Thesis (Ph.D.)--University of Missouri-Columbia, 2004. / Typescript. Vita. Includes bibliographical references (leaves 59-72). Also available on the Internet.

Dissertation (Ph.D.) -- University of Texas Southwestern Medical Center at Dallas, 2006. / Vita. Bibliography: pp. 193-208.

BACKGROUND: As the prevalence of metabolic risk factors in the American population has increased over time, so too has the diagnoses of non-alcoholic fatty liver disease (NAFLD). Within this spectrum of disease lies the potential for silent progression towards cirrhosis, leaving the patient with few options for treatment. Currently, the standard of care remains counseling on diet and exercise with the goal of reversing disease progression by addressing the underlying risk factors. LITERATURE REVIEW: Recent studies have shown that a correlation exists between low levels of serum 25-hydroxyvitamin D and hepatic injury from NAFLD. This has become an active area of research, due in part to the anti-inflammatory and immunoregulatory properties of vitamin D. The prospect of a simple and cost effective intervention that can exert its effects on the mechanisms behind the development of NAFLD is interesting and warrants further research. PROPOSED PROJECT: This proposal is for a double-blind, randomized, experimental study of vitamin D3 (cholecalciferol) versus placebo in a patient population of those with both clinically proven NAFLD and concomitant vitamin D deficiency. Liver fibrosis will be measured and staged with the use of FibroScan elastography. The statistical analysis thereafter will determine if a clinically significant reduction in hepatic fibrosis exists, compared with the results of the placebo group. CONCLUSIONS/SIGNIFICANCE: Should vitamin D prove to be an effective treatment option in reversing the progression of NAFLD, clinicians would be equipped with a simple and safe tool to augment their management of the patient. For those that experience barriers (i.e. lower socioeconomic status, other comorbidities, etc.) preventing them from improving diet and exercise, vitamin D would serve as an alternative therapy to aid in reducing their disease burden. Easier methods to treat their disease now projects improved quality of life years later.

This dissertation seeks to address the societal problems associated with alcohol abuse and alcohol dependency in relationship to problematic depictions that have appeared on the American stage. It examines plays that perpetuate stigmas as well as plays that seek to subvert stigmas and stereotypical depictions as a means of creating avenues for discourse. This study asks how we, as practitioners of the theatre, can use the theatre and the act of storytelling to initiate empathy and compassion toward what is still considered a marginalized topic of discussion. Cultural misconceptions regarding the development of and (mis)understandings of alcohol abuse/dependency are perpetuated in our everyday lives, and theatre too often falls into the trap that perpetuates false ideas, which only furthers the stigmas and stereotypes associated with alcoholism. Preceded by a brief Introduction that sets the tone for this study, Chapter One offers medical information to delineate terms associated with alcohol use/abuse. UNIT TWO, presented in two chapters, offers analyses of seven plays: Thornton Wilder's Our Town, Eugene O'Neill's Long Day's Journey into Night, Christopher Durang's The Marriage of Bette and Boo, Theresa Rebeck's The Scene, Paula Vogel's How I Learned to Drive, Tracy Letts' August: Osage County, and Stephen Adly Guirgis' The Motherfucker With the Hat. Chapter Two focuses on the first four plays of this list and how each presents a particular problematic and/or stereotypical depiction of an alcoholic character(s) and/or alcohol use/abuse; Chapter Three focuses on the three remaining plays, which offer depictions and/or characters that trouble/complicate the stigmas associated with alcohol abuse/dependency. UNIT THREE is also cast in two chapters: Chapter Four looks at practices and theories used to enhance audience engagement and introduces companies who are using theatre to directly confront issues of alcoholism. Lastly, Chapter Five is a preface for my own full-length play (provided in Appendix A), which acts as my contribution to the ongoing conversations and efforts to diminish the stigmas and stereotypes within alcohol abuse/dependency. The dissertation concludes with a summary and a look at how open conversations regarding alcohol abuse/dependency can lead to empathy and understanding, bringing the topic out from the shadows in an effort to humanize the topic and the individuals and families who are struggling and suffering from alcohol abuse/dependency.

It is generally accepted that alcohol impairs haemodynamic physiology in normal subjects. Alcohol is also thought to have a detrimental effect in shock states. However, most research has concentrated on haemorrhagic shock, whereas in cardiac tamponade, the pathophysiology of shock is very different. Although some studies have mentioned alcohol as a negative factor in patients with cardiac tamponade, none have adequately assessed its effect. In a clinical study of 50 patients who presented to Groote Schuur Hospital Trauma Unit with acute cardiac tamponade due to penetrating chest injury, those who were intoxicated fared the same as their sober counterparts. Although more patients in the intoxicated group were "moribund" or "in extremis" on admission, this did not lead to a higher overall mortality. Haemodynamic parameters and results of special investigations in the two groups were also similar. These findings suggested that intoxicated patients with cardiogenic shock, specifically acute cardiac tamponade, behaved differently from intoxicated patients with haemorrhagic shock. However, the multitude of variables and the stress involved in treating patients with life-threatening acute conditions, makes studies such as this difficult. Because of these limitations, an animal model of acute cardiac tamponade was developed, so that actions of alcohol on haemodynamic physiology could be studied in a controlled environment. Fourteen young pigs were randomly assigned to receive either 30% alcohol or tap-water via a gastrostomy. The former resulted in blood alcohol levels which were compatible with moderate to severe intoxication. Cardiac tamponade was then induced by instilling warmed plasmalyte-8 into the pericardia! sac using a pressure-cycled system. Despite the fact that animals in the tamponade/alcohol group were more hypotensive, and reflex increase in heart rate was inhibited, cardiac output was similar in the two groups. The actions of alcohol in isolation were also studied in eight sham-operated pigs. The only noticeable effect in this instance were higher pulmonary artery wedge pressures in the sham/non-alcohol group. In other words, cardiac performance in both the tamponade/alcohol and sham/alcohol groups was at least equal to, or even better than that in animals that did not receive alcohol. It would seem therefore, that alcohol does not have a negative effect on haemodynamic physiology of acute cardiac tamponade. Theoretically, alcohol may "protect" patients with acute cardiac tamponade by decreasing peripheral vascular resistance and "afterload". It is also possible that inhibitory actions on the respiratory centre may prevent hyperpnoea or tachypnoea, and thereby diminish competitive filling of the right and left ventricles. However, further studies of cardiac function in intoxicated subjects with tamponade using more sophisticated techniques are necessary, before mechanisms will become apparent. In practice, an aggressive approach should be adopted towards moribund patients with penetrating chest injuries; if they have acute cardiac tamponade and are intoxicated, their prognosis is not necessarily dismal. This is of particular relevance in Cape Town, where both alcohol abuse and assault are endemic. As for a therapeutic effect of alcohol, these studies do not support its use for pharmacological manipulation of cardiac tamponade.

Student Number : 0101826W - M Med dissertation - School of Clinical Medicine - Faculty of Health Sciences / Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease with hepatic histology that resembles alcoholic liver disease. It is a frequent cause of chronic liver disease and is attracting increasing scientific attention worldwide. I explored the possibility that increased gastrointestinal alcohol production may have a role as a “second hit” in the pathogenesis of NAFLD in study subjects with the metabolic syndrome. In an attempt to investigate this hypothesis, this study looked at blood, urine and breath levels of alcohol in patients with the metabolic syndrome versus matched age and ethnic group healthy controls. Of the twenty study subjects, 80% had dyslipidaemia, 60% had hypertension and 70% had type 2 diabetes mellitus. Their mean BMI was 35.1±8.2 kg/m² (mean ± SD, P < 0.0001 versus controls). The serum aminotransferases were significantly elevated in the study subjects, their ALT levels being 57.4±44.79 U/L versus 17.4±4.60 U/L in the controls (95% CI 18.02 – 61.42, P < 0.001), and their AST levels 52.5±36.21 U/L versus 23.4±4.86 U/L in the controls (95% CI 11.99 – 46.20, P < 0.01). Seventy five percent of the study group had sonar features suggestive of fatty liver disease. Two adipocytokines, adiponectin and leptin, mediators of insulin resistance, an important factor in the development and progression of NAFLD, were also measured. Adiponectin levels were significantly lower (6875 ng/L versus 15475 ng/L; median value, P < 0.01), and leptin concentration levels significantly higher (13.56 ng/L versus 3.05 ng/L; median value, P < 0.05) in the study subjects than in the control group. Alcohol was detected in 60% of the study subjects, of which 35% tested positive for ethanol, 55% tested positive for methanol, and 30% tested positive for both ethanol and methanol. This was a statistically significant result, as none of the control group tested positive for any of the alcohols. The ethanol concentration in the study subjects’ blood was 7.14±3.28 mg% (mean ± SD), in their urine 3.71± 12.87 mg% (mean ± SD) whilst none was detected in their breath. The methanol concentration in the study subjects’ blood was 16.17±17.95 mg% (mean ± SD), in their urine 6.8± 13.58 mg% (mean ± SD) while their breath level was 2.05±3.19 mg (mean ± SD). This study therefore suggests that endogenous alcohol production may be indeed be involved in the pathogenesis of NAFLD in subjects with the metabolic syndrome. Not only ethanol but also methanol was detected in the subjects tested. Endogenous alcohol may therefore be responsible for the ‘second hit’ theory in the pathogenesis of NAFLD, and it is likely that formaldehyde, the metabolite of methanol may be a more potent toxin of hepatocyte injury as opposed to acetaldehyde, the metabolite of ethanol. The most likely source of the alcohol is from intestinal bacterial flora. These findings provide further insight into the pathogenesis of NALFD, suggesting other therapeutic alternatives such as the use of antibiotics and probiotics as a potential treatment strategy for NAFLD.

Indiana University-Purdue University Indianapolis (IUPUI) / Non-alcoholic fatty liver disease, or NAFLD, is characterized by excess fat deposition in the liver. Cellular senescence is a critical hallmark of NAFLD. Cholangiocytes in the liver plays a significant role in the progression of fatty liver by contributing to senescence. p16 is the main senescent protein expressed by cholangiocytes in primary sclerosing cholangitis (PSC). Thus, we aimed to downregulate p16 by vivo-morpholino and evaluate the disease phenotypes and signaling mechanisms in a murine model of NAFLD. We found that downregulation of p16 reduced i) steatosis), ii) inflammation, iii) fibrosis, and cholangiocyte proliferation in HFD mice compared to the HFD-fed, control vivo-morpholino injected mice. Moreover, the downregulation of p16 reduced insulin-like growth factor-1 (IGF-1) in cholangiocytes, previously identified by our laboratory as a principal SASP factor secreted from cholangiocytes during NAFLD. By ingenuity pathway analysis, we found that p16 might regulates IGF-1 expression via the E2F1/FOXO1axis. Further analyses indicate that p16 downregulation reduces E2F1 mRNA transcription, inhibiting FOXO1 and subsequent IGF-1 expression in cholangiocytes. The presence of mast cells in the liver has been implicated in multiple cholangiopathies. Our lab demonstrated that mast cell stabilization by cromolyn sodium treatment reduced histamine secretion, fibrosis, and biliary proliferation in Mdr2-/- mice, a model of PSC. Thus, we aimed to determine mast cell stabilization as a therapeutic approach to managing NAFLD and its more advanced form, NASH. We found that cromolyn sodium ameliorated i) serum histamine levels, ii) intrahepatic mast cells, iii) inflammation, iv) fibrosis, v) steatosis, and cholangiocyte proliferation in methionine choline deficient diet-fed mice compared to the saline controls. Overall, we report that amelioration of senescence is a critical factor in improving the disease phenotypes in NAFLD. Biliary senescence plays a crucial role in modulating the disease progression in NAFLD, and mast cell stabilization can be used as a therapeutic approach to reduce pathological hallmarks of fatty liver. / 2024-05-22

Alkoholvården i Sverige kan vara utformad på många olika och skilda sätt. Det är ett område där det finns ett flertal olika åsikter kring vilken behandling som är lämpligast eller effektivast. Uppsatsens syfte är att titta närmare på hur diskursen kring alkoholvård kan se ut i Sverige idag genom närmare granskning av de två tidskrifterna Socionomen och Alkohol & Narkotika. Två stora tidningar inom praktiker av socialt arbete. För att uppnå syftet utgår uppsatsen från följande frågeställningar:-Vilka behandlingsmetoder för alkoholmissbruk diskuteras i tidskrifterna?-Hur problematiserar tidskrifterna kring olika behandlingsformer?-Hur lyfts för respektive nackdelar för behandlingsformerna upp?-Vad väljer tidskrifterna att lyfta fram i debatten kring alkoholvården? Som metod används kritisk diskursanalys för att synliggöra diskurserna i tidskrifterna. Analysen av tidskrifterna grundar sig på en analysmodell efter diskursanalytikern Fairclough och används främst för att synliggöra hur tidskrifterna förhåller sig till uppsatsens diskursordning. Diskursordningen som används är baserad på aktuell litteratur kring alkoholmissbruksbehandling och innefattar tre diskurser: Psykologisk, psykosocial och farmakologisk.Resultaten i uppsatsen visar att den psykosociala diskursen är dominerande i de båda tidskrifterna men att även den farmakologiska diskursen nämns. De behandlingsmetoder som tas upp är i de båda tidskrifterna kognitiv beteendeterapi (KBT) och motiverande samtal. Vidare visa uppsatsen att Socionomen efterfrågar en mer strukturerad, organiserad och evidensbaserad alkoholbehandling i allmänhet. Alkohol & Narkotika å andra sidan ifrågasätter den formella vårdapparaten kring alkoholmissbruk och beskriver den som otillgänglig och bristfällig. Som alternativ för att högkonsumenter av alkohol ska få tidig hjälp tar tidskriften upp olika självhjälps metoder grundade på KBT och motiverade samtal. / In Sweden, the treatment of alcoholism can be shaped in many various and separate ways. The subject of area contains various opinions regarding what treatment would be the most correct or effective. The aim in this essay is to look closer at the discourse of how the treatment of alcoholism may work in Sweden today. This will be done by closer examine the magazines, Socionomen and Alkohol & Narkotika, that are large papers within the practice of social work. To achieve the aim, this essay will start out from the following questions of issue:- What methods of treatment are discussed in the two magazines?- How do the magazines questions the various treatments? - How are the advantages and disadvantages in the different treatments highlighted?- What chooses the magazines to highlight in the debate of alcohol treatment?As the method, to make the discourses in the magazines visible, a critical analyze of discourse is being used. The analyze of the magazines is based on a model of analyzing by the discourse analyzer Fairclough, and is mainly used to make the magazines relations to the essay’s system of discourse visible. The system of discourse that is being used is based on actual literature in the area of treatment of alcohol addiction and contains three different discourses: psychological, psychosocial and pharmacological.The conclusion of this essay shows that the psychosocial discourse is the dominating discourse in both of the magazines but that the pharmacological discourse also is mentioned. The methods of treatment being raised in the magazines are cognitive behavioral therapy and motivational interviewing. Further more the essay shows that the paper Socionomen generally asks for a more structured, organized and evidence based treatment of alcoholism. In the other hand, the magazine Alkohol & Narkotika questions the formal care unit’s treatment of alcohol abuse and describes it as inaccessible and insufficient. As an alternative this magazine highlights the methods of self- help based on cognitive behavioral therapy and motivational interviewing so that those that are high consumers of alcohol will get help at an earlier stage of their abuse.

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Aroma is one of the most important attributes involved in wine quality. Current trend in winemaking consists of producing wines with different aroma nuances to offer variety of wines to a developing market. Several studies have demonstrated that low temperature fermentations favours aroma synthesis and retention. In this background, new wine yeasts able to perform fermentation at low temperatures improving wine aroma while maintaining good fermentation rates are necessary. This doctoral thesis explores the oenological traits of different Saccharomyces species and hybrids relevant for present-day wine industry, especially regarding aroma production, as well as the molecular bases underneath. This exploration has been possible using different biochemical, analytical chemistry and molecular techniques to perform enzymatic activity detection, aroma profile determination and transcriptome analysis in wine fermentations. Through this doctoral thesis the abilities of different Saccharomyces species and hybrids regarding primary aroma release and secondary aroma production, especially at low temperatures, has been elucidated in order to know the different possibilities that these yeasts offer to create new wines with different aromatic nuances. One of the general conclusions of this doctoral thesis is that production and release of aromas in winemaking depends on the strain carrying out the fermentation process. Nevertheless, sometimes there was a species tendency. On the other hand, the fact that fermentation temperature affects aroma synthesis but not always in the direction to aroma increase has been demonstrated. / Gamero Lluna, A. (2011). Study of the production and release of aromas during winemaking carried out by different Saccharomyces species and hybrids [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/10741