Tissue engineered micro and macrovasculature utilizing stromal vascular fraction.

This dissertation describes the use of stromal vascular fraction to tissue engineer 3D microvasculature and macrovasculature. Stromal vascular fraction is an easily isolatable cell source from adipose tissue depots. It has demonstrated remarkable potential both in vitro and in vivo for forming microcirculation capable of perfusion upon implantation. SVF is clinically utilized as a therapeutic cell source for anti-inflammation for osteoarthritis and is being studied for ischemic tissue application to stimulate revascularization. The work described herein is divided within four chapters. Chapter I provides an introductory overview and lists the aims and hypothesis for the dissertation. Chapter II describes experiments towards elucidating specific aim 1: determine the mechanism by which SVF forms neovascular networks in 3D fibrin gels in vitro. This was accomplished through a multitude of experiments describing SVF undergoing vasculogenesis and angiogenesis in a 2D automated in vitro assay, and the ability to inhibit these processes via NOTCH and PDGF-B/PDGFR-b interruption. These mechanisms, as well as integrin dependent mechanisms, were analyzed within 3D fibrin and 3D collagen I culture systems as well. It is believed that the activation of the fibrin specific integrin aVb3 plays a role in hyper-stimulating fibrin-embedded endothelial cells in a VEGF dependent manner. Chapter II describes experiments towards understanding specific aim 2: create deliverable tissue units of SVF-derived microvasculature or macrovasculature utilizing bioprinting, and electrospinning technologies. This was accomplished through bioprinting spheroids containing cells embedded in collagen I or fibrin using superhydrophobic surface technology or electrospinning varying porosities of PCL and pressure sodding SVF cells into the material. It is possible to automate and create dosable units of microvascular tissue in spheroid format using SVF cells, ECM such as fibrin or collagen I, and bioprinting technologies. Additionally, it is possible to create blood vessel mimics of multiple porosities in order to retain and allow cellular infiltration within the biomaterial. Chapter IV is an overall summary and conclusion of the dissertation. These studies could hopefully generate more knowledge on the creation of tissue engineered microvasculature and microvasculature for use in treating ischemic cardiomyopathies

Role of Nutrition in Alcoholic Liver Disease: Summary of the Symposium at the ESBRA 2017 Congress.

The symposium, "Role of Nutrition in Alcoholic Liver Disease", was held at the European Society for Biomedical Research on Alcoholism Congress on 9 October 2017 in Crete, Greece. The goal of the symposium was to highlight recent advances and developments in the field of alcohol and nutrition. The symposium was focused on experimental and clinical aspects in relation to the role of different types of dietary nutrients and malnutrition in the pathogenesis of alcoholic liver disease (ALD). The following is a summary of key research presented at this session. The speakers discussed the role of dietary fats and carbohydrates in the development and progression of alcohol-induced multi-organ pathology in animal models of ALD, analyzed novel nutrition-related therapeutics (specifically, betaine and zinc) in the treatment of ALD, and addressed clinical relevance of malnutrition and nutrition support in ALD. This summary of the symposium will benefit junior and senior faculty currently investigating alcohol-induced organ pathology as well as undergraduate, graduate, and post-graduate students and fellows

Stress Vulnerability And Alcohol Use And Consequences: From Human Laboratory Studies To Clinical Outcomes

It is well known that vulnerability to stress is a risk factor for alcohol use disorder (AUD). Chronic alcohol use can result in neuroadaptations in cortico-striatal pathways and hypothalamic pituitary adrenal (HPA) axis function that are manifested in altered behavioral and cognitive control functions contributing to alcohol craving, compulsive motivation, consumption and consequences. This symposium brings together studies utilizing novel approaches to help improve our understanding of stress – past, acute and chronic - on alcohol seeking and consumption and related outcomes using a combination of human laboratory models, neuroimaging and clinical measures. Examining factors that determine vulnerability as well as resilience to stress are of particular interest in the study of AUD because, in addition to increasing our understanding of the risk factors for AUD, such knowledge can be used to develop more effective treatments. Dr. Stangl presented a novel human experimental model that demonstrates, for the first time, stress-induced increases in alcohol self-administration in binge drinkers using a guided imagery paradigm combined with intravenous alcohol self-administration (IV-ASA). Dr. Blaine presented data demonstrating that glucocorticoid response to stress drives compulsive alcohol motivation and intake in binge/heavy drinkers. Dr. Plawecki presented data examining sex differences in the effect of two distinct stress paradigms – mood induction and abstinence – on IV-ASA in moderate drinkers. Dr. Schwandt presented clinical data providing a new perspective on the relationship between childhood trauma and AUD by suggesting possible underlying mechanisms that confer resilience, rather than vulnerability, to severe early life stress exposure

Alcohol, microbiome, life style influence alcohol and non-alcoholic organ damage

This paper is based upon the "8th Charles Lieber's Satellite Symposium" organized by Manuela G. Neuman at the Research Society on Alcoholism Annual Meeting, on June 25, 2016 at New Orleans, Louisiana, USA. The integrative symposium investigated different aspects of alcohol-induced liver disease (ALD) as well as non alcohol -induced liver disease (NAFLD) and possible repair. We revealed the basic aspects of alcohol metabolism that may be responsible for the development of liver disease as well as the factors that determine the amount, frequency and which type of alcohol misuse leads to liver and gastrointestinal diseases. We aimed to (1) describe the immuno-pathology of ALD, (2) examine the role of genetics in the development of alcoholic hepatitis (ASH) and NAFLD, (3) propose diagnostic markers of ASH and non-alcoholic steatohepatitis (NASH), (4) examine age and ethnic differences as well as analyze the validity of some models, (5) develop common research tools and biomarkers to study alcohol-induced effects, 6) examine the role of alcohol in oral health and colon and gastrointestinal cancer and (7) focus on factors that aggravate the severity of organ-damage. The present review includes pre-clinical, translational and clinical research that characterizes ALD and NAFLD. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD with simple fatty infiltrations and chronic alcoholic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular.and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes and cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human deficiency virus were discussed. Dysregulation of metabolism, as a result of ethanol exposure, in the intestine leads to colon carcinogenesis. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota have been suggested. The clinical aspects of NASH, as part of the metabolic syndrome in the aging population, have been presented. The symposium addressed mechanisms and biomarkers of alcohol induced damage to different organs, as well as the role of the microbiome in this dialog. The microbiota regulates and acts as a key element in harmonizing immune responses at intestinal mucosal surfaces. It is known that microbiota is an inducer of proinflammatory T helper 17 cells and regulatory T cells in the intestine. The signals at the sites of inflammation mediate recruitment and differentiation in order to remove inflammatory inducers and promote tissue homeostasis restoration. The change in the intestinal microbiota also influences the change in obesity and regresses the liver steatosis. Evidence on the positive role of moderate alcohol consumption on heart and metabolic diseases as well on reducing steatosis have been looked up. Moreover nutrition as a therapeutic intervention in alcoholic liver disease has been discussed. In addition to the original data, we searched the literature (2008-2016) for the latest publication on the described subjects. In order to obtain the updated data we used the usual engines (Pub Med and Google Scholar). The intention of the eighth symposia was to advance the international profile of the biological research on alcoholism. We also wish to further our mission of leading the forum to progress the science and practice of translational research in alcoholism. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe

NF-kB, a Prototypical Cytokine-Regulated Transcription Factor: Implications for Alcohol-Mediated Responses

Summary of the presentations and discussions held at the symposium NF-KB, a Prototypical Cytokine-Regulated Transcription Factor: Implications for Alcohol-Mediated Responses, held during the Joint RSMSBRA meeting in Washington, D.C. in June 1996

Mechanisms of alcohol-mediated hepatotoxicity in human-immunodeficiency-virus-infected patients

Clinical observations have demonstrated that excessive chronic alcohol use negatively affects human immunodeficiency virus (HIV) infection and contributes to the liver manifestations of the disease, even in HIV mono-infection. HIV/hepatitis C virus (HCV) co-infection is associated with increased progression of HVC liver disease compared to HCV infection alone, and both of these are negatively affected by alcohol use. Recent data suggest that alcohol use and HIV infection have common targets that contribute to progression of liver disease. Both HIV infection and chronic alcohol use are associated with increased gut permeability and elevated plasma levels of lipopolysaccharide; a central activator of inflammatory responses. Both alcoholic liver disease and HIV infection result in non-specific activation of innate immunity, proinflammatory cytokine cascade upregulation, as well as impaired antigen presenting cell and dendritic cell functions. Finally, alcohol, HIV and antiretroviral therapy affect hepatocyte functions, which contributes to liver damage. The common targets of alcohol and HIV infection in liver disease are discussed in this mini-review

Epidemiology of Moderate Alcohol Consumption and Breast Cancer: Association or Causation?

Epidemiological studies have been used to show associations between modifiable lifestyle habits and the incidence of breast cancer. Among such factors, a history of alcohol use has been reported in multiple studies and meta-analyses over the past decades. However, associative epidemiological studies that were interpreted as evidence that even moderate alcohol consumption increases breast cancer incidence have been controversial. In this review, we consider the literature on the relationship between moderate or heavy alcohol use, both in possible biological mechanisms and in variations in susceptibility due to genetic or epigenetic factors. We argue that there is a need to incorporate additional approaches to move beyond the associations that are reported in traditional epidemiological analyses and incorporate information on molecular pathologic signatures as a requirement to posit causal inferences. In particular, we point to the efforts of the transdisciplinary field of molecular pathological epidemiology (MPE) to evaluate possible causal relationships, if any, of alcohol consumption and breast cancer. A wider application of the principles of MPE to this field would constitute a giant step that could enhance our understanding of breast cancer and multiple modifiable risk factors, a step that would be particularly suited to the era of “personalized medicine”

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

Chronic inflammation is often associated with alcohol-related 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

Alcohol and the endocrine system /

"Printed 1993"--T.p. verso.Shipping list no.: 93-0420-P."Based on the workshop ... held in San Diego, California, May 6-9, 1992"--T.p. verso.Includes bibliographical references.activity : central mechanisms of neural modulation of immunity / Michael Irwin -- The potential for alcohol to affect the passage of peptide and protein hormones across the blood-brain barrier : a hypothesis for a disturbance in brain-body communication / William A. Banks and Abba J. Kastin.[2] Hypothalamic-pituitary-adrenal axis. Alcohol, the hypothalamic-pituitary-adrenal axis, and hormonal tolerance / Gary S. Wand -- Glucocorticoid neurotoxicity : is this effect relevant to alcoholic neurotoxicity? / Robert M. Sapolsky. [3] Hypothalamic-pituitary-thyroid axis. Regulation of the hypothalamic-pituitary-thyroid axis and the effects of alcohol / Ivor M.D. Jackson -- Alcohol, the liver, and thyroid hormones / David H. Van Thiel -- Alcohol exposure and maternal-fetal thyroid function : impact on biobehavioral maturation / John H. Hannigan. [4] Blood brain barrier, growth hormone, and the immune system. The effects of alcohol on growth hormone and growth hormone-regulated systems / Thomas M. Badger, Martin J.J. Ronis, Charles K. Lumpkin -- Prenatal alcohol exposure : endocrine function of offspring / Joanne Weinberg -- Stimulatory effects of cytokines on the hypothalamic-pituitary-adrenal axis of the rat : possible influence of alcohol / Catherine Rivier -- Alcoholism and natural killer cellEffects of alcohol on the endocrine system. [1] Hypothalamic-pituitary-gonadal axis. Chronic disturbances of the hypothalamic-pituitary-testicular axis : effects on sexual behavior and fertility / Andrzej Bartke -- The effects of alcohol on the neuroendocrine control of reproduction / Many Ann Emanuele ... [et al.] -- The female reproductive system : physiology and pathophysiology / Janet E. Hall -- An overview of the effects of alcohol on neuroendocrine function in women / Nancy K. Mello, Jack H. Mendelson, and Siew Koon Teoh -- Effects of alcohol use and abuse on the endocrine status in expanded study samples of postmenopausal women / Judith S. Gavaler -- Effects of alcohol on the hypothalamic-pituitary-gonadal axis / Vishnudutt Purohit -- Prenatal drugs : effects on sexually dimorphic neuroanatomical and behavioral traits / Annabell C. Segarra -- Influence of perinatal alcohol exposure on sexual differentiation / Robert F. McGivern and Edward P. Riley.Possible role of the endocrine system in alcohol consumption. The effects of alcohol on selected regulatory aspects of the stress axis / Robert L. Eskay ... [et al.] -- Interactions between alcohol and the endogenous opioid system / Janice C. Froelich -- The renin-angiotensin system as a regulator of alcohol consumption : a review and some new insights / Larry A. Grupp.Mode of access: Internet