Gastrointestinal Regions Research Articles

Polymeric Precipitation Inhibitor Assisted Supersaturable SMEDDS of Efavirenz Based on Experimental Observations and Molecular Mechanics.

Supersaturable SMEDDS, a versatile dosage form, was investigated for improving the biopharmaceutical attributes and eradicating the food effect of poorly water soluble drug efavirenz. The present research pursues the development of efavirenz loaded Supersaturable Self- Microemulsifying Drug Delivery System (SS SMEDDS) for improving biopharmaceutical performance. Preformulation studies were carried out to determine the optimized range of lipid excipients to develop stable supersaturated SMEDDS (ST SMEDDS). The SS SMEDD formulation was prepared by adding hydroxypropyl methylcellulose as a polymeric precipitation inhibitor. The developed SS SMEDDS were evaluated for supersaturation behavior by performing in vitro supersaturation studies and molecular simulations by in silico docking. Dissolution was performed in biorelevant media to simulate fed/fasted conditions in gastrointestinal regions. Absorption behavior was determined through in vivo pharmacokinetics approach. The optimized ST SMEDDS formulation containing Maisine® CC, Tween 80 and Transcutol-P exhibited thermodynamic stability with quick rate of emulsification. The optimized SS SMEDDS containing suitable polymeric precipitation inhibitor exhibited enhanced efavirenz concentration in in vitro supersaturation test. The theoretical simulations by molecular docking revealed strong intermolecular interactions with a docking score of -3.004 KJ/mol. The dissolution performance of marketed product in biorelevant dissolution media inferred the existence of food effect in the dissolution of efavirenz. However, in SS SMEDDS, no significant differences in drug release behavior under different fasted/fed conditions signify that the food effect was neutralized. In vivo pharmacokinetics revealed a significant increase in the absorption profile of efavirenz from SS SMEDDS than that of ST SMEDDS and marketed product. The designed delivery system indicated promising results in developing an effectual EFV formulation for HIV treatment.

Selective Regional Alteration of the Gut Microbiota by Diet and Antibiotics.

The small intestinal microbiota has recently been implicated in contributing to metabolic disease. We previously demonstrated that diets rich in saturated milk fat have a particularly strong impact on the small bowel microbiota as opposed to more distal gastrointestinal (GI) regions. However, the impact of antibiotics and diet on the small bowel microbiota has not been clearly demonstrated. Thus, we sought to determine how diet and antibiotics interact in modulating the regional landscape of the gut microbiota. We conducted a study using male mice on a high fat (HF) or a low fat (LF) diet (n = 15/group) that received either water control (n = 5/diet), rifaximin, (non-absorbable broad-spectrum antibiotic; n = 5/diet) or an antibiotic cocktail consisting of metronidazole, cefoperazone, vancomycin, and neomycin (Abx cocktail; n = 5/diet). 16S rRNA sequencing was performed on mucosal scrapings collected from the small intestine and cecum, as well as on stool samples. Interestingly, antibiotics had a significant effect on community composition throughout the small intestine, cecum and stool, whereas diet significantly affected only the jejunum and cecum microbiota. The antibiotic cocktail, regardless of diet, was most effective in increasing cecum size, reducing body fat percentage, and plasma lipid levels. Altogether, this study reveals a selective and divergent regional alteration of the gut microbiota by diet and antibiotics.

A novel intramuscular Interstitial Cell of Cajal is a candidate for generating pacemaker activity in the mouse internal anal sphincter

The internal anal sphincter (IAS) generates phasic contractions and tone. Slow waves (SWs) produced by interstitial cells of Cajal (ICC) underlie phasic contractions in other gastrointestinal regions. SWs are also present in the IAS where only intramuscular ICC (ICC-IM) are found, however the evidence linking ICC-IM to SWs is limited. This study examined the possible relationship between ICC-IM and SWs by recording Ca2+ transients in mice expressing a genetically-encoded Ca2+-indicator in ICC (Kit-Cre-GCaMP6f). A role for L-type Ca2+ channels (CavL) and anoctamin 1 (ANO1) was tested since each is essential for SW and tone generation. Two distinct ICC-IM populations were identified. Type I cells (36% of total) displayed localised asynchronous Ca2+ transients not dependent on CavL or ANO1; properties typical of ICC-IM mediating neural responses in other gastrointestinal regions. A second novel sub-type, i.e., Type II cells (64% of total) generated rhythmic, global Ca2+ transients at the SW frequency that were synchronised with neighbouring Type II cells and were abolished following blockade of either CavL or ANO1. Thus, the spatiotemporal characteristics of Type II cells and their dependence upon CavL and ANO1 all suggest that these cells are viable candidates for the generation of SWs and tone in the IAS.

Rome IV Functional Gastrointestinal Disorders and Health Impairment in Subjects With Hypermobility Spectrum Disorders or Hypermobile Ehlers-Danlos Syndrome

Individuals with hypermobility spectrum disorder or hypermobile Ehlers-Danlos Syndrome (HSD/hEDS) are increasingly encountered by gastroenterologists and pose complex clinical challenges. Uncontrolled studies have found functional gastrointestinal disorders (FGIDs) to be common in patients with HSD/hEDS. Some patients have somatic symptoms (medically unexplained symptoms) that might affect FGIDs. We performed a case-control study to determine the prevalence of and factors associated with Rome IV FGIDs in subjects with HSD/hEDS compared with age- and sex- matched population-based controls. An online general health survey was completed by 603 individuals with HSD/hEDS in October 2018 (cases) and 603 matched individuals from the population of the United Kingdom (controls) in 2015. The mean participant age was 39 yrs, and 96% were women. The survey included questions about Rome IV FGIDs, non-GI and non-musculoskeletal somatic symptoms (maximum number, 10), quality of life, medical history and healthcare use. The prevalence of FGIDs was compared between cases and controls, with subsequent logistic regression models - adjusting for the number of somatic symptoms - used to determine the associations for FGIDs in HSD/hEDS compared with controls. Nearly all subjects (98%) with HSD/hEDS fulfilled symptom-based criteria for 1 or more Rome IV FGIDs, compared with 47% of controls (P < .0001). The gastrointestinal regions most commonly affected by FGIDs in individuals with HSD/hEDS and control subjects were the bowel (90% vs 40% of controls), gastroduodenal (70% vs 13% of controls), esophageal (56% vs 6% of controls), and anorectal (53% vs 9% of controls); P < .0001. A higher proportion of subjects with HSD/hEDS had FGIDs in 2 or more regions (84% vs 15% of controls; P < .0001). Subjects with HSD/hEDS also reported a significantly higher number of non-GI and non-musculoskeletal somatic symptoms (7.1 vs 3.3 in controls), lower quality of life, and greater healthcare use, including abdominal surgeries and medication use (for example, 84% used analgesics compared with 29% of controls). Almost 40% of subjects with HSD/hEDS reported a diagnosis of chronic fatigue syndrome and/or fibromyalgia. Following adjustments for somatic symptoms, the association for FGIDs in subjects with HSD/hEDS was reduced by as much as 4-fold and in some instances was eliminated. In a large case-control study of persons with HSD/hEDS, almost all of the cases met criteria for Rome IV FGIDs, incurred considerable health impairment, and had high healthcare use. Patients with HSD/hEDS frequently have somatic symptoms that should be treated to reduce the high burden of gastrointestinal illness in this population.

Novel organic/inorganic hybrid nanoparticles as enzyme-triggered drug delivery systems: Dextran and Dextran aldehyde coated silica aerogels

Today, different therapeutic approaches are being developed because of the increased risk of colorectal cancer. In this context, we synthesized organic/inorganic hybrid nanoparticles using dextran (Dex) and dextran aldehyde (Dex-CHO) as organic polymers for the coating of inorganic silica aerogels. These Dex and Dex-CHO coated silica aerogels served as enzyme-triggered and colon targeted 5- Fluorouracil (5-FU) delivery systems. To improve the efficiency of drug loading and Dex/Dex-CHO coating, the surface of the silica aerogel was functionalized with 3-(aminopropyl)triethoxysilane (APTES). Enzyme-responsive drug release studies were performed with dextranase enzyme in simulated colonic fluid and cytotoxicity of aerogels on the colorectal adenocarcinoma cell line (Caco-2) were investigated by MTT assay. It was demonstrated that the release of 5-FU from Dex and Dex-CHO coated silica aerogels in simulated gastric and intestinal fluids was 1.7% and 3.4%, respectively, while the amount of 5-FU released from uncoated silica aerogels in these media was 86.4%. On the other hand, in the dextranase containing colonic medium 5-FU release in 12 h, straight after degradation of dextran by dextranase, was 24% and 13.4% from Dex and Dex-CHO coated silica aerogels, respectively. MTT assay results of unmodified, amine-modified, Dex and Dex-CHO coated silica aerogels did not show any significant cytotoxic effect on Caco-2 cells. However, MTT assay results of 5-FU loaded silica aerogels (unmodified, amine-modified, Dex and Dex-CHO coated) showed a decrease in the viability of Caco-2 cells. These results demonstrate that Dex and Dex-CHO coated silica aerogels are biocompatible nanoparticles that are not affected by the upper gastrointestinal regions and are powerful enzyme-triggered drug delivery systems for drug targeting to the colon area.

Characterisation and comparison of the mucosa-associated bacterial communities across the gastrointestinal tract of stranded green turtles, &lt;em&gt;Chelonia mydas&lt;/em&gt;

Chelonia mydas are primarily herbivorous long-distance migratory sea turtles that contribute to marine ecosystems. Extensive research has been conducted to restore the populations of green turtles. Little is known about their gut microbiota which plays a vital role in their health. We investigated the mucosa-associated bacterial communities across the gastrointestinal (GI) tract of a total four (3, juvenile and 1, adult) stranded green turtles. Samples taken from four GI regions including oesophagus, stomach, small intestine and large intestine were analysed by high-throughput sequencing targeting hypervariable V1-V3 regions of the bacterial 16S rRNA gene. Bacterial diversity and richness decreased longitudinally along the GI tract from oesophagus to the small intestine of stranded turtles. The large intestine showed a higher bacterial diversity and richness compared to small intestine. The bacterial community of green turtles' GI tract was largely dominated by Firmicutes, Proteobacteria, Actinobacteria, Bacteroidetes and Fusobacteria. Aerobic and facultative anaerobic bacteria prevailed primarily in the oesophagus while anaerobes (Lachnospiraceae, Peptostreptococcaceae and Ruminococcaceae) constituted the bulk of large intestinal microbiota. Firmicutes dominated the GI tract except within the small intestine where Proteobacteria prevailed. At the OTU level, six percent of the total OTUs (>1% relative abundance) were common in all GI regions. This is a comprehensive characterisation of bacterial microbiota across the GI tract in green turtles which will provide a reference for future studies on turtle gut microbiome and their metabolism to improve their health and nutrition during rehabilitation.

Calcium-oligochitosan-pectin microcarrier for colonic drug delivery

Pectin-based hydrogel microcarriers have shown promise for drug delivery to the colonic region. Microcarriers must remain stable throughout the upper gastrointestinal tract for effective colonic delivery, an issue that traditional pectin-based microcarriers have faced. The positively-charged natural biopolymer oligochitosan and divalent cation Ca2+ were used to dually cross-link pectin-based hydrogel microcarriers to improve carrier stability through simulated gastric and intestinal environments. Microcarriers were characterized with Scanning Electron Microscope and Fourier-Transform Infrared analysis. An optical microscope was used to observe the change of microcarrier size and morphology over time in the simulated gastrointestinal environments. Fluorescently-labeled Dextran was used as a model drug for this system. Calcium-Oligochitosan-Pectin microcarriers exhibited relatively small drug release in the upper gastrointestinal regions and were responsive to the high pH and enzymatic activity of simulated colonic environment (over 94% release after 2 h), suggesting great potential for colonic drug delivery.

Clinical outcome of personalised treatment guided by genome and transcriptome sequencing in patients with neuroendocrine neoplasms: Updated results from the German NCT/DKTK MASTER trial

Abstract Background Therapeutic options for neuroendocrine neoplasms (NEN) are limited, and only few NEN patients have been treated according to their individual genomic profile. We report the molecular and clinical characteristics of a large NEN cohort that was studied by prospective whole-genome (WGS), whole-exome (WES), and transcriptome sequencing (TS) within the NCT/DKTK MASTER precision oncology program. Methods Between 2013 and 2018, a total of 115 patients with advanced, heavily pretreated NEN were enrolled. Primary sites were gastrointestinal (n = 30), pancreatic/hepatic (n = 33), pulmonary (n = 20), genitourinary (n = 13), head/neck (n = 6), and other regions (n = 11). Grading according to the 2017 and 2019 WHO classification was neuroendocrine tumor (NET) G1, n = 12; NET G2, n = 31; NET G3, n = 12; neuroendocrine carcinoma, n = 36; mixed neuroendocrine-non-neuroendocrine neoplasm, n = 12; and other, n = 11. Results Of WES (n = 72) or WGS (n = 44) and TS (n = 92) were discussed in a multidisciplinary molecular tumor board. Recommendations were given in 103 cases (94%) for the following potential treatment alternatives: tyrosine or serine/threonine kinase inhibition (n = 67), PARP inhibition (n = 41), immunotherapy (n = 33), mTOR inhibition (n = 30), CDK4/6 inhibition (n = 19), MEK inhibition (n = 12), platinum-based chemotherapy (n = 7), BET inhibition (n = 7), anti-claudin18.2 (n = 5) or anti-DLL3 antibody treatment (n = 8). Somatic hypermutation (>10 mutations/megabase) was seen in 8.6% of patients. Treatment options could be implemented in 35 patients, of which 31 were evaluable for response: partial response, n = 10; mixed response, n = 1; stable disease, n = 11; progressive disease, n = 9; resulting in an overall response rate of 32% and a disease control rate of 71%. Conclusions Comprehensive genomic and transcriptomic characterization provides new insight into the molecular pathogenesis of NEN and creates therapeutic opportunities in a significant proportion of NEN patients who have exhausted standard treatment. Legal entity responsible for the study NCT Heidelberg & German Cancer Consortium. Funding German Cancer Research Center. Disclosure S. Kreutzfeldt: Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Honoraria (self): Novartis; Research grant / Funding (institution): Roche; Travel / Accommodation / Expenses: Pfizer. C.E. Heilig: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Honoraria (institution), Travel / Accommodation / Expenses: Lilly; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Celgene; Travel / Accommodation / Expenses: Teva; Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Pfizer. All other authors have declared no conflicts of interest.

Identification of pheasant ghrelin and motilin and their actions on contractility of the isolated gastrointestinal tract

Motilin and ghrelin were identified in the pheasant by molecular cloning, and the actions of both peptides on the contractility of gastrointestinal (GI) strips were examined in vitro. Molecular cloning indicated that the deduced amino acid sequences of the pheasant motilin and ghrelin were a 22-amino acid peptide, FVPFFTQSDIQKMQEKERIKGQ, and a 26-amino acid peptide, GSSFLSPAYKNIQQQKDTRKPTGRLH, respectively. In in vitro studies using pheasant GI strips, chicken motilin caused contraction of the proventriculus and small intestine, whereas the crop and colon were insensitive. Human motilin, but not erythromycin, caused contraction of small intestine. Chicken motilin-induced contractions in the proventriculus and ileum were not inhibited by a mammalian motilin receptor antagonist, GM109. Neither atropine (a cholinergic receptor antagonist) nor tetrodotoxin (a neuron blocker) inhibited the responses of chicken motilin in the ileum but both drugs decreased the responses to motilin in the proventriculus, suggesting that the contractile mechanisms of motilin in the proventriculus was neurogenic, different from that of the small intestine (myogenic). On the other hand, chicken and quail ghrelin did not cause contraction in any regions of pheasant GI tract. Since interaction of ghrelin and motilin has been reported in the house musk shrew, interaction of two peptides was examined. The chicken motilin-induced contractions were not modified by ghrelin, and ghrelin also did not cause any contraction under the presence of motilin, suggesting the absence of interaction in both peptides. In conclusion, both the motilin system and ghrelin system are present in the pheasant. Regulation of GI motility by motilin might be common in avian species. However, absence of ghrelin actions in any GI regions suggests the avian species-related difference in regulation of GI contractility by ghrelin.

Budesonide-Loaded Eudragit S 100 Nanocapsules for the Treatment of Acetic Acid-Induced Colitis in Animal Model.

Nanoparticles for colon-drug delivery were designed and evaluated to solve many discrepancy issues as insufficient drug amount at diseased regions, high adverse effects of released drugs, and unintentionally premature drug release to noninflamed gastrointestinal regions. Herein, the prepared budesonide-loaded Eudragit S 100/Capryol 90 nanocapsules for the treatment of inflammatory bowel disease. Nanocapsules were prepared efficiently by nanoprecipitation technique and composed mainly of the pH-sensitive Eudragit S 100 polymeric coat with a semisynthetic Capryol 90 oily core. Full 31 × 21 factorial design was applied to obtain optimized nanocapsules. Optimal nanocapsules showed mean particle size of 171nm with lower polydispersity index indicating the production of monodispersed system and negative zeta-potential of - 37.6mV. Optimized nanocapsules showed high encapsulation efficiency of 83.4% with lower initial rapid release of 10% for first 2h and higher rapid cumulative release of 72% after 6h. The therapeutic activity of the prepared budesonide-loaded nanocapsules was evaluated using a rat colitis model. Disease activity score, macroscopical examination, blood glucose level, and histopathological assessment showed marked improvements over that free drug suspension. Obtained results demonstrate that the budesonide-loaded Eudragit S 100 nanocapsules are an effective colon-targeting nanosystem for the treatment of inflammatory bowel disease. Capryol 90 was found to be a successful, and even preferred, alternative to benzyl benzoate, which is commonly employed as the oil core of such nanocapsules.

Gastrointestinal Targeted Sampling and Sensing via Embedded Packaging of Integrated Capsule System

Here, we introduce a wireless platform developed to leverage biochemical characteristics of various gastrointestinal (GI) secretions to selectively dissolve pH-sensitive polymers used as coatings over a 3-D printed biocompatible capsule, allowing fluid entry into sensing chambers containing capacitive sensors. Ingestible capsule technology is increasing prevalence in autonomously accessing regions of GI that otherwise require clinical intervention. Our platform is operated using a 3.3-V power source with sensors, possessing a 0.3–220-pF dynamic range with a sensitivity of $3.2\times10^{-3}$ pF/mV that relay the change in capacitance to a smart system-in-package, which is then transmitted via Bluetooth low energy to an external Android phone. The system is tested with a variety of polymers, which are used in the pharmaceutical industry, to control dissolution at different GI regions characteristic of a specific pH profile. This real-time, cost-effective, and user-friendly platform will ultimately be used to test alternative coating materials that respond to specific biomarkers present in GI secretions, offering significant potential for enhancing gut diagnostics. [2018-0249]

Generation of Spontaneous Tone by Gastrointestinal Sphincters.

An important feature of the gastrointestinal (GI) muscularis externa is its ability to generate phasic contractile activity. However, in some GI regions, a more sustained contraction, referred to as "tone," also occurs. Sphincters are muscles oriented in an annular manner that raise intraluminal pressure, thereby reducing or blocking the movement of luminal contents from one compartment to another. Spontaneous tone generation is often a feature of these muscles. Four distinct smooth muscle sphincters are present in the GI tract: the lower esophageal sphincter (LES), the pyloric sphincter (PS), the ileocecal sphincter (ICS), and the internal anal sphincter (IAS). This chapter examines how tone generation contributes to the functional behavior of these sphincters. Historically, tone was attributed to contractile activity arising directly from the properties of the smooth muscle cells. However, there is increasing evidence that interstitial cells of Cajal (ICC) play a significant role in tone generation in GI muscles. Indeed, ICC are present in each of the sphincters listed above. In this chapter, we explore various mechanisms that may contribute to tone generation in sphincters including: (1) summation of asynchronous phasic activity, (2) partial tetanus, (3) window current, and (4) myofilament sensitization. Importantly, the first two mechanisms involve tone generation through summation of phasic events. Thus, the historical distinction between "phasic" versus "tonic" smooth muscles in the GI tract requires revision. As described in this chapter, it is clear that the unique functional role of each sphincter in the GI tract is accompanied by a unique combination of contractile mechanisms.

Gastrointestinal parasites of common African toad (&lt;i&gt;Bufo regularis&lt;/i&gt;) in Umuahia South, Abia State, Nigeria

Information on the parasites of common African toads ( Bufo regularis ) is still limited, judging by the global efforts to conserve amphibians. This informed the decision to provide baseline data of the gastrointestinal parasites of B. regularis of Umuahia South Local Area (LGA) of Abia State, Nigeria. Using standard methods, 321 B. regularis comprised of males, n =145, 45.17% and females n =176, 54.83% were collected from five communities (Old Umuahia, Amakama, Okwu, Ubakala and Agbama) in Umuahia South LGA, between June and November 2014. They were later examined for gastrointestinal parasites using standard procedures. Data analysis revealed that male B. regularis had more (n = 61, 19.03%) gastrointestinal parasites than the females (n = 58, 18.69%). Different species of gastrointestinal parasites belonging to class Cestoda ( Osphiotaenia nigriocollis, Lanfrediella sp and Proteocephalid Cestode larva ); Trematoda ( Messoceolium monody and Echinostoma revolutum ), Nematoda ( Amplicaecum africanum, Rhabdias bufonis, Ascaridoid, Oswaldocruzia pipiens and Camallanus sp ) and Protozoa ( Nyctotheroides bambuiensis, Lankesterellla bufonis and Protoopolina sp ) were identified with prevalence 20.25%, 4.36%, 7.48% and 4.98%, respectively. Prevalence of parasites varied significantly (p<0.05) across the gastrointestinal regions. Though no symptom of disease condition was established in all the B. regularis examined, high presence of gastrointestinal parasites could pose a threat to their existence. Keywords : Bufo regularis; cestoda; gastrointestinal parasitism.

CAMP Catalyzing Phosphodiesterases Control Cholinergic Muscular Activity But Their Inhibition Does Not Enhance 5-HT4 Receptor-Mediated Facilitation of Cholinergic Contractions in the Murine Gastrointestinal Tract.

Background: As the signal transduction of 5-HT4 receptors on cholinergic neurons innervating smooth muscle is controlled by phosphodiesterase (PDE) 4 in porcine stomach and colon, and human large intestine, the in vivo gastroprokinetic effects of a 5-HT4 receptor agonist might be enhanced by combination with a selective PDE4 inhibitor. The presence of 5-HT4 receptors on cholinergic neurons towards murine gastrointestinal circular muscle was recently shown. If the control of this receptor pathway by PDE4 is also present in mice, this might be a good model for in vivo testing of the combination therapy. Therefore this study investigates the role of cAMP catalyzing PDEs in smooth muscle cell activity and in the intraneuronal signal transduction of the 5-HT4 receptors in the gastrointestinal tract of C57Bl/6J mice.Methods: In circular smooth muscle strips from murine fundus, jejunum, and colon, submaximal cholinergic contractions were induced by either electrical field stimulation (EFS) or by carbachol (muscarinic receptor agonist). The influence of the PDE inhibitors IBMX (non-selective), vinpocetine (PDE1), EHNA (PDE2), cilostamide (PDE3), and rolipram (PDE4) was tested on these contractions and on the facilitating effect of a submaximal concentration of prucalopride (5-HT4 receptor agonist) on EFS-induced contractions.Results: In the three gastrointestinal regions, IBMX and cilostamide concentration-dependently decreased carbachol- as well as EFS-induced contractions. Some inhibitory effect was also observed with rolipram. In the fundus a non-significant trend for an enhancement of the facilitating effect of prucalopride on EFS-induced contractions was observed with IBMX, but none of the selective PDE inhibitors enhanced the facilitating effect of prucalopride in fundus, jejunum or colon.Conclusion: In analogy with the porcine gastrointestinal tract, in murine fundus, jejunum, and colon circular smooth muscle PDE3 is the main regulator of the cAMP turnover, with some contribution of PDE4. In contrast to the porcine gastrointestinal tract, the in vitro facilitation of electrically induced cholinergic contractions by 5-HT4 receptor stimulation could not be enhanced by specific PDE inhibition. The C57Bl/6J murine model is thus not suitable for in vivo testing of a 5-HT4 receptor agonist combined with a selective PDE4 inhibitor.

Partial characterization, quantification and activity of pancreatic lipase in the gastrointestinal tract of Totoaba Macdonaldi

Lipids are one of the main macronutrients that constitute balanced feeds used in aquaculture. Adequate utilization of dietary lipid is influenced by the activity of pancreatic lipase, one of the enzymes that promotes digestion of dietary lipids in the gastrointestinal tract of fish. The culture of Totoaba macdonaldi is quite recent; its nutritional requirements have been partially established. Knowing the characteristics of pancreatic lipase for this species could help optimize the dietary lipids included in balanced feeds for its culture. Therefore, the aim of this work is to partially characterize and evaluate the enzymatic activity of pancreatic lipase for T. macdonaldi. Biological indices showed that experimental organisms had a good nutritional status. Pancreatic lipase molecular weight was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and its activity was evaluated in crude enzymatic extracts from different gastrointestinal tract regions. The molecular weight of lipase was estimated to be 70.4 kDa; the highest lipolytic activity was observed at 45?C and at a pH optimum of 8.0 in the anterior intestine and pyloric caeca, where the concentration and activity of the enzyme was significantly higher (P=0.004) compared to the distal parts of the intestine. Biochemical characteristics observed for the pancreatic lipase of T. macdonaldi are quite similar to other lipases of fish cultured worldwide; results provided in this study will help understand the role this lipolytic enzyme plays in the digestive process of this species.

Microanatomical profiles on the lymphatic system in the human ampulla of Vater (immunohistochemistry and scanning electron microscopy).

Little information is available regarding microanatomy of lymphatic system in the ampulla of Vater, though it is of critical importance for an understanding of tumor progression via the lymphatics and determination of surgical strategy. The present study, therefore, aimed to demonstrate the distribution and microanatomical profiles on the lymphatic system in the ampulla. The fine distribution and structure of the lymphatic vessels were investigated in the ampulla and the stomach by immunohistochemistry for lymphatic- (D2-40) and blood vascular- (CD31) specific markers and scanning electron microscopy. The densities of lymphatic and blood vessels were also compared. The duodenal papilla densely developed the lymphatics with distinct aspects of lymphatic capillaries, together with blood vessels. The density of lymphatic capillaries in the extramuscular layer in the ampulla was higher than those of both the other ampullary layers and the gastric extramuscular (subserosal) layer. The ampulla of Vater showed widespread lymphatic capillaries throughout the entire wall. The specific vascular system is suited to produce lymph everywhere and drain without via such a large vessel as lymphatic collector. This suggests that tumor cells invade the lymphatics and metastasize more easily in the ampulla than in the other gastrointestinal regions.

Expression profiling of Tas2r genes reveals a complex pattern along the mouse GI tract and the presence of Tas2r131 in a subset of intestinal Paneth cells.

The chemical variability of the intestinal lumen requires the presence of molecular receptors detecting the various substances naturally occurring in the diet and as a result of the activity of the microbiota. Despite their early discovery, intestinal bitter taste receptors (Tas2r) have not yet been assigned an unambiguous physiological function. Recently, using a CRE-recombinant approach we showed that the Tas2r131 gene is expressed in a subset of mucin-producing goblet cells in the colon of mice. Moreover, we also demonstrated that the expression of the Tas2r131 locus is not restricted to this region. In the present study we aimed at characterizing the presence of positive cells also in other gastrointestinal regions. Our results show that Tas2r131+ cells appear in the jejunum and the ileum, and are absent from the stomach and the duodenum. We identified the positive cells as a subpopulation of deep-crypt Paneth cells in the ileum, strengthening the notion of a defensive role for Tas2rs in the gut. To get a broader perspective on the expression of bitter taste receptors in the alimentary canal, we quantified the expression of all 35 Tas2r genes along the gastrointestinal tract by qRT-PCR. We discovered that the number and expression level of Tas2r genes profoundly vary along the alimentary canal, with the stomach and the colon expressing the largest subsets.

The role of surgical management in primary small bowel lymphoma: A single-center experience

IntroductionInformation on primary small intestinal lymphoma is more limited than for gastric lymphoma because most of the previous studies did not focus on the former. Few prognostic indicators in primary intestinal lymphoma have been reliably established because of limited patient numbers and variations in criteria for patient selection. In this study, we retrospectively reviewed the clinical and pathological characteristics of small intestinal lymphoma cases from our hospital, to determine prognostic factors and to clarify the effect of surgical resection on prognosis. MethodsEighty-two patients were enrolled in this retrospective study between January 1997 and December 2012. Patients were divided into two groups based on whether or not they underwent surgical management. Gross resection was defined as complete removal of the primary lesion(s), as confirmed by the naked eye. Combined therapy refers to concurrent surgery and chemotherapy. The clinicopathological characteristics and long-term outcomes of patients were analyzed and compared between the two groups. ResultsMost of the patients had abdominal pain (75.6%), and some had loss of body weight (29.3%) and bowel perforation (22.0%). Sixty-two patients (75.6%) underwent surgical management. Patients in the surgery group presented with fewer B symptoms (fever, night sweats, and weight loss; P = 0.035) but more bulky disease (P = 0.009). The ileocecal region was the most common site of solitary involvement (34.1%). The most common reason for surgery was for tumor-related complications (61.3%). Seven patients (11.3%) developed major complications of surgery, but these were not related to the indication, timing, or type of surgery. Only major surgical complications were statistically significant in relation to early mortality (P = 0.004). The estimated 5-year progression-free survival (PFS) was 35.1% and 5-year overall survival (OS) was 43.2%. Univariate analysis revealed that patients in the surgery group had improved 5-year PFS (P = 0.028). T-cell lymphoma, involvement of multiple gastrointestinal regions and extranodal involvement, higher scores for International Prognostic Index (IPI), more advanced Ann Arbor stage, lactate dehydrogenase (LDH) levels above 215 U/L, and management without combined therapy were prognostic for shorter PFS and OS in univariate analyses. Individuals who received R0 resection or gross resection had improved 5-year PFS and OS. Cox regression analysis demonstrated that primary T-cell lymphoma was an independent negative prognostic factor for both OS and PFS. ConclusionCombined therapy is an independent prognostic factor for long-term survival in small intestinal lymphoma. Gross resection is recommended in patients with small intestinal lymphoma and leads to improved PFS without significantly increasing the risk of complications. Emergency surgery does not lead to poor prognosis. However, caution is warranted in the management of all patients, because of the high risk of post-operative complications and potential for early mortality.

Comparative analysis on microbial community associated with different gastrointestinal regions of wild northern snakehead Channa argus Cantor, 1842

Microbial communities in different gastrointestinal regions (stomach, foregut, midgut, and hindgut) of the northern snakehead Channa argus (Cantor, 1842) were compared by polymerase chain reaction and partial 16S rDNA sequencing. A total of 194, 140, 212, and 122 OTUs were detected in the stomach, foregut, midgut, and hindgut, respectively. Significant differences were found in the Sobs, ACE, Shannon, and Simpson indices among samples (P < 0.05). The gastrointestinal microbial community of C. argus consisted predominantly of Proteobacteria with either Halomonas, Shewanella, Plesiomonas, or Sphingomonas. Fusobacteria, Firmicutes, and Bacteroidetes also existed in the gastrointestinal tracts. However, significant differences were found in the compositions of microbial community among the four regions (P < 0.05). Cyanobacteria and Spirochetes were significantly higher in the midgut and hindgut (P < 0.05). Fusobacteria and Firmicutes were dominant in the hindgut and foregut, respectively (P < 0.05). Proteobacteria was the lowest in the hindgut (P < 0.05). At genus level, Cetobacterium and Plesiomonas were significantly higher in the hindgut than in the other three samples (P < 0.05). Clostridium and Prevotella were the highest in the midgut (P < 0.05). Halomonas, Shewanella, and Sphingomonas were the highest in the foregut (P < 0.05). Paracoccus and Vibrio were the highest in the stomach. Several genera were only detected in certain regions, as follows:stomach, Paracoccus and Vibrio; foregut, Halomonas, Shewanella, and Sphingomonas; midgut, Clostridium and Prevotella; and hindgut, Cetobacterium and Plesiomonas (P < 0.05). At the species level, Acinetobacter rhizosphaerae was only detected in the stomach. Prevotella copri and Clostridium perfring were not detected in the foregut and midgut, respectively, whereas Prevotella copri and Faecalibacterium pra were not detected in the hindgut. These findings provide valuable information on the microbial community in each gastrointestinal region of C. argus. Moreover, this study indicated that microbial community was not only related to rearing environment but also to the physico-chemical characteristics of each gastrointestinal region.

Tissue Engineering Functional Gastrointestinal Regions: The Importance of Stem and Progenitor Cells.

The intestine shows extraordinary regenerative potential that might be harnessed to alleviate numerous morbid and lethal human diseases. The intestinal stem cells regenerate the epithelium every 5 days throughout an individual's lifetime. Understanding stem-cell signaling affords power to influence the niche environment for growing intestine. The manifold approaches to tissue engineering may be organized by variations of three basic components required for the transplantation and growth of stem/progenitor cells: (1) cell delivery materials or scaffolds; (2) donor cells including adult stem cells, induced pluripotent stem cells, and in vitro expansion of isolated or cocultured epithelial, smooth muscle, myofibroblasts, or nerve cells; and (3) environmental modulators or biopharmaceuticals. Tissue engineering has been applied to the regeneration of every major region of the gastrointestinal tract from esophagus to colon, with scientists around the world aiming to carry these techniques into human therapy.