Pharmacokinetics of different doses of methotrexate at steady state by in situ microdialysis in a rat model

1995 ◽  
Vol 36 (4) ◽  
pp. 283-289 ◽  
Author(s):  
Per O. Ekstr�m ◽  
Anders Andersen ◽  
David J. Warren ◽  
Karl E. Giercksky ◽  
L. Sl�rdal
1995 ◽  
Vol 36 (4) ◽  
pp. 283-289 ◽  
Author(s):  
Per O. Ekstr�m ◽  
Anders Andersen ◽  
David J. Warren ◽  
Karl E. Giercksky ◽  
Lars Sl�rdal

2000 ◽  
Vol 118 (4) ◽  
pp. A412
Author(s):  
Atsushi Takahashi ◽  
Takeshi Tomomasa ◽  
Hiroaki Kaneko ◽  
Toshio Watanabe ◽  
Masahiko Tabata ◽  
...  

2017 ◽  
Vol 45 (08) ◽  
pp. 1745-1759 ◽  
Author(s):  
Xin He ◽  
Zi-Jing Song ◽  
Cui-Ping Jiang ◽  
Chun-Feng Zhang

The flower bud of Daphne genkwa (Genkwa Flos) is a commonly used herbal medicine in Asian countries. Luteolin and apigenin are two recognized active flavonoids in Genkwa Flos. The aim of this study was to investigate the intestinal absorption mechanisms of Genkwa Flos flavonoids using in situ single-pass intestinal perfusion rat model. Using HPLC, we determined its major effective flavonoids luteolin, apigenin, as well as, hydroxygenkwanin and genkwanin in biological samples. The intestinal absorption mechanisms of the total flavonoids in Genkwa Flos (TFG) were investigated using in situ single-pass intestinal perfusion rat model. Comparing the TFG absorption rate in different intestinal segments, data showed that the small intestine absorption was significantly higher than that of the colon ([Formula: see text]). Compared with duodenum and ileum, the jejunum was the best small intestinal site for TFG absorption. The high TFG concentration (61.48[Formula: see text][Formula: see text]g/ml) yielded the highest permeability ([Formula: see text]). Subsequently, three membrane protein inhibitors (verapamil, pantoprazole and probenecid) were used to explore the TFG absorption pathways. Data showed probenecid, a multidrug resistance protein (or MRP) inhibitor, effectively enhanced the TFG absorption ([Formula: see text]). Furthermore, by comparing commonly used natural absorption enhancers on TFG, it was observed that camphor was the most effective. In Situ single-pass intestinal perfusion experiment shows that TFG absorption is much higher in the small intestine than in the colon, and the TFG is absorbed mainly via an active transport pathway with MRP-mediated efflux mechanism. Camphor obviously enhanced the TFG absorption, and this could be an effective TFG formulation preparation method to increase clinical effectiveness after Genkwa Flos administration. Our study elucidated the TFG absorption mechanisms, and provided new information for its formulation preparation.


Carbon ◽  
2017 ◽  
Vol 116 ◽  
pp. 766-776 ◽  
Author(s):  
Frederik Ossler ◽  
Louis J. Santodonato ◽  
Hassina Z. Bilheux

2011 ◽  
Vol 8 (5) ◽  
pp. 1333-1350 ◽  
Author(s):  
U. Gamnitzer ◽  
A. B. Moyes ◽  
D. R. Bowling ◽  
H. Schnyder

Abstract. The carbon isotopic composition (δ13C) of CO2 efflux (δ13Cefflux) from soil is generally interpreted to represent the actual isotopic composition of the respiratory source (δ13CRs). However, soils contain a large CO2 pool in air-filled pores. This pool receives CO2 from belowground respiration and exchanges CO2 with the atmosphere (via diffusion and advection) and the soil liquid phase (via dissolution). Natural or artificial modification of δ13C of atmospheric CO2 (δ13Catm) or δ13CRs causes isotopic disequilibria in the soil-atmosphere system. Such disequilibria generate divergence of δ13Cefflux from δ13CRs (termed "disequilibrium effect"). Here, we use a soil CO2 transport model and data from a 13CO2/12CO2 tracer experiment to quantify the disequilibrium between δ13Cefflux and δ13CRs in ecosystem respiration. The model accounted for diffusion of CO2 in soil air, advection of soil air, dissolution of CO2 in soil water, and belowground and aboveground respiration of both 12CO2 and 13CO2 isotopologues. The tracer data were obtained in a grassland ecosystem exposed to a δ13Catm of −46.9 ‰ during daytime for 2 weeks. Nighttime δ13Cefflux from the ecosystem was estimated with three independent methods: a laboratory-based cuvette system, in-situ steady-state open chambers, and in-situ closed chambers. Earlier work has shown that the δ13Cefflux measurements of the laboratory-based and steady-state systems were consistent, and likely reflected δ13CRs. Conversely, the δ13Cefflux measured using the closed chamber technique differed from these by −11.2 ‰. Most of this disequilibrium effect (9.5 ‰) was predicted by the CO2 transport model. Isotopic disequilibria in the soil-chamber system were introduced by changing δ13Catm in the chamber headspace at the onset of the measurements. When dissolution was excluded, the simulated disequilibrium effect was only 3.6 ‰. Dissolution delayed the isotopic equilibration between soil CO2 and the atmosphere, as the storage capacity for labelled CO2 in water-filled soil pores was 18 times that of soil air. These mechanisms are potentially relevant for many studies of δ13CRs in soils and ecosystems, including FACE experiments and chamber studies in natural conditions. Isotopic disequilibria in the soil-atmosphere system may result from temporal variation in δ13CRs or diurnal changes in the mole fraction and δ13C of atmospheric CO2. Dissolution effects are most important under alkaline conditions.


2005 ◽  
Vol 288 (3) ◽  
pp. L536-L545 ◽  
Author(s):  
Jackeline Agorreta ◽  
Javier J. Zulueta ◽  
Luis M. Montuenga ◽  
Mercedes Garayoa

Adrenomedullin (ADM) is upregulated independently by hypoxia and LPS, two key factors in the pathogenesis of acute lung injury (ALI). This study evaluates the expression of ADM in ALI using experimental models combining both stimuli: an in vivo model of rats treated with LPS and acute normobaric hypoxia (9% O2) and an in vitro model of rat lung cell lines cultured with LPS and exposed to hypoxia (1% O2). ADM expression was analyzed by in situ hybridization, Northern blot, Western blot, and RIA analyses. In the rat lung, combination of hypoxia and LPS treatments overcomes ADM induction occurring after each treatment alone. With in situ techniques, the synergistic effect of both stimuli mainly correlates with ADM expression in inflammatory cells within blood vessels and, to a lesser extent, to cells in the lung parenchyma and bronchiolar epithelial cells. In the in vitro model, hypoxia and hypoxia + LPS treatments caused a similar strong induction of ADM expression and secretion in epithelial and endothelial cell lines. In alveolar macrophages, however, LPS-induced ADM expression and secretion were further increased by the concomitant exposure to hypoxia, thus paralleling the in vivo response. In conclusion, ADM expression is highly induced in a variety of key lung cell types in this rat model of ALI by combination of hypoxia and LPS, suggesting an essential role for this mediator in this syndrome.


1993 ◽  
Vol 264 (6) ◽  
pp. C1395-C1400 ◽  
Author(s):  
L. E. Costa ◽  
S. Llesuy ◽  
A. Boveris

The spontaneous in situ liver chemiluminescence of female rats submitted to 4,400 m (simulated altitude) for 2 mo and of their corresponding controls at sea level was determined as an approach to the measurement of the intracellular steady-state concentrations of singlet oxygen and oxygen free radicals. Spontaneous liver chemiluminescence was decreased by approximately 40% in hypoxic rats, whereas CCl4-induced chemiluminescence was unchanged. Liver mitochondria isolated from hypoxic rats showed a 53% decreased rate of H2O2 production and an increased content of cytochrome b (36%), with normal content of cytochromes c1, c, and a-a3. Superoxide dismutase showed a 26% decrease in activity, whereas catalase and glutathione peroxidase activities were not significantly decreased by this extent of hypoxia. Cytochrome P-450 and glutathione contents were unchanged. There were no significant differences in the hydroperoxide-initiated chemiluminescence (an estimation of tissue chain-breaker antioxidants) of homogenates, mitochondria, and microsomes. Results suggest that in chronic hypoxia there is a lower rate of generation of active oxygen species in liver, leading to a decreased steady-state concentration of singlet oxygen.


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