Antibacterial effect, efflux pump inhibitory (NorA, TetK and MepA) of Staphylococcus aureus and in silico prediction of α, β and δ-damascone compounds

Objective: The present study aimed to evaluate the antibacterial effect and inhibitory capacity against NorA, TetK and MepA efflux pump of Staphylococcus aureus multiresistant by in vitro and in silico approach of α, β and δ-damascone compounds. Results: The compounds α, β and δ-damascone showed a clinically relevant effect against S. aureus ATCC 6538 standard strain. A modulating effect was also observed in association with antibiotics against MDR strains. Regarding the inhibition of the efflux pump, the compounds showed a modulating effect with antibiotics, against SA-1199, SA-1199B, SA IS-58 and K2068. Only δ-damascone demonstrated an efflux pump inhibitory effect. Regarding ADME properties, α, β and δ-damascone showed similar physicochemical properties with good pharmacokinetic characteristics, such as lipophilicity, oral bioavailability and low toxicity. In addition, they exhibited the binding energy and Ligand Efficiency (LE) −81.17 (5.4), −77.48(-5.4) and −64.55 (-5.1), which shows good interactions with the critical residues of the MepA receptor. Conclusions: From the results it is concluded that the compounds α, β and δ-damascone do not have antibacterial activity, but show a modulating effect in association with antibiotics, as well as not showing direct activity on the efflux pump, but they do have a modulating effect with antibiotics and with EtBr (α and β-damascone)

Clinical and epidemiological aspects of microcephaly in the state of Piauí, northeastern Brazil, 2015-2016

O artigo encontra-se em acesso aberto para download no site do Editor e do Scielo.Submitted by Sandra Infurna ([email protected]) on 2019-10-26T14:50:11Z No. of bitstreams: 1 JessicaPSantos_FilipeACCosta_etal_IOC_2109.pdf: 1780086 bytes, checksum: bc5a0af6fd21bec1dfa9dd1735fffa1c (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-10-26T15:12:33Z (GMT) No. of bitstreams: 1 JessicaPSantos_FilipeACCosta_etal_IOC_2109.pdf: 1780086 bytes, checksum: bc5a0af6fd21bec1dfa9dd1735fffa1c (MD5)Made available in DSpace on 2019-10-26T15:12:33Z (GMT). No. of bitstreams: 1 JessicaPSantos_FilipeACCosta_etal_IOC_2109.pdf: 1780086 bytes, checksum: bc5a0af6fd21bec1dfa9dd1735fffa1c (MD5) Previous issue date: 2019Governo do Estado do Piauí. Centro Regional de Referência Regional em Mocrocefalia. Teresina, PI, Brasil.Governo do Estado do Piauí. Centro Regional de Referência Regional em Mocrocefalia. Teresina, PI, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Governo do Estado do Piauí. Centro Regional de Referência Regional em Microcefalia. Teresina, PI, Brasil.Governo do Estado do Piauí. Centro Regional de Referência Regional em Microcefalia. Teresina, PI, Brasil.Governo do Estado do Piauí. Centro Regional de Referência Regional em Microcefalia. Teresina, PI, Brasil.Governo do Estado do Piauí. Centro Regional de Referência Regional em Microcefalia. Teresina, PI, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Escritório Regional Piauí. Teresina, PI, Brasil.Universidade Federal do Rio de Janeiro. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Escritório Regional Piauí. Teresina, PI, Brasil.Objetivos: Descrever os aspectos da epidemia de microcefalia no Estado do Piauí. Métodos: Foram incluídos todos os casos de microcefalia congênita confirmados no estado entre 2015-2016 (n = 100). Os formulários de investigac¸ão do Centro Regional de Referência em Microcefalia foram analisados. Os casos descartados (n = 63) foram usados como grupo de comparação. Resultados: Em outubro, novembro e dezembro de 2015, as taxas de incidência atingiram 4,46, 6,33 e 3,86/1.000 nascidos vivos, respectivamente; 44 casos foram relatados na capital do estado. Entre as mães de casos confirmados e descartados, a frequência de erupção cutânea durante a gravidez foi 50/97 (51,5%) e 8/51 (15,7%), respectivamente (p < 0,001); 33 casos confirmados (35,9%) apresentaram um escore z de perímetro cefálico entre -2 e -3, 23 (25%) entre -3 e -4 e 8 (8,7%) apresentaram escore z inferior a -4. As tomografias computadorizadas cerebrais revelaram calcificações em 78/95 (82,1%) dos casos. Lisencefalia, hidrocefalia e agenesia do corpo caloso também foram observadas com mais frequência. Os achados oftalmológicos incluíram rarefação e atrofia do epitélio pigmentar da retina. Foram observadas ausência de emissões otoacústicas em 21/70 casos. Um recém-nascido também apresentou atrofia muscular dos membros inferiores. Não houve diferenc¸as significativas nas taxas de vacinação para gripe, vacina difteria tétano e coqueluche acelular e hepatite B em qualquer grupo. Conclusões: O Estado do Piauí, como outros na região Nordeste, enfrentou, entre 2015 e 2016, uma epidemia de microcefalia congênita, supostamente relacionada à infecção congênita pelo vírus Zika, mais intensa na capital. Os desafios atuais incluem melhora do controle de vetores, pesquisa básica, ampliação de ferramentas de diagnóstico para exame pré-natal do vírus Zika, vacinas e cuidados de saúde para crianças afetadas.Objectives: To describe aspects of the microcephaly epidemic in the state of Piauí. Methods: All cases of congenital microcephaly confirmed in the state between 2015 and 2016 were included (n = 100). Investigation forms of the Regional Reference Center for Microcephaly were reviewed. Discarded cases (n = 63) were used as a comparison group. Results: In October, November, and December 2015 incidence rates reached 4.46, 6.33 and 3.86/1000 live births, respectively; 44 cases were reported in the state capital. Among the mothers of confirmed and discarded cases, the frequency of skin rash during pregnancy was 50/97 (51.5%) and 8/51 (15.7%), respectively (p < 0.001); 33 confirmed cases (35.9%) had a head circumference z-score between −2 and −3, 23 (25%) between −3 and −4, and 8 (8.7%) had a z-score of less than −4. Head computer tomography scans revealed calcifications in 78/95 (82.1%) cases. Lissencephaly, hydrocephalus and agenesis of the corpus callosum were also frequently observed. Ophthalmic findings included retinal pigment epithelium rarefaction and atrophy. Absence of otoacoustic emissions was observed in 21/70 cases. One newborn also presented lower limb muscle atrophy. There were no significant differences in vaccination rates for influenza, diphtheria-tetanus-acellular pertussis, and hepatitis B in either group. Conclusions: The state of Piauí, like others in the northeastern region, faced an epidemic of congenital microcephaly between 2015 and 2016, presumably related to congenital Zika virus infection, more intense in the capital. Current challenges include the improvement of vector control, basic research, scaling-up of diagnostic tools for pre-natal screening of Zika virus, vaccines, and health care for affected children

Mechanisms of Actions Involved in The Antinociceptive Effect of Estragole and its &beta;-Cyclodextrin Inclusion Complex in Animal Models

(1) Background: estragole is a monoterpene found in the essential oils of several aromatic plants, which can be used for several pharmacological activities. The aim of this study was to evaluate the antinociceptive effect of estragole (Es) and its &beta;-cyclodextrins inclusion complex (Es/&beta;-CD). (2) Methods: the effects of Es and Es/&beta;-CD on the central nervous system (CNS) were evaluated through open field and rota-rod assays, and the antinociceptive effect in formalin models, abdominal writhing induced by acetic acid, hot plate, tail flick test and plantar mechanical hyperalgesia. (3) Results: Es and Es/&beta;-CD showed no alterations on the CNS evaluated parameters and the results suggested there was an antinociceptive action in the formalin, abdominal writhing, hot plate, tail flick tests and plantar mechanical hyperalgesia, proposing the involvement of the nitric oxide, glutamatergic signaling pathways, cyclic guanosine monophosphate and vanilloid pathways. (4) Conclusion: the results suggest that Es and Es/&beta;-CD have a promising antinociceptive potential as a possible alternative for the pharmacological treatment of pain, also showing that the encapsulation of Es in &beta;-cyclodextrins probably improves its pharmacological properties, since the complexation process involves much lower amounts of the compound, contributing to better bioavailability and a lower probability of adverse effect development

<i>Ximenia americana</i> L.: Chemical Characterization and Gastroprotective Effect

Ximenia americana L., popularly known in Brazil as “ameixa do-mato, ameixa-brava, and ameixa-do-sertão,” is widely used in folk medicine to treat several intestinal disorders. The present study assessed the potential mechanisms of action underlying the gastroprotective activity of the hydroethanolic extract of Ximenia americana L. (EHXA) stem bark. The acute toxicity of EHXA was estimated, and later, the gastroprotective effect in mice was assessed through acute models of gastric lesions induced by acidified or absolute ethanol and indomethacin, where the following mechanisms were pharmacologically analyzed: the involvement of prostaglandins (PG), histamine (H2) receptors, ATP-dependent potassium channels, sulfhydryl groups (SH), α2 adrenergic receptors, nitric oxide (NO), myeloperoxidase (MPO), gastric mucus production, and acetylcholine-mediated intestinal motility. Regarding toxicity, EHXA did not cause deaths or signs of toxicity (LD50 greater than or equal to 2000 mg/kg/p.o.). When the gastroprotective effect was assessed, EHXA (50, 100, and 200 mg/kg/p.o.) reduced the rate of lesions induced by acidified ethanol by 65.63; 53.66, and 58.02% in absolute ethanol at 88.91, 78.82, and 74.68%, respectively, when compared to the negative control group. In the indomethacin-induced gastric injury model, the reductions were 84.69, 55.99, 55.99, and 42.50%, respectively. The study revealed that EHXA might stimulate mucus production and reduce intestinal motility through SH groups, NO production, and activation of α2 adrenergic receptors. The results indicated that EHXA had significant gastroprotective activity in the evaluated models. However, further investigation is required to elucidate the cellular and molecular events underlying the action of EHXA components and to correlate them with the modulation of the signaling pathways, as demonstrated by the current pharmacological approach. Therefore, the results demonstrated in the present study, as well as previously reported findings, support the recommendation of using this species in traditional communities in Brazil