Biomedical subjects

E S Foster

Publications and source records attributed to E S Foster.

At least 19 recordsLinked to original sources

PubMed1995

Diarrhea in the intensive care patient.

Approximately one third of patients admitted to the ICU develop diarrhea during their hospitalization. Diarrhea can lead to further complications, such as volume depletion and wound infection, and can significantly increase medical costs. The most common causative factors are medications, enteral feedings, and C. difficile infections. These may be implicated alone or in combination. Further investigations of the pathophysiology of ICU diarrhea as well as potential therapies are needed to clarify the proper approach to this important and complex problem.

Clostridioides difficile↗

PubMed1990

Contribution of Cl(-)-OH- exchange to electroneutral NaCl absorption in rat distal colon.

Neutral NaCl absorption is the predominant Na+ absorptive process in rat distal colon. Whether this neutral NaCl absorptive process represents Na(+)-Cl- cotransport or dual ion exchanges of Na(+)-H+ and Cl(-)-OH- has been uncertain. Recent studies using rat colonic brush-border membrane vesicles (BBMVs) have described a Na(+)-H+ exchange mechanism and have proposed that net NaCl absorption occurs via a dual ion exchange process. To date, however, an anion exchanger on the colonic apical membrane has not been identified. To determine whether a Cl(-)-OH- exchange process is present, 36Cl uptake was evaluated across rat distal colonic BBMVs. A pH gradient (7.7 in/5.5 out) stimulated active Cl- uptake. Cl- uptake was not significantly affected by the presence of a valinomycin-induced K+ diffusion potential (inside positive), suggesting that a Cl- conductive pathway is not present in these membranes. The pH gradient-stimulated Cl- uptake was a saturable function of the Cl- concentration with a Km of 14.3 +/- 5.0 mM and a Vmax of 20.4 +/- 5.5 nmol.mg protein-1.30 s-1 and was almost completely inhibited by 1 mM concentrations of SITS and DIDS, inhibitors of anion exchange processes in other epithelia. Inward gradients of Na+, K+, or Na+ and K+ did not further stimulate initial Cl- uptake, suggesting that coupling of Na+ and Cl- movement does not occur by a cotransport mechanism. Thus a Cl(-)-OH- exchange process is present in rat distal colonic BBMVs.(ABSTRACT TRUNCATED AT 250 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1989

Na+-H+ antiporter of rat colonic basolateral membrane vesicles.

The present experiments were conducted, using acridine orange and 22Na uptake techniques, to demonstrate the presence of an electroneutral Na+-H+ exchange process in rat colonic basolateral membrane vesicles. Results consistent with the existence of a distinct Na+-H+ antiporter in these vesicles include the following: 1) an outwardly directed Na+ gradient stimulated proton influx (Na+in, 100 mM; pHin 7.5/pHout 7.5) and an inwardly directed sodium gradient (Na+out, 5-50 mM; pHin 6.0/pHout 7.5) stimulated proton efflux; 2) sodium-stimulated proton influx was minimally decreased (approximately 10-25%) under voltage clamp conditions (addition of valinomycin in the presence of K+ on both sides of vesicles), indicating that Na+ for H+ exchange in these vesicles could not be explained solely on the basis of a membrane potential; 3) an outwardly directed proton gradient (pHin 5.5/pHout 7.5) stimulated 22Na uptake into these vesicles and a threefold "over-shoot" was observed; 4) 22Na uptake and sodium-stimulated proton efflux were saturable with a Km for Na+ of 5.8 +/- 0.9 and 7.0 +/- 0.3 mM, respectively; 5) amiloride (1 mM) significantly inhibited both sodium-stimulated proton efflux (approximately 69%) and 22Na uptake (approximately 89%), but other transport inhibitors (acetazolamide, 4-acetamido-4'isothiocyanostilbene-2,2'-disulfonic acid, and bumetanide) had no effect on 22Na uptake; 6) N-methylglucamine+ (a nonpermeant cation) did not affect pH gradient-stimulated 22Na uptake, whereas Li+ inhibited Na+ uptake; 7) an inwardly directed Li+ gradient stimulated proton efflux and the Km for Li+ was 12.5 +/- 1.5 mM. These findings establish the existence of an electroneutral Na+-H+ exchange mechanism in rat colonic basolateral membrane vesicles.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗

PubMed1988

Polycythemia vera in a cat with cardiac hypertrophy.

Polycythemia vera, a rare and poorly documented disease in cats, was diagnosed in a 4-year-old domestic shorthair cat admitted because of seizures. The diagnosis was made on the basis of high PCV, normal serum erythropoietin concentration (as determined by bioassay, using rabbit bone marrow cells), and elimination of secondary polycythemia as a diagnosis. Cardiac hypertrophy, which might have been secondary to blood hyperviscosity, also was diagnosed. The cat has been treated by periodic phlebotomy and has been without clinical signs of disease for more than 20 months.

Animals↗

PubMed1988

1,2-Dimethylhydrazine-induced alterations in Na+-H+ exchange in rat colonic brush-border membrane vesicles.

1,2-Dimethylhydrazine, in weekly subcutaneous (s.c.) doses of 20 mg/kg body weight, produces colonic tumors in virtually 100% of rodents, with a latency period of approximately 6 months. To determine whether alterations in Na+-H+ exchange existed before the development of dimethylhydrazine-induced colon cancer, rats were given s.c. injections of this agent (20 mg/kg body wt. per per week) or diluent for 5 weeks. Animals were then killed, rat colonic brush-border membrane vesicles prepared and amiloride-sensitive sodium-stimulated proton efflux was measured and compared in control and treated-preparations. The results of these studies demonstrated that dimethylhydrazine treatment: (1) significantly increased the Vmax of this exchange without altering the Km for sodium of this exchange process, utilizing the fluorescent pH-sensitive dye, acridine orange; 22Na flux experiments also demonstrated an increase in amiloride-sensitive proton-stimulated sodium influx across treated-membrane vesicles; (2) did not appear to significantly influence Na+ permeability or proton conductance in treated-preparations compared to their control counterparts; and (3) did not significantly affect the kinetic parameters of amiloride-sensitive sodium-stimulated proton efflux in renal cortex brush-border membrane vesicles using acridine orange. This data, therefore, suggests that alterations in Na+-H+ exchange in rat colonic brush-border membranes may be involved in the malignant transformation process induced by this procarcinogen in the large intestine.

1,2-Dimethylhydrazine↗

PubMed1987

Modulation of rat distal colonic brush-border membrane Na+-H+ exchange by dexamethasone: role of lipid fluidity.

Earlier studies by our laboratory have suggested a relationship between an amiloride-sensitive Na+-H+ exchange process and the physical state of the lipids of rat colonic brush-border membrane vesicles. To further assess this possible relationship, a series of experiments were performed to examine the effect of dexamethasone administration (100 micrograms/100 g body wt. per day) subcutaneously for 4 days on Na+-H+ exchange, lipid composition and lipid fluidity of rat distal colonic brush-border membrane vesicles. The results of these studies demonstrate that dexamethasone treatment significantly: (1) increased the Vmax of the Na+-H+ exchange without altering the Km for sodium of this exchange process, utilizing the fluorescent pH-sensitive dye, acridine orange. 22Na flux experiments also demonstrated an increase in amiloride-sensitive proton-stimulated sodium influx across dexamethasone-treated brush-border membrane vesicles; (2) increased the lipid fluidity of treated-membrane vesicles compared to their control counterparts, as assessed by steady-state fluorescence polarization techniques using three different lipid-soluble fluorophores; and (3) increased the phospholipid content of treated-membrane vesicles thereby, decreasing the cholesterol/phospholipid molar ratio of treated compared to control preparations. This data, therefore, demonstrates that dexamethasone administration can modulate amiloride-sensitive Na+-H+ exchange in rat colonic distal brush-border membrane vesicles. Moreover, it adds support to the contention that a direct relationship exists between Na+-H+ exchange activity and the physical state of the lipids of rat colonic apical plasma membranes.

Amiloride↗

PubMed1987

Modulation of Na+-H+ exchange by ethinyl estradiol in rat colonic brush-border membrane vesicles.

Prior studies by our laboratory have suggested that a relationship may exist between rat colonic brush-border membrane vesicular fluidity and Na+-H+ exchange. To further explore this possible relationship, in the present studies the effects of ethinyl estradiol (17 alpha-ethinyl-1,3,5-estratriene-3,17-beta-diol) administration subcutaneously (5 mg/kg body wt. per day) for 5 days, on rat colonic brush-border membrane fluidity and Na+-H+ exchange were examined. This treatment regimen has previously been shown to decrease the lipid fluidity of rat hepatic and rabbit small intestinal plasma membranes. In agreement with these prior studies, the present results demonstrate that this agent decreases the lipid fluidity of treated-rat colonic brush-border membranes compared to control membranes, as assessed by steady-state fluorescence polarization techniques using three different fluorophores. An increase in the cholesterol content and cholesterol/phospholipid molar ratio of treated-membranes appear to, at least partially, be responsible for the fluidity differences. Furthermore, examination of the kinetic parameters for amiloride-sensitive sodium-stimulated proton efflux in treated and control membrane vesicles, utilizing the pH-sensitive fluorescent dye, Acridine orange, revealed that ethinyl estradiol administration decreased the Vmax for this exchange mechanism, expressed in arbitrary fluorescence units, by approx. 25% but did not influence its Km for sodium. These data, therefore, lend further support to the contention that alterations in fluidity may modulate Na+-H+ exchange in rat colonic brush-border membrane vesicles.

Animals↗

PubMed1987

Mechanism of electroneutral sodium chloride absorption in distal colon of the rat.

This investigation was designed to establish the mechanism of sodium and chloride transport in the rat distal colon by determining ion fluxes across isolated mucosa under voltage clamp conditions. The net rates of sodium and chloride absorption in the distal colon of the rat were approximately equal (5.8 +/- 0.3 and 6.9 +/- 0.5 microEq/h X cm2, respectively) and significantly greater than the short circuit current (0.9 +/- 0.1 microEq/h X cm2). Net sodium absorption and net chloride absorption were markedly reduced by the removal of chloride and sodium, respectively, but were not affected by the absence of potassium from the mucosal bathing solution. Both net sodium absorption and net chloride absorption were also significantly inhibited by 1.0 mM amiloride and by 0.1 mM acetazolamide. In contrast, 0.1 mM amiloride and 1.0 mM furosemide did not inhibit either sodium or chloride absorption. These results confirm that electroneutral sodium chloride absorption is the predominant mechanism of sodium and chloride absorption and suggest that parallel ion (Na-H and Cl-HCO3) exchanges, rather than independent electrogenic sodium and chloride transport, coupled sodium-chloride cotransport, or coupled Na-K-2Cl cotransport, are most likely responsible for sodium chloride absorption in this epithelium.

Acetazolamide↗

PubMed1986

Regulation of Na+-H+ exchange by transmethylation reactions in rat colonic brush-border membranes.

Incubation of rat colonic brush-border membrane vesicles with 200 microM S-adenosyl-L-[Me-3H]methionine resulted in the labeling of both membrane phospholipids and proteins. This labeling was decreased approximately 50% by the methylation inhibitor S-adenosyl-L-homocysteine (2 mM). Utilizing the pH-sensitive fluorescent dye, acridine orange, as a means of determining Na+-H+ exchange, S-adenosyl-L-methionine (200 microM) significantly increased sodium-stimulated proton efflux in these vesicles at all concentrations of sodium (2.5-50 mM) tested. Examination of the kinetic parameters for sodium-stimulated proton efflux in the presence and absence of 200 microM S-adenosyl-L-methionine revealed that the methyl donor increased the Vmax for this exchange mechanism (expressed in arbitrary fluorescence units) by approx. 36% but did not influence its Km for sodium. S-Adenosyl-L-homocysteine (2 mM) inhibited S-adenosyl-L-methionine-mediated stimulation of this exchange process. The results demonstrate that methylation of membrane phospholipids and/or proteins can modulate Na+-H+ exchange in rat colonic brush-border membrane vesicles.

Animals↗

PubMed1986

Cutaneous lesion caused by Mycobacterium tuberculosis in a dog.

A 5-month-old female mixed-breed dog was examined because of nonhealing wounds in the right submandibular region. Treatment with antibiotics and surgical excision was ineffective. Specimens of the right mandibular lymph node and surrounding tissues were submitted for bacteriologic culturing, and Mycobacterium tuberculosis was isolated. The dog was euthanatized. The risk of infection of human beings who associate with dogs that have cutaneous wounds caused by mycobacteria is unknown.

Animals↗

PubMed1986

Synthesis of phosphatidylcholine by two distinct methyltransferases in rat colonic brush-border membranes: evidence for extrinsic and intrinsic membrane activities.

The enzymatic synthesis of phosphatidylcholine from phosphatidylethanolamine via a transmethylation pathway has not been shown to occur in the small intestine and has been assumed to be absent from the entire gut. The existence of this pathway, however, has not been investigated in the large intestine. Utilizing a recently developed method for the isolation of brush-border membranes from rat colonocytes, the present studies were designed to determine whether phospholipid methylation activity was present in the large intestine. The results demonstrate that this pathway for synthesis of phosphatidylcholine exists in rat colonic plasma membranes and involves at least two distinct methyltransferases. The predominant product of the first enzyme (methyltransferase I) is phosphatidyl-N-monomethylethanolamine; phosphatidylcholine and phosphatidyl-N-monomethylethanolamine are the principal products of the second enzyme (methyltransferase II). Methyltransferase I has an apparent Km for S-adenosyl-L-methionine of 100.0 microM and a pH optimum of 8.0, while methyltransferase II has an apparent Km of 0.3 microM and a pH optimum of 6.0. Additional evidence to support the presence of two distinct enzymes includes the differential effects of ATP, Triton X-100, trypsin treatment, and temperature on their activities.

Adenosine Triphosphate↗

PubMed1986

The lipid fluidity of rat colonic brush-border membrane vesicles modulates Na+-H+ exchange and osmotic water permeability.

Brush-border membrane vesicles were prepared from rat colonic epithelial cells. Steady-state fluorescence polarization techniques, using the fluorophores 1,6-diphenyl-1,3,5-hexatriene and DL-12-(9-anthroyl)stearic acid (12-AS), revealed that benzyl alcohol (25-75 mM) but not methyl alcohol (50-125 mM) significantly increased the fluidity of these vesicles. Benzyl alcohol (50 and 75 mM) but not methyl alcohol also increased amiloride-sensitive sodium-stimulated proton efflux from these vesicles at all concentrations of sodium tested (2.5-50.0 mM), as assessed by changes in the fluorescence of acridine orange. Benzyl alcohol, at 50 and 75 mM concentrations, increased the maximal velocity (Vmax) of this exchange process by approximately 58 and 75%, respectively. Neither concentration, however, altered the Km for sodium. Osmotic water flow, measured as rate constants of osmotic shrinkage of these vesicles using a stopped-flow nephelometric technique, was also increased by 75 mM benzyl alcohol but not by a similar concentration of methyl alcohol. The present data, therefore, demonstrate that the fluidity of rat colonic brush-border membranes can influence Na+-H+ exchange and osmotic water flow across these vesicles.

Animals↗

PubMed1986

Ba2+ inhibition of VIP- and A23187-stimulated Cl- secretion by T84 cell monolayers.

Addition of either 10(-8) M vasoactive intestinal polypeptide (VIP) or 10(-6) M A23187 to T84 cell monolayers, grown on permeable supports and mounted in Ussing chambers, stimulated net Cl- secretion. The effect of 10(-6) M A23187 on Cl- flux was consistently smaller than that observed with 10(-8) M VIP. In both cases the increase in net Cl- secretion accounted for the entire change in the observed short-circuit current (Isc). Since Cl- enters the cells through a basolaterally localized Na+-K+-Cl(-)-cotransport system (J. Clin. Invest. 75: 462, 1985), the fate of K+, which is cotransported with Cl- during VIP, and A23187-mediated Cl- secretion was explored. Unidirectional and net transepithelial 42K+ flux rates were negligible compared with 36Cl- flux rates (less than 4% of Cl- flux), indicating that little K+ was secreted along with Cl-. K+ recycling across the basolateral membrane was suggested from experiments in which 86Rb+ efflux (as a tracer for K+) was measured across the apical and basolateral membranes of 86Rb+ -preloaded monolayers under voltage-clamped conditions. In the absence of secretagogues, 86Rb+ efflux was 10-fold higher across the basolateral membrane than across the apical membrane. 86Rb+ efflux across the basolateral membrane was accelerated two- to threefold by addition of either VIP or A23187. In each case accelerated efflux was inhibited by 5 mM Ba2+. Cl- secretion induced by VIP or A23187 was also inhibited by serosal addition of Ba2+.(ABSTRACT TRUNCATED AT 250 WORDS)

Barium↗

PubMed1986

Na+-H+ exchange in rat colonic brush-border membrane vesicles.

To demonstrate the presence of a Na+-H+ exchange process in brush-border membrane vesicles from rat colonocytes, the fluorescence response of acridine orange was used to monitor the formation and dissipation of pH gradients. An inwardly directed Na+ gradient stimulated the outward flux of H+, whereas proton influx was stimulated by an outwardly directed Na+ gradient. Since the ionophore valinomycin in the presence of a K+ gradient did not alter Na+-stimulated proton efflux, the interrelationship of Na+ and H+ movement could not be explained solely on the basis of a membrane potential. Na+-stimulated proton efflux was saturable with a Km for Na+ of 20.1 +/- 1.6 mM. Inwardly directed Li+ gradients also stimulated proton efflux, and the Km for Li+ was 30.2 +/- 1.7 mM. In contrast, impermeant cations failed to stimulate the outward flux of H+. Amiloride (1 mM) inhibited both Na+-stimulated proton efflux and influx. Therefore, Na+-H+ exchange is present in rat colonic brush-border membranes and has characteristics similar to other Na+-H+ antiporters. This exchange process may be an important mechanism for Na+ absorption in the large intestine.

Acridine Orange↗

PubMed1986

Sodium and chloride transport in the large intestine of potassium-loaded rats.

Increased dietary potassium ("potassium loading") induces several adaptive changes in colonic function, including increased potential-dependent potassium secretion, active potassium secretion, and Na-K-ATPase activity, but does not alter net sodium absorption in vivo. To establish whether potassium loading stimulates active sodium transport, unidirectional, net sodium, and chloride fluxes were determined under voltage-clamp conditions across isolated rat distal colonic mucosa. In normal animals net sodium flux (JNanet), net chloride flux (JClnet) and short-circuit current (Isc) were 6.1 +/- 1.1, 8.4 +/- 1.0, and 0.7 +/- 0.1 mu eq X h-1. cm-2, respectively; potassium loading significantly increased JNanet and Isc by 4.9 +/- 1.4 and 3.5 +/- 0.7 mu eq X h-1 X cm-2, respectively, without changing JClnet. Amiloride (0.1 mM) inhibited the increases in JNanet and Isc produced by potassium loading. In Cl-free Ringer solution in normal animals JNanet was reduced to 0.6 +/- 0.3 mu eq X h-1 X cm-2. Potassium loading produced identical increases in JNanet and Isc, which were also completely inhibited by 0.1 mM amiloride. These studies establish that potassium loading induces amiloride-sensitive electrogenic sodium absorption without affecting electroneutral sodium-chloride absorption.

Adaptation, Physiological↗

PubMed1986

Dietary potassium modulates active potassium absorption and secretion in rat distal colon.

To determine the effect of variations in body stores of potassium on the rate of active potassium transport in the large intestine, unidirectional 42K fluxes were performed under short-circuit conditions across isolated distal colonic mucosa of control, dietary potassium-depleted and dietary potassium-loaded rats. Potassium depletion stimulated net potassium absorption (JK net) (0.87 +/- 0.19 vs. 0.49 +/- 0.04 mu eq X h-1 X cm-2, P less than 0.025) due to a 40% increase in mucosal-to-serosal potassium transport (JK m----s). In sodium-free Ringer solution JK net in the potassium-depleted group was also significantly greater than in controls (1.93 +/- 0.26 vs. 1.01 +/- 0.11 mu eq X h-1 X cm-2, P less than 0.005). In contrast, in chloride-free Ringer solution JK net was identical in the control and potassium-depleted groups (0.39 +/- 0.05 vs. 0.46 +/- 0.07 mu eq X h-1 X cm-2, P = NS). Potassium loading reversed net potassium absorption to net potassium secretion (-0.76 +/- 0.08 mu eq X h-1 X cm-2, P less than 0.001) as the result of a decrease in JK m----s and an increase in serosal-to-mucosal potassium transport (JK s----m). Net potassium secretion was abolished in the absence of either sodium or chloride from the bathing solution but not by mucosal amiloride. In sodium-free Ringer solution JK net was similar in control and potassium-loaded groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗

PubMed1986

Ion transport in proximal colon of the rat. Sodium depletion stimulates neutral sodium chloride absorption.

UNLABELLED: The model of sodium and chloride transport proposed for the colon is based on studies performed in the distal segment and tacitly assumes that ion transport is similar throughout the colon. In rat distal colon, neutral sodium-chloride absorption accounts for the major fraction of overall sodium absorption and aldosterone stimulates electrogenic, amiloride-sensitive sodium absorption. Since we have demonstrated qualitative differences in potassium transport in proximal and distal segments of rat colon, unidirectional 22Na and 36Cl fluxes were performed under short-circuit conditions across isolated proximal colon of control and sodium-depleted rats with secondary hyperaldosteronism. In the control group, net sodium absorption (JNanet) (7.4 +/- 0.5 mu eq/h . cm2) was greater than Isc (1.4 +/- 0.1 mu eq/h . cm2), and JClnet was 0 in Ringer solution. Residual flux (JR) was -5.2 +/- 0.5 mu eq/h . cm2 consistent with hydrogen ion secretion suggesting that neutral sodium absorption may represent sodium-hydrogen exchange. 1 mM mucosal amiloride, which inhibits sodium-hydrogen exchange in other epithelia, produced comparable decreases in JNanet and JR (4.1 +/- 0.6 and 3.2 +/- 0.6 mu eq/h . cm2, respectively) without a parallel fall in Isc. Sodium depletion stimulated JNanet, JClnet, and Isc by 7.0 +/- 1.4, 6.3 +/- 1.9, and 0.8 +/- 0.2 mu eq/h . cm2, respectively, and 1 mM amiloride markedly inhibited JNanet and JClnet by 6.0 +/- 1.1 and 4.0 +/- 1.6 mu eq/h . cm2, respectively, with only a minimal reduction in Isc. CONCLUSIONS: the predominant neutral sodium-absorptive mechanism in proximal colon is sodium-hydrogen exchange. Sodium depletion stimulates electroneutral chloride-dependent sodium absorption (most likely as a result of increasing sodium-hydrogen and chloride-bicarbonate exchanges), not electrogenic chloride-independent sodium transport. The model of ion transport in the proximal colon is distinct from that of the distal colon.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1985

The electrical basis for enhanced potassium secretion in rat distal colon during dietary potassium loading.

Previous studies in rat distal colon provide evidence for an active absorptive process for potassium under basal conditions, and for active potassium secretion during chronic dietary potassium loading. The present studies were performed with conventional and potassium-selective microelectrodes to determine the electrical basis for the increase in transcellular (active) potassium secretion observed during potassium loading. Compared to control tissues, potassium loading resulted in a 5-fold increase in transepithelial voltage (VT) and a 52% decrease in total resistance (RT) in the distal colon. The rise in VT was due to a decrease in apical membrane resistance and an increase in basolateral membrane voltage from -45 +/- 2 mV (cell interior negative) in control to -56 +/- 2 mV (p less than 0.001) in potassium loaded tissues. This difference in basolateral membrane voltage reflected in increase in intracellular potassium activity from 86 +/- 4 mM to 153 +/- 12 mM (P less than 0.001). In control tissues, the sequential mucosal addition of the sodium channel blocker amiloride (0.1 mM) and the potassium channel blocker tetraethylammonium chloride (TEA: 30 mM) produced no effect on the electrical measurements. However, in potassium loaded tissues, amiloride and TEA produced transepithelial changes consistent with inhibition of apical membrane conductances for sodium and potassium, respectively, reflected by increases in the resistance ratio, alpha (ratio of apical to basolateral membrane resistances). These data indicate that the decrease in apical membrane resistance during potassium loading was caused by an increase in apical membrane conductance for both potassium and sodium.

Amiloride↗