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Potential Mediators (potential + mediator)
Selected AbstractsTreatment of Social Phobia: Potential Mediators and ModeratorsCLINICAL PSYCHOLOGY: SCIENCE AND PRACTICE, Issue 1 2000Stefan G. Hofmann Although the efficacy of numerous psychosocial interventions for social phobia has been clearly demonstrated, little is known about the mediators and moderators of treatment change. Three potential mediators here are discussed that are derived from prominent psychological theories: negative cognitive appraisal (estimated social costs), perceived self-efficacy (perceived social skills), and perceived emotional control. Furthermore, the generalized subtype of social phobia and the additional diagnosis of avoidant personality disorder are considered as potential treatment moderators. [source] ,Lipoproteins, glycoxidation and diabetic angiopathy'DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2004Alicia J. Jenkins Abstract The chronic vascular complications of diabetes (nephropathy, retinopathy and accelerated atherosclerosis) are a major cause of morbidity and premature mortality. In spite of the more widespread availability of intensive diabetes management, approximately one in three people with diabetes develop aggressive complications and over 70% die of atherosclerosis-related diseases. Genetic and acquired factors are likely to be contributory. Potential mediators of vascular damage may include the interrelated processes of lipoprotein abnormalities, glycation, oxidation and endothelial dysfunction. Lipoprotein abnormalities encompass alterations in lipid concentrations, lipoprotein composition and subclass distribution and lipoprotein-related enzymes. Nonenzymatic glycation and oxidative damage to lipoproteins, other proteins and to vascular structures may also be deleterious. As atherosclerosis is a chronic condition commencing in youth, and because clinical events may be silent in diabetes, surrogate measures of vascular disease are important for early identification of diabetic patients with or at high risk of vascular damage, and for monitoring efficacy of interventions. The increasing array of biochemical assays for markers and mediators of vascular damage, noninvasive measures of vascular health, and therapeutic options should enable a reduction in the excessive personal and economic burden of vascular disease in type 1 and type 2 diabetes. Copyright © 2004 John Wiley & Sons, Ltd. [source] Self-expansion as a mediator of relationship improvements in a mindfulness interventionJOURNAL OF MARITAL AND FAMILY THERAPY, Issue 4 2007James W. Carson In a recent randomized controlled trial, couples participating in a mindfulness-based relationship enhancement program demonstrated significant improvements in relationship satisfaction and relationship distress (Carson, Carson, Gil, & Baucom, 2004). Here we report on a multiple mediation analysis of these couples' improvements. Potential mediators included measures of couples' engagement in exciting self-expanding activities, couples' ability to accept one another's difficult characteristics, and individual partners' ability to relax. Results indicate that to a large extent, the mindfulness-related relationship improvements can be attributed to partners' sense that they were participating in exciting self-expanding activities together during the course of the intervention. The implications of these findings for future mindfulness research are discussed. [source] Hypoxia induces cardiac malformations via A1 adenosine receptor activation in chicken embryos,BIRTH DEFECTS RESEARCH, Issue 3 2008Satish K. Ghatpande Abstract BACKGROUND: The current understanding of the effects of hypoxia on early embryogenesis is limited. Potential mediators of hypoxic effects include adenosine, which increases dramatically during hypoxic conditions and activates A1 adenosine receptors (A1ARs). METHODS: To examine the influences of hypoxia and adenosine signaling on cardiac development, chicken embryos were studied. Real time RT-PCR assay was used to examine the A1AR gene expression during embryogenesis and after siRNA- mediated knock down. Cell proliferation was determined by counting cell nuclei and PhosphoHistone H3 positive cells. Apoptosis was determined by TUNEL assay. RESULTS: A1ARs were found to be expressed in chicken embryos during early embryogenesis. Treatment of Hamburger and Hamilton stage 4 embryos with the A1AR agonist N6 -cyclopentyladenosine caused cardiac bifida and looping defects in 55% of embryos. Hamburger and Hamilton stage 4 embryos exposed to 10% oxygen for 6, 12, 18, and 24 h followed by recovery in room air until stage 11, exhibited cardia bifida and looping defects in 34, 45, 60, and 86% of embryos respectively. Hypoxia-induced abnormalities were reduced when A1AR signaling was inhibited by the A1AR antagonist 1,3 dipropyl-8-cyclopentylxanthine or by siRNA-targeting A1ARs. Hypoxia treatment did not increase apoptosis, but decreased embryonic cell proliferation. CONCLUSIONS: These data indicate that hypoxia adversely influences cardiac malformations during development, in part by A1AR signaling. Birth Defects Research (Part A), 2008. © 2008 Wiley-Liss, Inc. [source] Assessment of endothelial function and blood metabolite status following acute ingestion of a fructose-containing beverageACTA PHYSIOLOGICA, Issue 1 2010A. J. Bidwell Abstract Aim:, Fructose intake has increased concurrent with sugar intake and this increase has been implicated in contributing to the development of metabolic syndrome risk factors. Recent evidence suggests a role for uric acid (UA) as a potential mediator via suppression of nitric oxide (NO) bioavailability. The aim of this study was to explore this hypothesis by measuring changes in UA concentration and systemic NO bioavailability as well as endothelial function in response to acute ingestion of a glucose-fructose beverage. Methods:, Ten young (26.80 ± 4.80 years), non-obese (body mass index: 25.1 ± 2.55 kg m,2; percent body fat: 13.5 ± 6.9%) male subjects ingested either a glucose (100 g dextrose in 300 mL) or isocaloric glucose-fructose (glucose : fructose; 45 : 55 g in 300 mL) beverage. Blood was sampled pre- and every 15-min post-ingestion per 90 min and assayed for glucose, lactate, fructose, total nitrate/nitrate, UA and blood lipids. Forearm blood flow and pulse-wave velocity were recorded prior to and at 30 and 45 min time intervals post-ingestion, respectively, while heart rate, systolic and diastolic blood pressure were recorded every 15 min. Results:, The glucose-fructose ingestion was associated with a significant (P < 0.05) increase in plasma lactate concentration and altered free fatty acid levels when compared with glucose-only ingestion. However, UA was not significantly different (P = 0.08) between conditions (AUC: ,1018 ± 1675 vs. 2171 ± 1270 ,mol L,1 per 90 min for glucose and glucose-fructose conditions respectively). Consequently, no significant (P < 0.05) difference in endothelial function or systemic NO bioavailability was observed. Conclusion:, Acute consumption of a fructose-containing beverage was not associated with significantly altered UA concentration, endothelial function or systemic NO bioavailability. [source] Asymmetric dimethylarginine (ADMA): the silent transition from an ,uraemic toxin' to a global cardiovascular risk moleculeEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2005D. Fliser Abstract Endothelial dysfunction as a result of reduced bioavailability of nitric oxide (NO) plays a central role in the process of atherosclerotic vascular disease. In endothelial cells NO is synthesized from the amino acid l -arginine by the action of the NO synthase (NOS), which can be blocked by endogenous inhibitors such as asymmetric dimethylarginine (ADMA). Acute systemic administration of ADMA to healthy subjects significantly reduces NO generation, and causes an increase in systemic vascular resistance and blood pressure. Increased plasma ADMA levels as a result of reduced renal excretion have been associated with atherosclerotic complications in patients with terminal renal failure. However, a significant relationship between ADMA and traditional cardiovascular risk factors such as advanced age, high blood pressure and serum LDL-cholesterol, has been documented even in individuals without manifest renal dysfunction. As a consequence, the metabolism of ADMA by the enzyme dimethylarginine dimethylaminohydrolase (DDAH) has come into the focus of cardiovascular research. It has been proposed that dysregulation of DDAH with consecutive increase in plasma ADMA concentration and chronic NOS inhibition is a common pathophysiological pathway in numerous clinical conditions. Thus, ADMA has emerged as a potential mediator of atherosclerotic complications in patients with coronary heart disease, peripheral vascular disease, stroke, etc., being the culprit and not only an innocent biochemical marker of the atherosclerotic disease process. [source] Serum tumour necrosis factor-, levels in cancer patients are discontinuous and correlate with weight lossEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2000M. Bossola Tumour necrosis factor-, (TNF) has been regarded as a potential mediator of cancer cachexia. Assessment of TNF circulating levels in cancer patients and their correlation with weight loss has led to controversial results. We measured TNF circulating levels in 28 patients with gastrointestinal cancer and 29 controls with benign gastrointestinal diseases at different times (08.00 h, 14.00 h, 20.00 h) before operation. TNF activity was not detected in any of controls at any times. In cancer patients, TNF circulating levels were detectable in 18 cases (64·3%) and appeared to be discontinuous. TNF levels above the limit of detection were present in 15 patients (53·6%) at 08.00 h, in 14 (50%) at 014.00 h and in nine (32·1%) at 20.00 h. Mean TNF levels were 14·3 ± 4 pg mL,1 at 08.00 h, 16·7 ± 4·6 pg mL,1 at 14.00 h (P = 0·05) and 18·5 ± 10·2 pg mL,1 at 20.00 h (P < 0·05 vs. 08.00 h and 14.00 h). According to Spearman's analysis, the sum of TNF concentrations at the three times significantly correlated with the severity of weight loss (Spearman's correlation coefficient =,,0·420; P = 0·026). TNF concentrations were consistently and significantly higher in patients with severe weight loss than in those with moderate or light weight loss at 08.00 h (26·3 ± 8·3, 8·9 ± 4·2, 3·8 ± 2·1, respectively; P = 0·04 at one-way anova). TNF levels were higher in anorectic than in nonanorectic patients at any hour, but the differences were not statistically significant. The present study demonstrates that TNF is intermittently or discontinuously detectable in patients with gastrointestinal cancer and that its levels correlate with the severity of weight loss. [source] Territorial behaviour and immunity are mediated by juvenile hormone: the physiological basis of honest signalling?FUNCTIONAL ECOLOGY, Issue 1 2009Jorge Contreras-Garduño Summary 1The role of the juvenile hormone (JH) as a potential mediator in the trade-off between male,male competition and immune response has not been tested, but its study could reveal a potential mechanism that mediates resource allocation between these two traits. 2Controlling for body size, we tested whether males of the territorial damselfly Calopteryx virgo administrated with methoprene acid, an analog of the JH (JHa), compared to control males, increased their aggression and occupation time on territories but decreased their phenoloxidase (PO) activity (a key enzyme used during immune response after a bacterial challenge). We found an increase in aggression in JHa treated males compared to control males, but the opposite was found for PO activity. 3As fat load and muscle mass are also important traits during a contest, we tested whether JHa males compared to control males showed more fat and muscle content 2 h after JHa administration. Our results did not show a significant difference between both male groups, suggesting that JHa only increased aggression. 4These results and a review of other published articles, which have documented an effect of JH on a variety of functions in insects, suggest that JH may be a target of sexual selection: this hormone not only promotes the expression of secondary sexual characters but also seems condition-dependent and so its titers may indicate male condition. [source] Hyperglycemia and glucosamine-induced mesangial cell cycle arrest and hypertrophy: Common or independent mechanisms?IUBMB LIFE, Issue 7 2006Elodie Masson Abstract The Hexosamine Pathway (HP) is one hypothesis proposed to explain glucose toxicity and the alterations observed during the course of diabetic microvascular complication development. Glucosamine is a precursor of UDP-N-Acetylglucosamine (UDP-GlcNAc), the main product of the HP that has often been used to mimic its activation. The transfer of a UDP-GlcNAc residue onto proteins (O-GlcNAc modification) represents the final step of the HP and is considered as a major mechanism by which this pathway exerts its signalling effects. While it is well accepted that the HP promotes extracellular matrix accumulation in the context of diabetic nephropathy, its involvement in the perturbations of cell cycle progression and hypertrophy of renal cells has been poorly investigated. Nevertheless, in a growing number of studies, the HP and O-GlcNAc modification are emerging as important regulators of cell cycle progression. This review will focus on the role of glucosamine and O-GlcNAc modification in cell cycle regulation in the context of diabetic nephropathy. Special emphasis will be given into the role of the HP as a potential mediator of the effects of high glucose on the perturbations of renal cell growth. iubmb Life, 58: 381-388, 2006 [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] Body Weight Perception, Unhealthy Weight Control Behaviors, and Suicidal Ideation Among Korean AdolescentsJOURNAL OF SCHOOL HEALTH, Issue 12 2009Dong-Sik Kim DrPH ABSTRACT BACKGROUND: This study examined the mediating function of body weight perception (BWP) in the relation between body mass index (BMI) and unhealthy weight control behaviors (UWCBs; eg, fasting, using diet pills, or laxatives), and between BMI and suicidal ideation. It also explored the correlation between exposure to multiple UWCBs and suicidal ideation among Korean adolescents. METHODS: Data on BMI, BWP, UWCBs, and suicidal ideation were obtained from the 2006 Korean Youth Risk Behavior Web-based Survey, a school-based survey conducted on a nationally representative sample of students in grades 7,12 (36,463 boys and 33,433 girls). Data were analyzed using bivariate and multivariate logistic regression. RESULTS: BMI was significantly associated with both UWCB and suicidal ideation among boys and girls, even after controlling for covariates. However, the significance and magnitude of the association between BMI and UWCB were considerably attenuated when BWP was added to the model. When BWP was included, the association between overweight BMI status and suicidal ideation became nonsignificant in both sexes, whereas the association between underweight BMI status and suicidal ideation remained significant among boys. Adolescent boys and girls engaging in multiple UWCBs were at greater risk for experiencing suicidal thoughts. CONCLUSIONS: This study suggests that BWP represents a potential mediator between BMI and UWCB, and between BMI and suicidal ideation among both boys and girls. Thus, school programs addressing issues related to BWP should be developed and targeted at adolescents to reduce the potential risks for both UWCB and suicidal behavior. [source] Increased metastatic potential of tumor cells in von Willebrand factor-deficient miceJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 3 2006V. TERRAUBE Summary.,Background:,The key role played by von Willebrand factor (VWF) in platelet adhesion suggests a potential implication in various pathologies, where this process is involved. In cancer metastasis development, tumor cells interact with platelets and the vessel wall to extravasate from the circulation. As a potential mediator of platelet,tumor cell interactions, VWF could influence this early step of tumor spread and therefore play a role in cancer metastasis.Objectives:,To investigate whether VWF is involved in metastasis development.Methods:,In a first step, we characterized the interaction between murine melanoma cells B16-BL6 and VWF in vitro. In a second step, an experimental metastasis model was used to compare the formation of pulmonary metastatic foci in C57BL/6 wild-type and VWF-null mice following the injection of B16-BL6 cells or Lewis lung carcinoma cells.Results:,In vitro adhesion assays revealed that VWF is able to promote a dose-dependent adhesion of B16-BL6 cells via its Arg-Gly-Asp (RGD) sequence. In the experimental metastasis model, we found a significant increase in the number of pulmonary metastatic foci in VWF-null mice compared with the wild-type mice, a phenotype that could be corrected by restoring VWF plasma levels. We also showed that increased survival of the tumor cells in the lungs during the first 24 h in the absence of VWF was the cause of this increased metastasis.Conclusion:,These findings suggest that VWF plays a protective role against tumor cell dissemination in vivo. Underlying mechanisms remain to be investigated. [source] Inverse Association between T-Cell Immunoglobulin and Mucin Domain-1 and T-bet in a Mouse Model of Allergic Rhinitis,THE LARYNGOSCOPE, Issue 6 2007Geng Xu MD Abstract Background: It has been suggested that human hepatitis A virus cellular receptor, also known as T-cell immunoglobulin and mucin domain-1 (TIM-1), plays an important role in the development of allergic diseases on the basis of epidemiologic data, but the molecular mechanism has been unclear. In a murine model of ovalbumin (OVA)-sensitized allergic rhinitis (AR), we examined the expression of TIM-1 and its correlation with T helper1-associated transcription factor, T-bet, as a potential mediator of T-cell immunoglobulin expression. Methods: Mice were challenged intranasally with OVA to elicit AR. The expression of TIM-1 in nasal tissues was examined by real-time reverse-transcription polymerase chain reaction (RT-PCR), and the surface expression of TIM-1 in peripheral blood mononuclear cells was evaluated by means of flow cytometry. In addition, the expression of TIM-1 as well as T-bet in splenic lymphocytes was examined by Western blotting. Results: TIM-1 mRNA was increased significantly in nasal tissues (P < .05) as seen by real-time RT-PCR. Flow cytometry indicated a differential TIM-1 expression of 135.5 ± 34.2 in the AR group versus 51.1 ± 10.9 in the control group (P < .05). The mean values of normalized TIM-1 were 0.43 ± 0.18 and 0.21 ± 0.10 in AR and control groups, respectively, whereas the mean values of normalized T-bet were 0.22 ± 0.13 and 0.67 ± 0.17 in the AR and control groups, respectively. There was a significant difference in the production of TIM-1 as well as T-bet in AR mice versus control mice (P < .05). The increased production of TIM-1 correlated significantly with the decreased T-bet in spleen tissue of AR mice (r = ,0.52, P < .05). Conclusion: Our experimental model recapitulates an increase in lymphocyte TIM-1 expression seen in AR both locally and systemically. Our results also demonstrate an inverse relationship between lymphocyte TIM-1 and T-bet expression, suggesting a possible mechanism that TIM-1 influences the development of AR. [source] Kallikrein 4 is a potential mediator of cellular interactions between cancer cells and osteoblasts in metastatic prostate cancerTHE PROSTATE, Issue 4 2007Jin Gao Abstract BACKGROUND Prostate cancer (PCa) and bone cell interactions are critical in the metastatic phase. Kallikrein 4 (KLK4/hK4) is expressed in both PCa and mineralized tissues. We determined if KLK4/hK4 expression was associated with, and influenced by, the bone environment of metastatic PCa. METHODS Immunohistochemistry, in vitro co-culture, cell migration, and attachment assays. RESULTS hK4 was localized to tumor cells and osteoblasts in bone metastases. KLK4/hK4 increased in LNCaP and PC3 cells co-cultured with SaOs2 cells; SaOs2 KLK4/hK4 was unchanged. Co-culture did not affect cell proliferation but altered alkaline phosphatase activity/mRNA levels in SaOs2 cells. KLK4 -transfected PC3 cells had increased migration towards SaOs2 conditioned medium and greater attachment to the bone-matrix proteins, collagens I and IV. CONCLUSIONS hK4 expression and interaction with both tumor cells and osteoblasts suggests a role for hK4 in PCa bone metastasis. Whether this observation is unique to bone metastasis or reflects a role for hK4 in PCa metastasis generally is yet to be established. Prostate 67: 348,360, 2007. © 2007 Wiley-Liss, Inc. [source] Gene expression in the efferent ducts, epididymis, and vas deferens during embryonic development of the mouseDEVELOPMENTAL DYNAMICS, Issue 9 2010Elizabeth M. Snyder Abstract The tissues of the male reproductive tract are characterized by distinct morphologies, from highly coiled to un-coiled. Global gene expression profiles of efferent ducts, epididymis, and vas deferens were generated from embryonic day 14.5 to postnatal day 1 as tissue-specific morphologies emerge. Expression of homeobox genes, potential mediators of tissue-specific morphological development, was assessed. Twenty homeobox genes were identified as either tissue-enriched, developmentally regulated, or both. Additionally, ontology analysis demonstrated cell adhesion to be highly regulated along the length of the reproductive tract. Regulators of cell adhesion with variable expression between the three tissues were identified including Alcam, various cadherins, and multiple integrins. Immunofluorescence localization of the cell adhesion regulators POSTN and CDH2 demonstrated cell adhesion in the epithelium and mesenchyme of the epididymis may change throughout development. These results suggest cell adhesion may be modulated in a tissue-specific manner, playing an important role in establishing each tissue's final morphology. Developmental Dynamics 239:2479,2491, 2010. © 2010 Wiley-Liss, Inc. [source] Jarid2 is among a set of genes differentially regulated by Nkx2.5 during outflow tract morphogenesisDEVELOPMENTAL DYNAMICS, Issue 7 2010Jeremy L. Barth Abstract Nkx2.5, a transcription factor implicated in human congenital heart disease, is required for regulation of second heart field (SHF) progenitors contributing to outflow tract (OFT). Here, we define a set of genes (Lrrn1, Elovl2, Safb, Slc39a6, Khdrbs1, Hoxb4, Fez1, Ccdc117, Jarid2, Nrcam, and Enpp3) expressed in SHF containing pharyngeal arch tissue whose regulation is dependent on Nkx2.5. Further investigation shows that Jarid2, which has been implicated in OFT morphogenesis, is a direct target of Nkx2.5 regulation. Jarid2 expression was up-regulated in SHF mesoderm of Nkx2.5-deficient embryos. Chromatin immunoprecipitation analysis showed Nkx2.5 interaction with consensus binding sites in the Jarid2 promoter in pharyngeal arch cells. Finally, Jarid2 promoter activity and mRNA expression levels were down-regulated by Nkx2.5 overexpression. Given the role of Jarid2 as a regulator of early cardiac proliferation, these findings highlight Jarid2 as one of several potential mediators of the critical role played by Nkx2.5 during OFT morphogenesis. Developmental Dynamics 239:2024,2033, 2010. © 2010 Wiley-Liss, Inc. [source] Degradation in insulin sensitivity with increasing severity of the metabolic syndrome in obese postmenopausal womenDIABETES OBESITY & METABOLISM, Issue 3 2006A. D. Karelis Aim:, We investigated the relationship between insulin sensitivity and the graded increase in the number of features of the metabolic syndrome in a cross-sectional sample of obese postmenopausal women. We hypothesized that insulin sensitivity would deteriorate with an increased number of metabolic syndrome phenotypes. Methods:, Insulin sensitivity was measured in 75 obese postmenopausal women (age: 57.3 ± 5.3 years; BMI: 32.8 ± 4.5 kg/m2) by using both the hyperinsulinaemic,euglycaemic clamp and the homeostasis model assessment (HOMA-IR). Features of the metabolic syndrome included visceral fat (>130 cm2), HDL-cholesterol (<1.29 mmol/l), fasting triglycerides (,1.7 mmol/l), blood pressure (,130/,85 mmHg) and fasting glucose (,6.1 mmol/l). Participants were classified into three categories based on the presence of metabolic syndrome phenotypes: 0,1 vs. 2 vs. ,3 features of the metabolic syndrome. Results:, We found that insulin sensitivity decreased in a graded fashion (12.19 ± 3.2 vs. 11.80 ± 2.3 vs. 9.29 ± 2.6 mg/min/FFM) and HOMA-IR increased in a similar manner (2.95 ± 1.1 vs. 3.28 ± 1.3 vs. 4.65 ± 2.2), as the number of features of the metabolic syndrome increased from 0,1 to ,3. When insulin sensitivity was statistically adjusted for visceral fat (as measured by computed tomography) and plasma triglycerides, the differences among groups were abolished. Conclusions:, These findings suggest that a decreased insulin sensitivity is associated with increased features of the metabolic syndrome in obese postmenopausal women and that visceral fat as well as plasma triglyceride accumulation might be potential mediators of this relationship. [source] Islet adaptation to insulin resistance: mechanisms and implications for interventionDIABETES OBESITY & METABOLISM, Issue 1 2005B. Ahrén Abstract:, Insulin sensitivity and insulin secretion are reciprocally related such that insulin resistance is adapted by increased insulin secretion to maintain normal glucose and lipid homeostasis. The relation between insulin sensitivity and secretion is curvilinear and mathematically best described as a hyperbolic relation. Several potential mediators have been suggested to be signals for the beta cells to respond to insulin resistance such as glucose, free fatty acids, autonomic nerves, fat-derived hormones and the gut hormone glucagon-like peptide-1 (GLP-1). Failure of these signals or of the pancreatic beta cells to adequately adapt insulin secretion in relation to insulin sensitivity results in inappropriate insulin levels, impaired glucose intolerance (IGT) and type 2 diabetes. Therefore, treatment of IGT and type 2 diabetes should aim at restoring the normal relation between insulin sensitivity and secretion. Such treatment includes stimulation of insulin secretion (sulphonylureas, repaglinide and nateglinide) and insulin sensitivity (metformin and thiazolidinediones), as well as treatment aimed at supporting the signals mediating the islet adaptation (cholinergic agonists and GLP-1). Both, for correct understanding of diabetes pathophysiology and for development of novel treatment modalities, therefore, the non-linear inverse relation between insulin sensitivity and secretion needs to be acknowledged. [source] Twelve-Step affiliation and 3-year substance use outcomes among adolescents: social support and religious service attendance as potential mediatorsADDICTION, Issue 6 2009Felicia W. Chi ABSTRACT Aims Twelve-Step affiliation among adolescents is little understood. We examined 12-Step affiliation and its association with substance use outcomes 3 years post-treatment intake among adolescents seeking chemical dependency (CD) treatment in a private, managed-care health plan. We also examined the effects of social support and religious service attendance on the relationship. Design We analyzed data for 357 adolescents, aged 13,18, who entered treatment at four Kaiser Permanente Northern California CD programs between March 2000 and May 2002 and completed both baseline and 3-year follow-up interviews. Measures Measures at follow-up included alcohol and drug use, 12-Step affiliation, social support and frequency of religious service attendance. Findings At 3 years, 68 adolescents (19%) reported attending any 12-Step meetings, and 49 (14%) reported involvement in at least one of seven 12-Step activities, in the previous 6 months. Multivariate logistic regression analyses indicated that after controlling individual and treatment factors, 12-Step attendance at 1 year was marginally significant, while 12-Step attendance at 3 years was associated with both alcohol and drug abstinence at 3 years [odds ratio (OR) 2.58, P < 0.05 and OR 2.53, P < 0.05, respectively]. Similarly, 12-Step activity involvement was associated significantly with 30-day alcohol and drug abstinence. There are possible mediating effects of social support and religious service attendance on the relationship between post-treatment 12-Step affiliation and 3-year outcomes. Conclusions The findings suggest the importance of 12-Step affiliation in maintaining long-term recovery, and help to understand the mechanism through which it works among adolescents. [source] Cytotoxicity and oxidative stress caused by chemicals adsorbed on particulate matter,ENVIRONMENTAL TOXICOLOGY, Issue 5 2006Andrea Müller Abstract Air particulate matter (PM) and bound chemicals are potential mediators for adverse health effects. The cytotoxicity and changes in energy-providing processes caused by chemical compounds bound to PM of different size fractions were investigated in Tetrahymena pyriformis. The PM samplings were carried out using a high volume cascade impactor (6 size fractions between 10 ,m and less than 0.49 ,m) at three points of La Plata, Argentina: in an industrial area, a traffic-influenced urban area, and a control area. Extracts from respirable particles below 1 ,m initiated the highest cytotoxic effects, demonstrating their higher risk. In contrast, an increase on oxygen consumption was observed especially in tests of extracts from particles less than 1 ,m from urban and industrial areas. The increase on oxygen consumption could be caused by decoupling processes in the respiratory chain. Otherwise the ATP concentration was increased too, even though to a lower extent. The observed imbalance between oxygen consumption and ATP concentration in exposed T. pyriformis cells may be due to oxidative stress, caused by chemical compounds bound to the particles. Owing to the complexity of effects related to PM and their associated chemical compounds, various physiological parameters necessarily need to be investigated to obtain more information about their possible involvement in human relevant pathogenic processes. As shown here, effects on cell proliferation and on energy-providing processes are suitable indicators for the different impact of PM and adsorbed chemicals from various sampling locations. © 2006 Wiley Periodicals, Inc. Environ Toxicol 21: 457,463, 2006. [source] Endogenous ursodeoxycholic acid and cholic acid in liver disease due to cystic fibrosisHEPATOLOGY, Issue 6 2004Jeffery L. Smith Focal biliary cirrhosis causes significant morbidity and mortality in cystic fibrosis (CF). Although the mechanisms of pathogenesis remain unclear, bile acids have been proposed as potential mediators of liver injury. This study examined bile acid composition in CF and assessed altered bile acid profiles to determine if they are associated with incidence and progression of liver injury in CF-associated liver disease (CFLD). Bile acid composition was determined by gas,liquid chromatography/mass spectrometry in bile, urine, and serum samples from 30 children with CFLD, 15 children with CF but without liver disease (CFnoLD), and 43 controls. Liver biopsies from 29 CFLD subjects were assessed histologically by grading for fibrosis stage, inflammation, and disruption of the limiting plate. A significantly greater proportion of endogenous biliary ursodeoxycholic acid (UDCA) was demonstrated in CFnoLD subjects vs. both CFLD subjects and controls (2.4- and 2.2-fold, respectively; ANOVA, P = .04), and a 3-4 fold elevation in endogenous serum UDCA concentration was observed in both CFLD subjects and CFnoLD subjects vs. controls (ANOVA, P < .05). In CFLD, there were significant correlations between serum cholic acid and hepatic fibrosis, inflammation, and limiting plate disruption as well as the ratio of serum cholic acid/chenodeoxycholic acid to hepatic fibrosis, inflammation, and limiting plate disruption. In conclusion, elevated endogenous UDCA in CFnoLD suggests a possible protective role against liver injury in these patients. The correlation between both cholic acid and cholic acid/chenodeoxycholic acid levels with histological liver injury and fibrosis progression suggests a potential monitoring role for these bile acids in CFLD. (HEPATOLOGY 2004;39:1673,1682.) [source] Do maternal stress and home environment mediate the relation between early income-to-need and 54-months attentional abilities?INFANT AND CHILD DEVELOPMENT, Issue 5 2007Janean E. Dilworth-Bart Abstract Using Ecological Systems Theory and stage sequential modelling procedures for detecting mediation, this study examined how early developmental contexts impact preschoolers' performances on a measure of sustained attention and impulse control. Data from 1273 European-American and African-American participants in the NICHD Study of Early Child Care were used to identify the potential mediators of the relation between early household income-to-need (INR) and 54-month impulsivity and inattention. Exploratory analyses were also conducted to determine whether the relationships between early income, home environment, parenting stress, and the outcome variables differ for African-American versus European-American-American children. We found modest support for the study hypothesis that 36-month home environment quality mediated the INR/attention relationship. INR accounted for more home environment score variance and home environment accounted for more Impulsivity score variance for African-American children. Home environments were related to inattention in the European-American, but not African-American, group. Copyright © 2007 John Wiley & Sons, Ltd. [source] Enhanced Chondrogenesis and Wnt Signaling in PTH-Treated Fractures,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2007Sanjeev Kakar Abstract Studies have shown that systemic PTH treatment enhanced the rate of bone repair in rodent models. However, the mechanisms through which PTH affects bone repair have not been elucidated. In these studies we show that PTH primarily enhanced the earliest stages of endochondral bone repair by increasing chondrocyte recruitment and rate of differentiation. In coordination with these cellular events, we observed an increased level of canonical Wnt-signaling in PTH-treated bones at multiple time-points across the time-course of fracture repair, supporting the conclusion that PTH responses are at least in part mediated through Wnt signaling. Introduction: Since FDA approval of PTH [PTH(1,34); Forteo] as a treatment for osteoporosis, there has been interest in its use in other musculoskeletal conditions. Fracture repair is one area in which PTH may have a significant clinical impact. Multiple animal studies have shown that systemic PTH treatment of healing fractures increased both callus volume and return of mechanical competence in models of fracture healing. Whereas the potential for PTH has been established, the mechanism(s) by which PTH produces these effects remain elusive. Materials and Methods: Closed femoral fractures were generated in 8-wk-old male C57Bl/6 mice followed by daily systemic injections of either saline (control) or 30 ,g/kg PTH(1,34) for 14 days after fracture. Bones were harvested at days 2, 3, 5, 7, 10, 14, 21, and 28 after fracture and analyzed at the tissue level by radiography and histomorphometry and at the molecular and biochemical levels level by RNase protection assay (RPA), real-time PCR, and Western blot analysis. Results: Quantitative ,CT analysis showed that PTH treatment induced a larger callus cross-sectional area, length, and total volume compared with controls. Molecular analysis of the expression of extracellular matrix genes associated with chondrogenesis and osteogenesis showed that PTH treated fractures displayed a 3-fold greater increase in chondrogenesis relative to osteogenesis over the course of the repair process. In addition, chondrocyte hypertrophy occurred earlier in the PTH-treated callus tissues. Analysis of the expression of potential mediators of PTH actions showed that PTH treatment significantly induced the expression of Wnts 4, 5a, 5b, and 10b and increased levels of unphosphorylated, nuclear localized ,-catenin protein, a central feature of canonical Wnt signaling. Conclusions: These results showed that the PTH-mediated enhancement of fracture repair is primarily associated with an amplification of chondrocyte recruitment and maturation in the early fracture callus. Associated with these cellular effects, we observed an increase in canonical Wnt signaling supporting the conclusion that PTH effects on bone repair are mediated at least in part through the activation of Wnt-signaling pathways. [source] Role of serum cytokines tumour necrosis factor- , and interleukin-6 in the association between body weight and periodontal infectionJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 2 2009Tuomas Saxlin Abstract Aim: To study the role of serum cytokines tumour necrosis factor , (TNF- ,) and interleukin 6 (IL-6) as potential mediators in the association between body weight and periodontal infection among an adult population. Material and Methods: This study was based on a subpopulation of the Health 2000 Health Examination Survey, which included dentate non-diabetic, non-rheumatic subjects, aged between 45 and 64 years, who had never smoked and whose serum levels of TNF- , and IL-6 were analysed and whose periodontal status was clinically determined (effective n=425). The number of teeth with periodontal pockets of 4 mm or more and the number of teeth with periodontal pockets of 6 mm or more were used as outcome variables. Relative risks and 95% confidence intervals were estimated using Poisson regression models. Results: Serum IL-6, but not TNF- , associated with teeth with deepened periodontal pockets. Multivariate models showed that IL-6, but not TNF- ,, could mediate the effect of body weight on periodontium. Conclusion: In this population of non-diabetic and non-rheumatic subjects, who had never smoked, serum IL-6 was associated with periodontal infection. The results suggest that serum IL-6 could be one mediating factor that connects body weight and periodontal infection. [source] I think therefore i om: cognitive distortions and coping style as mediators for the effects of mindfulness meditation on anxiety, positive and negative affect, and hopeJOURNAL OF CLINICAL PSYCHOLOGY, Issue 6 2009Sharon Sears Abstract This study examined cognitive distortions and coping styles as potential mediators for the effects of mindfulness meditation on anxiety, negative affect, positive affect, and hope in college students. Our pre- and postintervention design had four conditions: control, brief meditation focused on attention, brief meditation focused on loving kindness, and longer meditation combining both attentional and loving kindness aspects of mindfulness. Each group met weekly over the course of a semester. Longer combined meditation significantly reduced anxiety and negative affect and increased hope. Changes in cognitive distortions mediated intervention effects for anxiety, negative affect, and hope. Further research is needed to determine differential effects of types of meditation. © 2009 Wiley Periodicals, Inc. J Clin Psychol 65: 1,13, 2009. [source] Veteran Status, Race-Ethnicity, and Marriage Among Fragile FamiliesJOURNAL OF MARRIAGE AND FAMILY, Issue 3 2009Margaret L. Usdansky We used data from the Fragile Families and Child Wellbeing Study (N = 2,679 ) to examine the impact of men's past military service on the likelihood that a couple will marry within 5 years of a nonmarital birth. Logistic regression analyses showed that men's past military service increased marriage odds by 54% for couples with Black fathers even after controlling for potential mediators. But veteran status had no effect on couples with White or Hispanic fathers. As a result, the large Black-White gap in postbirth marriage evident among couples with civilian fathers did not exist among couples with veteran fathers. Our findings bolster other evidence that military service exerts lasting and unique pro-marriage effects on Blacks. [source] Comparing Structural Equation Models That Use Different Measures of the Level of Response to AlcoholALCOHOLISM, Issue 5 2010Marc A. Schuckit Background:, The two measures of a low level of response (LR) to alcohol, an alcohol challenge and the retrospective Self-Report of the Effects of Alcohol questionnaire (SRE), each identify individuals at high risk for heavy drinking and alcohol problems. These measures also perform similarly in identifying subjects with unique functional brain imaging characteristics. However, few data are available regarding whether alcohol challenge-based and SRE-based LRs operate similarly in structural equation models (SEMs) that search for characteristics, which help to mediate how LR impacts alcohol outcomes. Methods:, Two hundred and ninety-four men from the San Diego Prospective Study were evaluated for their LR to alcohol using alcohol challenges at ,age 20. At ,age 35, the same subjects filled out the SRE regarding the number of drinks needed for effects 15 to 20 years earlier. The two different LR scores for these men were used in SEM analyses evaluating how LR relates to future heavy drinking and to drinking in peers (PEER), alcohol expectancies (EXPECT), and drinking to cope (COPE) as potential mediators of the LR to drinking pattern (ALCOUT) relationships. Results:, While the 2 LR measures that were determined 15 years apart related to each other at a modest level (r = 0.17, p < 0.01), the SEM results were similar regardless of the LR source. In both alcohol challenge-based and SRE-based LR models, LR related directly to ALCOUT, with partial mediation from PEER and COPE, but not through EXPECT in these 35-year-old men. Conclusions:, Consistent with the >60% overlap in prediction of outcomes for the 2 LR measures, and with results from functional brain imaging, alcohol challenge- and SRE-based LR values operated similarly in SEM models in these men. [source] The Role of Youth Problem Behaviors in the Path From Child Abuse and Neglect to Prostitution: A Prospective ExaminationJOURNAL OF RESEARCH ON ADOLESCENCE, Issue 1 2010Helen W. Wilson Behaviors beginning in childhood or adolescence may mediate the relationship between childhood maltreatment and involvement in prostitution. This paper examines 5 potential mediators: early sexual initiation, running away, juvenile crime, school problems, and early drug use. Using a prospective cohort design, abused and neglected children (ages 0,11) with cases processed during 1967,1971 were matched with nonabused, nonneglected children and followed into young adulthood. Data are from in-person interviews at approximately age 29 and arrest records through 1994. Structural equation modeling tested path models. Results indicated that victims of child abuse and neglect were at increased risk for all problem behaviors except drug use. In the full model, only early sexual initiation remained significant as a mediator in the pathway from child abuse and neglect to prostitution. Findings were generally consistent for physical and sexual abuse and neglect. These findings suggest that interventions to reduce problem behaviors among maltreated children may also reduce their risk for prostitution later in life. [source] Re-Examining Whether and Why Acculturation Relates to Drinking Outcomes in a Rigorous, National Survey of LatinosALCOHOLISM, Issue 12 2005Sarah E. Zemore Abstract: Background: Fundamental limitations have hampered conclusions surrounding acculturation's effects among Latinos. This research re-examines associations between acculturation and alcohol use, addressing the most troubling of these limitations. The research also explores mediators of the association, and the dimensional structure of acculturation. Methods: Linear regressions and scale analyses were used to analyze data from Latino adults in the U.S. (825 women, 761 men) sampled in the 1995 National Alcohol Survey. Analyses used a standard, reliable acculturation scale and well-validated drinking measures; systematically accounted for demographic covariates; and analyzed men and women separately. Results: As expected, higher acculturation was positively associated with a higher probability of drinking (vs. abstinence) among women, and higher average volumes and more frequent drunkenness among female drinkers. Acculturation was unrelated to alcohol use among men. Also as expected, mediational analyses of average volume supported expectations that gender-specific drinking norms would mediate acculturation's effects (though norms did not explain acculturation's associations with either drinking status or frequency of drunkenness). Analyses investigating depressive symptoms showed no support for the acculturation-stress model. Factor analyses of the acculturation scale supported the hypothesized distinctions between linguistic acculturation, attitudinal acculturation, and the social environment of acculturation. Further, items implying more intimate exposure to Anglo culture (i.e., language use) were most strongly related to drinking outcomes among women, supporting the normative interpretation of acculturation's effects on drinking. Conclusions: Results underline acculturation's influence on alcohol consumption among Latina women, and highlight the role of drinking norms in mediating this association. Results also suggest a multidimensional view of acculturation. The article recommends further research on drinking norms and other potential mediators of acculturation's effects among Latina women. [source] Integrating Person-Centered and Variable-Centered Approaches in the Study of Developmental Courses and Transitions in Alcohol Use: Introduction to the Special SectionALCOHOLISM, Issue 6 2000Marsha E. Bates This special section consists of research from the symposium "Integrating Person-Centered and Variable-Centered Approaches to the Study of Developmental Courses and Transitions in Alcohol Use," presented at the 1999 Annual Meeting of the Research Society on Alcoholism. The section focuses on ways to integrate variable-centered and person-centered approaches to better understand longitudinal trajectories of alcohol use and associated problems. Our aim is to increase awareness and discussion of alternative conceptual and quantitative approaches that involve both a person-centered and a variable-centered component, and to make these methods more accessible to alcohol and other drug researchers. The first paper provides a general latent variable modeling framework within which to conceptualize developmental questions that involve the combination of continuous latent variables and categorical variables that represent classifications of individuals into meaningful subgroups. This is followed by three empirical papers that use integrative methods to examine early adult outcomes of adolescent binge drinking; potential mediators of familial alcoholism effects on alcohol and tobacco use disorder comorbidity; and the ability of psychopathology, substance use, and parental history of alcohol problems to predict individual differences in the likelihood of transitions in drinking behavior during adolescence. The section concludes with a discussion of the statistical basis for integrating person-centered and variable-centered methods, a comparison of study findings, and directions for future research. [source] | ||||||||||||||||||||||