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T Y Ma

Publications and source records attributed to T Y Ma.

36 records · Page 2Linked to original sources
PubMed1994

Mechanisms and sites of mannitol permeability of small and large intestine in the rat.

Mannitol is commonly used as an intestinal permeability probe, yet the mechanisms of its penetration of the intestinal barrier are not entirely clear. Therefore, we studied mannitol's permeability of different segments of the intestine and studied the kinetics and influence of intraluminal factors on mannitol permeability in vivo in perfused intestinal segments of rats. There was linear relationship between permeability rate of mannitol and its luminal concentration (y = 7.2x + 1.7; r = 0.98), indicating that passive diffusion is involved in mannitol's permeability. Increased luminal fluid osmolarity from 0.3 to 0.6 osmol/liter resulted in decreased net water flux with a corresponding decrease in mannitol permeability in both jejunum and colon (P < 0.01), indicating the prominent influence of solvent drag on net mannitol permeability. The relationship between mannitol permeability and water absorption at different osmolarities was linear in the jejunum and colon. At luminal osmolarity of 0.3 osmol/liter, 34.6% of mannitol permeability was mediated by passive diffusion and 65.4% was mediated by solvent drag in the jejunum. Mannitol permeability was much more dependent on solvent drag in the colon (88.9%) than in the small intestine (65.4%). The net permeability rate of mannitol was similar in the jejunum and ileum but was much higher in the colon (P < 0.01). Addition of chenodeoxycholate (5 mM) to the perfusate resulted in a significant decrease in absorption of water (P < 0.01) with a corresponding decrease in mannitol permeability (P < 0.01). These studies indicate that mannitol permeability of the intestinal barrier is mediated by passive diffusion and solvent drag, with the latter accounting for a greater fraction of the total permeability.

Animals↗
PubMed1994

The utero-placental circulation, eugenics and the prevention and treatment of high risk pregnancies.

Through systematic experimental and clinical studies, the physiological regulation of utero-placental circulation and the relation of the disturbance in this acirculation to pathogenic mechanisms of high risk pregnancies-Intrauterine Growth Retardation (IUGR) and Pregnancy-induced hypertension (PIH) were explored. The pharmacological effects and mechanism of a Chinese herbal medicine-Qingxintong in improving, the utero-placental circulation and the therapeutic efficacy in treatment of IUGR and PIH, both accompanied by disturbance of utero-placental circulation, were investigated as well.

Acetophenones↗
PubMed1994

Mechanism of riboflavine uptake by Caco-2 human intestinal epithelial cells.

The cellular and molecular regulation of intestinal absorption of the water-soluble vitamin riboflavine (RF) is poorly understood. The availability of a suitable in vitro cultured system that possesses the transport characteristics of the native intestinal absorptive cells would provide a powerful means to address this issue. In this study, we examined RF uptake by the human-derived cultured Caco-2 intestinal epithelial cells. RF uptake was Na+ and pH independent and occurred without metabolic alterations of the transported RF. Initial rate of RF uptake was temperature dependent and saturable as a function of concentration at 37 degrees C but not at 4 degrees C (apparent Michaelis constant = 0.30 +/- 0.03 microM, maximal velocity = 209.90 +/- 24.40 pmol.mg protein-1.3 min-1). Unlabeled RF, lumiflavine, 8-amino-riboflavine, isoriboflavine, and lumichrome in the incubation solution caused significant inhibition of RF uptake. RF uptake was also energy dependent and was sensitive to the inhibitory effect of sulfhydryl group reagents. The membrane transport inhibitor amiloride, but not 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, 4-acetamide-4'-isothiocyanostilbene-2,2'-disulfonic acid, furosemide, or probenecid, inhibited RF uptake in a competitive (inhibitory constant = 0.48 mM) and reversible manner. Growing Caco-2 monolayers in a RF-deficient and oversupplemented media caused significant up- and downregulation of RF uptake, respectively. These results demonstrate the existence of a carrier-mediated system for RF uptake by Caco-2 cells and provide new information regarding amiloride sensitivity, involvement of sulfhydryl groups, and up- and downregulation by the substrate level and clarify the controversy regarding the role of Na+ in the uptake process.(ABSTRACT TRUNCATED AT 250 WORDS)

2,4-Dinitrophenol↗
PubMed1994

Regulation of riboflavin intestinal uptake by protein kinase A: studies with Caco-2 cells.

Although the mechanism of riboflavin (RF) intestinal uptake has been the subject of many studies, virtually nothing is known about the cellular regulation of the uptake process. In the present study, we investigated the role of protein kinase A (PKA)- and C (PKC)-mediated pathways in the regulation of RF intestinal uptake using the confluent Caco-2 monolayers. Treatment of Caco-2 cells with 3-isobutyl-1-methylxanthine (IBMX), forskolin, cholera toxin, or dibutyryl adenosine 3',5'-cyclic monophosphate caused a significant inhibition in RF uptake. The inhibitory effect of IBMX was reversible and resulted from a significant decrease in the maximal velocity of the RF uptake process with no change in its apparent Michaelis constant. The IBMX-induced inhibition in RF uptake was not mediated via inhibition in the synthesis of the RF carrier protein or through inhibition in the recruitment of preexisting carrier protein into the plasma membrane. Calyculin A also inhibited RF uptake when added alone and further potentiated the inhibitory effect of IBMX when added together. Phorbol 12-myristate 13-acetate or chelerythrine, on the other hand, showed no significant effect on RF uptake. These results demonstrate for the first time that compounds that increase intracellular cAMP levels downregulate RF intestinal uptake and that this effect is mediated via a decrease in the activity of the RF uptake carrier. It is suggested that a PKA-mediated pathway(s) plays an important role in regulating RF intestinal uptake.

1-Methyl-3-isobutylxanthine↗
PubMed1993

A clinical study of cytomegalovirus infections during pregnancy.

Enzyme-linked Immunosorbent Assay (ELISA) was adopted to detect the human cytomegalovirus (HCMV) specific IgG, IgM in the blood samples of 216 pregnant women and the umbilical cord blood, as well as the HCMV antigen in the urine specimens of 91 newborn infants. Emphasis was put on the occurrence of cytomegalovirus infection during pregnancy and influence on both the mother and the infant. Our experimental results showed that HCMV IgG positive rate in the maternal sera as well as in cord sera was 93.98%; HCMV IgM positive rates were 8.8% in maternal sera and 3.7% in cord sera, respectively. In maternal sera IgG-positive group, 31.6% cord sera showed also HCMV IgG positive results. In 91 urine specimens of newborn infants, HCMV-Ag positive specimens accounted for 10.98% (10 cases). The rates of abortion, congenital malformation, stillbirth, premature fetal death, and intrauterine growth retardation (IUGR) were all apparently higher in the HCMV-IgM positive pregnant group than in the HCMV-IgM negative group. The infants of HCMV-IgM positive mothers also showed lower birth weight, height, biparietal diameter, suboccipitobregmatic diameter, occipitofronatal diameter, occipito-mental diameter than the infants of HCMV-IgM negative mothers. Meanwhile, the growth and development indices of the former showed a tendency to decrease. Placenta histological examination showed that HCMV-IgM positive group had a higher incidence of pathological changes than HCMV-IgM negative group. Altogether, there were 8 cases of congenital infections.

Adult↗
PubMed1993

Autoradiographic determination of permeation pathway of permeability probes across intestinal and tracheal epithelia.

Mucosal permeability studies are used to assess intestinal and respiratory barrier functions. Our ability to interpret results of permeability studies are hampered by our lack of understanding of absorptive pathways of permeability markers. The aim of this study was to visually trace the pathway of permeability probes across the small intestinal and tracheal epithelia by using electron microscopic autoradiography and cytochemistry. We saw a constant rate of mucosal to serosal permeation of intestinal permeability probes polyethylene glycol 400 (PEG-400) and mannitol across the everted small intestinal sac and of the pulmonary permeability probe bovine serum albumin (BSA) across the tracheal epithelia. Electron microscopic tracing of the permeation pathways of tritiated PEG-400 and tritiated mannitol revealed that the majority of the probes traversed the intestinal epithelium paracellularly within 1 half distance (1650 A) of the intercellular space. It is interesting that we also found a small but significant transcellular transport of permeability probes. Goblet cells also absorbed permeability probes transcellularly, but in an "all or none" fashion. Similar pathways were identified in studies utilizing the commonly used pulmonary permeability probes iodine 125-labeled BSA and horseradish peroxidase to determine the routes of transfer in the airway epithelia. In the normal unperturbed trachea, these large permeability probes traversed the pulmonary epithelia transcellularly via endocytosis. On barrier disruption by cytochalasin D, the probes permeated predominantly via the paracellular pathway. This study also demonstrates some of the similarities and differences in transmucosal pathways shared by intestinal and pulmonary epithelia.

Animals↗
PubMed1993

[Effect of 3,4-dihydroxyacetophenone treatment on intrauterine growth retardation].

In this paper, the results of a pilot study of 3,4-dihydroxyacetophenone (DHAP) treatment for intrauterine growth retardation (IUGR) were reported. 20 out of 38 cases of IUGR were treated with DHAP and 18 with amino acid. Additionally, 170 normal pregnant women were served as control group. The following parameters have been observed and measured including uterine fundal height (UFH), body weight (BW), S/D ratio of umbilical artery (UmA), hemorheological indices, platelets aggregation, TXB2/6-keto-PGF1 alpha ratio and also fetal and neonatal various growth indices etc. After administration of DHAP, all the parameters almost restored to the normal range. The results expressed that the therapeutic effect of DHAP was much better than that of amino acid. It has also been verified by neonatal birth weight and fetal biparietal diameter. The clinical effective rate of DHAP treatment group was 90.00% which was significantly higher than that 74.00%, 79.00% of amino-acid treatment group. Meanwhile, the mechanism of DHAP has preliminarily been discussed.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Effect of aging and caloric restriction on intestinal permeability.

Intestinal permeability is increased in several disorders such as Crohn's disease or rheumatoid arthritis. Since aging leads to alteration of many biological functions, the effect of aging on intestinal permeability was studied by measuring the intestinal permeability in aging rats gavaged with different size permeability probes--mannitol, polyethylene glycol (PEG) 400, and inulin. In rats fed with control diet, there was a significant increase in intestinal permeability to medium size probes PEG 400 (14.8 +/- 0.4 and 21.0 +/- 1.1% at 3 and 28 months respectively, p less than .01) and mannitol (3.41 +/- 0.4 and 5.3 +/- 0.5% at 3 and 28 months, respectively, p less than .01). Intestinal permeability of the large macromolecule inulin did not change (0.42 +/- 0.03 and 0.38 +/- 0.02% at 3 and 28 months, respectively) with aging. There was no correlation between weight of the rats and their intestinal permeability. Because dietary caloric restriction has been found to prolong the life span, retard deterioration of several biological functions, and affect intestinal absorptive functions, we examined the effect of lifelong calorie restriction on intestinal permeability changes. Lifelong calorie-restricted diet did not affect age-related change in intestinal permeability. We conclude that intestinal permeability of medium size probes increases with aging and that lifelong caloric restriction does not prevent this change. We speculate that age-associated deterioration in intestinal barrier functions could permit increased systemic absorption of lumenal antigens and could perhaps contribute to the genesis of antigen-related age-associated diseases.

Aging↗
PubMed1992

IEC-18, a nontransformed small intestinal cell line for studying epithelial permeability.

Small intestinal epithelium is leaky and allows permeation of hydrophilic molecules of various sizes. Passively absorbed hydrophilic permeability probes have been shown to permeate across intestinal epithelium mainly through the paracellular pathways. In this study we introduce microporous filter-grown IEC-18 epithelial cells, a nontransformed small intestinal cell line, as a in vitro model of intestinal epithelium for the study of epithelial permeability. IEC-18 cells, originally derived from native rat ileal crypts, form confluent epithelium when grown on hydrated collagen-coated Millicell-CM permeable inserts (Millipore Corp., Bedford, Mass.). With scanning and transmission electron microscopy, the presence of tight junctions and desmosomes between cells and the development of microvilli at the apical surface were confirmed. Immunofluorescent labeling of ZO-1 proteins and desmoplakins verified the presence of tight-junctional proteins (ZO-1) and desmosomes in the intercellular junctions of confluent IEC-18 epithelium. The net electrical resistance of IEC-18 epithelium (28 omega-cm2) was similar to resistance values obtained from small intestinal tissue with (50 to 100 omega-cm2) or without (20 to 45 omega-cm2) muscularis and serosal layers. Assessment of mannitol and dextran permeation revealed early "maturation" of paracellular pathway, with increasing restriction of permeation to both probes through day 4. Resistance across IEC-18 epithelium also reached plateau levels between 4 and 7 days. Permeability studies with various probes indicate that cross-sectional diameter rather than molecular weight of the probe is the important determinant of permeation rate. IEC-18 epithelium selectively restricted the permeation of probes proportional to probe size; permeation of larger probes such as albumin was negligible. We conclude that cultured IEC-18 epithelial cells, because of their native crypt origin, similarity in resistance to small intestinal epithelia, retention of ability to differentiate into villus-like enterocytes, and permeability characteristics, are a useful model of intestinal epithelium for the study of permeability and paracellular transport.

Animals↗
PubMed1991

Oxygen free radical injury of IEC-18 small intestinal epithelial cell monolayers.

Oxygen radicals can cause endothelial and epithelial permeability changes and mucosal injury of the small intestine. There is no clear consensus concerning the relative injurious potential of individual oxygen radicals. In this study, the small intestinal cell line IEC-18 was used as an in vitro model to study the relative injurious effects of reactive oxygen metabolites. By introducing different combinations of oxygen metabolite-producing enzymes, xanthine oxidase, superoxide dismutase, and catalase, and an iron chelator, deferoxamine, to the fully confluent monolayers and to proliferating IEC-18 cells, the differential injurious effects of the oxygen metabolites O2-, H2O2, and OH. could be evaluated. The extent of cellular injury was assessed using [3H]thymidine uptake, 51Cr release, and morphological evaluations. Our results suggest that OH. produced as a by-product of O2- and H2O2 via the Haber-Weiss reaction was the most injurious oxygen species involved in cellular injury of IEC-18 monolayers induced by xanthine oxidase. O2- produced by xanthine oxidase appeared to be only minimally injurious, and H2O2 produced by xanthine oxidase and as a result of conversion of O2- by superoxide dismutase was moderately injurious. Superoxide dismutase and deferoxamine at appropriate concentrations were protective against xanthine/xanthine oxidase-induced monolayer injury. H2O2 added directly or produced indirectly by glucose oxidase was very injurious to the intestinal monolayers, and this injury was mitigated by catalase.

Animals↗
PubMed1991

Is the small intestinal epithelium truly "tight" to inulin permeation?

In this study, we evaluated the "leakiness" of intestinal epithelium through examination of small intestinal absorption of inulin in vivo by perfusing rat jejunum with 10 microM inulin. In physiological conditions, we found significant absorption of inulin at a rate of 44.6 nmol.100 cm-1.h-1 or absorption of 14.7%.100 cm-1.h-1 of the amount perfused. Increasing water flux by changing the luminal osmolarity resulted in linear (y = 31.1 + 2.4x, r = 0.97) increase in absorption of inulin, indicating a significant convective component of inulin absorption. There was large permeation of inulin at net water secretion and at zero net water fluxes (31.1 nmol.100 cm-1.h-1), indicating significant absorption of inulin by diffusive movement as well. The small intestinal tissue retention of inulin occurred rapidly within the first 15 min of perfusion, and the total tissue retention remained unchanged thereafter at approximately 10.8 nmol/100 cm. 16,16-Dimethylprostaglandin E2 decreased water flux, whereas cyclooxygenase inhibitors, indomethacin and acetylsalicylate, increased water flux. Inulin absorption closely paralleled changes in water flux induced by these agents. Taurocholate also caused parallel decrease in water and inulin absorption. Varying the resistance of unstirred water layer with changing luminal flow rate, the addition of mucolytic agent acetylcysteine, or alterations of luminal pH did not affect water or inulin absorption. We conclude that inulin permeates the small intestinal epithelium in significant amounts under normal physiological conditions, presumably through the paracellular pathways utilizing aqueous channels.

16,16-Dimethylprostaglandin E2↗
PubMed1990

Polyethylene glycol 400 penetration of the colonic epithelial barrier of the rat.

Permeability changes of polyethylene glycol 400 have been seen in patients with inflammatory bowel diseases. Because the colon can be involved in inflammatory bowel disease, the mechanisms, kinetics, and influence of intraluminal factors on polyethylene glycol 400 permeation of perfused colonic segments of rats were studied. The absorption rate of polyethylene glycol 400 was linearly related to its luminal concentration (r = 0.94), suggesting that passive diffusion is a significant mechanism involved in polyethylene glycol 400 absorption. Changing the perfusate pH from 6.0 to 7.5 did not affect water absorption or polyethylene glycol 400 permeation. Increasing luminal osmolarity significantly decreased water and polyethylene glycol 400 absorption (P less than 0.01). The relationship between polyethylene glycol 400 and water absorption at different luminal osmolarities was linear (r = 0.97). At luminal osmolarity of 0.3 osm/L, 14.3% of polyethylene glycol 400 absorption was mediated by passive diffusion and 85.7% was mediated by convection. The solvent drag reflection coefficient for polyethylene glycol 400 in the colon was 0.03. Taurocholic acid (10 mmol/L) and chenodeoxycholic acid (5 mmol/L) decreased polyethylene glycol 400 and water absorption (P less than 0.01). Addition of 1 micrograms/mL of 16,16-dimethyl prostaglandin E2, 2 mmol/L of dibutyryladenosine-3',5'-cyclic monophosphate, or 10 mmol/L of aminophylline significantly decreased water and polyethylene glycol 400 absorption (P less than 0.01). These studies demonstrate that polyethylene glycol 400 permeation of the colon is mediated by both passive diffusion and solvent drag. Convective absorption is the major mechanism of polyethylene glycol 400 permeation of the colon. Polyethylene glycol 400 permeation is modified by bile acids, prostaglandins, and cyclic nucleotides through changes in water flux.

16,16-Dimethylprostaglandin E2↗
PubMed1990

PEG 400, a hydrophilic molecular probe for measuring intestinal permeability.

There is a widely held misconception that low-molecular-weight polyethylene glycols are "highly lipophilic" permeability probes and therefore are transported across lipid cell membranes. The relative lipophilicity of polyethylene glycols 400 and 600 were examined by determining their partition coefficients (Kd) in water and organic solvents of increasing relative polarity. The Kd of polyethylene glycol 414 between hexane and water was 0.000015, indicating that there are only 1.5 parts of polyethylene glycol 414 in hexane for 100,000 parts of polyethylene glycol 414 in water. When the Kd was determined in organic solvents with increasing relative polarity or "water character", there was a linear increase in Kd. The relative urinary recovery of individual molecular weight fractions of polyethylene glycol 400 in normal volunteers was analyzed. After oral ingestion, there was a progressive decrease in relative urinary recovery of increasing molecular weight fractions of polyethylene glycol 400 suggesting that increase in the molecular size limited polyethylene glycol intestinal permeability. There was excellent correlation between the relative urinary recovery and the hydrophilicity of the intravenously administered polyethylene glycol 400 fractions. It is concluded that polyethylene glycols 400 and 600 are strongly hydrophilic. Since partitioning of polyethylene glycol into lipid phase is negligible in lipid/water mixtures, they are unlikely to be transported via lipid pathways. The intestinal permeability of polyethylene glycols are governed by their molecular size, and once in circulation their urinary excretion appears to be governed in part by their plasma or water solubility.

Adult↗
PubMed1989

Mechanisms of polyethylene glycol 400 permeability of perfused rat intestine.

Abnormal permeability to polyethylene glycol 400 (PEG 400) has been demonstrated in various disorders with defective intestinal barrier functions. To understand the basic mechanisms of PEG 400 permeability, we compared PEG 400 permeation in different segments of the intestine and studied the kinetics and influence of intraluminal factors on PEG 400 absorption in vivo in perfused intestinal segments of the rat. The permeation rate of PEG 400 was dependent on the luminal concentration (y = 12.99x + 3.5; r = 0.97), indicating that passive movement is the mechanism involved in PEG 400 absorption. Changing the perfusate pH from 6 to 7.4 or modifying the unstirred water layer resistance by changing luminal flow rate did not affect PEG 400 absorption. When luminal osmolarity was varied from 0.225 to 0.6 osmol/L, higher osmolarity decreased both water and PEG 400 absorption (p greater than 0.01). The relationship between PEG 400 and water absorption at different osmolarities was linear (y = 0.9x + 5.7; r = 0.98). At a luminal osmolarity of 0.3 osmol/L 43% of PEG 400 permeation was mediated by passive diffusion and 57% was mediated by solvent drag. Increasing water absorption by decreasing luminal osmolarity resulted in proportional increase of PEG 400 permeation through solvent drag or convection. The solvent drag reflection coefficient (sigma f) for PEG 400 permeation of the jejunum was 0.1. Taurocholic acid (10 mM) alone or with oleic acid (2.5 mM) did not affect PEG 400 absorption. Permeabilities of 1 mM PEG 400 and water were similar in jejunum and ileum but were markedly increased in the colon (p greater than 0.01). These studies demonstrate that PEG 400 is absorbed by both passive diffusion and by solvent drag, with the latter accounting for a greater fraction of the absorptive drive under normal conditions. Polyethylene glycol 400 uses aqueous pathways for its permeation across the intestinal epithelium.

Animals↗
PubMedDate not supplied

Role of protein kinase a pathway in epidermal growth factor-induced liver cell repair.

To gain a better understanding of the mechanisms that control the repair process in the injured liver, the actions of epidermal growth factor (EGF) and protein kinase A (PKA) were studied. Normal rat liver cells (clone 9) were grown to confluence. Standardized excisional wounds were made with a razor blade. The extent of hepatocyte migration into the wound was measured and determined at specific time intervals using a computerized digital analyzing system. Immunostaining of F-actin was performed with a fluorescein-labeled phalloidin. EGF significantly stimulated liver cell migration, whereas specific EGF-neutralizing antibody inhibited the EGF-induced migration. Agents that activate PKA at different stages of the PKA activation pathway, including 3-isobutyl-1-methylxanthine (IBMX), forskolin, and cholera toxin, inhibited EGF-induced migration. EGF triggered formation of actin stress fibers. PKA-activating agents inhibited actin stress fiber formation and stretching of cells at the wound margin. The following conclusions were drawn: (1) In excisional wounds of hepatocyte monolayers, both EGF and PKA exert action on actin microfilaments, which are stretched by EGF and inhibited by PKA; (2) the enhanced repair of wounded hepatocyte monolayers by EGF is blocked by activation of the PKA pathway at various levels; and (3) these actions of EGF and PKA indicate their important regulatory roles in controlling the rate of hepatocyte migration and restitution following the creation of excisional wounds.

Animals↗