The fate of sodium chlorite in simulated gastric and intestinal fluids and residues of chlorate in broiler chickens after oral administration of sodium chlorite.

The fate of sodium [36Cl]chlorite in simulated intestinal fluids and residues of chlorate in broiler chickens fed 0, 10, 100, or 1000 mg•kg-1 of dietary sodium chlorite for 7 days was determined. [36Cl]Chlorite was stable in water and simulated intestinal fluid during 6 h incubations but was rapidly degraded to chlorine dioxide, sodium chloride, and sodium chlorate in simulated gastric fluids. Addition of starch, citrate, or soybean shifted the relative proportions of chloroxyanions formed; addition of ferrous chloride caused quantitative formation of sodium chloride in gastric and intestinal fluids. [36Cl]Chlorite underwent reductive transformation when fortified into chicken serum. Residues of chlorate in broiler chickens ranged from 3.5 to 374 ng•g-1 in gizzard, were <6.8 to 126 ng•g-1 in liver and were <7.2 to 190 ng•g-1 in muscle when slaughtered with no withdrawal period. Data are presented suggesting that reductive processes govern the fate of chlorite when present in closed biological systems.

Plastic ingestion by freshwater turtles: a review and call to action.

Plastic pollution, and especially plastic ingestion by animals, is a serious global issue. This problem is well documented in marine systems, but it is relatively understudied in freshwater systems. For turtles, it is unknown how plastic ingestion compares between marine and non-marine species. We review the relevant turtle dietary literature, and find that plastic ingestion is reported for all 7 marine turtle species, but only 5 of 352 non-marine turtle species. In the last 10 years, despite marine turtles representing just 2% of all turtle species, almost 50% of relevant turtle dietary studies involved only marine turtles. These results suggest that the potential threat of plastic ingestion is poorly studied in non-marine turtles. We also examine plastic ingestion frequency in a freshwater turtle population, finding that 7.7% of 65 turtles had ingested plastic. However, plastic-resembling organic material would have inflated our frequency results up to 40% higher were it not for verification using Raman spectroscopy. Additionally, we showcase how non-native turtles can be used as a proxy for understanding the potential for plastic ingestion by co-occurring native turtles of conservation concern. We conclude with recommendations for how scientists studying non-marine turtles can improve the implementation, quality, and discoverability of plastic ingestion research.

Composition of Coloured Gastric Residuals in Extremely Preterm Infants-A Nested Prospective Observational Study.

Green gastric residuals (GR) are often considered as a sign of feed intolerance and discarded in preterm infants. Probiotics are known to enhance feed tolerance in preterm infants. To assess the composition (primary outcome) and volume of discarded green GRs, and feeding outcomes in extremely preterm (EP) infants in a probiotic trial, composition of pale and dark green GRs in the first two weeks of life from EP infants (<28 weeks) in a randomized controlled trial (RCT: SiMPro) of single vs. three-strain probiotics was assessed. Feeding outcomes included time to full feeds (TFF: 150 mL/kg/day) and duration of parenteral nutrition (PN). EP infants given placebo in our previous probiotic RCT served as the reference group. Analysis involved linear regression modelling with clustered standard errors for repeated measurements. GRs of 74/103 from 39 SiMPro infants (18: single-strain, 21: three-strain) were analyzed. Bile acid content was higher but statistically insignificant (825.79 vs. 338.1 µmol/L; p = 0.12) in dark vs. pale green GRs. Mean (95% confidence interval) fat, nitrogen, and carbohydrate loss in GRs over the study period was 0.02 g (0.01-0.03), 0.011 g (0.009-0.013), and 0.05 g (0.04-0.06), respectively. Overall, SiMPro infants had shorter median TFF (10 vs. 14 days, p = 0.02) and duration of PN (10 vs. 16 days, p = 0.022) compared with control group infants. Z scores for growth parameters at discharge were comparable. Discarding dark green GRs meant higher loss of bile acids during early enteral nutrition in EP infants. Probiotic supplementation was associated with reduced TFF and duration of PN.

Effect of Oral Glucose Water Administration 1 Hour Preoperatively in Children with Cyanotic Congenital Heart Disease: A Randomized Controlled Trial.

BACKGROUND Guidelines recommend a clear liquid fasting time of 2 h before surgery, which is often exceeded, leading to adverse reactions (ARs) such as discomfort, thirst, and dehydration. We assessed the gastric contents and ARs after oral glucose water administration 1 h prior to surgery in children with cyanotic congenital heart disease (CCHD). MATERIAL AND METHODS This was a non-inferiority randomized controlled trial of children with CCHD enrolled at the Fujian Medical University Union Hospital from 09/2014 to 05/2017 and randomized to receive oral glucose water (10 g of glucose in 100 ml of warm water, 5 ml/kg) 2 h (2-h group, n=174) or 1 h (1-h group, n=170) before surgery. The primary endpoint was gastric volume. Secondary endpoints included pH of gastric content, preoperative blood glucose, and risk factors for aspiration pneumonia. Pre- and intraoperative ARs were recorded. RESULTS The 1-h group showed smaller gastric content volumes (0.34±0.35 (95% CI: 0.29-0.39) vs. 0.43±0.33 (95% CI: 0.38-0.48) ml/kg, t=2.55, P<0.05) and higher blood glucose (6.21±0.78 (95% CI: 6.09-6.33) vs. 5.59±1.11 (95% CI: 5.43-5.76) mmol/L, t=-5.91, P<0.001). The 95% confidence interval of the volume difference between the 2 groups was 0.017-0.163, the upper limit value was 0.163

Early-life lactoferrin intervention modulates the colonic microbiota, colonic microbial metabolites and intestinal function in suckling piglets.

This study reports the effects of early-life lactoferrin (LF) intervention on the colonic microbiota, intestinal function and mucosal immunity in suckling piglets. A total of 60 Duroc × Landrace × Yorkshire suckling piglets from six sows were assigned to the control (CON) and LF groups in litters. The LF group piglets were fed 0.5 g/kg body weight of LF solution per day, and the CON group piglets were fed the same dose of physiological saline for a week. Six piglets from the two groups were randomly chosen and euthanised on days 8 and 21. The LF group piglets had higher ACE and Chao1 indices of colonic microbiota than the CON group piglets (P < 0.05). In addition, the LF group piglets had a higher abundance of Roseburia (P < 0.05) and a lower abundance of Escherichia-Shigella (P < 0.05) in the colonic digesta. The LF group piglets also had a higher concentration of butyrate (P < 0.05) in the colonic digesta. Moreover, the LF group piglets had a higher gene expression of occludin (P < 0.05) in the colonic mucosa. In addition, the gene expression of MUC4 was upregulated in the LF group piglets compared with that in the CON group on day 21 (P < 0.05), and the lower gene expression of TLR-4 was found in the LF group compared with the CON group on day 8 (P < 0.05). Furthermore, the concentration of IL-10 was increased in the LF group on day 8 (P < 0.05), while the LF group piglets had a higher concentration of sIgA and lower concentrations of IL-1α and IL-1ß (P < 0.05) in the colonic mucosa. These results suggest that early-life LF intervention can modulate the composition of colonic microbiota and improve the intestinal function in suckling piglets.Key Points• Early-life LF intervention significantly modulated colon microbiota.• Early-life LF intervention can improve the colon health.• The colon microbiota plays an important role in host health.

Treatment of corn with lactic acid or hydrochloric acid modulates the rumen and plasma metabolic profiles as well as inflammatory responses in beef steers.

BACKGROUND: High-grain diets that meet the energy requirements of high-producing ruminants are associated with a high risk of rumen disorders. Mild acid treatment with lactic acid (LA) has been used to modify the degradable characteristics of grains to improve the negative effects of high-grain diets. However, the related studies mainly focused on dairy cows and explored the effects on rumen fermentation, production performance, ruminal pH and so forth. And up to date, no studies have reported the hydrochloric acid (HA) treatment of grains for ruminant animals. Therefore, based on metabolomics analysis, the aim of this study was to evaluate the effects of treatment of corn by steeping in 1% LA or 1% HA for 48 h on the rumen and plasma metabolic profiles in beef steers fed a high corn (48.76%) diet with a 60:40 ratio of concentrate to roughage. The inflammatory responses of beef cattle fed LA- and HA-treated corn were also investigated. RESULTS: Based on ultra-high-performance liquid tandem chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) metabolomics and multivariate analyses, this study showed that steeping corn in 1% LA or 1% HA modulated the metabolic profiles of the rumen. Feeding beef steers corn steeped in 1% LA or 1% HA was associated with lower relative abundance of carbohydrate metabolites, amino acid metabolites, xanthine, uracil and DL-lactate in the rumen; with higher ruminal pH; with lower concentrations of acetate, iso-butyrate and iso-valerate; and with a tendency for lower ruminal lipopolysaccharide (LPS) concentrations. Moreover, the data showed lower concentrations of plasma C-reactive protein, serum amyloid A, haptoglobin, interleukin (IL)-1ß and IL-8 in beef steers fed 1% LA- or HA-treated corn. The 1% LA treatment decreased the concentrations of plasma LPS, LPS-binding protein and tumour necrosis factor-alpha and the relative abundance of L-phenylalanine, DL-3-phenyllactic acid and tyramine in plasma. The 1% HA treatment decreased the relative abundance of urea in plasma and increased the relative abundance of all amino acids in the plasma. CONCLUSIONS: These findings indicated that LA or HA treatment of corn modulated the degradation characteristics of starch, which contributed to improving the rumen and plasma metabolic profiles and to decreasing inflammatory responses in beef steers fed a high-concentrate diet.

A quantitative analysis linking sea turtle mortality and plastic debris ingestion.

Plastic in the marine environment is a growing environmental issue. Sea turtles are at significant risk of ingesting plastic debris at all stages of their lifecycle with potentially lethal consequences. We tested the relationship between the amount of plastic a turtle has ingested and the likelihood of death, treating animals that died of known causes unrelated to plastic ingestion as a statistical control group. We utilized two datasets; one based on necropsies of 246 sea turtles and a second using 706 records extracted from a national strandings database. Animals dying of known causes unrelated to plastic ingestion had less plastic in their gut than those that died of either indeterminate causes or due to plastic ingestion directly (e.g. via gut impaction and perforation). We found a 50% probability of mortality once an animal had 14 pieces of plastic in its gut. Our results provide the critical link between recent estimates of plastic ingestion and the population effects of this environmental threat.

Galactomannan More than Pectin Exacerbates Liver Injury in Mice Fed with High-Fat, High-Cholesterol Diet.

SCOPE: Galactomannan and citrus pectin are considered 'super fibers' known for altering gut microbiota composition and improving glucose and lipid metabolism. The study aims to investigate the fiber's effect on a nonalcoholic steatohepatitis (NASH) model. METHODS AND RESULTS: Two feeding experiments are carried out using groups of 7-8 week-old male C57BL/6J mice. The diets used are based on a high cholesterol/cholate diet (HCD), such as a nutritional NASH model. Mice are fed a diet with or without 15% fiber-citrus pectin (HCD-CP) or galactomannan (HCD-G) together with the HCD (first experiment), which commenced 3 weeks prior to the HCD (second experiment). Liver damage is evaluated by histological and biochemical parameters. Galactomannan leads to lesser weight gain and improved glucose tolerance, but increased liver damage. This is shown by elevated levels of liver enzymes compared to that with HCD alone. Fibers induce higher steatosis, as evaluated by liver histology. This intriguing result is linked to various changes in the gut microbiota, such as elevated Proteobacteria levels in the galactomannan group, which are correlated with disturbed metabolism and dysbiosis. CONCLUSIONS: In a NASH mouse model, galactomannan increases liver damage but improves glucose metabolism. Changes in the microbiota composition may answer this enigmatic observation.

Inclusion of dietary ß-mannanase improves performance and ileal digestibility and reduces ileal digesta viscosity of broilers fed corn-soybean meal based diet.

This study was aimed to evaluate the influence of dietary ß-mannanase inclusion on growth performance, apparent ileal digestibility, digesta viscosity, blood metabolites and excreta noxious gas emissions in broilers fed corn-soybean meal based diet. A total of 600 conventional healthy 1-d-old ROSS 308 broilers with body weight 45 ± 0.50 g (mean ± SD) were randomly assigned to 4 dietary treatments with 10 replicates cages, with 15 broilers in each and fed basal diet supplemented to corn-SBM based diets with 0, 2400, 4800, and 7200 MNU ß-mannanase/kg for 35 d feeding trial period. Significant results were observed on improved average daily gain and reduced feed conversion ratio during trial period and also reduced ileal digesta viscosity and improved apparent ileal digestibility of dry matter, nitrogen and energy. However, no significant effects were found on blood urea nitrogen and creatinine, excreta noxious gas emissions. In conclusion, the inclusion of dietary ß-mannanase had potential to improve daily gain and feed efficiency and apparent ileal digestibility while decreasing digesta viscosity of broiler.

Probabilistic risk model to assess the potential for resistance selection following the use of anti-microbial medicated feed in pigs.

The cross-contamination of non-medicated feed with residues of anti-microbials (AM) causes a public and animal health concern associated with the potential for selection and dissemination of resistance. To analyse the associated risks, a probabilistic model was built using @Risk® (Palisade Corporation®) to show the potential extent of the effect of cross-contaminated pig feed on resistance selection. The results of the model include estimations of the proportion of pigs per production stage with residues of doxycycline, chlortetracycline, sulfadiazine and trimethoprim in their intestinal contents, as a result of exposure to cross-contaminated feed with different carry-over levels, in Belgium. By using a semi-quantitative approach, these estimations were combined with experimental data on AM concentrations associated with potential for resistance-selection pressure. Based on this model, it is estimated that 7.76% (min = 1.67; max = 36.94) of sows, 4.23% (min = 1.01%; max = 18.78%) of piglets and 2.8% (min = 0.51%; max = 14.9%) of fatteners in Belgium have residues of doxycycline in their intestinal tract due to consumption of feed with at least 1% carry-over. These values were estimated to be almost triple for sulfadiazine, but substantially lower for chlortetracycline and trimethoprim. Doxycycline concentrations as low as 1 mg/L (corresponding to consumed feed with at least 1% carry-over) can select for resistant porcine commensal Escherichia coli in vitro and in vivo. Conclusions on this risk could not be drawn for other AM at this stage, due to the lack of data on concentrations associated with resistance development. However, since the possibility of resistance mechanisms (e.g. co-selection) occurring cannot be excluded, the results of this model highlight that the use of AM medicated feed should be minimised where possible. In case of medicated feed production, good practice should be followed thoroughly at all levels of production, distribution, storage and administration, with a special focus on the feed distributed to piglets and sows.

The effect of pH, buffer capacity and ionic strength on quetiapine fumarate release from matrix tablets prepared using two different polymeric blends.

The objective of this study was to investigate the effect of the different physiological parameters of the gastrointestinal (GI) fluid (pH, buffer capacity, and ionic strength) on the in vitro release of the weakly basic BCS class II drug quetiapine fumarate (QF) from two once-a-day matrix tablet formulations (F1 and F2) developed as potential generic equivalents to Seroquel® XR. F1 tablets were prepared using blends of high and low viscosity grades of hydroxypropyl methylcellulose (HPMC K4M and K100LV, respectively), while F2 tablets were prepared from HPMC K4M and PEGylated glyceryl behenate (Compritol® HD5 ATO). The two formulations attained release profiles of QF over 24 h similar to that of Seroquel® XR using the dissolution medium published by the Food and Drug Administration (FDA). A series of solubility and in vitro dissolution studies was then carried out using media that simulate the gastric and intestinal fluids and cover the physiological pH, buffer capacity and ionic strength range of the GIT. Solubility studies revealed that QF exhibits a typical weak base pH-dependent solubility profile and that the solubility of QF increases with increasing the buffer capacity and ionic strength of the media. The release profiles of QF from F1, F2 and Seroquel® XR tablets were found to be influenced by the pH, buffer capacity and ionic strength of the dissolution media to varying degrees. Results highlight the importance of studying the physiological variables along the GIT in designing controlled release formulations for more predictive in vitro-in vivo correlations.

Gastric Fluid Volume Change After Oral Rehydration Solution Intake in Morbidly Obese and Normal Controls: A Magnetic Resonance Imaging-Based Analysis.

BACKGROUND: Although preoperative fluid intake 2 hours before anesthesia is generally considered safe, there are concerns about delayed gastric emptying in obese subjects. In this study, the gastric fluid volume (GFV) change in morbidly obese subjects was investigated after ingesting an oral rehydration solution (ORS) and then compared with that in nonobese subjects. METHODS: GFV change over time after the ingestion of 500 mL of ORS containing 2.5% carbohydrate (OS-1) was measured in 10 morbidly obese subjects (body mass index [BMI], >35) scheduled for bariatric surgery and 10 nonobese (BMI, 19-24) using magnetic resonance imaging. After 9 hours of fasting, magnetic resonance imaging scans were performed at preingestion, 0 min (just after ingestion), and every 30 minutes up to 120 minutes. GFV values were compared between morbidly obese and control groups and also between preingestion and postingestion time points. RESULTS: The morbidly obese group had a significantly higher body weight and BMI than the control group (mean body weight and BMI in morbidly obese, 129.6 kg and 46.3 kg/m, respectively; control, 59.5 kg and 21.6 kg/m, respectively). GFV was significantly higher in the morbidly obese subjects compared with the control group at preingestion (73 ± 30.8 mL vs 31 ± 19.9 mL, P = .001) and at 0 minutes after ingestion (561 ± 30.8 mL vs 486 ± 42.8 mL; P < .001). GFV declined rapidly in both groups and reached fasting baseline levels by 120 minutes (morbidly obese, 50 ± 29.5 mL; control, 30 ± 11.6 mL). A significant correlation was observed between preingestion residual GFV and body weight (r = .66; P = .001). CONCLUSIONS: Morbidly obese subjects have a higher residual gastric volume after 9 hours of fasting compared with subjects with a normal BMI. However, no differences were observed in gastric emptying after ORS ingestion in the 2 populations, and GFVs reached baseline within 2 hours after ORS ingestion. Further studies are required to confirm whether the preoperative fasting and fluid management that are recommended for nonobese patients could also be applied to morbidly obese patients.

Gastric Residual Volume after Split-Dose Bowel Preparation versus Conventional Single-Dose Regimen before Anesthetic Colonoscopy.

The aim of this study was to compare gastric residual volume (GRV) in patients given a split-dose versus a conventional single-dose of polyethylene glycol (PEG) preparation before undergoing anesthetic colonoscopy. Methods. In a prospective observational study, we assessed GRV in outpatients undergoing same-day anesthetic gastroscopy and colonoscopy between October 8 and December 30 of 2016. Outpatients were assigned to the split-dose (1 L PEG in the prior evening and 1 L PEG 2-4 h before endoscopy) or single-dose (ingestion of 2 L PEG ≥ 6 h before endoscopy) regimen randomly. Bowel cleansing quality was assessed with the Boston Bowel Preparation Scale (BBPS). Results. The median GRV in the split-dose group (17 ml, with a range of 0-50 ml; N = 65) was significantly lower than that in the single-dose group (22 ml, with a range of 0-62 ml; N = 64; p = 0.005), with a better bowel cleansing quality (BBPS score 8.05 ± 0.82 versus 7.64 ± 1.21; p = 0.028). GRV was not associated with diabetes or the use of medications. Conclusions. GRV after a split-dose preparation and fasting for 2-4 hours is not larger than that after a conventional single-dose preparation and fasting for 6-8 hours. The data indicates that the split-dose bowel preparation might not increase the risk of aspiration.

Colon Hypersensitivity to Distension, Rather Than Excessive Gas Production, Produces Carbohydrate-Related Symptoms in Individuals With Irritable Bowel Syndrome.

BACKGROUND & AIMS: Poorly digested, fermentable carbohydrates may induce symptoms of irritable bowel syndrome (IBS) via unclear mechanisms. We performed a randomized trial with magnetic resonance imaging (MRI) analysis to investigate correlations between symptoms and changes in small- and large-bowel contents after oral challenge. METHODS: We performed a 3-period, cross-over study of 29 adult patients with IBS (based on Rome III criteria, with symptoms of abdominal pain or discomfort for at least 2 days/wk) and reported bloating. In parallel, we performed the same study of 29 healthy individuals (controls). Studies were performed in the United Kingdom from January 2013 through February 2015. On 3 separate occasions (at least 7 days apart), subjects were given a 500-mL drink containing 40 g of carbohydrate (glucose in the first period, fructose in the second, and inulin in the third, in a random order). Levels of breath hydrogen were measured and intestinal content was assessed by MRI before and at various time points after consumption of each drink. Symptoms were determined based on subjects' responses to the Hospital Anxiety and Depression Scale questionnaire and the Patient Health Questionnaire-15. The primary end point was whether participants had a clinically important symptom response during the 300 minutes after consumption of the drink. RESULTS: More patients with IBS reached the predefined symptom threshold after intake of inulin (13 of 29) or fructose (11 of 29) than glucose (6 of 29). Symptoms peaked sooner after intake of fructose than inulin. Fructose increased small-bowel water content in both patients and controls whereas inulin increased colonic volume and gas in both. Fructose and inulin increased breath hydrogen levels in both groups, compared with glucose; fructose produced an earlier increase than inulin. Controls had lower symptom scores during the period after drink consumption than patients with IBS, despite similar MRI parameters and breath hydrogen responses. In patients who reached the symptom threshold after inulin intake, peak symptom intensity correlated with peak colonic gas (r = 0.57; P < .05). Changes in MRI features and peak breath hydrogen levels were similar in patients who did and did not reach the symptom threshold. CONCLUSIONS: Patients with IBS and healthy individuals without IBS (controls) have similar physiological responses after intake of fructose or inulin; patients reported symptoms more frequently after inulin than controls. In patients with a response to inulin, symptoms related to levels of intraluminal gas, but peak gas levels did not differ significantly between responders, nonresponders, or controls. This indicates that colonic hypersensitivity to distension, rather than excessive gas production, produces carbohydrate-related symptoms in patients with IBS. Clinicaltrials.gov no: NCT01776853.

Effects of the replacement of concentrate and fibre-rich hay by high-quality hay on chewing, rumination and nutrient digestibility in non-lactating Holstein cows.

The aim of this study was to investigate the effects of high-quality hay with an elevated sugar content alone or with graded amounts of concentrate feed on chewing and ruminating activity, apparent total tract digestibility (ATTD) and ruminal pH at different time points after feeding in the free ruminal liquid (FRL) and the particle-associated ruminal liquid (PARL). Eight rumen cannulated non-lactating Holstein cows were arranged in a Latin square design in four experimental runs lasting 25 d each. The four diets tested were 60NQ (60% normal-quality hay + 40% concentrate), 60HQ (60% high-quality hay + 40% concentrate), 75HQ (75% high-quality hay + 25% concentrate) and 100HQ (100% high-quality hay). Normal and high-quality hays differed in sugar contents (11.3% vs. 18.7% in dry matter [DM]), neutral detergent fibre (NDF; 57.7% vs. 46.3% in DM), acid detergent fibre (ADF, 35.0% vs. 23.5% in DM) and crude protein (CP, 11.3% vs. 23.5% in DM). Data showed that ATTD of DM, CP, NDF and ADF was higher with the high-quality hay diets. Time spent eating was reduced with high-quality hay. However, time spent ruminating was longest in Group 100HQ. In all groups, ruminal pH of FRL and PARL decreased with time after the morning feeding. But 10 h later, pH of Group 100HQ was higher again compared with the other groups. Considering the average pH in FRL over all measured time points, cows in Groups 60NQ and 100HQ had higher pH values of 6.85 and 6.83, respectively. Regarding pH values in PARL, animals of Group 60NQ displayed the highest pH value (6.68), whereas the lowest value of 6.21 was found in Group 60HQ. Overall, results suggest that high-quality hay maintains the diet's structural effectiveness by stimulating rumination and stabilising ruminal pH while greatly improving ATTD. However, the structural effectiveness of the high-quality hay gets impaired with increasing proportion of concentrate feed in the diet.

Sodium Butyrate Reduces Colitogenic Immunoglobulin A-Coated Bacteria and Modifies the Composition of Microbiota in IL-10 Deficient Mice.

High levels of immunoglobulin A (IgA)-coated bacteria may have a role in driving inflammatory bowel disease (IBD). We therefore investigated the effect of sodium butyrate on microbiota in IBD prone interleukin (IL)-10-/- mice. At 8 weeks of age, mice were allocated into three groups (n = 4/group): normal (C57BL/6), IL-10-/-, and IL-10-/- treated with sodium butyrate (100 mM). Severity of colitis, inflammatory cytokine and short-chain fatty acid (SCFA) concentration in proximal colon contents, the percentage of IgA-coated bacteria and microbiota composition by 16S ribosomal RNA assessment of stool were measured after 4 weeks of treatment. Sodium butyrate ameliorated histological colitis and decreased levels of tumor necrosis factor (TNF)-α and IL-6 in IL-10-/- mice compared with those without treatment. At the phylum level, a reduction in Bacteroidetes and an increase in Firmicutes in IL-10-/- mice treated with sodium butyrate were observed. Additionally, Prevotellaceae species were reduced in IL-10-/- mice treated with sodium butyrate as compared with those without treatment. The level of biodiversity was slightly increased and the amount of IgA-coated bacteria decreased in IL-10-/- mice treated with sodium butyrate compared with those without treatment. Our results indicate that sodium butyrate protects against colitis, possibly through modifying the gut microbiota, enriching biodiversity and reducing the amount of colitogenic IgA-coated bacteria in IL-10-/- mice.

Pica in Rats as a Preclinical Model of Emesis.

The ability to assess the potential for gastrointestinal adverse events in a preclinical setting is a challenge in the development of new drugs, as the vast majority of in vivo research is conducted in rodent species lacking a vomiting reflex. The use of higher species capable of emesis is often limited by cost, technical experience, and relevant efficacy models to define a therapeutic index. Additionally, investigators should be mindful of ethical considerations when using more sentient species when an alternative in lower species is available. This unit describes the use of pica behavior in rodents as an alternative for evaluating emetic potential in vivo. After an acclimation period, the incidence of rats engaging in pica following the administration of a test article can be used to generate a dose-response curve of the pica behavior. When linked with an appropriate efficacy model, this allows compounds to be ranked based on therapeutic index. © 2016 by John Wiley & Sons, Inc.

Gastrointestinal dissolution, supersaturation and precipitation of the weak base indinavir in healthy volunteers.

This study investigated the impact of relevant gastrointestinal conditions on the intraluminal dissolution, supersaturation and precipitation behavior of the weakly basic drug indinavir. The influence of (i) concomitant PPI intake and (ii) the nutritional state on the gastrointestinal behavior of indinavir was assessed in order to identify the underlying mechanisms responsible for previously reported interactions. Five healthy volunteers were recruited into a crossover study containing the following arms: fasted state, fed state and fasted state with concomitant proton pump inhibitor (PPI) use. In each condition, one Crixivan® capsule (400mg indinavir) was orally administered with 240mL of water. Gastric and duodenal fluids, aspirated as a function of time, were monitored for total and dissolved indinavir concentrations on a UPLC-MS/MS system. Indinavir's thermodynamic solubility was determined in individual aspirates to evaluate supersaturation. The bioaccessible fraction of indinavir in aspirated duodenal fluids was determined in an ex vivo permeation experiment through an artificial membrane. A nearly complete dissolution of indinavir in the fasted stomach was observed (90±3%). Regardless of dosing conditions, less indinavir was in solution in the duodenum compared to the stomach. Duodenal supersaturation was observed in all three testing conditions. The highest degrees of duodenal supersaturation (6.5±5.9) were observed in the fasted state. Concomitant PPI use resulted in an increased gastric pH and a smaller fraction of indinavir being dissolved (58±24%), eventually resulting in lower intestinal concentrations. In fed state conditions, drug release from the capsule was delayed and more gradually, although a similar fraction of the intragastric indinavir dissolved compared to the fasted state (83±12%). Indinavir was still present in the lumen of the duodenum three hours after oral administration, although it already reached 70% (on average) of the fasted state concentrations (expressed as AUC0-3h). Based on a 2-h permeation experiment, the bioaccessible fraction of indinavir was 2.6-fold lower in a fed state sample compared to a fasted state sample. Our data indicate that the reported reduction in indinavir's bioavailability after concomitant PPI administration is caused by an elevated gastric pH resulting in less indinavir in solution in the stomach and, subsequently, reduced duodenal concentrations. In fed state conditions, however, intestinal micellar entrapment of indinavir appeared to cause the reported reduced bioavailability, regardless of duodenal concentrations.

Simultaneous determination of six short-chain fatty acids in colonic contents of colitis mice after oral administration of polysaccharides from Chrysanthemum morifolium Ramat by gas chromatography with flame ionization detector.

Short-chain fatty acids (SCFAs) produced by the intestinal bacteria are very critical for the intestinal barrier, mucosal cytoprotection and normal intestinal biology. However, accumulation of SCFAs promoted by the polysaccharides from Chrysanthemum morifolium Ramat remains unknown. Thus, it is necessary to investigate SCFAs in the colonic contents of dextran sulfate sodium (DSS) induced colitis mice after oral administration of the polysaccharides from C. morifolium Ramat which is very helpful to unravel how it works. In this study, a rapid and reliable gas chromatographic method with flame ionization detector (GC-FID) for simultaneous determination of six SCFAs such as acetic acid (AA), propionic acid (PA), butyric acid (BA), isobutyric acid (IBA), valeric acid (VA) and isovaleric acid (IVA) has been developed and validated. Under the optimized chromatographic conditions and sample extraction procedure, good separation for 6 target compounds was obtained on a HP-INNOWAX column within 12min. Results revealed that polysaccharides from C. morifolium Ramat positively affected the SCFAs intestinal production. The polysaccharides group had greater SCFAs concentration in colonic content than the DSS-treated group (P<0.05), which was decreased remarkably compared to the normal group (P<0.01). With the decrease of the polysaccharides dosage, the contents of AA, PA and VA increased gradually, while the change of BA concentration was the opposite. There was no significant difference in the content of IBA at the different administration concentrations. And the content of IVA reached the highest concentration 0.953mg/g at lower dose of the polysaccharides. Additionally, oral administration of the polysaccharides prominently attenuated the body weight loss, reduced the disease activity index, rectal bleeding and stool consistency, improved colon shortening and macroscopic score of colitis. Our results indicated that the polysaccharides of C. morifolium Ramat might be used as prebiotic agents to prevent gut dysbiosis and inflammatory bowel disease.