Gastrointestinal tract, protein

Mechanism of Action A third-generation cephalosporin that binds to bacterial cell membranes and inhibits cell wall synthesis. Therapeutic Effect Bactericidal. Pharmacokinetics Rapidly absorbed from the gastrointestinal tract. Protein binding 65%-77%. Excreted primarily in urine. Half-life 2-3 hr. 

The absorption of sulfonylureas from the upper gastrointestinal tract is faidy rapid and complete. The agents are transported in the blood as protein-bound complexes. As they are released from protein-binding sites, the free (unbound) form becomes available for diffusion into tissues and to sites of action. Specific receptors are present on pancreatic islet P-ceU surfaces which bind sulfonylureas with high affinity. Binding of sulfonylureas to these receptors appears to be coupled to an ATP-sensitive channel to stimulate insulin secretion. These agents may also potentiate insulin-stimulated glucose transport in adipose tissue and skeletal muscle. 

The human histamine Hi-receptor is a 487 amino acid protein that is widely distributed within the body. Histamine potently stimulates smooth muscle contraction via Hi-receptors in blood vessels, airways and in the gastrointestinal tract. In vascular endothelial cells, Hi-receptor activation increases vascular permeability and the synthesis and release of prostacyclin, plateletactivating factor, Von Willebrand factor and nitric oxide thus causing inflammation and the characteristic wheal response observed in the skin. Circulating histamine in the bloodstream (from, e.g. exposure to antigens or allergens) can, via the Hi-receptor, release sufficient nitric oxide from endothelial cells to cause a profound vasodilatation and drop in blood pressure (septic and anaphylactic shock). Activation of... 

Pituitary Adenylyl Cyclase-activating Polypeptide (PACAP) is a 38-amino acid peptide (PACAP-38), which is widely expressed in the central nervous system. PACAP is most abundant in the hypothalamus. It is also found in the gastrointestinal tract, the adrenal gland and in testis. Its central nervous system functions are ill-defined. In the periphery, PACAP has been shown to stimulate catecholamine secretion from the adrenal medulla and to regulate secretion from the pancreas. Three G-protein coupled receptors have been shown to respond to PACAP, PAQ (PACAP type I) specifically binds PACAP, VPACi and VPAC2 also bind vasoactive intestinal peptide (VDP). Activation of PACAP receptors results in a Gs-mediated activation of adenylyl cyclase. 

PARs are coupled to multiple G-proteins and mediate a number of well-defined cellular responses via classical second messenger and kinase pathways. PARs are differentially expressed in cells of the vasculature as well in the brain, lung, gastrointestinal tract, skin as well as other highly vascularised tissues and evidence suggests distinct physiological functions and roles in disease states [2]. 

Insulin must be administered via the parenteral route, usually the subcutaneous (SC) route Insulin cannot be administered orally because it is a protein and readily destroyed in the gastrointestinal tract. Regular insulin is the only insulin preparation given intravenously (IV). Regular insulin is given 30 to 60 minutes before a meal to achieve optimal results. 

Delivery of peptides and proteins via the gastrointestinal tract has not been successful because of poor penetration through the intestinal epithelium and high levels of proteolytic activity in the gastrointestinal tract. Liposomal encapsulation of proteins and peptides will not improve the efficiency and capacity of this absorption pathway considerably (e.g., Ryman et al., 1982 Machy and Leserman, 1987 Weiner and Chia-Ming Chiang, 1988). These difficulties in delivery via the oral route caused the parenteral route to remain the preferred route for the administration of therapeutic peptides... 

This occurs in the seromucous secretions such as saliva, tears, nasal secretions, sweat, colostrum and secretions of the lung, urinogenital and gastrointestinal tracts. Its purpose appears to be to protect the external surfaces of the body from microbial attack. It occurs as a dimer in these secretions but as a monomer in human plasma, where its function is not known. The function of IgA appears to be to prevent the adherence of microorganisms to the surface ofmucosal cells thus preventing them entering the body tissues. It is protected from proteolysis by combination with another protein—the secretory component. 

Distribution. Once inside the body, trichloroethylene is easily absorbed into and distributed through the circulatory system. The amount that is not absorbed initially on inhalation is expired unchanged (see Section 2.3.1.1). Absorption from the gastrointestinal tract often leads to a first pass through the liver, where toxic metabolites can form (see Section 2.3.3). Trichloroethylene and its metabolites may form adducts with blood proteins, and the metabolite glyoxylate may become incorporated into amino acids (Stevens et al. 1992), thus facilitating their distribution. The ability of these compounds to traverse membranes accounts for then-generalized systemic effects. 

The list of elements and their species listed above is not exhaustive. It is limited to the relatively simple compounds that have been determined by an important number of laboratories specializing in speciation analysis. Considering the economic importance of the results, time has come to invest in adequate CRMs. There is a steadily increasing interest in trace element species in food and in the gastrointestinal tract where the chemical form is the determinant factor for their bioavailability (Crews 1998). In clinical chemistry the relevance of trace elements will only be fully elucidated when the species and transformation of species in the living system have been measured (ComeUs 1996 Cornelis et al. 1998). Ultimately there will be a need for adequate RMs certified for the trace element species bound to large molecules, such as proteins. 

As patients lose exocrine function of the pancreas, they have decreased ability to absorb lipids and protein ingested with normal dietary intake. Weight loss from nutritional malabsorption is a common symptom of chronic pancreatitis not often seen in acute pancreatitis. Fatty- or protein-containing stools are also common carbohydrate absorption is usually unaffected. Even though patients with chronic pancreatitis have decreased ability to absorb lipid from the gastrointestinal tract, there does not appear to be an increased incidence of fat-soluble vitamin deficiency in these patients.34... 

Gout is caused by an abnormality in uric acid metabolism. Uric acid is a waste product of the breakdown of purines contained in the DNA of degraded body cells and dietary protein. Uric acid is water soluble and excreted primarily by the kidneys, although some is broken down by colonic bacteria and excreted via the gastrointestinal tract. 

Stirred tank models have been widely used in pharmaceutical research. They form the basis of the compartmental models of traditional and physiological pharmacokinetics and have also been used to describe drug bioconversion in the liver [1,2], drug absorption from the gastrointestinal tract [3], and the production of recombinant proteins in continuous flow fermenters [4], In this book, a more detailed development of stirred tank models can be found in Chapter 3, in which pharmacokinetic models are discussed by Dr. James Gallo. The conceptual and mathematical simplicity of stirred tank models ensures their continued use in pharmacokinetics and in other systems of pharmaceutical interest in which spatially uniform concentrations exist or can be assumed. 

Gastrointestinal absorption of lead is influenced by dietary and nutritional calcium and iron status. An inverse relationship has been observed between dietary calcium intake and PbB concentration (Mahaffey et al. 1986 Ziegler et al. 1978). Complexation with calcium (and phosphate) in the gastrointestinal tract and competition for a common transport protein have been proposed as possible mechanisms for this interaction (Barton et al. 1978a Heard and Chamberlain 1982). Absorption of lead from the... 

Steroid hormones are produced by the adrenal cortex, testes, ovaries, and placenta. Synthesized from cholesterol, these hormones are lipid soluble therefore, they cross cell membranes readily and bind to receptors found intracellularly. However, because their lipid solubility renders them insoluble in blood, these hormones are transported in the blood bound to proteins. Furthermore, steroid hormones are not typically preformed and stored for future use within the endocrine gland. Because they are lipid soluble, they could diffuse out of the cells and physiological regulation of their release would not be possible. Finally, steroid hormones are absorbed easily by the gastrointestinal tract and therefore may be administered orally. 

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