Molecular pathways leading to cancer cachexia
Humans; Animals; Cachexia/etiology/metabolism; Muscle; Blood Proteins/metabolism; Cytokines/metabolism; Adipose Tissue/metabolism; Neoplasms/complications/metabolism; Peptides/metabolism; Skeletal/metabolism
Loss of body weight in cancer patients strongly influences morbidity and mortality. Recent studies have suggested that both tumor and host factors play a major role in tissue catabolism in cachexia, leading to upregulation of degradative pathways in both skeletal muscle and adipose tissue.
2005
Tisdale MJ
Physiology (bethesda)
2005
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1152/physiol.00019.2005" target="_blank" rel="noreferrer">10.1152/physiol.00019.2005</a>
Bisphosphonates: a review of their pharmacokinetic properties
Humans; Animals; Protein Binding; Dose-Response Relationship; Drug; Clodronate; Structure-Activity Relationship; Biological Availability; Blood Proteins/metabolism; Diphosphonates/pharmacokinetics/urine; Intestinal Absorption/physiology; Tissue Distribution/physiology
Bisphosphonates are a unique class of drugs. As a family, they are characterized pharmacologically by their ability to inhibit bone resorption, whereas, pharmacokinetically, they are classified by their similarity in absorption, distribution, and elimination. Although all bisphosphonates have similar physicochemical properties, their antiresorbing activities differ substantially. Activity is dramatically increased when the amino group is contained in the aliphatic carbon chain. For example, alendronate, an aminobisphosphonate, is approximately 700-fold more potent than etidronate, both in vitro and in vivo. In general, bisphosphonates are poorly absorbed from the gastrointestinal tract as a result of their poor lipophilicity. In vitro and in vivo studies have shown that bisphosphonates are absorbed from the gastrointestinal tract via paracellular transport. Systemically available bisphosphonates disappear very rapidly from plasma, and are partly taken up by the bone and partly excreted by the kidney. The relative contribution of these two processes to overall plasma elimination differs significantly among bisphosphonates. To date, all bisphosphonates studied show no evidence of metabolism. Renal excretion is the only route of elimination. Studies with alendronate in rats indicate that the drug is actively secreted by an uncharacterized renal transport system, and not by the anionic or cationic renal transport systems. Bisphosphonates bind preferentially to bones which have high turnover rates, and their distribution in bone is not homogeneous. After bone uptake, the bisphosphonates are liberated again only when the bone in which they are deposited is resorbed. Thus, the half-life of bisphosphonates in bone is very long, ranging among different species from 1 to 10 years, depending largely on the rate of bone turnover.
1996
Lin JH
Bone
1996
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1016/8756-3282(95)00445-9" target="_blank" rel="noreferrer">10.1016/8756-3282(95)00445-9</a>