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PubMedDate not supplied

Percutaneous endoscopic gastrojejunostomy: a dual center safety and efficacy trial.

Although jejunal tube placement through a percutaneous endoscopic gastrostomy (PEG) has not been proven to be preferable to PEG feeding, it would be theoretically advantageous for those patients prone to gastrointestinal aspiration. However, reliable placement of a small bowel feeding tube through a PEG has been technically difficult. We have previously reported successful placement of a percutaneous endoscopic gastrojejunostomy (PEG/J) with minimal complications. These results are in contrast to other series that report technical difficulty, frequent tube dysfunction and gastric aspiration. We describe an over-the-wire PEG/J technique performed by multiple operators at two medical centers. Gastrostomy tube placement was successful in 94% of patients. Initial placement of the jejunal tube was successful in 88% of patients. Second attempts were 100% successful. The average procedure time was 36 minutes. The distal duodenal and jejunal placement of the jejunal tube resulted in no episodes of gastroduodenal reflux. Complications included jejunal tube migration (6%), clogging (18%), and unintentional removal (11%). The majority of patients were ultimately converted to either oral or intragastric feedings. We conclude that the PEG/J system is a reliable, reproducible method of small bowel feeding and is associated with no episodes of tube feeding reflux when the jejunal tube is positioned in the distal duodenum or beyond. Furthermore, it provides a temporary nutritional bridge for those patients who are later transitioned to either PEG or oral feeding.

Adult↗
PubMed2005

The influence of bile salts and mixed micelles on the pharmacokinetics of quinine in rabbits.

The bioavailability of orally administered drugs can be influenced by interactions with food components and by physico-chemical conditions in the upper gastrointestinal tract. Normally, bile salts enhance the transport of lipophilic drugs across mucosal membranes. Bile salts are able to form stable mixed micelles consisting of fatty acids and phospholipids. Conventional micellar systems are known to solubilize lipophilic drugs having a low bioavailability. The influence of bile salts and mixed micelles on the pharmacokinetics of the lipophilic drug quinine was investigated in rabbits. Female rabbits were given intraduadenally quinine (5 mg/kg body weight) without and with incorporation into the micellar or mixed micellar systems. Blood was collected every 30 min for 6 h. In plasma, concentration of quinine was measured using HPLC. The plasma concentration-time profiles of quinine were significantly lower within the first 2 h after administration in presence of both the sodium salt of glycodeoxycholic acid (above the critical micellar concentration) as well as of mixed micellar systems consisting of glycodeoxycholic acid and palmitic acid and/or lecithin. The pharmacokinetic parameters AUC (relative bioavailability) and c(max) of quinine were significantly decreased by micellar systems in rabbits. These mixed micellar systems lower and not as expected, increase the absorption of quinine in vivo. Therefore, quinine should be orally administered at least 1h before food intake, particularly before fat intake.

Animals↗
PubMedDate not supplied

Pharmacokinetics of antiretrovirals administered to HIV-infected children via gastrostomy tube.

BACKGROUND: Surgical placement of a gastrostomy tube (g-tube) directly into a patient's gastrointestinal system to support antiretroviral administration is occasionally used to increase adherence in HIV-infected children. Absorption and distribution characteristics of antiretrovirals after g-tube administration, however, are unknown. The goal of this pilot study was to describe the pharmacokinetic characteristics of protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) when administered to HIV-infected children via g-tube. METHOD: Nine HIV-infected children who were receiving a PI- or NNRTI-containing regimen via g-tube were enrolled. All antiretrovirals (excluding efavirenz) were administered under direct observation for the pharmacokinetic evaluation. Blood samples were collected at predose and at 1, 2, 4, 8, and 12 hours postdose. Antiretroviral concentrations were measured in plasma using high performance liquid chromatography with ultraviolet detection. RESULTS: Systemic exposure of PIs and NNRTIs in our 9 patients was similar to data from historical oral administration controls. Due to likely drug interactions, LPV exposure was decreased and one patient had low exposure of all antiretrovirals. When doses were increased, adequate exposure was attained. CONCLUSION: This pilot study suggests that administration of most PIs and NNRTIs by a g-tube to HIV-infected children provides systemic exposure comparable with that achieved after oral administration.

Area Under Curve↗
PubMed2001

Inhibition of gastrointestinal lipolysis by Orlistat during digestion of test meals in healthy volunteers.

The inhibition of digestive lipases by the antiobesity drug Orlistat along with lipolysis levels and fecal fat excretion were measured in healthy humans. Orlistat was found to be a powerful gastric lipase inhibitor, achieving 46.6--91.4% enzyme inhibition and thus greatly reducing gastric lipolysis of solid and liquid meals (11--33% of respective controls). Gastric lipase inhibition by Orlistat was extremely fast (half-inhibition time < 1 min). Duodenal lipolysis was reduced significantly by Orlistat given with the solid meal (32.6--37.6% of controls) but was only slightly reduced by Orlistat given with the liquid meal (74.5--100% of controls). Human pancreatic lipase (HPL) inhibition was found to be high (51.2--82.6%), however, regardless of the meal. These paradoxical results were explained when in vitro lipolysis experiments were performed. The rates of HPL inhibition by Orlistat were found to be similar with both types of meals (half-inhibition time 5--6 min), but the preemulsified triglycerides of the liquid meal were rapidly hydrolyzed by HPL before the enzyme was significantly inhibited by Orlistat. With the solid meal, the rate of hydrolysis of the meal triglycerides by HPL was slower than the rate of HPL inhibition by Orlistat. As predicted from the previous results, the effects of Orlistat on fat excretion levels were found to be much greater with the solid (40.5--57.4% of ingested fat) than with the liquid (4.2--18.8%) test meal.

Adult↗
PubMed2000

Gastrointestinal osmoreceptors and renal sodium excretion in humans.

The hypothesis that natriuresis can be induced by stimulation of gastrointestinal osmoreceptors was tested in eight supine subjects on constant sodium intake (150 mmol NaCl/day). A sodium load equivalent to the amount contained in 10% of measured extracellular volume was administered by a nasogastric tube as isotonic or hypertonic saline (850 mM). In additional experiments, salt loading was replaced by oral water loading (3.5% of total body water). Plasma sodium concentration increased after hypertonic saline (+3.1 +/- 0.7 mM), decreased after water loading (-3.8 +/- 0.8 mM), and remained unchanged after isotonic saline. Oncotic pressure decreased by 9.4 +/- 1.2, 3.7 +/- 1.2, and 10.7 +/- 1.3%, respectively. Isotonic saline induced an increase in renal sodium excretion (104 +/- 15 to 406 +/- 39 micromol/min) that was larger than seen with hypertonic saline (85 +/- 15 to 325 +/- 39 micromol/min) and water loading (88 +/- 11 to 304 +/- 28 micromol/min). Plasma ANG II decreased to 22 +/- 6, 35 +/- 6, and 47 +/- 5% of baseline after isotonic saline, hypertonic saline, and water loading, respectively. Plasma atrial natriuretic peptide (ANP) concentrations and urinary excretion rates of endothelin-1 were unchanged. In conclusion, stimulation of osmoreceptors by intragastric infusion of hypertonic saline is not an important natriuretic stimulus in sodium-replete subjects. The natriuresis after intragastric salt loading was independent of ANP but can be explained by inhibition of the renin-angiotensin system.

Adult↗
PubMed2006

Mechanism of the induction of brain c-Fos-positive neurons by lipid absorption.

Many gastrointestinal meal-related signals are transmitted to the central nervous system via the vagus nerve and thereby control changes in meal size. The c-Fos-positive neuron has been used as a marker of neuronal activation after lipid meals to examine the contribution of a selective macronutrient on brain neurocircuit activity. In rats fed Intralipid, the c-Fos-positive neurons were highly stimulated in the nucleus of the solitary tract (NTS) and in the hypothalamus, including the paraventricular nucleus (PVN), arcuate nucleus of the hypothalamus (ARC), and ventromedial hypothalamus at 4 h lipid feeding. However, c-Fos-like immunoreactivity was markedly attenuated in these brain regions when chylomicron formation/secretion was blocked by Pluronic L-81. After lymph was diverted from the lymph cannulated animals, the rats had a lower number of c-Fos-positive cells in the NTS and ARC. In contrast, the rats had higher c-Fos-positive neurons in PVN. The present study also revealed that c-Fos-positive neurons induced by feeding of Intalipid were abolished by CCK type 1 receptor antagonist, Lorglumide. We conclude that the formation and/or secretion of chylomicron are critical steps for initiating neuronal activation in the brain.

Animals↗
PubMedDate not supplied

The safety of percutaneous endoscopic gastrostomy tube placement in patients with existing ventriculoperitoneal shunts.

BACKGROUND: Because the insertion of percutaneous endoscopic gastrostomy tubes (PEG) involves disruption of the gastrointestinal tract with potential peritoneal contamination, patients with indwelling ventriculoperitoneal (VP) shunts could be at increased risk of meningitis, a potentially devastating infection. The safety of PEG placement in the presence of a VP shunt is unclear. METHODS: A retrospective chart review was performed that included all adult patients with existing VP shunts requiring PEG placement at a single university medical center over an approximate 9-year period from July 1995 to March 2004. RESULTS: Thirty-nine patients who underwent PEG placement 2-564 days after shunt placement were identified. Two patients (5%) subsequently developed meningitis. Cerebrospinal fluid cultures demonstrated Staphylococcus aureus and Enterococcus faecalis. These infections occurred 2 and 15 months after PEG placement, respectively. At the time of PEG placement, 17 patients (44%) were receiving antibiotics for reasons other than operative prophylaxis, and 11 patients (28%) received prophylactic antibiotics. Both infected patients had received antibiotics at the time of PEG placement. CONCLUSIONS: These data constitute the largest series of patients with existing VP shunts undergoing PEG placement reported to date. When compared with the published 2%-5% infection rate for patients with VP shunts alone, our data do not suggest an increased risk of infection for patients after PEG placement. As the total number of adult patients requiring a PEG after VP shunt placement is low, multicenter studies should be carried out to better stratify this risk.

Adult↗
PubMed2000

Comparison of zafirlukast (Accolate) absorption after oral and colonic administration in humans.

PURPOSE: This study characterized the gastrointestinal (GI) absorption of zafirlukast after oral and colonic administration in humans. METHODS: Five healthy subjects received zafirlukast solution (40 mg) orally and via an oroenteric tube into the colon in a randomized, crossover fashion. Two additional subjects were dosed into the distal ileum. Serial blood samples were obtained and plasma concentrations were quantitated by HPLC. RESULTS: Mean +/- SD pharmacokinetic parameters after oral vs. colonic administration were: AUC infinity of 2076 +/- 548 vs. 602 +/- 373 ng x h/mL, respectively, and Cmax of 697 +/- 314 vs. 194 +/- 316 ng/mL, respectively. Mean colon:oral AUCalpha and Cmax were 0.29 and 0.30, respectively. Median tmax values were 2.0 and 1.35 hr after oral and colonic administration. First-order absorption rate constants (Ka and Kac) were estimated from a two-compartment model with first-order elimination. Kac:Ka was <0.5 in 4 of the 5 subjects dosed in the colon. CONCLUSIONS: Zafirlukast was absorbed at multiple sites in the GI tract. The rate and extent of zafirlukast absorption was less after colonic than oral administration. Zafirlukast was significantly absorbed in the distal ileum. This study demonstrated that gamma scintigraphy, digital radiography, and fluoroscopy can be used to track the movement and confirm the location of the oroenteric tube in the GI tract.

Administration, Oral↗
PubMed2003

Gastrostomy tube insertion into intestinal-cutaneous tract fistulas is a new technique to improve fistula control.

BACKGROUND: The management of gastrointestinal-cutaneous fistulas may be complicated by the difficulty in obtaining adequate control of the fistula tract. This study describes a new method to obtain better fistula control utilizing a semi-rigid stent in the form of a gastrostomy tube. METHODS: Consecutive patients with intestinal-cutaneous fistulas of at least 3 weeks duration and treated by the new technique were analyzed. The technique involved the insertion of a guide wire into the fistula tract from the luminal side using an endoscope, snaring the wire with a Dormia basket inserted into the fistula tract from the cutaneous side and then exteriorized. The gastrostomy tube was then pulled with the guide wire from the lumen along the fistula tract and out through the skin. RESULTS: Five patients had had fistulas for a median duration of 42 (range 26-140) days before insertion of the gastrostomy tube. The gastrostomy tube was replaced with a smaller diameter tube in 4 of the patients (range 1-3 changes). The patients were discharged from the hospital at a median of 14 (range 12-23) days after the tube insertion but with the tube in situ. The median time from the insertion of the tube to its removal was 42 (range 32-108) days. CONCLUSIONS: Gastrostomy tube insertion using minimally invasive techniques may improve fistula control enabling patients to be discharged home sooner than otherwise and improve the rate of healing.

Adult↗
PubMed1997

A combined laparoscopic and endoscopic approach to acute primary gastric volvulus.

We describe the combined use of laparoscopic and endoscopic techniques in a case of acute primary gastric volvulus. Once the diagnosis is confirmed with a water-soluble upper gastrointestinal series, prompt intervention is required. With an atraumatic bowel grasper the stomach is re-oriented with the greater curvature in its normal anatomic position. Two transabdominal wall sutures are placed along the greater curvature to fix it to anterior abdominal wall. Upper endoscopy is then performed. Once confident that the gastric mucosa is viable, a 20F "pull-type" gastrostomy tube is placed endoscopically, guided by the external illumination and probing by the laparoscope. The gastrostomy tube now acts as an anterior anchor for the stomach allowing repositioning of the gastropexy sutures if necessary. Endoscopy confirms the placement of a broad, properly aligned gastropexy. Classically, gastric volvulus has been treated by laparotomy. Both endoscopic and laparoscopic techniques have been individually reported in the treatment of acute and chronic gastric volvulus, however, each has as its limitations. By combining the procedures we were able to better assess both the intra-abdominal and the intraluminal status of the stomach and its position before, during, and after fixation to the anterior abdominal wall. The postoperative stay seen with the combined technique was less than has been reported in patients treated by open surgery or by either the endoscopic or laparoscopic methods alone. The combined laparoscopic and endoscopic approach to acute gastric volvulus provides the benefit of a minimally invasive approach, to a better anterior gastropexy. This procedure should be considered when confronted with patients with acute primary, gastric volvulus.

Acute Disease↗
PubMed2006

Pre-operative oral carbohydrate loading in colorectal surgery: a randomized controlled trial.

OBJECTIVE: Surgery induces a catabolic response with stress hormone release and insulin resistance. The aim of this study was to assess the effect of pre-operative carbohydrate administration on grip strength, gastrointestinal function and hospital stay following elective colorectal surgery. METHODS: Thirty-six patients undergoing elective colonic resection were randomized into one of three groups. Group 1 were fasted; Group 2 were given pre-operative oral water, Group 3 received equivalent volumes of a Maltodextrin drink. Time to first flatus, first bowel movement and hospital stay were recorded. Muscle strength was measured pre-operatively, and on alternate days thereafter until discharge using a grip strength dynamometer. RESULTS: Patients in the carbohydrate group had a median postoperative hospital stay of 7.5 days compared with 13 days in the water group (P > 0.01) and 10 days in the fasted group (P = 0.06). The median time postsurgery to first flatus was 3 days for both the fasted and water groups compared with 1.5 days in the carbohydrate group (P = 0.13). First bowel movement occurred on day 3 in the carbohydrate group, day 4 in the fasting group and day 5 in the water group. The fasted group showed a significant reduction in postoperative grip strength (P < 0.05) with a median drop of 10% at discharge. Neither the water nor the carbohydrate groups showed significant reductions in muscle strength. CONCLUSION: We found that pre-operative administration of oral carbohydrate leads to a significantly reduced postoperative hospital stay, and a trend towards earlier return of gut function when compared with fasting or supplementary water.

Administration, Oral↗
PubMed2005

Unsedated transnasal percutaneous endoscopic gastrostomy placement in selected patients.

BACKGROUND AND STUDY AIMS: The placement of a percutaneous endoscopic gastrostomy (PEG) is the procedure of choice for the long-term management of dysphagic patients with neurological disease or with trauma or tumors of the head and neck. It is not always possible to perform conventional upper gastrointestinal endoscopy in such patients due to stenosis and/or occlusion of the mouth or pharynx and/or partial or complete trismus. The aim of this study was to show whether transnasal esophagogastroduodenoscopy (EGD) offers a feasible and effective alternative method for PEG placement in these selected patients. PATIENTS AND METHODS: PEG placement was required for 155 patients at our institution during a 27-month period. In 12 patients oral access of an endoscope into the esophagus was not possible. Unsedated transnasal EGD (T-EGD) was then performed using an ultrathin video gastroscope, which had a distal-end diameter of 5.9 mm. A 16-Fr polyurethane PEG tube with a conical, flexible, soft distal end and a collapsible bumper was used in all cases. The Gauderer-Ponsky pull technique was used for PEG placement. RESULTS: T-EGD and perendoscopic transnasal placement of a PEG tube was successfully performed in all 12 patients. No patient required sedation during the procedure. No immediate or late-onset procedure-related complications occurred in any of the 12 patients. CONCLUSIONS: In some dysphagic patients in whom the oral route is not accessible with a standard endoscope, a transnasal endoscopic approach allows the placement of a PEG tube. In these selected patients this technique has been shown to be safe and effective and does not require the use of sedation.

Adult↗
PubMed2000

[Clinical and experimental study on effect of rhubarb on gastrointestinal blood flow perfusion].

OBJECTIVE: To study the effect of rhubarb on gastrointestinal (GI) perfusion in critical illness and hemorrhagic shocked rats. METHODS: Clinical study: Sixty-four septic patients suffered from stress ulcer were treated with rhubarb at a dose of 25 mg/kg, 25 non-septic patients were taken as control. The GI perfusion was evaluated by intramural pH. Animal study: SD rats were anesthetized with intraperitoneal sodium pentobarbital at a dose of 20 mg/kg. Then the animals were blood-letting, the blood pressure reduced to 5.32 kPa and maintained for 120 minutes. They were resuscitated at the end of shock by reperfusing all the shed blood. The rats were divided into four groups: normal control, shock group, treated group (shocked rats were treated with 50 mg/kg rhubarb by the end of shock), and rhubarb group (normal rats were treated with rhubarb). Laser Doppler determination was applied to estimate the GI perfusion. RESULTS: Clinical study: The pH in septic patients was much lower than that in the control, whereas rhubarb could obviously elevate GI pH (P < 0.01). In addition, rhubarb also had a good effect on gastric hemorrhage caused by stress ulcer, the effectiveness was 73.4%. Animal study: Although the shocked rats were resuscitated completely, their GI perfusion was much lower than that in the control. Rhubarb could significantly improve the mucous membrane of GI and mesenterium perfusion (P < 0.01). Furthermore, rhubarb also increased the GI perfusion in normal rats. CONCLUSION: The rhubarb could improve the GI blood perfusion in critical illness and shocked rats.

Adolescent↗
PubMed2005

The ProSeal laryngeal mask airway in children.

BACKGROUND: The ProSeal (PLMA) is a new laryngeal mask device with a modified cuff to improve the seal and a drain tube to provide access to the gastrointestinal tract. We assessed the performance of the size 2 (which has no dorsal cuff) and size 3 (which has a dorsal cuff) in terms of insertion success, efficacy of seal, tidal volume, gas exchange, fiberoptic position, gastric tube placement and frequency of problems. METHODS: Eighty children undergoing minor surgery were studied (n = 40, size 2 PLMA, weight 10-25 kg; n = 40, size 3 PLMA, weight >25-50 kg). Induction was with remifentanil and propofol. Insertion was with the introducer tool and by experienced users. Maintenance was with propofol or sevoflurane and pressure controlled ventilation. RESULTS: The first-time and overall insertion success rate was 84 and 100%, respectively. Oropharyngeal leak pressure was 31 +/- 5 cmH2O. There were no gastric or drain tube air leaks. Tidal volume and gas exchange was adequate in all patients, other than two brief episodes of hypoxia because of airway reflex activation. The vocal cords and epiglottis were visible in 99 and 80%, respectively, via the airway tube. The first-time and overall insertion success rate for gastric tube insertion was 87 and 100%, respectively. During maintenance, the PLMA was removed in one patient with airway reflex activation and another required epinephrine for bronchospasm. There were no differences in performance between the sizes 2 and 3 PLMA. CONCLUSION: The PLMA is an effective airway device in children and isolates the glottis from the esophagus when correctly positioned. Despite the lack of a dorsal cuff, the performance of the size 2 was similar to the size 3 PLMA in the age groups tested.

Anesthesia, Intravenous↗
PubMed1998

The effect of the mode of administration on the hypolipidaemic activity of niacin: continuous gastrointestinal administration of low-dose niacin improves lipid-lowering efficacy in experimentally-induced hyperlipidaemic rats.

The effect of different routes and modes of administration of niacin (nicotinic acid) on its hypolipidaemic activity has been evaluated. Our working hypothesis was that the major sites of niacin action are located presystemically (i.e. in the gut wall or the liver, or both) which would make niacin a gastrointestinal drug. For such drugs continuous administration to the gastrointestinal tract is expected to augment their efficacy compared with bolus oral administration or parenteral administration. The hypothesis was examined in two rat models of experimentally induced hyperlipidaemia-Model A, based on a cholesterol-enriched diet, and Model B, in which acute hyperlipidaemia is induced by intraperitoneal administration of triton (225 mg kg(-1)). Continuous administration of niacin into the duodenum at 1.66 mg h(-1) (total dose 40 mg kg(-1) day(-1)) for up to 7 days (Model A) or at 2.22 mg h(-1) over 18 h (Model B) had significantly greater lipid-reducing effects both on total cholesterol and on triglyceride levels (15-25%) and elevation of high-density lipoprotein (HDL) cholesterol levels than did bolus oral administration of the same dose. Continuous duodenal infusion of niacin also had an even greater lipid-reducing effect than continuous intravenous infusion of the drug at the same rate and dose. The results indicate that the site(s) of action are located presystemically and that continuous duodenal administration of a low dose of niacin (40 mg kg(-1)) has a greater lipid-lowering effect than a higher dose (200 mg kg(-1)) administered by peroral bolus administration. These conclusions were validated by administration of a specially designed niacin sustained-release matrix tablet formulation that was non-invasively administered to hyperlipidaemic rats. The hypolipidaemic activity of the sustained-release tablet was of similar magnitude to that resulting from continuous duodenal administration, thus providing a pharmacodynamic rationale for this mode of administration.

Animals↗
PubMed1995

Absorption and presystemic metabolism of nefazodone administered at different regions in the gastrointestinal tract of humans.

PURPOSE: The absorption and disposition of nefazodone (NEF) and its metabolites hydroxynefazodone (HO-NEF), m-chlorophenylpiperazine (mCPP) and triazole dione (dione) were assessed in 10 healthy subjects following infusion of NEF solution into the proximal and distal regions of the intestine vs administration of NEF solution orally by mouth. METHODS: NEF HCl (400 mg) was infused over 5 hours into the proximal or distal intestine through a nasogastric tube, or orally ingested in 10 divided doses over 4.5 hours. The three treatments in the three-period crossover design were separated by one week. RESULTS: The bioavailability of NEF, based on AUC(INF), from proximal and distal regions relative to that from oral administration was 97% and 106%, respectively. NEF was absorbed equally well from all three treatments with median Tmax of 5.0 hours which coincided with the duration of infusion. Mean Cmax of NEF was not different between proximal and oral administrations, however, mean Cmax after distal instillation was 40% lower than that after oral administration. Exposure to HO-NEF, mCPP and dione, following proximal instillation was also comparable to that after oral administration. AUC(INF) of HO-NEF and dione was significantly lower after distal instillation compared to that after oral administration but AUC(INF) of mCPP was not. Cmax of all metabolites was significantly lower after distal administration in comparison to oral treatment. Terminal half-life for NEF, HO-NEF and mCPP after distal administration was longer than the other two treatments. CONCLUSIONS: NEF is absorbed throughout the length of the gastro-intestinal tract which supports the development of an extended-release formulation of NEF. The exposure to the metabolites (relative to NEF) was lower from the distal intestinal site compared to the proximal and oral site which may be explained by a reduced first pass of NEF by the cytochrome P450 3A4 in the distal intestine.

Adult↗
PubMed1968

Bile salt and micellar fat concentration in proximal small bowel contents of ileectomy patients.

Studies were carried out to test the hypothesis that abnormal bile salt metabolism (interruption of the enterohepatic circulation) is responsible for steatorrhea in patients with ileal disease and (or) ileectomy.Duodenal bile salt concentration after a single, standard meal eaten at 8 a.m. was measured in 8 patients with ileectomy steatorrhea and compared with 11 normal control subjects and 7 hospitalized patients without gastrointestinal disease. Mean bile salt concentration was approximately half normal in the ileectomy group, but some of the patients fell well within the normal range, even on repeat studies. However, it was shown that the second and third meals eaten during a single day were associated with a marked depression of duodenal bile salt concentration in ileectomy patients, which suggested that the first meals in these patients flush out a large fraction of the bile salt pool. Simultaneously measured turnover studies with taurocholate-(14)C showed at t((1/2)) of 3.1 hr in these patients compared with 29.5 and 32 hr in two control subjects, proving that the enterohepatic circulation had indeed been interrupted by ileectomy. Hepatic synthesis can apparently partially reconstitute the bile salt pool during the overnight period. Additional studies were carried out to determine the relation between bile salt and micellar fat concentration in proximal small bowel contents after ingestion of the same standard meal. Below a bile salt concentration of 1.7 mg/ml, less than 0.8 mg/ml of lipid existed in the micellar phase of intestinal contents, whereas when bile salt concentration exceeded this level the amount of fat in the micellar phase rose progressively. Only 1 of 11 samples from three ileectomy patients had a micellar fat concentration > 0.8 mg/ml, whereas 33 of 42 samples from control subjects had micellar fat concentration > 0.8 mg/ml.Thus, abnormally low duodenal bile salt concentration during at least a portion of the day, with the associated depression of micellar fat, appears to be a major cause of decreased fat absorption in patients with ileectomy steatorrhea.

Adult↗
PubMed1999

Biological fate of [14C]-1-nitropyrene in rats following intragastric administration.

1-Nitropyrene (1-NP), a weak carcinogen associated with diesel exhaust particles, has previously been detected in workplace atmospheres with in-use diesel engines and in the general environment. In order to gain insight in its biological fate, a single dose of [14C]-1-NP (27.6 microCi, 750 mg/kg body weight, b.w.) was administered intragastrically to rats and the presence of metabolites in blood and tissue homogenates, and radioactivity associated with blood proteins and tissue DNA, were studied. Early peak levels of radioactivity observed in blood and tissue homogenates indicated a rapid absorption of [14C]-1-NP from the gastrointestinal tract. Metabolite patterns observed in plasma, liver and kidney homogenates strongly suggested an important role of the intestinal microflora in the enterohepatic recirculation, but not in nitroreduction of 1-NP prior to absorption from the gastrointestinal tract. This might explain the low levels of radioactivity associated with blood proteins, since 1-nitrosopyrene, a product of nitroreduction of 1-NP, is likely to be involved in protein binding. Levels of radioactivity associated with plasma proteins were approximately four times higher than the levels of radioactivity associated with hemoglobin (401.0 and 84.1 pmol/g protein per micromol 1-NP kg b.w., respectively, at 24 h). Maximal 25% of the associated radioactivity was released following mild alkaline hydrolysis of either hemoglobin or plasma proteins. 1-Aminopyrene was the only released compound after hydrolysis of hemoglobin. In addition to 1-aminopyrene, two more polar unidentified metabolites were detected following hydrolysis of plasma proteins. Association of radioactivity with DNA was highest in the liver at the first moments of observation (7.4 pmol 14C Eq./mg DNA per micromol 1-NP kg b.w.), but decreased rapidly to levels lower than observed for kidney DNA (max. 3.0 pmol 14C Eq./mg DNA per micromol 1-NP kg b.w. at 24 h). In lungs 8-50 times less radioactivity was associated with DNA than observed in the liver and kidneys. The results of this study show, that 1-NP undergoes an extensive and complex biotransformation in vivo, resulting in a variety of metabolites present in blood and tissue homogenates and a diversity of blood protein adducts. Concentrations of plasma metabolites, blood protein adducts and DNA adducts were rather low. In addition, previous studies also showed relatively low concentrations of metabolites present in urine. Therefore, sensitive and selective methods will be needed in order to evaluate the biological fate of 1-NP, associated with diesel exhaust particles, in humans.

Animals↗