Alcohol,inflammation,and gut-liver-brain interactions in tissue damage and disease development

Chronic inflammation is often associated with alcoholrelated medical conditions. The key inducer of such inflammation, and also the best understood, is gut microflora-derived lipopolysaccharide (LPS). Alcohol can significantly increase the translocation of LPS from the gut. In healthy individuals, the adverse effects of LPS are kept in check by the actions and interactions of multiple organs. The liver plays a central role in detoxifying LPS and producing a balanced cytokine milieu. The central nervous system contributes to anti-inflammatory regulation through neuroimmunoendocrine actions. Chronic alcohol use impairs not only gut and liver functions, but also multi-organ interactions, leading to persistent systemic inflammation and ultimately, to organ damage. The study of these interactions may provide potential new targets for therapeutic intervention.

Increased expression level of corticotropin-releasing hormone in the amygdala and in the hypothalamus in rats exposed to chronic unpredictable mild stress

Objective Corticotropin-releasing hormone（CRH）plays an important role in neuroendocrine,autonomic and behavioral responses to stressors.In the present study,the effect of chronic unpredictable mild stress（CUMS）on CRH neurons was investigated in rat brain.Methods The rats were exposed to one of the stressors each day for 21 d.Immunostaining was performed to detect the CRH-positive neurons in the paraventricular nucleus（PVN）of the hypothalamus and in amygdala.Results After the stress protocol,the animals showed a reduction in body weight gain as well as reduced sucrose preference and locomotor activity.Interestingly,the CRH neurons in both PVN and central nucleus of the amygdala（CeA）were stimulated by CUMS.The densities of CRH-containing neurons in both PVN and CeA were significantly higher than those in control group.Conclusion The CRH systems in PVN and CeA may both contribute to depression-like behaviors during CUMS.

Effects of neuro-immuno-modulation on healing of wound combined with local radiation injury in rats

Purpose： To investigate effects of neuro-immuno-modulation on wound healing by observing changes of cytokines and hypothalamic-pituitary-adrenal （HPA） axis hormones in acute stress reaction in rats with wound and combined local radiation injury. Methods： Sixty female Wistar rats （weighting 200 ± 20 g） were randomly divided into normal control group, wound group and combined wound-local radiation （CWR） group （25 Gy local radiation post wound）, 20 rats in each group. Contents of IL-1β, IL-6 and IFN-γ and IL-4 in serum were measured and changes of adrenocorticotropic hormone （ACTH） and glucocorticoid （GC） in serum were analyzed by using enzyme-linked immunosorbent assay and radioimmunologic assay, respectively at different time points post wound and radiation. Results： （1） The level of IFN-γ, one of the Thl cell cytokines increased significantly at 14 d post CWIL which was markedly higher than that in control group and wound group. However, the level of IL-4, IL-1β and IL-6, one of the Th2 cell cytokines, did not show obvious change. （2） Ratio of Thl/Th2 （IFN-γ/IL-4） in wound group and CWR group increased significantly at 7 d after wound and radiation, which suggested that Thl/Th2 balance drifted to Thl immune response. The ratio of Thl/Th2 in wound group returned to the normal level up to 14 d after the wound and radiation, while the Thl/Th2 ratio in CWR group increased persistently and was much higher than that in control and wound groups. （3） Level of serous ACTH and CC in CWR group increased at 3 d post wound and radiation, and among them, level of CC showed statistically significant increase, which was much higher than that in control and wound groups. Conclusion： Level of serous neurohormone CC in rats increased significantly immediately after wound and radiation; while the level of IFN-γ showed significant increase only up to 14 d after wound and radiation, and the Th1/Th2 imbalance sustained till 28 d post wound and radiation. In order to reduce acute damage caused by CWR, organic immune system and nerve system showed up a marked regulate effects simultaneously and mutually. Nonetheless, the excessive stress induced by CWR causes distur- bance of immunoregulation, which is one of the key reasons for delayed wound healing in CWR.

Diagnosis and management of pediatric adrenal insufficiency

Background:Adrenal insufficiency(AI)is a wellknown cause of potentially life-threatening disorders.Defects at each level of the hypothalamic-pituitary-adrenal axis can impair adrenal function,leading to varying degrees of glucocorticoid(GC)deficiency.Iatrogenic AI induced by exogenous GCs is the most common cause of AI.The criteria for the diagnosis and management of iatrogenic AI,neonatal AI,and critical illness-related corticosteroid insuffi ciency(CIRCI)are not clear.Data sources:We reviewed the recent original publications and classical data from the literature,as well as the clinical,diagnostic and management strategies of pediatric AI.Results:Practical points in the diagnosis and management of AI with an emphasis on iatrogenic AI,neonatal AI,and CIRCI are provided.Given the lack of sensitive and practical biochemical tests for diagnosis of subtle AI,GC treatment has to be tailored to highly suggestive clinical symptoms and signs.Treatment of adrenal crisis is well standardized and patients almost invariably respond well to therapy.It is mainly the delay in treatment that is responsible for mortality in adrenal crisis.Conclusion:Education of patients and health care professionals is mandatory for timely interventions for patients with adrenal crisis.