Extrapolation of Diclofenac Clearance from in Vitro Microsomal Metabolism Data: Role of Acyl Glucuronidation and Sequential Oxidative Metabolism of the Acyl Glucuronide

2002 ◽  
Vol 303 (3) ◽  
pp. 969-978 ◽  
Author(s):  
Sanjeev Kumar ◽  
Koppara Samuel ◽  
Ramaswamy Subramanian ◽  
Matthew P. Braun ◽  
Ralph A. Stearns ◽  
...  
1982 ◽  
Vol 2 (3) ◽  
pp. 355-361 ◽  
Author(s):  
Thomas J. Sick ◽  
Leif Hertz ◽  
Joseph C. LaManna ◽  
Myron Rosenthal ◽  
Allan Flaggman ◽  
...  

The role of endogenous cerebral norepinephrine (NE) as a modulator of transmembrane cation transport and energy metabolism was evaluated by monitoring extracellular potassium ion activity ([K+]o) in vivo and by measuring cortical Na+,K+-ATPase activity and oxygen consumption in vitro, Ipsilateral cortical NE was depleted by unilateral 6-hydroxydopamine (6-OHDA) lesions of the locus ceruleus (LC). The contralateral cortex was used for control measurements. NE depletion had no effect on resting levels of cortical [K+]o or on the rate of K+ removal from the extracellular space following direct cortical stimulation. There was also no effect of NE depletion on Na+,K+-ATPase activity in cortical homogenates nor on oxygen consumption of cortical slices over a wide range of K+ concentrations. These results indicate that central NE depletion does not influence movements of cortical K+ either directly through an influence on Na+,K+-ATPase activity or indirectly through effects on oxidative metabolism. It is probable, therefore, that previously described effects of NE on cortical oxidative metabolism are mediated through changes in cerebral perfusion and/or modification of substrate availability in vivo.


Author(s):  
Janet H. Woodward ◽  
D. E. Akin

Silicon (Si) is distributed throughout plant tissues, but its role in forages has not been clarified. Although Si has been suggested as an antiquality factor which limits the digestibility of structural carbohydrates, other research indicates that its presence in plants does not affect digestibility. We employed x-ray microanalysis to evaluate Si as an antiquality factor at specific sites of two cultivars of bermuda grass (Cynodon dactvlon (L.) Pers.). “Coastal” and “Tifton-78” were chosen for this study because previous work in our lab has shown that, although these two grasses are similar ultrastructurally, they differ in in vitro dry matter digestibility and in percent composition of Si.Two millimeter leaf sections of Tifton-7 8 (Tift-7 8) and Coastal (CBG) were incubated for 72 hr in 2.5% (w/v) cellulase in 0.05 M sodium acetate buffer, pH 5.0. For controls, sections were incubated in the sodium acetate buffer or were not treated.


Author(s):  
David B. Warheit ◽  
Lena Achinko ◽  
Mark A. Hartsky

There is a great need for the development of a rapid and reliable bioassay to evaluate the pulmonary toxicity of inhaled particles. A number of methods have been proposed, including lung clearance studies, bronchoalveolar lavage analysis, and in vitro cytotoxicity tests. These methods are often limited in scope inasmuch as they measure only one dimension of the pulmonary response to inhaled, instilled or incubated dusts. Accordingly, a comprehensive approach to lung toxicity studies has been developed.To validate the method, rats were exposed for 6 hours or 3 days to various concentrations of either aerosolized alpha quartz silica (Si) or carbonyl iron (CI) particles. Cells and fluids from groups of sham and dust-exposed animals were recovered by bronchoalveolar lavage (BAL). Alkaline phosphatase, LDH and protein values were measured in BAL fluids at several time points postexposure. Cells were counted and evaluated for viability, as well as differential and cytochemical analysis. In addition, pulmonary macrophages (PM) were cultured and studied for morphology, chemotaxis, and phagocytosis by scanning electron microscopy.


2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.


Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
HM Lee ◽  
TG Ahn ◽  
CW Kim ◽  
HJ An
Keyword(s):  

1999 ◽  
Vol 81 (06) ◽  
pp. 951-956 ◽  
Author(s):  
J. Corral ◽  
R. González-Conejero ◽  
J. Rivera ◽  
F. Ortuño ◽  
P. Aparicio ◽  
...  

SummaryThe variability of the platelet GP Ia/IIa density has been associated with the 807 C/T polymorphism (Phe 224) of the GP Ia gene in American Caucasian population. We have investigated the genotype and allelic frequencies of this polymorphism in Spanish Caucasians. The T allele was found in 35% of the 284 blood donors analyzed. We confirmed in 159 healthy subjects a significant association between the 807 C/T polymorphism and the platelet GP Ia density. The T allele correlated with high number of GP Ia molecules on platelet surface. In addition, we observed a similar association of this polymorphism with the expression of this protein in other blood cell types. The platelet responsiveness to collagen was determined by “in vitro” analysis of the platelet activation and aggregation response. We found no significant differences in these functional platelet parameters according to the 807 C/T genotype. Finally, results from 3 case/control studies involving 302 consecutive patients (101 with coronary heart disease, 104 with cerebrovascular disease and 97 with deep venous thrombosis) determined that the 807 C/T polymorphism of the GP Ia gene does not represent a risk factor for arterial or venous thrombosis.


Sign in / Sign up

Export Citation Format

Share Document