Telmisartan Modulates the Oral Mucositis Induced by 5-Fluorouracil in Hamsters

Oral mucositis (OM) is a common adverse effect resulting from cancer therapy. The OM it has implications that may compromise oncologic treatment and decrease the patient’s quality of life. The therapeutic options to prevent or treat the symptoms of OM are scarce; there is no effective therapy that improves the symptoms. Based on the need for further research for the treatment of OM, the present study objective was to evaluate the effect of telmisartan (TELM) on the OM induced by 5-fluorouracil (5-FU), using as animal model Golden Syrian hamsters. 5-FU followed by mechanical trauma on day 4 was used to induce OM in hamsters. Euthanasia occurred on the day 10. The experiments were constituted by the groups saline, mechanical trauma, 5-FU, and TELM in three doses (1, 5, or 10 mg/kg). Macroscopic, histopathological, and immunohistochemical analyses as well as immunofluorescence experiments were performed on the oral mucosa of the animals. The samples also were used for analysis enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reactions (qPCR). TELM (5 or 10 mg/kg) was able to reduce the inflammatory ulceration and infiltration in the oral mucosa of the animals, decreasing the levels of the cytokines TNF-α and IL-1β. These treatments was minimize the immunostaining for cyclooxygenase-2, matrix metalloproteinase-9, transforming growth factor-β, and smad 2/3. The nuclear transcription factor kappa B (NFκB) p65 and inducible nitric oxide synthase were reduced in the oral mucosa. Finally, TELM (10 mg/kg) increased the PPARγ gene expression and reduced STAT1 and NFκB p65 gene expression relative to the 5-FU group. Therefore, TELM prevents the OM produced by 5-FU on animal model

The involvement of mast cells in the irinotecan-induced enteric neurons loss and reactive gliosis

Abstract Background The irinotecan (CPT-11) causes intestinal mucositis and diarrhea that may be related to changes in the enteric nervous system (ENS). In inflammatory condition, mast cells release a variety of pro-inflammatory mediators that can interact with the ENS cells. It has not been explored whether CPT-11 is able to alter the enteric glial and neuronal cell, and the role of mast cells in this effect. Therefore, this study was conducted to investigate the effect of CPT-11 on the enteric glial and neuronal cells, as well as to study the role of mast cells in the CPT-11-induced intestinal mucositis. Methods Intestinal mucositis was induced in Swiss mice by the injection of CPT-11 (60 mg/kg, i.p.) once a day for 4 days following by euthanasia on the fifth day. To investigate the role of mast cells, the mice were pretreated with compound 48/80 for 4 days (first day, 0.6 mg/kg; second day, 1.0 mg/kg; third day, 1.2 mg/kg; fourth day, 2.4 mg/kg) to induce mast cell degranulation before the CPT-11 treatment. Results Here, we show that CPT-11 increased glial fibrillary acidic protein (GFAP) and S100β gene and S100β protein expressions and decreased HuC/D protein expression in the small intestine segments. Concomitantly, CPT-11 enhanced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels and inducible nitric oxide synthase (iNOS) gene expression, associated with an increase in the total number macrophages (positive cells for ionized calcium-binding adapter molecule, Iba-1) and degranulated mast cells in the small intestine segments and caused significant weight loss. The pretreatment with compound 48/80, an inductor of mast cells degranulation, significantly prevented these CPT-11-induced effects. Conclusions Our data suggests the participation of mast cells on the CPT-11-induced intestinal mucositis, macrophages activation, enteric reactive gliosis, and neuron loss

Os desafios do controle interno governamental diante da reforma do estado: o caso do programa de modernização do controle interno do estado da Paraíba (Promocin)

Este artigo tem por objetivo desenvolver um estudo comparativo entre as atividades definidas no componenteauditoria e controle interno do Programa de Modernização do Controle Interno do Estado da Paraíba (Promocin) - coordenado pela Secretaria do Controle da Despesa Pública (SCDP) - e as diretrizes lançadas pelo processode reforma do Estado brasileiro para implantação do paradigma da administração pública gerencial no setor público. Esse paradigma aponta para um modelo de gestão do controle interno a posteriori, mais enfocado na avaliação dos resultados da aplicação dos recursos públicos do que no mero cumprimento das formalidades legaisaplicáveis às despesas públicas. O estudo foi realizado através de levantamentos bibliográficos e documentais acerca do tema, com o intuito de averiguar a consonância entre as atividades contempladas no Promocin e a tendência atual estabelecida pelos ventos da reforma do Estado para o perfil das entidades de auditoria e controle interno da esfera governamental. A pesquisa demonstrou a condição de vanguarda da Secretaria do Controle da Despesa Pública que, através do Promocin, vem procurando estabelecer ações de controle mais efetivas no processo de avaliação dos gastos públicos, possibilitando um considerável salto de qualidade nos serviços de auditoria interna no Poder Executivo estadual

Correction: Topical HPMC/S-Nitrosoglutathione Solution Decreases Inflammation and Bone Resorption in Experimental Periodontal Disease in Rats.

[This corrects the article DOI: 10.1371/journal.pone.0153716.]

Zooplankton From a Reef System Under the Influence of the Amazon River Plume

At the mouth of the Amazon River, a widespread carbonate ecosystem exists below the river plume, generating a hard-bottom reef (∼9500 km2) that includes mainly large sponges but also rhodolith beds. The mesozooplankton associated with the pelagic realm over the reef formation was characterized, considering the estuarine plume and oceanic influence. Vertical hauls were carried out using a standard plankton net with 200 μm mesh size during September 2014. An indicator index was applied to express species importance as ecological indicators in community. Information on functional traits was gathered for the most abundant copepod species. Overall, 179 zooplankton taxa were recorded. Copepods were the richest (92 species), most diverse and most abundant group, whereas meroplankton were rare and less abundant. Species diversity (>3.0 bits.ind-1) and evenness (>0.6) were high, indicating a complex community. Small holoplanktonic species dominated the zooplankton, and the total density varied from 107.98 ind. m-3 over the reef area to 2,609.24 ind. m-3 in the estuarine plume, with a significant difference between coastal and oceanic areas. The most abundant copepods were the coastal species ithona plumifera and Clausocalanus furcatus and early stages copepodites of Paracalanidae. The holoplanktonic Oikopleura, an important producer of mucous houses, was very abundant on the reefs. The indicator species index revealed three groups: (1) indicative of coastal waters under the influence of the estuarine plume [Euterpina acutifrons, Parvocalanus crassirostris, Oikopleura (Vexillaria) dioica and Hydromedusae]; (2) characterized coastal and oceanic conditions (Clausocalanus); (3) characterized the reef system (O. plumifera). Two major copepods functional groups were identified and sorted according to their trophic strategy and coastal-oceanic distribution. The species that dominated the coastal area and the area over the rhodolith beds are indicators of the estuarine plume and are mixed with species of the North Brazil Current. These species practically disappear offshore, where occur oceanic species commonly found in other oligotrophic tropical areas. This ecosystem shows a mixture of estuarine, coastal and oceanic communities coexisting in the waters over the Amazon reefs, with no significant differences among these areas. However, the MDS clearly separated the communities along the salinity gradient in the plume

S-Nitrosoglutathione Accelerates Recovery from 5-Fluorouracil-Induced Oral Mucositis

<div><p>Introduction</p><p>Mucositis induced by anti-neoplastic drugs is an important, dose-limiting and costly side-effect of cancer therapy.</p><p>Aim</p><p>To evaluate the effect of the topical application of S-nitrosoglutathione (GSNO), a nitric oxide donor, on 5-fluorouracil (5-FU)-induced oral mucositis in hamsters.</p><p>Materials and Methods</p><p>Oral mucositis was induced in male hamsters by two intraperitoneal administrations of 5-FU on the first and second days of the experiment (60 and 40 mg/kg, respectively) followed by mechanical trauma on the fourth day. Animals received saline, HPMC or HPMC/GSNO (0.1, 0.5 or 2.0 mM) 1 h prior to the 5-FU injection and twice a day for 10 or 14 days. Samples of cheek pouches were harvested for: histopathological analysis, TNF-α and IL-1β levels, immunohistochemical staining for iNOS, TNF-α, IL-1β, Ki67 and TGF-β RII and a TUNEL assay. The presence and levels of 39 bacterial taxa were analyzed using the Checkerboard DNA-DNA hybridization method. The profiles of NO released from the HPMC/GSNO formulations were characterized using chemiluminescence.</p><p>Results</p><p>The HPMC/GSNO formulations were found to provide sustained release of NO for more than 4 h at concentration-dependent rates of 14 to 80 nmol/mL/h. Treatment with HPMC/GSNO (0.5 mM) significantly reduced mucosal damage, inflammatory alterations and cell death associated with 5-FU-induced oral mucositis on day 14 but not on day 10. HPMC/GSNO administration also reversed the inhibitory effect of 5-FU on cell proliferation on day 14. In addition, we observed that the chemotherapy significantly increased the levels and/or prevalence of several bacterial species.</p><p>Conclusion</p><p>Topical HPMC/GSNO accelerates mucosal recovery, reduces inflammatory parameters, speeds up re-epithelization and decreases levels of periodontopathic species in mucosal ulcers.</p></div