Duodenal Segments Research Articles

PSXIII-7 Effect of Dietary Supplementation of Lactobacillus Rhamnosus on Blood Profiles, Intestinal Morphology, Immune Responses, and Gene Expression of Tight Junction Proteins and Cytokines of Weaned Pigs

Abstract Dietary probiotics were used in the animal feeds because of the beneficial effect of improving gut health and immune responses as one of the potential alternatives to antibiotics. This study was conducted to evaluate the effect of dietary supplementation of Lactobacillus rhamnosus (ILDONG Bioscience Co. Ltd., Pyeongtaek, Republic of Korea) on blood profiles, small intestinal morphology, immune responses, and gene expression of tight junction proteins and inflammatory cytokines in ileum of weaned pigs. A total of 40 weaned pigs [6.21 ± 0.55 kg of initial body weight (BW); 28-day old] were allotted to 2 dietary treatments (4 pigs/pen; 5 replicates/treatment) in a randomized complete block design (block: initial BW) and fed for 4 weeks. Dietary treatments were 1) a commercial basal nursery diet (CON), and 2) CON + 0.02% Lactobacillus rhamnosus IDCC 3201 (PRO). The blood samples were collected from randomly selected 1 pig per pen on day 1, 7, 14, and 28 for blood profiles and immune responses. On the last day of experiment, the pigs were euthanized to collect duodenal, jejunal, and ileal segments for intestinal morphology and gene expression analysis. Intestinal morphology was measured villus height, width, area, crypt depth, villus height to crypt depth ratio, and number of goblet cells by hematoxylin and eosin staining method. The blood profiles were measured by using an automated hematology analyzer. The serum samples were used to measure concentrations of cytokines and cortisol by using porcine immunoassay ELISA kits. The gene expression of tight junction proteins and cytokines were measured by qRT-PCR. Data were analyzed by PROC GLM procedure of SAS. Experimental unit was a pen. Statistical model for blood profiles, immune responses, and intestinal morphology included dietary treatment as a main effect and initial BW as a covariate. The t-test was used for ileal gene expression. Pigs fed PRO had lower (P < 0.05) platelet level, crypt depth in duodenum and ileum, serum tumor necrosis factor-α (TNF-α), and interleukin-6 than those fed CON. The pigs fed PRO downregulated (P < 0.05) TNF-α and interleukin-8 genes compared with those fed CON, but upregulated (P < 0.05) claudin-1 and claudin-2 genes. In conclusion, probiotic Lactobacillus rhamnosus supplementation in nursery diet improved gut health through modulating blood profiles and immune responses, enhancing intestinal morphology, and regulating tight junction protein genes expression in ileum of weaned pigs.

Giant gastric polyp mimicking a duodenal tumor

Inflammatory fibroid polyps are very rare gastrointestinal tumors. We present the case of a 66-year-old woman with severe anemia and a giant gastric polyp which had intermittent duodenal intussusception. Ultrasonography showed increased gastric wall thickness and suspected an ampulloma, as revealed also by endoscopy and computed tomography. Ultrasonography reassessment showed later the intragastric mass, which was confirmed by endosonography: giant pediculated hypervascular polyp suggesting malignancy. Challenging phenomena at different investigation methods were due to intermittent protrusion into the first duodenal segment mimicking an ampulloma, but without gastric outlet syndrome or a malignant component, despite the severe anemia. Abnormal US aspect of the stomach in clinical context of anemic syndrome, requires EUS with biopsies in order to confirm underlying lesions. The particularities of this case are the: discordance between imaging aspects and the protrusion into the first duodenal segments with consecutive cholestasis mimicking an ampulloma and the lack of gastric outlet syndrome.

Physiological Effects of Condensed Tannins from Black Currant (Ribes nigrum L.) on Isolated Rat Duodenal Contraction

Condensed tannins (CTs) extracted from various plants have been shown to possess antioxidant, antidiabetic, anthelmintic, anti-palatable and anti-diarrhea activity. Black currant (Ribes nigrum L.), a native plant of northern Europe and Asia, is rich in phenolic compounds, including CTs. Among the biological activities of CTs, their astringent property is likely to affect gastrointestinal motility. This study aimed to investigate the physiological effect of CTs from black currant (R. nigrum L.) leaves on isolated rat duodenal contraction. Duodenal segments were fixed in organ baths containing carbogen aerated Krebs solution at the resting tension of 0.7 - 0.8 g. The frequency, amplitude, and tone of duodenal contraction were recorded. Either CTs or acetylcholine (ACh) were cumulatively added into the bath at the concentration of between 0.001 - 10 µg/mL and 10–8 - 10–4 M, respectively. The mechanisms of CTs and ACh actions were studied using muscarinic receptor antagonist (atropine, 1.55×10–5 M) and calcium channel blocker (verapamil, 10–6 M). It is found that CTs at the concentration between 0.001 - 10 µg/mL had no direct effect on duodenal frequency, amplitude, and tone of contraction, whereas ACh showed a significant increase in tonic contraction, was suppressed by atropine. Interestingly, in the presence of atropine and verapamil, CTs showed a further significant decrease in the amplitude of duodenal contraction compared to the effect of these 2 blockers alone. It is concluded that CTs would synergize the activity of the muscarinic receptor antagonist and the calcium channel blocker at duodenal enteric neurons or smooth muscle membrane. However, the use of CTs from black currant (R. nigrum L.) leaves to treat gastro-intestinal disorders while having muscarinic receptor antagonist or calcium channel blocker need cautions.
 HIGHLIGHTS
 
 Black currant (Ribes nigrum L.), a native plant of northern Europe and Asia, is rich in phenolic compounds including condensed tannins (CTs) and their astringent property is likely to affect gastrointestinal motility
 CTs isolated from leaves of black currant (R. nigrum L.) at the physiological doses (0.001 - 10.0 µg/mL) have no direct effect on isolated rat duodenal contraction
 CTs may possess the synergistic or additive effect with either atropine, a nonselective muscarinic receptor, or verapamil, a calcium channel blocker on duodenal amplitude of contraction
 
 GRAPHICAL ABSTRACT

Cross-sectional Imaging of the Duodenum: Spectrum of Disease.

Cross-sectional Imaging of the Duodenum: Spectrum of Disease.

The association of Curcuma and Scutellaria plant extracts improves laying hen thermal tolerance and egg oxidative stability and quality under heat stress conditions

Chronic exposure to high ambient temperatures is detrimental to laying hen performance and egg quality. Plant secondary metabolites may alleviate effects, partly due to their antioxidant activities. Herein, we investigated the effects of dietary supplementation with a phytonutrient solution (PHYTO) consisting of a plant extract combination of Scutellaria baicalensis and Curcuma longa on young layers (25–32 wk of age) raised under naturally elevated temperature conditions. Four hundred, 24-wk-old Lohmann hens were allocated in 50 cages and, after a week of adaptation, were offered a diet either containing 2 g/kg of PHYTO or not, for 8 wk. Hen BW was measured at the beginning and end of the trial, and egg production and feed intake were recorded weekly. At week 32, four eggs per cage were collected to determine egg quality characteristics as well as the rate of lipid and albumen oxidation in fresh eggs. At the end of the trial, two hens per cage were blood sampled for assessment of biochemical markers, one of which was euthanized for histopathological evaluation of the liver and intestine and assessment of intestinal histomorphometry. The herbal mixture supplementation significantly increased egg production rate at weeks 28 and 29 and for the overall production period, and feed efficiency at weeks 26–29. In addition, the degree of liver necrosis and microvascular thrombosis was lower (P < 0.05) whereas intestinal villosity was greater in duodenal and jejunal segments (P < 0.05) in the PHYTO compared to the control group. Supplementation also reduced (P < 0.05) blood concentrations of corticosterone, alanine aminotransferase activity, and TBARS, and a reduction in catalase activity was observed. Egg quality characteristics were not affected, except for eggshell thickness, egg diameter, and eggshell breaking strength that were superior in the PHYTO group (P < 0.05). PHYTO supplementation significantly improved egg lipid oxidation status of fresh eggs. In conclusion, supplementation with PHYTO improved laying hen productivity and egg quality, which was associated with an improvement in laying hen thermotolerance.

Use of flavonoids with antioxidant potential to prevent morphophysiological intestinal damage induced by the antineoplastic fluorouracil

Intestinal mucositis is a common complication associated with 5‐Fluorouracil (5‐FU) treatment, a chemotherapeutic agent widely used for cancer treatment. Characterized by inflammatory and/or ulcerative processes, intestinal mucositis is pathophysiologically based on the promotion of direct damage to the epithelium resulting from oxidative stress from the generation of reactive oxygen species (ROS). Flavonoids such as rutin, troxerutin and isoquercitrin, obtained from D. Gardnerian, have been reported with antioxidant and anti‐inflammatory properties. The present study aimed to evaluate the effect of flavonoids obtained from D. Gardnerian on 5‐fluorouracil‐induced intestinal mucositis in Swiss mice and identification of possible interactions of flavonoids in pro‐ inflammatory proteins. The mice (25‐30g) were divided into 4 groups (n=6): Saline group (NaCl 0.9%), 5‐FU group, Troxerutin group (150mg/kg troxerutin, orally) and Rutin group (300mg/kg rutin, orally). All animals except the Saline group received 5‐ FU at a concentration of 450 mg/kg in the first experimental protocol. To investigate morphological changes, periodic acid Schiff (PAS), toluidine blue, hematoxylin and eosin staining were performed. For the oxidative damage evaluation, the levels of the reduced antioxidant glutathione and the lipid peroxidation product, malondylaldehyde, of duodenal segments were determined. In silico molecular docking assays of the complexes formed between flavonoids (rutin, troxerutin and isoquercitrin) and the COX‐2, TNF‐α and NF‐kB enzymes were performed. The results showed that the antineoplastic 5‐FU promoted oxidative stress, evidenced by a decrease in reduced glutathione (GSH) and an increase in malondialdehyde (MDA) when compared to the saline group (p &lt;0.05). Furthermore, the administration of flavonoids rutin and troxerutin promotes a decrease in MDA levels and an increase in GSH reserves (p &lt;0.05), which culminate in attenuation of the oxidative stress promoted by the antineoplastic agent. The antioxidant effect of flavonoids corroborates the histopathological results, which show that both flavonoids have a significant reversal of antineoplastic‐induced morphological changes (p &lt;0.05), such as reduction of villus height, deepening of the crypts, decrease in goblet cells and increase in mast cells and inflammatory infiltrate. Finally, molecular docking showed that the flavonoids rutin, troxerutin and isoquercitrin show stable binding to the target sites of COX‐2, NF‐kB, TNF‐α, important pro‐inflammatory proteins in inflammatory and ulcerative processes such as intestinal mucositis. It was concluded that the antioxidant effect promoted by flavonoids is one of the protective mechanisms of these natural products of the D. Gardnerian tree to prevent the morphophysiological damage of 5‐FU induced intestinal mucositis.

Pancreas-preserving limited duodenal resection: Minimizing morbidity without compromising oncological adequacy.

Backgrounds/AimsPancreaticoduodenectomy is the most common procedure for the management of duodenal pathologies. However, it is associated with substantial morbidity and a low risk of mortality. Pancreas-preserving limited duodenal resection (PPLDR) can be performed under specific scenarios. We share our experience with PPLDR and its outcome.MethodsWe retrospectively analyzed a prospectively maintained database of patients undergoing limited duodenal resection in the form of wedge (sleeve) resection or segmental resection of one or more duodenal segments from March 2016 to March 2021 at a tertiary care center in North India.ResultsDuring the study period, 10 patients (including 9 males) underwent PPLDR. Five of these 10 patients showed primary duodenal or proximal jejunal pathology, while the remaining five had duodenal pathology involving an adjacent organ tumor. Four patients underwent wedge (sleeve) resection, while the remaining six underwent segmental duodenal resection of one or more duodenal segments. Mean hospital stay was 6 days (range, 3-11 days) without 30-day mortality. Morbidity occurred in 4 patients (Grade I-II, n = 3; Grade III, n = 1). All patients were alive and disease-free at the time of last follow-up. The mean follow-up duration was 23 months (range, 2-48 months).ConclusionsPPLDR is a safe and effective alternative for pancreaticoduodenectomy when selected carefully for specific tumor types and location.

The Effects of L-Carnitine on Gastrointestinal Contractility and Histological Changes in Rat Intestinal Ischemia-Reperfusion Injury

Ischemia-reperfusion (I/R) of the small intestine causes serious abdominal pathologies including tissue dysfunction and organ failure. L-carnitine (L-C), a powerful antioxidant, may help lessen the severity of these pathological effects since it plays a key role in energy metabolism. In this work we aimed to study the effects of L-C on the isolated ileal and duodenal contractility and histological changes in intestinal ischemia and reperfusion injury. Twenty eight Wistar rats were divided into four groups. The first group is the control group. Second group, I/R group, had rats submitted to 45-minutes of intestinal ischemia and to 45-minutes reperfusion. The third group, I/R+ L-C group, rats were treated with L-C 5 minutes before reperfusion and than submitted to ischemia. The fourth group, included rats that were treated with L-C without ischemia or reperfusion. Intestinal ischemia was conducted by obstructing superior mesentery arteries by silk loop. The ileal and duodenal segments were isolated and suspended in tissue bath. Contractile responses were induced by acetylcholine (Ach) and relaxation was achieved with phenylephrine. At the same time the terminal ileal and duodenal segments were examined for histological changes. Ach-induced contraction responses were higher in the I/R+L-C group, the L-C group, and the control group compared to the I/R group, in both ileal and duodenal segments. On the other hand, the phenylephrine-induced relaxations were higher in the I/R+L-C and L-C groups, especially in duodenal segments. In I/R group intestinal morphology was observed to be severely damaged whereas in I/R+L-C group the damage was noticeably lower possibly due to protective properties of L-C. I/R injury caused severe cellular damage response within the muscularis resulting in decreased gastrointestinal motility. Treatment with the L-C has significantly affected the gastrointestinal contractility. Also L-C treatment reduced the damage in intestinal morphology that occurs after IR injury.

Comparative Analysis on the Duodenal Microbiota Community in Geese Fed with the All-grass or Basal Diet

Geese (Anser cygnoides) possess stronger ability of roughage digestion and utilization than other poultries, hence, it has become the focus of attention of scientists. Duodenal, jejunum and ileum were mainly participated in food digestion and nutrient absorption, while the cecum was responsible for biological fermentation. Effects on the geese’s cecal microbiota community by feeding with the all-grass diet have been investigated, however, whether it had an influence on the geese’s duodenal microbiota community remains unexplored. To address this problem, geese feeding with the basal diet for 28 days (G1), the basal diet for 28 days and the all-grass diet for the following 14 days (G2), the basal diet for 42 days (G3) were selected, respectively. The duodenal segments of geese were collected and the hypervariable V3-V4 region of the bacterial 16S rRNA gene was sequencing. A total of 4 main phyla and 16 main genera were identified. Moreover, we also successfully identified that two taxa including the Helcococcus and Clostridium could be used as distinguishing biomarkers specific to G2. The functional profiles of the duodenum microbiota were mainly involved in the membrane transport (e.g. ABC transporters), amino acid metabolism, energy metabolism, metabolism of cofactors and vitamins, and cellular processes and signaling pathways in geese feeding with the all-grass diet. In conclusion, the all-grass diet could impact the composition of duodenal microbiota. However, to resolve the underlying mechanism of the fiber digesting and utilization in geese’s gut microbiota, the whole intestinal system needs to be assessed by further studies.

Potential impacts of diabetes mellitus and anti-diabetes agents on expressions of sodium-glucose transporters (SGLTs) in mice.

Sodium-glucose transporters (SGLTs) are important targets for therapeutic intervention of type 2 diabetes. This study aims to evaluate the physiological influences of diabetes mellitus and the potential impacts of metformin and fluoxetine on SGLTs expressions. Alterations of SGLT1 and SGLT2 were measured in organs involved in glucose homeostasis (kidney, intestine, liver and pancreas) of streptozotocin (STZ) and high-fat diet (HFD) induced diabetic mice by western blotting and real-time PCR (RT-PCR) respectively. In kidney, duodenal segments of intestine, liver, and pancreas of HFD diabetic mice, expressions of SGLT2 were all elevated compared to control mice. The level of SGLT1 was significantly increased in intestine, but was decreased in pancreas. SGLT1 expression in kidney was unaffected, and SGLT1 was undetectable in hepatocytes. Similar results were obtained in STZ diabetic mice. More importantly, here we noticed metformin decreased levels of SGLT2 in kidney, intestine, and pancreas of HFD mice markedly. Expressions of SGLT1 in intestine and pancreas were reduced by metformin as well. In contrast, fluoxetine increased abundances of SGLT2 and SGLT1 in kidney of HFD mice, but decreased SGLT1 expression in intestine. The present study provided evidence that expressions of SGLT1 and SGLT2 were significantly modulated by diabetes mellitus as well as by metformin and fluoxetine, which indicated the efficacy of SGLT2 inhibitors might be impacted by these factors.

Comparison of a simple continuous versus simple interrupted suture pattern for the repair of a large, open duodenal defect with a jejunal serosal patch in a canine cadaveric model

To determine whether jejunal serosal patches could securely seal large, open defects in duodenal segments harvested from canine cadavers and to compare intraluminal pressures at which leakage first occurred and maximal intraluminal pressures for repaired duodenal segments between 2 suture patterns. Duodenal and jejunal segments from 9 canine cadavers. 20 constructs were created through repair of large, open duodenal defects with circumferential suturing of an intact jejunal segment (jejunal serosal patch). Constructs were randomly assigned to have the serosal patch anastomosed to the duodenal segment by a simple continuous or simple interrupted suture pattern. The pressure at which the first leakage was observed and the maximum pressure obtained during testing were recorded and compared between suture patterns. Initial leakage pressure was significantly higher with the simple interrupted pattern (mean ± SD, 68.89 ± 5.62 mm Hg), compared with the simple continuous pattern (59.8 ± 20.03 mm Hg). Maximum intraluminal pressures did not significantly differ between the simple interrupted (91 ± 8.27 mm Hg) and simple continuous patterns (90.7 ± 16.91 mm Hg). All constructs, regardless of suture pattern, withstood supraphysiologic pressures. Jejunal serosal patches adequately sealed large, open duodenal defects and prevented leakage in these constructs. Constructs with simple continuous or simple interrupted suture patterns withstood physiologic and supraphysiologic intraluminal pressures, although constructs with a simple interrupted suture pattern initially leaked at higher pressures. (Am J Vet Res 2020;81:985-991).

The relationship among gut microbiota, short-chain fatty acids, and intestinal morphology of growing and healthy broilers

The gut microbiota play an important role in the growth and intestinal health of broilers. The present study was to investigate the gut microbiota, short-chain fatty acids, and intestinal morphology of broilers at different ages. A total of 320 one-day-old male broilers were raised in 8 replicates and fed the same corn–soybean diets for 42 D. The duodenal, jejunal, and ileal segments and their and cecal microbiota were collected on day 1, 7, 14, 21, and 42, respectively. The villous height (VH), crypt depth (CD), and their ratio of VH:CD in the duodenum, jejunum, and ileum all increased (P < 0.05) with age. Caecal acetate, propionate, butyrate, valerate, and isovalerate increased (P < 0.01), but isobutyrate decreased (P < 0.001) with age. The cecum had the greatest (P < 0.001) alpha diversity of bacterial community in broilers at different ages. Beta diversities showed distinct differences in gut microbial compositions among different ages (R = 0.55, P < 0.002) and different intestinal segments (R = 0.53, P < 0.002). Lactobacillus was the most abundant genus in the duodenum (36∼97%), jejunum (39∼72%), and ileum (24∼96%) at all ages, and in the ileum, it was positively correlated with VH (R = 0.559, P < 0.03), VH:CD (R = 0.55, P < 0.03), and acetate contents (R = 0.541, P < 0.04) but negatively correlated (R = -0.50, P < 0.05) with isobutyrate contents. Escherichia–Shigella and Salmonella dominated in the cecum of newly hatched broilers, and then the Bacteroides dominated in the cecum on day 42. In the cecum, Escherichia–Shigella was positively correlated (R = 0.577∼0.662, P < 0.05) with isobutyrate contents and Salmonella negatively correlated (R = -0.539∼-0.843, P < 0.05) with isovalerate, butyrate, and acetate contents. These aforementioned results indicated that the most abundant Lactobacillus from the small intestine and the most diversity of microflora community and short-chain fatty acids in the cecum might contribute to the development of intestinal structure in the whole growing period of broilers.

Kinetics of selenium absorption in ligated small intestinal loops of chicks

Selenium (Se) is an essential trace element that has a large number of biological functions for broilers. However, the absorption kinetics of Se from sodium selenite in the small intestine of broilers remains unclear. Therefore, two experiments were conducted with 28-d-old commercial male broilers to study the kinetics of Se absorption in ligated small intestinal segments. In experiment 1, the Se absorption in duodenal, jejunal, and ileal segments at different post-perfusion time points (0, 20, 40, 60, 80, 100 and 120 min) were compared. In experiment 2, a kinetic study of Se absorption was conducted with the duodenal, jejunal, and ileal loops perfused with solutions containing 0, 0.0375, 0.075, 0.15, 0.30, or 0.60 μg mL−1 of Se as sodium selenite, and Se contents in perfusates were determined at 100 min after perfusion. The results from experiment 1 showed that the Se absorption increased in an asymptotic response (P<0.0001) to post-perfusion time within 120 min in all the small intestinal segments, but increased linearly (P<0.0001) at less than 100 min after perfusion in duodenal and ileal segments, while more than 96.0% of the maximum Se absorption occurred at 100 min after perfusion in each small intestinal segment. In experiment 2, there was no difference (P>0.05) in the Se absorption rate among different ligated small intestinal segments perfused with solutions containing 0.0375–0.15 μg mL−1 of Se, however, the Se absorption rate was higher (P<0.05) in the jejunum than that in the duodenum perfused with solutions containing 0.30–0.60 μg mL−1 of Se. The kinetic curves of Se absorption demonstrated that the Se absorption was a saturated carrier-mediated process in the duodenum, and the maximum absorption rate was 1 271 pg min−1 cm−1; whereas the Se absorptions were a non-saturated diffusion process in the jejunum and ileum, and the diffusive constants were 2 107 and 1 777 cm2 min−1, respectively. The results from the present study indicate that the jejunum is the main Se absorption site, and the Se absorption is a saturated carrier-mediated process in the duodenum, but a non-saturated diffusion process in the jejunum and ileum of broilers.

Rutin flavonoid attenuates oxidative stress and decreases morphological changes in experimental mucositis model

Intestinal mucositis is a frequent complication in the treatment of cancer with 5‐fluorouracil (5‐FU) chemotherapeutic agent. Rutin bioflavonoid extracted from Dimorphandra gardneriana has been reported as a potent anti‐inflammatory and antioxidant agent. Therefore, this study aims to investigate whether rutin reverses morphological elevations and oxidative stress promoted by 5‐fluorouracil in an experimental model of intestinal mucositis in mice. Swiss mice stratified into the following groups were used: Saline group (0.9% NaCl), 5‐FU group, Rutin group (RUT) (200 mg/kg Rutin, vo). For the oxidative damage evaluation, the levels of the reduced antioxidant glutathione and the lipid peroxidation product, malondylaldehyde, of the duodenal segments were determined. To investigate the morphological changes, hematoxylin and eosin staining was performed. The 5‐FU group showed a significant increase in MDA levels (8127 ± 561.5, p &lt;0.05) when compared to the saline group (4587 ± 367.5, p &lt;0.05). For GSH levels, 5‐FU (20.48 ± 4.89, p &lt;0.05) promoted a significant decrease in duodenum antioxidant levels when compared to the saline group (112.8 ± 19.45, p &lt;0.05). Pretreatment with RUT 200 mg/kg decreased MDA levels (3750 ± 405.3, p &lt;0.05) and increased GSH levels (74.67 ± 12.73, p &lt;0.05) when compared to the 5‐FU injury group. The results of the histopathological analysis showed that 5‐FU promoted structural alterations of the intestinal mucosa, reduction of villus height, deepening of the crypts and inflammatory infiltrate, compared to the Saline group, characterized by the integrity of the villi and crypts and absence of inflammatory infiltrate. Rutin‐treated animals showed a significant reversal of antineoplastic‐induced morphological changes. From the results we found that rutin promotes attenuation of oxidative stress by reducing the levels of Malonylaldehyde and increasing the levels of the antioxidant glutathione. In addition, we found that rutin reverses antineoplastic‐induced morphological changes.

In Silico Prediction of the Absorption and Disposition of Cefadroxil in Humans using an Intestinal Permeability Method Scaled from Humanized PepT1 Mice.

It is difficult to predict the pharmacokinetics and plasma concentration-time profiles of new chemical entities in humans based on animal data. Some pharmacokinetic parameters, such as clearance and volume of distribution, can be scaled allometrically from rodents, mammals, and nonhuman primates with good success. However, it is far more challenging to predict the oral pharmacokinetics of experimental drug candidates. In the present study, we used in situ estimates of intestinal permeability, obtained in silico and from rat, wild-type (WT), and humanized PepT1 (huPepT1) mice, to predict the systemic exposure of cefadroxil, an orally administered model compound, under a variety of conditions. Using the GastroPlus simulation software program (Simulations Plus, Lancaster, CA), we found that the C max and area under the plasma concentration-time curve from time zero to the last measurable concentration of cefadroxil were better predicted using intestinal permeability estimates (both segmental and jejunal) from huPepT1 than from WT mice, and that intestinal permeabilities based on in silico and rat estimates gave worse predictions. We also observed that accurate predictions were possible for cefadroxil during oral dose escalation (i.e., 5, 15, and 30 mg/kg cefadroxil), a drug-drug interaction study (i.e., 5 mg/kg oral cefadroxil plus 45 mg/kg oral cephalexin), and an oral multiple dose study [i.e., 500 mg (6.7 mg/kg) cefadroxil every 6 hours]. Finally, the greatest amount of cefadroxil was absorbed in duodenal and jejunal segments of the small intestine after a 5 mg/kg oral dose. Thus, by combining a humanized mouse model and in silico software, the present study offers a novel strategy for better translating preclinical pharmacokinetic data to oral drug exposure during first-in-human studies.

PSXVI-11 Effects of different level of guava extract on diet of japanese quail breeder (Coturnix coturnix japonica) on intestinal growth of neonate japanese quail.

The objective was to evaluate the use of guava extract (Psidium guajava L.) as an antioxidant additive in the diets of Japanese quails (Coturnix coturnix japonica) in laying phase and to verify the intestinal growth of the neonate quail. The experiment was conduced at Federal University of Goias. The extract contained 2.13% ellagic acid. A six hundred forty-eight (648) eggs of layer japanese quails fed with guava extract in the diet were incubated in a completely randomized design, in a single-stage incubator. Temperature of 37°C and humidity of 65% was maintained. Four levels of guava extract were added in the ration of the breeders (0.0%, 0.3%, 0.6% and 0.9%), with 162 replicates, each egg being considered an experimental unit. The incubation period and the hatch window totaled 408h and 40h, respectively. At the end of hatch window, 52 quails from eggs of each treatment were necropsied. The parameters of intestinal development studied were: villus height, crypt depth and villus:crypt ratio of duodenal segments. The results were submitted to analysis of variance and Tukey test at 5% probability. The levels of 0.3%, 0.6% and 0.9% of inclusion of the extract increasing the villus heigh and crypt depth higher than 0.0%. The use of guava extract as an antioxidant improved intestinal development. It is possible that antioxidant effect of ellagic acid preserved the lipidic structures of the membranes of the intestinal villi, avoiding their oxidation during the process of embryonic development. The use of up to 0.3% inclusion of the extract increased the villi:crypt ratio. It is concluded that the use of 0.3% inclusion of guava extract, contained ellagic acid in layer quail diets enhance the intestinal development of the neonate quail.

Stress-strain analysis of duodenal contractility in response to flow and ramp distension in rabbits fed low-fiber diet.

Previously we demonstrated that low-fiber diet in rabbits affects the passive mechanomorphological properties in the small intestine, resulting in reduced intestinal wall thickness and collagen content, as well as intestinal wall softening. The aim of the present study was to evaluate the contractility in rabbits on long-term low-fiber diet and specifically to compare the contraction threshold, the frequency, and the amplitude of flow-induced and distension-induced contractions in the duodenum between rabbits on normal diet and on long-term low-fiber diet. Ten rabbits were fed a low-fiber diet for 5months (Intervention group), and five rabbits were fed normal diet (Control group). The duodenal segments were used for determination of mechanical parameters for analyses of contractility. The duodenal experiments were carried out in organ baths containing physiological Krebs solution. Pressure and diameter changes induced by contractions in response to flow and ramp distension were measured. The frequencies and amplitude of contractions were analyzed. Distension-induced contraction thresholds and maximum contraction amplitude of flow-induced contractions were calculated in terms of mechanical stress and strain. Multiple linear regression analyses were applied to study dependencies between contractility parameters and wall thickness, wall area, and muscle layer thickness. During distension, the pressure, stress, and strain thresholds for induction of phasic contraction were biggest in the Intervention Group (P<0.05). In addition, the contraction frequencies during flow-induced contraction were highest in the Intervention Group (P<0.05), whereas the maximum contraction amplitudes in terms of pressure, diameter, stress, and strain were lowest in the Intervention Group (P<0.05). The contraction thresholds and contraction frequencies were negatively associated with the wall thickness, wall area, and muscle layer thickness, whereas maximum contraction amplitudes were positively associated with the wall thickness, wall area, and muscle layer thickness. Duodenal contractility in rabbits fed with long-term low-fiber diet exhibited low contraction amplitudes and high contraction thresholds and frequencies. The changes were associated with the low-fiber diet-induced histomorphological remodeling. Studies on detailed structural and functional diet-induced changes in smooth muscle and intestinal nerves are needed for better understanding the remodeling mechanisms.

Intravenous iron in post-bariatric abdominoplasty anaemia: a pragmatic approach

There is a paucity of data addressing the use of different iron preparations for the treatment of patients with anaemia in the postoperative period after bariatric surgery and abdominoplasty. This cohort of patients is deemed at higher risk of developing iron deficiency anaemia and associated complications. Iron deficiency is common in these patients because of several factors, including lack of iron intake, reduction in gastric acid secretion, and impaired iron absorption of the duodenal and jejunal segments as a consequence of bariatric surgery. In The Lancet Haematology Juan Carlos Montano-Pedroso and colleagues 1 Montano-Pedroso JC Bueno Garcia E Alcântara Rodrigues de Moraes M Francescato Veiga D Masako Ferreira L. Intravenous iron sucrose versus oral iron administration for the postoperative treatment of post-bariatric abdominoplasty anaemia: an open-label, randomised, superiority trial in Brazil. Lancet Haematol. 2018; 5: e310-e320 Summary Full Text Full Text PDF PubMed Scopus (10) Google Scholar report the results of a randomised controlled trial that assessed the effect of oral iron polymaltose versus intravenous iron sucrose in patients with anaemia after bariatric and abdominoplasty surgery. Intravenous iron sucrose versus oral iron administration for the postoperative treatment of post-bariatric abdominoplasty anaemia: an open-label, randomised, superiority trial in BrazilPostoperative intravenous administration of iron increased haemoglobin concentrations at 56 days post-operatively and reduced iron deficiency, without adverse events. Although superiority of intravenous iron was not shown, intravenous administration might be useful in post-bariatric patients, especially in those who have body-contouring treatment involving a second surgery within a short period of time. Larger trials, and trials using higher intravenous doses of iron, are needed to further assess the potential efficacy and safety of intravenous iron administration after post-bariatric plastic surgery. Full-Text PDF

Supplementation with curcumin inhibits intestinal cholesterol absorption and prevents atherosclerosis in high-fat diet–fed apolipoprotein E knockout mice

Atherosclerosis is a major cause of cardiovascular disease caused by high cholesterol. Reduced intestinal cholesterol absorption has been shown to exert strong cholesterol-lowering and antiatherogenic effects. Previously, we reported that curcumin reduced cholesterol absorption in high-fat diet–fed hamster by downregulating the intestinal expression of Niemann-Pick C1-like 1. Here, we tested the hypothesis that supplementation with curcumin can also reduce intestinal cholesterol absorption in high-fat diet–fed apolipoprotein E knockout (ApoE−/−) mice and prevent atherosclerosis development. ApoE−/− mice were fed a high-fat diet supplemented with or without curcumin (0.1% w/w) for 16 weeks. Aortic sinus sections revealed that curcumin supplementation reduced the extent of atherosclerotic lesions by 45%. Curcumin treatment also reduced cholesterol accumulation in the aortas by 56% and lowered plasma total cholesterol and low-density lipoprotein cholesterol levels. Moreover, the antiatherogenic and cholesterol-lowering effects of curcumin coincided with a significant decrease in intestinal cholesterol absorption. It was reduced by nearly 51%, and the decreased cholesterol absorption was modulated by inhibiting the intestinal expression of Niemann-Pick C1-like 1, predominantly in the duodenal and jejunal segments of the small intestine. These findings support the hypothesis that curcumin supplementation reduces intestinal cholesterol absorption and prevents atherosclerosis in high-fat diet–fed ApoE−/− mice. Curcumin affords a potent antiatherogenic action by inhibiting intestinal cholesterol absorption in the mouse.

Different pathways involved in the stimulatory effects of homocysteine on rat duodenal smooth muscle

Abstract Recent studies have confirmed that hyperhomocysteinemia is associated with gastrointestinal diseases; however, the direct effect of homocysteine on gastrointestinal reactivity still remains unknown. The aim of this study was to demonstrate how homocysteine may affect nitric oxide mediated duodenal relaxation and whether cholinergic receptors and K+ channels take part in stimulating motility, as well as to explore whether oxidative stress is associated with homocysteine-mediated effects. Experiments were carried out on male rats, body mass 250-300 g. Two groups of animals were treated by i.p. application of saline and D,L-Hcy (0.6 μmol/g bm). After 2h of incubation, the duodenal segments were prepared for biochemical analysis and contractile response measurements in an organ bath with Tyrode’s solution. Effects of TEA (10 mmol/L) and L-NAME (30 μmol/L) on duodenal contractility in the presence of D,L-Hcy (0.6 μmol/g bm) were investigated. Elevated homocysteine levels seem to be of crucial importance for the deterioration of contractility through nitric oxide mediated relaxation, and, in part, by activation of K+ channels. Hcy showed direct promuscarinic effects, since 30 min pretreatment of rat duodenum significantly enhanced the contractile effect of increasing concentrations of ACh (10−9-10−2 mol/L). Catalase activity, superoxide dismutase, glutathione peroxidase and the total antioxidant system were reduced while the thiobarbituric acid-reactive substances level was elevated. Our data showed a consistent profile of gastrointestinal injury elicited by sulfur-containing amino acid-homocysteine. This could contribute to explain, at least in part, the mechanisms involved in human gastrointestinal diseases associated to hyperhomocysteinemia.