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PubMed1975

Intravenous cholangiography in normal and subsequently liver-damaged dogs.

When a 30-minute infusion is chosen for intravenous cholangiography, the optimal dose in subjects with normal and decreased hepatic function seems to be 0.6 ml/kg iodipamide. Delayed visualization of the ducts and gallbladder occurs in hepatic dysfunction, therefore, radiographs should be taken up to eight hours after the start of the examination if the cholangiogram is not diagnostic sooner. Prolonged infusion time, increased dosage, or both did not improve the radiographic results significantly when this method was not diagnostic. Contary to what is seen in obstructive jaundice, a markedly reduced gallbladder size, compared to its own baseline, was found in hepatic dysfunction.

Animals↗
PubMed1979

Iosefamate meglumine: an iodinated contrast agent for hepatic computed tomography scanning.

Iosefamate meglumine, a water-soluble, iodinated compound which is chemically and pharmacologically similar to iodipamide, was studied as a contrast agent for hepatic CT scanning in dogs. The difference between the CT attenuation number of liver and blood increased by 16 EMI units after intravenous injection of iosefamate 150 mg l/kg. The agent may prove useful in improving the CT detection of isodense tumors within the liver.

Animals↗
PubMed1994

Intravenous cholangiography with helical CT: comparison with endoscopic retrograde cholangiography.

PURPOSE: To determine whether helical computed tomography (CT) performed during intravenous cholangiography can provide useful images of the biliary tree and to compare this technique with endoscopic retrograde cholangiography (ERC). MATERIALS AND METHODS: Eighteen adult patients with clinically suspected biliary disease who were referred for ERC were first examined with helical CT cholangiography performed 75 minutes after intravenous infusion of 100 mL of 10.3% iodipamide meglumine. RESULTS: Helical CT cholangiography revealed good opacification of the biliary tree in 13 of 14 patients with serum bilirubin levels less than 2 mg/dL (34 mumol/L) and poor opacification in three of four patients with levels greater than 2 mg/dL. In six of seven patients with choledocholithiasis, the diagnosis was made by means of helical CT cholangiography. CONCLUSION: Helical CT cholangiography may be a clinically useful method for visualization of the biliary tree in some patients with suspected biliary disease with normal bilirubin levels and in patients in whom attempts at ERC fail.

Adult↗
PubMed1993

Vascular exchange in the kidney. Regional characterization by multiple indicator tomography.

In previous work with the method of multiple indicator dilution (MID), we have established that a spatially distributed model of transcapillary exchange proposed by Goresky, Ziegler, and Bach (GZB) accurately describes, at the in vivo whole-organ level, the handling of extracellular indicators in the canine renal cortex. To date, however, it has not been possible to assess the key hypothesis that GZB corresponds to the actual local mechanism of exchange in vivo and is not just a compact summary of the kidney's average whole-organ behavior. By adapting the MID method to high speed computed tomography (CT), we are now able to report that the GZB mechanism is an accurate description of renal cortical transcapillary exchange down to volumes of cortical tissue comprising no more than a few per cent of the total cortical mass, i.e., containing no more than a few thousand nephrons. A small bolus of iohexol (radiopaque extracellular indicator) or iodipamide ethyl ester microparticles (radiopaque plasma indicator) injected into the renal artery was followed by CT as it passed through the kidney and into the renal vein. Time-attenuation value curves of the two contrast media obtained from the renal vein and from regions of interest in the cortex were then modeled with the GZB mechanism and with a more complex formulation that includes GZB as a limiting case. When applied to the data, the models converged to GZB as the best fit for each region examined. The GZB mechanism is found to provide excellent agreement with the regional data.

Animals↗
PubMed1969

Two hepatic cytoplasmic protein fractions, Y and Z, and their possible role in the hepatic uptake of bilirubin, sulfobromophthalein, and other anions.

Two hepatic cytoplasmic protein fractions, designated Y and Z, which bind sulfobromophthalein (BSP), bilirubin, and other organic anions, have been separated by G75 Sephadex gel filtration. The physiologic role of these protein fractions has been investigated. They are present in the 110,000 g supernatant fraction from the livers of all the species tested (rats, mice, guinea pigs, Rhesus monkeys, sheep, and man). Tissues which do not preferentially extract BSP or bilirubin from plasma do not contain these fractions, with the exception of small intestinal mucosa which contains Z. Anion binding by Y and Z fractions is not due to contamination with albumin. These fractions are responsible for the cytoplasmic localization of bilirubin in Gunn rats, and the fractions bind bilirubin, BSP, or indocyanine green (ICG), whether given in vivo or added in vitro to liver supernate from normal rats. Flavaspidic acid-N-methylglucaminate, bunamiodyl, and iodipamide, drugs known to interfere with the hepatic uptake mechanism, compete with bilirubin and BSP for binding to Z. These proteins appear to be important in the transfer of organic anions from plasma into the liver and provide a tool for the investigation of hepatic uptake mechanisms.

Animals↗
PubMed1979

Volume of distribution of contrast media in blood.

The volume of distribution of diatrizoate and iodipamide in blood in relation to hematocrit and contrast concentration was measured using 125I-labeled compounds. In concentration obtained after intravenous injection, the percentage volume of distribution of both contrast media is 100 minus hematocrit, except for high hematocrit values, which may cause uneven distribution of contrast media in smaller concentrations. No evidence of intracellular penetration was obtained.

Contrast Media↗
PubMed1994

Noninvasive imaging of the biliary tree before or after laparoscopic cholecystectomy: use of three-dimensional spiral CT cholangiography.

OBJECTIVE: The purpose of this study was to determine the feasibility of using three-dimensional spiral CT after IV administration of a cholangiographic agent for noninvasive detection of anatomic variations of the bile ducts and common bile duct stones before or after laparoscopic cholecystectomy. SUBJECTS AND METHODS: Three-dimensional spiral CT cholangiography was performed before laparoscopic cholecystectomy in 24 patients and after surgery in two patients who had recurrent symptoms. After slow infusion of 250 ml of iodipamide, spiral CT was performed. Three-dimensional images of the bile ducts and a secondary reformation through the long axis of the common bile duct were obtained. Visualization of the biliary tract was evaluated by two observers. Detection of anatomic variations and common bile duct stones was assessed in 19 patients for whom a gold standard (operative or retrograde cholangiogram) was available. RESULTS: In all 26 patients, the common bile duct and the confluence of the hepatic ducts were seen on three-dimensional spiral CT cholangiograms, and in 21 patients second- or higher-order branches were also seen. Seven patients had anatomic variations and two had common bile duct stones. These anomalies were proved by operative cholangiography in each case, except for a low junction of the cystic duct and a common bile duct stone, which were shown by retrograde cholangiography. Six of the seven anatomic variations were adequately detected with spiral CT cholangiography, as were the two cases of common bile duct stones. CONCLUSION: Three-dimensional spiral CT cholangiography is a feasible method for noninvasive detection of biliary anatomic variations and common bile duct stones before or after laparoscopic cholecystectomy.

Bile Ducts↗
PubMed1976

[The effect of tri-iodinated contrast media on acetylcholinesterase of human erythrocytes (author's transl)].

The side effects of water soluble iodinated contrast media often mimic the clinical picture of acetylcholine intoxication. This prompted us to determine the amount of inhibition of human acetylcholinesterase by the following contrast media in vivo and in vitro: methyl glucamineiodipamide (Biligrafin forte), methylglucamine iothalamate (Conray 60), sodium-iothalamate (Conray 80). In vivo no correlation could be found between clinically manifest adverse reaction and enzyme inhibition after contrast media application. The in vitro values for 50% inhibition of erythrocyte acetylcholinesterase are: methylglucamine-iodipamide: 0.036 M, methylglucamine-iothalamate: 0.158 M, sodium-iothalamate: 0.3 M. Since in vitro, the maximal inhibitory effect of a given dose of contrast media can only be registered after a time interval when most of the contrast media in vivo has already been excreted by the kidneys or extracted by the liver, it seems very improbable that the enzyme inhibition seen in vitro should have any consequence whatsoever under clinical conditions. The in vitro inhibition of acetylcholinesterase is quickly reversible, with nearly all the activity regained 15 min after the removal of the contrast media.

Acetylcholinesterase↗
PubMed1979

Cholic acid accumulation by the ciliary body and by the iris of the primate eye.

Cholic acid accumulates in both the ciliary body and the iris of the primate eye during in vitro incubations at 37 degrees C for 1 hr. Incubation at 0 degrees C depresses uptake in both tissues. The washout of preaccumulated cholic acid occurs some 3.4 times faster from the iris than from the ciliary body. The mechanism of cholic acid accumulation in both tissues is less sensitive to inhibition by high iodipamide concentrations and also is less sensitive to inhibition by high hippurate concentrations than the mechanism of p-aminohippurate (PAH) accumulation. Therefore, although overlap may exist, the cholic acid--uptake mechanism differs from the PAH-uptake mechanism in both the primate ciliary body and the primate iris.

Animals↗
PubMed1976

Organic cation uptake in vitro by the rabbit iris-ciliary body, renal cortex, and choroid plexus.

The uptake in vitro of radioactively labeled test substances was studied in tissues from albino rabbits. Choroid plexus, slices of outer renal cortex, and iris-ciliary body were incubated in a K-rich medium containing one of the cations 14C-Emepronium (Cetiprin), 14C-tetraethylammonium, 14C-choline, or 125I-o-iodobenzyltrimethylammonium and sometimes the anions 131I-o-iodohippurate and 125I-iodipamide. Choroid plexus and renal cortex accumulated all test substances, some to very high tissue-medium ratios. The iris-ciliary body preparation accumulated the anions well but the organic cations only weakly. The only convincing uptake was that of Emepronium. The affinity of this uptake system seemed to be similar to that in the kidney, half-saturating around 10(-4)M Emepronium.

Animals↗
PubMed1978

Alteration of renal cortical palmitate utilization and p-aminohippurate (PAH) accumulation after penicillin treatment of neonatal rabbits.

The renal organic anion transport system has been linked to the selective extraction of nonesterified fatty acids (NEFA) from arterial blood. Consequently, p-aminohippurate (PAH) and palmitate may compete for a common intracellular binding site or may be handled by a common enzymatic pathway. The purpose of this study was to identify sites of interaction by correlating alterations in PAH accumulation and palmitate metabolism after selective stimulation of the PAH transport system. Penicillin treatment of immature rabbits increased PAH accumulation by suspensions of proximal tubules prepared nonenzymatically) and altered distribation of incorporated palmitate[14C] within tubule lipid classes. Penicillin increased palmitate[14C] esterified to triglycerides and decreased 14C recovered as NEFA. Administration of iodipamide had no effect on PAH accumulation and did not alter palmitate utilization. Penicillin treatment of mature rabbits did not alter either tubule PAH accumulation or palmitate esterification. These results suggested that palmitate and PAH share a common intracellular binding site and that penicillin enhanced PAH accumulation by removing endogenous inhibitors (NEFA).

Aging↗
PubMed1997

Three-dimensional helical computed tomographic cholangiography: application to living related hepatic transplantation.

Variations in the anatomy of intrahepatic bile ducts complicate operations in living related hepatic transplantation (LRHT). Preoperative delineation of the biliary system is important to achieve successful results. The purpose of this study was to assess the utility and accuracy of three-dimensional helical computed tomographic cholangiography (3DHCTC) as a replacement for endoscopic retrograde cholangiography (ERC) in evaluating the anatomy of the intersegmental biliary connection of the potential donors in LRHT. Helical CT was performed in 16 potential donors after a slow infusion of 100 cm3 meglumine iodipamide. By using the maximum intensity projection and shaded surface displaced image reconstruction technique, three-dimensional images of the bile ducts were isolated from the surrounding hepatic parenchyma. Among the 16 potential donors, 3 cases underwent an ERC study and another 7 cases donated liver graft during LRHT. In all 16 cases the anatomy of the bilateral essential intrahepatic ducts was well displayed with and without the liver parenchyma background in an axial and three-dimensional fashion which had good correlation with images from ERC and intra-operative cholangiography. Two variants were found, including drainage of the right posterior intrahepatic duct into the left hepatic duct and direct drainage of the segment II bile duct into the common hepatic duct, respectively. It is concluded that unusual routes of intrahepatic ducts may necessitate a change in the cutting plane during graft retrieval and patterns of ductoenteral anastomosis to avoid potential complications to both donors and recipients. With the advantages of non-invasiveness and comparable accuracy in demonstrating biliary anatomy, 3DHCTC may replace the traditional ERC in the pre-transplant survey of potential donors for LRHT.

Adult↗
PubMed1978

Pharmacokinetics of iodoxamic acid in rhesus monkey: biliary excretion, plasma protein binding, and enterophepatic circulation.

The previously reported steady-state method allowed estimation of the capacity-limited pharmacokinetics of the cholangiographic agent, iodipamide. To circumvent the long time period required to establish each steady-state level, a dynamic method was applied to the study of the rate processes involved in the hepatic uptake and biliary excretion of a new cholangiographic agent, iodoxamic acid, in rhesus monkeys. The dynamic method has the advantage that the pharmacokinetic parameters involved in capacity-limited hepatic uptake or biliary excretion can be obtained from a single infusion experiment. The V max was 1.03 +/- 0.25 mumoles/kg/min (mean +/- SD); Km varied from animal to animal and ranged from 1.5 to 16.4 micrometer. Protein binding was estimated using equilibrium dialysis. The Freundlich isotherm yielded a linear plot when the natural logarithm of unbound iodoxamic acid concentration in plasma was plotted against the natural logarithm of its blood concentration. The plasma protein binding data also could be fitted to the Langmuir isotherm, presuming two independent classes of binding.

Animals↗
PubMed1988

Properties of phallotoxin uptake by basolateral plasma membrane vesicles from rat liver: evidence for a carrier-mediated transport.

The mechanism and driving forces for hepatocellular phallotoxin uptake were studied by a rapid-filtration technique using basolateral liver plasma membrane vesicles (blLPM). An inwardly directed Na+ gradient but not K+-gradient transiently stimulated taurocholate uptake into blLPM 1.4-1.7-fold above the equilibrium value (overshoot), demonstrating functionally intact vesicles. In contrast, overshooting phallotoxin uptake (1.15-1.2-fold intravesicular accumulation above equilibrium value) was observed in the presence of a K+ as well as of a Na+ gradient. Na+ could be replaced by K+ or Li+. In the presence of choline a distinct uptake reduction of 57% was seen. Counter-transport phenomena suggest phallotoxin transport rather than binding. Phallotoxin uptake was inhibited significantly by taurocholate, iodipamide and antamanide, but only slightly by alpha-amanitin. Creation of a negative intravesicular potential by altered accompanying anions or by valinomycin-induced K+ diffusion potential enhanced the initial uptake rate for phallotoxin, demonstrating rheogenic solute uptake. These findings provide evidence that hepatocellular uptake of phallotoxin is due to carrier-mediated transport. Hepatic uptake of phallotoxin is assumed to be driven by both a monovalent cation gradient (Na+ or K+) and a transmembranal potential difference.

Amanitins↗
PubMed1982

Lack of intestinal transport of [3H]-demethylphalloin: comparative studies with phallotoxins and bile acids on isolated small intestinal cells and ileal brush border membrane vesicles.

Several earlier studies suggested that the uptake of phallotoxins by liver cells is a carrier mediated process using a transport system normally handling bile acids (see Frimmer 1982). In this study we have shown whether ileal cells, well known to transport bile acids too, are able to take up phallotoxins. Isolated epithelial cells prepared from guinea pig ileum accumulated [14C]-cholate, whereas [3H]-demethylphalloin ([3H]-DMP) was not taken up. The same observation was made with isolated jejunal cells but the uptake of [14C]-cholate was much slower. [3H]-DMP, however, was partly bound to intestinal cells. This process was not inhibited by cholate, iodipamide, oligomycin and carbonylcyano-chlorophenylhydrazone (CCCP), compounds known to decrease the uptake of phallotoxins into liver cells. Substituting Na+ for choline+ and also Cl- for SCN- did not influence the binding of [3H]-DMP. Frozen intestinal cells from the guinea pig bound two time more [3H]-DMP after thawing compared with intact cells. Supplementary uptake experiments on isolated brush border membrane vesicles from rat ileum revealed that phalloidin does not inhibit taurocholate uptake and that taurocholate does not interfere with [3H]-DMP binding. The results suggest that [3H]-demethylphalloin is not recognized by the bile acid carrier of the guinea pig and the rat ileum. It is concluded that the transport system for bile acids present in ileal cell is different from that of liver cells.

Alkaloids↗
PubMed1980

Therapeutic embolization with detachable balloons.

In our first 18 months' clinical experience with embolization in the chest and abdomen using detachable balloons, successful results were obtained in 34 of 38 patients. One and 2-mm detachable silicone balloons, which can occlude vessels 4--8 mm in diameter, were employed. Prolonged balloon inflation was routinely achieved using iso-osmotic iodipamide meglumine as the filler and limiting inflation volumes to experimentally determined maximums. Improvements in introducer catheter design simplified delivery of the balloon into a variety of circulations. Detachable balloons are not suitable for all embolization purposes, and they are frequently used in conjunction with other agents. When used properly, balloons produce a permanent occlusion that is extremely selective and potentially reversible up to a certain point in the procedure. The balloon technique enables the angiographer to occlude vessels at distances of 2--10 mm beyond the introducer catheter, thus avoiding the need for subselective catheterization and minimizing the dangers of inadvertent embolization.

Angiography↗
PubMed1985

Further characterization of 3'-isothiocyanatobenzamido[3H]cholate binding to hepatocytes. Correlation with bile acid transport inhibition and protection by substrates and inhibitors.

Binding of 3'-isothiocyanatobenzamido[3H]cholate ([3H]IBCA) to hepatocytes correlates to its efficacy in inhibiting cholate uptake in isolated hepatocytes. The correlation is linear up to 20 microM [3H]IBCA. Labeling of polypeptides is proportional to the degree of inhibition particularly for a protein of molecular weight 50 000. Transported substrates, competitive and non-competitive inhibitors of cholate transport protect against IBCA inhibition. Additionally binding of [3H]IBCA to isolated plasma membranes is prevented by the same substrates and inhibitors of the cholate transport system. The prevention is achieved by taurocholate, iopodate, iodipamide, furosemide, BSP, cyclosporin A, and somatostatin analogs. Protection is correlated to the degree of transport inhibition and depends on the hydrophobicity of the compounds. Other inhibitors known to destroy the driving forces such as valinomycin do not protect membrane proteins against coupling with IBCA. Silybin, which preferentially alters membrane fluidity, has little effect on the labeling. The above results give further evidence that IBCA, when applied in concentrations below 20 microM, is a suitable label for the hepatocellular bile salt transporter.

Affinity Labels↗
PubMed1983

Peptide and non-peptide opioid-induced hyperthermia in rabbits.

Intracerebroventricular administration of all three prototype non-peptide opioid receptor (mu, kappa and sigma) agonists, morphine, ketocyclazocine and N-allyl-normetazocine (SKF 10,047) induced hyperthermia in rabbits. Similar administration of peptide opioids like beta-endorphin (BE), methionine-enkephalin (ME) and its synthetic analogue D-ala2-methionine-enkephalinamide (DAME) also caused hyperthermia. As expected, the synthetic enkephalin DAME was more potent than the parent enkephalin. Of the three anion transport systems (iodide, hippurate and liver-like or L) present in the choroid plexus, it is suggested that only the L transport system seems to be important to ventricular inactivation of BE and DAME since iodipamide (an inhibitor of the L transport system) augmented the hyperthermia produced by BE and DAME. Prostaglandins (PG) and norepinephrine (NE) were not involved in peptide and non-peptide opioid-induced hyperthermia because a PG synthesis inhibitor, indomethacin, and an alpha-adrenergic receptor blocker, phenoxybenzamine, had no thermolytic effect on them. Likewise cAMP was not required since a phosphodiesterase inhibitor, theophylline, did not accentuate the hyperthermia due to peptide and non-peptide opioids. Naloxone-sensitive receptors were involved in the induction of hyperthermia by morphine. BE, ME and DAME since naloxone attentuated them. In contrast, the hyperthermic response to ketocyclazocine and SKF 10,047 were not antagonized by naloxone.

Animals↗