Blood, microdialysis

The chromatogram and bar graph show results of a study of aspirin metabolism in a rat. Aspirin is converted into salicylic acid by enzymes in the bloodstream. To measure the conversion rate, aspirin was injected into a rat and dialysate from a microdialysis probe in a vein of the rat was monitored by liquid chromatography. If you simply withdrew blood for analysis, aspirin would continue to be metabolized by enzymes in the blood. Microdialysis separates the small aspirin molecule from large enzyme molecules. 

Paez X, Hernandez L. Simultaneous brain and blood microdialysis study with a new removable venous probe. Serotonin and 5-hydroxyindolacetic acid changes after D-norfenfluramine or fluoxetine. Life Sci 1996 58(15) 1209-1221. 

Tharakan, J. P., Lucas, A., and Chau, P. C. (1986). Hybridoma growth and antibody secretion in serum-supplemented and low protein serum-fiee media. J. Immunol. Methods 94(1-2), 225-235. Verbeeck, R. K. (2000). Blood microdialysis in pharmacokinetic and drug metabolism studies. Adv. Drug Deliv. Rev. 45(2-3), 217-228. 

FIGURE 1.10 Laser-doppler flowmetry (a) and NO measurement (b) from one subject. Upon heating the subject to 39°C, at 10 min, NO production and skin blood flow increased, which instantly returned to normal upon cooling the subject at 45 min. After heat stress and cooling, ACh was administered by intra-dermal microdialysis to confirm the ability of the microelectrode to measure NO concentrations. (Reprinted with permission from the American Physiological Society [125].)... 

A microdialysis study was carried out to examine transport of oxycodone into the brain of rats [67], Oxycodone was administered by i.v. infusion, and unbound drug concentrations were monitored in both vena jugularis and striatum. Steady-state equilibrium was reached rapidly and drug levels in the two compartments declined in parallel at the end of the infusion. An unbound brain to unbound plasma ratio of 3.0 was measured which is 3- to 10-fold higher than for other opioids, and explains the similar in vivo potency of oxycodone in spite of lower receptor affinity. The authors interpret these data as de facto evidence of the existence of an as-yet unidentified transporter that carries oxycodone across the blood-brain barrier. 

Originating from the neurosciences, the microdialysis technique has been used since several years to monitor drug absorption and disposition or the levels of endogenous substances in the extracellular space of different organs and fluids, such as bone, lung, liver, brain, and blood. The method has evolved from its use in different animal species to the human microdialysis during the late 80s [35],... 

Keywords Inner blood-retinal barrier Transporter Influx transport Efflux transport Microdialysis Cell line Drug delivery... 

In Vivo Vitreous/Retina-to-Blood Efflux Transport (Microdialysis Study)... 

K. Katayama, Y. Ohshima, M. Tomi, and K. Hosoya. Application of microdialysis to evaluate the efflux transport of estradiol 17-/7 glucuronide across the rat blood-retinal barrier. J. Neurosci. Methods 156 249-256 (2006). 

Scott DO, Lunte CE. 1993. In vivo microdialysis sampling in the bile, blood, and liver of rats to study the disposition of phenol. Pharmaceutical Res 10 335-342. 

Innovative methodologies for in vivo microdialysis in immature subjects have facilitated research in multiple areas. Clinically driven experimentation on neonatal anoxia, hypoxia, or ischemia indicates that perinatal manipulations of oxygen and blood flow result in acute and chronic disruptions of neurotransmission and transmitter turnover (Chen et al., 1997 Nakajima et al, 1999 Ogasawara et al., 1999). Recently, a role for toxic free radicals in brain damage induced by prenatal infection was also delineated by in vivo microdialysis in rat pups (Cambonie et al, 2000, 2004). More subtle neonatal manipulations, such as maternal separation or periodic neonatal isolation, coupled with subsequent in... 

Benveniste H, Drejer J, Schousboe A, Diemer NH. 1987. Regional cerebral glucose phosphorylation and blood flow after insertion of a microdialysis fiber through the dorsal hippocampus in the rat. J Neurochem 49(3) 729-734. 

Yergey JA, Heyes MR 1990. Brain eicosanoid formation following acute penetration injury as studied by in vivo microdialysis. J Cereb Blood FlowMetab 10(1) 143-146. 

The use of microdialysis has enabled unbound drug concentrations to be determined in ECF, providing another measurement of penetration across the blood-brain barrier and one more closely related to activity. A review of data obtained by microdialysis [7], showed that free drug exposure in the brain is equal to or less than free drug concentration in plasma or blood, with ratios ranging from 4% for the most polar compound (atenolol) to unity for lipophilic compounds (e.g. carbamazepine). This largely supports the similar conclusions from the CSF data shown above. This relationship is illustrated in Figure 4.4. 

Somewhat surprisingly, microdialysis has also revealed that the time to maximum concentration (T ax) within the CNS is close to the Tj ax value in blood or plasma, irrespective of lipophilicity. For example, the CNS Tj ax for atenolol (log D7 4 = - 1.8) occurs at 2 min in the rat after intravenous administration [8]. In addition the rate of elimination (half-life) of atenolol and other polar agents from the CNS is similar to that in plasma or blood. The implication of these data is that poorly permeable drugs do not take longer to reach equilibrium with CNS tissue than more lipophilic agents... 

Potschka, H., M. Fedrowitz, and W. Loscher. 2002. P-Glycoprotein-mediated efflux of phenobar-bital, lamotrigine, and felbamate at the blood-brain barrier Evidence from microdialysis experiments in rats. Neurosci Lett 327 173. 

Allen DD, Yokel RA. 1992. Dissimilar aluminum and gallium permeation of the blood-brain barrier demonstrated by in vivo microdialysis. J Neurochem 58 903-908. 

MICRODIALYSIS FOR CONTROL OF BLOOD GLUCOSE AND/OR DIABETES IN HUMANS... 

A straightforward way to collect solutes from the interstitial fluid (ISF) space would be to have a semipermeable, hollow fiber, membrane-based device as originally described by Bito et al.1 Two semipermeable membrane-based devices that have been used to collect different types of analytes from various mammalian tissues include microdialysis sampling probes (catheters) and ultrafiltration probes. The heart of each of these devices is the semipermeable polymeric membrane shown in Figure 6.1. The membranes allow for collection of analytes from the ISF that are below the membrane molecular weight cutoff (MWCO). Each of these devices provides a sample that has a significantly reduced amount of protein when compared to either blood or tissue... 

Both microdialysis and ultrafiltration collection obtain analytes from a sample in the reverse direction regardless of how a normal hemodialysis membrane is used. In hemodialysis, the blood is passed through the inner fiber lumen and filtrate is then collected on the outside of the hollow fiber. When these fibers are used as microdialysis or ultrafiltration devices for collection of samples, the outside of the fiber is interfaced with the sample and the analyte is collected into the inner fiber lumen of the hollow fiber. This is important particularly for the asymmetric membranes that have their large porous support layer on the outside facing the tissue sample. 

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