Social disruption stress exacerbates alpha-galactosylceramide-induced hepatitis in mice

Objective: Psychosocial stress has been suggested as a possible aggravating factor in liver diseases, however, the underlying mechanism has yet to be clarified. Recently, our research revealed that electric foot-shock stress aggravated NK1.1 Ag+ T cell-dependent a-galactosylceramide (alpha-GalCer)-induced hepatitis in mice via a mechanism mediated by endogenous glucocorticoids. In this study, we examined whether or not such aggravation could be applied to a psychosocially stressful situation, e.g. social disruption stress. Methods: Male wildtype C57BL/6 (B6) or B6 hepatitis virus type B surface antigen transgenic (HBs-tg) mice, a hepatitis B virus carrier mouse model, were exposed 3 times in 1 week to social disruption stress in which an 8-month-old aggressive male intruder was placed into their home cage (5 mice per group) for 2 h. Twelve hours after the final exposure to the stress, the wild-type and HBs-tg mice were intravenously injected with alpha-GalCer. Results:The stress-exposed wild-type mice exhibited significantly reduced thymus weight loss compared with the control animals. Moreover, this stress regimen led to a significant increase in serum alanine aminotransferase levels in both the wild-type and the HBs-tg mice, although the increase in the HBs-tg mice was higher than that in the wild-type mice. Conclusion: These findings demonstrated that, similar to electric foot-shock stress, social disruption stress exacerbated alpha-GalCer-induced hepatitis. Copyright (C) 2005 S. Karger AG, Basel

The hepatic sympathetic nerve plays a critical role in preventing Fas induced liver injury in mice

Background: Although previous studies have shown that the hepatic sympathetic nerve controls various physiological functions in the liver, the role of this nerve in liver injury has yet to be clarified.Aims: The purpose of this study was to elucidate the role of this nerve, based on our newly developed technique for selectively removing the activities of the hepatic sympathetic nerve.Subjects and methods: Male C57BL/6 mice were operated on for hepatic sympathetic denervation. Thereafter, mice were intravenously administered 0.25 or 0.35 mg/g weight of the Fas agonist antibody, Jo-2, after which mortality by fulminant hepatitis was evaluated. Apoptosis in the liver was also examined by both terminal deoxynucleotidyl transferase mediated dUTP nick end labelling and caspase-3 assay.Results: Mortality in sympathectomised mice was significantly higher than that in sham operated mice following administration of Jo-2. This result was also supported by apoptosis data in which sympathectomised livers exhibited a significant elevation in the number of apoptotic hepatocytes and caspase-3 activity after Jo-2 treatment compared with sham operated livers. Moreover, pretreatment with norepinephrine dose dependently inhibited the hepatic sympathectomy induced increase in mortality after Jo-2 injection. Antiapoptotic protein levels of FLICE inhibitory protein, Bcl-xL, and Bcl-2 in the liver were significantly lower in sympathectomised mice at one and two hours following Jo-2 treatment than in sham operated animals. In addition, interleukin 6 supplementation dose dependently suppressed the hepatic sympathectomy induced increase in mortality after Jo-2 treatment.Conclusions: These results suggest that norepinephrine released from the hepatic sympathetic nerve plays a critical role in protecting the liver from Fas mediated fulminant hepatitis, possibly via mechanisms including antiapoptotic proteins and interleukin 6

Electric foot-shock stress drives TNF-alpha production in the liver of IL-6-deficient mice

Objectives: Accumulating evidence has shown that interleukin-6 (IL-6) has pleiotropic effects on a variety of biological functions, including its antiapoptotic potential during liver injury. Our previous work demonstrated that restraint stress-induced elevation of plasma IL-6 negatively regulates plasma tumor necrosis factor-alpha (TNF-alpha). Herein, we further clarified the mechanism underlying the above finding and investigated the effect of IL-6 on liver apoptosis triggered by stress. Methods: Male C57BL/6J and IL-6-deficient C57BL/SV129 mice were exposed to 1 h of electric foot-shock stress. Thereafter, the serum, liver and spleen TNF-alpha levels were measured at several time points. Serum alanine aminotransferase (ALT), liver caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling ( TUNEL) activities were analyzed to evaluate the severity of liver injury and apoptosis. Results: The liver, but not the spleen, of the IL-6-deficient mice exhibited a significant increase in TNF-alpha level after stress in parallel with serum TNF-alpha elevation, whereas no such TNF-alpha responses were found in the wild animals. No significant differences in stress-induced elevation of serum ALT levels, liver caspase-3 activities and the number of TUNEL-positive hepatocytes were found between the wild and IL-6-deficient mice. Conclusions: Taken together, these results indicate that IL-6 may play a critical role in suppressing TNF-alpha production in the liver, thereby decreasing the blood TNF-alpha level. In contrast, IL-6 secretion was shown to have no protective effect on stress-triggered liver injury. Copyright (C) 2004 S. Karger AG, Basel

Behavior problems and prevalence of asthma symptoms among Brazilian children.

OBJECTIVE: Asthma is the most common chronic disease in childhood and has been designated a public health problem due to the increase in its prevalence in recent decades, the amount of health service expenditure it absorbs and an absence of consensus about its etiology. The relationships among psychosocial factors and the occurrence, symptomatology, and severity of asthma have recently been considered. There is still controversy about the association between asthma and a child's mental health, since the pathways through which this relationship is established are complex and not well researched. This study aims to investigate whether behavior problems are associated with the prevalence of asthma symptoms in a large urban center in Latin America. METHODS: It is a cross-section study of 869 children between 6 and 12 years old, residents of Salvador, Brazil. The International Study of Allergy and Asthma in Childhood (ISAAC) instrument was used to evaluate prevalence of asthma symptoms. The Child Behavior Checklist (CBCL) was employed to evaluate behavioral problems. RESULTS: 19.26% (n=212) of the children presented symptoms of asthma. 35% were classified as having clinical behavioral problems. Poisson's robust regression model demonstrated a statistically significant association between the presence of behavioral problems and asthma symptoms occurrence (PR: 1.43; 95% CI: 1.10-1.85). CONCLUSION: These results suggest an association between behavioral problems and pediatric asthma, and support the inclusion of mental health care in the provision of services for asthma morbidity

Daily life stress and the cortisol awakening response : testing the anticipation hypothesis

Acknowledgments We thank Paul Stewart for his contribution to data collection and Dr Matthew Jones for programming the handheld computers. Author Contributions Conceived and designed the experiments: WS DJP. Performed the experiments: DJP. Analyzed the data: WS. Wrote the paper: WS DJP.Peer reviewedPublisher PD

Quantum Fluctuation Theorems

Recent advances in experimental techniques allow one to measure and control systems at the level of single molecules and atoms. Here gaining information about fluctuating thermodynamic quantities is crucial for understanding nonequilibrium thermodynamic behavior of small systems. To achieve this aim, stochastic thermodynamics offers a theoretical framework, and nonequilibrium equalities such as Jarzynski equality and fluctuation theorems provide key information about the fluctuating thermodynamic quantities. We review the recent progress in quantum fluctuation theorems, including the studies of Maxwell's demon which plays a crucial role in connecting thermodynamics with information.Comment: As a chapter of: F. Binder, L. A. Correa, C. Gogolin, J. Anders, and G. Adesso (eds.), "Thermodynamics in the quantum regime - Fundamental Aspects and New Directions", (Springer International Publishing, 2018

Psychological well-being, cardiorespiratory fitness, and long-term survival

BACKGROUND: Psychological well-being is associated with mortality/survival. Although cardiorespiratory fitness (CRF) is one of the strongest predictors of mortality, studies examining the relationship between well-being and survival seldom account for the possible effects of CRF. PURPOSE: This study examined the independent associations of psychological well-being components (low level of negative emotion and high level of positive emotion) and CRF, as well as their combined effects, with survival. METHODS: Participants (N=4888) were examined in 1988-1997 and followed up for a median period of ∼15 years (212 deaths, 4.3%). CRF was assessed by a maximal exercise test on a treadmill. Low-level negative emotion was defined as the minimum score of the negative emotion subscale of the CES-D scale and high-level positive emotion as the maximum score of the positive emotion subscale. Results are presented as hazard ratios (95% CIs). Data were analyzed in 2009. RESULTS: After adjustment for a set of established risk factors, men and women with low levels of negative emotion had lower risk of death than those with higher levels of negative emotion, 0.66 (95% CI=0.50, 0.87). The association persisted after additional adjustment for CRF and positive emotion. High level of positive emotion was not associated with survival. A high level of CRF independently predicted lower risk of death, 0.54 (95% CI=0.37, 0.79), compared to a low level of CRF. The risk of death in participants with both a low level of negative emotion and a high level of CRF was 0.37 (95% CI=0.22, 0.63), compared to their peers with higher levels of negative emotion/low levels of CRF. CONCLUSIONS: Low levels of negative emotion and high levels of CRF are independent predictors of long-term survival in men and women. A strong combined effect was observed, as individuals with both a low level of negative emotion and a high level of CRF had a 63% lower risk of premature death than those with higher levels of negative emotion and a low level of CRF.This study was supported by NIH grants AG06945 and HL62508, and in part by an unrestricted research grant from The Coca-Cola Company. The study also was supported in part by Robert Wood Johnson Foundation's Pioneer Portfolio (grant number 63597); the Spanish Ministry of Education (EX-2008-0641, EX-2007-1124); the Swedish Council for Working Life and Social Research; and the Swedish Heart-Lung Foundation (20090635)