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D R Saunders

Publications and source records attributed to D R Saunders.

At least 37 records · Page 2Linked to original sources
PubMed1982

Effect of lactate and H+ on structure and function of rat intestine.

Segments of rat ileum and colon were infused in vivo to test if 0.1 M lactate, 10(-4) M H+, or both altered mucosal structure and function. In the first series of experiments, lactate concentration was kept at 0.1 M while H+ was varied from 10(-4) to 10(-7) M. Lactate and 10(-4) M H+ in the colon, and lactate and 10(-5) M H+ in the ileum depressed net water transport and caused sloughing of superficial absorptive cells. In the second series of experiments, H+ concentration was kept at 10(-4) by using carboxymethylcellulose, rather than organic acids, to buffer the infusion mixture; the concentration of lactate was varied from 0 to 0.1 M. Mucosa remained normal after infusions of 10(-4) M H+ alone. Addition to the 10(-4) M H+ infusion of 0.1 M lactate in the colon or 0.075 M lactate in the ileum caused increased mucosal sloughing. Thus lactate plus H+ (or unionized lactic acid) alters colonic and ileal mucosa. Because such high concentrations of lactate and H+ are found in subjects malabsorbing carbohydrates, the present experiments support the contention that H+ and organic acids are etiological factors in some cases of chronic fermentative diarrhea.

Animals↗
PubMed1982

Effect of ethanol on transport from rat intestine during high and low rates of oleate absorption.

Long-chain fatty acids (LCFA) are transported predominantly in the intestinal lymph when rates of LCFA absorption are high, and oral ethanol has been shown to enhance this lymphatic transport. A greater proportion of absorbed LCFA is transported via portal blood when rates of LCFA absorption are low. We tested the hypothesis in unanesthetized lymph-fistula rats that ethanol might also enhance the mucosal absorption and lymphatic transport of oleic acid when oleate absorption rates were low. The results did not support this hypothesis. Ethanol enhanced oleate absorption and transport from the intestine when 360 mumol, but not when 8 mumol of [14C] oleate was infused intraduodenally over 4 hr. There were major differences in intestinal mucosal metabolism of high and low loads of oleic acid. After the high load, the proportion of intestinal [14C] phospholipid to [14C] neutral lipid was 8:92. This ratio changed to 37:63, and the percentage of neutral 14C as triglyceride decreased from 87 to 68% when the low load of oleate was infused. We suggest that a portion of absorbed LCFA is incorporated into phospholipid and transported as high-density lipoproteins in portal blood. This portal pathway for LCFA was uninfluenced by ethanol in the present experiments.

Animals↗
PubMed1981

Iced saline lavage does not slow bleeding from experimental canine gastric ulcers.

The efficacy and safety of iced saline lavage for upper gastrointestinal bleeding is unproven. In this study, canine stomachs were lavaged in vivo to determine whether iced saline staunched bleeding from mechanically induced acute gastric ulcers. Each animal served as its own control. Bleeding rates were measured during an initial period of saline lavage at 37 degrees C. Saline at 4 degrees C, with or without added norepinephrine, was no more effective than saline at 37 degrees C in decreasing the rate of gastric hemorrhage. These data do not support the clinical practice of lavaging with iced saline or norepinephrine-containing solutions in human gastric hemorrhage.

Animals↗
PubMed1981

Linolenate transport by human jejunum: presumptive evidence for portal transport at low absorption rates.

Are the small quantities of linolenic acid (LA) in a meal absorbed via a different pathway than the higher concentrations of the other long-chain fatty acids (LCFA) in a mixed meal? To answer this question, varying LA concentrations were infused into the human jejunum via a quadruple-lumen hydraulic biopsy tube. After 0.01-mM LA infusion, no LA was found in triglyceride (TG) extracted from jejunal biopsies, although 58% of the phospholipid plus monoglyceride fraction (PL + MG) and 42% of the LCFA fraction were LA. In marked contrast, after 5.0-mM LA infusion, 60% of the TG, 28% of the PL + MG, and only 3% of the LCFA fractions were LA. By electron microscopy, mostly very low-density lipoprotein-sized (less than 750 A) particles were seen within jejunal fasting biopsies and in biopsies after 0.01, 0.1, or 1.0-mM LA infusions; mostly chylomicrons (greater than 750 A) were seen within jejunal biopsies after 5.0-mM LA infusion. We conclude that LA at its usual very low dietary concentrations is absorbed mostly as invisible LCFA and PL molecules; whereas at higher concentrations it is absorbed like most dietary fat via lacteals as TG and PL within visible chylomicrons.

Biological Transport↗
PubMed1981

Conservation of mannitol, lactulose, and raffinose by the human colon.

We measured fecal composition after giving oral doses of mannitol, lactulose, or raffinose to ileostomy patients and to normal subjects in order to determine the colon's capacity for metabolizing these carbohydrates and to decide whether volatile fatty acids (VFA) or unabsorbed carbohydrate initiated diarrhea. Seventy-four percent of mannitol, 100% of lactulose, and 88% of raffinose passed unabsorbed through the small intestine of six patients with ileostomies. Dose-response experiments revealed that normal subjects could tolerate 120-220 mmol of mannitol, 73-146 mmol of lactulose, or 80 mmol of raffinose before fecal output of water exceeded 400 ml in 48 h or before test carbohydrate appeared in the stool. Mannitol could be metabolized to glucose; lactulose to fructose, galactose, and glucose; and raffinose to sucrose, melibiose, fructose, galactose, and glucose. The output of VFA in fecal water did not correlate with the moles of carbohydrate metabolized, and it did not greatly exceed the output of VFA in stools of equal volume that were induced by nonfermentable MgSO4. We conclude that the human colon is capable of removing appreciable amounts of single doses of these carbohydrates from fecal water. When this capacity is exceeded, unabsorbed carbohydrate rather than VFA prompts an increased output of fecal water.

Adolescent↗
PubMed1981

Effects of Mg++ and Ca++ on water absorption from rodent and human intestine.

The effect of the soluble chlorides of Mg++ and of Ca++ on intestinal water absorption was compared in rodents and in humans because Mg++ is a laxative while Ca++ is reputed to be constipating. In rats, net water transport in vivo from segments of jejunum or of colon was similar during control periods with NaCl, 275 mosm/kg, and during test periods when 40 mM CaCl2, or MgCl2 (made isoosmolal with NaCl) was infused. Both CaCl2 and MgCl2 depressed water absorption in ileal segments by 30-40% compared with NaCl. In man, 6 ileostomy patients were given 60 mmole CaCl2 or MgCl2, orally over 24 h for 3 days in a randomized, cross-over trial. CaCl2 increased the average ileostomy output from 984 to 1,336 g/day; MgCl2 increased output from 939 to 1,352 g/day. A corollary of these results was that magnesium hydroxide would be less effective laxative when this insoluble hydroxide is not converted to soluble chloride by gastric juice. To test this inference, 5 totally gastrectomized patients were given 60 mmole of Mg(OH)2 or MgCl2 daily. Stool weight increased by 136 g after MgCl2 but not after Mg(OH)2.

Animals↗
PubMed1981

Rectal biopsy in the diagnosis of Crohn's disease: value of multiple biopsies and serial sectioning.

We performed a retrospective evaluation of 243 rectal biopsies from 90 patients who eventually had Crohn's disease proven clinically or by surgery. A portion of each rectal biopsy was serially sectioned. Twenty-five of the 90 patients (28%) had epithelioid granulomas. Half of these patients had an epithelioid granuloma in only one of two or more biopsies. Sixteen percent of these granulomas were so small as to be seen in only six or less successive serial 4-microM sections. This high yield of granulomas is probably attributable to the examination of at least 90 serial sections, usually from each of two rectal biopsies per patient. Using partial serial sectioning, epithelioid granulomas were found almost as frequently in grossly normal as in grossly abnormal appearing mucosa. No granulomas were seen in suitable controls including normals and patients with ulcerative colitis or other diseases. When the differential diagnosis between idiopathic ulcerative colitis and Crohn's disease is uncertain, we recommend taking two rectal biopsies and serially sectioning part of each.

Adolescent↗
PubMed1980

Portal venous transport of long-chain fatty acids absorbed from rat intestine.

We studied the route of transport of long-chain fatty acids (LCFA) from the rat intestine. Lauric (12:0), myristic (14:0), palmitic (16:0), stearic (18:0), linoleic (18:2), and linolenic (18:3) acids were infused intraduodenally for 4 h as micellar solutions into unanesthetized thoracic duct-fistula rats. Proportionally more of each LCFA was transported by the portal vein at infusion rates of 0.3 mumol/h than at 15 mumol/h. Of the LCFA absorbed at low rates of infusion, 72% of lauric, 58% of myristic, 41% of palmitic, 28% of stearic, 58% of linoleic, and 68% of linolenic acid bypassed the lymphatic pathway. To test the inference that 58% of absorbed linoleate was transported by the portal vein, [14C]linoleic acid was infused at 0.3 or 15 mumol/h into unanesthetized rats equipped with both thoracic duct and portal venous fistulas. Portal venous blood (0.1 ml) was withdrawn every 30 min for 4 h. Proportionally more [14C]linoleate was recovered in portal blood at the low infusion rate. To examine the morphology of fat absorption, segments of rat jejunum in anesthetized rats were infused with micellar linoleic acid at 3 or 150 mumol/h. At 3-mumol/h infusion rate, an appearance identical to the fasting state was seen by electron microscopy. At 150 mumol/h, many larger chylomicron-sized particles appeared in absorptive cells, intercellular spaces, and lymphatics. We conclude that a substantial proportion of unsaturated LCFA is transported from rat intestine in portal venous blood.

Animals↗
PubMed1980

Definition of Stroop interference in volunteers and non-volunteers.

It is proposed that the best measure of individual Stroop interference is the logarithm of the ratio between time to read the interference card and time to read the pure color card, i.e., logs(C/B). A review of the literature shows a very close correlation across studies between Stroop interference so-defined and (un)willingness to participate in psychological experiments, at least for studies involving the Stroop. Logs (C/B) provides a highly reliable index of this effect and should be routinely reported as a sample descriptor. (Pertinent data must be taken from the first administration of the Stroop.) Willingness to volunteer is seen as willingness to take on additional stress; low Stroop interference is seen as high tolerance for such stress.

Adult↗
PubMed1980

Ocular toxicity in beagle dogs with an experimental fluoromethane-sulfonanilide sympathomimetic agent.

ocular lesions were detected in Beagle dogs receiving high doses of BA6650, an experimental fluoremethane-sulfonanilide sympathomimetic agent, during a preclinical safety evaluation study. The oral dose of BA6650 was increased during the 14-day study from 20 mg/kg twice daily (bid) for days 1-3 to 30 mg/kg bid for days 4-6 and finally to 40 mg/kg bid for days 7-14. Two males and two females received BA6650 while one male and one female were not dosed. Intraocular pressure in the untreated controls fluctuated during the study between 17 and 22 mmHg. Intraocular pressure decreased in 3 of 4 BA6650 treated dogs from an initial mean value of 17 to a final mean value of 8 mmHg. Ocular lesions consisting of conjunctival hyperemia, corneal opacities, epiphora, mydriasis followed by miosis, corneal herniation, hypopyon, ptosis, and anterior synechia developed in three of the animals.

Animals↗
PubMed1979

Light dependence of the decay of the proton gradient in broken chloroplasts.

The initial rates and steady-state values of proton uptake by broken chloroplasts have been measured as functions of light intensity at various concentrations of chlorophyll, pyocyanine, supporting electrolyte, buffer, as well as pH and temperature. Kinetics analysis of the data shows that the rate of decay of proton gradient due to backward leakage depends on light intensity. Under steady illumination, the decay constant kL is equal to kD + mR0, where R0 is the initial rate of proton uptake which is a function of light intensity, kD is the decay constant in the dark and m is a parameter which is independent of light intensity. Treatment of chloroplasts with lysolecithin, neutral detergent, 2,4-dinitrophenol, or valinomycin in the presence of K+ increases kD without affecting m. Treatment with N,N'-dicyclohexylcarbodiimide or adenylyl imidodiphosphate under appropriate conditions decreases m without affectsity and hence m = 0. These results suggest that the light-dependent part (mR0) of kL is due to leakage of protons through the coupling factor (CF1-CF0) complex which can open or close depending on light intensity and that the light independent part (kD) of the decay constant kL is due to proton leakage elsewhere.

Adenylyl Imidodiphosphate↗
PubMed1979

Effect of calcium on absorption of fatty acid by rat jejunum in vitro.

The effect of Ca++ on jejunal osmiophilic particles was studied in a recirculating system which was not contaminated with plasma lipoproteins. An isolated, infused segment of rat jejunum was suspended in a bath of liquid paraffin. Transudate, containing osmiophilic particles, appeared like beads of sweat on the serosal surface, and fell to the bottom of the bath. In the range of 25-38 C, 30 C proved to be optimal for histological preservation of villous architecture. Production of transudate, 20 mg/min/g of jejunum, and transport of [14C] oleate proceeded nearly linearly after the first 30 min. Necrosis of mid-villus and crypt cells became obvious by light microscopy after one hour. Therefore, transudate was collected between the period of 30-60 min. Shadow casting of transudates, produced when saline was infused, revealed that 86 +/- 9 (SD) % of osmiophilic particles was less than 800 A in diameter; 13 +/- 8% was 800-1000 A; 0.4 +1- 0.5% was 1000 - 2000 A. Corresponding values were 58 +/- 10, 25 +/- 5, and 16 +/- 5% when 5 mM [14C] oleate + 2.5 mM monoolein was infused; 75% of the transported [14C] appeared in triglyceride. Adding 2 mM Ca++ to the infusion doubled the transport of [14C] triglyceride without increasing particle size further. We conclude that luminal Ca++ increases the absorption of luminal fatty acid by rat jejunum in vitro.

Albumins↗
PubMed1978

Effect of phenolphthalein on the function and structure of rodent and human intestine.

Phenolphthalein (PHE) is the active ingredient in at least 12 over-the-counter laxative preparations. It is alleged to have a minor effect in the small intestine compared with the colon where it is supposed to alter motor activity or water absorption or both. We measured water absorption from segments of rat intestine in vivo, and from the nearly intact small intestines of patients with established ileostomies. In rats, each intestinal segment served as its own control so that water absorption in a test period (PHE, 1--15 mg/100 ml) could be expressed as a percentage of the control period when buffer was infused. PHE inhibited water absorption, and the degree of inhibition was related linearly to log10 PHE concentration. The similarity of slopes of the regression lines suggested that all segments of the rat intestine were equally sensitive to PHE. In six patients, PHE, 100 mg four times a day, increased weight of ileostomy output by 30%, and Na+ output by 39%. These facts indicate that some of the laxative effects of PHE result from inhibition of water absorption in both large and small intestines.

Animals↗
PubMed1978

Apoprotein synthesis by human duodenojejunal mucosa.

We tested whether human duodenojejunal mucosa is able to synthesize apoproteins from amino acid precursors because lipoprotein-like particles are visualized by electron microscopy in human absorptive cells and because apoproteins are synthesized by the perfused rat intestine. Duodenojejunal biopsies from 21 normal fasting volunteers were incubated with L-[U-14C]leucine; 15.6 +/- 3.3 nmoles of the [14C]leucine was incorporated into protein by 100 mg wet weight of biopsies during an incubation of 2 hr. No [14C]leucine was incorporated by boiled biopsies. Homogenates of incubated biopsies were fractionated by ultracentrifugation: 43 +/- 2% of the incorporated 14C as found in the d less than 1.006 fraction; 3.2 +/- 0.6%, 8.1 +/- 1.0% and 48 +/- 2% were found to be associated with the d = 1.006 to 1.063, d = 1.063 to 1.25, and d greater than 1.25 fractions, respectively. The specific activity in the d less than 1.006 fraction was 5.6 times greater than that in the other fractions. Of the 14C incorporated into the d less than 1.006 fraction, 10.8, 7.2, and 7.1% were specifically precipitated by rabbit antihuman apoproteins A-I, A-II, and B, respectively. Of the 14C incorporated into the d = 1.006 to 1.063 fraction, 11.3 4.1, and 8.5% were specifically precipitated by rabbit antihuman apoprotein A-I, A-II, and B, respectively. Approximately 5% of the 14C incorporated by the d = 1.063 to 1.25 fractions were precipitated by rabbit antihuman apoprotein A-I or A-II. None of the d less than 1.25 fractions precipitated a significant amount of radioactivity with rabit antihuman apoprotein C-II, or antiarginine-rich apoprotein. None of the antibodies precipitated radioactivity from the d greater than 1.25 fraction. These experiments suggest that human duodenojejunal mucosa is able to synthesize in vitro apoproteins A-I, A-II, and B from amino acid precursors. The specificity of the immunoprecipitates was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis.

Adolescent↗
PubMed1977

Effect of bisacodyl on the structure and function of rodent and human intestine.

The effect of bisacodyl on intestinal structure and function was investigated. Net water transport was measured under steady state conditions in vivo during single pass infusions of rodent and of human intestinal segments. Each segment served as its own control. Bisacodyl inhibited water absorption in rat jejunum, ileum, and colon. The degree of inhibition was linearly related to the logarithm of the bisacodyl concentration over the range of 0.05 to 2.0 mg per 100 ml. In human jejunal segments, bisacodyl, 1 mg per 100 ml, caused net water secretion. Bisacodyl, 5 mg every 6 hr, increased ileostomy output by 15% when it was fed to 5 patients with established ileostomies. By light microscopy, bisacodyl, 2 mg per 100 ml, erased cytoplasmic and nuclear detail within surface absorptive cells of rat intestine. By electron microscopy, the involved cells contained sparse and abnormal cytoplasmic organelles and nuclei which were deficient in chromatin. These results suggest that the laxative effect of bisacodyl is related to its ability to inhibit intestinal water absorption. Reduced absorption may be secondary to changes in surface absorptive cells.

Animals↗