Demonstration microdialysis

Histamine is synthesised by decarboxylation of histidine, its amino-acid precursor, by the specific enzyme histidine decarboxylase, which like glutaminic acid decarboxylase requires pyridoxal phosphate as co-factor. Histidine is a poor substrate for the L-amino-acid decarboxylase responsible for DA and NA synthesis. The synthesis of histamine in the brain can be increased by the administration of histidine, so its decarboxylase is presumably not saturated normally, but it can be inhibited by a fluoromethylhistidine. No high-affinity neuronal uptake has been demonstrated for histamine although after initial metabolism by histamine A-methyl transferase to 3-methylhistamine, it is deaminated by intraneuronal MAOb to 3-methylimidazole acetic acid (Fig. 13.4). A Ca +-dependent KCl-induced release of histamine has been demonstrated by microdialysis in the rat hypothalamus (Russell et al. 1990) but its overflow in some areas, such as the striatum, is neither increased by KCl nor reduced by tetradotoxin and probably comes from mast cells. 

SSR-504734 is a potent, selective, and reversible inhibitor (IC50 = 18 nM) that is competitive with glycine [47,51]. The inhibitor rapidly and reversibly blocked the uptake of [14C]glycine in mouse cortical homogenates, which was sustained for up to 7 h. Complete cessation of blockade and return to glycine basal levels occurred prior to 24 h, which is in stark contrast to NFPS (>24 h). SSR-504734 potentiated a nearly twofold increase of NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) in rat hippocampal slices and produced an increase in contralateral rotations in mice when microinjected into the striatum. Microdialysis experiments indicated that the inhibitor induced a rapid and sustained increase in extracellular glycine levels in the PFC of freely moving rats [51]. The compound also demonstrated efficacy in a variety of psychosis models [51-53]. SSR-504734 was reportedly in clinical trials for schizophrenia but discontinued after Phase I (data not disclosed) [54]. 

BMS-505130 (7) is a potent and selective serotonin transporter inhibitor (SERT K< = 0.18 nM, NET K< — 4.6 gM, DAT K< — 2.1 (tM). In brain microdialysis studies, 7 demonstrated a dose-dependent increase in cortical serotonin levels. Compound 7 was also active in the mouse tail suspension model [15]. Following oral administration, peak plasma concentration of 7 was reached at 1.6 h and then declined to a concentration less than 10% of Cmax within 6 h. The short half-life of 7 might be advantageous for the treatment of PE where an acute effect to delay ejaculation followed by a relatively rapid fall in SSRI plasma concentration might be desirable. 

You can demonstrate the size of colloidal particles with a dialysis experiment in which two solutions are separated by a semipermeable membrane that has pores with diameters of 1—5 nm.3 Small molecules diffuse through these pores, but large molecules (such as proteins or colloids) cannot. (Collecting biological samples by microdialysis was discussed at the opening of Chapter 25.)... 

We report here the results obtained by the use of a screen-printed electrode as electrochemical probe to be coupled with a microdialysis fibre for continuous glucose monitoring. The most significant advance is represented by the introduction of a mediator (PB) as the principal factor for hydrogen peroxide measurement. The improved operational stability observed with the PB-modified screen-printed electrodes has demonstrated that these sensors could serve as tool to be applied for the continuous monitoring of many analytes. The application to diabetic care seems to be the most promising and advantageous area in which to test these sensors. 

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. 

Adipose tissue poses additional calibration differences for microdialysis sampling devices. The thickness of the tissue (e.g., lean versus obese individuals) and thus the capillary density will affect interindividual microdialysis sampling recovery values. This has been shown by Lutgers et al., who demonstrated decreases in glucose recovery of up to 50% between human volunteers with a skin fold thickness of 20 versus 45 mm.65 This points to how microdialysis sampling recovery is dependent upon analyte supply since glucose will be supplied better to the microdialysis probe in lean individuals with a higher density of capillaries per unit tissue than obese subjects with a lower density of capillaries and thus an increased mass transfer resistance to the probe. Additional reports have also shown less interindividual differences between microdialysis probes implanted in the forearm versus in the subcutaneous tissue.66... 

Kaptein WA, Zwaagstra JJ, Venema K, Korf J. Continuous ultraslow microdialysis and ultrafiltration for subcutaneous sampling as demonstrated by glucose and lactate measurements in rats. Analytical Chemistry 1998, 70, 4696-4700. 

Fig. 2. Transient retinal ischemia increases intravitreal glutamate in rat. Neurochemical data from microdialysis experiments carried out in anesthetized rats to demonstrate that ischemia/reperfusion insult increases intravitreal glutamate. The extracellular level of glutamate shows a moderate increase during the first 10 min of ischemia, more evident toward the end of the ischemic period, to reach statistical significance at 10 and 150 min of reperfusion. Baseline glutamate concentrations (basal values) are the mean concentrations obtained by averaging six samples collected consecutively at 10 min intervals immediately before the onset of ischemia (n — 6 rats). Glutamate values (pM) are expressed as mean S.E.M. Statistical significance was assessed by ANOVA followed by Dunnett s test for multiple comparisons. P < 0.05 and P < 0.001 versus basal values.

In reconstructed human epidermis the presence of vitamin C was required to normalize stratum corneum lipids, which was accompanied by an improvement of skin barrier formation.36 Interestingly the ascorbic acid concentration in the skin of atopic dermatitis37 and psoriatic patients38 measured in vivo by microdialysis was significantly lower than in healthy subjects. In psoriasis there was no significant difference in lesional versus nonlesional skin. There has also been demonstrated a decrease of ascorbic acid concentration in skin with increasing age.39... 

Other data have been interpreted to indicate that the nucleus accumbens is an important site for LI. In the original experiment Solomon and Staton (1982) demonstrated impaired latent inhibition following chronic ventral rather than dorsal striatal infusions of amphetamine, though they employed an active avoidance rather than a conditioned suppression procedure which may have been more compatible with psychomotor stimulant effects. Gray et al. (1995) reported in a review data indicating that mesolimbic DA depletion appeared to facilitate latent inhibition, also consistent with the results of microdialysis studies and the effects of DA receptor antagonists, described above (Gray et al., 1995). 

Microdialysis allows direct intracerebral administration of the drugs that normally do not cross the blood-brain barrier (BBB) or are metabolized in the circulation. It was demonstrated earlier (Ozaki et al., 1988 Westerink et al., 1990) that MPP+, a toxic metabolite of 1-methyl-4-phenyl-l, 2,3,6-tetrahydropyridine (MPTP), has a biphasic effect on TH activity when infused via the microdialysis probe for 20 minutes. Since, however, this drug does not penetrate the BBB, it was difficult to investigate its effects in vivo. Microdialysis overcomes this problem and has enabled the testing of a range of other modulators that previously could be studied only on in vitro preparations. 

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