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Extraction Ratio (extraction + ratio)
Selected AbstractsBNP and N-terminal proBNP are both extracted in the normal kidneyEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2006J. P. Goetze Abstract Background, Increased plasma concentrations of cardiac-derived B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (proBNP) are both associated with left ventricular dysfunction. Information on the regional elimination of the peptides is, however, still scarce. We therefore examined the renal and peripheral extraction of N-terminal proBNP and BNP. Materials and methods, The study comprised 18 patients with essential arterial hypertension, 51 with cirrhosis, and 18 control patients without kidney or liver disease. All patients underwent a haemodynamic investigation with catheterization of the femoral artery and femoral and renal veins. Blood sampling from the catheters allowed determination of the arteriovenous extraction ratio of N-terminal proBNP and BNP. Results, Neither the peripheral N-terminal proBNP (13, 11, 19 pmol L,1, NS) nor the BNP plasma concentrations (4, 12, 9 pmol L,1, NS) differed between the patient groups. In addition, similar renal extractions were observed in the groups. The renal extraction of N-terminal proBNP (0·16) was not different from that of BNP (0·16). In contrast, the N-terminal proBNP extraction in the lower extremity was markedly lower compared with BNP (0·00 vs. 0·125, P = 0·007). Conclusions, A comparable renal elimination of N-terminal proBNP and BNP is contrasted by a selective extraction of BNP in the lower extremity. Our results suggest a different elimination mechanism in the renal and peripheral circulation, which partly may explain the higher N-terminal proBNP compared with BNP concentrations in normal plasma. [source] Sex differences in cerebral injury after severe haemorrhage and ventricular fibrillation in pigsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2010E. SEMENAS Background: Experimental studies of haemorrhagic shock have documented a superior haemodynamic response and a better outcome in female animals as compared with male controls. Such sexual dimorphism has, nevertheless, not been reported after circulatory arrest that follows exsanguination and shock. We aimed to study differences in cerebral injury markers after exsanguination cardiac arrest in pre-pubertal piglets. The hypothesis was that cerebral injury is less extensive in female animals, and that this difference is independent of sexual hormones or choice of resuscitative fluid. Methods: Thirty-two sexually immature piglets (14 males and 18 females) were subjected to 5 min of haemorrhagic shock followed by 2 min of ventricular fibrillation and 8 min of cardiopulmonary resuscitation, using three resuscitation fluid regimens (whole blood, hypertonic saline and dextran, or acetated Ringers' solution plus whole blood and methylene blue). Haemodynamic values, cellular markers of brain injury and brain histology were studied. Results: After successful resuscitation, female piglets had significantly greater cerebral cortical blood flow, tended to have lower S-100, values and a lower cerebral oxygen extraction ratio. Besides, in female animals, systemic and cerebral venous acidosis were mitigated. Female piglets exhibited a significantly smaller increase in neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) expression in their cerebral cortex, smaller blood,brain-barrier (BBB) disruption and significantly smaller neuronal injury. Conclusion: After resuscitation from haemorrhagic circulatory arrest, cerebral reperfusion is greater, and BBB permeability and neuronal injury is smaller in female piglets. An increased cerebral cortical iNOS and nNOS expression in males implies a mechanistic relationship with post-resuscitation neuronal injury and warrants further investigation. [source] EFFECT OF PENTOSANASE ON DOUGH AND BREAD PROPERTIES PRODUCED BY DIFFERENT TYPES OF FLOURSJOURNAL OF FOOD QUALITY, Issue 2 2008ÖZKAN KOYUNCU ABSTRACT The effects of pentosanase at different doses (20, 60 and 100 ppm) on physical dough properties and bread quality were studied using three types of wheat flours. Flour A was a regular bread flour, flour B had a high hardness ratio and protein content, and flour C was prepared from the same blend of flour A but had a high extraction ratio. Regarding farinograph data, water absorption values of the high extraction (86%) flour C and high hardness (65%) blend flour B increased with introduction of pentosanase. Extensibility values of the flours increased moderately with pentosanase addition, while resistance and energy values decreased. The volume of breads made with flours C and B decreased upon addition of pentosanase. But loaf volume of breads prepared with regular bread flour A with 50% hardness and 76% extraction rate increased with high levels of pentosanase addition. In conclusion, flour A as a regular bread flour gave satisfactory results with pentosanase supplementations, whereas the harder-blend (65%) and higher-extraction-rate (85%) flours from the same cultivars did not. PRACTICAL APPLICATIONS Pentosanase addition was more effective on soluble pentosans than on insoluble ones. Because of these effects, it enhanced the bread-making properties of regular flour more effectively than those of the high-extraction and harder-blend flours of the same cultivars. [source] Selective extraction of organic compounds from transesterification reaction mixtures by using ionic liquidsAICHE JOURNAL, Issue 5 2010F. J. Hernández-Fernández Abstract In this article, we describe assays carried out to determine the suitability of 13 ionic liquids based on 1- n -alkyl-3-methylimidazolium and n -alkylpyridinium cations and a wide range of anions (hexafluorophophate, bis{(trifluoromethyl)sulfonyl}imide, tetrafluoroborate, methylsulfate, 2(2-methoxyethoxy)ethylsulfate, ethylsulfate, n -octylsulfate, dicyanamide, nitrate, tetrafluoroborate and chloride) to carry out the selective separation of the organic compounds involved in a transesterification reaction (butyl butyrate, vinyl butyrate, 1-butanol, and butyric acid) from hexane solutions. The assayed ionic liquids were shown to be suitable solvents for the selective separation of the target compounds, the extraction process being controlled by the hydrophobicity of the compounds. The anion composition of the ionic liquid was seen to strongly influence the average extraction ratio, the highest value being reached with the chloride-based ionic liquid. As regards the cation composition of the ionic liquids, it was seen that the average distribution ratio increased with decreasing length of alkyl chain. © 2010 American Institute of Chemical Engineers AIChE J, 2010 [source] Metabolism and disposition of resveratrol in the isolated perfused rat liver: Role of Mrp2 in the biliary excretion of glucuronidesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2008Alexandra Maier-Salamon Abstract In this study, the hepatic metabolism and transport system for resveratrol was examined in isolated perfused livers from Wistar and Mrp2-deficient TR, rats. Based on extensive metabolism to six glucuronides and sulfates (M1,M6), the hepatic extraction ratio and clearance of resveratrol was very high in Wistar and TR, rats (E: 0.998 vs. 0.999; Cl: 34.9 mL/min vs. 36.0 mL/min). However, biliary excretion and efflux of conjugates differs greatly in TR, rats. While cumulative biliary excretion of the glucuronides M1, M2, M3, and M5 dropped dramatically to 0,6%, their efflux into perfusate increased by 3.6-, 1.8-, 2.5-, and 1.5-fold. In contrast, biliary secretion of the sulfates M4 and M6 was partially maintained in the Mrp2-deficient rats (61% and 39%) with a concomitant decline of their efflux into perfusate by 33.2% and 78.1%. This indicates that Mrp2 exclusively mediates the biliary excretion of resveratrol glucuronides but only partly that of sulfates. Cumulative secretion of unconjugated resveratrol into bile of TR, rats was only reduced by 40%, and into perfusate by 19%, suggesting only a minor role of Mrp2 in resveratrol elimination. In summary, resveratrol was dose-dependently metabolized to several conjugates whereby the canalicular transporter Mrp2 selectively mediated the biliary excretion of glucuronides. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:1615,1628, 2008 [source] Prediction of human pharmacokinetics,gut-wall metabolismJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2007Urban Fagerholm Intestinal mucosal cells operate with different metabolic and transport activity, and not all of them are involved in drug absorption and metabolism. The fraction of these cells involved is dependent on the absorption characteristics of compounds and is difficult to predict (it is probably small). The cells also appear comparably impermeable. This shows a limited applicability of microsome intrinsic clearance (CLint)-data for prediction of gut-wall metabolism, and the difficulty to predict the gut-wall CL (CLGW) and extraction ratio (EGW). The objectives of this review were to evaluate determinants and methods for prediction of first-pass and systemic EGW and CLGW in man, and if required and possible, develop new simple prediction methodology. Animal gut-wall metabolism data do not appear reliable for scaling to man. In general, the systemic CLGW is low compared with the hepatic CL. For a moderately extracted CYP3A4-substrate with high permeability, midazolam, the gut-wall/hepatic CL-ratio is only 1/35. This suggests (as a general rule) that systemic CLGW can be neglected when predicting the total CL. First-pass EGW could be of importance, especially for substrates of CYP3A4 and conjugating enzymes. For several reasons, including those presented above and that blood flow based models are not applicable in the absorptive direction, it seems poorly predicted with available methodology. Prediction errors are large (several-fold on average; maximum-15-fold). A new simple first-pass EGW -prediction method that compensates for regional and local differences in absorption and metabolic activity has been developed. It has been based on human cell in-vitro CLint and fractional absorption from the small intestine for reference (including verapamil) and test substances, and in-vivo first-pass EGW -data for reference substances. First-pass EGW -values for CYP3A4-substrates with various degrees of gastrointestinal uptake and CLint and a CYP2D6-substrate were well-predicted (negligible errors). More high quality in-vitro CLint - and in-vivo EGW -data are required for further validation of the method. [source] The effects of the phytoestrogenic isoflavone genistein on the hepatic disposition of preformed and hepatically generated gemfibrozil 1- O -acyl glucuronide in the isolated perfused rat liverJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2003Anthony N. Lucas ABSTRACT Foods and complementary medicines contain phytoestrogenic isoflavones such as genistein, which undergo hepatic glucuronidation and excretion into bile and can potentially interfere with the hepatic elimination of other compounds. To investigate this potential, livers from Sprague-Dawley rats were perfused in single-pass mode with preformed gemfibrozil 1- O -acyl glucuronide (GG) (1 ,M, n = 12) for 60 min followed by a 30-min washout phase, or with gemfibrozil (1 ,M n = 10) for 120 min. Half of each group of livers were co-perfused with genistein (10 ,M) throughout the experiment. Perfusate and bile were analyzed for GG and gemfibrozil by HPLC. Co-perfusion with genistein significantly (P < 0.05) decreased the biliary extraction ratio of preformed GG from a mean of 0.82 to 0.65 and the first-order rate constant for transport of GG into bile from 0.054 + 0.010 to 0.032 + 0.008 min,1, but increased the first-order rate constant for sinusoidal efflux of GG from 0.128 + 0.023 to 0.227 + 0.078 min,1. Co-perfusion with genistein also significantly decreased the biliary extraction ratio of hepatically generated GG from 0.95 + 0.01 to 0.83 + 0.05. The findings confirm that genistein increases the potential for hepatic and systemic exposure to hepatically generated glucuronides, which may be important for patients on conventional drugs who consume isoflavones. [source] Neurological outcome after experimental cardiopulmonary resuscitation: a result of delayed and potentially treatable neuronal injury?ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2002X. L. Liu Background: In experimental cardiopulmonary resuscitation (CPR) aortic balloon occlusion, vasopressin, and hypertonic saline dextran administration improve cerebral blood flow. Free radical scavenger ,-phenyl-N-tert-butyl-nitrone (PBN) and cyclosporine-A (CsA) alleviate neuronal damage after global ischemia. Combining these treatments, we investigated neurological outcome after experimental cardiac arrest. Methods: Thirty anesthetized piglets, randomly allocated into three groups, were subjected to 8 min of ventricular fibrillation followed by 5 min of closed-chest CPR. The combined treatment (CT) group received all the above-mentioned modalities; group B was treated with balloon occlusion and epinephrine; and group C had sham balloon occlusion with epinephrine. Indicators of oxidative stress (8-iso-PGF2,), inflammation (15-keto-dihydro-PGF2,), energy crisis (hypoxanthine and xanthine), and anoxia/hypoxia (lactate) were monitored in jugular bulb venous blood. Neurological outcome was evaluated 24 h after CPR. Results: Restoration of spontaneous circulation (ROSC) was more rapidly achieved and neurological outcome was significantly better in the CT group, although there was no difference in coronary perfusion pressure between groups. The jugular venous PCO2 and cerebral oxygen extraction ratio were lower in the CT group at 5,15 min after ROSC. Jugular venous 8-iso-PGF2, and hypoxanthine after ROSC were correlated to 24 h neurological outcome Conclusions: A combination of cerebral blood flow promoting measures and administration of ,-phenyl-N-tert-butyl-nitrone and cyclosporine-A improved 24 h neurological outcome after 8 min of experimental normothermic cardiac arrest, indicating an ongoing neuronal injury in the reperfusion phase. [source] Switchgrass leaching requirements for solid-state fermentation by Acidothermus cellulolyticusBIOTECHNOLOGY PROGRESS, Issue 3 2010Jean S. VanderGheynst Abstract Growth of Acidothermus cellulolyticus in solid-state fermentation and its required growth conditions were investigated in this study. Extraction of switchgrass was required for growth. Under the experimental conditions, extraction ratio had the most significant effect on the growth of A. cellulolyticus. Heat treatment (in the form of autoclaving) of switchgrass did not have a significant effect on the growth rate; however, longer heat treatment times had a negative effect on the total growth. Moisture content adjustment had no effect on the release of inhibitors into extracts. Our results showed that leaching at a minimum 40:1 (gram water: gram dry biomass) removed inhibitory compound(s) from switchgrass. Upon extraction A. cellulolyticus colonized switchgrass in solid fermentation without exogenous addition of carbon and nitrogen sources. It is the first demonstration of growth of A. cellulolyticus in solid fermentation. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010 [source] Exercise capacity and cardiovascular changes in patients with ,-thalassaemia majorCLINICAL PHYSIOLOGY AND FUNCTIONAL IMAGING, Issue 6 2006Filippo Tocco Summary Despite the introduction of deferoxamine, 50% of thalassaemia major patients die before the age of 35 years predominantly from iron induced heart failure. Indeed, the assessment of myocardial performance may be of particular interest since it can reveal an early myocardial dysfunction. By using impedance cardiography and mass spectrometry, we studied the cardiac function and the oxygen extraction ratio (O2ER) of 14 thalassaemic patients and 15 control healthy subjects during an incremental cycle-ergometer test. The achieved mechanical power output and the relative O2 uptake did not reach any significant difference between groups. At the highest workload, O2ER reached significantly higher values in thalassaemic patients versus control subjects while the relationship between cardiac index (CI) and O2ER (CI/O2ER) decreased showing a lower contribution of cardiovascular system to maintain O2 uptake. Results of this study imply that CI/O2ER allows an early diagnosis of the iron induced myocardial dysfunction, whereas it is not clinically patent yet. To our knowledge, this is the first study revealing an O2ER pivotal role as compensatory mechanism to maintain a normal working capacity in subjects suffering from thalassaemia major. [source] In Vitro,Potential of,Ascophyllum nodosum,Phenolic Antioxidant-Mediated ,-Glucosidase and ,-Amylase InhibitionJOURNAL OF FOOD SCIENCE, Issue 3 2010E. Apostolidis ABSTRACT:,Ascophyllum nodosum,is a brown seaweed that grows abundantly in the Northeast coastal region. In this study, the potential of,A. nodosum,for type 2 diabetes management through antioxidant-mediated ,-glucosidase and ,-amylase inhibition was investigated. After the initial screening of 4 locally harvested seaweeds,,A. nodosum,was chosen for its highest phenolic content and was subjected to water extraction. Among extraction ratios of 50 g to 100 to 1000 mL at room temperature, 50 g/400 mL yielded the highest phenolic content of 4.5 mg/g wet weight. For evaluation of extraction temperature ranging from 20 to 80 °C, 50 g/400 mL was chosen as a minimum amount of extractant. Among temperatures studied, extraction at 80 °C resulted in the highest total phenolic contents (4.2 mg/g wet weight). All extracts had similar levels of antioxidant activity in the range of 60% to 70% in terms of 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity. The 80 °C extract had the highest ,-glucosidase and ,-amylase inhibitory activity with IC50 of 0.24 and 1.34 ,g phenolics, respectively, compared to the IC50 of acarbose, reference inhibitor, being 0.37 and 0.68 ,g. The results show that fresh,A. nodosum,has strong ,-glucosidase and mild ,-amylase inhibitory activities that correlated with phenolic contents. This study suggests a nutraceutical potential of,A. nodosum,based on phytochemical antioxidant and antihyperglycemia activities. [source] Pharmacokinetics of drugs in rats with diabetes mellitus induced by alloxan or streptozocin: comparison with those in patients with type I diabetes mellitusJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2010Joo H. Lee Abstract Objectives In rats with diabetes mellitus induced by alloxan (DMIA) or streptozocin (DMIS), changes in the cytochrome P450 (CYP) isozymes in the liver, lung, kidney, intestine, brain, and testis have been reported based on Western blot analysis, Northern blot analysis, and various enzyme activities. Changes in phase II enzyme activities have been reported also. Hence, in this review, changes in the pharmacokinetics of drugs that were mainly conjugated and metabolized via CYPs or phase II isozymes in rats with DMIA or DMIS, as reported in various literature, have been explained. The changes in the pharmacokinetics of drugs that were mainly conjugated and mainly metabolized in the kidney, and that were excreted mainly via the kidney or bile in DMIA or DMIS rats were reviewed also. For drugs mainly metabolized via hepatic CYP isozymes, the changes in the total area under the plasma concentration,time curve from time zero to time infinity (AUC) of metabolites, AUCmetabolite/AUCparent drug ratios, or the time-averaged nonrenal and total body clearances (CLNR and CL, respectively) of parent drugs as reported in the literature have been compared. Key findings After intravenous administration of drugs that were mainly metabolized via hepatic CYP isozymes, their hepatic clearances were found to be dependent on the in-vitro hepatic intrinsic clearance (CLint) for the disappearance of the parent drug (or in the formation of the metabolite), the free fractions of the drugs in the plasma, or the hepatic blood flow rate depending on their hepatic extraction ratios. The changes in the pharmacokinetics of drugs that were mainly conjugated and mainly metabolized via the kidney in DMIA or DMIS rats were dependent on the drugs. However, the biliary or renal CL values of drugs that were mainly excreted via the kidney or bile in DMIA or DMIS rats were faster. Summary Pharmacokinetic studies of drugs in patients with type I diabetes mellitus were scarce. Moreover, similar and different results for drug pharmacokinetics were obtained between diabetic rats and patients with type I diabetes mellitus. Thus, present experimental rat data should be extrapolated carefully in humans. [source] | |||||||||||||