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Biomedical subjects

J A Barrowman

Publications and source records attributed to J A Barrowman.

At least 37 records · Page 2Linked to original sources

Importance of interstitial matrix hydration in intestinal chylomicron transport.

We have shown previously that lymph flow has a profound effect on intestinal chylomicron transport. However, since lymph flow both determines the rate of convective movement of chylomicrons within the interstitium and reflects the degree of hydration of the interstitial matrix, we were unable to determine which factor was more important for the inverse relation between the chylomicron appearance time and lymph flow. In this investigation, we measured the chylomicron appearance time in rats with a normal lymph flow and expanded matrix (study A), in rats with a reduced lymph flow but expanded matrix (study B), and finally in rats with a dehydrated matrix (study C). The chylomicron appearance times were 11.7, 13.6, and 21.7 min for the rats from studies A-C, respectively. Thus, the data obtained from this study indicate that the matrix hydration may exert a more significant influence on chylomicron movement than lymph flow per se. In conclusion, the reduced chylomicron appearance time produced by expansion of the mucosal interstitium results from a diminished resistance of the interstitial matrix to chylomicron movement rather than a decreased transit time due to an enhanced convective flux of chylomicrons.

Animals↗

Relations among canine intestinal motility, blood flow, and oxygenation.

Blood flow, arteriovenous O2 difference, and lumen pressure were measured in isolated loops of canine ileum. Ileal pressure was increased by an intra-arterial infusion of either Met-enkephalin or acetylcholine. Pressures were quantitated using a motility index (MI = mean of the pressure peaks divided by number of contractions per minute). Both Met-enkephalin and acetylcholine increased MI in a dose-dependent fashion. The highest MI achieved with acetylcholine was 37.9 mmHg, while Met-enkephalin produced a maximal MI of 8.1 mmHg. Ileal oxygen uptake increased when MI reached values greater than 6. There was a direct linear relationship between oxygen uptake and MI. Distension of the lumen in the absence of motility resulted in a decrease in oxygen uptake when lumen pressure reached 15-20 mmHg. The results of these studies indicate that contractions of intestinal smooth muscle can increase intestinal oxygen uptake and may contribute to the overall oxygen demands of the gut under conditions of fasting and feeding. Furthermore, large (greater than 20 mmHg) increments in lumen pressure during enhanced motility may compromise intestinal oxygenation.

Acetylcholine↗

Bile salts as endogenous digitalis like factors.

Digitalis-like factors were assayed by radioimmunoassay of digoxin in 6 bile samples obtained from patients at autopsy and in plasma from three patients with combined hepatic and acute renal failure. None of the patients received digoxin. Digitalis like factor values in bile samples were 23 to 85 nmol digoxin equivalents/1. Bile salt concentrations ranged from 38-104 mmol/l in the bile and 28-184 mumol/l in the plasma of these subjects. Bile, plasma digitalis like factor extracts and bile salt standards (0.1-3 mM) showed concentration dependent displacement of [125I]-digoxin from digoxin antibody, inhibition of hog brain Na,K-ATPase and displacement of [3H]-ouabain from Na,K-ATPase. The concentration-displacement curves suggest that bile salts could account for 50-79% of the total digitalis like factors in the six bile samples and 2-7% in the plasma of the three patients. High performance liquid chromatographic fractionation of a bile sample showed digitalis like factor peaks co-eluating with standards of tauro- and glycocholate, tauro- and glycochenodeoxycholate and tauro- and glycodeoxycholate. These bile salt peaks accounted for 78% of the total digitalis like factors in all high performance liquid chromatographic peaks in bile, but only 7% of the total digitalis like factor activity in all high performance liquid chromatographic peaks in an extract of plasma from one of the patients with hepatic and renal failure. The bile salts appear to be examples of endogenous digitalis like compounds which do not act by simple competitive ligand binding to antidigoxin antibody and Na,K-ATPase. They make an important contribution to digitalis like factor activity in bile, but not in plasma.

Acute Kidney Injury↗

Relation between pancreatic growth and blood flow.

Male rats were treated with daily subcutaneous injections (3 micrograms/kg) of cholecystokinin octapeptide (CCK-OP), a synthetic CCK analogue, for 2, 4, 7, and 14 days, while control rats were injected with saline over the same intervals. Regional blood flows were measured with Sc46-labeled microspheres using the reference-organ method. Pancreatic wet and dry weights were determined in each treatment group. Total pancreatic DNA content was estimated with the diphenylamine reaction. Significant hyperplasia and increases in pancreatic wet weight occurred at 7 and 14 days, although hypertrophy was not evident in any of the treatment groups. No increases in small intestine wet weight or DNA content were evident in any treatment group. CCK-OP treatment induced a significant pancreatic hyperemia at 2 and 4 days of treatment. Pancreatic blood flow at 7 and 14 days was not different from control when expressed per unit tissue weight. The hyperemia seen at 2 and 4 days was not due to either a direct vascular effect of CCK-OP or an increase in pancreatic exocrine secretion. The hyperemia is therefore due to the growth stimulus and may be related to vasodilator metabolite accumulation during pancreatic tissue proliferation.

Animals↗

Similar bioavailability and lymphatic transport of benzo(a)pyrene when administered to rats in different amounts of dietary fat.

This study assessed the effect of concomitant lipid absorption on the bioavailability and lymphatic transport of benzo(a)pyrene (BP), a carcinogenic polycyclic aromatic hydrocarbon (PAH). Conscious, male Sprague-Dawley rats, equipped with biliary and mesenteric lymphatic catheters received intraduodenally a dose of 0.4 mumoles 3H-labeled BP completely dissolved in either 50 mumoles or 500 mumoles of olive oil. Diversion of mesenteric lymph allowed biliary and urinary excretion of 3H to be used as an indirect measurement of relative 3H portal transport. Total radiolabel recovered in a 24-hr period in each group was 20.0 +/- 2.6% of the 3H dose given in 50 mumoles of oil, and 17.0 +/- 1.0% of the 3H dose administered in 500 mumoles of oil. In animals receiving the low-fat test meal, 79.4 +/- 1.4% of the recovered radiolabel was found in bile; the corresponding value for the high fat dose was 78.5 +/- 2.6%. Thus a tenfold variation in the mass of the carrier vehicle (triglyceride oil) did not significantly effect the disposition of BP, and portal, not lymphatic transport, was the major route of post-absorptive transport. Although the chylomicrons produced from both fat doses were initially contaminated with BP, within 1-1.5 hr the radioactivity in lymph began to drop such that by 3 hr in the animals fed high fat, the chylomicrons were essentially free of BP. These results show that the rat enterocyte quickly adapts to PAH-contaminated dietary fat, even during the assimilation of a single dose of fat. Presumably, during the post-absorptive synthesis of chylomicrons from pre-chylomicrons, BP is metabolized and removed from the triglyceride oil droplets.

Animals↗

Effect of neurotensin on intestinal capillary permeability and blood flow.

Experiments were performed in 10 cats of either sex to ascertain the effects of postprandial arterial plasma concentrations of neurotensin (NT) on intestinal capillary permeability and blood flow. NT was infused intra-arterially into an isolated perfused loop of terminal ileum to produce a 182 +/- 15 (SE) pM plasma NT concentration. Intestinal lymph (L) and plasma (P) protein concentrations were measured at various venous pressures under control conditions and during NT infusion. The osmotic reflection coefficient (sigma d) was estimated under all conditions assuming sigma d = 1 - L/P at high capillary filtration rates. NT infusion significantly (P less than 0.001) reduced sigma d to 0.73 +/- 0.02 (SE) from a control level of 0.91 +/- 0.01. NT infusion also significantly increased intestinal blood flow [47.0 +/- 4.3 (SE) ml X min-1 X 100 g-1] versus control (36.6 +/- 3.2 ml X min-1 X 100 g-1), a 28.4% increase. Intestinal vascular resistance was decreased from 3.21 +/- 0.31 to 2.42 +/- 0.28 mmHg X min X ml-1 X 100 g in the absence of a change in local mean arterial blood pressure. Pore-stripping analysis of lymph and plasma solute fractions during NT infusion at high lymph flows predicted two populations of pores, 330-A and 46-A radius, accounting for 31 and 67%, respectively, of the total transcapillary hydraulic flow. NT infusion preferentially increased large-pore radius as a means of increasing intestinal capillary permeability. The rates of small- to large-pore areas and numbers were 106:1 and 5,225:1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Sympathetic stimulation and intestinal capillary fluid exchange.

Sympathetic nerve stimulation is generally considered not to alter intestinal capillary pressure or filtration rate because of appropriate adjustments in the pre-to-postcapillary resistance ratio. To directly assess this possibility, we measured lymph flow, capillary pressure, capillary filtration coefficient, and the transcapillary oncotic pressure gradient in the cat small intestine. Measurements were taken under control conditions and during the steady-state phase of periarterial nerve stimulation, i.e., following completion of the escape phase. Venous outflow pressure was held constant (0 mmHg) during the entire experiment. Nerve stimulation resulted in a significant reduction of lymph flow (by 65%), capillary filtration coefficient (by 75%), and capillary pressure (by 15%). Interstitial fluid pressure, calculated from the measured parameters in the Starling equation, was also reduced (from -0.74 to -2.53 mmHg) by nerve stimulation. The results of this study indicate that intestinal capillary pressure and capillary filtration rate are not "autoregulated" during sympathetic nerve stimulation. Capillary derecruitment appears to be largely responsible for the dramatic reduction in filtration rate associated with adrenergic stimulation.

Animals↗

Role of humoral factors in the intestinal hyperemia associated with chronic portal hypertension.

The role of neural, metabolic, physical, and humoral factors in the intestinal hyperemia associated with chronic portal hypertension was examined by use of the rat portal vein stenosis model. Intestinal blood flow and splenic pulp pressure were increased, while systemic arterial pressure and total vascular resistance were reduced in portal vein-stenosed rats as compared with controls. The reduction in total vascular resistance was entirely due to a fall in precapillary resistance and was accompanied by an increase in intestinal capillary pressure, which exceeded that produced by acute portal pressure elevation to the same level. Arteriovenous shunting of 15-micron microspheres was four times higher in portal-hypertensive rats. Cross-perfusion of control intestinal preparations with arterial blood from portal-hypertensive rats produced a 30% increase in blood flow. Plasma glucagon levels in portal-hypertensive rats were three times higher than in controls. Intra-arterial infusion of glucagon (at a rate that achieved the concentration measured in portal-hypertensive animals) produced a 20% reduction in intestinal vascular resistance. The results of these studies indicate that humoral factors, including glucagon, are primarily responsible for the hyperemia associated with portal hypertension.

Animals↗

Effects of experimental cirrhosis on splanchnic microvascular fluid and solute exchange in the rat.

In human cirrhosis, there is evidence that there are considerable alterations in fluid and solute exchange in the hepatic and intestinal microcirculations . Experimental cirrhosis was induced in rats by using oral phenobarbitone and carbon tetrachloride inhalation over an 8-wk period. Portal venous pressure, hepatic and intestinal lymph flows, and lymph and plasma protein concentrations were measured. Liver samples were obtained for histologic examination. Portal venous pressure increased from a normal value (control animals) of 9.0 (6.3-13.1) cmH2O to 17.9 (9.0-29.0) cmH2O in cirrhotic rats. There was a strong correlation between the degree of fibrotic change on histology and portal venous pressure. Lymph flows from the intestine and liver in cirrhotic animals were increased threefold and 30-fold, respectively, over values obtained from control animals. There was a good correlation between intestinal and liver lymph flows and portal venous pressure. Analysis of lymph/plasma protein concentration ratios at various lymph flow suggests that capillary permeability in the small intestine during sustained portal hypertension is comparable to that in normal animals. However, the highly permeable blood-lymph barrier of the normal liver becomes markedly restrictive in cirrhotic animals.

Animals↗

Role of the microcirculation in ethanol-induced mucosal injury in the dog.

The aim of the present study was to assess the role of the intestinal microcirculation in the mucosal injury induced by intraenteric ethanol. Mucosal injury was assessed histologically in the ileum and jejunum and quantitated in the ileum by measuring clearance of albumin (37 A, radius) and beta-lactoglobulin A (27 A, radius). A steady-state analysis of the forces and flows governing transcapillary fluid movement was performed in autoperfused segments of jejunum and ileum. In the jejunum and ileum ethanol induced the formation of subepithelial blisters in 10%-40% of the villi. In the ileum, ethanol (5%, vol/vol) increased the clearance of both proteins but the ratio of lactoglobulin to albumin clearance decreased, indicating that the selectivity of the mucosal membrane was diminished. In both the jejunum and ileum ethanol produced similar alterations in the forces governing transcapillary fluid exchange. Ethanol increased the filtration coefficient (35%-40%), but did not alter the osmotic reflection coefficient of intestinal capillaries, indicating that surface area increased whereas vascular permeability was not affected. Capillary pressure increased (2-3 mmHg) whereas interstitial (lymph) protein concentration decreased resulting in an increase in the transcapillary oncotic pressure gradient (1-2 mmHg). The net result of the alterations in the forces governing transcapillary movement was only a doubling of the transcapillary filtration rate (lymph flow). It is concluded that the ethanol-induced increase in mucosal permeability to macromolecules cannot be explained solely on the basis of alterations in the forces and flows governing transcapillary fluid exchange in the small intestine.

Albumins↗

Polycyclic hydrocarbon and polychlorinated biphenyl solubilization in aqueous solutions of mixed micelles.

To determine the physiochemical behavior of xenobiotic hydrocarbons in simulated intestinal content, we examined the partition of 7,12-dimethylbenzanthracene (DMBA), 3-methyl cholanthrene (MC), benzo(a)pyrene, and a polychlorinated biphenyl compound (PCB, Aroclor 1242) between an emulsified oil phase and a mixed micellar solution. In a mixed lipid-bile salt system, negligible amounts of hydrocarbon were present in aqueous solution below the critical micellar concentration (CMC) of sodium taurocholate. Once the CMC was obtained, the 4 hydrocarbons exhibited nearly identical partitions from the lipid into the micellar system which was enhanced by increased concentrations of bile salt, reduction of triglyceride concentration and the formation of mixed rather than pure bile salt micelles. The partition of DMBA and MC into micelles was optimized by long-chain monounsaturated oleic acid and monooleoylglycerol as compared to their octanoic or linoleic counterparts. Linoleic acid and monolinoleoylglycerol maximized the partition of PCB from the oil into the micellar phase. In a mixed micellar system excluding an oil phase and an excess of DMBA, a molar saturation ratio (mol hydrocarbon:mol bile salt) was calculated by regression analysis to be 0.162. This indicates that more than one molecule of hydrocarbon is solubilized per mixed micelle and that the aqueous solubilization of hydrocarbon may be attributed to true micellar solubilization.

Colloids↗

Double pylorus--in evolution.

Double pylorus is a rare abnormality. Over a 4-year period, we have found two cases of double pylorus in 2,500 endoscopic examinations, an incidence of 0.08%. In one patient, the development of double pylorus from a prepyloric ulcer was followed by serial endoscopies. Most cases of double pylorus are acquired from peptic ulcer disease.

Duodenal Diseases↗

Studies of the absorption and enterohepatic circulation of 7,12-dimethylbenz[a]anthracene in the rat.

This study was undertaken to examine intraluminal factors which might alter the bioavailability of an orally ingested hydrocarbon carcinogen, 7,12-dimethylbenz[a]anthracene, and to assess the extent of its enterohepatic circulation. Rats with biliary and duodenal fistulae were administered radiolabelled hydrocarbon dissolved in olive oil, safflower oil, or medium-chain triglyceride only or with exogenous bile. Subsequent biliary excretion and plasma levels of radiolabel were monitored. Luminal bile significantly enhanced biliary recovery of radiolabel following instillation in both long-chain triglyceride vehicles, but did not affect the recovery from the medium-chain oil. In the presence of luminal bile, plasma levels and biliary recovery of radiolabel using the medium-chain triglyceride were significantly less than with either long-chain triglyceride. Following intraduodenal infusions of the radiolabelled biliary products of the carcinogen, 33% of the administered radiolabel was subsequently re-excreted in the bile within 24 h. This study, therefore, demonstrates that, while bile is not absolutely necessary for the uptake of this orally ingested hydrocarbon carcinogen, it significantly facilitates absorption from a long-chain triglyceride vehicle. Under physiological conditions, a long-chain triglyceride vehicle will provide greater systemic availability than a medium-chain vehicle for the hydrocarbon, which then undergoes extensive biliary excretion and recycling.

9,10-Dimethyl-1,2-benzanthracene↗

Effects of the constituents of a corticosteroid enema preparation on colonic blood flow and oxygen uptake in the dog.

A number of currently available therapeutic agents for the management of idiopathic inflammatory bowel disease were studied with respect to their influence on blood flow and oxygen extraction in the dog colon. Some commercially available corticosteroid enemas including Cortenema and its vehicle and sulfasalazine and its split products were delivered intraluminally while arterial pressure, blood flow and oxygen extraction in autoperfused segments of the colon were continuously monitored. Of the agents studied, only Cortenema and its vehicle exerted any appreciable effect on colonic blood flow, producing a sustained 50% increase; this increase in blood flow was confined to the mucosa-submucosal layer. Of the constituents of Cortenema, methylparaben was responsible for 72% of the hyperemia whereas the remainder was due to carboxypolymethylene. The corticosteroid itself had no effect. Oxygen uptake by the colon was reduced by approximately 10% with Cortenema, this reduction being due entirely to polysorbate 80. In vitro analysis of the oxygen uptake effect indicates that the enema exerts a direct metabolic action.

Acrylic Resins↗

In vitro interaction of 7,12-dimethylbenz[a]anthracene and its biliary metabolites with dietary fiber.

This in vitro study examined the ability of various dietary fiber components to bind 7,12-dimethylbenz[a]anthracene (DMBA), a hydrocarbon carcinogen known to contaminate food. Bile salt solutions of DMBA were incubated with individual fiber materials under various conditions, and the degree of binding was assessed. Binding of DMBA from simple bile salt solution was greatest with delipidated bran greater than acid lignin greater than alpha-cellulose greater than unprocessed bran. Binding to acid lignin was slowly reversible, was constant within the pH range 4-8, and appeared independent of a bile salt-fiber interaction. Acid lignin bound DMBA from a mixed lipid-bile salt solution significantly, but less effectively than from pure bile salt solutions. DMBA biliary metabolites from Sprague-Dawley rats were bound less extensively to all the fiber materials than was the parent hydrocarbon, but following hydrolysis of the metabolites by beta-glucuronidase binding was significantly increased. These results indicate that there is considerable potential for dietary fiber to interact with DMBA and its metabolites in the lumen of the gastrointestinal tract, possibly influencing hydrocarbon carcinogen bioavailability.

9,10-Dimethyl-1,2-benzanthracene↗