RESUMO
Glutamine (GLN) avoids the inhibition of the intestinal Ca2+ absorption caused by menadione (MEN) through oxidative stress. The purpose of this study was to elucidate whether molecules of transcellular and/or paracellular pathways of intestinal Ca2+ absorption are involved in the GLN action and underlying mechanisms. One-month old chicks were divided in four groups: 1) controls, 2) MEN treated, 3) GLN treated and 4) GLNâ¯+â¯MEN treated. The morphology of intestinal villi, the intestinal Ca2+ absorption and the molecules involved in the transcellular and paracellular pathways were analyzed. Markers of autophagy and inflammation were also evaluated. The data demonstrated that GLN protected both transcellular and paracellular pathways. GLN avoided morphological changes in the intestine caused by MEN. GLN protected the gene expression of transporters involved in the transcellular pathway and the gene and protein expression of molecules belonging to the paracellular pathways altered by MEN. GLN increased the LC3-II protein expression and the number of acidic vesicular organelles, markers of autophagy, and blocked an increase in the NFkB protein expression in the nuclei and in the IL-6 gene expression caused by MEN. In conclusion, GLN protects both transcellular and paracellular pathways of intestinal Ca2+ absorption by increasing autophagy and blocking inflammation.
Assuntos
Cálcio/metabolismo , Galinhas/metabolismo , Glutamina/farmacologia , Absorção Intestinal/efeitos dos fármacos , Oxidantes/toxicidade , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Autofagia/efeitos dos fármacos , Autofagia/genética , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Duodeno/efeitos dos fármacos , Duodeno/metabolismo , Duodeno/ultraestrutura , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/patologia , Rutênio Vermelho/toxicidade , Vitamina K 3/farmacologiaRESUMO
Large oral doses of ACZ lower the intraocular pressure (IOP), but usually lead to a multitude of systemic side effects, including gastrointestinal upset. The present study was undertaken to evaluate the effect of ACZ on the histological structure of rat duodenal mucosa and to assess a possible protective role of the complex formation of ACZ with HP-ß-CD, either separately or in combination with a third compound, on the gut epithelial layer by histological and ultrastructural examinations of sections of rat duodenum exposed to ACZ or its formulations. In addition, the transport process of ACZ and its binary or ternary complexes across the duodenal mucosa by means of the single-pass intestinal perfusion (SPIP) method in rats was evaluated. Evidence was found that ACZ alters intestinal permeability and induces damage to the rat small intestine. In contrast, ACZ-induced intestinal injury may be abrogated by ACZ complexation. In addition, the complexation of ACZ with HP-ß-CD, alone or in combination with a third compound, facilitated significant levels of ACZ uptake across the rat duodenal segment. Ternary complexes of ACZ with HP-ß-CD in combination with TEA (triethanolamine) or calcium ions were found to provide an excellent approach that enabled an increased apparent permeability of ACZ across the duodenal epithelium, with a concomitant ability to preserve the integrity of the gut epithelium from ACZ-induced injury. These results could be useful for the design and development of novel ACZ formulations that can reduce GI toxicity, while still maintaining their essential therapeutic efficacies.
Assuntos
Acetazolamida , beta-Ciclodextrinas , 2-Hidroxipropil-beta-Ciclodextrina , Acetazolamida/administração & dosagem , Acetazolamida/química , Acetazolamida/farmacocinética , Acetazolamida/toxicidade , Animais , Cálcio/administração & dosagem , Cálcio/química , Cálcio/farmacocinética , Cálcio/toxicidade , Duodeno/efeitos dos fármacos , Duodeno/patologia , Duodeno/ultraestrutura , Etanolaminas/administração & dosagem , Etanolaminas/química , Etanolaminas/farmacocinética , Etanolaminas/toxicidade , Absorção Intestinal , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Intestinal/ultraestrutura , Masculino , Microscopia Eletrônica de Transmissão , Ratos Wistar , beta-Ciclodextrinas/administração & dosagem , beta-Ciclodextrinas/química , beta-Ciclodextrinas/farmacocinética , beta-Ciclodextrinas/toxicidadeRESUMO
It is well known that the iron content of the body is tightly regulated. Iron excess induces adaptive changes that are differentially regulated in each tissue. The pancreas is particularly susceptible to iron-related disorders. We studied the expression and regulation of key iron proteins in the pancreas, duodenum and liver, using an animal model of iron overload (female CF1 mice injected i.p. with iron saccharate, colloidal iron form). Divalent metal transporter 1, prohepcidin and ferritin (pancreas, duodenum, liver) were assessed by immunohistochemistry; divalent metal transporter 1 (pancreas, duodenum) by Western blot. In the iron overloaded mice, prohepcidin expression increased in islets of Langerhans and hepatocytes, and divalent metal transporter 1 expression decreased in cells of islets and in enterocytes. In the iron overloaded mice, ferritin expression decreased in islets of Langerhans and increased in acinar cells; hemosiderin was localized in connective tissue cells. The inverse relationship between divalent metal transporter 1 and prohepcidin may indicate a negative regulation by hepcidin, and hence reduction of iron stores in islets of Langerhans. Our data showed that in iron overloaded mice model, induced by colloidal iron form, a coordinated expression of key iron proteins in the pancreas, duodenum and liver may occur. Further research will be necessary to determine the adaptive responses induced by iron in the pancreas.
Assuntos
Proteínas de Transporte de Cátions/genética , Regulação da Expressão Gênica , Hepcidinas/genética , Sobrecarga de Ferro/fisiopatologia , Animais , Proteínas de Transporte de Cátions/metabolismo , Duodeno/metabolismo , Duodeno/ultraestrutura , Feminino , Hepcidinas/metabolismo , Immunoblotting , Camundongos , Pâncreas/metabolismo , Pâncreas/ultraestruturaRESUMO
Serotonin is an important neurotransmitter in the central (CNS) and peripheral (PNS) nervous systems. It is involved in a variety of physiological processes both in the gut and in the CNS. The present study examined the distribution of serotonin containing enterochromaffin cells in the gastrointestinal tract (GIT) of a vomit competent species, the least shrew. These cells were easily recognized by their globular granules stained with the H&E and serotonin immune-positive stain. The immunoreactive enterochromaffin cells (IERCs) were mainly confined to the basal portion of the glandular epithelium and were distributed throughout the shrew stomach, small and large intestine. None was found to be associated with the mucosal epithelial lining. Moreover, their distribution and count varied in different regions of the GIT suggesting specific functions for these regions. The highest concentration of IERCs was found in the colon followed by the Jejunum. Appreciable numbers of IERCs were found in the stomach especially at the esophageo-gastric junction. The gastric location of the IERCs was mainly in the basal portion of the gland. However, some IERCs were associated with the parietal cells of the stomach. Two types of IERCs were observed: One with globular secretory granules in their apical portion of the cytoplasm which were located within the glandular epithelial cells facing the glandular lumen which release their secretions into the lumen; and the second were basally located, facing the lamina propria of the mucosa. Their secretory granules were not distinct in shape, and are most probably paracrine in their mode of secretions...
La serotonina es un importante neurotransmisor del sistema nervioso central (SNC) y periférico (SNP). Está implicado en una variedad de procesos fisiológicos, tanto en el intestino y el SNC. El presente estudio examinó la distribución de la serotonina contenida en las células enterocromafines del tracto gastrointestinal (TGI) de una especie competente al vómito, la musaraña enana. Estas células se reconocen fácilmente por sus gránulos globulares teñidas con H-E y la inmuno-tinción positiva para serotonina. Las células enterocromafines inmunorreactivas (CEI) se limitan principalmente a la parte basal del epitelio glandular y se distribuyeron por todo el estómago, intestino delgado e intestino grueso de la musaraña. Ninguna célula se encontró asociada al revestimiento epitelial mucoso. Además, su distribución y el recuento varió en diferentes regiones del TGI sugiriendo funciones específicas de estas regiones. La mayor concentración de CEI se encuentran en el colon seguido por el yeyuno. Números apreciables de CEI se encontraron en el estómago, especialmente en la unión esofago-gástrica. La ubicación de las CEI gástricas fue principalmente en la porción basal de la glándula. Sin embargo, algunas CEI se asociaron con las células parietales del estómago. Dos tipos de CEI se observaron, una con gránulos secretores globulares en su porción apical del citoplasma que se encuentra dentro de las células epiteliales glandulares que enfrenta el lumen glandular que liberan sus secreciones en el lumen, y el segundo se encuentra basalmente, frente a la lámina propia de la mucosa. Sus gránulos secretores no fueron diferentes en forma, y probablemente son más paracrinas en su modo de secreción...
Assuntos
Animais , Células Enterocromafins , Musaranhos/anatomia & histologia , Serotonina , Trato Gastrointestinal/citologia , Trato Gastrointestinal/ultraestrutura , Colo/citologia , Colo/ultraestrutura , Duodeno/citologia , Duodeno/ultraestrutura , Estômago/citologia , Estômago/ultraestrutura , Imuno-Histoquímica , Íleo/citologia , Íleo/ultraestrutura , Microscopia Eletrônica , Jejuno/citologia , Jejuno/ultraestruturaRESUMO
This study was carried out to evaluate the immune response and the impact of Trichostrongylus colubriformis infections on the performance of growing Santa Ines lambs. Thirty male lambs, 3-4 months of age, were maintained in individual pens and restrictively randomised by weight into 3 treatment groups: (1) infected group, artificially infected with 2500 T. colubriformis larvae, three times a week, for 13 weeks, and fed ad libitum; (2) Pair-Fed Group, non-infected and fed with the same amount of food consumed by the infected animal of the same class on the previous day; and (3) control group, non-infected and fed ad libitum. Refused feed was weighed daily to assess the food intake of each lamb. Animals were weighed weekly and blood and fecal samples were collected. At the end of the trial, all lambs were euthanized to determine worm burden and collect intestinal tissues and mucus samples for histological and immunological analysis. The infected group presented eosinophilia, increased number of inflammatory cells in the mucosa, in addition to an increased production of specific immunoglobulins against T. colubriformis, which partially prevented the establishment of infective larvae. As a consequence of parasitism, the infected lambs presented reduced serum albumin concentrations and demonstrated severe small intestine lesions, such as villous atrophy and epithelial erosion, which impaired the digestion and absorption of nutrients, causing a significant loss in performance. The infected group presented a 37% reduction in daily weight gain (107.26 ± 10.8 g/day), when compared with the control group (171.07 ± 7.15 g/day). The infected lambs also demonstrated the worst food conversion, i.e., each animal needed to consume on average 10.05 ± 0.52 kg of food to gain 1 kg live weight. The voluntary hay intake depression in infected animals was small, and statistical difference (P<0.01) was seen only on two occasions (ninth and 12th weeks), in comparison with the control group. In conclusion, Santa Ines lambs infected with T. colubriformis demonstrated a reduction in performance, caused by the damages produced by the adult nematodes in intestinal mucosa, and also by the immunopathological changes associated with the infection.
Assuntos
Doenças dos Ovinos/parasitologia , Tricostrongilose/veterinária , Trichostrongylus/classificação , Animais , Duodeno/patologia , Duodeno/ultraestrutura , Ingestão de Alimentos , Eosinófilos , Fezes/parasitologia , Mucosa Intestinal/parasitologia , Mucosa Intestinal/patologia , Mucosa Intestinal/ultraestrutura , Ovinos , Doenças dos Ovinos/imunologia , Trichostrongylus/ultraestruturaRESUMO
Gerbils (Meriones unguiculatus) were intragastrically inoculated with axenic Giardia lamblia cultures from symptomatic and asymptomatic children. All isolates were able to colonize the duodenum. However, the colonization capacity of the symptomatic isolates was significantly higher compared to that of the asymptomatic ones. Despite the different colonization capacity of the isolates, the growth curves of infected animals were significantly lower than those of controls. The study demonstrates that acute giardia infections are capable of altering the corporal development of the host. These results may suggest that not only symptomatic, but also asymptomatic giardiasis in children, often unnoticed by parents and clinicians, could be causing a silent detriment in their nutritional status.
Assuntos
Portador Sadio/fisiopatologia , Modelos Animais de Doenças , Gerbillinae/parasitologia , Giardia lamblia/fisiologia , Giardíase/fisiopatologia , Transtornos do Crescimento/parasitologia , Doença Aguda , Animais , Portador Sadio/parasitologia , Criança , Duodeno/parasitologia , Duodeno/ultraestrutura , Gerbillinae/crescimento & desenvolvimento , Giardia lamblia/ultraestrutura , Giardíase/complicações , Giardíase/parasitologia , Humanos , Masculino , Microscopia Eletrônica de Varredura , Estado Nutricional , Aumento de PesoRESUMO
Diarrheal disease is still the most prevalent and important public health problem in developing countries, despite advances in knowledge, understanding, and management that have occurred over recent years. Diarrhea is the leading cause of death in children under 5 years of age. The impact of diarrheal diseases is more severe in the earliest periods of life, when taking into account both the numbers of episodes per year and hospital admission rates. This narrative review focuses on one of the major driving forces that attack the host, namely the enteropathogenic Escherichia coli (EPEC) and the consequences that generate malnutrition in an early phase of life. EPEC serotypes form dense microcolonies on the surface of tissue-culture cells in a pattern known as localized adherence (LA). When EPEC strains adhere to epithelial cells in vitro or in vivo they cause characteristic changes known as Attaching and Effacement (A/E) lesions. Surface abnormalities of the small intestinal mucosa shown by scanning electron microscopy in infants with persistent diarrhea, although non-specific, are intense enough to justify the severity of the clinical aspects displayed in a very young phase in life. Decrease in number and height of microvilli, blunting of borders of enterocytes, loss of the glycocalyx, shortening of villi and presence of a mucus pseudomembrane coating the mucosal surface were the abnormalities observed in the majority of patients. These ultrastructural derangements may be due to an association of the enteric enteropathogenic agent that triggers the diarrheic process and the onset of food intolerance responsible for perpetuation of diarrhea. An aggressive therapeutic approach based on appropriate nutritional support, especially the utilization of human milk and/or lactose-free protein hydrolyzate-based formulas and the adequate correction of the fecal losses, is required to allow complete recovery from the damage caused by this devastating enteropathogenic agent.
Assuntos
Diarreia Infantil/microbiologia , Infecções por Escherichia coli/complicações , Escherichia coli , Distúrbios Nutricionais/microbiologia , Doença Aguda , Brasil/epidemiologia , Pré-Escolar , Diarreia Infantil/mortalidade , Duodeno/ultraestrutura , Escherichia coli/classificação , Escherichia coli/isolamento & purificação , Fezes/microbiologia , Humanos , Lactente , Microscopia Eletrônica de Varredura , Microvilosidades , Estudos Prospectivos , SorotipagemRESUMO
Diarrheal disease is still the most prevalent and important public health problem in developing countries, despite advances in knowledge, understanding, and management that have occurred over recent years. Diarrhea is the leading cause of death in children under 5 years of age. The impact of diarrheal diseases is more severe in the earliest periods of life, when taking into account both the numbers of episodes per year and hospital admission rates. This narrative review focuses on one of the major driving forces that attack the host, namely the enteropathogenic Escherichia coli (EPEC) and the consequences that generate malnutrition in an early phase of life. EPEC serotypes form dense microcolonies on the surface of tissue-culture cells in a pattern known as localized adherence (LA). When EPEC strains adhere to epithelial cells in vitro or in vivo they cause characteristic changes known as Attaching and Effacement (A/E) lesions. Surface abnormalities of the small intestinal mucosa shown by scanning electron microscopy in infants with persistent diarrhea, although non-specific, are intense enough to justify the severity of the clinical aspects displayed in a very young phase in life. Decrease in number and height of microvilli, blunting of borders of enterocytes, loss of the glycocalyx, shortening of villi and presence of a mucus pseudomembrane coating the mucosal surface were the abnormalities observed in the majority of patients. These ultrastructural derangements may be due to an association of the enteric enteropathogenic agent that triggers the diarrheic process and the onset of food intolerance responsible for perpetuation of diarrhea. An aggressive therapeutic approach based on appropriate nutritional support, especially the utilization of human milk and/or lactose-free protein hydrolyzate-based formulas and the adequate correction of the fecal losses, is required to allow complete recovery from the damage caused by this devastating enteropathogenic agent
Assuntos
Humanos , Lactente , Pré-Escolar , Diarreia Infantil/microbiologia , Escherichia coli , Infecções por Escherichia coli/complicações , Distúrbios Nutricionais/microbiologia , Brasil/epidemiologia , Microscopia Eletrônica de Varredura , Sorotipagem , Estado Nutricional , Doença Aguda , Diarreia Infantil/mortalidade , Duodeno/ultraestrutura , Escherichia coli/isolamento & purificação , Escherichia coli/classificação , Fezes/microbiologia , MicrovilosidadesRESUMO
Foram estudadas 16 crianças menores de um ano, de ambos os sexos, hospitalizadas por diarréia persistente, com o objetivo de analisar a estrutura do epitélio do intestino delgado através das microscopias de luz e eletrônica de varredura. Foram pesquisados enteropatógenos nas fezes e no suco jejunal. Os pacientes foram submetidos a intubaçäo naso-jejunal com cápsula de Watson para obtençäo de secreçäo jejunal e biopsia de intestino delgado. Os fragmentos de duodeno foram fixados em formol 10 por cento para microscopia de luz, em cortes semi-finos, e em soluçäo de Karnowsky modificada para a varredura, sendo pós-incluídos em tetróxido de ósmio 1 por cento, desidratados numa série gradual de etanol, secados pelo método do ponto crítico, com CO2, cobertos com prata, e analisados através de um JEOL JSM 5300 Scanning Microscope. As coproculturas foram positivas em 11 (68,7 por cento) pacientes: EPEC 0111 em quatro; EPEC 0119 em um; EAggEC em cinco; Shigella flexneri em dois e Shigella sonnei em um; infecçöes mistas por EAggEC, associadas a EPEC 0111 foram caracterizadas em dois pacientes. A microscopia de luz, 56,2 por cento dos pacientes apresentaram enteropatia grau II e, em todos, foram observadas alteraçöes epiteliais como esfacelamento de microvilosidades, vacuolizaçäo citoplasmática, corpos muultivesiculares, e infiltrado linfocitário e eosinofílico, este inclusive no córion. A microscopia eletrónica de varredura, observaram-se, em todos os casos, vilosidades e células epiteliais achatadas e disformes, com ausência ou diminuiçäo das microvilosidades, e em metade dos casos a presença de um material mucoso recobrindo parte do epitélio. A aderência firme entre este material e o epitélio deu-lhe o aspecto de uma psedomembrana. Observou-se um infiltrado de linfócitos sobre a superfície apical dos enterócitos de uma espécime, ao lado de gotículas de gordura. Concluiu-se que as alteraçöes encontradas podem ser devidas a uma associaçäo genérica entre o agente enteropatogênico deflagador da diarréia e o surgimento de intolerância alimentar que a perpetua.
Assuntos
Humanos , Masculino , Feminino , Lactente , Diarreia Infantil/patologia , Intestino Delgado/ultraestrutura , Diarreia Infantil/microbiologia , Duodeno/ultraestrutura , Células Epiteliais/ultraestrutura , Epitélio/ultraestrutura , Microscopia Eletrônica de Varredura , Microvilosidades , Estudos ProspectivosRESUMO
Persistent diarrhea very often leads children to malnutrition. It has become the major cause of death resulting from acute diarrhea episodes in developing countries. In order to determine the ultrastructural alterations of the small bowel that occur in the syndrome, 16 infants with severe persistent diarrhea were studied, utilizing light microscopy and the scanning electron microscope. Stool and jejunal fluid samples were collected for culture, rotavirus, ova and parasite search. Enteropathogenic agents were isolated in stools from 11 (68.7%) patients and bacterial proliferation in the small bowel was detected in 11 (68.7%) patients. EPEC strains were the most frequent enteropathogenic agent isolated both from stool and jejunal fluid cultures. The stool cultures revealed the presence of the following enteropathogenic microorganisms: EPEC 0111 in four, EPEC 0119 in one, EAggEC in five, Shigella flexneri in two, and Shigella sonnei in one; mixed infections due to EAggEC associated with EPEC 0111 were seen in two patients. The light microscopic analysis revealed that 56.2% of the patients suffered moderate villous atrophy most frequently associated with effacement of the microvilli, intracytoplasmatic vacuolization, increased number of multivesicular bodied and increased lymphocytic and eosinophylic infiltration in the lamina propria. The scanning electron microscopic analysis revealed in all cases shortening of the villi and enterocyte derangements; very often there was a total lack and/or effacement of the microvilli; in half of the patients there was a mucoid material covering the enterocytes tightly adhered to the apical epithelium surface. The scanning ultrastructural alterations observed in these patients are probably due to an association of factors brought about by the presence of enteropathogenic microorganisms and the resulting food intolerance that is responsible for perpetuation of diarrhea.