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BARSOTTI, SIMONE. "Effects of 25-OH vitamin D supplementation on mesenchymal stromal cells in an animal model of Systemic Lupus Erythematosus (SLE)." Doctoral thesis, Università di Siena, 2019. http://hdl.handle.net/11365/1073480.
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In systemic lupus erythematous (SLE), mesenchymal stromal cells (MSCs) are defective and may present early signs of senescence. In a previous study we demonstrated as the treatment with hydroxychloroquine may influence the clonogenic potential of MSCs in a SLE animal model.
Vitamin D may influence several aspects of the innate and adaptative immune response and low serum levels of vitamin D are common in SLE patients and were correlated to higher disease activity and severity. The aim of this study is to identify the effect of 25-OH vitamin D, on MSCs characteristics in New Zealand Black/White F1 mice (NZ), that develop a disease very similar to human SLE.
We are treating 20 NZ with a diet enriched with 25-OH-vitamin-D 10.000 UI/Kg, mice starting from 8 weeks of age. We divided the mice in 4 experimental groups (5 mice each), the first group will be sacrificed before the start of the treatment (8 week of age) and the other groups will be sacrificed at 16, 26 and 36 weeks of age. Fifteen mice were enrolled as controls and they will be sacrificed at 16, 26 and 36 weeks of age.
We are evaluating disease activity parameters including total urinary protein parameters, anti-dsDNA autoantibody, 25OH vitamin D ant parathormone levels.
MSC phenotype is confirmed by cytofluorimetry (expression of Sca-1 and CD-106, negativity for CD45) and we also evaluate differentiation capability in adipogenic and osteoblast lineage. Clonogenic potential is evaluated in at the seeding (P0) and in the following 2 passages (P1 and P2 respectively one and two weeks after the seeding) with the Colony Forming Unit (CFU) assay.
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Reynolds, John. "Vitamin D and endothelial function and repair in Systemic Lupus Erythematosus." Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/vitamin-d-and-endothelial-function-and-repair-in-systemic-lupus-erythematosus(227cdd5f-8dbb-4d8c-8a27-5a0e4778c2aa).html.
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Introduction: Patients with Systemic Lupus Erythematosus (SLE) have increased cardiovascular risk, endothelial dysfunction, and abnormal endothelial repair mechanisms. Vitamin D deficiency is common in SLE and has been associated with active disease and increased vascular stiffness. Myeloid angiogenic cells (MACs) repair damaged vessels by secretion of angiogenic factors and may be a target for vitamin D. Vitamin D may therefore be a novel therapy to improve cardiovascular risk in SLE patients. This study aimed to determine the effects of vitamin D on endothelial function and repair in patients with SLE. Methods: The effects of the active form of vitamin D (1,25(OH)2D3) were studied on MACs from vitamin D deficient SLE patients ex vivo. Functional models were developed to study MAC migration, adhesion and interaction with endothelial cells. Additional experiments used a model of healthy MACs treated with IFN-alpha. An observational study of clinically stable vitamin D deficient SLE patients being treated with high dose vitamin D over 3 months was used to investigate the effects of vitamin D on endothelial function as measured by flow-mediated dilatation (FMD). Results: MACs expressed markers consistent with an M2 macrophage phenotype and they enhanced endothelial network formation in vitro. SLE patients had an increased number of MACs; however, these were dysfunctional compared to healthy controls. Vitamin D increased the number, changed the phenotype and improved the functional capacity of SLE MACs ex vivo. In addition, the angiogenic capacity of SLE MACs was restored toward that of healthy controls via a reduction in the anti-angiogenic cytokine IP10. Vitamin D-treated MACs were also more able to protect endothelial cells against TNF-mediated down-regulation of endothelial nitric oxide synthase (eNOS). In SLE patients treated with vitamin D, there was a strong correlation between the change in serum 25(OH)D and the change in the ratio of endothelium-dependent:independent dilatation (r=-0.650, p=0.006). This was accompanied by an increase in the number of MACs at 3 months (p=0.015). These observations were independent of changes in serum PTH, calcium or lupus disease activity. Conclusions: Vitamin D can target MACs and therefore offers a novel approach to improve endothelial repair in patients with SLE. In addition, vitamin D treatment in lupus patients resulted in an improvement in endothelial function, related to the change in vitamin D status. These results suggest that vitamin D could improve surrogate markers of cardiovascular disease and thus reduce cardiovascular risk in this patient group.
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Zhang, Xueming. "Vitamin D receptor deficiency and postnatal tooth formation." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2007. http://www.mhsl.uab.edu/dt/2007m/zhang.pdf.
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Omoike, Gracious. "Har D-vitamintillskott effekt vid behandling av Systemisk Lupus Erythematosus? : En litteraturstudie." Thesis, Linnéuniversitetet, Institutionen för kemi och biomedicin (KOB), 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-85942.
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Introduktion: Systemisk Lupus Erythematosus är en prototypisk autoimmun sjukdom som gör att immunförsvarets antikroppar angriper kroppens egna vävnader, vilket leder till kronisk inflammation i kroppens organsystem. Idag finns ingen verksam behandling för Systemisk Lupus Erythematosus. Syftet med denna studie var att undersöka hur Dvitamintillskott påverkar Systemisk Lupus Erythematosus. Metod: Artiklarna hittades i databasen ”Pubmed” med sökningen ”Systemic Lupus Erythematosus and vitamin D supplementation”. Bland sökresultaten fanns sex relevanta artiklar som hade undersökt effekten av D-vitamintillskott på SLE. Resultat: Mer än hälften av patienterna i samtliga studier nådde serum 25(OH) D-nivåer som ansågs vara tillräckliga. D-vitamintillskottet minskade Th1/Th17-cellerna men ökade också Treg-celler och Th2-celler. Tre studier visade sig ha en signifikant minskning i sjukdomsaktivitet och anti-dsDNA antikroppar. Komplement C3 minskade i studie 2. Diskussion: Fem av studierna tyder på att oral administrering av D-vitamin tillskott har gett positiv inverkan på SLE. Två av de granskade studierna rapporterades inge positiv klinisk effekt hos deltagarna. Slutsats: D-vitamintillskott dämpar immunsystemet genom att öka Treg-celler och Th-2-celler men även minska Th1/Th17-celler och B-celler samt produktionen av autoantikroppar och anti-dsDNA-antikroppar. Effekten av D-vitamintillskott på komplement C3 och C4 är oklar. Det krävs dock fler studier med fler deltagarantal för att dra en slutsats om Dvitamintillskott kan användas som behandling för SLE.Background: Systemic Lupus Erythematosus is a prototypical autoimmune disease in which antibodies attack healthy tissues in the body, causing inflammation in several organs. Aim: The aim of this literature study was to investigate the effect of Vitamin Dsupplementation on SLE. Method: The articles were searched in the database called ”Pubmed” using the search terms ”Systemic Lupus Erythematosus and Vitamin D supplementation”. Six of the articles which examined the effects of D-vitamin supplementation on SLE were relevant for this study. Result: More than half of the patients in all six studies reached sufficient serum 25(OH)D. Vitamin D-supplement reduced Th1/Th17-cells but increased Tregs-cells and Th2-cells. 3 studies showed a decrease in disease-activity and anti-dsDNA. C3 decreased in study 2. Discussion: Five studies indicated that the oral administration of vitamin-D supplementation had a positive effect on SLE. Two of the examined studies did not observe any clinical effect of the vitamin-D supplement. Conclusion: Vitamin-D supplement suppresses the immunesystem by increasing Treg cells and Th-2 cells but also reducing Th1/Th17-cells and B-cells as well as the production of autoantibodies and anti-dsDNA antibodies. The effect of vitamin D-supplement is unclear. More studies with more participants are required to determine if vitamin-D supplement can be used as a treatment for SLE.
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Naja, Roy Pascal. "The role of Vitamin D metabolic enzymes in bone development and repair /." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=115860.
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The CYP27B1 enzyme that synthesizes 1alpha,25-(OH) 2D, is expressed in chondrocytes, suggesting that local production of 1alpha,25-(OH)2D could play an autocrine or paracrine role in the differentiation of these cells. To test this hypothesis, we have engineered mutant mice that do not express the Cyp27b1 gene in chondrocytes. This led to increased width of the hypertrophic zone of the growth plate at E15.5, increased bone mass in neonatal long bones, and increased expression of the chondrocytic differentiation markers Indian Hedgehog and PTH/PTHrP receptor. VEGF mRNA levels were decreased, accompanied by decreased PECAM-1 immunostaining, suggesting a delay in vascularization. We have also engineered mice overexpressing a Cyp27b1 transgene in chondrocytes. The transgenic mice showed a partial mirror image phenotype compared to the tissue-specific inactivation model. These results support an autocrine/paracrine role of 1alpha,25-(OH) 2D in endochondral ossification and chondrocyte development in vivo.The CYP24A1 enzyme is involved in the catabolic breakdown of 1alpha,25-(OH)2D but also synthesizes the 24R,25-(OH) 2D metabolite. Studies in chicken suggest a role for 24R,25-(OH) 2D in fracture repair. We induced stabilized transverse mid-diaphysial fractures of the tibia in four-month-old wild-type and Cyp24a1-deficient mice. Examination of the callus sections showed delayed hard callus formation in the homozygous mutant animals compared to wild-type littermates. RT-qPCR showed perturbed levels of type X collagen transcripts in mutant mice at 14 and 21 days post-fracture, reflecting the delayed healing. Rescue of the impaired healing by subcutaneous injection of 24R,25-(OH)2D3 normalized the histological appearance of the callus, static histomorphometric index and type X collagen mRNA expression, while 1alpha,25-(OH)2D 3 did not. These results show that Cyp24a1 deficiency delays fracture repair and strongly suggest that vitamin D metabolites hydroxylated at position 24, such as 24R,25-(OH)2D, play an important role in the mechanisms leading to normal fracture healing.
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Weigert, Olivia [Verfasser]. "CD4+Foxp3+ regulatory T cells prolong drug-induced disease remission in (NZBxNZW) F1 lupus mice / Olivia Weigert." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2014. http://d-nb.info/1062949021/34.
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Schneider, Laiana. "Níveis de vitamina d e perfil de citocinas em pacientes com lúpus eritematoso sistêmico." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2014. http://hdl.handle.net/10183/108322.
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OBJETIVO: Avaliar a expressão dos perfis de citocinas Th1, Th2 e Th17 em pacientes com LES e verificar possíveis associações com os níveis séricos de vitamina D. MÉTODOS: Estudo transversal com inclusão de 172 pacientes acompanhados no ambulatório de reumatologia do Hospital de Clínicas de Porto Alegre. Os níveis de vitamina D foram medidos por quimiluminescência. Níveis séricos <20 ng/ml foram considerados como deficiência de vitamina D e níveis ≥20 ng/ml foram considerados normais. As citocinas foram medidas no soro após o descongelamento das amostras em uma única ocasião, usando Kit CBA (cytometric beads array) Th1/Th2/Th17. RESULTADOS: Cento e sessenta e um (94%) pacientes eram mulheres e 128 (74,4%) foram classificados como euro-descendentes. A idade média foi de 40,5±13,8 anos e a idade média no momento do diagnóstico foi de 31,5±13,4 anos. Na entrada do estudo, os pacientes tiveram mediana (intervalo interquartil) de atividade da doença (SLEDAI- systemic lupus erythematosus disease activity index) de 2 (1-4) e cronicidade (SLICC damage index- systemic lupus international collaborating clinics) de 0 (0-1). O nível médio de vitamina D foi de 25,4±11,04 ng/ml. Cinquenta e nove (34,3%) pacientes apresentavam deficiência de vitamina D e 113 (65,7%) tinham níveis considerados normais. Nenhuma associação e correlação estatisticamente significativa foram encontradas. Os níveis de INF-α e SLEDAI mostraram uma correlação positiva fraca (rs=0,22, p=0,04). Análise de regressão linear foi realizada para controlar possíveis fatores de confusão. CONCLUSÃO: A deficiência de vitamina D é prevalente em pacientes com LES, entretanto, não foram encontradas correlações e associações entre níveis de vitamina D e perfil de citocinas. Confirmamos a correlação existente entre o IFN-α e SLEDAI, conforme a literatura. Efeito in vitro de vitamina D no perfil de citocinas não foi reproduzido no presente estudo. Estudos longitudinais podem ajudar a esclarecer a influência da vitamina D na fisiopatogenia do LES.OBJECTIVES: To evaluate the expression of Th1, Th2 and Th17 cytokine profiles in SLE patients and verify possible associations with serum vitamin D levels. METHODS: Cross-sectional study with 172 SLE patients, followed at the outpatient clinic of rheumatology at Hospital de Clínicas de Porto Alegre were included. The levels of vitamin D were measured by chemiluminescence. Serum levels <20 ng/ml were considered as vitamin D deficiency. Normal vitamin D levels were defined as ≥20ng/ml. Cytokines were measured in serum after thawing the samples on a single occasion, using Kit CBA (cytometric beads array) Th1/Th2/Th17. RESULTS: One hundred sixty one (94%) patients were women and 128 (74.4%) were classified as European derived. The mean age of patients was 40.5±13.8 years and the mean age at diagnosis was 31.5±13.4 years. At the time of study entry, patients had median (IQR) of active disease (SLEDAI- systemic lupus erythematosus disease activity index) of 2 (1-4) and chronicity (SLICC damage index- systemic lupus international collaborating clinics) of 0 (0-1). Mean vitamin D levels were 25.4±11.04 ng/ml. Fifty-nine (34.3%) patients had vitamin D deficiency and 113 (65.7%) had normal levels. No association and statistically significant correlations was found. The levels of INF-α and SLEDAI showed a weak positive correlation (rs=0.22, p=0.04). Linear regression analysis was performed to control for possible confounding factors. CONCLUSION:Vitamin D deficiency is prevalent in patients with SLE, however, no statistically significant correlations and associations between vitamin D levels and cytokine profile were found. We confirm the correlation between IFN-α and SLEDAI, according to the literature. In vitro effect of vitamin D on the cytokine profile was not reproduced in this study. Longitudinal studies may help clarify the influence of vitamin D in the pathogenesis of SLE.
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Salman-Monte, Tarek Carlos. "Inflamación, insuficiencia de vitamina D y osteoporosis en el lupus eritematoso sistémico." Doctoral thesis, Universitat Autònoma de Barcelona, 2016. http://hdl.handle.net/10803/395204.
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El lupus eritematoso sistémico (LES) es una enfermedad sistémica autoinmune con una gran variedad de expresión clínica. Su manejo no es siempre fácil. A pesar de los avances científico-tecnológicos y la mejora en años de supervivencia, puede llegar a ser una enfermedad grave y sigue habiendo mecanismos que hacen que aparezca un daño irreversible en estos pacientes. El desarrollo de osteoporosis y la aparición de fracturas secundarias es uno de estos componentes que provocan daño irreversible en los pacientes con LES. Los estados de insuficiencia de vitamina D pueden estar implicados tanto en la baja DMO como en la aparición de fracturas. El grado exacto de cuánto influye la actividad inflamatoria de la enfermedad, per se, sobre los niveles plasmáticos de vitamina D y sobre la densidad mineral ósea, está todavía por dilucidar. La insuficiencia de vitamina D y la densidad mineral ósea reducida son dos comorbilidades que pueden ser prevenidas facilitando la mejoría de los pacientes afectos en una entidad de complejo manejo en la que los factores implicados en la calidad de vida de los pacientes merecen un cuidado especial.
Por todo lo mencionado previamente, se realizaron dos trabajos de investigación, el primero que evaluaba la insuficiencia de vitamina D en el LES y sus factores asociados y el segundo que evaluaba la baja DMO en el LES y sus factores asociados. Uno de los dos trabajos está publicado en una revista de Impacto Científico ("Prevalence and predictors of low bone density and fragility fractures in women with systemic lupus erythematosus in a Mediterranean region". Revista científica: Rheumatology International. 2015;35:509-15) y el otro ha sido enviado a una revista recientemente. Con ambos trabajos se ha confirmado que las alteraciones del metabolismo óseo en el LES tienen una alta prevalencia y aunque no se han podido relacionar ambas patologías con la actividad de la enfermedad lúpica (objetivo principal de la Tesis Doctoral), se han obtenido resultados científicamente relevantes como:
La insuficiencia global y la deficiencia de vitamina D se manifestaron respectivamente en un 46% y en un 22,5% en los pacientes con LES de una área concreta del noreste peninsular, de Cataluña, de la conurbación de Barcelona. Se halló insuficiencia de vitamina D en el 50% de las pacientes suplementadas versus el 60% de las pacientes no suplementadas. Entre las pacientes con LES no suplementadas de una área concreta del noreste peninsular, de Cataluña, de la conurbación de Barcelona, se encontró que las pacientes con insuficiencia de vitamina D mostraron más fatiga (p = 0,009) y recibieron más corticosteroides orales (p = 0,02) que aquellas con niveles normales. En el global de las pacientes, las pacientes con insuficiencia de vitamina D (suplementados y no suplementados) recibieron más corticosteroides orales que aquellas sin insuficiencia (p = 0,008).
La prevalencia de osteoporsis llegó hasta el 6% y de fractura al 4.4% en alguna de las regiones estudiadas de las pacientes con LES de una área concreta del noreste peninsular, de Cataluña, de la conurbación de Barcelona, la prevalencia de osteopenia llegó hasta el 40% en alguna de las regiones estudiadas de las pacientes, en concreto la prevalencia de osteopenia por localizaciones fue: cuello femoral 40.3%, columna lumbar 36.3% y cadera total 28.3%. Se halló relación significativa entre baja DMO y bajo IMC, datos ya evidenciados en pacientes con LES y en la población general. En ambos de los proyectos de investigación mostrados en esta Tesis Doctoral la región más afectada con baja DMO fue el cuello femoral, lo que confirma la necesidad de evaluar la DMO de esta región en los pacientes con LES.Management of sistemic lupus erythematosus (SLE), a sistemic autoimmune disease with a wide range of clinical expression, is often complicated. Despite recent scientific and technological advances and improved patient survival, SLE is still a dangerous disease that can cause irreversible damage to patients. Osteoporsis and secondary bone fractures are one of the major causes of irreparable injury in patients with SLE and vitamin D insufficiency may play a vital role in reduced DMO and the appearance of fractures. The exact degree to which inflammatory activity per se, over vitamin D plasma levels and DMO, contributes to fractures remains an open question. Preventing these two comorbilities, insufficuent vitamin D levels and reduced bone mimneral density, facilitates clinical improvement in patients with SLE, a condition in which preservation of all the factors implicated in quality of life is of the utmost importance. Two research projects were undertaken to address the issue described above. One evaluated vitamin D insufficiency in SLE and its associated factors and the second did the same for low DMO. The former study has been published in a peer reviewed journal ("Prevalence and predictors of low bone density and fragility fractures in Women with systemic lupus erythematosus in a Mediterranean region" Scientific Journal: Rheumatology International 2015; 35:509-15 ) and the second has recently been submitted. Both studies confirm the high prevalence of bone metabolism disorders in SLE. Despite not finding a significant association between these two disorders and SLE disease activity (the primary objective of this Thesis), we obtained various scientifically relevant results: Vitamin D insufficiency was exhibited by 46% of the patients and vitamin D deficiency was exhibited by 22.5% of the patients. We found patients with (n=62) and without (n=40) vitamin D supplementation. In non-supplemented female SLE patients Vitamin D insufficiency was exhibited by 60%. In supplemented female SLE patients Vitamin D insufficiency was exhibited by 50%. When comparing non-supplemented female SLE patients according to vitamin D plasma levels it was found that patients with Vitamin D insufficiency showed statistically more fatigue (p=0.009) and received more corticosteroids (p=0.02) than those with plasma level of Vitamin D >30. Osteoporosis prevalence reached 6% and fractures 4.4% in some of the skeletal regions studied. Prevalence of osteopenia reached up to 40% in certain regions and was as follows: femoral neck 40.3%, lumbar spine 36.3% and total hip 28.3%. We found a significant relationship between low DMO and low IMC as previously described in patients with SLE and the general population. The femoral neck was the most afected region with low DMO in both studies included in this Thesis confirming the importance of evaluating DMO in this region in patients with SLE.
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Monticielo, Odirlei André. "Estudo dos polimorfismos BsmI e FokI do receptor da vitamina D e avaliação dos níveis séricos da 25-hidroxivitamina D em pacientes com lúpus eritematoso sistêmico." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2011. http://hdl.handle.net/10183/28358.
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Introdução: A vitamina D tem ações pleiotrópicas em muitas doenças crônicas. A expressão do receptor da vitamina D (VDR - vitamin D receptor) em diversas células do sistema imune reforça a possível influência da vitamina D nas doenças autoimunes. Polimorfismos genéticos localizados no gene VDR podem determinar alterações nos mecanismos de ação da vitamina D, porém com resultados ainda pouco conhecidos. O polimorfismo BsmI do gene VDR foi associado com lúpus eritematoso sistêmico (LES) em pacientes asiáticos. Estudos com pacientes lúpicos no Brasil ainda não foram realizados. Objetivos: Investigar a possibilidade dos polimorfismos BsmI e FokI do gene VDR aumentarem o risco para o desenvolvimento do LES e avaliar a possível associação destes polimorfismos com manifestações clínicas e laboratoriais da doença. Determinar os níveis séricos da 25-hidroxivitamina D [25(OH)D)] nos pacientes e investigar a possível associação das suas concentrações com os polimorfismos estudados e expressões clínicas e laboratoriais do LES. Materiais e métodos: Estudo caso-controle envolvendo 195 pacientes com LES e 201 controles saudáveis da mesma área geográfica. Foram pesquisados os polimorfismos BsmI e FokI do gene VDR. Os níveis séricos da 25(OH)D foram dosados nos casos. A genotipagem foi realizada por Restriction Fragment Length Polymorphism-Polimerase Chain Reaction (RFLP-PCR), usando primers e enzimas de restrição específicas para cada polimorfismo. A dosagem da 25(OH)D foi realizada por quimioluminescência. Os dados clínicos e laboratoriais foram coletados dos prontuários. Resultados: Não houve diferença estatisticamente significativa nas frequências genotípicas e alélicas dos polimorfismos BsmI e FokI entre casos e controles eurodescendentes. Não houve associação entre as manifestações clínicas e laboratoriais do LES e os polimorfismos estudados. Os níveis séricos médios da 25(OH)D foram de 25,51±11,43 ng/ml nos pacientes com LES. Quando os pacientes foram classificados pelo estado de vitamina D, a seguinte distribuição foi observada: 55 (30,4%) normais (≥30 ng/ml), 63 (34,8%) insuficientes (20-30 ng/ml), 52 (28,7%) deficientes (<20 ng/ml) e 11 (6,1%) com níveis criticamente baixos (<10 ng/ml). Cinquenta e seis por cento dos pacientes com deficiência estavam usando pelo menos 800 UI de vitamina D por dia. Baseada na distribuição genotípica, a concentração da 25(OH)D foi significativamente maior nos pacientes com genótipo f/f, quando comparados com os pacientes com genótipo F/F (31,614,1 ng/ml versus 23,09,2 ng/ml, p=0,004). Níveis de vitamina D não foram associados com aspectos clínicos e laboratoriais do LES. Conclusões: Os polimorfismos BsmI e FokI não apresentaram associação com LES nos nossos pacientes eurodescendentes estudados. O polimorfimo FokI mostrou influência significativa nos níveis da 25(OH)D, o que reforça o papel deste polimorfismo na atividade funcional do VDR. Este achado poderia ser considerado em futuros estudos clínicos e experimentais envolvendo dosagem da vitamina D. A concentração da 25(OH)D necessária para manter o bom funcionamento do sistema musculoesquelético, cardiovascular e imunológico deveria ser individualizada para cada paciente e novas orientações sobre a suplementação de vitamina D poderiam ter que levar em consideração a ancestralidade genética. Assim, estudos adicionais são necessários para estabelecer definições dos níveis ideais de vitamina D geneticamente especificados.Introduction: Vitamin D has pleiotropic actions on many chronic diseases. The expression of the VDR (vitamin D receptor) in various cells of the immune system strengthens the possible influence of vitamin D on autoimmune diseases. Genetic polymorphisms located in VDR gene may determine changes in the mechanisms of action of vitamin D, but with results still unknown. The BsmI VDR polymorphism was associated with systemic lupus erythematosus (SLE) in Asian patients. Studies with SLE patients in Brazil have not been conducted. Objectives: To investigate the possibility of BsmI and FokI polymorphisms of VDR gene causing increased risk for development of SLE and to evaluate the possible association of these polymorphisms with clinical and laboratory manifestations of the disease. To determine serum levels of 25-hydroxyvitamin D [25(OH)D)] in patients and to investigate the possible association of their concentrations with the studied polymorphisms and clinical and laboratory expressions of SLE. Materials and methods: Case-control study involving 195 SLE patients and 201 healthy controls from the same geographical area. The BsmI and FokI polymorphisms of VDR gene were studied. Serum 25(OH)D levels were measured in the cases. Genotyping was performed by Restriction Fragment Length Polymorphism-Polymerase Chain Reaction (RFLP-PCR), using primers and restriction enzymes specific for each polymorphism. The measurement of 25(OH)D was performed by chemiluminescence. The clinical and laboratory data were collected from medical records. Results: There was no statistically significant difference in genotypic and allelic frequencies of BsmI and FokI polymorphisms among European-derived cases and controls. There was no association between clinical and laboratory features in SLE patients and the studied polymorphisms. The mean serum levels of 25(OH)D were 25.51±11.43 ng/ml in SLE patients. When patients were classified according to vitamin D status, the following distribution was observed: 55 (30.4%) had normal (≥30 ng/ml), 63 (34.8%) insufficient (20-30 ng/ml), 52 (28.7%) deficient (<20 ng/ml) and 11 (6,1%) critically low serum levels (<10 ng/ml). Fifty six percent of patients with deficiency received at least 800 IU of vitamin D per day. Based on genotype distribution, 25(OH)D levels were significantly higher in patients carrying the f/f genotype, when compared to patients carrying the F/F genotype (31.614.1 ng/ml versus 23.09.2 ng/ml, p=0.004). Vitamin D levels were not associated with clinical and laboratory features of SLE. Conclusions: The BsmI and FokI polymorphisms did not present association with SLE in our European-derived studied patients. The FokI polymorphism showed significant influence on 25(OH)D levels, reinforcing its role in functional activity of VDR. This finding may be considered in future clinical and experimental studies involving vitamin D measurements. Serum concentrations of 25(OH)D required to maintain optimal musculoskeletal, cardiovascular and immune health should be individualized for each patient and new guidelines about vitamin D supplementation may have to take into consideration the individual genetic background. Genetic-specific definitions of ideal levels of vitamin D in SLE should therefore be established in future studies.
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Wong, Kevin L. "Caveolae and Caveolin-1 are important for Vitamin D signalling." Thesis, Georgia Institute of Technology, 2010. http://hdl.handle.net/1853/37086.
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The most active form of Vitamin D, 1alpha,25(OH)2D3, modulates cells via receptor mediated mechanisms. While studies have elucidated the pathway via the classical nuclear Vitamin D Receptor (VDR), little is known about the membrane-associated Vitamin D Receptor (ERp60). Caveolae and its characteristic protein Caveolin-1 have been involved in many signaling pathways due to its specific structure and physical configuration. Other studies have shown that many components of the Vitamin D pathway have been found in caveolae. This study hypothesizes that caveolae and Caveolin-1 are important for the effects of 1,25 Vitamin D signaling via ERp60. Research up to date have shown that in rat and mouse growth zone chondrocytes, cells deprived of intact caveolae either through disruption through beta-Cyclodextrin or genetic knockout do not exhibit the characteristic responses to Vitamin D through ERp60 when compared to chondrocytes with functional caveolae. Studies using immunofluorescence co-localization and caveolae fractionation have shown that ERp60 is localized in the caveolae domains. Cellular fractionation was also performed to examine the localization of the ERp60 receptor in lipid rafts and caveolae. Histology and transmission electron microscopy were also used to examine the physiological importance of caveolae and Caveolin-1 in growth plate morphology and cellular characteristics.
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s, barsotti. "Effects of 25-OH vitamin D supplementation on mesenchymal stromal cells in an animal model of Systemic Lupus Erythematosus (SLE)." Doctoral thesis, Università di Siena, 2019. http://hdl.handle.net/11365/1094430.
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Background. 25OH Vitamin D (25-OH-D3) is a fat-soluble steroid-derived molecule involved in
the calcium homeostasis. Low levels of 25-OH-D3 are commonly found in patients with
systemic lupus erythematosus (SLE) and have been correlated to higher disease activity and
severity. Several recent studies have demonstrated that high dose Vitamin D may influence
several aspects of the innate and adaptative immune response and some authors hypothesized
that high dose 25-OH-D3 may have a role in the treatment of SLE. Despite these observations,
the immunomodulatory effect of high dose 25-OH-D3 in vivo still needs to be demonstrated.
Purpose: The aim of our study was to identify the effect of 25-OH-D3 on proteinuria, survival
and renal biopsy in New Zealand Black/White F1 mice (NZ), that develop a disease very similar
to human SLE nephritis.
Methods. We administered to 20 NZ mice a diet enriched with high dose 25-OH-D3 10.000
UI/Kg starting from 8 weeks of age. Mice were divided in 7 experimental groups (5 mice each).
The first group was sacrificed before the start of the treatment (8 week of age), three groups
were treated (treated mice – TM) with 25-OH-D3 and sacrificed at 16, 26 and 36 weeks of age.
Other three groups were enrolled as controls and sacrificed at 16, 26 and 36 weeks of age
respectively (untreated mice – UM). The parameters collected included: total urinary protein and
kidney histology for the evaluation of lupus nephritis (LN): glomerulonephritis, interstitial
nephritis and vascular lesions according to a 5 points scale to obtain a total score (ranging from
0 to 12). Additionally the study of mesenchymal stromal cells proliferation has been studied.
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Mumtaz, Imtiaz M. [Verfasser]. "Effects of immunosuppressive drugs and CD4+ T-cell depletion on plasma cell survival in lupus prone (NZB/W) mice / Imtiaz M. Mumtaz." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2009. http://d-nb.info/1023710315/34.
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Breslin, Leanne Catherine. "An investigation of vitamin D status in systemic lupus erythematosus - its relationship with disease activity, bone mineral density and quality of life." Thesis, Ulster University, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.587481.
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Vitamin D has the potential to modulate the immune system resulting in an inflammatory response which could lead to improved clinical outcomes for individuals diagnosed with systemic lupus erythematosus (SLE). The overall aim of this research was to investigate vitamin D status in SLE patients residing in Northern Ireland, to determine whether there was a relationship with disease activity, bone mineral density (BMD) and quality of life (QoL). To achieve this we undertook a pilot study in SLE patients (n=19) and age-and-sex matched control participants (n= 19), to investigate the vitamin D status of SLE patients. This was followed by a larger observational study to examine vitamin D status in SLE patients during winter months (November-March) and again in the summer months (June-July). A total of 52 SLE patients were recruited, of which, 50 completed the study. Serum 25-hydroxyvitamin D (25(OH)D) was assessed by liquid chromatography mass spectrometry and disease activity and damage were scored using Systemic Lupus Activity Measure (SLAM), British Isles Lupus Assessment Group (BILAG), Safety of Estrogen in Lupus Erythematosus National Assessment Trial Systemic Lupus Erythematosus Disease Activity Index (SELENA SLEDAI) and Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ ACR). BMD was measured by Dual Energy X-ray absorptiometry, fatigue was assessed by the fatigue severity score and percieved QoL was assessed using the 36-item short form health survey. BMD was measured during the winter assessment of the observational study and at both time points, associations between vitamin D, disease activity, fatigue and QoL were examined by means of correlation and regression analysis. Vitamin D inadequacy was prevalent in this cohort of SLE patients residing in Northern Ireland, although no significant difference in vitamin D status was observed between winter and summer (P=0.439). Some 98% of SLE patients presented with serum 25(OH)D concentration < 75 nmol/L at both timepoints and vitamin D concentration was inversely associated with BILAG during winter. Fatigue was present in 98% of the cohort during both time points and patients with fatigue had significantly lower vitamin D status compared to those without fatigue (P=0.030). Furthermore, BILAG was a useful predictor of future fatigue in this cohort. Osteoporosis and osteopenia were identified in 8% and 45% of the SLE patients respectively, none of whom were prescribed calcium/vitamin D supplements. The social functioning (P=0.023) and mental component scores (P=0.049) of the 36-item short form questionnaire were significantly decreased during the summer. This cohort of SLE patients appeared to have much lower QoL throughout the year than that of SLE patients reported in other studies and both fatigue and disease activity were shown to be associated with QoL. The findings of this research could impact on patient care, given the high prevalence of vitamin D inadequacy and its relationship with disease activity and fatigue. These novel results provide some evidence of a potential relationship between vitamin D and disease activity. If proven, increased vitamin D status could improve clinical outcomes such as fatigue and disease activity thereby indirectly improving QoL. Future research involving vitamin D supplementation in SLE patients to optimise status would strengthen the evidence for beneficial effects of vitamin D in SLE.
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Khodadadi, Laleh [Verfasser]. "Bortezomib plus continuous B cell depletion results in sustained plasma cell depletion and amelioration of lupus nephritis in NZB/WF1 mice / Laleh Khodadadi." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2016. http://d-nb.info/1111558752/34.
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McLane, Jesica Mata. "Investigation of 1alpha,25-dihydroxy vitamin D3 membrane receptor ERp60 in adipocytes from male and female lean and obese mice." Thesis, Atlanta, Ga. : Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/31793.
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Thesis (M. S.)--Biomedical Engineering, Georgia Institute of Technology, 2010.Committee Chair: Dr. Barbara Boyan; Committee Co-Chair: Dr. Zvi Schwartz; Committee Member: Dr. Hanjoong Jo. Part of the SMARTech Electronic Thesis and Dissertation Collection.
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Resende, Aline Lázara. "Doença óssea em pacientes com nefrite lúpica: aspectos inflamatórios." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/5/5148/tde-15082014-142821/.
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INTRODUÇÃO: O comprometimento ósseo em pacientes portadoras de nefrite lúpica é comum e multifatorial. O objetivo deste trabalho foi estudar a contribuição do componente inflamatório para o comprometimento ósseo destas pacientes. MÉTODOS: Foram estudadas 15 pacientes do sexo feminino (no menacme) com diagnóstico recente (<= 2 meses) de Lupus Eritematoso Sistêmico e Nefrite Lúpica (NL). Foram excluídos pacientes com história/evidência de doença renal ou óssea prévia. A avaliação laboratorial incluiu a dosagem de 25-hidroxivitamina D3 ([25(OH)D] e de citocinas inflamatórias associadas a fisiopatologia do lupus [Interleucina-6, Fator de necrose tumoral ? e Monocyte Chemoattractant Protein-1 (MCP-1)]. Além disso, as pacientes foram submetidas a biópsia óssea, com análise histomorfométrica, imunohistoquímica e cultura celular (estudo da proliferação e citometria de fluxo). RESULTADOS: As pacientes lúpicas apresentavam em média 29,5±10 anos, com uma proteinúria de 4,7±2,9 g/dia, e uma taxa de filtração glomerular estimada de 37(31-87) ml/min/1,73m², e estavam em uso de glicocorticóide por 34±12 dias. Todas as pacientes apresentavam níveis insuficientes de vitamina D (9,9±4,4ng/ml, variando de 4 a 20 ng/ml). Os níveis de 25(OH)D se correlacionaram negativamente com os de todas as citocinas inflamatórias estudadas. Os níveis de MCP-1 urinário se correlacionaram negativamente com os de 25(OH)D (r= -0,53, p=0,003) e positivamente com os de deoxipiridinolina (r=0,53, p=0,004). Não observamos diferença significativa entre pacientes e controles na proliferação de osteoblastos medida pela incorporação pela timidina (82,22±8,43 vs 56,06±23,73 contagem por minuto, p=0,21). Os osteoblastos provenientes dos fragmentos ósseos das pacientes lúpicas apresentaram uma maior expressão de MCP-1, medida pela intensidade média de fluorescência (32,0±9,1 vs 22,9±5,3, p=0,01). Quando comparadas a controles, as pacientes portadoras de nefrite lúpica apresentaram valores significativamente inferiores de dois parâmetros de formação óssea (volume e espessura osteoide). Além disso, detectamos também uma redução em dois parâmetros de mineralização óssea (superfície mineralizante e taxa de formação óssea). Por fim, as pacientes lúpicas apresentaram um aumento significativo da reabsorção óssea e da superfície osteoclástica. Com relação a imunohistoquímica, as pacientes lúpicas apresentaram uma menor expressão de osteoprotegerina (0,61±0,82 vs 1,08±0,50, p=0,003) e uma maior expressão do receptor ativador do fator nuclear-?B ligante (RANKL) (1,76±0,92 vs 0,41±0,28, p<0,001) quando comparadas aos controles. CONCLUSÕES: Pacientes com diagnóstico recente de nefrite lúpica, submetidas a um reduzido tempo de exposição e carga cumulativa de corticóide, apresentam um significativo comprometimento ósseo, caracterizado por uma redução da formação e mineralização óssea, associada a um aumento da reabsorção óssea. Os níveis de MCP-1 urinário se correlacionaram negativamente com os de 25-hidroxivitamina D3 e positivamente com os de deoxipiridinolina, sugerindo que fatores inflamatórios possam contribuir para a insuficiência de vitamina D e a reabsorção óssea. A expressão óssea aumentada de RANKL e reduzida de OPG, assim como o aumento da expressão de MCP-1 pelas células ósseas das pacientes lúpicas, reiteram a hipótese de que a inflamação per se possa influenciar a reabsorção óssea observada nestas pacientesINTRODUCTION: Bone disease in lupus nephritis patients is common and multifactorial. The aim of this study was evaluate the contribution of inflammatory factors to the bone disorder observed in these patients. METHODS: We studied 15 female pre-menopausal patients with <= 2 months of diagnosed Systemic Erythematosus Lupus and Lupus Nephritis (LN). Subjects with prior kidney or bone disease were excluded. We measured the levels of 25-hydroxyvitamin D3 [25(OH)D] and cytokines involved in LN physiopathology [Interleucin-6, Tumor Necrosis Factor ?, and Monocyte Chemoattractant Protein-1 (MCP-1)]. Patients were submitted to bone biopsy, followed by osteoblast culture (cell proliferation and flow cytometry), histomorphometric and immunohistochemistry analysis. RESULTS: LN patients presented a mean age of 29.5±10 years, a proteinuria of 4.7±2.9 g/day and an estimated glomerular filtration rate of 37(31-87) ml/min/1,73m². They were on glucocorticoid therapy for 34±12 days. All patients presented vitamin D insufficiency (9.9±4.4 ng/ml, range 4-20). Vitamin D levels were negatively correlated with all inflammatory cytokines. Urinary MCP-1 correlated negatively with 25-hydroxyvitamin D3 (r= -0.53, p=0.003) and positively with serum deoxypyridinoline (r=0.53, p=0.004). There were no differences between NL patients and controls in osteoblast proliferation measured by incorporation of thymidine (82.22±48.43 vs 56.07±23.73 counts per minute, respectively, p=0.21). Osteoblasts isolated from LN patients presented a significantly higher expression of MCP-1, as measured by mean fluorescence intensities (32.0±9.1 vs 22.9±5.3, p=0.01). LN patients presented a significantly reduction in two formation parameters (osteoid volume and osteoid thickness). They also presented a decrease in mineralization surface and bone formation rate, associated with an increased eroded surface and osteoclast surface. Patient\'s bone specimens demonstrated a reduced immunostaining for osteoprotegerin (0.61±0.82 vs 1.08±0.50%, p=0.003), and an increased expression of Receptor Activator of NF-kB ligand (RANKL) (1.76±0.92 vs 0.41±0.28%, p < 0.001) when compared to controls. CONCLUSION: Newly diagnosed lupus nephritis patients, submitted to a limited time of exposure and to a low cumulative dose of glucocorticoids, presented a significant disturbance in bone metabolism, characterized by an impaired bone formation and mineralization, associated with an increase in resorption parameters. The levels of urinary MCP-1 were negatively correlated to 25-hydroxyvitamin D3 and positively correlated to serum deoxypyridinoline, suggesting that inflammation may contribute to vitamin D insufficiency and bone resorption. Bone tissue overexpression of RANKL and underexpression of osteoprotegerin, as well as increased expression of MCP-1 by cultured bone explants cells reinforces inflammatory background contributing to bone resorption in LN bone disease
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Souza, Viviane Angelina de. "Níveis séricos de vitamina D em pacientes com lúpus eritematoso sistêmico: associação com nefrite lúpica, atividade da doença e densidade mineral óssea." Universidade Federal de Juiz de Fora (UFJF), 2012. https://repositorio.ufjf.br/jspui/handle/ufjf/4609.
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Atualmente, é descrito papel imunomodulador da vitamina D, além de seu já reconhecido efeito na manutenção da homeostase óssea. A insuficiência de vitamina D é considerada epidêmica, e pode influenciar a patogenia de doenças autoimunes, como o Lúpus Eritematoso Sistêmico (LES). Este estudo avaliou a prevalência de insuficiência de vitamina D em pacientes com LES comparados a controles saudáveis, além de associações entre vitamina D e manifestações clínicas, nefrite lúpica, atividade da doença e densidade mineral óssea (DMO). A vitamina D foi avaliada pela análise sérica da 25-hidroxivitamina D [25(OH)D] por cromatografia líquida de alta performance (HPLC) e níveis inferiores a 30 ng/mL foram considerados insuficientes. Foram avaliados 45 pacientes com LES e 25 controles saudáveis. A mediana (mínimo-máximo) da 25(OH)D foi 29,48 (20,83-44,23) ng/mL no grupo doente e 37,68 (22,91-44,07) ng/mL nos controles (p<0,0001). Ocorreu prevalência de insuficiência de 25(OH)D em 55% dos pacientes e 8% dos controles (p=0,001). A vitamina D associou-se com tempo de duração da doença (r=0,311; p=0,037) e uso de hidroxicloroquina (r=-0,337; p=0,024). Houve fraca evidência de associação inversa entre vitamina D e interleucina (IL)-6 (r=-0,276; p=0,066). Não houve associação entre 25(OH)D e nefrite lúpica ou densidade mineral óssea. O modelo de regressão logística multivariada evidenciou maior chance de ocorrer 25(OH)D < 30 ng/mL no grupo de pacientes lúpicos que nos controles (OR: 78,25;p=0,0001), quando ajustado para possíveis variáveis confundidoras. Nos pacientes lúpicos, a hipovitaminose D mostrou-se prevalente. A vitamina D associou-se com tempo de duração da doença e uso de hidroxicloroquina.
Currently, it is described an immunomodulator role of vitamin D besides its already known effect on bone homeostasis. Vitamin D insufficiency is considered to be epidemic and may influence the pathogenesis of autoimmune diseases, like Systemic Lupus Erythematosus (SLE). This study evaluated the prevalence of vitamin D insufficiency in patients with SLE compared to healthy controls, and the association between vitamin D and clinical parameters, lupus nephritis, disease activity and bone mineral density (BMD). Vitamin D was evaluated by serum analysis of 25-hydroxyvitamin D [25(OH)D] by high performance liquid chromatography (HPLC) and levels below 30 ng/mL were considered insufficient. We evaluated 45 patients with SLE and 25 healthy controls. Median (range) of 25(OH)D was 29,48 (20,83-44,23) ng/mL in lupus patients and 37,68 (22,91-44,07) ng/mL in controls (p<0,0001). The prevalence of 25(OH)D insufficiency was 55% in patients and 8% in controls (p=0,001). Vitamin D was associated with time of disease duration (r=0,311; p=0,037) and use of hydroxychloroquine (HXQ) (r=-0,337; p=0,024). There was a weak evidence of inverse association between vitamin D and interleukin (IL)-6 in patients with SLE (r=-0,276; p=0,066). No association between 25(OH)D and lupus nephritis or bone mineral density was found. Multivariate logistic regression analysis evidenced higher probability of 25(OH)D < 30 ng/mL in SLE patients than in controls (OR: 78,25; p=0,0001), when adjusted to possibly confounding variables. In lupus patients, hypovitaminosis D was prevalent. Vitamin D was associated with time of disease duration and use of hydroxychloroquine.
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Burniat, Agnès. "Etude de la tumorigenèse thyroïdienne et des effets anti-prolifératifs de la vitamine D active dans plusieurs modèles murins." Doctoral thesis, Universite Libre de Bruxelles, 2012. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209664.
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Le but de la première partie de ce travail était de mieux comprendre la tumorigenèse thyroïdienne àpartir de modèles murins transgéniques développant des tumeurs de la thyroïde. Nous avons ainsi
analysé par microarrays l’expression génique au sein de thyroïdes de souris Tg-RP3 exprimant le
réarrangement RET/PTC3, responsable de cancers papillaires de la thyroïde chez l’homme (PTC), et
de souris Tg-E7 exprimant l’oncogène E7, responsable de cancers du col de l’utérus chez la femme.
Ces deux gènes étaient exprimés exclusivement dans la thyroïde grâce à un promoteur thyroglobuline.
Nous avons comparé les profils d’expression entre les différents génotypes (sauvages, Tg-RP3 et Tg-
E7) mais également entre différents âges (2, 6 et 10 mois). Sur le plan histologique, les souris Tg-E7
développaient d’énormes goitres avec une dysplasie de plus en plus marquée, mais n’ont pas démontré
de réelles lésions de carcinomes aux différents âges étudiés. Les thyroïdes de souris Tg-RP3
démontraient quand à elle une prolifération cellulaire et une croissance plus modérées, mais des
remaniements tissulaires plus importants, présents dès 2 mois, avec apparition de lésions de carcinome
chez de nombreux animaux essentiellement à 6 et 10 mois. Les résultats de l’analyse de l’expression
génique par microarrays rejoignaient ces observations histologiques. Dans les thyroïdes E7, ce sont
essentiellement les gènes impliqués dans le cycle cellulaire qui ont démontré une surexpression
significative. Dans les thyroïdes RP3, les processus cellulaires les mieux représentés par les gènes
surexprimés étaient déjà décrits comme des processus ayant un rôle important dans la tumorigenèse
thyroïdienne humaine :l’inflammation, le remodelage du milieu extracellulaire et l’angiogenèse. De
plus, plusieurs gènes classiquement surexprimés dans les PTC humains, l’étaient également dans les
thyroïdes RP3. Parmi ceux-ci le récepteur de la vitamine D (VDR) et la 1-alpha-hydroxylase
(CYP27B1), responsable de la conversion de la 25-hydroxyvitamine D3 en 1,25-dihydroxyvitamine
D3, ont particulièrement retenu notre attention étant donné une littérature croissante sur les effets antiprolifératifs
et immuno-modulateurs de la 1,25-dihydroxyvitamine D3 (calcitriol). Nous avons donc
étudié dans la deuxième partie de notre travail les effets anti-prolifératifs et transcripionnels du
calitriol sur plusieurs modèles thyroïdiens in vitro et in vivo. Si nous n’avons pu démontrer d’effets
concluants sur des lignées de cancers thyroïdiens humains, nous avons par contre démontré un effet
anti-prolifératif, le plus souvent dose-réponse, du calcitriol sur des cultures primaires de thyroïdes de
souris sauvages, Tg-RP3, Tg-E7 et humaines. Seule la 24-hydroxylase, intervenant dans l’inactivation
de la vitamine D, et le récepteur à la TSH ont démontré une surexpression significative en présence de
calcitriol par RTQ-PCR. Une étude d’expression génique par microarrays sur des cultures primaires de
thyroïdes RP3 et humaines traitées par éthanol (contrôle) ou calcitriol a permis de mettre en évidence
3 gènes significativement régulés dans le même sens, en l’occurrence sous-exprimés, en présence de
calcitriol :la nébulette, la thymopoïétine et la cycline E2. Le rôle exact joué par ces trois protéines
dans l’effet anti-prolifératif observé reste à déterminer. Les études in vivo de carence alimentaire en
vitamine D de souris Tg-RP3 n’ont pas démontré de différences significatives entre le groupe carencé
et non carencé que ce soit en termes de croissance glandulaire ou d’expression génique, après 2 ou 6
mois de carence. Seule la 1-alpha-hydroxylase est apparue significativement surexprimée après 2
mois, surexpression disparaissant après 6 mois. Cette régulation pourrait témoigner d’un mécanisme
d’adaptation de la thyroïde qui tente de contrer la carence en vitamine D circulante en augmentant la
concentration locale de vitamine D active. Ce phénomène disparaissant à 6 mois, il serait intéressant
de prolonger la carence au-delà de 6 mois pour assurer une réelle carence locale en 1,25-
dihydroxyvitamin D3. Nous avons ensuite traité des souris Tg-RP3 puis Tg-E7 par des doses variables
de CD578, un analogue « non calcimimétique » du calcitriol. Il est apparu que la dose ayant un effet
significatif au niveau transcriptionnel (surexpression de la 24-hydroxylase) était également la dose la
plus toxique, entrainant une hypercalcémie parfois létale. Le protocole principal a du être écourté en
raison d’un excès de mortalité. Le petit nombre d’animaux ayant survécu ne nous a pas permis de
conclure à une différence d’expression significative du Ki67 dans les thyroïdes de souris traitées par
CD578 par rapport aux souris contrôles. De nouvelles expériences devront donc être réalisées aux
doses les moins toxiques, administrées sur une plus longue période et sur un plus grand nombre
d’animaux, afin d’augmenter la probabilité d’observer un effet sur la prolifération, voire la
différenciation tissulaire.
Doctorat en Sciences médicales
info:eu-repo/semantics/nonPublished
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Lima, Glauce Leão. "Avaliação da suplementação de vitamina D em pacientes com lúpus eritematoso de início juvenil: estudo clínico, randomizado, duplo-cego, controlado por placebo." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/5/5165/tde-14122015-120849/.
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Objetivos: O objetivo deste estudo foi avaliar o efeito da suplementação de vitamina D nos parâmetros clínicos, laboratoriais, atividade da doença, e fadiga em pacientes com lúpus eritematoso de início juvenil (LESj). Métodos: Este trabalho foi um estudo randomizado, duplo-cego, controlado por placebo por um período de 24 semanas. Quarenta pacientes foram randomizadas (1:1) para receber colecalciferol via oral 50.000 UI / semana (LESj-VITD) ou placebo (LESj-PL). A terapêutica destes pacientes foi mantida estável durante este período. As concentrações séricas de 25- hidroxivitamina D (25OHD) foram medidas por radioimunoensaio. A atividade da doença foi avaliada por meio do Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) e pelo European Consensus Lupus Activity Measurement (ECLAM). Fadiga foi avaliada usando a Kids Fatigue Severity Scale (K-FSS). Resultados: No início do estudo, os grupos foram semelhantes em relação à idade, índice de massa corporal, envolvimento de órgãos, dose de glicocorticoide, uso de drogas imunossupressoras, SLEDAI, ECLAM, K-FSS e concentrações séricas de 25OHD. Após 24 semanas, as concentrações séricas de 25OHD foram maiores no grupo LESj-VITD que no LESj-PL [(31,3 (8,7) vs. 16,5 (5,8), p < 0,001)]. Ao fim da intervenção, uma melhoria significativa no SLEDAI [Delta= 0 (- 4 - 5)_ vs. 1 (-12 - 6) p =0,011] e no ECLAM [Delta = 0 (-2 -1) vs. 0 (-6 - 3) p=0,006], foi observado no grupo LESj- VITD em comparação com o LESj-PL. Em relação à avaliação de fadiga, uma redução da fadiga relacionada com a vida social foi encontrada no grupo LESj-VITD em comparação com o grupo LESj-PL (p = 0,008). A suplementação de colecalciferol foi bem tolerada sem eventos adversos graves. Conclusões: Este estudo sugere que a suplementação com colecalciferol por 24 semanas é eficaz em diminuir a atividade da doença e melhorar a fadiga em pacientes com LESjObjective: The aim of this study was to evaluate the effect of vitamin D supplementation on disease activity and fatigue in Juvenile-onset Systemic Lupus Erythematosus (JoSLE). Methods: This study was a randomized double-blind placebo-controlled 24-week trial. Forty JoSLE patients were randomized (1:1) to receive oral cholecalciferol 50,000 IU/week (JoSLE-VitD) or placebo (JoSLE-PL). Medications remained stable throughout the study. Serum levels of 25OHD were measured using radioimmunoassay. Disease activity was assessed using the SLE Disease Activity Index (SLEDAI) and the European Consensus Lupus Activity Measurement (ECLAM). Fatigue was assessed using the Kids Fatigue Severity Scale (K-FSS). Results: At baseline, groups were similar regarding, age, body mass index, organ involvement, glucocorticoid dose, use of immunosuppressive drugs, SLEDAI, ECLAM, K-FSS and levels of 25OHD. After 24 weeks, the mean level of 25OHD was higher in the JoSLE-VitD group than in the JoSLE-PL [(31,3 (8,7) vs. 16,5 (5,8), p < 0,001)]. At the end of intervention, a significant improvement in SLEDAI [delta= 0 (- 4 - 5)_ vs. 1 (-12 - 6) p =0,011] and in ECLAM [delta = 0 (-2 -1) vs. 0 (-6 - 3) p=0,006] was observed in the JoSLE-VitD group compared to the JoSLE-PL. Regarding fatigue evaluation, a reduction of fatigue related to social life score was found in the JoSLE-VitD group compared to the JoSLE-PL group (p=0.008). Cholecalciferol was well tolerated with no serious adverse events. Conclusion: This study suggests that cholecalciferol supplementation for 24 weeks is effective in decreasing disease activity and improving fatigue in JoSLE patients
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Marziou, Alexandra. "Effet combiné de l’exercice physique et de la vitamine D en prévention tertiaire sur des souris c57bl/6j soumises à un régime riche en graisse et en sucre : aspects métaboliques de l’obésité et des désordres associés Vitamin D Supplementation Improves Adipose Tissue Inflammation and Reduces Hepatic Steatosis in Obese C57BL/6J Mice Artificial Sweeteners Impair Endothelial Vascular Reactivity: Preliminary Results In Rodents." Thesis, Avignon, 2021. http://www.theses.fr/2021AVIG0362.
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L’obésité est une maladie pandémique résultant de changements comportementaux dus à la modernisation de notre société actuelle, comprenant une augmentation de l’inactivité physique et une surconsommation d’aliments riches en graisse et en sucre mais également pauvres en micronutriments. Dans ce contexte, cette thèse a pour objectif d’évaluer les effets de l’exercice physique associé à la supplémentation en vitamine D en prévention tertiaire dans un modèle expérimental d’obésité. Tout d’abord, la consommation du régime obésogène a conduit au développement de l’obésité caractérisée par une augmentation de l’adiposité, une accumulation de lipides ectopiques dans le foie ainsi qu’à la mise en place d’une résistance à l’insuline et d’une inflammation. Dans un premier temps, nous nous sommes intéressés à l’effet de la vitamine D sur ces différents événements rencontrés au cours de l’obésité. Bien que nous n’ayons pas mis en évidence d’effet de la supplémentation en vitamine D sur les paramètres morphologiques, nous avons montré une baisse de l’inflammation du tissu adipeux par la limitation d’expression des chimiokines et de l’infiltration lipidique au niveau hépatique accompagnée d’une baisse d’expression des gènes impliqués dans la lipogenèse.Le deuxième objectif de cette thèse a été d’étudier les effets combinés de la supplémentation en vitamine D et de l’exercice physique volontaire. Contrairement à ce qui a été retrouvé par la supplémentation en vitamine D seule, l’exercice physique a induit une limitation de la prise de poids, accompagnée d’une réduction de l’adiposité médiée par une baisse de l’hypertrophie adipocytaire. De plus, la double intervention a permis de restaurer la sensibilité à l’insuline et d’abolir totalement l’infiltration lipidique au niveau hépatique. Ceci pourrait être expliqué par la diminution de l’inflammation adipocytaire et de la réduction d’infiltration macrophagique retrouvée à la fois dans le tissu adipeux et dans le foie. Ainsi, nos résultats démontrent pour la première fois l’intérêt de coupler l’exercice physique à la supplémentation en vitamine D pour lutter contre l’obésité et désordres métaboliques associésObesity is a pandemic disease arising from behavorial and social changes which are driven by modernization of actual society. These changes include an increase of physical inactivity and overconsumption of food rich in fat and sugar but also poor in micronutrients. In this context, the aim of this thesis was to evaluate physical exercise and vitamin D supplementation effects in tertiary prevention on an experimental model of obesity. First, obesogenic diet consumption led to obesity development characterized by increased adiposity, ectopic lipid accumulation in the liver as well as insulin resistance and inflammation. Firstly, we investigate vitamin D supplementation on these events occurring during obesity. While we did not observe modification of morphological parameters by vitamin D supplementation, we demonstrated that vitamin D supplementation decreased adipose tissue inflammation by limiting chemokine expression and hepatic lipid infiltration accompanied by decreased gene expression involved in lipogenesis.The second objective of this thesis was to investigate the combined effects of vitamin D supplementation and voluntary physical exercise. Unlike to what we observed by vitamin D supplementation alone, physical exercise induced a limitation in weight gain, accompanied by a reduction in adiposity mediated by decreased adipocyte hypertrophy. In addition, the double intervention restored insulin sensitivity and completely abolished hepatic lipid infiltration. This could be explained by decreased adipocyte inflammation and decreased macrophage infiltration found in both adipose tissue and liver. Thus, our results demonstrated for the first time the interest of combining physical exercise and vitamin D supplementation to fight obesity and associated metabolic disorders
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Lima, Ana Paula Calheiros de. "Efeitos in vitro de soro de pacientes com nefrite lúpica ativa em células de linhagem osteoblástica humana hFOB 1.19." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/5/5148/tde-20032019-084434/.
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INTRODUÇÃO: Perda óssea é um achado comum em pacientes com Nefrite Lúpica (NL), mesmo naqueles com diagnóstico recente. Algumas evidências indicam um aumento na osteoclastogênese como um dos distúrbios principais no processo de remodelamento ósseo. O objetivo deste estudo foi investigar algumas vias de sinalização (RANKL/OPG, Wnt/Beta-catenin and Th17/IL-17) possivelmente envolvidas na osteoclastogênese anormal detectada em mulheres jovens ao diagnóstico de nefrite lúpica ativa, assim como avaliar a ação da vitamina D (VitD) nesse cenário e sua correlação com fatores inflamatórios. MÉTODOS: Realizamos culturas com a linhagem de células osteoblásticas humanas hFOB 1.19 (ATCC) e as dividimos em um grupo suplementado com soro de pacientes lúpicas (NL) (n=15) e em um grupo com soro de controles saudáveis (CS) (n=15) em vez de soro fetal bovino (SFB). Em seguida, adicionamos 1,25-dihidroxivitamina D3 (1,25(OH)2D3) em dois subgrupos nas concentrações 10-9M e 10-7M, resultando em 6 grupos: CS, CS+vitD 10-9M, CS+vitD 10-7M, NL, NL+vitD 10-9M, NL+vitD 10-7M). Após 48h da adição de 1,25(OH)2D3 ao meio de cultura, células hFOB foram tripsinizadas e separado o lisato celular de cada grupo. Ensaios de citometria de fluxo e multiplex foram realizados para quantificação das seguintes proteínas do lisato cellular: CD166, CD54, fosfatase alcalina, RANKL, OPG, CD14, TLR4, NF-KappaB, SOST, DKK-1, Beta-catenina, IL-1-beta, IL-2, IL-6, TNF-alfa, IL-17A, IL-17F, IL-21 and IL-22. RT-PCR foi empregado para quantificação de mRNA dos genes RANKL, SOST, OPG e Beta-catenina. RESULTADOS: Pacientes com NL evidenciaram maiores níveis séricos de DKK-1 (2802,04 ± 1380,06 x 696,30 ± 421,22pg/ml, p < 0,001), OPG (560,12 ± 333,56 x 340,24 ± 102,08pg/ml, p=0,0212), TNF-alfa (9,63 ± 14,49 x 1,27 ± 0,35pg/ml, p=0,0337), IL-6 (15,58±39,08 x 8,02±3,49, p= 0,0053) and IL-2 (3,36 ± 3,06 x 1,54 ± 0,9pg/ml, p=0,0353) do que CS. Após exposição ao meio enriquecido com soro de pacientes com NL, células hFOB 1.19 apresentaram maior nível de mRNA de RANKL (p=0,045)) e menor nível de proteína OPG (178,81 ± 66,40 x 298,76 ± 114,94pg/mg, p=0,0016). Suplementação com 1,25(OH)2D3 aumentou a diferença da expressão das proteínas DKK-1 (673,03 ± 171,93 x 456,69 ± 234,53pg/mg, p=0,0215), IL-6 (0,80 ± 0,25pg/mg x 0,66 ± 0,18, p=0,0417) and IL-2 (4,97 ± 2,2 x 3,90 ± 1,66pg/mg, p=0,042) entre hFOB NL comparados com hFOB CS, enquanto diminuiu o nível de mRNA de Beta-catenina em células do grupo NL. DISCUSSÃO: Dentro das limitações deste estudo, os resultados sugerem que os maiores níveis séricos de citocinas pró-inflamatórias, como TNF-alfa, IL-6 e talvez IL-2, detectadas em pacientes com NL pode ter induzido a maior expressão osteoblástica de RANKL, representada pelo maior nível de mRNA RANKL em células do grupo NL, e suprimido OPG, conforme a diminuição observada na quantificação proteica de OPG nos lisatos celulares, o que pode ter contribuído para a aumentada osteoclastogênese evidenciada pela biópsia óssea dessas pacientes. A adição de 1,25(OH)2D3 não preveniu os efeitos inflamatórios do soro de pacientes com NL ativa em células hFOB 1.19 neste estudoINTRODUCTION: Bone loss is a common finding in Lupus Nephritis (LN) patients even in those recently diagnosed. Some evidences indicate an increased osteoclastogenesis as the main disturb of the bone remodeling process. The aim of this study was to investigate some pathways (RANK-L/OPG, Wnt/?-catenin and Th17/IL-17) possibly involved in the abnormal osteoclastogenesis detected in women at the diagnosis of proliferative LN as well as evaluating the action of vitamin D (vitD) in this scenario and their correlation with inflammatory factors. METHODS: We cultured the human osteoblastic cell line hFOB 1.19 (ATCC), and divided cultures into those supplemented with serum from healthy controls (HC) (n=15) and LN patients (n=15) instead of fetal bovine serum (FBS). Then 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] was added in two subgroups at the concentrations of 10-9M e 10-7M while vitD was absent in one subgroup in both HC and LN cultures (HC, HC+vitD 10-9M, HC+vitD 10-7M, LN, LN+vitD 10-9M, LN+vitD 10-7M) . After 48h of vitD addition, hFOB cultures were trypsinized. Flow cytometry and multiplex assays were performed to test CD166, CD54, alkaline phosphatase, RANKL, OPG, CD14, TLR4, NF-KappaB, SOST, DKK-1, ?-catenin, IL-1Beta, IL-2, IL-6, TNF-alfa, IL-17A, IL-17F, IL-21 and IL-22 concentrations in the cell lysates. Polymerase reaction chain (RT-PCR) assays analyzed the expression of RANKL, SOST, OPG and Beta-catenin mRNA. RESULTS: LN patients showed higher serum levels of DKK-1 (2802.04 ± 1380.06 x 696.3 ± 421.22pg/ml, p < 0.001), OPG (560.12 ± 333.56 x 340.24 ± 102.08pg/ml, p=0.0212), TNF-alfa (9.63 ± 14.49 x 1.27 ± 0.35pg/ml, p=0.0337), IL-6 (15.58±39.08 x 8.02±3.49, 0.0053) and IL-2 (3.36 ± 3.06 x 1.54 ± 0.9pg/ml, p=0.0353) than HCs. After exposure to medium enriched with LN serum, osteoblasts expressed higher RANKL mRNA (fold change 1.573, p=0.045) and lower OPG protein (178.81 ± 66.40 x 298.76 ± 114.94pg/mg, p=0.0016). 1,25(OH)2D3 supplementation increased the difference between LN and HC expression of DKK-1 (673.03 ± 171.93 x 456.69 ± 234.53pg/mg, p=0.0215), IL-6 (0.80 ± 0.25pg/mg x 0.66 ± 0.18, p=0.0417) and IL-2 (4.97 ± 2.2 x 3.90 ± 1,66pg/mg, p=0.042) proteins and diminished Beta-catenin mRNA in LN cells. DISCUSSION: Within the limitations of this study, the results suggest that the higher serum levels of proinflammatory cytokines, such as TNF-alfa, IL-6 and perhaps IL-2, detected in LN patients would possibly have induced RANKL genes, as demonstrated by an enhanced RANKL mRNA expression in LN osteoblasts, and suppressed OPG protein in cell lysates, which would have contributed to the increased osteoclastogenesis detected in bone biopsies of women with new onset of LN. 1,25(OH)2D3 addition to osteoblast cultures did not prevent the effects of inflammatory LN serum in vitro
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Filho, Victor Celso Nogueira Fonseca. "Influência da vitamina D por via intratumoral na proliferação e expressão de genes alvo de xenoenxerto de câncer de mama de pacientes pós-menopausadas." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/5/5155/tde-13012014-121103/.
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O efeito antiproliferativo do calcitriol foi detectado principalmente em linhagens de carcinoma mamário expostas in vitro a alta concentração hormonal (10 - 100nM), que é associado com hipercalcemia em seres humanos. Nossa hipótese era que a administração intratumoral de calcitriol permitiria maior concentração do hormônio e ativação da via genômica. Para testar esta hipótese, um modelo de enxerto tumoral que reproduz o mais próximo das características moleculares do tumor primário, foi estabelecida. As amostras de câncer de mama recolhidos foram enxertados em camundongos nude e depois da sexta semana, semana, os enxertos tumorais foram tratados semanalmente com injeções intra-tumorais de veículo (controle) ou o calcitriol 0,06 mcg (dose que pode permitir que picos séricos de calcitriol na faixa terapêutica prevista) durante seis semanas. A proliferação e apoptose do enxerto tumoral Veículo (controlo) ou o calcitriol 0,06 mcg (dose que pode permitir que o soro de pico, assim como, a expressão dos genes alvos foram avaliadas através de reações imunohistoquímica ou RT-PCR. A expressão de VDR foi detectada em todas as amostras, assim como uma tendência para maior expressão de mRNA CYP24A1 (indução 10-18 vezes) em amostras tratadas com calcitriol, indicando que a via genómica foi induzida pelo hormonio. O elevado índice proliferativo, avaliado pela expressão de Ki67, foi detectado. No entanto, não havia diferenças na expressão de marcadores de proliferação (incorporação de BrdU, Ki67 e CDKN1B expressão) nem marcadores de apoptose (caspase-3 clivada e BCL2 expressão) entre os enxertos tumorais tratados por veículo e calcitriol tratado. Além disso, não houve diferença entre os grupos detectada na expressão de mRNA do CDKN1A. Em resumo, os efeitos antitumorais não foram observados neste modelo de enxerto tumoral. A indução do gene alvo CYP24A1 pode ter em parte impedido os efeito antitumorais da vitamina DAntiproliferative effects of calcitriol were mainly detected in breast carcinoma lineages exposed in vitro to high hormone concentrations (10-100 nM), which is associated with hypercalcemia in human beings. Our hypothesis was that intra-tumoral administration of calcitriol would allow higher issue concentration of the hormone and activation of the genomic pathway. To test this hypothesis, a tumorgraft model, that more closely reproduces the molecular characteristics of the primary tumor, was established. Freshly collected breast cancer samples were grafted in nude mice and after the 6th week, tumorgrafts were treated weekly with intra-tumoral injections of vehicle (control) or calcitriol 0.06 mcg (dose that may allow peak serum calcitriol levels in the predicted therapeutic range) for six weeks. Tumorgraft proliferation and apoptosis, as well as expression of target genes, were evaluated through immnunohistochemistry reactions or RT-PCR. VDR expression was detected in all samples as well as a trend towards higher expression of CYP24A1 mRNA (10-18 fold induction) in calcitriol treated samples, indicating that the genomic pathway was induced by the hormone. A high proliferative index, evaluated by Ki67 expression, was detected. However, there were neither differences in the expression of proliferation markers (BrdU incorporation, Ki67 and CDKN1B expression) nor in apoptosis markers (cleaved caspase 3 and BCL2 expression) between vehicle and calcitriol treated tumorgrafts. In addition, no difference between groups was detected for the expression of CDKN1A mRNA. In summary, calcitriol antitumoral effects were not observed in this tumorgraft model. Calcitriol induction of the target gene CYP24A1, might have in part, precluded vitamin D antitumoral effects
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Fielding, Kristina Anne. "Effect of Early Life Vitamin D Supplementation on Bone Development." Thesis, 2012. http://hdl.handle.net/1807/42906.
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Vitamin D is important for bone development with immunomodulatory effects. This study investigated whether feeding CD-1 and interleukin 10 (IL-10) knockout (KO) dams low (25 IU/kg diet) or high (5,000 IU/kg diet) vitamin D affected bone health of dams as well as their offspring. Offspring were weaned to 1 of the 2 diets and followed to young adulthood. Unlike CD-1 dams, IL-10 KO dams experienced greater femur strength with high vitamin D. CD-1 male offspring had reduced femur neck strength and female offspring had smaller, weaker femurs, and weaker lumbar vertebra 2 (LV2) with high maternal vitamin D. IL-10 KO male offspring had larger femurs and female offspring had stronger femurs when weaned to high vitamin D. Low vitamin D did not adversely impact bone health but the optimal level of dietary vitamin D seems to differ between healthy and inflammatory states.
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Marinho, António Joaquim dos Santos Pereira Sá. "Vitamin D deficiency and resistance state association with clinical and immunological deregulation in systemic lupus erythematosus." Doctoral thesis, 2017. https://repositorio-aberto.up.pt/handle/10216/90347.
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Marinho, António Joaquim dos Santos Pereira Sá. "Vitamin D deficiency and resistance state association with clinical and immunological deregulation in systemic lupus erythematosus." Tese, 2017. https://repositorio-aberto.up.pt/handle/10216/90347.
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Perovic, Daniela [Verfasser]. "Changes in the kidney proteome of vitamin D receptor knock-out mice / Daniela Perovic." 2003. http://d-nb.info/985493690/34.
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Glenn, Andrea. "Effects of Vitamin D Supplementation on Intestinal Inflammation in Experimental Inflammatory Bowel Disease." Thesis, 2012. http://hdl.handle.net/1807/42388.
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Vitamin D may have immunomodulatory effects in the intestine. Our objective was to determine if exposure to vitamin D mitigates intestinal inflammation in IL-10 KO mice. Mice were randomized to a diet containing 25 IU (low) or 5000 IU (high) of vitamin D/kg of diet in utero and offspring were maintained on the same diet or switched to the other diet at weaning. Fecal samples were collected at 3 months of age. Vitamin D did not affect intestinal inflammation in male and female mice and did not affect KC cytokine concentration or regulate colonic gene expression in male mice. Vitamin D modulated the gut microbiota in a sex-specific manner and depending on timing of exposure. Females in the HH group had significantly higher fecal counts of C. coccoides
than the other vitamin D interventions. Therefore, vitamin D may favourably modulate microbiota composition without attenuating inflammation.
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Hsu, Yih-Jen, and 許儀禎. "The Immunological Effects of Vitamin B2 Deficiency Status on D-galactose Induced Aging in C57BL/ 6 mice." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/71927742488397381876.
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碩士輔仁大學
營養科學系
96
According to 〝Taiwan Elderly Nutrition and Health Survey〞 showed that the prevalence rates of vitamin B2 marginal deficient status for elderly people were around 30%. In order to study the immunological effects beyond different vitamin B2 status, we established 1% D-galactose (DG) induced aging in C57BL/6 male mice. Mice were divided to five groups including control group (subcutaneous (s.c.) PBS and received normal diet; NC), aging control (s.c. DG and received normal diet; AC), s.c. DG and combined with vitamin B2 deficiency diet (AD), s.c. DG and combined with vitamin B2 adequacy diet (AA), s.c. DG and combined with vitamin B2 marginal deficiency diet (AM). Besides, both AA and AM groups were pair-fed their diet in equally amounts refer to AD group. All groups receiving their special diet along with the period of study, on the 8th weeks of study, each mouse were s.c. injected with even PBS (NC group) or DG treatment (the other groups in spite of NA group) and after sixteen-week-feeding animals were sacrificed. There were no different on mice body weight, percentage of spleen weight relative to body weight, proliferation capacity of splenocytes, and percentage of splenocytes subpopulation among groups. Our data also indicated that the NK cell activity were increased, and the IgM and IgA titer in plasma were decreased as the vitamin B2 status towards deficiency. WBC contents were no difference in these groups, but higher counts were found in AC group as compared to NC group and paralleled with the decreasing as the vitamin B2 status reduced. In AD group, IFN-γ secretion of ConA stimulated splenocytes were significantly increased as compared to NC group. The levels of RAGE (receptor for advanced glycation end product) in plasma were increased with age, but in AD group it represented the lowest levels among groups. Vitamin B2 deficiency combined with DG treatment on C57BL/ 6 mice may induce some stress proteins expression which may compromise the following parameters, such as RAGE contents, leukocyte counts, levels of antibody secretion, enhanced NK cell activity and all contributed to modulating the immune response towards upregulating the innate immunity. Many studies reported that rat shown much higher growth rate than mice, which also explained that rat showed be more sensitive model to the change of vitamin B2 status. By the way, there were no documents reported that DG induced aging been applied on rat experimental model. So in the second part of this study, we compared 1 % or 5 % DG subcutaneous injection on SD rat, and fed with different vitamin B2 diets, than analytic its related immune function changes in the indicated groups: s.c. with PBS (NC), s.c. with 1 % DG combined with vitamin B2 adequacy diet (1A), s.c. with 5 % DG combined with vitamin B2 adequacy diet (5A), and s.c. with 5 % DG combined with vitamin B2 marginal diet (5M). Collected data show that these were no differences on the splenocyte proliferative response, the NK activity of splenocytes and phagocytosis activity of blood cells, among these three groups which treated with 1 % or 5 % DG (1A, 5A, 5M). The total leukocytes counts in 5M group were significantly lower than the 1A and 5A groups. In conclusion, DG induced aging seems not a proper study model for mimic the hyporesponsibility phenomenon occurs in natural aged individual. Interestly, our study also indicated that under the vitamin B2-deficiency status, related innate immune activity were upregulated and boosted.
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Lin, Ya-Ting, and 林雅婷. "Vitamin D and coenzyme Q10 supplementation improve muscle oxidative stress, inflammation and protein catabolism in high fat diet and streptozotocin induced diabetic mice." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/2u579y.
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碩士中山醫學大學
營養學系碩士班
106
Hyperglycemia in Type 1 diabetes through increases in inflammation and oxidative stress upregulates the ubiquitin-proteasome pathway (UPP) and the autophagy-lysosome pathway (ALP) which augment muscle protein catabolism resulting in muscle wasting. Hyperglycemia induced cachexia characterized by body and muscle weight loss could influence life quality and increase mortality in type 1 diabetic patients. Coenzyme Q10 known as ubiquinone, cofactor of the electron transporter in the respiratory chain to produce ATP, is potent in anti-oxidation and anti-inflammation. Vitamin D has healthy benefits in skeletal health, anti-cancer and anti-inflammation. In this study, the high fat diet and injection of streptozotocin (STZ, 50 mg/kg) for five continuous days to induce type 1 diabetes in C57BL/6J mice is used to assay the effect and possible mechanisms of dietary supplementation vitamin D with coenzyme Q10 on hyperglycemia induced muscle wasting. Compared with normal blood sugar mice, our data showed that hyperglycemia induced not only body weight loss, but also decreases in muscle weight and crosssection area as well as myosin heavy chain expression. Dietary supplementation vitamin D with coenzyme Q10 diminished hyperglycemia induced cachexia. Dietary supplementation vitamin D with coenzyme Q10 reduced hyperglycemia induced the activation of signal transducer and transcription factors related to muscle catabolism such as phosphorylated c-Jun N terminal kinase and Myostatin protein as well as nuclear protein expression of Forkhead transcription factor 1, Nuclear factor kappa B and Signal transducer and activator of transcription 3, respectively. Moreover, dietary supplementation vitamin D with coenzyme Q10 could decrease hyperglycemia induced UPP and ALP related molecules such as Atrogin-1, Muscle RING finger protein1mRNA, Microtubule-associated protein 1A/1B-light chain 3 and caspase-3 expression in gastrocnemius muscle. Compare with hyperglycemic mice, supplementation with vitamin D and coenzyme Q10 not only inhibited the tumor necrosis factor alpha, interleukins-1β and interleukins-6 mRNA but also reduced red blood cell, kidney, liver and quadriceps femoral muscle malondialdehyde concentration, and increase the expression of antioxidant enzymes such as catalase, glutathione reductase, Superoxide dismutase2 and Heme oxygenase-1 expression. Summarily, our data suggested that vitamin D and coenzyme Q10 supplementation decreased diabetes mellitus hyperglycemic induced muscle wasting is through decreases in JNK and Myostatin signal transduction, and FoxO1, NF-κB and STAT3 activation lessened UPP and ALP related molecules expression, ROS and pro-inflammatory cytokine production and upregulates antioxidant protein expression.