Pathway of entry

To enable a comparison of hazards from chemicals a Hazard Index (HI) can be calculated as the ratio to the ADI. In addition to dietary uptake the possible pathways of entry of POPs for humans are... 

It is recognized that there are two major pathways of entry of Ca2+ into the cells rapid Ca2+entry from the extracellular medium is regulated principally by macromolecules of the plasmic membrane, or Ca2+ may be released from the intracellular stores such as the Golgi, the endoplasmic and sarcoplasmic reticuli. In many cases, a Ca2+ signal is initiated by voltage- or receptor-gated opening of Ca2+ permeable plasmalemmal channels. Calcium channels can also... 

Aqueous solutions with a surface tension of around 70 mN m do not enter the stomatal pore, but penetration of the pore occurs when the surface tension is lowered by addition of surfactant [243]. The mechanism of penetration is by no means simple. The contact angle between the solution and the surface of the pore is important, but there is a suggestion that the morphology of the pore wall is equally important [244]. However, in the pear Pyrus communis L. cr. Bartlett, stomatal penetration of aqueous solution into leaves was promoted by surfactants according to their surface activity [245]. Dioctyl sodium sulphosuccinate was the most effective surfactant used and Tween 20 least effective. However, only 0.5 to 4.5 % of the stomata were penetrated suggesting that stomatal penetration is, indeed, a relatively unimportant pathway of entry to the leaf. 

The main pathway of entry of solvents from paints and varnishes to the body is by inhalation. Volatile paint compounds present a particularly high risk as do some forms of paint application (e.g., spray painting with the risk of inhalation of even less volatile and nonvolatile paint components). Other pathways should, however, also be considered as dermal contact. 

FIGURE 23.1 The pathways of gluconeogenesis and glycolysis. Species in blue, green, and peach-colored shaded boxes indicate other entry points for gluconeogenesis (in addition to pyruvate). 

The thiazide sensitive NaCI cotransporter (NCC) is the major pathway of NaCI entry in the distal convoluted tubule. Like NKCC2, NCC contains 12 putative transmembrane domains and long intracellular amino-and carboxy-tails. NCC and NKCC as well as the KC1 cotransporter KCC are members of the same gene family and have considerable homology. 

After uptake by the liver, free fatty acids are either P Oxidized to COj or ketone bodies or esterified to triacylglycerol and phospholipid. There is regulation of entry of fatty acids into the oxidative pathway by carnitine palmitojdtransferase-I (CPT-I), and the remainder of the fatty acid uptake is esterified. CPT-I activity is... 

Stevenson M. Portals of entry uncovering HIV nuclear transport pathways. Trends Cell Biol 1996 6(1) 9-15. 

The amino acid L-tryptophan is the precursor for the synthesis of 5-HT. The synthesis and primary metabolic pathways of 5-HT are shown in Figure 13-5. The initial step in the synthesis of serotonin is the facilitated transport of the amino acid L-tryptophan from blood into brain. The primary source of tryptophan is dietary protein. Other neutral amino acids, such as phenylalanine, leucine and methionine, are transported by the same carrier into the brain. Therefore, the entry of tryptophan into brain is not only related to its concentration in blood but is also a function of its concentration in relation to the concentrations of other neutral amino acids. Consequently, lowering the dietary intake of tryptophan while raising the intake of the amino acids with which it competes for transport into brain lowers the content of 5-HT in brain and changes certain behaviors associated with 5-HT function. This strategy for lowering the brain content of 5-HT has been used clinically to evaluate the importance of brain 5-HT in the mechanism of action of psychotherapeutic drugs. 

Capacitative Ca2+ entry is the predominant mode of regulated Ca2+ entry in nonexcitable cells but it also occurs in a number of excitable cell types. This pathway of Ca2+ entry is usually associated with the activation of phospholipase C, which mediates the formation of IP3 (see Ch. 20). Intracellular application of IP3 mimics the ability of hormones and neurotransmitters to activate calcium ion entry, and activation of calcium ion entry by hormones and neurotransmitters can be blocked by intracellular application of low-molecular-weight heparin, which potently antagonizes IP3 binding to its receptor. There is considerable evidence for the presence of an IP3 receptor in the plasma membrane of some cells types. 1(1,3,4,5)P4, a product of IP3 phosphorylation, has been shown in some cells to augment this action of IP3 in activating PM calcium ion entry, but in others IP3 alone is clearly sufficient. 

Figure 2 Proposed pathways for liposomal entry into the cell enhanced by peptides. These include direct cell entry suggested as the mechanism of entry by cell-penetrating peptides and receptor-mediated endocytosis by caveolae- and clathrin-dependent endocytosis.

Table 28.2 Pathways of Pollutant Entry Into the Ooean.

In C albicans, mutations that block cAMP/PKA pathway suppress or delay the apoptotic response to H2O2 and amphotericin B. By contrast, mutations that result in constitutive activation of the RAS pathway accelerate entry into the apoptotic pathway Apoptosis and quorum sensing in filamentous fungi are phenomena associated with stress responses, a recurring motif in morphogenesis and secondary metabolism. The treatment of Colletotrichum trifolii with proline, a known stress relief chemical, suppressed apoptosis associated with Ras as well as apoptosis associated with a variety of other stresses. 

This agent also has some class lA and class II effects. It is effective for the treatment of ventricular and supraventricular tachycardias (AV nodal and accessory pathway re-entry, atrial flutter and fibrillation). Propafenone is useful in converting recent-onset atrial fibrillation or flutter to sinus rhythm, and for terminating paroxysmal supraventricular tachycardia. Its pro-ariythmic and myocardial depressant effects limit its use, especially in patients with poor ventricular function. 

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