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1.
Artigo em Inglês | MEDLINE | ID: mdl-32320266

RESUMO

The purpose of this study was to characterize intestinal myoelectrical activity along the small intestine and investigate its responses to test meals with different glycemic index at different locations. Sixteen rats were implanted with electrodes in the serosal surface of the duodenum, jejunum, and ileum. Intestinal myoelectrical activities were recorded from these electrodes for 30 min in the fasting state and 3 h after four kinds of meals with different glycemic index, together with the assessment of blood glucose. The results were as follows: 1) in the fasting state, the percentage of normal intestinal slow waves (%NISW) showed no difference; however, the dominant frequency (DF), power (DP), and percentage of spike activity superimposed on the intestinal slow wave (NS/M) were progressively decreased along the entire small intestine; 2) regular solid meal and Ensure solicited no changes in any parameters of intestinal myoelectrical activity; whereas glucose and glucose + glucagon significantly altered the %NISW, DF, DP, and NS/M, and the effects on the proximal intestine were opposite to those in the distal intestine; and 3) postprandial blood glucose level was significantly correlated with %NISW along the entire small intestine. We found that that, in addition to the well-known frequency gradient, there is also a gradual decrease in the DP and spikes along the small intestine in the fasting state. Glucose and hyperglycemic meals inhibit myoelectrical activities in the proximal small intestine but result in enhanced but more dysrhythmic intestinal myoelectrical activities. There is a significant negative correlation between the normality of intestinal slow waves and blood glucose.


Assuntos
Glicemia/metabolismo , Dieta , Índice Glicêmico , Intestino Delgado/fisiologia , Complexo Mioelétrico Migratório , Ração Animal , Animais , Biomarcadores/sangue , Jejum/sangue , Masculino , Período Pós-Prandial , Ratos Sprague-Dawley , Fatores de Tempo
2.
J Pediatr Surg ; 55(6): 1107-1112, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32164986

RESUMO

BACKGROUND: Extracellular matrix (ECM) affects cell behavior, and vice versa. How ECM changes after small bowel resection (SBR) to support adaptive cellular processes has not been described. Here we characterize changes in ECM following SBR and integrate this with concomitant transcriptional perturbations. METHODS: A 50% proximal SBR or sham surgery was performed on mice. On postoperative day 7, ileal tissue was sequentially depleted of protein components to generate an ECM-enriched fraction. ECM was analyzed for protein composition using mass spectrometry with subsequent Ingenuity Pathway Analysis (IPA) to identify predicted pathways and upstream regulators. qPCR and RNA-sequencing (RNA-Seq) were performed to corroborate these predicted pathways. RESULTS: 3034 proteins were differentially regulated between sham and SBR, of which 95 were significant (P < 0.05). IPA analysis predicted PPARα agonism to be an upstream regulator of the observed proteomic changes (P < 0.001). qPCR and RNA-Seq with KEGG analysis confirmed significant engagement of the PPAR pathway (P < 0.05). CONCLUSION: Transcriptional signatures of adapting bowel predict subsequent ECM changes after SBR. How ECM communicates with surrounding cells to drive adaptation and vice versa merits further investigation. Our findings thus far suggest ECM supports tissue hyperplasia and altered metabolic demand following SBR.


Assuntos
Adaptação Fisiológica , Matriz Extracelular/fisiologia , Intestino Delgado/fisiologia , Intestino Delgado/cirurgia , Animais , Biomarcadores/metabolismo , Western Blotting , Masculino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos C57BL , Período Pós-Operatório , Proteínas/metabolismo , Proteômica , Transcriptoma
3.
Sci Rep ; 10(1): 475, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949225

RESUMO

Animal studies have shown that intestinal barrier function is compromised with aging. We aimed to assess the effects of aging on intestinal barrier function in humans in vivo and ex vivo. In this cross-sectional study, healthy subjects and subjects with irritable bowel syndrome (IBS) of older (65-75 years) and young adult age (18-40 years) were compared. In vivo gastrointestinal site-specific permeability was assessed by a multi-sugar test, taking into account potential confounders. Sigmoid biopsies were collected from subgroups of healthy young adults and elderly for ex vivo Ussing chamber experiments, gene transcription of barrier-related genes and staining of junctional proteins. No significant differences between healthy young adults and elderly were found for small intestinal, colonic and whole gut permeability (P ≥ 0.142). In IBS patients, gastroduodenal and colonic permeability did not differ significantly (P ≥ 0.400), but small intestinal and whole gut permeability were higher in elderly versus young adults (P ≤ 0.009), mainly driven by the IBS-diarrhea subtype. Ussing chamber experiments with or without stressor (P ≥ 0.052), and relative expression of intestinal barrier-related genes (P ≥ 0.264) showed no significant differences between healthy elderly and young adults, as confirmed by immunofluorescent stainings. Overall, the functional capacity of the intestinal barrier is maintained in elderly.


Assuntos
Envelhecimento , Permeabilidade da Membrana Celular , Mucosa Intestinal/fisiologia , Intestino Delgado/fisiologia , Síndrome do Intestino Irritável/fisiopatologia , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
4.
Infect Immun ; 88(3)2020 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-31818966

RESUMO

Modeling host-pathogen interactions with human intestinal epithelia using enteroid monolayers on permeable supports (such as Transwells) represents an alternative to animal studies or use of colon cancer-derived cell lines. However, the static monolayer model does not expose epithelial cells to mechanical forces normally present in the intestine, including luminal flow and serosal blood flow (shear force) or peristaltic forces. To determine the contribution of mechanical forces in the functional response of human small intestine to a virulence factor of a pathogenic intestinal bacterium, human jejunal enteroids were cultured as monolayers in microengineered fluidic-based Organ-Chips (Intestine-Chips) exposed to enterotoxigenic Escherichia coli heat-stable enterotoxin A (ST) and evaluated under conditions of static fluid, apical and basolateral flow, and flow plus repetitive stretch. Application of flow increased epithelial cell height and apical and basolateral secretion of cyclic GMP (cGMP) under baseline, unstimulated conditions. Addition of ST under flow conditions increased apical and basolateral secretion of cGMP relative to the level under static conditions but did not enhance intracellular cGMP accumulation. Cyclic stretch did not have any significant effect beyond that contributed by flow. This study demonstrates that fluid flow application initiates changes in intestinal epithelial cell characteristics relative to those of static culture conditions under both baseline conditions and with exposure to ST enterotoxin and suggests that further investigations of the application of these mechanical forces will provide insights into physiology and pathophysiology that more closely resemble intact intestine than study under static conditions.


Assuntos
GMP Cíclico/fisiologia , Escherichia coli Enterotoxigênica/fisiologia , Enterotoxinas/fisiologia , Infecções por Escherichia coli/fisiopatologia , Proteínas de Escherichia coli/fisiologia , Intestino Delgado/fisiologia , Transdução de Sinais/fisiologia , Estresse Mecânico , Toxinas Bacterianas , Humanos , Jejuno/citologia , Fatores de Virulência/fisiologia
5.
Animal ; 14(2): 269-276, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31405398

RESUMO

Rheological properties of digesta play a role in digesta passage kinetics through the gastrointestinal tract, in turn affecting nutrient absorption kinetics. Therefore, we studied the effects of diet viscosity on digesta passage and physicochemical properties in pigs. Twenty male growing pigs (35 kg body weight at the start) were assigned to one of five diets with increasing dietary concentrations of ß-glucans (BG; from 0 % to 10 %), in exchange for maize starch. After a 17-day adaptation period, pigs were euthanised and the mean retention time (MRT) of digesta solids (TiO2) and liquids (Cr-EDTA) in the stomach, and proximal and distal half of the small intestine was quantified. In the stomach, the MRT of liquids, but not of solids, increased when dietary BG level increased (6 min per % dietary BG, P = 0.008 and R2 = 0.35). Concomitantly, stomach DM content (5 g/kg per % dietary BG, P < 0.001 and R2 = 0.53) and apparent digesta viscosity (56 Pa × s at 1/s shear rate per % dietary BG, P = 0.003 and R2 = 0.41) decreased. In the proximal half of the small intestine, no effects of dietary BG level were observed. In the distal half of the small intestine, water-binding capacity (WBC) of digesta increased (0.11 g/g digesta DM per % dietary BG, P = 0.028 and R2 = 0.24) and starch digestibility decreased (0.3% per % dietary BG, P = 0.034 and R2 = 0.23) when dietary BG level increased. In the colon, apparent digesta viscosity at 45/s shear rate increased (0.1 Pa × s per % dietary BG, P = 0.03 and R2 = 0.24) in the proximal half of the colon, and digesta WBC increased (0.06 g/g digesta DM per % dietary BG, P = 0.024 and R2 = 0.26) in the distal half of the colon when dietary BG level increased. To conclude, increasing dietary BG level caused the MRT of liquids, but not that of solids, to increase in the stomach, resulting in reduced separation of the solid and liquid digesta fractions. This caused dilution of the stomach content and reduction in digesta viscosity when dietary BG levels increased. Effects of dietary BG level on physicochemical properties in the proximal small intestine were absent and may have been due to a low DM content. The WBC of digesta in the distal small intestine and colon increased when dietary BG level increased, as did apparent digesta viscosity in the proximal colon. This likely reflects the concentration of BG in digesta when moving through the gastrointestinal tract.


Assuntos
Ração Animal/análise , Suínos/fisiologia , beta-Glucanas/química , Animais , Peso Corporal , Dieta/veterinária , Digestão , Conteúdo Gastrointestinal/química , Trato Gastrointestinal/fisiologia , Intestino Delgado/fisiologia , Cinética , Masculino , Reologia , Estômago/fisiologia , Viscosidade
6.
Am J Physiol Gastrointest Liver Physiol ; 318(2): G225-G243, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31813235

RESUMO

The interstitial cells of Cajal associated with the myenteric plexus (ICC-MP) are a network of coupled oscillators in the small intestine that generate rhythmic electrical phase waves leading to corresponding waves of contraction, yet rhythmic action potentials and intercellular calcium waves have been recorded from c-kit-mutant mice that lack the ICC-MP, suggesting that there may be a second pacemaker network. The gap junction blocker carbenoxolone induced a "pinstripe" motor pattern consisting of rhythmic "stripes" of contraction that appeared simultaneously across the intestine with a period of ~4 s. The infinite velocity of these stripes suggested they were generated by a coupled oscillator network, which we call X. In c-kit mutants rhythmic contraction waves with the period of X traveled the length of the intestine, before the induction of the pinstripe pattern by carbenoxolone. Thus X is not the ICC-MP and appears to operate under physiological conditions, a fact that could explain the viability of these mice. Individual stripes consisted of a complex pattern of bands of contraction and distension, and between stripes there could be slide waves and v waves of contraction. We hypothesized that these phenomena result from an interaction between X and the circular muscle that acts as a damped oscillator. A mathematical model of two chains of coupled Fitzhugh-Nagumo systems, representing X and circular muscle, supported this hypothesis. The presence of a second coupled oscillator network in the small intestine underlines the complexity of motor pattern generation in the gut.NEW & NOTEWORTHY Physiological experiments and a mathematical model indicate a coupled oscillator network in the small intestine in addition to the c-kit-expressing myenteric interstitial cells of Cajal. This network interacts with the circular muscle, which itself acts as a system of damped oscillators, to generate physiological contraction waves in c-kit (W) mutant mice.


Assuntos
Motilidade Gastrointestinal/fisiologia , Células Intersticiais de Cajal/fisiologia , Plexo Mientérico/fisiologia , Rede Nervosa/fisiologia , Potenciais de Ação/fisiologia , Animais , Sinalização do Cálcio/fisiologia , Carbenoxolona/farmacologia , Feminino , Intestino Delgado/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Modelos Neurológicos , Modelos Teóricos , Contração Muscular , Músculo Liso Vascular/efeitos dos fármacos , Mutação , Junção Neuromuscular , Proteínas Proto-Oncogênicas c-kit/genética
7.
Food Funct ; 11(1): 606-616, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31859303

RESUMO

The stability, in vitro digestion profile and phase behavior of Pickering emulsions stabilized by milled cellulose were evaluated to investigate their feasibility as food-grade formulations for encapsulation and delivery of lipophilic bioactive compounds. Curcumin encapsulated in Pickering emulsions exhibited good stability with less than 50% degraded after 30 days' storage. The digestion profiles of emulsions were markedly influenced by lipid type used and digestion buffer employed in simulated small intestinal experiments. The rate and extent of lipolysis of emulsions with medium chain triglycerides were greater than emulsions with long chain triglycerides (soy bean oil and canola oil), reaching complete hydrolysis under both fed and fasted conditions. For comparison, the digestion behaviors of curcumin encapsulated in conventional emulsions were also evaluated. Although the initial digestion rate of Pickering emulsions with long chain triglycerides was slower than the corresponding conventional emulsions stabilized by Tween/Span 80, their total extent of lipolysis was higher than that of conventional emulsions. The bioaccessibility of curcumin encapsulated in Pickering emulsions was higher than in corresponding small molecular weight surfactant stabilized conventional emulsions.


Assuntos
Celulose/química , Curcumina/química , Composição de Medicamentos/métodos , Curcumina/farmacologia , Digestão , Composição de Medicamentos/instrumentação , Estabilidade de Medicamentos , Emulsões/química , Humanos , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/fisiologia , Lipólise/efeitos dos fármacos , Modelos Biológicos , Tamanho da Partícula
8.
Arch Anim Nutr ; 74(2): 107-120, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31852279

RESUMO

Inulin is a linear fructose polymer which may affect small intestinal physiology. The effects of dietary level of two inulin types on morphology, contractility and proinflammatory cytokine gene expression in the small intestine of piglets were investigated. Fifty six piglets were divided into seven groups fed diets without inulin addition or with 1%, 2% or 3% of inulin with an average degree of polymerisation of 10 (IN10) or 23 (IN23). All diets were offered from day 10 of life for 40 d. Feeding IN10 diets did not affect villous height to crypt depth ratio in the duodenum, while in the jejunum the 2% IN10 diet increased it as compared to other groups. Jejunal muscle contractions induced by electrical field stimulation were impaired by the 2% and 3% IN10 diets. The ileal expression of interleukin-12p40 was decreased by the 2% IN10 diet. There was no effect of IN23 level on villous height to crypt depth ratio in any segment of the small intestine as well as on jejunal motility. The 2% and 3% IN23 diets decreased the jejunal expression of tumour necrosis factor-α. In conclusion, IN10 is more active in the small intestine than IN23. At the 2% dietary level, it increases absorptive area in the jejunum, but may slightly impair smooth muscle contractions.


Assuntos
Citocinas/genética , Expressão Gênica/efeitos dos fármacos , Intestino Delgado/fisiologia , Inulina/metabolismo , Sus scrofa/fisiologia , Ração Animal/análise , Animais , Citocinas/metabolismo , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Intestino Delgado/anatomia & histologia , Intestino Delgado/imunologia , Inulina/administração & dosagem , Masculino , Contração Muscular/efeitos dos fármacos , Sus scrofa/genética , Sus scrofa/imunologia
9.
Tokai J Exp Clin Med ; 44(4): 108-112, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31769000

RESUMO

OBJECTIVE: This study of 45 patients aimed to retrospectively examine whether the relationships among the postoperative to preoperative body weight ratio (BWR), meal intake as a good indicator of quality of l ife (QOL), and absorptive kinetics from the small intestine could be expressed by the acetaminophen (AAP) concentration. METHODS: The postoperative/preoperative BWR and meal intake ratio (MIR) were evaluated in 30 patients who underwent open distal gastrectomy for advanced gastric cancer (ODG group) and 15 patients who underwent laparoscopic proximal gastrectomy for early gastric cancer (LPG group). In addition, all patients underwent functional evaluation using the AAP method. Correlation coefficients of the BWR and MIR with the plasma AAP concentration after meal intake were evaluated. RESULTS: There was a negative correlation between the AAP concentration at 15 min and the BWR in all patients (r = -0.438, P = 0.00259, n = 45) and a weak negative correlation between the AAP concentration at 15 min and the MIR (r = -0.309, P = 0.0368, n = 45). CONCLUSIONS: There were some relationships between slow intestinal absorption in the early postprandial phase and the maintenance of postoperative body weight and meal intake. Namely, operative methods that maintained preoperative slow intestinal absorption were thought to be better for maintaining postoperative QOL.


Assuntos
Gastrectomia/métodos , Laparoscopia/métodos , Procedimentos Cirúrgicos Reconstrutivos/métodos , Neoplasias Gástricas/cirurgia , Acetaminofen/sangue , Idoso , Peso Corporal , Ingestão de Alimentos , Feminino , Humanos , Absorção Intestinal/fisiologia , Intestino Delgado/fisiologia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Inquéritos e Questionários
10.
Biomed Pharmacother ; 120: 109515, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31600642

RESUMO

The process of absorption and permeation of PRL through the small intestine of 1-day-old piglet from the different compositions of solutions prepared for oral administration was investigated. This was achieved by determining the effect of hormone concentration (0.25 mg / ml or 0.5 mg / ml or 0.75 mg / ml), the concentration of stabilizing substances - trehalose (6 mg / ml or 12 mg / ml or 18 mg / ml) and mannitol (6 mg / ml or 12 mg / ml or 18 mg / ml) and the pH of the solution (2.5 or 3.0 or 3.5) on the degree of absorption and permeation of the PRL. The conditions for the absorption and penetration of PRL from solutions of various compositions for oral administration through the natural membrane (small intestine of the 1-day-old sucking piglet) in the in vivo conditions were simulated. The studies used an in vivo model in which the enzymatic profile in the body is not yet fully developed (no pepsin). It was found that in the studied range the absorption of PRL in the small intestine of the 1-day-old sucking piglet is significantly related to the concentration of the hormone and trehalose in the solution from which it is absorbed. In contrast, all factors studied (hormone concentration, trehalose and mannitol concentration, pH value of the solution) influence the process of penetration of the PRL in the studied range. It was also found that the hormone concentration significantly influences the rate of its absorption and permeation (the fastest occurs at a concentration of 0.5 mg/mL). The results suggest possibility of oral prolactin administration in order to ensure proper growth, development and increase the resistance and survival of sucking piglets.


Assuntos
Intestino Delgado/fisiologia , Prolactina/administração & dosagem , Prolactina/farmacocinética , Administração Oral , Animais , Animais Lactentes , Suínos
11.
Food Funct ; 10(9): 5361-5373, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31393487

RESUMO

The early postnatal stage is a critical period for suckling animals in developing intestinal function and stabilizing gut microbiota. Lactoferrin (LF) plays a critical role in promoting gut development and regulating gut microbiota. This study investigates the impact of early-life lactoferrin (LF) intervention on the growth performance, small intestinal function and gut microbiota in suckling piglets. Sixty suckling piglets (1.51 ± 0.05 kg) obtained from six sows (10 piglets per litter) were assigned to a control (CON) group and an LF group in each litter, which were sow-fed. Piglets in the LF group were orally administered 8-12 mL LF solution (0.5 g per kg body weight per day) for a week, and piglets in the CON group were orally administered the same dose of physiological saline. Six piglets (n = 6) from each group were euthanized on days 8 and 21. The early-life LF intervention increased growth performance, with higher villi height of the jejunum and greater disaccharidase activity of the jejunum and ileum (P < 0.05). Diarrhoea incidence decreased in the LF group from day 1 to day 7 (P < 0.05). Urinary lactulose-mannitol ratios decreased in the LF group, whereas the gene and protein expressions of jejunal occludin increased in the LF group on day 8 and day 21, and higher gene and protein levels of ileal occludin were observed on day 8 (P < 0.05). Additionally, the LF piglets had lower concentrations of IL-1ß and TNF-α, and higher concentration of IL-10 in the jejunum (P < 0.05). For the ileum, higher concentration of IL-10 and lower concentration of TNF-α were observed in the LF group (P < 0.05). LF piglets had a greater abundance of Lactobacillus and lower abundance of Veillonella and Escherichia-Shigella in the jejunum on day 8 (P < 0.05). In the ileum, the abundance of Actinobacillus was decreased in the LF piglets on day 8 and day 21 (P < 0.05). The early-life LF intervention enhanced the growth performance and decreased diarrhoea incidence in the suckling piglets by promoting the development of intestinal function and changing the microbiota in the small intestine.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Intestino Delgado/microbiologia , Lactoferrina/administração & dosagem , Suínos/crescimento & desenvolvimento , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bovinos , Feminino , Interleucina-10/genética , Interleucina-10/metabolismo , Intestino Delgado/crescimento & desenvolvimento , Intestino Delgado/fisiologia , Masculino , Suínos/microbiologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
12.
Eur J Pharm Biopharm ; 142: 307-314, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31288077

RESUMO

The influence of physiological factors on the solubility of drug compounds has been thoroughly investigated in humans. However, as these factors vary between species and since many in vivo studies are carried out in rats or mice, it has been difficult to establish sufficient in vitro in vivo relations. The aim of this study was to develop a physiologically relevant in vitro dissolution model simulating the gastrointestinal (GI) fluids of fasted rats and compare it to previously published in vitro and in vivo data. To develop the in vitro model, the pH was measured in situ in six segments of the GI tract of anesthetised rats, then the fluids from the stomach, the proximal and the distal small intestine were collected and characterized with regard to osmolality, and bile acid and phospholipid concentration. The pH and osmolality were found to increase throughout the GI tract. The bile acids and phospholipids were present in high concentrations in the proximal small intestine, and the bile acid concentration doubled in the distal part, where the phospholipid concentration decreased. Matrix-assisted laser desorption ionisation mass spectrometry imaging was applied on a cross section of the small intestine, to study which bile acids and phospholipid classes were present in the small intestine of rats. Both cholic acid, taurocholic acid and glycocholic acid were detected, and phosphatidylcholine (34:2) was found to be mainly present in the intestinal wall or mucus, whereas lysophosphatidylcholine (16:0) was also detected in the lumen. Based on these observations, biorelevant media were developed to simulate fluids in the stomach and the proximal part of the small intestine in fasted rats. The media were implemented in a two-step in vitro dissolution model, which was found to better predict the in vivo performance of furosemide, when compared to previously published in vitro and in vivo data.


Assuntos
Líquidos Corporais/metabolismo , Líquidos Corporais/fisiologia , Mucosa Gástrica/metabolismo , Intestino Delgado/metabolismo , Intestino Delgado/fisiologia , Preparações Farmacêuticas/metabolismo , Estômago/fisiologia , Animais , Humanos , Concentração de Íons de Hidrogênio , Masculino , Camundongos , Concentração Osmolar , Ratos , Ratos Sprague-Dawley , Solubilidade
13.
J Morphol ; 280(9): 1359-1369, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31301093

RESUMO

Flying mammals present unique intestinal adaptations, such as lower intestinal surface area than nonflying mammals, and they compensate for this with higher paracellular absorption of glucose. There is no consensus about the mechanistic bases for this physiological phenomenon. The surface area of the small intestine is a key determinant of the absorptive capacity by both the transcellular and the paracellular pathways; thus, information about intestinal surface area and micro-anatomical structure can help explain differences among species in absorptive capacity. In order to elucidate a possible mechanism for the high paracellular nutrient absorption in bats, we performed a comparative analysis of intestinal villi architecture and enterocyte size and number in microchiropterans and rodents. We collected data from intestines of six bat species and five rodent species using hematoxylin and eosin staining and histological measurements. For the analysis we added measurements from published studies employing similar methodology, making in total a comparison of nine species each of rodents and bats. Bats presented shorter intestines than rodents. After correction for body size differences, bats had ~41% less nominal surface area (NSA) than rodents. Villous enhancement of surface area (SEF) was ~64% greater in bats than in rodents, mainly because of longer villi and a greater density of villi in bat intestines. Both taxa exhibited similar enterocyte diameter. Bats exceeded rodents by ~103% in enterocyte density per cm2 NSA, but they do not significantly differ in total number of enterocytes per whole animal. In addition, there is a correlation between SEF and clearance per cm2 NSA of L-arabinose, a nonactively transported paracellular probe. We infer that an increased enterocyte density per cm2 NSA corresponds to increased density of tight junctions per cm2 NSA, which provides a partial mechanistic explanation for understanding the high paracellular absorption observed in bats compared to nonflying mammals.


Assuntos
Quirópteros/anatomia & histologia , Quirópteros/fisiologia , Absorção Intestinal , Intestinos/anatomia & histologia , Intestinos/fisiologia , Roedores/anatomia & histologia , Roedores/fisiologia , Animais , Arabinose/metabolismo , Peso Corporal , Dieta , Enterócitos/metabolismo , Intestino Delgado/anatomia & histologia , Intestino Delgado/fisiologia
14.
Biol Pharm Bull ; 42(7): 1230-1235, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257299

RESUMO

Calcineurin is a Ca2+/calmodulin-dependent protein phosphatase abundantly expressed in the nervous system. To investigate the roles of calcineurin in glial cells, we previously generated glial calcineurin B1-conditional knockout (CKO) mice and found that these mice displayed dysfunction of enteric glial cells, mucosal degeneration and inflammation in the small intestine, and growth retardation and postweaning death, suggesting a novel role of calcineurin in enteric glial cells. Although these findings raised a possibility that abnormalities in calcineurin B1-deficient enteric glial cells may cause dysregulation of gastrointestinal motility and result in maldigestion and/or malabsorption in the CKO mice, these issues remain to be elucidated. In the present study, we showed that gastrointestinal motility was reduced in the CKO mice. Degeneration of mucosal epithelium was observed in the small intestine. Glucose levels were decreased in serum, whereas starch, glucose, and lipid levels were increased in feces. Thus, calcineurin B1 deficiency in glial cells reduces gastrointestinal motility, induces mucosal epithelium degeneration in the small intestine, and results in maldigestion and/or malabsorption in mice, further supporting the important role of calcineurin in enteric glial cells.


Assuntos
Calcineurina/fisiologia , Motilidade Gastrointestinal , Neuroglia/fisiologia , Animais , Calcineurina/genética , Digestão , Fezes/química , Feminino , Glucose/metabolismo , Absorção Intestinal , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Intestino Delgado/patologia , Intestino Delgado/fisiologia , Metabolismo dos Lipídeos , Camundongos Knockout , Proteínas/metabolismo , Amido/metabolismo
15.
Rev. esp. enferm. dig ; 111(7): 530-536, jul. 2019. tab
Artigo em Inglês | IBECS | ID: ibc-190099

RESUMO

Background: transit times in the gastric cavity and the small bowel can be easily calculated using capsule endoscopy software. The factors that can influence these times and impact on diagnostic yield have not been completely assessed. Aims: to analyze the influence of demographic and clinical features on transit times and the impact on diagnostic yield. Methods: a retrospective, single-center study of examinations between January 2013 and November 2017 was performed. The analyzed features included gender, age, body mass index, diabetes, thyroid disease and indications. The association and correlation between the variables were assessed, as well as the presence of positive and significant findings. Results: six hundred and thirty-one patients were included in the study. Gastric and small bowel transit times were 36.10 +/- 48.50 and 251.82 +/- 116.42 minutes, respectively. Gastric time was not affected by any of the variables. Small bowel time was longer in males, patients over 60 years of age and diabetics. Prolonged small bowel time, male gender and older age were associated with a higher diagnostic yield. Age over 60 years was the only factor independently associated with positive findings (OR: 1.550 [1.369-1.754]; p: 0.007). Conclusions: patients over 60 years have a longer small bowel transit time and higher probability of having small bowel lesions. Males and diabetic patients also seem more likely to have longer transit times and higher rates of positive findings


No disponible


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Trânsito Gastrointestinal , Endoscopia por Cápsula/métodos , Intestino Delgado/fisiologia , Motilidade Gastrointestinal/fisiologia , Endoscopia por Cápsula/estatística & dados numéricos , Interpretação de Imagem Assistida por Computador/métodos , Estudos Retrospectivos , Efeito Idade
16.
Mol Cells ; 42(6): 470-479, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31250620

RESUMO

Interstitial cells of Cajal (ICCs) are pacemaker cells that exhibit periodic spontaneous depolarization in the gastrointestinal (GI) tract and generate pacemaker potentials. In this study, we investigated the effects of ghrelin and motilin on the pacemaker potentials of ICCs isolated from the mouse small intestine. Using the whole-cell patch-clamp configuration, we demonstrated that ghrelin depolarized pacemaker potentials of cultured ICCs in a dose-dependent manner. The ghrelin receptor antagonist [D-Lys] GHRP-6 completely inhibited this ghrelin-induced depolarization. Intracellular guanosine 5'-diphosphate-ß-S and pre-treatment with Ca2+free solution or thapsigargin also blocked the ghrelin-induced depolarization. To investigate the involvement of inositol triphosphate (IP3), Rho kinase, and protein kinase C (PKC) in ghrelin-mediated pacemaker potential depolarization of ICCs, we used the IP3 receptor inhibitors 2-aminoethoxydiphenyl borate and xestospongin C, the Rho kinase inhibitor Y-27632, and the PKC inhibitors staurosporine, Go6976, and rottlerin. All inhibitors except rottlerin blocked the ghrelin-induced pacemaker potential depolarization of ICCs. In addition, motilin depolarized the pacemaker potentials of ICCs in a similar dose-dependent manner as ghrelin, and this was also completely inhibited by [D-Lys] GHRP-6. These results suggest that ghrelin induced the pacemaker potential depolarization through the ghrelin receptor in a G protein-, IP3-, Rho kinase-, and PKC-dependent manner via intracellular and extracellular Ca2+ regulation. In addition, motilin was able to depolarize the pacemaker potentials of ICCs through the ghrelin receptor. Therefore, ghrelin and its receptor may modulate GI motility by acting on ICCs in the murine small intestine.


Assuntos
Grelina/farmacologia , Células Intersticiais de Cajal/efeitos dos fármacos , Potenciais da Membrana/efeitos dos fármacos , Motilina/farmacologia , Acetofenonas/farmacologia , Amidas/farmacologia , Animais , Benzopiranos/farmacologia , Compostos de Boro/metabolismo , Cálcio/metabolismo , Carbazóis/farmacologia , Motilidade Gastrointestinal/fisiologia , Receptores de Inositol 1,4,5-Trifosfato/antagonistas & inibidores , Células Intersticiais de Cajal/fisiologia , Intestino Delgado/fisiologia , Compostos Macrocíclicos/farmacologia , Camundongos , Camundongos Endogâmicos ICR , Oligopeptídeos/metabolismo , Oxazóis/farmacologia , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/metabolismo , Piridinas/farmacologia , Receptores de Grelina/antagonistas & inibidores , Receptores de Grelina/metabolismo , Transdução de Sinais , Estaurosporina/farmacologia , Tapsigargina/farmacologia , Quinases Associadas a rho/antagonistas & inibidores , Quinases Associadas a rho/metabolismo
17.
Mol Biol Rep ; 46(4): 3843-3856, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31049835

RESUMO

During summer days the extreme heat may cause damage to the integrity of animal intestinal barrier. Little information is available concerning morphological changes in the duck intestines in response to high temperature. And the molecular mechanisms underlying the pathogenesis of high temperature-induced intestinal injury remain undefined. MicroRNAs (miRNAs) are known to play key roles in post-transcriptional regulation of gene expression that influences various biological processes. The purpose of this study was to explore the changes in morphology and miRNA expression profiles of the three intestinal segments (duodenum, jejunum and ileum) of ducks in response to high temperature. Sixty female Shaoxing ducks (Anas platyrhynchos), 60 days old, were allocated in two groups, including control ducks kept at 25 °C, and ducks subjected to high ambient temperatures of 30-40 °C for 15 successive days, which mimicked the diurnal temperature variations experienced in hot seasons. Three ducks from each group were executed at the end of feeding experiment, and the samples of three intestinal segments were collected for morphological examination and Illumina deep sequencing analyses. Histopathological examination of the intestinal mucous membrane was performed with HE staining method. The results demonstrated that varying degrees of damage to each intestinal segment were found in heat-treated ducks, and there were more severe injuries in duodenum and jejunum than those in ileum. Illumina high-throughput sequencing and bioinformatic methods were employed in this study to identify the miRNA expression profile of three different intestinal tissues in control and heat-treated ducks. A total of 75,981,636, 88,345,563 and 100,179,422 raw reads were obtained from duodenum, jejunum and ileum, respectively, from which 74,797,633 clean reads in duodenal libraries, 86,406,445 clean reads in jejunal libraries, and 98,518,858 lean reads in ileal libraries were derived after quality control, respectively. And a total of 276 known and 182 novel miRNAs were identified in the three intestinal segments of ducks under control and heat-treated conditions. By comparing the same tissues in different conditions, 16, 18 and 15 miRNAs were found to be significantly differentially expressed between control and heat-treated ducks in duodenum, jejunum and ileum, respectively, of which 1 miRNA was expressed in both the duodenum and jejunum, 2 miRNAs were expressed in both the duodenum and ileum, and 3 miRNAs were found to be expressed in both the jejunum and ileum. In addition, two differentially expressed miRNAs in each comparison were randomly selected and validated by quantitative qRT-PCR. Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that the differentially expressed miRNAs may be involved in the high temperature-induced intestinal injury in ducks. Our work provides the comprehensive miRNA expression profiles of small intestines in the normal and heat-treated ducks. These findings suggest the involvement of specific molecular mechanisms of post-transcriptional regulation to explain the high temperature-induced changes in the duck small intestine.


Assuntos
Patos/genética , Intestino Delgado/metabolismo , MicroRNAs/genética , Animais , Biologia Computacional/métodos , Duodeno/metabolismo , Feminino , Perfilação da Expressão Gênica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Temperatura Alta/efeitos adversos , Íleo/metabolismo , Mucosa Intestinal/metabolismo , Intestino Delgado/fisiologia , Jejuno/metabolismo , RNA Mensageiro/genética , Temperatura , Transcriptoma/genética
18.
Pak J Pharm Sci ; 32(2 (Supplementary)): 751-757, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31103967

RESUMO

Gut microbiome, a new organ; represent targets to alter pharmacokinetics of orally administered drugs. Recently, in vitro trials endorsed the idea that orally administered drugs interact and some of their quantity may be taken up by normal microbiome during transit through gut. Such transport mechanisms in microbiome may compete for drug with the host itself. Currently, no data confirms specific transport system for paracetamol uptake by gut microbiome. In vivo trial was conducted in normal healthy male rats (n=36). Paracetamol was administered orally in a single dose of 75mg/kg to isolate microbial mass after transit of 2, 3, 4, 5 and 6 hours post drug administration. Paracetamol absorbance by microbiome was pursued by injecting extracted microbial lysate in RP-HPLC-UV with C18 column under isocratic conditions at 207nm using acetonitrile and water (25:75 v/v) pH 2.50 as mobile phase. Paracetamol absorbance (14.10±0.75µg/mg of microbial mass) and percent dose recovery (13.16±0.55%) seen at transit of 4 hours was significantly higher (P<0.05) compared to other groups. Study confirms the hypothesis of homology between membrane transporters of the gut microbiome and intestinal epithelium. Orally administered drugs can be absorbed by gut microbes competitively during transit in small intestine and it varies at various transit times.


Assuntos
Acetaminofen/farmacocinética , Microbioma Gastrointestinal/fisiologia , Acetaminofen/administração & dosagem , Acetaminofen/análise , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Microbioma Gastrointestinal/efeitos dos fármacos , Absorção Intestinal , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/fisiologia , Masculino , Ratos
19.
J Ethnopharmacol ; 240: 111953, 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31082513

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Nowadays, there is no specific effective western medicine for functional dyspepsia (FD), especially in children. Clinically, child compound Endothelium corneum (CCEC) has shown to be effective for the therapy of FD, however, the underlying mechanism has not been elucidated yet. MATERIALS AND METHODS: FD was induced in rats by irregular diet plus dilute hydrochloric acid feeding. Gastric emptying and small intestinal transit were examined by intragastric gavage with Evans blue. Histopathology was assessed by H&E staining. Gastrointestinal hormones and brain gut peptides were measured by ELISA assay. mRNA expression level was quantified by real-time PCR. Protein expression level was detected by western blotting assay. Gut microbiota was analyzed by 16S rRNA miseq sequencing. RESULTS: CCEC significantly enhanced gastric emptying and small intestinal transit of FD rats, and prominently suppressed gastrointestinal microinflammation. At phylum level, CCEC prevented the decrease of Firmicutes and the increase of Bacteroidetes in gut of FD rats. In stomach of FD rats, MTL, CCK and VIP levels were significantly increased, which could be repressed by CCEC; however, the decreased GAS level could not be elevated by CCEC. In small intestine of FD rats, MTL and GAS levels were decreased, while VIP content was increased. These alterations could be effectively reversed by CCEC. NPY levels in serum, small intestine and hypothalamus of FD rats were significantly decreased, which could be rescued by CCEC. Moreover, the over-activated POMC/Stat3/Akt pathway in hypothalamus of FD rats could be suppressed by CCEC. CONCLUSION: CCEC enhanced gastrointestinal motility probably through rebalancing the homeostasis of brain-gut-microbiota axis in FD rats. The novel findings may provide insightful theoretical basis for its clinical employment.


Assuntos
Dispepsia/tratamento farmacológico , Motilidade Gastrointestinal/efeitos dos fármacos , Animais , Ciclo-Oxigenase 2/genética , Dispepsia/metabolismo , Dispepsia/microbiologia , Dispepsia/fisiopatologia , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Homeostase/efeitos dos fármacos , Hipotálamo/microbiologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/fisiologia , Masculino , Medicina Tradicional Chinesa , Óxido Nítrico Sintase Tipo II/genética , Peroxidase/metabolismo , RNA Ribossômico 16S , Ratos Wistar , Estômago/efeitos dos fármacos , Estômago/fisiologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
20.
Exp Anim ; 68(3): 381-389, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-30971623

RESUMO

Upper gastrointestinal (GI) motility is affected by various drugs and diseases. However, changes in upper GI motility during these conditions are not well understood, as there are few quantitative in vivo methods that assess small intestinal motility in mice. Ultrasonography is a noninvasive method for imaging and evaluating the condition of the abdominal organs. The aim of the present study was to establish a novel method for evaluating small intestinal motility by using ultrasonography in mice. We measured GI motility with and without loperamide, an antidiarrheal medication, by intestinal transit using an orally administered dye, a 13C-octanoic acid breath test, and ultrasonography. Locomotion activity of the duodenal wall was used for quantifying the GI motility observed via ultrasonography. Our results showed that upper GI transit was significantly delayed by loperamide. The 13C-octanoic acid breath test revealed decreased gastric emptying in loperamide-treated mice. Through ultrasonography, large peristaltic movements were observed in the duodenum of the control mice. In contrast, after treatment with loperamide, these peristaltic movements were suppressed, and the duodenal lumen was enlarged, suggesting decreased duodenal motility. In accordance with these results, quantifiable locomotion activity was also significantly decreased. In conclusion, ultrasonography is an effective in vivo method to quantify small intestinal motility in mice.


Assuntos
Antidiarreicos/administração & dosagem , Motilidade Gastrointestinal/fisiologia , Intestino Delgado/fisiologia , Loperamida/administração & dosagem , Camundongos/fisiologia , Ultrassonografia/métodos , Animais , Feminino , Camundongos Endogâmicos C57BL , Modelos Animais
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