Portals of entry

Ca + enters myocytes via these channels, which allow entry only of Ca ions. The major portal of entry is the... 

To be successful, a pathogen must be able to survive at its initial portal of entry, fiequenlly... 

Skin functions as both, an important physical barrier to the absorption of toxic substances and simultaneously as a portal of entry of such substances. The stratum comeum of the epidermis is most significant in providing some degree of physical... 

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

The portals of entry for the smallpox virus are the mucous membranes of the upper respiratory tract. Smallpox is transmitted by large or small respiratory droplets and by contact with skin lesions or secretions. Patients are considered more infectious if they are actively coughing. Incubation period ranges from 10 to 14 days, but most... 

Patton JS, Fishbum CS, Weers JG (2004) The lungs as a portal of entry for systemic drug delivery. Proc Am Thorac Soc 1 338-344... 

Numerous studies have been published on the in vivo metabolism of peptides. However, these studies are concerned mainly with assessment of pharmacokinetic parameters such as half-life and clearance. Only seldom is the in vivo biotransformation of peptides that contain only common amino acids investigated in any detail, due to the difficulty of monitoring products of proteolysis that are identical to endogenous peptides and amino acids. More importantly, such studies fail to yield mechanistic and biochemical insights. For this reason, we begin here with a discussion of the metabolism of just a few peptides in some selected tissues, namely portals of entry (mouth, gastro-intestinal tract, nose, and skin), plasma, organs of elimination (liver, kidney), and pharmacodynamic sites (brain and cerebrospinal fluid). These examples serve as introduction for the presentation in Sect. 6.4.2 of the involvement of individual peptidases in peptide metabolism. 

An unusual case of intramolecular competition (chemoselectivity, see Chapt. 1 in [la]) between ester and oxirane occurs in the detoxification of (oxiran-2-yl)methyl 2-ethyl-2,5-dimethylhexanoate (10.49), one of the most abundant isomers of an epoxy resin. The compound is chemically very stable, i.e., resistant to aqueous hydrolysis, but is rapidly hydrolyzed in cytosolic and microsomal preparations by epoxide hydrolase and carboxylesterase, which attack the epoxide and ester groups, respectively [129], The rate of overall enzymatic hydrolysis was species dependent, decreasing in the order mouse > rat > human, but was relatively fast in all tissues examined (lung and skin as portals of entry, and liver as a further barrier). In mouse and rat lung microsomes, ester hydrolysis was 3-4 times faster than epoxide hydration, whereas the opposite was true in human lung microsomes. 

Conner SD, Schmid SL. Regulated portals of entry into the cell. Nature 2003 22(6927) 37 4. 

Systemic infections are those that have microorganisms (bacteria, viruses, yeasts, parasites) spread, usually via the bloodstream, beyond the portal of entry or original site of localized infection to multiple compartments of the body. When infections, either localized or systemic, are accompanied by signs and symptoms of a systemic inflammatory response (fever, rapid pulse, increase in white blood cells) the syndrome is called sepsis. Severe sepsis is defined by the additional occurrence of organ failure (either kidney, liver, brain, lungs), and is a potentially fatal condition (mortality around 50%). If there is hypotension not responding on fluid resuscitation it is called septic shock and the mortally is even higher (60-70%). 

Insecticidal control of the pink bollworm is yet another management practice used by growers in Arizona pink bollworm exit holes in cotton bolls might provide portals of entry for A. flavus (55). Unfortunately, it is not economically feasible to achieve 100% control of the pink bollworm in cotton through the hi -ftequency use of insecticides, and even relatively low levels of infestation by this insect pest is well correlated to high levels of A. flavus infection and subsequent aflatoxin contamination. 

An example of an extremely toxic carbamate is aldicarb [2-methyl-2-(methylthio) propionaldehyde]. Both oral and dermal routes are the primary portals of entry, and it has an oral LD50 of 1.0 mg/kg (rat)and a dermal LD50 of 20 mg/kg (rabbit). For this reason it is recommended for application to soils on crops such as cotton, citrus, and sweet potatoes. This compound moves readily through soil profiles and has contaminated groundwater supplies. 

The skin represents the largest organ in the human body, and one of its primary functions can be seen as a physical barrier to absorption of toxicants. The other major routes of toxicant entry into the body are through the respiratory and gastrointestinal tract, which can be seen to offer less resistance to toxicant absorption than the skin. In general, the respiratory tract offers the most rapid route of entry, and the dermal the least rapid. One reason for this major difference is primarily because membrane thickness, which is really the physical distance between the external environment (skin surface, air in the lung, or lumen of the gut) and the blood capillaries, varies across these portals of entry. The overall entry depends on both the amount present and the saturability of the transport processes involved. 

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