Papel das proteínas intracelulares Nod e da proteína adaptadora MyD88 na regulação de espressão de RANKL e modulação da resposta inflamatória induzidos por antígenos bacterianos in vitro: estudo em células relevantes de periodonto

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeitos da intrusão ortodôntica na reparação de lesões de furca grau III em cães, e da presença de TNFα e/ou IL-β 1 na mecanoresposta de células ósseas in vitro

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeitos determinados pela amitriptilina, administrada pela via subaracnóidea, sobre a medula e as meninges: estudo experimental em cães

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Antidiarrheal and intestinal antiinflammatory activities of a methanolic extract of Qualea parviflora Mart. in experimental models

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

Analysis of rocuronium in human plasma by liquid chromatography-tandem mass spectrometry with application in clinical pharmacokinetics

Rocuronium (ROC) is a neuromuscular blocking agent used in surgical procedures which is eliminated primarily by biliary excretion. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for analysis of ROC in human plasma. Separation of ROC and IS (verapamil) was performed using an endcapped C-18 column and a mixture of water:acetonitrile:trifluoracetic acid (50:50:0.1, v/v) as mobile phase. Aliquots of 100 mu L of human plasma were extracted at pH 3, using dichloromethane. The lower limit of quantification of 5 ng/mL shows the high sensitivity of this method. Intra- and inter-assay precision (as relative standard deviation) was all <= 14.2% and accuracy (as relative standard error) did not exceed 10.1%. The validated method was successfully applied to quantify ROC concentrations in patients under surgical procedures up to 6 h after the administration of the 0.4-0.9 mg/kg ROC. The pharmacokinetic parameter estimations of ROC showed AUC/dose of 563 mu g min/mL, total clearance of 2.5 mL/min/kg, volume of distribution at steady state of 190 mL/kg and mean residence time of 83 min. (C) 2013 Elsevier B.V. All rights reserved.

Influence of Parstatin on Experimental Periodontal Disease and Repair in Rats

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

Efeito protetor da proteína anti-inflamatória Galectina-1 sobre o processo de uveíte induzida pelo inflamógeno lipopolissacarídeo

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

Modelo experimental de conjuntivite alérgica: efeito do tratamento farmacológico com a proteína anti-inflamatória galectina - 1

Pós-graduação em Genética - IBILCE

RANKL expression is differentially modulated by TLR2 and TLR4 signaling in fibroblasts and osteoblasts

Resident, non-immune cells express various pattern-recognition receptors and produce inflammatory cytokines in response to microbial antigens, during the innate immune response. Alveolar bone resorption is the hallmark of destructive periodontitis and it is caused by the host response to bacteria and their mediators present on the biofilm. The balance between the expression levels of receptor activator of nuclear factorkappa B ligand (RANKL) and osteoprotegerin (OPG) is pivotal for osteoclast differentiation and activity and has been implicated in the progression of bone loss in periodontitis. To assess the contribution of resident cells to the bone resorption mediated by innate immune signaling, we stimulated fibroblasts and osteoblastic cells with LPS from. Escherichia coli (TLR4 agonist), Porphyromonas gingivalis (TLR2 and -4 agonist), and interleukin-1 beta (as a control for cytokine signaling through Toll/IL-1receptor domain) in time-response experiments. Expression of RANKL and OPG mRNA was studied by RT-PCR, whereas the production of RANKL protein and the activation of p38 MAPK and NF-kB signaling pathways were analyzed by western blot. We used biochemical inhibitors to assess the relative contribution of p38 MAPK and NF-kB signaling to the expression of RANKL and OPG induced by TLR2, -4 and IL1β in these cells. Both p38 MAPK and NFkB pathways were activated by these stimuli in fibroblasts and osteoblasts, but the kinetics of this activation varied in each cell type and with the nature of the stimulation. E. coli LPS was a stronger inducer of RANKL mRNA in fibroblasts, whereas LPS from P. gingivalis downregulated RANKL mRNA in periodontal ligament cells but increased its expression in osteoblasts. IL-1β induced RANKL in both cell types and without a marked effect on OPG expression. p38 MAPK was more relevant than NF-kB for the expression of RANKL and OPG in these cell types.

Galectin-1 exerts inhibitory effects during DENV-1 infection

Dengue virus (DENV) is an enveloped RNA virus that is mosquito-transmitted and can infect a variety of immune and non-immune cells. Response to infection ranges from asymptomatic disease to a severe disorder known as dengue hemorrhagic fever. Despite efforts to control the disease, there are no effective treatments or vaccines. In our search for new antiviral compounds to combat infection by dengue virus type 1 (DENV-1), we investigated the role of galectin-1, a widely-expressed mammalian lectin with functions in cell-pathogen interactions and immunoregulatory properties. We found that DENV-1 infection of cells in vitro exhibited caused decreased expression of Gal-1 in several different human cell lines, suggesting that loss of Gal-1 is associated with virus production. In test of this hypothesis we found that exogenous addition of human recombinant Gal-1 (hrGal-1) inhibits the virus production in the three different cell types. This inhibitory effect was dependent on hrGal-1 dimerization and required its carbohydrate recognition domain. Importantly, the inhibition was specific for hrGal-1, since no effect was observed using recombinant human galectin-3. Interestingly, we found that hrGal-1 directly binds to dengue virus and acts, at least in part, during the early stages of DENV-1 infection, by inhibiting viral adsorption and its internalization to target cells. To test the in vivo role of Gal-1 in DENV infection, Gal-1-deficient-mice were used to demonstrate that the expression of endogenous Galectin-1 contributes to resistance of macrophages to in vitro-infection with DENV-1 and it is also important to physiological susceptibility of mice to in vivo infection with DENV-1. These results provide novel insights into the functions of Gal-1 in resistance to DENV infection and suggest that Gal-1 should be explored as a potential antiviral compound.

Immunomodulatory Effects of Galectin-1 on an IgE-Mediated Allergic Conjunctivitis Model

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

Pharmacology of the glucagon-like peptide-1 analog exenatide extended-release in healthy cats

Exenatide extended-release (ER) is a microencapsulated formulation of the glucagon-like peptide 1-receptor agonist exenatide: It has a protracted pharmacokinetic profile that allows a once-weekly injection with comparable efficacy to insulin with an improved safety profile in type II diabetic people. Here, we studied the pharmacology of exenatide ER in 6 healthy cats. A single subcutaneous injection of exenatide ER (0.13 mg/kg) was administered on day 0. Exenatide concentrations were measured for 12 wk. A hyperglycemic clamp (target = 225 mg/dL) was performed on days 7 (clamp I) and 21 (clamp II) with measurements of insulin and glucagon concentrations. Glucose tolerance was defined as the amount of glucose required to maintain hyperglycemia during the clamp. Continuous glucose monitoring was performed on weeks 0, 2, and 6 after injection. Plasma concentrations of exenatide peaked at 1 h and 4 wk after injection. Comparing clamp I with clamp II, fasting blood glucose decreased (mean standard deviation = 11 8 mg/dL, P = 0.02), glucose tolerance improved (median [range] +33% 14%-138%], P = 0.04), insulin concentrations increased (+36.5% [-9.9% to 274.1%], P = 0.02), and glucagon concentrations decreased (-4.7% [0%-12.1%], P = 0.005). Compared with preinjection values on continuous glucose monitoring, glucose concentrations decreased and the frequency of readings <50 mg/dL increased at 2 and 6 wk after injection of exenatide ER. This did not correspond to clinical hypoglycemia. No other side effects were observed throughout the study. Exenatide ER was safe and effective in improving glucose tolerance 3 wk after a single injection. Further evaluation is needed to determine its safety, efficacy, and duration of action in diabetic cats. (C) 2015 Elsevier Inc. All rights reserved.

Galectin-1 exerts inhibitory effects during DENV-1 infection

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Role of cholinergic and adrenergic pathways of the medial septal area in the control of water intake and renal excretion in rats

In this study, we investigated an interaction between noradrenergic and cholinergic pathways of the medial septal area (MSA) on the control of water intake and urinary electrolyte excretion by means of injection of their respective agonists. Noradrenaline (a nonspecific α-adrenergic agonist) and clonidine (an α2-adrenergic agonist), but not phenylephrine (an α1-adrenergic agonist), induced natriuresis and kaliuresis. α-Adrenergic activation had no effect on the natriuresis and kaliuresis induced by carbachol (a cholinergic agonist) and it inhibited the antinatriuresis and antikaliuresis induced by isoproterenol (a ß-adrenergic agonist). Interactions related to volume excretion are complex. α-Adrenergic activation induced a mild diuresis and inhibited the antidiuresis induced by isoproterenol, but phenylephrine combined with carbachol induced antidiuresis. The water intake induced by carbachol was inhibited by clonidine and noradrenaline, but not phenylephrine. These results show an asymmetry in the interaction between α-adrenergic and cholinergic receptors concerning water intake and electrolyte excretion. © 1992.

Efeito Diabetes mellitus gestacional na modulação de genes relacionados ao metabolismo mitocondrial e a implicação na predisposiçao do recém-nascido à obesidade

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)