Generally, proton-pump inhibitors(PPIs) have great benefit for patients with acid related disease with less frequently occurring side effects. According to a recent report, PPIs provoke dysbiosis of the small intestin...Generally, proton-pump inhibitors(PPIs) have great benefit for patients with acid related disease with less frequently occurring side effects. According to a recent report, PPIs provoke dysbiosis of the small intestinal bacterial flora, exacerbating nonsteroidal anti-inflammatory drug-induced small intestinal injury.Several meta-analyses and systematic reviews have reported that patients treated with PPIs, as well as post-gastrectomy patients, have a higher frequency of small intestinal bacterial overgrowth(SIBO) compared to patients who lack the aforementioned conditions.Furthermore, there is insufficient evidence that these conditions induce Clostridium difficile infection. At this time, PPI-induced dysbiosis is considered a type of SIBO. It now seems likely that intestinal bacterial flora influence many diseases, such as inflammatory bowel disease, diabetes mellitus, obesity, nonalcoholic fatty liver disease, and autoimmune diseases.When attempting to control intestinal bacterial flora with probiotics, prebiotics, and fecal microbiota transplantation, etc., the influence of acid suppression therapy, especially PPIs, should not be overlooked.展开更多
According to the physiological and anatomical characteristics of small intestine,neglecting the effect of its motility on the distribution and absorption of drug and nutrient,Y.Miyamoto et al.proposed a model of two-d...According to the physiological and anatomical characteristics of small intestine,neglecting the effect of its motility on the distribution and absorption of drug and nutrient,Y.Miyamoto et al.proposed a model of two-dimensional laminar flow in a circular porous tube with permeable wall and calculated the concentration profile of drugby numerical analysis.In this paper,we give a steady-state analytical solution of the above model including deactivationterm.The obtained results are in agreement with the results of their numerical analysis. Moreover the analytical solution presented in this paper reveals the relation among the physiological parameters of the model and describes the basic absorption rule of drug and nutrient through the intestinal wall and hence pro- vides a theoretical basis for determining the permeability and reflection coefficient through in situ experiments.展开更多
AIM To compare the combinative andindividual effect of acarbose and gymnemic acid(GA) on maltose absorption and hydrolysis insmall intestine to determine whether nutrientcontrol in diabetic care can be improved bycomb...AIM To compare the combinative andindividual effect of acarbose and gymnemic acid(GA) on maltose absorption and hydrolysis insmall intestine to determine whether nutrientcontrol in diabetic care can be improved bycombination of them.METHODS The absorption and hydrolysis ofmaltose were studied by cyclic perfusion ofintestinal loops in situ and motility of theintestine was recorded with the intestinal ring invitro using Wistar rats.RESULTS The total inhibitory rate of maltoseabsorption was improved by the combination ofGA (0.1 g/L 1.0 g/L) and acarbose(0.1 mmol/L 2.0 mmol/L) throughout theireffective duration (P＜0.05, U test of Mann-Whitney), although the improvement only couldbe seen at a Iow dosage during the first hour.With the combination, inhibitory duration of acarbose on maltose absorption was prolonged to 3 h and the inhibitory effect onset of GA was fastened to 15min. GA suppressed the intestinal mobility with a good correlation (r-0.98) to the inhibitory effect of GA on maltose absorption and the inhibitory effect of 2mmol/L (high dose) acarbose on maltose hydrolysis was dual modulated by 1 g/L GA in vivo indicating that the combined effects involved the functional alteration of intestinal barriers.CONCLUSION There are augmented effects of acarbose and GA, which involve pre-cellular and paracellular barriers. Diabetic care can be improved by employing the combination.展开更多
Small intestine in vitro models play a crucial role in drug transport research.Although conventional 2 D cell culture models,such as Caco-2 monolayer,possess many advantages,they should be interpreted with caution bec...Small intestine in vitro models play a crucial role in drug transport research.Although conventional 2 D cell culture models,such as Caco-2 monolayer,possess many advantages,they should be interpreted with caution because they have relatively poor physiologically reproducible phenotypes and functions.With the development of 3 D culture technology,pluripotent stem cells(PSCs)and adult somatic stem cells(ASCs)show remarkable self-organization characteristics,which leads to the development of intestinal organoids.Based on previous studies,this paper reviews the application of intestinal 3 D organoids in drug transport mediated by P-glycoprotein(P-gp),breast cancer resistance protein(BCRP)and multidrug resistance protein 2(MRP2).The advantages and limitations of this model are also discussed.Although there are still many challenges,intestinal 3 D organoid model has the potential to be an excellent tool for drug transport research.展开更多
Non-steroidal anti-inflammatory drug Nindu cedsmall bowel injury is a topi that deserves attentionsin e the advent of apsule endos opy and balloon enteros opy. N enteropathy is ommon and is mostly asymptomati . Howeve...Non-steroidal anti-inflammatory drug Nindu cedsmall bowel injury is a topi that deserves attentionsin e the advent of apsule endos opy and balloon enteros opy. N enteropathy is ommon and is mostly asymptomati . However,massive bleeding,stri ture,or perforation may o ur. The pathogenesis of small intestine injury by N s is omplex and different from that of the upper gastrointestinal tra t. No drughas yet been developed that an ompletely preventor treat N enteropathy. There fore,a long-termr and omized study in hroni N users is needed.展开更多
Intestinal bacteria play a role in the development of non-steroidal anti-inflammatory drugs(NSAID)-induced small intestinal injury.Agents such as probiotics,able to modify the gut ecology,might theoretically be useful...Intestinal bacteria play a role in the development of non-steroidal anti-inflammatory drugs(NSAID)-induced small intestinal injury.Agents such as probiotics,able to modify the gut ecology,might theoretically be useful in preventing small intestinal damage induced by NSAIDs.The clinical studies available so far do suggest that some probiotic agents can be effective in this respect.展开更多
BACKGROUND The exact mechanism of proton pump inhibitors(PPIs)-induced hypomagnesemia(PPIH) is largely unknown. Previous studies proposed that PPIH is a consequence of intestinal Mg2+ malabsorption. However, the mecha...BACKGROUND The exact mechanism of proton pump inhibitors(PPIs)-induced hypomagnesemia(PPIH) is largely unknown. Previous studies proposed that PPIH is a consequence of intestinal Mg2+ malabsorption. However, the mechanism of PPIs-suppressed intestinal Mg2+ absorption is under debate.AIM To investigate the effect of 12-wk and 24-wk omeprazole injection on the total,transcellular, and paracellular Mg2+ absorption in the duodenum, jejunum, ileum,and colon of male Sprague-Dawley rats.METHODS The rats received 20 mg/kg·d subcutaneous omeprazole injection for 12 or 24 wk.Plasma and urinary Mg2+, Ca2+, and PO43-levels were measured. The plasma concentrations of 1α,25-dihydroxyvitamin D3(1α,25(OH)2D3), parathyroid hormone(PTH), fibroblast growth factor 23(FGF-23), epidermal growth factor(EGF), and insulin were also observed. The duodenum, jejunum, ileum, and colon of each rat were mounted onto individual modified Using chamber setups to study the rates of total, transcellular, and paracellular Mg2+ absorption simultaneously. The expression of transient receptor potential melastatin 6(TRPM6) and cyclin M4(CNNM4) in the entire intestinal tract was also measured.RESULTS Single-dose omeprazole injection significantly increased the intraluminal p H of the stomach, duodenum, and jejunum. Omeprazole injection for 12 and 24 wk induced hypomagnesemia with reduced urinary Mg2+ excretion. The plasma Ca2+ was normal but the urinary Ca2+ excretion was reduced in rats with PPIH. The plasma and urinary PO43-levels increased in PPIH rats. The levels of1α,25(OH)2D3 and FGF-23 increased, whereas that of plasma EGF decreased in the omeprazole-treated rats. The rates of the total, transcellular, and paracellular Mg2+ absorption was significantly lower in the duodenum, jejunum, ileum, and colon of the rats with PPIH than in those of the control rats. The percent suppression of Mg2+ absorption in the duodenum, jejunum, ileum, and colon of the rats with PPIH compared with the control rats was 81.86%, 70.59%, 69.45%,and 39.25%, respectively. Compared with the control rats, the rats with PPIH had significantly higher TRPM6 and CNNM4 expression levels throughout the intestinal tract.CONCLUSION Intestinal Mg2+ malabsorption was observed throughout the intestinal tract of rats with PPIH. PPIs mainly suppressed small intestinal Mg2+ absorption. Omeprazole exerted no effect on the intraluminal acidic pH in the colon. Thus, the lowest percent suppression of total Mg2+ absorption was found in the colon. The expression levels of TRPM6 and CNNM4 increased, indicating the presence of a compensatory response to Mg2+ malabsorption in rats with PPIH. Therefore, the small intestine is an appropriate segment that should be modulated to counteract PPIH.展开更多
AIM: To evaluate the effect of muscovite in preventing small bowel injury induced by nonsteroidal anti-inflammatory drugs(NSAIDs).METHODS: We recruited and screened thirty-two healthy volunteers who were randomly allo...AIM: To evaluate the effect of muscovite in preventing small bowel injury induced by nonsteroidal anti-inflammatory drugs(NSAIDs).METHODS: We recruited and screened thirty-two healthy volunteers who were randomly allocated equally into two groups: an NSAID control group, who received 75 mg slow-release diclofenac, twice daily for 14 d; and an NSAID-muscovite group, who received 3 g of muscovite in addition to the 75 mg of slow-release diclofenac, twice daily for 14 d. For gastroprotection, both groups were administered 20 mg/d of the proton pump inhibitor omeprazole. All eligible subjects underwent video capsule endoscopy(CE) prior to and 14 d after treatment.RESULTS: Thirty subjects(NSAID-muscovite group,n =16; NSAID control group, n =14) finally completed the whole trail. At the baseline CE examination, no statistically significant differences between the two groups have been observed. However, after 14 d of drug treatment, a significant difference was observed in the percentage of subjects with mucosal breaks when comparing the NSAID-muscovite group with the NSAID control group. While 71.4%(10/14) of subjects in the NSAID control group had at least one mucosal break, co-administration of muscovite in the NSAID-muscovite group reduced the rate to 31.3%(5/16)(P = 0.028). Moreover, higher number of mucosal breaks was found in the NSAID control group vs that in the NSAID-muscovite group(P < 0.05).CONCLUSION: Muscovite co-therapy reduced the incidence of small intestinal injury after 14 d of diclofenac administration.展开更多
Mycophenolate mofetil(MMF) is an important medication used for maintenance immunosuppression in solid organ transplants. A common gastrointestinal(GI) side effect of MMF is enterocolitis, which has been associated wit...Mycophenolate mofetil(MMF) is an important medication used for maintenance immunosuppression in solid organ transplants. A common gastrointestinal(GI) side effect of MMF is enterocolitis, which has been associated with multiple histological features. There is little data in the literature describing the histological effects of MMF in small intestinal transplant(SIT) recipients. We present a case of MMF toxicity in a SIT recipient, with histological changes in the donor ileum mimicking persistent acute cellular rejection(ACR). Concurrent biopsies of the patient's native colon showed similar changes to those from the donor small bowel, suggesting a non-graft specific process, raising suspicion for MMF toxicity. The MMF was discontinued and complete resolution of these changes occurred over three weeks. MMF toxicity should therefore be considered as a differential diagnosis for ACR and graftversus-host disease in SITs.展开更多
文摘Generally, proton-pump inhibitors(PPIs) have great benefit for patients with acid related disease with less frequently occurring side effects. According to a recent report, PPIs provoke dysbiosis of the small intestinal bacterial flora, exacerbating nonsteroidal anti-inflammatory drug-induced small intestinal injury.Several meta-analyses and systematic reviews have reported that patients treated with PPIs, as well as post-gastrectomy patients, have a higher frequency of small intestinal bacterial overgrowth(SIBO) compared to patients who lack the aforementioned conditions.Furthermore, there is insufficient evidence that these conditions induce Clostridium difficile infection. At this time, PPI-induced dysbiosis is considered a type of SIBO. It now seems likely that intestinal bacterial flora influence many diseases, such as inflammatory bowel disease, diabetes mellitus, obesity, nonalcoholic fatty liver disease, and autoimmune diseases.When attempting to control intestinal bacterial flora with probiotics, prebiotics, and fecal microbiota transplantation, etc., the influence of acid suppression therapy, especially PPIs, should not be overlooked.
基金The project supported by NSF of Shandong Province
文摘According to the physiological and anatomical characteristics of small intestine,neglecting the effect of its motility on the distribution and absorption of drug and nutrient,Y.Miyamoto et al.proposed a model of two-dimensional laminar flow in a circular porous tube with permeable wall and calculated the concentration profile of drugby numerical analysis.In this paper,we give a steady-state analytical solution of the above model including deactivationterm.The obtained results are in agreement with the results of their numerical analysis. Moreover the analytical solution presented in this paper reveals the relation among the physiological parameters of the model and describes the basic absorption rule of drug and nutrient through the intestinal wall and hence pro- vides a theoretical basis for determining the permeability and reflection coefficient through in situ experiments.
基金Supported by Grant for Promotion of Science from Tottori Bioscience Foundation(1997-1998)Japan and Japanese Government(Ministry of Education,Science and Culture of Japan,MONBUSHO)scholarship No.933241(1994-1999)Japan in part.Dr.Luo was supported by the scholarships.
文摘AIM To compare the combinative andindividual effect of acarbose and gymnemic acid(GA) on maltose absorption and hydrolysis insmall intestine to determine whether nutrientcontrol in diabetic care can be improved bycombination of them.METHODS The absorption and hydrolysis ofmaltose were studied by cyclic perfusion ofintestinal loops in situ and motility of theintestine was recorded with the intestinal ring invitro using Wistar rats.RESULTS The total inhibitory rate of maltoseabsorption was improved by the combination ofGA (0.1 g/L 1.0 g/L) and acarbose(0.1 mmol/L 2.0 mmol/L) throughout theireffective duration (P＜0.05, U test of Mann-Whitney), although the improvement only couldbe seen at a Iow dosage during the first hour.With the combination, inhibitory duration of acarbose on maltose absorption was prolonged to 3 h and the inhibitory effect onset of GA was fastened to 15min. GA suppressed the intestinal mobility with a good correlation (r-0.98) to the inhibitory effect of GA on maltose absorption and the inhibitory effect of 2mmol/L (high dose) acarbose on maltose hydrolysis was dual modulated by 1 g/L GA in vivo indicating that the combined effects involved the functional alteration of intestinal barriers.CONCLUSION There are augmented effects of acarbose and GA, which involve pre-cellular and paracellular barriers. Diabetic care can be improved by employing the combination.
基金supported in part by grants from the National Natural Science Foundation of China(No.81773808)the Science and Technology Commission of Shanghai Municipality(Nos.17140901000,17140901001 and 18430760400,China)
文摘Small intestine in vitro models play a crucial role in drug transport research.Although conventional 2 D cell culture models,such as Caco-2 monolayer,possess many advantages,they should be interpreted with caution because they have relatively poor physiologically reproducible phenotypes and functions.With the development of 3 D culture technology,pluripotent stem cells(PSCs)and adult somatic stem cells(ASCs)show remarkable self-organization characteristics,which leads to the development of intestinal organoids.Based on previous studies,this paper reviews the application of intestinal 3 D organoids in drug transport mediated by P-glycoprotein(P-gp),breast cancer resistance protein(BCRP)and multidrug resistance protein 2(MRP2).The advantages and limitations of this model are also discussed.Although there are still many challenges,intestinal 3 D organoid model has the potential to be an excellent tool for drug transport research.
文摘Non-steroidal anti-inflammatory drug Nindu cedsmall bowel injury is a topi that deserves attentionsin e the advent of apsule endos opy and balloon enteros opy. N enteropathy is ommon and is mostly asymptomati . However,massive bleeding,stri ture,or perforation may o ur. The pathogenesis of small intestine injury by N s is omplex and different from that of the upper gastrointestinal tra t. No drughas yet been developed that an ompletely preventor treat N enteropathy. There fore,a long-termr and omized study in hroni N users is needed.
文摘Intestinal bacteria play a role in the development of non-steroidal anti-inflammatory drugs(NSAID)-induced small intestinal injury.Agents such as probiotics,able to modify the gut ecology,might theoretically be useful in preventing small intestinal damage induced by NSAIDs.The clinical studies available so far do suggest that some probiotic agents can be effective in this respect.
基金Burapha University through National Research Council of Thailand,No.15/2562。
文摘BACKGROUND The exact mechanism of proton pump inhibitors(PPIs)-induced hypomagnesemia(PPIH) is largely unknown. Previous studies proposed that PPIH is a consequence of intestinal Mg2+ malabsorption. However, the mechanism of PPIs-suppressed intestinal Mg2+ absorption is under debate.AIM To investigate the effect of 12-wk and 24-wk omeprazole injection on the total,transcellular, and paracellular Mg2+ absorption in the duodenum, jejunum, ileum,and colon of male Sprague-Dawley rats.METHODS The rats received 20 mg/kg·d subcutaneous omeprazole injection for 12 or 24 wk.Plasma and urinary Mg2+, Ca2+, and PO43-levels were measured. The plasma concentrations of 1α,25-dihydroxyvitamin D3(1α,25(OH)2D3), parathyroid hormone(PTH), fibroblast growth factor 23(FGF-23), epidermal growth factor(EGF), and insulin were also observed. The duodenum, jejunum, ileum, and colon of each rat were mounted onto individual modified Using chamber setups to study the rates of total, transcellular, and paracellular Mg2+ absorption simultaneously. The expression of transient receptor potential melastatin 6(TRPM6) and cyclin M4(CNNM4) in the entire intestinal tract was also measured.RESULTS Single-dose omeprazole injection significantly increased the intraluminal p H of the stomach, duodenum, and jejunum. Omeprazole injection for 12 and 24 wk induced hypomagnesemia with reduced urinary Mg2+ excretion. The plasma Ca2+ was normal but the urinary Ca2+ excretion was reduced in rats with PPIH. The plasma and urinary PO43-levels increased in PPIH rats. The levels of1α,25(OH)2D3 and FGF-23 increased, whereas that of plasma EGF decreased in the omeprazole-treated rats. The rates of the total, transcellular, and paracellular Mg2+ absorption was significantly lower in the duodenum, jejunum, ileum, and colon of the rats with PPIH than in those of the control rats. The percent suppression of Mg2+ absorption in the duodenum, jejunum, ileum, and colon of the rats with PPIH compared with the control rats was 81.86%, 70.59%, 69.45%,and 39.25%, respectively. Compared with the control rats, the rats with PPIH had significantly higher TRPM6 and CNNM4 expression levels throughout the intestinal tract.CONCLUSION Intestinal Mg2+ malabsorption was observed throughout the intestinal tract of rats with PPIH. PPIs mainly suppressed small intestinal Mg2+ absorption. Omeprazole exerted no effect on the intraluminal acidic pH in the colon. Thus, the lowest percent suppression of total Mg2+ absorption was found in the colon. The expression levels of TRPM6 and CNNM4 increased, indicating the presence of a compensatory response to Mg2+ malabsorption in rats with PPIH. Therefore, the small intestine is an appropriate segment that should be modulated to counteract PPIH.
基金Supported by Medical and Health Scientific Research Foundation of Zhejiang Province,China,No.20112DA022
文摘AIM: To evaluate the effect of muscovite in preventing small bowel injury induced by nonsteroidal anti-inflammatory drugs(NSAIDs).METHODS: We recruited and screened thirty-two healthy volunteers who were randomly allocated equally into two groups: an NSAID control group, who received 75 mg slow-release diclofenac, twice daily for 14 d; and an NSAID-muscovite group, who received 3 g of muscovite in addition to the 75 mg of slow-release diclofenac, twice daily for 14 d. For gastroprotection, both groups were administered 20 mg/d of the proton pump inhibitor omeprazole. All eligible subjects underwent video capsule endoscopy(CE) prior to and 14 d after treatment.RESULTS: Thirty subjects(NSAID-muscovite group,n =16; NSAID control group, n =14) finally completed the whole trail. At the baseline CE examination, no statistically significant differences between the two groups have been observed. However, after 14 d of drug treatment, a significant difference was observed in the percentage of subjects with mucosal breaks when comparing the NSAID-muscovite group with the NSAID control group. While 71.4%(10/14) of subjects in the NSAID control group had at least one mucosal break, co-administration of muscovite in the NSAID-muscovite group reduced the rate to 31.3%(5/16)(P = 0.028). Moreover, higher number of mucosal breaks was found in the NSAID control group vs that in the NSAID-muscovite group(P < 0.05).CONCLUSION: Muscovite co-therapy reduced the incidence of small intestinal injury after 14 d of diclofenac administration.
文摘Mycophenolate mofetil(MMF) is an important medication used for maintenance immunosuppression in solid organ transplants. A common gastrointestinal(GI) side effect of MMF is enterocolitis, which has been associated with multiple histological features. There is little data in the literature describing the histological effects of MMF in small intestinal transplant(SIT) recipients. We present a case of MMF toxicity in a SIT recipient, with histological changes in the donor ileum mimicking persistent acute cellular rejection(ACR). Concurrent biopsies of the patient's native colon showed similar changes to those from the donor small bowel, suggesting a non-graft specific process, raising suspicion for MMF toxicity. The MMF was discontinued and complete resolution of these changes occurred over three weeks. MMF toxicity should therefore be considered as a differential diagnosis for ACR and graftversus-host disease in SITs.
