M V Pahl

University of California, Irvine, Irvine, CA, United States

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Publications (43)117.6 Total impact

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    ABSTRACT: End-stage renal disease (ESRD) causes accelerated atherosclerosis which is mediated by oxidative stress and inflammation. Activation and infiltration of monocytes represent the critical steps in atherogenesis which is advanced by oxidized LDL and inhibited by HDL. Via its main apolipoprotein (apoA-I) and constituent enzymes (paraoxonase; glutathione peroxidase (GPX), LCAT) HDL exerts potent antioxidant/anti-inflammatory functions. We have found marked reduction of HDL antioxidant/anti-inflammatory and heightened LDL pro-oxidant/pro-inflammatory activities in ESRD patients. Given the inseparable link between oxidative stress and inflammation, we tested the hypothesis that antioxidant therapy may improve anti-inflammatory (monocyte adhesion-promoting capacity) properties of plasma in ESRD patients. We studied 20 hemodialysis patients who after a 4-week wash-out period were treated with a potent antioxidant cocktail (vitamin (v) E, 800 IU; vC, 250 mg; vB6, 100 mg; vB12, 250 µg and folic acid 10 mg daily) for 8 weeks. Twelve healthy volunteers served as control. Pre-dialysis plasma samples were obtained at the onset and conclusion of the study. Markers of oxidative stress and inflammation, apoA-I, HDL-associated enzymes and monocyte adhesion assay were measured using cultured aortic endothelial cells. ESRD patients exhibited reduced plasma level of apoA-1 and antioxidant enzymes, elevated markers of oxidative stress and inflammation and heightened monocyte adhesion-promoting capacity. Antioxidant therapy failed to improve these abnormalities. High doses of antioxidant vitamins fail to improve oxidative stress, inflammation or plasma monocyte adhesion-promoting capacity in ESRD patients. Thus, high doses of vitamins beyond the routinely-prescribed supplements do not appear to be beneficial in this patient population.
    Clinical nephrology 10/2010; 74(4):273-81. · 1.29 Impact Factor
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    ABSTRACT: End-stage renal disease (ESRD) is simultaneously associated with inflammation, impaired immunity and increased susceptibility to microbial infections. Innate immune cells, monocytes and polymorphonuclear leukocytes (PMN) recognize pathogens via toll-like receptors (TLR) triggering phagocytosis, cellular activation and secretion of inflammatory cytokines. Data on expression and function of TLRs in ESRD are limited. Blood samples from 21 stable ESRD patients and 21 normal controls were processed for TLR2, TLR4, TLR7 and TLR 9 expression on monocytes and PMN by flow cytometry. TLR activity was examined by determining the response to TLR4 and TLR2 ligands. The ESRD group exhibited significant upregulation of TLR2 and TLR4 (but not TLR7 or TLR 9) expressions on monocytes and of TLR4 on PMN. This was coupled with heightened cytokine production in response to TLR4 activation with lipopolysaccharide. However, the response to TLR2 stimulation with peptidoglycan was unchanged in the ESRD group. Monocyte TLR2 and TLR4 and neutrophil TLR4 expressions and TLR4 activity are increased hemodialysis patients, representing another dimension of ESRD-associated inflammation.
    American Journal of Nephrology 01/2010; 31(3):247-54. · 2.62 Impact Factor
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    ABSTRACT: Although bacterial infections have dramatically declined as a cause of death in the general population, they remain a major cause of mortality in patients with end-stage renal disease (ESRD). Moreover, the response to vaccination is profoundly impaired in this population. Dendritic cells (DC) are the major antigen-presenting cells that bridge the innate and adaptive immune responses. Activation of DC by pathogens results in secretion of inflammatory cytokines and up-regulation of co-stimulatory molecules. The activated DC prime naïve T and B cells to the captured antigens. Using flow cytometry, the number and phenotype of circulating DC [myeloid DC (mDC) and plasmacytoid DC (pDC)] were quantified in pre- and post-dialysis blood samples from 20 ESRD patients maintained on haemodialysis. Ten normal individuals served as controls. In addition, the level of DC activation and their response to lipopolysaccharide (LPS) stimulation were determined by assessing expression of co-stimulatory molecule, CD86, and antigen-presenting molecule, HLA-DR, as well as production of TNFalpha, IFNalpha and IL-6. Compared to the control group, the circulating dendritic cell count was significantly reduced in the ESRD patients before dialysis and declined further after dialysis. The reduction in pDC numbers was more striking than mDC. The magnitude of the LPS-induced up-regulation of CD86 was comparable among the study groups as well as pre- and post-dialysis samples. However, LPS-induced TNFalpha production was significantly reduced in the post-dialysis samples with no significant difference in IL-6 and IFNalpha productions among the study groups and in pre- and post-dialysis samples. ESRD results in significant DC depletion which is largely due to diminished plasmacytoid DC subset. Haemodialysis procedure intensifies DC depletion and impairs LPS-induced TNFalpha production.
    Nephrology Dialysis Transplantation 11/2009; 25(3):737-46. · 3.37 Impact Factor
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    J W Yoon, M V Pahl, N D Vaziri
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    ABSTRACT: Oxidative stress and inflammation are common features and major mediators of atherosclerosis in end-stage renal disease (ESRD). Available evidence for oxidative stress in ESRD is indirect and based on accumulation of byproducts of interactions of reactive oxygen species (ROS) with various molecules. Inflammation is a major cause of oxidative stress. To explore the direct link between oxidative stress and inflammation in ESRD, we studied leukocyte integrin expression and ROS production in 18 ESRD patients and 18 controls. ESRD patients showed elevated plasma malondialdehyde (MDA) and increased superoxide and hydrogen peroxide (H(2)O(2)) production by granulocytes and monocytes before dialysis. Hemodialysis resulted in a further rise in plasma MDA and H(2)O(2) production by granulocytes and monocytes. Surface expression of Mac-1 (CD11b and CD18) on granulocytes and monocytes was significantly increased (denoting cell activation) in ESRD patients. Granularity of granulocytes was significantly reduced before dialysis and declined further after dialysis. The magnitude of ROS production by granulocytes and monocytes was directly related with CD11b expression as well as plasma ferritin and parathyroid hormone levels and was inversely related to protein catabolic rate. Thus, this study provides direct evidence of spontaneous leukocyte activation and increased ROS generation (hence the link between oxidative stress and inflammation) in ESRD patients.
    Kidney International 02/2007; 71(2):167-72. · 8.52 Impact Factor
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    ABSTRACT: End-stage renal disease (ESRD) is associated with increased propensity to infections, diminished response to vaccination, impaired cell-mediated immunity, and reduced CD4+/CD8+ T-lymphocyte ratio. Four subsets of CD4+ and CD8+ T cells have been recently identified: naïve cells (as yet uncommitted), central memory (CM) cells (previously programmed), and CD45RA-positive and CD45RA-negative effector memory (EM) cells (programmed to perform specific effector functions). The effect of ESRD on subpopulations of T lymphocytes is unclear and was studied here. Twenty-one hemodialysis patients and 21 age-matched controls were studied. Pre- and post-dialysis blood samples were obtained and analyzed by three-color flow cytometry. CD4+/CD8+ ratio and the numbers of the naïve and CM CD4+ and CD8+ T cells were significantly reduced, whereas the numbers of EM CD4+ and CD8+ T cells were unchanged in the ESRD group. The reduction of the naïve and CM T-cell counts in the ESRD group was associated with increased apoptosis of these cells. Negative correlations were found between severity of azotemia, oxidative stress, and hyperphosphatemia with the number of naïve T cells. Comparison of diabetic with non-diabetic ESRD patients revealed higher numbers of total CD8+ cells and EM CD8+ T cells in the diabetic group. Dialysis did not significantly change the naïve and CM CD4+ or CD8+ cell counts, but significantly lowered CD8+ EM cell count. Thus, ESRD results in increased apoptosis and diminished populations of naïve and CM T lymphocytes. This phenomenon may, in part, contribute to the impaired immune response in this population.
    Kidney International 08/2006; 70(2):371-6. · 8.52 Impact Factor
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    ABSTRACT: Boric acid (H(3)BO(3)) has been shown to cause developmental abnormalities in the offspring of pregnant rats. Comparative data on the renal clearance of boron (B) in rats and humans, both pregnant and nonpregnant, exposed to boric acid (BA) would reduce uncertainty in interspecies extrapolation from rats to humans. The purpose of this study was to evaluate the effect of pregnancy on the plasma half-life and renal clearance of boron in Sprague-Dawley rats given a single oral dose of boric acid. For the half-life study, nonpregnant and pregnant (gestation day 16) rats were given a single dose of 30 mg/kg of boric acid by gavage, and plasma samples were collected at 2-3 h intervals. The plasma half-life of boron was determined to be 2.9 +/- 0.2 and 3.2 +/- 0.3 h in nonpregnant and pregnant rats, respectively. In the clearance study, nonpregnant and pregnant (GD 16) rats were given a single gavage dose of 0.3, 3, or 30 mg/kg of boric acid. Boron clearance was slightly higher in pregnant rats (3.3 +/- 0.6, 3.2 +/- 0.5, and 3.4 +/- 0.5 ml/min/kg, respectively) compared to nonpregnant rats (3.1 +/- 0.8, 3.0 +/- 0.6, and 3.2 +/- 0.5 ml/min/kg, respectively), but the difference was not statistically significant and not dose-related. Boron clearance was less than creatinine clearance, suggesting tubular reabsorption in both groups. In conclusion, pregnancy did not appear to significantly alter the renal clearance or the plasma half-life of boron in Sprague-Dawley rats under the conditions of this study.
    Toxicological Sciences 05/2001; 60(2):257-63. · 4.33 Impact Factor
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    ABSTRACT: Boron occurs most frequently in nature as borates and boric acid, never as the free element. Its largest uses are in glass, detergents, and agriculture. Essential for higher plants, there is growing evidence for essentiality in vertebrates. Humans consume daily about a milligram of boron, mostly from fruit and vegetables. At high doses, boron is a developmental and reproductive toxin in animals. Pregnant rats were the most sensitive. An oral NOAEL of 9.6 mg B/kg/day was established for developmental toxicity in Sprague-Dawley rats fed boric acid. To extrapolate from the large, animal boron toxicity database to humans, especially to pregnant women, information on renal clearance of boron was needed. This study's purpose was to measure renal clearance of boron in pregnant and nonpregnant woman. In 16 second trimester women and 15 nonpregnant age-matched referents, dietary boron provided the blood and urine boron concentrations used for calculating boron clearance. The pregnant and nonpregnant boron intake was 1.35 and 1.31 mg boron/24 h, respectively. Blood for boron, creatinine, and urea was collected at the start, at 2 h, and at 24 h. Urine was collected during the first 2 h in the Clinical Research Center and during a 22-h period outside the center for measurement of volume, boron, and creatinine. Renal boron clearance measured over the initial 2 h, the most complete urine collection period, was 68.30ml/min/1.73 m(2) for pregnant subjects and 54.31ml/min/1.73 m(2) for nonpregnant subjects. Comparison of renal boron clearance with creatinine clearance indicated that tubular reabsorption of boron occurred in both pregnant and nonpregnant women.
    Toxicological Sciences 05/2001; 60(2):252-6. · 4.33 Impact Factor
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    ABSTRACT: Mesangial cell (MC) proliferation and matrix expansion are characteristics of many glomerulopathies. Heparin has been shown to inhibit MC proliferation in vitro and mitigate cell proliferation, matrix expansion, proteinuria, renal insufficiency, and hypertension in experimental glomerulonephritis and subtotal renal ablation. We examined the effect of standard heparin on MC proliferation and matrix protein expression in vitro which necessarily excludes the confounding influences of haemodynamic, inflammatory, haemostatic, and various other processes that are present in vivo. Gene expression and release of fibronectin (FN), collagen IV and laminin by cultured rat MC were tested in the presence and absence of heparin. In addition the effect of transforming growth factor-beta1 (TGF-beta1) on the gene expression of those matrix proteins was assessed. Within a 3-1000 microg/ml concentration range, heparin inhibited gene expression and release of FN by 10% fetal calf serum (FCS)-stimulated MC in a concentration-dependent manner. At concentrations of 300 and 1000 microg/ml, heparin inhibited fibronectin mRNA levels in TGF-beta1 (6 ng/ml) stimulated cells. However, heparin had no effect on gene expression or release of collagen IV or laminin under these conditions. Heparin markedly inhibited 10% FCS-stimulated MC proliferation in a concentration-dependent manner. Heparin inhibited MC growth and fibronectin production. These effects may, in part, account for the reported beneficial effects of heparin on the course of renal disease in experimental animals.
    Nephrology Dialysis Transplantation 01/1999; 13(12):3052-7. · 3.37 Impact Factor
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    ABSTRACT: Nephrotic syndrome (NS) results in hypercholesterolemia which is attributed to increased production and decreased removal of cholesterol-rich lipoproteins. Adjustments in intestinal absorption are reportedly involved in cholesterol homeostasis. We, therefore, studied the intestinal absorption and biliary excretion of cholesterol in NS. We studied intestinal absorption (by in vivo perfusion and in vitro everted sac incubation techniques) and biliary secretion (by common bile duct cannulation) of cholesterol in rats with puromycin-induced NS. The results were compared with those obtained from pair-fed control (PF) animals, those given free access to food (NL) or those fed a hypercholerolemic diet (H-chol group). Micellar solutions of Krebs' phosphate buffer containing trace amounts of [14C]inulin and [3H]cholesterol, as well as different concentrations of unlabeled cholesterol, were used for absorption studies. The NS and H-chol groups showed severe and comparable hypercholesterolemia. No significant difference was found in the rate of biliary cholesterol secretion among the study groups. Likewise, the rates of in vivo and in vitro cholesterol absorptions in the NS and H-chol groups were comparable with one another and similar to those found in the NL and PF groups. The rate of in vitro cholesterol absorption was directly proportional to its concentration in the incubation media at low concentrations. However, the absorption rate showed a pattern consistent with saturable transport at high cholesterol concentrations in all groups. We conclude that intestinal absorption and biliary secretion of cholesterol are not appreciably influenced by either nephrotic or diet-induced hypercholesterolemia in rats. The data further suggest that cholesterol absorption may be a saturable process.
    Nephrology Dialysis Transplantation 07/1998; 13(6):1446-51. · 3.37 Impact Factor
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    ABSTRACT: Recently, a low density lipoprotein (LDL) receptor has been identified in mesangial cells. However, the nature of intracellular signals in mesangial cells after exposure to LDL is unclear. We studied the effect of LDL on cultured rat mesangial cell [Ca++]i using spectrofluorometry. Addition of LDL (15 micrograms/mL) produced a rapid, transient, and dose-dependent rise in [Ca++]i within seconds, returning to baseline in 6 minutes. No further rise was observed at higher LDL concentrations. No significant rise in [Ca++]i was observed with LDL in cells placed in a Ca(++)-free medium. The [Ca++]i rise was greatly attenuated in magnitude and duration when lanthanum was used. In contrast, verapamil failed to block the LDL-induced rise in [Ca++]i. Addition of LDL did not alter production of inositol 1,4,5-triphosphate (IP3) by mesangial cells. Low density lipoprotein caused a transient rise in [Ca++]i in cultured rat mesangial cells. The observed rise in [Ca++]i was largely caused by influx of extracellular Ca++ through receptor-gated channels. Mobilization from intracellular stores and activation of IP3 were not involved. The rise in [Ca++]i may mediate the effects of LDL on mesangial cell function.
    Journal of Investigative Medicine 01/1997; 44(9):556-60. · 1.75 Impact Factor
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    ABSTRACT: Thrombin stimulates and heparin and heparan sulfate inhibit mesangial cell proliferation. In addition, heparin has been shown to inhibit thrombin-stimulated smooth muscle cell proliferation. The anticoagulant action of heparin is mediated by antithrombin III. This study investigated whether heparin's antiproliferative action is also mediated by antithrombin III. To this end, the effect of antithrombin III on thrombin-stimulated mesangial cell growth was examined. As expected, thrombin stimulated DNA synthesis and cell growth in cultured human mesangial cells. The effect of thrombin on DNA synthesis and mesangial cell proliferation was inhibited by standard heparin and antithrombin III, separately or together. The magnitude of the inhibitory action of antithrombin III was equal to that of equimolar concentrations of heparin and that observed with the combination of the two. Experiments carried out in serum (hence antithrombin III)-free medium revealed that heparin's inhibitory effects are independent of antithrombin III. It was concluded that antithrombin III, an endogenous inhibitor of thrombin's coagulant activity, is an equally effective inhibitor of thrombin's mitogenic action.
    Journal of the American Society of Nephrology 11/1996; 7(10):2249-53. · 8.99 Impact Factor
  • M V Pahl, N D Vaziri, E Gonzales
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    ABSTRACT: Acute spinal cord injury (SCI) is associated with a marked propensity to thromboembolism and a variety of coagulation abnormalities. However, data on blood coagulation profiles in patients with uncomplicated long-standing SCI are limited. These data were studied here. Eight men with uncomplicated chronic SCI and nine able-bodied normal men were studied. Plasma activities and/or antigen concentrations of high molecular weight kininogen (HMWK) and of factors XII, XI, IX, VIII, VII, X, V, II and XIII as well as von Willebrand factor (vWF), fibrinogen and fibronectin were measured by appropriate functional and or immunological assays. The SCI group exhibited normal values for factors XII, IX, VIII, vWF, VII, X and V as well as HMWK, vWF and fibronectin concentration. However, they showed slight reductions in plasma factor XI activity, factor XIII antigen concentration and modest increases in fibrinogen and factor II concentrations. No correlation was found between the parameters studied and either the duration or the level of injury. In conclusion, in contrast to acute SCI, the coagulation profile in uncomplicated chronic SCI is noted to be largely normal with only a few minor alterations of questionable clinical significance.
    The Journal of the American Paraplegia Society 08/1994; 17(3):133-5.
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    ABSTRACT: Systemic reactions resembling anaphylaxis have occurred after intravenous (IV) iron-dextran administration, a treatment modality that has acquired increased acceptance following the use of erythropoietin for the anemia of patients with chronic renal diseases. Three such patients sustained anaphylactoid reactions immediately after receiving IV test doses of iron-dextran which were their only known exposures. In an effort to determine the mechanism of their reactions, we applied tests for (1) basophil degranulation by iron-dextran, basophil histamine release; (2) a type I anaphylactic reaction, specific IgE antibodies; and (3) an immune complex activation, specific IgG antibodies against iron-dextran. Six other patients with renal diseases served as controls, three of whom had tolerated IV iron-dextran, and three without known exposure. One patient only had any test abnormalities. Her initial positive basophil histamine release and specific IgG antibodies reversed and declined respectively at a 4-month follow-up study. She had developed anaphylaxis, and her studies had been performed at a time after anaphylaxis earlier than the other two. The mechanisms of iron-dextran anaphylaxis may be multiple and not be detectable several months after the incident. Prospective studies will probably be required for a predictive test to be developed.
    Annals of allergy 04/1994; 72(3):224-8.
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    ABSTRACT: Management of acute renal failure (ARF) in surgical patients has relied on supportive measures including hemodialysis and peritoneal dialysis. An alternative technique currently available is continuous arteriovenous hemodiafiltration (CAVH-D). Records of 44 surgical patients with ARF who were treated with CAVH-D in our surgical intensive care unit from 1989 to 1992 were reviewed. Thirty-five patients underwent emergency operations, and 4 patients underwent elective operations. Thirty-three patients were hemodynamically unstable immediately prior to the institution of CAVH-D, making hemodialysis a contraindication. A total of 565 CAVH-D days with an average of 13 days per patient were evaluated. Seventeen patients survived, with recovery of renal function in 13 patients. Vascular access was obtained via 227 percutaneous femoral catheters and 4 Scribner shunts. Seven vascular complications occurred, including arteriovenous fistula, pseudoaneurysm, limb ischemia, femoral artery hemorrhage, and femoral vein thrombosis. Based on these data, we conclude that CAVH-D is a safe and effective alternative in surgical patients with ARF.
    The American Journal of Surgery 01/1994; 166(6):612-5; discussion 614-6. · 2.52 Impact Factor
  • Transplantation Proceedings 09/1993; 25(4):2727-31. · 0.95 Impact Factor
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    ABSTRACT: Linoleic acid (LA) transport in rats with experimental short-term and long-term renal failure (RF) was compared with that of sham-operated normal animals on liberal food intake and pair-fed animals. The perfusions in vivo and incubations in vitro were conducted using a micellar solution containing a wide range of LA concentrations. Both absorption in vivo and uptake in vitro of LA were significantly reduced in animals with short-term RF. Lipid extraction and separation by thin-layer chromatography revealed a marked LA trapping as trilinolein (TL) in the perfused intestinal tissue in the short-term RF group. The esterification process, as defined by the rate of LA incorporation into TL, was moderately reduced in short-term RF animals. The thickness of the unstirred water layer showed no significant difference among the groups studied. In contrast, animals with long-term RF exhibited normal absorption of LA in vivo at all concentrations tested. In conclusion, LA absorption is reduced in short-term RF and restored in long-term RF. Several steps including LA transport into and TL transport out of the enterocyte and the esterification process were impaired in short-term RF. These changes are not due to alteration in the unstirred water layer, anorexia, weight loss or a rapid effect of uraemic chemical environment or circulatory factors.
    British Journal Of Nutrition 12/1991; 66(3):467-77. · 3.30 Impact Factor
  • M V Pahl, N D Vaziri
    The International journal of artificial organs 02/1991; 14(1):10-2. · 1.76 Impact Factor
  • M V Pahl, N D Vaziri, M Seo
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    ABSTRACT: We studied carnitine absorption in rats rendered azotemic by subtotal nephrectomy (RF) and compared the results with those obtained in a sham-operated group on liberal food intake (NL) and those pair-fed (PF) with the RF group. Animals with short-term (2 weeks post-nephrectomy) and long-term (5-6 weeks post-nephrectomy) RF were studied. In vivo recirculating perfusion was used. A significant reduction in carnitine absorption (expressed per unit length) was noted in the short-term RF and PF groups when compared to the NL controls. When the data were corrected for intestine weight, the short-term RF and PF groups showed comparable absorption rates with the NL group. These findings suggest that in animals with short-term RF, weight loss is responsible for the observed alteration in carnitine absorption. Intestinal segments from PF and short-term RF animals had significantly greater carnitine accumulation suggesting decreased release into the circulation. In the long-term RF setting, RF and PF animals demonstrated reduced carnitine absorption. When the data were expressed per unit of weight the absorption rates normalized, implicating reduced intestinal mass as the factor responsible for reduced carnitine absorption. No significant difference was found in the amount of residual carnitine suggesting amelioration of impaired transport out of the enterocyte in chronic RF.
    Research communications in chemical pathology and pharmacology 01/1991; 70(3):337-47.
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    ABSTRACT: To examine whether the intestinal mucosa in uremia is more prone to injury, we studied acute intestinal mucosal injury in rats with experimental chronic renal failure (RF) and sham-operated and starved control animals. Intestinal injury was produced by perfusing intestinal segments in vivo with 5 mmol/L chenodeoxycholic acid. Histologic specimens were then taken from the proximal and distal perfused and unperfused intestinal segments. Quantitative morphometry was done with computerized image analysis, and samples of the unperfused intestine were assayed for protein and DNA content. Chronic RF did not significantly affect the functional or morphologic injury caused by chenodeoxycholic acid. However, it was noted that RF rats had consistently taller villi and deeper crypts in all the samples studied. The protein content and the ratio of DNA to protein was similar among the three groups. The mechanism of the increase in villus height and crypt depth in the RF rats was not related to increases in tissue water content or to alterations in protein or DNA content, and the mechanism thus remains unexplained. This study clearly demonstrates, however, that the intestinal mucosa of rats with chronic renal insufficiency is not more susceptible to mucosal injury by bile acids than is the mucosa of appropriate control animals.
    Journal of Laboratory and Clinical Medicine 06/1990; 115(5):572-8. · 2.62 Impact Factor
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    ABSTRACT: We studied intestinal absorption of vitamin E in rats with experimental renal failure (RF) and in sham-operated normal and pair-fed controls using in vivo perfusion and in vitro everted sacs. The in vivo absorption rates per unit of intestine length were significantly reduced in RF and pair-fed groups. Expression of data per unit of intestine weight gave normal values in the pair-fed but depressed values in the RF animals. Vitamin E uptake in vitro was significantly increased in RF animals, suggesting enhanced permeability. We conclude: (i) vitamin E absorption in vivo is impaired in experimental RF; (ii) this is in part due to reduced nutrient intake; and (iii) disparity between in vivo and in vitro results suggests the presence of some inhibitory influence(s) in intact animals with RF.
    Proceedings of The Society for Experimental Biology and Medicine 03/1990; 193(2):125-8.

Publication Stats

342 Citations
117.60 Total Impact Points

Institutions

  • 1988–2010
    • University of California, Irvine
      • • Department of Medicine
      • • Division of Nephrology and Hypertension
      Irvine, CA, United States
  • 2006–2007
    • Hallym University
      Sŏul, Seoul, South Korea
  • 2001
    • Colorado State University
      Fort Collins, Colorado, United States