Differential Recovery of Small Intestinal Segments after Partial-Body Irradiation in Non-Human Primates.

In the event of a radiological attack or accident, it is more likely that the absorbed radiation dose will be heterogeneous, rather than uniformly distributed throughout the body. This type of uneven dose distribution is known as partial-body irradiation (PBI). Partial exposure of the vital organs, specifically the highly radiosensitive intestines, may cause death, if the injury is significant and the post-exposure recovery is considerably compromised. Here we investigated the recovery rate and extent of recovery from PBI-induced intestinal damage in large animals. Rhesus macaques (Macaca mulatta) were randomly divided into four groups: sham-irradiated (0 Gy), 8 Gy PBI, 11 Gy PBI and 14 Gy PBI. A single dose of ionizing radiation was delivered in the abdominal region using a uniform bilateral anteroposterior and posteroanterior technique. Irradiated animals were scheduled for euthanasia on days 10, 28 or 60 postirradiation, and sham-irradiated animals on day 60. Intestinal structural injuries were assessed via crypt depth, villus height, and mucosal surface length in the four different intestinal regions (duodenum, proximal jejunum, distal jejunum and ileum) using H&E staining. Higher radiation doses corresponded with more injury at 10 days post-PBI and a faster recovery rate. However, at 60 days post-PBI, damage was still evident in all regions of the intestine. The proximal and distal ends (duodenum and ileum, respectively) sustained less damage and recovered more fully than the jejunum.

Small intestine remodeling in male Goto-Kakizaki rats.

BACKGROUND: Obesity is associated with the development of insulin resistance (IR) and type-2 diabetes mellitus (T2DM); however, not all patients with T2DM are obese. The Goto-Kakizaki (GK) rat is an experimental model of spontaneous and non-obese T2DM. There is evidence that the intestine contributes to IR development in GK animals. This information prompted us to investigate small intestine remodeling in this animal model. METHODS: Four-month-old male Wistar (control) and GK rats were utilized for the present study. After removing the small intestine, the duodenum, proximal jejunum, and distal ileum were separated. We then measured villi and muscular and mucosa layer histomorphometry, goblet cells abundance, total myenteric and submucosal neuron populations, and inflammatory marker expression in the small intestinal segments and intestinal transit of both groups of animals. KEY RESULTS: We found that the GK rats exhibited decreased intestinal area (p < 0.0001), decreased crypt depth in the duodenum (p = 0.01) and ileum (p < 0.0001), increased crypt depth in the jejunum (p < 0.0001), longer villi in the jejunum and ileum (p < 0.0001), thicker villi in the duodenum (p < 0.01) and ileum (p < 0.0001), thicker muscular layers in the duodenum, jejunum, and ileum (p < 0.0001), increased IL-1ß concentrations in the duodenum and jejunum (p < 0.05), and increased concentrations of NF-κB p65 in the duodenum (p < 0.01), jejunum and ileum (p < 0.05). We observed high IL-1ß reactivity in the muscle layer, myenteric neurons, and glial cells of the experimental group. GK rats also exhibited a significant reduction in submucosal neuron density in the jejunum and ileum, ganglionic hypertrophy in all intestinal segments studied (p < 0.0001), and a slower intestinal transit (about 25%) compared to controls. CONCLUSIONS: The development of IR and T2DM in GK rats is associated with small intestine remodeling that includes marked alterations in small intestine morphology, local inflammation, and reduced intestinal transit.

A further study on a disturbance of intestinal epithelial cell population and kinetics in APC1638T mice.

Adenomatous polyposis coli (APC), a well-known anti-oncogene, is considered to have multiple functions through its several binding domains. We have continuingly studied APC1638T/1638T mice (APC1638T mice) to elucidate the functions of APC other than tumor suppression. A distinctive feature of the APC1638T mice is they are tumor free and live as long as APC+/+ mice (WT mice). Previously, we found the length of crypt-villus axis in the jejunum was significantly elongated in APC1638T mice compared with that of WT mice. The populations of goblet cells, Paneth cells, and enteroendocrine cells were also disordered in APC1638T mice. Here, we further analyzed the intestinal dyshomeostasis in APC1638T mice, focusing on the proliferation and differentiation of intestinal stem cell (ISC) lineages, and apoptotic cell shedding at the villus tips. We found that the proliferation of ISC lineages was normally controlled; however, the shedding process of apoptosis cells was significantly delayed in the APC1638T mouse jejunum. Furthermore, the number of microfold cells (M cells) was significantly increased in the APC1638T mouse jejunum. Our data suggested both differentiation process of ISCs and turnover process of intestinal epithelia were disturbed in APC1638T mice, and that contributed to the villus elongation in the APC1638T mouse jejunum.

Hypothermia induces opposite response in vascular and non-vascular smooth muscles.

BACKGROUND AND AIM: The mechanism of cooling-induced response of smooth muscles remains little understood despite the increasing importance given to it in recent years. The aim of this study was to examine the possibility of releasing a relaxant or a contractile substance during cooling from vascular and non-vascular smooth muscles. METHODS: Assessing the effect of cooling for two different smooth muscles together, vascular (aorta or carotid) which induced relaxation, and non-vascular (jejunum or bladder) which induced contraction. Hanging a pair of smooth muscle strips from different body organs in the same organ bath filled with Krebs solution, each strip was connected to its own transducer and recorder and stepwise cooling was applied. Recordings of isometric tension using organ-bath techniques. RESULTS: Step-wise cooling (37 °C-4 °C) of aorta and carotid smooth muscle preparations induced reproducible graded relaxation while jejunum and bladder preparations induced reproducible graded tonic contractions, inversely proportional to temperature. The responses of all the smooth muscle preparations were the same magnitude either alone or as a pair in the organ bath. Cooling abolished rhythmic smooth muscle activity of jejunum and bladder. Cooling-induced contraction was reduced by incubation in Ca2+-free solution. The effect of cooling either relaxation or contraction was not enhanced or attenuated by the presence of the two different smooth muscles with opposite response in the same organ bath, proving the absence of a relaxant or a contractile substance released during cooling. CONCLUSIONS: Cooling of aorta and carotid artery induced relaxation while jejunum and bladder induced contraction. The response to cooling is inversely proportional to the temperature. There was neither a relaxant nor a contractile substance released from vascular or non-vascular smooth muscles during cooling. Our study suggested that the effect of cooling is through a thermal receptor with two subtype one in the vascular smooth muscle (deep blood vessels) which induces relaxation, and the second in non-vascular smooth muscles (non-vascular organs) that induces contraction and the responses depend on extracellular calcium.

Steroid Receptor Coactivator-3 Is Required for Inhibition of the Intestinal Muscularis Inflammatory Response of Postoperative Ileus in Mice.

Inflammation theory has suggested that the pathogenesis of postoperative ileus (POI) involves the steroid receptor coactivator-3 (SRC-3). Therefore, we investigated the role of SRC-3 in the muscles of the small intestine using a mouse POI model. Here, we reported that intestinal manipulation (IM) significantly reduced the extent of phenol red migration in the entire gastrointestinal tract, and the calculated geometric center (GC) value in wild-type (WT) mice at 24 h after surgery was higher than that in the knockout (KO) mice and in the sham-operated control group. The expression of SRC-3 was upregulated in the mouse intestinal muscularis at 24 h after surgical manipulation, and the mRNA and protein levels of inflammatory cytokines were upregulated compared with those in the control group. At 24 h after IM, the number of neutrophils in the experimental group was significantly higher than that in the control group; in the IM group, the number of neutrophils in the SRC-3-/- mice was markedly higher than that in the WT mice. At 24 h after IM, the myeloperoxidase (MPO) activity in the experimental group was significantly higher than that in the control group. In the IM group, the MPO activity of the SRC-3-/- mice was markedly higher than that of the WT mice. In summary, proinflammatory cytokines, the number of neutrophils, and the MPO activity were significantly increased in the muscularis of the jejunum and ileum of KO mice after IM compared with those of the WT mice, indicating that SRC-3 might play a protective role in POI.

Electroacupuncture ameliorates corticotrophin-releasing factor-induced jejunal dysmotility in a rat model of stress.

BACKGROUND: Central injection of corticotrophin-releasing factor (CRF) mimics the effect of stress on gastrointestinal (GI) responses, including inhibition of GI motility. This study was designed to explore the effects of electroacupuncture (EA) on disordered jejunal motility in a rat model of stress induced by intracisternal (IC) injection of CRF. METHODS: A stress model was established by IC injection of CRF in Sprague-Dawley rats. GI motility was evaluated by assessing gastric emptying (GE), gastrointestinal transit (GIT) and jejunal motility in vivo. EA was performed at ST36. The functional roles of CRF receptor subtype 1 and subtype 2 (CRFr1 and CRFr2) were examined by IC administration of the corresponding selective CRF antagonists. Protein expression of CRFr1 and CRFr2 in the hypothalamus and jejunum was detected by Western blotting. RESULTS: IC injection of CRF significantly inhibited GE, GIT and jejunal motility. EA treatment remarkably improved the disturbed GI motility. Intriguingly, the disordered jejunal motility induced by central CRF was abolished by IC injection of a selective CRFr2 antagonist, indicating the essential role of central CRFr2 in mediating the stress-induced jejunal motor disorder. EA at ST36 decreased central and peripheral expression of CRFr2, which might be one of the potential mechanisms underlying the beneficial effect of EA on jejunal dysmotility in this rat model of stress. CONCLUSION: This study suggested that EA at ST36 could ameliorate disordered jejunal motility induced by stress, and that this might be associated with the down-regulation of CRFr2.

Quantified small bowel motility in patients with ulcerative colitis and gastrointestinal symptoms: a pilot study.

BACKGROUND: Gastrointestinal (GI) symptoms are common in patients with ulcerative colitis (UC), even when the disease is in remission, possibly due to abnormalities in GI motility. Small bowel motility can be assessed globally and in specific intestinal regions during magnetic resonance enterography (MRE) using a displacement mapping technique. PURPOSE: To investigate whether small bowel motility in MRE differs between patients with UC and controls, and if altered motility correlates with GI symptoms. MATERIAL AND METHODS: In 2016-2018, patients who were admitted for MRE, regardless of clinical indication, were consecutively invited to the study. Healthy volunteers were recruited. The participants completed a questionnaire regarding GI symptoms and relevant clinical data were reviewed in the medical records. The dynamic imaging series obtained during MRE were sent for motility mapping and a motility index (MI) was calculated in jejunum, ileum and terminal ileum in all participants. RESULTS: In total, 224 patients and healthy volunteers were enrolled in the study. Fifteen were diagnosed with UC and 22 were considered healthy controls. In UC, the prevalence of GI symptoms was higher than in controls (P < 0.001), both in remission and in active disease. There was no correlation between GI symptoms and small bowel motility in UC. Jejunal motility was lower in UC than in controls (P = 0.049). CONCLUSION: Jejunal motility is decreased in UC compared with healthy controls, but there is no relationship between small bowel motility and GI symptoms in UC.

Chyme Reinfusion in Intestinal Failure Related to Temporary Double Enterostomies and Enteroatmospheric Fistulas.

Some temporary double enterostomies (DES) or entero-atmospheric fistulas (EAF) have high output and are responsible for Type 2 intestinal failure. Intravenous supplementations (IVS) for parenteral nutrition and hydration compensate for intestinal losses. Chyme reinfusion (CR) artificially restores continuity pending surgical closure. CR treats intestinal failure and is recommended by European Society for Clinical Nutrition and Metabolism (ESPEN) and American Society for Parenteral and Enteral Nutrition (ASPEN) when possible. The objective of this study was to show changes in nutritional status, intestinal function, liver tests, IVS needs during CR, and the feasibility of continuing it at home. A retrospective study of 306 admitted patients treated with CR from 2000 to 2018 was conducted. CR was permanent such that a peristaltic pump sucked the upstream chyme and reinfused it immediately in a tube inserted into the downstream intestine. Weight, plasma albumin, daily volumes of intestinal and fecal losses, intestinal nitrogen, and lipid absorption coefficients, plasma citrulline, liver tests, and calculated indices were compared before and during CR in patients who had both measurements. The patients included 185 males and 121 females and were 63 ± 15 years old. There were 37 (12%), 269 (88%) patients with EAF and DES, respectively. The proximal small bowel length from the duodeno-jejunal angle was 108 ± 67 cm (n = 232), and the length of distal small intestine was 117 ± 72 cm (n = 253). The median CR start was 5 d (quartile 25-75%, 2-10) after admission and continued for 64 d (45-95), including 81 patients at home for 47 d (28-74). Oral feeding was exclusive 171(56%), with enteral supplement 122 (42%), or with IVS 23 (7%). Before CR, 211 (69%) patients had IVS for nutrition (77%) or for hydration (23%). IVS were stopped in 188 (89%) 2 d (0-7) after the beginning of CR and continued in 23 (11%) with lower volumes. Nutritional status improved with respect to weight gain (+3.5 ± 8.4%) and albumin (+5.4 ± 5.8 g/L). Intestinal failure was cured in the majority of cases as evidenced by the decrease in intestinal losses by 2096 ± 959 mL/d, the increase in absorption of nitrogen 32 ± 20%, of lipids 43 ± 30%, and the improvement of citrulline 13.1 ± 8.1 µmol/L. The citrulline increase was correlated with the length of the distal intestine. The number of patients with at least one liver test >2N decreased from 84-40%. In cases of Type 2 intestinal failure related to DES or FAE with an accessible and functional distal small bowel segment, CR restored intestinal functions, reduced the need of IVS by 89% and helped improve nutritional status and liver tests. There were no vital complications or infectious diarrhea described to date. CR can become the first-line treatment for intestinal failure related to double enterostomy and high output fistulas.

Impact of viral disease hypophagia on pig jejunal function and integrity.

Pathogen challenges are often accompanied by reductions in feed intake, making it difficult to differentiate impacts of reduced feed intake from impacts of pathogen on various response parameters. Therefore, the objective of this study was to determine the impact of Porcine Reproductive and Respiratory Syndrome virus (PRRSV) and feed intake on parameters of jejunal function and integrity in growing pigs. Twenty-four pigs (11.34 ± 1.54 kg BW) were randomly selected and allotted to 1 of 3 treatments (n = 8 pigs/treatment): 1) PRRSV naïve, ad libitum fed (Ad), 2) PRRSV-inoculated, ad libitum fed (PRRS+), and 3) PRRSV naïve, pair-fed to the PRRS+ pigs' daily feed intake (PF). At 17 days post inoculation, all pigs were euthanized and the jejunum was collected for analysis. At days post inoculation 17, PRRS+ and PF pigs had decreased (P < 0.05) transepithelial resistance compared with Ad pigs; whereas fluorescein isothiocyanate-dextran 4 kDa permeability was not different among treatments. Active glucose transport was increased (P < 0.05) in PRRS+ and PF pigs compared with Ad pigs. Brush border carbohydrase activity was reduced in PRRS+ pigs compared with PF pigs for lactase (55%; P = 0.015), sucrase (37%; P = 0.002), and maltase (30%; P = 0.015). For all three carbohydrases, Ad pigs had activities intermediate that of PRRS+ and PF pigs. The mRNA abundance of the tight junction proteins claudin 2, claudin 3, claudin 4, occludin, and zonula occludens-1 were reduced in PRRS+ pigs compared with Ad pigs; however, neither the total protein abundance nor the cellular compartmentalization of these tight junction proteins differed among treatments. Taken together, this study demonstrates that the changes that occur to intestinal epithelium structure, function, and integrity during a systemic PRRSV challenge can be partially explained by reductions in feed intake. Further, long term adaptation to PRRSV challenge and caloric restriction does reduce intestinal transepithelial resistance but does not appear to reduce the integrity of tight junction protein complexes.

Clinicopathological study of intestinal smooth muscles, interstitial cells of Cajal, and enteric neurons in neonatal jejuno-ileal atresia with special reference to muscle morphometry.

PURPOSE: To assess the thickness of the intestinal smooth muscle layer and analyze the distribution and density of interstitial cells of Cajal (ICC) and enteric neurons in the proximal and distal segments of neonatal jejuno-ileal atresia. METHODS: This is an observational study done over a period of one year in which fifteen cases of jejuno-ileal atresia were included. All the cases underwent laparotomy and resection of the atretic segment with variable portions of the dilated proximal segment and distal segment. Histopathological analysis was done on the sections taken from proximal segments (at 3 cm, 5 cm & 8 cm) and the distal segment (at 2 cm) from the atretic portion. The mean thickness of the inner circular muscle layer (ICML) and outer longitudinal muscle layer (OLML) was assessed in the above segments using image morphometry. In addition, we also analyzed the distribution and density of the ICCs and enteric neurons in the different segments using immunohistochemistry for c-kit and S-100, respectively. Controls included normal jejuno-ileal segments resected from postmortem cases (n=7) and other nonrelated surgeries (n=3). The findings were then compared with each-other and with normal controls. RESULTS: Mean thickness of ICML and OLML of the proximal segments at 8 cm was significantly lower than at 3 cm and 5 cm of ileal and jejunal atresias (p≪ 0.5). The mean thickness of ICML and OLML of distal segments at 2 cm was similar to the controls in all the atretic cases (p≫ 0.5). The mean ICML thickness at proximal 8 cm segment was similar to the distal segment of both ileal & jejunal atresias (p= 0.06 & 0.37 respectively). The mean thickness of the OLML of the proximal 8 cm segments was significantly more than that at the distal segment (p=0.008) in ileal atresias but was similar in cases of jejunal atresias (p=0.07). Both the proximal and distal segments of ileal as well as jejunal atresias showed reduction in distribution and density of ICCs, as compared to normal controls. The density of ICCs in proximal segments at 3 cm and 5 cm was similar in both ileal (p=0.33) and jejunal segments (p=0.41) but was significantly lower than the proximal 8 cm segments (p≪0.05).The distribution of ICCs in the proximal segment at 8 cm was similar to the distal segments (p≪0.05). S-100 staining showed dense expression of neurons and glial cells with presence of submucosal giant ganglia within the proximal dilated segments as compared to the distal segments and the controls, which were more marked at 3 cm and 5 cm levels than at 8 cm level. CONCLUSION: Muscle morphometry using image analysis is a simple technique to assess the thickness of the intestinal smooth muscle layers. There is significant smooth muscle hypertrophy along with marked alteration in density and distribution of ICCs and ENS in the dilated proximal segments up to 5 cm, and relatively milder changes at 8 cm levels, as compared to the distal segments and the controls. TYPE OF STUDY: Prognosis study. LEVEL OF EVIDENCE: Level II.

Effects of dietary taurine supplementation on growth performance, jejunal morphology, appetite-related hormones, and genes expression in broilers subjected to chronic heat stress.

This study was aimed to elucidate effects of taurine supplementation on growth performance, jejunal histology, and appetite-related genes expressions of broilers under heat stress. A total of 144 broilers on 28 d were allocated to three groups with 6 cages each group, 8 broilers per cage. The experiment period is from 28 to 42 d of age. In normal control (NC) group, chickens were held at 22°C ambient temperature (thermoneutral) and fed a basal diet. In the heat stress (HS) group, chickens were raised to constant HS at 32°C and received a basal diet. In the HS+ taurine group, chickens were fed a basal diet with 5 g/kg taurine supplementation. The results showed that HS group had lower average daily feed intake, average daily gain, higher feed/gain ratio compared with the NC group (P < 0.05), while taurine addition did not ameliorate the lowered growth performance. Cloacal temperatures and respiration rates in the HS and heat taurine group were higher (P < 0.05) than in the NC group. Heat stress treatment elevated (P < 0.05) the concentrations of ghrelin and cholecystokinin (CCK) in serum and intestine, together with peptide YY and somatostatin (SS) in the intestine after 7 or 14 d of heat exposure. In addition, HS damaged the jejunal morphology by shortening villus height and deepening crypt depth (P < 0.05), upregulated (P < 0.05) the mRNA expression of taste receptor type 1 member 1 (T1R1), taste receptor type 1 member 3 (T1R3), CCK and ghrelin in the intestine. Taurine supplementation significantly mitigated the impairment of jejunal morphology, decreased the concentrations of serum ghrelin, increased the concentrations of somatostatin and peptide YY in the duodenum, elevated the mRNA expression levels of CCK in the jejunum compared with the HS group. In conclusion, taurine exerted no positive effects on the growth performance, while mitigated the impairment of jejunal morphology, increased some anorexic hormones secretion and mRNA expression of appetite-related genes in the intestine of broilers subjected to HS.

Machine learning for intraoperative prediction of viability in ischemic small intestine.

OBJECTIVE: Evaluation of intestinal viability is essential in surgical decision-making in patients with acute intestinal ischemia. There has been no substantial change in the mortality rate (30%-93%) of patients with acute mesenteric ischemia (AMI) since the 1980s. As the accuracy from the first laparotomy alone is 50%, the gold standard is a second-look laparotomy, increasing the accuracy to 87%-89%. This study investigates the use of machine learning to classify intestinal viability and histological grading in pig jejunum, based on multivariate time-series of bioimpedance sensor data. APPROACH: We have previously used a bioimpedance sensor system to acquire electrical parameters from perfused, ischemic and reperfused pig jejunum (7 + 15 pigs) over 1-16 h of ischemia and 1-8 h of reperfusion following selected durations of ischemia. In this study we compare the accuracy of using end-point bioimpedance measurements with a feedforward neural network (FNN), versus the accuracy when using a recurrent neural network with long short-term memory units (LSTM-RNN) with bioimpedance data history over different periods of time. MAIN RESULTS: Accuracies in the range of what has been reported clinically can be achieved using FNN's on a single bioimpedance measurement, and higher accuracies can be achieved when employing LSTM-RNN on a sequence of data history. SIGNIFICANCE: Intraoperative bioimpedance measurements on intestine of suspect viability combined with machine learning can increase the accuracy of intraoperative assessment of intestinal viability. Increased accuracy in intraoperative assessment of intestinal viability has the potential to reduce the high mortality and morbidity rate of the patients.

Increased jejunal permeability in human obesity is revealed by a lipid challenge and is linked to inflammation and type 2 diabetes.

Obesity and its metabolic complications are characterized by subclinical systemic and tissue inflammation. In rodent models of obesity, inflammation and metabolic impairments are linked with intestinal barrier damage. However, whether intestinal permeability is altered in human obesity remains to be investigated. In a cohort of 122 severely obese and non-obese patients, we analyzed intestinal barrier function combining in vivo and ex vivo investigations. We found tight junction impairments in the jejunal epithelium of obese patients, evidenced by a reduction of occludin and tricellulin. Serum levels of zonulin and LPS binding protein, two markers usually associated with intestinal barrier alterations, were also increased in obese patients. Intestinal permeability per se was assessed in vivo by quantification of urinary lactitol/mannitol (L/M) and measured directly ex vivo on jejunal samples in Ussing chambers. In the fasting condition, L/M ratio and jejunal permeability were not significantly different between obese and non-obese patients, but high jejunal permeability to small molecules (0.4 kDa) was associated with systemic inflammation within the obese cohort. Altogether, these results suggest that intestinal barrier function is subtly compromised in obese patients. We thus tested whether this barrier impairment could be exacerbated by dietary lipids. To this end, we challenged jejunal samples with lipid micelles and showed that a single exposure increased permeability to macromolecules (4 kDa). Jejunal permeability after the lipid load was two-fold higher in obese patients compared to non-obese controls and correlated with systemic and intestinal inflammation. Moreover, lipid-induced permeability was an explicative variable of type 2 diabetes. In conclusion, intestinal barrier defects are present in human severe obesity and exacerbated by a lipid challenge. This paves the way to the development of novel therapeutic approaches to modulate intestinal barrier function or personalize nutrition therapy to decrease lipid-induced jejunal leakage in metabolic diseases. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Adipocytes and intestinal epithelium dysfunctions linking obesity to inflammation induced by high glycemic index pellet-diet in Wistar rats.

We investigated the inflammatory effect of a pellet-diet with high glycemic index and load (HGLI) on the histological organization of adipocytes, intestinal epithelium, and fat in liver and pancreas in adult male Wistar rats. Two groups (n=10) received for 17 weeks: (1) HGLI diet or (2) Standard diet (Labina®). Histological analyses of adipose tissue, jejunum, liver, and pancreas were performed. Stereology analysis, visceral adiposity index, gene expression, and immunohistochemistry of tumor necrosis factor-α (TNF-α) in visceral adipose tissue and plasma TNF-α were also assessed. The HGLI diet-induced hypertrophy of adipocytes with adipocyte volume density equal to 97.0%, cross-sectional area of adipocytes equivalent to 1387 µm² and a total volume of adipocytes of 6.97 cm³ an elevation of 8%, 25%, and 58%, respectively. Furthermore, the HGLI diet increased liver and pancreatic fat deposition, altered and inflamed the intestinal epithelia, and increased TNF-α gene expression (P=0.014) with a positive immunostaining in visceral adipose tissue and high plasma TNF-α in comparison with standard diet. The results suggest that this diet was able to generate changes commonly caused to solid diets with high fat or fructose-rich beverages. To the best of our knowledge, this is the first report in the literature concerning the properties of low-cost, sucrose-rich pellet-diet presenting high glycemic index and high glycemic load efficient on the development of obesity complications in Wistar rats that were subjected to diet-induced obesity. Therefore, the HGLI pellet-diet may be considered an effective tool to be used by the scientific community in experimental research.

Reduced active transcellular intestinal oxalate secretion contributes to the pathogenesis of obesity-associated hyperoxaluria.

Most kidney stones are composed of calcium oxalate, and minor changes in urine oxalate affect the stone risk. Obesity is a risk factor for kidney stones and a positive correlation of unknown etiology between increased body size, and elevated urinary oxalate excretion has been reported. Here, we used obese ob/ob (ob) mice to elucidate the pathogenesis of obesity-associated hyperoxaluria. These ob mice have significant hyperoxaluria (3.3-fold) compared with control mice, which is not due to overeating as shown by pair-feeding studies. Dietary oxalate removal greatly ameliorated this hyperoxaluria, confirming that it is largely enteric in origin. Transporter SLC26A6 (A6) plays an essential role in active transcellular intestinal oxalate secretion, and ob mice have significantly reduced jejunal A6 mRNA (- 80%) and total protein (- 62%) expression. While net oxalate secretion was observed in control jejunal tissues mounted in Ussing chambers, net absorption was seen in ob tissues, due to significantly reduced secretion. We hypothesized that the obesity-associated increase in intestinal and systemic inflammation, as reflected by elevated proinflammatory cytokines, suppresses A6-mediated intestinal oxalate secretion and contributes to obesity-associated hyperoxaluria. Indeed, proinflammatory cytokines (elevated in ob mice) significantly decreased intestinal oxalate transport in vitro by reducing A6 mRNA and total protein expression. Proinflammatory cytokines also significantly reduced active mouse jejunal oxalate secretion, converting oxalate transport from net secretion in vehicle-treated tissues to net absorption in proinflammatory cytokines-treated tissues. Thus, reduced active intestinal oxalate secretion, likely secondary to local and systemic inflammation, contributes to the pathogenesis of obesity-associated hyperoxaluria. Hence, proinflammatory cytokines represent potential therapeutic targets.

Perioperative Fluid Accumulation Impairs Intestinal Contractility to a Similar Extent as Peritonitis and Endotoxemia.

BACKGROUND: Perioperative resuscitation with large amounts of fluid may cause tissue edema, especially in the gut, and thereby impairing its functions. This is especially relevant in sepsis where capillaries become leaky and fluid rapidly escapes to the pericapillary tissue. We assessed the effects of endotoxemia and peritonitis, and the use of high and moderate volume fluid resuscitation on jejunal contractility. We hypothesized that both endotoxemia and peritonitis impair jejunum contractility and relaxation, and that this effect is aggravated in peritonitis and with high fluid administration. METHODS: Pigs were randomized to endotoxin (n = 16), peritonitis (n = 16), or sham operation (n = 16), and either high (20 mL/kg/h) or moderate volume (10 mL/kg/h) fluid resuscitation for 24 h or until death. At the end of the experiment, jejunal contractility and relaxation were measured in vitro using acetylcholine and sodium nitroprusside reactivity, and the effect of nitric oxide synthase inhibition (NOS-I) was assessed. RESULTS: Mortality in the respective groups was 88% (peritonitis high), 75% (endotoxemia high), 50% (peritonitis moderate), 13% (endotoxemia moderate and sham operation high), and 0% (sham operation moderate volume resuscitation). Although gut perfusion was preserved in all groups, jejunal contractility was impaired in the two peritonitis and two endotoxemia groups, and similarly also in the sham operation group treated with high but not with moderate volume fluid resuscitation (model-fluid-contraction-interaction, P = 0.036; maximal contractility 136 ±â€Š28% [average of both peritonitis, both endotoxemia and sham operation high-volume groups) vs. 170 ±â€Š74% of baseline [sham operation moderate-volume group]). NOS-I reduced contractility (contraction-inhibition-interaction, P = 0.011) without significant differences between groups and relaxation was affected neither by peritonitis and endotoxemia nor by the fluid regimen. CONCLUSIONS: Intestinal contractility is similarly impaired during peritonitis and during endotoxemia. Moreover, perioperative high-volume fluid resuscitation in sham-operated animals also decreases intestinal contractility. This may have consequences for postoperative recovery.

Effects of porcine epidemic diarrhea virus infection on nursery pig intestinal function and barrier integrity.

The pig intestinal epithelium can be compromised by pathogens leading to reduced integrity and function. Porcine epidemic diarrhea virus (PEDV), recently detected in North America, exemplifies intestinal epithelial insult. Although several studies have investigated the molecular aspects and host immune response to PEDV, there are little data on the impact of PEDV on pig intestinal physiology. The objective of this study was to investigate the longitudinal impact of PEDV on nursery pig intestinal function and integrity. Fifty recently-weaned, 5-week-old barrows and gilts (BW=9.92±0.49kg) were sorted based on body weight (BW) and sex into two treatments: 1) Control or 2) PEDV inoculated. At 2, 5, 7, and 14days post inoculation (dpi), 4 pigs per treatment were euthanized and jejunum sections collected. PEDV antigen was detected in inoculated pigs by immunohistochemistry in 50% (2/4) at dpi 2, 100% (4/4) at dpi 5, and none at later time points. PEDV-infected pigs had reduced (P<0.05) villus height and decreased transepithelial resistance compared with controls. Total acidic mucins, particularly sialomucin, were reduced in PEDV pigs at dpi 2 and then increased compared with controls at dpi 7 and 14. In addition, PEDV pigs had increased stem cell proliferation (P<0.05) and a numerical increase in DNA fragmentation compared with controls through dpi 7 which coincided with an observed return of digestive function to that of controls. Collectively, these data reveal that PEDV infection results in time-dependent changes not only in intestinal morphology but also barrier integrity and function.

Abdominal CT Findings in Patients with Primary Lymphoma Causing Small Bowel Obstruction.

The purpose of this study was to investigate retrospectively CTfindings in patients with primary lymphoma causing small bowel obstruction. CTscans of 11 patients with small bowel lymphoma were separately analysed in terms of affected section of the small bowel, focality, wall thickness, pattern and degree of contrast enhancement, lymphadenopathy, organ involvement, perforation, and the presence of intraabdominal fluid. Eight patients had diffuse large B-cell lymphoma, and one patient each had marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT), T-cell lymphoma, and anaplastic T-cell lymphoma. Affected sections of the bowels involved were jejunum (n=5, 45.4%), ileum (n=2, 18.1%), and one case (9%) each of distal ileum, distal jejunum, distal jejunum and ileum, and distal jejunum and colon. Primary gastrointestinal (GI) lymphoma is an uncommon disease, that may lead to small bowel obstruction sometimes.

Alcohol Feeding in Mice Promotes Colonic Hyperpermeability and Changes in Colonic Organoid Stem Cell Fate.

BACKGROUND: Alcohol increases intestinal permeability to proinflammatory microbial products that promote liver disease, even after a period of sobriety. We sought to test the hypothesis that alcohol affects intestinal stem cells using an in vivo model and ex vivo organoids generated from jejunum and colon from mice fed chronic alcohol. METHODS: Mice were fed a control or an alcohol diet. Intestinal permeability, liver steatosis-inflammation, and stool short-chain fatty acids (SCFAs) were measured. Jejunum and colonic organoids and tissue were stained for stem cell, cell lineage, and apical junction markers with assessment of mRNA by PCR and RNA-seq. ChIP-PCR analysis was carried out for Notch1 using an antibody specific for acetylated histone 3. RESULTS: Alcohol-fed mice exhibited colonic (but not small intestinal) hyperpermeability, steatohepatitis, and decreased butyrate/total SCFA ratio in stool. Stem cell, cell lineage, and apical junction marker staining in tissue or organoids from jejunum tissue were not impacted by alcohol. Only chromogranin A (Chga) was increased in jejunum organoids by qPCR. However, colonic tissue and organoid staining exhibited an alcohol-induced significant decrease in cytokeratin 20+  (Krt20+) absorptive lineage enterocytes, a decrease in occludin and E-cadherin apical junction proteins, an increase in Chga, and an increase in the Lgr5 stem cell marker. qPCR revealed an alcohol-induced decrease in colonic organoid and tissue Notch1, Hes1, and Krt20 and increased Chga, supporting an alteration in stem cell fate due to decreased Notch1 expression. Colonic tissue ChIP-PCR revealed alcohol feeding suppressed Notch1 mRNA expression (via deacetylation of histone H3) and decreased Notch1 tissue staining. CONCLUSIONS: Data support a model for alcohol-induced colonic hyperpermeability via epigenetic effects on Notch1, and thus Hes1, suppression through a mechanism involving histone H3 deacetylation at the Notch1 locus. This decreased enterocyte and increased enteroendocrine cell colonic stem cell fate and decreased apical junctional proteins leading to hyperpermeability.