Scintigraphic demonstration of bile reflux after gastro-intestinal surgery

Energy Technology Data Exchange (ETDEWEB)

Gratz, K.F.; Creutzig, H.; Lieth, U. von der; Hundeshagen, H.

1983-04-01

Bile reflux may occur after a variety of reconstructive procedures in the gastro-intestinal tract and biliary system. The present paper deals with reflux into the duodenum, jejunum, stomach, oesophagus and into blind loops. The demonstration of reflux by sup(99m)Tc labelled IDA acid derivatives, and a possible quantitative approach, are discussed. The advantages of isotope methods are: 1. Direct demonstration of bile reflux without any intervention in the physiological process and with little trouble to the patient. 2. The ability to use the method for various reconstructive procedures and 3. the additional information obtained which may help in the differential diagnosis of blind loops, biliary obstruction, cholecystitis or liver metastases if there has been a gastrectomy for a malignant tumour. In combination with a second administration of a radio-isotope tracer, one may be able to demonstrate abnormalities in the motility of the stomach or gut, or pyloric stenosis or gastro-oesophageal reflux.

A study of blood and gastro-intestinal parasites in Edo state | Mordi ...

African Journals Online (AJOL)

A four-year study to determine the prevalence of both blood and gastro-intestinal parasites of man was done in all the eighteen local government areas of Edo State, Nigeria. The study, which commenced in January of 2000, ended in December of 2004. Of the 136,360 samples examined, 1000 that is 0.7% had parasites.

Tracking the fate of pasta (T. Durum semolina) immunogenic proteins by in vitro simulated digestion.

Science.gov (United States)

Mamone, Gianfranco; Nitride, Chiara; Picariello, Gianluca; Addeo, Francesco; Ferranti, Pasquale; Mackie, Alan

2015-03-18

The aim of the present study was to identify and characterize the celiacogenic/immunogenic proteins and peptides released during digestion of pasta (Triticum durum semolina). Cooked pasta was digested using a harmonized in vitro static model of oral-gastro-duodenal digestion. The course of pasta protein digestion was monitored by SDS-PAGE, and gluten proteins were specifically analyzed by Western blot using sera of celiac patients. Among the allergens, nonspecific lipid-transfer protein was highly resistant to gastro-duodenal hydrolysis, while other digestion-stable allergens such as α-amylase/trypsin inhibitors were not detected being totally released in the pasta cooking water. To simulate the final stage of intestinal degradation, the gastro-duodenal digesta were incubated with porcine jejunal brush-border membrane hydrolases. Sixty-one peptides surviving the brush-border membrane peptidases were identified by liquid chromatography-mass spectrometry, including several gluten-derived sequences encrypting different motifs responsible for the induction of celiac disease. These results provide new insights into the persistence of wheat-derived peptides during digestion of cooked pasta samples.

potentially pathogenic gastro-intestinal microorganisms (ID 1030, 2956, 2958, 2961, 2963, 2966, 2970), improved lactose digestion (ID 1030, 2956, 2958, 2961, 2963, 2966, 2970), “intestinal flora/digestive health” (ID 4231), defence against vaginal pathogens (ID 2950, 2957, 2967) and increasing IL-10

DEFF Research Database (Denmark)

Tetens, Inge

and reduction of gastro-intestinal discomfort, decreasing potentially pathogenic gastro-intestinal microorganisms, improved lactose digestion, “intestinal flora/digestive health”, defence against vaginal pathogens and increasing IL-10 production and/or enhancing the activity of natural killer cells. The food...

Endoscopic evaluation of upper and lower gastro-intestinal bleeding

Directory of Open Access Journals (Sweden)

Emeka Ray-Offor

2015-01-01

Full Text Available Introduction: A myriad of pathologies lead to gastro-intestinal bleeding (GIB. The common clinical presentations are hematemesis, melena, and hematochezia. Endoscopy aids localization and treatment of these lesions. Aims: The aim was to study the differential diagnosis of GIB emphasizing the role of endoscopy in diagnosis and treatment of GIB. Patients and Methods: A prospective study of patients with GIB referred to the Endoscopy unit of two health facilities in Port Harcourt Nigeria from February 2012 to August 2014. The variables studied included: Demographics, clinical presentation, risk score, endoscopic findings, therapeutic procedure, and outcome. Data were collated and analyzed using SPSS version 20 software. Results: A total of 159 upper and lower gastro-intestinal (GI endoscopies were performed during the study period with 59 cases of GI bleeding. There were 50 males and 9 females with an age range of 13-86 years (mean age 52.4 ΁ 20.6 years. The primary presentations were hematochezia, hematemesis, and melena in 44 (75%, 9 (15%, and 6 (10% cases, respectively. Hemorrhoids were the leading cause of lower GIB seen in 15 cases (41%. The majority of pathologies in upper GIB were seen in the stomach (39%: Gastritis and benign gastric ulcer. Injection sclerotherapy was successfully performed in the hemorrhoids and a case of gastric varices. The mortality recorded was 0%. Conclusion: Endoscopy is vital in the diagnosis and treatment of GIB. Gastritis and Haemorrhoid are the most common causes of upper and lower GI bleeding respectively, in our environment

MR imaging of the gastro-intestinal tract in children

Energy Technology Data Exchange (ETDEWEB)

Hoermann, Marcus [Medical University of Vienna/General Hospital, Department of General and Paediatric Radiology, Waehringerguertel 18-20, A-1090 Vienna (Austria)], E-mail: marcus.hoermann@meduniwien.ac.at

2008-11-15

MR imaging (MRI) is an established method for the evaluation of particularly inflammatory bowel disease in adults, as well as for acute abdominal pain in pregnant women. Despite the fact that MRI is ideally suited for the evaluation of children the method is still not established in these patients. The value of MRI in Crohn's disease, ulcerative colitis and appendicitis as well as intestinal tumors and malformations has been documented in children. There will be more indications in the future depending on the development of new imaging techniques, faster sequences, stronger gradients and increasing availability. Furthermore, the radiologist's attention must be drawn to decrease the radiation burden in children and to replace ionizing techniques especially in chronic disease with the need for repeated follow-up studies and in younger children. This review will discuss some general considerations for the use of MRI in evaluating the paediatric gastro-intestinal tract.

Lornoxicam gastro retentive floating matrix tablets: Design and in vitro evaluation.

Science.gov (United States)

Sathiyaraj, S; Devi, Ramya D; Hari, Vedha B N

2011-07-01

The objective of this present investigation is to prolong the gastric residence time of Lornoxicam by fabricating it into a floating sustained release matrix tablets. Lornoxicam, a potent oxicam group of non-steroidal anti-inflammatory drugs, suffers from relatively short half life of 2 to 3 hrs showing maximal absorption in proximal gastro intestinal tract region necessitating its need to be formulated as a floating sustained release matrix tablets. In this current investigation, hydroxyl propyl methyl cellulose K15M, a high viscous grade polymer with apparent viscosity of 15,000 cps, was kept as a variable (10-50%) and calcium carbonate (13%) was used as a gas generator. The prepared blends were subjected for its pre-formulation characterization. The directly compressed tablets were evaluated for physical parameters such as weight uniformity, hardness, friability, drug content, in-vitro buoyancy with axial and radial enlargement measurement, swelling index. From the investigation it was observed that the buoyancy lasted for up to 24 hrs. Fourier transform infra-red spectroscopy peaks assured the compatibility of the drug with excipients and confirmed the presence of pure drug in the formulation. It was supported by in-vitro dissolution studies; and the dissolution data was subjected to various release kinetic models to understand the mechanism of drug release.

Lornoxicam gastro retentive floating matrix tablets: Design and in vitro evaluation

Directory of Open Access Journals (Sweden)

S Sathiyaraj

2011-01-01

Full Text Available The objective of this present investigation is to prolong the gastric residence time of Lornoxicam by fabricating it into a floating sustained release matrix tablets. Lornoxicam, a potent oxicam group of non-steroidal anti-inflammatory drugs, suffers from relatively short half life of 2 to 3 hrs showing maximal absorption in proximal gastro intestinal tract region necessitating its need to be formulated as a floating sustained release matrix tablets. In this current investigation, hydroxyl propyl methyl cellulose K15M, a high viscous grade polymer with apparent viscosity of 15,000 cps, was kept as a variable (10-50% and calcium carbonate (13% was used as a gas generator. The prepared blends were subjected for its pre-formulation characterization. The directly compressed tablets were evaluated for physical parameters such as weight uniformity, hardness, friability, drug content, in-vitro buoyancy with axial and radial enlargement measurement, swelling index. From the investigation it was observed that the buoyancy lasted for up to 24 hrs. Fourier transform infra-red spectroscopy peaks assured the compatibility of the drug with excipients and confirmed the presence of pure drug in the formulation. It was supported by in-vitro dissolution studies; and the dissolution data was subjected to various release kinetic models to understand the mechanism of drug release.

In vitro characterization of cadmium and zinc uptake via the gastro-intestinal tract of the rainbow trout (Oncorhynchus mykiss): Interactive effects and the influence of calcium

International Nuclear Information System (INIS)

Ojo, Adeola A.; Wood, Chris M.

2008-01-01

An in vitro gut sac technique was employed to study whether Cd and Zn uptake mechanisms in the gastro-intestinal tract of the rainbow trout are similar to those at the gills, where both metals are taken up via the Ca transport pathway. Metal accumulation in surface mucus, in the mucosal epithelium, and transport into the blood space were assayed using radiolabelled Cd or Zn concentrations of 50 μmol L -1 in the luminal (internal) saline. Elevated luminal Ca (10 or 100 mmol L -1 versus 1 mmol L -1 ) reduced Cd uptake into all three phases by approximately 60% in the stomach, but had no effect in the anterior, mid, or posterior intestine. This finding is in accordance with recent in vivo evidence that Ca is taken up mainly via the stomach, and that high [Ca] diets inhibit Cd accumulation from the food specifically in this section of the tract. In contrast, 10 mmol L -1 luminal Ca had no effect on Zn transport in any section, whereas 100 mmol L -1 Ca stimulated Zn uptake, by approximately threefold, into all three phases in the stomach only. There was no influence of elevated luminal Zn (10 mmol L -1 ) on Cd uptake in the stomach or anterior intestine, or of high Cd (10 mmol L -1 ) on Zn uptake in these sections. However, high [Zn] stimulated Cd transport into the blood space but inhibited accumulation in the mucosal epithelium and/or mucus-binding in the mid and posterior intestine, whereas high [Cd] exerted a reciprocal effect in the mid-intestine only. We conclude that Cd uptake occurs via an important Ca-sensitive mechanism in the stomach which is different from that at the gills, while Cd transport mechanisms in the intestine are not directly Ca-sensitive. Zn uptake does not appear to involve Ca uptake pathways, in contrast to the gills. These results are discussed in the context of other possible Cd and Zn transport pathways, and the emerging role of the stomach as an organ of divalent metal uptake

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to Bimuno® GOS and reducing gastro-intestinal discomfort pursuant to Article 13(5) of Regulation (EC) No 1924/2006

DEFF Research Database (Denmark)

Tetens, Inge

the two human intervention studies which investigated the effect of Bimuno® GOS on symptoms related to gastro-intestinal discomfort. The remaining human studies, and the animal and in vitro studies, addressed the effects of either Bimuno® GOS or other galacto-oligosaccharides from a variety of sources...

In Vitro, in Silico, and in Vivo Assessments of Intestinal Precipitation and Its Impact on Bioavailability of a BCS Class 2 Basic Compound.

Science.gov (United States)

Kou, Dawen; Zhang, Chen; Yiu, Hiuwing; Ng, Tania; Lubach, Joseph W; Janson, Matthew; Mao, Chen; Durk, Matthew; Chinn, Leslie; Winter, Helen; Wigman, Larry; Yehl, Peter

2018-04-02

In this study, a multipronged approach of in vitro experiments, in silico simulations, and in vivo studies was developed to evaluate the dissolution, supersaturation, precipitation, and absorption of three formulations of Compound-A, a BCS class 2 weak base with pH-dependent solubility. In in vitro 2-stage dissolution experiments, the solutions were highly supersaturated with no precipitation at the low dose but increasing precipitation at higher doses. No difference in precipitation was observed between the capsules and tablets. The in vitro precipitate was found to be noncrystalline with higher solubility than the crystalline API, and was readily soluble when the drug concentration was lowered by dilution. A gastric transit and biphasic dissolution (GTBD) model was developed to better mimic gastric transfer and intestinal absorption. Precipitation was also observed in GTBD, but the precipitate redissolved and partitioned into the organic phase. In vivo data from the phase 1 clinical trial showed linear and dose proportional PK for the formulations with no evidence of in vivo precipitation. While the in vitro precipitation observed in the 2-stage dissolution appeared to overestimate in vivo precipitation, the GTBD model provided absorption profiles consistent with in vivo data. In silico simulation of plasma concentrations by GastroPlus using biorelevant in vitro dissolution data from the tablets and capsules and assuming negligible precipitation was in line with the observed in vivo profiles of the two formulations. The totality of data generated with Compound-A indicated that the bioavailability differences among the three formulations were better explained by the differences in gastric dissolution than intestinal precipitation. The lack of intestinal precipitation was consistent with several other BCS class 2 basic compounds in the literature for which highly supersaturated concentrations and rapid absorption were also observed.

Precision-cut intestinal slices as an in vitro model to predict NSAID induced intestinal toxicity

NARCIS (Netherlands)

Niu, Xiaoyu; van der Bijl, Henk; Groothuis, Geny; de Graaf, Inge

2013-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with high prevalence of gastro-intestinal side-effects. In vivo studies suggest that uncoupling of oxidative phosphorylation is an important cause of the toxicity and that the toxicity is aggravated by enterohepatic circulation.

Ontogeny of the VIP system in the gastro-intestinal tract of the Axolotl, Ambystoma mexicanum: successive appearance of co-existing PACAP and NOS.

Science.gov (United States)

Badawy, Gamal; Reinecke, Manfred

2003-03-01

Evidence for the presence and potential co-existence of vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP) and nitric oxide synthase (NOS) in gastro-intestinal endocrine cells and/or nerve fibers is conflicting and very few results exist on development. This immunofluorescence study aims to clarify the appearance and localization of VIP, PACAP and NOS in the gastro-intestinal tract of the Axolotl, Ambystoma mexicanum, during ontogeny. VIP-immunoreactivity appeared in nerve fibers as early as on day 3 after hatching likely indicating a particular role, such as a trophic action, of VIP in very early development. PACAP-immunoreactivity was observed 3 days later within the VIP-immunoreactive (-IR) fibers. From this time on, VIP- and PACAP-immunoreactivity exhibited complete co-existence. VIP/PACAP-IR fibers were found throughout the gastro-intestinal tract. They were most prominent in the myenteric plexus and the muscle layers and less frequent in the submucosa. NOS-immunoreactivity appeared as late as at the 1st (64 days) juvenile stage in a subpopulation of the VIP/PACAP-IR fibers that contacted submucosal arteries. We found only very few VIP/PACAP-IR perikarya, indicating that part of the VIP/PACAP-IR fibers is of extrinsic origin. On day 12 and in the 1st and 2nd (104 days) juvenile stage, infrequent PACAP-IR entero-endocrine cells were noted, while neither VIP- nor NOS-immunoreactivity occurred in endocrine cells at any stage of development. The complete coexistence of neuronal PACAP- and VIP-immunoreactivities and their very early appearance in ontogeny may suggest important and coordinated roles of both peptides in the control of Axolotl gastro-intestinal activity, while the VIP/ PACAP/NOS-IR fibers may be involved in the regulation of submucosal blood flow.

Changes in the serum protein profile during radiotherapy to the upper respiratory and gastro-intestinal tracts

International Nuclear Information System (INIS)

David, M.; Lobera, A.; Legrand, E.

1984-01-01

Patients with a cancer of the upper airways of upper gastro-intestinal tract present a state of malnutrition as a result of the disease itself and, more importantly, as a result of its localisation. Loco-regional radiotherapy often leads to an aggravation, of this state. The protein profile, consisting of nine serum proteins, was determined each week in 54 patients with cancer of the upper respirato-gastro-intestinal tract receiving radiotherapy. During the course of radiotherapy, the already altered nutritional state of these patients deteriorated further, as shown by a regular and significant downturn in the weight curve. The weekly monitoring of the protein profile showed a gradual and significant decrease in the levels of nutritional proteins (prealbumin, retinol binding protein, transferrin) and immunoglobulins (IgM, IgA) and a small variation in the levels of inflammatory proteins (haptoglobin, orosomucoid, C3 complement fraction, alpha 1 -antitrypsin). The protein profile, established on the basis of carefully selected proteins, can provide useful information in the monitoring of a patient's nutritional state [fr

Changes in the serum protein profile during radiotherapy to the upper respiratory and gastro-intestinal tracts

Energy Technology Data Exchange (ETDEWEB)

David, M; Lobera, A; Legrand, E [Fondation Bergorie, Bordeaux (France)

1984-01-01

Patients with a cancer of the upper airways on upper gastro-intestinal tract present a state of malnutrition as a result of the disease itself and, more importantly, as a result of its localisation. Loco-regional radiotherapy often leads to an aggravation, of this state. The protein profile, consisting of nine serum proteins, was determined each week in 54 patients with cancer of the upper respirato-gastro-intestinal tract receiving radiotherapy. During the course of radiotherapy, the already altered nutritional state of these patients deteriorated further, as shown by a regular and significant downturn in the weight curve. The weekly monitoring of the protein profile showed a gradual and significant decrease in the levels of nutritional proteins (prealbumin, retinol binding protein, transferrin) and immunoglobulins (IgM, IgA) and a small variation in the levels of inflammatory proteins (haptoglobin, orosomucoid, C3 complement fraction, alpha/sub 1/-antitrypsin). The protein profile, established on the basis of carefully selected proteins, can provide useful information in the monitoring of a patient's nutritional state.

Research on measurement and modeling of the gastro intestine's frictional characteristics

International Nuclear Information System (INIS)

Wang, Kun Dong; Yan, Guo Zheng

2009-01-01

The frictional characteristics of an intestine are required basically for the development of a noninvasive endoscope for the human intestine. The frictional force is tested by measuring the current of the motor hauling the frictional coupons at an even speed. A multifunction data acquisition device with model NI-6008 USB is used and the data process is performed on the Labview software. Two kinds of materials with aluminum and copper are used. The surfaces are designed as triangle, rectangular, cylindrical and plane forms. The tested results indicate that the frictional resistance force includes the nominal frictional force and the visco-adhesive force. When the surface contour changes from the triangle to the rectangular, to the cylindrical and finally to the plane, the nominal frictional coefficients will decrease and the visco-adhesive force will increase. The nominal frictional force is related to the elastic restoring force, the real frictional force and the contact angle. The cohesive force is determined by the contact area and the contact angle. This research will provide some preliminary references to the design and the parameter selection of locomotion devices in the human gastro-intestine

In vitro characterization of cadmium and zinc uptake via the gastro-intestinal tract of the rainbow trout (Oncorhynchus mykiss): Interactive effects and the influence of calcium

Energy Technology Data Exchange (ETDEWEB)

Ojo, Adeola A. [Department of Biology, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4K1 (Canada)], E-mail: adeolaojo25@yahoo.com; Wood, Chris M. [Department of Biology, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4K1 (Canada)], E-mail: woodcm@mcmaster.ca

2008-08-11

An in vitro gut sac technique was employed to study whether Cd and Zn uptake mechanisms in the gastro-intestinal tract of the rainbow trout are similar to those at the gills, where both metals are taken up via the Ca transport pathway. Metal accumulation in surface mucus, in the mucosal epithelium, and transport into the blood space were assayed using radiolabelled Cd or Zn concentrations of 50 {mu}mol L{sup -1} in the luminal (internal) saline. Elevated luminal Ca (10 or 100 mmol L{sup -1}versus 1 mmol L{sup -1}) reduced Cd uptake into all three phases by approximately 60% in the stomach, but had no effect in the anterior, mid, or posterior intestine. This finding is in accordance with recent in vivo evidence that Ca is taken up mainly via the stomach, and that high [Ca] diets inhibit Cd accumulation from the food specifically in this section of the tract. In contrast, 10 mmol L{sup -1} luminal Ca had no effect on Zn transport in any section, whereas 100 mmol L{sup -1} Ca stimulated Zn uptake, by approximately threefold, into all three phases in the stomach only. There was no influence of elevated luminal Zn (10 mmol L{sup -1}) on Cd uptake in the stomach or anterior intestine, or of high Cd (10 mmol L{sup -1}) on Zn uptake in these sections. However, high [Zn] stimulated Cd transport into the blood space but inhibited accumulation in the mucosal epithelium and/or mucus-binding in the mid and posterior intestine, whereas high [Cd] exerted a reciprocal effect in the mid-intestine only. We conclude that Cd uptake occurs via an important Ca-sensitive mechanism in the stomach which is different from that at the gills, while Cd transport mechanisms in the intestine are not directly Ca-sensitive. Zn uptake does not appear to involve Ca uptake pathways, in contrast to the gills. These results are discussed in the context of other possible Cd and Zn transport pathways, and the emerging role of the stomach as an organ of divalent metal uptake.

In Vitro Study of Adsorption Kinetics of Dextromethorphan Syrup onto Activated Charcoal in Simulated Gastric and Intestinal Fluids

Directory of Open Access Journals (Sweden)

Shobha Regmi

2017-01-01

Full Text Available Adsorption kinetics of dextromethorphan (DXM syrup in simulated gastric and intestinal fluids onto activated charcoal (AC were investigated in an in vitro model. The adsorption studies were performed as a function of time, initial concentration, and temperature. The quantification of DXM adsorbed onto AC was obtained from the Langmuir adsorption isotherms using HPLC. The maximum adsorption capacities (at 95% confidence limits of AC for DXM were 111.615 [106.38; 126.85] mg in simulated intestinal environment (pH 6.8 and 78.314 [86.206; 70.422] mg in simulated gastric environment (pH 1.2. The adsorption capacity of AC for DXM in simulated gastric fluid (pH 1.2 was not significantly different from the adoption capacity of AC for DXM in simulated intestinal fluid (pH 6.8. Moreover, the adsorption kinetics behavior of dextromethorphan onto AC followed pseudo-second-order kinetics. Our results show that AC in therapeutically acceptable doses can be beneficial in the majority of oral overdose of DXM.

Application of an in vitro digestion model for 210Po bioaccessibility assessment in seafood.

Science.gov (United States)

Roselli, Carla; Desideri, Donatella; Feduzi, Laura; Ugolini, Lucia; Meli, Maria Assunta

2017-12-01

This study aims to investigate the bioaccessibility of 210 Po in seafood and the impact of food preparation on this radionuclide. Polonium bioaccessibility is the fraction of 210 Po mobilised from food matrices into digestive extractants when applying an in vitro digestion model. The degree of bioaccessibility of 210 Po in food has important implications for estimating ingestion doses from this radionuclide. The simulation of gastrointestinal digestion was divided into three stages through the use of synthetic saliva, gastric and bile-pancreas solutions. Following pre-treatment with a saliva solution, raw and cooked seafood samples underwent one of the following treatments: (a) simulated gastric digestion only or (b) simulated complete gastrointestinal digestion (gastric digestion followed by bile-pancreas digestion). No significant difference (P > 0.05) in 210 Po mobility was found between samples that underwent gastric digestion compared to those that only underwent gastro-intestinal digestion. However, a significant difference (P 210 Po bioaccessibility was found between raw and cooked seafood undergoing both gastric and gastro-intestinal digestion.

Evaluation of new gastro-intestinal prokinetic (ENGIP-I) study.

Science.gov (United States)

Walwaikar, Pradeep P; Kulkarni, Sujay S; Bargaje, Rahul S

2005-10-01

The ENGIP-I study was conducted to investigate the efficacy, and safety of itopride in patients of gastro-oesophageal reflux disease. There were significant reductions in heartburn frequency, heartburn severity, gastro-oesophageal regurgitation frequency at day 3 only. ENGIP-I study concluded that itopride was well tolerated by patients and appears to be the drug of choice in patients with gastro-oesophageal reflux disease.

Viability of lactic acid bacteria coated as synbiotic during storage and gastro-intestinal simulation

Science.gov (United States)

Jamilah, It; Priyani, Nunuk; Lusia Natalia, Santa

2018-03-01

Lactic acid bacteria (LAB) has been added to various food products as a probiotic agent because it has been known to provide beneficial health effects in humans. In the application of LAB, cell viability often decreased as influenced by environment stresses. Encapsulation technique is one of the cell protection techniques using a coating material. Effective coating material is required to produce maximum protection of LAB cells. In this study, candidate of probiotic LAB (isolate US7) was encapsulated with alginate-mung bean flour and alginate-gram flour with inulin prebiotic by extrusion technique. Viability of encapsulated LAB cells were able to survive by up to 108CFU g‑1 after 4 weeks of storage at 4 °C. Beads were incubated in simulated liquid gastric acid (pH=2) for 2 hrs and simulated intestinal fluid (pH=6) for 3 hrs at 37 °C. The results showed that encapsulated LAB cells maintained the survival rate of 97% with the number of cells at 9.07 Log CFU g‑1in the simulated liquid gastric acid and then followed by releasing cells in simulated intestinal fluid. In general, this study indicates that encapsulation with alginate-mung bean flour and alginategram flour with inulin successfullyprotect probiotic bacteria against simulated human gastrointestinal conditions.

Isotopic in vitro tests in gastro-enterology and hepatology

Energy Technology Data Exchange (ETDEWEB)

Bottermann, P

1987-06-01

Especially during the last two decades a series of most interesting scientific findings has been made by means of radioimmunological techniques, according to which some intestinal peptides may be considered as incretine candidates. The question of the practical clinical relevance of the knowledge gathered up to now, however, still remains to be answered. Intensive studies conducted into gastro-intestinal factors have led to a better understanding of hormonally active pancreatic tumours. Some relatively rare clinical pictures such as the 'Verner-Morrison-Syndrome' and the 'Zollinger-Ellison-Syndrome' may be better analysed by identification of the hormones involved. Tumour-associated antigens are of essential clinical relevance for diagnosis and, above all, for the follow-up of malignancies in the GI-tract, especially in colorectal carcinomas and pancreatic carcinomas. 'Hepatitis serology' also facilitates diagnosis of the different types of viral hepatitis. Especially the determination of the different hepatitis antigens, or antibodies against these antigens, in hepatitis B offers very good approaches to follow-up the course of diseases and also allows tentative prognosis. (orig./TRV).

Trends in upper gastro-intestinal cancer among the elderly in Denmark, 1980-2012

DEFF Research Database (Denmark)

Schønnemann, Katrine R; Mortensen, Michael B; Krogh, Merete

2016-01-01

Background Upper gastro-intestinal cancer (UGIC) includes malignancies in esophagus, stomach and small intestine, and represents some of the most frequent malignancies worldwide. The aim of the present analysis was to describe incidence, mortality and survival in UGIC patients in Denmark from 1980...... to 2012 according to differences in age and time periods.Material and methods UGIC was defined as ICD-10 codes C15-C17. Data derived from the NORDCAN database with comparable data on cancer incidence mortality, prevalence and relative survival in the Nordic countries, where the Danish data were delivered...... from the Danish Cancer Registry and the Danish Cause of Death Registry with follow-up for death or emigration until the end of 2013.Results The proportion of male patients over the age of 70 years diagnosed with esophageal cancer was constant over time (around 42%) but increased in females to 49...

A sulphonamido-indanone derivative CGP 28237 (ZK 34228), a novel non-steroidal anti-inflammatory agent without gastro-intestinal ulcerogenicity in rats.

Science.gov (United States)

Böttcher, I; Schweizer, A; Glatt, M; Werner, H

1987-01-01

CGP 28237 (5-methylsulphonylamino-6-phenoxy-1-indanone) belongs to a series of structurally novel indanones. The compound is a weak acid (pK = 6.98), but it does not contain a carboxylic group. CGP 28237 exhibits potent anti-inflammatory activity in developing and established adjuvant arthritis in rats (ED40 approximately 0.5 mg/kg p.o.) and good activity in carrageenin oedema (ED40 approximately 3 mg/kg p.o.). It inhibits yeast-induced fever in rats with ED50 values of 1, 2 and 10 mg/kg p.o. at 1, 3 and 5 hours after drug administration. The antinociceptive activity in mice (phenyl-p-benzoquinone writhing) and rats (acetic-acid writhing) is weak. CGP 28237 has been shown to be non-ulcerogenic in rats under acute and chronic test conditions: it does not cause mucosal lesions in the stomach at 2 X 400 mg/kg p.o., it does not enhance gastro-intestinal blood loss during 10 days' oral treatment with 400 mg/kg p.o., and it did not induce gastro-intestinal lesions in a 4-week toxicity study up to 1000 mg/kg p.o. Although CGP 28237 is not a cyclooxygenase inhibitor in bovine seminal vesicle microsomes, it inhibits prostaglandin synthesis in zymosan-stimulated murine macrophages (IC50 approximately 3 X 10(-6) mol/l) and protects rabbits against arachidonic acid-induced lung embolism with 10 mg/kg p.o. CGP 28237 may represent a novel anti-inflammatory drug with excellent gastro-intestinal tolerability.

Open trial of cimetidine in the prevention of upper gastro-intestinal haemorrhage in patients with severe intracranial injury.

Science.gov (United States)

Mouawad, E; Deloof, T; Genette, F; Vandesteene, A

1983-01-01

The present study evaluates the efficacy of Cimetidine in the prevention of clinically important gastro-intestinal haemorrhage in patients suffering from severe head injury. Fifty patients (39 males and 11 females) were included in the study. We excluded from the trial patients on anticoagulant therapy or concomitant non-steroid anti-inflammatory agents, pregnant and lactating women, and patients with previous histories of peptic ulcer disease.

Scientific Opinion on the substantiation of health claims related to Saccharomyces cerevisiae var. boulardii CNCM I-1079 and defence against pathogenic gastro-intestinal microorganisms (ID 913, further assessment) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

DEFF Research Database (Denmark)

Tetens, Inge

. boulardii CNCM I-1079 and defence against pathogenic gastro-intestinal microorganisms. The food constituent that is the subject of the health claim, Saccharomyces cerevisiae var. boulardii CNCM I-1079, is sufficiently characterised. The claimed effect, defence against pathogenic gastro......-intestinal microorganisms, is a beneficial physiological effect. The proposed target population is the general population. The Panel notes that the evidence provided is not sufficient to establish that the strains Saccharomyces cerevisiae var. boulardii CNCM I-1079 and Saccharomyces cerevisiae var. boulardii Hansen CBS...... relationship has not been established between the consumption of Saccharomyces cerevisiae var. boulardii CNCM I-1079 and defence against pathogenic gastro-intestinal microorganisms....

The endemiology of helicobacter pylorus infection and gastro-intestinal disease in mine and related factory workers of Tongling city, Anhui

International Nuclear Information System (INIS)

He Xiangyang; Jiang Zhonglin; Yang Shunqi; Mei Yanyan; Wen Qin; Cheng Yingzi; Wang Jianmiao

2006-01-01

Objective: To investigate the endemiology of H. pylorus infection and related gastro-intestinal disease in mine and factory workers of Tong-Ling area. Methods: 14 C-urea breath test, serum IgG and cytotoxin-producing H. pylorus antibodies determinations were performed in 1076 randomly selected adults among the mine and related factory workers in Tong - Ling area. Gastroscopy was done in 156 subjects (cytotoxin-producing H. pylorus antibody CagA-HP positive 108 and Cag-HP negative 48). Results: Seven hundred and twenty-one subjects of the 1076 (67.0%) examined were positive with the 14 C-urea breath and serological tests, among which 350 (48.5% of the 721 ) were Cag-HP positive. Factors affecting positiveness of HP infection were in the order of: working environment, gastro-intestinal symptoms, past history, vocation, age, history of previous contact, sex and non- hygiene life-style. Conclusion: The HP infection rate in Tong-Ling area was slightly higher than nationwide but with a lower CagA - HP positive rate. HP infection was mostly related to the working environment and life-style. (authors)

Isoenergetic Replacement of Fat by Starch in Diets for African Catfish (Clarias gariepinus): Effect on Water Fluxes in the Gastro Intestinal Tract

NARCIS (Netherlands)

Harter, T.S.; Verreth, J.A.J.; Heinsbroek, L.T.N.; Schrama, J.W.

2013-01-01

The effect of an isoenergetic replacement of dietary fat by starch, on chyme characteristics and water fluxes in the gastro intestinal tract (GIT) was assessed. Adult African catfish (Clarias gariepinus) were fed a starch (SD) or fat (FD) diet and groups of fish were dissected at 2, 5 and 8 h after

Radio-isotopes in gastro-enterology

International Nuclear Information System (INIS)

Pettengell, K.E.; Houlder, A.

1988-01-01

Many recent advances in nuclear imaging have applications in gastro-enterology, and these have shown an increasing shift of emphasis away from the simple demonstration of anatomy towards methods suitable for the investigation of gastro-intestinal (GI) function and pathophysiology. Scintigraphic techniques are non-invasive, well tolerated by ill patients and perhaps most importantly permit quantitation of abnormal physiology. It is therefore not surprising that nuclear imaging is gaining an increasingly important place in routine patient management. This article discuss its value in the fields of GI bleeding, inflammatory bowel disease, tumour localisation and oesophageal motility

Application of a dynamic in vitro gastrointestinal tract model to study the availability of food mutagens, using heterocyclic aromatic amines as model compounds

NARCIS (Netherlands)

Krul, C.A.M.; Luiten-Schuite, A.; Baan, R.; Verhagen, H.; Mohn, G.; Feron, V.; Havenaar, R.

2000-01-01

The TNO gastro-Intestinal tract Model (TIM) is a dynamic computer-controlled in vitro system that mimics the human physiological conditions in the stomach and small intestine. In the current TIM physiological parameters such as pH, temperature, peristaltic movements, secretion of digestion enzymes,

In Vitro Pharmacodynamics of Benzimidazole and Tetrahydropyrimidine Derivatives in European Bison Gastro-Intestinal Nematodes

Directory of Open Access Journals (Sweden)

Laura CĂTANĂ

2017-11-01

Full Text Available The present study was aimed to evaluate the efficacy of anthelmintic agents against intestinal nematodes found in European bison. It was performed between October 2016 and May 2017, using Egg Hatch Assay (EHA and Larval Development Assay (LDA. The parasites were obtained from faecal samples, harvested from bisons in Romania and Sweden. The efficacy of albendazole (ABZ, mebendazole (MBZ thiabendazole (TBZ and pyrantel (PYR was tested. In EHA, the maximum efficacy was observed in MBZ (EC50 = - 0.227 μg/ml, and then TBZ (EC50 = - 0.2228. ABZ had a weaker result, EC50 being 0.326 μg/ml. All tested benzimidazoles registered hatching percentages below 50%, reflecting the lack of parasitic resistance. MIC obtained in the LDA tests were 0.2144 μg/ml for TBZ, 0.2792 μg/ml for PYR, 0.5429 μg/ml for MBZ, while ABZ came last (MIC = 0.8187 μg/ml. The in vitro tests proved the antiparasitic molecules efficacy against bisons nematode population and a limited risk of inducing resistance phenomena.

CHEMOTHERAPY OF GASTRO-INTESTINAL NAMATODES IN COMMON PEAFOWL (PAVO CRISTATUS

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M. Ashraf, Faisal Noman Waraich, I.G. Ahmad and K. Pervez

2002-04-01

Full Text Available The present study was undertaken to find out the prevalence of gastro-intestinal nematodes in common peafowl (Pavo cristatus at Lahore Zoo and to evaluate the comparative efficacy of albendazole, levamisole HCI and oxfendazole. Fifty-two faecal samples of the birds were examined in Medicine Laboratory, College of Veterinary Sciences, Lahore, with direct smear method for the identification of nematode ova. Forty two samples out of 52 were found positive (80.77% for single or mixed infection of Capillaria spp., Ascaridia galliand Heterakis gallinae, and the individual percentages being 59.62, 38.46 and 13.46 respectively. Out of 42 infected birds 40 were chosen for medication and divided into four groups, each consisting of 10 birds (A= treated with albendazole, B=treated with levamisole, C = treated with oxfendazole and group D= untreated control. Faecal samples of experimental birds were examined for counting of eggs per gram of faeces on day '0' (pre-medication. Faecal egg counts were again carried out on day 5 and 10 post-medication and percentage reduction of EPG was calculated. Oxfendazole was found to be the most effective (98.88% among the three anthelmintics, followed by levamisole (97.3% and albendazole (95.60%.

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to a combination of Lactobacillus rhamnosus CNCM I-1720 and Lactobacillus helveticus CNCM I-1722 and defence against pathogenic gastro-intestinal microorganisms (ID 939

DEFF Research Database (Denmark)

Tetens, Inge

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a health claim related to a combination of Lactobacillus rhamnosus CNCM I-1720 and Lactobacillus helveticus CNCM I-1722 and defence against...... pathogenic gastro-intestinal microorganisms. The food constituent that is the subject of the health claim, a combination of Lactobacillus rhamnosus CNCM I-1720 and Lactobacillus helveticus CNCM I-1722, is sufficiently characterised. The claimed effect, defence against pathogenic gastro...... and effect relationship has not been established between the consumption of a combination of Lactobacillus rhamnosus CNCM I-1720 and Lactobacillus helveticus CNCM I-1722 and defence against pathogenic gastro-intestinal microorganisms....

[Effect of rat intestinal flora on in vitro metabolic transformation of pumiloside].

Science.gov (United States)

Fang, Hui; Li, Meng-Xuan; Li, Hai-Bo; Liu, Wen-Jun; Meng, Zhao-Qing; Huang, Wen-Zhe; Wang, Zhen-Zhong; Xiao, Wei

2016-05-01

To study the metabolic transformation of pumiloside by rat intestinal flora in vitro and identify its metabolites. Pumiloside was incubated in the rat intestinal flora in vitro. HPLC was used to monitor the metabolic process, and HPLC-Q-TOF-MS was used to identify the structures of biotransformation products. In vitro, pumiloside was easily metabolized by rat intestinal flora, and with the prolongation of metabolic time, pumiloside was transformed into several metabolites. Three metabolites were initially identified in this experiment. The study indicated that pumiloside could be extensively metabolized in the rat intestinal flora in vitro. Copyright© by the Chinese Pharmaceutical Association.

Actinidin enhances protein digestion in the small intestine as assessed using an in vitro digestion model.

Science.gov (United States)

Kaur, Lovedeep; Rutherfurd, Shane M; Moughan, Paul J; Drummond, Lynley; Boland, Mike J

2010-04-28

This paper describes an in vitro study that tests the proposition that actinidin from green kiwifruit influences the digestion of proteins in the small intestine. Different food proteins, from sources including soy, meat, milk, and cereals, were incubated in the presence or absence of green kiwifruit extract (containing actinidin) using a two-stage in vitro digestion system consisting of an incubation with pepsin at stomach pH (simulating gastric digestion) and then with added pancreatin at small intestinal pH, simulating upper tract digestion in humans. The digests from the small intestinal stage (following the gastric digestion phase) were subjected to gel electrophoresis (SDS-PAGE) to assess loss of intact protein and development of large peptides during the in vitro simulated digestion. Kiwifruit extract influenced the digestion patterns of all of the proteins to various extents. For some proteins, actinidin had little impact on digestion. However, for other proteins, the presence of kiwifruit extract resulted in a substantially greater loss of intact protein and different peptide patterns from those seen after digestion with pepsin and pancreatin alone. In particular, enhanced digestion of whey protein isolate, zein, gluten, and gliadin was observed. In addition, reverse-phase HPLC (RP-HPLC) analysis showed that a 2.5 h incubation of sodium caseinate with kiwifruit extract alone resulted in approximately 45% loss of intact protein.

Intestinal subepithelial myofibroblasts support in vitro and in vivo growth of human small intestinal epithelium.

Directory of Open Access Journals (Sweden)

Nicholas Lahar

Full Text Available The intestinal crypt-niche interaction is thought to be essential to the function, maintenance, and proliferation of progenitor stem cells found at the bases of intestinal crypts. These stem cells are constantly renewing the intestinal epithelium by sending differentiated cells from the base of the crypts of Lieberkühn to the villus tips where they slough off into the intestinal lumen. The intestinal niche consists of various cell types, extracellular matrix, and growth factors and surrounds the intestinal progenitor cells. There have recently been advances in the understanding of the interactions that regulate the behavior of the intestinal epithelium and there is great interest in methods for isolating and expanding viable intestinal epithelium. However, there is no method to maintain primary human small intestinal epithelium in culture over a prolonged period of time. Similarly no method has been published that describes isolation and support of human intestinal epithelium in an in vivo model. We describe a technique to isolate and maintain human small intestinal epithelium in vitro from surgical specimens. We also describe a novel method to maintain human intestinal epithelium subcutaneously in a mouse model for a prolonged period of time. Our methods require various growth factors and the intimate interaction between intestinal sub-epithelial myofibroblasts (ISEMFs and the intestinal epithelial cells to support the epithelial in vitro and in vivo growth. Absence of these myofibroblasts precluded successful maintenance of epithelial cell formation and proliferation beyond just a few days, even in the presence of supportive growth factors. We believe that the methods described here can be used to explore the molecular basis of human intestinal stem cell support, maintenance, and growth.

Identification of glucose-fermenting bacteria present in an in vitro model of the human intestine by RNA-stable isotope probing

NARCIS (Netherlands)

Egert, M.; Graaf, A.A. de; Maathuis, A.; Waard, P. de; Plugge, C.M.; Smidt, H.; Deutz, N.E.P.; Dijkema, C.; Vos, W.M. de; Venema, K.

2007-01-01

16S rRNA-based stable isotope probing (SIP) and nuclear magnetic resonance (NMR) spectroscopy-based metabolic profiling were used to identify bacteria fermenting glucose under conditions simulating the human intestine. The TIM-2 in vitro model of the human intestine was inoculated with a GI tract

Antioxidant activity of camel milk casein before and after in vitro simulated enzymatic digestion

Directory of Open Access Journals (Sweden)

Zeineb Jrad

2014-11-01

Full Text Available The effect of a successive in vitro hydrolysis by pepsin and pancreatin on the free radical scavenging activity of camel milk casein was investigated in order to assess the effect of gastro-intestinal digestion. Hydrolysis of camel casein was controlled by reversed-phase high performance liquid chromatography. Anti-oxidant activity was measured by the 2,2’-azino-bis-(3-ethylbensothiazoline-6- sulfonic acid (ABTS method. The Trolox equivalent antioxidant capacity (TEAC values of camel casein and its hydrolysate were 1.6±0.12 μmol TE/mg protein and 0.25 μmol TE/μmol eq. NH2, respectively. After digestion, the scavenging activity of the casein peptides was more efficient than those reported in the literature regarding digestive hydrolysates of camel milk, colostrum and whey proteins.

Aspects of surgical treatment for gastro-intestinal stromal tumors; Chirurgische Therapieaspekte gastrointestinaler Stromatumoren

Energy Technology Data Exchange (ETDEWEB)

Hohenberger, P. [Medizinische Fakultaet Mannheim, Universitaet Heidelberg, Sektion Chirurgische Onkologie und Thoraxchirurgie, Chirurgische Universitaetsklinik, Mannheim (Germany)

2009-12-15

Gastro-intestinal stromal tumors (GIST) form the commonest subgroup of soft tissue sarcomas. They arise in the muscular layer of the esophagus, stomach, small intestines and rectum. Characteristic and important for the assessment of the extent of tumors is the peripheral rim vascularization of primary tumors and metastases. Indications for resection are given for tumors larger than 2 cm in size. Locally advanced GISTs can be advantageously treated with imatinib/sunitinib as neoadjuvant and it is often possible to select a low level of resection for this size of tumor and when the rim area is not hypervascularized. Even in the metastizing stage surgical treatment can be used for elimination of resistant metastases or for removal of residual tumor tissue in an attempt to counteract secondary tumor progression. The effect of this treatment is currently being tested in a randomized phase III study. (orig.) [German] Gastrointestinale Stromatumoren (GIST) stellen die haeufigste Subgruppe von Weichgewebesarkomen dar. Sie entstehen in der Muskularisschicht von Oesophagus, Magen, Duenndarm und Rektum. Charakteristisch und wichtig fuer die Einschaetzung des Tumorausmasses ist die Randvaskularisation von Primaertumoren und Metastasen. Die Indikation zur Resektion gilt fuer Tumoren ab 2 cm Groesse. Lokal fortgeschrittene GIST koennen sehr vorteilhaft mit Imatinib/Sunitinib neoadjuvant vorbehandelt werden, und es ist oft moeglich, bei der Tumorgroesse und wenn keine hypervaskularisierten Randbereiche vorliegen, ein geringeres Resektionsausmass zu waehlen. Auch im metastasierten Stadium hat die chirurgische Therapie einen Platz zur Eliminierung resistenter Metastasen bzw. zur Entfernung von Residualtumorgewebe als Versuch, einer sekundaeren Tumorprogression zu begegnen. Dieser Behandlungseffekt wird derzeit in einer randomisierten Phase-III-Studie ueberprueft. (orig.)

In vitro digestion and fermentation characteristics of canola co-products simulate their digestion in the pig intestine.

Science.gov (United States)

Woyengo, T A; Jha, R; Beltranena, E; Zijlstra, R T

2016-06-01

Canola co-products are sources of amino acid and energy in pig feeds, but their fermentation characteristics in the pig intestine are unknown. Thus, we determined the in vitro fermentation characteristics of the canola co-products Brassica juncea solvent-extracted canola meal (JSECM), Brassica napus solvent-extracted canola meal (NSECM), B. napus expeller-pressed canola meal (NEPCM) and B. napus cold-pressed canola cake (NCPCC) in comparison with soybean meal (SBM). Samples were hydrolysed in two steps using pepsin and pancreatin. Subsequently, residues were incubated in a buffer solution with fresh pig faeces as inocula for 72 h to measure gas production. Concentration of volatile fatty acids (VFA) per gram of dry matter (DM) of feedstuff was measured in fermented solutions. Apparent ileal digestibility (AID) and apparent hindgut fermentation (AHF) of gross energy (GE) for feedstuffs were obtained from pigs fed the same feedstuffs. On DM basis, SBM, JSECM, NSECM, NEPCM and NCPCC contained 15, 19, 22, 117 and 231 g/kg ether extract; and 85, 223, 306, 208 and 176 g/kg NDF, respectively. In vitro digestibility of DM (IVDDM) of SBM (82.3%) was greater (Pfermentation characteristics of canola co-products and SBM simulated their fermentation in the small and large intestine of pigs, respectively. The 30% greater VFA production for JSECM than NSECM due to lower lignified fibre of JSECM indicates that fermentation characteristics differ between canola species. The NSECM had the highest fermentability followed by NEPCM and then NCPCC, indicating that fat in canola co-products can limit their fermentability in the hindgut.

Biorelevant media resistant co-culture model mimicking permeability of human intestine.

Science.gov (United States)

Antoine, Delphine; Pellequer, Yann; Tempesta, Camille; Lorscheidt, Stefan; Kettel, Bernadette; Tamaddon, Lana; Jannin, Vincent; Demarne, Frédéric; Lamprecht, Alf; Béduneau, Arnaud

2015-03-15

Cell culture models are currently used to predict absorption pattern of new compounds and formulations in the human gastro-intestinal tract (GIT). One major drawback is the lack of relevant apical incubation fluids allowing mimicking luminal conditions in the GIT. Here, we suggest a culture model compatible with biorelevant media, namely Fasted State Simulated Intestinal Fluid (FaSSIF) and Fed State Simulated Intestinal Fluid (FeSSIF). Co-culture was set up from Caco-2 and mucus-secreting HT29-MTX cells using an original seeding procedure. Viability and cytotoxicity assays were performed following incubation of FeSSIF and FaSSIF with co-culture. Influence of biorelevant fluids on paracellular permeability or transporter proteins were also evaluated. Results were compared with Caco-2 and HT29-MTX monocultures. While Caco-2 viability was strongly affected with FeSSIF, no toxic effect was detected for the co-cultures in terms of viability and lactate dehydrogenase release. The addition of FeSSIF to the basolateral compartment of the co-culture induced cytotoxic effects which suggested the apical mucus barrier being cell protective. In contrast to FeSSIF, FaSSIF induced a slight increase of the paracellular transport and both tested media inhibited partially the P-gp-mediated efflux in the co-culture. Additionally, the absorptive transport of propranolol hydrochloride, a lipophilic β-blocker, was strongly affected by biorelevant fluids. This study demonstrated the compatibility of the Caco-2/HT29-MTX model with some of the current biorelevant media. Combining biorelevant intestinal fluids with features such as mucus secretion, adjustable paracellular and P-gp mediated transports, is a step forward to more realistic in-vitro models of the human intestine. Copyright © 2015. Published by Elsevier B.V.

Enzymatically structured emulsions in simulated gastrointestinal environment: impact on interfacial proteolysis and diffusion in intestinal mucus.

Science.gov (United States)

Macierzanka, Adam; Böttger, Franziska; Rigby, Neil M; Lille, Martina; Poutanen, Kaisa; Mills, E N Clare; Mackie, Alan R

2012-12-18

Fundamental knowledge of physicochemical interactions in the gastrointestinal environment is required in order to support rational designing of protein-stabilized colloidal food and pharmaceutical delivery systems with controlled behavior. In this paper, we report on the colloidal behavior of emulsions stabilized with the milk protein sodium caseinate (Na-Cas), and exposed to conditions simulating the human upper gastrointestinal tract. In particular, we looked at how the kinetics of proteolysis was affected by adsorption to an oil-water interface in emulsion and whether the proteolysis and the emulsion stability could be manipulated by enzymatic structuring of the interface. After cross-linking with the enzyme transglutaminase, the protein was digested with use of an in vitro model of gastro-duodenal proteolysis in the presence or absence of physiologically relevant surfactants (phosphatidylcholine, PC; bile salts, BS). Significant differences were found between the rates of digestion of Na-Cas cross-linked in emulsion (adsorbed protein) and in solution. In emulsion, the digestion of a population of polypeptides of M(r) ca. 50-100 kDa was significantly retarded through the gastric digestion. The persistent interfacial polypeptides maintained the original emulsion droplet size and prevented the system from phase separating. Rapid pepsinolysis of adsorbed, non-cross-linked Na-Cas and its displacement by PC led to emulsion destabilization. These results suggest that structuring of emulsions by enzymatic cross-linking of the interfacial protein may affect the phase behavior of emulsion in the stomach and the gastric digestion rate in vivo. Measurements of ζ-potential revealed that BS displaced the remaining protein from the oil droplets during the simulated duodenal phase of digestion. Diffusion of the postdigestion emulsion droplets through ex vivo porcine intestinal mucus was only significant in the presence of BS due to the high negative charge these

In vivo and In vitro Evaluations of Intestinal Gabapentin Absorption

DEFF Research Database (Denmark)

Larsen, Malte Selch; Frølund, Sidsel; Nøhr, Martha Kampp

2015-01-01

of gabapentin by both in vivo and in vitro investigations METHODS: Pharmacokinetic parameters were determined following a range of intravenous (5-100 mg/kg) and oral doses (10-200 mg/kg) in rats. Transepithelial transport (50 μM-50 mM) and apical uptake of gabapentin (0.01-50 mM) were investigated in Caco-2...... cells. The effect of co-application of the LAT-inhibitor, BCH, and the b(0,+)-substrate, L-lysine, on intestinal transport of gabapentin was evaluated in vivo and in vitro. RESULTS: Gabapentin showed dose-dependent oral absorption kinetics and dose-independent disposition kinetics. Co-application of BCH...... inhibited intestinal absorption in vivo and apical uptake in vitro, whereas no effect was observed following co-application of L-lysine. CONCLUSIONS: The present study shows for the first time that BCH was capable of inhibiting intestinal absorption of gabapentin in vivo. Furthermore, in Caco-2 cell...

Effect of ageing on the gastro-intestinal transit of a lactulose-supplemented mixed solid-liquid meal in humans.

Science.gov (United States)

Wegener, M; Börsch, G; Schaffstein, J; Lüth, I; Rickels, R; Ricken, D

1988-01-01

Gastro-intestinal transit of a mixed solid-liquid meal containing wheat bread, scrambled eggs, coffee labelled with 99mTc, orange juice with lactulose and indigocarmine was evaluated in 21 young control (mean age 33.5 years) and 25 elderly subjects (mean age 81.7 years) without gastrointestinal complaints or severe medical illness. The rate of gastric emptying was determined by an anterior gamma camera technique, mouth-to-caecum transit by the hydrogen breath test and whole-gut transit by the first stool passage of indigocarmine. Gastric emptying was significantly prolonged in older subjects: t1/2 = 136 +/- (SEM) 13 versus 81 +/- 4 min; p less than 0.001. Concerning mouth-to-caecum or whole-gut transit time, significant differences between the two study groups were not detected.

[A rare differential diagnosis of a somatoform autonomous disorder of the gastro-intestinal tract: the hepatocellular liver carcinoma in childhood].

Science.gov (United States)

Voll, Renate

2008-07-01

A severely ill 11-year-old boy came to the child psychiatric outpatient department of the Fachkrankenhaus Neckargemünd with the diagnosis of a somatoform disorder. Main symptoms included nausea, vomiting, abdominal pain and diarrhoea. He wished to be examined in order to enter the Stephen-Hawking-School for physically handicapped children in the town of Neckargemünd. Manual examination revealed a palpable mass in the right upper quadrant of the abdomen, which was imaged as a tumour of the liver. During the subsequent operation, a 500 ml hepatocellular carcinoma was found. The symptoms of the hepatocellular carcinoma, which rarely occurs in childhood, can perfectly mimic those of a somatoform disorder of the gastro-intestinal tract.

Release, partitioning and stability of isoflavones from enriched custards during mouth, stomach and intestine in vitro simulations

NARCIS (Netherlands)

Sanz, T.; Luyten, J.M.J.G.

2006-01-01

Custard desserts were enriched with a soy germ extract as source of isoflavones and the influence of the thickening agent (starch or carboxymethylcellulose (CMC)) and the presence of fat on the release, partitioning and stability of the isoflavones after mouth, stomach and small intestine in vitro

The dose-response relation in human volunteers for gastro-intestinal pathogens

NARCIS (Netherlands)

Teunis PFM; Heijden OG van der; Giessen JWB van der; Havelaar AH; MGB

1996-01-01

Published data on infection of human hosts with various protozoa, bacteria, and viruses causing gastro-enteritis are used to establish a quantitative relationship between ingested dose and the risk of infection. For all data sets analysed, this relationship is determined by fitting either an

Sporadic ganglioneuromatosis of esophagogastric junction in a patient with gastro-esophageal reflux disorder and intestinal metaplasia.

Science.gov (United States)

Siderits, Richard; Hanna, Iman; Baig, Zahid; Godyn, Janusz-J

2006-12-28

A 58-year-old female with a recurrent history of upper abdominal pain and intermittent dysphagia underwent endoscopic evaluation that demonstrated an irregular and nodular esophago-gastric (EG) junction and grade I erosive esophagitis. Biopsies showed prominent intestinal metaplasia of Barrett's type without dysplasia, chronic inflammation and multiple aggregates of large cells within the mucosal lamina propria, some with spindle shaped nuclei. Immunohistochemistry stains for keratins AE-1/AE-3 were negative, while S-100 and NSE were positive. This, together with routine stains, was diagnostic for mucosal ganglioneuromatosis. The background of chronic inflammation with intestinal type metaplasia was consistent with long-term reflux esophagitis. No evidence of achalasia was seen. Biopsies of gastric antrum and fundus were unremarkable, without ganglioneural proliferation. Colonoscopy was unremarkable. No genetic syndromes were identified in the patient including familial adenomatous polyposis and multiple endocrine neoplasia type IIb (MEN IIb). Iansoprazole (Prevacid) was started by oral administration each day with partial relief of symptoms. Subsequent esophagogastroscopy repeated at 4 mo showed normal appearing EG junction. Esophageal manometry revealed a mild non-specific lower esophageal motility disorder. Mild motor dysfunction is seen with gastro-esophageal reflux disease (GERD) and we feel that the demonstration of localized ganglioneuromatosis was not likely related etiologically. In the absence of findings that might suggest neural hypertrophy, such as achalasia, the nodular mucosal irregularity seen with this instance of ganglioneuromatosis may, however, have exacerbated the patient's reflux.

Histologic definition of gastro-esophageal reflux disease.

Science.gov (United States)

Chandrasoma, Parakrama T

2013-07-01

To review recent data supporting the development of new histology-based definitions of gastro-esophageal reflux disease (GERD). Three precisely definable columnar epithelial types--cardiac, oxyntocardiac and intestinal--may be interposed between esophageal squamous epithelium and gastric oxyntic (acid secreting) mucosa. This enables definition of a new histologic concept: the squamo-oxyntic gap. The squamo-oxyntic gap is zero or very small in autopsies performed on patients without evidence of GERD. The gap progressively increases in length with the severity of GERD, indicating that the squamo-oxyntic gap is a marker for chronic GERD. The distal part of the gap lines gastric-type rugal folds and, therefore, is distal to the present endoscopic definition of the gastro-esophageal junction. I contend that this distal gap segment (which has esophageal submucosal glands) is actually the dilated distal esophagus; this is the pathologic correlate of destruction of the abdominal segment of the lower esophageal sphincter. The dilated distal esophagus is mistaken for 'gastric cardia' by present endoscopic definitions. I believe that these data support the adoption of novel histologic definitions of GERD as follows: the presence of any squamo-oxyntic gap defines GERD; the length of the gap is a measure of severity of chronic GERD; and the presence of intestinal metaplasia in the gap defines Barrett esophagus and cancer risk.

Transmesocolic double gastro-enteric fistulas due to ingestion of 28 magnets

Directory of Open Access Journals (Sweden)

Adrian Surd

2018-05-01

Full Text Available Introduction: Accidental ingestion of magnetic foreign bodies has become more common due to increased availability of objects and toys with magnetic elements. The majority of them traverse the gastrointestinal system spontaneously without complication. However, ingestion of multiple magnets may require surgical resolution. Magnet ingestion usually does not cause serious complications, but in case of multiple magnet ingestion or ingestion of magnet and a metal object, it could cause intestinal obstruction, fistula formation or even perforation. Case report: We report case of a transmesocolic double gastro-enteric fistula formation following ingestion of 28 small magnets in a 17 months old boy. No history of foreign body ingestion could be obtained from parents therefore the patient was treated conservatively in a pediatric clinic for vomiting, dehydration, upper respiratory tract infection and suspicion of upper digestive tract bleeding. After 48 h he was sent in our clinic for surgical evaluation. Intraoperatively double transmesocolic gastro-enteric fistula was found. After separation of de gastric and enteral walls, resection of gastric wall and intestinal segment containing the two perforations was performed, followed by gastric suture in two layers and entero-enteric anastomosis. A total of 28 magnets were removed from the stomach and small intestine. Conclusion: Single magnet ingestion is treated as non-magnetic foreign body. Multiple magnet ingestion should be closely monitored and surgical approach could be the best option to prevent or to cure its complications. Keywords: Ingestion, Magnetic foreign body, Multiple magnets, Intestinal fistula, Children

Factors associated with gastro-duodenal disease in patients undergoing upper GI endoscopy at the Korle-Bu Teaching Hospital, Accra, Ghana.

Science.gov (United States)

Archampong, Timothy N A; Asmah, Richard H; Wiredu, Edwin K; Gyasi, Richard K; Nkrumah, Kofi N

2016-06-01

There is a high prevalence of gastro-duodenal disease in sub-Saharan Africa. Peptic ulcer disease in dyspeptic patients, 24.5%, was comparable to prevalence of gastro-duodenal disease among symptomatic individuals in developed countries (12 - 25%). Limited data exists regarding its associated risk factors despite accumulating evidence indicating that gastroduodenal disease is common in Ghana. This study investigates risk factors associated with gastro-duodenal disease at the Korle-Bu Teaching Hospital, Accra, Ghana. This study utilized a cross-sectional design to consecutively recruit patients referred with upper gastro-intestinal symptoms for endoscopy. The study questionnaire was administered to study participants. Helicobacter pylori infection was confirmed by rapid-urease examination at endoscopy. Of 242 patients sampled; 64 had duodenal ulcer, 66 gastric ulcer, 27gastric cancer and 64 non-ulcer dyspepsia. Nineteen (19) had duodenal and gastric ulcer while 2 had gastric ulcer and cancer. A third (32.6%) of patients had history of NSAID-use. H. pyloriwas associated with gastric ulcer (p=0.033) and duodenal ulcer (p=0.001). There was an increased prevalence of duodenal ulcer in H. pylori-infected patients taking NSAIDs, P=0.003. H. pylori was a major risk factor for peptic ulcer disease. However, NSAID-related gastro-duodenal injury has been shown to be common in H. pylori infected patients. It highlights the need for awareness of the adverse gastro-intestinal effects in a H. pylori endemic area.

Development and application of a low volume, increased throughput in vitro model simulating the passage through small intestine

DEFF Research Database (Denmark)

Cieplak, Tomasz Maciej

are unevenly distributed along the GIT, ranging from 101-103 cells/g in the stomach, through 103-108 cells/g in the small intestine and up to 1012 cells/g in the colon. In the last decade, numerous studies have been conducted focussing on the faecal microbiota composition and its impact on the host health...... conditions (fed, fasted) and the presence of small intestine microbiota influence intestine persistence of probiotic bacteria. In the same manuscript, we described for the first time the fully functional in vitro model prototype called “The Smallest Intestine (TSI)”. The model proved to be a cost...... and naked cells in the small intestine was investigated in both fed and fasted conditions in the TSI model. Results indicated a protective effect of xanthan/gellan gum for L. plantarum and decreased viability of coated A. muciniphila due to the desiccation effect of coating, which probably caused leakage...

In vitro and in vivo evaluation of a water-in-oil microemulsion system for enhanced peptide intestinal delivery.

Science.gov (United States)

Liu, Dongyun; Kobayashi, Taku; Russo, Steven; Li, Fengling; Plevy, Scott E; Gambling, Todd M; Carson, Johnny L; Mumper, Russell J

2013-01-01

Peptide and protein drugs have become the new generation of therapeutics, yet most of them are only available as injections, and reports on oral local intestinal delivery of peptides and proteins are quite limited. The aim of this work was to develop and evaluate a water-in-oil (w/o) microemulsion system in vitro and in vivo for local intestinal delivery of water-soluble peptides after oral administration. A fluorescent labeled peptide, 5-(and-6)-carboxytetramethylrhodamine labeled HIV transactivator protein TAT (TAMRA-TAT), was used as a model peptide. Water-in-oil microemulsions consisting of Miglyol 812, Capmul MCM, Tween 80, and water were developed and characterized in terms of appearance, viscosity, conductivity, morphology, and particle size analysis. TAMRA-TAT was loaded and its enzymatic stability was assessed in modified simulated intestinal fluid (MSIF) in vitro. In in vivo studies, TAMRA-TAT intestinal distribution was evaluated using fluorescence microscopy after TAMRA-TAT microemulsion, TAMRA-TAT solution, and placebo microemulsion were orally gavaged to mice. The half-life of TAMRA-TAT in microemulsion was enhanced nearly three-fold compared to that in the water solution when challenged by MSIF. The treatment with TAMRA-TAT microemulsion after oral administration resulted in greater fluorescence intensity in all intestine sections (duodenum, jejunum, ileum, and colon) compared to TAMRA-TAT solution or placebo microemulsion. The in vitro and in vivo studies together suggested TAMRA-TAT was better protected in the w/o microemulsion in an enzyme-containing environment, suggesting that the w/o microemulsions developed in this study may serve as a potential delivery vehicle for local intestinal delivery of peptides or proteins after oral administration.

EGFR gene amplification is relatively common and associates with outcome in intestinal adenocarcinoma of the stomach, gastro-oesophageal junction and distal oesophagus

International Nuclear Information System (INIS)

Birkman, Eva-Maria; Ålgars, Annika; Lintunen, Minnamaija; Ristamäki, Raija; Sundström, Jari; Carpén, Olli

2016-01-01

Approximately 50 % of gastric adenocarcinomas belong to a molecular subgroup characterised by chromosomal instability and a strong association with the intestinal histological subtype. This subgroup typically contains alterations in the receptor tyrosine kinase–RAS pathway, for example EGFR or HER2 gene amplifications leading to protein overexpression. In clinical practice, HER2 overexpressing metastatic gastric cancer is known to respond to treatment with anti-HER2 antibodies. By contrast, anti-EGFR antibodies have not been able to provide survival benefit in clinical trials, which, however, have not included patient selection based on the histological subtype or EGFR gene copy number analysis of the tumours. To examine the role of EGFR as a potential biomarker, we studied the prevalence, clinicopathological associations as well as prognostic role of EGFR and HER2 expression and gene amplification in intestinal adenocarcinomas of the stomach, gastro-oesophageal junction and distal oesophagus. Tissue samples from 220 patients were analysed with EGFR and HER2 immunohistochemistry. Those samples with moderate/strong staining intensity were further analysed with silver in situ hybridization to quantify gene copy numbers. The results were associated with clinical patient characteristics and survival. Moderate/strong EGFR protein expression was found in 72/220 (32.7 %) and EGFR gene amplification in 31/220 (14.1 %) of the tumours, while moderate/strong HER2 protein expression was detected in 31/220 (14.1 %) and HER2 gene amplification in 29/220 (13.2 %) of the tumours. EGFR and HER2 genes were co-amplified in eight tumours (3.6 %). EGFR gene amplification was more common in tumours of distal oesophagus/gastro-oesophageal junction/cardia than in those of gastric corpus (p = 0.013). It was associated with shortened time to cancer recurrence (p = 0.026) and cancer specific survival (p = 0.033). EGFR gene amplification is relatively common in intestinal adenocarcinomas

Intestinal health in carnivores

NARCIS (Netherlands)

Hagen-Plantinga, Esther A.; Hendriks, W.H.

2015-01-01

The knowledge on the influence of gastro-intestinal (GI) microbiota on the health status of humans and animals is rapidly expanding. A balanced microbiome may provide multiple benefits to the host, like triggering and stimulation of the immune system, acting as a barrier against possible pathogenic

Sustained-release diclofenac potassium-loaded solid lipid microparticle based on solidified reverse micellar solution: in vitro and in vivo evaluation.

Science.gov (United States)

Chime, Salome Amarachi; Attama, Anthony Amaechi; Builders, Philip F; Onunkwo, Godswill C

2013-01-01

To formulate sustained-release diclofenac potassium-loaded solid lipid microparticles (SLMs) based on solidified reverse micellar solution (SRMS) and to evaluate the in vitro and in vivo properties. SRMS consisting of mixtures of Phospholipon® 90H and Softisan® 154 were used to formulate diclofenac potassium-loaded SLMs. Characterization based on the particle size and morphology, stability and encapsulation efficiency (EE%) were carried out on the SLMs. In vitro release was carried out in simulated intestinal fluid (pH 7.5). Anti-inflammatory and ulcerogenic properties were studied using rats. Maximum EE% of 95%, 94% and 93% were obtained for SLMs formulated with SRMS 1:1, 2:1 and 1:2, respectively. In vitro release showed about 85-90% drug release at 13 h. Diclofenac potassium-loaded SLMs showed good anti-inflammatory and gastro-protective properties. Diclofenac potassium-loaded SLMs based on SRMS could be used orally or parenterally under controlled conditions, for once daily administration.

Congruent Strain Specific Intestinal Persistence of Lactobacillus plantarum in an Intestine-Mimicking In Vitro System and in Human Volunteers.

NARCIS (Netherlands)

Bokhorst-van de Veen, H. van; Swam, I. van; Wels, M.W.; Bron, P.A.; Kleerebezem, M

2012-01-01

BACKGROUND: An important trait of probiotics is their capability to reach their intestinal target sites alive to optimally exert their beneficial effects. Assessment of this trait in intestine-mimicking in vitro model systems has revealed differential survival of individual strains of a species.

Congruent Strain Specific Intestinal Persistence of Lactobacillus plantarum in an Intestine-Mimicking In Vitro System and in Human Volunteers

NARCIS (Netherlands)

Bokhorst-van de Veen, van H.; Swam, van I.; Wels, M.; Bron, P.A.; Kleerebezem, M.

2012-01-01

BACKGROUND: An important trait of probiotics is their capability to reach their intestinal target sites alive to optimally exert their beneficial effects. Assessment of this trait in intestine-mimicking in vitro model systems has revealed differential survival of individual strains of a species.

In vitro gastrointestinal digestion increases the translocation of polystyrene nanoparticles in an in vitro intestinal co-culture model.

Science.gov (United States)

Walczak, Agata P; Kramer, Evelien; Hendriksen, Peter J M; Helsdingen, Richard; van der Zande, Meike; Rietjens, Ivonne M C M; Bouwmeester, Hans

2015-01-01

The conditions of the gastrointestinal tract may change the physicochemical properties of nanoparticles (NPs) and therewith the bioavailability of orally taken NPs. Therefore, we assessed the impact of in vitro gastrointestinal digestion on the protein corona of polystyrene NPs (PS-NPs) and their subsequent translocation across an in vitro intestinal barrier. A co-culture of intestinal Caco-2 and HT29-MTX cells was exposed to 50 nm PS-NPs of different charges (positive and negative) in two forms: pristine and digested in an in vitro gastrointestinal digestion model. In vitro digestion significantly increased the translocation of all, except the "neutral", PS-NPs. Upon in vitro digestion, translocation was 4-fold higher for positively charged NPs and 80- and 1.7-fold higher for two types of negatively charged NPs. Digestion significantly reduced the amount of protein in the corona of three out of four types of NPs. This reduction of proteins was 4.8-fold for "neutral", 3.5-fold for positively charged and 1.8-fold for one type of negatively charged PS-NPs. In vitro digestion also affected the composition of the protein corona of PS-NPs by decreasing the presence of higher molecular weight proteins and shifting the protein content of the corona to low molecular weight proteins. These findings are the first to report that in vitro gastrointestinal digestion significantly affects the protein corona and significantly increases the in vitro translocation of differently charged PS-NPs. These findings stress the importance of including the in vitro digestion in future in vitro intestinal translocation screening studies for risk assessment of orally taken NPs.

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to foods with reduced lactose content and decreasing gastro-intestinal discomfort caused by lactose intake in lactose intolerant individuals (ID 646, 1224, 1238, 1339

DEFF Research Database (Denmark)

Tetens, Inge

claims in relation to foods with reduced lactose content and decreasing gastro-intestinal discomfort caused by lactose intake in lactose intolerant individuals. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims...... and references that EFSA has received from Member States or directly from stakeholders. The food constituent that is the subject of the health claim is lactose, which should be “decreased” or “reduced” in foods in order to obtain the claimed effect. The Panel considers that lactose is sufficiently characterised....... The claimed effects are “lactose intolerance”, “decrease lactose malabsorption symptoms” and “lactose digestion”. The target population is assumed to be lactose intolerant individuals. The Panel assumes that the claimed effects refer to decreasing gastro-intestinal discomfort caused by lactose intake...

Analytical sensitivity of Tc99m radionuclide 'milk' scanning in the detection of gastro-oesophageal reflux

Energy Technology Data Exchange (ETDEWEB)

Paton, J.Y.; Nanayakkara, C.S.; Cosgriff, P.S.

1985-09-01

The analytical sensitivity of radionuclide ''milk'' scans for detecting gastro-oesophageal reflux (GOR) has been assessed using an in vitro simulation test. Five factors were found to affect the ability to detect simulated reflux: isotope concentration, absolute gamma camera sensitivity, absorber thickness overlying the ''oesophagus'' and volume and duration of reflux. We found that a critical volume-duration product must be exceeded for reflux to be detected. Radionuclide milk scanning appears to be much less sensitive in detecting transient events like GOR than might be expected from previously reported static simulation studies.

Angiographic diagnosis of hemorrhage tumours of the small intestine

International Nuclear Information System (INIS)

Vadon, G.; Ehngloner, L.; Petri, K.

1980-01-01

2 angiographic investigations in small intestine tumors, accompanied with hemorrhage are considered. Conclusion is made that the most suitable moment for estimation of small intestine hemorrhage, according to the proper and literature data, is selective angiography. Wide application of the technique for preoperative detection of gastro-inestinal hemorrhage is recommended

In Silico Prediction of Drug Dissolution and Absorption with variation in Intestinal pH for BCS Class II Weak Acid Drugs: Ibuprofen and Ketoprofen§

Science.gov (United States)

Tsume, Yasuhiro; Langguth, Peter; Garcia-Arieta, Alfredo; Amidon, Gordon L.

2012-01-01

The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS Class III and BCS class II have been proposed, particularly, BCS class II weak acids. However, a discrepancy between the in vivo- BE results and in vitro- dissolution results for a BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH=6.0. Further the experimental dissolution of ibuprofen tablets in the low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol L-1/pH) was dramatically reduced compared to the dissolution in SIF (the average buffer capacity 12.6 mmol L -1/pH). Thus these predictions for oral absorption of BCS class II acids indicate that the absorption patterns largely depend on the intestinal pH and buffer strength and must be carefully considered for a bioequivalence test. Simulation software may be very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard. PMID:22815122

Transformation of trollioside and isoquercetin by human intestinal flora in vitro.

Science.gov (United States)

Yuan, Ming; Shi, Duo-Zhi; Wang, Teng-Yu; Zheng, Shi-Qi; Liu, Li-Jia; Sun, Zhen-Xiao; Wang, Ru-Feng; Ding, Yi

2016-03-01

The present study was designed to determine the intestinal bacterial metabolites of trollioside and isoquercetin and their antibacterial activities. A systematic in vitro biotransformation investigation on trollioside and isoquercetin, including metabolite identification, metabolic pathway deduction, and time course, was accomplished using a human intestinal bacterial model. The metabolites were analyzed and identified by HPLC and HPLC-MS. The antibacterial activities of trollioside, isoquercetin, and their metabolites were evaluated using the broth microdilution method with berberine as a positive control, and their potency was measured as minimal inhibitory concentration (MIC). Our results indicated that trollioside and isoquercetin were metabolized by human intestinal flora through O-deglycosylation, yielding aglycones proglobeflowery acid and quercetin, respectively The antibacterial activities of both metabolites were more potent than that of their parent compounds. In conclusion, trollioside and isoquercetin are totally and rapidly transformed by human intestinal bacteria in vitro and the transformation favors the improvement of the antibacterial activities of the parent compounds. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Impact of the degree of cooking on starch digestibility of rice - An in vitro study.

Science.gov (United States)

Tamura, Masatsugu; Singh, Jaspreet; Kaur, Lovedeep; Ogawa, Yukiharu

2016-01-15

The impact of cooking degree on the starch digestibility of a non-waxy, cooked rice was examined through a simulated gastro-small intestinal in vitro digestion model. The starch hydrolysis of both non-homogenised and homogenised cooked rice samples during simulated digestion was also compared in order to examine the impact of grain structure on starch digestibility. Polished rice grains were cooked in boiling water for 10min (partially cooked) and 20min (fully cooked) to obtain samples of different cooking degree. No significant differences in the equilibrium starch hydrolysis (%) were observed among the partially and fully cooked grains, although significant differences were observed among the uncooked and cooked samples. The equilibrium starch hydrolysis (%) of homogenised rice was higher than its non-homogenised counterpart. These results showed that rice starch digestibility should not be affected by the cooking degrees related to starch gelatinisation, but was influenced by the modification/destruction of the grain structure during mechanical processing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Alternative Functional In Vitro Models of Human Intestinal Epithelia

Directory of Open Access Journals (Sweden)

Amanda L Kauffman

2013-07-01

Full Text Available Physiologically relevant sources of absorptive intestinal epithelial cells are crucial for human drug transport studies. Human adenocarcinoma-derived intestinal cell lines, such as Caco-2, offer conveniences of easy culture maintenance and scalability, but do not fully recapitulate in vivo intestinal phenotypes. Additional sources of renewable physiologically relevant human intestinal cells would provide a much needed tool for drug discovery and intestinal physiology. We sought to evaluate and compare two alternative sources of human intestinal cells, commercially available primary human intestinal epithelial cells (hInEpCs and induced pluripotent stem cell (iPSC-derived intestinal cells to Caco-2, for use in in vitro transwell monolayer intestinal transport assays. To achieve this for iPSC-derived cells, our previously described 3-dimensional intestinal organogenesis method was adapted to transwell differentiation. Intestinal cells were assessed by marker expression through immunocytochemical and mRNA expression analyses, monolayer integrity through Transepithelial Electrical Resistance (TEER measurements and molecule permeability, and functionality by taking advantage the well-characterized intestinal transport mechanisms. In most cases, marker expression for primary hInEpCs and iPSC-derived cells appeared to be as good as or better than Caco-2. Furthermore, transwell monolayers exhibited high TEER with low permeability. Primary hInEpCs showed molecule efflux indicative of P-glycoprotein transport. Primary hInEpCs and iPSC-derived cells also showed neonatal Fc receptor-dependent binding of immunoglobulin G variants. Primary hInEpCs and iPSC-derived intestinal cells exhibit expected marker expression and demonstrate basic functional monolayer formation, similar to or better than Caco-2. These cells could offer an alternative source of human intestinal cells for understanding normal intestinal epithelial physiology and drug transport.

Food-Derived Hemorphins Cross Intestinal and Blood–Brain Barriers In Vitro

Directory of Open Access Journals (Sweden)

Dorothée Domenger

2018-04-01

Full Text Available A qualitative study is presented, where the main question was whether food-derived hemorphins, i.e., originating from digested alimentary hemoglobin, could pass the intestinal barrier and/or the blood–brain barrier (BBB. Once absorbed, hemorphins are opioid receptor (OR ligands that may interact with peripheral and central OR and have effects on food intake and energy balance regulation. LLVV-YPWT (LLVV-H4, LVV-H4, VV-H4, VV-YPWTQRF (VV-H7, and VV-H7 hemorphins that were previously identified in the 120 min digest resulting from the simulated gastrointestinal digestion of hemoglobin have been synthesized to be tested in in vitro models of passage of IB and BBB. LC-MS/MS analyses yielded that all hemorphins, except the LLVV-H4 sequence, were able to cross intact the human intestinal epithelium model with Caco-2 cells within 5–60 min when applied at 5 mM. Moreover, all hemorphins crossed intact the human BBB model with brain-like endothelial cells (BLEC within 30 min when applied at 100 µM. Fragments of these hemorphins were also detected, especially the YPWT common tetrapeptide that retains OR-binding capacity. A cAMP assay performed in Caco-2 cells indicates that tested hemorphins behave as OR agonists in these cells by reducing cAMP production. We further provide preliminary results regarding the effects of hemorphins on tight junction proteins, specifically here the claudin-4 that is involved in paracellular permeability. All hemorphins at 100 µM, except the LLVV-H4 peptide, significantly decreased claudin-4 mRNA levels in the Caco-2 intestinal model. This in vitro study is a first step toward demonstrating food-derived hemorphins bioavailability which is in line with the growing body of evidence supporting physiological functions for food-derived peptides.

Social environment and weather during early life influence gastro-intestinal parasite loads in a group-living mammal.

Science.gov (United States)

Rödel, Heiko G; Starkloff, Anett

2014-10-01

Conditions experienced during early life have been frequently shown to exert long-term consequences on an animal's fitness. In mammals and birds, the time around and shortly after weaning is one of the crucial periods early in life. However, little is known about how social and abiotic environmental conditions experienced around this time affect fitness-related traits such as endoparasite loads. We studied consequences of social interactions and rainy weather conditions around and after weaning on gastro-intestinal nematode loads in juvenile European rabbits Oryctolagus cuniculus. Infestations with the gastric nematode Graphidium strigosum and with the intestinal nematode Passalurus ambiguus were higher in animals experiencing more rain during early life. This might have been due to the higher persistence of nematodes' infective stages outside the host body together with the animals' lower energy allocation for immune defence under more humid and thus energetically challenging conditions. In contrast, infestations with P. ambiguus were lower in animals with more positive social interactions with mother and litter siblings. We propose that social support provided by familiar group members buffered negative stress effects on immune function, lowering endoparasite infestations. This is supported by the negative correlation between positive social behaviour and serum corticosterone concentrations, indicating lower stress in juveniles which integrated more successfully into the social network of their group. In conclusion, the findings offer a pathway showing how differences in the abiotic environment and social life conditions experienced early in life could translate into long-term fitness consequences via the effects on endoparasite loads.

Survival of Lactobacillus acidophilus NCFM® and Bifidobacterium lactis HN019 encapsulated in chocolate during in vitro simulated passage of the upper gastrointestinal tract

DEFF Research Database (Denmark)

Klindt-Toldam, Stine; Larsen, Susanne K.; Saaby, Lasse

2016-01-01

Probiotic microorganisms are exposed to different types of stress both before and after consumption which strongly influences probiotic survival. Here the viability of 2 different probiotic bacteria incorporated in different types of chocolate was investigated during storage and passage of the up......Probiotic microorganisms are exposed to different types of stress both before and after consumption which strongly influences probiotic survival. Here the viability of 2 different probiotic bacteria incorporated in different types of chocolate was investigated during storage and passage...... of the upper gastro-intestinal tract using both a static and a dynamic gastric in vitro model. Lactobacillus acidophilus NCFM® and Bifidobacterium lactis HN019 equalling a total concentration of 2 × 108, 2 × 109 and 2 × 1010 CFU/g chocolate were added to samples of milk chocolate, 57% and 72% dark chocolate...... dairy and juice based probiotic products, chocolate was an excellent carrier for probiotic delivery, because of very good survival of probiotics during simulated passage of the upper GI tract. The viability of B. lactis was slightly higher than Lb. acidophilus and survival rates were >6.5 log CFU...

Study of probiotic potential of four wild Lactobacillus rhamnosus strains.

Science.gov (United States)

Tuo, Yanfeng; Zhang, Weiqin; Zhang, Lanwei; Ai, Lianzhong; Zhang, Yingchun; Han, Xue; Yi, Huaxi

2013-06-01

The four wild Lactobacillus rhamnosus strains were examined in vitro for resistance to simulated gastro and intestinal juices, adhesion to HT-29 cells, antagonistic activity against enteric pathogens and immunomodulating activity. The strains L. rhamnosus SB5L, J5L and IN1L were able to survive in simulated gastro juice while the strain L. rhamnosus SB31L lost viability exposed to simulated gastro juice for 3 h. The four strains had high viability in simulated small intestinal juice with little loss (<1.0 cycle reduction). The strains SB5L, J5L and IN1L antagonized against Escherichia coli ATCC 25922, Salmonella enterica serovar Typhimurium ATCC 14028, Shigella sonnei ATCC 25931. The strain L. rhamnosus IN1L had the highest adhesive capability to HT-29 cells in vitro (251 bacteria cells per 100 HT-29 cells) compared to the other three L. rhamnosus strains. The live bacteria, cell wall and DNA of the four L. rhamnosus induced the secretion of pro-inflammatory cytokines IL-12 (p70), IFN-γ and TNF-α by human peripheral blood mononuclear cells (PBMCs). The levels of IL-12 (p70), IFN-γ and TNF-α produced by stimulated PBMCs were significantly higher (P < 0.05) than those of the control. Those data indicated that the four L. rhamnosus strains have the potential as the probiotic for human being use, although further studies are still needed. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

In silico prediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen.

Science.gov (United States)

Tsume, Yasuhiro; Langguth, Peter; Garcia-Arieta, Alfredo; Amidon, Gordon L

2012-10-01

The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS class III and BCS class II have been proposed, in particular, BCS class II weak acids. However, a discrepancy between the in vivo BE results and in vitro dissolution results for BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH of 6.0. Further the experimental dissolution of ibuprofen tablets in a low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol l (-1) /pH) was dramatically reduced compared with the dissolution in SIF (the average buffer capacity 12.6 mmol l (-1) /pH). Thus these predictions for the oral absorption of BCS class II acids indicate that the absorption patterns depend largely on the intestinal pH and buffer strength and must be considered carefully for a bioequivalence test. Simulation software may be a very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard. Copyright © 2012 John Wiley & Sons, Ltd.

Evaluation of new gastro-intestinal prokinetic (ENGIP-II) study.

Science.gov (United States)

Walwaikar, Pradeep P; Kulkarni, Sujay S; Bargaje, Rahul S

2005-12-01

Non-ulcer dyspepsia is a common clinical disorder characterised by reduced gastric motility. Safety concerns have restricted use of currently available prokinetic drugs. Itopride is a new safer prokinetic drug with dopamine D2 antagonism and acetylcholinesterase inhibitory actions. The ENGIP-II study was conducted to investigate the efficacy, and safety of itopride in patients of non-ulcer dyspepsia. There were significant reductions in upper abdominal pain, heartburn frequency, gastro-oesophageal regurgitation, nausea, bloating, early satiety after meals at day 3 only; whereas significant improvements were noted in belching, anorexia at day 6 and in vomiting at day 9. Thus, ENGIP-II study shows that itopride was well tolerated patients and appears to be the drug of choice in patients with non-ulcer dyspepsia.

The role of metabolism in Diclofenac-induced intestinal toxicity in human ex vivo

NARCIS (Netherlands)

Niu, Xiaoyu; Makkinje, Miriam; de Graaf, Inge; Groothuis, Genoveva

2012-01-01

The use of Diclofenac (DCF: 2-(2,6-dichloranilino) phenyl acetic acid ), a non-steroidal anti-inflammatory drug is associated with severe gastro-intestinal side-effects. In vivo rat studies suggest that reactive metabolites of DCF, produced by the liver, play an important role in the intestinal

Survival and metabolic activity of the GanedenBC30 strain of Bacillus coagulans in a dynamic in vitro model of the stomach and small intestine.

Science.gov (United States)

Maathuis, A J H; Keller, D; Farmer, S

2010-03-01

We have investigated the survival and activity of GanedenBC(30) during passage through the upper gastro-intestinal tract. GanedenBC(30) was tested in a dynamic, validated, in vitro model of the stomach and small intestine (TIM-1) on survival and its potential to aid in digestion of milk protein, lactose and fructose. The survival of GanedenBC(30) was high (70%), although germination of the spores was minimal (<10%) under the conditions tested. Survival of the strain in the presence of lactose and fructose was markedly lower (56-59%) than in the absence of the sugars. The amount of digested milk protein available for absorption was somewhat higher (+0.2 g) when GanedenBC(30) was added to the milk. When GanedenBC(30) was tested with lactose or fructose added to the meal, the cumulative amount of lactate produced was slightly higher (+0.12-0.18 mmol) compared to the GanedenBC(30) alone. In conclusion, although the differences in survival of GanedenBC(30) are small, these results show the potential of GanedenBC(30) to aid in protein digestion and in the digestion of lactose and fructose. If a larger fraction of the Bacillus coagulans cells had germinated, the influence on protein and carbohydrate digestion would probably have been much greater. Importance of the findings: the potential of GanedenBC(30) to aid in the digestion of lactose and fructose could be used to prevent occurrence of intestinal symptoms in individuals sensitive to these carbohydrates.

Conversion of major soy isoflavone glucosides and aglycones in in vitro intestinal models

NARCIS (Netherlands)

Islam, M.A.; Punt, A.; Spenkelink, A.; Murk, A.J.; Leeuwen, F.X.R.; Rietjens, I.

2014-01-01

ScopeThis study compares conversion of three major soy isoflavone glucosides and their aglycones in a series of in vitro intestinal models. Methods and resultsIn an in vitro human digestion model isoflavone glucosides were not deconjugated, whereas studies in a Caco-2 transwell model confirmed that

Supersaturation of zafirlukast in fasted and fed state intestinal media with and without precipitation inhibitors

DEFF Research Database (Denmark)

Madsen, Cecilie Maria; Boyd, Ben; Rades, Thomas

2016-01-01

by 40%. The aim of this study was to investigate the effect of simulated fasted and fed state intestinal media as well as the effect of HPMC and PVP on the supersaturation and precipitation of ZA in vitro. Supersaturation of aZA was studied in vitro in a small scale setup using the μDiss Profiler......™. Several media were used for this study: One medium simulating the fasted state intestinal fluids and three media simulating different fed state intestinal fluids. Solid state changes of the drug were investigated by small angle x-ray scattering. The duration wherein aZA was maintained at a supersaturated...... simulated intestinal media, but the concentration during supersaturation was higher. It was thus not possible to predict any positive or negative food effects from the dissolution/precipitation curves from different media. Lipolysis products in the fed state simulated media seemed to cause both a negative...

Clinical significance of determination of blood gastro-intestinal hormones levels in small for gestational age newborns

International Nuclear Information System (INIS)

Rong Lijun; Chen Yongsheng

2007-01-01

Objective: To investigate the changes of plasma motilin, plasma somatostatin and serum gastrin levels after beginning oral feeding in 68 small for gestational age neonates (pre-term 36, full-term 32). Methods: Blood levels of somatostatin (SS), motilin and gastrin were determined with RIA before beginning of oral feeding and on 7 th day after birth in 68 small for gestational age neonates and 30 controls. Results: The blood levels of motilin and gastrin before feeding and on 7 th day in the small for gestational age neonates were significantly lower than those in the controls, while the SS levels were significantly higher. The serum levels of the hormones rose gradually after birth and on 7 th day were all significantly higher than those before feeding respectively (P th day levels were positively correlated with gestational age, original levels before feeding and early feeding. For gastrin, the levels were also positively correlated with the amount of feeding. In this study, early oral feeding was practiced in all the neonates without any adverse effect. Conclusion: Although the blood levels of gastro-intestinal hormones were lower in small for gestational age newborns, early oral feeding was practiced in all the neonates with no adverse effect observed and more rapid elevation of the hormone levels. Therefore, early oral feeding should be encouraged. (authors)

Intestinal Stem Cell Niche Insights Gathered from Both In Vivo and Novel In Vitro Models

Directory of Open Access Journals (Sweden)

Nikolce Gjorevski

2017-01-01

Full Text Available Intestinal stem cells are located at the base of the crypts and are surrounded by a complex structure called niche. This environment is composed mainly of epithelial cells and stroma which provides signals that govern cell maintenance, proliferation, and differentiation. Understanding how the niche regulates stem cell fate by controlling developmental signaling pathways will help us to define how stem cells choose between self-renewal and differentiation and how they maintain their undifferentiated state. Tractable in vitro assay systems, which reflect the complexity of the in vivo situation but provide higher level of control, would likely be crucial in identifying new players and mechanisms controlling stem cell function. Knowledge of the intestinal stem cell niche gathered from both in vivo and novel in vitro models may help us improve therapies for tumorigenesis and intestinal damage and make autologous intestinal transplants a feasible clinical practice.

Congruent strain specific intestinal persistence of Lactobacillus plantarum in an intestine-mimicking in vitro system and in human volunteers.

Directory of Open Access Journals (Sweden)

Hermien van Bokhorst-van de Veen

Full Text Available BACKGROUND: An important trait of probiotics is their capability to reach their intestinal target sites alive to optimally exert their beneficial effects. Assessment of this trait in intestine-mimicking in vitro model systems has revealed differential survival of individual strains of a species. However, data on the in situ persistence characteristics of individual or mixtures of strains of the same species in the gastrointestinal tract of healthy human volunteers have not been reported to date. METHODOLOGY/PRINCIPAL FINDINGS: The GI-tract survival of individual L. plantarum strains was determined using an intestine mimicking model system, revealing substantial inter-strain differences. The obtained data were correlated to genomic diversity of the strains using comparative genome hybridization (CGH datasets, but this approach failed to discover specific genetic loci that explain the observed differences between the strains. Moreover, we developed a next-generation sequencing-based method that targets a variable intergenic region, and employed this method to assess the in vivo GI-tract persistence of different L. plantarum strains when administered in mixtures to healthy human volunteers. Remarkable consistency of the strain-specific persistence curves were observed between individual volunteers, which also correlated significantly with the GI-tract survival predicted on basis of the in vitro assay. CONCLUSION: The survival of individual L. plantarum strains in the GI-tract could not be correlated to the absence or presence of specific genes compared to the reference strain L. plantarum WCFS1. Nevertheless, in vivo persistence analysis in the human GI-tract confirmed the strain-specific persistence, which appeared to be remarkably similar in different healthy volunteers. Moreover, the relative strain-specific persistence in vivo appeared to be accurately and significantly predicted by their relative survival in the intestine-mimicking in vitro

Role of intestinal brush border peptidases in the simulated digestion of milk proteins.

Science.gov (United States)

Picariello, Gianluca; Miralles, Beatriz; Mamone, Gianfranco; Sánchez-Rivera, Laura; Recio, Isidra; Addeo, Francesco; Ferranti, Pasquale

2015-05-01

This study aimed to assess the impact of the "often neglected" intestinal brush border membranes (BBMs) hydrolases on dietary peptides, exploring the possibility that the disintegration of proteins progressed in the small intestine up to a "core" of intrinsically stable oligopeptides, persisting independently on the up-stream breakdown. Samples of sodium caseinate, skim milk powder, and whey protein isolate were submitted to in vitro simulated gastropancreatic digestion using two different procedures: (i) a simplified model involving the main compartmental specific proteases; (ii) a static digestion method based on a frameset of parameters inferred from in vivo. The gastroduodenal digesta were further hydrolyzed with peptidases from porcine jejunal BBM. The peptidomes arising from the two digestion models, characterized by combined HPLC and MS techniques, differed to some extent. However, only specific protein domains survived digestion, among which are potential bioactive or immunogenic (food allergy) peptides. The degree of hydrolysis (DH) after BBM digestion (70-77%) practically did not differ between the digestion models and significantly increased the DH after duodenal steps. Any in vitro digestion model should be supplemented with a jejunal phase to realistically determine the bioaccessibility and bioavailability of dietary peptides. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Morphoelastic control of gastro-intestinal organogenesis: Theoretical predictions and numerical insights

Science.gov (United States)

Balbi, V.; Kuhl, E.; Ciarletta, P.

2015-05-01

With nine meters in length, the gastrointestinal tract is not only our longest, but also our structurally most diverse organ. During embryonic development, it evolves as a bilayered tube with an inner endodermal lining and an outer mesodermal layer. Its inner surface displays a wide variety of morphological patterns, which are closely correlated to digestive function. However, the evolution of these intestinal patterns remains poorly understood. Here we show that geometric and mechanical factors can explain intestinal pattern formation. Using the nonlinear field theories of mechanics, we model surface morphogenesis as the instability problem of constrained differential growth. To allow for internal and external expansion, we model the gastrointestinal tract with homogeneous Neumann boundary conditions. To establish estimates for the folding pattern at the onset of folding, we perform a linear stability analysis supplemented by the perturbation theory. To predict pattern evolution in the post-buckling regime, we perform a series of nonlinear finite element simulations. Our model explains why longitudinal folds emerge in the esophagus with a thick and stiff outer layer, whereas circumferential folds emerge in the jejunum with a thinner and softer outer layer. In intermediate regions like the feline esophagus, longitudinal and circumferential folds emerge simultaneously. Our model could serve as a valuable tool to explain and predict alterations in esophageal morphology as a result of developmental disorders or certain digestive pathologies including food allergies.

The symbiotic intestinal ciliates and the evolution of their hosts

NARCIS (Netherlands)

Moon-van der Staay, S.Y.; Staay, G.W. van der; Michalowski, T.; Jouany, J.P.; Pristas, P.; Javorsky, P.; Kisidayova, S.; Varadyova, Z.; McEwan, N.R.; Newbold, C.J.; Alen, T. van; Graaf, R. de; Schmid, M.; Huynen, M.A.; Hackstein, J.H.

2014-01-01

The evolution of sophisticated differentiations of the gastro-intestinal tract enabled herbivorous mammals to digest dietary cellulose and hemicellulose with the aid of a complex anaerobic microbiota. Distinctive symbiotic ciliates, which are unique to this habitat, are the largest representatives

Use of a combination of in vitro models to investigate the impact of chlorpyrifos and inulin on the intestinal microbiota and the permeability of the intestinal mucosa.

Science.gov (United States)

Réquilé, Marina; Gonzàlez Alvarez, Dubàn O; Delanaud, Stéphane; Rhazi, Larbi; Bach, Véronique; Depeint, Flore; Khorsi-Cauet, Hafida

2018-05-28

Dietary exposure to the organophosphorothionate pesticide chlorpyrifos (CPF) has been linked to dysbiosis of the gut microbiota. We therefore sought to investigate whether (i) CPF's impact extends to the intestinal barrier and (ii) the prebiotic inulin could prevent such an effect. In vitro models mimicking the intestinal environment (the SHIME®) and the intestinal mucosa (Caco-2/TC7 cells) were exposed to CPF. After the SHIME® had been exposed to CPF and/or inulin, we assessed the system's bacterial and metabolic profiles. Extracts from the SHIME®'s colon reactors were then transferred to Caco-2/TC7 cultures, and epithelial barrier integrity and function were assessed. We found that inulin co-treatment partially reversed CPF-induced dysbiosis and increased short-chain fatty acid production in the SHIME®. Furthermore, co-treatment impacted tight junction gene expression and inhibited pro-inflammatory signaling in the Caco-2/TC7 intestinal cell line. Whereas, an isolated in vitro assessment of CPF and inulin effects provides useful information on the mechanism of dysbiosis, combining two in vitro models increases the in vivo relevance.

Gastro esophageal reflux: an over investigated entity in neonates and infants.

Science.gov (United States)

Khan, Zahid Anwar; Ahmad, Sarfraz; Sheikh, Muhammad Younus

2010-12-01

To determine the outcome of clinically suspected gastro esophageal reflux in neonates and infants. To find a protocol for evaluation of these patients in order to reduce unnecessary radiation to neonates and infants. Fifty three neonates and infants of up to 1 year of age with clinical suspicion of gastro esophageal reflux (GER) were referred for Upper gastro intestinal barium studies. This retrospective descriptive case study was carried out over a period of one year starting from October, 2006 to September, 2007. Positive cases were followed for another one year to see the final outcome. The neonate and infants of upto one year of age, referred from Neonatal intensive care unit (NICU), Paediatric ward and Out Patient Department (OPD) were included in this study. Out of 53 cases 32 were positive for G.E.R and no reflux could be identified in rest of the patients. Out of these positive cases only 4 had massive or severe G.E.R. These patients were prescribed conservative and medical treatment and were advised to follow up in the O.P.D where on subsequent follow ups the medical treatment was stopped as there were no further complaints .These patients showed normal weight gain on subsequent O.P.D visits. Other positive cases only had mild to moderate G.E.R and they were managed conservatively. These patients showed normal weight gain on subsequent O.P.D visits with complete resolution of symptoms. Regurgitation or gastro esophageal reflux is a common finding in the first 3 months of life (especially in preterm infants) and usually resolves by 6-12 months of age and should not be over investigated.

Transformation of intestinal stem cells into gastric stem cells on loss of transcription factor Cdx2

NARCIS (Netherlands)

Simmini, Salvatore; Bialecka, Monika; Huch, Meritxell; Kester, Lennart; van de Wetering, Marc; Sato, Toshiro; Beck, Felix; van Oudenaarden, Alexander; Clevers, Hans; Deschamps, Jacqueline

2014-01-01

The endodermal lining of the adult gastro-intestinal tract harbours stem cells that are responsible for the day-to-day regeneration of the epithelium. Stem cells residing in the pyloric glands of the stomach and in the small intestinal crypts differ in their differentiation programme and in the gene

Effect of temperature and relative humidity on stability following simulated gastro-intestinal digestion of microcapsules of Bordo grape skin phenolic extract produced with different carrier agents.

Science.gov (United States)

Kuck, Luiza Siede; Wesolowski, Júlia Lerina; Noreña, Caciano Pelayo Zapata

2017-09-01

The stability of microparticles of Bordo grape skin aqueous extract, produced by spray-drying and freeze-drying using polydextrose (5%) and partially hydrolyzed guar gum (5%), was evaluated under accelerated conditions (75 and 90% relative humidity, at 35, 45, and 55°C for 35days) and simulated gastrointestinal digestion. The temperature had a significant effect on the reduction of phenolics content, with retentions varying from 82.5 to 93.5%. The retention of total monomer anthocyanins were in the range of 3.9-42.3%. The antioxidant activity had a final retention of 38.5-59.5%. In the simulated gastrointestinal digestion, a maximum release was observed for the phenolic compounds in the intestinal phase (90.6% for the spray-dried powder and 94.9% for the freeze-dried powder), as well as the antioxidant activity (69.4% for the spray-dried powder and 67.8% for the freeze-dried powder). However, a reduction of monomeric anthocyanins was observed in the intestinal phase. Copyright © 2017 Elsevier Ltd. All rights reserved.

Innovative methods to study human intestinal drug metabolism in vitro : Precision-cut slices compared with Ussing chamber preparations

NARCIS (Netherlands)

van de Kerkhof, Esther G.; Ungell, Anna-Lena B.; Sjoberg, Asa K.; de Jager, Marina H.; Hilgendorf, Constanze; de Graaf, Inge A. M.; Groothuis, Geny M. M.

2006-01-01

Predictive in vitro methods to investigate drug metabolism in the human intestine using intact tissue are of high importance. Therefore, we studied the metabolic activity of human small intestinal and colon slices and compared it with the metabolic activity of the same human intestinal segments

Prevalence and Spectrum of Gastro Esophageal Reflux Disease in Bronchial Asthma.

Science.gov (United States)

Rameschandra, Sahoo; Acharya, Vishak; Kunal; Vishwanath, Tantry; Ramkrishna, Anand; Acharya, Preetam

2015-10-01

There exists a complex interplay between asthma and gastroesophageal reflux disease. Both these diseases are known to aggravate each other and amelioration of one is necessary for the control of the other. There is a paucity of studies in Indian population on this subject. To evaluate the clinical features and the endoscopic findings of the upper gastrointestinal tract in patients with bronchial asthma. Study was conducted at KMC group of hospitals, Mangalore in the Department of chest medicine in association with Department of gastroenterology. Subjects included 50 cases of bronchial asthma and controls were 58 non asthmatic patients with allergic rhinitis and chronic urticaria. All patients were queried about presence or absence of symptoms of upper gastro intestinal tract disorders by gastro oesophageal reflux disease (GERD) questionnaire and all the included patients underwent upper gastro intestinal endoscopy. The study showed that symptoms of gastroesophageal reflux were significantly more in asthmatics (52%) as compared to the controls (28%). The common presenting features of gastroesophageal reflux in asthmatics were heartburn (40%) retrosternal pain (24%), nocturnal cough (18%), dyspepsia (16%) and regurgitation (14%) and the above symptoms were significantly more common in asthmatics as compared to controls. Gastroesophageal reflux disease was found to be significantly more common in the asthmatics (58%) as compared to the control group where it was present in 32.75% of the subjects. Clinical or endoscopic evidence of any upper gastrointestinal disorder was found in 68% of the asthmatics as compared to 37.93% of the controls. This difference was found to be statistically significant. The study showed that gastroesophageal reflux disease was significantly more in asthmatics as compared to the controls. Upper gastrointestinal symptoms were more common in asthmatics as against controls. Clinical or endoscopic evidence of upper gastrointestinal disorder and

Bystander protein protects potential vaccine-targeting ligands against intestinal proteolysis.

Science.gov (United States)

Reuter, Fabian; Bade, Steffen; Hirst, Timothy R; Frey, Andreas

2009-07-20

Endowing mucosal vaccines with ligands that target antigen to mucosal lymphoid tissues may improve immunization efficacy provided that the ligands withstand the proteolytic environment of the gastro-intestinal tract until they reach their destination. Our aim was to investigate whether and how three renowned ligands - Ulex europaeus agglutinin I and the B subunits of cholera toxin and E. coli heat-labile enterotoxin - master this challenge. We assessed the digestive power of natural murine intestinal fluid (natIF) using assays for trypsin, chymotrypsin and pancreatic elastase along with a test for nonspecific proteolysis. The natIF was compared with simulated murine intestinal fluid (simIF) that resembled the trypsin, chymotrypsin and elastase activities of its natural counterpart but lacked or contained albumins as additional protease substrates. The ligands were exposed to the digestive fluids and degradation was determined. The studies revealed that (i) the three pancreatic endoproteases constitute only one third of the total protease activity of natIF and (ii) the ligands resist proteolysis in natIF and protein-enriched simIF over 3 h but (iii) are partially destroyed in simIF that lacks additional protease substrate. We assume that the proteins of natIF are preferred substrates for the intestinal proteases and thus can protect vaccine-targeting ligands from destruction.

In Vitro and in Vivo Selection of Potentially Probiotic Lactobacilli From Nocellara del Belice Table Olives

Directory of Open Access Journals (Sweden)

Barbara Guantario

2018-03-01

Full Text Available Table olives are increasingly recognized as a vehicle as well as a source of probiotic bacteria, especially those fermented with traditional procedures based on the activity of indigenous microbial consortia, originating from local environments. In the present study, we report characterization at the species level of 49 Lactic Acid Bacteria (LAB strains deriving from Nocellara del Belice table olives fermented with the Spanish or Castelvetrano methods, recently isolated in our previous work. Ribosomal 16S DNA analysis allowed identification of 4 Enterococcus gallinarum, 3 E. casseliflavus, 14 Leuconostoc mesenteroides, 19 Lactobacillus pentosus, 7 L. coryniformis, and 2 L. oligofermentans. The L. pentosus and L. coryniformis strains were subjected to further screening to evaluate their probiotic potential, using a combination of in vitro and in vivo approaches. The majority of them showed high survival rates under in vitro simulated gastro-intestinal conditions, and positive antimicrobial activity against Salmonella enterica serovar Typhimurium, Listeria monocytogenes and enterotoxigenic Escherichia coli (ETEC pathogens. Evaluation of antibiotic resistance to ampicillin, tetracycline, chloramphenicol, or erythromycin was also performed for all selected strains. Three L. coryniformis strains were selected as very good performers in the initial in vitro testing screens, they were antibiotic susceptible, as well as capable of inhibiting pathogen growth in vitro. Parallel screening employing the simplified model organism Caenorhabditis elegans, fed the Lactobacillus strains as a food source, revealed that one L. pentosus and one L. coryniformis strains significantly induced prolongevity effects and protection from pathogen-mediated infection. Moreover, both strains displayed adhesion to human intestinal epithelial Caco-2 cells and were able to outcompete foodborne pathogens for cell adhesion. Overall, these results are suggestive of beneficial

Branchial cadmium and copper binding and intestinal cadmium uptake in wild yellow perch (Perca flavescens) from clean and metal-contaminated lakes

International Nuclear Information System (INIS)

Klinck, J.S.; Green, W.W.; Mirza, R.S.; Nadella, S.R.; Chowdhury, M.J.; Wood, C.M.; Pyle, G.G.

2007-01-01

Branchial binding kinetics and gastro-intestinal uptake of copper and cadmium where examined in yellow perch (Perca flavescens) from a metal-contaminated lake (Hannah Lake, Sudbury, Ontario, Canada) and an uncontaminated lake (James Lake, North Bay, Ontario, Canada). An in vivo approach was taken for gill binding comparisons while an in vitro gut binding assay was employed for gastro-intestinal tract (GIT) uptake analysis. By investigating metal uptake at the gill and the gut we cover the two main routes of metal entry into fish. Comparisons of water and sediment chemistries, metal burdens in benthic invertebrate, and metal burdens in the livers of perch from the two study lakes clearly show that yellow perch from Hannah L. are chronically exposed to a highly metal-contaminated environment compared to a reference lake. We found that metal-contaminated yellow perch showed no significant difference in gill Cd binding compared to reference fish, but they did show significant decreases in new Cd binding and absorption in their GITs. The results show that gill Cd binding may involve low-capacity, high-affinity binding sites, while gastro-intestinal Cd uptake involves binding sites that are high-capacity, low-affinity. From this we infer that Cd may be more critically controlled at the gut rather than gills. Significant differences in branchial Cu binding (increased binding) were observed in metal-contaminated yellow perch. We suggest that chronic waterborne exposure to Cu (and/or other metals) may be the dominant influence in gill Cu binding rather than chronic exposure to high Cu diets. We give supporting evidence that Cd is taken up in the GIT, at least in part, by a similar pathway as Ca 2+ , principally that elevated dietary Ca 2+ reduces Cd binding and uptake. Overall our study reveals that metal pre-exposure via water and diet can alter uptake kinetics of Cu and Cd at the gill and/or the gut

Branchial cadmium and copper binding and intestinal cadmium uptake in wild yellow perch (Perca flavescens) from clean and metal-contaminated lakes

Energy Technology Data Exchange (ETDEWEB)

Klinck, J.S. [Department of Biology, McMaster University, Hamilton, Ont. L8S 4K1 (Canada)], E-mail: klinckjs@mcmaster.ca; Green, W.W.; Mirza, R.S. [Department of Biology, McMaster University, Hamilton, Ont. L8S 4K1 (Canada); Department of Biology, Nipissing University, North Bay, Ont. P1B 8L7 (Canada); Nadella, S.R.; Chowdhury, M.J.; Wood, C.M. [Department of Biology, McMaster University, Hamilton, Ont. L8S 4K1 (Canada); Pyle, G.G. [Department of Biology, Nipissing University, North Bay, Ont. P1B 8L7 (Canada)

2007-08-30

Branchial binding kinetics and gastro-intestinal uptake of copper and cadmium where examined in yellow perch (Perca flavescens) from a metal-contaminated lake (Hannah Lake, Sudbury, Ontario, Canada) and an uncontaminated lake (James Lake, North Bay, Ontario, Canada). An in vivo approach was taken for gill binding comparisons while an in vitro gut binding assay was employed for gastro-intestinal tract (GIT) uptake analysis. By investigating metal uptake at the gill and the gut we cover the two main routes of metal entry into fish. Comparisons of water and sediment chemistries, metal burdens in benthic invertebrate, and metal burdens in the livers of perch from the two study lakes clearly show that yellow perch from Hannah L. are chronically exposed to a highly metal-contaminated environment compared to a reference lake. We found that metal-contaminated yellow perch showed no significant difference in gill Cd binding compared to reference fish, but they did show significant decreases in new Cd binding and absorption in their GITs. The results show that gill Cd binding may involve low-capacity, high-affinity binding sites, while gastro-intestinal Cd uptake involves binding sites that are high-capacity, low-affinity. From this we infer that Cd may be more critically controlled at the gut rather than gills. Significant differences in branchial Cu binding (increased binding) were observed in metal-contaminated yellow perch. We suggest that chronic waterborne exposure to Cu (and/or other metals) may be the dominant influence in gill Cu binding rather than chronic exposure to high Cu diets. We give supporting evidence that Cd is taken up in the GIT, at least in part, by a similar pathway as Ca{sup 2+}, principally that elevated dietary Ca{sup 2+} reduces Cd binding and uptake. Overall our study reveals that metal pre-exposure via water and diet can alter uptake kinetics of Cu and Cd at the gill and/or the gut.

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to fructo-oligosaccharides (FOS) and decreasing potentially pathogenic gastro-intestinal microorganisms (ID 781), pursuant to Article 13(1) of Regulation (EC) No 1924/2006

DEFF Research Database (Denmark)

Tetens, Inge

claims in relation to fructo-oligosaccharides and decreasing potentially pathogenic gastro-intestinal microorganisms. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims and references that EFSA has received from......Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006. This opinion addresses the scientific substantiation of health...... conclusions could be drawn for the scientific substantiation of the claim were provided. On the basis of the data presented, the Panel concludes that a cause and effect relationship has not been established between the consumption of fructo-oligosaccharides and decreasing potentially pathogenic gastro...

Improved anticoagulant effect of fucosylated chondroitin sulfate orally administered as gastro-resistant tablets.

Science.gov (United States)

Fonseca, Roberto J C; Sucupira, Isabela D; Oliveira, Stephan Nicollas M C G; Santos, Gustavo R C; Mourão, Paulo A S

2017-04-03

Fucosylated chondroitin sulfate (FucCS) is a potent anticoagulant polysaccharide extracted from sea cucumber. Its anticoagulant activity is attributed to the presence of unique branches of sulfated fucose. Although this glycosaminoglycan exerts an antithrombotic effect following oral administration, high doses are necessary to achieve the maximum effect. The diminished activity of FucCS following oral administration is likely due to its degradation in the gastrointestinal tract and its limited ability to cross the intestinal cell membranes. The latter aspect is particularly difficult to overcome. However, gastro-resistant tablet formulation may help limit the degradation of FucCS in the gastrointestinal tract. In the present work, we found that the oral administration of FucCS as gastro-resistant tablets produces a more potent and prolonged anticoagulant effect compared with its administration as an aqueous solution, with no significant changes in the bleeding tendency or arterial blood pressure. Experiments using animal models of arterial thrombosis initiated by endothelial injury demonstrated that FucCS delivered as gastro-protective tablets produced a potent antithrombotic effect, whereas its aqueous solution was ineffective. However, there was no significant difference between the effects of FucCS delivered as gastro-resistant tablets or as aqueous solution in a venous thrombosis model, likely due to the high dose of thromboplastin used. New oral anticoagulants tested in these experimental models for comparison showed significantly increased bleeding tendencies. Our study provides a framework for developing effective oral anticoagulants based on sulfated polysaccharides from marine organisms. The present results suggest that FucCS is a promising oral anticoagulant.

In vitro intestinal bioaccessibility of alkylglycerols versus triacylglycerols as vehicles of butyric acid.

Science.gov (United States)

Martín, Diana; Morán-Valero, María I; Señoráns, Francisco J; Reglero, Guillermo; Torres, Carlos F

2011-03-01

Butyric acid has been the subject of much attention last years due to its bioactivity. However, the potential advantages of butyrate are limited by the problem to reach enough plasma concentrations; therefore, pro-drugs have been proposed as an alternative to natural butyrate. A comparative study on in vitro intestinal digestion of 2,3-dibutyroil-1-O-octadecyl glycerol (D-SCAKG) and tributyrin (TB), as potential pro-drugs of butyric acid, was performed. Aliquots were taken at different times of digestion for studying the extent and rate of hydrolysis of both substrates. The micellar phase (MP) and oily phase (OP) formed in the digestion media were separated and their composition in lipid products was analyzed. Initially, it was confirmed that the in vitro model reproduced physiological results by testing against olive oil as a standard lipid. The progress of in vitro intestinal digestion of D-SCAKG was slower than that of TB. TB hydrolyzed completely to butyric acid, whereas D-SCAKG mainly yielded 2-butyroil-1-O-octadecyl glycerol (M-SCAKG), followed by butyric acid and 1-O-octadecyl glycerol (AKG). The MP from both substrates mainly consisted of butyric acid. Minor levels of M-SCAKG and AKG were also found in the MP after hydrolysis of D-SCAKG, the M-SCAKG being mainly distributed in the OP. Therefore, D-SCAKG produced a stable form of esterified butyric acid as M-SCAKG after in vitro intestinal digestion, unlike TB. Additionally, such a product would integrate both bioactive compounds, butyric acid and alkylglycerol, within the same molecule. Free butyric acid and AKG would be also released, which are lipid products of interest as well.

Translocation of differently sized and charged polystyrene nanoparticles in in vitro intestinal cell models of increasing complexity

NARCIS (Netherlands)

Walczak, A.P.; Kramer, E.; Hendriksen, P.J.M.; Tromp, P.; Helsper, J.P.F.G.; Zande, M. van der; Rietjens, I.M.C.M.; Bouwmeester, H.

2015-01-01

Intestinal translocation is a key factor for determining bioavailability of nanoparticles (NPs) after oral uptake. Therefore, we evaluated three in vitro intestinal cell models of increasing complexity which might affect the translocation of NPs: a mono-culture (Caco-2 cells), a co-culture with

In Vitro Studies on the Absorption and Interactions of Zinc, Copper ...

African Journals Online (AJOL)

Background: The exact details of the processes of trace metals absorption and interactions in the gastro intestinal tract remain uncertain. Absorption for the most part, takes places in the small intestine. The exact site of maximum absorption, as defined either by kinetic rate or quantity has not been clearly defined. Similarly ...

Optimization of micro-fabricated porous membranes for intestinal epithelial cell culture and in vitro modeling of the human intestinal barrier

Science.gov (United States)

Nair Gourikutty Sajay, Bhuvanendran; Yin, Chiam Su; Ramadan, Qasem

2017-12-01

In vitro modeling of organs could provide a controlled platform for studying physiological events and has great potential in the field of pharmaceutical development. Here, we describe the characterization of in vitro modeling of the human intestinal barrier mimicked using silicon porous membranes as a substrate. To mimic an intestinal in vivo setup as closely as possible, a porous substrate is required in a dynamic environment for the cells to grow rather than a static setup with an impermeable surface such as a petri dish. In this study, we focus on the detailed characterization of Caco-2 cells cultured on a silicon membrane with different pore sizes as well as the effect of dynamic fluid flow on the model. The porous silicon membrane together with continuous perfusion of liquid applying shear stress on the cells enhances the differentiation of polarized cells by providing access to the both their basal and apical surfaces. Membranes with pore sizes of 0.5-3 µm were used and a shear stress of ~0.03 dyne cm-2 was created by applying a low flow rate of 20 nl s-1. By providing these optimized conditions, cells were able to differentiate with columnar morphology, which developed microvilli structures on their apical side and tight junctions between adjacent cells like those in a healthy human intestinal barrier. In this setup, it is possible to study the important cellular functions of the intestine such as transport, absorption and secretion, and thus this model has great potential in drug screening.

Seasonal egg output of gastro-intestinal parasites in wild ungulates in a mediterranean area (central Italy

Directory of Open Access Journals (Sweden)

Marta Magi

2006-03-01

Full Text Available Abstract Seasonal egg (or oocyst output of gastro-intestinal parasites of wild ungulates was studied in a Mediterranean protected area, the Monti Livornesi Park (Livorno, Tuscany region, Central Italy. Samples of faeces of wild boars (Sus scrofa and mouflons (Ovis ammon were collected monthly for one year. The observed trends of egg output were analysed taking into account seasonal variations of temperature and rainfall, life-cycle and survival strategy of parasites, and health condition of hosts. In our Mediterranean study area, the peaks of egg output appear in different months according to different biology and survival strategies of parasites. Riassunto Emissione stagionale di uova di parassiti gastrointestinali in cinghiali (Sus scrofa e in mufloni (Ovis ammon di un’area mediterranea (Italia centrale. E' stata studiata l'emissione stagionale di uova (o oocisti di parassiti nelle feci di ungulati selvatici in una zona mediterranea protetta, il Parco dei Monti Livornesi (Livorno, Toscana, Italia Centrale. Per un anno sono stati raccolti mensilmente campioni di feci di Cinghiale (Sus scrofa e di Muflone (Ovis ammon. Gli andamenti osservati di emissione di uova sono stati analizzati tenendo conto delle variazioni di temperatura e piovosità stagionali, del ciclo biologico e della strategia di sopravvivenza dei parassiti, e delle condizioni sanitarie dell'ospite. E’ risultato che in una zona mediterranea come quella considerata i picchi di emissione di uova appaiono in mesi differenti in relazione alla biologia e alle strategie di sopravvivenza dei diversi parassiti.

Dietary fibers from mushroom Sclerotia: 2. In vitro mineral binding capacity under sequential simulated physiological conditions of the human gastrointestinal tract.

Science.gov (United States)

Wong, Ka-Hing; Cheung, Peter C K

2005-11-30

The in vitro mineral binding capacity of three novel dietary fibers (DFs) prepared from mushroom sclerotia, namely, Pleurotus tuber-regium, Polyporous rhinocerus, and Wolfiporia cocos, to Ca, Mg, Cu, Fe, and Zn under sequential simulated physiological conditions of the human stomach, small intestine, and colon was investigated and compared. Apart from releasing most of their endogenous Ca (ranged from 96.9 to 97.9% removal) and Mg (ranged from 95.9 to 96.7% removal), simulated physiological conditions of the stomach also attenuated the possible adverse binding effect of the three sclerotial DFs to the exogenous minerals by lowering their cation-exchange capacity (ranged from 20.8 to 32.3%) and removing a substantial amount of their potential mineral chelators including protein (ranged from 16.2 to 37.8%) and phytate (ranged from 58.5 to 64.2%). The in vitro mineral binding capacity of the three sclerotial DF under simulated physiological conditions of small intestine was found to be low, especially for Ca (ranged from 4.79 to 5.91% binding) and Mg (ranged from 3.16 to 4.18% binding), and was highly correlated (r > 0.97) with their residual protein contents. Under simulated physiological conditions of the colon with slightly acidic pH (5.80), only bound Ca was readily released (ranged from 34.2 to 72.3% releasing) from the three sclerotial DFs, and their potential enhancing effect on passive Ca absorption in the human large intestine was also discussed.

Gastro-retentive drug delivery systems and their in vivo success: A recent update

Directory of Open Access Journals (Sweden)

Uttam Kumar Mandal

2016-10-01

Full Text Available Gastro-retentive drug delivery system (GRDDS has gained immense popularity in the field of oral drug delivery recently. It is a widely employed approach to retain the dosage form in the stomach for an extended period of time and release the drug slowly that can address many challenges associated with conventional oral delivery, including poor bioavailability. Different innovative approaches like magnetic field assisted gastro-retention, plug type swelling system, muco-adhesion technique, floating system with or without effervescence are being applied to fabricate GRDDS. Apart from in vitro characterization, successful GRDDS development demands well designed in vivo study to establish enhanced gastro-retention and prolonged drug release. Gama scintigraphy and MRI are popular techniques to evaluate in vivo gastric residence time. However, checking of their overall in-vivo efficacy still remains a major challenge for this kind of dosage form, especially in small animals like mice or rat. Reported in vivo studies with beagle dogs, rabbits, and human subjects are only a handful in spite of a large number of encouraging in vitro results. In spite of the many advantages, high subject variations in gastrointestinal physiological condition, effect of food, and variable rate of gastric emptying time are the challenges that limit the number of available GRDDS in the market. This review article highlights the in vivo works of GRDDS carried out in the recent past, including their limitations and challenges that need to be overcome in the near future.

Analyzing the functionality of the human intestinal microbiota by stable isotope probing

NARCIS (Netherlands)

Kovatcheva, P.P.

2010-01-01

Key words: gut bacteria, dietary carbohydrates, digestion, RNA-SIP, TIM-2, HITChip, human trial

The human gastro-intestinal (GI) tract comprises a series of complex and dynamic organs ranging from the stomach to the distal colon, which harbor immense microbial assemblages, with

Detection of gastro-oesophageal reflux disease

International Nuclear Information System (INIS)

Christiansen, T.; Ravnsbaek, J.; Toettrup, A.; Funch-Jensen, P.; Thommesen, P.; Aarhus Kommunehospital

1986-01-01

In a prospective study a barium examination combined with food stimulation was compared with the acid reflux test in 30 consecutive patients with symptoms of gastro-oesophageal reflux. Both methods were further compared with endoscopy and histology. Gastro-oesophageal reflux could be demonstrated by the radiologic examination in 22 patients and by the acid reflux test in 23 patients. By combining the two methods gastro-oesophageal reflux could be demonstrated in 27 patients. Comparing the two methods with symptoms, endoscopy, and histology they seemed to be of equal value. Accordingly, a food-stimulated barium examination is recommended as the first method for demonstrating gastro-oesophageal reflux because it is simple and well-tolerated by the patient. (orig.)

Multi-kinetics and site-specific release of gabapentin and flurbiprofen from oral fixed-dose combination: in vitro release and in vivo food effect.

Science.gov (United States)

Sonvico, Fabio; Conti, Chiara; Colombo, Gaia; Buttini, Francesca; Colombo, Paolo; Bettini, Ruggero; Barchielli, Marco; Leoni, Barbara; Loprete, Luca; Rossi, Alessandra

2017-09-28

In this work, a fixed-dose combination of gabapentin and flurbiprofen formulated as multilayer tablets has been designed, developed and studied in vitro and in vivo. The aim was to construct a single dosage form of the two drugs, able to perform a therapeutic program involving three release kinetics and two delivery sites, i.e., immediate release of gabapentin, intra-gastric prolonged release of gabapentin and intestinal (delayed) release of flurbiprofen. An oblong three-layer tablet was manufactured having as top layer a floating hydrophilic polymeric matrix for gastric release of gabapentin, as middle layer a disintegrating formulation for immediate release of a gabapentin loading dose and as bottom layer, an uncoated hydrophilic polymeric matrix, swellable but insoluble in gastric fluids, for delayed and prolonged release of flurbiprofen in intestinal environment. The formulations were studied in vitro and in vivo in healthy volunteers. The in vitro release rate assessment confirmed the programmed delivery design. A significant higher bioavailability of gabapentin administered 30min after meal, compared to fasting conditions or to dose administration 10min before meal, argued in favor of the gastro-retention of gabapentin prolonged release layer. The two drugs were delivered at different anatomical sites, since the food presence prolonged the gastric absorption of gabapentin from the floating layer and delayed the flurbiprofen absorption. The attainment of a successful delayed release of flurbiprofen was realized by a matrix based on a polymers' combination. The combined use of three hydrophilic polymers with different pH sensitivity provided the dosage form layer containing flurbiprofen with gastro-resistant characteristics without the use of film coating. Copyright © 2017 Elsevier B.V. All rights reserved.

In-vitro analysis of APA microcapsules for oral delivery of live bacterial cells.

Science.gov (United States)

Chen, H; Ouyang, W; Jones, M; Haque, T; Lawuyi, B; Prakash, S

2005-08-01

Oral administration of microcapsules containing live bacterial cells has potential as an alternative therapy for several diseases. This article evaluates the suitability of the alginate-poly-L-lysine-alginate (APA) microcapsules for oral delivery of live bacterial cells, in-vitro, using a dynamic simulated human gastro-intestinal (GI) model. Results showed that the APA microcapsules were morphologically stable in the simulated stomach conditions, but did not retain their structural integrity after a 3-day exposure in simulated human GI media. The microbial populations of the tested bacterial cells and the activities of the tested enzymes in the simulated human GI suspension were not substantially altered by the presence of the APA microcapsules, suggesting that there were no significant adverse effects of oral administration of the APA microcapsules on the flora of the human gastrointestinal tract. When the APA microcapsules containing Lactobacillus plantarum 80 (LP80) were challenged in the simulated gastric medium (pH = 2.0), 80.0% of the encapsulated cells remained viable after a 5-min incubation; however, the viability decreased considerably (8.3%) after 15 min and dropped to 2.6% after 30 min and lower than 0.2% after 60 min, indicating the limitations of the currently obtainable APA membrane for oral delivery of live bacteria. Further in-vivo studies are required before conclusions can be made concerning the inadequacy of APA microcapsules for oral delivery of live bacterial cells.

Computed tomography of the gastro-intestinal tract : its value

Energy Technology Data Exchange (ETDEWEB)

Reeders, J W.A.J. [Academic Medical Center, Amsterdam (Netherlands)

1996-12-31

The subject discussed include indications and accuracy of CT - computed tomography, technical considerations, common pitfalls in CT interpretation, parameters for CT evaluation, benign lesions, double halo and target signs, hyperattenuated, inflammatory bowel disease, intestinal ischaemia, primary adenocarcinoma of the GIT, lymphoma and leiomyosarcoma (3 refs.).

Computed tomography of the gastro-intestinal tract : its value

International Nuclear Information System (INIS)

Reeders, J.W.A.J.

1995-01-01

The subject discussed include indications and accuracy of CT - computed tomography, technical considerations, common pitfalls in CT interpretation, parameters for CT evaluation, benign lesions, double halo and target signs, hyperattenuated, inflammatory bowel disease, intestinal ischaemia, primary adenocarcinoma of the GIT, lymphoma and leiomyosarcoma (3 refs.)

. boulardii CNCM I-1079 and defence against pathogenic gastro-intestinal microorganisms (ID 3017, further assessment) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

DEFF Research Database (Denmark)

Tetens, Inge

, a combination of L. rhamnosus CNCM I-1720, L. helveticus CNCM I-1722, B. longum subsp. longum CNCM I-3470 and S. cerevisiae var. boulardii CNCM I-1079, is sufficiently characterised. The claimed effect which is proposed for further assessment, defence against pathogenic gastro-intestinal microorganisms......, is a beneficial physiological effect. The proposed target population is the general population. No human intervention studies which investigated the effect of a combination of L. rhamnosus CNCM I-1720, L. helveticus CNCM I-1722, B. longum subsp. longum CNCM I-3470 and S. cerevisiae var. boulardii CNCM I-1079 were...... provided. On the basis of the data presented, the Panel concludes that a cause and effect relationship has not been established between the consumption of a combination of L. rhamnosus CNCM I-1720, L. helveticus CNCM I-1722, B. longum subsp. longum CNCM I-3470 and S. cerevisiae var. boulardii CNCM I-1079...

Acylation of salmon calcitonin modulates in vitro intestinal peptide flux through membrane permeability enhancement

DEFF Research Database (Denmark)

Trier, Sofie; Linderoth, Lars; Bjerregaard, Simon

2015-01-01

hypothesize that tailoring the acylation may be used to optimize intestinal translocation. This work aims to characterize acylated analogues of the therapeutic peptide salmon calcitonin (sCT), which lowers blood calcium, by systematically increasing acyl chain length at two positions, in order to elucidate...... to be optimal, as elongating the chain causes greater binding to the cell membrane but similar permeability, and we speculate that increasing the chain length further may decrease the permeability. In conclusion, acylated sCT acts as its own in vitro intestinal permeation enhancer, with reversible effects...... on Caco-2 cells, indicating that acylation of sCT may represent a promising tool to increase intestinal permeability without adding oral permeation enhancers....

Intestinal metabolism of PAH: in vitro demonstration and study of its impact on PAH transfer through the intestinal epithelium

International Nuclear Information System (INIS)

Cavret, Severine; Feidt, Cyril

2005-01-01

Food would seem to be one of the main ways of animal and human contamination with polycyclic aromatic hydrocarbons (PAHs). In vivo studies suggest a transfer in intestinal epithelium by diffusion, which appears extensively governed by the physicochemical properties of PAHs, particularly lipophilicity. However, other mechanisms, such as metabolism, are considered to intervene. Our work aimed at testing in vitro intestinal metabolism and defining its impact on transepithelial transport of PAHs. Caco-2 cells were cultivated on permeable filters and incubated with 14 C-labeled benzo[a]pyrene (BaP), pyrene (Pyr), and phenanthrene (Phe), which differ in their physicochemical properties. The results showed that the cells were able to metabolize the compounds. In basal media, Phe appeared to be the least hydroxylated molecule (45% after a 6-h exposure), followed by Pyr (65%) and finally BaP (96%). Inhibition of PAH metabolism showed a determinant effect on kinetics profiles. Transfer in the basal compartment of BaP, Pyr, and Phe radioactivities was, respectively, 26, 4, and 2 times lower with inhibitors, corroborating that intestinal metabolism of PAHs would have a positive impact on their transfer, an impact that increased with their lipophilicity. Furthermore, after a 6-h incubation, metabolites were also detected in apical medium. These findings suggested that intestinal metabolism might play a key role in intestinal barrier permeability and thus in the bioavailability of tested micropollutants

Multi-walled carbon nanotubes: biodegradation by gastric agents in vitro and effect on murine intestinal system

Science.gov (United States)

Masyutin, A.; Erokhina, M.; Sychevskaya, K.; Gusev, A.; Vasyukova, I.; Smirnova, E.; Onishchenko, G.

2015-11-01

One of the main questions limiting application of fibrous carbon nanomaterials (CNM) in medicine and food industry concerns presumptive degradation of CNM in living organisms. In this study, we have investigated biodegradation of multi-walled carbon nanotubes (MWCNTs) by gastric agents in vitro and influence of ingested MWCNTs on murine intestine. Using scanning, conventional transmission and analytical electron microscopy, we demonstrated that industrial MWCNTs treated in vitro by 0.1 M hydrochloric acid (pH=1) and gastric juice (pH=2-3) isolated from murine stomach, are subjected to incomplete degradation. After 30 days of oral administration to experimental mice, we did find MWCNTs in the cells of small intestine, and it may indicate that agglomerates of MWCNTs do not penetrate into colon epithelia and do not accumulate in enterocytes. However, we observed local areas of necrotic damages of intestinal villi. It seems likely, therefore, that MWCNTs end up leaving gastrointestinal tract by excretion with the feces. Our results suggest that MWCNTs do not undergo complete degradation in gastrointestinal tract of mice, and passing through non-degraded particles may negatively affect intestinal system.

Pediatric GERD (Gastro-Esophageal Reflux Disease)

Science.gov (United States)

... Marketplace Find an ENT Doctor Near You Pediatric GERD (Gastro-Esophageal Reflux Disease) Pediatric GERD (Gastro-Esophageal ... What symptoms are displayed by a child with GERD? While GER and EER in children often cause ...

Tween 20 increases intestinal transport of doxorubicin in vitro but not in vivo

DEFF Research Database (Denmark)

Al-Sharaf, Amal; Holm, Rene; Nielsen, Carsten Uhd

2016-01-01

co-administered with P-gp inhibitors (non-ionic surfactants) in vitro and in vivo . The aim of the present study was thus to investigate if different non-ionic surfactants would have a similar effect on the in vitro and in vivo absorption of doxorubicin. This was investigated in vitro in Caco-2 cells...... and by oral co-administration of doxorubicin together with tween 20 to male Sprague Dawley rats. 200 μM (0.025%) tween 20 increased the intestinal absorptive permeability of doxorubicin in vitro by 48 ± 4% from 8.8 × 10(-6)cm/s to 13.0 × 10(-6)cm/s. Further, the efflux ratio was reduced from 2.2 ± 0.06 to 1.2...

Studies on the in vitro absorption of spice principles--curcumin, capsaicin and piperine in rat intestines.

Science.gov (United States)

Suresh, D; Srinivasan, K

2007-08-01

A comparative evaluation of the absorbability of three structurally similar and physiologically active spice principles in an in vitro system consisting of everted rat intestinal sacs was made. When everted sacs of rat intestines were incubated with 50-1000 microg of curcumin in 10 ml incubation medium, absorption of the spice principle was maximum at 100 microg concentration. The amount of absorbed curcumin present in the serosal fluid was negligible. This and the comparatively lower recovery of the original compound suggested that curcumin to some extent undergoes a modification during absorption. For similar concentrations of added piperine, about 44-63% of piperine disappeared from the mucosal side. Absorption of piperine which was maximum at 800 microg per 10 ml was about 63%. The absolute amounts of piperine absorbed in this in vitro system exceeded the amounts of curcumin. The absorbed piperine could be traced in both the serosal fluid and in the intestinal tissue, indicating that piperine did not undergo any metabolic change during the process of absorption. 7-12% of the absorbed piperine was found in the serosal fluid. When everted sacs of rat intestines were incubated with 10-500 microg of capsaicin, a maximum of 82-88% absorption could be seen in the lower concentrations, and the amount of absorbed capsaicin did not proportionately increase at higher concentrations. A relatively higher percentage of the absorbed capsaicin could be seen in the serosal fluid as compared to curcumin or piperine. When these spice active principles were associated with mixed micelles, their in vitro intestinal absorption was relatively higher. Curcumin absorption in everted intestinal sac increased from 48.7% to 56.1% when the same was present in micelles. In the case of capsaicin and piperine, increase in absorption was 27.8-44.4% and 43.4-57.4%, respectively, when they were present in micelles as compared to its native form.

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to Lactobacillus johnsonii NCC 533 (La1) (CNCM I-1225) and improving immune defence against pathogenic gastro-intestinal microorganisms (ID 896), and protection, of the skin from UV-induced damage (ID 900) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

DEFF Research Database (Denmark)

Tetens, Inge

claims in relation to Lactobacillus johnsonii NCC 533 (La1) (CNCM I-1225) and improving immune defence against pathogenic gastro-intestinal microorganisms, and protection of the skin from UV-induced damage. The scientific substantiation is based on the information provided by the Member States...

[Intestinal intussusception due to ileal gastrointestinal stromal tumor--a case report].

Science.gov (United States)

Andrei, S; Andrei, A; Tonea, A; Andronesi, D; Preda, C; Herlea, V; Popescu, I

2011-01-01

Intestinal occlusion due to intussusception produced by intestinal tumors is a very rare condition. Gastrointestinal stromal tumors are also rare digestive neopasias, with an impredictable malignant behavior, which are usually growing outside the intestinal wall, being rarely the initiators of an intestinal intussusception. We present the case of a 59 years old female, admitted in our hospital to elucidate the etiology of her iron deficient anaemia, which developed an intestinal occlusion at the intestinal preparation for colonoscopy. The abdominal CT scan performed in emergency conditions highlighted occlusive intestinal tumor complicated with intestinal intussusception. We performed an emergency laparotomy that revealed intestinal occlusion due to ileo-ileal intussusception produced by an ileal tumor. The surgical intervention consisted in segmental ileal enterectomy including the tumor with latero-lateral entero-enteral anastomosis. The patient recovered without complications. The histopathological and immunohisto-chemical examinations established the diagnose of gastro-intestinal stromal tumor with high risk malignant behavior, therefore the patient was guided in the oncological department for specific treatment and oncological surveillance.

Gastro-duodenal perforations: conventional plain film, US and CT findings in 166 consecutive patients

International Nuclear Information System (INIS)

Grassi, Roberto; Romano, Stefania; Pinto, Antonio; Romano, Luigia

2004-01-01

Introduction: Gastro-duodenal perforations may be suspected in patients with history of ulceration, who present with acute pain and abdominal wall rigidity, but radiological findings in these cases may be unable to confirm a clinical diagnosis. The aim of our study was to report our experience in the diagnosis of gastro-duodenal perforation by conventional radiography, US and CT examinations. Material and methods: We retrospectively reviewed medical records of 166 consecutive patients who presented in the last 2 years to our institutions with symptoms of acute abdomen and submitted to surgery at the Emergency Unit of the ''A.Cardarelli'' Hospital of Naples with a surgical finding of perforated gastro-duodenal ulcer. The evidence of free intraperitoneal air on abdominal plain film was considered as a direct or suggestive finding of perforation. Evidence of intraperitoneal free fluid and/or reduced intestinal peristalsis at sonographic examination were considered indirect signs of gastro-duodenal perforation. Evidence of free peritoneal gas at CT was considered as a direct evidence of gastro-duodenal perforation. Results: Twenty patients underwent immediate surgery with no preoperative imaging evaluation, in 10 of them the site of perforation was found in a juxta-pyloric region and in the others at level of duodenum. In 146 patients submitted to serial radiological investigations before surgery, the site of perforation was in 56 (38.3%) duodenal, in 52 (35.6%) juxta-pyloric, in 28 (19.1%) gastric and in 10 (6.8%) pyloric. The cause of perforation was in all cases gastric or duodenal ulceration, in seven cases involving pancreatic parenchyma. In 110 (75.4%) patients with direct findings of perforation, in 94 cases (85.5%) the correct diagnosis was established on abdominal plain film, in two (1.8%) with radiographic and sonographic examinations and in 14 (12.7%) on CT findings. In 36 (24,6%) patients with no direct findings of perforation, only 24 (16,4%) of them

Gastro-duodenal perforations: conventional plain film, US and CT findings in 166 consecutive patients

Energy Technology Data Exchange (ETDEWEB)

Grassi, Roberto; Romano, Stefania E-mail: stefromano@libero.it; Pinto, Antonio; Romano, Luigia

2004-04-01

Introduction: Gastro-duodenal perforations may be suspected in patients with history of ulceration, who present with acute pain and abdominal wall rigidity, but radiological findings in these cases may be unable to confirm a clinical diagnosis. The aim of our study was to report our experience in the diagnosis of gastro-duodenal perforation by conventional radiography, US and CT examinations. Material and methods: We retrospectively reviewed medical records of 166 consecutive patients who presented in the last 2 years to our institutions with symptoms of acute abdomen and submitted to surgery at the Emergency Unit of the ''A.Cardarelli'' Hospital of Naples with a surgical finding of perforated gastro-duodenal ulcer. The evidence of free intraperitoneal air on abdominal plain film was considered as a direct or suggestive finding of perforation. Evidence of intraperitoneal free fluid and/or reduced intestinal peristalsis at sonographic examination were considered indirect signs of gastro-duodenal perforation. Evidence of free peritoneal gas at CT was considered as a direct evidence of gastro-duodenal perforation. Results: Twenty patients underwent immediate surgery with no preoperative imaging evaluation, in 10 of them the site of perforation was found in a juxta-pyloric region and in the others at level of duodenum. In 146 patients submitted to serial radiological investigations before surgery, the site of perforation was in 56 (38.3%) duodenal, in 52 (35.6%) juxta-pyloric, in 28 (19.1%) gastric and in 10 (6.8%) pyloric. The cause of perforation was in all cases gastric or duodenal ulceration, in seven cases involving pancreatic parenchyma. In 110 (75.4%) patients with direct findings of perforation, in 94 cases (85.5%) the correct diagnosis was established on abdominal plain film, in two (1.8%) with radiographic and sonographic examinations and in 14 (12.7%) on CT findings. In 36 (24,6%) patients with no direct findings of perforation, only 24

Gastro-intestinal helminths of goliath frogs (Conraua goliath from the localities of Loum, Yabassi and Nkondjock in the Littoral Region of Cameroon

Directory of Open Access Journals (Sweden)

Nguiffo Nguete Daniel

2015-07-01

Full Text Available The gastro-intestinal helminth parasites of goliath frog (Conraua goliath from the Littoral Region of Cameroon in the Localities of Loum, Yabassi and Nkondjock were surveyed. Out of the 30 goliath frogs examined (13 males and 17 females between April and May 2013, 26 (85% contained at least one helminth parasite and yielded a total of nine hundred and seventy three (973 helminths comprising: Nematodes (90.5%, Trematodes (9.4% and Pentastomids (0.1%. Nematodes included: Africana taylori (60%, Oswaldocruzia perreti (0.2%, Aplectana sp. (21%, Gendria sp. (7.1%, Amphibiophilus sp. (0.2%, Strongyluris sp. (0.1%, Physalopteroides sp. (1.6%, and Oxyuridae gen. sp. (0.3%. Trematodes comprised: Mesocoelium sp. (7.3% and Diplodiscus subclavatus (2.1%. Pentastomids were represented by Sebekia sp. (0.1%. The mean species richness and diversity were 1.97±2.12 and 0.41±0.04 respectively. The intensity of parasite infection was correlated with host body weight, positively for Africana taylori, Aplectana sp., Diplodiscus subclavatus, and Mesocoeliumsp. Infection rates were influenced by land-use pattern. Thus higher prevalences were observed in Loum (intensive agricultural area.

Breads Fortified with Freeze-Dried Vegetables: Quality and Nutritional Attributes. Part II: Breads Not Containing Oil as an Ingredient

Directory of Open Access Journals (Sweden)

Viren Ranawana

2016-09-01

Full Text Available The present article describes the second part of a study investigating the effect of adding vegetables on the nutritional, physico-chemical, and oxidative properties of wheat bread, and specifically focuses on bread that does not contain oil as an added ingredient. Wheat flour breads fortified with freeze-dried carrot, tomato, beetroot or broccoli were developed and assessed for their nutritional composition, antioxidant potential, oxidative stability, and storage properties. Using a simulated in vitro model, the study also examined the impact of vegetable addition on the oxidative stability of macronutrients during gastro-intestinal digestion. Adding vegetables improved the nutritional and functional attributes of the oil-free breads. However, they demonstrated a lower antioxidant potential compared to their oil-containing counterparts. Similarly, the textural and storage properties of the oil-free vegetable breads were poorer compared to the oil-containing breads. As expected, in the absence of oil the oil-free breads were associated with lower lipid oxidation both in their fresh form and during gastro-intestinal digestion. Adding vegetables reduced protein oxidation in the fresh oil-free breads but had no effect during gastro-intestinal digestion. The impact of vegetables on macronutrient oxidation in the oil-free breads during digestion appears to be vegetable-specific with broccoli exacerbating it and the others having no effect. Of the evaluated vegetables, beetroot showed the most promising nutritional and physico-chemical benefits when incorporated into bread that does not contain added oil.

[Comparison of transformation of four processed rhubarb aqueous extracts in intestinal bacteria in vitro].

Science.gov (United States)

Song, Rui; Tian, Yuan; Zhang, Zunjian

2012-06-01

To compare the metabolic transformation of four processed rhubarb aqueous extracts in rat intestinal bacteria in vitro. Rat intestinal bacteria test solution and each of four processed rhubarb aqueous extracts were incubated under anaerobic conditions at 37 degrees C. High-performance liquid chromatography with diode-array detection (HPLC-DAD) and tandem mass spectrometry (HPLC-MS/MS) was used for the qualitative analysis on the components that can be bio-transformed by rat intestinal bacteria as well as the trend of metabolic transformation of each parent compounds according to the changes in chromatographic peak areas in different incubation times. Anthraquinones, glucose gallates and naphthalenes glucosides could be bio-transformed by rat intestinal bacteria. Of them, anthraquinones were undoubtedly the most prevalent parent compounds, as 12 out of the 17 metabolites were tentatively assigned as metabolites transformed from anthraquinones. Besides, it was also found that each parent compound in four processed rhubarb extract were diverse from each other with the incubation time. The preparations change composition and proportional relationship of ingredients contained in rhubarb and thus impacting their transformation effect in intestinal bacteria.

Vomiting and gastro-oesophageal reflux.

Science.gov (United States)

Paton, J Y; Nanayakkhara, C S; Simpson, H

1988-01-01

During radionuclide scans in 82 infants and children gastro-oesophageal reflux extending to the upper oesophageal/laryngeal level was detected in 636 one minute frames. Only 61 (9.6%) of these frames were associated with vomiting, defined as the appearance of milk at the mouth. Thus the absence of vomiting does not preclude appreciable gastro-oesophageal reflux. PMID:3415303

Human Primary Intestinal Epithelial Cells as an Improved In Vitro Model for Cryptosporidium parvum Infection

Science.gov (United States)

Cabada, Miguel M.; Nichols, Joan; Gomez, Guillermo; White, A. Clinton

2013-01-01

The study of human intestinal pathogens has been limited by the lack of methods for the long-term culture of primary human intestinal epithelial cells (PECs). The development of infection models with PECs would allow a better understanding of host-parasite interactions. The objective of this study was to develop a novel method for prolonged in vitro cultivation of PECs that can be used to study Cryptosporidium infection. We isolated intact crypts from human intestines removed during weight loss surgery. The fragments of intestinal layers were cultivated with culture medium supplemented with growth factors and antiapoptotic molecules. After 7 days, the PECs formed self-regenerating cell clusters, forming villi that resemble intestinal epithelium. The PECs proliferated and remained viable for at least 60 days. The cells expressed markers for intestinal stem cells, epithelial cells, and mature enterocytes. The PECs were infected with Cryptosporidium. In contrast to older models in which parasite numbers decay, the burden of parasites increased for >120 h. In summary, we describe here a novel method for the cultivation of self-regenerating human epithelial cells from small intestinal crypts, which contain both intestinal stem cells and mature villus cells. We present data that suggest these cells support Cryptosporidium better than existing cell lines. PECs should provide an improved tool for studying host-parasite interactions involving Cryptosporidium and other intestinal pathogens. PMID:23509153

In vitro dynamic model simulating the digestive tract of 6-month-old infants.

Science.gov (United States)

Passannanti, Francesca; Nigro, Federica; Gallo, Marianna; Tornatore, Fabio; Frasso, Annalisa; Saccone, Giulia; Budelli, Andrea; Barone, Maria V; Nigro, Roberto

2017-01-01

In vivo assays cannot always be conducted because of ethical reasons, technical constraints or costs, but a better understanding of the digestive process, especially in infants, could be of great help in preventing food-related pathologies and in developing new formulas with health benefits. In this context, in vitro dynamic systems to simulate human digestion and, in particular, infant digestion could become increasingly valuable. To simulate the digestive process through the use of a dynamic model of the infant gastroenteric apparatus to study the digestibility of starch-based infant foods. Using M.I.D.A (Model of an Infant Digestive Apparatus), the oral, gastric and intestinal digestibility of two starch-based products were measured: 1) rice starch mixed with distilled water and treated using two different sterilization methods (the classical method with a holding temperature of 121°C for 37 min and the HTST method with a holding temperature of 137°C for 70 sec) and 2) a rice cream with (premium product) or without (basic product) an aliquot of rice flour fermented by Lactobacillus paracasei CBA L74. After the digestion the foods were analyzed for the starch concentration, the amount of D-glucose released and the percentage of hydrolyzed starch. An in vitro dynamic system, which was referred to as M.I.D.A., was obtained. Using this system, the starch digestion occurred only during the oral and intestinal phase, as expected. The D-glucose released during the intestinal phase was different between the classical and HTST methods (0.795 grams for the HTST versus 0.512 for the classical product). The same analysis was performed for the basic and premium products. In this case, the premium product had a significant difference in terms of the starch hydrolysis percentage during the entire process. The M.I.D.A. system was able to digest simple starches and a more complex food in the correct compartments. In this study, better digestibility of the premium product was

In vitro dynamic model simulating the digestive tract of 6-month-old infants

Science.gov (United States)

Gallo, Marianna; Tornatore, Fabio; Frasso, Annalisa; Saccone, Giulia; Budelli, Andrea; Barone, Maria V.

2017-01-01

Background In vivo assays cannot always be conducted because of ethical reasons, technical constraints or costs, but a better understanding of the digestive process, especially in infants, could be of great help in preventing food-related pathologies and in developing new formulas with health benefits. In this context, in vitro dynamic systems to simulate human digestion and, in particular, infant digestion could become increasingly valuable. Objective To simulate the digestive process through the use of a dynamic model of the infant gastroenteric apparatus to study the digestibility of starch-based infant foods. Design Using M.I.D.A (Model of an Infant Digestive Apparatus), the oral, gastric and intestinal digestibility of two starch-based products were measured: 1) rice starch mixed with distilled water and treated using two different sterilization methods (the classical method with a holding temperature of 121°C for 37 min and the HTST method with a holding temperature of 137°C for 70 sec) and 2) a rice cream with (premium product) or without (basic product) an aliquot of rice flour fermented by Lactobacillus paracasei CBA L74. After the digestion the foods were analyzed for the starch concentration, the amount of D-glucose released and the percentage of hydrolyzed starch. Results An in vitro dynamic system, which was referred to as M.I.D.A., was obtained. Using this system, the starch digestion occurred only during the oral and intestinal phase, as expected. The D-glucose released during the intestinal phase was different between the classical and HTST methods (0.795 grams for the HTST versus 0.512 for the classical product). The same analysis was performed for the basic and premium products. In this case, the premium product had a significant difference in terms of the starch hydrolysis percentage during the entire process. Conclusions The M.I.D.A. system was able to digest simple starches and a more complex food in the correct compartments. In this study

In vitro and in vivo imaging and tracking of intestinal organoids from human induced pluripotent stem cells.

Science.gov (United States)

Jung, Kwang Bo; Lee, Hana; Son, Ye Seul; Lee, Ji Hye; Cho, Hyun-Soo; Lee, Mi-Ok; Oh, Jung-Hwa; Lee, Jaemin; Kim, Seokho; Jung, Cho-Rok; Kim, Janghwan; Son, Mi-Young

2018-01-01

Human intestinal organoids (hIOs) derived from human pluripotent stem cells (hPSCs) have immense potential as a source of intestines. Therefore, an efficient system is needed for visualizing the stage of intestinal differentiation and further identifying hIOs derived from hPSCs. Here, 2 fluorescent biosensors were developed based on human induced pluripotent stem cell (hiPSC) lines that stably expressed fluorescent reporters driven by intestine-specific gene promoters Krüppel-like factor 5 monomeric Cherry (KLF5 mCherry ) and intestine-specific homeobox enhanced green fluorescence protein (ISX eGFP ). Then hIOs were efficiently induced from those transgenic hiPSC lines in which mCherry- or eGFP-expressing cells, which appeared during differentiation, could be identified in intact living cells in real time. Reporter gene expression had no adverse effects on differentiation into hIOs and proliferation. Using our reporter system to screen for hIO differentiation factors, we identified DMH1 as an efficient substitute for Noggin. Transplanted hIOs under the kidney capsule were tracked with fluorescence imaging (FLI) and confirmed histologically. After orthotopic transplantation, the localization of the hIOs in the small intestine could be accurately visualized using FLI. Our study establishes a selective system for monitoring the in vitro differentiation and for tracking the in vivo localization of hIOs and contributes to further improvement of cell-based therapies and preclinical screenings in the intestinal field.-Jung, K. B., Lee, H., Son, Y. S., Lee, J. H., Cho, H.-S., Lee, M.-O., Oh, J.-H., Lee, J., Kim, S., Jung, C.-R., Kim, J., Son, M.-Y. In vitro and in vivo imaging and tracking of intestinal organoids from human induced pluripotent stem cells. © FASEB.

The gastro-oesophageal common cavity revisited

NARCIS (Netherlands)

Aanen, M. C.; Bredenoord, A. J.; Samsom, M.; Smout, A. J. P. M.

2006-01-01

The manometric common cavity phenomenon has been used as indicator of gastro-oesophageal reflux of liquid or gaseous substances. Using combined pH and impedance recording as reference standard the value of a common cavity as indicator of gastro-oesophageal reflux was tested. Ten healthy male

Impact of gastro-oesophageal reflux on microRNA expression, location and function.

Science.gov (United States)

Smith, Cameron M; Michael, Michael Z; Watson, David I; Tan, Grace; Astill, David St J; Hummel, Richard; Hussey, Damian J

2013-01-08

Ulceration of the oesophageal squamous mucosa (ulcerative oesophagitis) is a pathological manifestation of gastro-oesophageal reflux disease, and is a major risk factor for the development of Barrett's oesophagus. Barrett's oesophagus is characterised by replacement of reflux-damaged oesophageal squamous epithelium with a columnar intestinal-like epithelium. We previously reported discovery of microRNAs that are differentially expressed between oesophageal squamous mucosa and Barrett's oesophagus mucosa. Now, to better understand early steps in the initiation of Barrett's oesophagus, we assessed the expression, location and function of these microRNAs in oesophageal squamous mucosa from individuals with ulcerative oesophagitis. Quantitative real-time PCR was used to compare miR-21, 143, 145, 194, 203, 205 and 215 expression levels in oesophageal mucosa from individuals without pathological gastro-oesophageal reflux to individuals with ulcerative oesophagitis. Correlations between microRNA expression and messenger RNA differentiation markers BMP-4, CK8 and CK14 were analyzed. The cellular localisation of microRNAs within the oesophageal mucosa was determined using in-situ hybridisation. microRNA involvement in proliferation and apoptosis was assessed following transfection of a human squamous oesophageal mucosal cell line (Het-1A). miR-143, miR-145 and miR-205 levels were significantly higher in gastro-oesophageal reflux compared with controls. Elevated miR-143 expression correlated with BMP-4 and CK8 expression, and elevated miR-205 expression correlated negatively with CK14 expression. Endogenous miR-143, miR-145 and miR-205 expression was localised to the basal layer of the oesophageal epithelium. Transfection of miR-143, 145 and 205 mimics into Het-1A cells resulted in increased apoptosis and decreased proliferation. Elevated miR-143, miR-145 and miR-205 expression was observed in oesophageal squamous mucosa of individuals with ulcerative oesophagitis. These mi

Achalasia following gastro-oesophageal reflux.

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Smart, H L; Mayberry, J F; Atkinson, M

1986-01-01

Five patients initially presenting with symptomatic gastro-oesophageal reflux, proven by radiology or pH monitoring, subsequently developed achalasia, confirmed by radiology and manometry, after an interval of 2-10 years. During this period dysphagia, present as a mild and intermittent symptom accompanying the initial reflux in 3 of the 5, became severe and resulted in oesophageal stasis of food in all. Three of the 5 had a demonstrable hiatal hernia. In none was reflux a troublesome symptom after Rider-Moeller dilatation or cardiomyotomy undertaken for the achalasia. Gastro-oesophageal reflux does not protect against the subsequent development of achalasia. It is suggested that the autonomic damage eventually leading to achalasia may in its initial phases cause gastro-oesophageal reflux. Images Figure 1. A Figure 1. B Figure 2. PMID:3950898

Validity of two recently-proposed prognostic grading indices for lung, gastro-intestinal, breast and renal cell cancer patients with radiosurgically-treated brain metastases.

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Yamamoto, Masaaki; Serizawa, Toru; Sato, Yasunori; Kawabe, Takuya; Higuchi, Yoshinori; Nagano, Osamu; Barfod, Bierta E; Ono, Junichi; Kasuya, Hidetoshi; Urakawa, Yoichi

2013-02-01

We tested the validity of two prognostic indices for stereotactic radiosurgically (SRS)-treated patients with brain metastases (BMs) from five major original cancer categories. The two indices are Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) and our Modified Recursive Partitioning Analysis (RPA). Forty-six hundred and eight BM patients underwent gamma knife SRS during the 1998-2011 period. Primary cancer categories were non-small cell lung cancer (NSCLC, 2827 patients), small cell lung cancer (SCLC, 460), gastro-intestinal cancer (GIC, 582), breast cancer (BC, 547) and renal cell cancer (RCC, 192). There were statistically significant survival differences among patients stratified into four groups based on the DS-GPA systems (p failed to reach statistical significance with this system. There were, however, statistically significant MST differences (p < 0.001) among the three groups without overlapping of 95 % CIs between any two pairs of groups with the Modified RPA system in all five categories. The DS-GPA system is applicable to our set of patients with NSCLC only. However, the Modified RPA system was shown to be applicable to patients with five primary cancer categories. This index should be considered when designing future clinical trials involving BM patients.

Efficacy of the amino-acetonitrile derivative, monepantel, against experimental and natural adult stage gastro-intestinal nematode infections in sheep.

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Sager, Heinz; Hosking, Barry; Bapst, Béatrice; Stein, Philip; Vanhoff, Kathleen; Kaminsky, Ronald

2009-01-22

Multiple drug resistance by nematodes, against anthelmintics has become an important economic problem in sheep farming worldwide. Here we describe the efficacy of monepantel, a developmental molecule from the recently discovered anthelmintic class, the amino-acetonitrile derivatives (AADs). Efficacy was tested against adult stage gastro-intestinal nematodes (GINs) in experimentally and naturally infected sheep at a dose of 2.5mg/kg body weight when administered as an oral solution. Some of the isolates used in experimental infection studies were known to be resistant to the benzimidazoles or levamisole anthelmintics; strains resistant to the macrocyclic lactones were not available for these tests. Worm count-based efficacies of >98% were determined in these studies. As an exception, Oesophagostomum venulosum was only reduced by 88% in one study, albeit with a low worm burden in the untreated controls (geometric mean 15.4 worms). Similar efficacies for monepantel were also confirmed in naturally infected sheep. While the efficacy against most species was >99%, the least susceptible species was identified as Nematodirus spathiger, and although efficacy was 92.4% in one study it was generally >99%. Several animals were infected with Trichuris ovis, which was not eliminated after the treatment. Monepantel demonstrated high activity against a broad range of the important GINs of sheep, which makes this molecule an interesting candidate for use in this species, particularly in regions with problems of anthelmintic resistance. Monepantel was well tolerated by the treated sheep, with no treatment related adverse events documented.

Preparation and investigation of novel gastro-floating tablets with 3D extrusion-based printing.

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Li, Qijun; Guan, Xiaoying; Cui, Mengsuo; Zhu, Zhihong; Chen, Kai; Wen, Haoyang; Jia, Danyang; Hou, Jian; Xu, Wenting; Yang, Xinggang; Pan, Weisan

2018-01-15

Three dimensional (3D) extrusion-based printing is a paste-based rapid prototyping process, which is capable of building complex 3D structures. The aim of this study was to explore the feasibility of 3D extrusion-based printing as a pharmaceutical manufacture technique for the fabrication of gastro-floating tablets. Novel low-density lattice internal structure gastro-floating tablets of dipyridamole were developed to prolong the gastric residence time in order to improve drug release rate and consequently, improve bioavailability and therapeutic efficacy. Excipients commonly employed in the pharmaceutical study could be efficiently applied in the room temperature 3D extrusion-based printing process. The tablets were designed with three kinds of infill percentage and prepared by hydroxypropyl methylcellulose (HPMC K4M) and hydroxypropyl methylcellulose (HPMC E15) as hydrophilic matrices and microcrystalline cellulose (MCC PH101) as extrusion molding agent. In vitro evaluation of the 3D printed gastro-floating tablets was performed by determining mechanical properties, content uniformity, and weight variation. Furthermore, re-floating ability, floating duration time, and drug release behavior were also evaluated. Dissolution profiles revealed the relationship between infill percentage and drug release behavior. The results of this study revealed the potential of 3D extrusion-based printing to fabricate gastro-floating tablets with more than 8h floating process with traditional pharmaceutical excipients and lattice internal structure design. Copyright © 2017. Published by Elsevier B.V.

Gastro-Esophageal Reflux in Children

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Anna Rybak

2017-08-01

Full Text Available Gastro-esophageal reflux (GER is common in infants and children and has a varied clinical presentation: from infants with innocent regurgitation to infants and children with severe esophageal and extra-esophageal complications that define pathological gastro-esophageal reflux disease (GERD. Although the pathophysiology is similar to that of adults, symptoms of GERD in infants and children are often distinct from classic ones such as heartburn. The passage of gastric contents into the esophagus is a normal phenomenon occurring many times a day both in adults and children, but, in infants, several factors contribute to exacerbate this phenomenon, including a liquid milk-based diet, recumbent position and both structural and functional immaturity of the gastro-esophageal junction. This article focuses on the presentation, diagnosis and treatment of GERD that occurs in infants and children, based on available and current guidelines.

Gastro-Esophageal Reflux in Children.

Science.gov (United States)

Rybak, Anna; Pesce, Marcella; Thapar, Nikhil; Borrelli, Osvaldo

2017-08-01

Gastro-esophageal reflux (GER) is common in infants and children and has a varied clinical presentation: from infants with innocent regurgitation to infants and children with severe esophageal and extra-esophageal complications that define pathological gastro-esophageal reflux disease (GERD). Although the pathophysiology is similar to that of adults, symptoms of GERD in infants and children are often distinct from classic ones such as heartburn. The passage of gastric contents into the esophagus is a normal phenomenon occurring many times a day both in adults and children, but, in infants, several factors contribute to exacerbate this phenomenon, including a liquid milk-based diet, recumbent position and both structural and functional immaturity of the gastro-esophageal junction. This article focuses on the presentation, diagnosis and treatment of GERD that occurs in infants and children, based on available and current guidelines.

Hospital discharge diagnostic and procedure codes for upper gastro-intestinal cancer: how accurate are they?

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Stavrou Efty

2012-09-01

Full Text Available Abstract Background Population-level health administrative datasets such as hospital discharge data are used increasingly to evaluate health services and outcomes of care. However information about the accuracy of Australian discharge data in identifying cancer, associated procedures and comorbidity is limited. The Admitted Patients Data Collection (APDC is a census of inpatient hospital discharges in the state of New South Wales (NSW. Our aim was to assess the accuracy of the APDC in identifying upper gastro-intestinal (upper GI cancer cases, procedures for associated curative resection and comorbidities at the time of admission compared to data abstracted from medical records (the ‘gold standard’. Methods We reviewed the medical records of 240 patients with an incident upper GI cancer diagnosis derived from a clinical database in one NSW area health service from July 2006 to June 2007. Extracted case record data was matched to APDC discharge data to determine sensitivity, positive predictive value (PPV and agreement between the two data sources (κ-coefficient. Results The accuracy of the APDC diagnostic codes in identifying site-specific incident cancer ranged from 80-95% sensitivity. This was comparable to the accuracy of APDC procedure codes in identifying curative resection for upper GI cancer. PPV ranged from 42-80% for cancer diagnosis and 56-93% for curative surgery. Agreement between the data sources was >0.72 for most cancer diagnoses and curative resections. However, APDC discharge data was less accurate in reporting common comorbidities - for each condition, sensitivity ranged from 9-70%, whilst agreement ranged from κ = 0.64 for diabetes down to κ  Conclusions Identifying incident cases of upper GI cancer and curative resection from hospital administrative data is satisfactory but under-ascertained. Linkage of multiple population-health datasets is advisable to maximise case ascertainment and minimise false

Gastro-oesophageal reflux and cough.

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Abdulqawi, Rayid; Houghton, Lesley A; Smith, Jaclyn A

2013-05-01

Gastro-oesophageal reflux, either singly or in association with postnasal drip and/or asthma is considered to be a cause of chronic cough. The amount and nature of gastro-oesophageal reflux however is often normal with acid suppression having very little, if any therapeutic effect in these patients. This review examines the challenges posed when exploring the reflux-cough link, and discusses the merits and limitations of the proposed mechanisms of reflux leading to cough.

Dynamic characteristic of gastro-oesophageal reflux in ambulatory patients with gastro-oesophageal reflux disease and normal control subjects

NARCIS (Netherlands)

Weusten, B. L.; Akkermans, L. M.; vanBerge-Henegouwen, G. P.; Smout, A. J.

1995-01-01

BACKGROUND: The aim of the study was to investigate the dynamic characteristics of pathologic gastro-oesophageal reflux. METHODS: Five-channel ambulatory 24-h oesophageal pH monitoring was performed in 19 gastro-oesophageal reflux disease patients (age, 21-74 years) and in 19 healthy volunteers

In Vitro–In Vivo Correlation for Gliclazide Immediate-Release Tablets Based on Mechanistic Absorption Simulation

OpenAIRE

Grbic, Sandra; Parojcic, Jelena; Ibric, Svetlana; Djuric, Zorica

2010-01-01

The aim of this study was to develop a drug-specific absorption model for gliclazide (GLK) using mechanistic gastrointestinal simulation technology (GIST) implemented in GastroPlusTM software package. A range of experimentally determined, in silico predicted or literature data were used as input parameters. Experimentally determined pH-solubility profile was used for all simulations. The human jejunum effective permeability (Peff) value was estimated on the basis of in vitro measured Caco-2 p...

Chemical form of plutonium in foodstuffs - its influence on gastro-intestinal uptake

Energy Technology Data Exchange (ETDEWEB)

Cooper, J.R. (National Radiological Protection Board, Harwell (UK))

1984-01-01

A brief review is given of some studies of the chemical form of plutonium in food eaten by man and how this may influence gastrointestinal uptake. Phytate ligands, present in many foods, bind strongly to plutonium. High levels of enzyme phytase in rat intestines enhance the gastrointestinal uptake of plutonium phytate in rats compared to rabbits. Taking into account 1) the low levels of phytase in human intestine and 2) the possibility of competing precipitation reactions, it would seem unlikely that the phytate-mediated elevation of plutonium uptake seen in rats will apply to humans.

[Nutrient sensing by the gastro-intestinal nervous system and control of energy homeostasis].

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Gilles, Mithieux

2015-01-01

The gastrointestinal nerves are crucial in the sensing of nutrients and hormones and its translation in terms of control of food intake. Major macronutrients like glucose and proteins are sensed by the extrinsic nerves located around the portal vein walls, which signal to the brain and account for the satiety phenomenon they promote. Glucose is sensed in the portal vein by neurons expressing the glucose receptor SGLT3, which activates the main regions of the brain involved in the control of food intake. Proteins indirectly act on food intake by inducing intestinal gluconeogenesis and its sensing by the portal glucose sensor. The mechanism involves a prior antagonism by peptides of the μ-opioid receptors present in the portal vein nervous system and a reflex arc with the brain inducing intestinal gluconeogenesis. In a comparable manner, short chain fatty acids produced from soluble fibers act via intestinal gluconeogenesis to exert anti-obesity and anti-diabetic effects. In the case of propionate, the mechanism involves a prior activation of the free fatty acid receptor FFAR3 present in the portal nerves and a reflex arc initiating intestinal gluconeogenesis. © Société de Biologie, 2016.

Out-patient radiology in gastro-esophageal reflux

International Nuclear Information System (INIS)

Alessi, G.; Risi, D.; Accordino, M.E.; Meli, C.; Iascone, C.

1987-01-01

A retrospective analysis is reported of 131 symptomatic patients for gastro-esophageal reflux, comparing the radiological diagnosis to endoscopic, manometric and pH-metric results. A low incidence of x-ray examination is found. The role of radiology in gastro-esophageal reflux is considered and discussed

Development and evaluation of intestinal targeted mucoadhesive microspheres of Bacillus coagulans.

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Alli, Sk Md Athar; Ali, Sk Md Ajhar; Samanta, Amalesh

2011-11-01

Intestinal targeted mucoadhesive microsphere of probiotics may provide numerous associated health benefits. To develop mucoadhesive microspheres that will deliver viable probiotic cells into gut protectively against harsh environmental conditions of stomach for extended period. Core mucoadhesive microspheres of Bacillus coagulans were prepared using hypromellose, following coacervation and phase separation technique and were then coated with hypromellose phthalate to achieve their site-specific release. Microspheres were evaluated for percent yield, entrapment efficiency, surface morphology, particle size and size distribution, flow property, swelling property, mucoadhesion property by the in vitro wash-off and the ex vivo mucoadhesive strength tests, in vitro release profile and release kinetic, in vivo probiotic activity, and stability. The values for kinetic constant and regression coefficient of model-dependent approaches and the difference factor, the similarity factor, and the Rescigno index of model-independent approaches were determined for accessing and comparing in vitro performance. Microsphere formulation batches have percent yield value between 56.26% and 69.13% and entrapment efficiency value between 66.95% and 77.89%. Microspheres were coarser with spherical shape having mean particle size from 28.03 to 48.31 μm. In vitro B. coagulans release profile follows zero-order kinetics and depends on the grade of hypromellose and the B. coagulans-to-hypromellose ratio. Experimental microspheres rendered adequate stability to B. coagulans at room temperature. Microspheres had delivered B. coagulans in simulated intestinal condition following zero-order kinetics, protectively in simulated gastric condition, exhibiting appreciable mucoadhesion in intestinal condition, which could be useful to achieve site-specific delivery for extended period.

Bevacizumab plus capecitabine in patients with progressive advanced well-differentiated neuroendocrine tumors of the gastro-intestinal (GI-NETs) tract (BETTER trial)--a phase II non-randomised trial.

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Mitry, Emmanuel; Walter, Thomas; Baudin, Eric; Kurtz, Jean-Emmanuel; Ruszniewski, Philippe; Dominguez-Tinajero, Sophie; Bengrine-Lefevre, Leïla; Cadiot, Guillaume; Dromain, Clarisse; Farace, Françoise; Rougier, Philippe; Ducreux, Michel

2014-12-01

Gastro-intestinal neuroendocrine tumours (GI-NETs) are chemotherapy-resistant tumours. Bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF), has shown promising results in several phase II trials of gastro-entero-pancreatic-NETs. We assessed bevacizumab combined with capecitabine, specifically in GI-NET patients. BEvacizumab in The Treament of neuroEndocrine tumoRs (BETTER) was a multicentre, open-label, non-randomised, two-group phase II trial. Here we present the group of patients with progressive, metastatic, well-differentiated GI-NETs. Patients Eastern Cooperative Oncology Group-performance status (ECOG-PS)⩽2, Ki-67 proliferation rate <15% and no prior systemic chemotherapy were treated with bevacizumab (7.5 mg/kg/q3w) and capecitabine (1000 mg/m2 twice daily, orally d1-14, resumed on d22) for 6-24 months. The primary end-point was progression-free survival (PFS); secondary end-points included overall survival (OS), response rate, safety and quality of life. Of the 49 patients included, 53% were men, median age was 60 years (41-82), primary tumour site was ileal in 82% patients and Ki-67 was <15% in 48 patients and not available for one patient. After a maximum of 24 month follow-up per patient, the median PFS by investigator assessment was 23.4 months [95% confidence interval (CI): 13.2; not reached] and the overall disease control rate was 88% (18% partial response, 70% stable disease). The 2-year survival rate was 85%. Median OS was not reached. The most frequent grade 3-4 adverse events were hypertension (31%), diarrhoea (14%) and hand-foot syndrome (10%). The combination of bevacizumab and capecitabine showed clinical activity and a manageable safety profile in the treatment of GI-NETs that warrant confirmation in a randomised phase III trial. Copyright © 2014 Elsevier Ltd. All rights reserved.

The symbiotic intestinal ciliates and the evolution of their hosts.

Science.gov (United States)

Moon-van der Staay, Seung Yeo; van der Staay, Georg W M; Michalowski, Tadeusz; Jouany, Jean-Pierre; Pristas, Peter; Javorský, Peter; Kišidayová, Svetlana; Varadyova, Zora; McEwan, Neil R; Newbold, C Jamie; van Alen, Theo; de Graaf, Rob; Schmid, Markus; Huynen, Martijn A; Hackstein, Johannes H P

2014-04-01

The evolution of sophisticated differentiations of the gastro-intestinal tract enabled herbivorous mammals to digest dietary cellulose and hemicellulose with the aid of a complex anaerobic microbiota. Distinctive symbiotic ciliates, which are unique to this habitat, are the largest representatives of this microbial community. Analyses of a total of 484 different 18S rRNA genes show that extremely complex, but related ciliate communities can occur in the rumen of cattle, sheep, goats and red deer (301 sequences). The communities in the hindgut of equids (Equus caballus, Equus quagga), and elephants (Elephas maximus, Loxodonta africanus; 162 sequences), which are clearly distinct from the ruminant ciliate biota, exhibit a much higher diversity than anticipated on the basis of their morphology. All these ciliates from the gastro-intestinal tract constitute a monophyletic group, which consists of two major taxa, i.e. Vestibuliferida and Entodiniomorphida. The ciliates from the evolutionarily older hindgut fermenters exhibit a clustering that is specific for higher taxa of their hosts, as extant species of horse and zebra on the one hand, and Africa and Indian elephant on the other hand, share related ciliates. The evolutionary younger ruminants altogether share the various entodiniomorphs and the vestibuliferids from ruminants. Copyright © 2014 Elsevier GmbH. All rights reserved.

Radiologic quantitation of gastro-oesophageal reflux

International Nuclear Information System (INIS)

Christiansen, T.; Funch-Jensen, P.; Jacobsen, N.O.; Thommesen, P.; Kommunehospitalet, Aarhus; Kommunehospitalet, Aarhus

1987-01-01

In a prospective study, 26 patients with symptoms of reflux oesophagitis underwent a barium examination for gastro-oesophageal reflux after food stimulation, and endoscopy with biopsy from different levels of the oesophagus. Radiologic grading of the gastro-oesophageal reflux depending on the height of the reflux into the oesophagus was performed, and this was correlated to the microscopic appearance at different levels in the oesophagus. Complete agreement between the radiologic grading and the histology was found in 69 per cent of the cases, and when gastro-oesophageal reflux was demonstrated the agreement was 75 per cent. Accordingly, the results showed a good accordance between the two variants, indicating that the height of the reflux during the food stimulated test may be truly indicative of the reflux height under non-test conditions. (orig.)

Soymilk residue (okara) as a natural immobilization carrier for Lactobacillus plantarum cells enhances soymilk fermentation, glucosidic isoflavone bioconversion, and cell survival under simulated gastric and intestinal conditions.

Science.gov (United States)

Xiudong, Xia; Ying, Wang; Xiaoli, Liu; Ying, Li; Jianzhong, Zhou

2016-01-01

Cell immobilization is an alternative to microencapsulation for the maintenance of cells in a liquid medium. However, artificial immobilization carriers are expensive and pose a high safety risk. Okara, a food-grade byproduct from soymilk production, is rich in prebiotics. Lactobacilli could provide health enhancing effects to the host. This study aimed to evaluate the potential of okara as a natural immobilizer for L. plantarum 70810 cells. The study also aimed to evaluate the effects of okara-immobilized L. plantarum 70810 cells (IL) on soymilk fermentation, glucosidic isoflavone bioconversion, and cell resistance to simulated gastric and intestinal stresses. Scanning electron microscopy (SEM) was used to show cells adherence to the surface of okara. Lactic acid, acetic acid and isoflavone analyses in unfermented and fermented soymilk were performed by HPLC with UV detection. Viability and growth kinetics of immobilized and free L. plantarum 70810 cells (FL) were followed during soymilk fermentation. Moreover, changes in pH, titrable acidity and viscosity were measured by conventional methods. For in vitro testing of simulated gastrointestinal resistance, fermented soymilk was inoculated with FL or IL and an aliquot incubated into acidic MRS broth which was conveniently prepared to simulate gastric, pancreatic juices and bile salts. Survival to simulated gastric and intestinal stresses was evaluated by plate count of colony forming units on MRS agar. SEM revealed that the lactobacilli cells attached and bound to the surface of okara. Compared with FL, IL exhibited a significantly higher specific growth rate, shorter lag phase of growth, higher productions of lactic and acetic acids, a faster decrease in pH and increase in titrable acidity, and a higher soymilk viscosity. Similarly, IL in soymilk showed higher productions of daizein and genistein compared with the control. Compared with FL, IL showed reinforced resistance to simulatedgastric and intestinal

Soymilk residue (okara as a natural immobilization carrier for Lactobacillus plantarum cells enhances soymilk fermentation, glucosidic isoflavone bioconversion, and cell survival under simulated gastric and intestinal conditions

Directory of Open Access Journals (Sweden)

Xia Xiudong

2016-11-01

Full Text Available Cell immobilization is an alternative to microencapsulation for the maintenance of cells in a liquid medium. However, artificial immobilization carriers are expensive and pose a high safety risk. Okara, a food-grade byproduct from soymilk production, is rich in prebiotics. Lactobacilli could provide health enhancing effects to the host. This study aimed to evaluate the potential of okara as a natural immobilizer for L. plantarum 70810 cells. The study also aimed to evaluate the effects of okara-immobilized L. plantarum 70810 cells (IL on soymilk fermentation, glucosidic isoflavone bioconversion, and cell resistance to simulated gastric and intestinal stresses. Scanning electron microscopy (SEM was used to show cells adherence to the surface of okara. Lactic acid, acetic acid and isoflavone analyses in unfermented and fermented soymilk were performed by HPLC with UV detection. Viability and growth kinetics of immobilized and free L. plantarum 70810 cells (FL were followed during soymilk fermentation. Moreover, changes in pH, titrable acidity and viscosity were measured by conventional methods. For in vitro testing of simulated gastrointestinal resistance, fermented soymilk was inoculated with FL or IL and an aliquot incubated into acidic MRS broth which was conveniently prepared to simulate gastric, pancreatic juices and bile salts. Survival to simulated gastric and intestinal stresses was evaluated by plate count of colony forming units on MRS agar. SEM revealed that the lactobacilli cells attached and bound to the surface of okara. Compared with FL, IL exhibited a significantly higher specific growth rate, shorter lag phase of growth, higher productions of lactic and acetic acids, a faster decrease in pH and increase in titrable acidity, and a higher soymilk viscosity. Similarly, IL in soymilk showed higher productions of daizein and genistein compared with the control. Compared with FL, IL showed reinforced resistance to simulatedgastric and

Fluoroscopic-guided primary single-step percutaneous gastrostomy. Initial results using the Freka {sup registered} GastroTube; Primaere einzeitige durchleuchtungsgesteuerte perkutane Gastrostomie (PG). Erste Ergebnisse mit dem Freka {sup registered} GastroTube

Energy Technology Data Exchange (ETDEWEB)

Hahne, J.D.; Schoennagel, B.P.; Arndt, C.; Bannas, P.; Koops, A.; Adam, G.; Habermann, C.R. [Universitaetsklinikum Hamburg-Eppendorf (Germany). Zentrum fuer Radiologie; Herrmann, J. [Universitaetsklinikum Hamburg-Eppendorf (Germany). Zentrum fuer Radiologie; Universitaetsklinikum Hamburg-Eppendorf (Germany). Abt. Paediatrische Radiologie

2011-07-15

Purpose: To determine the practicability and outcome of fluoroscopic-guided primary one-step treatment of percutaneous gastrostomy (PG) with the system Freka {sup registered} Gastro Tube (Fresenius Kabi, Germany). Materials and Methods: In 39 patients (mean age 62.7 {+-} 12.0 years), primary PG was performed based on clinical indication from August 2009 to April 2010. The intervention was performed by an experienced radiologist under aseptic conditions by direct puncture with Freka {sup registered} Gastro Tube under fluoroscopic guidance. The clinical data and outcome as well as any complications originated from the electronic archive of the University Medical Center Hamburg-Eppendorf. Results: The intervention was technically successful in all 39 patients. Within the mean follow-up time of 155.3 {+-} 73.6 days, 29 patients (74.4 %) did not experience complications. 10 patients (25.6 %) had to be revised. Complications manifested after a mean of 135.6 {+-} 61.2 days and mainly corresponded to accidental dislocation (50 %). One patient had to be surgically revised under suspicion of a malpositioned tube and suspected intestinal perforation. Clinically relevant wound infections were not detected. The total costs per patient were 553.17 Euro for our single-step treatment (OPS 5 - 431.x) vs. 963.69 Euro (OPS 5 - 431.x and OPS 8 - 123.0) for the recommended two-step treatment. Conclusion: Fluoroscopic-guided primary single-step treatment with Freka {sup registered} Gastro Tube system is feasible and not associated with an increased complication rate when compared to published literature applying a two-step treatment approach. Material costs as well as human and time resources could be significantly reduced using the single-step treatment. (orig.)

Impact of gastro-oesophageal reflux on microRNA expression, location and function

Directory of Open Access Journals (Sweden)

Smith Cameron M

2013-01-01

Full Text Available Abstract Background Ulceration of the oesophageal squamous mucosa (ulcerative oesophagitis is a pathological manifestation of gastro-oesophageal reflux disease, and is a major risk factor for the development of Barrett’s oesophagus. Barrett’s oesophagus is characterised by replacement of reflux-damaged oesophageal squamous epithelium with a columnar intestinal-like epithelium. We previously reported discovery of microRNAs that are differentially expressed between oesophageal squamous mucosa and Barrett’s oesophagus mucosa. Now, to better understand early steps in the initiation of Barrett’s oesophagus, we assessed the expression, location and function of these microRNAs in oesophageal squamous mucosa from individuals with ulcerative oesophagitis. Methods Quantitative real-time PCR was used to compare miR-21, 143, 145, 194, 203, 205 and 215 expression levels in oesophageal mucosa from individuals without pathological gastro-oesophageal reflux to individuals with ulcerative oesophagitis. Correlations between microRNA expression and messenger RNA differentiation markers BMP-4, CK8 and CK14 were analyzed. The cellular localisation of microRNAs within the oesophageal mucosa was determined using in-situ hybridisation. microRNA involvement in proliferation and apoptosis was assessed following transfection of a human squamous oesophageal mucosal cell line (Het-1A. Results miR-143, miR-145 and miR-205 levels were significantly higher in gastro-oesophageal reflux compared with controls. Elevated miR-143 expression correlated with BMP-4 and CK8 expression, and elevated miR-205 expression correlated negatively with CK14 expression. Endogenous miR-143, miR-145 and miR-205 expression was localised to the basal layer of the oesophageal epithelium. Transfection of miR-143, 145 and 205 mimics into Het-1A cells resulted in increased apoptosis and decreased proliferation. Conclusions Elevated miR-143, miR-145 and miR-205 expression was observed in

Evaluation of the Impact of Excipients and an Albendazole Salt on Albendazole Concentrations in Upper Small Intestine Using an In Vitro Biorelevant Gastrointestinal Transfer (BioGIT) System.

Science.gov (United States)

Kourentas, Alexandros; Vertzoni, Maria; Khadra, Ibrahim; Symillides, Mira; Clark, Hugh; Halbert, Gavin; Butler, James; Reppas, Christos

2016-09-01

An in vitro biorelevant gastrointestinal transfer (BioGIT) system was assessed for its ability to mimic recently reported albendazole concentrations in human upper small intestine after administration of free base suspensions to fasted adults in absence and in presence of supersaturation promoting excipients (hydroxypropylmethylcellulose and lipid self-emulsifying vehicles). The in vitro method was also used to evaluate the likely impact of using the sulfate salt on albendazole concentrations in upper small intestine. In addition, BioGIT data were compared with equilibrium solubility data of the salt and the free base in human aspirates and biorelevant media. The BioGIT system adequately simulated the average albendazole gastrointestinal transfer process and concentrations in upper small intestine after administration of the free base suspensions to fasted adults. However, the degree of supersaturation observed in the duodenal compartment was greater than in vivo. Albendazole sulfate resulted in minimal increase of albendazole concentrations in the duodenal compartment of the BioGIT, despite improved equilibrium solubility observed in human aspirates and biorelevant media, indicating that the use of a salt is unlikely to lead to any significant oral absorption advantage for albendazole. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Food-stimulated gastro-oesophageal reflux demonstrated by barium examination

Energy Technology Data Exchange (ETDEWEB)

Christiansen, T.; Thommesen, P.

A prospective investigation on gastro-oesophageal reflux in 97 consecutive patients has been carried out by means of a barium examination employing the conventional method and after food stimulation. Gastro-oesophageal reflux was observed in 38 patients with and 15 patients without oesophageal symptoms. Gastro-oesophageal reflux was induced by two mechanisms, an active component after food stimulation and a passive component after the conventional method including respiratory manoeuvres and leg raising. In 32 patients, only the active component could be demonstrated and in 6 patients only the passive component. In the remaining 15 patients both active and passive components occurred. The clinical significance of the active and passive components in gastro-oesophageal reflux needs further investigation.

Food-stimulated gastro-oesophageal reflux demonstrated by barium examination

International Nuclear Information System (INIS)

Christiansen, T.; Thommesen, P.

1986-01-01

A prospective investigation on gastro-oesophageal reflux in 97 consecutive patients has been carried out by means of a barium examination employing the conventional method and after food stimulation. Gastro-oesophageal reflux was observed in 38 patients with and 15 patients without oesophageal symptoms. Gastro-oesophageal reflux was induced by two mechanisms, an active component after food stimulation and a passive component after the conventional method including respiratory manoeuvres and leg raising. In 32 patients, only the active component could be demonstrated and in 6 patients only the passive component. In the remaining 15 patients both active and passive components occurred. The clinical significance of the active and passive components in gastro-oesophageal reflux needs further investigation. (orig.)

In vivo and in vitro toxicological effects of titanium dioxide nanoparticles on small intestine

Science.gov (United States)

Tassinari, Roberta; La Rocca, Cinzia; Stecca, Laura; Tait, Sabrina; De Berardis, Barbara; Ammendolia, Maria Grazia; Iosi, Francesca; Di Virgilio, Antonio; Martinelli, Andrea; Maranghi, Francesca

2015-06-01

In European Union, titanium dioxide (TiO2) as bulk material is a food additive (E171) and - as nanoparticle (NP) - is used as a white pigment in several products (e.g. food, cosmetics, drugs). E171 contains approximately 36% of particles less than 100 nm in at least one dimension and TiO2 NP exposure is estimated fairly below 2.5 mg/person/day. The gastrointestinal tract is a route of entry for NPs, thus representing a potential target of effects. In in vivo study, the effects of TiO2 NP in adult rat small intestine have been evaluated by oral administration of 0 (CTRL), 1 and 2 mg/kg body weight per day - relevant to human dietary intake. Detailed quali/quantitative histopathological analyses were performed on CTRL and treated rat samples. Scanning electron microscopy (SEM) analysis was performed on small intestine. An in vitro study on Caco-2 cells was also used in order to evaluate the potential cytotoxic effects directly on enterocytes through the lactate dehydrogenase (LDH) assay. Suspensions of TiO2 NPs for in vitro and in vivo study were characterized by EM. Histomorphometrical data showed treatment-related changes of villus height and widths in male rats. Significantly different from CTRL decreased LDH levels in the medium were detected in vitro at 24h with 2.5, 5, 10 and 20 µg/cm2 levels of TiO2 NPs. SEM analysis showed no damaged areas. Overall the results showed that enterocytes may represent a target of TiO2 NP toxicity by direct exposure both in vivo and in vitro models.

In vivo and in vitro toxicological effects of titanium dioxide nanoparticles on small intestine

International Nuclear Information System (INIS)

Tassinari, Roberta; La Rocca, Cinzia; Tait, Sabrina; De Berardis, Barbara; Ammendolia, Maria Grazia; Iosi, Francesca; Di Virgilio, Antonio; Martinelli, Andrea; Maranghi, Francesca; Stecca, Laura

2014-01-01

In European Union, titanium dioxide (TiO 2 ) as bulk material is a food additive (E171) and - as nanoparticle (NP) - is used as a white pigment in several products (e.g. food, cosmetics, drugs). E171 contains approximately 36% of particles less than 100 nm in at least one dimension and TiO 2 NP exposure is estimated fairly below 2.5 mg/person/day. The gastrointestinal tract is a route of entry for NPs, thus representing a potential target of effects. In in vivo study, the effects of TiO 2 NP in adult rat small intestine have been evaluated by oral administration of 0 (CTRL), 1 and 2 mg/kg body weight per day - relevant to human dietary intake. Detailed quali/quantitative histopathological analyses were performed on CTRL and treated rat samples. Scanning electron microscopy (SEM) analysis was performed on small intestine. An in vitro study on Caco-2 cells was also used in order to evaluate the potential cytotoxic effects directly on enterocytes through the lactate dehydrogenase (LDH) assay. Suspensions of TiO 2 NPs for in vitro and in vivo study were characterized by EM. Histomorphometrical data showed treatment-related changes of villus height and widths in male rats. Significantly different from CTRL decreased LDH levels in the medium were detected in vitro at 24h with 2.5, 5, 10 and 20 µg/cm 2 levels of TiO 2 NPs. SEM analysis showed no damaged areas. Overall the results showed that enterocytes may represent a target of TiO 2 NP toxicity by direct exposure both in vivo and in vitro models

Motor disorders of the oesophagus in gastro-oesophageal reflux.

OpenAIRE

Mahony, M J; Migliavacca, M; Spitz, L; Milla, P J

1988-01-01

Mechanisms of gastro-oesophageal reflux were studied by oesophageal manometry and pH monitoring in 33 children: nine controls, 15 with gastro-oesophageal reflux alone, and nine with reflux oesophagitis. A total of 122 episodes of reflux were analysed in detail: 82 (67%) were synchronous with swallowing and 40 (33%) asynchronous. Infants with trivial symptoms had gastro-oesophageal reflux synchronous with swallowing, whereas those with serious symptoms had slower acid clearance and asynchronou...

Anthelmintic resistance and multidrug resistance in sheep gastro-intestinal nematodes in France, Greece and Italy.

Science.gov (United States)

Geurden, Thomas; Hoste, Herve; Jacquiet, Philippe; Traversa, Donato; Sotiraki, Smaragda; Frangipane di Regalbono, Antonio; Tzanidakis, Nikolaos; Kostopoulou, Despoina; Gaillac, Christie; Privat, Simon; Giangaspero, Annunziata; Zanardello, Claudia; Noé, Laura; Vanimisetti, Bindu; Bartram, David

2014-03-17

Anthelmintic resistance (AR) in ovine gastro-intestinal nematodes has been reported to affect the health and productivity of sheep globally. The objective of the present study was to evaluate the efficacy of commonly used oral drenches in sheep in France, Greece and Italy. In each country, 10 farms were selected. On each farm, 50 animals were blocked based on the pre-treatment faecal egg count (FEC). Within each block, animals were randomly allocated to one of 5 treatment groups. In addition to an untreated control group, there were 4 groups treated per oral route: moxidectin (MOX) and ivermectin (IVM), both at 0.2mg/kg bodyweight, levamisole (LEV; at 7.5mg/kg bodyweight) and a benzimidazole (BZ; at 3.75-5mg/kg bodyweight). In France, animals were not treated with LEV, but with netobimin (NET; at 7.5mg/kg bodyweight). The FEC was monitored using a modified McMaster technique. Two weeks after treatment, individual faecal samples were taken from all animals and efficacy was calculated as the difference between arithmetic mean FEC of the control group versus each respective treatment group. The results of the present study indicate the high efficacy of treatment with oral formulations of MOX (99-100%) and IVM (98-100%) on all farms, except on 1 farm in Greece. On this farm, multi drug resistance (MDR) was identified involving 4 anthelmintics (efficacy MOX: 91%; IVM: 0%; BZ: 58% and LEV: 87%). In Greece and Italy, AR against LEV and BZ was observed on some farms, with MDR involving both anthelmintics on 3 farms in Greece and on 2 farms in Italy. In France, AR against BZ and NET was observed on all 10 farms included. In all countries, Teladorsagia sp. was the most common nematode larva identified after treatment, followed by Haemonchus sp. and Trichostrongylus sp., with differences among farms and treatments. The current study confirms the high efficacy of oral treatments with MOX and IVM, even on farms with worm populations resistant to BZ, LEV or NET. This study also

Motor disorders of the oesophagus in gastro-oesophageal reflux.

Science.gov (United States)

Mahony, M J; Migliavacca, M; Spitz, L; Milla, P J

1988-01-01

Mechanisms of gastro-oesophageal reflux were studied by oesophageal manometry and pH monitoring in 33 children: nine controls, 15 with gastro-oesophageal reflux alone, and nine with reflux oesophagitis. A total of 122 episodes of reflux were analysed in detail: 82 (67%) were synchronous with swallowing and 40 (33%) asynchronous. Infants with trivial symptoms had gastro-oesophageal reflux synchronous with swallowing, whereas those with serious symptoms had slower acid clearance and asynchronous reflux. There were significant differences in lower oesophageal sphincter pressure and amplitude of oesophageal contractions between controls and patients with both gastro-oesophageal reflux and reflux oesophagitis. In reflux oesophagitis there was a decrease in lower oesophageal sphincter pressure and the contractions had a bizarre waveform suggesting a neuropathic process. PMID:3202640

Influence of Cisapride on food-stimulated gastro-oesophageal reflux: A radiological study

International Nuclear Information System (INIS)

Gelineck, J.; Aksglade, K.; Funch-Jensen, P.; Thommesen, P.

1990-01-01

The influence of Cisapride on food-stimulated gastro-oesophageal reflux meachanisms was studied in a double-blind cross-over investigation in 24 consecutive patients selected by endoscopy, 12 with microscopical evidence of gastro-oesophageal reflux and 12 with additional macroscopic oesoghagitis. 63% had food-stimulated gastro-oesophageal reflux, and Cisapride significantly reduced the tendency to gastro-oesophageal reflux and mucosal contact time between gastric content and the oesophageal mucosa in 73% of these patients. It is concluded that Cisapride could be valuable in the treatment of gastro-oesophageal reflux. (orig.) [de

Effects of Achyrocline satureioides Inflorescence Extracts against Pathogenic Intestinal Bacteria: Chemical Characterization, In Vitro Tests, and In Vivo Evaluation

Directory of Open Access Journals (Sweden)

Karla Suzana Moresco

2017-01-01

Full Text Available Three Achyrocline satureioides (AS inflorescences extracts were characterized: (i a freeze-dried extract prepared from the aqueous extractive solution and (ii a freeze-dried and (iii a spray-dried extract prepared from hydroethanol extractive solution (80% ethanol. The chemical profile, antioxidant potential, and antimicrobial activity against intestinal pathogenic bacteria of AS extracts were evaluated. In vitro antioxidant activity was determined by the total reactive antioxidant potential (TRAP assay. In vivo analysis and characterization of intestinal microbiota were performed in male Wistar rats (saline versus treated animals with AS dried extracts by high-throughput sequencing analysis: metabarcoding. Antimicrobial activity was tested in vitro by the disc diffusion tests. Moisture content of the extracts ranged from 10 to 15% and 5.7 to 17 mg kg−1 of fluorine. AS exhibited antioxidant activity, especially in its freeze-dried form which also exhibited a wide spectrum of antimicrobial activity against intestinal pathogenic bacteria greater than those observed by the antibiotic, amoxicillin, when tested against Bacillus cereus and Staphylococcus aureus. Antioxidant and antimicrobial activities of AS extracts seemed to be positively correlated with the present amount of flavonoids. These findings suggest a potential use of AS as a coadjuvant agent for treating bacterial-induced intestinal diseases with high rates of antibiotic resistance.

Hormone replacement therapy is associated with gastro-oesophageal reflux disease: a retrospective cohort study

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Close Helen

2012-05-01

Full Text Available Abstract Background Oestrogen and progestogen have the potential to influence gastro-intestinal motility; both are key components of hormone replacement therapy (HRT. Results of observational studies in women taking HRT rely on self-reporting of gastro-oesophageal symptoms and the aetiology of gastro-oesophageal reflux disease (GORD remains unclear. This study investigated the association between HRT and GORD in menopausal women using validated general practice records. Methods 51,182 menopausal women were identified using the UK General Practice Research Database between 1995–2004. Of these, 8,831 were matched with and without hormone use. Odds ratios (ORs were calculated for GORD and proton-pump inhibitor (PPI use in hormone and non-hormone users, adjusting for age, co-morbidities, and co-pharmacy. Results In unadjusted analysis, all forms of hormone use (oestrogen-only, tibolone, combined HRT and progestogen were statistically significantly associated with GORD. In adjusted models, this association remained statistically significant for oestrogen-only treatment (OR 1.49; 1.18–1.89. Unadjusted analysis showed a statistically significant association between PPI use and oestrogen-only and combined HRT treatment. When adjusted for covariates, oestrogen-only treatment was significant (OR 1.34; 95% CI 1.03–1.74. Findings from the adjusted model demonstrated the greater use of PPI by progestogen users (OR 1.50; 1.01–2.22. Conclusions This first large cohort study of the association between GORD and HRT found a statistically significant association between oestrogen-only hormone and GORD and PPI use. This should be further investigated using prospective follow-up to validate the strength of association and describe its clinical significance.

The paradoxical effect of extra-virgin olive oil on oxidative phenomena during in vitro co-digestion with meat.

Science.gov (United States)

Martini, Serena; Cavalchi, Martina; Conte, Angela; Tagliazucchi, Davide

2018-07-01

Extra-virgin olive oil is an integral part of the Mediterranean diet and its consumption has been associated with a reduction risk of chronic diseases. Here we tested the potential of extra-virgin olive oil to limit the oxidative phenomena during in vitro gastro-intestinal co-digestion with turkey breast meat. The extra-virgin olive oil was particularly rich in oleuropein aglycone isomers, which represented the 66.8% of total phenolic determined with MS/MS experiments. Meals supplemented with extra-virgin olive oil equivocally affected lipid peroxidation. At low concentration (2.5% respect to meat), a significant inhibition of lipid oxidation was observed, whereas lipid peroxidation was greatly enhanced when the amount of extra-virgin olive oil was increased in the gastro-intestinal system. The inhibitory effect observed at 2.5% extra-virgin olive oil was due to the antioxidant properties of extra-virgin olive oil phenolic compounds. At high concentration, extra-virgin olive oil phenolic compounds (especially hydroxytyrosol-derivative) behaved as pro-oxidants increasing the generation of lipid hydroperoxides from meat. At the same time, the presence in the digestive system of catalysers from meat induced the peroxidation of extra-virgin olive oil fatty acids, which was further intensified by the pro-oxidant activity of extra-virgin olive oil phenolic compounds. Our study underlined the importance of the timing and amount of consumption of extra-virgin olive oil as well as its phenolic composition in limiting the peroxidative phenomena on meat lipids during digestion. Copyright © 2018 Elsevier Ltd. All rights reserved.

Use of collagen gel as an alternative extracellular matrix for the in vitro and in vivo growth of murine small intestinal epithelium.

Science.gov (United States)

Jabaji, Ziyad; Sears, Connie M; Brinkley, Garrett J; Lei, Nan Ye; Joshi, Vaidehi S; Wang, Jiafang; Lewis, Michael; Stelzner, Matthias; Martín, Martín G; Dunn, James C Y

2013-12-01

Methods for the in vitro culture of primary small intestinal epithelium have improved greatly in recent years. A critical barrier for the translation of this methodology to the patient's bedside is the ability to grow intestinal stem cells using a well-defined extracellular matrix. Current methods rely on the use of Matrigel(™), a proprietary basement membrane-enriched extracellular matrix gel produced in mice that is not approved for clinical use. We demonstrate for the first time the capacity to support the long-term in vitro growth of murine intestinal epithelium in monoculture, using type I collagen. We further demonstrate successful in vivo engraftment of enteroids co-cultured with intestinal subepithelial myofibroblasts in collagen gel. Small intestinal crypts were isolated from 6 to 10 week old transgenic enhanced green fluorescent protein (eGFP+) mice and suspended within either Matrigel or collagen gel; cultures were supported using previously reported media and growth factors. After 1 week, cultures were either lysed for DNA or RNA extraction or were implanted subcutaneously in syngeneic host mice. Quantitative real-time polymerase chain reaction (qPCR) was performed to determine expansion of the transgenic eGFP-DNA and to determine the mRNA gene expression profile. Immunohistochemistry was performed on in vitro cultures and recovered in vivo explants. Small intestinal crypts reliably expanded to form enteroids in either Matrigel or collagen in both mono- and co-cultures as confirmed by microscopy and eGFP-DNA qPCR quantification. Collagen-based cultures yielded a distinct morphology with smooth enteroids and epithelial monolayer growth at the gel surface; both enteroid and monolayer cells demonstrated reactivity to Cdx2, E-cadherin, CD10, Periodic Acid-Schiff, and lysozyme. Collagen-based enteroids were successfully subcultured in vitro, whereas pure monolayer epithelial sheets did not survive passaging. Reverse transcriptase-polymerase chain reaction

Survival of Lactobacillus delbrueckii UFV H2b20 in fermented milk under simulated gastric and intestinal conditions.

Science.gov (United States)

da Conceição, L L; Leandro, E S; Freitas, F S; de Oliveira, M N V; Ferreira-Machado, A B; Borges, A C; de Moraes, C A

2013-09-01

The survival of Lactobacillus delbrueckii UFV H2b20 was assessed in fermented milk, both during the storage period and after exposure to simulated gastric and intestinal juices, as well the detection of the gene fbpA involved in adherence to human gastrointestinal tract. L. delbrueckii UFV H2b20 remained stable and viable for 28 days under refrigerated storage conditions. After one day of storage, that strain exhibited a one-log population reduction following exposure in tandem to simulated gastric and intestinal juices. After 14 days of storage, a two-log reduction was observed following 90 min of exposure to the simulated gastric conditions. However, the strain did not survive following exposure to the simulated intestinal juice. The observed tolerance to storage conditions and resistance to the simulated gastric and intestinal conditions confirm the potential use of L. delbrueckii UFV H2b20 as a probiotic, which is further reinforced by the detection of fbpA in this strain.

Factors associated with gastro-duodenal disease in patients ...

African Journals Online (AJOL)

Background: There is a high prevalence of gastro-duodenal disease in sub Saharan Africa. Peptic ulcer disease in dyspeptic patients, 24.5%, was comparable to prevalence of gastro-duodenal disease among symptomatic individuals in developed countries (12 – 25%). Limited data exists regarding its associated risk ...

Heartburn, gastro-oesophageal reflux disease and non-erosive ...

African Journals Online (AJOL)

Heartburn, gastro-oesophageal reflux disease and non-erosive reflux disease. Haley Smith. Abstract. Reflux is a normal process that occurs in healthy infants, children and adults. Most episodes are short-lived and do not cause bothersome symptoms of complications. Gastro-oesophageal reflux disease (GORD) develops ...

Relationship between sleep and acid gastro-oesophageal reflux in neonates.

Science.gov (United States)

Ammari, Mohamed; Djeddi, Djamal; Léké, André; Delanaud, Stéphane; Stéphan-Blanchard, Erwan; Bach, Véronique; Telliez, Frédéric

2012-02-01

The aim of the present study was to investigate the impact of gastro-oesophageal acid reflux on sleep in neonates and, reciprocally, the influence of wakefulness (W) and sleep stages on the characteristics of the reflux (including the retrograde bolus migration of oesophageal acid contents). The pH and multichannel intraluminal impedance were measured during nocturnal polysomnography in 25 infants hospitalised for suspicion of gastro-oesophageal reflux. Two groups were constituted according to whether or not the infants displayed gastro-oesophageal reflux (i.e. a reflux group and a control group). There were no differences between the reflux and control groups in terms of sleep duration, sleep structure and sleep state change frequency. Vigilance states significantly influenced the gastro-oesophageal reflux pattern: the occurrence of gastro-oesophageal reflux episodes was greater during W (59 ± 32%) and active sleep (AS; 35 ± 30%) than during quiet sleep (QS; 6 ± 11%), whereas the mean duration of gastro-oesophageal reflux episodes was higher in QS than in W and AS. The percentage of retrograde bolus migrations of distal oesophageal acid content was significantly higher in AS (62 ± 26%) than in W (42 ± 26%) and QS (4.5 ± 9%). In neonates, gastro-oesophageal reflux occurred more frequently during W, whereas the physiological changes associated with sleep state increase the physiopathological impact of the gastro-oesophageal reflux. The duration of oesophagus-acid contact was greater during sleep; AS facilitated the retrograde migration of oesophageal acid content, and QS was characterised by the risk of prolonged acid mucosal contact. © 2011 European Sleep Research Society.

Radiologic diagnosis of gastro-oesophageal reflux

Energy Technology Data Exchange (ETDEWEB)

Fransson, S.G.; Soekjer, H.; Johansson, K.E.; Tibbling, L.

In 149 patients, a standardized radiologic method for the detection of gastro-oesophageal reflux was applied and compared with the results obtained at endoscopy and by a manometric reflux test. Radiologic reflux was recorded in 53 patients, of whom 25 had reflux without abdominal compression and 51 with compression. At least one of the other two types of examination disclosed pathologic conditions in all but 2 of 53 patients. Oesophagitis was significantly more severe among the patients with reflux observed at radiography. The presence of hiatal incompetence with reflux only to the hiatal hernia but not to the oesophagus was not a strong indicator of gastro-oesophageal reflux disease. Hiatal hernia was present in a significantly larger number of the patients with reflux at radiography than in those without reflux. Increased width of the hiatus gave stronger evidence for reflux disease than in patients with a normal hiatus. Thus, the width of the hiatus also had a bearing on the diagnosis of gastro-oesophageal reflux disease.

In vivo and in vitro toxicological effects of titanium dioxide nanoparticles on small intestine

Energy Technology Data Exchange (ETDEWEB)

Tassinari, Roberta; La Rocca, Cinzia; Tait, Sabrina; De Berardis, Barbara; Ammendolia, Maria Grazia; Iosi, Francesca; Di Virgilio, Antonio; Martinelli, Andrea; Maranghi, Francesca, E-mail: francesca.maranghi@iss.it [Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Stecca, Laura [European Commission-Joint Research Centre, Institute for Health and Consumer Protection Chemical assessment and Testing Unit, Via E. Fermi, 2749I-21027 Ispra (Italy)

2015-06-23

In European Union, titanium dioxide (TiO{sub 2}) as bulk material is a food additive (E171) and - as nanoparticle (NP) - is used as a white pigment in several products (e.g. food, cosmetics, drugs). E171 contains approximately 36% of particles less than 100 nm in at least one dimension and TiO{sub 2} NP exposure is estimated fairly below 2.5 mg/person/day. The gastrointestinal tract is a route of entry for NPs, thus representing a potential target of effects. In in vivo study, the effects of TiO{sub 2} NP in adult rat small intestine have been evaluated by oral administration of 0 (CTRL), 1 and 2 mg/kg body weight per day - relevant to human dietary intake. Detailed quali/quantitative histopathological analyses were performed on CTRL and treated rat samples. Scanning electron microscopy (SEM) analysis was performed on small intestine. An in vitro study on Caco-2 cells was also used in order to evaluate the potential cytotoxic effects directly on enterocytes through the lactate dehydrogenase (LDH) assay. Suspensions of TiO{sub 2} NPs for in vitro and in vivo study were characterized by EM. Histomorphometrical data showed treatment-related changes of villus height and widths in male rats. Significantly different from CTRL decreased LDH levels in the medium were detected in vitro at 24h with 2.5, 5, 10 and 20 µg/cm{sup 2} levels of TiO{sub 2} NPs. SEM analysis showed no damaged areas. Overall the results showed that enterocytes may represent a target of TiO{sub 2} NP toxicity by direct exposure both in vivo and in vitro models.

Use of multiple pinhole external scintigraphy to monitor tablet disintegration in vivo

International Nuclear Information System (INIS)

Theodorakis, M.C.; Devous, M.D.; Simpson, D.R.

1982-01-01

External scintigraphy is useful for observing the disintegration of capsules and tablets in the gastro-intestinal tract of man and animals. The sites of disintegration, completeness of disintegration, effectiveness of coatings and rate of transition through the intestinal tract can be investigated by this technique. Gamma cameras are coupled to a digital data processor, video image processor and image magnifier, for increased resolution. Disintegration times in vitro and in vivo are compared. (U.K.)

The chemical form of plutonium in foodstuffs - its influence on gastro-intestinal uptake

International Nuclear Information System (INIS)

Cooper, J.R.

1984-01-01

A brief review is given of some studies of the chemical form of plutonium in food eaten by man and how this may influence gastrointestinal uptake. Phytate ligands, present in many foods, bind strongly to plutonium. High levels of enzyme phytase in rat intestines enhance the gastrointestinal uptake of plutonium phytate in rats compared to rabbits. Taking into account 1) the low levels of phytase in human intestine and 2) the possibility of competing precipitation reactions, it would seem unlikely that the phytate-mediated elevation of plutonium uptake seen in rats will apply to humans. (U.K.)

Gastro-esophageal reflux disease and exacerbations in chronic obstructive pulmonary disease.

Science.gov (United States)

Ingebrigtsen, Truls S; Marott, Jacob L; Vestbo, Jørgen; Nordestgaard, Børge G; Hallas, Jesper; Lange, Peter

2015-01-01

We tested the hypothesis that gastro-esophageal reflux disease is a risk factor for exacerbations in individuals with chronic obstructive pulmonary disease (COPD). Among 9622 participants in the Copenhagen City Heart Study, we identified 1259 individuals with COPD and information on gastro-esophageal reflux disease and the regular use of acid inhibitory treatment. These individuals were followed for 5 years with regard to medically treated COPD exacerbations, which we defined as a short course treatment with oral corticosteroids alone or in combination with antibiotics. We applied a multivariable Cox regression analysis with adjustment for well-established risk factors associated with COPD exacerbations or gastro-esophageal reflux disease, including COPD severity, and symptoms. Individuals with COPD and gastro-esophageal reflux disease had more chronic bronchitis (31 vs 21%, P = 0.004), more breathlessness (39 vs 22%, P gastro-esophageal reflux disease. Among individuals with COPD and gastro-esophageal reflux disease, those who did not use acid inhibitory treatment regularly had an increased risk of COPD exacerbations during follow-up, hazards ratio (HR): HR = 2.7 (1.3-5.4, P = 0.006). Individuals with gastro-esophageal reflux disease, using acid inhibitory treatment regularly did not have an increased risk of exacerbations, HR = 1.2 (0.6-2.7, P = 0.63). Gastro-esophageal reflux disease was associated with an increased risk of medically treated exacerbations of COPD, but only in those individuals who did not use acid inhibitory treatment regularly. © 2014 Asian Pacific Society of Respirology.

Primary culture of cat intestinal epithelial cells in vitro and the cDNA library construction.

Science.gov (United States)

Zhao, Gui Hua; Liu, Ye; Cheng, Yun Tang; Zhao, Qing Song; Qiu, Xiao; Xu, Chao; Xiao, Ting; Zhu, Song; Liu, Gong Zhen; Yin, Kun

2018-06-26

Felids are the only definitive hosts of Toxoplasma gondii. To lay a foundation for screening the T. gondii-felids interaction factors, we have developed a reproducible primary culture method for cat intestinal epithelial cells (IECs). The primary IECs were isolated from a new born cat's small intestine jejunum region without food ingress, and respectively in vitro cultured by tissue cultivation and combined digestion method with collagenase XI and dispase I, then purified by trypsinization. After identification, the ds cDNA of cat IECs was synthesized for constructing pGADT7 homogenization three-frame plasmid, and transformed into the yeast Y187 for generating the cDNA library. Our results indicated that cultivation of primary cat IECs relays on combined digestion to form polarized and confluent monolayers within 3 days with typical features of normal epithelial cells. The purified cells cultured by digestion method were identified to be nature intestinal epithelial cells using immunohistochemical analysis and were able to maintain viability for at least 15 passages. The homogenizable ds cDNA, which is synthesized from the total RNA extracted from our cultured IECs, distributed among 0.5-2.0 kb, and generated satisfying three-frame cDNA library with the capacity of 1.2 × 106 and the titer of 5.2 × 107 pfu/mL. Our results established an optimal method for the culturing and passage of cat IECs model in vitro, and laid a cDNA library foundation for the subsequent interaction factors screening by yeast two-hybrid.

Effects of intestinal bacteria-derived p-cresyl sulfate on Th1-type immune response in vivo and in vitro

International Nuclear Information System (INIS)

Shiba, Takahiro; Kawakami, Koji; Sasaki, Takashi; Makino, Ikuyo; Kato, Ikuo; Kobayashi, Toshihide; Uchida, Kazumi; Kaneko, Kimiyuki

2014-01-01

Protein fermentation by intestinal bacteria generates various compounds that are not synthesized by their hosts. An example is p-cresol, which is produced from tyrosine. Patients with chronic kidney disease (CKD) accumulate high concentrations of intestinal bacteria-derived p-cresyl sulfate (pCS), which is the major metabolite of p-cresol, in their blood, and this accumulation contributes to certain CKD-associated disorders. Immune dysfunction is a CKD-associated disorder that frequently contributes to infectious diseases among CKD patients. Although some studies imply pCS as an etiological factor, the relation between pCS and immune systems is poorly understood. In the present study, we investigated the immunological effects of pCS derived from intestinal bacteria in mice. For this purpose, we fed mice a tyrosine-rich diet that causes the accumulation of pCS in their blood. The mice were shown to exhibit decreased Th1-driven 2, 4-dinitrofluorobenzene-induced contact hypersensitivity response. The concentration of pCS in blood was negatively correlated with the degree of the contact hypersensitivity response. In contrast, the T cell-dependent antibody response was not influenced by the accumulated pCS. We also examined the in vitro cytokine responses by T cells in the presence of pCS. The production of IFN-γ was suppressed by pCS. Further, pCS decreased the percentage of IFN-γ-producing Th1 cells. Our results suggest that intestinal bacteria-derived pCS suppressesTh1-type cellular immune responses. - Highlights: • Mice fed a tyrosine-rich diet accumulated p-cresyl sulfate in their blood. • p-Cresyl sulfate negatively correlated with contact hypersensitivity response. • The in vitro production of IFN-γ was suppressed by p-cresyl sulfate. • p-Cresyl sulfate decreased the percentage of IFN-γ-producing Th1 cells in vitro

Effects of intestinal bacteria-derived p-cresyl sulfate on Th1-type immune response in vivo and in vitro

Energy Technology Data Exchange (ETDEWEB)

Shiba, Takahiro, E-mail: takahiro-shiba@yakult.co.jp; Kawakami, Koji; Sasaki, Takashi; Makino, Ikuyo; Kato, Ikuo; Kobayashi, Toshihide; Uchida, Kazumi; Kaneko, Kimiyuki

2014-01-15

Protein fermentation by intestinal bacteria generates various compounds that are not synthesized by their hosts. An example is p-cresol, which is produced from tyrosine. Patients with chronic kidney disease (CKD) accumulate high concentrations of intestinal bacteria-derived p-cresyl sulfate (pCS), which is the major metabolite of p-cresol, in their blood, and this accumulation contributes to certain CKD-associated disorders. Immune dysfunction is a CKD-associated disorder that frequently contributes to infectious diseases among CKD patients. Although some studies imply pCS as an etiological factor, the relation between pCS and immune systems is poorly understood. In the present study, we investigated the immunological effects of pCS derived from intestinal bacteria in mice. For this purpose, we fed mice a tyrosine-rich diet that causes the accumulation of pCS in their blood. The mice were shown to exhibit decreased Th1-driven 2, 4-dinitrofluorobenzene-induced contact hypersensitivity response. The concentration of pCS in blood was negatively correlated with the degree of the contact hypersensitivity response. In contrast, the T cell-dependent antibody response was not influenced by the accumulated pCS. We also examined the in vitro cytokine responses by T cells in the presence of pCS. The production of IFN-γ was suppressed by pCS. Further, pCS decreased the percentage of IFN-γ-producing Th1 cells. Our results suggest that intestinal bacteria-derived pCS suppressesTh1-type cellular immune responses. - Highlights: • Mice fed a tyrosine-rich diet accumulated p-cresyl sulfate in their blood. • p-Cresyl sulfate negatively correlated with contact hypersensitivity response. • The in vitro production of IFN-γ was suppressed by p-cresyl sulfate. • p-Cresyl sulfate decreased the percentage of IFN-γ-producing Th1 cells in vitro.

Effects of ethanolic Chavill extract on growth of lactobacillus and salmonella bacteria, in skimmed milk and imaging gastric-intestine media in vitro

Directory of Open Access Journals (Sweden)

R naghiha

2015-08-01

Full Text Available Introduction & aim: To achieve high performance and health, it’s better to use additives in the human diet which have beneficial effects on good bacteria and damaging effect on the harmful bacteria. For this purpose, effects of Chavill extract on growth, viability and death of lactobacillus and salmonella, in skimmed milk and imaging gastric-intestine media were studied in vitro conditions. Methods: This study was investigated in two completely randomized experiments with three levels of Chavill extract. In the first experiment, ability of the Chavill extract in Skim Milk medium was examined to survey survival, proliferation and death of beneficial and pathogenic gut bacteria. The second experiment which was down in the simulation of simulated gastric juice and simulated small intestine juice, the effect of Chavill extract on survival, proliferation and death of the bacteria were investigated. Treatments in both of experiments were three levels of Chavill extract (0, 1, and 3 % for three probiotic bacteria species. Data were analyzed with SAS 9.1 software and their means were compared by Duncan’s Multiple Range test at a significance level of 5 %. Results: By increasing of Chavill extract concentration to 1%, probiotic bacterial counts significantly increase compared to control treatment and the differences were significant and the count of Salmonella typhimurium difference with control significantly decreased. Using 3% Chavill extract compared to 1% extract, increased number of Lactobacillus acidophilus and Lactobacillus plantarum, decreased number of Lactobacillus casei, inhibit growth of Salmonella typhimurium bacterium and block growth of this bacterium. The second experiment on simulated gastric juice showed that numbers of Lactobacillus acidophilus and Lactobacillus plantarum bacteria increased and Lactobacillus casei and Salmonella typhimurium decreased. Also, findings of bacterial survival on simulated small intestine juice showed

Evaluation of nutritional status as an independent predictor of post-operative complications and morbidity after gastro-intestinal surgery.

Science.gov (United States)

van der Kroft, G; Janssen-Heijnen, M L G; van Berlo, C L H; Konsten, J L M

2015-08-01

Nutritional Risk Screening-2002 (NRS-2002) and the Malnutrition Universal Screening Tool (MUST) are screening tools for nutritional risk that have also been used to predict post-operative complications and morbidity, though not all studies confirm the reliability of nutritional screening. Our study aims to evaluate the independent predictive value of nutritional risk screening in addition to currently documented medical, surgical and anesthesiological risk factors for post-operative complications, as well as length of hospital stay. This study is a prospective observational cohort study of 129 patients undergoing elective gastro-intestinal-surgery. Patients were screened for nutritional risk upon admission using both MUST and NRS-2002 screening tools. Univariate and multivariate analyses were performed to investigate the independent predictive value of nutritional risk for post-operative complications and length of hospital stay. MUST ≥2 (OR 2.87; 95% CI 1.05-7.87) and peri-operative transfusion (OR 2.78; 95% CI 1.05-7.40) were significant independent predictors for the occurrence of post-operative complications. Peri-operative transfusion (HR 2.40; 95% CI 1.45-4.00), age ≥70 (HR 1.50; 95% CI 1.05-2.16) and open surgery versus laparoscopic surgery (HR 1.39; 95% CI 0.94-2.05) were independent predictors for increased length of hospital stay, whereas American Society of Anesthesiology Score (ASA) and MUST were not. Nutritional risk screening (MUST ≥2) is an independent predictor for post-operative complications, but not for increased length of hospital stay. Copyright © 2015 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

In vitro and in vivo evaluation of gastro-retentive carvedilol loaded chitosan beads using Gastroplus™.

Science.gov (United States)

Praveen, Radhakrishnan; Prasad Verma, Priya Ranjan; Venkatesan, Jayachandran; Yoon, Dong-Han; Kim, Se-Kwon; Singh, Sandeep Kumar

2017-09-01

The objective of present investigation was to develop gastro-retentive controlled release system of carvedilol using biological macromolecule, chitosan. 3 2 full factorial design was adopted for optimization of tripolyphosphate (X 1 ) and curing time (X 2 ). Bead stability in 0.1N HCl, buoyancy duration, density, drug loading, dissolution efficiency and cumulative percentage release at 8th hour were evaluated as dependent variables. The levels of X 1 and X 2 of optimized formulation having maximum desirability was found to 2.0% w/v and 62.66min, respectively. The in silico predicted responses and observed response were found to be in good agreement (percent bias error: -13.295 to +13.269). SEM images showed numerous pores in the cross sectional image that renders buoyancy. AUC 0-∞ of optimized formulation was 1.47 times higher as compared to suspension corroborating enhanced extent of absorption. T max and mean residence time were significantly higher from optimized formulation vis a vis suspension. In silico study indicated maximum regional absorption from the duodenum (94.1%) followed by jejunum (5.6%). Wagner-Nelson and Loo-Reigelman method were the preferred deconvolution approach over numerical deconvolution to establish IVIVC. In conclusion, the study showed that gastro-retentive controlled release system prepared using chitosan could be a potential drug carrier of carvedilol with improved bioavailability. Copyright © 2017 Elsevier B.V. All rights reserved.

In-vitro activity of solithromycin against anaerobic bacteria from the normal intestinal microbiota.

Science.gov (United States)

Weintraub, Andrej; Rashid, Mamun-Ur; Nord, Carl Erik

2016-12-01

Solithromycin is a novel fluoroketolide with high activity against bacteria associated with community-acquired respiratory tract infections as well as gonorrhea. However, data on the activity of solithromycin against anaerobic bacteria from the normal intestinal microbiota are scarce. In this study, 1024 Gram-positive and Gram-negative anaerobic isolates from the normal intestinal microbiota were analyzed for in-vitro susceptibility against solithromycin and compared to azithromycin, amoxicillin/clavulanic acid, ceftriaxone, metronidazole and levofloxacin by determining the minimum inhibitory concentration (MIC). Solithromycin was active against Bifidobacteria (MIC 50 , 0.008 mg/L) and Lactobacilli (MIC 50 , 0.008 mg/L). The MIC 50 for Clostridia, Bacteroides, Prevotella and Veillonella were 0.5, 0.5, 0.125 and 0.016 mg/L, respectively. Gram-positive anaerobes were more susceptible to solithromycin as compared to the other antimicrobials tested. The activity of solithromycin against Gram-negative anaerobes was equal or higher as compared to other tested agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Transformations of Phenolic Compounds in an in vitro Model Simulating the Human Alimentary Tract

Directory of Open Access Journals (Sweden)

Aleksandra Duda-Chodak

2009-01-01

Full Text Available The aim of this work is to establish the antioxidant properties of polyphenolic compounds of selected fruits before and after their transformations during digestion. The experiment was conducted in in vitro conditions on a set of dialysis membranes which simulated the human digestive tract. Apples of the Šampion, Malinowka and Golden Delicious cultivars, black chokeberry, banana, Wegierka zwykla blue plum, melon and Lukasowka pear were chosen for examination. It was found that compounds obtained after simulated digestion of chokeberries, pears and bananas showed lower antioxidant potential than fresh fruits, while the opposite results were obtained for apples and plums. All dialysates obtained after digestion were characterized by lower content of total polyphenols in comparison with raw material (fresh fruits. It was found that the polyphenols were hydrolyzed, especially glycosides of quercetin and cyanidin. Phenolic acids and cyanidin were characterized by low availability for absorption, whereas catechin and quercetin had a very high level of accessibility in the model small intestine.

Establishment of gastro-intestinal helminth infections in free-range chickens: a longitudinal on farm study.

Science.gov (United States)

Wongrak, Kalyakorn; Daş, Gürbüz; Moors, Eva; Sohnrey, Birgit; Gauly, Matthias

2014-01-01

The objective of this study was to monitor establishment and development of gastro-intestinal helminth infections in chickens over two production years (PY) on a free-range farm in Lower Saxony, Germany. The data were collected between July 2010 and June 2011 (PY1) and July 2011 and January 2013 (PY2), respectively. During PY1, Lohmann Brown classic (LB classic, N = 450) was tested, while in PY2 two different genotypes (230 LB classic, 230 LB plus) were used. The hens were kept in two mobile stalls that were moved to a new position at regular intervals. In both PY1 and PY2, 20 individual faecal samples per stall were randomly collected at monthly intervals in order to calculate the number of internal parasite eggs per gram of faeces (EPG). At the end of the laying periods, approximately 10% (N = 42) or more than 50% (N = 265) of hens were subjected to post-mortem parasitological examinations in PY1 and PY2, respectively. No parasite eggs were found in the faecal samples during PY1, whereas almost all of the hens (97.6%) were infected with Heterakis gallinarum (36 worms/hen) at the end of the period. In PY2, nematode eggs in faeces were found from the third month onwards at a low level, increasing considerably towards the final three months. There was no significant difference between the two genotypes of brown hens neither for EPG (P = 0.456) or for overall prevalence (P = 0.177). Mortality rate ranged from 18.3 to 27.4% but did not differ significantly between genotypes or production years. Average worm burden was 207 worms/hen in PY2. The most prevalent species were H. gallinarum (98.5%) followed by Ascaridia galli (96.2%) and Capillaria spp. (86.1%). Furthermore, three Capillaria species, C. obsignata, C. bursata and C. caudinflata were differentiated. In conclusion chickens kept on free-range farms are exposed to high risks of nematode infections and have high mortality rates with no obvious link to parasite infections. Once the farm environment is contaminated

Neural influences on human intestinal epithelium in vitro.

Science.gov (United States)

Krueger, Dagmar; Michel, Klaus; Zeller, Florian; Demir, Ihsan E; Ceyhan, Güralp O; Slotta-Huspenina, Julia; Schemann, Michael

2016-01-15

We present the first systematic and, up to now, most comprehensive evaluation of the basic features of epithelial functions, such as basal and nerve-evoked secretion, as well as tissue resistance, in over 2200 surgical specimens of human small and large intestine. We found no evidence for impaired nerve-evoked epithelial secretion or tissue resistance with age or disease pathologies (stomach, pancreas or colon cancer, polyps, diverticulitis, stoma reversal). This indicates the validity of future studies on epithelial secretion or resistance that are based on data from a variety of surgical specimens. ACh mainly mediated nerve-evoked and basal secretion in the small intestine, whereas vasoactive intestinal peptide and nitric oxide were the primary pro-secretory transmitters in the large intestine. The results of the present study revealed novel insights into regional differences in nerve-mediated secretion in the human intestine and comprise the basis by which to more specifically target impaired epithelial functions in the diseased gut. Knowledge on basic features of epithelial functions in the human intestine is scarce. We used Ussing chamber techniques to record basal tissue resistance (R-basal) and short circuit currents (ISC; secretion) under basal conditions (ISC-basal) and after electrical field stimulation (ISC-EFS) of nerves in 2221 resectates from 435 patients. ISC-EFS was TTX-sensitive and of comparable magnitude in the small and large intestine. ISC-EFS or R-basal were not influenced by the patients' age, sex or disease pathologies (cancer, polyps, diverticulitis). Ion substitution, bumetanide or adenylate cyclase inhibition studies suggested that ISC-EFS depended on epithelial cAMP-driven chloride and bicarbonate secretion but not on amiloride-sensitive sodium absorption. Although atropine-sensitive cholinergic components prevailed for ISC-EFS of the duodenum, jejunum and ileum, PG97-269-sensitive [vasoactive intestinal peptide (VIP) receptor 1

The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice

Energy Technology Data Exchange (ETDEWEB)

Ogawa, Eiichi [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Hosokawa, Masaya [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Faculty of Human Sciences, Tezukayama Gakuin University, Osaka (Japan); Harada, Norio; Yamane, Shunsuke; Hamasaki, Akihiro; Toyoda, Kentaro; Fujimoto, Shimpei; Fujita, Yoshihito; Fukuda, Kazuhito [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Tsukiyama, Katsushi; Yamada, Yuichiro [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Department of Internal Medicine, Division of Endocrinology, Diabetes and Geriatric Medicine, Akita University School of Medicine, Akita (Japan); Seino, Yutaka [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Kansai Electric Power Hospital, Osaka (Japan); Inagaki, Nobuya, E-mail: inagaki@metab.kuhp.kyoto-u.ac.jp [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); CREST of Japan Science and Technology Cooperation (JST), Kyoto (Japan)

2011-01-07

Research highlights: {yields} Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. {yields} Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. {yields} The GIP-receptor-mediated action in intestine does not involve in GLP-1-mediated pathway. -- Abstract: Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic {beta} cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [{sup 14}C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [{sup 14}C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin

The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice

International Nuclear Information System (INIS)

Ogawa, Eiichi; Hosokawa, Masaya; Harada, Norio; Yamane, Shunsuke; Hamasaki, Akihiro; Toyoda, Kentaro; Fujimoto, Shimpei; Fujita, Yoshihito; Fukuda, Kazuhito; Tsukiyama, Katsushi; Yamada, Yuichiro; Seino, Yutaka; Inagaki, Nobuya

2011-01-01

Research highlights: → Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. → Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. → The GIP-receptor-mediated action in intestine does not involve in GLP-1-mediated pathway. -- Abstract: Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic β cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [ 14 C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [ 14 C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin-mediated pathway rather

Fractionation and determination of total antioxidant capacity, total ...

African Journals Online (AJOL)

DEYAKS PLC

2014-01-29

Jan 29, 2014 ... the treatment of stomach and rheumatic pains, inflamma- tory disorders ... reagent and expressed as gallic acid equivalent (GAE). Exactly. 0.25 ml .... anthocyanins and antioxidant activity following simulated gastro- intestinal ...

A strategy for early-risk predictions of clinical drug-drug interactions involving the GastroPlusTM DDI module for time-dependent CYP inhibitors.

Science.gov (United States)

Sohlenius-Sternbeck, Anna-Karin; Meyerson, Gabrielle; Hagbjörk, Ann-Louise; Juric, Sanja; Terelius, Ylva

2018-04-01

1. A set of reference compounds for time-dependent inhibition (TDI) of cytochrome P450 with available literature data for k inact and K I was used to predict clinical implications using the GastroPlus TM software. Comparisons were made to in vivo literature interaction data. 2. The predicted AUC ratios (AUC +inhibitor /AUC control ) could be compared with the observed ratios from literature for all compounds with detailed information about in vivo administration, pharmacokinetics and in vivo interactions (N = 21). For this dataset, the difference between predicted and observed AUC ratios for interactions with midazolam was within twofold for all compounds except one (telaprevir, for which non-CYP-mediated metabolism likely plays a role after multiple dosing). 3. The sensitivity, specificity and accuracy of the GastroPlus TM predictions using a binary classification as no-to-weak interaction versus moderate-to-strong interaction for all compounds with available in vivo interaction data, were 80%, 82% and 81%, respectively (N = 31). 4. As a result of our evaluations of the DDI module in GastroPlus TM , we have implemented an early TDI risk assessment decision tree for our drug discovery projects involving in vitro screening and early GastroPlus TM predictions. Shifted IC 50 values are determined and k inact /K I estimated (by using a regression line established with in house-shifted IC 50 values and literature k inact /K I ratios), followed by GastroPlus TM predictions.

Efficacy of the nematode-trapping fungus Duddingtonia flagrans against three species of gastro-intestinal nematodes in laboratory faecal cultures from sheep and goats.

Science.gov (United States)

Waghorn, T S; Leathwick, D M; Chen, L-Y; Skipp, R A

2003-12-30

The ability of the nematode-killing fungus Duddingtonia flagrans to reduce number of infective larvae of three species of gastro-intestinal parasitic nematodes developing in dung was investigated in both goats and sheep. Groups of lambs and kids (12-20 weeks old) were given mono-specific infections of Haemonchus contortus, Ostertagia (Teladorsagia) circumcincta or Trichostrongylus colubriformis. Following patency of the infections (t1) faecal samples were collected for determination of faecal nematode egg count (FEC) and culture of parasite larvae. Groups of animals were then dosed on 2 consecutive days with one of the two dose rates of the fungus (250,000 or 500,000 spores/kg liveweight). One (t2) and 5 (t3) days after the second dose of fungus samples were again collected for FEC and culture. The number of larvae recovered from the faecal cultures at t1 and t3 were used as controls to assess the efficacy of the experimental treatment at t2. Average efficacy was 78% with group means ranging from 40 to 93%. Dose rate of fungus appeared to influence efficacy against O. circumcincta but not against H. contortus or T. colubriformis. Overall, there were no differences in the efficacy of the fungus against any of the parasite species or in either host animal. The results of this trial indicate the potential use of this fungus as a broad spectrum anti-parasite agent for use in both goats and sheep.

[No inhibition of intestinal motility following ketamine-midazolam anesthesia. A comparison of anesthesia with enflurane and fentanyl/midazolam].

Science.gov (United States)

Freye, E; Knüfermann, V

1994-02-01

Postoperative intestinal atonia is a complication which is likely to occur in patients predisposed for constipation and in patients after intra-abdominal operations. The postoperative delay of bowel movement, however, is often also related to the type of anaesthesia being used. In order to evaluate the magnitude of an anaesthetic-induced postoperative delay of bowel movement, two types of intravenous-based anaesthesia using fentanyl/midazolam (1 mg/25 mg; dosage 0.1 ml/kg/h), and ketamine/midazolam (250 mg/25 mg; dosage 0.1 ml/kg/h) respectively were compared with a volatile anaesthetic technique (enflurane; mean concentration 1.5 vol%). METHODS. In three groups of patients (each n = 15) undergoing elective surgery of the lower extremities, induction of anaesthesia was accomplished with methohexital (1-1.5 mg/kg) to facilitate intubation. For the maintenance of muscle relaxation vecuronium bromide was used. All patients were given droperidol to prevent postoperative emesis, and they were artificially ventilated with N2O/O2 (60:40) to normal end-expiratory CO2 concentrations. No anticholinergic agents were used at the end of operation since they are known to interfere with bowel motility. In order to determine gastro-intestinal motility, the H2 exhalation test was used. For this purpose 40 g lactulose in 100 ml of water was given to all patients via a gastral tube shortly before extubation. Lactulose is broken down by bacteria once it enters the colon, and H2 is released, taken up by the vascular system and exhaled. Postoperatively, patients were asked to exhale into a 20-ml syringe every 10 min. The content was analysed for hydrogen (ppm), using an electrochemical sensor (GMI exhaled hydrogen monitor). From the time of lactulose instillation to a threefold increase in end-expiratory hydrogen concentration (compared to the preoperative value), gastro-coecal transit time was computed. RESULTS. All three groups of patients were comparable in age, height and body

The relationship between helicobacter pylori infection and gastro-esophageal reflux disease

OpenAIRE

Batool M Mahdi

2011-01-01

Background : Gastro-esophageal reflux disease is a common condition, affecting 25%-40% of the population. Increasing attention has been paid to the relationship between Helicobacter pylori infection and reflux esophagitis. Aim: The aim of this study was to investigate the association between CagA+ H. pylori and endoscopically proven gastro-esophageal reflux disease. Patients and Methods: The study group included 60 hospital patients with gastro-esophageal reflux disease between 2007 and 2009 ...

Anti-inflammatory Effects of Fungal Metabolites in Mouse Intestine as Revealed by In vitro Models

Directory of Open Access Journals (Sweden)

Dominik Schreiber

2017-08-01

Full Text Available Inflammatory bowel diseases (IBD, which include Crohn's disease and ulcerative colitis, are chronic inflammatory disorders that can affect the whole gastrointestinal tract or the colonic mucosal layer. Current therapies aiming to suppress the exaggerated immune response in IBD largely rely on compounds with non-satisfying effects or side-effects. Therefore, new therapeutical options are needed. In the present study, we investigated the anti-inflammatory effects of the fungal metabolites, galiellalactone, and dehydrocurvularin in both an in vitro intestinal inflammation model, as well as in isolated myenteric plexus and enterocyte cells. Administration of a pro-inflammatory cytokine mix through the mesenteric artery of intestinal segments caused an up-regulation of inflammatory marker genes. Treatment of the murine intestinal segments with galiellalactone or dehydrocurvularin by application through the mesenteric artery significantly prevented the expression of pro-inflammatory marker genes on the mRNA and the protein level. Comparable to the results in the perfused intestine model, treatment of primary enteric nervous system (ENS cells from the murine intestine with the fungal compounds reduced expression of cytokines such as IL-6, TNF-α, IL-1β, and inflammatory enzymes such as COX-2 and iNOS on mRNA and protein levels. Similar anti-inflammatory effects of the fungal metabolites were observed in the human colorectal adenocarcinoma cell line DLD-1 after stimulation with IFN-γ (10 ng/ml, TNF-α (10 ng/ml, and IL-1β (5 ng/ml. Our results show that the mesenterially perfused intestine model provides a reliable tool for the screening of new therapeutics with limited amounts of test compounds. Furthermore, we could characterize the anti-inflammatory effects of two novel active compounds, galiellalactone, and dehydrocurvularin which are interesting candidates for studies with chronic animal models of IBD.

Gastro-oesophageal reflux disease

NARCIS (Netherlands)

Bredenoord, Albert J.; Pandolfino, John E.; Smout, André J. P. M.

2013-01-01

Gastro-oesophageal reflux disease is one of the most common disorders of the gastrointestinal tract. Over past decades, considerable shifts in thinking about the disease have taken place. At a time when radiology was the only diagnostic test available, reflux disease was regarded as synonymous with

A proposition for the diagnosis and treatment of gastro-oesophageal reflux disease in children: A report from a working group on gastro-oesophageal reflux disease

NARCIS (Netherlands)

Y. Vandenplas (Yvan); A. Ashkenazi (A.); D. Belli (D.); N. Boige (N.); J. Bouquet (Jan); S. Cadranel (S.); J.P. Cezard (J.); S. Cucchiara (S.); C. Dupont (C.); K. Geboes (K.); F. Gottrand; H.S.A. Heymans (Hugo); C. Jasinski (C.); C.M.F. Kneepkens (Frank); S. Koletzko (Sybille); P. Milla (Peter); J.F. Mougenot (J.); D. Nusslé (D.); J. Navarro (J.); S.J. Newell (S.); E. Olafsdottir (E.); S. Peeters (S.); A. Ravelli (A.); I. Polanco (I.); B. Sandhu; J.J. Tolboom (Jules)

1993-01-01

textabstractIn this paper, a Working Group on Gastro-Oesophageal Reflux discusses recommendations for the first line diagnostic and therapeutic approach of gastro-oesophageal reflux disease in infants and children. All members of the Working Group agreed that infants with uncomplicated

The relationship between helicobacter pylori infection and gastro-esophageal reflux disease.

Science.gov (United States)

Mahdi, Batool M

2011-03-01

Gastro-esophageal reflux disease is a common condition, affecting 25%-40% of the population. Increasing attention has been paid to the relationship between Helicobacter pylori infection and reflux esophagitis. The aim of this study was to investigate the association between CagA+ H. pylori and endoscopically proven gastro-esophageal reflux disease. The study group included 60 hospital patients with gastro-esophageal reflux disease between 2007 and 2009 as compared with 30 healthy patients from a control group that was age and sex matched. Helicobacter pylori CagA+ was identified by an immunological test (Immunochromatography test) (ACON, USA). Helicobacter pyloriCagA+ was present in 42/60 (70%) of the patients with gastro-esophageal reflux disease and in 11/30 (36.6%) patients in the control group (p=0.002). The Odds ratio = 0.8004 with 95% Confidence Interval = from 0.3188 to 2.0094. The relative risk=1.35 that indicates an association between Helicobacter pylori and disease. The presence of Helicobacter pylori is significantly increased in patients with gastro-esophageal reflux disease as compared with the control group.

The effects of sleeve gastectomy on gastro-esophageal reflux and gastro-esophageal motility.

Science.gov (United States)

Hayat, Jamal O; Wan, Andrew

2014-05-01

Sleeve gastrectomy is an increasingly performed bariatric procedure associated with low morbidity and good short to medium term effects on weight loss and comorbid conditions. Studies assessing the prevalence of post-operative gastro-esophageal reflux disease (GERD), show sleeve gastrectomy may provoke de novo GERD symptoms or worsening of pre-existing GERD. Pathophysiological mechanisms of GERD after sleeve gastrectomy include a hypotensive lower esophageal sphincter, increased gastro-esophageal pressure gradient and intra-thoracic migration of the remnant stomach. A reduction in the compliance of the gastric remnant may provoke an increase in transient lower esophageal sphincter relaxations. Time-resolved MRI suggests relative gastric stasis in the proximal remnant and increased emptying from the antrum. A lack of standardisation of technique, along with heterogeneity of studies assessing GERD may explain the wide variability in reported results. Simultaneous and careful repair of an associated hiatus hernia may result in a reduction in the prevalence of post-operative GERD.

Identification of glucose-fermenting bacteria present in an in-vitro model of the human inetstine by RNA-stable isotope probing

NARCIS (Netherlands)

Egert, M.G.G.; Graaf, de A.A.; Maathuis, A.; Waard, de P.; Plugge, C.M.; Smidt, H.; Deutz, N.E.P.; Dijkema, C.; Vos, de W.M.; Venema, K.

2007-01-01

16S rRNA-based stable isotope probing (SIP) and nuclear magnetic resonance (NMR) spectroscopy-based metabolic profiling were used to identify bacteria fermenting glucose under conditions simulating the human intestine. The TIM-2 in vitro model of the human intestine was inoculated with a GI tract

Gastro-esophageal reflux disease and exacerbations in chronic obstructive pulmonary disease

DEFF Research Database (Denmark)

Ingebrigtsen, Truls S; Marott, Jacob L; Vestbo, Jørgen

2015-01-01

BACKGROUND AND OBJECTIVE: We tested the hypothesis that gastro-esophageal reflux disease is a risk factor for exacerbations in individuals with chronic obstructive pulmonary disease (COPD). METHODS: Among 9622 participants in the Copenhagen City Heart Study, we identified 1259 individuals with COPD...... applied a multivariable Cox regression analysis with adjustment for well-established risk factors associated with COPD exacerbations or gastro-esophageal reflux disease, including COPD severity, and symptoms. RESULTS: Individuals with COPD and gastro-esophageal reflux disease had more chronic bronchitis...... and information on gastro-esophageal reflux disease and the regular use of acid inhibitory treatment. These individuals were followed for 5 years with regard to medically treated COPD exacerbations, which we defined as a short course treatment with oral corticosteroids alone or in combination with antibiotics. We...

A new approach to predict human intestinal absorption using porcine intestinal tissue and biorelevant matrices

NARCIS (Netherlands)

Westerhout, J.; Steeg, E. van de; Grossouw, D.; Zeijdner, E.E.; Krul, C.A.M.; Verwei, M.; Wortelboer, H.M.

2014-01-01

A reliable prediction of the oral bioavailability in humans is crucial and of high interest for pharmaceutical and food industry. The predictive value of currently used in silico methods, in vitro cell lines, ex vivo intestinal tissue and/or in vivo animal studies for human intestinal absorption,

In vitro assessment of potential intestinal absorption of some phenolic families and carboxylic acids from commercial instant coffee samples.

Science.gov (United States)

López-Froilán, R; Ramírez-Moreno, E; Podio, N S; Pérez-Rodríguez, M L; Cámara, M; Baroni, M V; Wunderlin, D A; Sánchez-Mata, M C

2016-06-15

Coffee is one of the most consumed beverages in the world, being a source of bioactive compounds as well as flavors. Hydroxycinnamic acids, flavonols, and carboxylic acids have been studied in the samples of instant coffee commercialized in Spain. The studies about contents of food components should be complemented with either in vitro or in vivo bioaccessibility studies to know the amount of food components effectively available for functions in the human body. In this sense, a widely used in vitro model has been applied to assess the potential intestinal absorption of phenolic compounds and organic acids. The contents of hydroxycinnamic acids and flavonols were higher in instant regular coffee samples than in the decaffeinated ones. Bioaccessible phenolic compounds in most analyzed samples account for 20-25% of hydroxycinnamic acids and 17-26% of flavonols. This could mean that a great part of them can remain in the gut, acting as potential in situ antioxidants. Quinic, acetic, pyroglutamic, citric and fumaric acids were identified in commercial instant coffee samples. Succinic acid was found in the coffee blend containing chicory. All carboxylic acids showed a very high bioaccessibility. Particularly, acetic acid and quinic acid were found in higher contents in the samples treated with the in vitro simulation of gastrointestinal processes, compared to the original ones, which can be explained by their cleavage from chlorogenic acid during digestion. This is considered as a positive effect, since quinic acid is considered as an antioxidant inducer.

Assessment of in Vitro Digestibility of Dietary Carbohydrates Using Rat Small Intestinal Extract.

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Ferreira-Lazarte, Alvaro; Olano, Agustín; Villamiel, Mar; Moreno, F Javier

2017-09-13

There are few studies on the assessment of digestibility of nondigestible carbohydrates, despite their increasingly important role in human health. In vitro digestibility of a range of dietary carbohydrates classified as digestible (maltose, sucrose, and lactose), well-recognized (lactulose, fructooligosaccharides (FOS), and two types of galactooligosaccharides (GOS) differing in the predominant glycosidic linkage), and potential (lactosucrose and GOS from lactulose, OsLu) prebiotics using a rat small intestinal extract (RSIE) under physiological conditions of temperature and pH is described. Recognized and potential prebiotics were highly resistant to RSIE digestion although partial hydrolysis at different extents was observed. FOS and lactulose were the most resistant to digestion, followed closely by OsLu and more distantly by both types of GOS and lactosucrose. In GOS, β(1 → 6) linkages were more resistant to digestion than β(1 → 4) bonds. The reported in vitro digestion model is a useful, simple, and cost-effective tool to evaluate the digestibility of dietary oligosaccharides.

INTESTINAL OBSTRUCTION

Science.gov (United States)

Whipple, G. H.; Stone, H. B.; Bernheim, B. M.

1913-01-01

Closed duodenal loops may be made in dogs by ligatures placed just below the pancreatic duct and just beyond the duodenojejunal junction, together with a posterior gastro-enterostomy. These closed duodenal loop dogs die with symptoms like those of patients suffering from volvulus or high intestinal obstruction. This duodenal loop may simulate closely a volvulus in which there has been no vascular disturbance. Dogs with closed duodenal loops which have been washed out carefully survive a little longer on the average than animals with unwashed loops. The duration of life in the first instance is one to three days, with an average of about forty-eight hours. The dogs usually lose considerable fluid by vomiting and diarrhea. A weak pulse, low blood pressure and temperature are usually conspicuous in the last stages. Autopsy shows more or less splanchnic congestion which may be most marked in the mucosa of the upper small intestine. The peritoneum is usually clear and the closed loop may be distended with thin fluid, or collapsed, and contain only a small amount of pasty brown material. The mucosa of the loop may show ulceration and even perforation, but in the majority of cases it is intact and exhibits only a moderate congestion. Simple intestinal obstruction added to a closed duodenal loop does not modify the result in any manner, but it may hasten the fatal outcome. The liver plays no essential role as a protective agent against this poison, for a dog with an Eck fistula may live three days with a closed loop. A normal dog reacts to intraportal injection and to intravenous injection of the toxic substance in an identical manner. Drainage of this loop under certain conditions may not interfere with the general health over a period of weeks or months. Excision of the part of the duodenum included in this loop causes no disturbance. The material from the closed duodenal loops contains no bile, pancreatic juice, gastric juice, or split products from the food. It can be

Intestinal obstruction in germ-free dogs.

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Heneghan, J B; Robinson, J W; Menge, H; Winistörfer, B

1981-08-01

Mechanical occlusions were created in the intestines of four germ-free dogs. At the time of the operation, a control loop of mid-intestine was perfused in vivo and then excised for examinations in vitro, which included the determination of the equilibrium uptake of phenylalanine and of beta-methyl-glucoside, the influx kinetics of phenylalanine and morphometric analysis of the mucosa by microdissection and stereological techniques. Seven days after establishment of the occlusion the abdomen was reopened, and loops above and below the occlusion were perfused, and then excised for the same tests in vitro. Unlike occluded loops of conventional dogs, the intestine of the germ-free animal above the occlusion does not secrete water and electrolytes into the lumen. Its transport properties in vitro do not differ from those of the control loop, and the morphometric analyses reveal only slight changes in villus structure. The loop below the obstruction undergoes marked atrophy, as has been observed in conventional dogs. The results suggest that the copious secretion that occurs above an intestinal obstruction in normal animals is due to the presence of an abundant bacterial population in the obstruction fluid.

Synthesis of New Fluoro-Benzimidazole Derivatives as an Approach towards the Discovery of Novel Intestinal Antiseptic Drug Candidates.

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Cevik, Ulviye Acar; Saglik, Begum Nurpelin; Ozkay, Yusuf; Canturk, Zerrin; Bueno, Juan; Demirci, Fatih; Koparal, Ali Savas

2017-01-01

In the present study, nineteen new fluoro-benzimidazole derivatives, including nifuroxazide analogs, were synthesized by microwave-supported reactions and tested against a panel of pathogenic microorganisms consisting of resistant strains. The synthesized compounds were characterized and identified by FT-IR, 1H- and 13C-NMR, mass spectroscopy, and elemental analyses, respectively. In vitro antimicrobial and cytotoxic effects of the synthesized compounds were determined by microdilution and by [3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide] (MTT) assay. The compound 4-[5(6)-fluoro-1H-benzimidazol-2-yl)-N'-(2- methylbenzylidene)]benzohydrazide (18) showed particularly high inhibitory activity against the gastro-intestinal pathogens, such as Escherichia coli O157:H7, Escherichiacoli ATCC 8739, Escherichia coli ATCC 35218 and Salmonella typhimurium ATCC 13311 standard strains, with minimum inhibitory concentrations (MIC90) ranging from 0.49-0.98 μg/mL. The microbial panel contained a total of ten pathogens including Klebsiella sp., Mycobacterium sp., MRSA, etc., for which the level of inhibitory activity measured was higher than that exhibited by the tested concentrations (MIC > 1000 μg/mL). In vitro cytotoxicity results revealed that the inhibitory concentration (IC50) value (210.23 μg/mL) of compound 18 against CCD 841 CoN cells (human intestinal epithelial cell line) is about 430 times higher than its MIC90 value against the tested Escherichia coli strains. Furthermore, the docking study of compound 18 suggested that its structure is very compatible with the active site pocket of the phosphofructokinase-2 enzyme. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Intestinal

International Nuclear Information System (INIS)

Cardenas, Rene; Haro, Elfa

2002-01-01

The paper present the diagnosic sensitivit of gastro esophagic scintigraphy (GCE) in children with suspiction of gastro esophagic reflux (RGE), as well as to evidence bronchial aspiratin in cases with suspected RGE. There was studied two groups of children: group A: Include 73 childs with documented diagnosis of RGE, by meas of cine esophagography. Group B: Include 22 children with symptoms of suspiction of. (The author)

Quantification of Salmonella Survival and Infection in an In vitro Model of the Human Intestinal Tract as Proxy for Foodborne Pathogens

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Lucas M. Wijnands

2017-06-01

Full Text Available Different techniques are available for assessing differences in virulence of bacterial foodborne pathogens. The use of animal models or human volunteers is not expedient for various reasons; the use of epidemiological data is often hampered by lack of crucial data. In this paper, we describe a static, sequential gastrointestinal tract (GIT model system in which foodborne pathogens are exposed to simulated gastric and intestinal contents of the human digestive tract, including the interaction of pathogens with the intestinal epithelium. The system can be employed with any foodborne bacterial pathogens. Five strains of Salmonella Heidelberg and one strain of Salmonella Typhimurium were used to assess the robustness of the system. Four S. Heidelberg strains originated from an outbreak, the fifth S. Heidelberg strain and the S. Typhimurium strain originated from routine meat inspections. Data from plate counts, collected for determining the numbers of surviving bacteria in each stage, were used to quantify both the experimental uncertainty and biological variability of pathogen survival throughout the system. For this, a hierarchical Bayesian framework using Markov chain Monte Carlo (MCMC was employed. The model system is able to distinguish serovars/strains for in vitro infectivity when accounting for within strain biological variability and experimental uncertainty.

Bile Salt Micelles and Phospholipid Vesicles Present in Simulated and Human Intestinal Fluids

DEFF Research Database (Denmark)

Elvang, Philipp A; Hinna, Askell H; Brouwers, Joachim

2016-01-01

Knowledge about colloidal assemblies present in human intestinal fluids (HIFs), such as bile salt micelles and phospholipid vesicles, is regarded of importance for a better understanding of the in vivo dissolution and absorption behavior of poorly soluble drugs (Biopharmaceutics Classification...... System class II/IV drugs) because of their drug-solubilizing ability. The characterization of these potential drug-solubilizing compartments is a prerequisite for further studies of the mechanistic interplays between drug molecules and colloidal structures within HIFs. The aim of the present study...... and HIF indicate that the simulated intestinal fluids (FaSSIF-V1 and FeSSIF-V1) represent rather simplified models of the real human intestinal environment in terms of coexisting colloidal particles. It is hypothesized that the different supramolecular assemblies detected differ in their lipid composition...

Identification of intestinal loss of a drug through physiologically based pharmacokinetic simulation of plasma concentration-time profiles.

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Peters, Sheila Annie

2008-01-01

Despite recent advances in understanding of the role of the gut as a metabolizing organ, recognition of gut wall metabolism and/or other factors contributing to intestinal loss of a compound has been a challenging task due to the lack of well characterized methods to distinguish it from first-pass hepatic extraction. The implications of identifying intestinal loss of a compound in drug discovery and development can be enormous. Physiologically based pharmacokinetic (PBPK) simulations of pharmacokinetic profiles provide a simple, reliable and cost-effective way to understand the mechanisms underlying pharmacokinetic processes. The purpose of this article is to demonstrate the application of PBPK simulations in bringing to light intestinal loss of orally administered drugs, using two example compounds: verapamil and an in-house compound that is no longer in development (referred to as compound A in this article). A generic PBPK model, built in-house using MATLAB software and incorporating absorption, metabolism, distribution, biliary and renal elimination models, was employed for simulation of concentration-time profiles. Modulation of intrinsic hepatic clearance and tissue distribution parameters in the generic PBPK model was done to achieve a good fit to the observed intravenous pharmacokinetic profiles of the compounds studied. These optimized clearance and distribution parameters are expected to be invariant across different routes of administration, as long as the kinetics are linear, and were therefore employed to simulate the oral profiles of the compounds. For compounds with reasonably good solubility and permeability, an area under the concentration-time curve for the simulated oral profile that far exceeded the observed would indicate some kind of loss in the intestine. PBPK simulations applied to compound A showed substantial loss of the compound in the gastrointestinal tract in humans but not in rats. This accounted for the lower bioavailability of the

Impact of the Fenton process in meat digestion as assessed using an in vitro gastro-intestinal model.

Science.gov (United States)

Oueslati, Khaled; de La Pomélie, Diane; Santé-Lhoutellier, Véronique; Gatellier, Philippe

2016-10-15

The production of oxygen free radicals catalysed by non-haem iron was investigated in an in vitro mimetic model of the digestive tract using specific chemical traps. Superoxide radicals (O2(∗-)) and their protonated form (hydroperoxyl radicals, HO2(∗)) were detected by the reduction of nitroblue tetrazolium into formazan, and hydroxyl radicals (OH(∗)) were detected by the hydroxylation of terephthalate. Under gastric conditions, O2(∗-)/HO2(∗) were detected in higher quantity than OH(∗). Increasing the pH from 3.5 to 6.5 poorly affected the kinetics of free radical production. The oxidations generated by these free radicals were estimated on myofibrils prepared from pork rectus femoris muscle. Myofibrillar lipid and protein oxidation increased with time and oxidant concentration, with a negative impact on the digestibility of myofibrillar proteins. Plant food antioxidants considerably decreased free radical production and lipid oxidation but not protein oxidation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Radiologic quantitation of gastro-oesophageal reflux. Correlation between height of food stimulated gastro-oesophageal reflux and level of histologic changes in reflux oesophagitis

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Christiansen, T.; Funch-Jensen, P.; Jacobsen, N.O.; Thommesen, P.

In a prospective study, 26 patients with symptoms of reflux oesophagitis underwent a barium examination for gastro-oesophageal reflux after food stimulation, and endoscopy with biopsy from different levels of the oesophagus. Radiologic grading of the gastro-oesophageal reflux depending on the height of the reflux into the oesophagus was performed, and this was correlated to the microscopic appearance at different levels in the oesophagus. Complete agreement between the radiologic grading and the histology was found in 69 per cent of the cases, and when gastro-oesophageal reflux was demonstrated the agreement was 75 per cent. Accordingly, the results showed a good accordance between the two variants, indicating that the height of the reflux during the food stimulated test may be truly indicative of the reflux height under non-test conditions.

Prevalence of Helicobacter pylori in patients with gastro-oesophageal reflux disease: systematic review

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Raghunath, Anan; Hungin, A Pali S; Wooff, David; Childs, Susan

2003-01-01

Objectives To ascertain the prevalence of Helicobacter pylori in patients with gastro-oesophageal reflux disease and its association with the disease. Design Systematic review of studies reporting the prevalence of H pylori in patients with and without gastro-oesophageal reflux disease. Data sources Four electronic databases, searched to November 2001, experts, pharmaceutical companies, and journals. Main outcome measure Odds ratio for prevalence of H pylori in patients with gastro-oesophageal reflux disease. Results 20 studies were included. The pooled estimate of the odds ratio for prevalence of H pylori was 0.60 (95% confidence interval 0.47 to 0.78), indicating a lower prevalence in patients with gastro-oesophageal reflux disease. Substantial heterogeneity was observed between studies. Location seemed to be an important factor, with a much lower prevalence of H pylori in patients with gastro-oesophageal reflux disease in studies from the Far East, despite a higher overall prevalence of infection than western Europe and North America. Year of study was not a source of heterogeneity. Conclusion The prevalence of H pylori infection was significantly lower in patients with than without gastro-oesophageal reflux, with geographical location being a strong contributor to the heterogeneity between studies. Patients from the Far East with reflux disease had a lower prevalence of H pylori infection than patients from western Europe and North America, despite a higher prevalence in the general population. What is already known on this topicThe relation between H pylori infection and gastro-oesophageal reflux disease is controversialStudies on the prevalence of H pylori in patients with gastro-oesophageal reflux disease have given conflicting resultsRecent guidelines recommend eradication of H pylori in patients requiring long term proton pump inhibitors, essentially for reflux diseaseWhat this study addsDespite heterogeneity between studies, the prevalence of H pylori was

Effects of Digested Onion Extracts on Intestinal Gene Expression: An Interspecies Comparison Using Different Intestine Models.

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Nicole J W de Wit

Full Text Available Human intestinal tissue samples are barely accessible to study potential health benefits of nutritional compounds. Numbers of animals used in animal trials, however, need to be minimalized. Therefore, we explored the applicability of in vitro (human Caco-2 cells and ex vivo intestine models (rat precision cut intestine slices and the pig in-situ small intestinal segment perfusion (SISP technique to study the effect of food compounds. In vitro digested yellow (YOd and white onion extracts (WOd were used as model food compounds and transcriptomics was applied to obtain more insight into which extent mode of actions depend on the model. The three intestine models shared 9,140 genes which were used to compare the responses to digested onions between the models. Unsupervised clustering analysis showed that genes up- or down-regulated by WOd in human Caco-2 cells and rat intestine slices were similarly regulated by YOd, indicating comparable modes of action for the two onion species. Highly variable responses to onion were found in the pig SISP model. By focussing only on genes with significant differential expression, in combination with a fold change > 1.5, 15 genes showed similar onion-induced expression in human Caco-2 cells and rat intestine slices and 2 overlapping genes were found between the human Caco-2 and pig SISP model. Pathway analyses revealed that mainly processes related to oxidative stress, and especially the Keap1-Nrf2 pathway, were affected by onions in all three models. Our data fit with previous in vivo studies showing that the beneficial effects of onions are mostly linked to their antioxidant properties. Taken together, our data indicate that each of the in vitro and ex vivo intestine models used in this study, taking into account their limitations, can be used to determine modes of action of nutritional compounds and can thereby reduce the number of animals used in conventional nutritional intervention studies.

Combining in vitro and in silico methods for better prediction of surfactant effects on the absorption of poorly water soluble drugs-a fenofibrate case example.

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Berthelsen, Ragna; Sjögren, Erik; Jacobsen, Jette; Kristensen, Jakob; Holm, René; Abrahamsson, Bertil; Müllertz, Anette

2014-10-01

The aim of this study was to develop a sensitive and discriminative in vitro-in silico model able to simulate the in vivo performance of three fenofibrate immediate release formulations containing different surfactants. In addition, the study was designed to investigate the effect of dissolution volume when predicting the oral bioavailability of the formulations. In vitro dissolution studies were carried out using the USP apparatus 2 or a mini paddle assembly, containing 1000 mL or 100mL fasted state biorelevant medium, respectively. In silico simulations of small intestinal absorption were performed using the GI-Sim absorption model. All simulation runs were performed twice adopting either a total small intestinal volume of 533 mL or 105 mL, in order to examine the implication of free luminal water volumes for the in silico predictions. For the tested formulations, the use of a small biorelevant dissolution volume was critical for in vitro-in silico prediction of drug absorption. Good predictions, demonstrating rank order in vivo-in vitro-in silico correlations for Cmax, were obtained with in silico predictions utilizing a 105 mL estimate for the human intestinal water content combined with solubility and dissolution data performed in a mini paddle apparatus with 100mL fasted state simulated media. Copyright © 2014. Published by Elsevier B.V.

SIMULATING PROTEIN DIGESTION ON TROUT A RAPID AND INEXPENSIVE METHOD FOR DOCUMENTING FISH MEAL QUALITY AND SCREENING NOVEL PROTEIN SOURCES FOR USE IN AQUAFEEDS

OpenAIRE

M Bassompierre; A Kjar; Ewen McLean

1997-01-01

A novel in vitro digestion system, which simulated rainbow trout gastric and intestinal digestion was developed. The method was employed to evaluate the impact of the gastric phase of digestion upon degradation of three fish meals od differing quality. Results illustrated that two-phase gastric-intestinal digestion increased the discriminatory powers of the system when compared to one-step intestinal digestion. A comparison of the system with pH-STAT methods demonstrated that the in vitro tec...

Atrial Fibrillation and Gastro-Oesophageal Reflux Disease - Controversies and Challenges.

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Floria, Mariana; Barboi, Oana; Rezus, Ciprian; Ambarus, Valentin; Cijevschi-Prelipcean, Cristina; Balan, Gheorghe; Drug, Vasile Liviu

2015-01-01

Atrial fibrillation and gastro-oesophageal reflux are common manifestations in daily practice. The atria and the oesophagus are closely located and have similar nerve innervations. Over the last years, it has been observed that atrial fibrillation development and reflux disease could be related. Atrial fibrillation occurrence could be due to vagal nerve overstimulation. This, in association with vagal nerve-mediated parasympathetic stimulation, has also been observed in patients with gastro-oesophageal reflux. These mechanisms, in addition to inflammation, seem to be implicated in the pathophysiology of both diseases. Despite these associations supported by clinical and experimental studies, this relationship is still considered controversial. This review summarizes critical data regarding the association of gastro-oesophageal reflux and atrial fibrillation as well as their clinical implications.

[Gastro-oesophageal reflux in infants].

Science.gov (United States)

de Jong, Trudy; Kamphuis, Mascha; Kivit-Schwengle, Lilly

2014-01-01

A more prominent role for the youth healthcare physician: Youth Healthcare physicians reflect on the Dutch Paediatric Association (NVK) guideline entitled 'Gastro-oesophageal reflux (disease) in children aged 0-18 years'. This guideline states that medicinal treatment is given to these children too often. Dutch Youth Healthcare physicians see a large number of children with gastro-oesophageal reflux, with or without additional symptoms. The most common symptoms (crying and diminished weight gain) might be present even in the absence of reflux. Parents should be given advice and support when they are worried about reflux, crying or low weight gain. A lower weight gain curve on the growth chart is normal in breastfed children, and crying might be due to factors such as lack of routine or stimulus reduction. Overfeeding might also be the cause. Parents should be supported and followed up, with or without treatment, as necessary. Youth Healthcare professionals could perform this task.

Measuring intestinal fluid transport in vitro: Gravimetric method versus non-absorbable marker.

Science.gov (United States)

Whittamore, Jonathan M; Genz, Janet; Grosell, Martin; Wilson, Rod W

2016-04-01

The gut sac is a long-standing, widely used in vitro preparation for studying solute and water transport, and calculation of these fluxes requires an accurate assessment of volume. This is commonly determined gravimetrically by measuring the change in mass over time. While convenient this likely under-estimates actual net water flux (Jv) due to tissue edema. We evaluated whether the popular in vivo volume marker [(14)C]-PEG 4000, offers a more representative measure of Jvin vitro. We directly compared these two methods in five teleost species (toadfish, flounder, rainbow trout, killifish and tilapia). Net fluid absorption by the toadfish intestine based on PEG was significantly higher, by almost 4-fold, compared to gravimetric measurements, compatible with the latter under-estimating Jv. Despite this, PEG proved inconsistent for all of the other species frequently resulting in calculation of net secretion, in contrast to absorption seen gravimetrically. Such poor parallelism could not be explained by the absorption of [(14)C]-PEG (typically gravimetric method therefore remains the most reliable measure of Jv and we urge caution in the use of PEG as a volume marker. Copyright © 2016 Elsevier Inc. All rights reserved.

[Effect of vitamins B1, B2, B6, folic acid and vitamin C on the motor activity of chicken's intestines in chronic experiments and in vitro].

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Nagórna-Stasiak, B; Wawrzeńska, M

1987-01-01

The studies were carried out on 33 chickens of the broiler breed in chronic experiments and in vitro. In the chronic experiments the motility of the jejunum under the influence of vitamins of group B and vitamine C was recorded in 8 chickens. The vitamins were used at concentrations from 10 mg/l to 2.5 x 10(3) mg/l. In the experiments in vitro, the motility of the isolated segment of the jejunum was recorded by the method of Magnus. In this part of experiments the chickens were divided into 3 groups, of which group I (15 chickens) were fed with DKA finischer mixture, group II (5 hens) received, besides the mixture, per os 200 mg of vitamin C for 2 weeks, group III (5 hens) received the mixture and for 2 weeks intraperitoneally 200 mg of vitamin C. The effect of vitamins of group B in vitro was determined in chickens of group I, whereas that of vitamin C in chickens of group I, II and III. At the same time the level of vitamin C in the wall of the jejunum was determined by the method of Roe-Kuenther. It was shown that vitamin B2 and folic acid caused stimulation of intestine motility in the chickens, while vitamin B1, B6 and C decreased the motoric activity. Increased level of vitamin C in the intestinal wall resulted in increased intestine sensitivity. Chicken intestines sensitivity to vitamins was 10 times stronger to vitamins than that of the intestines of rabbits.

Cyanidin-3-O-Glucoside Modulates the In Vitro Inflammatory Crosstalk between Intestinal Epithelial and Endothelial Cells

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Daniela Ferrari

2017-01-01

Full Text Available Intestinal epithelium represents a protective physical barrier and actively contributes to the mucosal immune system. Polarized basolateral intestinal secretion of inflammatory mediators, followed by activation of NF-κB signaling and inflammatory pathways in endothelial cells, efficiently triggers extravasation of neutrophils from the vasculature, therefore contributing to the development and maintenance of intestinal inflammation. Proper regulation of NF-κB activation at the epithelial interface is crucial for the maintenance of physiological tissue homeostasis. Many papers reported that anthocyanins, a group of compounds belonging to flavonoids, possess anti-inflammatory effects and modulate NF-κB activity. In this study, by using a coculture in vitro system, we aimed to evaluate the effects of TNF-α-stimulated intestinal cells on endothelial cells activation, as well as the protective effects of cyanidin-3-glucoside (C3G. In this model, TNF-α induced nuclear translocation of NF-κB and TNF-α and IL-8 gene expression in Caco-2 cells, whereas C3G pretreatment dose-dependently reduced these effects. Furthermore, TNF-α-stimulated Caco-2 cells induced endothelial cells activation with increased E-selectin and VCAM-1 mRNA, leukocyte adhesion, and NF-κB levels in HUVECs, which were inhibited by C3G. We demonstrated that selective inhibition of the NF-κB pathway in epithelial cells represents the main mechanism by which C3G exerts these protective effects. Thus, anthocyanins could contribute to the management of chronic gut inflammatory diseases.

EFECTO DE LA FERTILIZACIÓN NITROGENADA Y DE LA EDAD DE CORTE SOBRE LA DIGESTIBILIDAD INTESTINAL In vitro DE LA PROTEÍNA DEL PASTO KIKUYO (Pennisetum clandestinum Hochst NITROGEN FERTILIZATION EFFECT AND CUT AGE ON THE In vitro INTESTINAL DIGESTIBILITY OF KIKUYO GRASS (Pennisetum clandestinum Hochst PROTEIN

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Marcelo Castañeda Colorado

2008-12-01

Full Text Available Con la finalidad de evaluar el efecto de la fertilización nitrogenada y de la edad de corte sobre la digestibilidad intestinal In vitro de la proteína del pasto kikuyo (Pennisetum clandestinum Hochst, se seleccionaron 16 parcelas a las cuales se les asignó uno de los siguientes tratamientos (cuatro parcelas/tratamiento: T1 (30 días de corte y 0 kg/N/Ha/Corte, T2 (60 días de corte y 0 kg/N/Ha/Corte, T3 (60 días de corte y 50 kg/N/Ha/Corte y T4 (30 días de corte y 50 kg/N/Ha/Corte. Luego de 120 días de tratamiento se recolectaron 5 submuestras de cada parcela con las que se conformó una muestra final para cada parcela en las que se analizó el contenido de proteína cruda y se realizó la prueba de degradabilidad ruminal a 16 horas y la prueba de digestibilidad intestinal In vitro de la proteína por el método de los tres pasos. Los resultados mostraron que no hubo efecto de la edad de corte, ni de la fertilización nitrogenada sobre el porcentaje de proteína cruda del pasto kikuyo. Los valores de digestibilidad intestinal como porcentaje de la proteína no degradable en rumen fueron: 52,51%, 56,14% para las praderas sin fertilizar con edad de corte de 30 y 60 días respectivamente y 43,38%, 45,40% para las praderas fertilizadas con edad de corte de 30 y 60 días respectivamente.With the purpose of evaluating the effect of the nitrogen fertilization and cut age on the In vitro intestinal digestibility of kikuyo grass (Pennisetum clandestinum Hochst protein, 16 plots were made, everyone assigned one of the following treatments (four plots per treatment: T1 (30 cut -day and 0 kg/ N/ Ha/ cut, T2 (60 cut-day and 0 kg/ N/ Ha/ cut, T3 (60 cut-day and 50 kg/ N/ Ha/ cut and T4 (30 cut-day and 50kg/ N/ Ha/ cut. 120 days after the treatment, 5 sub-samples were harvested of each plot, which were defined as final samples for each plot and, were realized to these samples a ruminal degradability trial for 16 hours and In vitro three-step method of

Gastro-oesophageal reflux in children--what's the worry?

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Allen, Katie; Ho, Shaun S C

2012-05-01

Gastro-oesophageal reflux is common and benign in children, especially during infancy. Distinguishing between gastrooesophageal reflux, gastro-oesophageal reflux disease and other illnesses presenting as chronic vomiting can be difficult. The general practitioner has a key role to play in identifying if a child requires referral for further investigation. This article outlines the main differential diagnoses to be considered in children presenting with chronic vomiting and/ or regurgitation. We also discuss key management decisions regarding gastro-oesophageal reflux disease in children and when to refer to a specialist for further investigation. Chronic vomiting and regurgitation frequently occurs in infancy and is most commonly due to simple, benign gastrooesophageal reflux, which is usually self limiting without requirement for further investigation. In contrast, gastrooesophageal reflux disease requires considered management and may be a presenting symptom of food allergy requiring more intensive therapy than simple acid suppression. Regular review by the general practitioner to ascertain warning signs will ensure that other serious illnesses are not overlooked and that appropriate investigation and specialist referral are made.

Clinical and pH-metric characteristics of gastro-oesophageal reflux secondary to cows' milk protein allergy.

Science.gov (United States)

Cavataio, F; Iacono, G; Montalto, G; Soresi, M; Tumminello, M; Carroccio, A

1996-01-01

AIMS: The primary aim was to assess whether there were differences in symptoms, laboratory data, and oesophageal pH-metry between infants with primary gastro-oesophageal reflux and those with reflux secondary to cows' milk protein allergy (CMPA). PATIENTS AND METHODS: 96 infants (mean(SD) age 7.8(2.0) months) with either primary gastro-oesophageal reflux, reflux with CMPA, CMPA only, or none of these (controls) were studied. Symptoms, immunochemical data, and oesophageal pH were compared between the four groups and the effect of a cows' milk protein-free diet on the severity of symptoms was also assessed. RESULTS: 14 out of 47(30%) infants with gastro-oesophageal reflux had CMPA. These infants had similar symptoms to those with primary gastro-oesophageal reflux but higher concentrations of total IgE and circulating eosinophils (p gastro-oesophageal reflux secondary to CMPA and in 24 of 25 infants with CMPA only. No infants with primary gastro-oesophageal reflux and none of the controls had this pattern. A cows' milk protein-free diet was associated with a significant improvement in symptoms only in infants with gastro-oesophageal reflux with CMPA. CONCLUSION: A characteristic oesophageal pH pattern is useful in distinguishing infants with gastro-oesophageal reflux associated with CMPA. PMID:8813871

Evaluation of anti-GERD activity of gastro retentive drug delivery system of itopride hydrochloride.

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Satapathy, Trilochan; Panda, Prasana K; Goyal, Amit K; Rath, Goutam

2010-08-01

The present work describes the formulation and evaluation of the gastroretentive system of Itopride hydrochloride. In this research, we have formulated floating hydrogel-based microspheres employing calcium carbonate (CaCO(3)) as a gas forming agent dispersed in alginate matrix. In vitro characterizations such as drug content, particle size, and drug release were carried out. GI motility was determined by administration of charcoal meal to rats. Results demonstrated that prepared microspheres were spherical in shape with smooth surface, good loading efficiency, and excellent buoyancy. The gastro retentive dosage form of itiopride demonstrated significant antacid, anti-ulcer, and anti-GERD activity after 12 hours in comparison with the conventional dosage form.

Sleeve gastrectomy and gastro-oesophageal reflux disease: a complex relationship.

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Mahawar, Kamal K; Jennings, Neil; Balupuri, Shlok; Small, Peter K

2013-07-01

Sleeve gastrectomy is rapidly becoming popular as a standalone bariatric operation. At the same time, there are valid concerns regarding its long-term durability and postoperative gastro-oesophageal reflux disease. Though gastric bypass remains the gold standard bariatric operation, it is not suitable for all patients. Sleeve gastrectomy is sometimes the only viable option. Patients with inflammatory bowel disease, liver cirrhosis, significant intra-abdominal adhesions involving small bowel and those reluctant to undergo gastric bypass could fall in this category. It is widely recognised that some patients report worsening of their gastro-oesophageal reflux disease after sleeve gastrectomy. Still, others develop de novo reflux. This review examines if it is possible to identify these patients prior to surgery and thus prevent postoperative gastro-oesophageal reflux disease after sleeve gastrectomy.

Scintigraphy for diagnosis of special problems in gastro-enterology

International Nuclear Information System (INIS)

Kempken, K.

1987-01-01

Nuclear medical studies have been used for many years in gastro-enterology to search for intrahepatic masses (static scintigram) and to clarify icterus and acute cholecystitis (hepatobiliary function scintigraphy). However, the range of indications for scintigraphic procedures is much broader still, and special questions in gastro-enterology, therefore, may often be answered, too. The methods discussed in the following all are non-invasive and may be applied not only in larger hospitals but also in private practices for nuclear medicine. (orig.) [de

[Influence of chest physiotherapy on gastro-œsophageal reflux in children].

Science.gov (United States)

Reychler, G; Jacques, L; Arnold, D; Scheers, I; Smets, F; Sokal, E; Stephenne, X

2015-05-01

Chest physiotherapy is regularly prescribed for children, particularly in cystic fibrosis. Gastro-oesophageal reflux is common in this disease and is associated with certain chest physiotherapy manoeuvres. To evaluate the influence of two chest physiotherapy techniques on gastro-oesophageal reflux in children. Twenty-nine children were investigated by routine pHmetry. During the examination, they performed two chest physiotherapy manoeuvres in a seated position for 10 minutes each with a 5 minutes rest between them. The two manoeuvres used were a slow expiration technique (ELPr) and positive expiratory pressure (PEP). It was a prospective study and the order of manoeuvres was randomised. The pH traces were analysed blindly when all the studies had been completed. In the sample, 21% of children had gastro-oesophageal reflux during the physiotherapy session. No relationship was found between reflux during physiotherapy and pathological reflux (P=0.411) nor the physiotherapy technique used (P=0.219). The use of these two chest physiotherapy techniques in children in a seated position can produce gastro-oesophageal reflux. Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Structural changes of bovine milk fat globules during in vitro digestion.

Science.gov (United States)

Gallier, S; Ye, A; Singh, H

2012-07-01

An in vitro digestion model that simulated gastric and intestinal fasting conditions was used to monitor the physical, chemical, and structural changes of fat globules from raw bovine milk. During in vitro gastric digestion, the fat globules were stable under low-acidic conditions. Some peptides and β-lactoglobulin were resistant to proteolysis by pepsin. Phospholipids, proteins, and peptides stabilized the globules in the stomach model. During in vitro intestinal digestion, most of the β-lactoglobulin and residual peptides were hydrolyzed by trypsin and chymotrypsin, and the lipolytic products, released from the hydrolysis of the triglyceride core of the globules, led to destabilization and coalescence of the globules. By accumulating at the surface of the fat globules, the lipolytic products formed a lamellar phase and their solubilization by bile salts resulted in the formation of disk-shaped micelles. This study brings new interesting insights on the digestion of bovine milk. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Pattern of food intolerance in patients with gastro-esophageal reflux symptoms.

Science.gov (United States)

Caselli, Michele; Lo Cascio, Natalina; Rabitti, Stefano; Eusebi, Leonardo H; Zeni, Elena; Soavi, Cecilia; Cassol, Francesca; Zuliani, Giovanni; Zagari, Rocco M

2017-12-01

Many food items have been involved in gastro-esophageal reflux disease pathogenesis and dietary modification has been proposed as first-line treatment. Test-based exclusion diets have shown to significantly reduce reflux symptoms. We aimed to assess the patterns of food intolerance in a series of patients with typical gastro-esophageal reflux symptoms (GERS). We retrospectively evaluated all patients with typical reflux symptoms, attending the Centre Study Association on Food Intolerance and Nutrition of Ferrara from January 2010 to October 2015, who resulted positive to at least one food item at the Leucocytotoxic Test. The presence and severity of typical GERS (heartburn and/or acid regurgitation) were assessed using the Gastro-esophageal Reflux Disease Impact Scale (GIS) questionnaire. Only individuals with a GIS Score of at least 5 points were included. Almost all patients (91.1%) were intolerant to at least 5 food items. The most frequent food intolerance (more than 33% of patients) were found for milk (55.4%), lettuce (46.4%), coffee (43.7%), brewer's yeast (42.9%), pork (42.9%), tuna (37.5%), rice (35.7%), sole (34.8%), asparagus (34.8%) and eggs (33.9%). Nine different clusters of food intolerance were detected. Patients with typical gastro-esophageal reflux symptoms seem to have intolerance to multiple food items, some of which (lettuce, brewer's yeast, tuna, rice, sole and asparagus) have not yet been associated to gastro-esophageal reflux disease.

Phenolic profile and fermentation patterns of different commercial gluten-free pasta during in vitro large intestine fermentation.

Science.gov (United States)

Rocchetti, Gabriele; Lucini, Luigi; Chiodelli, Giulia; Giuberti, Gianluca; Gallo, Antonio; Masoero, Francesco; Trevisan, Marco

2017-07-01

The fate of phenolic compounds, along with short-chain fatty acids (SCFAs) production kinetics, was evaluated on six different commercial gluten-free (GF) pasta samples varying in ingredient compositions, focussing on the in vitro faecal fermentation after the gastrointestinal digestion. A general reduction of both total phenolics and reducing power was observed in all samples, together with a substantial change in phenolic profile over 24h of faecal fermentation, with differences among GF pasta samples. Flavonoids, hydroxycinnamics and lignans degraded over time, with a concurrent increase in low-molecular-weight phenolic acids (hydroxybenzoic acids), alkylphenols, hydroxybenzoketones and tyrosols. Interestingly, discriminant analysis also identified several alkyl derivatives of resorcinol as markers of the changes in phenolic profile during in vitro fermentation. Furthermore, degradation pathways of phenolics by intestinal microbiota have been proposed. Considering the total SCFAs and butyrate production during the in vitro fermentation, different fermentation kinetics were observed among GF pasta post-hydrolysis residues. Copyright © 2017 Elsevier Ltd. All rights reserved.

Incidence of gastro-oesophageal reflux in geriatric clinical patients - a radiological study

Energy Technology Data Exchange (ETDEWEB)

Brackins-Romero, J.; Bruening, B.; Beyer, H.K.

1984-05-01

Gastro-oesophageal reflux is obviously caused by an insufficiency of the dilatable lower end of the oesophagus. The physiological pressure acting on it corresponds to 15-30 mm Hg so that the gastric juice is prevented from entering the oesophagus. Reflux is associated with a reduction of that pressure. Many causes may be responsible, although hiatal hernia, where confirmed, will only play a secondary part. In half of the 74 examined elderly patients, gastro-oesophageal reflux was confirmed by radiology. About half of these suffered also from hiatal hernia which was a sliding hernia in 75 per cent of the cases. In about 25 per cent of the patients suffering from gastro-oesophageal reflux, signs of oesophagitis were discovered by radiology. There was no correlation between overweight and the incidence of reflux, but hiatus hernia and a positive Broca test were distinctly related to one another. In patients with gastro-oesophageal reflux, vomiting as a key symptom was more frequently confirmed than in patients without reflux.

The management of gastro-oesophageal reflux disease.

Science.gov (United States)

Keung, Charlotte; Hebbard, Geoffrey

2016-02-01

If there are no features of serious disease, suspected gastro-oesophageal reflux disease can be initially managed with a trial of a proton pump inhibitor for 4-8 weeks. This should be taken 30-60 minutes before food for optimal effect. Once symptoms are controlled, attempt to withdraw acid suppression therapy. If symptoms recur, use the minimum dose that controls symptoms. Patients who have severe erosive oesophagitis, scleroderma oesophagus or Barrett's oesophagus require long-term treatment with a proton pump inhibitor. Lifestyle modification strategies can help gastro-oesophageal reflux disease. Weight loss has the strongest evidence for efficacy. Further investigation and a specialist referral are required if there is no response to proton pump inhibitor therapy. Atypical symptoms or signs of serious disease also need investigation.

Stability of [6]-gingerol and [6]-shogaol in simulated gastric and intestinal fluids.

Science.gov (United States)

Bhattarai, Sushila; Tran, Van H; Duke, Colin C

2007-11-30

The degradation kinetics of [6]-gingerol and [6]-shogaol were investigated in simulated gastric (pH 1) and intestinal (pH 7.4) fluids at 37 degrees C. Degradation products were quantitatively determined by HPLC (Lichrospher 60 RP select B column, 5 microm, 125 mm x 4 mm; mobile phase: methanol-water-acetic acid (60:39:1 v/v); flow rate: 0.6 ml/min; detection UV: 280 nm). In simulated gastric fluid (SGF) [6]-gingerol and [6]-shogaol underwent first-order reversible dehydration and hydration reactions to form [6]-shogaol and [6]-gingerol, respectively. The degradation was catalyzed by hydrogen ions and reached equilibrium at approximately 200 h. In simulated intestinal fluid (SIF) both [6]-gingerol and [6]-shogaol showed insignificant interconversion between one another. Addition of amino acids glycine, 3-amino propionic acid (beta-alanine) and gamma-amino butyric acid (GABA), and ammonium acetate at a range of concentrations of 0.05-0.5mM had no effect on the rate of degradation of [6]-shogaol in SGF and 0.1M HCl solution. However, at exceedingly high concentration (0.5M) of ammonium acetate and glycine, significant amounts of [6]-shogaol ammonia and glycine adducts were detected. The degradation profile of [6]-gingerol and [6]-shogaol under simulated physiological conditions reported in this study will provide insight into the stability of these compounds when administered orally.

Pathophysiology of gastro-oesophageal reflux disease

NARCIS (Netherlands)

Smout, A. J. P. M.

2003-01-01

Gastro-oesophageal reflux disease (GERD), defined as symptoms or mucosal damage caused by reflux of gastric contents into the esophageal body, is a multifactorial disorder. Malfunctioning of the anti-reflux barrier at the esophagogastric junction, consisting of the right diaphragmatic crus and the

Simulation of lung alveolar epithelial wound healing in vitro.

Science.gov (United States)

Kim, Sean H J; Matthay, Michael A; Mostov, Keith; Hunt, C Anthony

2010-08-06

The mechanisms that enable and regulate alveolar type II (AT II) epithelial cell wound healing in vitro and in vivo remain largely unknown and need further elucidation. We used an in silico AT II cell-mimetic analogue to explore and better understand plausible wound healing mechanisms for two conditions: cyst repair in three-dimensional cultures and monolayer wound healing. Starting with the analogue that validated for key features of AT II cystogenesis in vitro, we devised an additional cell rearrangement action enabling cyst repair. Monolayer repair was enabled by providing 'cells' a control mechanism to switch automatically to a repair mode in the presence of a distress signal. In cyst wound simulations, the revised analogue closed wounds by adhering to essentially the same axioms available for alveolar-like cystogenesis. In silico cell proliferation was not needed. The analogue recovered within a few simulation cycles but required a longer recovery time for larger or multiple wounds. In simulated monolayer wound repair, diffusive factor-mediated 'cell' migration led to repair patterns comparable to those of in vitro cultures exposed to different growth factors. Simulations predicted directional cell locomotion to be critical for successful in vitro wound repair. We anticipate that with further use and refinement, the methods used will develop as a rigorous, extensible means of unravelling mechanisms of lung alveolar repair and regeneration.

Role of non-acid gastro-esophageal reflux in children with respiratory symptoms.

Science.gov (United States)

Zenzeri, Letizia; Quitadamo, Paolo; Tambucci, Renato; Ummarino, Dario; Poziello, Antonio; Miele, Erasmo; Staiano, Annamaria

2017-05-01

Respiratory symptoms are a possible atypical clinical picture of gastro-esophageal reflux disease (GERD). However, a significant number of patients with GERD-related respiratory symptoms do not report improvement despite aggressive acid-suppressive therapy. Some of these refractory cases may be due to the recently appreciated entity of non-acid or weakly acidic reflux. The aim of our study is to assess the pH-impedance features of GER inducing airway symptoms, compared with GER inducing typical gastro-intestinal (GI) symptoms. We prospectively enrolled infants and children with GERD-related respiratory symptoms from January 2015 to December 2015. Age- and sex-matched patients with GERD-related GI symptoms were enrolled as comparison group. The overall number, the acidity pattern, and the height of reflux episodes were compared between the two groups. Forty patients (M/F: 20/20; mean age: 58.3 months) were enrolled in the study group and 40 in the comparison group. The mean acid exposure index was 7.9% within the study group and 15.9% within the comparison group (p:0.026). Children with respiratory symptoms versus children with GI symptoms had a mean of 40.8 acid reflux episodes versus 62.4 (p:0.001), a mean of 2.2 weakly acid reflux episodes versus 20.1 (p:0.002), and a mean of 22.1 weakly alkaline reflux episodes versus 10.2 (P 1 year with GERD-related respiratory symptoms showed a significantly higher number of weakly alkaline refluxes than children with GERD-related GI symptoms. This supports the hypothesis that respiratory symptoms are less related to acidity than GI symptoms. Pediatr Pulmonol. 2017;52:669-674. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Anaesthesia in patients undergoing esophago-gastro-duodenoscopy for suspected bleeding

DEFF Research Database (Denmark)

Helsø, Ida; Risom, Martin; Vestergaard, Therese Risom

2017-01-01

INTRODUCTION: Upper gastrointestinal bleeding (UGIB) is a common emergency. Currently, there are no agreed guidelines on the level of anaesthetic support required in patients undergoing acute esophago-gastro-duodendoscopy (EGD). METHODS: An online questionnaire comprising 19 questions was distrib......INTRODUCTION: Upper gastrointestinal bleeding (UGIB) is a common emergency. Currently, there are no agreed guidelines on the level of anaesthetic support required in patients undergoing acute esophago-gastro-duodendoscopy (EGD). METHODS: An online questionnaire comprising 19 questions...

Role of non-steroidal anti-inflammatory drugs on intestinal permeability and nonalcoholic fatty liver disease.

Science.gov (United States)

Utzeri, Erika; Usai, Paolo

2017-06-14

The use of non-steroidal anti-inflammatory drugs (NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of digestive system complications in the course of their use. Recent data suggests that the complications of the lower gastro-intestinal tract may be as frequent and severe as those of the upper tract. NSAIDs enteropathy is due to enterohepatic recycling of the drugs resulting in a prolonged and repeated exposure of the intestinal mucosa to the compound and its metabolites. Thus leading to so-called topical effects, which, in turn, lead to an impairment of the intestinal barrier. This process determines bacterial translocation and toxic substances of intestinal origin in the portal circulation, leading to an endotoxaemia. This condition could determine a liver inflammatory response and might promote the development of non-alcoholic steatohepatitis, mostly in patients with risk factors such as obesity, metabolic syndrome and a high fat diet, which may induce a small intestinal bacterial overgrowth and dysbiosis. This alteration of gut microbiota may contribute to nonalcoholic fatty liver disease and its related disorders in two ways: firstly causing a malfunction of the tight junctions that play a critical role in the increase of intestinal permeability, and then secondly leading to the development of insulin resistance, body weight gain, lipogenesis, fibrogenesis and hepatic oxidative stress.

Gastro-oesophageal reflux and belching revisited

NARCIS (Netherlands)

Bredenoord, Albert Jan

2006-01-01

In this thesis recent studies into the pathophysiology of gastro-oesophageal reflux disease and belching are described. The thesis is divided into four parts. Part I describes studies in which the technique of impedance monitoring is validated. With impedance monitoring reflux of liquid and gas can

Gastro-protective strategies in primary care in Italy: the "Gas.Pro." survey.

Science.gov (United States)

Bianco, Maria A; Rotondano, Gianluca; Buri, Luigi; Tessari, Francesco; Cipolletta, Livio

2010-05-01

Risk of gastrointestinal injury is relevant among users of anti-inflammatory or cardio-protective drugs. Adequate gastro-protection is warranted in high-risk patients. To assess the perceptions and practices of Italian primary care physicians regarding gastro-protective strategies. Nationwide cross-sectional observational study. A 14-question survey questionnaire was administered to 112 primary care physicians throughout Italy. Data collection covered consecutive outpatient candidates for the prescription of a potentially GI harmful medication, observed in the physicians' office over a 3-week period. Cohort included 3943 cases (2489 naïve and 1463 chronic NSAID/ASA users). Mean age and prevalence of cardiovascular comorbidity were significantly higher in the latter subgroup. Non-selective NSAIDs and low-dose aspirin were the most commonly prescribed drugs. Combined NSAIDS/ASA plus steroids/anticoagulant/antiplatelets were recorded in 161 cases. Helicobacter pylori status was known in only 38% of naïve and 33.2% of chronic users, being negative in 85.3% and 89.5%, respectively. When positive, H. pylori was eradicated by almost all physicians (97.9%), but in case of unknown H. pylori status, the presence of infection was investigated in only 8.6% and 14.9% of patients in the two subgroups. Gastro-protection was endorsed in 80.7% of patients, mostly PPIs (91%). In patients aged over 70, pantoprazole and lansoprazole were the preferred gastro-protective agents. There is a significant over-use of gastro-protection in the primary care setting in Italy and the role H. pylori is largely overlooked. Educational efforts should be directed to a more targeted gastro-protection only for at-risk patients as well as improved adherence to recommendations for testing and treating H. pylori infection. Copyright 2009 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Incidence of gastro-oesophageal reflux in geriatric clinical patients - a radiological study

International Nuclear Information System (INIS)

Brackins-Romero, J.; Bruening, B.; Beyer, H.K.

1984-01-01

Gastro-oesophageal reflux is obviously caused by an insufficiency of the dilatable lower end of the oesophagus. The physiological pressure acting on it corresponds to 15-30 mm Hg so that the gastric juice is prevented from entering the oesophagus. Reflux is associated with a reduction of that pressure. Many causes may be responsible, although hiatal hernia, where confirmed, will only play a secondary part. In half of the 74 examined elderly patients, gastro-oesophageal reflux was confirmed by radiology. About half of these suffered also from hiatal hernia which was a sliding hernia in 75 per cent of the cases. In about 25 per cent of the patients suffering from gastro-oesophageal reflux, signs of oesophagitis were discovered by radiology. There was no correlation between overweight and the incidence of reflux, but hiatus hernia and a positive Broca test were distinctly related to one another. In patients with gastro-oesophageal reflux, vomiting as a key symptom was more frequently confirmed than in patients without reflux. (orig./WU) [de

Polyphenols from artichoke heads (Cynara cardunculus (L.) subsp. scolymus Hayek): in vitro bio-accessibility, intestinal uptake and bioavailability.

Science.gov (United States)

D'Antuono, Isabella; Garbetta, Antonella; Linsalata, Vito; Minervini, Fiorenza; Cardinali, Angela

2015-04-01

Artichoke is a rich source of health promoting compounds such as polyphenols, important for their pharmaceutical and nutritional properties. In this study, the potential for bioavailability of the artichoke polyphenols was estimated by using both in vitro digestion and Caco-2 human intestinal cell models. In vitro digestive recoveries (bio-accessibility) were found to be 55.8% for total artichoke phenolics and in particular, 70.0% for chlorogenic acid, 41.3% for 3,5-O-dicaffeoylquinic acid, and 50.3% for 1,5-O-dicaffeoylquinic acid, highlighting potential sensitivity of these compounds to gastric and small intestinal digestive conditions. Uptake of artichoke polyphenols was rapid with peak accumulation occurring after 30 min with an efficiency of 0.16%, according to the poor uptake of dietary polyphenols. Some compounds, such as coumaric acid, caffeic acid and caffeic acid derivatives, were also detected in the basolateral side assuming extra and intracellular esterase activities on chlorogenic acid. Only apigenin-7-O-glucoside was transported through the Caco-2 monolayer demonstrating its bioavailability to the extent of 1.15% at 60 min. In addition, permeability coefficient (Papp = 2.29 × 10(-5) cm s(-1)), involving apical to basolateral transport of apigenin 7-O-glucoside, was calculated to facilitate estimation of transport through the Caco-2 monolayer. Finally, the mono and dicaffeoylquinic acids present in artichoke heads exert an antioxidant activity on the human low density lipoprotein system correlated to their chemical structure. In conclusion, the utilized in vitro models, although not fully responding to the morphological and physiological features of human in vivo conditions, could be a useful tool for investigating mechanistic effects of polyphenols released from the food matrix.

Characterization of in vitro glucuronidation clearance of a range of drugs in human kidney microsomes: comparison with liver and intestinal glucuronidation and impact of albumin.

Science.gov (United States)

Gill, Katherine L; Houston, J Brian; Galetin, Aleksandra

2012-04-01

Previous studies have shown the importance of the addition of albumin for characterization of hepatic glucuronidation in vitro; however, no reports exist on the effects of albumin on renal or intestinal microsomal glucuronidation assays. This study characterized glucuronidation clearance (CL(int, UGT)) in human kidney, liver, and intestinal microsomes in the presence and absence of bovine serum albumin (BSA) for seven drugs with differential UDP-glucuronosyltransferase (UGT) 1A9 and UGT2B7 specificity, namely, diclofenac, ezetimibe, gemfibrozil, mycophenolic acid, naloxone, propofol, and telmisartan. The impact of renal CL(int, UGT) on accuracy of in vitro-in vivo extrapolation (IVIVE) of glucuronidation clearance was investigated. Inclusion of 1% BSA for acidic drugs and 2% for bases/neutral drugs in incubations was found to be suitable for characterization of CL(int, UGT) in different tissues. Although BSA increased CL(int, UGT) in all tissues, the extent was tissue- and drug-dependent. Scaled CL(int, UGT) in the presence of BSA ranged from 2.22 to 207, 0.439 to 24.4, and 0.292 to 23.8 ml · min(-1) · g tissue(-1) in liver, kidney, and intestinal microsomes. Renal CL(int, UGT) (per gram of tissue) was up to 2-fold higher in comparison with that for liver for UGT1A9 substrates; in contrast, CL(int, UGT) for UGT2B7 substrates represented approximately one-third of hepatic estimates. Scaled renal CL(int, UGT) (in the presence of BSA) was up to 30-fold higher than intestinal glucuronidation for the drugs investigated. Use of in vitro data obtained in the presence of BSA and inclusion of renal clearance improved the IVIVE of glucuronidation clearance, with 50% of drugs predicted within 2-fold of observed values. Characterization and consideration of kidney CL(int, UGT) is particularly important for UGT1A9 substrates.

Cardiac mucosa at the gastro-oesophageal junction: indicator of gastro-oesophageal reflux disease? Data from a prospective central European multicentre study on histological and endoscopic diagnosis of oesophagitis (histoGERD trial).

Science.gov (United States)

Langner, Cord; Schneider, Nora I; Plieschnegger, Wolfgang; Schmack, Bertram; Bordel, Hartmut; Höfler, Bernd; Eherer, Andreas J; Wolf, Eva-Maria; Rehak, Peter; Vieth, Michael

2014-07-01

The origin and significance of cardiac mucosa at the gastro-oesophageal junction are controversial. In the prospective Central European multicentre histoGERD trial, we aimed to assess the prevalence of cardiac mucosa, characterized by the presence of glands composed of mucous cells without parietal cells, and to relate its presence to features related to gastro-oesophageal reflux disease (GORD). One thousand and seventy-one individuals (576 females and 495 males; median age 53 years) were available for analysis. Overall, in biopsy specimens systematically taken from above and below the gastro-oesophageal junction, cardiac mucosa was observed in 713 (66.6%) individuals. Its presence was associated with patients' symptoms and/or complaints (P = 0.0025), histological changes of the squamous epithelium (P gastro-oesophageal junction. Its association with reflux symptoms, histological changes indicating GORD and the endoscopic diagnosis of oesophagitis suggests that injury and repair related to GORD contribute to its development and/or expansion. © 2014 John Wiley & Sons Ltd.

Rectal swabs for analysis of the intestinal microbiota.

Directory of Open Access Journals (Sweden)

Andries E Budding

Full Text Available The composition of the gut microbiota is associated with various disease states, most notably inflammatory bowel disease, obesity and malnutrition. This underlines that analysis of intestinal microbiota is potentially an interesting target for clinical diagnostics. Currently, the most commonly used sample types are feces and mucosal biopsy specimens. Because sampling method, storage and processing of samples impact microbiota analysis, each sample type has its own limitations. An ideal sample type for use in routine diagnostics should be easy to obtain in a standardized fashion without perturbation of the microbiota. Rectal swabs may satisfy these criteria, but little is known about microbiota analysis on these sample types. In this study we investigated the characteristics and applicability of rectal swabs for gut microbiota profiling in a clinical routine setting in patients presenting with various gastro-intestinal disorders. We found that rectal swabs appeared to be a convenient means of sampling the human gut microbiota. Swabs can be performed on demand, whenever a patient presents; swab-derived microbiota profiles are reproducible, whether they are gathered at home by patients or by medical professionals in an outpatient setting and may be ideally suited for clinical diagnostics and large-scale studies.

Radioisotope monitoring of gastro-esophageal reflux in patients with achalasia cardiae after surgical treatment

International Nuclear Information System (INIS)

Tran Dinh Ha; Szilvasi, J.

1994-01-01

Results of a radioisotope method of the gastro-esophageal reflux are presented in patients with achalasia cardiae after different types of surgical treatment. Both Belsey-Mark and modified Nissen techniques are effective in preventing spontaneous gastroesophageal reflux, however 2 patients after Nissen fundoplication demonstrated gastro-esophageal reflux provoked by abdominal compression. This simple, noninvasive and physiologic method is an appropriate diagnostic tool for evaluating the efficiency of different anti reflux surgical techniques and is recommended for follow-up studies of patients after gastro-esophageal surgical intervention. (N.T.). 8 refs., 1 fig

Assessment of gastro-esophageal dysfunction in children

International Nuclear Information System (INIS)

Heyman, S.

1997-01-01

Scintigraphic methods to assess esophageal transit, gastro-esophageal reflux and gastric emptying are widely used in pediatric patients. This review describes the methodology and considers the clinical application of these techniques as well as the utility of alternative diagnostic studies

Assessment of gastro-esophageal dysfunction in children

Energy Technology Data Exchange (ETDEWEB)

Heyman, S. [The Children`s Hospital, Philadelphia (United States). Div. of Nuclear Medicine

1997-12-01

Scintigraphic methods to assess esophageal transit, gastro-esophageal reflux and gastric emptying are widely used in pediatric patients. This review describes the methodology and considers the clinical application of these techniques as well as the utility of alternative diagnostic studies.

In vitro activities of ramoplanin, teicoplanin, vancomycin, linezolid, bacitracin, and four other antimicrobials against intestinal anaerobic bacteria.

Science.gov (United States)

Citron, D M; Merriam, C V; Tyrrell, K L; Warren, Y A; Fernandez, H; Goldstein, E J C

2003-07-01

By using an agar dilution method, the in vitro activities of ramoplanin, teicoplanin, vancomycin, linezolid, and five other agents were determined against 300 gram-positive and 54 gram-negative strains of intestinal anaerobes. Ramoplanin was active at Eubacterium, Actinomyces, Propionibacterium, and Peptostreptococcus spp. were inhibited by spp. were >or=256 microg/ml. Ramoplanin displays excellent activity against C. difficile and other gram-positive enteric anaerobes, including vancomycin-resistant strains; however, it has poor activity against most gram-negative anaerobes and thus potentially has a lesser effect on the ecological balance of normal fecal flora.

Aminoazo dye-protein-adduct enhances inhibitory effect on digestibility and damages to Gastro-Duodenal-Hepatic axis.

Directory of Open Access Journals (Sweden)

Li-Yun Lin

Full Text Available 4-Dimethylaminoazobenzene (DAB, methyl yellow, or butter yellow, a human carcinogen, has been banned for use in foods since 1988. In 2014, DAB adulteration in Tofu occurred in Taiwan. We hypothesize that DAB can form [DAB•SBP]adduct adduct with soybean protein (SBP which could damage Gastro-Duodenal-Hepatic axis. Sprague-Dawley rats gavage fed [DAB•SBP]adduct adduct revealed severely reduced body weight and damaged duodenum, liver, hepatic mitochondria, and spleen. Hepatic levels of glutathione and ATP were severely reduced. Serum GOT and GPT were substantially elevated. Analysis by the adsorption isotherm clearly revealed DAB formed very stable [DAB•SBP]adduct adduct at 1:1 molar ration (Phase A. The equilibrium constant of this colloidal adduct [DAB•SBP]adduct was KeqA = ∝, behaving as the most stable and toxic species. At higher protein concentration (Phase C it formed conjugate [DAB×SBPgross]conjugate, with KeqC = 3.23×10-2 mg/mL, implicating a moderately strong adsorption. The in vitro pepsin digestibility test showed apparently reduced digestibility by 27% (by Ninhydrin assay or 8% (by Bradford assay. Conclusively, this is the first report indicating that [DAB•SBP]adduct potentially is capable to damage the Gastro-Duodenal-Hepatic axis.

compuGUT: An in silico platform for simulating intestinal fermentation

Science.gov (United States)

Moorthy, Arun S.; Eberl, Hermann J.

The microbiota inhabiting the colon and its effect on health is a topic of significant interest. In this paper, we describe the compuGUT - a simulation tool developed to assist in exploring interactions between intestinal microbiota and their environment. The primary numerical machinery is implemented in C, and the accessory scripts for loading and visualization are prepared in bash (LINUX) and R. SUNDIALS libraries are employed for numerical integration, and googleVis API for interactive visualization. Supplementary material includes a concise description of the underlying mathematical model, and detailed characterization of numerical errors and computing times associated with implementation parameters.

The in vivo pharmacokinetics, tissue distribution and excretion investigation of mesaconine in rats and its in vitro intestinal absorption study using UPLC-MS/MS.

Science.gov (United States)

Liu, Xiuxiu; Tang, Minghai; Liu, Taohong; Wang, Chunyan; Tang, Qiaoxin; Xiao, Yaxin; Yang, Ruixin; Chao, Ruobing

2017-12-27

1. Mesaconine, an ingredient from Aconitum carmichaelii Debx., has been proven to have cardiac effect. For further development and better pharmacological elucidation, the in vivo process and intestinal absorptive behavior of mesaconine should be investigated comprehensively. 2. An ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantitation of mesaconine in rat plasma, tissue homogenates, urine and feces to investigate the in vivo pharmacokinetic profiles, tissue distribution and excretion. The intestinal absorptive behavior of mesaconine was investigated using in vitro everted rat gut sac model. 3. Mesaconine was well distributed in tissues and a mass of unchanged form was detected in feces. It was difficultly absorbed into blood circulatory system after oral administration. The insufficient oral bioavailability of mesaconine may be mainly attributed to its low intestinal permeability due to a lack of lipophilicity. The absorption of mesaconine in rat's intestine is a first-order process with the passive diffusion mechanism.

Asia-Pacific consensus on the management of gastro-oesophageal reflux disease: an update focusing on refractory reflux disease and Barrett's oesophagus.

Science.gov (United States)

Fock, Kwong Ming; Talley, Nicholas; Goh, Khean Lee; Sugano, Kentaro; Katelaris, Peter; Holtmann, Gerald; Pandolfino, John E; Sharma, Prateek; Ang, Tiing Leong; Hongo, Michio; Wu, Justin; Chen, Minhu; Choi, Myung-Gyu; Law, Ngai Moh; Sheu, Bor-Shyang; Zhang, Jun; Ho, Khek Yu; Sollano, Jose; Rani, Abdul Aziz; Kositchaiwat, Chomsri; Bhatia, Shobna

2016-09-01

Since the publication of the Asia-Pacific consensus on gastro-oesophageal reflux disease in 2008, there has been further scientific advancement in this field. This updated consensus focuses on proton pump inhibitor-refractory reflux disease and Barrett's oesophagus. A steering committee identified three areas to address: (1) burden of disease and diagnosis of reflux disease; (2) proton pump inhibitor-refractory reflux disease; (3) Barrett's oesophagus. Three working groups formulated draft statements with supporting evidence. Discussions were done via email before a final face-to-face discussion. We used a Delphi consensus process, with a 70% agreement threshold, using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria to categorise the quality of evidence and strength of recommendations. A total of 32 statements were proposed and 31 were accepted by consensus. A rise in the prevalence rates of gastro-oesophageal reflux disease in Asia was noted, with the majority being non-erosive reflux disease. Overweight and obesity contributed to the rise. Proton pump inhibitor-refractory reflux disease was recognised to be common. A distinction was made between refractory symptoms and refractory reflux disease, with clarification of the roles of endoscopy and functional testing summarised in two algorithms. The definition of Barrett's oesophagus was revised such that a minimum length of 1 cm was required and the presence of intestinal metaplasia no longer necessary. We recommended the use of standardised endoscopic reporting and advocated endoscopic therapy for confirmed dysplasia and early cancer. These guidelines standardise the management of patients with refractory gastro-oesophageal reflux disease and Barrett's oesophagus in the Asia-Pacific region. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The Significance of Variceal Haemorrhage in Ghana: A Retrospective Review.

Science.gov (United States)

Archampong, T N A; Tachi, K; Agyei, A A; Nkrumah, K N

2015-09-01

This study describes the burden of bleeding oesophageal varices at the main tertiary referral centre in Accra. Retrospective design to describe the endoscopic spectrum and review mortality data following acute upper gastro-intestinal bleeding at the Korle-Bu Teaching Hospital. Endoscopic data was reviewed in the Endoscopy Unit between 2007 and 2010. Mortality data was collated from the Department of Medicine between 2010 and 2013. The study questionnaire compiled clinical and demographic characteristics, endoscopic diagnoses, length of hospital admission and treatment regimens. Aetiology and time-trend analysis of mortality rates following acute upper gastro-intestinal bleeding; variceal bleeding treatment modalities. On review of the endoscopic diagnoses, gastro-oesophageal varices were identified in 21.9% of cases followed by gastritis 21.7%, duodenal ulcer, 17.0%, and gastric ulcer, 13.2%. Gastro-oesophageal varices were the predominant cause of death from acute upper gastro-intestinal haemorrhage from 46% in 2010 to 76% in 2013. Outcomes following acute upper gastro-intestinal bleeding were dismal with some 38% of fatalities occurring within the first 24 hours. Injection sclerotherapy was the dominant endoscopic modality for secondary prevention of variceal bleeding in comparison with band ligation, mainly as a result of cost and availability. At the tertiary centre in Accra, variceal bleeding is an increasingly common cause of acute upper gastro-intestinal haemorrhage in comparison with previous reviews in Ghana. Its significantly high in-hospital mortality reflects inadequate facilities to deal with this medical emergency. A strategic approach to care with endoscopic services equipped with all the necessary therapeutic interventions will be vital in improving the outcomes of variceal bleeding in Ghana.

Detection of gastro-oesophageal reflux disease. The clinical value of a barium examination after food stimulation

Energy Technology Data Exchange (ETDEWEB)

Christiansen, T.; Ravnsbaek, J.; Toettrup, A.; Funch-Jensen, P.; Thommesen, P.

In a prospective study a barium examination combined with food stimulation was compared with the acid reflux test in 30 consecutive patients with symptoms of gastro-oesophageal reflux. Both methods were further compared with endoscopy and histology. Gastro-oesophageal reflux could be demonstrated by the radiologic examination in 22 patients and by the acid reflux test in 23 patients. By combining the two methods gastro-oesophageal reflux could be demonstrated in 27 patients. Comparing the two methods with symptoms, endoscopy, and histology they seemed to be of equal value. Accordingly, a food-stimulated barium examination is recommended as the first method for demonstrating gastro-oesophageal reflux because it is simple and well-tolerated by the patient.

potentially pathogenic gastrointestinal microorganisms (ID 2972), improved lactose digestion (ID 2972) and increasing IL-10 production (ID 2973) (further assessment) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

DEFF Research Database (Denmark)

Tetens, Inge

of Lactobacillus paracasei CNCM I-1688 and Lactobacillus salivarius CNCM I-1794 and reduction of gastro-intestinal discomfort, decreasing potentially pathogenic gastro-intestinal microorganisms, improved lactose digestion and increasing IL-10 production. The food constituent that is the subject of the health......-intestinal discomfort, is a beneficial physiological effect for the general population. The claimed effect, decreasing potentially pathogenic gastro-intestinal microorganisms, might be a beneficial physiological effect for the general population. The claimed effect, improved lactose digestion, is a beneficial...... physiological effect for individuals with lactose maldigestion. No human intervention studies were provided from which conclusions could be drawn for the scientific substantiation of the above-mentioned claims. On the basis of the data provided, the Panel concludes that a cause and effect relationship has...

Gaviscon and domperidon responsive apnea episodes associated with gastro-esophageal reflux disease in twins.

Science.gov (United States)

Bilgin, Huseyin; Eren, Abdulkadir; Kara, Semra

2015-01-01

The possible pathophysiology of the relationship between gastro-esophageal reflux disease and apnea of prematurity has been widely investigated. Various physiological protective reflex responses provide a plausible biological link between gastro-esophageal reflux and apnea of prematurity. It is uncertain whether or not there is a causal relationship between the two diseases. PATIENT'S FINDINGS: Twins were admitted to the neonatal intensive care unit due to feeding problems. Physical examination was normal except for reticulated, blueviolet skin changes. Short apneic attacks occurred on the first day in twin 1 and on the second day in twin 2, and these were initially treated by stimulation and increased ambient O2 concentration. Then, we conducted methylxanthine and continuous positive airway pressure treatment. Laboratory and radiological analysis were normal. As gastro-esophageal reflux disease was thought to be the causes of the treatment-refractory apnea, therapy with gaviscon and domperidon was begun for both cases. Apneic attacks did not recur after gaviscon and domperidon therapy. Pharmacological therapy for gastro-esophageal reflux disease has not definitively been shown to be effective in improving symptoms and hence, should be reserved especially for infants with treatment refractory apnea episodes suspected as being gastro-esophageal reflux in premature infants.

Gastro-oesophageal reflux disease in 20 dogs (2012 to 2014).

Science.gov (United States)

Muenster, M; Hoerauf, A; Vieth, M

2017-05-01

To describe the clinical features of canine gastro-oesophageal reflux disease. A search of our medical records produced 20 dogs with clinical signs attributable to oesophageal disease, hyper-regeneratory oesophagopathy and no other oesophageal disorders. The clinical, endoscopic and histological findings of the dogs were analysed. The 3-year incidence of gastro-oesophageal reflux disease was 0·9% of our referral dog population. Main clinical signs were regurgitation, discomfort or pain (each, 20/20 dogs) and ptyalism (18/20 dogs). Oesophagoscopy showed no (5/20 dogs) or minimal (13/20 dogs) mucosal lesions. In oesophageal mucosal biopsy specimens, there were hyperplastic changes of the basal cell layer (13/20 dogs), stromal papillae (14/20 dogs) and entire epithelium (9/20 dogs). Eleven dogs received omeprazole or pantoprazole and regurgitation and ptyalism improved in eight and pain diminished in six of these dogs within three to six weeks. Our findings suggest that canine gastro-oesophageal reflux disease is a more common clinical problem than hitherto suspected. © 2017 British Small Animal Veterinary Association.

characterisation of gastro- enteritis-associated adenoviruses in ...

African Journals Online (AJOL)

Objective. To analyse adenovirus (Ad) numbers and types associated with paediatric gastro-enteritis in South Africa. Setting. Gauteng, 1994-1996. Metfwds. A total of 234 paediatric diarrhoeal stool samples were screened for Ad using commercial enzyme-linked. iInmunosorbent assays (EUSAs). Adenoviral isolates were.

Gastro-Resistant Insulin Receptor-Binding Peptide from Momordica charantia Improved the Glucose Tolerance in Streptozotocin-Induced Diabetic Mice via Insulin Receptor Signaling Pathway.

Science.gov (United States)

Lo, Hsin-Yi; Li, Chia-Cheng; Chen, Feng-Yuan; Chen, Jaw-Chyun; Hsiang, Chien-Yun; Ho, Tin-Yun

2017-10-25

Momordica charantia is a commonly used food and has been used for the management of diabetes. Our previous study has identified an insulin receptor (IR)-binding protein (mcIRBP) from Momordica charantia. Here we identified the gastro-resistant hypoglycemic bioactive peptides from protease-digested mcIRBP. By in vitro digestion and IR kinase activity assay, we found that a 9-amino-acid-residue peptide, mcIRBP-9, was a gastro-resistant peptide that enhanced IR kinase activities. mcIRBP-9 activated IR signaling transduction pathway, which resulted in the phosphorylation of IR, the translocation of glucose transporter 4, and the uptake of glucose in cells. Intraperitoneal and oral administration of mcIRBP-9 stimulated the glucose clearance by 30.91 ± 0.39% and 32.09 ± 0.38%, respectively, in streptozotocin-induced diabetic mice. Moreover, a pilot study showed that daily ingestion of mcIRBP-9 for 30 days decreased the fasting blood glucose levels and glycated hemoglobin (HbA1c) levels by 23.62 ± 6.14% and 24.06 ± 1.53%, respectively. In conclusion, mcIRBP-9 is a unique gastro-resistant bioactive peptide generated after the digestion of mcIRBP. Furthermore, oral administration of mcIRBP-9 improves both the glucose tolerance and the HbA1c levels in diabetic mice via targeting IR signaling transduction pathway.

Kinetic stability and membrane structure of liposomes during in vitro infant intestinal digestion: Effect of cholesterol and lactoferrin.

Science.gov (United States)

Liu, Weilin; Wei, Fuqiang; Ye, Aiqian; Tian, Mengmeng; Han, Jianzhong

2017-09-01

The effects of cholesterol and lactoferrin on the kinetic stability and membrane structural integrity of negatively charged liposomes under in vitro infant intestinal digestion conditions were elucidated using dynamic light scattering, pH-stat titration, Fourier transform infrared spectroscopy, and pyrene steady state fluorescence probes. The liposomes had a smaller particle diameter, a wider size distribution, and a greater negative charge after digestion. The incorporation of cholesterol into the phospholipid bilayers resulted in a more ordered conformation in the aliphatic tail region and reduced micropolarity, indicating that cholesterol can improve the structural stability of liposomal membranes against intestinal environmental stress. Lactoferrin coverage facilitated the release of free fatty acids and increased the microfluidity of the bilayers, reducing the structural integrity of the liposomes. This study provides useful information on the design of liposomes and other microcapsules with improved and controlled release properties during digestion for particular groups of people. Copyright © 2017 Elsevier Ltd. All rights reserved.

Miniaturised optical fiber pH sensor for gastro-esophageal applications

Science.gov (United States)

Baldini, F.; Chiavaioli, F.; Cosi, F.; Giannetti, A.; Tombelli, S.; Trono, C.

2013-05-01

Monitoring pH for long periods, usually 24 h, in the stomach and in the esophagus may be essential in the diagnosis of gastro-esophageal diseases. The clinical range of interest is quite extended, between 1 to 8 pH units. Methyl red, after its covalent immobilization on controlled pore glass (CPG), is characterized by a working range which fits well with the clinical one. A novel probe, suitable for gastro-esophageal applications, was designed in order to optimize the performances of the colored CPG. This leads to a very simple probe configuration characterized by a very fast response.

SAGES Guidelines: Prevention and management of gastro ...

African Journals Online (AJOL)

SAGES Guidelines: Prevention and management of gastro-oesophageal varices and variceal haemorrhage in cirrhosis. J F Botha. Abstract. No Abstract South African Gastroenterology Review Vol. 6 (1) 2008: pp. 23-25. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT.

Accelerating the dissolution of enteric coatings in the upper small intestine: evolution of a novel pH 5.6 bicarbonate buffer system to assess drug release.

Science.gov (United States)

Varum, Felipe J O; Merchant, Hamid A; Goyanes, Alvaro; Assi, Pardis; Zboranová, Veronika; Basit, Abdul W

2014-07-01

Despite rapid dissolution in compendial phosphate buffers, gastro resistant (enteric coated) products can take up to 2 h to disintegrate in the human small intestine, which clearly highlights the inadequacy of the in vitro test method to predict in vivo behaviour of these formulations. The aim of this study was to establish the utility of a novel pH 5.6 bicarbonate buffer, stabilized by an Auto pH™ System, as a better surrogate of the conditions of the proximal small intestine to investigate the dissolution behaviour of standard and accelerated release enteric double coating formulations. Prednisolone tablets were coated with 3 or 5 mg/cm(2) of partially neutralized EUDRAGIT(®) L 30 D-55, HP-55 or HPMC adjusted to pH 6 or 8. An outer layer of EUDRAGIT(®) L 30 D-55 was applied at 5mg/cm(2). For comparison purposes, a standard single layer of EUDRAGIT(®) L 30 D-55 was applied to the tablets. Dissolution was carried out using USP II apparatus in 0.1 M HCl for 2 h, followed by pH 5.6 bicarbonate buffer. EUDRAGIT(®) L 30 D-55 single-coated tablets showed a slow drug release with a lag time of 75 min in buffer, whereas release from the EUDRAGIT(®) L 30 D-55 double-coated tablets was accelerated. These in vitro lag times closely match the in vivo disintegration times for these coated tablets reported previously. Drug release was further accelerated from modified double coatings, particularly in the case of coatings with a thinner inner layer of HP-55 or HPMC (pH 8 and KH2PO4). This study confirms that the pH 5.6 bicarbonate buffer system offers significant advantages during the development of dosage forms designed to release the drug in the upper small intestine. Copyright © 2014. Published by Elsevier B.V.

Gastro-Oesophageal Reflux in Noncystic Fibrosis Bronchiectasis

Directory of Open Access Journals (Sweden)

Annemarie L. Lee

2011-01-01

Full Text Available The clinical presentation of noncystic fibrosis bronchiectasis may be complicated by concomitant conditions, including gastro-oesophageal reflux (GOR. Increased acidic GOR is principally caused by gastro-oesophageal junction incompetence and may arise from lower oesophageal sphincter hypotension, including transient relaxations, hiatus hernia, and oesophageal dysmotility. Specific pathophysiological features which are characteristic of respiratory diseases including coughing may further increase the risk of GOR in bronchiectasis. Reflux may impact on lung disease severity by two mechanisms, reflex bronchoconstriction and pulmonary microaspiration. Symptomatic and clinically silent reflux has been detected in bronchiectasis, with the prevalence of 26 to 75%. The cause and effect relationship has not been established, but preliminary reports suggest that GOR may influence the severity of bronchiectasis. Further studies examining the implications of GOR in this condition, including its effect across the disease spectrum using a combination of diagnostic tools, will clarify the clinical significance of this comorbidity.

compuGUT: An in silico platform for simulating intestinal fermentation

Directory of Open Access Journals (Sweden)

Arun S. Moorthy

2017-01-01

Full Text Available The microbiota inhabiting the colon and its effect on health is a topic of significant interest. In this paper, we describe the compuGUT — a simulation tool developed to assist in exploring interactions between intestinal microbiota and their environment. The primary numerical machinery is implemented in C, and the accessory scripts for loading and visualization are prepared in bash (LINUX and R. SUNDIALS libraries are employed for numerical integration, and googleVis API for interactive visualization. Supplementary material includes a concise description of the underlying mathematical model, and detailed characterization of numerical errors and computing times associated with implementation parameters.

Intestinal absorption of the antiepileptic drug substance vigabatrin is altered by infant formula in vitro and in vivo

DEFF Research Database (Denmark)

Nielsen, Carsten Uhd

2014-01-01

Vigabatrin is an antiepileptic drug substance mainly used in pediatric treatment of infantile spasms. The main source of nutrition for infants is breast milk and/or infant formula. Our hypothesis was that infant formula may affect the intestinal absorption of vigabatrin. The aim was therefore...... to investigate the potential effect of coadministration of infant formula with vigabatrin on the oral absorption in vitro and in vivo. The effect of vigabatrin given with an infant formula on the oral uptake and transepithelial transport was investigated in vitro in Caco-2 cells. In vivo effects of infant...... formula and selected amino acids on the pharmacokinetic profile of vigabatrin was investigated after oral coadministration to male Sprague–Dawley rats using acetaminophen as a marker for gastric emptying. The presence of infant formula significantly reduced the uptake rate and permeability of vigabatrin...

Food-Associated Lactobacillus plantarum and Yeasts Inhibit the Genotoxic Effect of 4-Nitroquinoline-1-Oxide

Directory of Open Access Journals (Sweden)

Roberta Prete

2017-11-01

Full Text Available Lactic acid bacteria and yeasts, representing the prevailing microbiota associated with different foods generally consumed without any cooking, were identified and characterized in vitro for some functional properties, such as acid-bile tolerance and antigenotoxic activity. In particular, 22 Lactobacillus plantarum strains and 14 yeasts were studied. The gastro-intestinal tract tolerance of all the strains was determined by exposing washed cell suspensions at 37°C to a simulated gastric juice (pH 2.0, containing pepsin (0.3% w/v and to a simulated small intestinal juice (pH 8.0, containing pancreatin (1 mg mL-1 and bile extract (0.5%, thus monitoring changes in total viable count. In general, following a strain-dependent behavior, all the tested strains persisted alive after combined acid-bile challenge. Moreover, many strains showed high in vitro inhibitory activity against a model genotoxin, 4-nitroquinoline-1-oxide (4-NQO, as determined by the short-term method, SOS-Chromotest. Interestingly, the supernatants from bacteria- or yeasts-genotoxin co-incubations exhibited a suppression on SOS-induction produced by 4-NQO on the tester strain Escherichia coli PQ37 (sfiA::lacZ exceeding, in general, the value of 75%. The results highlight that food associated microorganisms may reach the gut in viable form and prevent genotoxin DNA damage in situ. Our experiments can contribute to elucidate the functional role of food-associated microorganisms general recognized as safe ingested with foods as a part of the diet.

SIMULATING PROTEIN DIGESTION ON TROUT A RAPID AND INEXPENSIVE METHOD FOR DOCUMENTING FISH MEAL QUALITY AND SCREENING NOVEL PROTEIN SOURCES FOR USE IN AQUAFEEDS

Directory of Open Access Journals (Sweden)

M Bassompierre

1997-10-01

Full Text Available A novel in vitro digestion system, which simulated rainbow trout gastric and intestinal digestion was developed. The method was employed to evaluate the impact of the gastric phase of digestion upon degradation of three fish meals od differing quality. Results illustrated that two-phase gastric-intestinal digestion increased the discriminatory powers of the system when compared to one-step intestinal digestion. A comparison of the system with pH-STAT methods demonstrated that the in vitro technique was superior. The presented method provides an ethical and cost effective means for rapid evaluation of fish meals and potentially, alternative protein sources for aquafeeds.

Effect of coffee on gastro-oesophageal reflux in patients with reflux disease and healthy controls

NARCIS (Netherlands)

Boekema, P. J.; Samsom, M.; Smout, A. J.

1999-01-01

BACKGROUND: Many patients with gastro-oesophageal reflux disease (GORD) report that coffee aggravates their symptoms and doctors tend to discourage its use in GORD. OBJECTIVE: To assess the effect of coffee ingestion on gastro-oesophageal acid reflux. DESIGN: A randomized, controlled, crossover

Potential countersample materials for in vitro simulation wear testing.

Science.gov (United States)

Shortall, Adrian C; Hu, Xiao Q; Marquis, Peter M

2002-05-01

Any laboratory investigation of the wear resistance of dental materials needs to consider oral conditions so that in vitro wear results can be correlated with in vivo findings. The choice of the countersample is a critical factor in establishing the pattern of tribological wear and in achieving an efficient in vitro wear testing system. This research investigated the wear behavior and surface characteristics associated with three candidate countersample materials used for in vitro wear testing in order to identify a possible suitable substitute for human dental enamel. Three candidate materials, stainless steel, steatite and dental porcelain were evaluated and compared to human enamel. A variety of factors including hardness, wear surface evolution and frictional coefficients were considered, relative to the tribology of the in vivo situation. The results suggested that the dental porcelain investigated bore the closest similarity to human enamel of the materials investigated. Assessment of potential countersample materials should be based on the essential tribological simulation supported by investigations of mechanical, chemical and structural properties. The selected dental porcelain had the best simulating ability among the three selected countersample materials and this class of material may be considered as a possible countersample material for in vitro wear test purposes. Further studies are required, employing a wider range of dental ceramics, in order to optimise the choice of countersample material for standardized in vitro wear testing.

, 971, 975, 983, 985, 994, 996, 998, 1006, 1014), decreasing potentially pathogenic gastro-intestinal microorganisms (ID 960, 967, 969, 971, 975, 983, 985, 994, 996, 998, 1006, 1014), and stimulation of immunological responses (ID 962, 968, 970, 972, 976, 984, 986, 995, 997, 999, 1007, 1015) (further, assessment) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

DEFF Research Database (Denmark)

Tetens, Inge

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to provide a scientific opinion on health claims pursuant to Article 13 of Regulation (EC) No 1924/2006 in the framework of further assessment related to various microorganisms...... and changes in bowel function, and digestion and absorption of nutrients, decreasing potentially pathogenic gastro-intestinal microorganisms, and stimulation of immunological responses. The food constituents, Bifidobacterium animalis subsp. lactis THT 010801, Bifidobacterium longum subsp. infantis THT 010201...... 030802, Lactobacillus salivarius THT 031001 and Streptococcus thermophilus THT 070102, are sufficiently characterised. The evidence provided did not establish that the proposed claimed effect, stimulation of immunological responses, is a beneficial physiological effect. The references provided...

The pharmacological profile of CGP 28238, a novel highly potent anti-inflammatory compound.

Science.gov (United States)

Wiesenberg-Boettcher, I; Schweizer, A; Green, J R; Mueller, K; Maerki, F; Pfeilschifter, J

1989-01-01

CGP 28238 (6-(2,4-difluorophenoxy)-5-methylsulfonylamino-1-indanone ) exhibits very potent anti-inflammatory activity in rat adjuvant arthritis (ED40 = 0.05 mg/kg, p.o.) and pronounced analgesic and antipyretic activity in acute models in mice and rats (ED50 2-5 mg/kg, p.o.), but has clear advantages over reference NSAIDs with respect to gastro-intestinal tolerability. Threshold doses for gastro-intestinal ulcerogenicity in rats after single and repeated (10x) doses were found to be 30 mg/kg, p.o., and prostaglandin (PGE2) production in rat gastric and ileal mucosa was only marginally inhibited (ED50 greater than 30 mg/kg, p.o.). On the other hand, PGE2 production in rat inflammatory exudate and thromboxane synthesis in rat blood were inhibited with ED50 values of less than or equal to 2 mg/kg, p.o. Although CGP28238 does not inhibit cyclooxygenase in bovine seminal vesicle microsomal preparations (IC50 greater than 10(-3) mol/l), potent inhibition of prostaglandin synthesis was shown in various in vitro systems using human and animal cells with IC50 values of less than 10(-6) mol/l. IL-1-stimulated bone resorption and PGE2 production in murine calvarial cultures were inhibited with IC50 values of 3 x 10(-7) and 2 x 10(-8) mol/l, respectively. 5-Lipoxygenase (murine macrophages), phospholipase A2 (human PMN) and phospholipase C (human platelets) were not inhibited. CGP 28238 may represent a novel highly potent anti-inflammatory compound with improved gastro-intestinal safety.

Ascaris Suum Infection Downregulates Inflammatory Pathways in the Pig Intestine In Vivo and in Human Dendritic Cells In Vitro

DEFF Research Database (Denmark)

Midttun, Helene L. E.; Acevedo, Nathalie; Skallerup, Per

2018-01-01

similar transcriptional pathways in human dendritic cells (DCs) in vitro. DCs exposed to ABF secreted minimal amounts of cytokines and had impaired production of cyclooxygengase-2, altered glucose metabolism, and reduced capacity to induce interferon-gamma production in T cells. Our in vivo and in vitro......Ascaris suum is a helminth parasite of pigs closely related to its human counterpart, A. lumbricoides, which infects almost 1 billion people. Ascaris is thought to modulate host immune and inflammatory responses, which may drive immune hyporesponsiveness during chronic infections. Using...... transcriptomic analysis, we show here that pigs with a chronic A. suum infection have a substantial suppression of inflammatory pathways in the intestinal mucosa, with a broad downregulation of genes encoding cytokines and antigen-processing and costimulatory molecules. A. suum body fluid (ABF) suppressed...

Relationship between gastro-intestinal complaints and endotoxaemia, cytokine release and the acute-phase reaction during and after a long-distance triathlon in highly trained men.

Science.gov (United States)

Jeukendrup, A E; Vet-Joop, K; Sturk, A; Stegen, J H; Senden, J; Saris, W H; Wagenmakers, A J

2000-01-01

The aim of the present study was to establish whether gastro-intestinal (GI) complaints observed during and after ultra-endurance exercise are related to gut ischaemia-associated leakage of endotoxins [lipopolysaccharide (LPS)] into the circulation and associated cytokine production. Therefore we collected blood samples from 29 athletes before, immediately after, and 1, 2 and 16 h after a long-distance triathlon for measurement of LPS, tumour necrosis factor-alpha and interleukin-6 (IL-6). As the cytokine response would trigger an acute-phase response, characteristic variables of these responses were also measured, along with creatine kinase (CK) to obtain an indicator of muscle damage. There was a high incidence (93% of all participants) of GI symptoms; 45% reported severe complaints and 7% of the participants abandoned the race because of severe GI distress. Mild endotoxaemia (5-15 pg/ml) was evident in 68% of the athletes immediately after the race, as also indicated by a reduction in IgG anti-LPS levels. In addition, we observed production of IL-6 (27-fold increase immediately after the race), leading to an acute-phase response (20-fold increase in C-reactive protein and 12% decrease in pre-albumin 16 h after the race). The extent of endotoxaemia was not correlated with the GI complaints or the IL-6 response, but did show a correlation with the elevation in C-reactive protein (r(s) 0.389; P=0.037). Creatine kinase levels were increased significantly immediately post-race, and increased further in the follow-up period. Creatine kinase levels did not correlate with those of either IL-6 or C-reactive protein. It is therefore concluded that LPS does enter the circulation after ultra-endurance exercise and may, together with muscle damage, be responsible for the increased cytokine response and hence GI complaints in these athletes.

An analysis of the gastro-intestinal side-effects of non-steroidal anti-inflammatory drugs, with particular reference to comparative studies in man and laboratory species.

Science.gov (United States)

Rainsford, K D

1982-01-01

A critical analysis has been performed of reports published on the incidence of gastro-intestinal (GI) side-effects found in arthritic patients being treated with non-steroid anti-inflammatory (NSAI) drugs. The results show the following: 1. The incidence of GI ulceration (as revealed by gastroscopy) and haemorrhage in arthritic patients taking NSAI drugs may be higher than suspected from clinical trial data. 2. Incidence of all GI side-effects (including ulceration and haemorrhage) may be lower with some of the new NSAI drugs than with traditional drugs (e.g. aspirin, indomethacin and phenylbutazone). 3. Arthritic patients may be more susceptible to the ulcerogenic actions of NSAI drugs. Experiments with animals, together with evidence from clinical studies, indicate that stress factors and the presence of decreased mucosal resistance in the diseased state may contribute to the enhanced susceptibility of the GI tract towards the ulcerogenicity of NSAI drugs. 4. Comparison of data on gastroscopic observations in man with the author's data on the effects of NSAI drugs in stress-sensitized rats shows the latter technique appears to be a useful means of predicting the ulcerogenic potential of NSAI drugs in man. The comparison has also been used to predict the ulcerogenicity of drug - alcohol combinations; alcohol being a common ulcerogen consumed by many patients. Some NSAI drugs with low ulcerogenic activity (i.e. azapropazone, benoxaprofen and fenclofenac) in the stressed-rat assay show little or no interaction with alcohol. These studies using laboratory animals show the importance of employing conditions to mimic environmental factors (e.g. stress and alcohol consumption) which might predispose individuals to ulcerogenic or other side-effects of NSAI drugs. From these studies it appears possible to construct 'predictive profiles' of the relative ulcerogenicity of NSAI drugs which may be applicable to the clinical situation in man.

Low morbidity after palliation of obstructing gastro-oesophageal adenocarcinoma to restore swallowing function

DEFF Research Database (Denmark)

Kofoed, Steen Christian; Lundsgaard, Martin; Ellemann, Ann-Camilla

2012-01-01

This study describes the procedure-related complications and survival after deployment of self-expanding metal stents (SEMS) or use of argon plasma coagulation (APC) in patients with obstructing gastro-oesophageal junction (GEJ) adenocarcinoma.......This study describes the procedure-related complications and survival after deployment of self-expanding metal stents (SEMS) or use of argon plasma coagulation (APC) in patients with obstructing gastro-oesophageal junction (GEJ) adenocarcinoma....

Breads Fortified with Freeze-Dried Vegetables: Quality and Nutritional Attributes. Part 1: Breads Containing Oil as an Ingredient

Directory of Open Access Journals (Sweden)

Viren Ranawana

2016-03-01

Full Text Available There is increasing emphasis on reformulating processed foods to make them healthier. This study for the first time comprehensively investigated the effects of fortifying bread (containing oil as an ingredient with freeze-dried vegetables on its nutritional and physico-chemical attributes. Breads fortified with carrot, tomato, beetroot or broccoli were assessed for nutrition, antioxidant potential, storage life, shelf stability, textural changes and macronutrient oxidation. Furthermore, using an in vitro model the study for the first time examined the impact of vegetable addition on the oxidative stability of macronutrients during human gastro-intestinal digestion. As expected, adding vegetables improved the nutritional and antioxidant properties of bread. Beetroot and broccoli significantly improved bread storage life. None of the vegetables significantly affected bread textural changes during storage compared to the control. Lipid oxidation in fresh bread was significantly reduced by all four types of vegetables whilst protein oxidation was lowered by beetroot, carrot and broccoli. The vegetables demonstrated varying effects on macronutrient oxidation during gastro-intestinal digestion. Beetroot consistently showed positive effects suggesting its addition to bread could be particularly beneficial.

if, when and how to treat gastro-oesophageal reflux

African Journals Online (AJOL)

persistent occult gastro-oesophageal reflux; (iiz) persistence ... deterioration of bronchopulmonary disease. From this the reader ... problem by means of simple barium studies, to management ... Gastroesophageal reflux in the preterm infant.

Factors Affecting the Prevalence of Gastro-oesophageal Reflux in Childhood Corrosive Oesophageal Strictures

Directory of Open Access Journals (Sweden)

Serdar H. İskit

2014-06-01

Full Text Available Background: Gastro-oesophageal reflux may accompany the corrosive oesophageal damage caused by the ingestion of corrosive substances and affect its treatment. The factors that affect the development of reflux in these cases and their effects on treatment still remain unclear. Aims: Our aim is to investigate the prevalence of gastro-oesophageal reflux in children with corrosive oesophageal strictures, the risk factors affecting this prevalence and the effects of gastro-oesophageal reflux on treatment. Study Design: Case-control study. Methods: We enrolled 52 patients with oesophageal stricture due to corrosive substance ingestion who were referred to our clinic between 2003 and 2010. Groups, which were determined according to the presence of gastro-oesophageal reflux (GER, were compared with each other in terms of clinical findings, results of examination methods, characteristics of the stricture and success of the treatment. Results: The total number of patients in our study was 52; 30 of them were male and 22 of them were female. The mean age of our study population was 4.2±2.88 years. Thirty-three patients had gastro-oesophageal reflux (63.5%. Patients who had strictures caused by the ingestion of alkali substances were 1.6-times more likely to have reflux. There were no differences between patients with or without reflux in terms of number and localisation of strictures. Mean distance of stricture was longer in patients with reflux (3.7±1.8 cm than in patients without (2.2±1.0 cm (p0.05. Conclusion: Corrosive oesophageal stricture was usually accompanied by gastro-oesophageal reflux and the length of stricture is an important risk factor. Negative effects of reflux over dilatation treatment have not yet been demonstrated in the short-term. Nevertheless, this frequent rate of reflux may eventually increase the risk of oesophagitis and Barrett’s oesophagus; therefore, we suggest that these effects should be prospectively evaluated in a

Upper aerodigestive tract disorders and gastro-oesophageal reflux disease.

Science.gov (United States)

Ciorba, Andrea; Bianchini, Chiara; Zuolo, Michele; Feo, Carlo Vittorio

2015-02-16

A wide variety of symptoms and diseases of the upper aerodigestive tract are associated to gastro-oesophageal reflux disease (GORD). These disorders comprise a large variety of conditions such as asthma, chronic otitis media and sinusitis, chronic cough, and laryngeal disorders including paroxysmal laryngospasm. Laryngo-pharyngeal reflux disease is an extraoesophageal variant of GORD that can affect the larynx and pharynx. Despite numerous research efforts, the diagnosis of laryngopharyngeal reflux often remains elusive, unproven and controversial, and its treatment is then still empiric. Aim of this paper is to review the current literature on upper aerodigestive tract disorders in relation to pathologic gastro-oesophageal reflux, focusing in particular on the pathophysiology base and results of the surgical treatment of GORD.

Laparoscopic surgery for gastro-esophageal acid reflux disease

NARCIS (Netherlands)

Schijven, Marlies P.; Gisbertz, Suzanne S.; van Berge Henegouwen, Mark I.

2014-01-01

Gastro-esophageal reflux disease is a troublesome disease for many patients, severely affecting their quality of life. Choice of treatment depends on a combination of patient characteristics and preferences, esophageal motility and damage of reflux, symptom severity and symptom correlation to acid

Análisis estadístico multivariante de las principales enfermedades gastroéntericas en el cantón Guayaquil

OpenAIRE

Romero Saltos, Cristina Marisela; Ramirez Figueroa, John Alex

2009-01-01

La presente investigación desarrolla el Análisis Multivariado de las principales enfermedades gastroéntericas que afectan a la ciudad de Guayaquil. Consideramos que las principales enfermedades gastroéntericas son: Fiebre Tifoidea, Salmonelosis y Enfermedades Diarreicas Agudas. En el primer capítulo se enfoca la problemática de las enfermedades gastroéntericas en el Ecuador y en la ciudad de Guayaquil, de la misma manera se presenta la descripción de las principales enfermedades gastroént...

Similar uptake profiles of microcystin-LR and -RR in an in vitro human intestinal model

International Nuclear Information System (INIS)

Zeller, P.; Clement, M.; Fessard, V.

2011-01-01

Highlights: → First description of in vitro cellular uptake of MCs into intestinal cells. → OATP 3A1 and OATP 4A1 are expressed in Caco-2 cell membranes. → MC-LR and MC-RR show similar uptake in Caco-2 cells. → MCs are probably excreted from Caco-2 cells by an active mechanism. -- Abstract: Microcystins (MCs) are cyclic hepatotoxins produced by various species of cyanobacteria. Their structure includes two variable amino acids (AA) leading to more than 80 MC variants. In this study, we focused on the most common variant, microcystin-LR (MC-LR), and microcystin-RR (MC-RR), a variant differing by only one AA. Despite their structural similarity, MC-LR elicits higher liver toxicity than MC-RR partly due to a discrepancy in their uptake by hepatic organic anion transporters (OATP 1B1 and 1B3). However, even though ingestion is the major pathway of human exposure to MCs, intestinal absorption of MCs has been poorly addressed. Consequently, we investigated the cellular uptake of the two MC variants in the human intestinal cell line Caco-2 by immunolocalization using an anti-MC antibody. Caco-2 cells were treated for 30 min to 24 h with several concentrations (1-50 μM) of both variants. We first confirmed the localization of OATP 3A1 and 4A1 at the cell membrane of Caco-2 cells. Our study also revealed a rapid uptake of both variants in less than 1 h. The uptake profiles of the two variants did not differ in our immunostaining study neither with respect to concentration nor the time of exposure. Furthermore, we have demonstrated for the first time the nuclear localization of MC-RR and confirmed that of MC-LR. Finally, our results suggest a facilitated uptake and an active excretion of MC-LR and MC-RR in Caco-2 cells. Further investigation on the role of OATP 3A1 and 4A1 in MC uptake should be useful to clarify the mechanism of intestinal absorption of MCs and contribute in risk assessment of cyanotoxin exposure.

Does the Use of Pacifier Affect Gastro-Esophageal Reflux in Preterm Infants?

Science.gov (United States)

Corvaglia, Luigi; Martini, Silvia; Corrado, Maria Francesca; Mariani, Elisa; Legnani, Elena; Bosi, Isabella; Faldella, Giacomo; Aceti, Arianna

2016-05-01

This crossover study showed that non-nutritive sucking, provided with a pacifier in 30 preterm infants, had no effect on acid and nonacid gastro-esophageal reflux evaluated by esophageal pH-impedance, and thus may be reasonably used in preterm neonates with symptoms of gastro-esophageal reflux. ClinicalTrials.gov: NCT02023216. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of a combination of inulin and polyphenol-containing adzuki bean extract on intestinal fermentation in vitro and in vivo.

Science.gov (United States)

Nagata, Ryuji; Echizen, Mao; Yamaguchi, Yukari; Han, Kyu-Ho; Shimada, Kenichiro; Ohba, Kiyoshi; Kitano-Okada, Tomoko; Nagura, Taizo; Uchino, Hirokatsu; Fukushima, Michihiro

2018-03-01

The effect of a combination of inulin (INU) and polyphenol-containing adzuki bean extract (AE) on intestinal fermentation was examined in vitro using fermenters for 48 h and in vivo using rats for 28 d. The total short-chain fatty acid concentrations in the fermenters were decreased by a combination of INU and AE, but the concentration in the INU + AE group was higher than the cellulose (CEL) and CEL + AE groups. The cecal propionate concentration was increased by a combination of INU and AE compared with their single supplement. The ammonia-nitrogen concentration in the fermenters and rat cecum was decreased by INU and AE. Cecal mucin levels were increased by INU and AE respectively. Therefore, our observations suggested that the combination of INU and AE might be a material of functional food that includes several healthy effects through intestinal fermentation.

Digestive recovery of sulfur-methyl-L-methionine and its bioaccessibility in Kimchi cabbages using a simulated in vitro digestion model system.

Science.gov (United States)

Lee, Hae-Rim; Cho, Sun-Duk; Lee, Woon Kyu; Kim, Gun-Hee; Shim, Soon-Mi

2014-01-15

Sulfur-methyl-L-methionine (SMM) has been known to provide various biological functions such as radical scavenging effect, inhibition of adipocyte differentiation, and prevention of gastric mucosal damage. Kimchi cabbages are known to be a major food source providing SMM but its bioaccessibility has not been studied. The objective of current study was to determine both the digestive stability of SMM and the amount released from Kimchi cabbages under a simulated in vitro digestion model system. The in vitro digestion model system simulating a human gastrointestinal tract was carried out for measuring digestive recovery and bioaccessibility of SMM. SMM was quantified by using high-performance liquid chromatography with a fluorescence detector. Recovery of an SMM standard after digestion was 0.68 and 0.65% for fasted and fed conditions, respectively, indicating that the digestive stability of the SMM standard was not affected by dietary energy or co-ingested food matrix. The SMM standard was also significantly stable in acidic pH (P < 0.05). The bioaccessibility of SMM from Kimchi cabbages was measured under a fasted condition, resulted in 8.83, 14.71 and 10.88%, for salivary, gastric and small intestinal phases, respectively. Results from our study suggest that SMM from Kimchi cabbages, a component of food sources, is more bioavailable than SMM by itself. © 2013 Society of Chemical Industry.

Formulation and evaluation of co-prodrug of flurbiprofen and methocarbamol

Directory of Open Access Journals (Sweden)

Neela Bhatia

2016-06-01

Full Text Available The current work envisages synthesis of an ester prodrug of flurbiprofen whereby its carboxylic group was condensed with a skeletal muscle relaxant methocarbamol, with the aim of synergistic activity of two drugs, avoid flurbiprofen mediated gastro-intestinal damage and minimize the ulceration tendency of flurbiprofen. The synthesized prodrug was characterized and confirmed by physicochemical and spectroscopic studies. Solubility and partition coefficient studies indicated an increased lipophilicity and thus better suitability for oral administration than the parent drugs and the protein binding studies revealed a low protein binding capacity of the mutual prodrug. Subsequently, in-vitro hydrolysis was studied in different pH, simulated gastric fluid, simulated intestinal fluid and plasma and quantitative evaluation was performed by high performance liquid chromatography. It was found that the prodrug remained unhydrolyzed in the stomach after absorption however, underwent rapid cleavage by the esterases in blood to give the parent drug. Furthermore, the mutual ester prodrug was evaluated for its anti-inflammatory, analgesic, skeletal muscle relaxation, ulcerogenic and total acid content activity and was found to possess comparable activity with that of the parent drugs. Microscopic structures of the stomach tissues revealed significant reduction in gastric ulcer formation of mice gastric mucosa as compared to parent carboxylic acid drug.

Psidium guajava Linn confers gastro protective effects on rats.

Science.gov (United States)

Livingston Raja, N R; Sundar, K

2012-02-01

The best alternatives to synthetic medicines, available, for the treatment of gastric ulcer disorders, are the natural products found in plants. They are known to exhibit a variety of activities. The present study is aimed at the screening of Psidium (P.) guajava Linn for its gastro protective effect. The methanol extracts of the leaves of P. guajava were tested in three different ulcer models viz. aspirin (ASP), pyloric ligation (PL) and ethanol (EtoH) induced ulcer models in rats. The treatment of P. guajava at varying doses (100 mg/kg and 200 mg/kg) significantly (p guajava may be responsible for the anti-ulcer property exhibited. The results further suggest that P. guajava possess gastro protective as well as ulcer healing properties which might also be due to its anti-secretory properties.

Simulation of Food Folate Digestion and Bioavailability of an Oxidation Product of 5-Methyltetrahydrofolate.

Science.gov (United States)

Ringling, Christiane; Rychlik, Michael

2017-09-01

Generating bioavailability data from in vivo studies is time-consuming and expensive. In vitro simulation can help to investigate factors influencing bioavailability or facilitate quantifying the impact of such factors. For folates, an efficient deconjugation of polyglutamates to the corresponding monoglutamates is crucial for bioavailability and highly dependent on the food matrix. Therefore, the bioaccessibility of folates of different foodstuffs was examined using a simulated digestion model with respect to folate stability and the efficiency of deconjugation. For realistic simulated deconjugation, porcine brush border membrane was used during the phase of the simulated digestion in the small intestine. For a better understanding of folate behaviour during digestion, single folate monoglutamates were also investigated with this in vitro digestion model. The results for bioaccessibility were compared with data from a human bioavailability study. They support the idea that both stability and deconjugation have an influence on bioaccessibility and thus on bioavailability. Tetrahydrofolate is probably lost completely or at least to a high extent and the stability of 5-methyltetrahydrofolate depends on the food matrix. Additionally, 5-methyltetrahydrofolate can be oxidised to a pyrazino-s-triazine (MeFox), whose absorption in the human intestinal tract was shown tentatively.

The Role of Esophageal PH-metri Test on Gastro-Esophageal Reflux Disease Diagnosis

OpenAIRE

Setyawati, Katharina; Abdullah, Murdani; Syam, Ari Fahrial; Fauzi, Achmad; Makmun, Dadang; Simadibrata, Marcellus; Manan, Chudahman; Rani, Abdul Aziz

2008-01-01

Gastro-esophageal reflux disease is a pathological condition of esophagus which is caused by gastric content reflux into esophagus. There is an increased prevalence of gastro-esophageal reflux disease. The roles of esophageal pH-metry in clinical application include looking for abnormal acid exposure on esophagus with no abnormality found in endoscopy; evaluating patients following the anti-reflux surgery who are being suspected for abnormal esophageal reflux; evaluating patients with normal ...

Biological effect of food additive titanium dioxide nanoparticles on intestine: an in vitro study.

Science.gov (United States)

Song, Zheng-Mei; Chen, Ni; Liu, Jia-Hui; Tang, Huan; Deng, Xiaoyong; Xi, Wen-Song; Han, Kai; Cao, Aoneng; Liu, Yuanfang; Wang, Haifang

2015-10-01

Titanium dioxide nanoparticles (TiO2 NPs) are widely found in food-related consumer products. Understanding the effect of TiO2 NPs on the intestinal barrier and absorption is essential and vital for the safety assessment of orally administrated TiO2 NPs. In this study, the cytotoxicity and translocation of two native TiO2 NPs, and these two TiO2 NPs pretreated with the digestion simulation fluid or bovine serum albumin were investigated in undifferentiated Caco-2 cells, differentiated Caco-2 cells and Caco-2 monolayer. TiO2 NPs with a concentration less than 200 µg ml(-1) did not induce any toxicity in differentiated cells and Caco-2 monolayer after 24 h exposure. However, TiO2 NPs pretreated with digestion simulation fluids at 200 µg ml(-1) inhibited the growth of undifferentiated Caco-2 cells. Undifferentiated Caco-2 cells swallowed native TiO2 NPs easily, but not pretreated NPs, implying the protein coating on NPs impeded the cellular uptake. Compared with undifferentiated cells, differentiated ones possessed much lower uptake ability of these TiO2 NPs. Similarly, the traverse of TiO2 NPs through the Caco-2 monolayer was also negligible. Therefore, we infer the possibility of TiO2 NPs traversing through the intestine of animal or human after oral intake is quite low. This study provides valuable information for the risk assessment of TiO2 NPs in food. Copyright © 2015 John Wiley & Sons, Ltd.

Gastrointestinal behavior of nano- and microsized fenofibrate: In vivo evaluation in man and in vitro simulation by assessment of the permeation potential.

Science.gov (United States)

Hens, Bart; Brouwers, Joachim; Corsetti, Maura; Augustijns, Patrick

2015-09-18

The purpose of this study was (i) to evaluate the gastrointestinal behavior of micro- and nanosized fenofibrate in humans and (ii) to develop a simple yet qualitatively predictive in vitro setup that simulates the observed absorption-determining factors. Commercially available micro- and nanoparticles of fenofibrate (Lipanthyl® and Lipanthylnano®, respectively) were administered orally to five healthy volunteers in fasting and postprandial conditions. Intraluminal and systemic drug concentrations were determined as reference data for the development of a predictive in vitro setup. To capture the observed solubility/permeability interplay, in vitro dissolution testing was performed in the presence of a permeation bag with sink conditions. In fasting conditions, intake of nanosized fenofibrate generated increased duodenal concentrations compared to microsized fenofibrate, which was reflected in an improved systemic exposure. In postprandial conditions, duodenal concentrations were greatly enhanced for both formulations, however without an accompanying increase in systemic exposure. It appeared that micellar encapsulation of the highly lipohilic fenofibrate limited its potential to permeate from fed state intestinal fluids. To capture these in vivo observations in an in vitro setup, classic dissolution testing was combined with permeation assessment into a permeation bag with sink conditions. In case of fasting conditions, the dissolution/permeation approach allowed for an improved discriminative power between micro- and nanosized fenofibrate by better simulating the dynamic interplay of dissolution and absorption. In case of postprandial conditions, the observed solubility-permeability interplay could be simulated using the dissolution/permeation approach in combination with biorelevant media (FeSSGFFortimel and FeSSIF-V2) to mimic micellar entrapment and reduced permeation potential of fenofibrate. For the first time, reduced permeation of a lipophilic drug

Can computed tomography aid in diagnosis of intramural hematomas of the intestinal wall?

Science.gov (United States)

Ulusan, Serife; Pekoz, Burcak; Sariturk, Cagla

2015-12-01

We sought to use computed tomography (CT) data to support the correct differential diagnosis of patients with spontaneous intramural hematomas of the gastrointestinal tract, to aid in the clinical management of those using oral anticoagulants. Patient data were retrospectively analyzed and patients were divided into two groups. The first group contained 10 patients (5 females, 5 males, median age 65 years [range 35-79 years]) who had been diagnosed with spontaneous intramural hematomas of the gastrointestinal tract. The second group contained nine patients (5 females, 4 males, median age 41 years [range 24-56 years]) who exhibited intestinal wall thickening on CT, and who had been diagnosed with ulcerative colitis, Crohn's disease, ameboma, and lymphoma. The enhancement patterns in the CT images of the two groups were compared by an experienced and inexperienced radiologist. The differences in values were subjected to ROC analysis. Inter-observer variability was excellent (0.84) when post-contrast CT images were evaluated, as were the subtraction values (0.89). The subtracted values differed significantly between the two groups (p=0.0001). A cutoff of +31.5 HU was optimal in determining whether a hematoma was or was not present. Contrast enhancement of an intestinal wall hematoma is less than that of other intestinal wall pathologies associated with increased wall thickness. If the post-contrast enhancement of a thickened intestinal wall is less than +31.5 HU, a wall hematoma is possible. © Acta Gastro-Enterologica Belgica.

Studying furosemide solubilization using an in vitro model simulating gastrointestinal digestion and drug solubilization in neonates and young infants

DEFF Research Database (Denmark)

Klitgaard, Mette; Sassene, Philip Jonas; Selen, Arzu

2017-01-01

-2months). METHODS: The utilized in vitro model was designed to mimic the digestion and drug solubilization processes occurring in the stomach, and the small intestine of the neonate and young infant population, using physiologically relevant media, volumes and digestive enzymes. Overall the experimental...

In vitro co-culture experiments on prostate cancer and small intestine cells irradiated with carbon ions and x-rays

International Nuclear Information System (INIS)

Neubeck, C. von; Weyrather, W.-K.; Durante, M.

2009-01-01

Intensity modulated radiotherapy (IMRT) delivers the dose in many small irradiation fields of different beam direction to achieve a 3 dimensional tumour conformal dose overlapping with a maximum of normal tissue protection. In 2006 a study was started at GSI to treat prostate cancer patients with a boost irradiation of carbon ions in combination with an IMRT treatment administered at the Uniklinikum Heidelberg. The carbon ions are delivered in two opposing fields. So IMRT irradiation includes more normal tissue than carbon ion treatment but even here parts of the rectum and the bladder are in the irradiated field. This raises the question whether the irradiated tumor cells influence the normal cells (irradiated/ unirradiated) but also whether the normal irradiated cells influences normal tissue in a different way for carbon and photon irradiation. To study this problem, we established an in vitro co-culture model of prostate cancer and small intestine cells of the rat to simulate the patient treatment situation for analyzing tissue reaction exemplary. For characterization of the cells lines the parameters alpha and beta (linear quadratic model) for clonogenic survival were determined for x-rays and for carbon ions of different energies. For co-culture experiments unirradiated and irradiated cells were seeded together and the survival was analyzed

Small intestinal sulphoxidation of albendazole.

Science.gov (United States)

Villaverde, C; Alvarez, A I; Redondo, P; Voces, J; Del Estal, J L; Prieto, J G

1995-05-01

1. The in vitro sulphoxidation of Albendazole (ABZ) by rat intestinal microsomes has been examined. The results revealed intestinal sulphoxidation of ABZ by intestinal microsomes in a NADPH-dependent enzymatic system. The kinetic constants for sulphoxidase activity were Vmax = 46 pmol/min/mg protein and Michaelis constant Km = 6.8 microM. 2. The possible effect of inducers (Arochlor 1254 and ABZ pretreatment) and inhibitors (erythromycin, methimazole, carbon monoxide and fenbendazole), was also studied. In rat pretreated with Arochlor 1254, Vmax was 52 pmol/min/mg protein, whereas oral administration of ABZ increased the intestinal sulphoxidation of the drug, Vmax being 103 pmol/min/mg protein. 3. Erythromycin did not change the enzymatic bioconversion of ABZ, but methimazole and carbon monoxide inhibited the enzyme activity by approximately 60 and 30% respectively. Fenbendazole (a structural analogue of ABZ) was a competitive inhibitor of the sulphoxidation process, characterized by a Ki or 69 microM. 4. These data demonstrate that the intestinal enzymes contributing to the initial sulphoxidation of ABZ may be similar to the hepatic enzymes involved in the biotransformation process by the P450 and FMO systems, a conclusion that needs to be further established.

Effects of macro-nutrient, micro-nutrient composition and cooking conditions on in vitro digestibility of meat and aquatic dietary proteins.

Science.gov (United States)

Luo, Jiaqiang; Taylor, Cheryl; Nebl, Thomas; Ng, Ken; Bennett, Louise E

2018-07-15

Animal and aquatic meats represent important sources of dietary protein and micro-nutrients. Although red and processed meats carry some risks for human health, sensory and nutritional advantages drive meat consumption. Therefore, it is important to understand how meat processing and cooking influence healthiness. The research aim was to investigate relationships of meat composition (proximates, amino acids and minerals) and cooking conditions (raw, 90 s microwave, 200 °C oven for 10 or 30 min) on protein digestibility, for a selection of four animal (beef, chicken, pork, kangaroo) and four aquatic meats (salmon, trout, prawn, oyster). Lean meats were minced before cooking followed by in vitro gastro-intestinal digestion and analysed for progress of hydrolysis, and size ranges of peptides using MALDI-TOF-MS. Correlation matrix analysis between compositional and functional parameters indicated that digestibility was significantly linked with protein and metal concentrations, likely reflecting moisture-dependent solubility and inter-mixing of sarcoplasmic metallo-proteins and insoluble myofibrillar proteins. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

Global prevalence of, and risk factors for, gastro-oesophageal reflux symptoms: a meta-analysis.

Science.gov (United States)

Eusebi, Leonardo H; Ratnakumaran, Raguprakash; Yuan, Yuhong; Solaymani-Dodaran, Masoud; Bazzoli, Franco; Ford, Alexander C

2018-03-01

Gastro-oesophageal reflux symptoms are common in the community, but there has been no definitive systematic review and meta-analysis of data from all studies to estimate their global prevalence, or potential risk factors for them. Medline, Embase and Embase Classic were searched (until September 2016) to identify population-based studies that reported the prevalence of gastro-oesophageal reflux symptoms in adults (≥15 years); gastro-oesophageal reflux was defined using symptom-based criteria or questionnaires. The prevalence was extracted for all studies, and according to the criteria used to define it. Pooled prevalence, according to study location and certain other characteristics, OR and 95% CIs were calculated. Of the 14 132 citations evaluated, 102 reported the prevalence of gastro-oesophageal reflux symptoms in 108 separate study populations, containing 460 984 subjects. Prevalence varied according to country (from 2.5% in China to 51.2% in Greece) and criteria used to define gastro-oesophageal reflux symptoms. When only studies using a weekly frequency of heart burn or regurgitation to define presence were considered, pooled prevalence was 13.3% (95% CI 12.0% to 14.6%). Prevalence was higher in subjects ≥50 years (OR 1.32; 95% CI 1.12 to 1.54), smokers (OR 1.26; 95% CI 1.04 to 1.52), non-steroidal anti-inflammatory drug (NSAID)/aspirin users (OR 1.44; 95% CI 1.10 to 1.88) and obese individuals (OR 1.73; 95% CI 1.46 to 2.06). The prevalence of gastro-oesophageal reflux symptoms varied strikingly among countries, even when similar definitions were used to define their presence. Prevalence was significantly higher in subjects ≥50 years, smokers, NSAID users and obese individuals, although these associations were modest. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Simulated rat intestinal fluid improves oral exposure prediction for poorly soluble compounds over a wide dose range

Directory of Open Access Journals (Sweden)

Joerg Berghausen

2016-03-01

Full Text Available Solubility can be the absorption limiting factor for drug candidates and is therefore a very important input parameter for oral exposure prediction of compounds with limited solubility. Biorelevant media of the fasted and fed state have been published for humans, as well as for dogs in the fasted state. In a drug discovery environment, rodents are the most common animal model to assess the oral exposure of drug candidates. In this study a rat simulated intestinal fluid (rSIF is proposed as a more physiologically relevant media to describe drug solubility in rats. Equilibrium solubility in this medium was tested as input parameter for physiologically-based pharmacokinetics (PBPK simulations of oral pharmacokinetics in the rat. Simulations were compared to those obtained using other solubility values as input parameters, like buffer at pH 6.8, human simulated intestinal fluid and a comprehensive dissolution assay based on rSIF. Our study on nine different compounds demonstrates that the incorporation of rSIF equilibrium solubility values into PBPK models of oral drug exposure can significantly improve the reliability of simulations in rats for doses up to 300 mg/kg compared to other media. The comprehensive dissolution assay may help to improve further simulation outcome, but the greater experimental effort as compared to equilibrium solubility may limit its use in a drug discovery environment. Overall, PBPK simulations based on solubility in the proposed rSIF medium can improve prioritizing compounds in drug discovery as well as planning dose escalation studies, e.g. during toxicological investigations.

Gastro-jejunostomy tube related intestinal perforation in an infant presenting incidentally with a splenic abscess

Directory of Open Access Journals (Sweden)

Kathryn Bell

2018-07-01

Conclusion: While complications from GJTs are well described, this case uniquely highlights the risk of intestinal perforation from GJT, with a delayed and subtle presentation. We suggest that patients, specifically those under 12 months of age and weighing under 10 kg, be monitored closely for complications post-operatively, and the use of modified GJTs with jejunal limbs employing smaller/thinner feeding tubes that are placed well beyond LOT be strongly considered.

The diagnosis of gastro-esophageal reflux disease cannot be made with barium esophagograms.

Science.gov (United States)

Saleh, C M G; Smout, A J P M; Bredenoord, A J

2015-02-01

For over 50 years, barium studies have been used to diagnose gastro-esophageal reflux disease (GERD), but the value of this test is controversial. Our study aimed to determine if barium esophagograms can be used to diagnose GERD. Barium esophagograms and pH-impedance measurement were performed in 20 subjects with reflux symptoms. pH-impedance measurements were used as gold standard for the diagnosis of GERD. Gastro-esophageal reflux measured with the barium study was defined as a positive outcome. 50% of patients presented gastro-esophageal reflux on the barium esophagogram. No significant differences were observed in acid exposure time between subjects with (median: 7.4%; interquartile range, IQR: 8.4%) or without reflux at barium esophagography (median: 5.95%; IQR: 13.05%; p > 0.05). Nor did we find differences in median proximal extent of reflux measured with impedance monitoring between patients with a positive (median: 6.7%; IQR: 1.95%) and negative barium study (median: 7.1%; IQR: 0.68%; p > 0.05). Patients with reflux on barium esophagogram did not have a positive symptom association probability more often than those who did not have reflux at barium esophagography. Lastly, there were no differences in numbers of acid, weakly acidic or total reflux episodes between those with positive or negative barium esophagogram (p > 0.05). No correlations were found between the maximum proximal extent of gastro-esophageal reflux during esophagography and pH-impedance parameters. Presence or absence of gastro-esophageal reflux during barium esophagography does not correlate with incidence or extent of reflux observed during 24-h pH-impedance monitoring and is not of value for the diagnosis of GERD. © 2014 John Wiley & Sons Ltd.

Differential gene expression and adherence of Escherichia coli O157:H7 in vitro and in ligated pig intestines.

Directory of Open Access Journals (Sweden)

Xianhua Yin

Full Text Available BACKGROUND: Escherichia coli O157:H7 strain 86-24 grown in MacConkey broth (MB shows almost no adherence to cultured epithelial cells but adheres well in pig ligated intestines. This study investigated the mechanisms associated with the difference between in-vitro and in-vivo adherence of the MB culture. METHODOLOGY/PRINCIPAL FINDINGS: It was found that decreased adherence in vitro by bacteria grown in MB was mainly due to lactose, possibly implicating the involvement of carbon catabolite repression (CCR. Expression of selected virulence-related genes associated with adherence and CCR was then examined by quantitative PCR. When bacteria were grown in MB and Brain Heart Infusion with NaHCO(3 (BHIN plus lactose, pH was reduced to 5.5-5.9 and there was a significant decrease in expression of the locus of enterocyte effacement (LEE genes eae, tir, espD, grlA/R and ler, and an increase in cya (cAMP, and two negative regulators of the LEE, gadE and hfq. Putative virulence genes stcE, hlyA, ent and nleA were also decreased in vitro. Reversal of these changes was noted for bacteria recovered from the intestine, where transcripts for qseF and fis and putative virulence factors AidA(15, TerC and Ent/EspL2 were significantly increased, and transcripts for AIDA(48, Iha, UreC, Efa1A, Efa1B, ToxB, EhxA, StcE, NleA and NleB were expressed at high levels. CONCLUSIONS/SIGNIFICANCE: Presence of lactose resulted in decreased expression of LEE genes and the failure of EHEC O157:H7 to adhere to epithelial cells in vitro but this repression was overcome in vivo. CCR and/or acidic pH may have played a role in repression of the LEE genes. Bacterial pathogens need to integrate their nutritional metabolism with expression of virulence genes but little is known of how this is done in E. coli O157:H7. This study indicates one aspect of the subject that should be investigated further.

Erlotinib promotes endoplasmic reticulum stress-mediated injury in the intestinal epithelium

Energy Technology Data Exchange (ETDEWEB)

Fan, Lu; Hu, Lingna; Yang, Baofang; Fang, Xianying; Gao, Zhe; Li, Wanshuai; Sun, Yang; Shen, Yan; Wu, Xuefeng [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093 (China); Shu, Yongqian [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029 (China); Gu, Yanhong, E-mail: guluer@163.com [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029 (China); Wu, Xudong, E-mail: xudongwu@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093 (China); Xu, Qiang, E-mail: molpharm@163.com [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093 (China)

2014-07-01

Erlotinib, a popular drug for treating non-small cell lung cancer (NSCLC), causes diarrhea in approximately 55% of patients receiving this drug. In the present study, we found that erlotinib induced barrier dysfunction in rat small intestine epithelial cells (IEC-6) by increasing epithelial permeability and down-regulating E-cadherin. The mRNA levels of various pro-inflammatory cytokines (Il-6, Il-25 and Il-17f) were increased after erlotinib treatment in IEC-6 cells. Erlotinib concentration- and time-dependently induced apoptosis and endoplasmic reticulum (ER) stress in both IEC-6 and human colon epithelial cells (CCD 841 CoN). Intestinal epithelial injury was also observed in male C57BL/6J mice administrated with erlotinib. Knockdown of C/EBP homologous protein (CHOP) with small interference RNA partially reversed erlotinib-induced apoptosis, production of IL-6 and down-regulation of E-cadherin in cultured intestinal epithelial cells. In conclusion, erlotinib caused ER stress-mediated injury in the intestinal epithelium, contributing to its side effects of diarrhea in patients. - Highlights: • Erlotinib destroyed barrier integrity both in vitro and in vivo. • Erlotinib induced inflammation both in vitro and in vivo. • Erlotinib induced apoptosis both in vitro and in vivo. • ER stress contributed to erlotinib-induced barrier dysfunction.

Erlotinib promotes endoplasmic reticulum stress-mediated injury in the intestinal epithelium

International Nuclear Information System (INIS)

Fan, Lu; Hu, Lingna; Yang, Baofang; Fang, Xianying; Gao, Zhe; Li, Wanshuai; Sun, Yang; Shen, Yan; Wu, Xuefeng; Shu, Yongqian; Gu, Yanhong; Wu, Xudong; Xu, Qiang

2014-01-01

Erlotinib, a popular drug for treating non-small cell lung cancer (NSCLC), causes diarrhea in approximately 55% of patients receiving this drug. In the present study, we found that erlotinib induced barrier dysfunction in rat small intestine epithelial cells (IEC-6) by increasing epithelial permeability and down-regulating E-cadherin. The mRNA levels of various pro-inflammatory cytokines (Il-6, Il-25 and Il-17f) were increased after erlotinib treatment in IEC-6 cells. Erlotinib concentration- and time-dependently induced apoptosis and endoplasmic reticulum (ER) stress in both IEC-6 and human colon epithelial cells (CCD 841 CoN). Intestinal epithelial injury was also observed in male C57BL/6J mice administrated with erlotinib. Knockdown of C/EBP homologous protein (CHOP) with small interference RNA partially reversed erlotinib-induced apoptosis, production of IL-6 and down-regulation of E-cadherin in cultured intestinal epithelial cells. In conclusion, erlotinib caused ER stress-mediated injury in the intestinal epithelium, contributing to its side effects of diarrhea in patients. - Highlights: • Erlotinib destroyed barrier integrity both in vitro and in vivo. • Erlotinib induced inflammation both in vitro and in vivo. • Erlotinib induced apoptosis both in vitro and in vivo. • ER stress contributed to erlotinib-induced barrier dysfunction

Influence of in vitro gastrointestinal digestion of fruit juices enriched with pine bark extract on intestinal microflora.

Science.gov (United States)

López-Nicolás, Rubén; González-Bermúdez, Carlos A; Ros-Berruezo, Gaspar; Frontela-Saseta, Carmen

2014-08-15

The selective antimicrobial effect of fruit juices enriched with pine bark extract (PBE) (0.5 g/L) has been studied before and after in vitro gastrointestinal digestion. PBE (a concentrate of water-soluble bioflavonoids, mainly including phenolic compounds) has been proven to have high stability to the digestion process. Pure phenolic compounds such as gallic acid had a high antimicrobial effect on Staphylococcus aureus and Escherichia coli, maintaining the lactic acid bacteria population (≈100%). Otherwise, E. coli O157:H7 only growth 50% when PBE was added to the culture media, while a slight increase on the growth of lactobacilli and bifidobacteria was observed after exposition to the bark extract. Fresh fruit juices enriched with PBE showed the highest inhibitory effect on pathogenic intestinal bacterial growth, mainly E. coli and Enterococcus faecalis. The in vitro digestion process reduced the antibacterial effect of juices against most pathogenic bacteria in approximately 10%. However, the beneficial effect of fruit juices enriched with PBE (0.5 g/L) on gut microbiota is still considerable after digestion. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of Sub-lethal Concentrations of Silver Nanoparticles on a Simulated Intestinal Prokaryotic–Eukaryotic Interface

Directory of Open Access Journals (Sweden)

Elisa Garuglieri

2018-01-01

Full Text Available Nanotechnology applications are expected to bring a range of benefits to the food sector, aiming to provide better quality and conservation. In this research, the physiological response of both an Escherichia coli mono-species biofilm and Caco-2 intestinal cells to sub-lethal concentrations of silver nanoparticles (AgNPs has been investigated. In order to simulate the anaerobic and aerobic compartments required for bacteria and intestinal cells growth, a simplified semi-batch model based on a transwell permeable support was developed. Interaction between the two compartments was obtained by exposing Caco-2 intestinal cells to the metabolites secreted by E. coli biofilm after its exposure to AgNPs. To the best of the authors’ knowledge, this study is the first to investigate the effect of AgNPs on Caco-2 cells that takes into consideration previous AgNP-intestinal biofilm interactions, and at concentrations mimicking real human exposure. Our data show that 1 μg/mL AgNPs in anaerobic conditions (i promote biofilm formation up to 2.3 ± 0.3 fold in the first 72 h of treatment; (ii increase reactive oxygen species (ROS production to 84 ± 21% and change the physiological status of microbial cells after 96 h of treatment; (iii seriously affect a 72-h old established biofilm, increasing the level of oxidative stress to 86 ± 21%. Moreover, the results indicate that oxygen renders the biofilm more adequate to counteract AgNP effects. Comet assays on Caco-2 cells demonstrated a protective role of biofilm against the genotoxic effect of 1 μg/mL AgNPs on intestinal epithelial cells.

Validation of an in vitro digestive system for studying macronutrient decomposition in humans.

Science.gov (United States)

Kopf-Bolanz, Katrin A; Schwander, Flurina; Gijs, Martin; Vergères, Guy; Portmann, Reto; Egger, Lotti

2012-02-01

The digestive process transforms nutrients and bioactive compounds contained in food to physiologically active compounds. In vitro digestion systems have proven to be powerful tools for understanding and monitoring the complex transformation processes that take place during digestion. Moreover, the investigation of the physiological effects of certain nutrients demands an in vitro digestive process that is close to human physiology. In this study, human digestion was simulated with a 3-step in vitro process that was validated in depth by choosing pasteurized milk as an example of a complex food matrix. The evolution and decomposition of the macronutrients was followed over the entire digestive process to the level of intestinal enterocyte action, using protein and peptide analysis by SDS-PAGE, reversed-phase HPLC, size exclusion HPLC, and liquid chromatography-MS. The mean peptide size after in vitro digestion of pasteurized milk was 5-6 amino acids (AA). Interestingly, mostly essential AA (93.6%) were released during in vitro milk digestion, a significantly different relative distribution compared to the total essential AA concentration of bovine milk (44.5%). All TG were degraded to FFA and monoacylglycerols. Herein, we present a human in vitro digestion model validated for its ability to degrade the macronutrients of dairy products comparable to physiological ranges. It is suited to be used in combination with a human intestinal cell culture system, allowing ex vivo bioavailability measurements and assessment of the bioactive properties of food components.

Effect of in vitro digested cod liver oil of different quality on oxidative, proteomic and inflammatory responses in the yeast Saccharomyces cerevisiae and human monocyte-derived dendritic cells

DEFF Research Database (Denmark)

Larsson, Karin; Istenič, Katja; Wulff, Tune

2015-01-01

BACKGROUND: Upon oxidation of the polyunsaturated fatty acids in fish oil, either before ingestion or, as recently shown, during the gastro-intestinal passage, a cascade of potentially cytotoxic peroxidation products, such as malondialdehyde and 4-hydroxy-2-hexenal, can form. In this study, we di...... in yeast and immunomodulation of dendritic cells....

[AETIOLOGY AND PATHOGENESIS GASTRO-DUODENALES ULCERATIVE LESIONS IN ELDERLY].

Science.gov (United States)

Chernekhovskaya, N E; Povalayev, A V; Layshenko, G A

2015-01-01

In review today conceptions of view to aetiology and pathogenesis gastro-duodenales ulcerative lesions in elderly. Atherosclerosis, ischemic disease of the heart and hypertension are reasons of acute ulcers and erosions in elderly. The breaking of microcirculation are very importance.

Gastro-umbilical fistula as a rare complication of benign gastric ulcer perforation: a case report

Energy Technology Data Exchange (ETDEWEB)

Lee, Ju Young; Jang, Kyung Mi; Yoon, Hoi Soo; Kim, Min Jeong; Lee, Kwan Seop; Lee, Yul; Bae, Sang Hoon [College of Medicine, Hallym University, Anyang (Korea, Republic of)

2007-11-15

As fistula occurring between the stomach and other abdominal internal organs or to the surface of the body is usually encountered as a complication of stomach cancer or colon cancer, peptic ulcer disease, or other variable causes. The most common type of gastric fistula is a gastro-colic fistula that is mainly found as a complication of a gastric carcinoma or of a carcinoma of the transverse colon invading each other. Sometimes, a benign gastric ulcer perforation also can cause a gastro-colic fistula. However, as far as we know, a fistula occurring between the stomach and the umbilicus has not been reported. Here we present a case report of a gastro-umbilical fistula in a young woman that manifested as a umbilical discharge.

Gastro-umbilical fistula as a rare complication of benign gastric ulcer perforation: a case report

International Nuclear Information System (INIS)

Lee, Ju Young; Jang, Kyung Mi; Yoon, Hoi Soo; Kim, Min Jeong; Lee, Kwan Seop; Lee, Yul; Bae, Sang Hoon

2007-01-01

As fistula occurring between the stomach and other abdominal internal organs or to the surface of the body is usually encountered as a complication of stomach cancer or colon cancer, peptic ulcer disease, or other variable causes. The most common type of gastric fistula is a gastro-colic fistula that is mainly found as a complication of a gastric carcinoma or of a carcinoma of the transverse colon invading each other. Sometimes, a benign gastric ulcer perforation also can cause a gastro-colic fistula. However, as far as we know, a fistula occurring between the stomach and the umbilicus has not been reported. Here we present a case report of a gastro-umbilical fistula in a young woman that manifested as a umbilical discharge

A case of positive 68Ga-DOTATOC-PET/CT pancreatic heterotopia mimicking an intestinal neuroendocrine tumor.

Science.gov (United States)

Zilli, Alessandra; Fanetti, Ilaria; Conte, Dario; Massironi, Sara

Gallium-68 DOTA-peptide positron emission tomography/computed tomography ( 68 Ga-PET/CT) has emerged as a promising tool for the diagnosis and staging of gastro-entero-pancreatic neoplasms, thanks to its high sensitivity and specificity. Heterotopic pancreas, which is relatively rare, has never been reported as a possible cause of false positives of 68 Ga-PET/CT. We report on the first case of a heterotopic pancreas showing pathological uptake at 68 Ga-PET/CT, thus mimicking an intestinal neuroendocrine tumor. The present case suggests that heterotopic pancreas should be included among the possible causes of false positives at 68 Ga PET. Copyright © 2018 Elsevier Inc. All rights reserved.

Cephalic pancreaticoduodenectomy with preservation of a right coronary artery bypass graft using the right gastro-epiploic artery: a case report.

Science.gov (United States)

Homsy, K; Paquay, J-L; Farghadani, H

2018-02-20

Pancreatic cancer is a rare disease with a high mortality rate, for which complete surgical resection, when possible, is the preferred therapeutic. Pancreaticoduodenectomy represents the surgical technique of choice. Abdominal surgeons can be faced with the challenge of patients with a history of coronary artery bypass graft in which the right gastro-epiploic artery is used. We report the case of a patient with an adenocarcinoma of the pancreatic head, stage IIA, having previously undergone a triple coronary artery bypass, one of which being a right gastro-epiploic graft. Our challenge was underlined by the necessity of a complete oncological resection through a cephalic pancreaticoduodenectomy while preserving the necessary cardiac perfusion via the right gastro-epiploic artery. We have been able to preserve a right gastro-epiploic artery as a coronary bypass during a cephalic pancreaticoduodenectomy for a cephalic pancreatic adenocarcinoma. We have successfully been able to preserve and re-implant the right gastro-epiploic artery to the origin of the gastroduodenal artery while insuring R0 resection of the tumor. A coronary artery bypass using the right gastro-epiploic artery should therefore not be considered as an obstacle to a Whipple's procedure if total oncological resection is obtainable.

Computer simulation in cell radiobiology

International Nuclear Information System (INIS)

Yakovlev, A.Y.; Zorin, A.V.

1988-01-01

This research monograph demonstrates the possible ways of using stochastic simulation for exploring cell kinetics, emphasizing the effects of cell radiobiology. In vitro kinetics of normal and irradiated cells is the main subject, but some approaches to the simulation of controlled cell systems are considered as well: the epithelium of the small intestine in mice taken as a case in point. Of particular interest is the evaluation of simulation modelling as a tool for gaining insight into biological processes and hence the new inferences from concrete experimental data, concerning regularities in cell population response to irradiation. The book is intended to stimulate interest among computer science specialists in developing new, more efficient means for the simulation of cell systems and to help radiobiologists in interpreting the experimental data

Linking stem cell function and growth pattern of intestinal organoids.

Science.gov (United States)

Thalheim, Torsten; Quaas, Marianne; Herberg, Maria; Braumann, Ulf-Dietrich; Kerner, Christiane; Loeffler, Markus; Aust, Gabriela; Galle, Joerg

2018-01-15

Intestinal stem cells (ISCs) require well-defined signals from their environment in order to carry out their specific functions. Most of these signals are provided by neighboring cells that form a stem cell niche, whose shape and cellular composition self-organize. Major features of this self-organization can be studied in ISC-derived organoid culture. In this system, manipulation of essential pathways of stem cell maintenance and differentiation results in well-described growth phenotypes. We here provide an individual cell-based model of intestinal organoids that enables a mechanistic explanation of the observed growth phenotypes. In simulation studies of the 3D structure of expanding organoids, we investigate interdependences between Wnt- and Notch-signaling which control the shape of the stem cell niche and, thus, the growth pattern of the organoids. Similar to in vitro experiments, changes of pathway activities alter the cellular composition of the organoids and, thereby, affect their shape. Exogenous Wnt enforces transitions from branched into a cyst-like growth pattern; known to occur spontaneously during long term organoid expansion. Based on our simulation results, we predict that the cyst-like pattern is associated with biomechanical changes of the cells which assign them a growth advantage. The results suggest ongoing stem cell adaptation to in vitro conditions during long term expansion by stabilizing Wnt-activity. Our study exemplifies the potential of individual cell-based modeling in unraveling links between molecular stem cell regulation and 3D growth of tissues. This kind of modeling combines experimental results in the fields of stem cell biology and cell biomechanics constituting a prerequisite for a better understanding of tissue regeneration as well as developmental processes. Copyright © 2017 Elsevier Inc. All rights reserved.

In vitro dissolution methodology, mini-Gastrointestinal Simulator (mGIS), predicts better in vivo dissolution of a weak base drug, dasatinib.

Science.gov (United States)

Tsume, Yasuhiro; Takeuchi, Susumu; Matsui, Kazuki; Amidon, Gregory E; Amidon, Gordon L

2015-08-30

USP apparatus I and II are gold standard methodologies for determining the in vitro dissolution profiles of test drugs. However, it is difficult to use in vitro dissolution results to predict in vivo dissolution, particularly the pH-dependent solubility of weak acid and base drugs, because the USP apparatus contains one vessel with a fixed pH for the test drug, limiting insight into in vivo drug dissolution of weak acid and weak base drugs. This discrepancy underscores the need to develop new in vitro dissolution methodology that better predicts in vivo response to assure the therapeutic efficacy and safety of oral drug products. Thus, the development of the in vivo predictive dissolution (IPD) methodology is necessitated. The major goals of in vitro dissolution are to ensure the performance of oral drug products and the support of drug formulation design, including bioequivalence (BE). Orally administered anticancer drugs, such as dasatinib and erlotinib (tyrosine kinase inhibitors), are used to treat various types of cancer. These drugs are weak bases that exhibit pH-dependent and high solubility in the acidic stomach and low solubility in the small intestine (>pH 6.0). Therefore, these drugs supersaturate and/or precipitate when they move from the stomach to the small intestine. Also of importance, gastric acidity for cancer patients may be altered with aging (reduction of gastric fluid secretion) and/or co-administration of acid-reducing agents. These may result in changes to the dissolution profiles of weak base and the reduction of drug absorption and efficacy. In vitro dissolution methodologies that assess the impact of these physiological changes in the GI condition are expected to better predict in vivo dissolution of oral medications for patients and, hence, better assess efficacy, toxicity and safety concerns. The objective of this present study is to determine the initial conditions for a mini-Gastrointestinal Simulator (mGIS) to assess in vivo

In vitro solubility, dissolution and permeability studies combined with semi-mechanistic modeling to investigate the intestinal absorption of desvenlafaxine from an immediate- and extended release formulation.

Science.gov (United States)

Franek, F; Jarlfors, A; Larsen, F; Holm, P; Steffansen, B

2015-09-18

Desvenlafaxine is a biopharmaceutics classification system (BCS) class 1 (high solubility, high permeability) and biopharmaceutical drug disposition classification system (BDDCS) class 3, (high solubility, poor metabolism; implying low permeability) compound. Thus the rate-limiting step for desvenlafaxine absorption (i.e. intestinal dissolution or permeation) is not fully clarified. The aim of this study was to investigate whether dissolution and/or intestinal permeability rate-limit desvenlafaxine absorption from an immediate-release formulation (IRF) and Pristiq(®), an extended release formulation (ERF). Semi-mechanistic models of desvenlafaxine were built (using SimCyp(®)) by combining in vitro data on dissolution and permeation (mechanistic part of model) with clinical data (obtained from literature) on distribution and clearance (non-mechanistic part of model). The model predictions of desvenlafaxine pharmacokinetics after IRF and ERF administration were compared with published clinical data from 14 trials. Desvenlafaxine in vivo dissolution from the IRF and ERF was predicted from in vitro solubility studies and biorelevant dissolution studies (using the USP3 dissolution apparatus), respectively. Desvenlafaxine apparent permeability (Papp) at varying apical pH was investigated using the Caco-2 cell line and extrapolated to effective intestinal permeability (Peff) in human duodenum, jejunum, ileum and colon. Desvenlafaxine pKa-values and octanol-water partition coefficients (Do:w) were determined experimentally. Due to predicted rapid dissolution after IRF administration, desvenlafaxine was predicted to be available for permeation in the duodenum. Desvenlafaxine Do:w and Papp increased approximately 13-fold when increasing apical pH from 5.5 to 7.4. Desvenlafaxine Peff thus increased with pH down the small intestine. Consequently, desvenlafaxine absorption from an IRF appears rate-limited by low Peff in the upper small intestine, which "delays" the predicted

Intestinal transporters for endogenic and pharmaceutical organic anions

DEFF Research Database (Denmark)

Grandvuinet, Anne Sophie; Vestergaard, Henrik Tang; Rapin, Nicolas

2012-01-01

This review provides an overview of intestinal human transporters for organic anions and stresses the need for standardization of the various in-vitro methods presently employed in drug-drug interaction (DDI) investigations....

Transport of sennosides and sennidines from Cassia angustifolia and Cassia senna across Caco-2 monolayers--an in vitro model for intestinal absorption.

Science.gov (United States)

Waltenberger, B; Avula, B; Ganzera, M; Khan, I A; Stuppner, H; Khan, S I

2008-05-01

Laxative effects of Senna preparations are mainly mediated by rheinanthrone, a metabolite formed in the intestinal flora from dianthrones. Nevertheless, it was not clear whether dianthrones are bioavailable at all and contribute to the overall effects of this important medicinal plant. Using the Caco-2 human colonic cell line as an in vitro model of the human intestinal mucosal barrier, the bioavailability of dianthrones was studied in apical to basolateral (absorptive) and basolateral to apical (secretive) direction. Permeability coefficients (P(c)) and percent transport were calculated based on quantitations by HPLC. From the data obtained it was concluded that sennosides A and B, as well as their aglycones sennidine A and B are transported through the Caco-2 monolayers in a concentration-dependent manner and their transport was linear with time. The absorption in apical to basolateral direction was poor and P(c) values were comparable to mannitol. The transport was higher in the secretory direction, indicating a significant efflux (e.g. by efflux pumps) of the (poorly) absorbed compounds in the intestinal lumen again. Our findings support the general understanding that the laxative effects of Senna are explainable mainly by metabolites and not by the natively present dianthrones.

[Proton pump inhibitors in gastro-oesophageal reflux disease: what is the further step?].

Science.gov (United States)

Simon, Mireille; Zerbib, Frank

2013-01-01

Optimisation of proton pump inhibitors use may improve reflux symptoms in 20-25% of the patients. Pathological gastro-oesophageal reflux should be documented in a patient with refractory reflux symptoms using upper endoscopy and/or pH testing. While on proton pump inhibitors twice daily, persistent symptoms are not related to gastro-oesophageal refluxdisease(GERD) in 50% of the patients. The new anti-reflux compounds have yet a limited efficacy and side effects that currently limit their development. Copyright © 2012. Published by Elsevier Masson SAS.

Upper Gastro - intestinal Haemorrhage.

African Journals Online (AJOL)

Single-contrast barium meal examination will not provide much information, especially in the absence of screening facilities. In the district hospi- tal it is best to work on the assumption that bleeding originates from oesophageal varices if there is splenomegaly, and, in the absence of a palpable spleen, that bleeding comes ...

Gastro-oesophageal reflux in young babies: who should be treated?

Science.gov (United States)

Puntis, John W

2015-10-01

Recent guidelines focus on a non-interventionist approach to management of gastro-oesophageal reflux in infancy and emphasise the importance of explanation, reassurance and simple measures such as attention to feeding. Relying on clinical history alone leads to over diagnosis of disease, and widely used medications are often ineffective for symptom relief and carry significant risk of harm. The association between vomiting in infancy and other problems such as crying and poor feeding should not be interpreted as implying causality. When there are strong pointers to underlying gastro-oesophageal reflux disease, invasive investigations are required in order to formulate appropriate intervention. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Frequency, types and complications of barrett's esophagus in patients with symptoms of gastro-esophageal reflux

International Nuclear Information System (INIS)

Ansari, A.L.; Sadiq, S.

2004-01-01

Objective: This study was carried out to evaluate the frequency, types and complications of Barrett's esophagus in symptomatic gastro-esophageal reflux patients. Subjects: A total of 100 patients of gastro-esophageal reflux were studied to evaluate the frequency, types and complications of Barrett's esophagus. Endoscopic biopsies were taken and examined with H and E and various special stains like PAS, Alcian blue/PAS, high iron diamine/ Alcian blue and Giemsa stains. Results: Of 100 cases studied, 32 were found to have Barrett's esophagus on microscopy. The remaining 68 cases showed low and high grade changes of gastro-esophageal reflux. Conclusion: In comparison with studies from western countries, Barrett's esophagus was found to be relatively more common in our population. However, the frequency of complications like ulcer, stricture, dysplasia and adenocarcinoma was lesser. (author)

pH-sensitive thiolated nanoparticles facilitate the oral delivery of insulin in vitro and in vivo

Science.gov (United States)

Zhang, Yan; Lin, Xia; Du, Xuli; Geng, Sicong; Li, Hongren; Sun, Hong; Tang, Xing; Xiao, Wei

2015-02-01

In this work, we designed and developed a delivery system composed of enteric Eudragit L100-cysteine/reduced glutathione nanoparticles (Eul-cys/GSH NPs) for oral delivery of insulin. First, interactions between Eul-cys and mucin glycoproteins, which are believed to be the result of disulfide bonds, were confirmed using rheology experiments. Subsequently, the insulin-loaded Eul-cys/GSH NPs were prepared by the diffusion method using the rich gel network multipore structure at the surface of the Eul-cys when the pH was higher than the p Ka of Eul-cys polymer. The Eul-cys/GSH NPs obtained were characterized by dynamic light scattering, transmission electron microscopy, and atomic force microscopy. The results obtained showed that the average particle size ranged from 240 to 280 nm, and the particles were almost spherical in shape. The in vitro drug release results showed that the Eul-cys/GSH NPs retained a large amount of insulin in simulated gastric fluid, while a significant insulin release was found in simulated intestinal fluid. The in situ release study suggested that NPs released a greater amount of FITC-insulin (49.2 %) into the intestinal mucus layer compared with that of FITC-insulin solution (16.4 %), which facilitating insulin delivery through the intestinal mucosa. Eul-cys/GSH NPs exhibited promising mucoadhesive properties demonstrated using an in vitro cell model. Consequently, NPs were introduced into the ileum loop of healthy rats, thus enhancing the intestinal absorption of insulin and providing a prolonged reduction in blood glucose levels. These results suggest that Eul-cys/GSH NPs may be a promising delivery system for the treatment of diabetes.

pH-sensitive thiolated nanoparticles facilitate the oral delivery of insulin in vitro and in vivo

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yan [Shenyang University, Normal College (China); Lin, Xia; Du, Xuli; Geng, Sicong [Shenyang Pharmaceutical University, Department of Pharmaceutics (China); Li, Hongren; Sun, Hong [Shenyang University, Normal College (China); Tang, Xing, E-mail: tanglab@126.com [Shenyang Pharmaceutical University, Department of Pharmaceutics (China); Xiao, Wei, E-mail: wzhzh-nj@tom.com [Jiangsu Kanion Pharmaceutical Co., Ltd (China)

2015-02-15

In this work, we designed and developed a delivery system composed of enteric Eudragit L100-cysteine/reduced glutathione nanoparticles (Eul-cys/GSH NPs) for oral delivery of insulin. First, interactions between Eul-cys and mucin glycoproteins, which are believed to be the result of disulfide bonds, were confirmed using rheology experiments. Subsequently, the insulin-loaded Eul-cys/GSH NPs were prepared by the diffusion method using the rich gel network multipore structure at the surface of the Eul-cys when the pH was higher than the pKa of Eul-cys polymer. The Eul-cys/GSH NPs obtained were characterized by dynamic light scattering, transmission electron microscopy, and atomic force microscopy. The results obtained showed that the average particle size ranged from 240 to 280 nm, and the particles were almost spherical in shape. The in vitro drug release results showed that the Eul-cys/GSH NPs retained a large amount of insulin in simulated gastric fluid, while a significant insulin release was found in simulated intestinal fluid. The in situ release study suggested that NPs released a greater amount of FITC-insulin (49.2 %) into the intestinal mucus layer compared with that of FITC-insulin solution (16.4 %), which facilitating insulin delivery through the intestinal mucosa. Eul-cys/GSH NPs exhibited promising mucoadhesive properties demonstrated using an in vitro cell model. Consequently, NPs were introduced into the ileum loop of healthy rats, thus enhancing the intestinal absorption of insulin and providing a prolonged reduction in blood glucose levels. These results suggest that Eul-cys/GSH NPs may be a promising delivery system for the treatment of diabetes.

pH-sensitive thiolated nanoparticles facilitate the oral delivery of insulin in vitro and in vivo

International Nuclear Information System (INIS)

Zhang, Yan; Lin, Xia; Du, Xuli; Geng, Sicong; Li, Hongren; Sun, Hong; Tang, Xing; Xiao, Wei

2015-01-01

In this work, we designed and developed a delivery system composed of enteric Eudragit L100-cysteine/reduced glutathione nanoparticles (Eul-cys/GSH NPs) for oral delivery of insulin. First, interactions between Eul-cys and mucin glycoproteins, which are believed to be the result of disulfide bonds, were confirmed using rheology experiments. Subsequently, the insulin-loaded Eul-cys/GSH NPs were prepared by the diffusion method using the rich gel network multipore structure at the surface of the Eul-cys when the pH was higher than the pKa of Eul-cys polymer. The Eul-cys/GSH NPs obtained were characterized by dynamic light scattering, transmission electron microscopy, and atomic force microscopy. The results obtained showed that the average particle size ranged from 240 to 280 nm, and the particles were almost spherical in shape. The in vitro drug release results showed that the Eul-cys/GSH NPs retained a large amount of insulin in simulated gastric fluid, while a significant insulin release was found in simulated intestinal fluid. The in situ release study suggested that NPs released a greater amount of FITC-insulin (49.2 %) into the intestinal mucus layer compared with that of FITC-insulin solution (16.4 %), which facilitating insulin delivery through the intestinal mucosa. Eul-cys/GSH NPs exhibited promising mucoadhesive properties demonstrated using an in vitro cell model. Consequently, NPs were introduced into the ileum loop of healthy rats, thus enhancing the intestinal absorption of insulin and providing a prolonged reduction in blood glucose levels. These results suggest that Eul-cys/GSH NPs may be a promising delivery system for the treatment of diabetes

Intestinal ameliorative effects of traditional Ogi-tutu, Vernonia ...

African Journals Online (AJOL)

tutu, Vernonia amygdalina and Psidium guajava on intestinal histopathology of experimental mice infected with V. cholerae. Methods: Preliminary investigation of in vitro vibriocidal activities of these alternatives were carried out using agar cup ...

Pneumopatias e doença de refluxo gastroesofágico Lung diseases and gastro-oesophageal reflux disease

Directory of Open Access Journals (Sweden)

João Cláudio Barroso Pereira

2009-10-01

Full Text Available A doença do refluxo gastro esofágico decorre do refluxo patológico do estômago para o esófago. Quando esse refluxo ocorre fora do esófago denomina-se doença de refluxo extraesofágico. O autor propõe uma revisão sobre as doenças pulmonares associadas ao refluxo. É avaliado, previamente, de forma resumida o conceito de cada doença e, em seguida, de modo sistemático, são discutidos a prevalência do refluxo sobre as pneumopatias, os mecanismo que explicam essas interações e o impacto do tratamento do refluxo gastroesofagiano sobre as doenças pulmonares. O autor conclui que é inegável a existência de uma conexão entre doença de refluxo gastro esofágico e várias doenças pulmonares, sendo mister estudos complementares para corroborar essa associação.Gastro-oesophageal Reflux Disease is a consequence of pathological reflux from stomach to oesophagus. Whenever the refluxed contents extended beyond the oesophagus itself, is called Extraoesophageal Reflux Disease. The author proposes a review about pulmonary disorders and gastroesophageal reflux. Previously, it is evaluated in an abridged way, the concepts of each diseases and after that, in a systematic form, it is discussed the prevalence of gastro-oesophageal reflux in lung diseases, all the mechanisms studies and the impact of gastro-oesophageal treatment on lung disorders. The author concludes that is undeniable the link between Gastro-oesophageal reflux and lung diseases and further reaserch is mandatory in order to corroborate this association.

Effects of chemical composition and baking on in vitro digestibility of proteins in breads made from selected gluten-containing and gluten-free flours.

Science.gov (United States)

Wu, Tong; Taylor, Cheryl; Nebl, Thomas; Ng, Ken; Bennett, Louise E

2017-10-15

Breads prepared from cereal grains are a dietary staple, providing a significant proportion of daily energy, but not necessarily of dietary protein. However, good digestibility of proteins in bread is important to avoid potential immunogenic effects of undigested peptides, including for those gluten-intolerant. Four gluten-containing (white wheat, wholemeal wheat, spelt and rye) and four gluten-free (chick pea, lupin, buckwheat, amaranth) flours were used to make yeast-leavened breads standardized for protein. In vitro gastro-intestinal digestion of pre-mixes, doughs and breads baked for 20 and 35min was conducted followed by correlation analysis between fitted parameters of digestion profiles, chemical composition (protein, non-fibre carbohydrates, fibre, ash and total polyphenolics) and amino acid profiles. The results indicated that digestibility generally increased during proofing and decreased during baking. Relatively higher protein digestibility was correlated with ratio of non-fibre carbohydrate to protein and lower digestibility with increasing contents of fibre and total polyphenolics in pre-mixes. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Efficacy of pectin solution for preventing gastro-esophageal reflux events in patients with percutaneous endoscopic gastrostomy.

Science.gov (United States)

Adachi, Kyoichi; Furuta, Kenji; Aimi, Masahito; Fukazawa, Kousuke; Shimura, Shino; Ohara, Shunji; Nakata, Shuji; Inoue, Yukiko; Ryuko, Kanji; Ishine, Junichi; Katoh, Kyoko; Hirata, Toshiaki; Ohhata, Shuzo; Katoh, Setsushi; Moriyama, Mika; Sumikawa, Masuko; Sanpei, Mari; Kinoshita, Yoshikazu

2012-05-01

The aim of this study was to determine the efficacy of pectin solution, which increases the viscosity of liquid nutrient, for prevention of gastro-esophageal reflux in comparison with half-solid nutrient. The subjects were 10 elderly patients undergoing percutaneous endoscopic gastrostomy feeding. Twenty-four-hour esophageal multichannel intraluminal impedance and pH testing was performed during intake of half-solid nutrient and a combination of pectin solution and liquid nutrient. During 4 h after delivery, there was no significant difference in the total number of gastro-esophageal reflux events between the feeding of the half-solid nutrient and the combination of pectin solution and liquid nutrient (5.7 ± 1.2 vs 5.3 ± 1.0/4 h). Acidic reflux after delivery of the half-solid nutrient was significantly more frequent than that after delivery of the combination of pectin solution and liquid nutrient (80.7% vs 60.4%, p = 0.018). The incidence of gastro-esophageal reflux reaching the upper portion of the esophagus tended to be higher during delivery of the half-solid nutrient than during delivery of the combination of pectin solution and liquid nutrient (47.4% vs 34.0%, p = 0.153). In conclusion, the usage of pectin solution combined with liquid nutrient is effective for preventing acidic gastro-esophageal reflux and gastro-esophageal reflux reaching the upper portion of the esophagus.

Modeling the growth dynamics of multiple Escherichia coli strains in the pig intestine following intramuscular ampicillin treatment

DEFF Research Database (Denmark)

Ahmad, Amais; Zachariasen, Camilla; Christiansen, Lasse Engbo

2016-01-01

using a mathematical model to simulate the competitive growth of E. coli strains in a pig intestine under specified plasma concentration profiles of ampicillin. Results : In vitro growth results demonstrated that the resistant strains did not carry a fitness cost for their resistance, and that the most...... with ampicillin resistance in E. coli. Besides dosing factors, epidemiological factors (such as number of competing strains and bacterial excretion) influenced resistance development and need to be considered further in relation to optimal treatment strategies. The modeling approach used in the study is generic......Background : This study evaluated how dosing regimen for intramuscularly-administered ampicillin, composition of Escherichia coli strains with regard to ampicillin susceptibility, and excretion of bacteria from the intestine affected the level of resistance among Escherichia coli strains...

Stability of Anthocyanins from Commercial Black Currant Juice under Simulated Gastrointestinal Digestion

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Alija Uzunović

2008-08-01

Full Text Available Anthocyanins are effective antioxidants but they have also been proposed to have other biological activities independent of their antioxidant capacities that produce health benefits. Examples range from inhibition of cancer cell growth in vitro, induction of insulin production in isolated pancreatic cells, reduction of starch digestion through inhibition of a-glucosidase activity, suppression of inflammatory responses as well as protection against age-related declines in cognitive behavior and neuronal dysfunction in the central nervous system. However, to achieve any biological effect in a specific tissue or organ, anthocyanins must be bioavailable; i.e. effectively absorbed from the gastrointestinal tract (GIT into the circulation and delivered to the appropriate location within the body. In this study, we assess the stability of anthocyanins from commercial Black currant (Ribes nigrum L. juice using an in vitro digestion procedure that mimics the physiochemical and biochemical conditions encountered in the gastrointestinal tract (GIT. The main objective of this work was the evaluation of stability of anthocyanins during in vitro digestion in gastric and intestinal fluid regarding whether appropriate enzyme (pepsin or pancreatin was added or not. Anthocyanins present in commercial black currant juice remain stable during in vitro digestion in gastric fluid regardless whether pepsin was added into the medium or not. Also, they remain stable during in vitro digestion in simulated intestinal fluid without pancreatin. The stability studies of anthocyanins in the intestinal fluid containing pancreatin indicated reduced stability, which also mainly contribute to slight reduction of total anthocyanins content (1,83%- in commercial black currant juice.

Anaesthesia in patients undergoing esophago-gastro-duodenoscopy for suspected bleeding

DEFF Research Database (Denmark)

Helsø, Ida; Risom, Martin; Vestergaard, Therese Risom

2017-01-01

INTRODUCTION: Upper gastrointestinal bleeding (UGIB) is a common emergency. Currently, there are no agreed guidelines on the level of anaesthetic support required in patients undergoing acute esophago-gastro-duodendoscopy (EGD). METHODS: An online questionnaire comprising 19 questions...

Edible Safety Assessment of Genetically Modified Rice T1C-1 for Sprague Dawley Rats through Horizontal Gene Transfer, Allergenicity and Intestinal Microbiota.

Science.gov (United States)

Zhao, Kai; Ren, Fangfang; Han, Fangting; Liu, Qiwen; Wu, Guogan; Xu, Yan; Zhang, Jian; Wu, Xiao; Wang, Jinbin; Li, Peng; Shi, Wei; Zhu, Hong; Lv, Jianjun; Zhao, Xiao; Tang, Xueming

2016-01-01

In this study, assessment of the safety of transgenic rice T1C-1 expressing Cry1C was carried out by: (1) studying horizontal gene transfer (HGT) in Sprague Dawley rats fed transgenic rice for 90 d; (2) examining the effect of Cry1C protein in vitro on digestibility and allergenicity; and (3) studying the changes of intestinal microbiota in rats fed with transgenic rice T1C-1 in acute and subchronic toxicity tests. Sprague Dawley rats were fed a diet containing either 60% GM Bacillus thuringiensis (Bt) rice T1C-1 expressing Cry1C protein, the parental rice Minghui 63, or a basic diet for 90 d. The GM Bt rice T1C-1 showed no evidence of HGT between rats and transgenic rice. Sequence searching of the Cry1C protein showed no homology with known allergens or toxins. Cry1C protein was rapidly degraded in vitro with simulated gastric and intestinal fluids. The expressed Cry1C protein did not induce high levels of specific IgG and IgE antibodies in rats. The intestinal microbiota of rats fed T1C-1 was also analyzed in acute and subchronic toxicity tests by DGGE. Cluster analysis of DGGE profiles revealed significant individual differences in the rats' intestinal microbiota.

Edible Safety Assessment of Genetically Modified Rice T1C-1 for Sprague Dawley Rats through Horizontal Gene Transfer, Allergenicity and Intestinal Microbiota.

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Kai Zhao

Full Text Available In this study, assessment of the safety of transgenic rice T1C-1 expressing Cry1C was carried out by: (1 studying horizontal gene transfer (HGT in Sprague Dawley rats fed transgenic rice for 90 d; (2 examining the effect of Cry1C protein in vitro on digestibility and allergenicity; and (3 studying the changes of intestinal microbiota in rats fed with transgenic rice T1C-1 in acute and subchronic toxicity tests. Sprague Dawley rats were fed a diet containing either 60% GM Bacillus thuringiensis (Bt rice T1C-1 expressing Cry1C protein, the parental rice Minghui 63, or a basic diet for 90 d. The GM Bt rice T1C-1 showed no evidence of HGT between rats and transgenic rice. Sequence searching of the Cry1C protein showed no homology with known allergens or toxins. Cry1C protein was rapidly degraded in vitro with simulated gastric and intestinal fluids. The expressed Cry1C protein did not induce high levels of specific IgG and IgE antibodies in rats. The intestinal microbiota of rats fed T1C-1 was also analyzed in acute and subchronic toxicity tests by DGGE. Cluster analysis of DGGE profiles revealed significant individual differences in the rats' intestinal microbiota.

Two cases of esophageal eosinophilia: eosinophilic esophagitis or gastro-esophageal reflux disease?

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Ozlem Yilmaz

2014-06-01

Full Text Available Eosinophilic esophagitis (EoE and gastro-esophageal reflux disease are among the major causes of isolated esophageal eosinophilia. Isolated esophageal eosinophilia meeting criteria for EoE may respond to proton pump inhibitor (PPI treatment. This entity is termed proton pumps inhibitor responsive esophageal eosinophilia (PPI-REE. Gastro-esophageal reflux is thought to comprise a subgroup of patients with PPI-REE. According to the latest guidelines, PPI responsiveness distinguishes people with PPI-REE from patients having EoE (non-responders. In this report, two unusual cases with findings belonging to both EoE and PPI-REE are discussed with known and unknown facts.

Esophageal Dysmotility, Gastro-esophageal Reflux Disease, and Lung Transplantation: What Is the Evidence?

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Wood, Richard K

2015-12-01

Lung transplantation is an effective and life-prolonging therapy for patients with advanced lung disease (ALD). However, long-term patient survival following lung transplantation is primarily limited by development of an inflammatory and fibrotic process involving the lung allograft known as bronchiolitis obliterans syndrome (BOS). Although the precise cause of BOS remains uncertain and is likely multifactorial, chronic aspiration of gastro-duodenal contents is one possible contributing factor. Multiple small, cross-sectional studies performed over the past two decades have reported a high prevalence of gastro-esophageal reflux disease (GERD) and esophageal dysmotility in the ALD population and several investigations suggest the prevalence may increase following lung transplantation. More recent studies evaluating the direct effect of gastro-duodenal contents on airways have demonstrated a possible biologic link between GERD and BOS. Despite the recent advances in our understanding of BOS, further investigations are needed to establish GERD as a causative factor in its development. This review will discuss the existing literature that has identified an association of GERD with ALD and post-transplant populations, with a focus on recent advances in the field.

Effect of heme oxygenase-1 transduced bone marrow mesenchymal stem cells on damaged intestinal epithelial cells in vitro.

Science.gov (United States)

Cao, Yi; Wu, Ben-Juan; Zheng, Wei-Ping; Yin, Ming-Li; Liu, Tao; Song, Hong-Li

2017-07-01

In this study, we explored the effects of mesenchymal stem cells (MSCs) from bone marrow overexpressing heme oxygenase-1 (HO-1) on the damaged human intestinal epithelial barrier in vitro. Rat MSCs were isolated from bone marrow and transduced with rat HO-1 recombinant adenovirus (HO-MSCs) for stable expression of HO-1. Colorectal adenocarinoma 2 (Caco2) cells were treated with tumor necrosis factor-α (TNF-α) to establish a damaged colon epithelial model. Damaged Caco2 were cocultured with MSCs, Ad-MSCs, Ad-HO + MSCs or HO-MSCs. mRNA and protein expression of Zona occludens-1 (ZO-1) and human HO-1 and the release of cytokines were measured. ZO-1 and human HO-1 in Caco2 were significantly decreased after treatment with TNF-α; and this effect was reduced when coculture with MSCs from bone marrow. Expression of ZO-1 was not significantly affected by Caco2 treatment with TNF-α, Ad-HO, and MSCs. In contrast, ZO-1 and human HO-1 increased significantly when the damaged Caco2 was treated with HO-MSCs. HO-MSCs showed the strongest effect on the expression of ZO-1 in colon epithelial cells. Coculture with HO-MSCs showed the most significant effects on reducing the expression of IL-2, IL-6, IFN-γ and increasing the expression of IL-10. HO-MSCs protected the intestinal epithelial barrier, in which endogenous HO-1 was involved. HO-MSCs play an important role in the repair process by reducing the release of inflammatory cytokines and increasing the release of anti-inflammatory factors. These results suggested that HO-MSCs from bone marrow were more effective in repairing the damaged intestinal epithelial barrier, and the effectiveness of MSCs was improved by HO-1 gene transduction, which provides favorable support for the application of stem cell therapy in the intestinal diseases. © 2017 The Authors. Cell Biology International Published by John Wiley & Sons Ltd on behalf of International Federation of Cell Biology.

Paclitaxel Encapsulated in Halloysite Clay Nanotubes for Intestinal and Intracellular Delivery.

Science.gov (United States)

Yendluri, Raghuvara; Lvov, Yuri; de Villiers, Melgardt M; Vinokurov, Vladimir; Naumenko, Ekaterina; Tarasova, Evgenya; Fakhrullin, Rawil

2017-10-01

Naturally formed halloysite tubules have a length of 1 μm and lumens with a diameter of 12-15 nm which can be loaded with drugs. Halloysite's biocompatibility allows for its safe delivering to cells at a concentration of up to 0.5 mg/mL. We encapsulated the anticancer drug paclitaxel in halloysite and evaluated the drug release kinetics in simulated gastric and intestinal conditions. To facilitate maximum drug release in intestinal tract, halloysite tubes were coated with the pH-responsive polymer poly(methacrylic acid-co-methyl methacrylate). Release kinetics indicated a triggered drug release pattern at higher pH, corresponding to digestive tract environment. Tablets containing halloysite, loaded with paclitaxel, as a compression excipient were formulated with drug release occurring at a sustained rate. In vitro anticancer effects of paclitaxel-loaded halloysite nanotubes were evaluated on human cancer cells. In all the treated cell samples, polyploid nuclei of different sizes and fragmented chromatin were observed, indicating a high therapeutic effect of halloysite formulated paclitaxel. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Effect of the Novel Polysaccharide PolyGlycopleX® on Short-Chain Fatty Acid Production in a Computer-Controlled in Vitro Model of the Human Large Intestine

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Raylene A. Reimer

2014-03-01

Full Text Available Many of the health benefits associated with dietary fiber are attributed to their fermentation by microbiota and production of short chain fatty acids (SCFA. The aim of this study was to investigate the fermentability of the functional fiber PolyGlyopleX® (PGX® in vitro. A validated dynamic, computer-controlled in vitro system simulating the conditions in the proximal large intestine (TIM-2 was used. Sodium hydroxide (NaOH consumption in the system was used as an indicator of fermentability and SCFA and branched chain fatty acids (BCFA production was determined. NaOH consumption was significantly higher for Fructooligosaccharide (FOS than PGX, which was higher than cellulose (p = 0.002. At 32, 48 and 72 h, acetate and butyrate production were higher for FOS and PGX versus cellulose. Propionate production was higher for PGX than cellulose at 32, 48, 56 and 72 h and higher than FOS at 72 h (p = 0.014. Total BCFA production was lower for FOS compared to cellulose, whereas production with PGX was lower than for cellulose at 72 h. In conclusion, PGX is fermented by the colonic microbiota which appeared to adapt to the substrate over time. The greater propionate production for PGX may explain part of the cholesterol-lowering properties of PGX seen in rodents and humans.

Real-time measurements to characterize dynamics of emulsion interface during simulated intestinal digestion.

Science.gov (United States)

Pan, Yuanjie; Nitin, N

2016-05-01

Efficient delivery of bioactives remains a critical challenge due to their limited bioavailability and solubility. While many encapsulation systems are designed to modulate the digestion and release of bioactives within the human gastrointestinal tract, there is limited understanding of how engineered structures influence the delivery of bioactives. The objective of this study was to develop a real-time quantitative method to measure structural changes in emulsion interface during simulated intestinal digestion and to correlate these changes with the release of free fatty acids (FFAs). Fluorescence resonant energy transfer (FRET) was used for rapid in-situ measurement of the structural changes in emulsion interface during simulated intestinal digestion. By using FRET, changes in the intermolecular spacing between the two different fluorescent probes labeled emulsifier were characterized. Changes in FRET measurements were compared with the release of FFAs. The results showed that bile salts and pancreatic lipase interacted immediately with the emulsion droplets and disrupted the emulsion interface as evidenced by reduction in FRET efficacy compared to the control. Similarly, a significant amount of FFAs was released during digestion. Moreover, addition of a second layer of polymers at emulsion interface decreased the extent of interface disruption by bile salts and pancreatic lipase and impacted the amount or rate of FFA release during digestion. These results were consistent with the lower donor/acceptor ratio of the labeled probes from the FRET result. Overall, this study provides a novel approach to analyze the dynamics of emulsion interface during digestion and their relationship with the release of FFAs. Copyright © 2016 Elsevier B.V. All rights reserved.

Temporary intestinal ischemia for radiation protection

International Nuclear Information System (INIS)

Lote, K.

1983-01-01

The most important determinant of cellular radiosensivity is the tissue oxygen content at the time of irradiation. The purpose of the present experimental work was to assess a new iscemia-inducing method in order to reduce normal tissue radiation damage during radiotherapy. Temporary ischemia was induced in a cat small intestine by degraded starch microspheres. Regional arterial and tissue blod flow immediately fell by 85% with subsequent normalization within 26 minutes after microsphere injection. No tendency of small vessel thrombosis caused by starch sphere embolization in combination with previous or current intestinal irradiation was detected. Starch sphere remenants were rapidly engulfed by, and persisted within tissue macrophages for 14 days without causing intestinal inflammatory reactions. In vitro studies showed that human platelets neither adhered to nor were aggregated by starch microspheres. The new method, wich occlude arteriolar vessels distal to the mesentric arterial arcades and thus largely excludes collateral blood flow, seems suited to provide effictive and selective feline small intestinal hypoxic radiation protection. This conclusion may also be valid in man

Gastro-oesophageal Reflux Disease: An Update

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T Murphy

2015-09-01

Full Text Available Gastro-oesophageal reflux disease (GERD is a disorder in which reflux of stomach contents causes troublesome symptoms and/or complications and which affects health-related quality of life. It is one of the commonest disorders and appears to be increasing in incidence. The mechanisms leading to reflux are complex and multifactorial. The lower oesophageal sphincter (LES is an important part of the gastro-oesophageal barrier. Transient LES relaxations (TLESRs lead to reflux as these vagally mediated motor patterns cause relaxation of the LES and also result in oesophageal shortening and inhibition of the crural diaphragm. Heartburn and regurgitation are the characteristic symptoms of GERD. A clinical diagnosis of GERD can be made with typical symptoms. Oesophagitis is seen in a minority of patients with GERD. Lifestyle modification is widely advocated for patients with GERD. For short-term relief of symptoms of mild GERD, antacids/alginates are frequently used but they do not heal oesophagitis. Both histamine 2 receptor antagonists (H2RA and proton pump inhibitors (PPI have been shown to heal and prevent relapse of oesophagitis, although PPIs have been shown to be superior. The PPIs are the recommended first-line therapy for erosive oesophagitis and initial management of non-erosive reflux disease. Maintenance PPI therapy should be given to patients with oesophagitis, those who have recurrence of symptoms after discontinuation of medication and for those with complications of GERD.

Resilience of small intestinal beneficial bacteria to the toxicity of soybean oil fatty acids

Science.gov (United States)

Di Rienzi, Sara C; Jacobson, Juliet; Kennedy, Elizabeth A; Bell, Mary E; Shi, Qiaojuan; Waters, Jillian L; Lawrence, Peter; Brenna, J Thomas; Britton, Robert A; Walter, Jens

2018-01-01

Over the past century, soybean oil (SBO) consumption in the United States increased dramatically. The main SBO fatty acid, linoleic acid (18:2), inhibits in vitro the growth of lactobacilli, beneficial members of the small intestinal microbiota. Human-associated lactobacilli have declined in prevalence in Western microbiomes, but how dietary changes may have impacted their ecology is unclear. Here, we compared the in vitro and in vivo effects of 18:2 on Lactobacillus reuteri and L. johnsonii. Directed evolution in vitro in both species led to strong 18:2 resistance with mutations in genes for lipid biosynthesis, acid stress, and the cell membrane or wall. Small-intestinal Lactobacillus populations in mice were unaffected by chronic and acute 18:2 exposure, yet harbored both 18:2- sensitive and resistant strains. This work shows that extant small intestinal lactobacilli are protected from toxic dietary components via the gut environment as well as their own capacity to evolve resistance. PMID:29580380

Role of dietary fibers on health of the gastro-intestinal system and related types of cancer

OpenAIRE

Guiné, Raquel

2015-01-01

Dietary fibers are classified into water soluble or insoluble, and most plant foods include in their composition variable amounts of a mixture of soluble and insoluble fibers. This soluble or insoluble nature of fiber is related to its physiological effects. Insoluble fibers are characterized by high porosity, low density and the ability to increase fecal bulk, and act by facilitating intestinal transit, thus reducing the exposure to carcinogens in the colon and therefore acting as protectors...

Survival after adjuvant chemoradiotherapy or surgery alone in resectable adenocarcinoma at the gastro-esophageal junction

DEFF Research Database (Denmark)

Kofoed, Steen Christian; Muhic, A; Jensen, Lene Bæksgaard

2012-01-01

Longterm survival after curative resection for adenocarcinoma at the gastro-esophageal junction (GEJ) range between 18% and 50%. In the pivotal Intergroup-0116 Phase III trial by Macdonald et all, adjuvant chemoradiotherapy improved both disease-free and overall survival in curatively resected pa...... patients with mainly gastric adenocarcinoma. We compared survival data for curatively resected patients with adeno-carcinoma solely at the gastro-esophageal junction (GEJ), treated with surgery alone or surgery and adjuvant chemoradio-therapy....

In vitro activated CD4+ T cells from interferon-gamma (IFN-gamma)-deficient mice induce intestinal inflammation in immunodeficient hosts

DEFF Research Database (Denmark)

Bregenholt, S; Brimnes, J; Nissen, Mogens Holst

1999-01-01

To investigate the role of IFN-gamma in the immunopathogenesis of inflammatory bowel disease (IBD), severe combined immunodeficient (SCID) mice were transplanted with in vitro activated CD4+ T cells from either wild-type (WT) or IFN-gamma-deficient (IFN-gammaKO) BALB/c mice. In vitro, the two types...... of T cells displayed comparable proliferation rates and production of tumour necrosis factor-alpha (TNF-alpha), IL-2, IL-4 and IL-10 after concanavalin A (Con A) stimulation. When transplanted into SCID mice, WT CD4+ blasts induced a lethal IBD, whereas IFN-gammaKO blasts induced a less severe...... intestinal inflammation with moderate weight loss. Intracellular cytokine staining of lamina propria lymphocytes (LPL) revealed comparable fractions of CD4+ T cells positive for TNF-alpha, IL-2 and IL-10 in the two groups of transplanted SCID mice, whereas a two-to-three-fold increase in the fraction of IL-4...

Screening for in vitro metabolites of kakkalide and irisolidone in human and rat intestinal bacteria by ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry.

Science.gov (United States)

Zhang, Guozhe; Gong, Tianxing; Kano, Yoshihiro; Yuan, Dan

2014-02-01

Kakkalide and irisolidone, the main isoflavones of Flos Puerariae, exhibit a wide spectrum of bioactivities. Intestinal bacteria biotransformation plays an important role in the metabolic pathways of flavones, and is directly related to the bioactivities of the prodrugs after oral administration. To the best of our knowledge, the metabolic pathways of kakkalide and irisolidone in vitro have not been comprehensively studied yet. This paper describes the strategy using ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF MS) for the rapid analysis of the metabolic profiles of kakkalide and irisolidone after incubated with human and rat intestinal bacteria. Bacteria incubated samples were prepared and analyzed after incubated under anaerobic conditions for 48 h. A total of 17 metabolites, including parent compounds, were detected in human and rat intestinal bacteria incubated samples. The results obtained indicate that hydrolysis, dehydroxylation, demethoxylation, demethylation, hydroxylation, decarbonylation, and reduction were the detected metabolic pathways of kakkalide and irisolidone in vitro. The conversion rate of irisolidone in human and rat bacteria was 8.57% and 6.51%, respectively. Biochanin A was the relatively main metabolite of irisolidone, and the content of biochanin A in human and rat bacteria was 3.68% and 4.25%, respectively. The conversion rate of kakkalide in human and rat bacteria was 99.92% and 98.58%, respectively. Irisolidone was the main metabolite of kakkalide, and the content of irisolidone in human and rat bacteria was 89.58% and 89.38%, respectively. This work not only provides the evidence of kakkalide and irisolidone metabolites in vivo, but also demonstrates a simple, fast, sensitive, and inexpensive method for identification of metabolites of other compounds transformed by intestinal bacteria. Copyright © 2013 Elsevier B.V. All rights reserved.

RUMINAL AND INTESTINAL DIGESTION OF MAIZE (Zea mays AND SORGHUM (Sorghum bicolor L. MOENCH USING DIFFERENT DIGESTIBILITY TECHNIQUES (IN VIVO, IN VITRO AND IN SACCO

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Ulises A Gonzalez Garcia

2017-08-01

Full Text Available The knowledge of the digestibility of the food is basic to establish its nutritive value and bioavailability of the nutrients. Numerous laboratory tests have been used to estimate the ruminal and intestinal digestion of the food such as in vitro (Gas and Daisy production and in sacco, to be compared with the in vivo method. Sorghum presented the highest (P 0.05 were found between grains. With regard to the digestibility methods, the DMD was lower (P 0.01 for the in sacco and in vitro methods (Daisy. The production of VFA's was similar for both cereals. In situ and in vitro techniques (DaisyII® allow the determination of digestibility quick and easy compared to conventional methods. Sorghum grinding improves its nutritional value by increasing its digestibility, which represents an alternative to maize for feeding calves for fattening.

Probiotic features of Lactobacillus plantarum mutant strains.

Science.gov (United States)

Bove, Pasquale; Gallone, Anna; Russo, Pasquale; Capozzi, Vittorio; Albenzio, Marzia; Spano, Giuseppe; Fiocco, Daniela

2012-10-01

In this study, the probiotic potential of Lactobacillus plantarum wild-type and derivative mutant strains was investigated. Bacterial survival was evaluated in an in vitro system, simulating the transit along the human oro-gastro-intestinal tract. Interaction with human gut epithelial cells was studied by assessing bacterial adhesive ability to Caco-2 cells and induction of genes involved in innate immunity. L. plantarum strains were resistant to the combined stress at the various steps of the simulated gastrointestinal tract. Major decreases in the viability of L. plantarum cells were observed mainly under drastic acidic conditions (pH ≤ 2.0) of the gastric compartment. Abiotic stresses associated to small intestine poorly affected bacterial viability. All the bacterial strains significantly adhered to Caco-2 cells, with the ΔctsR mutant strain exhibiting the highest adhesion. Induction of immune-related genes resulted higher upon incubation with heat-inactivated bacteria rather than with live ones. For specific genes, a differential transcriptional pattern was observed upon stimulation with different L. plantarum strains, evidencing a possible role of the knocked out bacterial genes in the modulation of host cell response. In particular, cells from Δhsp18.55 and ΔftsH mutants strongly triggered immune defence genes. Our study highlights the relevance of microbial genetic background in host-probiotic interaction and might contribute to identify candidate bacterial genes and molecules involved in probiosis.

The role of hiatus hernia in gastro-oesophageal reflux disease

NARCIS (Netherlands)

van Herwaarden, MA; Samsom, M; Smout, AJPM

This article gives an overview of the role of sliding hiatus hernia in gastro-oesophageal reflux disease (GORD). The crural diaphragm acts as an external sphincter of the antireflux barrier. Contractions of the crural diaphragm increase lower-oesophageal-sphincter (LOS) pressure during each

Oral absorption of peptides and nanoparticles across the human intestine: Opportunities, limitations and studies in human tissues.

Science.gov (United States)

Lundquist, P; Artursson, P

2016-11-15

In this contribution, we review the molecular and physiological barriers to oral delivery of peptides and nanoparticles. We discuss the opportunities and predictivity of various in vitro systems with special emphasis on human intestine in Ussing chambers. First, the molecular constraints to peptide absorption are discussed. Then the physiological barriers to peptide delivery are examined. These include the gastric and intestinal environment, the mucus barrier, tight junctions between epithelial cells, the enterocytes of the intestinal epithelium, and the subepithelial tissue. Recent data from human proteome studies are used to provide information about the protein expression profiles of the different physiological barriers to peptide and nanoparticle absorption. Strategies that have been employed to increase peptide absorption across each of the barriers are discussed. Special consideration is given to attempts at utilizing endogenous transcytotic pathways. To reliably translate in vitro data on peptide or nanoparticle permeability to the in vivo situation in a human subject, the in vitro experimental system needs to realistically capture the central aspects of the mentioned barriers. Therefore, characteristics of common in vitro cell culture systems are discussed and compared to those of human intestinal tissues. Attempts to use the cell and tissue models for in vitro-in vivo extrapolation are reviewed. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

An Advanced In Vitro Technology Platform to Study the Mechanism of Action of Prebiotics and Probiotics in the Gastrointestinal Tract.

Science.gov (United States)

Marzorati, Massimo; Van de Wiele, Tom

The gastrointestinal tract (GIT) hosts the most complex microbial community in the human body. Given the extensive metabolic potential which is present in this community, this additional organ is of key importance to maintain a healthy status and several diseases are frequently correlated with an alteration of the composition/functionality of the gut microbiota. Consequently, there is a great interest in identifying potential approaches that could modulate the microbiota and its metabolism to bring about a positive health effect. A classical approach to reach this goal is the use of prebiotics and/or probiotics. How to study the potential effect of new prebiotics/probiotics and how to localize this effect along the full GIT? Human intervention trials are the golden standard to validate functional properties of food products. Yet, most studies on gut microbiota are based on the analysis of fecal samples because they are easily collected in a non-invasive manner. A complementary option is represented by well-designed in vitro simulation technologies. Among all the available systems, the Simulator of Human Intestinal Microbial Ecosystem has already been shown to be a useful model for nutrition studies in terms of analysis of the intestinal microbial community composition and activity. The Simulator of Human Intestinal Microbial Ecosystem is a scientifically validated platform representing the physiology and microbiology of the adult human GIT. Furthermore, recent advances in in vitro modelling also allow to combine the study of bacteria-host interactions, such as mucosal adhesion and interaction with the immune system, thereby further increasing the value of the scientific output.

A novel optical probe for pH sensing in gastro-esophageal apparatus

Science.gov (United States)

Baldini, F.; Ghini, G.; Giannetti, A.; Senesi, F.; Trono, C.

2011-03-01

Monitoring gastric pH for long periods, usually 24 h, may be essential in analyzing the physiological pattern of acidity, in obtaining information on changes in activity during peptic ulcer disease, and in assessing the effect of antisecretory drugs. Gastro-esophageal reflux, which causes a pH decrease in the esophagus content from pH 7 even down to pH 2, can determine esophagitis with possible strictures and Barrett's esophagus. One of the difficulties of the optical measurement of pH in the gastro-esophageal apparatus lies in the required extended working range from 1 to 8 pH units. The present paper deals with a novel optical pH sensor, using methyl red as optical pH indicator. Contrary to all acidbase indicators characterized by working ranges limited to 2-3 pH units, methyl red, after its covalent immobilization on controlled pore glass (CPG), is characterized by a wide working range which fits with the clinical requirements. The novel probe design here described is suitable for gastro-esophageal applications and allows the optimization of the performances of the CPG with the immobilised indicator. This leads to a very simple configuration characterized by a very fast response time.

The biowaiver extension for BCS class III drugs: the effect of dissolution rate on the bioequivalence of BCS class III immediate-release drugs predicted by computer simulation.

Science.gov (United States)

Tsume, Yasuhiro; Amidon, Gordon L

2010-08-02

The Biopharmaceutical Classification System (BCS) guidance issued by the FDA allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release (IR) solid oral dosage forms only for BCS class I drugs. However, a number of drugs within BCS class III have been proposed to be eligible for biowaivers. The World Health Organization (WHO) has shortened the requisite dissolution time of BCS class III drugs on their Essential Medicine List (EML) from 30 to 15 min for extended biowaivers; however, the impact of the shorter dissolution time on AUC(0-inf) and C(max) is unknown. The objectives of this investigation were to assess the ability of gastrointestinal simulation software to predict the oral absorption of the BCS class I drugs propranolol and metoprolol and the BCS class III drugs cimetidine, atenolol, and amoxicillin, and to perform in silico bioequivalence studies to assess the feasibility of extending biowaivers to BCS class III drugs. The drug absorption from the gastrointestinal tract was predicted using physicochemical and pharmacokinetic properties of test drugs provided by GastroPlus (version 6.0). Virtual trials with a 200 mL dose volume at different drug release rates (T(85%) = 15 to 180 min) were performed to predict the oral absorption (C(max) and AUC(0-inf)) of the above drugs. Both BCS class I drugs satisfied bioequivalence with regard to the release rates up to 120 min. The results with BCS class III drugs demonstrated bioequivalence using the prolonged release rate, T(85%) = 45 or 60 min, indicating that the dissolution standard for bioequivalence is dependent on the intestinal membrane permeability and permeability profile throughout the gastrointestinal tract. The results of GastroPlus simulations indicate that the dissolution rate of BCS class III drugs could be prolonged to the point where dissolution, rather than permeability, would control the overall absorption. For BCS class III drugs with intestinal absorption patterns

Curcumin Encapsulated in Milk Exosomes Resists Human Digestion and Possesses Enhanced Intestinal Permeability in Vitro.

Science.gov (United States)

Vashisht, Monika; Rani, Payal; Onteru, Suneel Kumar; Singh, Dheer

2017-11-01

Exosomes, the extracellular secretary nano-vesicles, act as carriers of biomolecules to the target cells. They exhibit several attributes of an efficient drug delivery system. Curcumin, despite having numerous bioactive and therapeutic properties, has limited pharmaceutical use due to its poor water solubility, stability, and low systemic bioavailability. Hence, this study aims to enhance the therapeutic potential of curcumin, a model hydrophobic drug, by its encapsulation into milk exosomes. In the present study, we investigated the stability of free curcumin and exosomal curcumin in PBS and in vitro digestive processes. Additionally, their uptake and trans-epithelial transport were studied on Caco-2 cells. Curcumin in milk exosomes had higher stability in PBS, sustained harsh digestive processes, and crossed the intestinal barrier than free curcumin. In conclusion, the encapsulation of curcumin into the exosomes enhances its stability, solubility, and bioavailability. Therefore, the present study demonstrated that milk exosomes act as stable oral drug delivery vehicles.

The role of hiatus hernia in gastro-oesophageal reflux disease

NARCIS (Netherlands)

van Herwaarden, Margot A.; Samsom, Melvin; Smout, André J. P. M.

2004-01-01

This article gives an overview of the role of sliding hiatus hernia in gastro-oesophageal reflux disease (GORD). The crural diaphragm acts as an external sphincter of the anti-reflux barrier. Contractions of the crural diaphragm increase lower-oesophageal-sphincter (LOS) pressure during each

Volatilisation of diacetylmorphine: in vitro simulation of 'chasing the dragon'

NARCIS (Netherlands)

Klous, M. G.; Lee, W. C.; van den Brink, W.; van Ree, J. M.; Beijnen, J. H.

2006-01-01

In preparation for a trial on co-prescription of heroin to chronic treatment-resistant addicts, a pharmaceutical dosage form for smokable heroin was developed. During development of this product (a mixture of diacetylmorphine and caffeine), in vitro experiments were performed simulating 'chasing the

Generation and transcriptional programming of intestinal dendritic cells: essential role of retinoic acid

DEFF Research Database (Denmark)

Zeng, R.; Bscheider, M; Lahl, Katharina

2016-01-01

programs, and suppressing proinflammatory nuclear factor-κB-dependent gene expression. Thus, RA is required for transcriptional programming and maturation of intestinal cDC, and with GM-CSF and Flt3L provides a minimal environment for in vitro generation of intestinal cDC1- and cDC2-like cDC from...

Comparative potency of obeticholic acid and natural bile acids on FXR in hepatic and intestinal in vitro cell models.

Science.gov (United States)

Zhang, Yuanyuan; LaCerte, Carl; Kansra, Sanjay; Jackson, Jonathan P; Brouwer, Kenneth R; Edwards, Jeffrey E

2017-12-01

Obeticholic acid (OCA) is a semisynthetic farnesoid X receptor (FXR) agonist, an analogue of chenodeoxycholic acid (CDCA) which is indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA). OCA efficiently inhibits bile acid synthesis and promotes bile acid efflux via activating FXR-mediated mechanisms in a physiologically relevant in vitro cell system, Sandwich-cultured Transporter Certified ™ human primary hepatocytes (SCHH). The study herein evaluated the effects of UDCA alone or in combination with OCA in SCHH. UDCA (≤100 μmol/L) alone did not inhibit CYP7A1 mRNA, and thus, no reduction in the endogenous bile acid pool observed. UDCA ≤100 μmol/L concomitantly administered with 0.1 μmol/L OCA had no effect on bile acid synthesis beyond what was observed with OCA alone. Furthermore, this study evaluated human Caco-2 cells (clone C2BBe1) as in vitro intestinal models. Glycine conjugate of OCA increased mRNA levels of FXR target genes in Caco-2 cells, FGF-19, SHP, OSTα/β, and IBABP, but not ASBT, in a concentration-dependent manner, while glycine conjugate of UDCA had no effect on the expression of these genes. The results suggested that UDCA ≤100 μmol/L did not activate FXR in human primary hepatocytes or intestinal cell line Caco-2. Thus, co-administration of UDCA with OCA did not affect OCA-dependent pharmacological effects. © 2017 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.

Role of intestinal bacteria in gliadin-induced changes in intestinal mucosa: study in germ-free rats.

Directory of Open Access Journals (Sweden)

Jana Cinova

Full Text Available BACKGROUND AND AIMS: Celiac disease (CD is a chronic inflammatory disorder of the small intestine that is induced by dietary wheat gluten proteins (gliadins in genetically predisposed individuals. The overgrowth of potentially pathogenic bacteria and infections has been suggested to contribute to CD pathogenesis. We aimed to study the effects of gliadin and various intestinal bacterial strains on mucosal barrier integrity, gliadin translocation, and cytokine production. METHODOLOGY/PRINCIPAL FINDINGS: Changes in gut mucosa were assessed in the intestinal loops of inbred Wistar-AVN rats that were reared under germ-free conditions in the presence of various intestinal bacteria (enterobacteria and bifidobacteria isolated from CD patients and healthy children, respectively and CD-triggering agents (gliadin and IFN-γ by histology, scanning electron microscopy, immunofluorescence, and a rat cytokine antibody array. Adhesion of the bacterial strains to the IEC-6 rat cell line was evaluated in vitro. Gliadin fragments alone or together with the proinflammatory cytokine interferon (IFN-γ significantly decreased the number of goblet cells in the small intestine; this effect was more pronounced in the presence of Escherichia coli CBL2 and Shigella CBD8. Shigella CBD8 and IFN-γ induced the highest mucin secretion and greatest impairment in tight junctions and, consequently, translocation of gliadin fragments into the lamina propria. Shigella CBD8 and E. coli CBL2 strongly adhered to IEC-6 epithelial cells. The number of goblet cells in small intestine increased by the simultaneous incubation of Bifidobacterium bifidum IATA-ES2 with gliadin, IFN-γ and enterobacteria. B. bifidum IATA-ES2 also enhanced the production of chemotactic factors and inhibitors of metalloproteinases, which can contribute to gut mucosal protection. CONCLUSIONS: Our results suggest that the composition of the intestinal microbiota affects the permeability of the intestinal mucosa

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to Saccharomyces cerevisiae var. boulardii CNCM I-3799 and reducing gastrointestinal discomfort pursuant to Article 13(5) of Regulation (EC) No 1924/2006

DEFF Research Database (Denmark)

Tetens, Inge

substantiation of a health claim related to Saccharomyces cerevisiae var. boulardii CNCM I-3799 and reducing gastro-intestinal discomfort. The food constituent that is the subject of the health claim, S. cerevisiae var. boulardii CNCM I-3799, is sufficiently characterised. The claimed effect, reduction of gastro....... cerevisiae var. boulardii CNCM I-3799), except for two animal studies and one in vitro study. Upon an EFSA request, the applicant indicated that the rest of the studies provided were conducted with the strain produced by Biocodex Laboratories (S. cerevisiae var. boulardii HANSEN CBS 5926). The applicant also...... stated that the strain, which is the subject of the claim, S. cerevisiae var. boulardii CNCM I-3799, is equivalent to S. cerevisiae var. boulardii HANSEN CBS 5926, based on a comparative PCR inter-delta element analysis of both strains provided in the application. The Panel considered that the evidence...

The streptomycin-treated mouse intestine selects Escherichia coli envZ missense mutants that interact with dense and diverse intestinal microbiota.

Science.gov (United States)

Leatham-Jensen, Mary P; Frimodt-Møller, Jakob; Adediran, Jimmy; Mokszycki, Matthew E; Banner, Megan E; Caughron, Joyce E; Krogfelt, Karen A; Conway, Tyrrell; Cohen, Paul S

2012-05-01

Previously, we reported that the streptomycin-treated mouse intestine selected nonmotile Escherichia coli MG1655 flhDC deletion mutants of E. coli MG1655 with improved colonizing ability that grow 15% faster in vitro in mouse cecal mucus and 15 to 30% faster on sugars present in mucus (M. P. Leatham et al., Infect. Immun. 73:8039-8049, 2005). Here, we report that the 10 to 20% remaining motile E. coli MG1655 are envZ missense mutants that are also better colonizers of the mouse intestine than E. coli MG1655. One of the flhDC mutants, E. coli MG1655 ΔflhD, and one of the envZ missense mutants, E. coli MG1655 mot-1, were studied further. E. coli MG1655 mot-1 is more resistant to bile salts and colicin V than E. coli MG1655 ΔflhD and grows ca. 15% slower in vitro in mouse cecal mucus and on several sugars present in mucus compared to E. coli MG1655 ΔflhD but grows 30% faster on galactose. Moreover, E. coli MG1655 mot-1 and E. coli MG1655 ΔflhD appear to colonize equally well in one intestinal niche, but E. coli MG1655 mot-1 appears to use galactose to colonize a second, smaller intestinal niche either not colonized or colonized poorly by E. coli MG1655 ΔflhD. Evidence is also presented that E. coli MG1655 is a minority member of mixed bacterial biofilms in the mucus layer of the streptomycin-treated mouse intestine. We offer a hypothesis, which we call the "Restaurant" hypothesis, that explains how nutrient acquisition in different biofilms comprised of different anaerobes can account for our results.

Effect of zinc source and picolinic acid on 65Zn uptake in an in vitro continuous-flow perfusion system for pig and poultry intestinal segments

International Nuclear Information System (INIS)

Hill, D.A.; Peo, E.R. Jr.; Lewis, A.J.

1987-01-01

Twenty weanling pigs and fourteen 9-wk-old broiler chickens were used in three continuous-flow in vitro perfusion experiments using noneverted intestinal sacs to 1) determine differences in 65 Zn absorption due to location within the intestinal tract, 2) evaluate 65 Zn uptake from ZnCl 2 and Zn-methionine (ZnMet) with or without added picolinic acid (PA) in pig intestinal sacs and 3) evaluate 65 Zn uptake from ZnCl 2 and ZnMet in chicken intestinal sacs. No differences in 65 Zn uptake due to gut segment position were observed in the pigs. A Zn source x PA interaction was observed for 65 Zn uptake into the pig gut tissue and for 65 Zn uptake to the serosal side of the gut sacs. Total 65 Zn absorption in the pig gut sacs from the two Zn sources was not different, but the addition of a 5 M ratio of PA to Zn depressed 65 Zn absorption. No differences were observed in total 65 Zn absorption or 65 Zn uptake in poultry gut sac tissue. There was, however, greater uptake of 65 Zn from ZnCl 2 to the serosal side of the sacs than from ZnMet. The data indicate that 65 Zn from ZnCl 2 and ZnMet is similar in total absorption and that the addition of PA depresses Zn uptake

The Effects of Biopolymer Encapsulation on Total Lipids and Cholesterol in Egg Yolk during in Vitro Human Digestion

Directory of Open Access Journals (Sweden)

Si-Kyung Lee

2013-08-01

Full Text Available The purpose of this study was to examine the effect of biopolymer encapsulation on the digestion of total lipids and cholesterol in egg yolk using an in vitro human digestion model. Egg yolks were encapsulated with 1% cellulose, pectin, or chitosan. The samples were then passed through an in vitro human digestion model that simulated the composition of mouth saliva, stomach acid, and the intestinal juice of the small intestine by using a dialysis tubing system. The change in digestion of total lipids was monitored by confocal fluorescence microscopy. The digestion rate of total lipids and cholesterol in all egg yolk samples dramatically increased after in vitro human digestion. The digestion rate of total lipids and cholesterol in egg yolks encapsulated with chitosan or pectin was reduced compared to the digestion rate of total lipids and cholesterol in other egg yolk samples. Egg yolks encapsulated with pectin or chitosan had lower free fatty acid content, and lipid oxidation values than samples without biopolymer encapsulation. Moreover, the lipase activity decreased, after in vitro digestion, in egg yolks encapsulated with biopolymers. These results improve our understanding of the effects of digestion on total lipids and cholesterol in egg yolk within the gastrointestinal tract.

The Effects of Biopolymer Encapsulation on Total Lipids and Cholesterol in Egg Yolk during in Vitro Human Digestion

Science.gov (United States)

Hur, Sun-Jin; Kim, Young-Chan; Choi, Inwook; Lee, Si-Kyung

2013-01-01

The purpose of this study was to examine the effect of biopolymer encapsulation on the digestion of total lipids and cholesterol in egg yolk using an in vitro human digestion model. Egg yolks were encapsulated with 1% cellulose, pectin, or chitosan. The samples were then passed through an in vitro human digestion model that simulated the composition of mouth saliva, stomach acid, and the intestinal juice of the small intestine by using a dialysis tubing system. The change in digestion of total lipids was monitored by confocal fluorescence microscopy. The digestion rate of total lipids and cholesterol in all egg yolk samples dramatically increased after in vitro human digestion. The digestion rate of total lipids and cholesterol in egg yolks encapsulated with chitosan or pectin was reduced compared to the digestion rate of total lipids and cholesterol in other egg yolk samples. Egg yolks encapsulated with pectin or chitosan had lower free fatty acid content, and lipid oxidation values than samples without biopolymer encapsulation. Moreover, the lipase activity decreased, after in vitro digestion, in egg yolks encapsulated with biopolymers. These results improve our understanding of the effects of digestion on total lipids and cholesterol in egg yolk within the gastrointestinal tract. PMID:23965957

An insight of in vitro transport of PEGylated non-ionic surfactant vesicles (NSVs) across the intestinal polarized enterocyte monolayers.

Science.gov (United States)

Primavera, Rosita; Palumbo, Paola; Celia, Christian; Cinque, Benedetta; Carata, Elisabetta; Carafa, Maria; Paolino, Donatella; Cifone, Maria Grazia; Di Marzio, Luisa

2018-06-01

PEGylated non-ionic surfactant-based vesicles (NSVs) are promising drug delivery systems for the local, oral and systemic administrations of therapeutics. The aim of this study was to test the cellular biocompatibility and transport of Nile Red-loaded NSVs (NR-NSVs) across the Caco-2-cell monolayers, which represent an in vitro model of human intestinal epithelium. The NR-NSVs assumed a spherical shape with a mean size of 140 nm, and a narrow size distribution. The NR-NSVs did not modify Caco-2 cell viability, which remained unaltered in vitro up to a concentration of 1 mM. The transport studies demonstrated that the NR-NSVs moved across the Caco-2 monolayers without affecting the transepithelial electrical resistance. These results were supported by flow cytometry analysis, which demonstrated that NR-NSVs were internalized inside the Caco-2 cells. Nanoparticle tracking and Transmission Electron Microscopy (TEM) analysis showed the presence of NR-NSVs in the basolateral side of the Caco-2 monolayers. TEM images also showed that NSVs were transported intact across the Caco-2 monolayers, thus demonstrating a predominant transcytosis mechanism of transport through endocytosis. The NSVs did not affect the integrity of the membrane barrier in vitro, and can potentially be used in clinics to increase the oral bioavailability and delivery of therapeutics. Copyright © 2018 Elsevier B.V. All rights reserved.

Review article: The measurement of non-acid gastro-oesophageal reflux

NARCIS (Netherlands)

Smout, A. J. P. M.

2007-01-01

BACKGROUND: Oesophageal pH monitoring has been used for three decades to study gastro-oesophageal reflux, but it does not allow detection of non-acid reflux episodes. AIM: To discuss the techniques by which non-acid reflux can be measured and to evaluate the clinical relevance of such measurements.

The jagged-2/notch-1/hes-1 pathway is involved in intestinal epithelium regeneration after intestinal ischemia-reperfusion injury.

Directory of Open Access Journals (Sweden)

Guoqing Chen

Full Text Available Notch signaling plays a critical role in the maintenance of intestinal crypt epithelial cell proliferation. The aim of this study was to investigate the role of Notch signaling in the proliferation and regeneration of intestinal epithelium after intestinal ischemia reperfusion (I/R injury.Male Sprague-Dawley rats were subjected to sham operation or I/R by occlusion of the superior mesenteric artery (SMA for 20 min. Intestinal tissue samples were collected at 0, 1, 2, 4, and 6 h after reperfusion. Proliferation of the intestinal epithelium was evaluated by immunohistochemical staining of proliferating nuclear antigen (PCNA. The mRNA and protein expression levels of Notch signaling components were examined using Real-time PCR and Western blot analyses. Immunofluorescence was also performed to detect the expression and location of Jagged-2, cleaved Notch-1, and Hes-1 in the intestine. Finally, the γ-secretase inhibitor DAPT and the siRNA for Jagged-2 and Hes-1 were applied to investigate the functional role of Notch signaling in the proliferation of intestinal epithelial cells in an in vitro IEC-6 culture system.I/R injury caused increased intestinal crypt epithelial cell proliferation and increased mRNA and protein expression of Jagged-2, Notch-1, and Hes-1. The immunofluorescence results further confirmed increased protein expression of Jagged-2, cleaved Notch-1, and Hes-1 in the intestinal crypts. The inhibition of Notch signaling with DAPT and the suppression of Jagged-2 and Hes-1 expression using siRNA both significantly inhibited the proliferation of IEC-6 cells.The Jagged-2/Notch-1/Hes-1 signaling pathway is involved in intestinal epithelium regeneration early after I/R injury by increasing crypt epithelial cell proliferation.

Effect of oils on drug absorption

OpenAIRE

Palin, K.J.

1981-01-01

Oil and emulsion vehicles have been shown to alter the oral absorption of many drugs. This may be due to enhanced lymph flow and/or altered gastro-intestinal motility in the presence of the oils. The oral absorption of a model compound (DOT) in the presence of three chemically different oils, arachis oil, Miglyol 812 and liquid paraffin was investigated in rats, the influence of lymphatic absorption and gastro-intestinal motility being determined. The findings were applied to the for.mulation...

Respiratory manifestations of gastro-oesophageal reflux in children.

Science.gov (United States)

de Benedictis, Fernando Maria; Bush, Andrew

2018-03-01

Gastro-oesophageal reflux disease (GORD) is a complex problem in children. Suspected respiratory manifestations of GORD, such as asthma, chronic cough and laryngitis, are commonly encountered in the paediatric practice, but continue to be entities with more questions than answers. The accuracy of diagnostic tests (ie, pH or pH-impedance monitoring, laryngoscopy, endoscopy) for patients with suspected extraoesophageal manifestations of GORD is suboptimal and therefore whether there is a causal relationship between these conditions remains largely undetermined. An empiric trial of proton pump inhibitors can help individual children with undiagnosed respiratory symptoms and suspicion of GORD, but the response to therapy is unpredictable, and in any case what may be being observed is spontaneous improvement. Furthermore, the safety of these agents has been called into question. Poor response to antireflux therapy is an important trigger to search for non-gastro-oesophageal reflux causes for patients' symptoms. Evidence for the assessment of children with suspected extraoesophageal manifestations of GORD is scanty and longitudinal studies with long-term follow-up are urgently required. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effects of xylitol on carbohydrate digesting enzymes activity, intestinal glucose absorption and muscle glucose uptake: a multi-mode study.

Science.gov (United States)

Chukwuma, Chika Ifeanyi; Islam, Md Shahidul

2015-03-01

The present study investigated the possible mechanism(s) behind the effects of xylitol on carbohydrate digesting enzymes activity, muscle glucose uptake and intestinal glucose absorption using in vitro, ex vivo and in vivo experimental models. The effects of increasing concentrations of xylitol (2.5%-40% or 164.31 mM-2628.99 mM) on alpha amylase and alpha glucosidase activity in vitro and intestinal glucose absorption and muscle glucose uptake were investigated under ex vivo conditions. Additionally, the effects of an oral bolus dose of xylitol (1 g per kg BW) on gastric emptying and intestinal glucose absorption and digesta transit in the different segments of the intestinal tract were investigated in normal and type 2 diabetic rats at 1 hour after dose administration, when phenol red was used as a recovery marker. Xylitol exhibited concentration-dependent inhibition of alpha amylase (IC₅₀ = 1364.04 mM) and alpha glucosidase (IC₅₀ = 1127.52 mM) activity in vitro and small intestinal glucose absorption under ex vivo condition. Xylitol also increased dose dependent muscle glucose uptake with and without insulin, although the uptake was not significantly affected by the addition of insulin. Oral single bolus dose of xylitol significantly delayed gastric emptying, inhibited intestinal glucose absorption but increased the intestinal digesta transit rate in both normal and diabetic rats compared to their respective controls. The data of this study suggest that xylitol reduces intestinal glucose absorption via inhibiting major carbohydrate digesting enzymes, slowing gastric emptying and fastening the intestinal transit rate, but increases muscle glucose uptake in normal and type 2 diabetic rats.

Desarrollo de una metodología in vitro para estimar la tasa de fermentación de los forrajes en el intestino grueso del cerdo

Directory of Open Access Journals (Sweden)

Leterme Pascal

2005-12-01

Full Text Available La metodología para estimar la tasa de fermentación de los forrajes se desarrolló en dos etapas. La primera, de digestibilidad enzimática, simula la digestión ocurrida en el estómago e intestino delgado, mediante el empleo de pepsina y pancreatina; en esta se determina la digestibilidad de la materia seca. La segunda etapa de fermentación simula la fermentación que ocurre en el intestino grueso utilizando como inóculo heces de cerdo; en esta se determina la cantidad de gas producido durante la fermentación de los forrajes y la degradación de la fibra detergente neutra (FDN. Las dos etapas presentaron buena repetibilidad en el tiempo. Abstract Develop of an in vitro methodology to determine the forages fermentation in to the large intestine. The methodology was developing in two phases. The first phase (enzymatic digestibility simulates the digestion occurred in the stomach and small intestine, by means of the employment of pepsin and pancreatin; and the digestibility of the dry matter is determined. The second phase (in vitro fermentation simulates the fermentation that occurs in the large intestine utilizing pig faeces; the quantity of gas produced during the fermentation of the feedstuff is determined and determine the degradation of neutral detergent fiber (NDF. All the phases show a good repeatability throw the time. Key words: digestibility in vitro, pigs, fermentación, forages (Azolla filiculoides, Xanthosoma saggitifolium, Morus alba, Trichanthera gigantea y Salvinia molesta.

Exhaled breath concentrations of acetic acid vapour in gastro-esophageal reflux disease

Czech Academy of Sciences Publication Activity Database

Dryahina, Kseniya; Pospíšilová, Veronika; Sovová, Kristýna; Shestivska, Violetta; Kubišta, Jiří; Spesyvyi, Anatolii; Pehal, F.; Turzíková, J.; Votruba, J.; Španěl, Patrik

2014-01-01

Roč. 8, č. 3 (2014), 037109 ISSN 1752-7155 Institutional support: RVO:61388955 Keywords : SIFT-MS * gastro-esophageal reflux * acetic acid Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 4.631, year: 2014

Preparation and in vitro-in vivo evaluation of none gastric resident dipyridamole (DIP) sustained-release pellets with enhanced bioavailability.

Science.gov (United States)

Xu, Lishuang; Luo, Yanfei; Feng, Jia; Xu, Ming; Tao, Xiaoguang; He, Haibing; Tang, Xing

2012-01-17

The objective of this study was to develop none gastric resident sustained-release pellets loaded with dipyridamole with a high bioavailability. Two different kinds of core pellets, one containing citric acid as a pH-modifier (CAP) and, the other without pH-modifier (NCAP) were prepared by extrusion-spheronization and then coated with mixtures of enteric soluble and insoluble polymers (referred to as CAP(1) and NCAP(1)) or insoluble polymer alone (referred to as CAP(2) and NCAP(2)). The relative bioavailability of the sustained-release pellets was studied in fasted beagle dogs after oral administration using a commercially available immediate release tablet (IRT) as a reference. The in vitro release, in vivo absorption and in vitro-in vivo correlation were also evaluated. Results revealed that the plasma drug concentrations after administration of CAP(2), NCAP(1) and NCAP(2) were undetectable, indicating that the drug release was almost zero from the preparations throughout the gastro-intestinal tract. The C(max), T(max) and AUC((0→24)) of CAP(1) were 0.78 ± 0.23 (μg/ml), 3.80 ± 0.30 (h), and 6.74 ± 0.47 (μg/mlh), respectively. While the corresponding values were 2.23 ± 0.32 (μg/ml), 3.00 ± 0.44 (h) and 9.42 ± 0.69 (μg/mlh) for IRT. The relative bioavailability of CAP(1) was 71.55% compared with IRT. By combined incorporation of a pH-modifier into the core of pellets to modify the inner micro-environment and employing mixtures of enteric soluble and insoluble polymers as a retarding layer, drugs with high solubility in stomach and limited solubility in small intestine, such as DIP, could be successfully formulated as sustained release preparations with no pH-dependence in drug release and enhanced bioavailability. Copyright © 2011 Elsevier B.V. All rights reserved.

A framework for 2-stage global sensitivity analysis of GastroPlus™ compartmental models.

Science.gov (United States)

Scherholz, Megerle L; Forder, James; Androulakis, Ioannis P

2018-04-01

Parameter sensitivity and uncertainty analysis for physiologically based pharmacokinetic (PBPK) models are becoming an important consideration for regulatory submissions, requiring further evaluation to establish the need for global sensitivity analysis. To demonstrate the benefits of an extensive analysis, global sensitivity was implemented for the GastroPlus™ model, a well-known commercially available platform, using four example drugs: acetaminophen, risperidone, atenolol, and furosemide. The capabilities of GastroPlus were expanded by developing an integrated framework to automate the GastroPlus graphical user interface with AutoIt and for execution of the sensitivity analysis in MATLAB ® . Global sensitivity analysis was performed in two stages using the Morris method to screen over 50 parameters for significant factors followed by quantitative assessment of variability using Sobol's sensitivity analysis. The 2-staged approach significantly reduced computational cost for the larger model without sacrificing interpretation of model behavior, showing that the sensitivity results were well aligned with the biopharmaceutical classification system. Both methods detected nonlinearities and parameter interactions that would have otherwise been missed by local approaches. Future work includes further exploration of how the input domain influences the calculated global sensitivity measures as well as extending the framework to consider a whole-body PBPK model.

Thioredoxin interacting protein and its association with clinical outcome in gastro-oesophageal adenocarcinoma

Directory of Open Access Journals (Sweden)

Caroline M. Woolston

2013-01-01

Full Text Available The overall prognosis for operable gastro-oesophageal adenocarcinoma remains poor and therefore neoadjuvant chemotherapy has become the standard of care, in addition to radical surgery. Certain anticancer agents (e.g. anthracyclines and cisplatin generate damaging reactive oxygen species as by-products of their mechanism of action. Drug effectiveness can therefore depend upon the presence of cellular redox buffering systems that are often deregulated in cancer. The expression of the redox protein, thioredoxin interacting protein, was assessed in gastro-oesophageal adenocarcinomas. Thioredoxin interacting protein expression was assessed using conventional immunohistochemistry on a tissue microarray of 140 adenocarcinoma patients treated by primary surgery alone and 88 operable cases treated with neoadjuvant chemotherapy. In the primary surgery cases, high thioredoxin interacting protein expression associated with a lack of lymph node involvement (p=0.005, no perineural invasion (p=0.030 and well/moderate tumour differentiation (p=0.033. In the neoadjuvant tumours, high thioredoxin interacting protein expression was an independent marker for improved disease specific survival (p=0.002 especially in cases with anthracycline-based regimes (p=0.008. This study highlights the potential of thioredoxin interacting protein as a biomarker for response in neoadjuvant treated gastro-oesophageal adenocarcinoma and may represent a useful therapeutic target due to its association with tumour progression.

In Vitro Culture Conditions for Maintaining a Complex Population of Human Gastrointestinal Tract Microbiota

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Bong-Soo Kim

2011-01-01

Full Text Available A stable intestinal microbiota is important in maintaining human physiology and health. Although there have been a number of studies using in vitro and in vivo approaches to determine the impact of diet and xenobiotics on intestinal microbiota, there is no consensus for the best in vitro culture conditions for growth of the human gastrointestinal microbiota. To investigate the dynamics and activities of intestinal microbiota, it is important for the culture conditions to support the growth of a wide range of intestinal bacteria and maintain a complex microbial community representative of the human gastrointestinal tract. Here, we compared the bacterial community in three culture media: brain heart infusion broth and high- and low-carbohydrate medium with different growth supplements. The bacterial community was analyzed using denaturing gradient gel electrophoresis (DGGE, pyrosequencing and real-time PCR. Based on the molecular analysis, this study indicated that the 3% fecal inoculum in low-concentration carbohydrate medium with 1% autoclaved fecal supernatant provided enhanced growth conditions to conduct in vitro studies representative of the human intestinal microbiota.

Cardiovasculaire en gastro-intestinale risico's bij selectieve en niet-selectieve NSAID's

NARCIS (Netherlands)

van den Bemt, B.J.F.; Benraad, H.B.; Rasker, Johannes J.

2007-01-01

- Er is veel discussie geweest over de cardiovasculaire en gastro-intestinale veiligheid van cyclo-oxygenase(COX)-2-selectieve en traditionele NSAID’s. De nationale en internationale richtlijnen zijn hierover niet eenduidig. - COX-2-selectieve NSAID’s lijken de kans op ernstige maag-darmcomplicaties

Transplantation of Expanded Fetal Intestinal Progenitors Contributes to Colon Regeneration after Injury

DEFF Research Database (Denmark)

Fordham, Robert P; Yui, Shiro; Hannan, Nicholas R F

2013-01-01

Regeneration and homeostasis in the adult intestinal epithelium is driven by proliferative resident stem cells, whose functional properties during organismal development are largely unknown. Here, we show that human and mouse fetal intestine contains proliferative, immature progenitors, which can...... be expanded in vitro as Fetal Enterospheres (FEnS). A highly similar progenitor population can be established during intestinal differentiation of human induced pluripotent stem cells. Established cultures of mouse fetal intestinal progenitors express lower levels of Lgr5 than mature progenitors and propagate...... in the presence of the Wnt antagonist Dkk1, and new cultures can be induced to form mature intestinal organoids by exposure to Wnt3a. Following transplantation in a colonic injury model, FEnS contribute to regeneration of colonic epithelium by forming epithelial crypt-like structures expressing region...

Factors Affecting the Prevalence of Gastro-oesophageal Reflux in Childhood Corrosive Oesophageal Strictures.

Science.gov (United States)

Iskit, Serdar H; Ozçelik, Zerrin; Alkan, Murat; Türker, Selcan; Zorludemir, Unal

2014-06-01

Gastro-oesophageal reflux may accompany the corrosive oesophageal damage caused by the ingestion of corrosive substances and affect its treatment. The factors that affect the development of reflux in these cases and their effects on treatment still remain unclear. Our aim is to investigate the prevalence of gastro-oesophageal reflux in children with corrosive oesophageal strictures, the risk factors affecting this prevalence and the effects of gastro-oesophageal reflux on treatment. Case-control study. We enrolled 52 patients with oesophageal stricture due to corrosive substance ingestion who were referred to our clinic between 2003 and 2010. Groups, which were determined according to the presence of gastro-oesophageal reflux (GER), were compared with each other in terms of clinical findings, results of examination methods, characteristics of the stricture and success of the treatment. The total number of patients in our study was 52; 30 of them were male and 22 of them were female. The mean age of our study population was 4.2±2.88 years. Thirty-three patients had gastrooesophageal reflux (63.5%). Patients who had strictures caused by the ingestion of alkali substances were 1.6-times more likely to have reflux. There were no differences between patients with or without reflux in terms of number and localisation of strictures. Mean distance of stricture was longer in patients with reflux (3.7±1.8 cm) than in patients without (2.2±1.0 cm) (preflux. Patients with long stricture were 1.9-times more likely to have reflux. Dilatation treatment was successful in 69.6% of patients with reflux and in 78.9% of patients without. The mean treatment period was 8.41±6.1 months in patients with reflux and 8.21±8.4 months in the other group. There was no significant difference between groups in terms of frequency of dilatation and dilator diameters (p>0.05). Corrosive oesophageal stricture was usually accompanied by gastro-oesophageal reflux and the length of stricture is an

Review article: oesophageal complications and consequences of persistent gastro-oesophageal reflux disease

NARCIS (Netherlands)

Pisegna, J.; Holtmann, G.; Howden, C. W.; Katelaris, P. H.; Sharma, P.; Spechler, S.; Triadafilopoulos, G.; Tytgat, G.

2004-01-01

The major oesophageal complications associated with persistent gastro-oesophageal reflux disease (GERD) include erosive oesophagitis, ulceration, strictures and gastrointestinal (GI) bleeding. Although the causes of these complications are uncertain, studies indicate that erosive oesophagitis may

Consequences of Mrp2 deficiency for diclofenac-induced toxicity in rat intestine in vitro

NARCIS (Netherlands)

Niu, Xiaoyu; van de Vegte, Dennis; Makkinje, Miriam; de Graaf, Inge; Groothuis, Genoveva

Diclofenac (DCF), a widely used non-steroidal anti-inflammatory drug (NSAID), is associated with high prevalence of severe intestinal side-effects. The reactive metabolite diclofenac acylglucuronide (DAG) formed in the liver, and transported by bile into the intestine was reported to be involved in

Combined multichannel intraluminal impedance and pH monitoring is helpful in managing children with suspected gastro-oesophageal reflux disease.

Science.gov (United States)

Rossi, Paolo; Isoldi, Sara; Mallardo, Saverio; Papoff, Paola; Rossetti, Danilo; Dilillo, Anna; Oliva, Salvatore

2018-04-05

Gastro-oesophageal reflux is very common in the paediatric age group. There is no single and reliable test to distinguish between physiologic and pathological gastro-oesophageal reflux, and this lack of clear distinction between disease and normal can have a negative impact on the management of children. To evaluate the usefulness of 24-h oesophageal pH-impedance study in infants and children with suspected gastro-oesophageal reflux disease. Patients were classified by age groups (A-C) and reflux-related symptoms (typical and atypical). All underwent pH-impedance study. If the latter suggested an abnormal reflux, patients received therapy in accordance with NASPGHAN/ESPGHAN recommendations, while those with normal study had an additional diagnostic work-up. The efficacy of therapy was evaluated with a specific standardized questionnaire for different ages. The study was abnormal in 203/428 patients (47%) while normal in 225/428 (53%). Of those with abnormal study, 109 exhibited typical symptoms (54%), and 94 atypical (46%). The great majority of the patients with abnormal study were responsive to medical anti-reflux therapy. We confirm the utility of prolonged oesophageal pH-impedance study in detecting gastro-oesophageal reflux disease in children and in guiding therapy. Performing oesophageal pH-impedance monitoring in children with suspected gastro-oesophageal reflux disease is helpful to establish the diagnosis and avoid unnecessary therapy. Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

[Endoparasitic infections in sheep from the Swabian Alb].

Science.gov (United States)

Rehbein, S; Visser, M; Winter, R

1998-11-01

The endoparasite fauna of 59 slaughtered sheep (30 lambs, 29 ewes) from the Swabian Alb, Germany, was examined. One species of trematodes, 3 species of cestodes, 29 species of nematodes (23 species of gastro-intestinal and 6 species of lung nematodes), 1 species of arthropodes and 1 species of protozoa were recorded. All animals were infected with Dicrocoelium dentriticum as well as gastro-intestinal and lung nematodes, 45.8% with Moniezia spp., 15.3% with Cysticercus tenuicollis, 55.9% with Oestrus ovis and 11.9% with Sarcocystis gigantea. The most important gastro-intestinal nematodes were Ostertagia circumcincta and Cooperia curticei, which were recorded in all sheep, Ostertagia trifurcata and Chabertia ovine (98.3% each), Oesophagostumum venulosum (96.6%), Nematodirus filicollis (81.4% each), Ostertagia pinnata (78.0%), Trichuris ovis and Trichostrongylus colubriformis (76.3% each). The ewes harboured more abomasal and small intestinal nematodes (1819 and 3702) than the lambs (695 and 1730), which haboured more large intestinal nematodes (177) than those (56). The most often recorded lungworms were Cystocaulus ocreatus (74.6%) and Muellerius capillaris (72.9%), followed by Neostrongylus linearis (57.6%), Dictyocaulus filaria (50.8%), Protostrongylus brevispiculum (37.3%) and Protostrongylus rufescens (28.8%). The ewes carried higher lungworm burdens than the lambs.

Novel ion exchange resin-based combination drug-delivery system for treatment of gastro esophageal reflux diseases

Directory of Open Access Journals (Sweden)

Mangesh Ramesh Bhalekar

2010-06-01

Full Text Available The present study involves preparation and characterization of a combination tablet of ranitidine in immediate release form and domperidone in sustained release form, using ion exchange resins. Ranitidine lowers acid secretion, while domperidone release over a prolonged period improves gastric motility thus justifying this combination in gastro esophageal reflux diseases (GERD and ensuring patient compliance. Drug loading was carried out by batch method & resinates were characterized using FTIR, XRPD. Resinates were formulated as a combination tablet and evaluated for tablet properties & in vitro drug release. Resinates provided sustained release of domperidone and immediate release of ranitidine. IR and X-ray studies indicate complexation of drug and resin along with monomolecular distribution of drugs in amorphous form in the resin matrix. The tablets of resinate combination showed good tablet properties. In-vitro drug release gave desired release profiles and ex-vivo drug absorption studies carried out by placing everted rat intestine in dissolution medium indicated statistically significant similarity in absorption from test and marketed formulation. The novelty of this study is that the retardation in release of domperidone from resinates is achieved by presence of weak resin in the formulation.O presente estudo envolve a preparação e a caracterização de associação do comprimido de ranitidina de liberação imediata e domperidona de liberação prolongada, utilizando resinas de troca iônica. A ranitidina diminui a secreção ácida, enquanto a liberação prolongada de domperidona melhora a motilidade gástica, justificando, dessa forma, a associação em doenças de refluxo gastroesofágico (DRGE e garantindo a adesão do paciente. A carga de fármaco foi efetuada pelo método em batelada e os resinatos, caracterizados utilizando-se FTIR e XRPD. Os resinatos foram formulados como comprimido da associação e avaliados com rela

Non-alcoholic fatty liver disease is associated with high prevalence of gastro-oesophageal reflux symptoms.

Science.gov (United States)

Miele, Luca; Cammarota, Giovanni; Vero, Vittoria; Racco, Simona; Cefalo, Consuelo; Marrone, Giuseppe; Pompili, Maurizio; Rapaccini, Gianlodovico; Bianco, Alessandro; Landolfi, Raffaele; Gasbarrini, Antonio; Grieco, Antonio

2012-12-01

Gastro-oesophageal reflux symptoms are usually reported by patients with obesity and metabolic syndrome. Aim of this study was to assess the prevalence and clinical characteristics of gastro-oesophageal reflux symptoms in subjects with non-alcoholic fatty liver disease. Cross-sectional, case-control study of 185 consecutive patients with non-alcoholic fatty liver disease and an age- and sex-matched control group of 112 healthy volunteers. Participants were interviewed with the aid of a previously validated questionnaire to assess lifestyle and reflux symptoms in the 3 months preceding enrolment. Odds ratios were determined before and after adjustment for body mass index, increased waist circumference, physical activity, metabolic syndrome and proton pump inhibitors and/or antiacid medication. The prevalence of heartburn and/or regurgitation and of at least one of gastro-oesophageal reflux symptoms was significantly higher in the non-alcoholic fatty liver disease group. Non-alcoholic fatty liver disease subjects were associated to higher prevalence of heartburn (adjusted odds ratios: 2.17, 95% confidence intervals: 1.16-4.04), regurgitation (adjusted odds ratios: 2.61, 95% confidence intervals: 1.24-5.48) and belching (adjusted odds ratios: 2.01, 95% confidence intervals: 1.12-3.59) and had higher prevalence of at least one GER symptom (adjusted odds ratios: 3.34, 95% confidence intervals: 1.76-6.36). Non-alcoholic fatty liver disease is associated with a higher prevalence of gastro-oesophageal reflux symptoms. Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Minimal differences in prevalence and spectrum of organic disease at upper gastrointestinal endoscopy between selected secondary care patients with symptoms of gastro-oesophageal reflux or dyspepsia.

Science.gov (United States)

Irvine, Andrew J; Pinto-Sanchez, Maria Ines; Bercik, Premysl; Moayyedi, Paul; Ford, Alexander C

2017-04-01

Gastro-oesophageal reflux and dyspepsia are felt to be separate upper gastrointestinal (GI) conditions. We aimed to measure the degree of overlap between them, and assess whether endoscopic findings differed. Demographic, symptom, upper GI endoscopy and histology data were collected from consecutive adults in secondary care. Patients were categorised according to whether they reported gastro-oesophageal reflux alone, dyspepsia alone or both, and patient demographics and endoscopic findings were compared. Of 1167 patients, 97 (8.3%) had gastro-oesophageal reflux alone, 571 (48.9%) dyspepsia alone, and 499 (42.8%) overlap. Patients with overlap symptoms were more likely to smoke, compared with those with gastro-oesophageal reflux alone, or dyspepsia alone (p = .009), but there were no other differences. Patients with gastro-oesophageal reflux alone or overlap had a higher prevalence of erosive oesophagitis (18.6% and 15.4% respectively, p Gastro-oesophageal reflux and dyspepsia symptoms commonly overlap. There were minimal differences in demographics or spectrum of underlying organic disease between various symptom groups, suggesting that restrictive classifications according to predominant symptom may not be clinically useful.

Scintigraphic scoring system for grading severity of gastro-esophageal reflux on 99mTc sulfur colloid gastro-esophageal reflux scintigraphy: A prospective study of 39 cases with pre and post treatment assessment.

Science.gov (United States)

Puranik, Ameya D; Nair, Gopinathan; Aggarwal, Rajiv; Bandyopadhyay, Abhijit; Shinto, Ajit; Zade, Anand

2013-04-01

The study aimed at developing a scoring system for scintigraphic grading of gastro-esophageal reflux (GER), on gastro-esophageal reflux scintigraphy (GERS) and comparison of clinical and scintigraphic scores, pre- and post-treatment. A total of 39 cases with clinically symptomatic GER underwent 99mTc sulfur colloid GERS; scores were assigned based on the clinical and scintigraphic parameters. Post domperidone GERS was performed after completion of treatment. Follow up GERS was performed and clinical and scintigraphic parameters were compared with baseline parameters. Paired t-test on pre and post domperidone treatment clinical scores showed that the decline in post-treatment scores was highly significant, with P value reflux and also for following children post-treatment.

Flux analysis of the human proximal colon using anaerobic digestion model 1.

Science.gov (United States)

Motelica-Wagenaar, Anne Marieke; Nauta, Arjen; van den Heuvel, Ellen G H M; Kleerebezem, Robbert

2014-08-01

The colon can be regarded as an anaerobic digestive compartment within the gastro intestinal tract (GIT). An in silico model simulating the fluxes in the human proximal colon was developed on basis of the anaerobic digestion model 1 (ADM1), which is traditionally used to model waste conversion to biogas. Model calibration was conducted using data from in vitro fermentation of the proximal colon (TIM-2), and, amongst others, supplemented with the bio kinetics of prebiotic galactooligosaccharides (GOS) fermentation. The impact of water and solutes absorption by the host was also included. Hydrolysis constants of carbohydrates and proteins were estimated based on total short chain fatty acids (SCFA) and ammonia production in vitro. Model validation was established using an independent dataset of a different in vitro model: an in vitro three-stage continuous culture system. The in silico model was shown to provide quantitative insight in the microbial community structure in terms of functional groups, and the substrate and product fluxes between these groups as well as the host, as a function of the substrate composition, pH and the solids residence time (SRT). The model confirms the experimental observation that methanogens are washed out at low pH or low SRT-values. The in silico model is proposed as useful tool in the design of experimental setups for in vitro experiments by giving insight in fermentation processes in the proximal human colon. Copyright © 2014. Published by Elsevier Ltd.

Effects of probiotics and antibiotics on the intestinal homeostasis in a computer controlled model of the large intestine

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Rehman Ateequr

2012-03-01

Full Text Available Abstract Background Antibiotic associated diarrhea and Clostridium difficile infection are frequent complications of broad spectrum antibiotic therapy. Probiotic bacteria are used as therapeutic and preventive agents in these disorders, but the exact functional mechanisms and the mode of action are poorly understood. The effects of clindamycin and the probiotic mixture VSL#3 (containing the 8 bacterial strains Streptococcus thermophilus, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei and Lactobacillus delbrueckii subsp. Bulgaricus consecutively or in combination were investigated and compared to controls without therapy using a standardized human fecal microbiota in a computer-controlled in vitro model of large intestine. Microbial metabolites (short chain fatty acids, lactate, branched chain fatty acids, and ammonia and the intestinal microbiota were analyzed. Results Compared to controls and combination therapy, short chain fatty acids and lactate, but also ammonia and branched chain fatty acids, were increased under probiotic therapy. The metabolic pattern under combined therapy with antibiotics and probiotics had the most beneficial and consistent effect on intestinal metabolic profiles. The intestinal microbiota showed a decrease in several indigenous bacterial groups under antibiotic therapy, there was no significant recovery of these groups when the antibiotic therapy was followed by administration of probiotics. Simultaneous application of anti- and probiotics had a stabilizing effect on the intestinal microbiota with increased bifidobacteria and lactobacilli. Conclusions Administration of VSL#3 parallel with the clindamycin therapy had a beneficial and stabilizing effect on the intestinal metabolic homeostasis by decreasing toxic metabolites and protecting the endogenic microbiota from destruction. Probiotics could be a reasonable

NSAID-induced gastro-duodenal bleeding: risk of development and patient management

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A P Rebrov

2008-01-01

Full Text Available A.P. Rebrov, E.l. Koshkina, A.A. Antonyan, R.V. Lyakisheva NSAID-induced gastro-duodenal bleeding: risk of development and patient management. Retrospective analysis of gastro-duodenal bleeding (GDB report forms was performed. Pts admitted to the department of internal diseases of Saratov regional clinical hospital from 1999 to 2004 were included. 354 cases of GDB were recorded ( 282 from 1999 to 2001 and 72 from 2002 to 2004. Cause ofbleeding, influence of NSAID administration on appearance and relapse ofbleeding, source ofbleeding and pt management were assessed. NSAJD administration was considered trigger factor of GDB in 24% in 1999-2001 and in 18% in 2002-2004. The results of the study show some tendency to decrease of NSAID- induced gastropathy frequency among causes of GDB. The main risk factors ofbleeding during NSAID treatment were age of more than 30 years, ulcer history, the first month of NSAID administration. GDB frequency did not depend on regularity of treatment and NSAID dosage.

The effect of prebiotics on production of antimicrobial compounds, resistance to growth at low pH and in the presence of bile, and adhesion of probiotic cells to intestinal mucus.

Science.gov (United States)

Brink, M; Todorov, S D; Martin, J H; Senekal, M; Dicks, L M T

2006-04-01

Screening of five bile salt-resistant and low pH-tolerant lactic acid bacteria for inhibitory activity against lactic acid bacteria and bacterial strains isolated from the faeces of children with HIV/AIDS. Determining the effect of prebiotics and soy milk-base on cell viability and adhesion of cells to intestinal mucus. Lactobacillus plantarum 423, Lactobacillus casei LHS, Lactobacillus salivarius 241, Lactobacillus curvatus DF 38 and Pediococcus pentosaceus 34 produced the highest level of antimicrobial activity (12,800 AU ml(-1)) when grown in MRS broth supplemented with 2% (m/v) dextrose. Growth in the presence of Raftilose Synergy1, Raftilose L95 and Raftiline GR did not lead to increased levels of antimicrobial activity. Cells grown in the presence of Raftilose Synergy1 took longer to adhere to intestinal mucus, whilst cells grown in the absence of prebiotics showed a linear rate of binding. A broad range of gram-positive and gram-negative bacteria were inhibited. Dextrose stimulated the production of antimicrobial compounds. Adhesion to intestinal mucus did not increase with the addition of prebiotics. The strains may be incorporated in food supplements for HIV/AIDS patients suffering from gastro-intestinal disorders.

GASTRO INTESTINAL HYPERPERMEABILITY: A REVIEW

African Journals Online (AJOL)

2003-06-06

Jun 6, 2003 ... Many of these transcellular transport processes require. ATP, and any factor, which .... regulation of blood flow, regulation of gut permeability and in the defense .... Analytical procedures (gas-liquid or high- performance liquid ...

The gastrointestinal-brain axis in humans as an evolutionary advance of the root-leaf axis in plants: A hypothesis linking quantum effects of light on serotonin and auxin.

Science.gov (United States)

Tonello, Lucio; Gashi, Bekim; Scuotto, Alessandro; Cappello, Glenda; Cocchi, Massimo; Gabrielli, Fabio; Tuszynski, Jack A

2018-01-01

Living organisms tend to find viable strategies under ambient conditions that optimize their search for, and utilization of, life-sustaining resources. For plants, a leading role in this process is performed by auxin, a plant hormone that drives morphological development, dynamics, and movement to optimize the absorption of light (through branches and leaves) and chemical "food" (through roots). Similarly to auxin in plants, serotonin seems to play an important role in higher animals, especially humans. Here, it is proposed that morphological and functional similarities between (i) plant leaves and the animal/human brain and (ii) plant roots and the animal/human gastro-intestinal tract have general features in common. Plants interact with light and use it for biological energy, whereas, neurons in the central nervous system seem to interact with bio-photons and use them for proper brain function. Further, as auxin drives roots "arborescence" within the soil, similarly serotonin seems to facilitate enteric nervous system connectivity within the human gastro-intestinal tract. This auxin/serotonin parallel suggests the root-branches axis in plants may be an evolutionary precursor to the gastro-intestinal-brain axis in humans. Finally, we hypothesize that light might be an important factor, both in gastro-intestinal dynamics and brain function. Such a comparison may indicate a key role for the interaction of light and serotonin in neuronal physiology (possibly in both the central nervous system and the enteric nervous system), and according to recent work, mind and consciousness.

Development of Functional Microfold (M Cells from Intestinal Stem Cells in Primary Human Enteroids.

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Joshua D Rouch

Full Text Available Intestinal microfold (M cells are specialized epithelial cells that act as gatekeepers of luminal antigens in the intestinal tract. They play a critical role in the intestinal mucosal immune response through transport of viruses, bacteria and other particles and antigens across the epithelium to immune cells within Peyer's patch regions and other mucosal sites. Recent studies in mice have demonstrated that M cells are generated from Lgr5+ intestinal stem cells (ISCs, and that infection with Salmonella enterica serovar Typhimurium increases M cell formation. However, it is not known whether and how these findings apply to primary human small intestinal epithelium propagated in an in vitro setting.Human intestinal crypts were grown as monolayers with growth factors and treated with recombinant RANKL, and assessed for mRNA transcripts, immunofluorescence and uptake of microparticles and S. Typhimurium.Functional M cells were generated by short-term culture of freshly isolated human intestinal crypts in a dose- and time-dependent fashion. RANKL stimulation of the monolayer cultures caused dramatic induction of the M cell-specific markers, SPIB, and Glycoprotein-2 (GP2 in a process primed by canonical WNT signaling. Confocal microscopy demonstrated a pseudopod phenotype of GP2-positive M cells that preferentially take up microparticles. Furthermore, infection of the M cell-enriched cultures with the M cell-tropic enteric pathogen, S. Typhimurium, led to preferential association of the bacteria with M cells, particularly at lower inoculum sizes. Larger inocula caused rapid induction of M cells.Human intestinal crypts containing ISCs can be cultured and differentiate into an epithelial layer with functional M cells with characteristic morphological and functional properties. This study is the first to demonstrate that M cells can be induced to form from primary human intestinal epithelium, and that S. Typhimurium preferentially infect these cells in an

In Vitro characterization of Lactococcus lactis strains Isolated from Iranian Traditional Dairy Products as a Potential Probiotic

OpenAIRE

Fatemeh Nejati; Tobias Oelschlaeger

2015-01-01

Few studies have been reported regarding probiotic properties of Lactococcus lactis strains although they are extensively used as starter cultures in the production of dairy products. In this study 8 wild isolates of Lactococcus lactis were evaluated in vitro with regard to resistance to simulated gastric and intestinal juices, adherence ability to Caco-2 cells and HT29-MTX-E12 cell lines, anti-microbial activity, hydrophobicity and antibiotic susceptibility. The results revealed that all iso...

Effect of Saccharomyces cerevisiae var. Boulardii and β-galactomannan oligosaccharide on porcine intestinal epithelial and dendritic cells challenged in vitro with Escherichia coli F4 (K88

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Badia Roger

2012-01-01

Full Text Available Abstract Probiotic and prebiotics, often called "immune-enhancing" feed additives, are believed to deal with pathogens, preventing the need of an immune response and reducing tissue damage. In this study, we investigated if a recently developed β-galactomannan (βGM had a similar protective role compared to Saccharomyces cerevisiae var. Boulardii (Scb, a proven probiotic, in the context of enterotoxigenic Escherichia coli (ETEC infection. ETEC causes inflammation, diarrhea and intestinal damage in piglets, resulting in large economic loses worldwide. We observed that Scb and βGM products inhibited in vitro adhesion of ETEC on cell surface of porcine intestinal IPI-2I cells. Our data showed that Scb and βGM decreased the mRNA ETEC-induced gene expression of pro-inflammatory cytokines TNF-α, IL-6, GM-CSF and chemokines CCL2, CCL20 and CXCL8 on intestinal IPI-2I. Furthermore, we investigated the putative immunomodulatory role of Scb and βGM on porcine monocyte-derived dendritic cells (DCs per se and under infection conditions. We observed a slight up-regulation of mRNA for TNF-α and CCR7 receptor after co-incubation of DC with Scb and βGM. However, no differences were found in DC activation upon ETEC infection and Scb or βGM co-culture. Therefore, our results indicate that, similar to probiotic Scb, prebiotic βGM may protect intestinal epithelial cells against intestinal pathogens. Finally, although these products may modulate DC activation, their effect under ETEC challenge conditions remains to be elucidated.

Degradabilidade ruminal e digestibilidade intestinal da proteína de capim-elefante com três idades de corte Rumen degradability and intestinal digestibility of protein of elephant-grass at three cutting ages

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J.P.G. Soares

2009-04-01

Full Text Available Determinaram-se a degradabilidade potencial (DP e a digestibilidade intestinal da proteína não degradada no rúmen (DIPNDR do capim-elefante em diferentes idades de rebrote (30, 45 e 60 dias e comparou-se a técnica do saco de náilon móvel (in situ com o método de três estádios (in vitro. Para tanto, utilizaram-se seis novilhos mestiços canulados no rúmen e duodeno alimentados exclusivamente com capim-elefante picado. O ensaio de degradabilidade foi realizado com amostras do capim incubadas no rúmen por 3, 6, 9, 12, 24, 48, 72, 96 e 120h. A digestibilidade intestinal foi determinada utilizando-se os resíduos de incubação por 24 horas. Na técnica in situ os resíduos em sacos de náilon foram colocados no duodeno e recuperados nas fezes. No método in vitro, os resíduos foram submetidos à digestão com HCl-pepsina-pancreatina. Em amostras de capim com idades de 30, 45 e 60 dias foram observados valores de DP da proteína de 87,5; 87,8 e 83,8%, respectivamente. A DIPNDR variou com a idade do capim e foi semelhante entre os métodos in situ e in vitro somente para o capim com 60 dias. O método in situ apresentou estimativa de digestibilidade intestinal mais coerente com as mudanças na composição química do capim-elefante decorrentes do envelhecimento.The potential degradability (PD and intestinal digestibility of ruminal escape protein (IDREP of elephant-grass at 30, 45, and 60 days of regrowth were determined and the mobile bag technique (in situ was compared to the three-stage method (in vitro. Thus, six cross-bred steers with rumen and duodenum canulas were used and fed exclusively with chopped elephant grass. The degradability trial was carried out with grass samples incubated in rumen by 3, 6, 9, 12, 24, 48, 72, 96, and 120 h. The intestinal digestibility was determined using 24-h ruminal incubation residue. In the in situ technique, residues in nylon bags were placed in duodenum and recovered in feces. In the in vitro

Fermentation of animal components in strict carnivores: a comparative study with cheetah fecal inoculum.

Science.gov (United States)

Depauw, S; Bosch, G; Hesta, M; Whitehouse-Tedd, K; Hendriks, W H; Kaandorp, J; Janssens, G P J

2012-08-01

The natural diet of felids contains highly digestible animal tissues but also fractions resistant to small intestinal digestion, which enter the large intestine where they may be fermented by the resident microbial population. Little information exists on the microbial degradability of animal tissues in the large intestine of felids consuming a natural diet. This study aimed to rank animal substrates in their microbial degradability by means of an in vitro study using captive cheetahs fed a strict carnivorous diet as fecal donors. Fresh cheetah fecal samples were collected, pooled, and incubated with various raw animal substrates (chicken cartilage, collagen, glucosamine-chondroitin, glucosamine, rabbit bone, rabbit hair, and rabbit skin; 4 replicates per substrate) for cumulative gas production measurement in a batch culture technique. Negative (cellulose) and positive (casein and fructo-oligosaccharides; FOS) controls were incorporated in the study. Additionally, after 72 h of incubation, short-chain fatty acids (SCFA), including branched-chain fatty acids (BCFA), and ammonia concentrations were determined for each substrate. Glucosamine and glucosamine-chondroitin yielded the greatest organic matter cumulative gas volume (OMCV) among animal substrates (P carnivore, and indicates that animal tissues have potentially similar functions as soluble or insoluble plant fibers in vitro. Further research is warranted to assess the impact of fermentation of each type of animal tissue on gastro-intestinal function and health in the cheetah and other felid species.

Diagnostic and therapeutic capsules and method of producing

International Nuclear Information System (INIS)

Morcos, N.A.; Haney, T.A.; Wedeking, P.W.

1981-01-01

An article of manufacture comprising a pharmaceutical radioactive capsule formed essentially of a non-toxic, water soluble material adapted to being ingested and rapidly disintegrating on contract with fluids of the gastro-intestinal tract, and having a filler material supporting a pharmaceutically useful radioactive compound absorbable from the gastro-intestinal tract said filler material being supported by said capsule. And a method of filling a pharmaceutical radioactive capsule comprising providing filler material supporting a pharmaceutically useful radioactive compound and transporting said filler material carrying a pharmaceutically useful radioactive compound into the chamber of said capsule

Epicutaneous immunotherapy (EPIT blocks the allergic esophago-gastro-enteropathy induced by sustained oral exposure to peanuts in sensitized mice.

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Lucie Mondoulet

Full Text Available Food allergy may affect the gastrointestinal tract and eosinophilia is often associated with allergic gastrointestinal disorders. Allergy to peanuts is a life-threatening condition and effective and safe treatments still need to be developed. The present study aimed to evaluate the effects of sustained oral exposure to peanuts on the esophageal and jejunal mucosa in sensitized mice. We also evaluated the effects of desensitization with epicutaneous immunotherapy (EPIT on these processes.Mice were sensitized by gavages with whole peanut protein extract (PPE given with cholera toxin. Sensitized mice were subsequently exposed to peanuts via a specific regimen and were then analysed for eosinophilia in the esophagus and gut. We also assessed mRNA expression in the esophagus, antibody levels, and peripheral T-cell response. The effects of EPIT were tested when intercalated with sensitization and sustained oral peanut exposure.Sustained oral exposure to peanuts in sensitized mice led to severe esophageal eosinophilia and intestinal villus sub-atrophia, i.e. significantly increased influx of eosinophils into the esophageal mucosa (136 eosinophils/mm(2 and reduced villus/crypt ratios (1.6±0.15. In the sera, specific IgE levels significantly increased as did secretion of Th2 cytokines by peanut-reactivated splenocytes. EPIT of sensitized mice significantly reduced Th2 immunological response (IgE response and splenocyte secretion of Th2 cytokines as well as esophageal eosinophilia (50 eosinophils/mm(2, p<0.05, mRNA expression of Th2 cytokines in tissue--eotaxin (p<0.05, IL-5 (p<0.05, and IL-13 (p<0.05--GATA-3 (p<0.05, and intestinal villus sub-atrophia (2.3±0.15. EPIT also increased specific IgG2a (p<0.05 and mRNA expression of Foxp3 (p<0.05 in the esophageal mucosa.Gastro-intestinal lesions induced by sustained oral exposure in sensitized mice are efficaciously treated by allergen specific EPIT.

Humoral immunity provides resident intestinal eosinophils access to luminal antigen via eosinophil-expressed low affinity Fc gamma receptors

Science.gov (United States)

Smith, Kalmia M.; Rahman, Raiann S.; Spencer, Lisa A.

2016-01-01

Eosinophils are native to the healthy gastrointestinal tract, and are associated with inflammatory diseases likely triggered by exposure to food allergens (e.g. food allergies and eosinophilic gastrointestinal disorders). In models of allergic respiratory diseases and in vitro studies, direct antigen engagement elicits eosinophil effector functions including degranulation and antigen presentation. However, it was not known whether intestinal tissue eosinophils that are separated from luminal food antigens by a columnar epithelium might similarly engage food antigens. Using an intestinal ligated loop model in mice, here we determined that resident intestinal eosinophils acquire antigen from the lumen of antigen-sensitized but not naïve mice in vivo. Antigen acquisition was immunoglobulin-dependent; intestinal eosinophils were unable to acquire antigen in sensitized immunoglobulin-deficient mice, and passive immunization with immune serum or antigen-specific IgG was sufficient to enable intestinal eosinophils in otherwise naïve mice to acquire antigen in vivo. Intestinal eosinophils expressed low affinity IgG receptors, and the activating receptor FcγRIII was necessary for immunoglobulin-mediated acquisition of antigens by isolated intestinal eosinophils in vitro. Our combined data suggest that intestinal eosinophils acquire lumen-derived food antigens in sensitized mice via FcγRIII antigen focusing, and may therefore participate in antigen-driven secondary immune responses to oral antigens. PMID:27683752

Humoral Immunity Provides Resident Intestinal Eosinophils Access to Luminal Antigen via Eosinophil-Expressed Low-Affinity Fcγ Receptors.

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Smith, Kalmia M; Rahman, Raiann S; Spencer, Lisa A

2016-11-01

Eosinophils are native to the healthy gastrointestinal tract and are associated with inflammatory diseases likely triggered by exposure to food allergens (e.g., food allergies and eosinophilic gastrointestinal disorders). In models of allergic respiratory diseases and in vitro studies, direct Ag engagement elicits eosinophil effector functions, including degranulation and Ag presentation. However, it was not known whether intestinal tissue eosinophils that are separated from luminal food Ags by a columnar epithelium might similarly engage food Ags. Using an intestinal ligated loop model in mice, in this study we determined that resident intestinal eosinophils acquire Ag from the lumen of Ag-sensitized but not naive mice in vivo. Ag acquisition was Ig-dependent; intestinal eosinophils were unable to acquire Ag in sensitized Ig-deficient mice, and passive immunization with immune serum or Ag-specific IgG was sufficient to enable intestinal eosinophils in otherwise naive mice to acquire Ag in vivo. Intestinal eosinophils expressed low-affinity IgG receptors, and the activating receptor FcγRIII was necessary for Ig-mediated acquisition of Ags by isolated intestinal eosinophils in vitro. Our combined data suggest that intestinal eosinophils acquire lumen-derived food Ags in sensitized mice via FcγRIII Ag focusing and that they may therefore participate in Ag-driven secondary immune responses to oral Ags. Copyright © 2016 by The American Association of Immunologists, Inc.

Sequential transformation of the structural and thermodynamic parameters of the complex particles, combining covalent conjugate (sodium caseinate + maltodextrin) with polyunsaturated lipids stabilized by a plant antioxidant, in the simulated gastro-intestinal conditions in vitro.

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Antipova, Anna S; Zelikina, Darya V; Shumilina, Elena A; Semenova, Maria G

2016-10-01

The present work is focused on the structural transformation of the complexes, formed between covalent conjugate (sodium caseinate + maltodextrin) and an equimass mixture of the polyunsaturated lipids (PULs): (soy phosphatidylcholine + triglycerides of flaxseed oil) stabilized by a plant antioxidant (an essential oil of clove buds), in the simulated conditions of the gastrointestinal tract. The conjugate was used here as a food-grade delivery vehicle for the PULs. The release of these PULs at each stage of the simulated digestion was estimated. Copyright © 2016 Elsevier Ltd. All rights reserved.

Gastro-oesophageal reflux monitoring: review and consensus report on detection and definitions of acid, non-acid, and gas reflux

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Sifrim, D; Castell, D; Dent, J; Kahrilas, P J

2004-01-01

To date, most concepts on the frequency of gastro-oesophageal reflux episodes and the efficiency of the antireflux barrier have been based on inferences derived from measurement of oesophageal pH. The development of intraluminal impedance monitoring has highlighted the fact that pH monitoring does not detect all gastro-oesophageal reflux events when little or no acid is present in the refluxate, even if special pH tracing analysis criteria are used. In November 2002, a workshop took place at which 11 specialists in the field of gastro-oesophageal reflux disease discussed and criticised all currently available techniques for measurement of reflux. Here, a summary of their conclusions and recommendations of how to achieve the best results from the various techniques now available for reflux measurement is presented. PMID:15194656

Evaluation of a Solid Dispersion of Curcumin With Polyvinylpyrrolidone and Boric Acid Against Salmonella Enteritidis Infection and Intestinal Permeability in Broiler Chickens: A Pilot Study

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Daniel Hernandez-Patlan

2018-06-01

Full Text Available In the present study, in vitro assays were conducted to evaluate the solubility of curcumin (CUR alone or with polyvinylpyrrolidone (PVP at different pH, as well as its permeability in Caco-2 cells. Results confirmed that the solid dispersion of CUR with PVP (CUR/PVP at a 1:9 ratio, significantly increased (P < 0.05 solubility and permeability compared to CUR alone. Then, the antimicrobial activity of CUR/PVP, boric acid (BA, and a combination of 0.5% CUR/PVP and 0.5% BA (CUR/PVP-BA against Salmonella Enteritidis (SE was determined using an in vitro digestion model that simulates crop, proventriculus, and intestine. The results revealed that in the proventriculus and intestinal compartments significant reductions of SE were observed in all the experimental treatments, but 1% BA eliminated SE in the intestinal compartment and CUR/PVP-BA showed a synergistic effect on antimicrobial activity against SE. To complement these findings, two independent in vivo trials were conducted to determine the effect of 0.1% CUR/PVP; 0.1% BA; or the combination of 0.05% CUR/PVP (1:9 ratio and 0.05% BA (CUR/PVP-BA on the antimicrobial activity against SE, intestinal permeability and inflammatory responses in broiler chickens. BA at 0.1% had no significant in vivo effects against SE. However, the combination of 0.05% BA and 0.05% CUR/PVP and 0.05% BA was sufficient to reduce crop and intestinal SE colonization in broiler chickens in two independent trials, confirming the synergic effect between them. A similar antimicrobial impact against SE intestinal colonization was observed in chickens treated with 0.1% CUR/PVP at a 1:9 ratio, which could be due to the increase in solubility of CUR by PVP. Furthermore, 0.1% CUR/PVP reduced the intestinal permeability of FITC-d and total intestinal IgA, as well as increase the activity of SOD when compared to control, while, CUR/PVP-BA only decreased SOD activity. Further studies to confirm and expand the in vivo results obtained

Deoxynivalenol affects in vitro intestinal epithelial cell barrier integrity through inhibition of protein synthesis

International Nuclear Information System (INIS)

Van De Walle, Jacqueline; Sergent, Therese; Piront, Neil; Toussaint, Olivier; Schneider, Yves-Jacques; Larondelle, Yvan

2010-01-01

Deoxynivalenol (DON), one of the most common mycotoxin contaminants of raw and processed cereal food, adversely affects the gastrointestinal tract. Since DON acts as a protein synthesis inhibitor, the constantly renewing intestinal epithelium could be particularly sensitive to DON. We analyzed the toxicological effects of DON on intestinal epithelial protein synthesis and barrier integrity. Differentiated Caco-2 cells, as a widely used model of the human intestinal barrier, were exposed to realistic intestinal concentrations of DON (50, 500 and 5000 ng/ml) during 24 h. DON caused a concentration-dependent decrease in total protein content associated with a reduction in the incorporation of [ 3 H]-leucine, demonstrating its inhibitory effect on protein synthesis. DON simultaneously increased the paracellular permeability of the monolayer as reflected through a decreased transepithelial electrical resistance associated with an increased paracellular flux of the tracer [ 3 H]-mannitol. A concentration-dependent reduction in the expression level of the tight junction constituent claudin-4 was demonstrated by Western blot, which was not due to diminished transcription, increased degradation, or NF-κB, ERK or JNK activation, and was also observed for a tight junction independent protein, i.e. intestinal alkaline phosphatase. These results demonstrate a dual toxicological effect of DON on differentiated Caco-2 cells consisting in an inhibition of protein synthesis as well as an increase in monolayer permeability, and moreover suggest a possible link between them through diminished synthesis of the tight junction constituent claudin-4.

Small intestinal eosinophils regulate Th17 cells by producing IL-1 receptor antagonist.

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Sugawara, Reiko; Lee, Eun-Jung; Jang, Min Seong; Jeun, Eun-Ji; Hong, Chun-Pyo; Kim, Jung-Hwan; Park, Areum; Yun, Chang Ho; Hong, Sung-Wook; Kim, You-Me; Seoh, Ju-Young; Jung, YunJae; Surh, Charles D; Miyasaka, Masayuki; Yang, Bo-Gie; Jang, Myoung Ho

2016-04-04

Eosinophils play proinflammatory roles in helminth infections and allergic diseases. Under steady-state conditions, eosinophils are abundantly found in the small intestinal lamina propria, but their physiological function is largely unexplored. In this study, we found that small intestinal eosinophils down-regulate Th17 cells. Th17 cells in the small intestine were markedly increased in the ΔdblGATA-1 mice lacking eosinophils, and an inverse correlation was observed between the number of eosinophils and that of Th17 cells in the small intestine of wild-type mice. In addition, small intestinal eosinophils suppressed the in vitro differentiation of Th17 cells, as well as IL-17 production by small intestinal CD4(+)T cells. Unlike other small intestinal immune cells or circulating eosinophils, we found that small intestinal eosinophils have a unique ability to constitutively secrete high levels of IL-1 receptor antagonist (IL-1Ra), a natural inhibitor of IL-1β. Moreover, small intestinal eosinophils isolated from IL-1Ra-deficient mice failed to suppress Th17 cells. Collectively, our results demonstrate that small intestinal eosinophils play a pivotal role in the maintenance of intestinal homeostasis by regulating Th17 cells via production of IL-1Ra. © 2016 Sugawara et al.

Idiopathic megaoesophagus and intermittent gastro-oesophageal intussusception in a cat.

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van Geffen, C; Saunders, J H; Vandevelde, B; Van Ham, L; Hoybergs, Y; Daminet, S

2006-08-01

An eight-month-old domestic shorthair cat was presented with chronic vomiting for three months, with an acute increase in frequency during the past two days. A diagnosis of megaoesophagus was made by chest radiography. Diagnostic work-up for megaoesophagus was performed. A gastro-oesophageal intussusception was identified during endoscopy. Medical and nutritional therapy was instituted with a good response to the treatment.

Selye's general adaptation syndrome: stress-induced gastro-duodenal ulceration and inflammatory bowel disease.

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Fink, George

2017-03-01

Hans Selye in a note to Nature in 1936 initiated the field of stress research by showing that rats exposed to nocuous stimuli responded by way of a 'general adaptation syndrome' (GAS). One of the main features of the GAS was the 'formation of acute erosions in the digestive tract, particularly in the stomach, small intestine and appendix'. This provided experimental evidence for the view based on clinical data that gastro-duodenal (peptic) ulcers could be caused by stress. This hypothesis was challenged by Marshall and Warren's Nobel Prize (2005)-winning discovery of a causal association between Helicobacter pylori and peptic ulcers. However, clinical and experimental studies suggest that stress can cause peptic ulceration in the absence of H. pylori Predictably, the etiological pendulum of gastric and duodenal ulceration has swung from 'all stress' to 'all bacteria' followed by a sober realization that both factors play a role, separately as well as together. This raises the question as to whether stress and H. pylori interact, and if so, how? Stress has also been implicated in inflammatory bowel disease (IBD) and related disorders; however, there is no proof yet that stress is the primary etiological trigger for IBD. Central dopamine mechanisms seem to be involved in the stress induction of peptic ulceration, whereas activation of the sympathetic nervous system and central and peripheral corticotrophin-releasing factor appears to mediate stress-induced IBD. © 2017 Society for Endocrinology.

Protective effect of NSA on intestinal epithelial cells in a necroptosis model.

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Dong, Wei; Zhang, Min; Zhu, Yaxi; Chen, Yuanhan; Zhao, Xingchen; Li, Ruizhao; Zhang, Li; Ye, Zhiming; Liang, Xingling

2017-10-17

This study aimed to investigate the protective effect of the necroptosis inhibitor necrosulfonamide (NSA) on intestinal epithelial cells using a novel in vitro necroptosis model that mimics inflammatory bowel disease (IBD). 2,4,6-trinitrobenzenesulfonic acid (TNBS) was perfused into the rectum of BALB/c mice to established a colitis model. Pathologic injury and cell death were evaluated. A novel in vitro model of necroptosis was established in Caco-2 cells using TNF- α and Z-VAD-fmk, and the cells were treated with or without NSA. Morphologic changes, manner of cell death and the levels of phosphorylation of receptor-interacting protein kinase 3 (p-RIPK3) and mixed-lineage kinase domain-like (p-MLKL) were detected. In the TNBS-induced colitis in mice, TUNEL-positive and caspase-3-negative cells were observed in the intestinal mucosa, and p-RIPK3 was found to be elevated. Under the stimulation of TNF- α and Z-VAD-fmk, the morphologic damage in the Caco-2 cells was aggravated, the proportion of necrosis was increased, and the level of p-RIPK3 and p-MLKL were increased, confirming that the regulated cell death was necroptosis. NSA reversed the morphological abnormalities and reduced necrotic cell death induced by TNF- α and Z-VAD-fmk. NSA can inhibit necroptosis in intestinal epithelial cells in vitro and might confer a potential protective effect against IBD.

[Application of percutaneous trans esophageal gastro-tubing (PTEG) in to home care for a patient with terminal stage of gastric cancer].

Science.gov (United States)

Oishi, H; Murata, J; Shirotani, N; Kameoka, S

1998-12-01

Since 1994, we devised and have continued to develop a percutaneous trans esophageal gastro-tubing (PTEG) as an effective technique to drain gastrointestinal contents of critical patients suffering from gastric carcinoma. Here we report our satisfactory experience with a critical gastric cancer patient for whom we improved QOL by the application of the PTEG technique. The patient suffered from severe stenosis or obstruction of the digestive tract. This method was found to be effective enough to enable the patient to receive further medical care at home. The patient was a 36-year-old female who had far-advanced, inoperable gastric carcinoma. It was therefore decided to use the PTEG method. The PTEG method was performed using a rupture-free balloon (RFB) catheter to drain the gastrointestinal contents. A reservoir-port for IVH use was embedded to control the patient's nutrition. A morphine hydrochloride suppository was then given for the pain. PTEG was found to be effective, safe and simple; moreover, it is a less-invasive, intestine-maintaining method, which enabled the patient to continue receiving further medical treatment at home.

In vitro fermentation of lupin seeds (Lupinus albus) and broad beans (Vicia faba): dynamic modulation of the intestinal microbiota and metabolomic output.

Science.gov (United States)

Gullón, Patricia; Gullón, Beatriz; Tavaria, Freni; Vasconcelos, Marta; Gomes, Ana Maria

2015-10-01

Broad beans (Vicia faba) and lupin seeds (Lupinus albus) are legumes rich in a wide range of compounds, which may represent a useful dietary approach for modulating the human gut microbiome. In this work, after in vitro digestion, legume samples were used as carbon sources in anaerobic batch cultures to evaluate their impact on the intestinal microbiota composition and on their metabolic products. The fermentations were monitored by a decrease in pH, generation of short chain fatty acids (SCFA) and lactate and the changes in the dynamic bacterial populations by fluorescence in situ hybridization (FISH). The total SCFA at the end of fermentation was 81.52 mM for lupin seeds and 78.41 mM for broad beans accompanied by a decrease of the pH for both legumes. The microbial groups that increased significantly (P spp., Lactobacillus-Enterococcus, Atopobium, Bacteroides-Pretovella, Clostridium coccoides-Eubacterium rectale, Faecalibacterium prausnitzii and Roseburia intestinalis. This impact on the intestinal microbiota suggests that lupin seeds and broad beans may be used in the development of novel functional foods, which can be included in dietary strategies for human health promotion.

Preoperative endoscopy may reduce the need for revisional surgery for gastro-oesophageal reflux disease following laparoscopic sleeve gastrectomy.

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Madhok, B M; Carr, W R J; McCormack, C; Boyle, M; Jennings, N; Schroeder, N; Balupuri, S; Small, P K

2016-08-01

Laparoscopic sleeve gastrectomy is a safe and effective bariatric operation, but postoperative reflux symptoms can sometimes necessitate revisional surgery. Roux-en-Y gastric bypass is the preferred operation in morbidly obese patients with gastro-oesophageal reflux disease. In 2011, we introduced preoperative endoscopy to assess for hiatus hernia or evidence of oesophagitis in conjunction with an assessment of gastro-oesophageal reflux symptoms for all patients undergoing bariatric surgery with a view to avoid sleeve gastrectomy for these patients. A prospectively maintained database was used to identify patients who underwent sleeve gastrectomy before and after we changed the unit policy. The need for revisional surgery in patients with troublesome gastro-oesophageal reflux disease was examined. Prior to 2011, 130 patients underwent sleeve gastrectomy, and 11 (8.5%) of them required conversion to Roux-en-Y gastric bypass for symptomatic reflux disease. Following the policy change, 284 patients underwent sleeve gastrectomy, and to date, only five (1.8%) have required revisional surgery (p = 0.001). Baseline demographics were comparable between the groups, and average follow-up period was 47 and 33 months, respectively, for each group. Preoperative endoscopy and a detailed clinical history regarding gastro-oesophageal reflux symptoms may improve patient selection for sleeve gastrectomy. Avoiding sleeve gastrectomy in patients with reflux disease and/or hiatus hernia may reduce the incidence of revisional surgery. © 2016 World Obesity.

The formation of intestinal organoids in a hanging drop culture.

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Panek, Malgorzata; Grabacka, Maja; Pierzchalska, Malgorzata

2018-01-25

Recently organoids have become widely used in vitro models of many tissue and organs. These type of structures, originated from embryonic or adult mammalian intestines, are called "mini guts". They organize spontaneously when intestinal crypts or stem cells are embedded in the extracellular matrix proteins preparation scaffold (Matrigel). This approach has some disadvantages, as Matrigel is undefined (the concentrations of growth factors and other biologically active components in it may vary from batch to batch), difficult to handle and expensive. Here we show that the organoids derived from chicken embryo intestine are formed in a hanging drop without embedding, providing an attractive alternative for currently used protocols. Using this technique we obtained compact structures composed of contiguous organoids, which were generally similar to chicken organoids cultured in Matrigel in terms of morphology and expression of intestinal epithelial markers. Due to the simplicity, high reproducibility and throughput capacity of hanging drop technique our model may be applied in various studies concerning the gut biology.

Behaviour of lactic acid bacteria populations in Pecorino di Carmasciano cheese samples submitted to environmental conditions prevailing in the gastrointestinal tract: evaluation by means of a polyphasic approach.

Science.gov (United States)

Ricciardi, Annamaria; Blaiotta, Giuseppe; Di Cerbo, Alessandro; Succi, Mariantonietta; Aponte, Maria

2014-06-02

The survival of the autochthonous microflora, of samples collected during Pecorino di Carmasciano cheese manufacturing, was evaluated along the passage through a model mimicking the gastro-intestinal tract. The aim was the selection of lactic acid bacteria potentially able to arrive alive and metabolically active to the colon. The dynamics of lactic microbiota, throughout simulated digestion of cheese samples, were evaluated by means of an approach PCR-DGGE-based. Dominant species after cheese digestion could be related to the Lactobacillus plantarum and Lactobacillus casei groups. Sixty-three strains, which survived to simulated gastro-intestinal transit, were further evaluated for technological features and tolerance to human digestion in several experimental conditions, according to routinely used protocols. Bacterial survival appeared to be, more than strain-specific, strongly affected by experimental conditions, i.e. some strains showed an acceptable survival when resuspended in skim milk but not in ewe milk and vice versa. Nevertheless according to data, one gram of fresh Pecorino di Carmasciano cheese may convey to human colon about the same amount of viable LAB of a probiotic drink. Although it cannot be assumed that lactobacilli introduced with Pecorino have beneficial effects on the host, the healthy impact of autochthonous lactic acid bacteria of naturally fermented food has a broad consensus in the current literature. Copyright © 2014 Elsevier B.V. All rights reserved.

Mucin dynamics in intestinal bacterial infection.

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Sara K Lindén

Full Text Available Bacterial gastroenteritis causes morbidity and mortality in humans worldwide. Murine Citrobacter rodentium infection is a model for gastroenteritis caused by the human pathogens enteropathogenic Escherichia coli and enterohaemorrhagic E. coli. Mucin glycoproteins are the main component of the first barrier that bacteria encounter in the intestinal tract.Using Immunohistochemistry, we investigated intestinal expression of mucins (Alcian blue/PAS, Muc1, Muc2, Muc4, Muc5AC, Muc13 and Muc3/17 in healthy and C. rodentium infected mice. The majority of the C. rodentium infected mice developed systemic infection and colitis in the mid and distal colon by day 12. C. rodentium bound to the major secreted mucin, Muc2, in vitro, and high numbers of bacteria were found in secreted MUC2 in infected animals in vivo, indicating that mucins may limit bacterial access to the epithelial surface. In the small intestine, caecum and proximal colon, the mucin expression was similar in infected and non-infected animals. In the distal colonic epithelium, all secreted and cell surface mucins decreased with the exception of the Muc1 cell surface mucin which increased after infection (p<0.05. Similarly, during human infection Salmonella St Paul, Campylobacter jejuni and Clostridium difficile induced MUC1 in the colon.Major changes in both the cell-surface and secreted mucins occur in response to intestinal infection.

Mechanisms of Intestinal Serotonin Transporter (SERT Upregulation by TGF-β1 Induced Non-Smad Pathways.

Directory of Open Access Journals (Sweden)

Saad Nazir

Full Text Available TGF-β1 is an important multifunctional cytokine with numerous protective effects on intestinal mucosa. The influence of TGF-β1 on serotonin transporter (SERT activity, the critical mechanism regulating the extracellular availability of serotonin (5-HT, is not known. Current studies were designed to examine acute effects of TGF-β1 on SERT. Model human intestinal Caco-2 cells grown as monolayer's or as cysts in 3D culture and ex vivo mouse model were utilized. Treatment of Caco-2 cells with TGF-β1 (10 ng/ml, 60 min stimulated SERT activity (~2 fold, P<0.005. This stimulation of SERT function was dependent upon activation of TGF-β1 receptor (TGFRI as SB-431542, a specific TGF-βRI inhibitor blocked the SERT stimulation. SERT activation in response to TGF-β1 was attenuated by inhibition of PI3K and occurred via enhanced recruitment of SERT-GFP to apical surface in a PI3K dependent manner. The exocytosis inhibitor brefeldin A (2.5 μM attenuated the TGF-β1-mediated increase in SERT function. TGF-β1 increased the association of SERT with the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE syntaxin 3 (STX3 and promoted exocytosis of SERT. Caco-2 cells grown as cysts in 3D culture recapitulated the effects of TGF-β1 showing increased luminal staining of SERT. Ussing chamber studies revealed increase in 3H-5-HT uptake in mouse ileum treated ex vivo with TGF-β1 (10 ng/ml, 1h. These data demonstrate a novel mechanism rapidly regulating intestinal SERT via PI3K and STX3. Since decreased SERT is implicated in various gastro-intestinal disorders e.g IBD, IBS and diarrhea, understanding mechanisms stimulating SERT function by TGF-β1 offers a novel therapeutic strategy to treat GI disorders.

Advanced three-dimensional culture of equine intestinal epithelial stem cells.

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Stewart, A Stieler; Freund, J M; Gonzalez, L M

2018-03-01

Intestinal epithelial stem cells are critical to epithelial repair following gastrointestinal injury. The culture of intestinal stem cells has quickly become a cornerstone of a vast number of new research endeavours that range from determining tissue viability to testing drug efficacy for humans. This study aims to describe the methods of equine stem cell culture and highlights the future benefits of these techniques for the advancement of equine medicine. To describe the isolation and culture of small intestinal stem cells into three-dimensional (3D) enteroids in horses without clinical gastrointestinal abnormalities. Descriptive study. Intestinal samples were collected by sharp dissection immediately after euthanasia. Intestinal crypts containing intestinal stem cells were dissociated from the underlying tissue layers, plated in a 3D matrix and supplemented with growth factors. After several days, resultant 3D enteroids were prepared for immunofluorescent imaging and polymerase chain reaction (PCR) analysis to detect and characterise specific cell types present. Intestinal crypts were cryopreserved immediately following collection and viability assessed. Intestinal crypts were successfully cultured and matured into 3D enteroids containing a lumen and budding structures. Immunofluorescence and PCR were used to confirm the existence of stem cells and all post mitotic, mature cell types, described to exist in the horse intestinal epithelium. Previously frozen crypts were successfully cultured following a freeze-thaw cycle. Tissues were all derived from normal horses. Application of this technique for the study of specific disease was not performed at this time. The successful culture of equine intestinal crypts into 3D "mini-guts" allows for in vitro studies of the equine intestine. Additionally, these results have relevance to future development of novel therapies that harness the regenerative potential of equine intestine in horses with gastrointestinal disease

Modeling the growth dynamics of multiple Escherichia coli strains in the pig intestine following intramuscular ampicillin treatment.

Science.gov (United States)

Ahmad, Amais; Zachariasen, Camilla; Christiansen, Lasse Engbo; Græsbøll, Kaare; Toft, Nils; Matthews, Louise; Nielsen, Søren Saxmose; Olsen, John Elmerdahl

2016-09-06

This study evaluated how dosing regimen for intramuscularly-administered ampicillin, composition of Escherichia coli strains with regard to ampicillin susceptibility, and excretion of bacteria from the intestine affected the level of resistance among Escherichia coli strains in the intestine of nursery pigs. It also examined the dynamics of the composition of bacterial strains during and after the treatment. The growth responses of strains to ampicillin concentrations were determined using in vitro growth curves. Using these results as input data, growth predictions were generated using a mathematical model to simulate the competitive growth of E. coli strains in a pig intestine under specified plasma concentration profiles of ampicillin. In vitro growth results demonstrated that the resistant strains did not carry a fitness cost for their resistance, and that the most susceptible strains were more affected by increasing concentrations of antibiotics that the rest of the strains. The modeling revealed that short treatment duration resulted in lower levels of resistance and that dosing frequency did not substantially influence the growth of resistant strains. Resistance levels were found to be sensitive to the number of competing strains, and this effect was enhanced by longer duration of treatment. High excretion of bacteria from the intestine favored resistant strains over sensitive strains, but at the same time it resulted in a faster return to pre-treatment levels after the treatment ended. When the duration of high excretion was set to be limited to the treatment time (i.e. the treatment was assumed to result in a cure of diarrhea) resistant strains required longer time to reach the previous level. No fitness cost was found to be associated with ampicillin resistance in E. coli. Besides dosing factors, epidemiological factors (such as number of competing strains and bacterial excretion) influenced resistance development and need to be considered further in

Human mini-guts: new insights into intestinal physiology and host-pathogen interactions.

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In, Julie G; Foulke-Abel, Jennifer; Estes, Mary K; Zachos, Nicholas C; Kovbasnjuk, Olga; Donowitz, Mark

2016-11-01

The development of indefinitely propagating human 'mini-guts' has led to a rapid advance in gastrointestinal research related to transport physiology, developmental biology, pharmacology, and pathophysiology. These mini-guts, also called enteroids or colonoids, are derived from LGR5 + intestinal stem cells isolated from the small intestine or colon. Addition of WNT3A and other growth factors promotes stemness and results in viable, physiologically functional human intestinal or colonic cultures that develop a crypt-villus axis and can be differentiated into all intestinal epithelial cell types. The success of research using human enteroids has highlighted the limitations of using animals or in vitro, cancer-derived cell lines to model transport physiology and pathophysiology. For example, curative or preventive therapies for acute enteric infections have been limited, mostly due to the lack of a physiological human intestinal model. However, the human enteroid model enables specific functional studies of secretion and absorption in each intestinal segment as well as observations of the earliest molecular events that occur during enteric infections. This Review describes studies characterizing these human mini-guts as a physiological model to investigate intestinal transport and host-pathogen interactions.

Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function.

Science.gov (United States)

Clemente, M G; De Virgiliis, S; Kang, J S; Macatagney, R; Musu, M P; Di Pierro, M R; Drago, S; Congia, M; Fasano, A

2003-02-01

Despite the progress made in understanding the immunological aspects of the pathogenesis of coeliac disease (CD), the early steps that allow gliadin to cross the intestinal barrier are still largely unknown. The aim of this study was to establish whether gliadin activates a zonulin dependent enterocyte intracellular signalling pathway(s) leading to increased intestinal permeability. The effect of gliadin on the enterocyte actin cytoskeleton was studied on rat intestinal epithelial (IEC-6) cell cultures by fluorescence microscopy and spectrofluorimetry. Zonulin concentration was measured on cell culture supernatants by enzyme linked immunosorbent assay. Transepithelial intestinal resistance (Rt) was measured on ex vivo intestinal tissues mounted in Ussing chambers. Incubation of cells with gliadin led to a reversible protein kinase C (PKC) mediated actin polymerisation temporarily coincident with zonulin release. A significant reduction in Rt was observed after gliadin addition on rabbit intestinal mucosa mounted in Ussing chambers. Pretreatment with the zonulin inhibitor FZI/0 abolished the gliadin induced actin polymerisation and Rt reduction but not zonulin release. Gliadin induces zonulin release in intestinal epithelial cells in vitro. Activation of the zonulin pathway by PKC mediated cytoskeleton reorganisation and tight junction opening leads to a rapid increase in intestinal permeability.

Validation of a numerical FSI simulation of an aortic BMHV by in vitro PIV experiments.

Science.gov (United States)

Annerel, S; Claessens, T; Degroote, J; Segers, P; Vierendeels, J

2014-08-01

In this paper, a validation of a recently developed fluid-structure interaction (FSI) coupling algorithm to simulate numerically the dynamics of an aortic bileaflet mechanical heart valve (BMHV) is performed. This validation is done by comparing the numerical simulation results with in vitro experiments. For the in vitro experiments, the leaflet kinematics and flow fields are obtained via the particle image velocimetry (PIV) technique. Subsequently, the same case is numerically simulated by the coupling algorithm and the resulting leaflet kinematics and flow fields are obtained. Finally, the results are compared, revealing great similarity in leaflet motion and flow fields between the numerical simulation and the experimental test. Therefore, it is concluded that the developed algorithm is able to capture very accurately all the major leaflet kinematics and dynamics and can be used to study and optimize the design of BMHVs. Copyright © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

In vitro chemopreventive properties of peptides released from quinoa (Chenopodium quinoa Willd.) protein under simulated gastrointestinal digestion.

Science.gov (United States)

Vilcacundo, Rubén; Miralles, Beatriz; Carrillo, Wilman; Hernández-Ledesma, Blanca

2018-03-01

Because of the continuous and direct interaction between the digestive tract and foods, dietary compounds represent an interesting source of chemopreventive agents for gastrointestinal health. In this study, the influence of a standardized static in vitro gastrointestinal digestion model on the release of peptides with chemopreventive potential from quinoa protein was investigated. Gastroduodenal digests and fractions collected by ultrafiltration were evaluated for their in plate oxygen radical absorbance capacity and in vitro colon cancer cell viability inhibitory activity. Highest effects were observed in the digests obtained during the intestinal phase, with fraction containing peptides 5kDa showing the greatest anti-cancer effects. Seventeen potential bioactive peptides derived from quinoa proteins have been identified. These proteins might be utilized as new ingredients in the development of functional foods or nutraceuticals with the aim of reducing oxidative stress-associated diseases, including cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Predictive value of routine esophageal high-resolution manometry for gastro-esophageal reflux disease

NARCIS (Netherlands)

van Hoeij, F. B.; Smout, A. J.; Bredenoord, A. J.

2015-01-01

Using conventional manometry, gastro-esophageal reflux disease (GERD) was associated with a reduced lower esophageal sphincter (LES) pressure and impaired peristalsis. However, with a large overlap between GERD patients and controls, these findings are of limited clinical relevance. It is uncertain

Évaluation d'une forme galénique à base d'alpha cyclodextrine et d'huile végétale pour l'administration par voie orale de molécules actives peu solubles dans l'eau

OpenAIRE

Hamoudi , Mounira Chérifa

2012-01-01

The general aim of this thesis was the study of the potential of beads, made of α-cyclodextrin and soybean oil, for the oral delivery of poorly water soluble drugs. We have first verified that it was possible to encapsulate in beads, active molecules (progesterone and indomethacin), other than retinoid and diazepam, with a high drug loading and a satisfying yied. The study of the behaviour of freeze-dried naked beads, in terms of stability and drug release in simulated gastro-intestinal fluid...

Gastro-tracheal fistula - unusual and life threatening complication after esophagectomy for cancer: a case report

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Droissart Raphaël

2009-11-01

Full Text Available Abstract Background A gastro-tracheal fistula following esophagectomy for cancer is a rare but potentially lethal complication. We report the successful surgical closure after failed endoscopic treatment, of a gastro-tracheal fistula following esophago-gastrectomy for cancer after induction chemo-radiotherapy. Case presentation A 58 year-old male patient presented with a distal third uT3N1 carcinoma of the esophagus. After induction chemo-radiotherapy, he underwent an esophago-gastrectomy with radical lymphadenectomy and reconstruction by gastric pull-up. Immediate postoperative outcome was uneventful. On the 15th postoperative day however, our patient was readmitted in the Intensive Care Unit with severe bilateral basal pneumonia. Three days later a gastro-tracheal fistula was diagnosed upon gastroscopy and bronchoscopy. His good general condition allowed for an endoscopic primary approach which consisted in the insertion of a covered stent in the trachea along with clipping and glueing of the gastric fistular orifice. Two attempts proved unsuccessful. Conclusion After several weeks of conservative measures, surgical re-intervention through a right thoracotomy with transection of the fistula and closure by primary interrupted sutures of both fistular orifices along with intercostal muscle flap interposition led to excellent patient outcome. Oral feeding was started and our patient was discharged.

Postprandial gastro-oesophageal reflux demonstrated by radiology

Energy Technology Data Exchange (ETDEWEB)

Pedersen, P.R.; Mohr Madsen, K.; Naeser, A.; Thommesen, P. (Aarhus Univ. (Denmark). Dept. of Diagnostic Radiology)

1991-05-01

An investigation to detect food-stimulated gastro-oesophageal (GE) reflux was carried out in 54 consecutive fasting patients, 35 of whom experienced reflux while 19 did not. All patients then received a standard meal (566 kcal), and the investigation was repeated 1 h afterward. Of the 35 with GE reflux in the fasting state, 33 also had GE reflux in the postprandial state, and 17 of the 19 patients with no GE reflux while fasting also had none in the postprandial state. It is concluded that the radiological method can identify most patients in whom food-stimulated GE reflux could be of clinical significance. (orig.).

Metabolism of sinigrin (2-propenyl glucosinolate) by the human colonic microflora in a dynamic in vitro large-intestinal model.

Science.gov (United States)

Krul, Cyrille; Humblot, Christèle; Philippe, Catherine; Vermeulen, Martijn; van Nuenen, Marleen; Havenaar, Robert; Rabot, Sylvie

2002-06-01

Cruciferous vegetables, such as Brassica, which contain substantial quantities of glucosinolates, have been suggested to possess anticarcinogenic activity. Cutting and chewing of cruciferous vegetables releases the thioglucosidase enzyme myrosinase, which degrades glucosinolates to isothiocyanates and other minor metabolites. Cooking of cruciferous vegetables inactivates the myrosinase enzyme, allowing intact glucosinolates to reach the large intestine, where they can be degraded by the indigenous microflora into isothiocyanates. This local release of isothiocyanates may explain the protective effect of cruciferous vegetables on the colon epithelium. However, little is known about the amounts and identities of glucosinolate metabolites produced by the human microflora. The production of allyl isothiocyanate from sinigrin was investigated in a dynamic in vitro large-intestinal model, after inoculation with a complex microflora of human origin. Sinigrin and allyl isothiocyanate concentrations were analysed in the lumen and dialysis fluid of the model. Peak levels of allyl isothiocyanate were observed between 9 and 12 h after the addition of sinigrin. The model was first set up with a pooled and cultured human microflora, in which 1 and 4% of, respectively, 1 and 15 mM sinigrin, was converted into AITC. However, the conversion rate was remarkably higher if different individual human microflora were used. Between 10% and 30% (mean 19%) of the sinigrin was converted into allyl isothiocyanate. The results of this study suggest that allyl isothiocyanate is converted further into other, yet unknown, metabolites.

Establishment of primary bovine intestinal epithelial cell culture and clone method.

Science.gov (United States)

Zhan, Kang; Lin, Miao; Liu, Ming-Mei; Sui, Yang-Nan; Zhao, Guo-Qi

2017-01-01

The aim of this study was to establish bovine intestinal epithelial cell (BIEC) line and provide a novel clone cell method. Although various strategies of bovine cell culture and clone techniques have been reported, these methods remain not established. Here, we culture successfully primary BIECs and establish a novel clone cell method. Our result showed that BIECs could be successfully cultured and passaged about generation 5. These cellular aggregates and clusters were adherent loosely at day 2 of culture. Cell aggregates and clusters start to proliferate after approximately 4 d. The BIECs showed positive reaction against cytokeratin 18, E-cadherin, and characteristics of epithelial-like morphology. In addition, the fatty acid-binding proteins (FABPs), villin, and intestinal peptidase (IP) band were positive in BIECs. Our results suggest that the establishment of culturing and clone BIEC methods will apply to isolate and clone other primary cells. These BIECs could therefore contribute to the study of bovine intestinal nutrient absorption and regulation, immune regulation, and the pathogenesis of the bovine intestinal disease, which will provide intestinal cell model in vitro.

In Silico Modeling of Gastrointestinal Drug Absorption: Predictive Performance of Three Physiologically Based Absorption Models.

Science.gov (United States)

Sjögren, Erik; Thörn, Helena; Tannergren, Christer

2016-06-06

Gastrointestinal (GI) drug absorption is a complex process determined by formulation, physicochemical and biopharmaceutical factors, and GI physiology. Physiologically based in silico absorption models have emerged as a widely used and promising supplement to traditional in vitro assays and preclinical in vivo studies. However, there remains a lack of comparative studies between different models. The aim of this study was to explore the strengths and limitations of the in silico absorption models Simcyp 13.1, GastroPlus 8.0, and GI-Sim 4.1, with respect to their performance in predicting human intestinal drug absorption. This was achieved by adopting an a priori modeling approach and using well-defined input data for 12 drugs associated with incomplete GI absorption and related challenges in predicting the extent of absorption. This approach better mimics the real situation during formulation development where predictive in silico models would be beneficial. Plasma concentration-time profiles for 44 oral drug administrations were calculated by convolution of model-predicted absorption-time profiles and reported pharmacokinetic parameters. Model performance was evaluated by comparing the predicted plasma concentration-time profiles, Cmax, tmax, and exposure (AUC) with observations from clinical studies. The overall prediction accuracies for AUC, given as the absolute average fold error (AAFE) values, were 2.2, 1.6, and 1.3 for Simcyp, GastroPlus, and GI-Sim, respectively. The corresponding AAFE values for Cmax were 2.2, 1.6, and 1.3, respectively, and those for tmax were 1.7, 1.5, and 1.4, respectively. Simcyp was associated with underprediction of AUC and Cmax; the accuracy decreased with decreasing predicted fabs. A tendency for underprediction was also observed for GastroPlus, but there was no correlation with predicted fabs. There were no obvious trends for over- or underprediction for GI-Sim. The models performed similarly in capturing dependencies on dose and

Comparison of barium swallow and ultrasound in diagnosis of gastro-oesophageal reflux in children.

Science.gov (United States)

Naik, D R; Bolia, A; Moore, D J

1985-01-01

Fifty one infants and older children with suspected gastro-oesophageal reflux entered a study comparing the diagnostic accuracy of a standard barium swallow examination with that of ultrasound scanning. All children were examined by both techniques. In 40 cases there was unequivocal agreement between the examinations. Of the remaining patients, four had definite reflux by ultrasonic criteria but showed no evidence of reflux on barium swallow examination, four had positive findings on ultrasound but showed only minimal reflux on barium swallow, and one showed minimal reflux on ultrasound but had a negative barium meal result. In two children the ultrasound study was inconclusive. Ultrasound has an important role in the diagnosis and follow up of patients under the age of 5 years with gastro-oesophageal reflux. Images FIG 1 FIG 2 PMID:3924317

[Digitalization, archival storage and use of image documentation in the GastroBase-II system].

Science.gov (United States)

Kocna, P

1997-05-14

"GastroBase-II" is a module of the clinical information system "KIS-ComSyD"; The main part is represented by structured data-text with an expert system including on-line image digitalization in gastroenterology (incl. endoscopic, X-ray and endosonography pictures). The hardware and software of the GastroBase are described as well as six-years experiences with application of digitalized image data. An integration of a picture into text, reports, slides for a lecture or an electronic atlas is documented with examples. Briefly are reported out experiences with graphic editors (PhotoStyler), text editor (WordPerfect) and slide preparation for lecturing with the presentation software PowerPoint. The multimedia applications on the CD-ROM illustrate a modern trend using digitalized image documentation for pregradual and postgradual education.

A pSMAD/CDX2 Complex Is Essential for the Intestinalization of Epithelial Metaplasia

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Luigi Mari

2014-05-01

Full Text Available The molecular mechanisms leading to epithelial metaplasias are poorly understood. Barrett's esophagus is a premalignant metaplastic change of the esophageal epithelium into columnar epithelium, occurring in patients suffering from gastroesophageal reflux disease. Mechanisms behind the development of the intestinal subtype, which is associated with the highest cancer risk, are unclear. In humans, it has been suggested that a nonspecialized columnar metaplasia precedes the development of intestinal metaplasia. Here, we propose that a complex made up of at least two factors needs to be activated simultaneously to drive the expression of intestinal type of genes. Using unique animal models and robust in vitro assays, we show that the nonspecialized columnar metaplasia is a precursor of intestinal metaplasia and that pSMAD/CDX2 interaction is essential for the switch toward an intestinal phenotype.

Absence of correlation between serum CRP levels and mitochondrial D-loop DNA mutations in gastro-oesophageal adenocarcinoma

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Benjamin H. L. Tan

2014-01-01

Full Text Available Introduction: Both inflammation and mitochondrial DNA (mtDNA mutation are thought to play a role in the many human cancers. The aim of this study was to evaluate the relationship between inflammation and accumulation of mitochondrial DNA (mtDNA mutations in the D-loop region in carcinogenesis of gastro-oesophageal adenocarcinomas. Materials and Methods: Blood samples of 20 patients with gastro-oesophageal adenocarcinoma were taken for measurement of serum C-reactive protein (CRP concentration. Direct sequencing of mtDNA in the D-loop region was done in the 20 adenocarcinoma samples and their corresponding surrounding non-cancerous tissue. Sequences were compared with existing mtDNA databases to identify mutations. Results: mtDNA mutations in the D-loop region occur commonly with almost identical frequency in both non-cancerous tissue (3.0 ΁ 1.6 and adenocarcinoma (3.1 ΁ 1.9 (P = 0.916, paired t-test. CRP levels are not predictive of the number of D-loop mutations in both adenocarcinoma (β: -0.131; 95% CI: -2.354-1.364; P = 0.583 and non-cancerous tissue samples (β: 0.130; 95% CI: -1.125-1.933; P = 0.586. Five new mutations were identified that were not recorded previously in mtDNA databases. Conclusion: D-loop mtDNA mutations are common in both gastro-oesophageal adenocarcinoma and surrounding non-cancerous tissue. However, the accumulation of such mutations appears to occur independent of systemic inflammation. The frequency of D-loop mutations is likely not useful as a marker for carcinogenesis in gastro-oesophageal adenocarcinoma.

Diagnostic and therapeutic radio pharmaceutical capsules

International Nuclear Information System (INIS)

Haney, T.A.; Wedeking, P.W.; Morcos, N.A.

1981-01-01

An improved pharmaceutical radioactive capsule consisting of a non-toxic, water soluble material adapted to being ingested and rapidly disintegrating on contact with fluids of the gastro-intestinal tract is described. Each capsule is provided with filler material supporting a pharmaceutically useful radioactive compound absorbable from the gastro-intestinal tract. The capsule is preferably of gelatin, methyl cellulose or polyvinyl alcohol and the filler is a polyethylene glycol. The radioactive compound may be iodine e.g. sodium radioiodide I-131 or 123. The capsule may also contain a reducing agent e.g. sodium thiosulphate, sulphite, or bisulphite. (author)

Matrix tablets: the effect of hydroxypropyl methylcellulose/anhydrous dibasic calcium phosphate ratio on the release rate of a water-soluble drug through the gastrointestinal tract I. In vitro tests.

Science.gov (United States)

Mamani, Pseidy L; Ruiz-Caro, Roberto; Veiga, María D

2012-12-01

Different hydroxypropyl methylcellulose (HPMC)/anhydrous dibasic calcium phosphate (ADCP) matrix tablets have been developed aiming to evaluate the influence of both components ratio in the control release of a water-soluble drug (theophylline). In order to characterise the matrix tablets, swelling, buoyancy and dissolution studies have been carried out in different aqueous media (demineralised water, progressive pH medium, simulated gastric fluid, simulated intestinal fluid and simulated colonic fluid). The HPMC/ADCP ratio has turned out to be the determinant in the matrix behaviour: the HPMC characteristic swelling behaviour was modulated, in some cases, by the ADCP characteristic acidic dissolution. When the HPMC/ADCP ratio was ≥0.69, buoyancy, continuous swelling and low theophylline dissolution rate from the matrices (H1, H2 and H3) were observed in all dissolution media. Consequently, these formulations could be adequate as gastro-retentive drug delivery systems. Additionally, HPMC/ADCP ratio ≤0.11 (H5 and H6) induces a pH-dependent drug release which could be applied to design control drug release enteric formulations (with a suitable enteric coating). Finally, a HPMC/ADCP ratio between 0.11 and 0.69 (H4) yield a gastrointestinal controlled drug release, due to its time-dependent buoyancy (7 h) and a total drug delivery in 17 h in simulated colonic fluid.

The intestinal barrier in irritable bowel syndrome: subtype-specific effects of the systemic compartment in an in vitro model.

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Samefko Ludidi

Full Text Available Irritable bowel syndrome (IBS is a disorder with multifactorial pathophysiology. Intestinal barrier may be altered, especially in diarrhea-predominant IBS (IBS-D. Several mediators may contribute to increased intestinal permeability in IBS.We aimed to assess effects of tryptase and LPS on in vitro permeability using a 3-dimensional cell model after basolateral cell exposure. Furthermore, we assessed the extent to which these mediators in IBS plasma play a role in intestinal barrier function.Caco-2 cells were grown in extracellular matrix to develop into polarized spheroids and were exposed to tryptase (10 - 50 mU, LPS (1 - 50 ng/mL and two-fold diluted plasma samples of 7 patients with IBS-D, 7 with constipation-predominant IBS (IBS-C and 7 healthy controls (HC. Barrier function was assessed by the flux of FITC-dextran (FD4 using live cell imaging. Furthermore, plasma tryptase and LPS were determined.Tryptase (20 and 50 mU and LPS (6.25 - 50 ng/mL significantly increased Caco-2 permeability versus control (all P< 0.05. Plasma of IBS-D only showed significantly elevated median tryptase concentrations (7.1 [3.9 - 11.0] vs. 4.2 [2.2 - 7.0] vs. 4.2 [2.5 - 5.9] μg/mL; P<0.05 and LPS concentrations (3.65 [3.00 - 6.10] vs. 3.10 [2.60-3.80] vs. 2.65 [2.40 - 3.40] EU/ml; P< 0.05 vs. IBS-C and HC. Also, plasma of IBS-D increased Caco-2 permeability versus HC (0.14450 ± 0.00472 vs. 0.00021 ± 0.00003; P < 0.001, which was attenuated by selective inhibition of tryptase and LPS (P< 0.05.Basolateral exposure of spheroids to plasma of IBS-D patients resulted in a significantly increased FD4 permeation, which was partially abolished by selective inhibition of tryptase and LPS. These findings point to a role of systemic tryptase and LPS in the epithelial barrier alterations observed in patients with IBS-D.

Crosstalk between Inflammation and ROCK/MLCK Signaling Pathways in Gastrointestinal Disorders with Intestinal Hyperpermeability

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Lijun Du

2016-01-01

Full Text Available The barrier function of the intestine is essential for maintaining the normal homeostasis of the gut and mucosal immune system. Abnormalities in intestinal barrier function expressed by increased intestinal permeability have long been observed in various gastrointestinal disorders such as Crohn’s disease (CD, ulcerative colitis (UC, celiac disease, and irritable bowel syndrome (IBS. Imbalance of metabolizing junction proteins and mucosal inflammation contributes to intestinal hyperpermeability. Emerging studies exploring in vitro and in vivo model system demonstrate that Rho-associated coiled-coil containing protein kinase- (ROCK- and myosin light chain kinase- (MLCK- mediated pathways are involved in the regulation of intestinal permeability. With this perspective, we aim to summarize the current state of knowledge regarding the role of inflammation and ROCK-/MLCK-mediated pathways leading to intestinal hyperpermeability in gastrointestinal disorders. In the near future, it may be possible to specifically target these specific pathways to develop novel therapies for gastrointestinal disorders associated with increased gut permeability.

Phasic and tonic stress-strain data obtained in intact intestinal segment in vitro

DEFF Research Database (Denmark)

Zhao, Jingbo; Liao, Donghua; Gregersen, Hans

2008-01-01

segments were isolated from ten Wistar rats and put into an organ bath containing 37 degrees C aerated Krebs solution. Ramp distension was done on active and passive intestinal segments at longitudinal stretch ratios of 0, 10, and 20%. Ramp pressures from 0 to 7.5 cmH(2)O were applied to the intestinal...... was defined as the total stress minus the passive stress. The total and passive circumferential stresses increased exponentially as a function of the strain. The amplitude of both the total and passive stress was biggest in the jejunum. The total circumferential stress decreased whereas the passive...

In vitro bioaccessibility of copper azole following simulated dermal transfer from pressure-treated wood

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U.S. Environmental Protection Agency — In vitro bioaccessibility of copper azole following simulated dermal transfer from pressure-treated wood. This dataset is associated with the following publication:...

Transient lower oesophageal sphincter relaxations--a pharmacological target for gastro-oesophageal reflux disease?

NARCIS (Netherlands)

Hirsch, D. P.; Tytgat, G. N. J.; Boeckxstaens, G. E. E.

2002-01-01

The oesophago-gastric junction functions as an anti-reflux barrier preventing increased exposure of the oesophageal mucosa to gastric contents. Failure of this anti-reflux barrier results in gastro-oesophageal reflux disease, and may lead to complications such as oesophagitis, Barrett's oesophagus

Selected Tea and Tea Pomace Extracts Inhibit Intestinal α-Glucosidase Activity in Vitro and Postprandial Hyperglycemia in Vivo

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Jungbae Oh

2015-04-01

Full Text Available Type 2 diabetes mellitus (T2DM is a metabolic disorder characterized by postprandial hyperglycemia, which is an early defect of T2DM and thus a primary target for anti-diabetic drugs. A therapeutic approach is to inhibit intestinal α-glucosidase, the key enzyme for dietary carbohydrate digestion, resulting in delayed rate of glucose absorption. Although tea extracts have been reported to have anti-diabetic effects, the potential bioactivity of tea pomace, the main bio waste of tea beverage processing, is largely unknown. We evaluated the anti-diabetic effects of three selected tea water extracts (TWE and tea pomace extracts (TPE by determining the relative potency of extracts on rat intestinal α-glucosidase activity in vitro as well as hypoglycemic effects in vivo. Green, oolong, and black tea bags were extracted in hot water and the remaining tea pomace were dried and further extracted in 70% ethanol. The extracts were determined for intestinal rat α-glucosidases activity, radical scavenging activity, and total phenolic content. The postprandial glucose-lowering effects of TWE and TPE of green and black tea were assessed in male Sprague-Dawley (SD rats and compared to acarbose, a known pharmacological α-glucosidase inhibitor. The IC50 values of all three tea extracts against mammalian α-glucosidase were lower or similar in TPE groups than those of TWE groups. TWE and TPE of green tea exhibited the highest inhibitory effects against α-glucosidase activity with the IC50 of 2.04 ± 0.31 and 1.95 ± 0.37 mg/mL respectively. Among the specific enzymes tested, the IC50 values for TWE (0.16 ± 0.01 mg/mL and TPE (0.13 ± 0.01 mg/mL of green tea against sucrase activity were the lowest compared to those on maltase and glucoamylase activities. In the animal study, the blood glucose level at 30 min after oral intake (0.5 g/kg body wt of TPE and TWE of both green and black tea was significantly reduced compared to the control in sucrose-loaded SD

Phase II study of biweekly cetuximab in combination with irinotecan as second-line treatment in patients with platinum-resistant gastro-oesophageal cancer

DEFF Research Database (Denmark)

Schønnemann, K R; Yilmaz, Mette Karen; Bjerregaard, J K

2012-01-01

The purpose of this phase II trial was to evaluate the efficacy and safety of cetuximab and irinotecan as second-line treatment in patients with gastro-oesophageal adenocarcinoma.......The purpose of this phase II trial was to evaluate the efficacy and safety of cetuximab and irinotecan as second-line treatment in patients with gastro-oesophageal adenocarcinoma....

Identification of a botanical inhibitor of intestinal diacylglyceride acyltransferase 1 activity via in vitro screening and a parallel, randomized, blinded, placebo-controlled clinical trial.

Science.gov (United States)

Velliquette, Rodney A; Grann, Kerry; Missler, Stephen R; Patterson, Jennifer; Hu, Chun; Gellenbeck, Kevin W; Scholten, Jeffrey D; Randolph, R Keith

2015-01-01

Diacylglyceride acyltransferase 1 (DGAT1) is the enzyme that adds the final fatty acid on to a diacylglyceride during triglyceride (TG) synthesis. DGAT1 plays a key role in the repackaging of dietary TG into circulating TG rich chylomicrons. A growing amount of research has indicated that an exaggerated postprandial circulating TG level is a risk indicator for cardiovascular and metabolic disorders. The aim of this research was to identify a botanical extract that inhibits intestinal DGAT1 activity and attenuates postprandial hypertriglyceridemia in overweight and obese humans. Twenty individual phytochemicals and an internal proprietary botanical extract library were screened with a primary cell-free DGAT1 enzyme assay that contained dioleoyl glycerol and palmitoleoyl Coenzyme A as substrates plus human intestinal microsomes as the DGAT1 enzyme source. Botanical extracts with IC50 values botanical extracts were then evaluated in a parallel, double-blind, placebo-controlled clinical trial. Ninety healthy, overweight and obese participants were randomized to receive 2 g daily of placebo or individual botanical extracts (the investigational product) for seven days. Serum TG levels were measured before and after consuming a high fat meal (HFM) challenge (0.354 L drink/shake; 77 g fat, 25 g carbohydrate and 9 g protein) as a marker of intestinal DGAT1 enzyme activity. Phenolic acids (i.e., gallic acid) and polyphenols (i.e., cyanidin) abundantly found in nature appeared to inhibit DGAT1 enzyme activity in vitro. Four polyphenolic rich botanical extracts were identified from in vitro evaluation in both cell-free and cellular model systems: apple peel extract (APE), grape extract (GE), red raspberry leaf extract (RLE) and apricot/nectarine extract (ANE) (IC50 = 1.4, 5.6, and 10.4 and 3.4 μg/mL, respectively). In the seven day clinical trial, compared to placebo, only GE significantly reduced the baseline subtracted change in serum TG AUC following

Use of Fluorescein Isothiocyanate-Inulin as a Marker for Intestinal Ischemic Injury.

Science.gov (United States)

AlKukhun, Abedalrazaq; Caturegli, Giorgio; Munoz-Abraham, Armando Salim; Judeeba, Sami; Patron-Lozano, Roger; Morotti, Raffaella; Rodriguez-Davalos, Manuel I; Geibel, John P

2017-06-01

Intestinal ischemia is observed in conditions such as mesenteric ischemia, or during traumatic events such as intestinal transplantation. Intestinal ischemia leads to pathophysiologic disruptions that present as increased fluid secretion into the intestinal lumen. We propose a novel method to detect real-time ischemic injury that is used in an in vitro model applicable to intestinal transplantation. Small intestine segments from rats were procured. The segments were attached to customized perfusion chambers. Both intestines were perfused on the vascular side with a Ringer buffer solution. The experimental buffer solution was bubbled with 100% nitrogen to mimic ischemia. Both lumens were perfused with 3 mL HEPES-Ringer solution containing 50 μM fluorescein isothiocyanate (FITC)-inulin. Intraluminal samples were collected at 15-minute intervals to measure FITC-inulin concentration using a nanofluorospectrophotometer. Intestinal tissue samples were processed and evaluated by a blinded pathologist using the Park/Chiu scoring system for grading intestinal ischemia. Samples collected from the ischemic intestine showed a significant decrease in FITC-inulin fluorescence compared with the control intestine, indicating enhanced fluid secretion. Histopathologic samples from the experimental arm exhibited higher scores of ischemic injury in comparison with the control arm, confirming the FITC-inulin as a correlation to ischemia. Fluorescein isothiocyanate-inulin can be used as a real-time volume marker to monitor the ischemic state of intestinal tissue. A positive correlation between the degree of fluid shift and presence of ischemic injury. The changes in fluorescence signal provide a potential selective method to measure real-time fluid changes inside an intestinal graft to evaluate viability. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Smooth muscle adaptation after intestinal transection and resection.

Science.gov (United States)

Thompson, J S; Quigley, E M; Adrian, T E

1996-09-01

Changes in motor function occur in the intestinal remnant after intestinal resection. Smooth muscle adaptation also occurs, particularly after extensive resection. The time course of these changes and their interrelationship are unclear. Our aim was to evaluate changes in canine smooth muscle structure and function during intestinal adaptation after transection and resection. Twenty-five dogs underwent either transection (N = 10), 50% distal resection (N = 10), or 50% proximal resection (N = 5). Thickness and length of the circular (CM) and longitudinal (LM) muscle layers were measured four and 12 weeks after resection. In vitro length-tension properties and response to a cholinergic agonist were studied in mid-jejunum and mid-ileum. Transection alone caused increased CM length in the jejunum proximal to the transection but did not affect LM length or muscle thickness. A 50% resection resulted in increased length of CM throughout the intestine and thickening of CM and LM near the anastomosis. Active tension of jejunal CM increased transiently four weeks after resection. Active tension in jejunal LM was decreased 12 weeks after transection and resection. Sensitivity of CM to carbachol was similar after transection and resection. It is concluded that: (1) Structural adaptation of both circular and longitudinal muscle occurs after intestinal resection. (2) This process is influenced by the site of the intestinal remnant. (3) Only minor and transient changes occur in smooth muscle function after resection. (4) Factors other than muscle adaptation are likely involved in the changes in motor function seen following massive bowel resection.

Influence of Intestinal Microbiota on the Catabolism of Flavonoids in Mice.

Science.gov (United States)

Lin, Weiqun; Wang, Wenting; Yang, Hai; Wang, Dongliang; Ling, Wenhua

2016-12-01

Although in vitro studies have shown that flavonoids are metabolized into phenolic acids by the gut microbiota, the biotransformation of flavonoids by intestinal microbiota is seldom studied in vivo. In this study, we investigated the impact of the gut microbiota on the biotransformation of 3 subclasses of flavonoids (flavonols, flavones, and flavanones). The ability of intestinal microbiota to convert flavonoids was confirmed with an in vitro fermentation model using mouse gut microflora. Simultaneously, purified flavonoids were administered to control and antibiotic-treated mice by gavage, and the metabolism of these flavonoids was evaluated. p-Hydroxyphenylacetic acid, protocatechuic acid, p-hydroxybenzoic acid, vanillic acid, hydrocaffeic acid, coumaric acid, and 3-(4-hydroxyphenyl)propionic acid were detected in the serum samples from the control mice after flavonoid consumption. The serum flavonoid concentrations were similar in both groups, whereas the phenolic metabolite concentrations were lower in the antibiotic-treated mice than in the control mice. We detected markedly higher flavonoids excretion in the feces and urine of the antibiotic-treated mice compared to the controls. Moreover, phenolic metabolites were upregulated in the control mice. These results suggest that the intestinal microbiota are not necessary for the absorption of flavonoids, but are required for their transformation. © 2016 Institute of Food Technologists®.

[Adult intestinal malrotation associated with intestinal volvulus].

Science.gov (United States)

Hernando-Almudí, Ernesto; Cerdán-Pascual, Rafael; Vallejo-Bernad, Cristina; Martín-Cuartero, Joaquín; Sánchez-Rubio, María; Casamayor-Franco, Carmen

Intestinal malrotation is a congenital anomaly of the intestinal rotation and fixation, and usually occurs in the neonatal age. Description of a clinical case associated with acute occlusive symptoms. A case of intestinal malrotation is presented in a previously asymptomatic woman of 46 years old with an intestinal obstruction, with radiology and surgical findings showing an absence of intestinal rotation. Intestinal malrotation in adults is often asymptomatic, and is diagnosed as a casual finding during a radiological examination performed for other reasons. Infrequently, it can be diagnosed in adults, associated with an acute abdomen. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Parasites gastro-intestinaux d'antilopes et de buffles (Syncerus caffer brachyceros du ranch de gibier de Nazinga au Burkina Faso

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Belem AMG.

2009-01-01

Full Text Available Gastro-intestinal parasites of antelopes and buffalos (Syncerus caffer brachyceros from the Nazinga game ranch in Burkina Faso. Parasitological survey done on the digestive tracts of antelopes [roans (Hippotragus equinus koba, hartebeests (Alcelaphus buselaphus major, defassa waterbucks (Kobus ellipsiprymnus defassa, oribis (Ourebia ourebi quadriscopa] and buffalos (Syncerus caffer brachyceros from the Nazinga game ranch in Burkina Faso allowed the identification of gastrointestinal parasites and the estimation of their prevalence and load. Nine different nematode species and three cestode species were found. Females and larvae of Cooperia were not identified up to the species level and were recognized as Cooperia spp. The nematode species found were: Haemonchus contortus, Trichostrongylus axei, Cooperia curticei, Cooperia spatulata, Skrjabinema sp., Trichostrongylus colubriformis, Trichuris ovis, Bunostomum phlebotomum, and Oesophagostomum sp. Cestodes’ species were: Moniezia expansa, Avitellina centripunctata, and Stilesia globipunctata. It was also noted without a thorough investigation the presence of Setaria labiato-papillosa in the abdominal cavity and paramphistomes in the rumen. In spite of the presence of parasites on the antelopes and buffalos, their killing out percentages (47.5 to 54.7% indicated a good physical status.

In vitro protease cleavage and computer simulations reveal the HIV-1 capsid maturation pathway

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Ning, Jiying; Erdemci-Tandogan, Gonca; Yufenyuy, Ernest L.; Wagner, Jef; Himes, Benjamin A.; Zhao, Gongpu; Aiken, Christopher; Zandi, Roya; Zhang, Peijun

2016-12-01

HIV-1 virions assemble as immature particles containing Gag polyproteins that are processed by the viral protease into individual components, resulting in the formation of mature infectious particles. There are two competing models for the process of forming the mature HIV-1 core: the disassembly and de novo reassembly model and the non-diffusional displacive model. To study the maturation pathway, we simulate HIV-1 maturation in vitro by digesting immature particles and assembled virus-like particles with recombinant HIV-1 protease and monitor the process with biochemical assays and cryoEM structural analysis in parallel. Processing of Gag in vitro is accurate and efficient and results in both soluble capsid protein and conical or tubular capsid assemblies, seemingly converted from immature Gag particles. Computer simulations further reveal probable assembly pathways of HIV-1 capsid formation. Combining the experimental data and computer simulations, our results suggest a sequential combination of both displacive and disassembly/reassembly processes for HIV-1 maturation.

Bovine lactoferrin regulates cell survival, apoptosis and inflammation in intestinal epithelial cells and preterm pig intestine.

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Nguyen, Duc Ninh; Jiang, Pingping; Stensballe, Allan; Bendixen, Emøke; Sangild, Per T; Chatterton, Dereck E W

2016-04-29

Bovine lactoferrin (bLF) may modulate neonatal intestinal inflammation. Previous studies in intestinal epithelial cells (IECs) indicated that moderate bLF doses enhance proliferation whereas high doses trigger inflammation. To further elucidate cellular mechanisms, we profiled the porcine IEC proteome after stimulation with bLF at 0, 0.1, 1 and 10g/L by LC-MS-based proteomics. Key pathways were analyzed in the intestine of formula-fed preterm pigs with and without supplementation of 10g/L bLF. Levels of 123 IEC proteins were altered by bLF. Low bLF doses (0.1-1g/L) up-regulated 11 proteins associated with glycolysis, energy metabolism and protein synthesis, indicating support of cell survival. In contrast, a high bLF dose (10g/L) up-regulated three apoptosis-inducing proteins, down-regulated five anti-apoptotic and proliferation-inducing proteins and 15 proteins related to energy and amino acid metabolism, and altered three proteins enhancing the hypoxia inducible factor-1 (HIF-1) pathway. In the preterm pig intestine, bLF at 10g/L decreased villus height/crypt depth ratio and up-regulated the Bax/Bcl-2 ratio and HIF-1α, indicating elevated intestinal apoptosis and inflammation. In conclusion, bLF dose-dependently affects IECs via metabolic, apoptotic and inflammatory pathways. It is important to select an appropriate dose when feeding neonates with bLF to avoid detrimental effects exerted by excessive doses. The present work elucidates dose-dependent effects of bLF on the proteomic changes of IECs in vitro supplemented with data from a preterm pig study confirming detrimental effects of enteral feeding with the highest dose of bLF (10g/L). The study contributes to further understanding on mechanisms that bLF, as an important milk protein, can regulate the homeostasis of the immature intestine. Results from this study urge neonatologists to carefully consider the dose of bLF to supplement into infant formula used for preterm neonates. Copyright © 2016 Elsevier B

Development and gamma scintigraphy evaluation of gastro retentive calcium ion-based oral formulation: an innovative approach for the management of gastro-esophageal reflux disease (GERD).

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Sharma, Braj Gaurav; Khanna, Kushagra; Kumar, Neeraj; Nishad, Dhruv K; Basu, Mitra; Bhatnagar, Aseem

2017-11-01

Calcium chloride is an essential calcium channel agonist which plays an important role in the contraction of muscles by triggering calcium channel. First time hypothesized about its role in the treatment of GER (gastro-esophageal reflux) and vomiting disorder due to its local action. There are two objectives covered in this study as first, the development and optimization of floating formulation of calcium chloride and another objective was to evaluate optimized formulation through gamma scintigraphy in human subjects. Gastro retentive formulation of calcium chloride was prepared by direct compression method. Thirteen tablet formulations were designed with the help of sodium chloride, HPMC-K4M, and carbopol-934 along with effervescing agent sodium bicarbonate and citric acid. Formulation (F8) fitted best for Korsmeyer-Peppas equation with an R 2 value of 0.993. The optimized formulation was radiolabelled with 99m Tc-99 m pertechnetate for its evaluation by gamma scintigraphy. Gastric retention (6 h) was evaluated by gamma scintigraphy in healthy human subjects and efficacy of present formulation confirmed in GER positive human subjects. Gamma scintigraphy results indicated its usefulness in order to manage GERD. Stability studies of the developed formulation were carried out as per ICH guidelines for region IV and found out to be stable for 24 months.

De novo MEIS2 mutation causes syndromic developmental delay with persistent gastro-esophageal reflux.

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Fujita, Atsushi; Isidor, Bertrand; Piloquet, Hugues; Corre, Pierre; Okamoto, Nobuhiko; Nakashima, Mitsuko; Tsurusaki, Yoshinori; Saitsu, Hirotomo; Miyake, Noriko; Matsumoto, Naomichi

2016-09-01

MEIS2 aberrations are considered to be the cause of intellectual disability, cleft palate and cardiac septal defect, as MEIS2 copy number variation is often observed with these phenotypes. To our knowledge, only one nucleotide-level change-specifically, an in-frame MEIS2 deletion-has so far been reported. Here, we report a female patient with a de novo nonsense mutation (c.611C>G, p.Ser204*) in MEIS2. She showed severe intellectual disability, moderate motor/verbal developmental delay, cleft palate, cardiac septal defect, hypermetropia, severe feeding difficulties with gastro-esophageal reflux and constipation. By reviewing this patient and previous patients with MEIS2 point mutations, we found that feeding difficulty with gastro-esophageal reflux appears to be one of the core clinical features of MEIS2 haploinsufficiency, in addition to intellectual disability, cleft palate and cardiac septal defect.

Synergistic effect of PLGA nanoparticles and submicron triglyceride droplets in enhancing the intestinal solubilisation of a lipophilic weak base.

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Joyce, Paul; Prestidge, Clive A

2018-06-15

A novel hybrid microparticulate system composed of poly(lactic-co-glycolic) acid (PLGA) nanoparticles and submicron medium-chain triglyceride (MCT) droplets was fabricated to overcome the pH-dependent solubility and precipitation challenges associated with a model poorly water-soluble weak base, cinnarizine (CIN). Molecular CIN was confined within both the lipid and polymer phase of PLGA-lipid hybrid (PLH) and PLGA-lipid-mannitol hybrid (PLMH) particles, which offered significant biopharmaceutical advantages in comparison to the unformulated drug, submicron MCT droplets and PLGA nanoparticles. This was highlighted by a substantial reduction in the pH-induced precipitation during in vitro gastrointestinal two-step dissolution studies. A >2.5-fold solubilisation enhancement was observed for the composite particles during simulated intestinal conditions, compared to pure CIN. Furthermore, the drug solubilisation capacity during in vitro intestinal digesting conditions was ~2-2.5 times greater for PLMH particles compared to the precursor emulsion droplets and PLGA nanoparticles. The observations from this study indicate that a synergy exists between the degradation products of PLGA nanoparticles and lipid droplets, whereby the dual-phase release and dissolution mechanism of the hybrid particles aids in prolonging pH-provoked precipitation. Subsequently, the ability for PLGA polymers and oligomers to act as polymeric precipitation inhibitors has been highlighted for the first time. Copyright © 2018 Elsevier B.V. All rights reserved.

Postoperative Feeding Difficulties after Repair of Congenital ...

African Journals Online (AJOL)

Of these, 24 (37.5%) developed feeding difficulties in the immediate post operative period. The causes of the feeding difficulties were Gastro-oesophageal reflux (GOR) 9, Recurrent diaphragmatic hernia 8, Adhesive intestinal obstruction 4, Poor intestinal motility 2, Campylobacter enteritis, 1, Hypertrophic pyloric stenosis, 1.

Regulation of Bicarbonate Secretion in Marine Fish Intestine by the Calcium-Sensing Receptor

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Sílvia F. Gregório

2018-04-01

Full Text Available In marine fish, high epithelial intestinal HCO3− secretion generates luminal carbonate precipitates of divalent cations that play a key role in water and ion homeostasis. The present study was designed to expose the putative role for calcium and the calcium-sensing receptor (CaSR in the regulation of HCO3− secretion in the intestine of the sea bream (Sparus aurata L.. Effects on the expression of the CaSR in the intestine were evaluated by qPCR and an increase was observed in the anterior intestine in fed fish compared with unfed fish and with different regions of intestine. CaSR expression reflected intestinal fluid calcium concentration. In addition, anterior intestine tissue was mounted in Ussing chambers to test the putative regulation of HCO3− secretion in vitro using the anterior intestine. HCO3− secretion was sensitive to varying calcium levels in luminal saline and to calcimimetic compounds known to activate/block the CaSR i.e., R 568 and NPS-2143. Subsequent experiments were performed in intestinal sacs to measure water absorption and the sensitivity of water absorption to varying luminal levels of calcium and calcimimetics were exposed as well. It appears, that CaSR mediates HCO3− secretion and water absorption in marine fish as shown by responsiveness to calcium levels and calcimimetic compounds.

Experimental studies on cytogenetic dosimetry for in vitro simulated and in vivo partial body exposure

International Nuclear Information System (INIS)

Han Baoguang; Chen Di; Jin Cuizhen; Liu Xiulin; Luo Yisheng

1993-01-01

The feasibility was examined of the contaminated Poisson distribution method as applied to dose estimation of in vitro simulated and in vivo partial body exposure of New Zealand rabbits. For this purpose, the preparatory experiments were conducted. Aberration yields were obtained for mixed cultures prepared from normal and irradiated peripheral lymphocytes with volume ratio 3 to 7 and for pure cultures of irradiated cells. Comparison of the dicentric yields from these two types of cultures indicated that the probability of cultured irradiated cells entering M 1 phase was exponentially decreased as the absorbed dose increased with a D 37 value of 2.41 Gy. Analysis of the dicentric yields obtained from pure cultures demonstrated that the dose-response relationship of dicentric yields was represented by a linear-quadratic model. Partial body exposures with irradiated fractions ranging from 90% to 30% were simulated by irradiating rabbit blood in vitro with 5 Gy 60 Co γ rays. The contaminated Poisson distribution method was utilized to derive the fraction of irradiated blood in the mixed culture and its absorbed dose. The results showed the estimations are in good agreement with true values. Moreover, the same results were arrived at for in vivo partial body irradiation in spite of many complicated factors inhered. Two groups of rabbits were irradiated in vivo on right halves along their backbones at 3.6 Gy and 5.0 Gy respectively. Heart blood was sampled 24 hours later. The result analysed by the same method approximated the true values. Before the in vivo irradiation, heart blood was sampled and irradiated in vitro to simulate half body and whole body exposure, which provided self-control for its in vivo data. These offered further proof for the previous results of in vitro simulated partial body exposure

Hepatic and intestinal glucuronidation of mono(2-ethylhexyl) phthalate, an active metabolite of di(2-ethylhexyl) phthalate, in humans, dogs, rats, and mice: an in vitro analysis using microsomal fractions.

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Hanioka, Nobumitsu; Isobe, Takashi; Kinashi, Yu; Tanaka-Kagawa, Toshiko; Jinno, Hideto

2016-07-01

Mono(2-ethylhexyl) phthalate (MEHP) is an active metabolite of di(2-ethylhexyl) phthalate (DEHP) and has endocrine-disrupting effects. MEHP is metabolized into glucuronide by UDP-glucuronosyltransferase (UGT) enzymes in mammals. In the present study, the hepatic and intestinal glucuronidation of MEHP in humans, dogs, rats, and mice was examined in an in vitro system using microsomal fractions. The kinetics of MEHP glucuronidation by liver microsomes followed the Michaelis-Menten model for humans and dogs, and the biphasic model for rats and mice. The K m and V max values of human liver microsomes were 110 µM and 5.8 nmol/min/mg protein, respectively. The kinetics of intestinal microsomes followed the biphasic model for humans, dogs, and mice, and the Michaelis-Menten model for rats. The K m and V max values of human intestinal microsomes were 5.6 µM and 0.40 nmol/min/mg protein, respectively, for the high-affinity phase, and 430 µM and 0.70 nmol/min/mg protein, respectively, for the low-affinity phase. The relative levels of V max estimated by Eadie-Hofstee plots were dogs (2.0) > mice (1.4) > rats (1.0) ≈ humans (1.0) for liver microsomes, and mice (8.5) > dogs (4.1) > rats (3.1) > humans (1.0) for intestinal microsomes. The percentages of the V max values of intestinal microsomes to liver microsomes were mice (120 %) > rats (57 %) > dogs (39 %) > humans (19 %). These results suggest that the metabolic abilities of UGT enzymes expressed in the liver and intestine toward MEHP markedly differed among species, and imply that these species differences are strongly associated with the toxicity of DEHP.

The Circadian Clock Gene BMAL1 Coordinates Intestinal RegenerationSummary

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Kyle Stokes

2017-07-01

Full Text Available Background & Aims: The gastrointestinal syndrome is an illness of the intestine caused by high levels of radiation. It is characterized by extensive loss of epithelial tissue integrity, which initiates a regenerative response by intestinal stem and precursor cells. The intestine has 24-hour rhythms in many physiological functions that are believed to be outputs of the circadian clock: a molecular system that produces 24-hour rhythms in transcription/translation. Certain gastrointestinal illnesses are worsened when the circadian rhythms are disrupted, but the role of the circadian clock in gastrointestinal regeneration has not been studied. Methods: We tested the timing of regeneration in the mouse intestine during the gastrointestinal syndrome. The role of the circadian clock was tested genetically using the BMAL1 loss of function mouse mutant in vivo, and in vitro using intestinal organoid culture. Results: The proliferation of the intestinal epithelium follows a 24-hour rhythm during the gastrointestinal syndrome. The circadian clock runs in the intestinal epithelium during this pathologic state, and the loss of the core clock gene, BMAL1, disrupts both the circadian clock and rhythmic proliferation. Circadian activity in the intestine involves a rhythmic production of inflammatory cytokines and subsequent rhythmic activation of the JNK stress response pathway. Conclusions: Our results show that a circadian rhythm in inflammation and regeneration occurs during the gastrointestinal syndrome. The study and treatment of radiation-induced illnesses, and other gastrointestinal illnesses, should consider 24-hour timing in physiology and pathology. Keywords: Intestine, Circadian Rhythms, Gastrointestinal Syndrome, TNF, Intestinal Stem Cells

Present Concepts in Internal Medicine, Nutritional Support Symposium. Volume 14, Number 1. Summer 1983,

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