Fortaleza, Brazil
Fortaleza, Brazil

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Costa C.L.,Federal University of Ceará | Lopez-Urena D.,University of Costa Rica | de Oliveira Assis T.,Federal University of Ceará | de Oliveira Assis T.,Federal University of Paraiba | And 13 more authors.
Anaerobe | Year: 2016

The epidemiology of Clostridium difficile infections is highly dynamic as new strains continue to emerge worldwide. Here we present a detailed analysis of a new C. difficile strain (ICC-45) recovered from a cancer patient in Brazil that died from severe diarrhea. A polyphasic approach assigned a new PCR-ribotype and PFGE macrorestriction pattern to strain ICC-45, which is toxigenic (tcdA+, tcdB+ and ctdB+) and classified as ST41 from MLST Clade 2 and toxinotype IXb. Strain ICC-45 encodes for a variant TcdB that induces a distinct CPE in agreement with its toxinotype. Unlike epidemic NAP1/027 strains, which are also classified to MLST Clade 2, strain ICC-45 is susceptible to fluoroquinolones and does not overproduce toxins TcdA and TcdB. However, supernatants from strain ICC-45 and a NAP1/027 strain produced similar expression of pro-inflammatory cytokines, epithelial damage, and oxidative stress response in the mouse ileal loop model. These results highlight inflammation and oxidative stress as common features in the pathogenesis of C. difficile Clade 2 strains. Finally, this work contributes to the description of differences in virulence among various C. difficile strains. © 2016 Elsevier Ltd.


Leite C.A.V.G.,Federal University of Ceará | Leite C.A.V.G.,Haroldo Juacaba Hospital | Alencar V.T.L.,Federal University of Ceará | Melo D.L.R.,Federal University of Ceará | And 11 more authors.
Journal of Urology | Year: 2015

Purpose Hemorrhagic cystitis is an important dose limiting side effect of ifosfamide based cancer chemotherapy. Despite chemoprophylaxis inflammation can still be found in cystoscopy guided biopsies. Previous studies confirmed the role of TNF-α and IL-1β. We evaluated the protective effect of the IL-1R antagonist anakinra and the anti-TNF-α antibody infliximab in experimental ifosfamide induced hemorrhagic cystitis. Materials and Methods Hemorrhagic cystitis was induced by an injection of ifosfamide (400 mg/kg intraperitoneally) in Swiss wild-type C57Bl/6, IL-1R-/-, TNFR1-/- or TNFR1/R2-/- mice. Mice were treated 30 minutes before ifosfamide with anakinra (100 mg/kg intraperitoneally), infliximab (5 mg/kg intraperitoneally) or vehicle. Visceral nociception was evaluated after hemorrhagic cystitis induction. At 12 hours the animals were sacrificed. Bladders were harvested to assess bladder wet weight, vascular permeability, macroscopic and microscopic findings, muscle contractility, and for cystometrography. Inflammatory cell infiltration was assessed by myeloperoxidase assay and flow cytometry. Results Anakinra attenuated hemorrhage, edema, neutrophil infiltration, visceral hyperalgesia and bladder dysfunction. IL-1R-/- mice also showed milder hemorrhagic cystitis. Infliximab inhibited bladder edema and visceral hyperalgesia without preventing hemorrhage, bladder dysfunction, neutrophils or accumulation. Additionally, the lack of TNFR1 decreased bladder edema but not cell infiltration whereas concomitant deficiency of TNFR1 and TNFR2 resulted in worse hemorrhagic cystitis. Conclusions Anakinra is effective for preventing experimentally ifosfamide induced hemorrhagic cystitis. It seems that neutrophil and macrophage infiltration in this circumstance depends on IL-1 signaling through IL1R. Possibly TNFR2 has a protective role in hemorrhagic cystitis. © 2015 American Urological Association Education and Research, Inc.


Carvalho K.M.M.B.,Federal University of Ceará | Marinho Filho J.D.B.,Federal University of Ceará | De Melo T.S.,Federal University of Ceará | Araujo A.J.,Federal University of Ceará | And 11 more authors.
Evidence-based Complementary and Alternative Medicine | Year: 2015

Herbal compounds rich in triterpenes are well known to regulate glucose and lipid metabolism and to have beneficial effects on metabolic disorders. The present study investigated the antiobesity properties of resin from Protium heptaphyllum (RPH) and the possible mechanisms in mice fed a high-fat diet (HFD) for 15 weeks. Mice treated with RPH showed decreases in body weight, net energy intake, abdominal fat accumulation, plasma glucose, amylase, lipase, triglycerides, and total cholesterol relative to their respective controls, which were RPH unfed. Additionally, RPH treatment, while significantly elevating the plasma level of ghrelin hormone, decreased the levels of insulin, leptin, and resistin. Besides, HFD-induced increases in plasma levels of proinflammatory mediators TNF-α, IL-6, and MCP-1 were significantly lowered by RPH. Furthermore, in vitro studies revealed that RPH could significantly inhibit the lipid accumulation in 3T3-L1 adipocytes (measured by Oil-Red O staining) at concentrations up to 50 g/mL. These findings suggest that the antiobese potential of RPH is largely due to its modulatory effects on various hormonal and enzymatic secretions related to fat and carbohydrate metabolism and to the regulation of obesity-associated inflammation. © 2015 Karine Maria Martins Bezerra Carvalho et al.


Bastos Moura J.F.,Federal University of Ceará | Bastos Moura J.F.,Haroldo Juacaba Hospital | Mota J.M.S.C.,University of Sao Paulo | Leite C.A.V.,Federal University of Ceará | And 7 more authors.
International Journal of Radiation Biology | Year: 2015

Purpose: To design a novel model to study Cobalt-60 (Co-60)-induced radiation mucositis and to describe the pathways involved in its development. Materials and methods: Hamsters' cheeks were treated with Co-60 radiation (10, 20, 30 or 35 Gy). Three days later, oral mucosa scarification was performed with a needle. The animals were euthanized at day 13 (D + 13) after irradiation. Gross and microscopic alterations were evaluated by a new score system that we developed. Also, neutrophil infiltration, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-10, inducible nitric oxide synthase (iNOS), nitric oxide (NO) and nitrite were assessed in oral mucosa. We also tried to establish the roles of TNF-α and IL-1β and iNOS in our model using pharmacological approaches with pentoxiphylline (PTX) and aminoguanidine (AMG), respectively. Results: We found that a single administration of 35 Gy of Co-60, followed by mechanical scratches 3 days later, induced oral mucositis in hamsters. Animals with mucositis lost weight and had a survival median of 13 days, the time at which peak inflammation occurs. We noticed increased levels of NO, iNOS, TNF-α and IL-1β and a reduced concentration of IL-10. PTX partially prevented the mucositis phenotype by reducing the levels of inflammatory mediators and iNOS expression. Additionally, AMG, a selective inhibitor of iNOS, reduced Co-60-induced oral mucositis through reducing NO production. Conclusion: We described a novel model of megavoltage radiation-induced oral mucositis in hamsters. TNF-α, IL-1β and NO seem to play a role in the pathophysiology of this model. © 2015 Informa UK, Ltd.


Carvalho K.M.M.B.,Federal University of Ceará | de Melo T.S.,Federal University of Ceará | de Melo K.M.,Federal University of Ceará | Quindere A.L.G.,Federal University of Ceará | And 11 more authors.
Planta Medica | Year: 2016

Obesity remains a global problem. In search of phytochemicals that have antiobesity potential, this study evaluated α,β-amyrin, a triterpenoid mixture from Protium heptaphyllum, on high-fat diet-induced obesity in mice. Groups of mice (n = 8) were fed a normal diet or a high-fat diet, and were orally treated or not treated with either α,β-amyrin (10 or 20 mg/kg) or sibutramine (10 mg/kg) for 15 weeks. Variables measured at termination were body weight, visceral fat accumulation, adipocyte surface area, peroxisome proliferator-activated receptor gamma, and lipoprotein lipase expressions in adipose tissue, the levels of plasma glucose and insulin, the satiety hormones ghrelin and leptin, the digestive enzymes amylase and lipase, and the inflammatory mediators TNF-α, interleukin-6, and MCP-1. Results showed that α,β-amyrin treatment resulted in lower high-fat diet-induced increases in body weight, visceral fat content, adipocyte surface area, peroxisome proliferator-activated receptor gamma, and lipoprotein lipase expressions, and blood glucose and insulin levels. Additionally, the markedly elevated leptin and decreased ghrelin levels seen in the high-fat diet-fed control mice were significantly modulated by α,β-amyrin treatment. Furthermore, α,β-amyrin decreased serum TNF-α and MCP-1. These results suggest that α,β-amyrin could be beneficial in reducing high-fat diet-induced obesity and associated disorders via modulation of enzymatic, hormonal, and inflammatory responses. Copyright © 2016, Georg Thieme Verlag KG. All rights reserved.


PubMed | Federal University of Ceará, State University of Ceará, Federal University of Piauí and Haroldo Juacaba Hospital
Type: | Journal: Evidence-based complementary and alternative medicine : eCAM | Year: 2015

Herbal compounds rich in triterpenes are well known to regulate glucose and lipid metabolism and to have beneficial effects on metabolic disorders. The present study investigated the antiobesity properties of resin from Protium heptaphyllum (RPH) and the possible mechanisms in mice fed a high-fat diet (HFD) for 15 weeks. Mice treated with RPH showed decreases in body weight, net energy intake, abdominal fat accumulation, plasma glucose, amylase, lipase, triglycerides, and total cholesterol relative to their respective controls, which were RPH unfed. Additionally, RPH treatment, while significantly elevating the plasma level of ghrelin hormone, decreased the levels of insulin, leptin, and resistin. Besides, HFD-induced increases in plasma levels of proinflammatory mediators TNF-, IL-6, and MCP-1 were significantly lowered by RPH. Furthermore, in vitro studies revealed that RPH could significantly inhibit the lipid accumulation in 3T3-L1 adipocytes (measured by Oil-Red O staining) at concentrations up to 50g/mL. These findings suggest that the antiobese potential of RPH is largely due to its modulatory effects on various hormonal and enzymatic secretions related to fat and carbohydrate metabolism and to the regulation of obesity-associated inflammation.


De Assis Castro Bomfim F.,Walter Cantidio Hospital | De Oliveira Mendes W.,Federal University of Ceará | Moreira Veras I.,Regional Center for Integrated Oncology | Catunda De Freitas J.,Federal University of Ceará | And 2 more authors.
Journal of Medical Case Reports | Year: 2013

Introduction. Extramammary Paget's disease is a rare histological type of intraepithelial adenocarcinoma that mainly affects apocrine sweat gland-rich areas. Predilection sites include the anogenital region and, less commonly, the axillae. These tumors rarely occur in non-apocrine regions. The aim of this case report is to describe a case of extramammary Paget's disease in the external auditory canal with extensive temporal bone involvement and skull base invasion. Case presentation. A 40-year-old Caucasian man presented with a progressively growing, vegetating lesion localized in his right-hand external auditory canal. He had peripheral facial nerve paralysis and complete ipsilateral hearing loss. An incisional biopsy suggested extramammary Paget's disease, and the immunohistochemical analysis confirmed the diagnosis. The tumor was considered inoperable because of the extensive skull base involvement, and he was referred for palliative radiotherapy. Conclusion: We report here the third case of extramammary Paget's disease affecting the external auditory canal to be described in the literature. In all the three cases, the prognosis was unfavorable despite treatment. © 2013 Bomfim et al.; licensee BioMed Central Ltd.


Sampaio J.P.A.,Federal University of Ceará | Cavalcante J.R.,Federal University of Ceará | Furtado F.N.N.,Federal University of Ceará | Lima-Junior R.C.P.,Federal University of Ceará | And 3 more authors.
Journal of Pharmacological and Toxicological Methods | Year: 2014

Introduction: Tissue microarray (TMA) was first designed to enable more efficient immunohistochemical screening of antibodies and tissues. However, due to the high cost of commercial TMA builder instrument, such method is not affordable for many pathology laboratories. Then, methodological adaptations have been proposed in order to reduce TMA-associated cost. Methods: A manual leather puncher with an inner diameter of 2. mm was used to collect a tissue sample from the donor paraffin block. The conventional TMA method was adopted as a control group. Results: Empty paraffin recipient blocks were prepared and a standard 2-mm crochet needle was used to create 24 equidistant holes in the recipient block. Tissue cores obtained from the donor blocks were transferred to the holes in the recipient blocks and routine histopathological techniques were then performed. Discussion: In this study we proposed a new approach to produce TMA recipient blocks as an alternative to the conventional TMA. © 2014 Elsevier Inc.


Costa C.L.,Federal University of Ceará | Quesada-Gomez C.,University of Costa Rica | Carvalho C.B.M.D.,Federal University of Ceará | Gonzalez R.H.,Haroldo Juacaba Hospital | And 3 more authors.
International Journal of Infectious Diseases | Year: 2014

Clostridium difficile is the most important cause of nosocomial diarrhea, mainly associated with antibiotic use and immunodeficiency. Although, an increased incidence of community-acquired C. difficile infection (CA-CDI) has been reported worldwide, this infection has been under-diagnosed in Latin America. This is the first report of a CA-CDI case in Latin America, in an HIV-positive patient with cancer. © 2014 The Authors.


Furtado F.N.N.,Federal University of Ceará | Sampaio J.P.A.,Federal University of Ceará | Maia-Filho J.T.A.,Federal University of Ceará | Vieira R.B.,Federal University of Ceará | And 4 more authors.
Comparative Clinical Pathology | Year: 2015

Changes in metalloproteinase (MMP) and tissue inhibitor of metalloproteinases (TIMP) have been associated with tumor progression in colorectal cancer. However, the role of MMP-14 and TIMP-2 has yet to be determined. We investigated the differential expression of MMP-14 and TIMP-2 in colorectal carcinomas of the left and the right colon, as well as in mononuclear cells in primary tumors and their lymph node metastases. We performed an immunohistochemistry analysis of tumor samples obtained from 50 cases of colorectal cancer. We found that MMP-14 staining was positive in 100 % of cases, in contrast to normal mucosa (86 % positivity, P = 0.0451). Additionally, neoplastic cells showed a higher frequency of TIMP-2-positive staining (70 % versus 14 % of normal mucosa, P = 0.0004). Furthermore, MMP-14 expression in primary tumor-associated mononuclear cells was higher in cases without lymph node metastases (N0) in comparison to more advanced carcinomas (N1–N3) (P = 0.0353). MMP-14 and TIMP-2 expression was observed in neoplastic cells in primary tumors, with a higher frequency of increased expression of MMP-14 (82 %) than increased expression of TIMP-2 (22 %, P < 0.0001). The expression of MMP-14 and TIMP-2 was evaluated in each cell type and at each site, and the frequency of TIMP-2 expression in colonic lesions and in the lymph nodes was significantly higher than in tumor-infiltrating mononuclear cells (P = 0.0003 and P = 0.0406, respectively). Expression of MMP-14 and TIMP-2 in primary colorectal carcinomas and in their lymph node metastases suggests the involvement of these proteins in local invasion and tumor progression. © 2015, Springer-Verlag London.

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