Anti-inflammatory effect of MAPK phosphatase-1 local gene transfer in inflammatory bone loss

Alveolar bone loss associated with periodontal diseases is the result of osteoclastogenesis induced by bacterial pathogens. The mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) is a critical negative regulator of immune response as a key phosphatase capable of dephosphorylating activated MAPKs. In this study, rat macrophages transduced with recombinant adenovirus (Ad.)MKP-1 specifically dephosphorylated activated MAPKs induced by lipopolysaccharide (LPS) compared with control cells. Bone marrow macrophages from MKP-1 knockout (KO) mice exhibited higher interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, and select chemokine compared with wild-type (WT) mice when stimulated by LPS. In addition, bone marrow cultures from MKP-1 KO mice exhibited significantly more osteoclastogenesis induced by LPS than when compared with WT mice. Importantly, MKP-1 gene transfer in bone marrow cells of MKP-1 KO mice significantly decreased IL-6, IL-10, TNF-α and chemokine levels, and formed fewer osteoclasts induced by LPS than compared with control group of cells. Furthermore, MKP-1 gene transfer in an experimental periodontal disease model attenuated bone resorption induced by LPS. Histological analysis confirmed that periodontal tissues transduced with Ad. MKP-1 exhibited less infiltrated inflammatory cells, less osteoclasts and less IL-6 than compared with rats of control groups. These studies indicate that MKP-1 is a key therapeutic target to control of inflammation-induced bone loss.

Effect of light-curing on the antibacterial activity of dentin bonding agents

Aim: This study evaluated the effect of light-activation on the antibacterial activity of dentin bonding systems. Methods: Inocula of Streptococcus mutans and Lactobacillus casei cultures were spread on the surface of BHI agar and the materials were applied and subjected or not to light-activation. Zones of bacterial growth inhibition around the discs were measured. Results: Excite, Single Bond and the bond of Clearfil SE Bond (SE) and Clearfil Protect Bond (CP) did not show any antibacterial activity. The strongest inhibitory activity was observed for the primers of CP and Prompt (PR) against S. mutans and the primers of SE and PB against L. casei. Conclusion: Light-activation significantly reduced or suppressed the antibacterial activity of the initially active uncured dentin bonding systems

Ph and antimicrobial activity of portland cement associated with different radiopacifying agents

The aim of this study was to evaluate the antimicrobial activity and pH changes induced by Portland cement (PC) alone and in association with radiopacifiers. Methods. The materials tested were pure PC, PC + bismuth oxide, PC + zirconium oxide, PC + calcium tungstate, and zinc oxide and eugenol cement (ZOE). Antimicrobial activity was evaluated by agar diffusion test using the following strains: Micrococcus luteus, Streptococcus mutans, Enterococcus faecalis, Pseudomonas aeruginosa, and Candida albicans. After 24 hours of incubation at 37°C, inhibition of bacterial growth was observed and measured. For pH analysis, material samples (n=10) were placed in polyethylene tubes and immersed in 10 mL of distilled water. After 12, 24, 48, and 72 hours, the pH of the solutions was determined using a pH meter. Results. All microbial species were inhibited by the cements evaluated. All materials composed of PC with radiopacifying agents promoted pH increase similar to pure Portland cement. ZOE had the lowest pH values throughout all experimental periods. Conclusions. All Portland cement-based materials with the addition of different radiopacifiers (bismuth oxide, calcium tungstate, and zirconium oxide) presented antimicrobial activity and pH similar to pure Portland cement.

Terminalia catappa L.: A medicinal plant from the Caribbean pharmacopeia with anti-Helicobacter pylori and antiulcer action in experimental rodent models

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antibacterial activity of alkyl gallates is a combination of direct targeting of FtsZ and permeabilization of bacterial membranes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Eferocitose na presença de PAMP estimula ativação de macrófagos de perfil misto M1/M2

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of light-activation on the antibacterial activity of dentin bonding agents

Aim: This study evaluated the effect of light-activation on the antibacterial activity of dentin bonding systems. Methods: Inocula of Streptococcus mutans and Lactobacillus casei cultures were spread on the surface of BHI agar and the materials were applied and subjected or not to light-activation. Zones of bacterial growth inhibition around the discs were measured. Results: Excite, Single Bond and the bond of Clearfil SE Bond (SE) and Clearfil Protect Bond (CP) did not show any antibacterial activity. The strongest inhibitory activity was observed for the primers of CP and Prompt (PR) against S. mutans and the primers of SE and PB against L. casei. Conclusion: Light-activation significantly reduced or suppressed the antibacterial activity of the initially active uncured dentin bonding systems.

Prospecção de substâncias anti histoplasma capsulatum nas formas planctônica e biofilme e análise proteômica

Pós-graduação em Biociências e Biotecnologia Aplicadas à Farmácia - FCFAR

Medicamentos anti-hipertensivos na gestação e puerpério

Pregnancy toxemia is a multisystemic disease, which occurs mainly at the end of pregnancy, characterized by clinical manifestations such as hypertension, edema and proteinuria. It is the most commonly occurred medical complication in pregnancies and the main cause for perinatal and maternal morbimortalities. The purpose of this article is to review the main aspects concerning the use of antihypertensive agents during pregnancy and puerperium. The data has been collected from Pubmed and Bireme, from 2006 to 2010 using the words “anti-hipertensivo e gravidez” and “antihypertensive and pregnancy”. The knowledge regarding hypertension during pregnancy and its therapy is evolving; the search for medication that could protect the mother from acute dangers and to ensure a healthy newborn must be the focus. Evidence is still lacking regarding the best therapy, beginning period, duration and results. In spite of the pharmacological advances, there are still no drugs completely exempt of compromises to the mother and the conceptus.

Endophytic microorganisms isolated from coffee leaves, roots and branches as plant growth promoters and biocontrol agents of coffee leaf rust

Suppression of plant diseases and growth promotion due to the action of endophytic microorganisms has been demonstrated in several pathosystems. Experiments under controlled conditions involving 234 endophytic bacteria and fungi isolated from coffee leaves, roots and branches were conducted with the objective of evaluating the germination inhibition of Hemileia vastatrix urediniospores, the control of coffee leaf rust development in tests with leaf discs and on plastic bags seedling, and to promote growth of coffee seedlings. None of the fungal isolates induced plant growth or reduced disease severity. The bacterial isolates (identified by the fatty acids profile analysis) 85G (Escherichia fergusonii), 161G, 163G, 160G, 150G (Acinetobacter calcoaceticus) and 109G (Salmonella enterica) increased plant growth, the maximum being induced by 85G. This isolate produced in vitro phosphatase and indol acetic acid. In assay to control rust on coffee leaf disc, nine bacterial isolates, 64R, 137G, 3F (Brevibacillus choshinensis), 14F (Salmonella enterica), 36F (Pectobacterium carotovorum), 109G (Bacillus megaterium), 115G (Microbacterium testaceum), 116G and 119G (Cedecea davisae) significantly reduced disease severity, when applied 72 or 24h before challenging with the pathogen. In seedling tests most disease severity reduction was achieved by the isolates 109G and 119G. There was no correspondence between the organisms that promoted seedling growth and those that reduced rust severity on seedlings or leaf discs.

Avaliação da atividade anti-hRSV da quercetina e seus derivados acetilados

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

In vitro Metabolism of Grandisin, a Lignan with Anti-chagasic Activity

Tetrahydrofuran lignans represent a well-known group of phenolic compounds capable of acting as antiparasitic agents. In the search for new medicines for the treatment of Chagas disease, one promising compound is grandisin which has shown significant activity on trypomastigote forms of Trypanosoma cruzi. In this work, the in vitro metabolism of grandisin was studied in the pig cecum model and by biomimetic phase I reactions, aiming at an ensuing a preclinical pharmacokinetic investigation. Although grandisin exhibited no metabolization by the pig microbiota, one putative metabolite was formed in a biomimetic model using Jacobsen catalyst. The putative metabolite was tested against T. cruzi revealing loss of activity in comparison to grandisin.

Anti-Aversive Effects of Cannabidiol on Innate Fear-Induced Behaviors Evoked by an Ethological Model of Panic Attacks Based on a Prey vs the Wild Snake Epicrates cenchria crassus Confrontation Paradigm

Several pharmacological targets have been proposed as modulators of panic-like reactions. However, interest should be given to other potential therapeutic neurochemical agents. Recent attention has been given to the potential anxiolytic properties of cannabidiol, because of its complex actions on the endocannabinoid system together with its effects on other neurotransmitter systems. The aim of this study was to investigate the effects of cannabidiol on innate fear-related behaviors evoked by a prey vs predator paradigm. Male Swiss mice were submitted to habituation in an arena containing a burrow and subsequently pre-treated with intraperitoneal administrations of vehicle or cannabidiol. A constrictor snake was placed inside the arena, and defensive and non-defensive behaviors were recorded. Cannabidiol caused a clear anti-aversive effect, decreasing explosive escape and defensive immobility behaviors outside and inside the burrow. These results show that cannabidiol modulates defensive behaviors evoked by the presence of threatening stimuli, even in a potentially safe environment following a fear response, suggesting a panicolytic effect. Neuropsychopharmacology (2012) 37, 412-421; doi:10.1038/npp.2011.188; published online 14 September 2011

Synthesis, anti-inflammatory activity and molecular docking studies of 2,5-diarylfuran amino acid derivatives

A series of 2,5-diaryl substituted furans functionalized with several amino acids were synthesized and evaluated as the cyclooxygenases COX-1 and COX-2 enzymes inhibitors. The proline-substituted compound inhibited PGE(2) secretion by LPS-stimulated neutrophils, suggesting selectivity for COX-2. Molecular docking studies in the binding site of COX-2 were performed. (C) 2011 Elsevier Masson SAS. All rights reserved.

Optimization of anti-Trypanosoma cruzi oxadiazoles leads to identification of compounds with efficacy in infected mice

We recently showed that oxadiazoles have anti-Trypanosoma cruzi activity at micromolar concentrations. These compounds are easy to synthesize and show a number of clear and interpretable structure-activity relationships (SAR), features that make them attractive to pursue potency enhancement. We present here the structural design, synthesis, and anti-T. cruzi evaluation of new oxadiazoles denoted 5a-h and 6a-h. The design of these compounds was based on a previous model of computational docking of oxadiazoles on the T. cruzi protease cruzain. We tested the ability of these compounds to inhibit catalytic activity of cruzain, but we found no correlation between the enzyme inhibition and the antiparasitic activity of the compounds. However, we found reliable SAR data when we tested these compounds against the whole parasite. While none of these oxadiazoles showed toxicity for mammalian cells, oxadiazoles 6c (fluorine), 6d (chlorine), and 6e (bromine) reduced epimastigote proliferation and were cidal for trypomastigotes of T. cruzi Y strain. Oxadiazoles 6c and 6d have IC50 of 9.5 +/- 2.8 and 3.5 +/- 1.8 mu M for trypomastigotes, while Benznidazole, which is the currently used drug for Chagas disease treatment, showed an IC50 of 11.3 +/- 2.8 mu M. Compounds 6c and 6d impair trypomastigote development and invasion in macrophages, and also induce ultrastructural alterations in trypomastigotes. Finally, compound 6d given orally at 50 mg/kg substantially reduces the parasitemia in T. cruzi-infected BALB/c mice. Our drug design resulted in potency enhancement of oxadiazoles as anti-Chagas disease agents, and culminated with the identification of oxadiazole 6d, a trypanosomicidal compound in an animal model of infection. (C) 2012 Elsevier Ltd. All rights reserved.