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At least 163 records · Page 9Linked to original sources

PubMed1991

Hepatocellular uptake of peptides by bile acid transporters: relationship of carrier-mediated transport of linear peptides with renin-inhibiting activity to multispecific bile acid carriers.

The uptake of a linear peptide with renin-inhibiting activity (code number EMD 51921) was characterized in isolated rat liver cells. Isolated hepatocytes take up EMD 51921 in a time-, concentration-, energy- and temperature-dependent manner. Transport of the peptide follows mixed-type kinetics. Diffusion occurs at a rate of 8.123 x 10(-6) cm/sec at 6 degrees C. For the saturable part of uptake, a Km of 2.0 microM and a Vmax of 160 pmol/mg per min were calculated. Various substrate analogues inhibit the uptake of EMD 51921. Absence of oxygen or decreased cellular ATP content (e.g., by metabolic inhibitors or xylulose) blocks hepatocellular uptake of EMD 51921. Temperatures above 20 degrees C accelerate the uptake. The activation energy was calculated to be 58.3 kJ/mol. The apparently active uptake of EMD 51921 was not sodium dependent. The membrane potential is a driving force for the accumulation of EMD 51921. Mutual competitive transport inhibition of EMD 51921, cholate and taurocholate is indicative of a common transport system. Benzamidotaurocholate and a cyclosomatostatin analog 008, not phalloidin and iodipamide, however, considerably decrease the uptake of EMD 51921. AS 30D ascites hepatoma cells, unable to accumulate bile acids and certain cyclopeptides, also fail to transport EMD 51921. BSP, a foreign substrate of the bilirubin carrier, noncompetitively inhibits the transport of EMD 51921. The inhibition of the uptake of EMD 51921 by rifampicin, a further substrate of the bilirubin carrier, is mixed: competitive at high EMD 51921 concentrations and uncompetitive at low EMD 51921 concentrations. The uptake of rifampicin into isolated rat liver cells, however, is not influenced by EMD 51921. Substrates of the transport systems for cations, amino acids, long chain fatty acids and hexoses did not influence the transport of EMD 51921.

Animals↗

PubMed1991

Ultrasound properties of liver with and without particulate contrast agents.

Basic acoustic parameters are examined in rabbit liver with and without a solid contrast agent used for tumor detection. In normal liver, backscatter, attenuation, and sound speed are found to decrease with increasing water content. The addition of micron-sized particles made from iodipamide ethyl ester (IDE) can increase backscatter and attenuation depending on size and concentration. A discrepancy of the increased backscatter from theoretical predictions based on random scatterers is attributed to the particle's biodistribution in the liver.

Absorption↗

PubMedDate not supplied

Modification of chemical toxicity by selenium deficiency.

Selenium deficiency causes a number of hepatic metabolic alterations in the rat which could lead to changes in chemical toxicity. It causes a decrease in glutathione peroxidase activity, an increase in glutathione S-transferase activity, and an increase in the rate of glutathione synthesis. The hepatotoxicities of three compounds which bind to glutathione S-transferase; iodipamide, acetaminophen, and aflatoxin B1, are decreased by selenium deficiency. The toxicity of redox cycling compounds is generally increased by selenium deficiency and is accompanied by evidence of lipid peroxidation. Thus, nitrofurantoin (100 mg/kg) causes renal tubular necrosis in selenium-deficient rats but not in controls. Selenium-deficient rats are much more sensitive to diquat toxicity than are controls. Lethality of diquat in selenium-deficient rats appears to be causally linked to lipid peroxidation. Lethality of diquat in control rats is not linked to lipid peroxidation. The effect of selenium does not appear to be mediated by glutathione peroxidase, however, indicating that selenium has another oxidant defense function. Another interesting observation made was that increases in inspired O2 tension decreased ethane production (lipid peroxidation) in selenium-deficient and in control rats given diquat. Thus, O2 appears to prevent diquat-induced lipid peroxidation.

Acetaminophen↗

PubMed1995

Hepatic uptake of octreotide, a long-acting somatostatin analogue, via a bile acid transport system.

The hepatic transport mechanism of octreotide (Sandostatin), a somatostatin analogue, was studied using freshly prepared rat hepatocytes. The initial uptake rate of octreotide represented exclusively a saturable transport process. The half-saturation constant, Kt, and the maximum uptake-rate, Jmax, for the uptake of octreotide were 91.1 +/- 28.4 microM and 104.6 +/- 19.7 pmol/mg protein/min, respectively. An energy requirement was demonstrated for [14C]octreotide uptake since metabolic inhibitors (DNP, rotenone, antimycin and NaCN) significantly reduced the initial uptake rate. [14C]octreotide uptake was also significantly inhibited by ouabain. [14C]octreotide uptake was reduced in the absence of Na+ in the uptake medium. [14C]octreotide uptake was significantly inhibited by bile acids, iodipamide, d-tubocurarine, whereas it was not inhibited by bilirubin, TEMA and insulin. Competitive inhibition of taurocholic acid was observed for octreotide uptake with the inhibition constant, Ki, of 82 +/- 17 microM. Moreover, a significant inhibitory effect of octreotide was observed for the Na+ dependent uptake of [14C]taurocholic acid. These results suggest that octreotide is transported into hepatocytes via a bile acid carrier-mediated system.

Amino Acid Sequence↗

PubMed1985

Is 125I iothalamate an ideal marker for glomerular filtration?

The triiodinated angiographic contrast medium, iothalamate, has (usually labelled 125I) been used extensively as a marker for glomerular filtration. We have studied the renal handling of 125I iothalamate (IOT) in vivo and in vitro in several species. In renal cortical slices from chicken, rabbit, rat, and monkey, the tissue-to-medium ratio of IOT was twice that of 51Cr-EDTA (EDTA) at 37 degrees C; a difference that was abolished at 0 degree C and markedly reduced by added o-iodohippurate or iodipamide. In five chickens the steady-state renal clearance of IOT (CIOT) was twice (P less than 0.05) that of EDTA (CEDTA) or 3H inulin (C1); a difference that was abolished by administration of 100 mg/kg/hr of novobiocin, an organic anion transport inhibitor. CEDTA was similar to C1 before as well as after transport inhibition. Utilizing the Sperber technique the mean apparent tubular excretion fraction (ATEF) of IOT was 8%, while that of EDTA was 1% (P less than 0.01; N = 10). After novobiocin coinfusion (new steady-state) ATEFIOT was significantly reduced (P less than 0.01) and not different from that of EDTA (-1%). In the same animals the total urinary recovery of IOT was 84 and 57% (P less than 0.01) before and after novobiocin, respectively, while corresponding values for EDTA was unchanged by the inhibitor. In seven rats the renal extraction of IOT was reduced from 29 to 17% (P less than 0.05) by coinfusion of probenecid (5 mg/kg/hr). Corresponding extractions were 82 to 34% (P less than 0.005) and 22% (unchanged) for PAH and EDTA, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1977

Iodinated radiological contrast media as radiosensitizers.

This paper describes the radiosensitizing effects of diatrizoic (DA) and iothalamic (ITA) acids and of iodipamide (IP) on the survival of E coli B/r irradiated with X-rays and with high-intensity electron pulses. All compounds at concentrations between 10 and 50 mM display a strong sensitizing effect in the presence of oxygen (DMF between 0-1 and 0-3) and are much less effective in nitrogen. In N2O the degree of sensitization is intermediate between oxygen and nitrogen. The situation is the same at pH 7 or 5-6. Solutions of DA, ITA and IP irradiated at pH lower than 6 become highly toxic to bacteria added after irradiation, for several hours after X-irradiation or several minutes after pulsed irradiation. The maximum toxic effect occurs with 2 krad of X-ray and with 6-8 krad of electrons. Oxygen must be present in order to observe the bactericidal activity. This is not affected by scavenging hydrated electrons with nitrate, but is completely cancelled by scavenging OH radicals with formate. It is also cancelled by adding thiosulphate to the irradiated solutions immediately before the bacteria. In the presence of nutrient broth, the radiosensitizing effect is absent after irradiation with pulsed electrons; whereas after X-irradiation it is reduced when the concentration of sensitizers is 50 mM. The experimental data appear to be compatible with a mechanism operated by short and long-lived transients resulting from the radiolysis of iodinated contrast media.

Cell Survival↗

PubMedDate not supplied

Combined cholangiography and cholecystography using sodium iopanoate.

Cholangiography and cholecystography were performed in fasted dogs and human subjects using sodium iopanoate given intraduodenally in doses of 10 and 20 mg/kg. The same studies were performed after intraduodenal administration of fat or after intravenous administration of cholecystokinin (CCK) in dogs and after a fatty meal, to stimulate endogenous release of CCK, in human subjects. In both the animals and human subjects, peak blood iodine concentrations were reached by 30 minutes after iopanoate administration. At a dose of 10 mg/kg, radiographic visualization of both bile ducts and gallbladder was inconsistent. At 20 mg/kg (one-half the clinical dose for standard oral cholecystography,) the common bile duct was visualized within 60 minutes and the gallbladder within 90 minutes. Gallbladder density increased over the next 6 hours. Prior administration of fat or CCK led to earlier and denser gallbladder opacification. The common bile ducts opacified with the use of iopanoate were small in caliber, averaging only 3 mm. This probably reflects the fact that, unlike iodipamide, iopanoate has little or no choleretic effect. Therefore, because it would not increase the volume of bile in the duct, iopanoate would not increase duct size.

Adult↗

PubMedDate not supplied

Computed tomographic cholangiography in a canine model of biliary obstruction.

The CT scanner was used to generate the time-density relationship for hepatic parenchyma following Iodipamide (Cholografin, E.R. Squibb Co., New York, N.Y.) infusion. The curves which resulted from the normal, acutely obstructed, and chronically obstructed biliary system are shown. The peak enhancement of parenchyma is seen to be blunted in acute obstruction prior to anatomic evidence of dilated ducts. This finding may be of value in the early diagnosis of obstructive jaundice.

Absorptiometry, Photon↗

PubMedDate not supplied

Contrast media and pain in peripheral arteriography.

Pain caused by x-ray contrast media in peripheral arteriography was assessed by behavioral changes of nonanesthetized, unrestrained rats. All ionic monomeric contrast media caused severe pain in a concentration of 300 mg I/ml. Dilution of contrast media markedly reduced pain. Sodium salt solutions were considerably more painful than meglumine salt solutions. The intravenous cholegraphic agent iodipamide did not cause vascular pain in a concentration of 300 mg I/ml, although its systemic toxicity is high. Pain in arteriography was attributable primarily to the high osmotic pressure of contrast media solutions rather than to their chemotoxicity.

Angiography↗

PubMed2002

Multidetector computed tomographic cholangiography in the evaluation of potential living liver donors.

BACKGROUND: Lacking awareness of biliary variations causes complications in adult living donor liver transplantation. The study was performed to determine the diagnostic value of preoperative multidetector computed tomographic cholangiography (MDCT-CA). METHODS: MDCT-CA after the intravenous administration of meglumine iodipamide was performed in 12 potential liver donors. MDCT angiography was added to depict the topographic relationship between biliary and vascular structures. MDCT findings were correlated with intraoperative findings (n=7). RESULTS: MDCT-CA was diagnostic in all 12 patients. Nine patients revealed variants in biliary anatomy: drainage from liver segment four into right hepatic duct (n=4), additional segmental ducts draining into common (n=4) or left hepatic duct (n=2), and trifurcation at the upper confluence (n=1). Biliary vascular topography was variable and well depicted. Intraoperative assessment confirmed the preoperative findings. CONCLUSIONS: Variations in biliary anatomy appear to be the rule rather than the exception. MDCT-CA represents a noninvasive means for accurately assessing biliary morphology.

Adult↗

PubMed1980

The in vitro effect of levamisole on lymphocyte proliferation, polymorphonuclear leucocyte chemotaxis, basophil histamine release and platelet serotonin release in patients with atopic dermatitis.

The in vitro effect of levamisole (LMS) on lymphocyte, neutrophil, basophil and platelet function was investigated in patients with severe atopic dermatitis and hyperimmunoglobulinaemia E. Lymphocyte stimulation by several concentrations of PHA, con A and PWM, polymorphonuclear leukocyte chemotaxis and basophil histamine release were unaffected by LMS (10 micrograms/ml). Platelet serotonin release induced by iodipamide was decreased in patient and control groups by LMS but release induced by methacholine, epinephrine and thrombin was not.

Basophils↗

PubMed1993

Hepatic kinetics and magnetic resonance imaging of gadolinium ethoxybenzyl diethylenetriaminepentacetic acid (Gd-EOB-DTPA) in dogs.

This complex study was designed to measure the transport and excretion characteristics of gadolinium ethoxybenzyl diethylenetriaminepentacetic acid (Gd-EOB-DTPA) in dog's livers following bolus and infusion. Simultaneous T1 magnetic resonance imaging was performed to measure maximum signal enhancement. Anaesthetized dogs had cannulation of the common bile duct and urinary bladder for collections and cannulation of the femoral artery and vein for monitoring, blood sampling and infusion. Gd-EOB-DTPA was administered by bolus (range 12.5-200 mumol/kg) and infusion (range 0.4-6.4 mumol/min per kg). An hepatic transport maximum 0.09-0.15 mumol/min/kg was achieved with a blood concentration of 0.03-0.06 mumol/mL. Marked hepatic affinity for Gd-EOB-DTPA was demonstrated with measurements of liver concentration. Maximum T1 signal enhancement was achieved with blood Gd-EOB-DTPA concentration of 0.02-0.03 mumol/mL and a liver concentration of 1-2 mumol/g. The transport maximum for Gd-EOB-DTPA in the dog was similar to that for ipodate and iodipamide and effective imaging was achieved with sub-maximal doses. The maximum signal enhancement at blood concentrations less than required for maximum transport suggest a wide latitude for effective clinical imaging.

Animals↗

PubMed1998

Transformation of the ionic X-ray contrast agent diatrizoate and related triiodinated benzoates by Trametes versicolor.

Iodinated X-ray contrast agents are considered to be nondegradable by microorganisms. The decomposition of the ionic X-ray contrast agents Diatrizoate (3,5-di(acetamido)-2,4,6-triiodobenzoic acid) and Iodipamide (3,3'-adipoyl-diimino-di(2,4,6-triiodobenzoic acid) and related triiodinated benzoates (Acetrizoate [3-acetylamino-2,4, 6-triiodobenzoic acid] and Aminotrizoate [3-amino-2,4, 6-triiodobenzoic acid]) by Trametes versicolor has been investigated. The fungus was able to transform all tested triiodinated benzoates cometabolically. During transformation of these compounds, iodide was released, but deiodination was not complete. T. versicolor liberated traces of 14CO2 from uniformly ring-14C-labeled Diatrizoate (3,5-di(acetamido)-2,4,6-triiodobenzoate). Various extracellular metabolites were detected during transformation of the different substances. In the transformation of Diatrizoate, the three main metabolites were identified as 3,5-di(acetamido)-2, 6-diiodobenzoic acid, 3,5-di(acetamido)-2,4-diiodobenzoic acid, and 3,5-di(acetamido)-2-iodobenzoic acid, suggesting reductive deiodinations in steps as initial transformation steps.

Benzoates↗

PubMed1976

The biliary and urinary excretion of iopanoic acid: pharmacokinetics, influence of bile salts, and choleretic effect. An experimental study in bile-fistula dogs.

The biliary and urinary excretion and the choleretic effect of iopanoic acid (Telepaque) were studied in nonanesthetized bile-fistula dogs using a stepwise increase of infusion rates of iopanoic acid and a constant infusion of sodium taurocholate at a rate of either 0.5 or 2.0 mumoles/min./kg. The maximum rate of bile excretion (0.671 mumoles/min./kg) when taurocholate was infused at the lower rate nearly doubled (1.325 mumoles/min./kg) when given at the higher rate. Maximum biliary concentrations of iopanoic acid at both rates of taurocholate infusion (70-77 mumoles/ml) were almost double the maximum concentration previously determined for iodipamide (Cholografin) (42 mumoles/ml).

Animals↗

PubMed2004

Biliary tract depiction in living potential liver donors: comparison of conventional MR, mangafodipir trisodium-enhanced excretory MR, and multi-detector row CT cholangiography--initial experience.

PURPOSE: To compare biliary tract depiction in living potential liver donors at conventional magnetic resonance (MR), mangafodipir trisodium-enhanced excretory MR, and multi-detector row computed tomographic (CT) cholangiography. MATERIALS AND METHODS: Eight living potential liver donors underwent iodipamide meglumine-enhanced CT cholangiography. Eight different potential liver donors then underwent conventional MR cholangiography and mangafodipir trisodium-enhanced excretory MR cholangiography. Two readers independently scored all first-, second-, and third-order biliary branches with a four-point scale from 0 (not seen) to 3 (excellent visualization). Interobserver agreement was calculated by using the weighted kappa statistic. Scores were compared between imaging modalities by using generalized estimating equations. Imaging findings of second-order biliary tract anatomy were compared with intraoperative findings for nine patients. RESULTS: Interobserver agreement for overall biliary tract visualization was good for CT, conventional MR, and excretory MR cholangiography (with weighted kappa values of 0.76, 0.66, and 0.79, respectively). The mean second-order biliary branch visualization scores for readers 1 and 2, respectively, were significantly higher at CT cholangiography (2.81 and 2.75) than at conventional MR (1.84 and 1.75, P <.001), excretory MR (2.00 and 2.06, P <.001), and combined conventional and excretory MR cholangiography (2.31 and 2.25, P <.01). At CT, conventional MR, and excretory MR cholangiography, respectively, second-order biliary branching anatomy was discernible in eight, five, and seven patients, with second-order biliary branch variants seen in three, two, and two patients. Surgical findings confirmed the pattern of second-order biliary branching seen at CT in five patients, that seen at conventional MR imaging in one patient, and that seen at excretory MR cholangiography in three patients. At surgery, one case of variant biliary anatomy was found to have been missed at CT cholangiography. CONCLUSION: In living potential liver donors, CT cholangiography enables significantly better biliary tract visualization than conventional or excretory MR cholangiography either alone or in combination.

Adolescent↗

PubMed1989

Dacryocystography: comparison of water-soluble and oil-based contrast agents.

Dacryocystography has been widely used in the assessment of the nasolacrimal duct system, particularly in patients with epiphora. Our study was undertaken to evaluate image quality and level of patient discomfort during examinations with water-soluble contrast agents (iohexol [Omnipaque 240], iopamidol [Isovue 200 and 300], and 52.7% diatrizoate meglumine and 26.9% iodipamide meglumine [Sinografin]) compared with the iodized oil-based contrast agent Lipiodol. Fifty-five dacryocystograms were obtained from 41 consecutive patients. The procedure was performed first with a water-soluble contrast agent, then repeated with Lipiodol. A distention technique was used with conventional radiography. Patients were asked to evaluate their level of discomfort (none, mild, moderate, severe). The images were evaluated separately by two radiologists, blinded to which water-soluble agent was employed, and the images were graded on a five-point scale. Images obtained with Lipiodol were significantly better than those with other agents (P less than .02), and image quality deteriorated as iodine concentration decreased. Use of Isovue 300 and Sinografin produced significantly more patient discomfort (P less than .03) than the use of other agents. The authors conclude that, in most instances, Lipiodol is the contrast agent of choice with regard to both highest level of patient comfort and greatest conventional radiographic image quality among the agents compared.

Contrast Media↗

PubMed1989

Uptake of bumetanide into isolated rat hepatocytes and primary liver cell cultures.

Uptake of bumetanide into rat liver cells was investigated using isolated hepatocytes and primary cell cultures. The kinetics of [3H]-bumetanide uptake revealed two saturable components in addition to an unsaturable component. Saturable bumetanide uptake consists of a high-affinity, sodium-dependent uptake and a low-affinity transport system. Bumetanide uptake into isolated rat hepatocytes is energy dependent and temperature sensitive. At low temperatures, bumetanide uptake is due to diffusion with a permeability coefficient of 1.16 x 10(-6) cm/s. In primary liver cell cultures, uptake of bumetanide decreases rapidly over 3 days. AS-30D ascites hepatoma cells do not take up bumetanide but bind small amounts of the loop diuretic. Hepatocytes metabolized bumetanide extensively. The metabolites were secreted into the surrounding incubation buffer. Two hydroxylated and at least one conjugated biotransformation product could be separated by thin-layer chromatography. Isolated rat hepatocytes possess carrier proteins for uptake of bumetanide and very likely also for uptake of other loop diuretics like furosemide, piretanide, and torasemide. Several inhibitors of multispecific transport systems in the kidney and liver were tested as potential inhibitors of hepatocellular bumetanide or furosemide uptake. Probenecid, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, iodipamide, digitoxin, bile acids, and bromosulfophthalein inhibited uptake of loop diuretics. Inhibition by taurocholic acid was competitive with a Ki of 24 microM. Taurocholic acid inhibited [3H]bumetanide uptake in the presence but not in the absence of Na+. Deoxycholic acid and bromosulfophthalein were noncompetitive inhibitors of hepatocellular bumetanide uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Affinity Labels↗

PubMed1979

In vitro histamine and serotonin release studies in atopic dermatitis.

6 patients suffering from severe atopic dermatitis with high serum IgE were investigated. 3 of the patients had elevated plasma histamine levels (1.5-2.0 ng/ml). Compared to 9 nonatopic normal volunteers, the patient showed increased in vitro histamine release from peripheral leukocytes after stimulation with iothalamate and methacholine: while there was no significant histamine release at a methacholine concentration of 10(-4) M in normals, 4 of the patients with atopic dermatitis showed measurable histamine release under these conditions in vitro. The uptake of radiolabeled serotonin by platelets in vitro was decreased in 2 of the patients. There was no significant difference in serotonin release induced in vitro by different concentrations of thrombin, epinephrine and methacholine; 2 patients showed an increased platelet release reaction after iodipamide stimulation. It is concluded that a general tendency to release vasoactive mediators, even after 'nonimmunologic' stimulation, might play a role in the pathogenesis of atopic dermatitis.

Adult↗