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1.
Arq. gastroenterol ; 59(2): 238-243, Apr.-June 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1383855

ABSTRACT

ABSTRACT Background: Inflammatory bowel disease (IBD) comprises the spectrum between Crohn's disease (CD) and ulcerative colitis (UC), a condition whose prevalence in countries such as Brazil has increased significantly in recent years. Changes in the intestinal epithelial barrier function and, consequently, an increase in intestinal permeability, have been suggested as important factors in the pathogenesis of different autoimmune conditions, including IBD. Therefore, there is a need for a practical tool to assess gut barrier integrity in these patients. Objective: To study factors associated with serum zonulin levels, a marker of intestinal permeability, in patients with IBD. Methods: This was a cross-sectional observational study that included 117 patients with IBD and 32 healthy controls. Disease activity was assessed by the Simple Clinical Colitis Activity Index (SCCAI) in UC and by the Harvey-Bradshaw Index (HBI) in CD subjects. Zonulin levels were measured by ELISA and inflammatory cytokines by Cytometric Bead Array, using commercially available kits. Results: The mean age of IBD patients was 44.0±15.9 years, 66.7% were female, 57 subjects were diagnosed with CD and 60 with UC. At evaluation, clinical remission was observed in 56.7% of CD patients and in 59.2% of UC subjects. No differences were observed in zonulin levels when comparing IBD patients with the control group (95.28 ng/mL vs 96.61 ng/mL, P=0.573) and when comparing patients with CD to those with UC (79.68 ng/mL vs 106.10 ng/mL, P=0.887). Among IBD group, zonulin concentrations were higher among females, correlated positively with body mass index (BMI) and age; and negatively with hemoglobin and hematocrit. In patients with UC, zonulin correlated negatively with hemoglobin, hematocrit, and albumin; and positively with BMI and SCCAI. Among CD patients, zonulin was positively correlated with age and BMI, but not with HBI. No correlations were observed between zonulin and circulating cytokines in IBD patients. Conclusion: In this cohort mostly comprised of patients in clinical remission, serum zonulin levels were not higher in patients with IBD than healthy controls, and correlated with variables not linked to baseline disease, such as sex, age and BMI. However, zonulin correlated with clinical and laboratory parameters of disease severity and activity among subjects with UC, but not among patients with CD. These findings indicate a potential role for zonulin as a biomarker in IBD, particularly in UC.


RESUMO Contexto: A doença inflamatória intestinal (DII) compreende o espectro entre a doença de Crohn (DC) e a colite ulcerativa, condição esta cuja prevalência em países como o Brasil vem aumentando significativamente nos últimos anos. Alterações na função da barreira epitelial intestinal e, consequentemente, um aumento da permeabilidade intestinal, têm sido sugeridos como fatores importantes envolvidos na patogênese de diferentes condições autoimunes, dentre elas, a DII. Desta forma, existe a necessidade de uma ferramenta prática para avaliar a integridade da barreira epitelial intestinal nestes pacientes. Objetivo: Estudar os fatores associados com os níveis séricos de zonulina, um marcador da permeabilidade intestinal, em pacientes com DII. Métodos: Estudo observacional transversal que incluiu 117 pacientes com DII e 32 indivíduos que compuseram o grupo controle. A atividade da doença foi avaliada pelo Simple Cliniical Colitis Activity Index (SCCAI) na colite ulcerativa e pelo índice de Harvey-Bradshaw (IHB) em pacientes com DC. Os níveis de zonulina foram quantificados por ELISA e os níveis das citocinas inflamatórias pelo Cytometric Bead Array, utilizando kits comercialmente disponíveis. Resultados: A média de idade dos pacientes com DII foi de 44,0±15,9 anos, 66,7% eram do sexo feminino, 57 pacientes eram portadores de DC e 60 pacientes eram portadores de colite ulcerativa. No momento da avaliação clínico-laboratorial, 56,7% dos pacientes com DC encontravam-se em remissão clínica e, dentre os pacientes com colite ulcerativa, 59,2% deles assim se encontravam. Não foram observadas diferenças nos níveis séricos de zonulina entre pacientes com DII e grupo controle (95,28 ng/mL vs 96,61 ng/mL; P=0,573), assim como entre pacientes com DC e pacientes com colite ulcerativa (79,68 ng/mL vs 106,10 ng/mL, P=0,887). Dentre os pacientes com DII, as concentrações de zonulina foram mais elevadas no sexo feminino e correlacionaram-se positivamente com o índice de massa corporal (IMC) e com a idade, correlacionando-se negativamente com os níveis de hemoglobina e hematócrito. Nos pacientes com colite ulcerativa, as concentrações de zonulina correlacionaram-se negativamente com os parâmetros hemoglobina, hematócrito e albumina e, positivamente, com o IMC e com o SCCAI. Dentre os pacientes com DC, a zonulina sérica correlacionou-se positivamente com a idade e com o IMC, mas não com o IHB. Não foram observadas correlações entre os níveis de zonulina e as citocinas circulantes nos pacientes com DII. Conclusão: Nesta coorte constituída majoritariamente por pacientes em remissão clínica, os níveis séricos de zonulina não se mostraram aumentados em pacientes com DII em relação a indivíduos controles e correlacionaram-se com variáveis não relacionadas à doença de base, como com o sexo, com a idade e com o IMC. No entanto, os níveis séricos de zonulina correlacionaram-se com parâmetros clínicos e laboratoriais de gravidade e atividade da doença dentre os pacientes com colite ulcerativa, mas não dentre os pacientes com DC. Estes achados indicam um potencial papel da zonulina sérica como um biomarcador na DII, principalmente na colite ulcerativa.

2.
Acta Pharmaceutica Sinica B ; (6): 1667-1675, 2021.
Article in English | WPRIM | ID: wpr-888827

ABSTRACT

Transcellular permeation enhancers are known to increase the intestinal permeability of enalaprilat, a 349 Da peptide, but not hexarelin (887 Da). The primary aim of this paper was to investigate if paracellular permeability enhancers affected the intestinal permeation of the two peptides. This was investigated using the rat single-pass intestinal perfusion model with concomitant blood sampling. These luminal compositions included two paracellular permeation enhancers, chitosan (5 mg/mL) and ethylenediaminetetraacetate (EDTA, 1 and 5 mg/mL), as well as low luminal tonicity (100 mOsm) with or without lidocaine. Effects were evaluated by the change in lumen-to-blood permeability of hexarelin and enalaprilat, and the blood-to-lumen clearance of

3.
Article in Chinese | WPRIM | ID: wpr-879076

ABSTRACT

This study aims to investigate the preventive effect of Dendrobium officinale in LPS-induced intestinal mucosal damage. Forty SPF-grade C57 BL/6 J male mice were randomly divided into normal group(NC), model group(LPS), and two superfine powder groups of Dendrobium officinale(DOF)(DOF-L, 0.30 g·kg~(-1)and DOF-H, 0.60 g·kg~(-1), respectively), with 10 mice in each group. DOF superfine powder suspension was given via oral administration to mice for 7 days, while the mice in NC and LPS groups received the same volume of saline for 7 days. On the eighth day, the mice in LPS group and DOF treatment groups were injected with LPS(5 mg·kg~(-1)) by intraperitoneal injection to establish the intestinal mucosal injury model, while the mice in NC group were injected with the same volume of sterile saline in the same manner. Six hours after injection with LPS or saline, plasma and the intestinal tissue were collected. The diamine oxidase(DAO) and D-lactate levels in plasma were detected with a biochemical method. The levels of proinflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in plasma were detected by ELISA. The histomorphology and ultrastructure of mouse ileum tissues were observed by hematoxylin-eosin(HE) staining in optical microscope and transmission electron microscope(TEM). The expression and distribution of tight junction(TJ) proteins claudin-1, occludin and F4/80 were detected by immunohistochemistry while the protein expression levels of Toll-like receptor 4(TLR-4) and nuclear factor kappa B p65(NF-κB p65) in jejunum were detected by Western blot. The experimental results showed that continuous intragastric administration of D. officinale superfine powder for 7 days obviously alleviated the damage and ultrastructural changes of intestinal mucosa induced by LPS; significantly decreased DAO and D-lactate levels in plasma in model group(P<0.05); up-regulated the protein expression of claudin-1 and occludin in ileum tissues; down-regulated the protein expression of TLR-4 and NF-κB p65 in jejunum tissues(P<0.01); significantly decreased TNF-α and IL-6 levels in plasma(P<0.05); and decreased the infiltration of F4/80~+ macrophage cells. Our results suggested that D. officinale had significant protective effects on LPS-induced intestinal mucosal damage and reduced intestinal permeability. The mechanism might be related to its effects of inhibiting inflammation via TLR-4/NF-κB p65, and up-regulating the expression of tight junction proteins.


Subject(s)
Animals , Dendrobium , Intestinal Mucosa , Lipopolysaccharides , Male , Mice , NF-kappa B , Powders , Tumor Necrosis Factor-alpha/genetics
4.
Article in Chinese | WPRIM | ID: wpr-873744

ABSTRACT

Objective To explore the mechanism of the intestinal barrier damage caused by Blastocystis hominis infections in rats. Methods Thirty SD rats were randomly divided into the control group, and the 1-, 3-, 6- and 9-week-infection groups, of 6 rats in each group. Rats in each infection group were orally infected with B. hominis trophozoites at a density of 2 × 108 parasites per rat, and the control group was given an equal volume of phosphate buffered saline solution. The 7-hour urine samples were collected 1, 3, 6 and 9 weeks post-infection for the measurement of the intestinal permeability. Then, rats were sacrificed using the cervical dislocation method, and the cecum specimens were collected for the detection of the intestinal epithelial cell permeability. The expression of tight junction-related Occludin and Claudin - 1 genes and apoptosis-related Bcl - 2 and Bax genes was quantified in cecum epithelial cells using the real-time fluorescent quantitative PCR (qPCR) assay, and cell apoptosis was detected in the rat cecum using the TdT-mediated dUTP nick-end labeling (TUNEL) assay. Results The median urinary lactolose to mannitol ratios were 0.29, 0.72, 0.44, 0.46 and 0.38 in the control group, and the 1-, 3-, 6- and 9-week-infection groups, respectively, and the difference was statistically significant (H = 12.09, P < 0.05). B. hominis invasion and epithelial injury were observed in intestinal epithelial cells of rats infected with B. hominis, and transmission electron microscopy displayed the destruction of tight junctions between intestinal epithelial cells. The relative expression of Occludin, Claudin-1, Bcl-2 and Bax genes was 1.04, 0.62, 0.71, 0.68 and 0.96; 1.03, 0.61, 0.63, 0.76 and 0.86; 1.08, 0.70, 0.75, 0.74 and 1.03; and 1.00, 1.57, 1.33, 1.35 and 1.10 in the control group and the 1-, 3-, 6- and 9-week-infection groups, respectively, and all differences were statistically significant (F = 2.86, 2.85, 3.37 and 4.45, all P values < 0.05). The median number of positive staining cells were 1.00, 13.00, 9.00, 3.50 and 1.00 in rat cecum specimens in the control group, and the 1-, 3-, 6- and 9-week-infection groups, respectively, and the difference was statistically significant (H = 22.95, P < 0.01). Conclusion B. hominis infection may cause an increase in the rat intestinal permeability through triggering the apoptosis of intestinal epithelial cells to destroy the tight junction between intestinal epithelial cells, thereby destroying the intestinal barrier function.

5.
Arch. endocrinol. metab. (Online) ; 64(5): 597-607, Sept.-Oct. 2020. tab, graf
Article in English | LILACS | ID: biblio-1131128

ABSTRACT

ABSTRACT Objectives Yacon flour is rich in bioactive compounds (phenolic compounds and fructooligosaccharides (FOS)), and may therefore reduce the risk of diseases associated with excess body weight. However, its effect on fecal short chain fatty acids (SCFA), intestinal permeability, oxidative stress and inflammation markers has not been studied in adult humans with excess body weight. Thus, we evaluated the effect of the consumption of yacon flour on these variables. Materials and methods Twenty-six excess body weight (30.4 ± 2.4 kg/m2) adults (31.3 ± 8.5y) were randomized to one of two groups (yacon flour or control; n = 13) on a double blind clinical trial. Subjects received a breakfast drink containing or not yacon flour (25g) associated with an energy restricted diet, for six weeks. The flour chemical characterization, FOS and total phenolics contents were evaluated. Antioxidant capacity was evaluated in vitro and in vivo (plasma). Intestinal permeability, fecal SCFA, oxidative stress and inflammatory markers also were evaluated in vivo. Results Yacon flour was well tolerated. It presented an in vitro and in vivo antioxidant capacity, increased plasma total antioxidant capacity (ΔYAC: 49.16 (-4.20; 156.63)) and reduced protein carbonyl concentrations (ΔYAC: -0.98 (-1.54; -0.42)). A reduction in SCFAs was observed in both groups (Δacetic: -3.16 (-5.07; -0.95) vs. -1.05 (-2.65; 1.11); Δpropionic: -1.05 (-2.60;-0.38) vs. -0.41 (-2.08; 0.09); Δbutyric: -0.75 (-1.38; -0.04) vs. -0.28 (-0.98; 0.11), for YAC and CON, respectively). Other variables did not change. Conclusion The yacon flour increased the plasma antioxidant capacity, decreased oxidative stress and SCFAs in adults with obesity or overweight.


Subject(s)
Humans , Adult , Asteraceae , Flour , Permeability , Oxidative Stress , Diet , Overweight , Fatty Acids, Volatile , Inflammation , Obesity
6.
Braz. j. med. biol. res ; 53(5): e9211, 2020. tab, graf
Article in English | LILACS | ID: biblio-1098114

ABSTRACT

Strenuous exercise triggers deleterious effects on the intestinal epithelium, but their mechanisms are still uncertain. Here, we investigated whether a prolonged training and an additional exhaustive training protocol alter intestinal permeability and the putative effect of alanyl-glutamine (AG) pretreatment in this condition. Rats were allocated into 5 different groups: 1) sedentary; 2 and 3) trained (50 min per day, 5 days per week for 12 weeks) with or without 6 weeks oral (1.5 g/kg) AG supplementation; 4 and 5) trained and subjected to an additional exhaustive test protocol with or without oral AG supplementation. Venous blood samples were collected to determine gasometrical indices at the end of the 12-week protocol or after exhaustive test. Lactate and glucose levels were determined before, during, and after the exhaustive test. Ileum tissue collected after all experimental procedures was used for gene expression analysis of Zonula occludens 1 (ZO-1), occludin, claudin-2, and oligopeptide transporter 1 (PepT-1). Intestinal permeability was assessed by urinary lactulose/mannitol test collected after the 12-week protocol or the exhaustive test. The exhaustive test decreased pH and base excess and increased pCO2. Training sessions delayed exhaustion time and reduced the changes in blood glucose and lactate levels. Trained rats exhibited upregulation of PEPT-1, ZO-1, and occludin mRNA, which were partially protected by AG. Exhaustive exercise induced intestinal paracellular leakage associated with the upregulation of claudin-2, a phenomenon protected by AG treatment. Thus, AG partially prevented intestinal training adaptations but also blocked paracellular leakage during exhaustive exercise involving claudin-2 and occludin gene expression.


Subject(s)
Animals , Male , Rats , Permeability/drug effects , Physical Conditioning, Animal/physiology , Dipeptides/administration & dosage , Intestinal Mucosa/drug effects , Intestinal Mucosa/physiopathology , Rats, Wistar , Models, Animal
7.
Article in Chinese | WPRIM | ID: wpr-793067

ABSTRACT

To investigate the protective effect of salvianolic acid B(SAB)on the intestinal tract of rats after intestinal ischemia-reperfusion injury(IIRI). Forty-eight healthy male SD rats were equally randomized into IIRI group,SAB+IIRI group,sham control group,and SAB+sham control group. The malonyldialdehyde(MDA)level and superoxide dismutase(SOD)activity in the ileum were measured in each group according to the kit instructions,the transcription levels of inflammatory factors in the ileum of rats were detected by real-time fluorescence quantitative RT-PCR,the secretion level of inflammatory factors was detected by ELISA,and the effects of intestinal ischemia-reperfusion on intestinal permeability and histological lesions were measured by histopathology. The MDA level in IIRI group was significantly higher than those in negative control group(=0.005)and SAB+IIRI group(=0.012). SOD activity of IIRI group was significantly lower than those of negative control group(=0.006)and SAB+IIRI group(=0.017). The optical densities of tumor necrosis factor-α(TNF-α)(=0.003,=0.009),interleukin(IL)-1β(=0.026,=0.005),IL-6(=0.015,=0.003),and nuclear factor kappa-B(NF-κB)(=0.007,=0.015)in IIRI group were significantly higher than those in sham control group and SAB+IIRI group. The TNF-α(=0.002,=0.006),IL-1β(=0.002,=0.006),IL-6(=0.008,=0.002),and NF-κB(=0.026,=0.005)levels in IIRI group were significantly higher than those in sham control group and SAB+IIRI group. The inulin level in IIRI group was significantly lower than that in negative control group(=0.015)and significantly higher than that in SAB+IIRI group(=0.011). The dextran level in IIRI group was significantly lower than those in sham control group(=0.011)and SAB+IIRI group(=0.012). The dextran gel level in IIRI group was significantly higher than those in sham control group(=0.031)and SAB+IIRI group(=0.020). SAB pretreatment remarkably improved the edema,necrosis,and villus stripping of the intestinal mucosa in the ileum of rats. The Chiu score was significantly higher in SAB+sham control group than in sham control group(=0.001)and was significantly lower in SAB+IIRI group than in IIRI group(=0.001). SAB pretreatment can alleviate IIRI in rat models,and this protective effect may be achieved by alleviating oxidative stress and inflammation in the intestinal tract.

8.
Article | IMSEAR | ID: sea-195898

ABSTRACT

Background & objectives: In acute pancreatitis (AP) gut barrier dysfunction is considered as an important predisposing factor leading to increased intestinal permeability (IP). In this study a pooled analysis of data published in our previous four studies on various aspects of gut permeability and endotoxaemia in patients with AP was attempted to find an association between increased IP and severity of disease and associated complications. Methods: This study was a pooled analysis of data of four previously published prospective studies on AP. Gut permeability, assessed by lactulose/mannitol excretion in urine and endotoxin core antibodies type IgG and IgM (EndoCab IgG and IgM) were measured on days zero and seven (D0 and D7) of admission. All patients received standard treatment of AP. We studied whether IgG and IgM anti-endotoxin titres and lactulose-mannitol ratio (LMR) at admission and D7 were associated with organ failure, infection and mortality. Results: The titres of anti-endotoxin IgG and IgM were lower in all patients of AP (n=204), both in mild AP (n=24) and severe AP (n=180) in the first week, compared to controls (n=15). There was no significant difference in serum IgG and IgM anti-endotoxin levels and LMR at baseline and at D7 among patients with organ failure, infection and mortality. Interpretation & conclusions: Our findings showed that serum IgG and IgM anti-endotoxin titres and LMR at admission and at day 7 were not associated with organ failure, infection, and death of patients with AP.

9.
Article in Chinese | WPRIM | ID: wpr-773667

ABSTRACT

The research on biopharmaceutics classification system of Chinese materia medica( CMMBCS) should be finally implemented to the holistic research level of traditional Chinese medicine compounds,while the overall biopharmaceutical properties of traditional Chinese medicine compounds are not only the sum of solubility and permeability of each component. In this study,Gegen Qinlian Tablets was used as the research object,and the contents of 12 representative components,i.e. puerarin,daidzin,baicalin,daidzein,wogonoside,baicalein,wogonin,glycyrrhizic acid,coptisine hydrochloride,epiberberine,berberine hydrochloride and palmatine hydrochloride,were simultaneously determined by HPLC to obtain the mass weight of each component. The in vitro lipopolysaccharide( LPS)-induced RAW264. 7 cells inflammation model was established to investigate the anti-inflammatory effects of 12 representative components and obtain the efficacy weight of each component. In order to obtain the number of doses and effective permeability coefficient which can represent the overall biopharmaceutical properties of Gegen Qinlian Tablets,mass weight was combined with efficacy weight to integrate the solubility and permeability data of each component determined by typical shake flask method and in situ single pass intestinal perfusion model respectively. The results indicated that Gegen Qinlian Tablets should be categorized Ⅳ drug of the CMMBCS with low solubility and low permeability.


Subject(s)
Anti-Inflammatory Agents , Pharmacology , Biopharmaceutics , Classification , Drugs, Chinese Herbal , Classification , Pharmacology , Materia Medica , Classification , Tablets
10.
Article in Chinese | WPRIM | ID: wpr-802202

ABSTRACT

Objective:To observe the effect of Changji'an prescription on intestinal permeability in diarrhea-predominant irritable bowel syndrome (IBS-D) rats and explore its mechanism for treatment of IBS-D. Method:Male SD neonatal rats were randomly divided into five groups:normal group, model group, pinaverium bromide group(0.018 g·kg-1), high-dose(33.48 g·kg-1) and low-dose (16.74 g·kg-1)Changji'an prescription groups. Except for the normal group, the IBS-D model was established by the combination of maternal and infant separation+acetic acid stimulation+restraint stress. After drug treatment, the ultrastructure of rat intestinal mucosa was observed by using transmission electron microscopy and the plasma D-lactate level was detected by enzyme-linked immunosorbent assay (ELISA). The expression levels of tight junction proteins Occludin and Claudin-1 were detected by Western blot. The mRNA expression levels of Occludin,Claudin-1 and zonula occluden(ZO)-1 were detected by real time polymerase chain reaction (Real-time PCR). Result:As compared with the normal group, the intestinal mucosal epithelial cells were damaged in IBS-D model group, and the microvilli arrangement was sparse and tight junction was widened, and some were not obvious,and the plasma D-lactate level in IBS-D rats was increased significantly (PPD-lactate level in pinaverium bromide group and high-dose Changji'an prescription group was significantly decreased (PD-lactate level in the low-dose group Changji'an prescription group had a tendency to decrease with no statistical difference. The mRNA and protein expression levels of Occludin and Claudin-1 and the mRNA expression of ZO-1 in the colon of rats in each administration group were higher than those in the model group (PConclusion:The therapeutic effect of Changji'an prescription on IBS-D may be achieved by improving the intestinal permeability.

11.
Article in Chinese | WPRIM | ID: wpr-850999

ABSTRACT

The research methods of serum pharmacology and serum biochemistry of traditional Chinese medicine isolate and identify serum transitional components from the serum of normal and disease model animals in order to find the material basis of pharmacodynamics. There are some limitations in this method for identifying the components of traditional Chinese medicine to play its pharmacological activities. Most active ingredients of traditional Chinese medicine belong to low-solubility and low-permeability drugs in the classification system of biopharmaceutics. Their bioavailability is low, but their overall biological effects are high. The classical pharmacokinetic-pharmacodynamic theory of serum pharmacology can not explain and evaluate the pharmacological effects of their non-serum transitional components. Based on the complexity of the chemical components of traditional Chinese medicine, the osmotic interaction of traditional Chinese medicine components may affect their osmotic behavior and form different oral absorption prescriptions. Therefore, the study on the permeability of traditional Chinese medicine components, especially under the condition of multi-component coexistence, is one of the topics worth to solve the problem of the functional substance basis of traditional Chinese medicine. This paper first outlines the in vitro and in vivo screening experimental models and their respective application value for the evaluation of intestinal permeability and trans-biological barrier permeability of traditional Chinese medicines. Then, the advantages and disadvantages of each model are compared, and the relationship between the structure and osmotic kinetics of common active components of traditional Chinese medicines based on osmotic model is discussed, especially the research progress of quantitative structure-kinetics relationship in permeability study of traditional Chinese medicines. Finally, based on the relationship between permeability experimental model and structure-kinetics, the recent progress in the study of multi-component osmotic dynamics and osmotic mechanism of traditional Chinese medicine is reviewed. It is found that the osmotic absorption of components can be affected by increasing or promoting drug transport or forming ion compatibility among components of traditional Chinese medicine. The prospects of its application are forecasted. In conclusion, this paper is expected to provide some references for searching and predicting the law of permeability of complex chemical constituents of traditional Chinese medicine and the mechanism of interaction between components and its application value.

12.
Article in Chinese | WPRIM | ID: wpr-824334

ABSTRACT

Objective To explore the synergism efficacy and mechanism of Warm Purgative and Strengthening Spleen (WPSS) therapy combined with antibiotics in the treatment of sepsis. Methods Thirty-two SPF Spargue-Dawley (SD) rats were used to replicate the rat sepsis model by cecum ligation perforation (CLP) method and equally divided into model control (MC) group, ceftriaxone group, Chinese herbal medicine (CHM) group and ceftriaxone +CHM group. Eight SD rats underwent sham surgery were used as a sham operation (Sham) group. Rats in Sham and MC groups were administered with 0.9% normal saline (NS) by intraperitoneal injection and gavage. Rats in CHM group were administered with modified Dahuang Fuzi Decoction (DFD, 8 mg/kg) by gavage + 0.9% NS by intraperitoneal injection, Bid. Rats in ceftriaxone group were administered with 0.9% NS by gavage and ceftriaxone (120 mg/kg) by intraperitoneal injection, Bid. Rats in ceftriaxone + CHM group were administered with modified DFD (8 mg/kg) by gavage and ceftriaxone (120 mg/kg) intraperitoneal injection, Bid. The drugs were given for 2 days. The mortality of rats in each group was observed after treatment. The intestinal flora changes and intestinal permeability [intestinal mucosa injury index (IMII), intestinal mucosa secretory immunoglobulin (sIgA), serum D-lactic acid, diamine oxidase (DAO) and sIgA] were detected. Meanwhile, the levels of serum inflammation indexes [lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] were detected. Results ① Mortality: ceftriaxone+CHM group (25.0%) < CHM group (37.5%) and ceftriaxone group (37.5%) < MC group (50.0%), the differences between groups were statistically significant (all P < 0.05). ② 16S rDNA sequencing analysis: the ratio of Bacteroidetesin in MC group was lower than that in the Sham group [(24.36±7.15)% vs. (45.20±6.05)%], and the ratio of Proteobacteria in MC group was higher than that in Sham group [(10.03±7.55)% vs. (0.41±0.21)%]. The diversity of intestinal flora in ceftriaxone group was significantly lower than that in Sham and CHM groups (404.60±17.09 vs. 470.80±16.97, 469.20±14.59), the differences between groups were statistically significant (all P < 0.05). The principal component analysis (PCA) suggested that the composition of CHM group was closer to that of Sham group, which indicated that WPSS therapy could reduce intestinal flora disorders in rats with sepsis. ③The pathological changes of intestinal mucosa: light microscope showed the intestinal mucosa of Sham group was intact; the intestinal mucosa became thinner, and local inflammatory cells had infiltration in MC group. The thickness of intestinal mucosa in CHM, ceftriaxone and CHM+ceftriaxone groups was slightly thicker, and the infiltration of local inflammatory cells was less than that in MC group. The thickness of intestinal mucosa in CHM group and ceftriaxone+CHM group was slightly thicker than that in the ceftriaxone group, and the arrangement was more regular than that in MC group and ceftriaxone group.④Intestinal mucosa permeability and inflammatory state: IMII, D-lactic acid, DAO, LPS, TNF-α and IL-6 of rats in MC group were higher than those of rats in Sham group [IMII: 4.37±0.56 vs. 0.26±0.29, D-lactic acid (mg/L):12.35±0.83 vs. 7.30±1.29, DAO (kU/L): 2.16±0.43 vs. 0.32±0.06, LPS (kU/L): 0.663±0.012 vs. 0.095±0.003, TNF-α (μg/L): 251.03±82.69 vs. 52.15±6.25, IL-6 (μg/L): 160.50±4.77 vs. 54.30±3.36], while sIgA in MC group was lower than that in Sham group (mg/L: 11.57±0.17 vs. 26.76±1.99). IMII, D-lactic acid, DAO, LPS, TNF-α and IL-6 of rats in CHM, ceftriaxone and CHM+ ceftriaxone groups were significantly lower than those of rats in MC group, while sIgA in CHM, ceftriaxone and CHM+ceftriaxone groups were significantly higher than that of rats in MC group. The change of CHM+ceftriaxone group was more significant than those of CHM group and ceftriaxone group [IMII:1.78±0.23 vs. 1.96±0.62, 3.39±0.43, D-lactic acid (mg/L): 8.56±0.37 vs. 9.62±0.57,11.42±0.39, DAO (kU/L):1.14±0.12 vs. 1.72±0.24, 2.01±0.32, sIgA (mg/L): 25.34±1.49 vs. 23.99±7.85, 17.46±1.20, LPS (kU/L):0.302±0.007 vs. 0.387±0.004, 0.715±0.013, TNF-α (μg/L): 57.10±3.98 vs. 101.49±21.49, 141.91±20.20, IL-6 (μg/L): 93.71±2.39 vs. 87.12±7.31, 104.27±1.84]. Conclusion WPSS therapy may improve the efficacy of antibiotics in the treatment of sepsis by regulating the intestinal flora and reducing the intestinal mucosa permeability and inflammation level.

13.
China Pharmacy ; (12): 207-211, 2019.
Article in Chinese | WPRIM | ID: wpr-816722

ABSTRACT

OBJECTIVE: To observe the effects of endotoxin affinity adsorbent SPV on intestinal permeability and bacterial translocation in hemorrhagic shock model rats.  METHODS: Totally 85 male SD rats were randomly divided into normal group (5 rats), shock group (each 5 rats at each time point, 20 rats in total), SPV low-dose, medium-dose and high-dose groups (Montmorillonite powder 0.3 g, Polymyxin B sulfate 0.5 mg, Vitamin B6 5 mg dissolved in normal saline to obtain SPV solution 5 mL, as low dose; medium and high dose were 2 or 3 times as high as low dose. Each 5 rats of each group at each time point, 60 rats in total). Administration groups were given SPV solution intragastrically 5, 10, 15 mL once, respectively; normal group and shock group were given normal saline 5 mL intragastrically once. Thirty minutes after last medication, other groups received femoral artery catheterization and bleeding to induce hemorrhagic shock model, except for normal group. The activities or contents of diamine oxidase (DAO), endotoxin and D-lactic acid, positive rates of intestinal bacterial translocation were detected in each group at 1, 4, 8, 16 h after recovery. RESULTS: Compared with normal group, the activities of DAO of rats in shock group were enhanced significantly, and the serum contents of endotoxin and D-lactic acid were increased significantly (P<0.05). Compared with shock group, the activities of DAO were decreased significantly in SPV groups (at each time point during 1-16 h); the serum contents of endotoxin and D-lactic acid (at each time point during 1-16 h), positive rates of intestinal bacterial translocation (SPV low-dose group at each time point during 4-16 h, SPV medium-dose and high-dose groups at each time point during 1-16 h) were decreased significantly (P<0.05). Above indexes in SPV medium-dose and high-dose groups (at each time point during 1-16 h) were significantly lower than those of SPV low-dose group (P<0.05). There was no statistical significance in above indexes between SPV medium-dose group and high-dose group (P>0.05). CONCLUSIONS: The endotoxin affinity adsorbent SPV can improve the permeability of the intestinal wall and inhibit bacterial translocation in hemorrhagic shock model rats in dose-dependent manner. The effects of which may be associated with reducing the activities or contents of serum DAO, endotoxin, D-lactic acid, and down-regulating the positive rate of bacterial translocation.

14.
Acta bioquím. clín. latinoam ; 52(4): 417-422, dic. 2018. graf
Article in Spanish | LILACS | ID: biblio-1001065

ABSTRACT

La enfermedad celíaca (EC) es una condición inflamatoria crónica del intestino delgado causada por intolerancia al gluten. El tratamiento consiste en la dieta libre de gluten (DLG). Los anticuerpos anti Saccharomyces cerevisiae (ASCA) están dirigidos contra la pared celular de la levadura, se asocian a enfermedades autoinmunes, y se propone la permeabilidad intestinal alterada como causa de activación de la inmunidad humoral. El objetivo del trabajo fue determinar la prevalencia de ASCA IgG e IgA en pacientes celíacos bajo tratamiento y evaluar la asociación de ASCA con el grado de adherencia a la DLG. Se analizaron 59 sueros de pacientes adultos celíacos con alta o baja adherencia a la DLG, y se determinó ASCA IgG e IgA. Se halló una prevalencia de ASCA IgG y/o IgA del 44%. Se encontró asociación entre ASCA-IgG y adherencia a DLG (OR 4,04 IC 95%: 1,32-12,38). La prevalencia de ASCA en la población celíaca estudiada es similar a la reportada en la bibliografía. La menor prevalencia de ASCA IgG en pacientes con una estricta DLG respecto de aquellos con baja adherencia, indicaría que su presencia depende del nivel de ingesta de gluten, sugiriéndolos como herramienta complementaria en el seguimiento del paciente celíaco.


Celiac disease (CD) is a chronic inflammatory condition of the small intestine caused by gluten intolerance. The treatment consists of gluten free diet (GFD). Anti Saccharomyces cerevisiae antibodies (ASCA) are directed against the cell wall of yeast, associated with autoimmune diseases, and an altered intestinal permeability is proposed as a cause of activation of humoral immunity. The objective of this work was to determine the prevalence of IgG and IgA ASCA in celiac patients under treatment and to evaluate the association of ASCA with the degree of adherence to GFD. Fifty-nine serum samples from adult celiac patients with high or low adherence to GFD were analyzed, determining IgG and IgA ASCA. A 44% prevalence of IgG and/or IgA ASCA was found. An association was discovered between IgG ASCA and GFD adherence (OR 4.04, 95% CI: 1.32-12.38). The prevalence of ASCA in the studied celiac population is similar to that reported in the literature. The lower prevalence of IgG ASCA in patients with a strict GFD compared to those with low adherence would indicate that their presence depends on the level of gluten intake, suggesting them as a complementary tool in the follow-up of the celiac patient.


A doença celíaca (DC) é uma condição inflamatória crônica do intestino delgado causada pela intolerância ao glúten. O tratamento consiste na dieta sem glúten (DSG). Os anticorpos anti Saccharomyces cerevisiae (ASCA) são dirigidos contra a parede celular da levedura, associados a doenças autoimunes, e à permeabilidade intestinal alterada como causa da ativação da imunidade humoral. O objetivo foi determinar a prevalência de ASCA IgG e IgA em pacientes celíacos em tratamento; avaliar a associação de ASCA com o grau de adesão ao DSG. Foram analisados 59 soros de pacientes celíacos adultos com alta ou baixa adesão ao DSG, determinando ASCA IgG e IgA. Foi encontrada uma prevalência de SCA IgG/ou IgA de 44%. Foi encontrada uma associação entre ASCA-IgG e a adesão ao DSG (OR 4,04 IC 95% 1,32-12,38). A prevalência de ASCA na população celíaca estudada é semelhante à relatada na literatura. A menor prevalência de ASCA IgG em pacientes com rigorosa DSG, em comparação àqueles com baixa adesão, indicaria que sua presença depende do nível de ingestão de glúten, sugerindo-os como uma ferramenta complementar no seguimento do paciente celíaco.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Saccharomyces cerevisiae/immunology , Celiac Disease/diet therapy , Celiac Disease/microbiology , Diet, Gluten-Free , Treatment Adherence and Compliance , Antibodies, Fungal/blood , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Prevalence , Cross-Sectional Studies , Cohort Studies
15.
Acta Pharmaceutica Sinica ; (12): 993-1001, 2018.
Article in Chinese | WPRIM | ID: wpr-779962

ABSTRACT

In current study, adefovir dipivoxil (AD)-acetaminophen (AP) cocrystal (molar ratio, 1:1) was prepared by slow evaporation from acetonitrile, followed by physicochemical characterizations using differential scanning calorimetry, powder X-Ray diffraction and Fourier transform infrared spectroscopy. Molecular modeling showed that the phosphoester group of AD was connected with the amide group of AP through hydrogen bonds. In comparison to crystalline AD, the solubility and dissolution rate of AD from AD-AP cocrystal were significantly enhanced by 1.5-fold and 1.6-fold, respectively. In addition, based on the rat single-pass intestinal perfusion study, the permeabilities of AD in various intestinal sections (i.e., duodenum, jejunum, ileum and colon) were significantly improved (e.g., about 3-fold enhancement in duodenum) after cocrystallization with AP by inhibiting P-glyprotein mediated efflux of AD, which will benefit absorption in vivo and subsequent oral bioavailability of poorly permeable drug AD.

16.
Acta Pharmaceutica Sinica ; (12): 727-734, 2018.
Article in Chinese | WPRIM | ID: wpr-779928

ABSTRACT

Intestinal permeability is one of key factors determing absorption of oral drug products. It is a big challenge to assess permeability of compounds with high accuracy and high efficacy during research and development process. In this review, the principles, strengths, weaknesses and advances of common intestinal permeability models are summarized, with focus on Ussing chamber and parallel artificial membrane permeability assay. In addition, future trends of permeability models are briefly discussed. This review may provide a reference to accessing permeability of lead compounds.

17.
Chinese Acupuncture & Moxibustion ; (12): 1043-1046, 2018.
Article in Chinese | WPRIM | ID: wpr-777273

ABSTRACT

OBJECTIVE@#To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on the inflammatory response and intestinal permeability after laparoscopic radical surgery for colon cancer, so as to explore the protective mechanism for perioperative organs.@*METHODS@#Sixty patients with laparoscopic intestinal resection were randomly assigned into an observation group and a control group, 30 cases in each group. TEAS at Zusanli (ST 36), Neiguan (PC 6) and Hegu (LI 4) was used in the observation group on the day of operation and within 3 days after surgery, 2 Hz, within 2 mA. The interventions in the control group were the same as those in the observation group, except opening the current source. Central venous blood was collected before TEAS and 12 h, 24 h, 48 h, 72 h after surgery. The level of the inflammatory indexes of tumor necrosis factor-α(TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6) and intestinal mucosal barrier response indexes of endotoxin (LPS) and D-lactate were detected.@*RESULTS@#Compared with the control group, the levels of IL-1, IL-6 and TNF-α decreased in the observation group 24 h, 48 h and 72 h after surgery (all 0.05).@*CONCLUSION@#TEAS can reduce the inflammatory reaction after laparoscopic radical surgery for colon cancer, but has no effect on the intestinal permeability.


Subject(s)
Acupuncture Points , Humans , Laparoscopy , Perioperative Period , Permeability , Transcutaneous Electric Nerve Stimulation
18.
Article in Chinese | WPRIM | ID: wpr-697727

ABSTRACT

Objective To investigate the effect of Clostridium butyricum on the intestinal permeability and expression of tight junction proteins in rats with intrahepatic cholestasis.Methods Forty SD rats were random-ly divided into normal control group(Con),model group(Mod),group with low(CBL)and high dose(CBH)of Clostridium butyricum. Animal models of intrahepatic cholestasis were induced by alpha-naphthylisothiocyanate. Then different drugs were administrated via oral gavage for 7 days after modeling.After the last administration,the activities of serum alanin aminotransferase(ALT),aspartate aminotransferase(AST),diamineoxidase(DAO)and the contents of total bilirubin(T-BIL)in serum were detected. Pathological changes of liver tissue were observed. The expression level of Occludin and ZO-1 in small intestine was analysed by Western blot. Results Compared with the normal control group,the levels of ALT,AST,DAO,and T-BIL in mordel group were significantly in-creased. The expression of Occludin and ZO-1 in small intestine was reduced(P < 0.05). Compared with the mordel group,the levels of ALT,AST,DAO,and T-BIL and the expression of Occludin and ZO-1 decreased sig-nificantly(P<0.05)and the liver pathologic changes were improved in CBL and CBH group.Conclusions Clos-tridium butyricum can protect the liver and improve the intestinal permeability in rats with intrahepatic cholestasis, and he mechanism may be related with upregulation of Occludin and ZO-1.

19.
Braz. J. Pharm. Sci. (Online) ; 53(1): e16081, 2017. tab, graf
Article in English | LILACS | ID: biblio-839460

ABSTRACT

ABSTRACT 6-Methylcoumarin (6MC) is a semisynthetic coumarin with important in vitro and in vivo anti-inflammatory activity. In order to continue the pre-clinical characterization of this molecule, in vitro intestinal permeability, plasma profile and tissue distribution after oral administration in rats were studied. The permeability of 6MC was evaluated by the Caco-2 cellular model in both the apical-basal (A-B) and basal-apical (B-A) directions. The pharmacokinetics and biodistribution were evaluated in rats after oral and intraperitoneal administration at doses of 200 mg/kg. Transport experiments with Caco-2 cells showed that 6MC presented high permeability at all concentrations evaluated. This finding suggested that 6MC could be transported across the gut wall by passive diffusion. The plasma concentration-time curve showed that the maximum concentration (Cmax) was 17.13 ± 2.90 µg/mL at maximum time (Tmax) of 30 min for the oral route and Cmax 26.18 ± 2.47 µg/mL at 6.0 min for the intraperitoneal administration, with elimination constant of (Ke ) 0.0070 min-1 and a short life half time of (T1/2 ) lower that 120 min. The distribution study showed that 6MC has high accumulation in the liver, and widespread distribution in all the organs evaluated.


Subject(s)
Animals , Male , Female , Rats , Permeability , In Vitro Techniques/instrumentation , Administration, Oral , Rats, Wistar/classification , Coumarins/analysis , Pharmacokinetics , Peritoneal Absorption , Intestinal Diseases/classification
20.
Article in Chinese | WPRIM | ID: wpr-620506

ABSTRACT

Objective To investigate the effects of somatostatin combined with early enteral nutrition on inflammatory factors and intestinal permeability in patients with severe acute pancreatitis (SAP).Methods 70 patients with severe acute pancreatitis were randomly divided into the control group (35 cases) and the observation group (35 cases).The control group were given double somatostatin, the observation group were received double somatostatin combined with early enteral nutrition support.Before and after treatment in the two gorups, TNF-a and IL-1 levels were measured by ELISA;intestinal permeability index was indirect calculated by high performance liquid chromatography.Clinical curative effect and inflammatory factors and intestinal permeability were compared in the two groups.Results Seven days after treatment, the secondary infection rate, operation rate and mortality in the observation were lower than those in the control group (P<0.05);before treatment, TNF-a and IL-1 level in the two groups had no significant difference;Seven days after treatment, TNF-a and IL-1 in the observation group were lower than those in the control group (P<0.05);seven days after treatment,blood lactate levels in the observation group was higher than that in the control group and diamineoxidase was lower than that in the control group (P<0.05).Conclusion Double somatostatin combined with early enteral nutrition support can improve inflammatory factors and intestinal permeability in patients with severe acute pancreatitis, and is worthy of popularization and application.

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