Dysregulation

A state of chronic deviation of a regulatory system from its normal (homeostatic) operating level is defined as an allostatic state. In the context of drug addiction this term has been introduced by George Koob and Michel Le Moal and represents a chronic deviation of reward set point by dysregulation of reward circuits and brain stress systems that provide a negative motivational state that drives addictive behavior. 

Coadministration of dexrazoxane Chelation of iron in the heart, correction of iron dysregulation or mitigation of free radical formation Approved for use in patients who continue DOX above 300 mg/m2 or require another anthracycline after a prior exposure to 300 mg of DOX/m2... 

Umetsu DT, Dekmyff RH (2006) Immune dysregulation in asthma. Curr Opin Immunol 18 727-732. 

Several diseases involving dysregulation of MR function have been described although most of them are not causatively linked to the receptor itself. Pseudohypoaldosteronism for example is a syndrome of mineralocorticoid resistance characterized by urinary salt loss and dehydration. However, only very rarely mutations in the MR gene have been found in these patients so far. In most cases, this syndrome appears to be linked to defects in the subunits of the amiloride-sensitive sodium channel ENaC, a major target of mineralocorticoid action in the kidney. 

Ras is a G protein that cycle between two conformations, an activated Ras-GTP or inactivated form Ras-GDP. Ras, attached to the cell membrane by lipidation, is a key component in many signalling cascades, which couple growth factor receptors to downstream effectors that control such processes as cytoskeletal integrity, proliferation, cell adhesion, apoptosis and cell migration. Mutations and dysregulations of the Ras protein leading to increased invasion and metastasis, and decreased apoptosis are very common in cancers. 

Growth factor and hormone signalling cascades link mTORCl dysregulation to cancer and Hamartoma syndromes. 

Because chronic cocaine use appears to reduce the efficiency of central dopamine neurotransmission, a number of dopaminergic compounds, including amantadine, bromocriptine, mazindol, and methylphenidate, have been examined as treatments for cocaine abuse. It is thought that these relatively slow-onset dopaminergic agents, with low or relatively low abuse potential, would correct the dopamine dysregulation and alleviate withdrawal symptoms following chronic stimulant use. 

Koob GF, LeMoal M Dmg addiction, dysregulation of reward, and allostatis. Neuropsychopharmacology 24 97—129, 2001... 

McDougle CJ, Price LH, Palumbo JM, et al Dopaminergic responsivity during cocaine abstinence a pilot smdy. Psychiatry Res 43 77-85, 1992 McDougle CJ, Black JE, Malison RT, et al Noradrenergic dysregulation during discontinuation of cocaine use in addicts. Arch Gen Psychiatry 51 713-719,1994 Misra L, Kofoed L Risperidone treatment of methamphetamine psychosis (letter). Am J Psychiatry 154 1170, 1997... 

O, Buch S (2006) CXCLlO-induced cell death in neurons role of calcium dysregulation. Eur J NeuroSci 23(4) 957-964... 

Wesselingh SL, Glass J et al (1994) Cytokine dysregulation in HIV-associated neurological disease. Adv Neuroimmunol 4(3) 199-206... 

Sui Y, Potula R, Dhillon N, Pinson D, Li S, Nath A, Anderson C, Turchan J, Kolson D, Narayan O, Buch S (2004) Neuronal apoptosis is mediated by CXCLIO overexpression in simian human immunodeficiency virus encephalitis. Am J Pathol 164 1557-1566 Sui Y, Stehno-Bittel L, Li S, Loganathan R, DhUlon NK, Pinson D, Nath A, Kolson D, Narayan O, Buch S (2006) CXCLlO-induced cell death in neurons role of calcium dysregulation. Eur J NeuroSci 23 957-964... 

Tocotrienols are another group of phytochemicals of rice bran which have a chemopreventive effect and have been demonstrated to inhibit breast cancer (Nesaremam et al., 1998). The polysaccharides of rice bran contain a-glucan, the anti-tumor effect of which has been demonstrated by its inhibition of gastrointestinal carcinogenesis (Akeshita et al., 1992). Rice bran agglutinin has been shown to induce apoptosis of cancer cells by the mechanism of cell cycle dysregulation (Miyoshi et al., 2001). 

MIYOSHI N, KOYAMA Y, KATSUNO Y, HAYAKAWA S, MITA T, OHTA T, KAJI K, ISEMURA M (2001) Apoptosis induction associated with cell cycle dysregulation by rice bran agglutinin. JBiochem, (Tokyo) 130 799-805. 

Enteric nerves control intestinal smooth muscle action and are connected to the brain by the autonomic nervous system. IBS is thought to result from dysregulation of this brain-gut axis. The enteric nervous system is composed of two gan-glionated plexuses that control gut innervation the submucous plexus (Meissner s plexus) and the myenteric plexus (Auerbach s plexus). The enteric nervous system and the central nervous system (CNS) are interconnected and interdependent. A number of neurochemicals mediate their function, including serotonin (5-hydroxytryptamine or 5-HT), acetylcholine, substance P, and nitric oxide, among others. 

Because disturbances in fluid balance are routinely encountered in clinical medicine, it is essential to have a thorough understanding of body fluid compartments and the therapeutic use of fluids. Similarly, disturbances in serum sodium, potassium, calcium, phosphorus, and magnesium are ubiquitous and must be mastered by all clinicians. Dysregulation of fluid and/or electrolyte status has serious implications regarding the concepts of drug absorption, volumes of distribution, and toxicity. Similarly, many medications can disrupt fluid and/or electrolyte balance as an unintended consequence. 

While such models of depression are quite useful in conceptualizing the mechanisms behind antidepressant activity, they are assuredly an oversimplification of the actual pathophysiologic process of the disorder. Depression probably involves a complex dysregulation of monoamine systems, and these systems, in turn, modulate and are modulated by other neurobio-logic systems. Thus, the underlying cause of depression may well extend beyond dysfunction of the monoamine system.10... 

VSMCs 4. Angiogenesis. 5. Dysregulation of MMPs myocardial necrosis. 

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