Diffusion intracellular

Oral metronidazole and tinidazole are readily absorbed and permeate all tissues by simple diffusion. Intracellular concentrations rapidly approach extracellular levels. Peak plasma concentrations are reached in 1-3 hours. Protein binding of both drugs is low (10-20%) the half-life of unchanged drug is 7.5 hours for metronidazole and 12-14 hours for tinidazole. Metronidazole and its metabolites are excreted mainly in the urine. Plasma clearance of metronidazole is decreased in patients with impaired liver function. 

Many Plasma Membrane Receptors Generate a Diffusible Intracellular Signal... 

Most membrane receptors generate a diffusible intracellular signal called a second messenger. Five intracellular messengers are currently known Cyclic AMP, cyclic GMP, inositol triphosphate, diacylglyc-erol, and calcium. Second messengers usually activate or inhibit the action of one or more enzymes. 

Luby-Phelps, K. (2000) Cytoarchitecture and physical properties of cytoplasm volume, viscosity, diffusion, intracellular surface area. Int. Rev. Cytol, 192. 

The following properties are important for the function of diffusible intracellular messengers ... 

In-labeled white blood cells (WBC) have also been clinically used for infection and inflammation imaging. The neutral, lipid-soluble "In(oxine)3 (oxine = 8-hydroxyquinoline) complex penetrates cellular membranes and is used to label WBC. After diffusing intracellularly, the "In(oxine)3 complex dissociates and the " In is bound to nuclear and cytoplasmic proteins. Labeling of WBCs is done in plasma to avoid transchelation with transferrin in blood. The procedure consists of withdrawal of blood from patient, separation of red blood cells from white blood cells, purification of leucocytes, radiolabeling, followed by reinjection of the radiolabeled cells into the patient. The WBCs migrate to inflamed area and can lead to positive imaging. 

The first messengers act from one cell to another, and the second messenger acts within the cell (Rose and Wilkie, 2000). Activation of most membrane-associated receptors/effec-tors generates a diffusable intracellular signal called the second messenger. Major second... 

Initial work on radiolabeling of autologous polymorphonuclear leukocytes was performed by McAfee and Thakur [30]. One of the compounds they examined was the nonpolar, lipid-soluble complex 8-hydroxyquinoline (oxine) (Fig. 2). Indium forms a neutral, lipid-soluble complex with oxine which will penetrate cellular membranes. Subsequently, studies showed that this technique could be used to label leukocytes and platelets with retention of biological activity [31]. After diffusing intracellularly, the ln-oxine complex dissociates and the " In is bound to nuclear and cytoplasmic proteins (Fig. 3) [32-34]. Due to the high stability of indium with the blood protein transferrin, it is necessary to label platelets or WBCs in the absence of plasma. In addition, a final wash of the labeled cells using plasma will remove any loosely bound indium by complexation with transferrin [35,36]. 

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