filaments of strains 3841 and VF39SM, respectively. Mutation of <it>flaA </it>resulted in non-motile VF39SM and extremely reduced motility in 3841. Individual mutations of <it>flaB </it>and <it>flaC </it>resulted in shorter flagellar filaments and consequently reduced swimming and swarming motility for both strains. Mutant VF39SM strains carrying individual mutations in <it>flaD, flaE, flaH</it>, and <it>flaG </it>were not significantly affected in motility and filament morphology. The flagellar filament and the motility of 3841 strains with mutations in <it>flaD </it>and <it>flaG </it>were not significantly affected while <it>flaE </it>and <it>flaH </it>mutants exhibited shortened filaments and reduced swimming motility.</p> <p>Conclusion</p> <p>The results obtained from this study demonstrate that FlaA, FlaB, and FlaC are major components of the flagellar filament while FlaD and FlaG are minor components for <it>R. leguminosarum </it>strains 3841 and VF39SM. We also observed differences between the two strains, wherein FlaE and FlaH appear to be minor components of the flagellar filaments in VF39SM but these flagellin subunits may play more important roles in 3841. This paper also demonstrates that the flagellins of 3841 and VF39SM are possibly glycosylated.</p

7-Nitroindazole reduces L-DOPA-induced dyskinesias in non-human Parkinsonian primate

©2023. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Submitted, Accepted, Published, version of a Published Work that appeared in final form in Open Biology. To access the final edited and published work see https://doi.org/10.1098/rsob.22037

Exploiting the therapeutic potential of ready-to-use drugs: Repurposing antibiotics against amyloid aggregation in neurodegenerative diseases

Neurodegenerative diseases are chronic and progressive disorders that affect specific regions of the brain, causing gradual disability and suffering that results in a complete inability of patients to perform daily functions. Amyloid aggregation of specific proteins is the most common biological event that is responsible for neuronal death and neurodegeneration in various neurodegenerative diseases. Therapeutic agents capable of interfering with the abnormal aggregation are required, but traditional drug discovery has fallen short. The exploration of new uses for approved drugs provides a useful alternative to fill the gap between the increasing incidence of neurodegenerative diseases and the long-term assessment of classical drug discovery technologies. Drug re-profiling is currently the quickest possible transition from bench to bedside. In this way, experimental evidence shows that some antibiotic compounds exert neuroprotective action through anti-aggregating activity on disease-associated proteins. The finding that many antibiotics can cross the blood-brain barrier and have been used for several decades without serious toxic effects makes them excellent candidates for therapeutic switching towards neurological disorders. The present review is, to our knowledge, the first extensive evaluation and analysis of the anti-amyloidogenic effect of different antibiotics on well-known disease-associated proteins. In addition, we propose a common structural signature derived from the antiaggregant antibiotic molecules that could be relevant to rational drug discovery.Fil: Socias, Sergio Benjamin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Biológica; ArgentinaFil: González Lizarraga, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Biológica; ArgentinaFil: Avila, Cesar Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Biológica; ArgentinaFil: Vera Ocampo, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Biológica; ArgentinaFil: Acuña, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Biológica; Argentina. Centre National de la Recherche Scientifique; Francia. Universite de la Sorbona Nouvelle; FranciaFil: Sepúlveda Díaz, Julia E.. Universite de la Sorbona Nouvelle; Francia. Centre National de la Recherche Scientifique; FranciaFil: del Bel Belluz Guimaraes, Elaine. Universidade de Sao Paulo; BrasilFil: Raisman Vozari, Rita. Universite de la Sorbona Nouvelle; Francia. Centre National de la Recherche Scientifique; FranciaFil: Chehin, Rosana Nieves. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Biológica; Argentin

First Results from the IBIS/ISGRI Data Obtained During the Galactic Plane Scan. II. The Vela Region

We report on INTEGRAL/IBIS observations of the Vela region during a Galactic Plane Scan (hereafter GPS) presenting the IBIS in-flight performances during these operations. Among all the known sources in the field of view we clearly detect 4U 0836-429, Vela X-1, Cen X-3, GX 301-2, 1E 1145.1-6141, and H0918-549 in the 20-40 keV energy range. Only Vela X-1 and GX 301-2 are detected in the 40-80 keV energy range, and no sources are visible above. We present the results of each individual observation (~2200 s exposure), as well as those from the mosaic of these scans.Comment: 4 pages, 3 color figures, accepted for publication in the INTEGRAL special edition of A&A Letter

IVIg and LPS Co-stimulation Induces IL-10 Production by Human Monocytes, Which Is Compromised by an FcγRIIA Disease-Associated Gene Variant

Intravenous Immunoglobulin (IVIg) is used to treat autoimmune or inflammatory diseases, but its mechanism of action is not completely understood. We asked whether IVIg can induce interleukin-10 (IL-10) and reduce pro-inflammatory cytokine production in human monocytes, and whether this response is reduced in monocytes from people with an Fcγ receptor IIA (FcγRIIA) gene variant, which is associated with increased risk of inflammatory diseases and poor response to antibody-based biological therapy. IVIg increased IL-10 production and reduced pro-inflammatory cytokine production in response to bacterial lipopolysaccharide (LPS), which required FcγRI and FcγRIIB and activation of MAPKs, extracellular signal-regulated kinase 1/2 (ERK1/2), and p38. IL-10 production was lower and pro-inflammatory cytokine production was higher in monocytes from people with the FcγRIIA risk variant and the risk variant prevented IL-10 production in response to (IVIg+LPS). Finally, we show that IVIg did not induce MAPK activation in monocytes from people with the risk variant. Our results demonstrate that IVIg can skew human monocytes to an anti-inflammatory, IL-10-producing activation state, which is compromised in monocytes from people with the FcγRIIA risk variant. This research has profound implications for the use of IVIg because 25% of the population is homozygous for the FcγRIIA risk variant and its efficacy may be reduced in those individuals. In addition, this research may be useful to develop new therapeutic strategies to replace IVIg by cross-linking FcγRIs and FcγRIIBs to promote anti-inflammatory macrophage activation, independent of the FcγRIIA genotype

Differential association between S100A4 levels and insulin resistance in prepubertal children and adult subjects with clinically severe obesity

Objectives: S100A4 has been recently identified as an adipokine associated with insulin resistance (IR) in adult subjects with obesity. However, no data about its levels in children with obesity and only a few approaches regarding its potential mechanism of action have been reported. To obtain a deeper understanding of the role of S100A4 in obesity, (a) S100A4 levels were measured in prepubertal children and adult subjects with and without obesity and studied the relationship with IR and (b) the effects of S100A4 in cultured human adipocytes and vascular smooth muscle cells (VSMCs) were determined. Methods: Sixty-five children (50 with obesity, age 9.0 ±1.1 years and 15 normal weight, age 8.4 ±0.8 years) and fifty-nine adults (43 with severe obesity, age 46 ±11 years and 16 normal weight, age 45 ±9 years) were included. Blood from children and adults and adipose tissue samples from adults were obtained and analysed. Human adipocytes and VSMC were incubated with S100A4 to evaluate their response to this adipokine. Results: Circulating S100A4 levels were increased in both children (P =.002) and adults (P <.001) with obesity compared with their normal-weight controls. In subjects with obesity, S100A4 levels were associated with homeostatic model assessment-insulin resistance (HOMA-IR) in adults (βstd =.42, P =.008) but not in children (βstd =.12, P =.356). Human adipocytes were not sensitive to S100A4, while incubation with this adipokine significantly reduced inflammatory markers in VSMC. Conclusions: Our human data demonstrate that higher S100A4 levels are a marker of IR in adults with obesity but not in prepubertal children. Furthermore, the in vitro results suggest that S100A4 might exert an anti-inflammatory effect. Further studies will be necessary to determine whether S100A4 can be a therapeutic target for obesity