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  • 1
    Electronic Resource
    Electronic Resource
    s.l. ; Stafa-Zurich, Switzerland
    Advanced materials research Vol. 15-17 (Feb. 2006), p. 65-70 
    ISSN: 1662-8985
    Source: Scientific.Net: Materials Science & Technology / Trans Tech Publications Archiv 1984-2008
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: The aim of this report was to investigate the behavior of human mesenchymal stem cells(hMSCs) when cultured on different porous 3D scaffolds, having natural or synthetic origination.Natural scaffolds were obtained by hand made processing of human bone tissue (allograft), becauseits well known osteoconductive features, using different procedures to eliminate the donor cellularphase. Cancellous bone was frozen, heated or demineralized before being loaded with hMSCs.Among the variety of synthetic materials, biodegradable polymeric spongy matrices were chosenand comparatively tested as scaffolds for hMSCs growth
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  • 2
    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.
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  • 3
    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.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 56 (2000), S. 81-87 
    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.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 56 (2000), S. 477-479 
    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.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 56 (2000), S. 659-664 
    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.
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  • 7
    ISSN: 1572-9648
    Keywords: Biological structures ; Cardiac mechanics ; Gardenhose effect ; Biomechanics.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract A structural model of the left ventricle is presented. It is a cylindricalthick-walled model composed of muscle fibre models and coronaryvessel models. The ventricular wall is divided in ten layers to accountfor the transmural variation of myofibre and coronary vessel orientation.These structures give the global performance of the ventricular modeldepending on their own behaviour and on the way they are interfaced. The results refer both to the global ventricular performance and thebehaviour of the different components. In particular they suggest anappreciable contribute of the coronary capillary during the early fillingphase in enlarging the ventricle; during this phase the capillary vesselsexert an extensive force in the radial direction, due to inner coronarypressure, equal to 20--30 percent -- depending on the layer -- of the forceexerted by the fibres. This occurrence explains, in our opinion, theobserved cardiac function improvement when the arterial coronarypressure is increased, known as ’gardenhose‘ effect.
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  • 8
    Publication Date: 1980-06-01
    Print ISSN: 0008-0624
    Electronic ISSN: 1126-5434
    Topics: Mathematics
    Published by Springer
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  • 9
    Publication Date: 2009-11-01
    Print ISSN: 0016-0032
    Electronic ISSN: 1879-2693
    Topics: Mathematics , Technology
    Published by Elsevier
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  • 10
    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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