RESUMO
OBJECTIVES To evaluate the frequency of prescription of proton pump inhibitors (PPIs) and their indications in patients hospitalized at the Hospital de Clínicas of the Federal University of Uberlândia (HC-UFU). METHODS This is a quantitative cross-sectional observational study that analyzes data obtained from patient records on prescriptions of PPIs for patients hospitalized at the HC-UFU and from a questionnaire applied to assistant physicians on the indications of the drug in each case and evaluates the indication based on literature data. RESULTS On a pre-determined day, of a total of 462 inpatients, there was a prescription of PPI for 183 (39.3%), with a higher frequency (73.5%) in the Intensive Care Unit (ICU), followed by the infirmaries and the Emergency Room. The assistant physician was located in 116 cases, and the main motivation referred to prescription was prophylaxis of digestive hemorrhage (77%). However, after reviewing medical records, it was noticed that in 50.8% of the cases, the prescription was not supported by the literature. CONCLUSION The frequency of PPI prescriptions for inpatients in the HC-UFU is among the lowest described in the literature, but there are still unnecessary prescriptions. Instruction and awareness of the assisting team can minimize these numbers.
Assuntos
Prescrições de Medicamentos , Inibidores da Bomba de Prótons , Brasil , Estudos Transversais , Humanos , Padrões de Prática Médica , Inibidores da Bomba de Prótons/uso terapêutico , Centros de Atenção TerciáriaRESUMO
SUMMARY OBJECTIVES To evaluate the frequency of prescription of proton pump inhibitors (PPIs) and their indications in patients hospitalized at the Hospital de Clínicas of the Federal University of Uberlândia (HC-UFU). METHODS This is a quantitative cross-sectional observational study that analyzes data obtained from patient records on prescriptions of PPIs for patients hospitalized at the HC-UFU and from a questionnaire applied to assistant physicians on the indications of the drug in each case and evaluates the indication based on literature data. RESULTS On a pre-determined day, of a total of 462 inpatients, there was a prescription of PPI for 183 (39.3%), with a higher frequency (73.5%) in the Intensive Care Unit (ICU), followed by the infirmaries and the Emergency Room. The assistant physician was located in 116 cases, and the main motivation referred to prescription was prophylaxis of digestive hemorrhage (77%). However, after reviewing medical records, it was noticed that in 50.8% of the cases, the prescription was not supported by the literature. CONCLUSION The frequency of PPI prescriptions for inpatients in the HC-UFU is among the lowest described in the literature, but there are still unnecessary prescriptions. Instruction and awareness of the assisting team can minimize these numbers.
RESUMO OBJETIVOS Avaliar a frequência da prescrição de inibidores da bomba de prótons (IBPs) e suas indicações em pacientes internados no Hospital de Clínicas da Universidade Federal de Uberlândia (HC-UFU). MÉTODOS Estudo observacional transversal quantitativo, análise de dados obtidos em prontuários sobre prescrições de IBPs para pacientes internados no HC-UFU, aplicação de questionário aos médicos assistentes sobre as indicações do medicamento em cada caso e avaliação dessas indicações com base em dados da literatura. RESULTADOS Em um dia predeterminado, de 462 pacientes internados, houve prescrição de IBP para 183 (39,3%), com maior frequência (73,5%) em Unidade de Terapia Intensiva (UTI), seguida das enfermarias e do pronto-socorro (PS). O médico assistente foi localizado em 116 casos, a principal motivação referida para prescrição foi a profilaxia de hemorragia digestiva (77%). Entretanto, após revisão de prontuários, percebeu-se que em 50,8% a prescrição não era respaldada por literatura. CONCLUSÃO A frequência de prescrição de IBP para pacientes internados no HC-UFU está entre as menores descritas na literatura, mas ainda há prescrições desnecessárias. Orientação e conscientização da equipe assistente podem minimizar esses números.
Assuntos
Humanos , Prescrições de Medicamentos , Padrões de Prática Médica , Brasil , Estudos Transversais , Inibidores da Bomba de Prótons/uso terapêutico , Centros de Atenção TerciáriaRESUMO
Liver diseases are a major health problem worldwide leading to high mortality rates and causing a considerable economic burden in many countries. Cellular therapies as potential treatments for liver diseases have proven beneficial in most of the conditions. In recent years, studies involving therapy with bone marrow cells have been implemented to promote liver regeneration and to reduce hepatic fibrosis, however identifying the cell population present in the bone marrow that is responsible for hepatic improvement after therapy is still necessary. The aim of the present study was the evaluation of the therapeutic efficacy of monocytes obtained from bone marrow in fibrosis resulting from S. mansoni infection in C57BL/6 mice. Monocytes were isolated by immunomagnetic separation and administered to the infected animals. The effects of treatment were evaluated through morphometric, biochemical, immunological and molecular analyzes. Monocyte therapy promoted reduction of liver fibrosis induced by S. mansoni infection, associated with a decrease in production of inflammatory and pro-fibrogenic mediators. In addition, monocyte infusion caused downregulation of factors associated with the M1 activation profile, as well as upregulation of M2reg markers. The findings altogether reinforce the hypothesis that the predominance of M2reg macrophages, producers of immunosuppressive cytokines, may favor the improvement of hepatic fibrosis in a preclinical model, through fibrous tissue remodeling, modulation of the inflammatory response and fibrogenesis.
Assuntos
Transferência Adotiva/métodos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Cirrose Hepática/terapia , Regeneração Hepática , Monócitos/transplante , Schistosoma mansoni/patogenicidade , Esquistossomose mansoni/terapia , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/imunologia , Diferenciação Celular , Citocinas/genética , Citocinas/imunologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Fígado/imunologia , Fígado/parasitologia , Fígado/patologia , Cirrose Hepática/imunologia , Cirrose Hepática/parasitologia , Cirrose Hepática/patologia , Macrófagos/citologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/citologia , Monócitos/imunologia , Schistosoma mansoni/crescimento & desenvolvimento , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/parasitologia , Esquistossomose mansoni/patologiaRESUMO
Schistosomiasis affects approximately 240 million people in the world. Schistosoma mansoni eggs in the liver induce periportal fibrosis and hepatic failure driven by monocyte recruitment and macrophage activation, resulting in robust Th2 response. Here, we suggested a possible involvement of Galectin-3 (Gal-3), histone deacetylases (HDACs), and Hedgehog (Hh) signaling with macrophage activation during Th1/Th2 immune responses, fibrogranuloma reaction, and tissue repair during schistosomiasis. Gal-3 is highly expressed by liver macrophages (Kupffer cells) around Schistosoma eggs. HDACs and Hh regulate macrophage polarization and hepatic stellate cell activation during schistosomiasis-associated fibrogenesis. Previously, we demonstrated an abnormal extracellular matrix distribution in the liver that correlated with atypical monocyte-macrophage differentiation in S. mansoni-infected, Gal-3-deficient (Lgals3-/-) mice. New findings explored in this review focus on the chronic phase, when wild-type (Lgals3+/+) and Lgals3-/- mice were analyzed 90 days after cercariae infection. In Lgals3-/- infected mice, there was significant inflammatory infiltration with myeloid cells associated with egg destruction (hematoxylin and eosin staining), phagocytes (specifically Kupffer cells), numerically reduced and diffuse matrix extracellular deposition in fibrotic areas (Gomori trichrome staining), and severe disorganization of collagen fibers surrounding the S. mansoni eggs (reticulin staining). Granuloma-derived stromal cells (GR cells) of Lgals3-/- infected mice expressed lower levels of alpha smooth muscle actin (α-SMA) and eotaxin and higher levels of IL-4 than Lgals3+/+ mice (real-time PCR). The relevant participation of macrophages in these events led us to suggest distinct mechanisms of activation that culminate in defective fibrosis in the liver of Lgals3-/- infected mice. These aspects were discussed in this review, as well as the possible interference between Gal-3, HDACs, and Hh signaling during progressive liver fibrosis in S. mansoni-infected mice. Further studies focused on macrophage roles could elucidate these questions and clear the potential utility of these molecules as antifibrotic targets.
Assuntos
Galectina 3/metabolismo , Ouriços/metabolismo , Histona Desacetilases/metabolismo , Cirrose Hepática/metabolismo , Esquistossomose/complicações , Animais , Galectina 3/genética , Ouriços/genética , Histona Desacetilases/genética , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/genética , Esquistossomose/parasitologia , Esquistossomose Japônica/parasitologia , Transdução de SinaisRESUMO
Eicosanoids are bioactive lipids derived from enzymatic metabolism of arachidonic acid via the cyclooxygenase (COX) and lipoxygenase (LOX) pathways. These lipids are newly formed and nonstorable molecules that have important roles in physiological and pathological processes. The particular interest to determine intracellular compartmentalization of eicosanoid-synthetic machinery has emerged as a key component in the regulation of eicosanoid synthesis and in delineating functional intracellular and extracellular actions of eicosanoids. In this chapter, we discuss the EicosaCell protocol, an assay that enables the intracellular detection and localization of eicosanoid lipid mediator-synthesizing compartments by means of a strategy to covalently cross-link and immobilize eicosanoids at their sites of synthesis followed by immunofluorescent-based localization of the targeted eicosanoid. EicosaCell assays have been successfully used to identify different intracellular compartments of synthesis of prostaglandins and leukotrienes upon cellular activation. This chapter covers basics of EicosaCell assay including its selection of reagents, immunodetection design as well as some troubleshooting recommendations.
Assuntos
Bioensaio/métodos , Eicosanoides/biossíntese , Animais , Imunofluorescência , Processamento de Imagem Assistida por Computador/métodos , Espaço Intracelular/metabolismo , Metabolismo dos Lipídeos , Camundongos , Microscopia de Fluorescência , Imagem Molecular/métodos , Imagem Óptica , Fagossomos , Software , Coloração e Rotulagem/métodosRESUMO
BACKGROUND: Hepatic myofibroblasts are relevant for pathogenesis of S. mansoni infection. In normal liver, these perisinusoidal cells are quiescent, express the lipocyte phenotype, and are located in the Disse's space, being the major site of vitamin A storage. When activated, they convert to myofibroblasts and contribute to granulomatous and diffuse liver fibrosis. In the present work, we observed that myofibroblasts obtained from granulomatous periovular inflammatory reactions in schistosome-infected mice (GR-MF) produce in vitro immunomodulatory cytokines for eosinophil activation: IL-5 and eotaxin. METHODS AND RESULTS: The secretory activity of GR-MF was detected after TGF-ß and IL-13 stimulation using 2D and 3D cell culture systems. In a mixed co-culture system using GR-MF with hematopoietic bone marrow cells from infected mice, we observed eosinophil survival that was dependent upon IL-5 and eotaxin, since antibodies against this cytokines decreased eosinophil population, as measured by eosinophil peroxidase activity. CONCLUSION: These results indicate that GR-MF may contribute to maintenance of local eosinophilia in schistosomal hepatic granulomas, and can function as immunoregulatory cells, besides their role in production of fibrosis.
Assuntos
Quimiocina CCL11/metabolismo , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Interleucina-5/metabolismo , Fígado/parasitologia , Miofibroblastos/metabolismo , Schistosoma mansoni/crescimento & desenvolvimento , Animais , Modelos Animais de Doenças , Granuloma/patologia , Fígado/patologia , Camundongos , Esquistossomose mansoni/parasitologia , Esquistossomose mansoni/patologiaRESUMO
Hepatic stellate cells (HSCs) have a critical role in liver physiology, and in the pathogenesis of liver inflammation and fibrosis. Here, we investigated the interplay between leukotrienes (LT) and TGF-ß in the activation mechanisms of HSCs from schistosomal granulomas (GR-HSCs). First, we demonstrated that GR-HSCs express 5-lipoxygenase (5-LO), as detected by immunolocalization in whole cells and confirmed in cell lysates through western blotting and by mRNA expression through RT-PCR. Moreover, mRNA expression of 5-LO activating protein (FLAP) and LTC(4)-synthase was also documented, indicating that GR-HSCs have the molecular machinery required for LT synthesis. Morphological analysis of osmium and Oil-Red O-stained HSC revealed large numbers of small lipid droplets (also known as lipid bodies). We observed co-localization of lipid droplet protein marker (ADRP) and 5-LO by immunofluorescence microscopy. We demonstrated that GR-HSCs were able to spontaneously release cysteinyl-LTs (CysLTs), but not LTB(4,) into culture supernatants. CysLT production was highly enhanced after TGF-ß-stimulation. Moreover, the 5-LO inhibitor zileuton and 5-LO gene deletion were able to inhibit the TGF-ß-stimulated proliferation of GR-HSCs, suggesting a role for LTs in HSC activation. Here, we extend the immunoregulatory function of HSC by demonstrating that HSC from liver granulomas of schistosome-infected mouse are able to release Cys-LTs in a TGF-ß-regulated manner, potentially impacting pathogenesis and liver fibrosis in schistosomiasis.
Assuntos
Granuloma/parasitologia , Leucotrienos/metabolismo , Fígado/patologia , Schistosoma mansoni/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Araquidonato 5-Lipoxigenase/metabolismo , Sequência de Bases , Western Blotting , Primers do DNA , Leucotrienos/biossíntese , Fígado/parasitologia , Camundongos , Microscopia de Fluorescência , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Schistosoma mansoni/isolamento & purificaçãoRESUMO
As células conjuntivas hepáticas possuem um papel importante na patogênese da infecção por S. mansoni, e dentre essas células destacam-se as células estreladas hepáticas.As células estreladas hepáticas derivadas do granuloma esquistossomóticos podemser cultivadas in vitro, sendo denominadas células GR. No estado fisiológico, essas células estão situadas no espaço de Disse de maneira quiescente, e representam as principais células armazenadoras de vitamina A do organismo. Quando ativadas, essas células perdem sua capacidade de armazenamento e passam a ter o fenótipo de miofibroblastos, contribuindo na resposta granulomatosa e no processo fibrótico durante a infecção por S. mansoni. No entanto, ainda não foi descrito o envolvimento dessas células na intensa eosinofilia tecidual que é característica da esquistossomose. A fim de melhor entender o envolvimento da GR na ativação de eosinófilos, o objetivo deste trabalho foi identificar a produção de mediadores eosinopoéticos, assim como a presença dos corpúsculos lipídicos nas células GR. Demonstramos que as células GR expressam RNAm para Interceucina-5 (IL-5) e eotaxina, e também para 5-Lipoxigenase (5-LO), FLAP e LTC4-sintase, enzimas necessárias para a síntesede leucotrienos. No entanto, só foi detectada a presença de cisteinil leucotrienos (cysLTs)no sobrenadante dessas células em cultura. Além disso, observamos que parte da 5-LO expressa pelas células GR é compartimentalizada nos corpúsculos lipídicos, que são estruturas citoplasmáticas ricas em lipídeos presentes em células inflamatórias. Dessa forma, concluímos que as células GR parecem contribuir na eosinofilia observada durante a esquistossomose mansônica, através da expressão de mediadores eosinofílicos.