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Slow elimination of nonylphenol from rat intestine.

Nonylphenol, a possible endocrine disrupter, tends to persist in rat liver tissue after detoxification as a glucuronide conjugate by UDP-glucuronosyltransferase 2B1 expressed in the liver. In the intestine, however, the metabolism and dynamics of nonylphenol remain to be elucidated. The objectives of this study were to clarify the metabolism and excretion of nonylphenol having a long alkyl chain in the first barrier intestine and to estimate whether the nonylphenol alkyl chain governs the speed of excretion from intestinal tissue. Organ tissue glucuronidation activity toward alkylphenols (C2, C9) was investigated using microsomes prepared from intestinal tissue. To elucidate the elimination pathway of alkylphenols (C2, C4, C6, C9), a perfusion study was conducted on everted intestine. After oral administration (5 mg) of alkylphenols (C2, C9) to rats, gastrointestinal contents and related organ tissues (gastrointestinal tissue, liver, and kidney), blood, and urine were analyzed for alkylphenols (C2, C9) and glucuronides. The intestine showed strong glucuronidation activity toward alkylphenols (C2, C9). In everted intestinal assay, nonylphenol was glucuronidated within the intestinal wall, as was the case for other alkylphenols (C2, C4, C6), but nonylphenol-glucuronide was not excreted from intestinal tissue. Orally administered nonylphenol remained for long periods in gastrointestinal tissue as both the parent compound and glucuronide. The present study confirmed that intestinal tissue possesses an alkylphenol elimination system using UDP-glucuronosyltransferase; however, this system is impaired by the marginal transport of alkylphenol-glucuronide possessing long alkyl chain, such as nonylphenol.

Administration, Oral↗

Gastrointestinal tissue polyamine contents of patients with Barrett's esophagus treated with alpha-difluoromethylornithine.

alpha-Difluoromethylornithine (DFMO), an investigational chemopreventive agent, suppresses polyamine contents and decreases epithelial carcinogenesis in experimental models. The ability of this drug to decrease polyamine contents in human esophageal tissues has not yet been determined. Eight patients with Barrett's esophagus were treated with DFMO at a dose of 1.5 g/m2/day for 12 weeks. Four sites (Barrett's lesion, adjacent normal squamous esophagus, gastric tissue, and small bowel) were biopsied in each patient before, during, and after DFMO treatment in order to assess the effects of this drug on tissue polyamine levels. Ornithine decarboxylase activities and polyamine contents varied in each site analyzed. The rank orders were Barrett's > small bowel congruent to normal esophagus > gastric tissue for ODC activities, and small bowel > or = Barrett's congruent to normal esophagus > gastric tissue for putrescine contents. Spermidine, but not spermine, contents in the Barrett's lesions and normal squamous esophageal tissue were suppressed by systemic DFMO treatment and recovered to untreated control values when DFMO therapy was discontinued. Systemic DFMO treatment did not affect the levels of either of these two amines in gastric tissue and small bowel. Since DFMO can suppress polyamine contents in several gastrointestinal tissues, including Barrett's mucosa, we conclude that it is an effective agent with which to test the hypothesis that depletion of spermidine contents may prevent the development of adenocarcinoma of the esophagus in this specific patient group.

Aged↗

Effect of niacin supplementation on the concentration of niacin in rumen and duodenal digesta and in whole blood of sheep.

1. Niacin concentrations in rumen liquor, duodenal digesta and blood, and daily duodenal flow of niacin were measured in four wethers which were fed an oatstraw grain concentrate diet (with normal niacin content) or an oatstraw maize diet (with low niacin content). The effect of an intraruminal supplementation of 2 mmoles nicotinic acid (NIA) or nicotinamide (NAM) on concentrations of NIA and NAM in gastrointestinal contents and blood and on daily duodenal flow of NIA and NAM was studied. The animals were equipped with rumen fistula and duodenal re-entrant cannulae. 2. NIA concentration in strained rumen liquor was 384 and 264 nmol/ml and daily duodenal flow of niacin was 616 and 528 mumoles/d in animals fed normal or low niacin diet, respectively. Intraruminal administrations of 2 mmoles of NIA or NAM raised NIA concentration in strained rumen liquor for approximately 6 h. About 20% of the administered dose of NIA or NAM passed out of the rumen and resulted in a 41% increase in daily duodenal flow of niacin. The remaining 80% of the administered dose of NIA or NAM disappeared from rumen liquor without being washed out. 3. Supplemented NAM was rapidly hydrolyzed to NIA and ammonia when administered into the rumen. 4. NAM concentration in blood appeared to be unaffected by the dietary content of NIA or by niacin supplementation. 5. The NIA concentration in strained rumen liquor was positively related with niacin content of the diet. Increases in duodenal flow of niacin had no marked effect on concentration of NAM in blood. It appeared that feeding diets with different NIA content affected apparent niacin synthesis in the rumen.

Animal Feed↗

Pneumoperitoneography: a special radiological technic used in nonhuman primate medicine.

Visualization of abdominal structures was difficult in survey radiographs of nonhuman primates due to the paucity of intra-abdominal fat and the presence of gastrointestinal contents. Simple pneuoperitoneography combined with contrast gastrointestinal studies provided valuable information, ie, size, shape, and position, of abdominal structures. After ip injection of carbon dioxide, a series of positional radiographs were exposed to delineate the various abdominal organs. The positioning device used in the examination was illustrated and described and the clinical indications and diagnostic value of pneumoperitoneography discussed.

Animals↗

Chronic exposure to secoisolariciresinol diglycoside alters lignan disposition in rats.

Mammalian lignans from colonic bacterial action on secoisolariciresinol diglycoside (SDG) may mediate the anticarcinogenic effect of prolonged SDG feeding in rats. To elucidate lignan bioactivity, our objective was to determine 3H-SDG disposition in rats with acute or chronic SDG treatment over 48 h. After food deprivation overnight, female Sprague-Dawley rats (70-72 d old) were given a single gavage of 3H-SDG (3.7 kBq/g body weight) either immediately (acute, n = 12) or after 10 d of gavage with 1.5 mg unlabeled SDG/d (chronic, n = 12). Rats were killed at 12, 24, 36 and 48 h after gavage, and samples collected and analyzed for radioactivity by liquid scintillation counting. Radioactivity was 1- to 16-fold higher at 12 vs. 48 h for tissues, blood and gastrointestinal contents (P < 0.05). By 48 h, >80% of the recovered dose was excreted in both groups (feces > 50%, urine = 28-32%). Tissue radioactivity was highest (by 0.5- to 176-fold) in the cecum (P < 0.05). Levels in the liver, kidney and uterus (12 h) were 0.2- to 7.5-fold higher than in other nongastrointestinal tissues. At 12 h, fecal radioactivity was negligible, and cecal content, liver and adipose radioactivity were one- to threefold greater in rats with chronic SDG exposure than in those acutely exposed (P < 0.05). Blood radioactivity, present mostly in the plasma fraction (0.4% of dose), suggested that lignan concentrations could be 3000 times higher than peak estrogen levels in rats. Thus, SDG metabolites accumulated in the liver, kidney, intestinal tissues and uterus. Chronic SDG exposure delayed fecal excretion while increasing liver and adipose lignan levels.

Animals↗

Synthesis, characterization and in vitro release of 5-aminosalicylic acid and 5-acetyl aminosalicylic acid of polyanhydride--P(CBFAS).

A novel polyanhydride, poly[(5-carboxybutyl formamide)-2-acetyl salicylic anhydride] (P(CBFAS)), with 5-aminosalicylic acid (5-ASA) incorporated into the polymer backbone was synthesized and characterized by infrared, (1)H-nuclear magnetic resonance, differential scanning calorimetry, vapor pressure osmometry, etc. The polyanhydride was subjected to degradation and simultaneously released 5-ASA and its derivative 5-acetyl aminosalicylic acid (5-acetyl ASA) in vitro under various conditions. The factors influencing the release profiles of 5-ASA and 5-acetyl ASA, including polymer molecular weights, pH value, enzyme and rat gastrointestinal contents, were examined. The results showed that the release rate of 5-ASA and 5-acetyl ASA increases with increasing pH value and with decreasing molecular weights. In PBS (pH 8.0, 37 degrees C) total ASA released was 8.0% for P(CBFAS)(1) (Mn 10770) in 13 h, but only 1.1 and 2.6% at pH 2.0 and 6.5, respectively. Enzymes including pepsin and trypsin, as well as rat gastric and jejunum contents had little effect on the release rate of 5-ASA and 5-acetyl ASA at pH 2.0 and 6.5 (less than 4% in 13 h). However, the release rate of 5-ASA and 5-acetyl ASA was much fast in PBS(pH 8.0) containing 5% of cecal contents, the total ASA released was 13.6% for the polymer in 13 h. Considering the high drug loading of the polymer (50.2% of 5-ASA moieties in the backbones) and the degradation characters, it is possible to reach high local concentration of 5-ASA in the colon site via oral administration. Therefore, P(CBFAS) may be potentially useful in the colon specific delivery of 5-ASA.

Aminosalicylic Acids↗

Pharmacokinetics and metabolism of hydroxytyrosol, a natural antioxidant from olive oil.

3,4-Dihydroxyphenylethanol (DOPET) is the major o-diphenol detectable in extra virgin olive oil, either in free or esterified form. Despite its relevant biological effects, mainly related to its antioxidant properties, little data have been reported so far on its toxicity and metabolism. The aim of the present work is to evaluate DOPET toxicity and to investigate its molecular pharmacokinetics by using the (14)C-labeled diphenol. When orally administered to rats, the molecule does not show appreciable toxicity up to 2 g/kg b.wt. To identify and quantify its metabolites, [(14)C]DOPET has been synthesized and intravenously injected in rats. The pharmacokinetic analysis indicates a fast and extensive uptake of the molecule by the organs and tissues investigated, with a preferential renal uptake. Moreover, 90% of the administered radioactivity is excreted in urine collected up to 5 h after injection, and about 5% is detectable in feces and gastrointestinal content. The characterization of the labeled metabolites, extracted from the organs and urine, has been performed by high-pressure liquid chromatography analysis. In all the investigated tissues, DOPET is enzymatically converted in four oxidized and/or methylated derivatives. Moreover, a significant fraction of total radioactivity is associated with the sulfo-conjugated forms, which also represent the major urinary excretion products. On the basis of the reported results, an intracellular metabolic pathway of exogenously administered DOPET, implying the involvement of catechol-O-methyltransferase, alcohol dehydrogenase, aldehyde dehydrogenase, and phenolsulfotransferase, has been proposed.

Administration, Oral↗

Stunting syndrome in broilers: physical, physiological, and behavioral aspects.

The effect of stunting syndrome (SS) on young broilers induced by orally administering an inoculum prepared from intestines of SS-affected broiler chicks was studied in two experiments. Depression of growth, feed intake, and feed utilization, respectively, was negatively related to the age of inoculation, i.e., highest at posthatch inoculation (63, 57, and 61%), and intermediate at the ages of 3 (42, 45, and 50%) and 7 d (29, 34, and 53%), whereas at the age of 14 d inoculation was ineffectual and the inoculated chicks performed similarly to the naive controls. Eating behavior was determined by periodically recording the number of chicks in each treatment group exhibiting this behavior, i.e., pecking mash in the feeder or pecking the litter. Eating activity was much higher in inoculated chicks (about 20 to 24%) than in the naive controls (6 to 12%) and as with performance negatively related to the age of inoculation. In chicks inoculated at the age of 14 d, eating activity was quite similar to that of the naive control chicks. Noninoculated chickens raised in the same room as their inoculated counterparts were infected by the disease agents. In some respects the consequences of horizontal infection were similar to those observed in inoculated chicks, i.e., depressed feed intake, growth, and feed utilization and a heavier heart, crop, proventriculus, gizzard, intestine, and gastrointestinal contents. In contrast, the activities of the pancreatic digestive enzymes were more similar to those of the naive controls than to those of the inoculated groups. At the age of 14 d, activities of amylase, trypsin, chymotrypsin, and lipase in the pancreas were lower in the inoculated than in the naive control birds. At the age of 21 d, the results were reversed and activity in the inoculated birds was higher than in the naive control birds. During both periods, the activity of pancreatic lipase was higher in the naive controls than in the inoculated birds. The hyperactivity estimated via a determination of eating activity suggests that SS is an affliction not only of digestion but also of metabolism.

Aging↗

Hypocholesterolemic effect of soybean protein in rats and mice after peptic digestion.

Analyses of gastrointestinal contents of rats fed soybean protein isolate and casein showed that soybean protein was readily digested in the stomach but migrated slowly in the small intestine. The soluble fraction of the stomach contents of rats fed soybean protein was separated by gel-filtration on Sephadex G25 into large and small molecular fractions, the latter was not found in rats fed casein. The formation of low-molecular-weight peptides was pH dependent, and analogous peptides were produced by pepsin in vitro not only from soybean protein but also from casein. In rats the peptic digest of soybean protein was found to be as hypocholesterolemic as intact soybean protein. Meanwhile, the cholesterol-lowering action of the large molecular fraction of the peptic digest tended to be greater than that of the small molecular fraction in mice. These observations suggest a significant role of peptic digestion in the cholesterol-lowering action of soybean protein.

Amino Acids↗

Effects of chemical sympathectomy on dopamine and noradrenaline content of the dog gastrointestinal tract.

The content of dopamine and noradrenaline in the mucosa-submucosa and muscular layers of different gastrointestinal areas of the dog, and its modification by 6-hydroxydopamine or pargyline plus 6-hydroxydopamine was studied by means of high pressure liquid chromatography with electrochemical detection. The amounts of dopamine and noradrenaline show a cephalocaudal increase but their physiological levels were rather low when compared with those reported in other tissues. This finding was consistent with the sparse noradrenergic innervation classically described for the gut with histochemical methodologies. On the basis that noradrenergic neurones are considered more susceptible to 6-hydroxydopamine than dopaminergic neurones, a difference abolished by previous treatment with pargyline, our findings did not suggest the existence of dopaminergic neurones in the gastrointestinal tract of the dog. In the muscular layer of the duodenum, jejunum and ileum it was observed that catecholamine depletion by both treatments was smaller than that obtained in the mucosa-submucosa. Due to the resistance to both kinds of chemical sympathectomy exhibited by the dopamine content, the existence of dopamine-containing enterochromaffin cells is proposed in the mucosa-submucosa of different portions of the stomach and small intestine.

Animals↗

Isolated trans-hiatal colonic herniation.

Isolated herniation of the colon through congenital or traumatic diaphragmatic defects are well documented. However, trans-hiatal herniation of the colon in the absence of an intrathoracic stomach has been reported only once. A 67-year-old man presented with intragastric abdominal pain and a chest x-ray film documenting a posterior mediastinal air-fluid level. Computed tomography showed gastrointestinal contents within the thorax. The findings on an upper gastrointestinal film with small bowel follow-through were normal. Finally, a barium enema identified transverse colon within the thoracic cavity. At laparoscopy, the entire transverse colon was reduced with the hernia sac. The crural defect was repaired, and a Toupet fundoplication was performed. A gastropexy was also added. The patient was discharged on postoperative day 2 able to tolerate a regular diet, and he has been asymptomatic for 5 months. This defect most likely represents a congenital deformity of the diaphragm with intact posterior gastric attachments, including the posterior phrenoesophageal ligament. An intact gastric mesentery enabled isolated colonic herniation with retention of the stomach its normal anatomic position. An antireflux procedure was performed in addition to the crural repair because of the circumferential dissection of the esophagus. This article is the second report of an isolated trans-hiatal herniation of the colon and the first report of laparoscopic repair of this entity.

Aged↗

Measures to test placement of nasogastric and nasointestinal feeding tubes: a review.

A literature review regarding commonly recommended bedside measures to test nasogastric and nasointestinal feeding tube placement is presented in this article. Among the methods discussed are: aspiration of recognizable gastrointestinal contents, auscultation of insufflated air, measurement of pH of gastrointestinal secretions, and observing for coughing and choking, inability to speak, and the appearance of bubbles from the end of the tube when it is held under water. Fallibilities in these methods as well as discrepancies in recommendations for their implementation and interpretation are discussed along with implications for current practice and needed areas for research.

Auscultation↗

Citrobacter freundii septicemia in two dogs.

A 4-month-old Maltese puppy and a 7.5-year-old Collie were diagnosed with septicemia associated with Citrobacter freundii. The puppy died soon, after developing weakness and mucohemorragic diarrhea. The Collie had immune-mediated hemolytic anemia and thrombocytopenia and was treated with immunosuppressive drugs before being euthanized. Gross examination of the puppy revealed mucohemorrhagic intestinal contents. Focal necrotic hepatitis, fibrinous peritonitis, interstitial pneumonia, and hemorrhagic gastrointestinal contents were observed in the older dog. Histologically, there was a diffuse, moderate, histiocytic meningitis in the puppy and a focal fibrinonecrotic hepatitis in the adult dog. Lesions in both dogs contained numerous gram-negative rods. Citrobacter freudii is a potential cause of monomicrobic bacteraemia-septicemia in puppies or immunocompromized adult dogs. The gastrointestinal tract is probably the main site of entry.

Animals↗

Unanticipated full stomach at anesthesia induction in a type I diabetic patient with asymptomatic gastroparesis.

We encountered a case of unanticipated full stomach at anesthesia induction, despite a 12-h fasting period, in a type I diabetes patient with diabetic neuropathy presenting for elective vitrectomy for proliferative diabetic retinopathy. The patient had ingested seaweed 24 h prior to the surgery, and it was later found in the aspirated gastric content. Gastrointestinal dysfunction due to diabetic neuropathy and the high fiber content of the ingested seaweed are the probable causes of unanticipated full stomach in our case.

Adult↗

Design and evaluation of a Lactobacillus group-specific ribosomal RNA-targeted hybridization probe and its application to the study of intestinal microecology in pigs.

The potential importance of anaerobic bacteria belonging to the Lactobacillus group has been well documented. Appropriate methods to rapidly evaluate species diversity and fluctuations in their population levels within the Lactobacillus group are being developed. Molecular tools such as hybridization probes based on rRNA sequences are well suited to these studies. The work reported here was undertaken to test the specificity of an hybridization probe to specifically recognize microorganisms of the Lactobacillus group and assess its usefulness as a quantitative tool to study fluctuations of the Lactobacillus population relative to the total bacterial population in gastrointestinal contents of pigs. We have designed a 25-mer oligonucleotide that targets a region common to and specific for the Lactobacillus group 16S rRNA sequences within the available database. The optimal wash temperature of the probe was experimentally determined to be 54 degrees C. The results obtained using the Lactobacillus group-specific probe (LGP) shows that Lactobacillus populations vary along the different segments of the gastrointestinal tract (GIT). In weaning piglets, the relative Lactobacillus signal intensity obtained constituted 100% of the relative RNA index in the stomach contents as determined by a bacterial domain probe (BDP), and between 90 to 100% in the duodenum. The signal of the Lactobacillus population decreased and reached its minimum in the distal part of the GIT. The same trend was observed in adult pigs, but in the stomach they constituted no more than 30% as determined by the BDP, and were present at lower levels in the other parts of the GIT. These studies document the quantitative importance of the lactobacilli in the stomach and small intestine of pigs. Further studies to investigate the role of lactobacilli in promoting the ecological balance of gut bacteria for probiotic therapy are being undertaken.

Animals↗

Chemical body composition of 20 Thoroughbred foals at 160 days of age, and preliminary investigation of techniques used to predict body fatness.

AIMS: To determine the chemical body composition of Thoroughbred foals born in two consecutive years, and to investigate several techniques used to predict body composition in foals born in the second year, with particular reference to fat. METHODS: The chemical composition of 20 foals at around 160 days of age, born in two years, was determined. In vivo techniques to predict body composition were assessed in 23 foals born in Year 2, before and after euthanasia; 10 of these foals were used for chemical body composition analysis. Techniques to assess body composition in vivo included liveweight (LW), overall and regional condition scores, ultrasonic fat thickness measurements over the ribs and rump, linear measurements and bioelectrical impedance analysis. Correlations were determined between ultrasonic fat thickness, and bioelectrical impedance analysis, before and after euthanasia. Stepwise regression analysis was used to determine the relationships between in vivo techniques used to assess body composition and the chemical body composition of 10 animals. RESULTS: Foals used for analysis of chemical composition weighed between 220.5 and 260.0 kg before euthanasia. Fat content ranged from 5.5-13.0% of the partial empty bodyweight (LW less head, gastrointestinal contents, distal limbs and skin). Fillies had significantly more fat mass and percentage fat than colts (p=0.031 for both measurements). The mean chemical composition of the fat-free partial empty body was 73.2% (SD 0.6) water, 22.7% (SD 0.9) protein, and 4.1% (SD 0.4) ash. Most of the variation in the concentration of empty body water was associated with variation in the concentration of fat (p<0.001). The live animal overall condition scores were correlated with fat mass and concentration (p=0.006 and p=0.013, respectively; n=10). Condition score over the rib region was highly correlated with fat mass and fat concentration (p=0.004 and p<0.001; n=10). Ultrasound measurements taken 10 cm cranial to the tailhead and 4 cm from midline, used to assess the thickness of rump fat, were correlated with condition score (p=0.001), and explained 71% of the variation in body fat mass (p=0.002; n=10).Nearly 50% of the variation in fat-free mass and partial empty body water mass were associated with variation in the impedance indices calculated from length and bioelectrical impedance analysis measurements (p=0.023 and p=0.026, respectively; n=10). CONCLUSIONS: At around 42% of expected mature weight, fillies were significantly more fat than colts. Condition scores were correlated with partial empty body fat mass, and there was a trend for higher scores in fillies compared to colts. Much of the variation in water or protein mass of the partial empty body could be explained by variations in LW. CLINICAL RELEVANCE: Measurements of LW, rump fat and condition score are useful predictors of the chemical composition of foals at 5 months of age.

Journal Article↗