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1.
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
2.
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
3.
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
4.
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
5.
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
6.
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
7.
Biofabrication ; 11(3): 035023, 2019 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-30943455

RESUMO

A novel strategy of cryogenic 3D bioprinting assisted by free-from extrusion printing has been developed and applied to printing of a decellularized small intestinal submucosa (dSIS) slurry. The rheological properties, including kinetic viscosity, storage modulus (G'), and loss modulus (G″), were appropriate for free-from extrusion printing of dSIS slurry. Three different groups of scaffolds, including P500, P600, and P700, with filament distances of 500, 600, and 700 µm, respectively were fabricated at a 5 mm s-1 working velocity of the platform (V xy) and 25 kPa air pressure of the dispensing system (P) at -20 °C. The fabricated scaffolds were crosslinked via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) which resulted in a polyporous microstructure. The variations in the filament diameter and pore size were evaluated in the initial frozen state after printing, the lyophilized state, and after immersion in a PBS solution. The Young's modulus of the P500, P600, and P700 scaffolds was measured in wet and dry states for EDC-crosslinked scaffolds. The cell experiment results showed improved cell adhesion, viability, and proliferation both on the surface and within the scaffold, indicating the biocompatibility and suitability of the scaffold for 3D cell models. Further, gene and protein expression of normal skin fibroblasts on dSIS scaffolds demonstrated their ability to promote the production of some extracellular matrix proteins (i.e. collagen I, collagen III, and fibronectin) in vitro. Overall, this study presents a new potential strategy, by combining cryogenic 3D bioprinting with decellularized extracellular matrix materials, to manufacture ideal scaffolds for skin tissue engineering applications.


Assuntos
Bioimpressão/métodos , Mucosa Intestinal/fisiologia , Intestino Delgado/fisiologia , Pele/metabolismo , Engenharia Tecidual/métodos , Animais , Materiais Biocompatíveis/farmacologia , Proliferação de Células/efeitos dos fármacos , Reagentes para Ligações Cruzadas/química , Módulo de Elasticidade , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Ratos Sprague-Dawley , Reologia , Pele/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier , Sus scrofa , Tecidos Suporte/química
8.
J Pediatr Surg ; 54(6): 1245-1249, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30879746

RESUMO

BACKGROUND: Enteric serotonin influences intestinal homeostasis and functions as a mucosal growth factor. Previously, we demonstrated increased mucosal surface area and enhanced crypt cell proliferation in serotonin reuptake transporter (SERT)-deficient mice. Therefore, we hypothesized that serotonin-mediated mucosal growth would also result in enhanced carbohydrate and lipid absorption. MATERIAL AND METHODS: Wild-type C57Bl/6 (WT) and SERT-knockout (SERTKO) mice were fasted then gavaged with D-xylose or boron-dipyrromethene (BODIPY) FL-C12 medium-chain fatty acid analog. Serum D-xylose and BODIPY concentrations were serially measured from blood drawn at 30 to 360 min post-gavage. Small intestine was harvested from both groups for comparison of morphometric parameters. Area under the curve of plotted graphs was calculated, and means were compared with Student's t-test to a significance of p < 0.05. RESULTS: Villus height and crypt depth were significantly greater in the middle and distal small intestine of SERTKO animals compared to WT. Overall absorption of D-xylose and BODIPY was greater in SERTKO animals compared to WT animals. Absorption of D-xylose was persistently elevated in SERTKO animals, while there was an initial delay in BODIPY absorption followed by a sustained and significantly greater absorption in SERTKO animals at 60-360 min after gavage. CONCLUSION: Potentiation of serotonin signaling in SERTKO mice results in small intestinal mucosal growth and enhanced carbohydrate and fat absorption in vivo. These functional increases support the concept of targeting the serotonin signaling system to augment intestinal adaptation in the setting of intestinal failure.


Assuntos
Carboidratos da Dieta/metabolismo , Gorduras na Dieta/metabolismo , Intestino Delgado , Proteínas da Membrana Plasmática de Transporte de Serotonina , Serotonina/metabolismo , Transdução de Sinais/fisiologia , Animais , Intestino Delgado/metabolismo , Intestino Delgado/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo
9.
Toxicol In Vitro ; 57: 76-80, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30763608

RESUMO

In previous experiments, human and rat small bowel samples have been successfully used to study the spasmolytic effect of (potential) therapeutics in carbamate-constricted bowel specimens. Additionally, transferability from rat to human data was shown in the previous study. In the present study, the effects of atropine, scopolamine, MB327, HI-6 as well as obidoxime were examined in organophosphorus-poisoned human small bowel specimens. All substances were tested with at least seven concentrations in samples previously exposed to the nerve agent sarin. Furthermore, the cholinesterase reactivation potential of all substances was investigated. The test substances displayed a spasmolytic effect allowing the calculation of dose-response curves and EC50s. The parasympatholytic compound scopolamine had the strongest relaxing effect (EC50 = 0.05 µM) followed by atropine (EC50 = 0.07 µM). HI-6 and obidoxime were capable to reactivate the sarin-inhibited cholinesterase activity in small bowel samples. Both substances restored AChE activity in a dose-dependent way, with HI-6 being more potent (HI-6 EC50 = 3.8 µM vs obidoxime EC50 = 197.8 µM). Summarizing, our isolated human small bowel setup is a suitable tool to investigate the smooth muscle relaxing effect of (candidate) therapeutics for organophosphorus compound poisoning i.e. sarin exposure in a complex 3D tissue model.


Assuntos
Inibidores da Colinesterase/toxicidade , Reativadores da Colinesterase/farmacologia , Intestino Delgado/efeitos dos fármacos , Intoxicação por Organofosfatos , Sarina/toxicidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Colinesterases/metabolismo , Feminino , Humanos , Intestino Delgado/fisiologia , Masculino , Pessoa de Meia-Idade , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , Adulto Jovem
10.
EMBO J ; 38(4)2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30635334

RESUMO

During homeostasis, the colonic epithelium is replenished every 3-5 days by rapidly cycling Lgr5 + stem cells. However, various insults can lead to depletion of Lgr5 + stem cells, and colonic epithelium can be regenerated from Lgr5-negative cells. While studies in the small intestine have addressed the lineage identity of the Lgr5-negative regenerative cell population, in the colon this question has remained unanswered. Here, we set out to identify which cell(s) contribute to colonic regeneration by performing genetic fate-mapping studies of progenitor populations in mice. First, using keratin-19 (Krt19) to mark a heterogeneous population of cells, we found that Lgr5-negative cells can regenerate colonic crypts and give rise to Lgr5 + stem cells. Notch1 + absorptive progenitor cells did not contribute to epithelial repair after injury, whereas Atoh1 + secretory progenitors did contribute to this process. Additionally, while colonic Atoh1 + cells contributed minimally to other lineages during homeostasis, they displayed plasticity and contributed to epithelial repair during injury, independent of Lgr5 + cells. Our findings suggest that promotion of secretory progenitor plasticity could enable gut healing in colitis.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Colite/prevenção & controle , Colo/citologia , Intestino Delgado/citologia , Receptores Acoplados a Proteínas-G/metabolismo , Regeneração , Células-Tronco/citologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Células Cultivadas , Colite/induzido quimicamente , Colite/patologia , Colo/fisiologia , Homeostase , Intestino Delgado/fisiologia , Queratina-19/genética , Queratina-19/metabolismo , Camundongos , Receptor Notch1/genética , Receptor Notch1/metabolismo , Receptores Acoplados a Proteínas-G/genética , Células-Tronco/fisiologia
11.
Mucosal Immunol ; 12(2): 503-517, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30617302

RESUMO

Mucosal healing occurs through migration and proliferation of cells within injured epithelium, yet these processes may be inadequate for mucosal healing after significant injury where the mucosa is denuded. We hypothesize that extra-intestinal cells can contribute to mucosal healing after injury to the small and large intestine. We generated parabiotic pairs between wild-type and tdTomato mice, which were then subjected to radiation-induced enteritis and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. We now show that as compared with singleton mice, mice with a parabiotic partner were protected against intestinal damage as revealed by significantly reduced weight loss, reduced expression of pro-inflammatory cytokines, reduced enterocyte apoptosis, and improved crypt proliferation. Donor cells expressed CD45-, Sca-1+, c-kit+, and CXCR4+ and accumulated around the injured crypts but did not transdifferentiate into epithelia, suggesting that extra-intestinal cells play a paracrine role in the healing response, while parabiotic pairings with Rag1-/- mice showed improved healing, indicating that adaptive immune cells were dispensable for mucosal healing. Strikingly, ablation of the bone marrow of the donor parabionts removed the protective effects. These findings reveal that the recruitment of extra-intestinal, bone marrow-derived cells into the injured intestinal mucosa can promote mucosal healing, suggesting novel therapeutic approaches for severe intestinal disease.


Assuntos
Células da Medula Óssea/fisiologia , Movimento Celular , Colite/terapia , Enterite/terapia , Mucosa Intestinal/fisiologia , Intestino Delgado/fisiologia , Parabiose/métodos , Lesões Experimentais por Radiação/terapia , Animais , Antígenos Ly/metabolismo , Colite/induzido quimicamente , Modelos Animais de Doenças , Feminino , Humanos , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Comunicação Parácrina , Receptores CXCR4/metabolismo , Ácido Trinitrobenzenossulfônico , Cicatrização
12.
J Anim Physiol Anim Nutr (Berl) ; 103(1): 8-16, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30484913

RESUMO

Eighteen Nellore and 18 Angus young bulls with BW of 381 ± 12 kg were randomly assigned into two feeding groups (whole shelled corn [WSC] or ground corn with silage [GC]) to evaluate the interaction of breed and diet on total nutrient digestibility, pancreatic α-amylase, and maltase activity and SLC5A1expression in the small intestine. Experimental diets (DM basis) included (a) a diet containing 30% corn silage and 70% GC and soya bean meal-based concentrate and (b) a diet containing 85% WSC and 15% of a soya bean meal- and mineral-based pelleted supplement. The treatments were Nellore fed GC diet; Nellore fed WSC diet; Angus fed GC diet; and Angus fed WSC diet. Total faecal collection for the digestibility trial occurred from day 48 until day 50 of the experimental period. Feeding the WSC diet reduced DM and NDF intake (p < 0.01). Angus had greater DM and nutrient intake in kg/day (p < 0.01). However, there was no breed effect on DM and nutrient intakes based on percentage of BW (p > 0.19). Angus had greater starch digestibility (p = 0.03) than Nellore. Cattle fed the WSC diet had greater DM, NDF and starch digestibility (p < 0.01) compared with those fed the GC diet. The activity of pancreatic α-amylase (U/g of protein) was greater in Nellore (p < 0.01) and was not affected by diet (p = 0.52). In duodenum, maltase activity (U/g of protein) was greater in bulls fed GC diet (p = 0.02). Expression of the gene SLC5A1was not affected by breed or diet (p > 0.05). In conclusion, Nellore had less capacity to digest starch. However, they did not have less pancreatic α-amylase and duodenal maltase activity compared to Angus. The use of the WSC diet increases DM and total nutrient digestibility.


Assuntos
Ração Animal/análise , Bovinos/fisiologia , Dieta/veterinária , Digestão/fisiologia , Intestino Delgado/fisiologia , Zea mays/química , Fenômenos Fisiológicos da Nutrição Animal , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Distribuição Aleatória , Amido/metabolismo
13.
Neuromodulation ; 22(6): 723-729, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30525253

RESUMO

BACKGROUND/AIMS: Patients with gastroparesis often have biliary/pancreatic and small bowel symptoms but the effects of gastric electrical stimulation on small bowel electrical activity of the mid-gut have not been studied. Animal model aim: Establish gastric and upper small bowel/biliary slow wave activity relationships with electrical stimulation. Human study aim: Demonstrate improvement in symptoms associated with proximal small bowel dysmotility in gastric stimulated patients. MATERIALS AND METHODS: Animal model: In vivo evoked responses of duodenal and Sphincter of Oddi measures recorded during gastric electrical stimulation in a nonsurvival swine model (N = 3). High-resolution electrical slow wave mapping of frequency, amplitude, and their ratio, for duodenal and Sphincter of Oddi electrical activity were recorded. Human study: Patients (N = 8) underwent temporary gastric stimulation with small bowel electrodes. Subjective and objective data was collected before and after temporary gastric stimulation. Symptom scores, gastric emptying times, and mucosal electrograms via low-resolution mapping were recorded. RESULTS: Animal gastric stimulation resulted in some changes in electrical activity parameters, especially with the highest energies delivered but the changes were not statistically significant. Human study revealed improvement in symptom and illness severity scores, and changes in small bowel mucosal slow wave activity. CONCLUSIONS: Gastric electrical stimulation in an animal model seems to show nonsignificant effects small bowel slow wave activity and myoelectric signaling, suggesting the existence of intrinsic neural connections. Human data shows more significance, with possible potential for therapeutic use of electrical stimulation in patients with gastroparesis and pancreato-biliary and small bowel symptoms of the mid-gut. This study was limited by the nonsurvival pig model, small sample size, and open label human study.


Assuntos
Terapia por Estimulação Elétrica/métodos , Eletrodos Implantados , Motilidade Gastrointestinal/fisiologia , Gastroparesia/terapia , Enteropatias/terapia , Intestino Delgado/fisiologia , Pancreatite/terapia , Adulto , Animais , Modelos Animais de Doenças , Feminino , Gastroparesia/diagnóstico , Gastroparesia/fisiopatologia , Humanos , Enteropatias/diagnóstico , Enteropatias/fisiopatologia , Intestino Delgado/inervação , Masculino , Pessoa de Meia-Idade , Pancreatite/diagnóstico , Pancreatite/fisiopatologia , Projetos Piloto , Suínos , Resultado do Tratamento
14.
Animal ; 13(8): 1641-1650, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30458891

RESUMO

Glutathione (GSH) is considered to play an important role in maintaining the integrity of the small intestine. In piglets, altered mucosal GSH levels might therefore be involved in weaning-induced changes of the small intestinal morphology and barrier function. To test this hypothesis, we aimed to challenge the mucosal GSH redox status during the first 28 days after weaning, by feeding diets containing 5% fresh linseed oil (CON), or 2.5% (OF1) or 5% (OF2) peroxidized linseed oil (peroxide value 225 mEq O2/kg oil) and exploring the effects on gut integrity. Piglets were pair-fed and had a total daily feed allowance of 32 g/kg BW. A fourth treatment included animals that were fed the control diet ad libitum (ACON). Animals were sampled at days 5 and 28 post-weaning. The malondialdehyde (MDA) concentration and GSH redox status (GSH/GSSG Eh) were determined in blood, liver and small intestinal mucosa. Histomorphology of the duodenal and jejunal mucosa was determined, and Ussing chambers were used to assess fluorescein isothiocyanate dextran (FD4) and horseradish peroxidase (HRP) fluxes across the mucosa. Results show that peroxidized linseed oil imposed an oxidative challenge at day 28, but not at day 5 post-weaning. At day 28, increasing levels of dietary peroxides to pair-fed pigs linearly increased MDA levels in duodenal and jejunal mucosa. Moreover, FD4 fluxes were significantly increased in OF1 (+75%) and OF2 (+64%) in the duodenum, and HRP fluxes tended (P=0.099) to show similar differences, as compared to CON. This co-occurred with a significant 11 mV increase of the hepatic GSH/GSSG Eh, potentiated by a significantly increased GSH peroxidase activity for treatments OF1 (+47%) and OF2 (+63%) in liver as compared to CON. Furthermore; duodenal HRP flux significantly correlated with the hepatic glutathione disulphide (GSSG) level (r=0.650), as also observed in the jejunum for hepatic GSSG (r=0.627) and GSH/GSSG Eh (r=0.547). The jejunal permeability was not affected, but FD4 and HRP fluxes significantly correlated with the local GSH (r=0.619; r=0.733) and GSSG (r=0.635; r=0586) levels. Small intestinal histomorphology was not affected by dietary lipid peroxides, nor were there any correlations found with the GSH redox system. To conclude, under oxidative stress conditions, jejunal barrier function is related to the local and hepatic GSH redox system. It is suggested that the hepatic GSH system participates in the elimination of luminal peroxides, and thereby impacts on duodenal barrier function.


Assuntos
Glutationa/metabolismo , Intestino Delgado/efeitos dos fármacos , Óleo de Semente do Linho/farmacologia , Suínos/metabolismo , Ração Animal , Animais , Dieta/veterinária , Suplementos Nutricionais , Dissulfeto de Glutationa/metabolismo , Intestino Delgado/metabolismo , Intestino Delgado/fisiologia , Óleo de Semente do Linho/administração & dosagem , Óleo de Semente do Linho/química , Malondialdeído/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Desmame
15.
Poult Sci ; 98(3): 1280-1287, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30289530

RESUMO

Two experiments were conducted to validate a method to prepare simulated small intestinal fluid (SSIF) for in vitro digestion in ducks. Experiment 1 compared the in vitro digestible energy (IVDE) of SSIF to endogenous small intestinal fluid (ESIF) on four feeds. The ESIF 1 or 2 obtained from two groups of jejunal cannulated ducks offered diet 1 (3,050 kcal/kg of ME and 19.95% of CP) or 2 (2,801 kcal/kg of ME and 14.90% of CP) was purified into raw enzyme power (REP) 1 or 2. SSIF 1 to 3 or 4 to 6 were prepared to mimic ESIF 1 or 2, respectively. The enzyme sources were REP 1 for SSIF 1 and 4, REP 2 for SSIF 2 and 5 or reagent enzymes for SSIF 3 and 6, respectively. The IVDE of each feed was determined with SSIF or ESIF. Experiment 2 was to validate whether REP 1 was more effective than only reagent enzymes to prepare SSIF. Ten feeds were determined with pepsin following SSIF 1 or 3 for IVDE 1 or 2, respectively. The accuracy of prediction model of true metabolizable energy (TME) from IVDE 1 or 2 was evaluated to validate the efficacy of SSIF. In experiment 1, higher activities of amylase, trypsin and chymotrypsin were observed in ESIF 1 than ESIF 2 (P < 0.05). The IVDE determined with SSIF 1 and 2 or 3 and 4 were more comparable to that of ESIF 1 or 2 than determinations with SSIF 3 or 6. In experiment 2, the mean IVDE 1 or 2 was 97.22% or 96.23% relative to TME, respectively, and both were highly correlated with TME (P < 0.01; R2 ≥ 0.98). However, the residual SD of TME prediction model with IVDE 1 was less than that generated with IVDE 2 (55 vs. 71 kcal/kg). In conclusion, the IVDE determined with in vitro digestion of pepsin following SSIF prepared with REP can predict accurately TME of feed for ducks.


Assuntos
Ração Animal/análise , Patos/metabolismo , Metabolismo Energético/fisiologia , Intestino Delgado/fisiologia , Animais , Conteúdo Gastrointestinal/enzimologia , Técnicas In Vitro/veterinária , Intestino Delgado/enzimologia , Pepsina A/química
16.
J Anim Physiol Anim Nutr (Berl) ; 103(1): 221-230, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30280433

RESUMO

The influence of medium-chain glycerides on performance and gastrointestinal well-being in weaning piglets was assessed. First, caproic (C6), caprylic (C8) and capric (C10) acid activity against Escherichia coli was screened in vitro. Pig flora of the whole small intestine was used as inoculum. Seven in vitro incubations were done in duplicate at pH = 3 and 5: C10 (15 mM), C8 (12 mM), C6 (15, 12, 10 mM), a non-incubated-negative control and incubated negative control. Culture suspensions were plated on E. coli-selective agar. Controls showed bacterial growth. C6 and C8 showed no growth at both pH-values, where C10 showed growth at pH = 5. Secondly, an in vivo study was done with 80 weaned piglets over 42 days, housed in pens of eight animals (five pens/treatment), fed a basal diet containing broken rice/soya bean meal/fish meal and supplemented with C6 and C8 in medium-chain glyceride form (MCT6/8, 0.175%) or antibiotic growth promoter (AGP, 0.020%) (Kasetsart University, Thailand) serving as control. Feed intake, daily gain and feed-to-gain ratio did not differ between MCT6/8 and AGP. Per replicate, two random selected piglets were challenged intravenously with E. coli-lipopolysaccharide (LPS) or saline solution (S) at Days 21 and 28. All challenged animals were sacrificed; blood and digestive tract samples (jejunum/ileum) were collected at Day 35. LPS challenge consistently reduced villus height and crypt depth for MCT6/8 and AGP. However, LPS-challenged piglets supplemented with MCT6/8 restored villus height, where AGP did not. MCT6/8 piglets had higher serum IgA, more jejunal IgA-positive plasma cells and goblet cells than AGP. At the ileal level, results were similar, though less pronounced. The present study offers new insight in the benefits of MCT6/8 over AGP in the post-weaning period. There is in vitro anti-microbial action of C6 and C8 on E. coli. In vivo, MCT6/8 also has protective effects in the small intestine that may result in growth promotion.


Assuntos
Escherichia coli , Ácidos Graxos/metabolismo , Glicerídeos/farmacologia , Células Caliciformes/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Suínos , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , Digestão/fisiologia , Imunoglobulina A/sangue , Intestino Delgado/microbiologia , Intestino Delgado/fisiologia , Lipopolissacarídeos/toxicidade , Distribuição Aleatória
17.
Gut Microbes ; 10(2): 235-240, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30136893

RESUMO

Our recently published paper "Small Intestine Microbiota Regulate Digestive and Absorptive Adaptive Responses to Dietary Lipids" in Cell Host & Microbe explored the neglected small intestine microbiota and demonstrated its critical role as a regulator of fat digestion and absorption. This work generated the following important take home messages: 1) small intestinal microbes are particularly sensitive to high fat diets and turn on host processes regulating fat digestion and transport, 2) this action is very likely orchestrated by a consortium of microbes, each having different specific effects and targets, and 3) the actions of this consortium appear to be mediated by bacteria-derived small molecules or bioactive components. These findings are expected to provide insight into developing treatments for conditions of under- or over-nutrition. The goal of this addendum is to summarize our findings, address issues related to gut microbiota and gnotobiotic research specifically regarding technology and experimental design, discuss this work in the context of relevant literature, and lastly provide considerations for future research.


Assuntos
Microbioma Gastrointestinal/fisiologia , Intestino Delgado/microbiologia , Intestino Delgado/fisiologia , Metabolismo dos Lipídeos , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Dieta Hiperlipídica , Digestão , Interações entre Hospedeiro e Microrganismos , Absorção Intestinal
18.
Compr Physiol ; 9(1): 343-373, 2018 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-30549024

RESUMO

The small intestine mediates the absorption of amino acids after ingestion of protein and sustains the supply of amino acids to all tissues. The small intestine is an important contributor to plasma amino acid homeostasis, while amino acid transport in the large intestine is more relevant for bacterial metabolites and fluid secretion. A number of rare inherited disorders have contributed to the identification of amino acid transporters in epithelial cells of the small intestine, in particular cystinuria, lysinuric protein intolerance, Hartnup disorder, iminoglycinuria, and dicarboxylic aminoaciduria. These are most readily detected by analysis of urine amino acids, but typically also affect intestinal transport. The genes underlying these disorders have all been identified. The remaining transporters were identified through molecular cloning techniques to the extent that a comprehensive portrait of functional cooperation among transporters of intestinal epithelial cells is now available for both the basolateral and apical membranes. Mouse models of most intestinal transporters illustrate their contribution to amino acid homeostasis and systemic physiology. Intestinal amino acid transport activities can vary between species, but these can now be explained as differences of amino acid transporter distribution along the intestine. © 2019 American Physiological Society. Compr Physiol 9:343-373, 2019.


Assuntos
Sistemas de Transporte de Aminoácidos/metabolismo , Aminoácidos/metabolismo , Intestino Delgado/metabolismo , Sistemas de Transporte de Aminoácidos/genética , Aminoácidos/classificação , Animais , Humanos , Absorção Intestinal , Intestino Delgado/fisiologia
19.
J Nutr ; 148(11): 1743-1750, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30383281

RESUMO

Background: Actinidin, a cysteine protease in kiwifruit (KF), increases both the gastric digestion and gastric-emptying rate of beef muscle protein. Objective: This study aimed to determine the relation between the rate of digested nitrogen entering the small intestine (SI; a function of the extent of gastric digestion and gastric-emptying rate) and the disappearance of amino acids (AAs) in different parts of the SI at set times postfeeding. Methods: Male 9-wk-old pigs (n = 90; mean ± SD body weight: 28 ± 2.9 kg) were fed a diet containing 14% beef for 3 d. The beef-based diet was supplemented with green KF pulp (containing actinidin), gold KF pulp supplemented with actinidin, or gold KF pulp alone (no actinidin). The KF or actinidin amounts corresponded to the intake of 2 KFs/human meal. On day 3, pigs were killed at 0.5, 1, 3, 5, and 7 h postprandially. Stomach chyme was analyzed to determine the rate of digested nitrogen entering the SI. Apparent AA digestibility at set times was determined in the proximal, medial, and distal SI. Polynomial and correlation analyses were conducted. Results: The rate of digested nitrogen entering the SI was higher (P < 0.001) with actinidin (e.g., >44% at 5 h postprandially). Actinidin also increased the apparent AA digestibility at the proximal and medial SI (P ≤ 0.05) at set times (e.g., 42% and 15% greater for arginine, respectively), but not in general for the distal SI (P > 0.05). At the proximal SI, apparent AA digestibility was correlated more strongly with the digested nitrogen entering the SI (r = 0.73, P < 0.001; n = 57) than with gastric emptying (r = 0.64, P < 0.001) or gastric protein digestion (r = 0.57, P < 0.001). Similar trends were observed for the medial SI. Conclusion: The rate of digested nitrogen entering the SI is an accurate predictor of the rate of AA digestibility and the location of AA absorption in the pig SI.


Assuntos
Aminoácidos/metabolismo , Proteínas na Dieta/metabolismo , Intestino Delgado/fisiologia , Suínos/fisiologia , Actinidia , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Animais , Bovinos , Dieta , Suplementos Nutricionais , Digestão/fisiologia , Motilidade Gastrointestinal , Masculino , Carne/análise , Distribuição Aleatória
20.
Biomed Mater Eng ; 29(6): 839-848, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30282338

RESUMO

BACKGROUND: There are no reports to prove the repeatability of gastric transit time (GTT) and small bowel transit time (SBTT) in capsule endoscopy (CE). OBJECTIVE: To clarify the repeatability and factors that affect GTT/SBTT in CE. METHODS: We analyzed the data of 150 healthy subjects from our previous randomized controlled trial that compared small intestinal injuries between two 14-day treatment groups: 1) celecoxib and 2) loxoprofen + lansoprazole. Correlation of GTT/SBTT with pre- and post-treatment CE was analyzed. In addition, the associations of pre-treatment CE SBTT with physical factors, post-treatment CE SBTT and the presence of small intestinal mucosal injuries were analyzed. RESULTS: Analyses of 148 subjects pre-treatment CE and 146 subjects post-treatment CE were performed. There were no significant differences between mean GTT and SBTT before and after treatment. Both GTT (𝜌 = 0.22, p < 0.01) and SBTT (𝜌 = 0.47, p < 0.0001) showed positive correlations between pre- and post-treatment CE. In pre-treatment CE, physical factors and the presence of small intestinal mucosal injury had no associations with SBTT. CONCLUSIONS: Moderate correlation in SBTT and slight correlation in GTT were shown on repeated CE. The factors affecting SBTT were not clarified in this analysis.


Assuntos
Endoscopia por Cápsula , Trânsito Gastrointestinal , Intestino Delgado/fisiologia , Estômago/fisiologia , Adulto , Idoso , Peso Corporal , Celecoxib/administração & dosagem , Feminino , Voluntários Saudáveis , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Intestino Delgado/lesões , Lansoprazol/administração & dosagem , Masculino , Pessoa de Meia-Idade , Fenilpropionatos/administração & dosagem , Reprodutibilidade dos Testes , Fatores de Tempo
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