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Dive into the research topics where Patricia Gnieslaw de Oliveira is active.

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Featured researches published by Patricia Gnieslaw de Oliveira.


Peptides | 2008

Effects of an antagonist of the bombesin/gastrin-releasing peptide receptor on complete Freund's adjuvant-induced arthritis in rats

Patricia Gnieslaw de Oliveira; Claiton Viegas Brenol; Maria Isabel Albano Edelweiss; João Carlos Tavares Brenol; F. Petronilho; Rafael Roesler; F. Dal-Pizzol; Gilberto Schwartsmann; Ricardo Machado Xavier

OBJECTIVE To determine the effects of RC-3095 in clinical and histopathologic parameters and inflammatory mediators on complete Freunds adjuvant-induced arthritis (CFA). METHODS The arthritis was induced by injection of CFA into the left hind footpad. The animals were divided into control, vehicle injected control, placebo group (saline subcutaneously 50ml/kg, once daily for 8 days after modeling), treatment group (0.3mg/kg of RC-3095 subcutaneously, once daily for 8 days after induction). Clinical evaluation was accomplished daily, through scoring of the paw edema. The animals were sacrificed 15 days after induction for collection of hind foot joints for histology. We used a histological scoring system which was previously described, and interferon (INF)-gamma, interleukin (IL)-1beta, tumor necrosis factor (TNF), interleukin (IL)-6 and interleukin (IL)-10 were measured by ELISA. RESULTS There was a significant inhibition of joint histological findings in the RC-3095 treated group, including synovial inflammatory infiltration and hyperplasia, cartilage and bone erosion. IFN-gamma, IL-1beta, TNF, IL-6 and IL-10 serum levels were significantly lower in the treated group. Paw swelling and subcutaneous inflammation, evaluated clinically, were not different between CFA-induced groups. CONCLUSIONS RC-3095 was able to improve experimental arthritis, attenuate joint damage and decrease serum levels of IFN-gamma, IL-1beta, TNF, IL-6 and IL-10. These data indicate that interference with GRP pathway is a potential new strategy for the treatment of RA that needs further investigational studies.


Arthritis & Rheumatism | 2011

Protective Effect of RC-3095, an Antagonist of the Gastrin-Releasing Peptide Receptor, in Experimental Arthritis

Patricia Gnieslaw de Oliveira; Renata Grespan; Larissa G. Pinto; Luíse Meurer; João Carlos Tavares Brenol; Rafael Roesler; Gilberto Schwartsmann; Fernando Q. Cunha; Ricardo Machado Xavier

OBJECTIVE To evaluate the antiinflammatory effects of RC-3095 in 2 experimental models of arthritis, collagen-induced arthritis (CIA) and antigen-induced arthritis (AIA), and to determine the mechanisms of action involved. METHODS RC-3095 was administered daily to mice with CIA and mice with AIA, after induction of disease with methylated bovine serum albumin. Disease incidence and severity were assessed using a clinical index and evaluation of histologic features, respectively. In mice with CIA, gastrin-releasing peptide receptor (GRPR) was detected by immunohistochemical analysis, while in mice with AIA, migration of neutrophils, presence of glycosaminoglycans, and lymphocyte proliferation, determined using the MTT assay, were assessed. Expression of cytokines interleukin-17 (IL-17), IL-1β, and tumor necrosis factor α (TNFα) was evaluated in all mouse knees using enzyme-linked immunosorbent assay. Treg cell production was assessed by flow cytometry in the joints of mice with AIA. RESULTS In mice with AIA, administration of RC-3095 reduced neutrophil migration, mechanical hypernociception, and proteoglycan loss. These findings were associated with inhibition of the levels of all 3 proinflammatory cytokines, decreased lymphocyte proliferation, and increased Treg cell numbers. In the CIA model, treatment with RC-3095 led to a significant reduction in arthritis clinical scores and the severity of disease determined histologically. Synovial inflammation, synovial hyperplasia, pannus formation, and extensive erosive changes were all dramatically reduced in the arthritic mice treated with RC-3095. Furthermore, arthritic mice treated with RC-3095 showed a significant reduction in the concentrations of IL-17, IL-1β, and TNFα, and showed a diminished expression of GRPR. CONCLUSION These findings suggest that the GRP pathway has a significant role in chronic arthritis, and its inhibition can be explored as a possible therapeutic strategy in rheumatoid arthritis.


Lipids in Health and Disease | 2008

Weight loss and brown adipose tissue reduction in rat model of sleep apnea

Denis Martinez; Luiz Felipe Teer de Vasconcellos; Patricia Gnieslaw de Oliveira; Signorá Peres Konrad

Background -Obesity is related to obstructive sleep apnea-hypopnea syndrome (OSAHS), but its roles in OSAHS as cause or consequence are not fully clarified. Isocapnic intermittent hypoxia (IIH) is a model of OSAHS. We verified the effect of IIH on body weight and brown adipose tissue (BAT) of Wistar rats.MethodsNine-month-old male breeders Wistar rats of two groups were studied: 8 rats submitted to IIH and 5 control rats submitted to sham IIH. The rats were weighed at the baseline and at the end of three weeks, after being placed in the IIH apparatus seven days per week, eight hours a day, in the lights on period, simulating an apnea index of 30/hour. After experimental period, the animals were weighed and measured as well as the BAT, abdominal, perirenal, and epididymal fat, the heart, and the gastrocnemius muscle.ResultsBody weight of the hypoxia group decreased 17 ± 7 grams, significantly different from the variation observed in the control group (p = 0,001). The BAT was 15% lighter in the hypoxia group and reached marginally the alpha error probability (p = 0.054).ConclusionOur preliminary results justify a larger study for a longer time in order to confirm the effect of isocapnic intermittent hypoxia on body weight and BAT.


Experimental Biology and Medicine | 2013

Muscle wasting in collagen-induced arthritis and disuse atrophy

Vivian de Oliveira Nunes Teixeira; Lidiane Isabel Filippin; Paula Ramos Viacava; Patricia Gnieslaw de Oliveira; Ricardo Machado Xavier

The mechanisms of muscle wasting and decreased mobility have a major functional effect in rheumatoid arthritis, but they have been poorly studied. The objective of our study is to describe muscular involvement and the pathways in an experimental model of arthritis compared to the pathways in disuse atrophy. Female Wistar rats were separated into three groups: control (CO), collagen-induced arthritis (CIA), and immobilized (IM). Spontaneous locomotion and weight were evaluated weekly. The gastrocnemius muscle was evaluated by histology and immunoblotting to measure the expression of myostatin (a negative regulator), LC3 (autophagy), MuRF-1 (proteasome-mediated proteolysis), MyoD, and myogenin (satellite-cell activation). The significance level was set at P < 0.05, and histological analysis of joints confirmed the severity of the arthropathy. There was a significant difference in spontaneous locomotion in the CIA group. Animal body weight, gastrocnemius muscle weight, and relative muscle weight decreased 20%, 30%, and 20%, respectively, in the CIA rats. Inflammatory infiltration and swelling were present in the gastrocnemius muscles of the CIA rats. The mean cross-sectional area was reduced by 30% in the CIA group and by 60% in the IM group. The expressions of myostatin and LC3 between the groups were similar. There was increased expression of MuRF-1 in the IM (1.9-fold) and CIA (3.1-fold) groups and of myogenin in the muscles of the CIA animals (1.7-fold), while MyoD expression was decreased in the IM (20%) rats. This study demonstrated that the development of experimental arthritis is associated with decreased mobility, body weight, and muscle loss. Both IM and CIA animal models presented muscle atrophy, but while proteolysis and the regeneration pathways were activated in the CIA model, there was no activation of regeneration in the IM model. We can assume that muscle atrophy in experimental arthritis is associated with the disease itself and not simply with decreased mobility.


Clinical and Experimental Medicine | 2007

Subcutaneous inflammation (panniculitis) in tibio-tarsal joint of rats inoculated with complete Freund’s adjuvant

Patricia Gnieslaw de Oliveira; C. V. Brenol; Maria Isabel Albano Edelweiss; Luíse Meurer; João Carlos Tavares Brenol; Ricardo Machado Xavier

Complete Freund’s adjuvant (CFA)-induced arthritis in rats, which presents similar features to rheumatoid arthritis, is a model widely used in aetiopathogenetic and investigational drug studies. In this model, arthritis is induced by intradermal injection of Mycobacterium tuberculosis suspended in mineral oil in the hind footpad. Although the histopathology findings in the joint are well described, the marked subcutaneous features of panniculitis that concomitantly occur in this model have received no attention. The objective of this paper is to describe the subcutaneous histopathological features in 8 Wistar rats after intraplantar injection of CFA. We studied the subcutaneous histopathological features in 8 Wistar rats after intraplantar injection of CFA in the left hind paw. The levels of subcutaneous inflammation of the animals in this study were evaluated for the histological characteristics present in the tissue and scored with 4 parameters (acute inflammation, chronic inflammation with fibrosis, subcutaneous and profound soft tissue necrosis, and the presence of giant cells, neutrophils, macrophages and lymphocytes) on days 4, 7, 11 and 15 after induction. All animals developed intense subcutaneous inflammation characteristic of panniculitis, with predominance of acute changes in the initial period, with progression to a self-perpetuating chronic fibrotic process on day 15. These observations precede the joint changes. Besides being an interesting model for better studying diseases with panniculitis, our observations bring up issues concerning the possible relations between subcutaneous and joint inflammatory changes.


International Journal of Experimental Pathology | 2013

Characterization of joint disease in mucopolysaccharidosis type I mice

Patricia Gnieslaw de Oliveira; Guilherme Baldo; Fabiana Quoos Mayer; Bárbara Zambiasi Martinelli; Luíse Meurer; Roberto Giugliani; Ursula da Silveira Matte; Ricardo Machado Xavier

Mucopolysaccharidoses (MPS) are lysosomal storage disorders characterized by mutations in enzymes that degrade glycosaminoglycans (GAGs). Joint disease is present in most forms of MPS, including MPS I. This work aimed to describe the joint disease progression in the murine model of MPS I. Normal (wild‐type) and MPS I mice were sacrificed at different time points (from 2 to 12 months). The knee joints were collected, and haematoxylin–eosin staining was used to evaluate the articular architecture. Safranin‐O and Sirius Red staining was used to analyse the proteoglycan and collagen content. Additionally, we analysed the expression of the matrix‐degrading metalloproteinases (MMPs), MMP‐2 and MMP‐9, using immunohistochemistry. We observed progressive joint alterations from 6 months, including the presence of synovial inflammatory infiltrate, the destruction and thickening of the cartilage extracellular matrix, as well as proteoglycan and collagen depletion. Furthermore, we observed an increase in the expression of MMP‐2 and MMP‐9, which could conceivably explain the degenerative changes. Our results suggest that the joint disease in MPS I mice may be caused by a degenerative process due to increase in proteases expression, leading to loss of collagen and proteoglycans. These results may guide the development of ancillary therapies for joint disease in MPS I.


The Open Rheumatology Journal | 2013

Effect of Aqueous Extract of Giant Horsetail (Equisetum giganteum L.) in Antigen-Induced Arthritis

Mirian Farinon; Priscila Schmidt Lora; Leandro Nicolodi Francescato; Valquiria Linck Bassani; Amelia Teresinha Henriques; Ricardo Machado Xavier; Patricia Gnieslaw de Oliveira

Equisetum giganteum is a plant used in traditional medicine as diuretic. From our knowledge this is the first time this plant is tested in an in vivo model of acute inflammation. To evaluate the effect of aqueous extract of giant horsetail (AEGH) as immunomodulatory therapy, antigen-induced arthritis (AIA) was generated in mice with methylated bovine serum albumin (mBSA). Inflammation was evaluated by articular nociception, leukocytes migration and lymphocyte proliferation. AEGH reduced nociception at 3, 6 and 24 h (P < 0.01), decreased leukocyte migration (P < 0.015), and inhibited lymphocyte proliferation stimulated with Concanavalin A and Lipopolysaccharide (P < 0.05). In conclusion, AEGH has an anti-inflammatory potential in acute model of inflammation, as well as immunomodulatory effect on both B and T lymphocytes, with an action independent of cytotoxicity.


European Journal of Pharmacology | 2017

Disease modifying anti-rheumatic activity of the alkaloid montanine on experimental arthritis and fibroblast-like synoviocytes

Mirian Farinon; Vanessa Schuck Clarimundo; Graziele Pereira Ramos Pedrazza; Pércio S. Gulko; Jose Angelo Silveira Zuanazzi; Ricardo Machado Xavier; Patricia Gnieslaw de Oliveira

Abstract Montanine is an alkaloid isolated from Rhodophiala bifida bulb with potential anti‐arthritic activity. In this context, we evaluated whether montanine has a disease modifying anti‐rheumatic activity in two arthritis models and its effect in vitro on lymphocyte proliferation and on invasiveness of fibroblast‐like synoviocytes (FLS). Antigen‐induced arthritis (AIA) was performed in Balb/C mice with methylated bovine serum albumin, and nociception and leukocytes migration into the knee joint were evaluated. Collagen‐induced arthritis (CIA) was performed in DBA/1 J mice, and arthritis development and severity were assessed by clinical and histological scoring and articular nociception. Montanine was administered intraperitoneally twice a day. Lymphocyte proliferation stimulated by concanavalin A in 48 h was performed with MTT assay, while FLS invasion in 24 h was assayed in a Matrigel‐coated transwell system. Administration of montanine decreased nociception (P<0.001) and leukocyte articular migration (P<0.001) in mice with AIA. In mice with CIA, treatment with montanine reduced severity of arthritis and joint damage assessed by clinical (P<0.001) and histological (P<0.05) scores and ameliorated articular nociception (P<0.05). In vitro, montanine inhibited lymphocyte proliferation stimulated with ConA (P<0.001) and decreased FLS invasion (P<0.05) by 54%, with an action independent of cytotoxicity. Our findings suggest that montanine can be further explored as an innovative pharmacological approach for autoimmune diseases such as arthritis. Graphical abstract Figure. No caption available.


International Journal of Pharmaceutics | 2018

Intra-articular nonviral gene therapy in mucopolysaccharidosis I mice

Juliana Bidone; Roselena Silvestri Schuh; Mirian Farinon; Édina Poletto; Gabriela Pasqualim; Patricia Gnieslaw de Oliveira; Michelle Fraga; Ricardo Machado Xavier; Guilherme Baldo; Helder Ferreira Teixeira; Ursula da Silveira Matte

ABSTRACT Mucopolysaccharidosis type I (MPS I) is caused by the lysosomal accumulation of glycosaminoglycans (GAGs) due to the deficiency of the enzyme alpha‐L‐iduronidase (IDUA). Currently available treatments may improve several clinical manifestations, but they have limited effects on joint disease, resulting in persistent orthopedic complications and impaired mobility. Thus, this study aimed to perform an intra‐articular administration of cationic nanoemulsions complexed with the plasmid encoding for the IDUA protein (pIDUA) targeting MPS I gene therapy for the synovial joints. Formulations composed of DOPE, DOTAP, MCT (NE), and DSPE‐PEG (NE‐PEG) were prepared by high‐pressure homogenization, and the pIDUA plasmid was associated by adsorption onto the surface of nanoemulsions (pIDUA/NE or pIDUA/NE‐PEG). The physicochemical characterization showed that the presence of DSPE‐PEG in pIDUA/NE‐PEG formulations led to small and highly stable droplets even when incubated with simulated synovial fluid (SSF), when compared to the non‐pegylated complexes (pIDUA/NE). Uptake by fibroblast‐like synoviocytes (FLS) was demonstrated, and high cell viability (70%) in addition with increased IDUA activity (2.5% of normal) were observed after incubation with pIDUA/NE‐PEG. The intra‐articular injection of pIDUA/NE‐PEG complexes in MPS I mice showed that the complexes were localized in the joints, were able to transfect synovial cells, and thus promoted an increase in IDUA activity and expression in the synovial fluid, with no significant activity in other tissues (kidney, liver, lung, and spleen). The overall results demonstrated a contained, safe, tolerable, and effective in situ approach of nonviral intra‐articular gene therapy targeting the reduction or prevention of the debilitating orthopedic complications of MPS I disorder.


Peptides | 2017

Gastrin-releasing peptide and its receptor increase arthritis fibroblast-like synoviocytes invasiveness through activating the PI3K/AKT pathway

Vanessa Schuck Clarimundo; Mirian Farinon; Renata Ternus Pedó; Vivian de Oliveira Nunes Teixeira; Carolina Nör; Pércio S. Gulko; Ricardo Machado Xavier; Patricia Gnieslaw de Oliveira

&NA; Rheumatoid arthritis (RA) is an autoimmune disease that leads to joint destruction. The fibroblast‐like synoviocytes (FLS) has a central role on the disease pathophysiology. The present study aimed to examine the role of gastrin‐releasing peptide (GRP) and its receptor (GRPR) on invasive behavior of mice fibroblast‐like synoviocytes (FLS), as well as to evaluate GRP‐induced signaling on PI3K/AKT pathway. The expression of GRPR in FLS was investigated by immunocytochemistry, western blot (WB) and qRT‐PCR. The proliferation and invasion were assessed by SRB and matrigel‐transwell assay after treatment with GRP and/or RC‐3095 (GRPR antagonist), and/or Ly294002 (inhibitor of PI3K/AKT pathway). Finally, AKT phosphorylation was assessed by WB. GRPR protein was detected in FLS and the exposure to GRP increased FLS invasion by nearly two‐fold, compared with untreated cells (p < 0.05), while RC‐3095 reversed that effect (p < 0.001). GRP also increased phosphorylated AKT expression in FLS. When Ly294002 was added with GRP, it prevented the GRP‐induced increased cell invasiveness (p < 0.001). These data suggest that GRPR expression in FLS and that exogenous GRP are able to activate FLS invasion. This effect occurs at least in part through the AKT activation. Therefore, understanding of the GRP/GRPR pathway could be relevant in the development of FLS‐targeted therapy for RA. HighlightsFibroblast‐like synoviocytes express gastrin‐releasing receptor protein.GRP increased FLS invasiveness and RC‐3095 reverse that effect.The effect of GRP could be through activation of PI3K/AKT pathway.GRP/GRPR signaling could be a new target for the treatment of arthritis.

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Ricardo Machado Xavier

Universidade Federal do Rio Grande do Sul

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Mirian Farinon

Universidade Federal do Rio Grande do Sul

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Vanessa Schuck Clarimundo

Universidade Federal do Rio Grande do Sul

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Lidiane Isabel Filippin

Universidade Federal do Rio Grande do Sul

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Vivian de Oliveira Nunes Teixeira

Universidade Federal do Rio Grande do Sul

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Gilberto Schwartsmann

Universidade Federal do Rio Grande do Sul

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João Carlos Tavares Brenol

Universidade Federal do Rio Grande do Sul

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Luíse Meurer

Universidade Federal do Rio Grande do Sul

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Graziele Pereira Ramos Pedrazza

Universidade Federal do Rio Grande do Sul

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Jose Angelo Silveira Zuanazzi

Universidade Federal do Rio Grande do Sul

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