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Nyarambi, Arnold. "Neonatal Abstinence Syndrome, Maternal Opioid and Marijuana Dependency During Pregnancy: Implications to Special Education." Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/etsu-works/8233.
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MacVicar, Sonya. "IBriS study : intervention supporting breastfeeding in substance dependency." Thesis, Robert Gordon University, 2016. http://hdl.handle.net/10059/2119.
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Introduction: Breastfeeding offers the substance exposed mother and child potential short and long-term health benefits, with breast milk shown to alleviate the severity of Neonatal Abstinence Syndrome. Substance dependent women, however, have limited success establishing breastfeeding with physical, psychological and institutional factors cited as barriers. This study aimed to develop and test the feasibility of an evidence informed and theory based intervention to support continued breastfeeding for this group. Methods: The research was a two-phase feasibility study. Phase 1 informed intervention development using a mixed methodology approach which included (a) a comprehensive systematic literature review of breastfeeding support for women from disadvantaged groups (b) expert advisory group recommendations and (c) ‘think aloud’ verbal protocols with opioid dependent women. Phase 2 underpinned the evidence with the theoretical constructs of behaviour change, prior to testing the acceptability and implementation fidelity of the intervention in a feasibility study with an embedded small-scale randomised controlled trial. Results: Phase 1 identified the barriers to breastfeeding continuation as low maternal self-efficacy; neonatal feeding difficulties associated with withdrawal and unsupportive healthcare practices. Evidence and theory synthesis resulted in an integrated breastfeeding support model founded on practical, informational, psychological, person-centred and environmental components. Phase 2 demonstrated that the intervention was feasible to implement and acceptable to participants. The randomised controlled trial reported higher rates of continued breastfeeding and a greater level of maternal confidence in breastfeeding ability in the intervention group compared to the control group. Breastfed infants were less likely to require pharmacological management and had corresponding shorter durations of hospitalisation than formula fed infants. Conclusion: The research provided an original contribution to the development of a complex healthcare intervention which is meaningful to both existing research and clinical practice. The findings highlighted the potential of the intervention to support breastfeeding for the substance exposed mother and baby, which has wide ranging implications for the improved health and social equalities of this group.
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Pritham, Ursula A. "Pharmacologic Treatment of Opiod Dependency in Pregnancy: Methadone Versus Buprenorphine and Subsequent Neonatal Abstinence Syndrome." Fogler Library, University of Maine, 2009. http://www.library.umaine.edu/theses/pdf/PrithamUA2009.pdf.
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Dupuy, Emma. "Impact d'une déficience somesthésique sur les mécanismes de régulation du contrôle postural : un nouveau modèle, le syndrome d'Ehlers-Danlos de type hypermobile." Thesis, Normandie, 2019. http://www.theses.fr/2019NORMC402/document.
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Le syndrome d’Ehlers-Danlos (SED) est un groupe mixte de maladies héréditaires dont la caractéristique commune est une altération d’origine génétique du tissu conjonctif. Sa forme hypermobile (SEDh) se caractérise par une hypermobilité articulaire généralisée, associée à une hyperélasticité cutanée, générant toutes deux un déficit somesthésique. Or, le système somesthésique est, avec les systèmes visuel et vestibulaire, crucialement impliqué dans le fonctionnement du système sensorimoteur. Ce travail de thèse visait donc à comprendre comment le déficit somesthésique propre au SEDh modifie les mécanismes perceptifs et sensorimoteurs sous-tendant le contrôle postural. L’appréhension de ces mécanismes s’est articulée autour de deux types d’approches : l’une indirecte, au travers de l’étude des mécanismes sensoriels sous-tendant la perception de la verticale, et l’autre directe, au travers d’analyses posturographiques approfondies.Le premier objectif de travail visait à déterminer comment le déficit somesthésique affecte l’utilisation des cadres de référence spatiale (allocentré, égocentré et géocentré) pour la perception de la verticale visuelle. Pour ce faire, nous avons conduit deux études évaluant respectivement la perception de la verticale avec ou sans indices visuels (test de la baguette et du cadre, RFT ; test de verticale visuelle subjective, VVS). Ces deux études ont montré que le déficit somesthésique diminuait la contribution du référentiel égocentré (axe corporel) à la perception de la verticale. En réponse, les patients présentent une plus grande dépendance au champ visuel et s’appuient donc préférentiellement sur le référentiel allocentré. Le second axe de travail visait à identifier les stratégies sensorielles adoptées par ces patients, et à évaluer les répercussions de celles-ci sur les mécanismes de régulation posturale. Ces questions ont été investiguées au moyen d’évaluations posturographiques approfondies, utilisant à la fois des paradigmes de perturbation sensorielle et de double tâche, ainsi que des analyses linéaires et non-linéaires. Nous avons ainsi observé que le déficit somesthésique des patients altérait la contribution de la proprioception musculaire aux mécanismes en charge de la régulation automatique de l’équilibre postural. Ces modifications dans la régulation posturale se répercutent par une augmentation du monitoring actif des oscillations posturales par le système nerveux central. En retour, les patients SEDh développent une visuodépendance, et mettent en place des stratégies adaptatives basées sur une rigidification des mécanismes correctifs à long terme. Enfin, deux études pilotes ont été conduites afin de tester l’effet de stratégies de remédiation proprioceptive, à savoir les orthèses somesthésiques et la reprogrammation sensorimotrice, sur le contrôle postural de ces patients. Chacune de ces prises en charge semble exercer un effet bénéfique sur leur contrôle postural, qui se traduit par une augmentation de la stabilité posturale lors du port des orthèses somesthésiques, et une amélioration de l’efficacité du contrôle postural suite à la reprogrammation sensorimotrice. Néanmoins, les résultats indiquent également que l’effet immédiat opéré par les dispositifs orthétiques de suppléance somesthésique est limité puisqu’il ne permet pas de diminuer la visuodépendance des patients. Cet effet est, en revanche, induit par l’action de la reprogrammation sensorimotrice, qui, par le renforcement du système proprioceptif, libère les patients SEDh de leur visuodépendance. Ainsi, ces observations nous ont permis de caractériser les spécificités de la régulation posturale chez les patients SEDh, et, de façon préliminaire, d’observer la façon dont celles-ci évoluent en réponse à des prises en charge spécifiquement orientées sur la remédiation sensorielleEhlers-Danlos syndrome (EDS) is the clinical manifestation of hereditary connective tissue disorders, comprising several clinical forms. The EDS hypermobility type (EDSh) is characterized by generalized joint hypermobility and variable skin hyperextensibility, which both generate somatosensory impairment. Somatosensory system is, together with visual and vestibular systems, crucially involved in sensorimotor system functioning. The aim of this work was to understand the impact of impaired proprioception on perceptive and sensorimotor mechanisms underlying postural control in EDSh patients. Evaluation of postural control was structured around two approaches. The first one was indirect, and evaluated the sensory mechanism underlying vertical perception. The second one was direct, and used detailed stabilometric analyses to investigate postural control.The first objective of this work was to evaluate how somatosensory impairment affects the contribution of spatial frame of reference (allocentric, egocentric, and geocentric) to visual vertical perception. Two types of tests were conducted to assess the vertical perception with and without visual information (Rod and Frame Test, RFT; Subjective visual vertical, SVV). These two studies showed that somatosensory impairment reduces the contribution of egocentric frame of reference (body axis) to vertical perception. In response, patients increase their visual field dependence, and thus, use preferentially allocentric frame of reference. The second axis aimed to identify sensory strategies adopted by these patients and their repercussion on postural regulation mechanisms. To investigate this question, a thorough postural assessment was conducted, using sensory perturbation and dual-task paradigm, and linear and non-linear analyses. We observed that somatosensory impairment impacts muscular proprioceptive contribution to automatic regulation mechanism involved in postural control. These modifications in postural regulation induce an increase of active monitoring of postural sway. In response, EDSh patients develop a visual dependence, and produce adaptive strategies based on stiffening of corrective mechanisms acting in long term. Finally, two pilot studies were conducted to test the impact of proprioceptive remediation, somatosensory orthoses and sensorimotor rehabilitation program, on postural control of these patients. Both of these two therapeutic solutions seem to induce a beneficial effect on postural control. This effect is reflected by an improvement of postural stability when patients wore somatosensory orthoses, and an enhancement of postural efficiency in response to sensorimotor rehabilitation. However, results also indicate that the immediate effect induced by orthotic device of somatosensory substitution is limited, because it did not help to decrease visual dependency. Hence, these observations allowed us to identify the postural regulation specificities in EDSh patients, and, in a preliminary way, to observe how they change in response to therapeutic solutions based on sensory remediation
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Santos, Tarcísio dos. "RELIGIÃO E ALCOOLISMO - ESTUDO DA PRÁTICA PASTORAL DA IGREJA METODISTA FRENTE A SÍNDROME DA DEPENDÊNCIA DO ÁLCOOL À LUZ DO CREDO SOCIAL." Universidade Metodista de São Paulo, 2010. http://tede.metodista.br/jspui/handle/tede/565.
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The research work done in Religious Praxis and Society critically analyses the Social Creed of the Methodist Church, a document that completed it´s first centennial in the year of 2008, whose content presents the social responsability of the Methodist Church as a guide to the pastorals deeds regarding social issues. Having it as a guide line, I intend to ground a pastoral praxis directed to the prevention and monitoring of the people affected by the Alcohol Dependency Syndrome, a problem that strikes an endless number of people, regardless of age, sex or culture. The research combines the inferred meaning of alcohol dependency and health, interpreting it as a moral deviation. For such, it seeks support among numerous sources such as the Alcoholics Anonymous, that develop an esteemed work in this context, relating its precepts to the groundings of the Social Creed. The relevance of the research is in the fact that it demonstrates the Methodist Church´s emplacement fighting vehemently the alcohol addiction, avoiding it as well as alleging everyone to be teetotaler, allowing the construction of new pastorals praxis in this new century initiated by the Social Creed. The work is developed in three chapters which respectively bring the history of the Social Creed since its creation, the different editions it went through, its importance regarding the fight against addiction, among other relevances in the life of both the church and the comunnity. It refers to alcohol as a beverage and also to its historical path, its conceptualizations according to the World Health Organization, culminating in the consequences of its dependency. In conclusion, the third chapter brings the correlation of the previous chapters, fundamenting the pastoral praxis, highlighting pertinent actions and attitudes used by the Methodist Church throughout the years regarding the use of alcoholic drinks, as well as contextualizing the Social Creed in the position and pastoral praxis.
O trabalho de pesquisa, situado na área de Práxis Religiosa e Sociedade analisa criticamente o Credo Social da Igreja Metodista, documento que completou o seu primeiro centenário no ano de 2008, cujo teor é apresentar a responsabilidade social da Igreja Metodista como norteador das ações pastorais frente às questões sociais. Tendo-o como referencial busco fundamentar uma práxis pastoral direcionada a prevenção e ao acompanhamento dos portadores da síndrome da dependência do álcool, problema que atinge um sem número de pessoas, independente da idade e sexo ou cultura. A pesquisa traz a conotação da dependência do álcool vinculada à saúde, interpretando-a como doença que necessita de acompanhamento e cuidado, desvinculando-a do desvio moral. Para tal, busca respaldo entre diversas fontes como os Alcoólicos Anônimos que desenvolvem respeitado trabalho neste âmbito, relacionando seus preceitos às fundamentações do Credo Social. A relevância da pesquisa está em demonstrar a posição da Igreja Metodista em combater veementemente o vício do álcool, evitando-o, bem como preconizando que todos sejam abstêmios, possibilitando a construção de novas práxis pastorais para este novo século iniciado pelo Credo Social. O trabalho é desenvolvido em três capítulos que respectivamente trazem a história do Credo Social desde sua criação, as diferentes edições pelas quais passou, sua importância em relação ao combate aos vícios, dentre outras relevâncias na vida da igreja e da comunidade. Trata do álcool como bebida e sua trajetória histórica, suas conceituações conforme a Organização Mundial de saúde, culminando nas consequências da dependência. Finalizando, o erceiro capítulo traz a correlação dos dois anteriores, undamentando a práxis pstoral, ressaltando ações e posturas pertinentes adotadas pela Igreja Metodista ao longo dos anos em relação ao uso de bebidas alcoolicas, bem como contextualiza o Credo Social na postura e práxis pastoral.
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De, Villiers Sabina. "Active immunization against nicotine dependence." Stockholm, 2010. http://diss.kib.ki.se/2010/978-91-7409-829-7/.
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Davidson, Robin James. "The validation and internal homogeneity of the short alcohol dependence (SADD) questionnaire." Thesis, University of Ulster, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.253833.
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Cross, Robert Michael. "Dependent Personality Characteristics and Clinical Symptomatology in Three Clinical Syndromes in Inpatient vs Outpatient Settings." Thesis, University of North Texas, 1992. https://digital.library.unt.edu/ark:/67531/metadc332671/.
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The purpose of this exploratory study was to investigate the differences between dependent personality characteristics and clinical symptomology as measured by the MCMI-II, in three major psychiatric syndromes in inpatient and outpatient treatment settings. Results show differences in profile in all groups. Treatment setting differences show higher scores on alcohol and drug dependence and major depression for inpatients. The affective group exhibited higher scores on dependent personality, dysthymic and major depression, confirming previous research on depressive disorders and dependent personality.
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Lu, Simin. "Calcium Dependent Regulatory Mechanism in Wolfram Syndrome: A Dissertation." eScholarship@UMMS, 2002. http://escholarship.umassmed.edu/gsbs_diss/733.
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Wolfram syndrome is a genetic disorder characterized by diabetes and neurodegeneration. Two causative genes have been identified so far, WFS1 and WFS2, both encoding endoplasmic reticulum (ER) localized transmembrane proteins. Since WFS1 is involved in the ER stress pathway, Wolfram syndrome is considered an ER disease. Despite the underlying importance of ER dysfunction in Wolfram syndrome, the molecular mechanism linking ER to the death of β cells and neurons has not been elucidated.
The endoplasmic reticulum (ER) is an organelle that forms a network of enclosed sacs and tubes that connect the nuclear membrane and other organelles including Golgi and mitochondria. ER plays critical functions in protein folding, protein transport, lipid metabolism, and calcium regulation. Dysregulation of ER function disrupts normal cell metabolism and activates an array of anti-survival pathways, eventually leading to disease state.
Here we show that calpain is involved in both prototypes of Wolfram syndrome. Calpain 2 activity is negatively regulated by WFS2 protein, and hyper-activation of calpain 2 by WFS2-knockdown leads to cell death. Calpain hyper-activation is also present in WFS1 loss of function cells due to the high cytosolic calcium. Extensive calpain activation exists in the Wolfram syndrome mouse model as well as in patient cells. A compound screen targeting ER homeostasis reveals that dantrolene, a ryanodine receptor inhibitor, can prevent cell death in cell models of Wolfram syndrome. Our results demonstrate that the pathway leading to calpain activation provides potential therapeutic targets for Wolfram syndrome and other ER diseases.
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Lu, Simin. "Calcium Dependent Regulatory Mechanism in Wolfram Syndrome: A Dissertation." eScholarship@UMMS, 2015. https://escholarship.umassmed.edu/gsbs_diss/733.
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Wolfram syndrome is a genetic disorder characterized by diabetes and neurodegeneration. Two causative genes have been identified so far, WFS1 and WFS2, both encoding endoplasmic reticulum (ER) localized transmembrane proteins. Since WFS1 is involved in the ER stress pathway, Wolfram syndrome is considered an ER disease. Despite the underlying importance of ER dysfunction in Wolfram syndrome, the molecular mechanism linking ER to the death of β cells and neurons has not been elucidated.
The endoplasmic reticulum (ER) is an organelle that forms a network of enclosed sacs and tubes that connect the nuclear membrane and other organelles including Golgi and mitochondria. ER plays critical functions in protein folding, protein transport, lipid metabolism, and calcium regulation. Dysregulation of ER function disrupts normal cell metabolism and activates an array of anti-survival pathways, eventually leading to disease state.
Here we show that calpain is involved in both prototypes of Wolfram syndrome. Calpain 2 activity is negatively regulated by WFS2 protein, and hyper-activation of calpain 2 by WFS2-knockdown leads to cell death. Calpain hyper-activation is also present in WFS1 loss of function cells due to the high cytosolic calcium. Extensive calpain activation exists in the Wolfram syndrome mouse model as well as in patient cells. A compound screen targeting ER homeostasis reveals that dantrolene, a ryanodine receptor inhibitor, can prevent cell death in cell models of Wolfram syndrome. Our results demonstrate that the pathway leading to calpain activation provides potential therapeutic targets for Wolfram syndrome and other ER diseases.
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Li, Zheng. "The mechanisms of ethanol-induced damage to the developing cerebellum effects on the cerebellar granule cells /." Morgantown, W. Va. : [West Virginia University Libraries], 2003. http://etd.wvu.edu/templates/showETD.cfm?recnum=3134.
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Thesis (Ph. D.)--West Virginia University, 2003.Title from document title page. Document formatted into pages; contains vii, 146 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references.
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Arumugam, Ganeshkumar [Verfasser], and Tanja [Akademischer Betreuer] Vogel. "Role of noncoding RNAs in FOXG1 dependent atypical Rett syndrome." Freiburg : Universität, 2020. http://d-nb.info/1237220637/34.
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Matthews, Gareth David Kingsley. "The rate-dependence of pro-arrhythmic properties in murine SCN5A+/- hearts modeling the Brugada syndrome." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648741.
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Ekwall, Olov. "Pteridine dependent hydroxylases as autoantigens in autoimmune polyendocrine syndrome type 1." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2001. http://publications.uu.se/theses/91-554-4941-7/.
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Minić, Marina. "Investigation of a syndrome of non insulin-dependent hypoglycaemia and overgrowth." Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708929.
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Acaye, Richard. "Relief Aid Dependency Syndromes| A Case for Disaster-Prone Moroto District in Uganda." Thesis, Walden University, 2016. http://pqdtopen.proquest.com/#viewpdf?dispub=3746206.
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Humanitarian aid, while useful in the short run, sometimes has the effect of contributing to poverty and poor economic conditions in the long run. This occurs when recipients of relief aid lose their initiative to fend for themselves and become reliant on external aid. The purpose of this mixed method study was to evaluate the degree to which dependency on long term aid has contributed to chronic poverty in the Moroto district of Uganda. This study was grounded on Harvey & Lind’s conceptualization of the dependency syndrome. The research questions addressed the relationship between household production and investment pattern with number of year as aid beneficiary, while exploring the beneficiaries’ perceptions on the roles of relief aid in their livelihood. Survey data were acquired from 75 participants from five sampled villages in Moroto District; qualitative data were acquired from the same villages involving five focus group discussions with 15 key informants per village. Quantitative data were analyzed using multivariate regression analysis and resulted in a finding of a statistically significant negative relationship between household production and investment with number of years spent as aid beneficiary. Qualitative data were inductively coded, and then organized around key themes. These findings suggest that many rural Ugandans believe that if aid were to cease, they would either migrate to an area where aid was available, or die of starvation. Implications for positive social change are connected to a recommendation to organizations offering humanitarian aid to package relief aid with other programs that support the recipients’ resilience building capacity in order to save lives and reduce chronic poverty that is common in disaster-prone areas around the world.
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Acaye, Richard. "Relief Aid Dependency Syndromes: A Case for Disaster-Prone Moroto District in Uganda." ScholarWorks, 2015. https://scholarworks.waldenu.edu/dissertations/1872.
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Humanitarian aid, while useful in the short run, sometimes has the effect of contributing to poverty and poor economic conditions in the long run. This occurs when recipients of relief aid lose their initiative to fend for themselves and become reliant on external aid. The purpose of this mixed method study was to evaluate the degree to which dependency on long term aid has contributed to chronic poverty in the Moroto district of Uganda. This study was grounded on Harvey & Lind's conceptualization of the dependency syndrome. The research questions addressed the relationship between household production and investment pattern with number of year as aid beneficiary, while exploring the beneficiaries' perceptions on the roles of relief aid in their livelihood. Survey data were acquired from 75 participants from five sampled villages in Moroto District; qualitative data were acquired from the same villages involving five focus group discussions with 15 key informants per village. Quantitative data were analyzed using multivariate regression analysis and resulted in a finding of a statistically significant negative relationship between household production and investment with number of years spent as aid beneficiary. Qualitative data were inductively coded, and then organized around key themes. These findings suggest that many rural Ugandans believe that if aid were to cease, they would either migrate to an area where aid was available, or die of starvation. Implications for positive social change are connected to a recommendation to organizations offering humanitarian aid to package relief aid with other programs that support the recipients' resilience building capacity in order to save lives and reduce chronic poverty that is common in disaster-prone areas around the world.
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Christo, George. "Post substance dependence stress syndrome : a complex post-traumatic stress disorder (PTSD) conceptualisation of residual psychopathology during abstinence after substance dependence." Thesis, University of Surrey, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.362327.
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Gould, Rebekah. "Dose and time dependence of alcohol exposure in relation to craniofacial dysmorphisms in fetal alcohol syndrome." Thesis, Boston University, 2013. https://hdl.handle.net/2144/21158.
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Thesis (M.A.) PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.The National Institutes of Health defines Fetal Alcohol Syndrome (FAS) as a debilitating collection of birth defects that include craniofacial dysmorphisms, neurological and motor insufficiencies, growth retardation, and behavioral and social discrepancies. Characteristic craniofacial abnormalities, which include smooth philtrum, thin vermillion border, short palpebral fissures, and microcephaly, are used as a diagnostic tool for FAS. There is agreement across the literature that the characteristic craniofacial dysmorphisms are induced as a result of prenatal alcohol exposure in very specific doses, and during very particular time periods during embryonic development. However, ambiguity still exists about the critical time and dose relationship of prenatal alcohol exposure in the production of FAS. In regards to the critical timing, researchers have concluded that prenatal alcohol exposure during the second half of the first trimester, defined as days 43-94 postconception, was found to cause an increased incidence of smooth philtrum, thin vermillion border, microcephaly and reduced birth weight. Conversely, other studies found that prenatal alcohol exposure on day 7 of gestation in mice, which corresponds to week 3 of human gestation, induced craniofacial abnormalities comparable to those seen in humans with FAS. In regards to the critical dose, there is a linear relationship between the dose of prenatal alcohol exposure and the incidence of FAS-related craniofacial abnormalities, with no safe threshold. It was also found that a binge pattern of drinking was more significantly associated with the craniofacial abnormalities seen in FAS than a continuous or less condensed pattern of drinking, even if the binge pattern involved a smaller absolute dose of alcohol. These results regarding both dose and pattern on prenatal alcohol exposure, suggest that binge-drinking patterns are most significantly associated with craniofacial abnormalities if consumed before pregnancy or during late pregnancy, whereas absolute high doses of alcohol in a non-binge pattern were most significantly associated with craniofacial abnormalities in the first trimester. Further research is required for clarification of the critical time and dose relationships involved in the production of the characteristic craniofacial dysmorphisms seen in FAS. A definite conclusion will aid in the public education and prevention programs for FAS if solid information can be provided about the harms of alcohol consumption during pregnancy in regards to timing and dose.
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Walker, Pieter Everard. "A test battery devised to screen alcohol dependent persons for Korsakoff's Syndrome /." Title page, table of contents and abstract only, 1990. http://web4.library.adelaide.edu.au/theses/09ARPS/09arpsw1772.pdf.
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Leung, Hiu-lan Nancy, and 梁曉灡. "Mechanism of antibody-dependent enhancement in severe acute respiratory syndrome coronavirus infection." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B47327066.
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Severe lymphopenia is a clinical feature of Severe Acute Respiratory Syndrome
(SARS) patients. However, lymphocytes do not express receptor for SARS-CoV,
neither the widely accepted viral receptor angiotensin converting enzyme 2 (ACE2)
nor the putative receptors Dendritic Cell- and Liver/lymph-Specific Intercellular
adhesion molecule-3-Grabbing Non-integrin (DC-SIGN and L-SIGN). Our group
previously showed in vitro that, SARS-CoV Spike pseudotyped particles (SARSCoVpp)
could infect human B cells only when inoculated in presence of anti-SARSCoV
Spike immune serum. Such observations raised concerns about the possible
occurrence of antibody-dependent enhancement (ADE) of infection, a phenomenon
during which a virus bounded by antibodies could gain entry into cells through
mechanisms involving complement receptors or Fc receptors. Recently, we have
demonstrated the participation of the human Fc gamma receptor II (hFcγRII)
molecules in granting SARS-CoV an opportunity to infect human immune cells.
The aim of this study was to decipher the molecular mechanism leading to antibodymediated,
FcγRII-dependent infection of immune cells by SARS-CoV. By using
transduction experiment, I highlighted that different members of the hFcγRII family
(namely hFcγRIIA, hFcγRIIB1 and hFcγRIIB2) could confer susceptibility to ADE of
SARS-CoVpp infection. I further demonstrated that purified anti-viral
immunoglobulin G, but not other soluble factor(s) from heat-inactivated immune
serum, was the determinant for occurrence of ADE infection. Additionally, with the
development of a cell-cell fusion assay, I illustrated that in contrast to the ACE2-
dependent pathway, ADE infection did not occur at the plasma membrane, but rather
require internalization of virus/antibodies immune complexes by the target cells. In
line with this hypothesis, my results using a panel of FcγRII-expressing mutants
demonstrated that binding of immune complexes to cell surface FcγRII was a
prerequisite but was not sufficient to trigger ADE infection. In these experiments,
only FcγRII signaling-competent constructions conferred susceptibility to ADE of
SARS-CoVpp infection.
Altogether my results point toward a role of the anti-SARS-CoV Spike IgG in vitro in
granting SARS-CoV an opportunity to infect cells bearing signaling-competent
FcγRII receptors. If further confirmed, such observations could have implications for
understanding SARS-CoV tropism and SARS pathogenesis, as well as warrant for
careful design of SARS vaccines and immunotherapy based on anti-viral antibodies.published_or_final_version
Microbiology
Master
Master of Philosophy
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Alderton, Gemma K. "The contribution of defects in ATR-dependent signalling to human dysmorphic syndromes." Thesis, University of Sussex, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.424401.
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Reimers, Mark J. "Ethanol-dependent developmental toxicity in zebrafish /." Connect to full text via ProQuest. IP filtered, 2005.
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Thompson, Miles. "Mutation screening of dopamine and serotonin candidate genes in Tourette's syndrome and alcohol-dependent patients." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ29330.pdf.
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Nyström, Anna-Maja. "RAS-MAPK syndromes - a Clinical and Molecular Investigation." Doctoral thesis, Uppsala universitet, Institutionen för genetik och patologi, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-100804.
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The RAS-MAPK syndromes are a group of clinically and genetically related disorders, characterized by cardiac defects, facial dysmorphism, cutaneous abnormalities and neurocognitive impairment. The pathogenesis is dysregulation of the RAS-MAPK pathway, and several genes within the pathway are involved. The present thesis aimed at identifying genetic causes in three of the RAS-MAPK syndromes - Noonan syndrome (NS), cardio-facio-cutaneous syndrome (CFC) and Neurofibromatosis-Noonan syndrome (NFNS) - and at correlating genotype with phenotype. A mutation analysis of six genes associated with the RAS-MAPK syndromes in NS and CFC patients revealed mutations in 10/31 patients. The results suggested more complex genetic overlap and genetic heterogeneity among these syndromes than previously believed. Subsequently, gene dosage imbalances of seven RAS-MAPK-syndrome-related genes were investigated in mutation-negative patients. A multiplex ligation-dependent probe amplification strategy was developed that excluded copy number changes of these genes as a common mechanism in NS. Genetic causes of clinical variability in NS were investigated where an atypical and severe NS patient was described. In addition, multiple café-au-lait (CAL) spots affected the patient and four otherwise healthy family members. Molecular analysis of four candidate genes revealed a previously described de novo PTPN11 mutation and an inherited NF1 variant in the patient. Neither of them explained the CAL spots trait, which consequently represented a distinct entity. The results suggested that the atypical and severe phenotype in the patient could be a consequence of an additive effect. Finally, a family displaying NFNS was investigated clinically and molecularly revealing a novel mutation in the GAP-domain of NF1. Furthermore, the results suggested that other RAS-MAPK-syndrome-related genes are not involved in NFNS. A proposal of prioritizing the GAP-domain of NF1 in NFNS was presented. Conclusively, these studies contribute to further understanding of the RAS-MAPK syndromes and facilitate the diagnostic process and future prognosis prediction.
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Taponen, S. (Saara). "Metabolic and clinical characteristics of women with self-reported symptoms of polycystic ovary syndrome." Doctoral thesis, University of Oulu, 2004. http://urn.fi/urn:isbn:9514273176.
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Abstract
Oligomenorrhea (menstrual disturbances) and hirsutism (excessive growth of body hair) are typical symptoms of polycystic ovary syndrome, a common endocrine disorder with long-term health risks among fertile-age women.
Associations between body size development and polycystic ovary syndrome symptoms in a cohort design (528 symptomatic and 1479 asymptomatic women) and endocrine, metabolic and clinical characteristics of women with self-reported symptoms of oligomenorrhea or hirsutism in a nested case-control design (518 cases and 1036 controls) were investigated in this general population-based study. Gynecologic ultrasonographic examinations were performed in 196 cases and 67 controls to assess the morphology of the ovaries and its relationship to biochemical and clinical parameters. The study population was derived from the Northern Finland Birth Cohort 1966, which included all births with expected birth dates in 1966 in Northern Finland and is well representative of the general female population.
Polycystic ovary syndrome symptoms in adulthood were associated with obesity, particularly abdominal obesity, in adolescence and in adulthood, but not with birth weight or being small for gestational age. Hormonal changes typical of polycystic ovary syndrome, i.e. higher circulating concentrations of testosterone, luteinizing hormone (LH) and insulin and lower levels of sex hormone-binding globulin (SHBG), were detected in women with self-reported symptoms of oligomenorrhea and/or hirsutism compared with the controls. Less favorable metabolic cardiovascular disease risk factor profiles, higher body mass index (BMI), waist-hip ratio (WHR), and triglyceride and C-reactive protein (CRP) concentrations and lower high density lipoprotein cholesterol (HDL-C) levels, were detected in women with symptoms, being the most severe among women who reported both hirsutism and oligomenorrhea. Unfavorable characteristics were pronounced in the presence of overweight or obesity. Women with symptoms more often had features characteristic of polycystic ovarian morphology associated with an endocrine and clinical profile reflecting polycystic ovary syndrome.
This study shows that questioning in regard to symptoms of oligomenorrhea and hirsutism is useful in detecting women at risk of polycystic ovary syndrome and associated health risks. Avoidance of being overweight is important among young women to prevent the development of insulin resistance. Systematic follow-up of women with symptoms of oligomenorrhea and hirsutism is justified for prevention and early detection of long-term health risks.
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Lehnert, Claudia. "24 hour hormone and serum electrolyte levels of dogs with pituitary-dependent hyperadrenocorticism treated with trilostane." Giessen : VVB Laufersweiler, 2007. http://geb.uni-giessen.de/geb/volltexte/2007/4678/index.html.
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Luzi, Nicole. "An Enzymology and Inhibition Study of a cAMP-Dependent Protein Kinase Linked to ACTH-Independent Cushing's Syndrome." VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/6058.
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Cyclic-AMP dependent protein kinase (PKA) is a key intracellular signal transduction kinase that is modulated by Gs- and Gi-coupled GPCRs. Under normal physiological conditions, PKA exists as an inactive holoenzyme made up of two catalytic subunits and two regulatory subunits. Upon cAMP binding to the regulatory subunits, the catalytic subunits (PKACa) are released to perform various downstream phosphorylation events. However, aberrant PKA activation can cause various diseases including Cushing’s Syndrome, which is an endocrine disorder caused by the overproduction of cortisol by the hypothalamus-pituitary-adrenal hormone system. This disorder can be caused by pituitary adenomas that release unregulated amounts of ACTH, adrenal adenomas that release unregulated amounts of cortisol without ACTH stimulation, and ectopic tumors outside the hypothalamus-pituitary-adrenal axis that produce ACTH. In recent genomic studies of patients with ACTH-independent Cushing’s Syndrome, the L205R-PKACamutant has been discovered. Through various studies on the mutant enzyme multiple research groups learned that the single point mutation causes a loss in sensitivity to cAMP signaling, a loss in binding to PKA regulatory subunits, and unregulated phosphorylation of PKACasubstrates, which ultimately leads to the increased cortisol biosynthesis in these patients.
The first part of this work describes the enzymology and inhibition studies of known inhibitors against both wt- and L205R-PKACa. Early in the enzymology studies we developed at medium throughput endpoint assay that used Rhodamine-kemptide as the substrate and as a chromophore separating substrate and phosphorylated product using a reverse-phase HPLC method. The analysis of the substrate peptide against both wild-type and mutant enzyme showed a 6-fold decrease in the KMand a 2-fold decrease in kcat, and a similar but lower order of magnitude effect was observed for the studies with ATP. The inhibition studies were performed using the substrate competitive inhibitor PKI(5-24), which showed a 253-fold higher potency towards the wild-type enzyme over the mutant while the ATP-competitive inhibitor was determined to be equipotent. Using this information we used modeling studies to aid in the development of mutant selective functional inhibitors for the substrate-binding pocket. Additionally, we begun to explore the use of Proteolysis Targeting Chimeras, or PROTACs, as another means for targeting the L205R mutant enzyme.
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Ebert, Jane Louise. "A neuropsychological study of visual, spatial and verbal memory in Korsakoff's syndrome patients and alcohol dependent drinkers /." Title page, contents and abstract only, 1995. http://web4.library.adelaide.edu.au/theses/09ARPS/09arpse16.pdf.
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Hudecova, Miriam. "Reproductive and Metabolic Consequences of the Polycystic Ovarian Syndrome." Doctoral thesis, Uppsala universitet, Institutionen för kvinnors och barns hälsa, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-123248.
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Polycystic ovary syndrome (PCOS) is a complex clinical condition characterized by hyperandrogenism and chronic oligo/anovulation. Infrequent ovulation and metabolic alterations in women with PCOS are associated with subfertility and probably increased miscarriage rates compared with normal fertile women. The overall risk of developing type 2 diabetes and impaired glucose tolerance (IGT) is three- to sevenfold higher in PCOS women, and the onset of glucose intolerance seems to occur at an earlier age than in healthy controls. Women with PCOS also have several risk factors for cardiovascular disease, although it is unclear whether they actually experience more cardiovascular events than other women. Very few studies assessing the long-term reproductive and metabolic consequences in older women with previously confirmed PCOS have been conducted. In this long-term follow-up of women with PCOS, 84 women with a diagnosis of PCOS between 1987 and 1995 and age at the follow-up > 35 years and an age-matched population-based group of control women participated. Data on reproductive outcome, ovarian reserve, endothelial function, insulin sensitivity and beta-cell function were collected. According to our results most women with PCOS had given birth and the rate of spontaneous pregnancies was relatively high. The rate of miscarriages was not increased in PCOS patients and the ultrasound findings together with increased levels of anti-müllerian hormone suggested that their ovarian reserve is superior to women of similar age. PCOS women displayed signs of endothelial dysfunction, but this was largely due to the increased prevalence of independent risk factors for cardiovascular disease such as increased BMI, triglycerides and blood pressures. IGT and type 2 diabetes occurred more often in PCOS women. Free androgen levels and beta-cell function decreased over time whereas insulin sensitivity remained unchanged. Obesity at young age and progressive weight-gain rendered them more prone to be insulin resistant at the follow-up. Beta-cell function was increased in PCOS women in comparison with control subjects but declined over time. Independent of PCOS phenotype at the index assessment and persistence of PCOS symptoms at the follow-up investigation, premenopausal women with PCOS had lower insulin sensitivity and increased beta cell function in comparison with control subjects. Conclusion: The long-term reproductive outcomes of PCOS are similar compared to women with normal ovaries. Although symptoms and androgen levels are normalized over time, women with PCOS continue to display reduced insulin sensitivity and increased beta-cell function and they also have an increased risk of IGT and type 2 diabetes.
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Kompella, Sindura, Sylvester Olubolu Orimaye, Nigel Dsouza, Karl Goodkin, Steven Kendell, Susan Wallace, and Tracy Willson. "Behavioral Correlates for Quitting Opioids among Opioid-Dependent Pregnant and Non-Pregnant Women of Childbearing Age in Rural Appalachia." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/asrf/2018/schedule/31.
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Background: The opioid epidemic is particularly worrisome in the pregnant population, wherein concerns are raised about the health of a mother and her child, resulting in an alarming incidence and prevalence of Neonatal Abstinence Syndrome (NAS). The 2016 National Survey on Drug Use and Health (NSDUH) show the rate of illicit psychoactive substance use among the females aged 12 or older was 15.5% in the past year. Among pregnant women aged 15 to 44, 6.3% were illicit psychoactive substance users. In Tennessee, the number of hospital discharged NAS cases from 2002 to 2013 increased from 1.50 to 16.6 cases per 1,000 live births. This number is triple the national incidence of NAS cases over the same time period. Between 2013 and 2016, at least 52.5% of children diagnosed with NAS in Tennessee have had exposure to one prescription drug, while 27.2% were exposed to a combination of prescribed medications and illicit substances. We examined the behavioral correlates that determine the wish to quit opioids or not to quit opioids among opioid-dependent pregnant and non-pregnant women in rural Appalachia.
Methods: Ten women of childbearing age, whether pregnant or not, who were receiving prescribed opioids, were recruited to join the study. All the participating women were also receiving physician-managed Medication Assisted Treatment (MAT) therapy for the treatment of severe opioid use disorder, or are currently being prescribed an opioid medication. Study variables included age, Hamilton Depression Rating Scale (HAM-D), Visual Analogue Scale – Pain (VAS-P), the Modified Opiate Craving Scale (MOCS), the Visual Analog Commitment to Quit Opiates, the McGill Pain Index (MPI), prescriptions, tobacco and nicotine use, illicit substance use, the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES), and the Adverse Childhood Experience (ACE) questionnaire. The HAM-D, MOCS, MPI, and SOCRATES scores were log-transformed to approximate a normal distribution. Descriptive statistics and the Spearman’s rank correlation (with a 95% Confidence Interval) were conducted to examine significant behavioral correlates for quitting opioids.
Results: Descriptive statistics show that women with higher HAM-D and MOCS scores are not likely to express willingness to quit opioids. There is a statistically significant strong positive correlation of 0.679 (pppp
Conclusion: Women who recognize the need to quit opioids or are “taking steps” to quit are more likely to quit opioids. Women with high depression and pain scores are not likely to quit opioids. Non-opioid medications may reduce the number of opioid-dependent pregnant and non-pregnant women of childbearing age, and, in turn, lower the currently high incidence and prevalence rates of NAS.
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Burkhardt, Gerrit [Verfasser], and Oliver [Akademischer Betreuer] Pogarell. "Using machine learning to predict individual severity estimates of alcohol withdrawal syndrome in patients with alcohol dependence / Gerrit Burkhardt ; Betreuer: Oliver Pogarell." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2021. http://d-nb.info/1238518869/34.
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Gerber, Katherine Maureen. "THE CAPACITY TO SECRETE INSULIN IS DOSE-DEPENDENT TO EXTEMELY HIGH GLUCOSE CONCENTRATIONS: A KEY ROLE FOR ADENYLYL CYCLASE." Ohio University Honors Tutorial College / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1619178997628352.
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Saathoff, Katharina [Verfasser]. "Deletion Mapping and Phenotype-Genotype Analysis by Multiplex Ligation-dependent Probe Amplification in German Patients with Williams-Beuren-Syndrome / Katharina Saathoff." Hamburg : Staats- und Universitätsbibliothek Hamburg Carl von Ossietzky, 2020. http://d-nb.info/1237415020/34.
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Killian, Martin. "Nouvelles immunothérapies dans le traitement du syndrome de Sjögren et autres maladies interféron-dépendantes." Thesis, Lyon, 2019. http://www.theses.fr/2019LYSES051.
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Durant mon travail de thèse, je me suis particulièrement intéressé au lien entre les maladies auto-immunes et le système des interférons (IFN). Ces cytokines sont bien connues pour leur rôle dans la lutte antivirale, mais leurs effets dépassent largement ce cadre, avec une implication maintenant bien documentée dans la physiopathologie de nombreuses maladies dysimmunes comme le lupus érythémateux systémique (LES), le syndrome de Sjögren (SjS), les myosites ou encore la sclérodermie systémique, en particulier concernant les IFNs de type 1. C’est donc assez logiquement que nous nous sommes arrêtés, en premier lieu, sur l’IFNα, principal représentant des IFNs de type 1. Après la conduite d’une réflexion autour du choix et de l’utilisation actuelle des modèles animaux de SjS, en particulier à propos de la pertinence de la dichotomie entre SjS dit primaire ou secondaire, la première partie de mon travail a consisté en l’évaluation d’une stratégie innovante de vaccination thérapeutique anti-IFNα, appelée IFN-Kinoïde (IFN-K), dans un modèle murin de SjS systémique, le modèle MRL/MpJ-Faslpr/lpr (MRL/lpr). Nous avons obtenu des résultats particulièrement intéressants, en terme d’immunogénicité et de tolérance, et une amélioration (fonctionnelle et morphologique) des atteintes glandulaires, neurologique périphérique et de la signature IFN, ce qui est de bon augure pour l’avenir, sachant que l’équivalent humain de ce traitement est en cours de développement clinique dans le LES chez l’Homme. Ces résultants nous ont permis de mener un autre essai préclinique avec l’IFN-K (dont je présente ici des résultats préliminaires) dans un modèle de SjS développant des lymphomes B : le modèle transgénique pour l’interleukine 14α humaine.Le travail autour de cette première approche thérapeutique nous a mené à d’autres pistes de recherche que nous présentons également dans une deuxième partie. Je me suis intéressé aux mécanismes à l’origine de l’activation de la voie des IFNs dans le SjS, ce qui nous a conduit à mettre en place un essai clinique interrégional, pour évaluer l’intérêt d’un nouveau biomarqueur pour le SjS, les anticorps anti-Ro60/SSA d’isotype immunoglobuline E. Pour finir, je rapporte ici le 1er cas humain de patient atteint de SjS et traité avec succès par inhibiteur de JAK, le ruxolitinib, en raison d’une forme systémique particulièrement rare et sévère incluant une myélofibrose auto-immune (atteinte hématologique centrale). L’ensemble des données produites dans ce travail de thèse permet d’éclaircir quelques aspects du rôle des IFNs dans le SjS, en particulier de l’IFNα, et permet d’ouvrir la voie à de nouvelles pistes thérapeutiquesMy PhD thesis focused on the link between autoimmune diseases and the interferons’ (IFN) system. These cytokines are well known for their antiviral effects, but their role goes far beyond this, with a growing body of evidence concerning their implication in many autoimmune diseases, such as systemic lupus erythematosus (SLE), Sjögren’s syndrome (SjS), myositis and systemic sclerosis (SSc), especially concerning type 1 IFNs. Hence, we mainly focused on IFNα, which is the main representative of type 1 IFNs. After an in-depth thinking on the choice and current use of mouse models in SjS, especially about the concept of primary and secondary SjS, the first part of my work was dedicated to the conduct of a preclinical trial evaluating IFN-Kinoid (IFN-K) in a systemic SjS mouse model, MRL/MpJ-Faslpr/lpr (MRL/lpr) mice. We obtained good results, in terms of immunogenicity and tolerance, and improved the glandular manifestations, peripheral neuropathy and IFN signature in these mice, which paves the way towards IFN-K’s future clinical development in SjS, as it is already the case for SLE. These results allowed us to conduct another preclinical trial with IFN-K in a SjS model developing B lymphomas: the human interleukin 14α transgenic mouse model.In the second part of my PhD thesis, I studied some of the mechanisms leading to the activation of the IFN pathways in SjS, especially the effects of anti-Ro60/SSA immunoglobulin E autoantibodies, and we conducted a regional clinical trial to evaluate this new biomarker in the disease. Finally, I have reported here the first human case of a patient with systemic SjS (including autoimmune myelofibrosis), successfully treated with the JAK inhibitor, ruxolitinib.The set of data produced in this PhD thesis clarifies some aspects about the role of IFNs (especially IFNα) in SjS, and paves the way towards new therapeutic leads
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Oliva, Ana Lígia. "Apoio social para dependentes do álcool." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/17/17139/tde-08042008-143441/.
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O consumo abusivo do álcool e suas conseqüências vêm aumentando significativamente, constituindo sério problema para a saúde pública. Esses problemas representam alto custo social e comprometem diversas áreas da saúde. O presente estudo é do tipo descritivo e tem como objetivo identificar o apoio social para dependentes do álcool e analisar suas relações. A amostra foi composta por 50 usuários, cadastrados, e em atendimento no Centro de Atenção Psicossocial -Álcool e Drogas - CAPS ad.II, de Ribeirão Preto, com diagnóstico de síndrome de dependência do álcool. Para a coleta de dados foi utilizado questionário estruturado com perguntas fechadas, dividido em três partes: as informações sociodemográficas, o teste de identificação do uso do álcool (Audit) e o instrumento de apoio social Medical Outcomes Study (MOS). Resultados: 43(86%) do sexo masculi no, 26(46%) solteiros, 26(52%) adultos, faixa etária entre 30 e 49 anos, com baixo nível de escolaridade 31(62%), pois tinham o ensino fundamental completo ou incompleto, e 21(42%) estavam desempregados. Com relação ao uso do álcool, 44(88%) apresentaram níveis de provável dependência, ou dependência, do álcool, e 31(62%) iniciaram o uso do álcool na adolescência, entre 12 e 18 anos. Referente ao apoio social (apoio material, apoio afetivo mais interação social positiva, apoio emocional mais apoio de informação) de um modo geral, observou-se que os usuários apresentaram apoio social baixo, quando comparados os tipos de apoio, encontrou-se associação entre apoio afetivo e interação social positiva e a faixa etária, principalmente na idade de 50 anos, pois a chance de não terem apoio é 15 vezes maior quando comparado aos mais jovens. Os achados do presente estudo apontam para o desenvolvimento de programas direcionados a fortalecer o apoio social durante e após o tratamento do uso abusivo o álcool.Binge drinking and its consequences have been increasing significantly, thus becoming a serious health problem. Such problems represent a high social cost and they adversely affect several health sectors.The present descriptive study aims to identify social support among alcohol dependent individuals and evaluate their association. The sample consisted of fifty alcohol users who signed up for treatment at the Center for Psychosocial Attention- Alcohol and Drugs (CAPS ad.II) in Ribeirão Preto, diagnosed with Alcohol Dependence Syndrome. For data collection, a questionnaire, divided into three parts, containing closed ended questions on social demographic information, the Alcohol Use Identification Test (Audit), and the Social Support Instrument Medical Outcomes Study (MOS) was used.RESULTS: 43 (86%) of the subjects were male, 26 (52%) were single, 26 (52%) were adults between thirty and forty nine years old with low educational level (they had not completed elementary school), and 21 (42%) were unemployed. As for alcohol use, 44 (88%) of the subjects presented level of probable dependence or alcohol dependence and 31 62%) started using alcohol between the age of twelve or eighteen. As regards social support, (material support, affective support plus positive social interaction, emotional support plus information support) subjects were found to count on low social support. When types of support were compared, an association between affective support and positive social interaction and age group emerged, mainly around the age of 50, for this age group is one fifteenth times as likely to count on social support when compared with younger subjects. These findings present indicators for the development of programs aiming to strengthen social support during and after binge drinking treatment.
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Sun, Xiaoguang, Biji Mathew, Saad Sammani, Jeffrey R. Jacobson, and Joe G. N. Garcia. "Simvastatin-induced sphingosine 1−phosphate receptor 1 expression is KLF2-dependent in human lung endothelial cells." SAGE PUBLICATIONS INC, 2017. http://hdl.handle.net/10150/623874.
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We have demonstrated that simvastatin and sphingosine 1-phosphate (S1P) both attenuate increased vascular permeability in preclinical models of acute respiratory distress syndrome. However, the underlying mechanisms remain unclear. As Kruppel-like factor 2 (KLF2) serves as a critical regulator for cellular stress response in endothelial cells (EC), we hypothesized that simvastatin enhances endothelial barrier function via increasing expression of the barrier-promoting S1P receptor, S1PR1, via a KLF2-dependent mechanism. S1PR1 luciferase reporter promoter activity in human lung artery EC (HPAEC) was tested after simvastatin (5 mu M), and S1PR1 and KLF2 protein expression detected by immunoblotting. In vivo, transcription and expression of S1PR1 and KLF2 in mice lungs were detected by microarray profiling and immunoblotting after exposure to simvastatin (10 mg/kg). Endothelial barrier function was measured by trans-endothelial electrical resistance with the S1PR1 agonist FTY720-(S)-phosphonate. Both S1PR1 and KLF2 gene expression (mRNA, protein) were significantly increased by simvastatin in vitro and in vivo. S1PR1 promoter activity was significantly increased by simvastatin (P < 0.05), which was significantly attenuated by KLF2 silencing (siRNA). Simvastatin induced KLF2 recruitment to the S1PR1 promoter, and consequently, significantly augmented the effects of the S1PR1 agonist on EC barrier enhancement (P < 0.05), which was significantly attenuated by KLF2 silencing (P < 0.05). These results suggest that simvastatin upregulates S1PR1 transcription and expression via the transcription factor KLF2, and consequently augments the effects of S1PR1 agonists on preserving vascular barrier integrity. These results may lead to novel combinatorial therapeutic strategies for lung inflammatory syndromes.
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Scharkowski, Franziska Verfasser], and Martin [Akademischer Betreuer] [Korte. "Spine development and activity-dependent plasticity in the hippocampus of a mouse model of the fragile X syndrome / Franziska Scharkowski ; Betreuer: Martin Korte." Braunschweig : Technische Universität Braunschweig, 2017. http://d-nb.info/1175818003/34.
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Kul, Ufuk Emre [Verfasser], and Oliver [Gutachter] Stork. "Reversibility of the pathology in a mouse model of fragile X-associated tremor/ataxia syndrome : exploring time-dependence and intervention strategies / Ufuk Emre Kul ; Gutachter: Oliver Stork." Magdeburg : Universitätsbibliothek Otto-von-Guericke-Universität, 2020. http://d-nb.info/1219936685/34.
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Ninichuk, Volha. "The role of chemokine receptor CCR1-dependent macrophage recruitment for the progression of chronic kidney disease in murine Alport syndrome or type 2 diabetes." Diss., lmu, 2008. http://nbn-resolving.de/urn:nbn:de:bvb:19-79657.
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Confettura, Alessandro Dario [Verfasser], and Eckart D. [Gutachter] Gundelfinger. "Neddylation-dependent protein degradation is a nexus between the metabolic syndrome, synaptic insulin resistance and Alzheimer's Disease / Alessandro Dario Confettura ; Gutachter: Eckart D. Gundelfinger." Magdeburg : Universitätsbibliothek Otto-von-Guericke-Universität, 2019. http://d-nb.info/1219964883/34.
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JOHNSON, BRIAN REAVES. "THE ROLE OF ATAXIA TELANGIECTASIA-MUTATED AND NIJMEGEN BREAKAGE SYNDROME PROTEIN-1 IN THE ACCUMULATION OF UVC-INDUCED DNA REPLICATION-DEPENDENT DOUBLE STAND BREAKS." University of Cincinnati / OhioLINK, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1022158038.
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Song, Jun. "Neuronal Adaptations in Rat Hippocampal CA1 Neurons during Withdrawal from Prolonged Flurazepam Exposure: Glutamatergic System Remodeling." Connect to Online Resource-OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=mco1177519349.
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Thesis (Ph.D.)--University of Toledo, 2007."In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Sciences." Major advisor: Elizabeth Tietz. Includes abstract. Title from title page of PDF document. Bibliography: pages 88-94, 130-136, 178-189, 218-266.
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Sarmento, Solange d. Avila Melo. "Um olhar psicanalítico sobre o desenvolvimento emocional de adultos com limitação intelectual moderada: a (in)sustentável leveza entre autonomia e dependência." Universidade do Estado do Rio de Janeiro, 2009. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=6504.
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Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorEste trabalho explora as possibilidades de contribuição da psicanálise para a compreensão do processo de construção de identidade e busca de autonomia de adultos com limitação intelectual moderada. Parte da ideia de que estas pessoas apresentam formas diversas de subjetivação e que, como todos, ao longo da vida são passíveis de encontros e desencontros provocadores dos mais diversos sentimentos. Reconhece a importância dos aspectos orgânicos, e afastando-se dos mesmos, desenvolve a ideia de que, para além do substrato orgânico, os aspectos emocionais são fatores fundamentais para a construção da autonomia. A hipótese básica é a de que os limites e as possibilidades de aquisição da autonomia são variáveis e que os aspectos emocionais são importantes neste processo. Há aspectos da dependência ambiental que são insuperáveis nestes casos, o que não quer dizer que sejam fixos ou imutáveis. Mesmo levando-se em consideração as restrições impostas pela base orgânica dos quadros estudados, as ligações familiares, primordialmente representadas pela relação da mãe com seu filho, colocam-se como fator importante quando se propõe a compreender e trabalhar com estas pessoas. O trabalho aborda a articulação possível entre a dependência e a autonomia levantando algumas consequências: nas práticas sociais, na construção da subjetividade e nos tratamentos. Pretende desenvolver a ideia de que a teoria do desenvolvimento emocional primitivo de Winnicott traz uma importante contribuição para a compreensão deste processo.
This paper explores some possible psychoanalytical contributions in understanding the process of identity construction and autonomy of adults with moderate intellectual limitations. This work is based on the idea that this group shows different forms of subjectivity and, like all of us, has its share of encounters and disencounters experienced in life with every kind of feelings about this. Although recognizing the importance of the organic aspects, it searches further than those looking for the emotional aspects which are essential to the construction of autonomy. The basic concept adopted is that the limits and possibilities of the conquest of autonomy vary from person to person and the emotional aspects embedded are crucial in the process. There are aspects of enviromental dependency that are insuperable in those cases, although it doesnt mean that they are fixed or that they cannot change. Even considering the organic restrictions of the studied cases, the family connections (essentialy represented by mother and son relationship) are very important in understanding and working with those cases. This work aims a possible articulation between dependency and autonomy enlightening some consequences in social practices, in the construction of subjectivity and in treatment. It intends to develop the idea that Winnicotts primitive emotional development concepts offer an important contribution to this process.
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Soria, Rodríguez Guadalupe. "Sistemas cannabinoide y purinérgico: posibles sustratos neurobiológicos de la drogadicción." Doctoral thesis, Universitat Pompeu Fabra, 2006. http://hdl.handle.net/10803/7101.
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La adicción es un trastorno crónico de la conducta caracterizado por la búsqueda y el consumo compulsivos de la droga, la pérdida de control para limitar dicho consumo, a aparición de un estado emocional negativo cuando el acceso a la droga está impedido y la recaída en el proceso incluso tras largos períodos de abstinencia. El sistema dopaminérgico mesolímbico cortical ha sido propuesto como la principal base neurobiológica de la adicción, sin embargo existen otros sistemas de neurotransmision que participan en la consolidación del proceso adictivo.El sistema endocannabinoide, a traves del receptor CB1, participa en las propiedades adictivas de diferentes drogas de abuso como el delta9-tetrahidrocannabinol, la nicotina y la morfina. Sin embargo, hasta el momento de iniciar este trabajo, pocos estudios han demostrado una clara implicación del sistema endocannabinoide en las propiedades reforzantes de los psicoestimulantes. Mediante el uso de ratones CB1 knockout, hemos demostrado que el receptor CB1 participa en la eficacia reforzante de la cocaína. Además, la presencia de dicho receptor es necesaria para los procesos de consolidación de una conducta operante mantenida por la autoadministración de cocaína. Este estudio demuestra la importancia de dicho receptor CB1 en las propiedades adictivas de la cocaína, confirmando que el sistema endocannabinoide es un sustrato común para la adicción de drogas de abuso.
Por otra parte, el sistema purinérgico modula numerosos sistemas de neurotransmisión en el SNC. La estrecha relación a nivel celular y funcional entre los receptores de adenosina y los receptores dopaminérgicos proporciona evidencias de que el sistema purinérgico podría modular los sistemas de recompensa. Utilizando diferentes modelos animales, hemos demostrado que los receptores de adenosina A2A son necesarios para que las propiedades adictivas de las drogas de abuso como los cannabinoides, los opioides, la nicotina y los psicoestimulantes se produzcan de un modo completo.
Nuestros estudios nos permiten afirmar que ambos sistemas, el cannabinoide y el purinérgico podría suponer la existencia de nuevos sistemas de modulación común de los procesos adictivos. Asi, sería de gran interés desarrollar nuevas estrategias de bloqueo de los receptores A2A y CB1 para atenuar e incluso prevenir el desarrollo de la adicción.
Drug addiction is a chronically relapsing disorder that is defined by a compulsion to take the drug intake, a loss of control in limiting intake and a withdrawal-negative affect state when the access to the drug is interrupted. Mesolimbic dopaminergic system has been proposed as a fundamental neurobiological substrate for drug addiction. However, there is evidence for other neurotransmitter systems involved in the consolidation of the addictive process.
The endocannabinoid system, through the activation of CB1 receptor, participates in the addictive properties of different drugs of abuse such as delta9-tetrahydrocannabinol, morphine and nicotine. Nevertheless, few studies have revealed an important implication of CB1 receptor in the reinforcing properties of psychostimulants. By using CB1 knockout mice, we have demonstrated that CB1 receptor participates in the reinforcing efficacy of cocaine. Moreover, this receptor is necessary for the consolidation processes involved in cocaine maintained intravenous self-administration. Therefore, this study reveals an essential role of CB1 receptor in cocaine addictive properties, confirming that the endocannabinoid system is a common substrate of addiction to drugs of abuse.
On the other hand, the purinergic system modulates different neurotransmitter systems in the CNS. Adenosine receptors are closely related to dopaminergic receptors at both cellular and functional levels, suggesting that purinergic system could modulate the reward systems. By using different animal models, we have demonstrated that A2A adenosine receptors are necessary for the development of the addictive properties of drugs of abuse such as opioids, cannabinoids, nicotine and cocaine.
Our studies suggest that both cannabinoid and purinergic systems could represent new and common modulatory systems of addictive processes. Thus, it would be of interest to develop new therapeutic targets blocking CB1 and A2A receptors to attenuate the development of addiction.
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Honjo, Rachel Sayuri. "Detecção da microdeleção 7q11.23 por MLPA® e estudo clínico dos pacientes com síndrome de Williams-Beuren." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/5/5141/tde-13082012-100426/.
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INTRODUÇÃO: A síndrome de Williams-Beuren (SWB) é uma doença genética causada por uma microdeleção na região 7q11.23 e caracterizada por dismorfismos faciais típicos, deficiência intelectual, comportamento hipersociável, cardiopatia congênita, principalmente a estenose aórtica supravalvar (EASV), e outras malformações variáveis. MÉTODOS: Foram avaliados 65 pacientes (40 do sexo masculino, 25 do sexo feminino), com idades entre 2 e 59 anos (mediana = 14 anos), com características clínicas sugestivas de SWB. Todos os pacientes eram filhos de pais normais. A técnica de Multiplex Ligation-dependent Probe Amplification® (MLPA®) foi usada com kit específico com sondas da região da SWB (MRC Holland). As sondas foram hibridadas ao DNA e os fragmentos ligados foram amplificados por PCR e analisados com software específico. RESULTADOS: A deleção de todas as sondas da região 7q11.23 testadas foi detectada por MLPA® em 55/65 pacientes. Um caso de deleção atípica, ou seja, menor que 1,5 Mb, foi observada em um paciente com quadro clínico parcial da síndrome. Os nove pacientes sem deleção tinham um diagnóstico clínico duvidoso da SWB. Dois pacientes tiveram MLPA® positivo para SWB embora apresentassem resultados de FISH negativos. Os achados clínicos dos pacientes com deleção típica foram: fácies típica (98,2%), atraso do desenvolvimento neuropsicomotor (98,2%), comportamento hipersociável (94,5%), hiperacusia (94,5%) e cardiopatia (81,8%). Dentre os pacientes com cardiopatia, 42,2% apresentavam EASV (isolada ou associada a outras anomalias cardíacas), 26,7% apresentavam estenose pulmonar e 31,1% apresentavam outras cardiopatias isoladas ou em associação. Outros achados dos pacientes com deleção foram: anormalidades geniturinárias (85,4%), escoliose (56,4%), baixa estatura (43,6%), hérnias inguinais e/ou umbilicais (36,4%), hipertensão arterial (36,4%, com 20% destes apresentando estenose de artérias renais), estrabismo (34,5%), microcefalia (30,9%), sinostose radioulnar (10,9%), hipotireoidismo (14,5%) e hipotireoidismo subclínico (7,3%). Hipercalcemia foi detectada em um paciente apenas. Outros dois pacientes apresentaram nefrocalcinose e um paciente apresentou hipercalciúria, com níveis de cálcio sérico normais. Três pacientes adolescentes foram a óbito por causas cardiovasculares, incluindo um caso de óbito após transplante cardíaco. CONCLUSÕES: A técnica de MLPA® foi eficaz na detecção da microdeleção na região 7q11.23 possibilitando a confirmação diagnóstica da SWB em 84,6% dos pacientes estudados. Além disso, foi possível detectar uma deleção menor atípica em um paciente com fenótipo parcial e confirmar o diagnóstico em dois pacientes com quadro clínico típico de SWB e resultados de FISH negativos. Portanto, o MLPA® constitui-se um método promissor na investigação diagnóstica da SWB. Por ser uma doença multissistêmica, a SWB exige cuidados multidisciplinares e acompanhamento específico a fim de se prevenir complicaçõesINTRODUCTION: Williams-Beuren syndrome (WBS) is a genetic disorder caused by a microdeletion in 7q11.23 region. It is characterized by typical facial dysmorphisms, mental retardation, hipersociable behavior, congenital heart disease, mainly supravalvular aortic stenosis (SVAS), and other variable congenital malformations. METHODS: 65 patients (40 males, 25 females), aged 2-59 years old (median = 14 years old), with clinical characteristics suggesting WBS, were evaluated. All patients had normal parents. Multiplex Ligation-dependent Probe Amplification® (MLPA®) was performed with a kit with probes in WBS region (MRC Holland). The probes were hybridized to the DNA and the ligated fragments were amplified by PCR and analyzed with specific software. RESULTS: The deletion for all tested probes in the 7q11.23 region was detected by MLPA® in 55/65 patients. One case of atypical deletion, smaller than 1.5 Mb, was observed in one patient with partial clinical picture of the syndrome. The nine patients without the deletion did not have a definitive clinical diagnosis of WBS. Two patients had positive MLPA® results even though they had negative FISH for WBS. The clinical characteristics of the patients with the typical deletion were: typical facies (98.2%), neuropsicomotor delay (98.2%), hypersociable behavior (94.5%), hyperacusis (94.5%) and congenital heart disease (81.8%). Among the patients with cardiac abnormalities, 42.2% had SVAS (isolated or not), 26.7% had pulmonary valve stenosis and 31.1% had other cardiac anomalies (isolated or grouped). Other findings in patients with deletion comprised: genitourinary abnormalities (85.4%), scoliosis (56.4%), short stature (43.6%), inguinal and/or umbilical hernias (36.4%), arterial hypertension (36.4%, with 20% of these presenting renal arteries stenosis), strabismus (34.5%), microcephaly (30.9%), radioulnar synostosis (10.9%), hypothyroidism (14.5%), and subclinical hypothyroidism (7.3%). Hypercalcaemia was detected in only one patient. Two other patients had nephrocalcinosis and one patient had hypercalciuria, with normal serum calcium levels. Three adolescents died due to cardiovascular problems, including one case that died after a cardiac transplantation. CONCLUSIONS: MLPA® was effective to detect the microdeletion in 7q11.23 region confirming the diagnosis of WBS in 84.6% of the patients. It was also possible to detect a small atypical deletion in one patient with partial phenotype and confirm the diagnosis in two patients with typical clinical characteristics of WBS and negative FISH results. Thus, MLPA® is a promising method in the diagnostic investigation of WBS. WBS is a multisystemic disorder and therefore requires multidisciplinary care and specific follow-up in order to prevent complications
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Goodfellow, Molly Jo. "Altered NMDA Receptor Composition and Function Contribute to Deficits in Forebrain-Dependent Learning and Memory in Adult Rats Exposed to Ethanol as Neonates." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1392976475.
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Silva, Carlos Alberto da. "Treinamento aeróbio de alta intensidade melhora a vasodilatação dependente do endotélio em pacientes com síndrome metabólica ou diabetes mellitus tipo 2." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2006. http://hdl.handle.net/10183/8506.
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Introdução: A doença cardiovascular é a principal causa de morbidade e mortalidade em pacientes com síndrome metabólica ou diabetes mellitus tipo 2. Como a disfunção endotelial precede o desenvolvimento da doença cardiovascular, seria desejável identificar e tratar a disfunção endotelial antes que a aterosclerose se desenvolva. Hoje, existe evidência clara para sustentar o efeito protetor do exercício físico regular em pacientes com síndrome metabólica ou diabetes mellitus. O que está menos claro é a relação da intensidade de treinamento e melhora na função endotelial. Objetivo: Avaliar o efeito de um programa de exercício físico, de alta e baixa intensidade, na função endotelial de pacientes com Síndrome Metabólica ou Diabetes Mellitus Tipo 2. Métodos: Foram estudados 31 pacientes com diabetes melittus tipo 2 ou síndrome metabólica, de idade média (±DP) de 58±6 anos, randomizados para treinamento aeróbio de alta intensidade (AI: 75 a 85% freqüência cardíaca máxima, n = 10), treinamento aeróbio de baixa intensidade (BI: 50 a 60% freqüência cardíaca máxima, n = 10) e controle (n = 11). O treinamento foi realizado por 50 minutos, 4 vezes por semana. Antes e após 6 semanas de treinamento, os sujeitos realizaram teste de esforço e estudo da função endotelial, por ultra-som de alta resolução da artéria braquial, avaliados após hiperemia reativa (dependente do endotélio) e após administração de nitrato (independente do endotélio). Resultados: O programa de treinamento aeróbio de alta intensidade resultou em um maior aumento da capacidade funcional, avaliado pelo tempo máximo tolerado no teste de esforço (AI antes 9,39±1,22 minutos e depois 12,12±1,24 minutos; BI antes 8,84s±1,82 minutos e depois 10,41±1,99 minutos; Controle antes 9,36±.1,21minutos e depois 8,96±.1,35minutos; p < 0,05). A diferença no diâmetro do vaso após hiperemia foi significativamente maior para o grupo de alta intensidade (AI antes 4,28±.0,73mm e depois 5,62±.0,95mm; BI antes 4,24±.0,49mm e depois 5,01±.0,56mm; Controle antes 4,31±.0,37mm e depois 4,23±.0,23mm; p < 0,05). Após nitrato, não houve diferença significativa para nenhum dos grupos (AI antes 5,13±.1,17mm e depois 5,20±.1,10mm; BI antes 4,93±.0,88mm e depois 5,07±.0,70mm; Controle antes 4,96±.0,36mm e depois 4,62±.0,36mm; p = 0,565). Conclusões: Quando comparado ao treinamento aeróbio de baixa intensidade e controle, o treinamento aeróbio de alta intensidade melhorou a capacidade funcional e resposta vasodilatadora dependente do endotélio, em pacientes com síndrome metabólica ou diabetes mellitus tipo 2. Estes achados sugerem que o treinamento físico de alta intensidade possa ser considerado como alternativa preventiva nestes pacientes.Introduction: Cardiovascular disease is the major cause of morbidity and mortality in patients with the metabolic syndrome or diabetes mellitus type 2. As the endothelial dysfunction precedes the development of cardiovascular disease, it would be desirable to identify and treat the endothelial dysfunction before the development of atherosclerosis. There is currently clear evidence to support the protective effect of regular physical exercise on patients with metabolic syndrome or diabetes mellitus. What is less clear is the relationship between training intensity and improvement in endothelial function. Objective: Evaluate effect of a physical exercise program, of high and low intensity, on endothelial function of patients with Metabolic Syndrome or Diabetes Mellitus Type 2. Methods: Thirty one patients with Diabetes Mellitus type 2 or metabolic syndrome were studied, with mean age (±SD) of 58±6 years, randomized for high intensity aerobic training (AI: 75-85% of maximum heart rate, n = 10), low intensity aerobic training (BI: 50-60% maximum heart rate, n = 10) and control (n = 11). The training was performed for 50 minutes, four times a week. Before and after 6 weeks of training, subjects performed the exercise testing and had been studied for endothelial function, by high resolution ultrasound of the brachial artery, assessed after reactive hyperemia (endothelium dependent) and after nitrate administration (endothelium independent). Results: The high intensity aerobic training resulted in a higher increase of the functional capacity, assessed by maximum tolerated time on the exercise testing (AI before 9.39±1.22 minutes and after 12.12±1.24 minutes; BI before 8.84s±1.82 minutes and after 10.41±1.99 minutes; Controls before 9.36±.1.21minutes and after 8.96±.1.35minutes; p < 0.05). The diameter difference of the vessel after hyperemia was significantly higher for the high intensity group (AI before 4.28±0.73mm and after 5.62±0.95mm; BI before 4.24±0.49mm and after 5.01±0.56mm; Controls before 4.31±0.37mm and after 4.23±.0.23mm; p < 0.05). After nitrate, there was no significant difference for none of the groups (AI before 5.13±.1.17mm and after 5.20±.1.10mm; BI before 4.93±.0.88mm and after 5.07±.0.70mm; Controls before 4.96±.0.36mm and after 4.62±.0.36mm; p = 0.565). Conclusions: When compared to the low intensity aerobic training and controls, the high intensity aerobic training improved the functional capacity and vasodilator response endothelium-dependent in patients with metabolic syndrome and diabetes mellitus type 2. These findings suggest that physical training of high intensity might be considered as a preventive alternative in those patients.
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Monroe, Diaz Francisco Javier, Del Mar Solania Tello, and Bueno María Fernanda Torres. "Prevalencia y asociación entre la dependencia funcional y síntomas depresivos en el adulto mayor de un centro público de atención residencial geronto-geriátrico de Lima-Perú." Bachelor's thesis, Universidad Peruana de Ciencias Aplicadas (UPC), 2015. http://hdl.handle.net/10757/621622.
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Introducción: Los adultos mayores institucionalizados (AMI), constituyen una población vulnerable porque pierden autonomía al adaptarse a un nuevo ambiente lo cual predispone la aparición de síntomas depresivos y dependencia funcional. El objetivo del estudio es determinar la asociación entre síntomas depresivos y funcionalidad en esta población. Materiales y Métodos: Estudio transversal analítico con la aplicación de instrumentos estandarizados para evaluar síntomas depresivos (Escala de depresión geriátrica de Yesavage) y dependencia funcional para actividades básicas de la vida diaria (Índice de Barthel) y la extracción de datos de historias clínicas en un Centro Geronto-Geriátrico en Lima- Perú durante Febrero- Abril del 2013. Resultados: 153 AMI fueron enrolados con una media de 80,8 ±7,3 años a predominio masculino, solteros, y de bajo nivel educativo. El 47,1% tenía algún grado dependencia funcional y el 62,1% algún síntoma depresivo. El coeficiente de Spearman entre los puntajes de Yesavage y Barthel mostró con una correlación negativa no significativa (-0,14, p=0,08). En el análisis de regresión lineal multivariado las covariables educación secundaria (p<0,01), hipertensión arterial (p<0,01), y dependencia funcional escasa (p=0,01) estuvieron asociadas a un mayor puntaje de sintomatología depresiva. Conclusiones: Existe asociación significativa entre los síntomas depresivos y dependencia funcional. Por ello, la identificación precoz de la dependencia funcional escasa en los AMI debe ser considerada como un indicador evitar la aparición de síntomas depresivos.Introduction: Institutionalized Elderly (IE) constitute a vulnerable population because they lose their autonomy to adapt to a new environment which predisposes the onset of depressive symptoms and functional dependency. The aim of the study is determine the relationship between depressive symptoms and functional dependency in public old age homes. Materials and Methods: Analytical cross- sectional study using standardized scales to evaluate depressive symptoms (Yesavague’s Geriatric Depression Scale) and functional dependency on activities of daily living (Barthel Scale) and extracting data manually from medical records in a Gerontological- Geriatric Center in Lima Peru from February to April, 2013. Results: 153 IE were enrolled in the study with a mean age of 80.8, +/- 7.3 years. They were predominantly men, single and with low educational level, 47.1% had some degree of functional dependency and 62.09% some symptom of depression. The Spearman coefficient between Yesavage and Barthel illustrated non-significant negative correlation (-0.14, p=0.08). In the multivariate linear regression analysis, the covariates secondary education (<0.01), arterial hypertension (p<0.01) and functional dependency (p=0.01) were associated with a higher score of depressive symptoms. Conclusions: There is a significant association between depressive symptoms and functional dependency. Thus, the early identification of low functional dependency in IE should be considered as an early indicator to avoid depressive symptoms.
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Machado, Marcio Carlos. "Estudo da expressão do receptor da vasopressina (AVPR1B), do receptor do hormônio liberador de corticotrofina (CRHR1) e do receptor dos secretagogos de GH (GHSR-1a) em pacientes portadores de síndrome de Cushing ACTH-dependente: correlação clínico-molecular." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/5/5135/tde-31102006-131430/.
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INTRODUÇÃO: O diagnóstico diferencial da síndrome de Cushing (SC) ACTH-dependente é um dos maiores desafios da endocrinologia, devido ao comportamento clínico e laboratorial semelhante de alguns tumores carcinóides com a doença de Cushing (DC). Assim, testes dinâmicos de secreção de ACTH e cortisol têm sido utilizados com o objetivo de identificar respostas que sejam preditivas e específicas no diagnóstico diferencial. O padrão dessas respostas é atribuído à superexpressão de receptores; entretanto, poucos estudos foram realizados para comprovar tal associação. O objetivo deste estudo foi verificar se a secreção de ACTH e cortisol em resposta aos testes do CRH humano (hCRH), da desmopressina, e do peptídeo liberador do GH (GHRP-6) é dependente da magnitude de expressão dos seus respectivos receptores (CRHR1, AVPR1B e GHSR-1a) em amostras de tumores de pacientes portadores da SC ACTH-dependente. CASUÍSTICA E MÉTODOS: Entre 2002 e 2004, foram avaliados 22 pacientes (20 com DC e dois com Secreção Ectópica de ACTH [SEA], carcinóide de pulmão e timo), idade mediana de 32 anos (15-54 anos), sendo 18 do sexo feminino e quatro do sexo masculino, provenientes da Disciplina de Endocrinologia e Metabologia da Faculdade de Medicina da Universidade de São Paulo. Os pacientes foram submetidos aos testes do hCRH (100 µg), desmopressina (10 µg) e GHRP-6 (1 µg/kg) com dosagens de ACTH e cortisol e também de GH no caso do GHRP-6. Vinte e um indivíduos controles, pareados por sexo e idade, foram submetidos ao teste do GHRP-6. Durante o ato operatório, fragmentos de tumor foram coletados para posterior extração do RNA total. O estudo da expressão foi feito por meio de PCR quantitativo em tempo real dos genes CRHR1, AVPR1B e GHSR-1a em relação ao GAPDH. Fragmentos de tecidos normais (hipófise, pulmão e timo) procedentes de necropsias foram utilizados como controles. RESULTADOS: Observamos maior expressão de GHSR-1a nos pacientes responsivos ao GHRP-6, tanto naqueles com DC quanto no paciente com carcinóide pulmonar. Não houve maior expressão dos receptores CRHR1 e AVPR1B nos pacientes com DC responsivos aos respectivos testes, observando-se, no entanto, uma forte associação entre respostas in vivo e a expressão desses receptores nos pacientes com SEA. As concentrações de ACTH e cortisol induzidas pela administração de GHRP-6 foram mais elevadas nos pacientes com DC quando comparados aos controles, havendo, no entanto, superposição entre as respostas. Observamos também elevação dos níveis séricos de GH nos indivíduos controles e, em menor intensidade, nos pacientes com DC. CONCLUSÕES: Houve maior expressão do receptor GHSR-1a em pacientes com SC ACTH-dependente responsivos ao GHRP-6, estabelecendo-se uma relação direta entre a expressão do receptor e a resposta in vivo ao secretagogo, tanto em pacientes com DC quanto nos portadores de SEA. Uma associação entre a expressão dos receptores CRHR1 e AVPR1B com a resposta in vivo aos respectivos secretagogos foi observada nos pacientes com SEA e não nos pacientes com DC. Tendo em vista a resposta ao GHRP-6 em paciente com SEA, limita-se o uso desse peptídeo no diagnóstico diferencial da SC ACTH-dependente.INTRODUCTION: The differential diagnosis of ACTH-dependent Cushing\'s syndrome (CS) is one of the major challenges in endocrinology, especially in view of the similar clinical and laboratorial behavior between some carcinoid tumors and Cushing\'s disease (CD). Hence, dynamic tests of ACTH and cortisol release have been carried out with the aim to identify predictive and specific responses for this differential diagnosis. The pattern of the responses has been attributed to receptors overexpression, yet few studies have been undertaken to confirm such association. The aim of the present study was to verify whether ACTH and cortisol release in response to human CRH (hCRH), desmopressin, and GH releasing peptide (GHRP-6) depends on the magnitude of expression of their respective receptors (CRHR1, AVPR1B e GHSR-1a) in samples of tumors from patients with ACTH-dependent CS. PATIENTS AND METHODS: Twenty two patients (20 with CD and 2 with Ectopic ACTH Syndrome [EAS], lung and thymus carcinoid tumors) from the Division of Endocrinology and Metabolism of University of Sao Paulo School of Medicine, median age of 32 years (15-54 years), being 18 females and 4 males, were evaluated between 2002 and 2004. The patients were submitted to dynamic tests with hCRH (100 µg), desmopressin (10 µg) and GHRP-6 (1 µg/kg), with measurement of ACTH and cortisol levels, and also of GH in the case of GHRP-6 stimulation. Twenty one age and sex-matched controls were submitted to the GHRP-6 test. During surgery, tumor fragments were collected and subsequently processed for total mRNA extraction. Gene expression of CRHR1, AVPR1B and GHSR-1a relative to GAPDH was quantitated by real-time qPCR. Tissue samples of normal pituitary, lung and thymus from necropsy were used as controls. RESULTS: Greater expression of GHSR-1a was observed in patients responsive to the GHRP-6 test, both in those with CD and in the one with pulmonary carcinoid tumor. No enhanced expression of receptors CRHR1 and AVPR1B was found in CD patients responsive to the respective dynamic tests, yet there was a strong association between the in vivo responses and the expression of those receptors in the two patients with EAS. GHRP-6 -induced ACTH and cortisol release was more marked in patients with CD as compared with control individuals, but there was overlap of the responses. GH stimulation was observed in control individuals and, to a lesser extent, in patients with CD. CONCLUSIONS: There was greater expression of GHSR-1a in patients with ACTH-dependent CS who responded to GHRP-6, establishing a direct association between receptor gene expression and the in vivo response to the secretagogue in both CD patients and those with EAS. An association between expression of CRHR1 and AVPR1B and the in vivo response to the respective secretagogues was found in patients with EAS but not in those with CD. In view of the response to GHRP-6 in a patient with EAS, we considered the use of this peptide in the differential diagnosis of ACTH-dependent CS of limited value.