Different outcomes of neonatal and adult Zika virus infection on startle reflex and prepulse inhibition in mice.

Zika virus (ZIKV) infection causes severe neurological consequences in both gestationally-exposed infants and adults. Sensorial gating deficits strongly correlate to the motor, sensorial and cognitive impairments observed in ZIKV-infected patients. However, no startle response or prepulse inhibition (PPI) assessment has been made in patients or animal models. In this study, we identified different outcomes according to the age of infection and sex in mice: neonatally infected animals presented an increase in PPI and delayed startle latency. However, adult-infected male mice presented lower startle amplitude, while a PPI impairment was observed 14 days after infection in both sexes. Our data further the understanding of the functional impacts of ZIKV on the developing and mature nervous system, which could help explain other behavioral and cognitive alterations caused by the virus. With this study, we support the startle reflex testing in ZIKV-exposed patients, especially infants, allowing for early detection of functional neuromotor damage and early intervention.

New insights into pharmacological profile of LASSBio-579, a multi-target N-phenylpiperazine derivative active on animal models of schizophrenia.

Previous behavioral and receptor binding studies on N-phenylpiperazine derivatives by our group indicated that LASSBio-579, LASSBio-580 and LASSBio-581 could be potential antipsychotic lead compounds. The present study identified LASSBio-579 as the most promising among the three compounds, since it was the only one that inhibited apomorphine-induced climbing (5 mg/kg p.o.) and apomorphine-induced hypothermia (15 mg/kg p.o.). Furthermore, LASSBio-579 (0.5 mg/kg p.o.) was effective in the ketamine-induced hyperlocomotion test and prevented the prepulse inhibition deficits induced by apomorphine, DOI and ketamine with different potencies (1 mg/kg, 0.5 mg/kg and 5 mg/kg p.o., respectively). LASSBio-579 also induced a motor impairment, catalepsy and a mild sedative effect but only at doses 3-120 times higher than those with antipsychotic-like effects. In addition, LASSBio-579 (0.5 and 1 mg/kg p.o.) reversed the catalepsy induced by WAY 100,635, corroborating its action on both dopaminergic and serotonergic neurotransmission and pointing to the contribution of 5-HT(1A) receptor activation to its pharmacological profile. Moreover, co-administration of sub-effective doses of LASSBio-579 with sub-effective doses of clozapine or haloperidol prevented the apomorphine-induced climbing without induction of catalepsy. In summary, our results characterize LASSBio-579 as a multi-target ligand active in pharmacological animal models of schizophrenia, confirming that this compound could be included in development programs aiming at a new drug for treating schizophrenia.

Assessment of Salvia officinalis(L) hydroalcoholic extract for possible use in cosmetic formulation as inhibitor of pathogens in the skin / Avaliação do extrato hidroalcoólico de Salvia officinalis(L) para possível uso em formulações cosméticas como inibidor de patógenos da pele

Salvia officinalis (L.), or common sage, is an aromatic herb that has been used in medicine and cooking since ancient times and has been investigated for the treatment of various diseases, especially infections and skin inflammation. We conducted phytochemical prospecting and quality control with hydroalcoholic extracts of dried sage, to identify active compounds in the plant. The aim was to assess antibacterial and antifungal activity against Staphylococcus aureus, Streptococcus agalactiae, Candida albicans and Candida tropicalis. Antimicrobial susceptibility was investigated in vitro by agar-overlay and well-diffusion techniques, in which disc and well were used. Salvia officinalis (L.) was not effective against Streptococcus agalactiae, Candida albicans or Candida tropicalis, but best results were observed for antibacterial activity against Staphylococcus aureus. Considering the results of the inhibition tests presented here, we suggest that cosmetic formulations containing Salvia officinalis (L.) could contribute to inhibitor of pathogens in the skin microbiota.

A Salvia officinalis (L.) é uma planta com uso difundido, utilizada no tratamento de diversas patologias, principalmente para infecções e inflamações cutâneas. Neste trabalho foi realizada prospecção fitoquímica e controle de qualidade com a planta seca e extrato hidroalcoólico para identificação dos compostos ativos da sálvia, tendo como finalidade comprovar sua atividade antibacteriana e antifúngica frente à Staphylococcus aureus, Streptococcus agalactiae Candida albicans e Candida tropicalis. Os métodos de escolha para avaliação in vitro foram ensaios de sensibilidade antimicrobiana por difusão em ágar com discos e cilindros. Dentre os ensaios realizados a sálvia não se mostrou efetiva para Streptococcus agalactiae, Candida albicans e Candida tropicalis, sendo o melhor resultado obtido com Staphylococcus aureus, em que se pode verificar-se atividade antibacteriana. Diante dos resultados obtidos, propôs-se uma formulação de sabonete líquido com extrato hidroalcoólico de Salvia officinalis (L.), para atuar na higiene da pele.

Design of new dopamine D2 receptor ligands: biosynthesis and pharmacological evaluation of the hydroxylated metabolite of LASSBio-581.

LASSBio-581 is a N-phenylpiperazine derivative designed for the treatment of schizophrenia. In this study, four strains of filamentous fungi were screened for their capabilities to biotransform LASSBio-581. Cunninghamella echinulata ATCC 9244 was chosen to scale up the biosynthesis of the p-hydroxylated metabolite of LASSBio-581. The chemical structure of the metabolite was confirmed by NMR, LC-MS and X-ray crystallography. Binding studies performed on brain homogenate indicated that the p-hydroxylated metabolite can be considered more selective for dopamine receptors than LASSBio-581, and, therefore, can be used to design new selective dopamine inhibitors.