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Secondary Mediators (secondary + mediator)
Selected AbstractsPathways mediating sexual abuse and eating disturbance in childrenINTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 3 2001Stephen Wonderlich Abstract Objective To examine the relationship between childhood maltreatment and eating disorders in a sample of children. Method Twenty 10,15-year-old female children who were receiving treatment following reported childhood sexual abuse and 20 age-matched controls were compared on a series of measures assessing eating disorder behaviors, body image concerns, substance use, mood, impulsive behavior, and self-concept. Results Sexually abused children reported higher levels of eating disorder behaviors, impulsive behaviors, and drug abuse than controls. Furthermore, behavioral impulsivity provided the strongest mediational effect between a history of childhood sexual abuse and purging and restrictive dieting behavior. Drug use proved to be a significant secondary mediator of the childhood sexual abuse eating disorder behavior association. Discussion These data support the hypothesis that childhood sexual abuse is related to disordered eating in children, and extend similar findings that have been previously reported with adults. Behavioral impulsivity and drug use appear to be significant mechanisms that influence eating disorder behavior following childhood sexual abuse. © 2001 by John Wiley & Sons, Inc. Int J Eat Disord 29: 270,279, 2001. [source] Acute Alcohol Intoxication Increases REDD1 in Skeletal MuscleALCOHOLISM, Issue 5 2008Charles H. Lang Background:, The mechanism by which acute alcohol (EtOH) intoxication decreases basal muscle protein synthesis via inhibition of the Ser/Thr kinase mammalian target of rapamycin (mTOR) is poorly defined. In this regard, mTOR activity is impaired after over expression of the regulatory protein REDD1. Hence, the present study assessed the ability of REDD1 as a potential mediator of the EtOH-induced decrease in muscle protein synthesis. Methods:, The effect of acute EtOH intoxication on REDD1 mRNA and protein was determined in striated muscle of rats and mouse myocytes using an RNase protection assay and Western blotting, respectively. Other components of the mTOR signaling pathway were also assessed by immunoblotting. For comparison, REDD1 mRNA/protein was also determined in the muscle of rats chronically fed an alcohol-containing diet for 14 weeks. Results:, Intraperitoneal (IP) injection of EtOH increased gastrocnemius REDD1 mRNA in a dose- and time-dependent manner, and these changes were associated with reciprocal decreases in the phosphorylation of 4E-BP1, which is a surrogate marker for mTOR activity and protein synthesis. No change in REDD1 mRNA was detected in the slow-twitch soleus muscle or heart. Acute EtOH produced comparable increases in muscle REDD1 protein. The EtOH-induced increase in gastrocnemius REDD1 was independent of the route of EtOH administration (oral vs. IP), the nutritional state (fed vs. fasted), gender, and age of the rat. The nonmetabolizable alcohol tert -butanol increased REDD1 and the EtOH-induced increase in REDD1 was not prevented by pretreatment with the alcohol dehydrogenase inhibitor 4-methylpyrazole. In contrast, REDD1 mRNA and protein were not increased in the isolated hindlimb perfused with EtOH or in C2C12 myocytes incubated with EtOH, under conditions previously reported to decrease protein synthesis. Pretreatment with the glucocorticoid receptor antagonist RU486 failed to prevent the EtOH-induced increase in REDD1. Finally, the EtOH-induced increase in REDD1 was not associated with altered formation of the TSC1,TSC2 complex or the phosphorylation of TSC2 which is down stream in the REDD1 stress response pathway. In contradistinction to the changes observed with acute EtOH intoxication, REDD1 mRNA/protein was not changed in gastrocnemius from chronic alcohol-fed rats despite the reduction in 4E-BP1 phosphorylation. Conclusions:, These data indicate that in fast-twitch skeletal muscle (i) REDD1 mRNA/protein is increased in vivo by acute EtOH intoxication but not in response to chronic alcohol feeding, (ii) elevated REDD1 in response to acute EtOH appears due to the production of an unknown secondary mediator which is not corticosterone, and (iii) the EtOH-induced decrease in protein synthesis can be dissociated from a change in REDD1 suggesting that the induction of this protein is not responsible for the rapid decrease in protein synthesis after acute EtOH administration or for the development of alcoholic myopathy in rats fed an alcohol-containing diet. [source] Composite estimates of physiological stress, age, and diabetes in American SamoansAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 3 2007Douglas E. Crews Abstract Composite estimates of physiological stress such as allostatic load (AL) were developed to help assess cumulative impacts of psychosocial and physical stressors on the body. Physiological responses to stress generally accelerate somatic wear-and-tear and chronic degenerative conditions (CDCs). Following McEwen (Neuropsychopharmacology 22 (1999) 108,124) and others, primary physiological mediators of somatic stress responses include glucocorticoids (cortisol), catecholamines (adrenaline and noradrenaline), and serum dihydroepiandosterone-sulfate (DHEA-S). Conversely, blood pressure (BP), serum HDL and total cholesterol, glycated hemoglobin (HbA1c), and waist/hip (w/h) ratio are modulated by such hormones, thereby acting as secondary mediators of stress response. When these risk factors are aggregated into a composite score, higher stress loads are associated with increased risks for days of school/work missed, functional losses, morbidity, and mortality in US samples. To examine stress loads in American Samoans, data on all 6 secondary mediators along with estimates of body habitus (i.e. height, weight, circumferences, skinfolds) and physiology (i.e. fasting insulin, LDLc, triglycerides, fasting glucose) were measured on 273 individuals residing on Tutuila Island in 1992. Four combinations of these physiological factors were used to determine composite estimates of stress. These were then assessed by sex for associations with age and the presence of diabetes. Composite estimates of stress load were higher in Samoan women than men. Associations with age tended to be low and negative in men, but positive in women, appearing to reflect cultural circumstances and population history. Stress load scores also were higher among those with diabetes than those without among both men and women. These results suggest that composite estimates of stress may be useful for assessing future risks of CDC's and the senescent processes that may underlie them in cross-cultural research. Am J Phys Anthropol, 2007. © 2007 Wiley-Liss, Inc. [source] Endothelin-1 increases cholinergic nerve-mediated contraction of human bronchi via tachykinin synthesis inductionBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2001Bruno D'Agostino In some asthmatics, muscarinic receptor antagonists are effective in limiting bronchoconstrictor response, suggesting an abnormal cholinergic drive in these subjects. There is a growing body of evidences indicating that cholinergic neurotransmission is also enhanced by endothelin-1 (ET-1) in rabbit bronchi, mouse trachea and in human isolated airway preparations. We investigated the role of secondary mediators in ET-1 induced potentiation of cholinergic nerve-mediated contraction in human bronchi, in particular the possible role of neuropeptides in this phenomenon. Bronchial tissues after endothelin treatment were exposed to a standard electrical field stimulation (EFS) (30% of EFS 30Hz)-induced contraction. In addition, in some experiments, preparations were treated with a tachykinin NK2 receptor antagonist and subsequently exposed to the same protocol. HPLC and RIA were performed on organ bath fluid samples. Moreover, the human bronchi were used for the ,-PPT (preprotachykinin) mRNA extraction and semiquantitative reverse transcription polymerase chain reaction (RT , PCR), prior to and 30 , 40 min following ET-1 challenge. The selective tachykinin NK2 receptor antagonist, SR48968, was effective to reduce ET-1 potentiation of EFS mediated contraction. HPLC or RIA showed significant increased quantities of NKA in organ bath effluents after EFS stimulation in bronchi pretreated with ET-1. Finally, ,-PPT mRNA level after stimulation of bronchi with ET-1 was increased about 2 fold respect to control untreated bronchi. In conclusion, this study demonstrated that, at least in part, the ET-1 potentiation of cholinergic nerve-mediated contraction is mediated by tachykinin release, suggesting that in addition to nerves, several type of cells, such as airway smooth muscle cell, may participate to neuropeptide production. British Journal of Pharmacology (2001) 134, 1447,1454; doi:10.1038/sj.bjp.0704395 [source] Nitric oxide (NO) modulation of PAF-induced cardiopulmonary action: interaction between NO synthase and cyclo-oxygenase-2 pathwaysBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2001Fulvia Fabi To further investigate into the mechanisms of PAF-induced cardiopulmonary actions, we examined the effects of the nitric oxide synthase (NOS) inhibitor L -N, -nitro- L -arginine (L -NNA), of the specific cyclooxygenase-2 (COX-2) inhibitor NS 398, and of the combined presence of both COX and NOS inhibitors on the PAF responses in the heart lung preparation of guinea-pig (HLP). In HLPs perfused with homologous blood, dose-response curves for the haemodynamic and bronchial effects of PAF (1 , 32 ng) were carried out in the absence or presence of L -NNA (200 ,M). L -NNA caused an increase in the resting pulmonary arterial pressure (PAP) without affecting the other basal values, and strongly potentiated the bronchoconstriction and pulmonary hypertension elicited by PAF. An enhancement of the PAF-induced actions on right atrial pressure (RAP) and cardiac output (CO) was also observed. All the effects of L -NNA were antagonized by L -arginine (2 mM). The presence of L -NNA in the perfusing blood of HLPs failed to affect the pulmonary hypertensive and bronchoconstrictor responses induced by the thromboxane A2 mimetic U46619 (0.05 , 1.6 ,g), 5-hydroxytryptamine (0.1 , 1.6 ,g), and histamine (0.1 , 1.6 ,g), thus suggesting that these PAF secondary mediators are not responsible for the hyper-responsiveness to PAF induced by L -NNA. Blocking COX-2 pathway with NS 398 (15 , 30 ,M) did not alter the cardiopulmonary resting variables. However, a reduction of the PAF-mediated pulmonary hypertension, but not of bronchoconstriction, was observed. When L -NNA was added to the perfusing medium of HLPs pre-treated with NS 398 or with indomethacin (15 ,M), the basal PAP values were enhanced. However, in the combined presence of COX and NOS inhibitors, only a slight increase in the hypertensive responses to the highest doses of PAF was observed, whereas the PAF mediated actions at bronchial and cardiac level were unaffected. This study indicates that (i) the cardiopulmonary actions induced by PAF are specifically modulated by endogenous NO through the NOS pathway, and (ii) COX-2 isoform is involved in the pulmonary hypertensive, but not bronchoconstrictor, effects of PAF. Furthermore, an interaction between PAF stimulated COX, particularly COX-2, and NOS pathways appears to take a functional role at both bronchial and cardiovascular level. British Journal of Pharmacology (2001) 134, 777,788; doi:10.1038/sj.bjp.0704311 [source] | ||||||||||