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PubMed1991

Bilirubin accumulation by the rabbit choroid plexus in vitro.

The postnatal development of bilirubin accumulation by the choroid plexus was studied in vitro. Choroid plexus of the fourth and lateral cerebral ventricles from adult or 1-, 7-, 15- or 21-day-old rabbits were incubated in a potassium-rich medium with 70 nmol/l of 3H-bilirubin for 5 min. The tissue/medium (T/M) ratio for 3H-bilirubin was considerable even 1 day post partum and increased during the next 2-3 weeks of life. In adults the 3H-bilirubin T/M ratio returned to the level of 1-day-old rabbits. The biliary excreted contrast agent iodipamide, added as a transport inhibitor, reduced the 3H-bilirubin T/M ratio in the choroid plexus, but to a relatively lesser extent in the 1-day-old rabbits than in the older ones.

Aging↗
PubMed1979

Roentgenographic contrast agents inhibit triiodothyronine binding to nuclear receptors in vitro.

The ability of roentgenographic contrast agents to inhibit binding of [125I]T3 to nuclear receptors was studied during incubation of rat liver nuclei or nuclear extracts in vitro and after ip administration of the agents in vivo. Ipodate, iodipamide, iopanoic acid, and diatrizoate inhibited binding of [125I]T3 in vitro. The most potent inhibitor was ipodate, which produced 50% inhibition of binding at 1.2 X 10(-4) M. When given orally in acute in vivo experiments, ipodate did not diminish binding to liver nuclear receptors. Ipodate appeared to inhibit in vivo metabolism of [125I]T3.

Animals↗
PubMed1985

The effects of radiographic contrast agents and other compounds on the nuclear binding of L-[125I]triiodothyronine in dispersed human skin fibroblasts.

Using a dispersed intact cell assay system, we screened a number of compounds for their ability to compete for nuclear binding of L-[125I]T3 in cultured human skin fibroblasts incubated for 90 min at 37 degrees C. T3 inhibited nuclear [125I]T3 binding by 50% at a concentration of 3.4 +/- 0.3 (+/- SE) X 10(-10) M. 3,5-Dimethyl-3'-isopropyl-thyronine, a nonhalogenated thyroid hormone agonist, had an affinity for the nuclear thyroid hormone receptor (4.4 X 10(-9) M, as judged by 50% inhibition of nuclear [125I]T3 binding) that correlates well with its thyromimetic potency. Of several radiographic contrast agents and other compounds tested (iodipamide, iopanoic acid, sodium ipodate, sodium diatrizoate, sodium tyropanoate, diphenylhydantoin, carbamazepine, amiodarone hydrochloride, propylthiouracil, propranolol, and potassium iodide), only sodium ipodate (Oragrafin) and iopanoic acid (Telepaque) interfered with nuclear [125I]T3 binding, with 50% inhibition at 5 X 10(-5) and 1.8 X 10(-4) M, respectively. Interestingly, diphenylhydantoin and amiodarone, two compounds previously thought to interact with thyroid hormone receptors, did not impair fibroblast nuclear [125I]T3 binding at concentrations up to 10(-3) M. We conclude that this in vitro assay system with intact human cells is useful in evaluating the nuclear T3 receptor affinity of compounds that affect thyroid hormone action or metabolism. These studies more closely approximate in vivo conditions and, therefore, provide information not obtainable by studies with isolated nuclei or nuclear extracts.

Binding, Competitive↗
PubMed1975

Prolonged drip-infusion cholangiography.

Previous experimenttal work in animals has shown that the hpatic excretion of iodipamide and ioglycamide is subject to a transport maximum (TM). Doses in excess of this TM are largely excreted in the urine. In the present study the TM for man was estimated in three subjects with indwelling T-tubes: figures of 19-23 mg/minute for ioglycamide were obtained. It was thought that prolonged administration of contrast at levels slightly above the TM might have advantages in patients with impaired liver function. In obstruction the gradual excretion of contrast could improve the chances of filling the ducts completely, while in hepato-cellular disease the gall bladder might have time to concentrate the contrast. Ioglycamide was therefore given by slow overnight infusion, equivalent to 35 mg/minute, to patients in whom standard cholangiography had been unsuccessful. The overall success rate was 75 per cent with similar improvement in obstructive and hepatocellular disease.

Adult↗
PubMed1977

The concentration maximum concept in intravenous cholangiography.

The excretion of ioglycamate in the bile of the rhesus monkey was measured at 5% and at 100% bile diversion following an intravenous bolus injection of ioglycamate. At 100% diversion the bile volume was reduced and the concentration of ioglycamate was increased, but the quantity excreted was unchanged. A similar study using iodipamide reported previously gave the same result. When the ioglycamate was given by intravenous infusion, the effect of 100% bile diversion was quite different. The concentration of ioglycamate in the bile was unchanged by the bile diversion but the excretion was reduced. These results indicate that the transport maximum for the excretion of ioglycamate in bile is not a constant and is reduced by interruption of the enterohepatic circulation of bile salts. The maximum concentration of ioglycamate in bile was constant and was independent of the reduction in bile salt output produced by 100% bile diversion. Following a single bolus injection however, the reduction in bile flow produced by 100% bile diversion increased the biliary concentration of ioglycamate. These results suggest that the excretion of ioglycamate is limited by a maximum concentration rather than a transport maximum. The maximum rate of transport (Tm) is dependent on two factors--the maximum concentration of ioglycamate in the bile and the rate of bile flow. The maximum concentration is achieved by an infusion technique and not by a single bolus injection and this supports the view that an infusion technique should be used for intravenous cholangiography.

Animals↗
PubMed1987

Inhibitory effect of various radiographic contrast agents on secretion of thyroxine by the dog thyroid and on peripheral and thyroidal deiodination of thyroxine to tri-iodothyronine.

In previous studies we have found that the cholecystographic contrast agent ipodate induced a rapid, sustained and reversible inhibition of thyroxine (T4) secretion from perfused dog thyroid lobes. This type of inhibition of thyroid secretion has not been observed previously. To evaluate whether this effect is unique for ipodate, ten other iodine-containing radiographic contrast agents were tested. The four agents used for cholecystography (iocetamate, iodipamide, ioglycamate and iotroxate) all induced rapid inhibition of T4 secretion from TSH-stimulated perfused dog thyroid lobes, while none of six agents predominantly excreted through the kidneys (amidotrizoate, metrizamid, metrizoate, iodamide, diodone and ioxithalamate) influenced T4 secretion significantly. All the cholecystographic agents inhibited T4 deiodinases from dog thyroid and liver. Diodone also inhibited the deiodinases while none of the other compounds tested had any effect. The results indicate that the structure necessary to inhibit thyroid secretion is common to a number of cholecystographic agents and that it could be related to the structure responsible for the inhibitory effect of cholecystographic agents on T4 deiodinases.

Animals↗
PubMed1994

Movement of carboxyfluorescein across the isolated rabbit iris-ciliary body.

The movement of carboxyfluorescein across the isolated iris-ciliary body of the albino rabbit was analyzed using an Ussing chamber under short-circuit conditions with carboxyfluorescein concentrations ranging from 10 to 100 microM. At a concentration of 50 microM, the outward permeability (from the aqueous to the stromal side) was 4.0 +/- 0.2 x 10(-6) cm/sec and the inward permeability (from the stromal to the aqueous side) was 1.3 +/- 0.2 x 10(-6) cm/sec (Mean +/- SE, N = 6). The former was significantly greater than the latter (P < 0.001). Inward movement of carboxyfluorescein showed a linear increase in relation to the concentrations tested. Neither ouabain (100 microM), 2,4-dinitrophenol (10 microM) nor probenecid (100 microM) significantly inhibited the inward movement of carboxyfluorescein. The net outward movement of carboxy-fluorescein became saturated, as concentration was increased, and a Lineweaver--Burke plot gave an apparent Km of 28 microM and Vmax of 0.67 x 10(-9) mole/hr/cm2. In addition, outward carboxyfluorescein movement was significantly inhibited by ouabain (100 microM), 2,4-dinitrophenol (10 microM), probenecid (100 microM), iodipamide (1.0 mM), hippurate (1.0 mM), low temperature or low external Na+ concentration. These results suggest that outward carboxyfluorescein movement across the tissue largely depends on carrier-mediated active transport, while inward movement occurs by passive diffusion.

Animals↗
PubMed1983

Uptake of iopanoic acid and its glucuronide conjugate by rat hepatocytes in primary culture.

Uptake of iopanoic acid (IOP) and iopanoate glucuronide (IOP-G) was studied in 3-day primary cultures of rat hepatocytes isolated by the collagenase perfusion method. 125I activity of cells after incubation with 125I-IOP (10-100 microM) and 125I-IOP-G (10-100 microM) was used as a measure of uptake. At each concentration, uptake was linear for the first 45 sec. In the absence of albumin, the initial uptake velocity was directly proportional to the concentration or IOP or IOP-G and was nonsaturable up to 100 microM. The calculated uptake rate constants for IOP and for IOP-G were 0.059 and 0.048 nmole/(mg protein X min X microM), respectively. IOP uptake was not inhibited by sodium taurocholate nor by the contrast agents iodipamide, ipodate, and iopronic acid. The data indicate that the enhancement of IOP excretion by bile salts noted in vivo does not occur at the uptake step and that the hepatic uptake of both IOP and IOP-G in the absence of albumin is limited by diffusion.

Adsorption↗
PubMed1978

Nonimmunologic complement activation in normal human serum induced by radiographic contrast media.

Two different radiographic contrast media (RCM), iothalamate and iodipamide, induced the activation of several complement (C) components in normal, genetically C2-deficient and agammaglobulinemic human sera in vitro. This activation was dose dependent and demonstrable by a reduction in whole C as well as C4, C2, C3, and C5 hemolytic activities. C6, C8, and C9 hemolytic activities were unaffected. Concommitant with the loss of C3 hemolytic activity was the appearance of C3 proteolytic cleavage products that were identified by immunoelectrophoresis. Both the loss of C3 hemolytic activity and the production of C3 fragments occurred in the presence of 10 mM EDTA, indicating RCM-induced C3 cleavage occurred without participation of the multicomponent C3/C5 convertases of either the classical or alternative C pathways. Furthermore, loss of C3 hemolytic activity was not due to the direct alteration of the C3 molecule by RCM because purified C3 was unaffected upon incubation with RCM at a concentration that induced 80% reduction in the C3 hemolytic activity in normal human serum. Serum samples obtained from 40 patients, before and 30 min after undergoing i.v. pyelography, revealed no significant change in total hemolytic C activity; 34 patients received sodium and methylglucamine diatrizoate and six received sodium iothalamate. Hemolytic C3 levels were also determined for the six patients before and 30 min after administration of sodium iothalamate and no significant change in activity was detectable.

Agammaglobulinemia↗
PubMed1976

IgE-mediated adverse reactivity to a radiographic contrast medium.

In a patient with a previous history of a serious reaction after intravenous injection of the cholangiographic agent ioglycamic acid (Bilivistan), intravenous cholangiography appeared to be necessary. Therefore intradermal tests were performed in the patient and four controls with three radiographic contrast media closely related in chemical structure. In addition a Prausnitz-Kustner test with heated and unheated patient serum was performed. These tests demonstrated the presence in this patient of selective immediate-type reactivity to ioglycamic acid which was probably IgE mediated. Intravenous cholangiography with iodipamide seemed justified and resulted in no adverse reactions. Although this case may be exceptional, the results suggest that intradermal skin tests at proper concentrations may be useful in choosing the administration of radiographic contrast medium to patients with a history of prior adverse reactions.

Cholangiography↗
PubMed1991

[Kinetic study of movement of fluorescein across the isolated rabbit retinal pigment epithelium--choroid].

Using an Ussing-type chamber, the transport of fluorescein (F) across the isolated retinal pigment epithelium (RPE)-choroid of the rabbit was studied. The outward movement (from the vitreous to the choroidal side) of F was significantly greater than the inward movement (from the choroidal to the vitreous side) and was suppressed by the application of 10(-4)M probenecid, 30mM hippurate or 5mM iodipamide to 41%, 45% or 39% of the control, respectively, while the inward movement was not affected by any of these agents. As the F concentration in the chamber increased, the inward movement of F also increased in a linear fashion, but the outward movement showed nonlinearity. The difference between the outward and inward movement of F was thought to represent the net flux of F across the RPE-Choroid and this value showed nonlinearity and saturation as the F concentration increased. The Lineweaver-Burk plot of the reciprocals of the net flux of F concentration gave the apparent Km of 4.5 x 10(-5)M and apparent Vmax of 2.27 nmoles/hr/cm2, which suggested that the F transport system in the rabbit RPE-Choroid had a greater affinity to the substrate but lower transporting capacity as compared with the F transport system in the rabbit iris-ciliary body or the ascorbate transport system in the iris-ciliary body.

Animals↗
PubMed1986

Molecular aspects of cytoprotection by modified somatostatins.

Somatostatin and cyclic modifications of this molecule inhibit the development of protrusions on the surface of isolated hepatocytes in presence of phalloidin. This prevention of phalloidin injury is caused by competitive inhibition of the phallotoxin uptake. Transport inhibition is not a hormonal effect of somatostatin. The concentrations needed are in the micromolar range. The most protective somatostatin modifications lack hormonal activity (GH release). Somatostatin and its analogs are substrates of a hepatocellular transporter which also translocates other cyclopeptides, among them phalloidin, antamanide, and several organic anions, such as iodipamide and fusidic acid. Physiological substrates of this multispecific transport system are bile acids. The protection of phallotoxin injury by somatostatin is a specific mechanism only representative for liver cells. No other cell contains the above multispecific transporter.

Affinity Labels↗
PubMedDate not supplied

Product selection criteria for intravascular ionic contrast media.

The chemistry, clinical use, pharmacokinetics, adverse reactions, dosages, and formulary recommendations for intravascular ionic contrast media routinely used in radiologic procedures are reviewed. The meglumine, sodium, or combined meglumine-sodium salts of triiodinated benzoic acid derivatives, diatrizoic and iothalamic acid, are commonly used as intravascular ionic contrast media for radiographic visualization of blood vessels and the urinary tract. Meglumine salts of iodoxamate and iodipamide are used for intravenous cholangiography. The iodine in the contrast medium is responsible for the absorption of x-rays and the resulting opacification of the organ system or other area under investigation. Adverse reactions to intravascular ionic contrast media broadly include hypersensitivity and chemotoxic reactions. The incidence of major life-threatening hypersensitivity reactions, such as severe hypotension, cardiac arrhythmias or arrest, pulmonary or laryngeal edema, and convulsions, is estimated at 0.01-0.1% of the population receiving these agents. Dose- and concentration-dependent chemotoxic reactions result from the direct effects of the contrast medium on the blood vessels or organs being perfused. The meglumine salts of diatrizoic acid and iothalamic acid are less toxic in the cerebral circulation than sodium salts; hence, diatrizoate meglumine or iothalamate meglumine are recommended for cerebral angiography. In coronary angiographic examinations, combined meglumine and sodium (6.6 parts meglumine to 1 part sodium) formulations of diatrizoate are recommended because they consist predominantly of the meglumine salt with minimal but adequate amounts of sodium to prevent ventricular fibrillation. Predominantly meglumine salts of diatrizoic and iothalamic acid are also used for peripheral angiography, computerized tomography, and digital subtraction angiography. The dosages of ionic contrast media vary considerably depending on the nature of the radiological examination, the respective technique employed, and the age and condition of the patient. The cost differences between diatrizoate and iothalamate media are typically minimal. Formulary recommendations regarding the appropriate chemical nature of these media are based on the reported adverse reactions with these agents.

Animals↗
PubMed1979

[Endotoxin recognition with myelopoiesis of monocytes and macrophages].

Cells from the monocyte-macrophage pathway release colony-stimulating factors. The release of colony-stimulating activity is increased upon endotoxin activation in the presence of fresh serum. Heat-inactivation of serum (56 degrees C, 30 minutes) abolishes the endotoxin-mediated activation of macrophages. Decomplementation with zymosan, iodipamide and the use of commercially serum deficient in C3 provide indirect evidence for a complement dependence of the endotoxin-macrophage interaction, which leads to release of colony-stimulating activity.

Colony-Forming Units Assay↗
PubMed1980

Liver slice uptake of intravenous and oral biliary contrast media.

Using the liver slice technique, the uptake of five intravenous (including iodipamide, ioglycamide, iotroxamide, and iodoxamide) and one oral (iopodate) biliary contrast media into the rat liver was investigated. For all six compounds a saturable high-affinity and a nonsaturable low-affinity uptake system could be identified. There is no great difference of the liver uptake of the five intravenous compounds, but the oral compound iopodate is taken up by the rat liver to a much higher extent than the intravenous compounds. Since the liver slice uptake of the biliary contrast media was not clearly depending on metabolic energy, the presented results favor intracellular binding more than an active carrier as uptake mechanism. Human serum albumin strongly reduces hepatic uptake of all six compounds. The inhibition of the uptake was directly depending on the degree of serum albumin binding. No evidence for a carrier role of serum albumin within the uptake process could be found. The uptake mechanism of the liver for the biliary contrast media failed to be very specific, since liver slice uptake could be inhibited by iopanoate, bromosulfthalein, ouabain, and taurocholate and by each of the contrast media itself.

Administration, Oral↗
PubMed1993

Movement of fluorescein and its glucuronide across retinal pigment epithelium-choroid.

PURPOSE: To characterize movement of fluorescein and its glucuronide across the blood-retinal barrier. METHODS: Retinal pigment epithelium (RPE)-choroid preparations from New Zealand albino rabbit were sealed in an Ussing-type chamber in a stabilized condition for 3 hr, where movement of fluorescein and fluorescein glucuronide across the RPE-choroid was studied under a short circuit condition. RESULTS: The outward (vitreous-choroid) permeability to fluorescein determined at a concentration of 15 mumol/l was about 4 times greater than the inward (choroid-vitreous) permeability (P < 0.01). The outward permeability was significantly decreased by 50-65% by metabolic or competitive inhibitors (1 mumol/l ouabain, 10 mumol/l 2,4-dinitrophenol, 100 mumol/l probenecid, 30 mmol/l hippurate, or 5 mmol/l iodipamide), whereas the inward permeability was not affected by any of the above competitive inhibitors. As the fluorescein concentration was increased from 15 to 150 mumol/l, the net fluorescein movement across the tissue indicated saturation, and a Lineweaver-Burk plot gave an apparent Km of 26 mumol/l and Vmax of 1.56 nmol/hr/cm2. The outward permeability to fluorescein glucuronide determined at 15 mumol/l was about double the inward permeability (P < 0.01) and about 1/3 of the outward permeability to fluorescein (P < 0.01). The outward permeability to fluorescein glucuronide was significantly decreased by about 50% by 1 mumol/l ouabain, 10 mumol/l 2,4-dinitrophenol, or 100 mumol/l probenecid, whereas the inward permeability was not affected by 100 mumol/l probenecid. CONCLUSION: These results suggest that the majority of the outward fluorescein movement across the tissue and part of that of fluorescein glucuronide depends on an active transport mechanism, whereas the inward movement of both fluorescein and fluorescein glucuronide occurs by a passive mechanism.

2,4-Dinitrophenol↗
PubMed1977

Mechanism of complement activation by radiographic contrast media.

Activation of the complement system by radiographic contrast media (RCM) was demonstrated by in vitro haemolytic and immunological assays. Such activation was found to be a function of the RCM molar concentration. Iodipamide was the most active of five RCM tested. When RCM was incubated with normal human serum (NHS) in the presence of ethylene glycol-tetra-acetic acid and magnesium ions, conditions which block activation of the classical pathway but permit activation of the alternative pathway, haemolytically active C3, properdin and factor B were found to be decreased but haemolytically active C4 was normal. Using counterimmunoelectrophoresis, the activation of complement was further demonstrated by detection of C3 and factor B-split products. Finally, when radiolabelled complement proteins were reacted with RCM in vitro and studied by density-gradient ultracentrifugation, it was demonstrated that a large complex was formed with a sedimentation of 22S, similar in characteristics to the C5b-C9 complex. It was postulated that the mechanisms of in vitro consumption of complement by RCM was mainly through the alternative pathway.

Complement C3↗
PubMed1996

[Spiral cholangioscanners and tridimensional reconstructions of the biliary tract in children].

PURPOSE: endoscopic retrograde cholangiography may be difficult or unfeasible in children. It also may be complicated by acute pancreatitis. The purpose of this study was to determine the diagnostic contribution of spiral CT cholangiography in pediatric patients. SUBJECTS AND METHODS: seven patients, age ranging from 10 months to 13 years were explored without general anesthesia. Eight spiral CT cholangiographies were performed. The patients were suspected to have biliary or pancreatic lesions. Spiral CT was performed 60 minutes after slow infusion of iodipamide (Transbilix-Guerbet). The dose was correlated to the body surface. 3D reconstructions were done using the surface rendering or the MIP technique. RESULTS: biliary tract opacification and 3D reconstructions were considered of good quality in 6 out of 8 studies. It was normal in 2 cases. A duplication of the duodenum communicating with the choledocus was found in 1 case. Biliary lithiasis with a stone in the cystic duct was found in 1 case. Two choledocal cysts with bile ducts dilatation were diagnosed. A post operative biliary leak with bile ducts dilatation was found in one case. The spiral CT was not diagnostic in 2 patients: a case of choledocal cyst, the study was of poor quality due to inadequate sedation and a case of Caroli's disease with a high serum bilirubin level. Four patients had an endoscopic or a percutaneous cholangiography: to explore the pancreatic ducts (2 cases), poor CT study due to the inadequate sedation in 1 child, and the case of Caroli's disease. CONCLUSION: spiral CT is feasible even in young children. It should reduce the indications for endoscopic or percutaneous cholangiography. It has to be performed as the first examination in cases of biliary or pancreatic diseases when surgery is contemplated.

Adolescent↗