Dysfunctional organization

Box 36.1 Erectile dysfunction organic, psychological or mixed aetiology ... 

Resist change. This is a small number these are often dysfunctional organizations that may never get it. 

For that reason some centers have developed a standardized aggressive approach to donor management that allows functional resuscitation of dysfunctional organs which initially fall outside the transplant acceptance criteria (Boucek et al. 1993 Laks 1995 Wheeldon et al. 1995). 

Vinpocetine (2), another dmg initially categorized as a cerebral vasodilator, is a member of the vinca alkaloid family of agents (7). However, interest in this compound as a potential dmg for learning and memory deficits comes from its abiUty to act as a neuronal protectant. This compound was evaluated in 15 patients with AD over a one-year period and was ineffective in improving cognitive deficits or slowing the rate of decline (8). However, in studies of patients with chronic vascular senile cerebral dysfunction (9) and organic psycho syndrome (10), vinpocetine showed beneficial results. 

Pseudohypoparathyroidism is characterized by end-organ resistance to parathyroid hormone (98,108). This disease takes various forms, including Albright s hereditary osteodystrophy, which has unusual physical features and a generalized resistance to G-protein-linked hormones that function through cAMP as a second messenger. This defect is associated with a deficiency in the levels of the a-subunit of (109). Because this defect may be generalized, such patients also have olfactory dysfunction (110). 

Another class of therapeutic agents is used for the treatment of certain genetic diseases or other enzymatic disorders caused by the dysfunction or absence of one particular enzyme. This often leads to an unwanted accumulation or imbalance of metaboUtes in the organism. Eor example, some anticonvulsive agents are inhibitors for y-aminobutyric acid aminotransferase [9037-67-6]. An imbalance of two neurotransmitters, glutamate and y-aminobutyric acid, is responsible for the symptoms. Inhibition of the enzyme leads to an increase of its substrate y-aminobutyric acid, decreasing the imbalance and subsequently relieving the symptoms of the disease. 

Kenakin, T. P., Ambrose, J. R., and Irving, P. E. (1991). The relative efficiency of beta-adrenoceptor coupling to myocardial inotropy and diastolic relaxation Organ-selective treatment of diastolic dysfunction. J. Pharmacol. Exp. Ther. 257 1189—1197. 

Acute over-activation of NHE1 results in a marked elevation in intracellular sodium concentration with a subsequent increase in intracellular calcium, via the Na +/Ca++ exchanger. This in turn triggers a cascade of injurious events that can culminate in tissue dysfunction and ultimately apoptosis and necrosis. This is commonly seen in organs such as the heart, brain and kidneys as a consequence of ischemia-reperfusion. 

For more information on biomarkers for renal and hepatic effects of chemicals, see ATSDR/CDC Subcommittee Report on Biomarkers of Organ Damage and Dysfunction (1990) and for information on biomarkers for neurological effects, see OTA (1990). 

ATSDR/CDC. 1990. Summary Report Subcommittee report on biological indicators of organ damage and dysfunction. Agency for Toxic Substances and Disease Registry, Centers for Disease Control and Prevention, Atlanta, GA. 

Hontela A, Dumont P, Duclos D, Fortin R. 1995. Endocrine and metabolic dysfunction in yellow perch, Perea flavescens, exposed to organic contaminants and heavy metals in the St. Lawrence River. Environ Toxicol Chem 14 725-731. 

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