Gastrointestinal dysmotility in 5-fluorouracil-induced intestinal mucositis outlasts inflammatory process resolution

Aim To evaluate gastrointestinal motility during 5-fluorouracil (5-FU)-induced intestinal mucositis. Materials and methods Wistar rats received 5-FU (150 mg kg(-1), i.p.) or saline. After the 1st, 3rd, 5th, 15th and 30th day, sections of duodenum, jejunum and ileum were removed for assessment of epithelial damage, apoptotic and mitotic indexes, MPO activity and GSH concentration. In order to study gastrointestinal motility, on the 3rd or 15th day after 5-FU treatment, gastric emptying in vivo was measured by scintilographic method, and stomach or duodenal smooth muscle contractions induced by CCh were evaluated in vitro. Results On the third day of treatment, 5-FU induced a significant villi shortening, an increase in crypt depth and intestinal MPO activity and a decrease in villus/crypt ratio and GSH concentration. On the first day after 5-FU there was an increase in the apoptosis index and a decrease in the mitosis index in all intestinal segments. After the 15th day of 5-FU treatment, a complete reversion of all these parameters was observed. There was a delay in gastric emptying in vivo and a significant increase in gastric fundus and duodenum smooth muscle contraction, after both the 3rd and 15th day. Conclusions 5-FU-induced gastrointestinal dysmotility outlasts intestinal mucositis.

Gastric damage induced by different doses of indomethacin in rats is variably affected by inhibiting iNOS or leukocyte infiltration

Aim: To evaluate the effect of inhibiting inducible nitric oxide synthase (iNOS), by aminoguanidine, or leukocyte infiltration, by fucoidin, on gastropathy induced by two different doses of indomethacin in rats. Methods: Rats were treated with saline, aminoguanidine (50 or 100 mg.kg(-1), i. p.) or fucoidin (25 mg.kg(-1), i. v.). Indomethacin was then given at a dose of 5 or 20 mg.kg(-1). At the end of 3 h, macroscopic gastric damage and myeloperoxidase (MPO) activity were assessed. Results: Aminoguanidine reduced the gastric damage induced by indomethacin at 20 mg.kg(-1), but increased gastric MPO activity. However, aminoguanidine did not influence the gastric damage induced by indomethacin at 5 mg.kg(-1). Fucoidin prevented both the gastric damage and the increase in gastric MPO activity induced by indomethacin at 20 mg. kg(-1), but not at 5 mg.kg(-1). Conclusion: Indomethacin at a dose of 20 mg.kg(-1), but not at 5 mg.kg(-1), induced gastropathy dependent on neutrophil infiltration and iNOS-generated NO.

Agglutinin isolated from the red marine alga Hypnea cervicornis J. Agardh reduces inflammatory hypernociception: Involvement of nitric oxide

Hypnea cervicornis agglutinin (HCA), a lectin isolated from the red marine alga has been previously shown to have an antinociceptive effect. In the present study in rats, mechanisms of action of HCA were addressed regarding mechanical hypernociception induced by carrageenan, ovalbumin (as antigen), and also by prostaglandin E(2) in rats. The lectin administered intravenously inhibited carrageenan- and antigen-induced hypernociception at 1,3, 5 and 7 h. This inhibitory effect was completely prevented when lectin was combined with mucin, demonstrating the role of carbohydrate-binding sites. The inhibition of inflammatory hypernociception by HCA was associated with the prevention of neutrophil recruitment to the plantar tissue of rats but was not associated with the inhibition of the release of pro-hypernociceptive cytokines (TNF-alpha, IL-1 beta and CINC-1). HCA also blocked mechanical hypernociception induced by PGE(2), which was prevented by the administration of nitric oxide synthase inhibitors. These results were corroborated by the increased circulating levels of NO metabolites following HCA treatment. These findings suggest that the anti-hypernociceptive effects of HCA are not associated with the inhibition of pro-inflammatory cytokine production. However, these effects seem to involve the inhibition of neutrophil migration and also the increase in NO production. (C) 2010 Elsevier Inc. All rights reserved.

Role of platelet-activating factor in the pathogenesis of 5-fluorouracil-induced intestinal mucositis in mice

Gastrointestinal mucositis is a common side effect of cancer chemotherapy. Platelet-activating factor (PAF) is produced during gut inflammation. There is no evidence that PAF participates in antineoplastic-induced intestinal mucositis. This study evaluated the role of PAF in 5-fluorouracil (5-FU)-induced intestinal mucositis using a pharmacological approach and PAF receptor knockout mice (PAFR(-/-)). Wild-type mice or PAFR(-/-) mice were treated with 5-FU (450 mg/kg, i.p.). Other mice were treated with saline or BN52021 (20 mg/kg, s.c.), an antagonist of the PAF receptor, once daily followed by 5-FU administration. After the third day of treatment, animals were sacrificed and tissue samples from the duodenum were removed for morphologic evaluation. In addition, myeloperoxidase activity and the cytokine concentration were measured. 5-FU treatment decreased the duodenal villus height/crypt depth ratio, increased MPO activity, and increased the concentration of TNF-alpha, IL-1 beta and KC in comparison with saline-treated animals. In PAFR(-/-) mice and PAFR antagonist-treated mice, 5-FU-dependent intestinal damage was reduced and a decrease in duodenal villus height/crypt depth ratio was attenuated. However, the 5-FU-dependent increase in duodenum MPO activity was not affected. Without PAFR activation, 5-FU treatment did not increase the TNF-alpha, IL-1 beta and KC concentration. In conclusion, our study establishes the role of PAFR activation in 5-FU-induced intestinal mucositis. This study implicates treatment with PAFR antagonists as novel therapeutic strategy for this condition.

Pharmacological analysis of the neutrophil migration induced by D. rostrata lectin: Involvement of cytokines and nitric oxide

In the present study, we investigated the involvement of resident cell and inflammatory mediators in the neutrophil migration induced by chemotactic activity of a glucose/mannose-specific lectin isolated from Dioclea rostrata seeds (DrosL). Rats were injected i.p. with DrosL (125-1000 mu g/cavity), and at 2-96 h thereafter the leukocyte counts in peritoneal fluid were determined. DrosL-induced a dose-dependent neutrophil migration accumulation, which reached maximal response at 24 h after injection and declines thereafter. The carbohydrate ligand nearly abolished the neutrophil influx. Pre-treatment of peritoneal cavities with thioglycolate which increases peritoneal macrophage numbers, enhanced neutrophil migration induced by DrosL by 303%. However, the reduction of peritoneal mast cell numbers by treatment of the cavities with compound 48/80 did not modify DrosL-induced neutrophil migration. The injection into peritoneal cavities of supernatants from macrophage cultures stimulated with DrosL (125, 250 and 500 mu g/ml) induced neutrophil migration. In addition, DrosL treatment induced cytokines (TNF-alpha, IL-1 beta and CINC-1) and NO release into the peritoneal cavity of rats. Finally, neutrophil chemotaxis assay in vitro showed that the lectin (15 and 31 mu g/ml) induced neutrophil chemotaxis by even 180%. In conclusion, neutrophil migration induced by D. rostrata lectin occurs by way of the release of NO and cytokines such as IL-1 beta, TNF-alpha and CINC-1. (C) 2009 Elsevier Ltd. All rights reserved.

Antinociceptive activity and toxicology of the lectin from Canavalia boliviana seeds in mice

The aim of the present study was to evaluate the potential antinociceptive and toxicity of Canavalia boliviana lectin (CboL) using different methods in mice. The role of carbohydrate-binding sites was also investigated. CboL given to mice daily for 14 days at doses of 5 mg/kg did not cause any observable toxicity. CboL (1, 5, and 10 mg/kg) administered to mice intravenously inhibited abdominal constrictions induced by acetic acid and the two phases of the formalin test. In the hot plate and tail immersion tests, the same treatment of CboL induced significant increase in the latency period. In the hot plate test, the effect of CboL (5 mg/kg) was reversed by naloxone (1 mg/kg), indicating the involvement of the opioid system. In the open-field and rota-rod tests, the CboL treatment did not alter animals` motor function. These results show that CboL presents antinociceptive effects of both central and peripheral origin, involving the participation of the opioid system via lectin domain.

Stigmatization of alcohol and other drug users by primary care providers in Southeast Brazil

This study reports on the views of Primary Health Care (PHC) providers in Southeast Brazil on the use of alcohol and other drugs which reflect stigma, moralization, or negative judgment. Six hundred nine PHC professionals from the Brazilian states of Sao Paulo and Minas Gerais took part in the study. The majority (86.5%) of these professionals were female. Attitudes toward the use of alcohol and other drugs were evaluated in comparison to Hansen`s disease, obesity, depression, schizophrenia. HIV/AIDS, and tobacco use. The use of tobacco, marijuana/cocaine, and alcohol were the most negatively judged behaviors (p < 0.05). Nursing assistants and community health care workers demonstrated the severest judgment of alcohol use. In addition, marijuana/cocaine addicts and alcoholics suffered the highest rate of rejection by professionals. The hypothesis that the use of alcohol and other drugs is a behavior stigmatized by health professionals being confirmed, it is important to develop strategies for changing provider attitudes in order to provide a higher quality of service to these patients. This study is important as a first study among PHC professionals about social stigma of alcohol and other drugs users. (C) 2009 Elsevier Ltd. All rights reserved.

LOW-INTENSITY ULTRASOUND APPLICATION IN DISTAL RADIUS METAPHYSEAL BONE DEFECTS OF DOGS

We assessed the repair of transverse, 3-mm wide bone gaps created at the distal radius in 28 dogs that were randomly divided into two 14-animal groups; one was the control group and the other received a daily, 20-min application of low-intensity pulsed ultrasound for 100 days. Sequential radiographs, histomorphometrics, bone fluorescent histology and bone vascularity assessments found that all animals from both groups obtained a stage of hypertrophic-type nonunion with fibrocartilage tissue formation throughout the region of osteotomy. However, treated animals exhibited areas of endochondral ossification within the fibrocartilage region. There was no difference in type of vascularity or the newly formed bone process obtained by tetracycline labeling. Application of low-intensity ultrasound was not capable of significantly changing the reparative process and it may not be sufficiently powerful to overcome a combination of local deleterious effects on bone healing, created by gapping, excessive motion and periosteal resection. (E-mail: jbvolpon@fmrp.usp.br) (C) 2010 World Federation for Ultrasound in Medicine & Biology.

Human immature dental pulp stem cells` contribution to developing mouse embryos: production of human/mouse preterm chimaeras

In this study, we aimed at determining whether human immature dental pulp stem cells (hIDPSC) would be able to contribute to different cell types in mouse blastocysts without damaging them. Also, we analysed whether these blastocysts would progress further into embryogenesis when implanted to the uterus of foster mice, and develop human/mouse chimaera with retention of hIDPSC derivates and their differentiation. hIDPSC and mouse blastocysts were used in this study. Fluorescence staining of hIDPSC and injection into mouse blastocysts, was performed. Histology, immunohistochemistry, fluorescence in situ hybridization and confocal microscopy were carried out. hIDPSC showed biological compatibility with the mouse host environment and could survive, proliferate and contribute to the inner cell mass as well as to the trophoblast cell layer after introduction into early mouse embryos (n = 28), which achieved the hatching stage following 24 and 48 h in culture. When transferred to foster mice (n = 5), these blastocysts with hIDPSC (n = 57) yielded embryos (n = 3) and foetuses (n = 6); demonstrating presence of human cells in various organs, such as brain, liver, intestine and hearts, of the human/mouse chimaeras. We verified whether hIDPSC would also be able to differentiate into specific cell types in the mouse environment. Contribution of hIDPSC in at least two types of tissues (muscles and epithelial), was confirmed. We showed that hIDPSC survived, proliferated and differentiated in mouse developing blastocysts and were capable of producing human/mouse chimaeras.

Immunoprofile of Kuttner tumor (chronic sclerosing sialadenitis)

In the present study, the immunoprofile of chronic sclerosing sialadenitis, also known as Kuttner tumor, was analyzed. Two,cases that occurred in the submandibular gland of male patients were submitted to immunohistochemical reactions to different antibodies. Histological examinations showed a submandibular gland exhibiting various degrees of atrophy with destruction of acini, infiltration by inflammatory cells, and periductal fibrosis. Reactions to cytokeratins (CKs) showed acini and duct remnants positive to CKs 7, 8, 19, and 13. CK14 stained myoepithelial cells around preserved acini and intercalated duct, and also basal cell of excretory ducts, but was negative in proliferating and branching ducts. Smooth muscle actin (SMA) was expressed by myofibroblasts in periductal fibrosis, and an intense expression of extracellular components was also seen. Lymphocyte markers showed, besides mature follicles, a higher presence of CD45RO positive cells. Thus, the immunoprofile of Kuttner is much more in keeping with an inflammatory-induced degenerative disease than with a preneoplastic lesion.

X-ray fluorescence with synchrotron radiation to elemental analysis of lead and calcium content of primary teeth

Primary teeth were analyzed by micro-SRXRF. The aim of this study was to determine the elemental distribution of lead and calcium in different regions of primary incisor of children living in a notoriously contaminated area (Santo Amaro da Purificacao, Bahia State, Brazil). The measurements were performed in standard geometry of 45 incidence, exciting with a white beam and using a conventional system collimation (orthogonal slits) in the XRF beamline at the Synchrotron Light National Laboratory (Campinas, Brazil). (C) 2009 Elsevier Ltd. All rights reserved.

Intraempreendedorismo e a inova????o na gest??o p??blica federal

O objetivo deste artigo ?? apresentar tr??s a????es empreendedoras em organiza????es p??blicas premiadas pela ENAP no concurso Inova????o na Gest??o P??blica Federal. A partir da revis??o de literatura e estudo de caso, ser??o confrontados os diversos tipos e modelos de processos de inova????o, para identificar as dificuldades apontadas e as solu????es adotadas nas a????es premiadas. Foram selecionados tr??s casos de iniciativas inovadoras no INSS, apontando a origem, caracter??sticas, amplitude e o modelo do processo. Nosso quadro te??rico de refer??ncia est?? estruturado no sentido de aprofundar a percep????o, bem como nos dar condi????es de comparar alguns estudos e apontar lacunas, se existentes. A pesquisa foi realizada por meio de metodologia qualitativa, explorat??ria e adotando a estrat??gia de investiga????o do estudo de caso. A revis??o de literatura teve como objetivo identificar o que se encontra dispon??vel em livros, artigos, teses e, inclusive, experi??ncias. A conclus??o alcan??ada no artigo ?? a de que, apesar dos alegados entraves e limita????es, o intraempreendedorismo se faz presente nas organiza????es p??blicas e vem crescentemente sendo adotado pelas chefias ou mesmo por funcion??rios sem nenhum tipo de fun????o comissionada, como relatado em um dos casos. A inova????o nas organiza????es p??blicas, representada pelo intraempreendedorismo das experi??ncias premiadas pelo concurso, confirma nosso quadro te??rico na medida em que a????es empreendedoras geradoras de inova????o se fazem presentes nas organiza????es p??blicas, em todos os seus processos e meios.

Investigando a financeirização pelos seus teóricos / Pedro Rozales Rodero Dominczak

Partimos do fato de que, nas últimas décadas, em especial a partir da década de 1980, o capital retoma parte da lucratividade perdida na década anterior. Essa retomada da lucratividade, contudo, se dá sobre características fortemente diferenciadas da acumulação que marcou o crescimento do período conhecido como os “30 anos dourados” do capitalismo (sobretudo para a perspectiva das classes dominantes dos países centrais). Nesse sentido, nosso pressuposto é que, desde a virada operada pela crise estrutural da década de 1970, a esfera financeira ganhou autonomia em relação ao ciclo global da reprodução capitalista. E, decorrente dessa autonomia, a esfera financeira salta à condição de dominância em relação ao ciclo global. Assim, o objetivo geral desta dissertação é analisar os trabalhos que, pela perspectiva crítica, têm como objeto a esfera financeira. E nosso objetivo específico é compreender como a esfera financeira se relaciona com o ciclo global da reprodução capitalista. Dessa forma, quais seriam as principais características deste novo momento? Quais as causas que teriam impulsionado um crescimento tão acelerado da esfera financeira? Se vivemos em uma fase do capitalismo com forte influência financeira, em que consiste a financeirização, termo que aqui adotamos? E, principalmente, qual o seu relacionamento com o ciclo global do capital? Ela contribuiu para o desenvolvimento da acumulação capitalista ou pode ser considerada como refratária ao desenvolvimento e à expansão do capitalismo? Estas serão as questões que serão trabalhadas ao longo da dissertação.

Crítica à concepção hegemônica de "erradicação da pobreza" : um estudo sobre a estratégia de naturalização e gestão da barbárie no Espírito Santo

Com base em pesquisa bibliográfica e documental, e fazendo uso da análise de conteúdo, este trabalho tem como objetivo geral analisar a meta erradicar a pobreza até 2025, constituinte do Plano de Desenvolvimento Espírito Santo 2025. Compreendemos que essa meta faz parte do modelo de ―desenvolvimento sustentado‖ elaborado pela burguesia capixaba, organizada no Movimento Empresarial Espírito Santo em Ação, e em articulação com o executivo estadual e a Petrobrás, sem que tenha havido participação de trabalhadores na elaboração do Plano mencionado. Seguem-se as principais conclusões. A meta em questão foi construída sob o marco ideopolítico e teórico da ―internacionalização do combate à pobreza‖, transpondo-se para o território estadual o discurso hegemônico de erradicação daquela condição social, entendida como sendo, em última análise, de responsabilidade do indivíduo, e não enquanto consequência direta do modo de produção capitalista. Além disso, os pobres são compreendidos, na elaboração da meta, de forma dual: ora identificados através do ―pressuposto da falta‖, ora enquanto ―agentes‖ livres para construir seu próprio futuro. Em consequência dessa dualidade, são propostas duas vias de ação tidas como essenciais para ―erradicar a pobreza‖: uma, centrada na transferência de renda para os que vivem na pobreza mais acentuada, e outra, na concessão de (micro)crédito para os pobres não miseráveis, com vistas a possibilitar que se tornem ―empreendedores‖. A meta analisada visa contribuir para promover a ―paz social‖, através da contenção dos pobres e de sua latente revolta diante de sua degradada condição de vida em território espírito-santense, o que demonstra sua funcionalidade para naturalizar e gerir a barbárie que marca a contemporaneidade capitalista.

Adesão ao tratamento por cuidadores de crianças e adolescentes soropositivos para o HIV

Objetivou-se investigar o padrão de adesão ao tratamento por cuidadores de crianças e adolescentes HIV positivos e identificar as estratégias de enfrentamento adotadas diante de estressores da soropositividade. Participaram 30 cuidadores e utilizou-se entrevista semiestruturada, Escala Modos de Enfrentamento de Problemas e prontuário clínico, este como fonte de dados secundários. Os cuidadores foram classificados em Grupo Adesão e Grupo Não-Adesão com base em seus relatos sobre condutas de uso dos medicamentos antirretrovirais e outros critérios. Vinte e cinco cuidadores foram incluídos no Grupo Adesão. Não se observaram diferenças significativas quanto ao enfrentamento entre os grupos, excetuando a busca de práticas religiosas/pensamento fantasioso. Os resultados dão subsídios para intervenções visando reduzir impactos psicossociais da soropositividade a cuidadores, crianças e adolescentes. ______________________________________________________________________________ ABSTRACT