Inhibited junction

A more effective carrier confinement is offered by a double heterostmcture in which a thin layer of a low band gap material (the active layer) is sandwiched between larger band gap layers. The physical junction between two materials of different band gaps, and chemical compositions, is called a heterointerface. A schematic representation of the band diagram of such a stmcture is shown in Figure 4. Electrons injected under forward bias across the p—N junction into the lower band gap material encounter a potential barrier, AE at thep—P junction which inhibits their motion away from the junction. The holes see a potential barrier of AE at the N—p heterointerface which prevents their injection into the N region. The result is that the injected minority... 

Ansamacrolides. Antibiotics ia the ansamacroHde family ate also referred to as ansamycias. They are benzenoid or naphthalenoid aromatic compounds ia which nonadjacent positions are bridged by an aliphatic chain to form a cycHc stmcture. One of the aliphatic—aromatic junctions is always an amide bond. Rifampin is a semisyntheticaHy derived member of this family and has clinical importance. It has selective antibacterial activity and inhibits RNA polymerase. 

The principal arninoglycoside toxicides are neuromuscular paralysis, ototoxicity, and nephrotoxicity. Neuromuscular paralysis is a relatively rare complication resulting from high aminoglycoside concentrations at the neuromuscular junctions following, for example, rapid bolus intravenous injection or peritoneal instillation, rather than the normal intravenous infusion. The mechanism apparentiy involves an inhibition of both the presynaptic release of acetylcholine and the acetylcholine postsynaptic receptors (51). 

Enzyme Inhibition. Some materials produce toxic effects by inhibition of biologically vital enzyme systems, leading to an impairment of normal biochemical pathways. The toxic organophosphates, for example, inhibit the cholinesterase group of enzymes. An important factor in thek acute toxicity is the inhibition of acetylocholinesterase at neuromuscular junctions, resulting in an accumulation of the neurotransmitter material acetylcholine and causing muscle paralysis (29) (see Neuroregulators). 

The blood-brain barrier (BBB) forms a physiological barrier between the central nervous system and the blood circulation. It consists of glial cells and a special species of endothelial cells, which form tight junctions between each other thereby inhibiting paracellular transport. In addition, the endothelial cells of the BBB express a variety of ABC-transporters to protect the brain tissue against toxic metabolites and xenobiotics. The BBB is permeable to water, glucose, sodium chloride and non-ionised lipid-soluble molecules but large molecules such as peptides as well as many polar substances do not readily permeate the battier. 

Cholinesterases (ChEs), polymorphic carboxyles-terases of broad substrate specificity, terminate neurotransmission at cholinergic synapses and neuromuscular junctions (NMJs). Being sensitive to inhibition by organophosphate (OP) poisons, ChEs belong to the serine hydrolases (B type). ChEs share 65% amino acid sequence homology and have similar molecular forms and active centre structures [1]. Substrate and inhibitor specificities classify ChEs into two subtypes ... 

Imidazole antimycotics, ketoconazole, clotrimazole, and miconazole are potent inhibitors of various cytochrome P450-isoenzymes that also affect the metabolism of retinoids. They were fust shown to inhibit the metabolism of RA in F9 embryonal carcinoma cells. When tested in vitm liarazole, a potent CYP-inhibitor, suppressed neoplastic transformation and upregulated gap junctional communication in murine and human fibroblasts, which appeared to be due to the presence of retinoids in the serum component of the cell culture medium. Furthermore, liarazole magnified the cancer chemopreventive activity of RA and (3-carotene in these experiments by inhibiting RA-catabolism as demonstrated by absence of a decrease in RA-levels in the culture medium in the presence of liarazole over 48 h, whereas without liarazole 99% of RA was catabolized. In vivo, treatment with liarazole and ketoconazole reduced the accelerated catabolism of retinoids and increased the mean plasma all-irans-RA-concentration in patients with acute promyelocytic leukemia and other cancels. 

FIGURE 29-1. The blood-brain barrier selectively inhibits certain substances from entering the interstitial spaces of the brain and spinal fluid. It is thought that certain cells within the brain form tight junctions that prevent or slow the passage of certain substances. Levodopa passes the blood-brain barrier, whereas dopamine is unable to pass. 

In the venom of C. geographus and other fish-hunting species, the conotoxins isolated so far can be divided into three major classes (1-4) o -conotoxms which block neuronal calcium channels at the presynaptic terminus of the neuromuscular junction, a-conotoxins which inhibit the acetylcholine receptor at the postsynaptic terminus, and x-conotoxins which block Na channels on the muscle membrane. 

Different types of apparently beneficial activities have been demonstrated in vitro for carotenoid oxidation products, including induction of gap-junctional communications, " growth inhibition of leukemia and cancer cells, induction of apoptosis... 

Another study showed that a mixture of oxidative metabolites of P-carotene, but not P-carotene, was able to increase the binding of benzo[a]pyrene to DNA. Other mixtures of P-carotene cleavage products have been shown to induce oxidative stress in vitro,exert cytotoxic and genotoxic effects, and inhibit gap junction intercellular communications. It has been suggested that these detrimental effects could possibly occur in vivo following the intake of high doses of carotenoids. 

Yeh, S.L. and Hu, M.L., Oxidized [beta]-carotene inhibits gap junction intercellular communication in the human lung adenocarcinoma cell line A549, Food Chem. Toxicol., 41, 1677, 2003. 

Ecothiophate iodide and denecarium bromide inhibit acetylcholinesterase. Inhibition of this enzyme increases the availability of acetylcholine at the nerve junction, thus increasing the stimulation of the muscarinic (M3) receptors of the ciliary... 

The in vitro system we have been using to study the transepithelial transport is cultured Madin-Darby canine kidney (MDCK) epithelial cells (11). When cultured on microporous polycarbonate filters (Transwell, Costar, Cambridge, MA), MDCK cells will develop into monolayers mimicking the mucosal epithelium (11). When these cells reach confluence, tight junctions will be established between the cells, and free diffusion of solutes across the cell monolayer will be markedly inhibited. Tight junction formation can be monitored by measuring the transepithelial electrical resistance (TEER) across the cell monolayers. In Figure 1, MDCK cells were seeded at 2 X 104 cells per well in Transwells (0.4 p pore size) as described previously. TEER and 14C-sucrose transport were measured daily. To determine 14C-sucrose... 

Hossain, M. Z., L. R. Wilkens, P. P. Mehta, W. Loewenstein, and J. S. Bertram. 1989. Enhancement of gap junctional communication by retinoids correlates with their ability to inhibit neoplastic transformation. Carcinogenesis 10(9) 1743-1748. 

Livny, O., I. Kaplan, R. Reifen et al. 2002. Lycopene inhibits proliferation and enhances gap-junction communication of KB-1 human oral tumor cells. J Nutr 132(12) 3754—3759. 

Zhang, L. X., R. V. Cooney, and J. S. Bertram. 1991. Carotenoids enhance gap junctional communication and inhibit lipid peroxidation in C3H/10T1/2 cells Relationship to their cancer chemopreventive action. Carcinogenesis 12(11) 2109—2114. 

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