Sample records for bromosulfophthalein
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Biliary clearance of bromosulfophthalein in healthy and ketotic Holstein cows
Directory of Open Access Journals (Sweden)
Danijela Kirovski
2013-09-01
Full Text Available Ketosis is a metabolic disorder closely associated with liver lipidosis. Numerous tests have been developed to detect hepatic dysfunction in dairy cows. Bromosulfophthalein (BSP clearance is established as a sensitive index of hepatic function. The objective of this study was to examine the difference of biliary excretion of BSP between ketotic and healthy Holstein cows and to correlate this excretion with other indicators of liver dysfunction. Twenty puerperal Holstein cows divided in two groups (10 cows each were involved in the study. The first group included healthy and the second group ketotic cows. Blood samples were taken 10 days after parturition. Concentrations of total protein, albumin, total bilirubin, Ca, P, total lipids, urea and glucose were determined. Immediately after blood sampling, BSP test was performed. Blood samples were taken 5 and 45 minutes after injection, and the percentage of retained pigment in the sample obtained at minute 45 was calculated. Blood albumin and glucose concentrations were significantly higher in healthy then ketotic cows. Total bilirubin concentration was significantly higher in ketotic than healthy cows. BSP excretion was significantly higher in ketotic compared to healthy cows. There was a significant positive correlation between BSP values and total bilirubin concentrartions in both healthy and ketotic cows and a significant negative correlation between BSP values and glucose concentrartions in both healthy and ketotic cows. In conclusion, biliary clearance of BSP may be used as a reliable method for the detection of hepatic dysfunction associated with clinical symptoms of ketosis in dairy cows.
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International Nuclear Information System (INIS)
Ankermann, K.J.; Klinger, W.; Mueller, D.
1979-01-01
In studying the effects of UV light alone and combined with the phenobarbital inductor, a shortening of the barbital and hexobarbital lateral position time, a lowering of the bilirubin concentration and an acceleration of the bromosulfophthalein (BSP) clearance could be revealed. Effects not accompanied with an increase of biotransformation reactions such as cytochrome P 450 concentration in liver microsomes and binding of BSP on cytoplasmic acceptor proteins Y and Z of the liver as well as the amidopyridine N demethylation remained unchanged
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International Nuclear Information System (INIS)
Tapalaga, D.; Suciu, A.; Schvartz, M.; Duca, S.
1979-01-01
In order to establish whether the increased bromosulfophthalein (BSP) secretion in the bile following phenobarbital administration is the consequence of change in the bile output or of the enzymatic induction, the dynamics of the elimination of 131 I-BSP was studied in animals treated with alpha-naphthylisothiocyanate (ANIT) and pehnobarbital in the conditions of isolated perfused liver. At the same time the levels of the conjugation enzyme of BSP were also determined. It was noted that after phenobarbital the biliary elimination of 131 I-BSP is in correlation with the important increase of the output; in the animals treated with ANIT, on the other hand, the biliary excretion of BSP is minimal. The biliary elimination is directly proportional to the increase of the bile output and reflects the changes found in the perfusate. Our findings allow us to assume that the increased biliary BSP excretion is the consequence of the increase of the bile output and in a smaller extent the result of the stimulation of the BSP, conjugation with glutathion. (author)
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Shen, Hong; Liu, Tongtong; Morse, Bridget L; Zhao, Yue; Zhang, Yueping; Qiu, Xi; Chen, Cliff; Lewin, Anne C; Wang, Xi-Tao; Liu, Guowen; Christopher, Lisa J; Marathe, Punit; Lai, Yurong
2015-07-01
The contribution of organic anion transporter OAT2 (SLC22A7) to the renal tubular secretion of creatinine and its exact localization in the kidney are reportedly controversial. In the present investigation, the transport of creatinine was assessed in human embryonic kidney (HEK) cells that stably expressed human OAT2 (OAT2-HEK) and isolated human renal proximal tubule cells (HRPTCs). The tubular localization of OAT2 in human, monkey, and rat kidney was characterized. The overexpression of OAT2 significantly enhanced the uptake of creatinine in OAT2-HEK cells. Under physiologic conditions (creatinine concentrations of 41.2 and 123.5 µM), the initial rate of OAT2-mediated creatinine transport was approximately 11-, 80-, and 80-fold higher than OCT2, multidrug and toxin extrusion protein (MATE)1, and MATE2K, respectively, resulting in approximately 37-, 1850-, and 80-fold increase of the intrinsic transport clearance when normalized to the transporter protein concentrations. Creatinine intracellular uptake and transcellular transport in HRPTCs were decreased in the presence of 50 µM bromosulfophthalein and 100 µM indomethacin, which inhibited OAT2 more potently than other known creatinine transporters, OCT2 and multidrug and toxin extrusion proteins MATE1 and MATE2K (IC50: 1.3 µM vs. > 100 µM and 2.1 µM vs. > 200 µM for bromosulfophthalein and indomethacin, respectively) Immunohistochemistry analysis showed that OAT2 protein was localized to both basolateral and apical membranes of human and cynomolgus monkey renal proximal tubules, but appeared only on the apical membrane of rat proximal tubules. Collectively, the findings revealed the important role of OAT2 in renal secretion and possible reabsorption of creatinine and suggested a molecular basis for potential species difference in the transporter handling of creatinine. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.
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Radiopharmaceuticals in Czechoslovakia
International Nuclear Information System (INIS)
Hron, M.; Kronrad, L.; Svoboda, K.; Melichar, F.
1986-01-01
The history is briefly described of the production of radiopharmaceuticals in Czechoslovakia for nuclear medicine purposes. 131 I-labelled orthoiodohippurate and rose Bengal were first produced. Currently, 99m Tc is the most frequently requested radionuclide for radiopharmaceutical labelling. The preparation of 99m Tc is described in detail, a flow chart is shown and the network of 99m Tc distribution to hospitals outlined. In addition of 99m Tc and 131 I, UJV Rez produces other radionuclides for nuclear medicine, such as 113m In, 67 Ga, 35 S, 32 P, 203 Hg, 85 Sr. The methods are being developed of the production of 201 Tl, 125 I and 131 I-labelled bromosulfophthalein. (E.S.)
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International Nuclear Information System (INIS)
Heyder, R.
1980-01-01
The aim of the study consisted first of all in working out a procedure to determine the liver clearance of 131 J-bromosulfophthalien according to the Oberhausen method and to inquire into the usability and sphere of validity of the Oberhausen approach. Subsequently a collective of patients was to be tested in order to find out whether it is possible with the aid of the clearance value to differentiate between persons with healthy livers and persons with liver disturbances respectively to assess the severity of a functional liver disorder. As the investigations were carried through as a part of the clinical routine, the information obtained by the clearance concept as compared to sequential scintiscanning and compartment analysis was to be investigated at the same time. (orig./MG) [de
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Directory of Open Access Journals (Sweden)
D.T. Ito
2007-03-01
Full Text Available Animal studies and premarketing clinical trials have revealed hepatotoxicity of statins, primarily minor elevations in serum alanine aminotransferase levels. The combined chronic use of medicines and eventual ethanol abuse are common and may present a synergistic action regarding liver injury. Our objective was to study the effect of the chronic use of atorvastatin associated with acute ethanol administration on the liver in a rat model. One group of rats was treated daily for 5 days a week for 2 months with 0.8 mg/kg atorvastatin by gavage. At the end of the treatment the livers were perfused with 72 mM ethanol for 60 min. Control groups (at least 4 animals in each group consisted of a group of 2-month-old male Wistar EPM-1 rats exposed to 10% ethanol (v/v ad libitum replacing water for 2 months, followed by perfusion of the liver with 61 nM atorvastatin for 60 min, and a group of animals without chronic ethanol treatment whose livers were perfused with atorvastatin and/or ethanol. The combination of atorvastatin with ethanol did not increase the release of injury marker enzymes (alanine aminotransferase, aspartate aminotransferase, and lactic dehydrogenase from the liver and no change in liver function markers (bromosulfophthalein clearance, and oxygen consumption was observed. Our results suggest that the combination of atorvastatin with ethanol is not more hepatotoxic than the separate use of each substance.
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Data-based mathematical modeling of vectorial transport across double-transfected polarized cells.
Bartholomé, Kilian; Rius, Maria; Letschert, Katrin; Keller, Daniela; Timmer, Jens; Keppler, Dietrich
2007-09-01
Vectorial transport of endogenous small molecules, toxins, and drugs across polarized epithelial cells contributes to their half-life in the organism and to detoxification. To study vectorial transport in a quantitative manner, an in vitro model was used that includes polarized MDCKII cells stably expressing the recombinant human uptake transporter OATP1B3 in their basolateral membrane and the recombinant ATP-driven efflux pump ABCC2 in their apical membrane. These double-transfected cells enabled mathematical modeling of the vectorial transport of the anionic prototype substance bromosulfophthalein (BSP) that has frequently been used to examine hepatobiliary transport. Time-dependent analyses of (3)H-labeled BSP in the basolateral, intracellular, and apical compartments of cells cultured on filter membranes and efflux experiments in cells preloaded with BSP were performed. A mathematical model was fitted to the experimental data. Data-based modeling was optimized by including endogenous transport processes in addition to the recombinant transport proteins. The predominant contributions to the overall vectorial transport of BSP were mediated by OATP1B3 (44%) and ABCC2 (28%). Model comparison predicted a previously unrecognized endogenous basolateral efflux process as a negative contribution to total vectorial transport, amounting to 19%, which is in line with the detection of the basolateral efflux pump Abcc4 in MDCKII cells. Rate-determining steps in the vectorial transport were identified by calculating control coefficients. Data-based mathematical modeling of vectorial transport of BSP as a model substance resulted in a quantitative description of this process and its components. The same systems biology approach may be applied to other cellular systems and to different substances.
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Rojanathammanee, Lalida; Rakoczy, Sharlene; Brown-Borg, Holly M
2014-10-01
Ames dwarf mice are deficient in growth hormone (GH), prolactin, and thyroid-stimulating hormone and live significantly longer than their wild-type (WT) siblings. The lack of GH is associated with stress resistance and increased longevity. However, the mechanism underlying GH's actions on cellular stress defense have yet to be elucidated. In this study, WT or Ames dwarf mice were treated with saline or GH (WT saline, Dwarf saline, and Dwarf GH) two times daily for 7 days. The body and liver weights of Ames dwarf mice were significantly increased after 7 days of GH administration. Mitochondrial protein levels of the glutathione S-transferase (GST) isozymes, K1 and M4 (GSTK1 and GSTM4), were significantly higher in dwarf mice (Dwarf saline) when compared with WT mice (WT saline). GH administration downregulated the expression of GSTK1 proteins in dwarf mice. We further investigated GST activity from liver lysates using different substrates. Substrate-specific GST activity (bromosulfophthalein, dichloronitrobenzene, and 4-hydrox-ynonenal) was significantly reduced in GH-treated dwarf mice. In addition, GH treatment attenuated the activity of thioredoxin and glutaredoxin in liver mitochondria of Ames mice. Importantly, GH treatment suppressed Trx2 and TrxR2 mRNA expression. These data indicate that GH has a role in stress resistance by altering the functional capacity of the GST system through the regulation of specific GST family members in long-living Ames dwarf mice. It also affects the regulation of thioredoxin and glutaredoxin, factors that regulate posttranslational modification of proteins and redox balance, thereby further influencing stress resistance. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Meier-Abt, F; Hammann-Hänni, A; Stieger, B; Ballatori, N; Boyer, J L
2007-02-01
Organic anion transporting polypeptides (rodent Oatp; human OATP) mediate cellular uptake of numerous organic compounds including xenobiotic toxins into mammalian hepatocytes. In the little skate Leucoraja erinacea a liver-specific Oatp (Oatp1d1, also called sOatp) has been identified and suggested to represent an evolutionarily ancient precursor of the mammalian liver OATP1B1 (human), Oatp1b2 (rat), and OATP1B3 (human). The present study tested whether Oatp1d1 shares functional transport activity of the xenobiotic oligopeptide toxins phalloidin and microcystin with the mammalian liver Oatps/OATPs. The phalloidin analogue [(3)H]-demethylphalloin was taken up into skate hepatocytes with high affinity (Km approximately 0.4 microM), and uptake could be inhibited by phalloidin and a variety of typical Oatp/OATP substrates such as bromosulfophthalein, bile salts, estrone-3-sulfate, cyclosporine A and high concentrations of microcystin-LR (Ki approximately 150 microM). When expressed in Xenopus laevis oocytes Oatp1d1 increased uptake of demethylphalloin (Km approximately 2.2 microM) and microcystin-LR (Km approximately 27 microM) 2- to 3-fold over water-injected oocytes, whereas the alternative skate liver organic anion transporter, the dimeric Ostalpha/beta, exhibited no phalloidin and only minor microcystin-LR transport. Also, the closest mammalian Oatp1d1 orthologue, the human brain and testis OATP1C1, did not show any phalloidin transport activity. These results demonstrate that the evolutionarily ancient Oatp1d1 is able to mediate uptake of cyclic oligopeptide toxins into skate liver. The findings support the notion that Oatp1d1 is a precursor of the liver-specific mammalian Oatps/OATPs and that its transport properties are closely associated with certain forms of toxic liver injury such as for example protein phosphatase inhibition by the water-borne toxin microcystin.
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International Nuclear Information System (INIS)
Meier-Abt, F.; Hammann-Haenni, A.; Stieger, B.; Ballatori, N.; Boyer, J.L.
2007-01-01
Organic anion transporting polypeptides (rodent Oatp; human OATP) mediate cellular uptake of numerous organic compounds including xenobiotic toxins into mammalian hepatocytes. In the little skate Leucoraja erinacea a liver-specific Oatp (Oatp1d1, also called sOatp) has been identified and suggested to represent an evolutionarily ancient precursor of the mammalian liver OATP1B1 (human), Oatp1b2 (rat), and OATP1B3 (human). The present study tested whether Oatp1d1 shares functional transport activity of the xenobiotic oligopeptide toxins phalloidin and microcystin with the mammalian liver Oatps/OATPs. The phalloidin analogue [ 3 H]-demethylphalloin was taken up into skate hepatocytes with high affinity (Km ∼ 0.4 μM), and uptake could be inhibited by phalloidin and a variety of typical Oatp/OATP substrates such as bromosulfophthalein, bile salts, estrone-3-sulfate, cyclosporine A and high concentrations of microcystin-LR (Ki ∼ 150 μM). When expressed in Xenopus laevis oocytes Oatp1d1 increased uptake of demethylphalloin (Km ∼ 2.2 μM) and microcystin-LR (Km ∼ 27 μM) 2- to 3-fold over water-injected oocytes, whereas the alternative skate liver organic anion transporter, the dimeric Ostα/β, exhibited no phalloidin and only minor microcystin-LR transport. Also, the closest mammalian Oatp1d1 orthologue, the human brain and testis OATP1C1, did not show any phalloidin transport activity. These results demonstrate that the evolutionarily ancient Oatp1d1 is able to mediate uptake of cyclic oligopeptide toxins into skate liver. The findings support the notion that Oatp1d1 is a precursor of the liver-specific mammalian Oatps/OATPs and that its transport properties are closely associated with certain forms of toxic liver injury such as for example protein phosphatase inhibition by the water-borne toxin microcystin
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Pharmaceutical excipients influence the function of human uptake transporting proteins.
Engel, Anett; Oswald, Stefan; Siegmund, Werner; Keiser, Markus
2012-09-04
Although pharmaceutical excipients are supposed to be pharmacologically inactive, solubilizing agents like Cremophor EL have been shown to interact with cytochrome P450 (CYP)-dependent drug metabolism as well as efflux transporters such as P-glycoprotein (ABCB1) and multidrug resistance associated protein 2 (ABCC2). However, knowledge about their influence on the function of uptake transporters important in drug disposition is very limited. In this study we investigated the in vitro influence of polyethylene glycol 400 (PEG), hydroxypropyl-β-cyclodextrin (HPCD), Solutol HS 15 (SOL), and Cremophor EL (CrEL) on the organic anion transporting polypeptides (OATP) 1A2, OATP2B1, OATP1B1, and OATP1B3 and the Na(+)/taurocholate cotransporting polypeptide (NTCP). In stably transfected human embryonic kidney cells we analyzed the competition of the excipients with the uptake of bromosulfophthalein in OATP1B1, OATP1B3, OATP2B1, and NTCP, estrone-3-sulfate (E(3)S) in OATP1A2, OATP1B1, and OATP2B1, estradiol-17β-glucuronide in OATP1B3, and taurocholate (TA) in OATP1A2 and NTCP cells. SOL and CrEL were the most potent inhibitors of all transporters with the strongest effect on OATP1A2, OATP1B3, and OATP2B1 (IC(50) < 0.01%). HPCD also strongly inhibited all transport proteins but only for substrates containing a sterane-backbone. Finally, PEG seems to be a selective and potent modulator of OATP1A2 with IC(50) values of 0.05% (TA) and 0.14% (E(3)S). In conclusion, frequently used solubilizing agents were shown to interact substantially with intestinal and hepatic uptake transporters which should be considered in drug development. However, the clinical relevance of these findings needs to be evaluated in further in vivo studies.
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Evaluation of 131I (monoiodide) BSP for Clinical Studies
International Nuclear Information System (INIS)
Lio, Masahiro; Yamada, Hideo; Iwase, Tohru; Migita, Tohru; Kameda, Haruo; Ueda, Hideo; Kato, Sadatake; Kurata, Kunio; Sato, Noboru; Ide, Kazuko; Wakebayashi, Takao
1971-01-01
In 1925 Rosenthal and White introduced a bromosulfophthalein (BSP) dye retention test as a sensitive indicator of liver function. Even now it is regarded as one of the most sensitive agents for the detection of non-icteric liver disease (liver cirrhosis, early stage of acute-hepatitis and hepatic tumor). BSP accumulates in the liver cells, conjugates with glutathione and is excreted into the bile. Therefore, a disorder in its excretion is due to a disturbance of one of these processes. Since bilirubin and BSP compete for uptake by the liver and increased serum bilirubin interferes with the colorimetric determination of BSP, it has been considered that BSP test is inappropriate for the differential diagnosis of jaundice conditions. It has been generally said that when jaundice is present, the BSP test is useless and should not be performed. In 1955, Taplin et al. labeled rose bengal, a dye similarly metabolized in the liver as BSP, with 131 I and measured the hepatic excretion of this dye by external monitoring. Laster, Blahd et al. applied this method to the determination of the peripheral pool, succeeding in the diagnosis of chronic and subacute hepatic diseases without colorimetry. In 1968, Yamada, Taplin et al. suggested the possibility of differentiating so-called medical jaundice from surgical jaundice by scanning the subjects during 24 to 48 hours following intravenous injection of 131 I-labeled rose bengal. As mentioned before, many authorities hold the opinion that BSP is not proper for the differential diagnosis of jaundice states. Some have tried to diagnose biliary tract obstruction by a malignant tumor by measuring BSP excretion into duodenal fluid and others by quantitating changes in serum levels of conjugated and free BSP. Furthermore, Burton et al. reported that in patients with extrahepatic obstructive jaundice, BSP retention was observed for 24 days after its administration. From a consideration of all these finding we came to a conclusion that
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Evaluation of {sup 131}I (monoiodide) BSP for Clinical Studies
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Lio, Masahiro; Yamada, Hideo; Iwase, Tohru; Migita, Tohru; Kameda, Haruo; Ueda, Hideo; Kato, Sadatake; Kurata, Kunio; Sato, Noboru; Ide, Kazuko; Wakebayashi, Takao [Second Department of Medicine, Tokyo University, Takyo (Japan)
1971-03-15
In 1925 Rosenthal and White introduced a bromosulfophthalein (BSP) dye retention test as a sensitive indicator of liver function. Even now it is regarded as one of the most sensitive agents for the detection of non-icteric liver disease (liver cirrhosis, early stage of acute-hepatitis and hepatic tumor). BSP accumulates in the liver cells, conjugates with glutathione and is excreted into the bile. Therefore, a disorder in its excretion is due to a disturbance of one of these processes. Since bilirubin and BSP compete for uptake by the liver and increased serum bilirubin interferes with the colorimetric determination of BSP, it has been considered that BSP test is inappropriate for the differential diagnosis of jaundice conditions. It has been generally said that when jaundice is present, the BSP test is useless and should not be performed. In 1955, Taplin et al. labeled rose bengal, a dye similarly metabolized in the liver as BSP, with {sup 131}I and measured the hepatic excretion of this dye by external monitoring. Laster, Blahd et al. applied this method to the determination of the peripheral pool, succeeding in the diagnosis of chronic and subacute hepatic diseases without colorimetry. In 1968, Yamada, Taplin et al. suggested the possibility of differentiating so-called medical jaundice from surgical jaundice by scanning the subjects during 24 to 48 hours following intravenous injection of {sup 131}I-labeled rose bengal. As mentioned before, many authorities hold the opinion that BSP is not proper for the differential diagnosis of jaundice states. Some have tried to diagnose biliary tract obstruction by a malignant tumor by measuring BSP excretion into duodenal fluid and others by quantitating changes in serum levels of conjugated and free BSP. Furthermore, Burton et al. reported that in patients with extrahepatic obstructive jaundice, BSP retention was observed for 24 days after its administration. From a consideration of all these finding we came to a