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  • 1
    Electronic Resource
    Electronic Resource
    Variability in the rate of 6-mercaptopurine methylation in the erythrocytes, liver and kidney in an Italian population (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 23-29 
    Details
    ISSN: 1432-1041
    Keywords: Key words 6-Mercaptopurine ; Thiopurine methyltransferase ; Polymorphism; erythrocytes ; liver ; kidney ; newborns ; adults
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective. The polymorphism of erythrocyte thiopurine methyltransferase (TPMT) is genetically regulated as an autosomal codominant trait, and so should be congenital. Results. We tested this hypothesis by measuring TPMT activity in erythrocyte preparations from adults and newborns and observed polymorphic distribution of TPMT activity in the adult and newborn erythrocytes. The activity of TPMT was higher in red cells from the newborns than adults. The frequency distribution of TPMT activity was also investigated in the liver and kidney. In the kidney, TPMT activity fell into two subgroups, whereas in the liver the distribution pattern was more complex. The activity of TPMT in erythrocytes and liver from the same subject was correlated, but the values of only half the cases fell within the 95% confidence limits, suggesting that the control of hepatic and/or erythrocyte TPMT is multifactorial.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050155
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  • 2
    Electronic Resource
    Electronic Resource
    Catechol-O-methyltransferase: variation in enzyme activity and inhibition by entacapone and tolcapone (1998)
    Springer
    European journal of clinical pharmacology 54 (1998), S. 215-219 
    Details
    ISSN: 1432-1041
    Keywords: Key words Entacapone ; Tolcapone ; Parkinson's disease ; Methyltransferase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The aim of this investigation was to study the variation of catechol-O-methyltransferase (COMT) activity in the human liver, duodenal mucosa and renal cortex, and to investigate the inhibition of COMT by entacapone and tolcapone. This study included 87 samples of human liver, 94 samples of the duodenum and 72 samples of the renal cortex. Results: The activity of COMT was measured with 3,4-dihydroxybenzoic acid (242 μmol · l−1), the methyl acceptor substrate, and adenosyl-l-methionine (44 μmol · l−1), the methyl donor substrate. The hepatic activity of COMT activity was significantly higher in men than in women, whereas it was not sex-dependent in the duodenum or renal cortex. The activity of COMT varied 4.4-fold in the liver of men, 2.6-fold in the duodenum and 5.3-fold in the renal cortex. The median estimates of COMT activity were 577, 499, 103 and 159 pmol · min−1 · mg−1 in the liver of men and women, in the duodenum and in the renal cortex, respectively. Conclusion: Entacapone and tolcapone were powerful inhibitors of COMT and their IC50 estimates were 151 and 773 nM (P = 0.008), respectively, in the liver; consistent results were obtained with the other tissues.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050448
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  • 3
    Electronic Resource
    Electronic Resource
    Inhibition of human liver phenol sulfotransferase by nonsteroidal anti-inflammatory drugs (2000)
    Springer
    European journal of clinical pharmacology 56 (2000), S. 81-87 
    Details
    ISSN: 1432-1041
    Keywords: Key words Sulfotransferase ; Anti-inflammatory drugs ; Mefenamic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The aim of this investigation was to study the inhibition of 11 nonsteroidal anti-inflammatory drugs (NSAIDs) on the human liver phenol sulfotransferases (HL-PST) and catechol sulfotransferase (HL-CST). Methods: The activities of HL-PST and HL-CST were measured with 4 μM 4-nitrophenol and 60 μM dopamine (the sulfate acceptors) and 0.4 μM 3′-phosphoadenosine-5′-phosphosulfate [35S] (the sulfate donor). Samples of liver were obtained from five patients, aged 55–79 years, undergoing clinically indicated hepatectomy. The inhibition curves were constructed with at least five concentrations of the inhibitor. Results: With the exception of piroxicam, NSAIDs inhibited HL-PST, and the estimates of the inhibitory concentration for 50% of responses (IC50; μM) were: 0.02 (mefenamic acid), 3.7 (diflunisal), 5.4 (nimesulide), 9.5 (diclofenac), 30 (salicylic acid), 41 (ketoprofen), 74 (indomethacin), 159 (ibuprofen), 245 (ketoralac) and 473 (naproxen). With 4-nitrophenol as the variable substrate, the inhibition of salicylic acid on HL-PST was non-competitive and the Ki and Kies were 18 μM and 21 μM (n = 5; P = 0.548), respectively. HL-CST was less susceptible than HL-PST to inhibition by NSAIDs, with only five drugs inhibiting this enzyme. The IC50 estimates for these drugs (μM) were 76 (mefenamic acid), 79 (diflunisal), 103 (indomethacin), 609 (salicylic acid) and 753 (diclofenac). Conclusion: The comparison of the IC50 estimates of HL-PST with the therapeutic plasma concentrations of NSAIDs corrected for the plasma unbound fraction was consistent with the view that mefenamic acid and salicylic acid, when administered at therapeutic doses, should impair the hepatic sulfation of those compounds that are substrates of phenol sulfotransferase.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050725
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  • 4
    Electronic Resource
    Electronic Resource
    Differential inhibition of hepatic and duodenal sulfation of (−)-salbutamol and minoxidil by mefenamic acid (2000)
    Springer
    European journal of clinical pharmacology 56 (2000), S. 477-479 
    Details
    ISSN: 1432-1041
    Keywords: Key words Sulfotransferase ; Salbutamol ; Minoxidil ; Liver ; Intestine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The aim of this investigation was to determine whether mefenamic acid and salicylic acid inhibit the sulfation of (−)-salbutamol and minoxidil in the human liver and duodenum, and if so, to ascertain whether the 50% inhibitory concentration (IC50) estimates are different in the two tissues. Methods: Sulfotransferase activities were measured for 10 mM (−)-salbutamol and 5 mM minoxidil, and the concentration of 3′-phosphoadenosine-5′-phosphosulphate-[35S] was 0.4 μM. Results: The IC50 estimates for (−)-salbutamol and minoxidil sulfation of mefenamic acid were 72 ± 5.4 nM and 1.5 ± 0.6 μM (liver), respectively, and 161 ± 23 μM and 420 ± 18 μM (duodenum), respectively. The figures for the liver were significantly lower (P 〈 0.0001) than those for the duodenum. The IC50 estimates for (−)-salbutamol sulfation of salicylic acid were 93 ± 11 μM (liver) and 705 ± 19 μM (duodenum, P 〈 0.0001). Salicylic acid was a poor inhibitor of minoxidil sulfation. Conclusion: The IC50 estimates for (−)-salbutamol sulfation of mefenamic acid and salicylic acid are lower than their unbound plasma concentrations after standard dosing, suggesting that mefenamic acid and salicylic acid should inhibit the hepatic sulfation of (−)-salbutamol in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280000168
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  • 5
    Electronic Resource
    Electronic Resource
    Mycophenolic acid glucuronidation and its inhibition by non-steroidal anti-inflammatory drugs in human liver and kidney (2000)
    Springer
    European journal of clinical pharmacology 56 (2000), S. 659-664 
    Details
    ISSN: 1432-1041
    Keywords: Mycophenolic acid Mycophenolate mofetil Glucuronosyl transferase Liver Kidney
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract. Objective: The aims of this investigation were to study the glucuronidation of mycophenolic acid (MPA) in human liver and kidney and to search for a compound that inhibits MPA glucuronidation among the non-steroidal anti-inflammatory drugs (NSAIDs). Methods: A sensitive and reproducible radiometric assay was developed to measure the rate of MPA glucuronidation in human liver and kidney microsomes. The assay employed uridine 5′-diphosphate-[U-14C]-glucuronic acid (UDPGA) and MPA-glucuronide was isolated by TLC. The final concentrations of UDPGA and MPA necessary were 1 mM (liver), and MPA concentration was 0.5 mM (kidney). The inhibition of MPA glucuronidation was studied with 18 NSAIDs and tacrolimus. Results: Glucuronosyl transferase activity followed Michaelis-Menten kinetics and the K m (mean±SD; mM) was 0.31±0.06 (liver; n=5) and 0.28±0.07 (kidney; n=5; P=0.555); the Vmax (mean±SD; nmol/mg per minute) was 5.2±1.4 (liver; n=5) and 10.5±1.2 (kidney; n=5; P=0.0005). The MPA glucuronidation rates (mean±SD; nmol/min/mg) were 3.3±0.9 (liver; n=10) and 7.8±1.5 (kidney; n=10; P=0.0002). The rate of MPA glucuronidation ranged between 2.0 and 5.1 nmol/mg per minute with a 2.5-fold variation (liver) and between 5.7 and 9.8 nmol/mg per minute with a 1.7-fold variation (kidney). The inhibition study was performed in liver and revealed that the percentage of control ranged from 8%±3% (niflumic acid) to 119%±16% (Ketoralac). The inhibition curves for MPA glucuronidation rate were determined with the four most effective inhibitors: niflumic acid, flufenamic acid, mefenamic acid and diflunisal. Their IC50 estimates (µM) were 8±1, 19±9, 63±8 and 109±15, respectively (liver), and 8±2, 13±2, 49±4 and 122±18, respectively (kidney). The IC50 estimate for niflumic acid was eightfold lower than the peak plasma levels after a single oral dose of 250 mg of this drug. Conclusion: The human liver and kidney are important sites of MPA glucuronidation. MPA glucuronidation was inhibited to various extents by different NSAIDs and the four most effective inhibitors were niflumic acid, flufenamic acid, mefenamic acid and diflunisal. These drugs have similar molecular structures consisting of two aromatic rings bearing a carboxylic group.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280000227
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  • 6
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    Molecular and cellular signatures of human vaccine adjuvants (2008)
    National Academy of Sciences
    Details
    Publication Date: 2008-07-23
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 7
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    Coxsackie B4 virus infection of beta cells and natural killer cell insulitis in recent-onset type 1 diabetic patients (2007)
    National Academy of Sciences
    Details
    Publication Date: 2007-03-14
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 8
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    Petrological constraints on the tectonic setting of the Kathmandu Nappe in the Langtang–Gosainkund–Helambu regions, central Nepal Himalaya (2016)
    Wiley
    Details
    Publication Date: 2016-08-20
    Description: The Gosainkund–Helambu region in central Nepal occupies a key area for the development of Himalayan kinematic models, connecting the well-investigated Langtang area to the north with the Kathmandu Nappe, whose interpretation is still debated, to the south. In order to understand the structural and metamorphic architecture of the Greater Himalayan Sequence (GHS) in this region, a detailed petrological study was performed, focusing on selected metapelite samples from both the Gosainkund–Helambu and Langtang transects. The structurally lowest sample investigated belongs to the Lesser Himalayan Sequence (LHS); its metamorphic evolution is characterized by a narrow hairpin P–T path with peak P–T conditions of 595 ± 25 °C, 7.5 ± 1 kbar. All of the other samples here investigated belong to the GHS. Along the Langtang section, two tectono-metamorphic units have been distinguished within the GHS: the Lower Greater Himalayan Sequence (L–GHS), characterized by peak P–T conditions at 728 ± 11 °C, 10 ± 0.5 kbar (corresponding to a T/ depth ratio of 22 ± 1 °C km −1 ), and the structurally higher Upper Greater Himalayan Sequence (U–GHS), with peak metamorphic conditions at 780 ± 20 °C, 7.8 ± 0.8 kbar (corresponding to a T/ depth ratio of 31 ± 4 °C km −1 ). This confirms the existence of a main tectono-metamorphic discontinuity within the GHS, as previously suggested by other authors. The results of petrological modelling of the metapelites from the Gosainkund–Helambu section show that this region is entirely comprised within a sub-horizontal and thin L–GHS unit: the estimated peak metamorphic conditions of 734 ± 19 °C, 10 ± 0.8 kbar correspond to a uniform T/ depth ratio of 23 ± 3 °C km −1 . The metamorphic discontinuity identified along the Langtang transect and dividing the GHS in two tectono-metamorphic units is located at a structural level too high to be intersected along the Gosainkund–Helambu section. Our results have significant implications for the interpretation of the Kathmandu Nappe (KN) and provide a contribution to the more general discussion of the Himalayan kinematic models. We demonstrate that the structurally lower unit of the KN (known as Sheopuri Gneiss) can be correlated to the L–GHS unit; this result strongly supports those models that correlate the KN to the Tethyan Sedimentary Sequence (TSS) and that suggest the merging of the South Tibetan Detachment System and the Main Central Thrust on the northern side of the KN. Moreover we speculate that, in this sector of the Himalayan chain, the most appropriate kinematic model able to explain the observed tectono-metamorphic architecture of the GHS is the duplexing model, or hybrid models which combine the duplexing model with another end-member model. This article is protected by copyright. All rights reserved.
    Print ISSN: 0263-4929
    Electronic ISSN: 1525-1314
    Topics: Geosciences
    Published by Wiley
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  • 9
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    The gas isotope interpretation tool: A novel method to better predict production decline (2017)
    American Association of Petroleum Geologists (AAPG)
    Details
    Publication Date: 2017-08-16
    Description: Production decline prediction is important to understand the performance and life span of oil and gas wells. The most common prediction method is decline curve fitting based on available production rate data. Such data are fit with different equations that extrapolate to future time. However, the parameters are commonly poorly constrained, especially when the production rate data are limited. In this study, we establish a novel gas isotope interpretation tool to better predict the resource quantity and life span of producing gas wells. This tool is based on the evolution of methane carbon isotope ratios ( 13 C1) caused by different gas-releasing processes during production. It requires (1) real-time methane carbon isotope ratio data, (2) continuous gas production rate data for a certain period of time, and (3) basic geological and engineering conditions. We successfully applied the production decline prediction tool to a producing shale gas well in the Barnett Shale. We obtained real-time 13 C1 data for approximately 1 yr using our proprietary, field-deployable gas chromatography–infrared isotope ratio analyzer. The prediction in this well from the isotope method showed a total reserve of up to 7.34–7.75 BCF (2.07–2.19 x 10 8 m 3 ), which was used to constrain the production decline trend of the study well. The measured production rate data were first fit using the Arps equation, which then joined to an exponential decline curve smoothly at approximately 10 yr, such that the cumulative production calculation from integration of the product rate curve equaled to the total reserve predicted by the isotope method. The novel production decline prediction method thus provided important constraint on the future well production and expected ultimate recoverable reserves.
    Print ISSN: 0149-1423
    Electronic ISSN: 0149-1423
    Topics: Geosciences
    Published by American Association of Petroleum Geologists (AAPG)
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  • 10
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    Inhibition of human liver phenol sulfotransferase by nonsteroidal anti-inflammatory drugs (2000)
    Springer
    Details
    Publication Date: 2000-04-26
    Print ISSN: 0031-6970
    Electronic ISSN: 1432-1041
    Topics: Chemistry and Pharmacology , Medicine
    Published by Springer
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