Alcohol intoxication accelerates aging: Assessment of biomarkers of healthy aging in alcohol consumers
Individuals over the age of 65 currently represent a substantial percentage of the population, and their numbers are predicted to increase in the future. Older individuals have an elevated systemic basal inflammatory state referred to as “inflamm-aging,” which has been implicated in the greater prevalence of chronic diseases associated with aging. Inflamm-aging may also contribute to increased mortality after acute illness, namely infection, among older people. The immune system of older people is impaired; yet, the exact mechan ism(s) by which this occurs remain poorly understood, making specific clinical intervention...
Source: Alcohol - March 1, 2017 Category: Addiction Authors: L.A. Boule, J. Gaydos, E.L. Burnham, E.J. Kovacs Source Type: research
Alcohol exacerbates an ulcerative colitis flare period
Ulcerative colitis (UC) is a cyclical, life-long illness characterized by disease remission and active disease flares causing abdominal pain, weight loss, intestinal inflammation, rectal bleeding, and dehydration. We sought to determine whether alcohol exposure exacerbates UC flare period. Male C57BL/6 were divided into two groups: dextran sodium sulfate (DSS) and sham. In DSS group, mice received 2% DSS ad libitum in their drinking water for 5 days to induce UC. Mice in sham received water. On day 5, mice in DSS and sham group were subdivided into two subgroups: mice gavaged with alcohol ( ∼3g/kg) or with water on days ...
Source: Alcohol - March 1, 2017 Category: Addiction Authors: A.R. Cannon, A.M. Hammer, N.L. Morris, R.C. Gagnon, P. Kuprys, X. Li, M.A. Choudhry Source Type: research
Long-term alcohol exposure impairs allogeneic heterotopic heart transplant rejection in a mouse model
Various reports have demonstrated chronic alcohol consumption results in an immunosuppressed state that increases susceptibility to infections. Researchers have also shown that long-term alcohol consumption impairs the innate, and adaptive immune responses, although the underlying mechanism involved in disrupting the T cell compartment remains unanswered. We hypothesized that chronic alcohol consumption leads to premature aging of T cells, which impairs T cell function. To test this hypothesis, an allogeneic heterotopic heart transplantation system was used, whereby C57BL/6 and B6-(Cg)-Tyrc-2J/J (B6.Albino) mice were fed w...
Source: Alcohol - March 1, 2017 Category: Addiction Authors: T. Cisneros, X. Qu, D. Dillard, C. Esquivel, S. Krams, O. Martinez Source Type: research
Alcohol, brain neuroimmune/inflammatory signaling, and neurodamage
Chronic alcohol (ethanol) abuse is a major and yet underappreciated facilitative reason world-wide for adult brain damage and dementia. Accumulating experimental evidence indicates that severe, repetitive binge alcohol exposure evokes a cascade of brain processes involving neuroinflammatory and neuroimmune molecules which trigger oxidative stress, synaptic loss and/or neurodegeneration. We have examined these signaling processes using in vivo and in vitro models (adult rats and adult-age rat brain organotypic slice cultures) subjected to binge alcohol intoxication over several days. (Source: Alcohol)
Source: Alcohol - March 1, 2017 Category: Addiction Authors: M.A. Collins, N. Tajuddin, E.J. Neafsey, H.-Y. Kim Source Type: research
Butyrate protects intestinal immune response during chronic-binge ethanol exposure
Following injury, an immune response needs to be adequately mounted and resolved for proper organ function homeostasis. Immune responses following exposure to ethanol (EtOH) differ. While chronic EtOH exposure is pro-inflammatory, acute EtOH can dampen immune responses. Since butyrate, a fermentation byproduct of the gut microbiota, influences gut inflammation and immunity, we studied the butyrate ’s impact on intestinal innate immune responses following chronic-binge EtOH exposure. C57BL/6J mice exposed to 5% v/v EtOH-containing diet for 10 days received a single EtOH gavage (5g/kg) 9 hrs prior to euthanasia. (Source: Alcohol)
Source: Alcohol - March 1, 2017 Category: Addiction Authors: G.A. Cresci, B. Glueck, L.E. Nagy Source Type: research
Alcohol intoxication and advanced age impair the pulmonary inflammatory response to infection
Alcohol use disorder (AUD) patients have increased susceptibility to bacterial pneumonias. Alveolar macrophages (AMs) isolated from AUD subjects have skewed cytokine and chemokine profiles. Advanced age is associated with compromised immunity and elevated basal inflammation, known as inflamm-aging, which primes the lungs to generate an excessive inflammatory reaction in response to infection. Aged mice (18-20 months) given an intratracheal Pseudomonas aeruginosa infection had reduced survival, increased circulating granulocytes, and defective neutrophil directional migration, when compared to young (2-4 months) infected mi...
Source: Alcohol - March 1, 2017 Category: Addiction Authors: B.J. Curtis, J.M. Albright, D.M. Boe, E.J. Kovacs Source Type: research
Mechanistic role of Per2 and PPAR-gamma in ethanol mediated hyperpermeability
This study examined mechanisms of ethanol induced intestinal permeability using an in vitro model of the intestinal epithelium. The circadian clock regulates the intestinal barrier function. Chronic ethanol exposure increases the expression of circadian protein Per2 that is required to increase leakiness through a mechanism that is not fully characterized. Peroxisome proliferator-activated receptor gamma (PPAR-gamma) has been closely associated with intestinal barrier recovery. Research suggests that oxidative stress may disrupt nucleocytoplasmic trafficking of circadian proteins. (Source: Alcohol)
Source: Alcohol - March 1, 2017 Category: Addiction Authors: B.T. Davis, M. Shaikh, C.B. Forsyth, A. Keshavarzian Source Type: research
PPAR- γ agonists suppress neuroinflammation in a FASD animal model
Fetal Alcohol Spectrum Disorders (FASD) result from maternal alcohol consumption, and can lead to developmental abnormalities, including those in the central nervous system (CNS). FASD is associated with lifetime disabilities and is the leading cause of mental retardation in the U.S. There are no effective treatments for FASD. Using our third trimester-equivalent mouse model of FASD, in which postnatal day 4-9 mice are treated with 4 g/kg ethanol per day via intra-esophageal gavage, we demonstrated that ethanol produces both loss of neurons and microglia. (Source: Alcohol)
Source: Alcohol - March 1, 2017 Category: Addiction Authors: P.D. Drew, J.C. Douglas, J.W. Johnson, K.D. Phelan, C.J.M. Kane Source Type: research
IL-18 inhibition protects intestines from excessive inflammation independent of IL-22 administration following alcohol and burn injury
Excessive consumption of alcohol has been shown to increase the incidence of traumatic injury, including burn injury. Previous studies in hospitalized patients have found those who have consumed alcohol prior to burn injury have higher incidence of infection, multiple organ failure, and mortality. We have also observed substantial increases in inflammatory markers IL-6, KC, and IL-18 in the small intestine of mice following alcohol and burn injury. However, the mechanisms of how alcohol exacerbates post-burn pathogenesis remain elusive. (Source: Alcohol)
Source: Alcohol - March 1, 2017 Category: Addiction Authors: A.M. Hammer, N.L. Morris, A.R. Cannon, R.C. Gagnon, P.V. Kuprys, X. Li, M.A. Choudhry Source Type: research
PX-478 prevents gut inflammation and normalizes the expression of tight junction proteins following ethanol and burn injury
Ethanol continues to be a major confounding factor in post burn injury pathology. Many of the adverse effects following ethanol and burn injury are associated with an impaired intestinal barrier. A compromised barrier could allow bacteria or bacterial products to translocate from the gut into extra-intestinal sites resulting in a systemic inflammatory response, sepsis and multiple organ failure. Previous studies from our laboratory have shown that ethanol combined with burn injury results in gut inflammation and barrier disruption. (Source: Alcohol)
Source: Alcohol - March 1, 2017 Category: Addiction Authors: N.L. Morris, A.M. Hammer, A.R. Cannon, R. Gagnon, X. Li, M.A. Choudhry Source Type: research
Acute alcohol intoxication combined with burn injury alters the HSP-27 level in mouse hepatocytes
Background: Small heat shock proteins (HSPs) are critical for cell survival under adverse environmental conditions like sepsis, cancer, inflammation, and other kinds of trauma. Studies indicate that acute alcohol intoxication combined with injury causes suppression of the immune functions, increases tissue edema and release of inflammatory mediators. This can lead to multiple organ failure. Using a well-validated murine burn and ethanol paradigm as a model of critical illness, we tested a hypothesis that alcohol and burn injury alters HSP27 expression level that may regulate the inflammatory response in the hepatocytes of ...
Source: Alcohol - March 1, 2017 Category: Addiction Authors: T. Murungi, A.C. Azim Source Type: research
Histone H4 modification landscape due to chronic alcohol treatment in human monocyte-derived dendritic cells (MDDCs)
The dismal effects of chronic alcohol exposure in the liver, brain, heart and immune system are widely known. In the immune system, alcohol has been shown to modulate inflammation and susceptibility to infections. Many studies have been done with an aim to comprehend adverse effects of alcohol; however, researchers are still trying to elucidate the molecular mechanisms associated with alcohol effects. Therefore, studying epigenetic modulations due to alcohol could give us a deeper understanding of its mechanism of action. (Source: Alcohol)
Source: Alcohol - March 1, 2017 Category: Addiction Authors: T. Parira, G. Figueroa, A. Laverde, G. Casteleiro, M. Agudelo Source Type: research
Oxidation of airway cilia localized protein phosphatase 1 drives alcohol-induced ciliary dysfunction
Background: There is a strong association between infectious lung disease and alcohol use disorders. We previously identified that prolonged alcohol exposure activates protein phosphatase 1 (PP1) to impair airway cilia motility, a key innate defense against inhaled pathogens, known as alcohol-induced ciliary dysfunction (AICD). Furthermore, AICD is associated with S-nitrosylation of PP1 on cysteine 155 in a putative oxidoreductase activation site. Despite this, the exact mechanism of PP1 activation in AICD is unknown. (Source: Alcohol)
Source: Alcohol - March 1, 2017 Category: Addiction Authors: M.E. Price, A.J. Case, M.C. Zimmerman, T.A. Wyatt, J.H. Sisson Source Type: research
Alcohol activates FoxO-specific signaling in mesenchymal stem cells: Implications for MSC osteo-chondrodifferentiation
The process of fracture healing is complex, and poor or incomplete healing remains a significant health problem. Normally, fractures heal largely through endochondral ossification. This is a process by which resident mesenchymal stem cells (MSCs) differentiate first into chondrocytes, to form the cartilaginous callus, and then osteoblasts, to ossify the collagen matrix. Previous data from our laboratory has shown that alcohol (ethanol) administration leads to a decrease in cartilage formation and subsequent endochondral ossification within the fracture callus of rodents during healing. (Source: Alcohol)
Source: Alcohol - March 1, 2017 Category: Addiction Authors: P.M. Roper, P. Abbasnia, J.J. Callaci Source Type: research
Analysis of the respiratory tract microbial biogeography in alcohol use disorder populations
Host defense mechanisms are adversely affected by excessive alcohol intake, particularly among individuals with alcohol use disorders (AUDs) that include alcohol abuse and dependence. In addition, alcohol use significantly increases the risk of oropharyngeal aspiration, suggesting that alcohol consumption may directly influence the microbial biogeography of the upper and lower respiratory tract. Investigations of the lung microbiome in the setting of AUDs have not been conducted. To determine the microbial biogeography of the upper and lower respiratory tract in healthy individuals with AUDs compared to healthy non-AUD sub...
Source: Alcohol - March 1, 2017 Category: Addiction Authors: D.R. Samuelson, E.L. Burnham, V.J. Maffei, W. Vandivier, E.E. Blanchard, J.E. Shellito, M. Luo, C.M. Taylor, D.A. Welsh Source Type: research
