Quantitative liver imaging using 131-I Rose Bengal as an index of liver function and prognosis.
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A technique for assessing quantitatively hepatic function by direct measurement of liver parenchymal cell uptake of 131I Rose Bengal using a scintillation camera with a digital store and retrieval system is described. Ninety-four studies were performed on 84 patients with a variety of hepatic disorders over a two-year period, the diagnosis in each case being established by liver biopsy or laparotomy. The results were compared with the clinical, biochemical and histological assessment of the patients. A good correlation was found between the half-time for hepatic uptake of 131I Rose Bengal and the histological changes, as well as with clinical prognosis measured in terms of clinical improvement or deterioration to death. The rate of liver uptake was found to be a better index than the clearance of radioisotope from the blood and was superior to conventional biochemical investigations in both icteric and anicteric patients. The test was not shown to be of clinical value in discriminating between intra- and extrahepatic causes of jaundice. It is suggested that this technique may provide a safe and sensitive method for assessing the severity of liver dysfunction and also for monitoring clinical progress, especially in situations where liver biopsy may be unreliable or hazardous. (+info)
Hepatic clearance mechanism of Tc-99m-HIDA and its effect on quantitation of hepatobiliary function: Concise communication.
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Parameters affecting the hepatobiliary clearance of Tc-99m N(2,6-dimethylphenyl carbamoylmethyl) iminodiacetic acid (Tc-HIDA) were evaluated in dogs. Competitive clearance studies, were performed with Tc-HIDA after infusion to plasma saturation levels of an anion, sodium sulfobromophthalein (BSP), and a cation, oxyphenonium. The results demonstrated that Tc-HIDA is transported through hepatocytes by a carrier-mediated organic-anion pathway. The data are consistent with an alteration of the elimination kinetics of Tc-HIDA induced by elevations in the serum bilirubin level, and it is predicted that serum bilirubin at some increased concentration will dominate the distribution and elimination kinetics of Tc-HIDA independently of hepatobiliary status. A quantitative description of liver function in terms of regional distribution and elimination rate constants will require either a pharmacokinetic model that expressly includes the effects of bilirubin, the development of new anionic hepatobiliary agents capable of displacing endogenous bilirubin from transport binding sites, or the development of new hepatobiliary agents that use a different clearance mechanism from that used by bilirubin. (+info)
Effect of reactive oxygen species on NH4+ permeation in Xenopus laevis oocytes.
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To investigate the effects of reactive oxygen species (ROS) on NH4+ permeation in Xenopus laevis oocytes, we used intracellular double-barreled microelectrodes to monitor the changes in membrane potential (V(m)) and intracellular pH (pH(i)) induced by a 20 mM NH4Cl-containing solution. Under control conditions, NH4Cl exposure induced a large membrane depolarization (to V(m) = 4.0 +/- 1.5 mV; n = 21) and intracellular acidification [reaching a change in pH(i) (DeltapH(i)) of 0.59 +/- 0.06 pH units in 12 min]; the initial rate of cell acidification (dpH(i)/dt) was 0.06 +/- 0.01 pH units/min. Incubation of the oocytes in the presence of H2O2 or beta-amyloid protein had no marked effect on the NH4Cl-induced DeltapH(i). By contrast, in the presence of photoactivated rose bengal (RB), tert-butyl-hydroxyperoxide (t-BHP), or xanthine/xanthine oxidase (X/XO), the same experimental maneuver induced significantly greater DeltapH(i) and dpH(i)/dt. These increases in DeltapH(i) and dpH(i)/dt were prevented by the ROS scavengers histidine and desferrioxamine, suggesting involvement of the reactive species (1)DeltagO2 and.OH. Using the voltage-clamp technique to identify the mechanism underlying the ROS-measured effects, we found that RB induced a large increase in the oocyte membrane conductance (G(m)). This RB-induced G(m) increase was prevented by 1 mM diphenylamine-2-carboxylate (DPC) and by a low Na+ concentration in the bath. We conclude that RB, t-BHP, and X/XO enhance NH4+ influx into the oocyte via activation of a DPC-sensitive nonselective cation conductance pathway. (+info)
Protection by isoprene against singlet oxygen in leaves.
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Isoprene (2-methyl-1,3-butadiene) protection against effects of singlet oxygen was investigated in Myrtus communis and Rhamnus alaternus. In M. communis, singlet oxygen produced in the leaves by Rose Bengal (RB) led to a 65% decrease in net assimilation rates within 3 h, whereas isoprene emission rates showed either a 30% decrease at ambient CO2 concentrations or a 70% increase under high CO2. In both cases, these changes led to an increase in calculated internal isoprene concentrations. The isoprene protection effect was directly demonstrated by fumigation of young (non-emitting) leaves, treated with RB or bromoxynil (simulating photoinhibition). There was 42% and 29% reduction in the damage to net assimilation compared with non-fumigated leaves for RB or bromoxynil, respectively. In R. alaternus, similar effects of RB on net assimilation were observed, and additional fluorescence measurements showed a significantly smaller decrease in Fv/Fm in isoprene-fumigated young leaves treated with RB (from 0.78 to 0.52), compared with non-fumigated leaves (from 0.77 to 0.27). The internal isoprene concentrations used in this study and possible rate of 1O2 production in leaves indicate that the protective effects observed should be beneficial also under natural conditions. (+info)
Photodynamic activation of ion transport through lipid membranes and its correlation with an increased dielectric constant of the membrane.
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Illumination of biological membranes with visible light in the presence of membrane-active sensitizers (e.g. rose bengal) is known to inactivate transport proteins such as ion channels and ion pumps. In some cases, however, illumination gives rise to an activation of transport. This is shown here for ion channels formed by alamethicin in lipid membranes, and for porin channels, which were isolated from the outer membrane of E. coli (OmpC) and from the outer membrane of mitochondria (VDAC) and were reconstituted in lipid membranes. An activation (in the form of an increased conductance) was also observed in the presence of the cation carriers valinomycin and nonactin. The activation phenomena were only present, if the membranes were made from lipids containing unsaturated double bonds. Activation was reduced in the presence of the antioxidant vitamin E. We suggest that the activation of the different transport systems has a common physical basis, namely an increase of the dielectric constant, epsilon(m), of the membrane interior by the presence of polar oxidation products of photodynamically induced lipid peroxidation. Experimental evidence for an enhanced dielectric constant was obtained from the finding of a light-induced increase of the membrane capacitance in the presence of rose bengal. (+info)
Improvement of corneal fluorescein staining in post cataract surgery of diabetic patients by an oral aldose reductase inhibitor, ONO-2235.
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AIM: While the mechanism in the pathogenesis of diabetic corneal disease is unclear, aldose reductase has been implicated in corneal disease. The effects of an oral aldose reductase inhibitor (ARI) on the ocular surface of diabetic patients after cataract surgery were studied. METHODS: This clinical trial was designed to be randomised, double blinded, and placebo controlled. Pseudophakic patients with diabetes were randomly assigned to treatment with either oral ARI (ONO-2235) (n=12) or placebo (n=9) for 12 weeks. The vital staining of the ocular surface, tear production and clearance, break up time in tears (BUT), corneal and conjunctival sensation, and symptom score before treatments were examined as well as 4, 8, 12 weeks after the administration. Specular microscopic evaluation was also performed. RESULTS: After a 12 week period of oral ARI administration, fluorescein staining scores (from 2.04 (SD 1.12) to 1.46 (1.18); p=0.016), conjunctival sensation (from 1.15 (0.37) to 1.36 (0.31); p=0.0006), and symptom scores (from 5.38 (1.932) to 4.00 (2.07); p=0.0002) recovered significantly. Fluorescein staining of oral ARI administration also decreased compared with placebo (p=0.017). Rose bengal staining, tear clearance, and corneal sensation were improved although this increase was minor. Tear production, BUT, and specular microscopic evaluation of the corneal epithelium and endothelium did not demonstrate a significant change. CONCLUSION: Oral ARI opposes the ocular surface changes caused by diabetes, by recovery of ocular surface sensitivity as demonstrated through an improvement in vital staining. (+info)
Technetium-99m-pyridoxylideneglutamate, a new agent for gallbladder imaging: comparison with 131I-rose bengal.
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Two agents used for hepatobiliary studies, 131I-rose bengal and 99mTc-pyridoxylideneglutamate, have been compared in rabbits. The 99mTc radiopharmaceutical is rapidly cleared from the blood by the liver and rapidly excreted through the common bile duct into the duodenum. Because of its rapid removal from the liver, visualization of the gallbladder and biliary passages was obtained within 15 min after injection in experimental animals. (+info)
Liver scan in Budd-Chiari syndrome.
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Seventeen liver scans were performed in seven patients with occulsion of hepatic veins: the Budd-Chiari syndrome. When some, but not all liver veins were occluded, markedly diminished uptake over the affected segments was usually seen (absence of uptake may occur in acute infarction and in chronic cases). When all major liver veins are occluded, markedly diminished uptake is seen over the peripheral parts of the right and left lobes with a triangular midline area of normal or excessive activity. The latter effect is probably caused by uptake in segments surrounding the inferior vena cava (frequently the caudate lobe) that have direct venous drainage. This liver-scan appearance is characteristic enough to warrant consideration of the Budd-Chiari syndrome as the first diagnosis. Good correlation existed between selective venography and liver-scan findings. The usefulness of liver scans in the followup after portocaval shunting is illustrated in one patient. (+info)