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OUERFELLI, OUATHEK. "Nouvelles voies d'acces au cycle a du dihydroxy-1s, 25 cholecalciferol." Paris 6, 1988. http://www.theses.fr/1988PA066685.
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Alves, Teixeira Maraiza. "Cholecalciferol (vitamin D3) has a direct protective activity in C2C12 myotubes." Doctoral thesis, Università del Piemonte Orientale, 2021. http://hdl.handle.net/11579/127832.
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Skeletal muscle depletion occurs, among other conditions, in oncologic patients. Cancer cachexia is a multicomponent syndrome which physiopathology involves metabolic alterations, like hormonal imbalance. One of the hormones that are dysregulated in cancer cachexia is Vitamin D (VD). Besides its important role in bone mineralization, regulating calcium and phosphate homeostasis, VD affects skeletal muscle. In fact, VD deficiency has been associated with a wide range of muscle disorders, such as a decrease in muscle mass and functionality. Even though VD deficiency is highly prevalent among advanced cancer patients with cachexia, the administration of VD in these subjects showed inconclusive results, with VD supplementation being ineffective to prevent muscle wasting in both cachectic patients and tumor-bearing animals.
We show how different VD metabolites trigger contrasting effects on skeletal muscle in vitro, depending on the sites of hydroxylation or doses, thus explaining the limitations of VD-based therapy in vivo, once VD systems of biosynthesis and catabolism are dysregulated in cancer.
We find that also cholecalciferol (VD3), the non-hydroxylated upstream VD metabolite, has a direct effect on muscle cells. This finding might help to make future progress in developing VD analogs with a restricted capacity to undergo hydroxylation. Then overcoming the limitations of VD supplementation in cancer-related cachexia.
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Bhoora, Sachin. "Potential anticancer actions of cholecalciferol on a cervical squamous carcinoma cell line." Diss., University of Pretoria, 2020. http://hdl.handle.net/2263/78171.
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Cervical cancer is the fourth most common female malignancy worldwide and is substantively higher in low-income and middle-income countries. In South Africa, cervical cancer is a leading cause of mortality amongst women.
The anti-cancer actions of the vitamin D and its numerous metabolites are an active field of research. The family of vitamin D metabolites regulate numerous cellular pathways which are implicated in tumorigenesis. Pre-clinical studies and clinical studies have yielded promising, although conflicting results in various cancers.
Some healthy and cancerous tissue express an autocrine vitamin D metabolising system (VDMS) which is capable of tightly regulating intracellular metabolism and growth. The VDMS expresses activating and inactivating enzymes and a vitamin D receptor (VDR). At the cellular level, the VDMS can activate and inactivate vitamin D precursors and transduce signals to the nucleus to regulate various cell health genes, including cell growth, metabolism and survival. Healthy and cancerous cervical tissue express a VDMS.
The anti-cancer actions of cholecalciferol, an early precursor of activated vitamin D, is poorly studied in cervical cancer. This study aimed to characterise cholecalciferol’s action on cell growth, cell death and the VDMS in a high-grade cervical cancer cell line, SiHa.
SiHa cell cultures were treated with a range of cholecalciferol doses (26 nM, 104 nM, 260 nM and 2600 nM) for 72 hours. Cell count and viability were assessed by crystal violet and trypan blue assays, respectively. Cell proliferation was enumerated by Ki67 nuclear antigen and the cell cycle profile analysed by flow cytometry. Apoptotic cell death was investigated by measuring mitochondrial membrane potential (∆Ψm), phosphatidylserine (PS) externalisation, effector caspase activation and evaluation of DNA damage markers by flow cytometric analysis. The biochemical markers microtubule-associated proteins 1A/1B light chain 3B-II (LC3-II) and lactate dehydrogenase (LDH) were also measured by flow cytometry and spectrophotometric analysis to identify autophagic cell death and necrosis, respectively. In addition, brightfield microscopy and transmission electron microscopy (TEM) were respectively used to characterise morphological and ultrastructural features of apoptosis, autophagic cell death and necrosis. The VDMS in SiHa control and experimental cultures were characterised by the investigation of intracellular gene and protein expression of the cholecalciferol activating (CYP2R1 and CYP27A1) and inactivating (CYP24A1) enzymes, and the VDR. Qualitative microscopical analysis evaluated classical characteristics of cell death and semi-quantitative analysis of apoptosis was performed. Data were analysed using a one-way ANOVA and Bonferroni post-hoc test. p < 0.05 was considered statistically significant.
A significant decrease in cell count and cell viability was identified in SiHa cell cultures treated with 2600 nM cholecalciferol. Furthermore, significant increase in biochemical markers of apoptosis were identified including, decreased ∆Ψm; PS exposure; terminal caspase activation; and nuclear damage at 2600 nM cholecalciferol treatment of SiHa cell cultures. Moreover, the biochemical findings were supported by brightfield microscopy and TEM, which observed classical apoptotic features viz. membrane blebbing, apoptotic bodies and nuclear fragmentation. Also, a significantly increased number of apoptotic cells were enumerated. There was no evidence of autophagic cell death and necrosis. Additionally, a significant increase in 25-hydroxylase (CYP2R1) gene and protein expression was identified in SiHa cells treated with 2600 nM cholecalciferol. Conversely, a significant decrease in 1α-hydroxylase (CYP27B1) gene and protein expression was identified in SiHa cells treated with 2600 nM cholecalciferol. Furthermore, significant increase in both 24-hydroxylase (CYP24A1) and VDR expression at gene and protein levels were observed in 2600 nM experimental SiHa cultures.
In conclusion, cholecalciferol exerts growth inhibition and apoptosis in SiHa cells at 2600 nM. This is accompanied by CYP2R1 and VDR upregulation which suggests autocrine activation to calcidiol and intracellular nuclear signalling, respectively. It is therefore hypothesised that calcidiol synthesised de novo binds to VDR and induces apoptosis in SiHa cell line.Dissertation (MSc (Chemical Pathology))--University of Pretoria, 2020.
Chemical Pathology
MSc (Chemical Pathology)
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DAOUST-MALEVAL, ISABELLE. "Synthese stereocontrolee d'un precurseur de l'unite cd du dihydroxy-1s,25 cholecalciferol." Paris 6, 1990. http://www.theses.fr/1990PA066098.
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Apres une revue des methodes de synthese permettant l'acces au controle des centres c#1#7 et c#2#0, situes sur une chaine laterale flexible de steroides, un rappel est fait sur la reaction de cycloaddition entre la methyl-2 cyclopentenone et une ynamine correctement fonctionnalisee. Une nouvelle synthese, rapide (3 etapes) et a l'echelle preparative de la methyl-2 cyclopentenone, est proposee. Une etude porte sur toutes les voies d'acces a la serie chirale pour la matiere premiere de la synthese de la cetone de windaus-grundmann. Le substrat est une methyl-2 cyclopentenone, porteuse d'une fonction acide carboxylique sur la chaine laterale. On tente d'obtenir ce substrat chiral par induction asymetrique d'une ynamine chirale, porteuse d'une copule methoxymethyl-2(s) pyrrolidine, sur la methyl-2 cyclopentenone. Une saponification enantioselective par l'esterase de foie de truie, est essayee, et un protocole d'evaluation d'exces enantiomeriques sur des quantites de substrats n'excedant pas la dizaine de milligrammes, est mis au point. Des tentatives de reduction enantioselective par les microorganismes (mucor racemosus, rhizopus arrhizus, et la levure de boulangerie), sont operees. Dans ce cadre, on effectue une etude de l'influence comparee des substituants (portes en 2 et en 3) sur la stereochimie de l'addition de reactifs nucleophiles (l selectride, borohydrure de sodium) sur la cyclopentenone 2,3-disubstituee. Le dedoublement est finalement reussi par recristallisation fractionnee de sels diastereoisomeres de la naphtylethylamine levogyre. On obtient un rendement de 80% en enantiomere pur. Celui-ci est utilise dans la synthese d'un precurseur chiral de la cetone de grundmann. Enfin, une synthese d'un modele du cycle d est egalement decrite
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Garcia-Lopes, Miriam Ghedini [UNIFESP]. "Suplementação com cholecalciferol em pacientes com doença renal crônica e hipovitaminose D." Universidade Federal de São Paulo (UNIFESP), 2011. http://repositorio.unifesp.br/handle/11600/10101.
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Previous issue date: 2011-02-22Considerando a elevada prevalência de hipovitaminose D em pacientes na fase não dialítica da doença renal crônica (DRC) e os efeitos benéficos da restauração do estado nutricional de vitamina D nos pacientes com DRC nos parâmetros do metabolismo mineral, os guias de práticas clínicas para prevenção e tratamento dos distúrbios do metabolismo mineral ósseo, Kidney Disease Outcomes Quality Initiative (K-DOQI) e Kidney Disease Improving Global Outcomes (KDIGO), sugerem a suplementação com vitamina D (ergocalciferol ou colecalciferol) para pacientes com DRC na fase não dialítica com hipovitaminose D. No entanto, poucos estudos avaliaram o efeito da suplementação nessa população. Dessa forma, este estudo tem como objetivo investigar os efeitos da suplementação com colecalciferol sobre marcadores séricos do metabolismo mineral de pacientes com hipovitaminose D na fase não dialítica da DRC. Estudo 1. Suplementacao com colecalciferol na doenca renal cronica: restauracao do estado nutricional de vitamina D e impacto sobre o paratormonio. O estudo foi prospectivo com duracao de 6 meses. Foram incluidos 45 pacientes com deficiencia de vitamina D 25-hidroxivitamina D [25(OH)D] < 15 ng/mL. Os pacientes foram suplementados com 50.000 UI/semana de colecalciferol durante 3 meses, sendo que naqueles que alcancaram niveis de 25(OH)D„d 30 ng/mL a dose foi modificada para 50.000 UI/mes durante os proximos 3 meses. Para os demais pacientes, a mesma dose inicial foi mantida por mais 3 meses. Apos o inicio da suplementacao observou-se um aumento significativo nos niveis de 25(OH)D no tempo 3 e no tempo 6. Nos primeiros 3 meses de suplementacao, 78% dos pacientes atingiram niveis de 25(OH)D„d 30 ng/mL. No entanto, apos o ajuste da dose, somente 43% mantiveram esses niveis. Houve uma diminuicao nos niveis de paratormonio (PTH) no tempo 3, periodo em que os pacientes receberam a maior dose de colecalciferol. As mudancas nos niveis de 25(OH)D durante os 3 meses correlacionaram-se positivamente com as mudancas dos niveis de 1,25-diidroxivitamina D [1,25(OH)2D] (r= 0,37; P= 0,01). As variacoes nos niveis de PTH correlacionaram-se inversamente com as mudancas nos niveis de calcio serico (r= -0,42; P= 0,004) e diretamente com as mudancas na creatinina serica (r= 0,38; P= 0,01). A analise de regressao logistica incluindo a proteinuria do inicio do estudo e as mudancas nos niveis sericos de creatinina, demonstrou que o excesso de adiposidade foi o principal fator associado com uma menor resposta a suplementacao nos primeiros 3 meses (IMC „d 25 kg/m2: ƒÒ= 2,35, EP= 1,15, P= 0,04; indice de gordura do tronco: ƒÒ= 2,59, EP= 1,13, P= 0,02). Este estudo concluiu que o tratamento com 50.000 UI por semana de colecalciferol foi efetivo em restaurar o estado nutricional de vitamina D na maioria dos pacientes sem apresentar efeitos adversos. A restauracao dos niveis de vitamina D resultou na diminuicao do PTH mesmo com uma reducao da funcao renal. Estudo 2. Suplementacao com colecalciferol em pacientes com doenca renal cronica e insuficiencia de vitamina D. O estudo foi prospectivo com duracao de 6 meses, randomizado e cego. Foram incluidos 75 pacientes com insuficiencia de vitamina D [25(OH) D „d 15 e < 30 ng/mL. Os pacientes foram tratados de acordo com a recomendacao de suplementacao proposta pelo K-DOQI para pacientes com insuficiencia de vitamina D (50.000 UI de colecalciferol mensalmente durante 6 meses). Os mesmos foram aleatoriamente alocados em dois grupos: Grupo Colecalciferol (n= 38 pacientes) ou Grupo Placebo (n= 37 pacientes). O grupo colecalciferol recebeu durante todo periodo de estudo 50.000 UI de colecalciferol mensalmente. Todos os pacientes incluidos no estudo receberam protetor solar durante o periodo de suplementacao. Apos o periodo de suplementacao houve um aumento significativo nos niveis de 25(OH)D no grupo colecalciferol. Com relacao aos demais parametros do metabolismo mineral, nao foram observados modificacoes em nenhum dos parametros durante o seguimento. Apos 6 meses de suplementacao, 46% dos pacientes tratados nao atingiram niveis de 25(OH)D > 30 ng/mL. Esses pacientes apresentaram uma maior quantidade de gordura corporal quando comparados com aqueles que alcancaram esses niveis. Ja no grupo placebo, 40,5% dos pacientes atingiram niveis de 25(OH)D > 30 ng/mL no tempo 6. A epoca da coleta (verao/outono) para a determinacao dos niveis de 25(OH)D no tempo 6 foi o unico parametro que diferiu dos demais pacientes que mantiveram os niveis de 25(OH)D< 30 ng/mL. Em resumo, os resultados do presente estudo demonstram que o protocolo de tratamento proposto pelo K-DOQI parece nao ser adequado para restaurar o estado nutricional de vitamina D em pacientes com insuficiencia desta vitamina. No entanto, a gordura corporal e a epoca da coleta sao fatores que podem ter contribuido para o achado negativo deste estudo.
Background: The effective protocol for treatment of hypovitaminosis D in non-dialysis dependent chronic kidney disease (NDD-CKD) patients has not yet been defined. In the present study we aimed to investigate the impact of cholecalciferol supplementation on serum markers of bone and mineral metabolism using the K/DOQI recommendation for NDD-CKD patients with vitamin D insufficiency. Methods: This was a prospective, randomized, single-blinded interventional study with 6 month of follow-up. This study included 75 patients, randomly assigned for the cholecalciferol group (n=38; 50,000 IU per month for 6 months) or for the placebo group (n=37). Results: After cholecalciferol supplementation, 25(OH)D levels increased significantly at 3 and 6 months in the intervention group and was maintained in the placebo group. No change was found in serum parathyroid hormone as well as in the other serum markers of mineral metabolism studied during the follow-up in both groups. In the end of the study, 46% of the treated patients did not achieve 25(OH)D levels higher than 30 ng/mL. This group of patients had a greater body fat index when compared with those who achieved this level. In the placebo group 40.5% increased 25(OH)D levels higher than 30 ng/mL after 6 months. The season (summer/autumn) when blood was collected for 25(OH)D determination was the only parameter that differed from the group of patients who maintained 25(OH)D levels below 30 ng/mL. Conclusion: Our results indicate that the protocol for treatment of vitamin D insufficiency proposed by the K/DOQI guideline seems not to be adequate for completely restore the vitamin D status of NDD-CKD patients. The lack of adequate response to cholecalciferol supplementation together with the unpredicted restoration of vitamin D status in the placebo group may account, at least in part, for the negative results of the present study.
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Nelson, Monica. "Serum 25-Hydroxyvitamin D Response to Daily Oral Supplementation with 800 IU Cholecalciferol in Premenopausal Women Living in Maine." Fogler Library, University of Maine, 2007. http://www.library.umaine.edu/theses/pdf/NelsonM2007.pdf.
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Wylon, Katharina Sophie [Verfasser]. "Immunologische Wirkung einer Einmalgabe von 100.000 I.E. Cholecalciferol (Vitamin D) / Katharina Sophie Wylon." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2015. http://d-nb.info/107108870X/34.
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Фадєєва, Ганна Анатоліївна, Анна Анатольевна Фадеева, Hanna Anatoliivna Fadieieva, Ольга Миколаївна Чернацька, Ольга Николаевна Чернацкая, and Olha Mykolaivna Chernatska. "Improving of Metabolic Profile With Vitamin D Supplements in Pregnant Women." Thesis, Elsevier, 2021. https://essuir.sumdu.edu.ua/handle/123456789/83387.
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Background. Serum 25-hydroxy-vitamin D deficiency is related to metabolic diseases as polycystic ovary syndrome, obesity, insulin resistance, cardiovascular diseases, cancer, gestational diabetes mellitus (GDM). Objective: To evaluate the effect of vitamin D therapy on metabolic parameters in pregnant women. Methods: There was a 16-week study of 62 participants with gestational diabetes mellitus. All pregnant women followed an appropriate diet and physical activity. Management of 37 women included 2,000 IU/day of cholecalciferol per os. Body mass index (BMI), hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), plasma 25- (OH) vitamin D, low‐density lipoprotein cholesterol (LDL‐C), homeostatic model assessment of insulin resistance (HOMA-ir) were estimated in pregnant women with GDM before and after the 16-week period. Quantitative data are expressed as the mean ± SD. The correlation between variables was assessed using the Pearson correlation coefficient. P-value <0.05 was considered statistically significant. All information was processed with SPSS 21.0. Results: The mean BMI was (30,2±2,34) kg/m2, baseline serum 25-(OH) vitamin D levels in all women were in a deficient limit (less than 30 nmol/L). HOMA in both groups was more than 3. The mean LDL‐C was (3,3±0,63) mmol/l and didn`t differ in the two groups. 25-(OH) vitamin D levels were inversely associated with BMI (r=–0.4; P=0.05), HOMA (r=–0.6; P=0.005), LDL‐C (r=–0.3; P=0.04). Vitamin D therapy has had significant improvement in plasma LDL‐C concentration, HbA1c, FPG in women with GDM (P<0.05). Compared with the Ist group cholecalciferol therapy had lead to a reduction of HOMA in the IInd group by (2,3±0,94) in 4 months (P < 0.05). Conclusions. The daily intake of vitamin D was accompanied by the significant glycemic improvement and the majority of women achieved diabetes control without insulin injections. Strong inverse correlation between 25 (OH) vitamin D levels and HOMA, reduction of HOMA can indicate improved sensitivity to insulin and benefits of vitamin D supplementation for the management of insulin resistance in GDM with vitamin D insufficiency.
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Tay, Jing Q. "The roles of vitamin D in cutaneous wound healing: In vitro and ex vivo studies of the effect of 1,25(OH)2D3 and its precursors on human dermal fibroblasts and epidermal keratinocytes in cutaneous wound healing." Thesis, University of Bradford, 2018. http://hdl.handle.net/10454/17350.
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In humans, the epidermis is the main site for the synthesis of Vitamin D3 (cholecalciferol) from 7-dehydrocholesterol. Cholecalciferol undergoes further hydroxylation in the liver and kidney to produce the active form of the circulating hormone 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). In target cells, 1,25(OH)2D3 interacts with the specific intracellular vitamin D receptor (VDR), a member of the nuclear receptor superfamily. However, epidermal keratinocytes, in addition to being target cells, have enzymes required for autocrine production of 1,25(OH)2D3. They can convert cholecalciferol to 1,25(OH)2D3 via 25-hydroxylase (CYP2R1) and 1α-hydroxylase (CYP27B1). Another enzyme, 24-hydroxylase (CYP24A1), regulates local levels by inactivating 1,25(OH)2D3. While recent studies have shown that absence of VDR or 1,25(OH)2D3 impairs formation of granulation tissue during wound healing in mice, little is known about the autocrine and paracrine regulation of biologically active vitamin D3 by human dermal fibroblasts during cutaneous wound healing.
Primary cultures of human keratinocytes and fibroblasts expressed VDR and all the cytochrome enzymes necessary for autocrine production of vitamin D. The relative expression of VDR mRNA was higher in dermal fibroblasts than donor-matched keratinocytes. In contrast, epidermal keratinocytes had a higher mRNA expression of vitamin D3 metabolising enzymes. A scratch wound assay confirmed that 1,25(OH)2D3 stimulated keratinocyte migration, but paradoxically inhibited fibroblast migration as early as 4h, yet neither cholecalciferol nor 25-hydroxyvitamin D3 had any effect. VDR knockdown using small interfering RNA (siRNA) abolished the inhibitory effect of 1,25(OH)2D3 on fibroblast migration, demonstrating the requirement for the VDR in this response.
Immunofluorescent staining revealed that 1,25(OH)2D3 increased nuclear VDR protein expression, without a corresponding increase in VDR mRNA transcription only in mechanically wounded dermal fibroblasts, indicating activation of the receptors. Incubation with either 1,25(OH)2D3, cholecalciferol or 25(OH)D3 up-regulated CYP24A1 transcription. This response was most pronounced with 1,25(OH)2D3, suggesting a tightly regulated feedback control on 1,25(OH)2D3 bioavailability within the dermis. In addition, cholecalciferol also increased CYP2R1 and CYP27B1 mRNA expression in scratched dermal fibroblasts, providing evidence for autocrine regulation of 1,25(OH)2D3 by dermal fibroblasts.
Expression of α-SMA protein was up-regulated in cultured dermal fibroblasts following scratching, which was down-regulated in the presence of 1,25(OH)2D3. These observations suggest that 1,25(OH)2D3 may restrict differentiation of wounded dermal fibroblasts into pro-fibrotic myofibroblasts. 1,25(OH)2D3 also down-regulated MMP-2 secretion and collagen type I to III ratio in scratched dermal fibroblasts. Using a human ex vivo wound healing model, it was demonstrated that 1,25(OH)2D3, but not cholecalciferol, stimulated the rate of wound closure.
In summary, this study has confirmed that human dermal fibroblasts express the transcriptional machinery for autocrine production of 1,25(OH)2D3, and a higher VDR expression suggests they are more responsive than keratinocytes. Changes in CYP and VDR expression in the presence of cholecalciferol, 25-hydroxyvitamin D3 or 1,25(OH)2D3 indicate fine-tuning of the bioavailability of vitamin D in the dermis after wounding. Down-regulation of α-SMA, MMP-2 secretion and the collagen type I to III ratio by 1,25(OH)2D3 highlight an important role for 1,25(OH)2D3 in modulating wound healing and the scarring process.
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Comer, Shawna Beth. "Cholecalciferol Protects Against Deoxycholic Acid-Induced Loss of EphB2 in Human Colorectal Cancer Cells." Thesis, The University of Arizona, 2007. http://hdl.handle.net/10150/193312.
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Research has identified a linear relationship between saturated fat intake and colon cancer, and has demonstrated that high fat diets enhance tumorigenesis through elevation of secondary bile acids such as deoxycholic acid (DCA). We and others have shown that DCA can manipulate cell adhesion by decreasing expression of E-cadherin and increasing expression of beta-catenin. We have also shown that DCA significantly reduces EphB2 expression, which regulates cell positioning and segregation. Importantly, vitamin D can reinstate membranous E-cadherin/beta-catenin interactions and increase E-cadherin expression. In the present study, we sought to analyze the effects of DCA and vitamin D (cholecalciferol) treatment on EphB2 in colorectal cancer cells. Pre-treatment with cholecalciferol restored EphB2 expression in a dose-dependent manner, even with combined DCA treatment. This observation may be EGFR-dependent, suggesting that cholecalciferol may antagonize the effects of DCA. Taken together, these results suggest that cholecalciferol may represent an adjuvant therapy for colorectal cancer patients.
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Pankiv, I. V. "Effect of myo-inositol and cholecalciferol on thyroid function and autoimmunity in patients with subclinical hypothyroidism." Thesis, БДМУ, 2021. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/18835.
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Abbott, Kellie, Emilee Starnes, and Charles C. Collins. "Development of a Robust Dissolution Method for Vitamin D3." Digital Commons @ East Tennessee State University, 2020. https://dc.etsu.edu/asrf/2020/presentations/41.
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Vitamin D3 (cholecalciferol) (Vit D3) is a form of vitamin D (Vit D) that is essential for normal body function in humans. Vit D is a fat-soluble vitamin used to prevent osteoporosis in adults, prevent rickets in children, and supplement Vit D deficiencies which are seen worldwide. Physicians usually recommend 2,000 International Units (IU) Vit D3 for these deficiencies, but due to the poor aqueous solubility of Vit D3, this dose can be insufficient for patients. It would be more beneficial to recommend 5,000 IU. In 1994, the Dietary Supplement Health and Education Act was passed defining vitamins as “dietary supplements” and no longer required FDA registration prior to marketing. Dissolution results are expressed as the percent of the content released into solution, with a target of 85 to 125%. There is not an effective dissolution test existing for Vit D3 product evaluation, so an optimized dissolution test for Vit D3 was developed and used to evaluate non-prescription Vit D3 products. The current FDA guideline for Vit D3 dissolution is USP Apparatus II with 500 mL of 0.3% sodium dodecyl sulfate (SDS) in water. Since Vit D3 is not very water soluble, a surfactant is required for it to go into solution. The research was started with a larger volume (1 L) and with commonly used pharmaceutical grade surfactants: Triton X-100, Tween 80, Span 20, and sodium lauryl sulfate (SLS). SDS was eliminated due to interference with the HPLC analysis. Using two Vit D3 test products, which previous research found to have consistent drug content, each of these surfactants were tested at 0.8%. After evaluating the HPLC results, Triton and Tween were eliminated due to too much interference with the analysis process. The interference consisted of a large initial solvent front peak, elevated baseline, overlap with the drug peak, and required significant decrease in the mobile phase flow rate. Changing the mobile phase to 50/50 methanol/1-propanol solved the flow rate issue and peak separation overlap, but not the large solvent peak or elevated baseline. Dissolution testing continued using SLS and Span using 0.6%. Dissolution of the two test products, designated A and B, with 2 representing 2000 IU and 5 being 5000 IU, yielded higher values using SLS (A2 75.5%; A5 152.8%; B2 30.9%; B5 36.6%) compared to Span (A2 15%; A5 136%; B2 20.3%; B5 63%). Additional work continued to determine the best concentration of SLS. Better dissolution results were obtained using 1.2% (A2 88.1%; A5 156.7%) when compared to 0.3% (A2 87.4%; A5 153.2%), 0.6% (A2 70.7%; A5 132.2%), and 0.9% (A2 79.7%; A5 150.5%). Use of 1.5% did not yield a significant improvement (A2 84% vs 86.8%; A5 146.4% vs 144.6%), so 1.2% was chosen as this would minimize the amount of surfactant in the samples. The final dissolution method was created using a USP Apparatus II in 1000 mL containing 1.2% SLS in water. Based upon these characteristics, SLS 1.2% gave a good balance of minimizing surfactant concentration and analytical interference while maximizing Vit D3 dissolution.
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LAING, CHRISTOPHER JAMES. "Comparative Studies on Plasma Vitamin D Binding Protein." University of Sydney, 2000. http://hdl.handle.net/2123/359.
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The plasma vitamin D binding protein (DBP) is an a-glycoprotein, synthesised and secreted by the liver, which binds specifically vitamin D and its metabolites. The DBP molecule, has a single high affinity binding site for its ligands, and is present in blood in concentrations about 1000-fold greater than the sum of all its vitamin D ligands. Previous studies have not found any change in the concentration of DBP related to various derangements in mineral homeostasis. Therefore the general view is that DBP has a passive role in the physiology of vitamin D and its metabolites, and simply acts to solubilise and transport these hydrophobic ligands in the aqueous extracellular fluid. However, differences which have been described in its affinity for various vitamin D metabolites suggest that there have been evolutionary influences on the properties of this protein. Furthermore, plasma DBP concentration has been found to change in response to a number of physiological factors, such as changing sex steroid hormone secretion. The aim of the studies presented in this thesis was to investigate variation in the plasma concentration of the DBP in a range of vertebrate species, and in response to a variety of physiological factors. The results suggest that DBP may have an active role in regulating the bioavailability, and hence the utilisation and metabolism of its ligands. DBP concentration has traditionally been measured using immunological techniques. These techniques, although fast and simple, have a number of draw-backs which can be overcome by the use of assays which rely upon functional aspects of the DBP. A saturation binding assay was modified from those described previously. Using this technique, it was found that both the circulating concentration of the DBP and its affinity for 25-hydroxyvitamin D3 (25(OH)D3) varied significantly among a wide range of species of reptiles and birds. This variation did not reflect phylogenetic relationships among the study species, suggesting that the variation was more likely to be the result of selective pressure in response to individual ecological or physiological circumstance, rather than to random mutation. In support of this, both the plasma concentration of DBP, and its affinity for 25(OH)D3 were significantly associated with a number of ecological factors which might be considered to have some significance to vitamin D and calcium homeostasis. In addition, comparative binding data suggests that the ability of the DBP to bind 25-hydroxyvitamin D2 with equal affinity to 25(OH)D3 is an evolutionary innovation of mammalian vertebrates. In order to extend the idea of genetic variation in the concentration and affinity of plasma DBP, two strains of broiler (meat-type) chickens were studied. It was found that both the concentration and the affinity of plasma DBP for 25(OH)D3 was characteristic for each strain, emphasising the sensitivity of DBP to genetic variation. A number of factors have been found to modulate the genetically determined plasma concentration of DBP. Deficiencies of dietary protein and dietary energy, and variation in concentrations of sex steroids were found to affect the circulating concentration of DBP. However, species differences were still apparent, suggesting that the sensitivity of DBP to these physiological modifiers may have developed independently in different species, and may be secondary to genetic determinants of DBP properties. The plasma DBP concentration and specific binding affinity both determine the availability of its ligands for cellular uptake. It is likely that this process is complex, and involves a combination of protein mediated and non-mediated uptake events. This makes DBP a potentially important determinant of the biological actions of its ligands. The studies in this thesis have produced two main lines of argument supporting an active role for DBP in the regulation of vitamin D metabolism and utilisation. The first is that genetic variation in the properties of plasma DBP appears to be genetically determined, and is selected for, both at the between-species, and the within-species level, than it is to random mutation. Secondly, the ability of physiological and environmental factors to modify the circulating concentration of DBP suggests that this protein is responsive to homeostatic processes. It is proposed that DBP is an active regulator of the physiological economy of vitamin D and its metabolites by being itself regulated by a number of genetic and non-genetic factors.
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Dobberke, Jeanette [Verfasser]. "Vergleichende Untersuchungen zur Wirkung von serieller UV-Bestrahlung und oraler Substitution von Cholecalciferol bei leichter essentieller Hypertonie / Jeanette Dobberke." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2009. http://d-nb.info/1023583054/34.
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PALMIERI, SERENA. "IMPACT OF CHOLECALCIFEROL SUPPLEMENTATION ON SKELETAL AND NON-SKELETAL MANIFESTATIONS IN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM SUBMITTED TO PARATHYROIDECTOMY OR FOLLOWED UP WITHOUT SURGERY: CARDIOVASCULAR OUTCOMES." Doctoral thesis, Università degli Studi di Milano, 2021. http://hdl.handle.net/2434/865447.
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Context: Cardiovascular (CV) complications are a still debated issue in patients with biochemically mild primary hyperparathyroidism (PHPT) and may be related to both the PHPT condition itself and the hypovitaminosis D.
Objective: To evaluate the prevalence, nature and reversibility of CV disease and associated risk factors in a large cohort of postmenopausal mild PHPT patients surgically cured (PTx Group) or observed for two years without surgical intervention (no-PTx Group). To preliminarily assess, in both group, if the administration of two different doses (800 UI and 2000 UI) of cholecalciferol (VitD) versus no supplementation could affect the CV disease evolution.
Design: Randomized longitudinal prospective open label study.
Settings: The study was conducted in the Endocrinology Unit of two university hospitals.
Participants: 91 post-menopausal women with PHPT (38 in the PTx Group and 53 in the no-PTx Group) participated in the study.
Outcome Measures: Cardiac and vascular damage (blood pressure, transthoracic echocardiography and carotid ultrasonography), lipids and glucose metabolism, renin-angiotensin system (RAAS) activity.
Results: Arterial hypertension (AH) was found in 50.5% of patients and was not associated with PHPT after adjusting data for major CV risk factor. Diastolic dysfunction, LV hypertrophy and valve calcifications were diagnosed in 54.9%, 13.2% and 12.1% of patients and were respectively predicted by body mass index (BMI) and advancing age, by the presence of AH and by advancing age and the presence of AH, respectively. Similarly, advancing age was the only significant predictor of the presence of carotid plaque and AH was the only significant predictor of carotid intima-media thickness. We did not find any association between calcium, PTH or 25OHD and all glycemic parameters. No activation of RAAS was found in normotensive mild PHPT patients. All CV complications and risk factors were neither reversed nor significantly improved by surgery and/or VitD administration up to 24 months’ follow-up.
Conclusions: The high incidence of CV disease and metabolic derangements reported in mild PHPT may be primarily related to the coexistence of AH, advanced age or increased BMI. Moreover, the administration of VitD supplements would seem to have a neutral effect at least as regards CV complications and CV risk factors in mild PHPT patients.
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Marques, Rafael Henrique [UNESP]. "Suplementação de ração de codornas com vitaminas A, D e E sobre o desempenho e qualidade dos ovos." Universidade Estadual Paulista (UNESP), 2010. http://hdl.handle.net/11449/96612.
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Objetivou-se verificar o desempenho, concentração das vitaminas na gema e qualidade dos ovos armazenados em diferentes períodos e condições, quando codornas japonesas foram submetidas a suplementações acima das exigências de vitaminas A, D e E na dieta. Foram utilizadas 192 codornas, com 6 repetições e 8 aves por parcela, distribuídas em delineamento inteiramente casualizado. Foram avaliadas características de desempenho, concentração das vitaminas, qualidade interna e externa dos ovos frescos e armazenados. O método utilizado para quantificar as vitaminas na gema foi a Cromatografia Líquida de Alta Eficiência. A suplementação das vitaminas não proporcionou melhora no desempenho produtivo e na qualidade interna e externa dos ovos, com exceção da suplementação de vitamina D que proporcionou aumento no consumo. Quanto ao armazenamento dos ovos, pode-se concluir que a suplementação de ambas as vitaminas não influenciou estatisticamente as características estudadas. Em relação ao período de armazenamento, os resultados mostraram que a qualidade dos ovos não se alterou até os 30 primeiros dias de armazenamento. A condição de armazenamento influenciou todos os parâmetros estudados, mostrando que em temperatura refrigerada os ovos apresentaram melhor estado de conservação. Quanto à incorporação das vitaminas na gema dos ovos, verificou-se aumento de 536,27% de vitamina A para o nível de 30000 UI/kg, 13,43% de vitamina D para o nível de 1500 UI/kg e 479,05% de vitamina E para o nível de 600 UI/kg, sugerindo que o valor nutricional dos ovos, relacionado à vitamina, pode ser aumentado pela suplementação na dieta das codornas
The objective of this study was to evaluate the performance, concentration of vitamins and yolk quality of eggs stored at different times and conditions when Japanese quail were subjected to A, D and E vitamins supplementation above the diets requirements. One hundred and ninety two laying quails were used, with 6 replicates of 8 birds per unit distributed in a completely randomized design. We evaluated the performance characteristics, concentration of vitamins in the yolk, internal quality (Haugh unit, yolk index, percentage of yolk and albumen), external quality (specific weight, shell thickness, shell percent) of fresh and stored eggs. Supplementation of vitamins did not improve the performance and the internal and external quality of eggs, except for supplementation of vitamin D that provided an increase in consumption. Supplementation of both vitamins did not influence statistically the characteristics studied for stored eggs. The results showed that egg quality has not changed over the first 30 days of storage. The storage temperature influenced all traits studied and the under refrigeration than those stored in environment temperature had better quality. The incorporation of vitamins into the egg yolk could be verified. There was an increase of 536.27% of vitamin A to the level of 30000 IU / kg, 13.43% of vitamin D to the level of 1500 IU / kg and 479.05% of vitamin E to the level of 600 IU / kg, suggesting that the nutritional value of eggs, related to the vitamins may be increased by supplementation in the diet of quails
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Maboshe, Wakunyambo. "Investigating the effects of dietary-derived and sunlight-derived vitamin D3 on markers of immune function." Thesis, University of Aberdeen, 2018. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=237073.
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Primarily synthesised via cutaneous exposure to solar ultraviolet B (UVB) radiation, serum vitamin D concentrations, measured as 25-hydroxyvitamin D (25(OH)D), fluctuate according to solar availability. Seasonal variations in vitamin D are common in areas of high or low latitude determined by the distance from the sun. Seasonal variations in blood pressure, immune markers and some diseases including influenza, have also been reported. However, the contributions of UVB light or vitamin D on the immune markers have not been fully determined. Against this background, the purpose of this research was to investigate the effects of UVB light therapy and dietary vitamin D supplementation on markers of immune function. The D SIRe1 study aimed to assess whether dietary-derived 25(OH)D could have similar effects on immune function as light-derived 25(OH)D. The study was an 8-week comparative intervention trial in healthy adults randomised to receive either 3 times weekly UVB radiation (equivalent to doses received during a Grampian-summer) for 4 weeks; or oral vitamin D3 (1000 IU a day for 8 weeks). Total 25(OH)D was measured by dual tandem mass spectrometry of serum samples following removal of protein and de-lipidation, whilst regulatory T cells (Tregs), known for maintaining immune system homeostasis, by flow cytometry. The study showed similar short-term effects between oral vitamin D and UVB exposure on measured outcomes. However, study interpretation was limited by the lack of a placebo group, yet, to our knowledge, this was the first study to directly compare dose-matched UVB therapy and vitamin D supplementation in healthy participants. Using similar laboratory techniques, the D-SIRe2 study, a placebo-controlled trial, assessed short-term (12 weeks) and long-term (43 weeks) effects of vitamin D supplementation on immune markers. Commencing in spring (March) and finishing in winter (January) 2015/2016, the study showed seasonal fluctuations in most immune markers. The fluctuations did not change according to variations in 25(OH)D concentrations nor were they correlated with solar UVB doses, with the exception of T cell proliferative responses, which were positively correlated with daily solar UVB doses. An interesting finding from this study was the prevention of increases in pro-inflammatory IFN-γ cytokine concentrations in the spring and summer time in the vitamin D3 supplemental group versus placebo. IFN-γ concentrations were raised from 7940 pg/mL at baseline in March, to roughly 12400 pg/mL at week 4 and to 13909 pg/mL at week 12 in the placebo group. The concentrations were roughly 1.3 times the mean concentrations measured in the vitamin D group at the timepoints following baseline concentrations of 10678 pg/mL, and 10013 pg/mL and 10233 pg/mL at weeks 4 and 12, respectively. The interactions between solar light or seasonal effects and oral vitamin D supplementation, as well as their individual and combined effects on immune function, are yet to be fully determined. Moreover, the metabolic and physiological implications of seasonal variation in serum 25(OH)D concentration and markers of immune function are currently unknown, requiring further investigation.
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Hosseinpour, Fardin. "Cytochrome P450 Enzymes in the Metabolism of Vitamin D3." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2002. http://publications.uu.se/theses/91-554-5242-6/.
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Milone, Cristiana. "Association between Serum Vitamin D Concentrations and Depression in the US Population: National Health and Nutrition Examination Survey, 1988-1994." Digital Archive @ GSU, 2009. http://digitalarchive.gsu.edu/nutrition_theses/5.
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Background: The role of nutrients in mental health has recently been recognized and investigated. Vitamin D has been known to play a role in a wide range of diseases, such as bone, cardiovascular, and autoimmune diseases, and cancers. Recently, its role in cognitive function and mental health has been reported. Vitamin D receptor and hydroxylases have been mapped throughout the brain, suggesting a role for vitamin D in brain tissue. An inverse association between vitamin D and depression was observed in European epidemiologic studies. There is a paucity of data on the association between vitamin D concentrations and depression in the U.S. population. Objective: The objective of this study was to investigate the association between serum vitamin D concentrations and depression in a large, nationally representative sample survey, the third National Health and Nutrition Examination Survey 1988-1994 (NHANES III). Methods: The study sample included 7970 adults, ages 15-39 years, who completed the Diagnostic Interview Schedule for depression and had vitamin D concentrations measured. SAS and SUDAAN statistical software packages were used in data analysis. Multivariate logistic regression was used to estimate the likelihood of having depression in vitamin D deficient persons in relation to vitamin D sufficient persons, after taking several confounding variables into consideration. Significance was set at α < 0.05. Results: The prevalence of vitamin D deficiency was higher in women than in men (24 % vs. 15%), higher in African-Americans than in whites (60% vs. 10%), higher in people living in metropolitan rather than in rural areas (25% vs. 14%), and higher in subjects below the poverty threshold than in higher income subjects (29% vs. 14%). The prevalence of vitamin D deficiency increased as BMI increased. The diagnostic variables for depression did not show an association with vitamin D deficiency after adjusting for several confounding factors. However, subjects having a depressive episode at the time of the interview, were significantly more likely to exhibit vitamin D deficiencies (OR = 1.85; P = 0.0210). Conclusions: This is the first large epidemiologic study on the association between vitamin D and depression in a US representative sample survey. A significant positive association was found between subjects having an episode of depression and vitamin D deficiency. However, a causal relationship could not be established due to the cross-sectional nature of the study. Further studies need to investigate the mechanistic and causal relation between vitamin D and depression.
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Chaves, Matheus Andrade. "Coencapsulação de curcumina e vitamina D3 em lipossomas multilamelares." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/74/74132/tde-14062017-093408/.
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Atualmente, a demanda por alimentos com apelo funcional tem se tornado cada vez mais recorrente dentre os consumidores devido a uma crescente busca por hábitos de vida mais saudáveis. Sendo assim, o desenvolvimento de técnicas que possibilitem uma adição mais efetiva de ingredientes funcionais em matrizes alimentícias se torna uma necessidade. Essas técnicas devem possibilitar principalmente (i) a incorporação de mecanismos de liberação sustentada na formulação; (ii) o aumento da bioacessibilidade e biodisponibilidade aos ingredientes, a partir do controle da microestrutura do alimento. Esse projeto visa contemplar essas duas premissas, ao propor a encapsulação de dois bioativos hidrofóbicos, a curcumina e a vitamina D3, conhecidos pelas suas propriedades antioxidantes e nutracêuticas, em carreadores de origem lipídica, os lipossomas, estabilizando-os com diferentes hidrocoloides - goma xantana, goma guar e inulina. Os lipossomas foram produzidos por hidratação de prolipossomas e suas propriedades físico-químicas foram caracterizadas ao longo de 42 dias de armazenagem, a partir de análises de diâmetro médio hidrodinâmico, potencial zeta, colorimetria instrumental e quantificação de bioativos encapsulados. Análises que permitiram a caracterização da microestrutura das dispersões produzidas também foram realizadas, sendo elas: calorimetria diferencial de varredura (DSC), espalhamento de raios-X a baixos ângulos (SAXS) e ensaios reológicos. As análises de SAXS mostraram que lipossomas produzidos na presença de curcumina são mais estáveis que àqueles produzidos na ausência da mesma e que não houve mudança na estrutura da bicamada lipídica das vesículas após a adição de vitamina D3, mesmo quando uma alta concentração foi incorporada ao sistema (80.000 UI). Por fim, verificou-se que a coencapsulação foi possível em lipossomas multilamelares estabilizados apenas com gomas guar e xantana, resultado que pode ser comprovado pelo alto teor de retenção dos bioativos ao longo do tempo de armazenagem.Currently, the demand for food with functional appeal has become increasingly recurrent among the consumers due to a growing search for healthier living habits. Therefore, the development of techniques that allow a more effective addition of functional ingredients in food matrices becomes a necessity. These techniques should mainly enable to (i) incorporate a sustained release mechanisms into the formulation; (ii) increase the bioaccessibility and bioavailability to these ingredients, from the control of the food microstructure. This project aims to contemplate these two premises by proposing the encapsulation of two hydrophobic bioactives, curcumin and vitamin D3, known for their antioxidant and nutraceutical properties, in liposomes - lipid carriers - stabilizing them with different hydrocolloids - xanthan gum, guar gum and inulin. Liposomes were produced by proliposomes hydration and their physicochemical properties were characterized during 42 days of storage, including analyzes of hydrodynamic average diameter, zeta potential, instrumental colorimetry and quantification of encapsulated bioactives. Analyzes that allowed the microstructure characterization of the produced dispersions were also performed, including: differential scanning calorimetry (DSC), small-angle X-ray scattering and rheological tests. The SAXS analysis showed that liposomes produced in the presence of curcumin were more stable when compared to the empty ones and that there was no change in the lipid bilayer of the vesicles after the addition of vitamin D3, even when a high concentration was incorporated into the system (80,000 IU). Finally, it was concluded that the coencapsulation was possible in multilamellar liposomes stabilized with guar and xanthan gums, a result that can be evidenced by the high content of bioactives retained throughout the storage time.
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Chen, Jiaxuan. "The role of Pdia3 in vitamin D signaling in osteoblasts." Diss., Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/50147.
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1a,25-Dihydroxyvitamin D3 (1a,25(OH)2D3) is a major functional metabolic form of vitamin D. 1a,25(OH)2D3 has drawn increasing attention due to its functions in addition to maintaining calcium phosphate homeostasis. It directly regulates mineralization by osteoblasts, matrix production and remodeling by chondrocytes, and contraction of cardiomyocytes. 1a,25(OH)2D3 and its analogues have shown beneficial effects in treating multiple sclerosis, diabetes and various types of cancer. In order to maximize the pharmaceutical potential of 1a,25(OH)2D3, a better understanding its cell signaling pathway is necessary. 1a,25(OH)2D3 regulates osteoblasts through both classical nuclear vitamin D receptor (nVDR) mediated genomic effects and plasma membrane receptor-mediated rapid responses. The identity of the plasma membrane receptor for 1a,25(OH)2D3 is controversial. Protein disulfide isomerase associated 3 (Pdia3) has been hypothesized as one of the putative plasma membrane receptors for 1a,25(OH)2D3. The overall goal of this thesis was to understand the general role and the molecular mechanism of Pdia3 in 1a,25(OH)2D3-initiated rapid responses, and to determine the role of Pdia3 and its dependent signaling in osteoblast biology. The results show that Pdia3 is required for membrane-mediated responses of 1a,25(OH)2D3. Moreover, both Pdia3 and nVDR are critical components of the plasma membrane receptor complex for 1a,25(OH)2D3. Finally, Pdia3 and signaling via Pdia3 regulate osteoblast differentiation and mineralization. Taken together, this study demonstrates the role of Pdia3 in rapid responses to 1a,25(OH)2D3 and osteoblast biology, reveals the unexpected complexity of the 1a,25(OH)2D3 plasma receptor complex and opens the new target, Pdia3, for pharmaceutical application and tissue engineering.
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Schnor, Stella [Verfasser], and Markus [Akademischer Betreuer] Rodehutscord. "Vergleich der Wirksamkeit von 25-Hydroxycholecalciferol und konventionellem Cholecalciferol in der Fütterung von Zuchtsauen anhand von Blutmetaboliten, Leistungs- und Knochendaten / Stella Schnor ; Betreuer: Markus Rodehutscord." Hohenheim : Kommunikations-, Informations- und Medienzentrum der Universität Hohenheim, 2017. http://d-nb.info/1129779629/34.
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Marques, Rafael Henrique. "Suplementação de ração de codornas com vitaminas A, D e E sobre o desempenho e qualidade dos ovos /." Jaboticabal : [s.n.], 2010. http://hdl.handle.net/11449/96612.
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Resumo: Objetivou-se verificar o desempenho, concentração das vitaminas na gema e qualidade dos ovos armazenados em diferentes períodos e condições, quando codornas japonesas foram submetidas a suplementações acima das exigências de vitaminas A, D e E na dieta. Foram utilizadas 192 codornas, com 6 repetições e 8 aves por parcela, distribuídas em delineamento inteiramente casualizado. Foram avaliadas características de desempenho, concentração das vitaminas, qualidade interna e externa dos ovos frescos e armazenados. O método utilizado para quantificar as vitaminas na gema foi a Cromatografia Líquida de Alta Eficiência. A suplementação das vitaminas não proporcionou melhora no desempenho produtivo e na qualidade interna e externa dos ovos, com exceção da suplementação de vitamina D que proporcionou aumento no consumo. Quanto ao armazenamento dos ovos, pode-se concluir que a suplementação de ambas as vitaminas não influenciou estatisticamente as características estudadas. Em relação ao período de armazenamento, os resultados mostraram que a qualidade dos ovos não se alterou até os 30 primeiros dias de armazenamento. A condição de armazenamento influenciou todos os parâmetros estudados, mostrando que em temperatura refrigerada os ovos apresentaram melhor estado de conservação. Quanto à incorporação das vitaminas na gema dos ovos, verificou-se aumento de 536,27% de vitamina A para o nível de 30000 UI/kg, 13,43% de vitamina D para o nível de 1500 UI/kg e 479,05% de vitamina E para o nível de 600 UI/kg, sugerindo que o valor nutricional dos ovos, relacionado à vitamina, pode ser aumentado pela suplementação na dieta das codornasAbstract: The objective of this study was to evaluate the performance, concentration of vitamins and yolk quality of eggs stored at different times and conditions when Japanese quail were subjected to A, D and E vitamins supplementation above the diets requirements. One hundred and ninety two laying quails were used, with 6 replicates of 8 birds per unit distributed in a completely randomized design. We evaluated the performance characteristics, concentration of vitamins in the yolk, internal quality (Haugh unit, yolk index, percentage of yolk and albumen), external quality (specific weight, shell thickness, shell percent) of fresh and stored eggs. Supplementation of vitamins did not improve the performance and the internal and external quality of eggs, except for supplementation of vitamin D that provided an increase in consumption. Supplementation of both vitamins did not influence statistically the characteristics studied for stored eggs. The results showed that egg quality has not changed over the first 30 days of storage. The storage temperature influenced all traits studied and the under refrigeration than those stored in environment temperature had better quality. The incorporation of vitamins into the egg yolk could be verified. There was an increase of 536.27% of vitamin A to the level of 30000 IU / kg, 13.43% of vitamin D to the level of 1500 IU / kg and 479.05% of vitamin E to the level of 600 IU / kg, suggesting that the nutritional value of eggs, related to the vitamins may be increased by supplementation in the diet of quails
Orientadora: Vera Maria Barbosa de Moraes
Coorientadora: Sandra Aidar de Queiroz
Banca: Otto Mack Junqueira
Banca: Antonio Carlos de Laurentiz
Mestre
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Machado, Carla da Silva. "Avaliação da instabilidade genômica, estresse oxidativo e modulação da expressão gênica pela vitamina D em modelo de ratos espontaneamente hipertensos." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/17/17135/tde-04012017-094931/.
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A vitamina D3 é um micronutriente obtido da dieta ou pela conversão do 7- dehidrocolesterol na epiderme após exposição à radiação UVB. A vitamina D (D2 ou D3) atua sobre o sistema renina-angiotensina-aldosterona, e sua deficiência vem sendo associada ao desenvolvimento da hipertensão. O objetivo deste estudo foi avaliar o efeito da suplementação ou deficiência de vitamina D3 em ratos espontaneamente hipertensos (SHR - spontaneously hypertensive rats) e seus controles normotensos (Wistar Kyoto - WKY) sobre a pressão arterial sistólica, danos ao DNA e cromossomos, marcadores bioquímicos do estresse oxidativo, burst oxidativo dos neutrófilos, análise de fibrose no rim e perfil de expressão de genes relacionados com a hipertensão arterial no rim e coração. Os animais foram alimentados com dieta controle (1.000 UI/kg), suplementada (10.000 UI/kg) ou deficiente (0 UI/kg) em vitamina D3 ao longo de 12 semanas. A quantificação plasmática de vitamina D3 foi avaliada pelo método ELISA (Enzyme-Linked Immunosorbent Assay) e a pressão arterial sistólica foi aferida semanalmente, por método não invasivo de pletismografia da artéria caudal. Os danos ao material genético foram avaliados pelo ensaio do cometa nas células do sangue periférico, rim e coração e pelo teste do micronúcleo nos eritrócitos da medula óssea e sangue periférico; o estresse oxidativo foi avaliado pelos ensaios de quantificação das substâncias reativas ao ácido tiobarbitúrico (TBARS - Thiobarbituric Acid Reactive Substances) e glutationa (GSH) no rim e coração; o burst oxidativo em neutrófilos do sangue periférico; a quantificação de fibrose por histologia renal e a expressão gênica por RT2 ProfilerTM PCR Arrays no rim e coração. Os resultados obtidos com os ratos SHR mostraram que a suplementação com vitamina D3 reduziu a pressão arterial sistólica, não induziu danos ao DNA e aos cromossomos, estresse oxidativo ou fibrose renal, e regulou a expressão de quatro genes envolvidos com a hipertensão arterial no rim (Ace, Agt, Ren e Edn1) e cinco genes no coração (Ace, Avp, Ephx2, Mylk3 e Ren). A deficiência em vitamina D3 aumentou a pressão arterial sistólica, os danos ao DNA e aos cromossomos, a peroxidação lipídica no rim e coração, o burst oxidativo dos neutrófilos, o percentual de fibrose no rim, e a expressão de treze genes envolvidos com a hipertensão arterial no rim (Ace, Acta2, Agt, Agtr1a, Agtr1b, Alox5, Cacna1c, Ece1, Ednra, Kcnma1, P2rx4, Scnn1g e Slc7a1) e nove genes no coração (Ace, Agtr1b, Cacna1c, Drd5, Mylk2, Nostrin, Scnn1a, Scnn1g e Sphk1). Nos animais WKY, a dieta suplementada alterou a expressão do gene Ren no rim e de dez genes no coração (Ace2, Bdkrb2, Drd3, Drd5, Itpr1, Itpr2, Itpr3, Ptgs1, Scnn1a e Scnn1g); e a dieta deficiente em vitamina D3 aumentou os danos ao DNA nos eritrócitos, induziu fibrose no rim e alterou a expressão de três genes no rim (Ace, Cps1 e Arg2) e de seis genes no coração (Ace, Cacna1c, Edrna, Ephx2, Itpr1 e Itpr2). Nos parâmetros pressão arterial sistólica, danos aos cromossomos, peroxidação lipídica e burst oxidativo, os ratos WKY alimentados com as dietas suplementada ou deficiente em vitamina D3 não diferiram em relação aos animais que receberam a dieta controle. Em conclusão, a variação da concentração de vitamina D3 da dieta alterou a fisiologia da hipertensão arterial, atuando como um anti-hipertensivo na suplementação e agravando os efeitos da hipertensão na deficiência.Vitamin D3 is a micronutrient obtained from diet or by conversion of 7- dehydrocholesterol in the skin after exposure to UVB radiation. Vitamin D (D2 or D3) acts on the renin-angiotensin-aldosterone system, and its deficiency has been associated with hypertension development. This study aimed to evaluate the effect of vitamin D3 supplementation or deficiency in spontaneously hypertensive rats (SHR - spontaneously hypertensive rats) and their normotensive controls (Wistar Kyoto - WKY) on systolic blood pressure, DNA and chromosomes damage, biochemical markers of oxidative stress, oxidative burst in neutrophils, renal fibrosis and the gene expression profile of genes related to hypertension in kidney and heart. The rats were fed a vitamin D3 control diet (1,000 IU/kg) supplemented diet (10,000 IU/kg) or deficient diet (0 IU / kg) during 12 weeks. Vitamin D3 plasma quantification was performed by ELISA (Enzyme-Linked Immunosorbent Assay) technique and systolic blood pressure was measured weekly by noninvasive plethysmography of the caudal artery. DNA and chromosomal damage was evaluated by the comet assay in the peripheral blood, kidney and heart cells and by the micronucleus test in erythrocytes from bone marrow and peripheral blood; oxidative stress was evaluated by thiobarbituric acid reactive substances (TBARS) and glutathione (GHS) assays in kidney and heart; oxidative burst in neutrophils of peripheral blood; renal fibrosis by histology and gene expression by RT2 ProfilerTM PCR Arrays in kidney and heart. The results obtained for SHR rats showed that vitamin D3 supplementation reduced systolic blood pressure, did not induced DNA or chromosomal damage, oxidative stress or renal fibrosis, and regulated the expression of four genes involved with hypertension in the kidney (Ace, Agt, Ren and Edn1) and five genes in the heart (Ace, Avp, Ephx2, Mylk3 and Ren). Vitamin D3 deficiency increased systolic blood pressure, DNA damage in erythrocytes, lipid peroxidation in kidney and heart, oxidative burst in neutrophils and the renal fibrosis, and regulates the expression of thirteen genes involved with hypertension in kidney (Ace, Acta2, Agt, Agtr1a, Agtr1b, Alox5, Cacna1c, Ece1, Ednra, Kcnma1, P2rx4, Scnn1g and Slc7a1) and nine genes in heart (Ace, Agtr1b, Cacna1c, Drd5, Mylk2, Nostrin, Scnn1a, Scnn1g and Sphk1). In WKY rats, vitamin D3 supplementation altered the expression of Ren gene in the kidney and of ten genes in the heart (Ace2, Bdkrb2, Drd3, Drd5, Itpr1, Itpr2, Itpr3, Ptgs1, Scnn1a and Scnn1g); and vitamin D3 deficiency increased DNA damage in erythrocytes and renal fibrosis, and altered the expression of three genes in the kidney (Ace, Cps1 and Arg2) and six genes in the heart (Ace, Cacna, Ednra, Ephx2, Itpr1 and Itpr2). In the parameters systolic blood pressure, chromosomal damage, lipid peroxidation and oxidative burst, WKY rats fed with vitamin D3 supplemented or deficient diet did not differ compared to rats that received vitamin D3 control diet. In conclusion, the variation of dietary vitamin D3 levels altered the physiology of hypertension, acting as an antihypertensive in supplementation and aggravating the hypertension effects in its deficiency.
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Towers, Terri L. "Vitamin D3-mediated transcriptional repression : of the granulocyte-macrophage colony stimulating factor gene /." Access full-text from WCMC, 1998. http://proquest.umi.com/pqdweb?did=733066141&sid=3&Fmt=2&clientId=8424&RQT=309&VName=PQD.
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Scalcon, Márcia Regina Rosa. "EFEITO DE DOSE ÚNICA DE VITAMINA D NAS CONCENTRAÇÕES SÉRICAS DE CITOCINAS EM MULHERES IDOSAS NA PÓS-MENOPAUSA." Universidade Federal de Santa Maria, 2014. http://repositorio.ufsm.br/handle/1/9031.
Full textAbstract:
Vitamin D is an important immunomodulator. Epidemiological studies have shown that vitamin D deficiency impairs the immune functions and participates in the pathogenesis of infectious and autoimmune diseases. Vitamin D supplementation has shown significant changes on circulating concentrations of inflammatory markers in different clinical conditions. However, the effect of single large-dose of vitamin D3 in immune system in elderly people remains unclear. We carried out a randomized, double-blind, placebo-controlled clinical trial to evaluate the possible benefic effect of single oral dose of 300.000 IU of vitamin D3 on inflammatory markers in elderly post-menopausal women. A total of 40 women aged over 60 years were selected to receive 300.000 IU of cholecalciferol (n = 20) or placebo (n = 20) at baseline. Serum 25-hydroxyvitamin D [25(OH)D] were similar in both group at baseline [16.4 ng/ml (± 3.8) in vitamin D group and 15 ng/ml (± 3.7) in placebo groups, p = 0.23]. Serum levels of IL-6, TNF-α and IL-10 were measured by ELISA at baseline, and 30, 60 and 90 days after intervention. In the vitamin D group, we found a significant median percent decline in levels of IL-6 (30.8%, p = 0.006) and TNF-α (48.6%, p < 0.0001), associated with a significant median percent increase in levels of IL-10 (68.4%, p < 0.0001) after 90 days. We concluded that a single oral dose of 300.000 IU of cholecalciferol, in the short time, is able to improve the cytokines profile in elderly women with vitamin D deficiency.A vitamina D é um importante imunomodulador. Estudos epidemiológicos têm demonstrado que a deficiência de vitamina D prejudica as funções imunológicas e participa na patogênese de doenças infecciosas e autoimunes. A suplementação de vitamina D tem demonstrado significativas alterações nas concentrações circulantes de marcadores inflamatórios em diferentes condições clínicas. No entanto, o efeito de dose única e elevada de vitamina D3 no sistema imune de pessoas idosas, permanece obscuro. Nós realizamos um ensaio clínico, randomizado, duplo-cego, controlado por placebo para avaliar o possível efeito benéfico de uma dose oral única de 300.000 UI de vitamina D3 em marcadores inflamatórios em mulheres idosas na pós-menopausa. Um total de 40 mulheres com idade superior a 60 anos foram selecionados para receber 300.000 UI de colecalciferol (n = 20) ou placebo (n = 20) no início do estudo. As dosagens de 25-hidroxivitamina D séricas [25(OH)D] foram semelhantes em ambos os grupos no início do estudo [16,4 ng/ml (± 3,8) no grupo vitamina D e 15 ng/ml (± 3,7) no grupo placebo, p = 0,23]. Os níveis séricos de IL-6, TNF-α e IL-10 foram medidos por ELISA no início do estudo e 30, 60 e 90 dias após a intervenção. No grupo da vitamina D, verificou-se uma diminuição significativa na percentagem média dos níveis de IL-6 (30.8 %, p = 0.006) e TNF-α (48.6 %, p < 0.0001), associada com um aumento percentual médio significativo nos níveis de IL-10 (68.4 %, p < 0.0001) após 90 dias. Concluímos que uma dose oral única de 300.000 UI de colecalciferol, em um curto espaço de tempo, é capaz de melhorar o perfil das citocinas em mulheres idosas com deficiência de vitamina D.
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Vogt, Barbara Perez. "Efeitos da suplementação de vitamina D e treinamento físico aeróbico sobre a função muscular e composição corporal de pacientes em hemodiálise crônica." Botucatu, 2017. http://hdl.handle.net/11449/150250.
Full textAbstract:
Orientador: Jacqueline Costa Teixeira CaramoriResumo: Background: function and muscle mass depletion is frequent in hemodialysis patients, as well as vitamin D deficiency. Vitamin D supplementation exerts positive effects on muscles, and clinical trials combining vitamin D supplementation and physical training have promoted improvements on functional capacity and muscle quality in elderly. Objective: to assess the effects of vitamin D supplementation and intradialytic aerobic training (IDAT) on biochemical parameters, body composition, and muscle function in patients on maintenance hemodialysis. Methods: clinical trial with two arms: randomized, controlled, and double-blind for vitamin D, and randomized, controlled and open-label for IDAT. Patients were randomized in one of the four groups: vitamin D supplementation and IDAT, placebo and IDAT, vitamin D supplementation, and placebo. Muscle mass was assessed by dual-energy X-ray absorptiometry and muscle function was assessed by handgrip strength. Intervention lasted 16 weeks. IDAT program was performed using cycle ergometer, three times a week during hemodialysis session. Vitamin D supplementation was cholecalciferol 50,000 IU per week and vitamin D status was evaluated by serum 25-hydroxyvitamin D (25(OH)D) levels. Results: twenty-nine patients were enrolled in this trial. Nine were excluded during the intervention. Serum vitamin D significantly rose in both groups supplemented with cholecalciferol (baseline: 30.1 ± 6.26 ng/ml; post-intervention: 41.3 ± 9.85 ng/ml; p<0.001). Th... (Resumo completo, clicar acesso eletrônico abaixo)
Doutor
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Mak, Jenson Chun Sum. "Vitamin D replenishment and vitamin D status in functional outcomes following hip fracture surgery." Thesis, The University of Sydney, 2015. http://hdl.handle.net/2123/13825.
Full textAbstract:
Background: Older people presenting with hip fractures requiring surgery have a high prevalence of hypovitaminosis D, which is an important modifiable risk factor for falls and fractures. Inadequate sun exposure is the main reason for vitamin D deficiency in older people. Vitamin D supplements, with or without calcium have been shown to reduce falls and fracture risk in this population. Undertreated pain is a risk factor for delirium and a barrier to rehabilitation interventions following a hip fracture. A small number of randomised controlled trials (RCTs) have shown increased 25-OHD levels with a loading dose of vitamin D may improve falls and fractures. Low vitamin D levels have also been implicated in pain generally, as well as static and dynamic pain responses to mobility. It is not known whether oral vitamin D replenishment using a loading dose is effective, and if it is, what is the interplay this is with patient characteristics, in particular self-reported pain rating levels, lower limb mobility and 25-OHD levels. Aims: The aims of this research were (1) to characterise the predictive factors of 25-OHD levels; (2) to characterise the predictive factors of self-reported pain after hip fracture; (3) to determine the benefit of early loading-dose oral vitamin D replenishment and determine the 25-OHD response; (4) to evaluate safety profile of an initial high-dose (250,000IU) vitamin D followed by daily maintenance for 6 months; (5) to monitor its effects on functional mobility, falls, fractures, grip strength, health related quality of life and mortality. Methods: Participants of the REVITAHIP RCT cohort (mean age of 220 participants was 83.9 (SD 7.2) years and 77.1% were women): Active (111) and Placebo (107) participants were randomised to loading dose (250000IU vitamin D3) vs placebo followed by 6 months maintenance oral therapy (vitamin D3/calcium: 800IU/600mg) daily. Primary outcome measures are 2.4m gait-velocity, with secondary outcome measures of falls, fractures (Week-4), 25-OHD levels, quality-of-life measure (EQ-5D), mortality at weeks-2, 4 and 26 with additional measures of pain (via the numerical rating scale [NRS]) were correlated with patient characteristics in this cohort. Results: Hypovitaminosis D (25-OHD <50nmol/L) was present in 46.8% of participants and 15.4% had 25-OHD levels lower than 30nmol/L. Multivariate regression models demonstrated higher baseline vitamin D levels were significantly associated with higher premorbid Barthel Index scores and lower post-operative NRS pain levels. Further, the mean (SD) NRS pain score was 3.5 (2.3). More than half (61.9%, n=113) had NRS>3 and 18.1% (n=52) had NRS>5. Using the EQ-5D pain sub-score, 78.1% had moderate pain or discomfort and 7.9% had extreme pain or discomfort. Using a multivariate regression model, postoperative NRS was significantly higher in persons with a higher comorbidity count, those previously living independently alone, and surgical fixation with hemiarthroplasty. After loading dosing administration, 25-OHD levels were significantly higher for the Active group when compared to the Placebo group at 2 weeks (73 vs 66 nmol/L; p=.019) and at 4 weeks (83 vs 75nmol/L; p=.030). At week 4, the Active group had a significantly lower percentage of people with suboptimal 25-OHD levels (3.2% vs 15.4%, p=.019). At week 4, participants in the Active group had a gait velocity over 2.4m of 0.42m/s compared with 0.39m/s in the placebo group (p=.490). To week 4, seven (6.3%) participants in the Active group reported 1 or more falls compared to twenty-three (21.1%) in the Placebo group (χ2 = 4.327; p=.024) but there were no differences in fractures (2.7% vs 2.8%, p=.964) or grip strength. The number of deaths was non-significantly lower in the Active group compared with the Placebo group at 4 weeks (1 vs 3, p = .295). There was a trend for Active participants to have a higher total EQ-5D scores at Week 26 (88.1+/-13.2 vs 84.3+/-15.8, F=2.87, p=.092). Active participants were significantly more likely to present with ‘no pain or discomfort’ at Week 26 (96.4% vs 88.8%, p=.037). One case of hypercalcemia at 2 weeks was noted in the Active group which normalised after 4 and 26 weeks. Discussion and Conclusions: This study cohort shared similar demographic characteristics and comorbidities with other cohorts of people with hip fracture. Hypovitaminosis D was not as prevalent as previously documented. Patients taking vitamin D supplements and with higher premorbid Barthel Index, reflecting greater independence and activity, tended to have higher 25-OHD levels at baseline. Further, lower NRS pain ratings following surgery were associated with higher vitamin D levels. Overall, the levels of pain reported by this cohort are acceptable although approximately 10% to 15% had higher than reasonable levels of pain. Despite a higher than expected baseline 25-OHD level and moderate increases in 25-OHD levels, participants in the Active REVITAHIP group resulted in a greater percentage with target 25-OHD levels (>50nmol/L) compared with the placebo group with no significant differences in gait velocity at 4 weeks. Lower numbers of falls and improved pain control were noted in the Active group over the study period. In this cohort, there was a higher than expected baseline 25OH level which could have underestimated the effect of the intervention in a group with lower baseline 25-OHD levels.
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Jehan, Frédéric. "Etude de la régulation de la synthèse du NGF : implication des hormones stéroïdes, des seconds messagers et des proto-oncogènes des familles Fos et Jun." Angers, 1993. http://www.theses.fr/1993ANGE0013.
Full textAbstract:
Le nerve growth factor (NGF) est une protéine, secrétée par différents types cellulaires, qui agit sur la survie et la différenciation de diverses populations neuronales, dans les systèmes nerveux périphérique et central. Le présent travail a pour objet de préciser certains mécanismes cellulaires et moléculaires impliques dans la régulation de la production de ce facteur. Il est d'abord montré que la 1,25(oh)2d3 et un de ses analogues pharmacologiques, le composé mc903, moins actif sur le métabolisme du calcium et donc moins toxique, stimulent la synthèse du NGF dans les cellules fibroblastiques l929. A l'inverse, les glucocorticoïdes inhibent les effets promoteurs induits par ces deux composés, ce qui suggère que l'équilibre entre les concentrations circulantes de 1,25-(oh)2d3 et de glucocorticoïdes pourrait aboutir à une altération des niveaux de NGF in vivo, comme on l'observe chez des animaux atteints de neuropathies liées au diabète. Les résultats présentés dans une seconde partie, montrent que l'hormone thyroïdienne, qui se lie à un récepteur proche de celui de la 1,25-(oh)2d3 est également active sur l'expression du gène NGF, puisque son injection a des rats thyroïdectomises rétablit des niveaux normaux de NGF dans le cerveau. La 3ème partie du travail porte sur l'implication des voies de transduction mettant en jeu divers messagers secondaires, dans les mécanismes de contrôle du gène du NGF. L'activation des protéines kinases C par les esters de phorbol aboutit à un fort accroissement des niveaux de NGF dans les fibroblastes l929 ou dans les astrocytes en culture primaire. Une augmentation de l'AMPC par la forskoline ou l'augmentation du calcium intracellulaire inhibent fortement l'effet promoteur de la protéine kinase C. A l'inverse, 1,25-(oh)2d3 et protéine kinase C ont un effet additif. Ce travail met en évidence la complexité des mécanismes régulateurs impliques dans la synthèse du NGF.
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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.
Full textAbstract:
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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Lehmann, Bodo, Peter Knuschke, and Michael Meurer. "A Novel Pathway for Hormonally Active Calcitriol." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-134532.
Full textAbstract:
Calcitriol [1α,25(OH)2D3], the hormonally active form of vitamin D3 (D3) is produced in both renal and extrarenal tissues. Our findings demonstrate that physiological doses of UVB radiation at 300 nm induce the conversion of 7-dehydrocholesterol (7-DHC) via preD3 and D3 into calcitriol in the pmol range in epidermal keratinocytes. The hydroxylation of photosynthesized D3 to calcitriol is strongly suppressed by ketoconazole, a known inhibitor of cytochrome P450 mixed function oxidases. The UVB-induced formation of calcitriol in human skin is demonstrable in vivo by the microdialysis technique. These results suggest that human skin is an autonomous source of hormonally active calcitriolDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
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Bella, Leonardo Mendes. "Estudo da suplementação de vitamina D em modelo experimental de diabetes mellitus." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/9/9136/tde-04052015-090905/.
Full textAbstract:
O diabetes mellitus (DM) é uma doença com prevalência e morbidade elevadas em todo o mundo, sendo que o DM1 é responsável por 5-10% dos casos. A vitamina D, hormônio de ação pleiotrópica, pode melhorar o curso do DM1, embora os mecanismos não estejam completamente elucidados. Dessa forma, ampliar o conhecimento sobre a ação desse hormônio pode auxiliar no prognóstico, bem como na compreensão dos possíveis mecanismos envolvidos na prevenção do DM. Neste trabalho, foram avaliados os efeitos fisiológicos da suplementação de vitamina D (800 UI/dia/sete dias; via oral) em camundongos machos (n=31; linhagem C57BL/6) distribuídos em quatro grupos: Controle + Água (CA; n=9); Controle + Vitamina D (CV; n=9); Diabético + Água (DA; n=6) e Diabético + Vitamina D (DV; n=7). Os camundongos tornados diabéticos (aloxana, 60 mg/Kg, intravenosa), quando comparados aos controles, exibiram redução do peso corporal e concentrações plasmáticas de glicose mais elevadas durante o período experimental de 10 dias (características do estado insulinopênico). Entretanto, a suplementação com vitamina D não alterou essa condição. Camundongos tornados diabéticos, em relação aos controles, exibiram redução do peso corporal (p<0,05) e concentrações plasmáticas de glicose (p<0,001) mais elevadas durante o período experimental. Animais suplementados com vitamina D apresentaram, em relação aos controles, níveis de 25(OH)D mais elevados (CA vs CV, p<0,001; DA vs DV, p<0,001). Níveis séricos maiores de ureia (CA vs DA, p<0,05; CA vs DV, p<0,01; CV vs DA, p<0,05; CV vs DV, p<0,01) e creatinina (CA vs DA, p<0,001; CA vs DV, p<0,001; CV vs DA, p<0,001; CV vs DV, p<0,001), espessamento da cápsula de Bowman, hipertrofia glomerular e destruição de hepatócitos foram observados em camundongos diabéticos em relação aos controles. Entretanto, a suplementação com vitamina D não alterou estas condições. O grupo DA apresentou menor nível sérico de albumina em relação aos grupos CA (p<0,05) e CV (p<0,05); níveis inferiores de hemoglobina (p<0,05) e hematócrito (p<0,05) em relação ao grupo DV; e menor leucometria (p<0,05) e mononucleares sanguíneos (p<0,05) em relação ao grupo CA. Os resultados sugerem que a vitamina D possa influenciar a resposta imunológica em animais diabéticos, modulando hematócrito, hemoglobina, bem como os níveis séricos de albuminaDiabetes mellitus (DM) is a disease with high prevalence and morbidity worldwide, and the DM1 is responsible for 5-10% of cases. The vitamin D hormone pleiotropic action, can improve the course of T1DM, although the mechanisms are not fully elucidated. Thus, better understanding the action of this hormone can aid in prognosis as well as in understanding the possible mechanisms involved in the prevention of diabetes. We evaluated the physiological effects of vitamin D (800 IU/day/seven days, v.o.) in male mice (n=31, C57BL/6 strain) divided into four groups: Control + Water (CW, n=9); Control Vitamin D + (CV n=9); Diabetic + Water (DW, n=6) Diabetic + Vitamin D (VD, n=7). The mice induced-diabetes by alloxan (60 mg/kg, i.v.), when compared to controls, exhibited reduced body weight and plasma glucose concentrations were higher during the experimental period of 10 days (features insulinopenic state). However, vitamin D supplementation did not alter this condition. Diabetic mice, compared to controls, exhibited reduced body weight (p<0,05) and plasma glucose concentrations (p <0.001) higher during the trial period. Animals supplemented with vitamin D showed higher levels of 25 (OH) D than controls (CW vs CV, p <0,001; DW vs DV, p<0,001). Higher serum urea (CW vs. DW, p <0,05; CW vs DV, p <0,01; CV vs DA, p <0,05; CV vs DV, p <0,01) and creatinine (CW vs. DW, p <0,001; CW vs DV, p <0,001; CV vs DW, p <0,001; CV vs DW, p <0,001), thickening of Bowman\'s capsule, glomerular hypertrophy and destruction of hepatocytes were observed in diabetic mice compared to controls. However, vitamin D supplementation did not alter these conditions. The DW group showed lower serum albumin compared to CW (p<0,05) and CV (p<0,05) groups; lower hemoglobin (p<0,05) and hematocrit (p <0,05) compared to the DV group; and lower leukocyte counts compared to CW (p <0,05) and mononuclear blood (p <0,05) compared to the CW group. The results suggest that Vitamin D may influence the immune response in diabetic animals, modulating hematocrit, hemoglobin and serum albumin
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Castillo, Hilda S. "Mutational analysis and engineering of the human vitamin D receptor to bind and activate in response to a novel small molecule ligand." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/39502.
Full textAbstract:
Nuclear receptors (NRs) are ligand-activated transcription factors that regulate the expression of genes involved in all physiological activities. Disruption in NR function (e.g. mutations) can lead to a variety of diseases; making these receptors important targets for drug discovery. The ability to bind a broad range of 'drug-like' molecules also make these receptors attractive candidates for protein engineering, such that they can be engineered to bind novel small molecule ligands, for several applications. One application is the creation of potential molecular switches, tools that can be used for controlling gene expression.
Gaining knowledge of specific molecular interactions that occur between a receptor and
its ligand is of interest, as they contribute towards the activation or repression of target genes. The focus of this work has been to investigate the structural and functional relationships between the human vitamin D receptor (hVDR) and its ligands. To date, mutational assessments of the hVDR have focused on alanine scanning and residues typically lining the ligand binding pocket (LBP)that are involved in direct interactions with the ligand. A comprehensive analysis of the tolerance of these residues in the binding and activation of the receptor by its ligands has not been performed. Furthermore, residues not in contact with the ligand or that do not line the LBP may also play an important role in determining the activation profiles observed for NRs, and therefore need to be explored further.
In order to engineer and use the hVDR in chemical complementation, a genetic selection
system in which the survival of yeast is linked to the activation of a NR by an agonist, the hVDR
gene was isolated from cDNA. To gain insight into how chemical and physical changes within the ligand binding domain (LBD) affect receptor-ligand interactions, libraries of hVDR variants exploring the role and tolerance of hVDR residues were created. To develop a comprehensive mutational analysis while also engineering the hVDR to bind a novel small molecule ligand, a rational and a random mutagenic approach were used to create the libraries. A variant, hVDRC410Y, that displayed enhanced activity with lithocholic acid (LCA), a known hVDR ligand, and novel activation with cholecalciferol (chole), a precursor of the hVDR's natural ligand known not to activate the wild-type hVDR, was discovered.
The presence of a tyrosine at the C410 position resulting in novel activation profiles with both LCA and chole, and the fact that this residue does not line the hVDR's LBP led to interest in determining whether a physical or chemical property of the residue was responsible for the observed activity. When residue C410 was further assessed for its tolerance to varying amino acids, the results indicated that bulkiness at this end of the pocket is important for activation with these ligands. Both LCA and chole have reduced molecular volumes compared to the natural ligand, 1alpha, 25(OH)2D3. As a result, increased bulkiness at the C410 position may contribute additional molecular interactions between the receptor and ligands.
Results obtained throughout this work suggest that the end of the hVDR's LBP consisting
of two ligand anchoring residues, H305 and H397, and residue C410 tolerates structural variations, as numerous variants with mutations at these positions displayed enhanced activity. The receptor contains two tyrosines, Y143 and Y147, which were targeted for mutagenesis in one
of the rationally designed libraries, located at the exact opposite end of the pocket. In an effort to gain further insight into the role of these residues at the other end of the LBP, mutagenesis
assessing the tolerance of tyrosines 143 and 147 was performed. Overall, most changes at these
positions proved to be detrimental to the function of the receptor supporting the hypothesis that
this end of the LBP is less tolerant of structural changes, compared to the opposite end consisting
of residues H305, H397 and C410.
Overall, a better understanding of the structural and functional relationships between the human vitamin D receptor (hVDR) and its ligands was achieved. The effects of residue C410 on specificity and activation with the different ligands studied were unforeseen, as this residue does not line the receptor's ligand binding pocket (LBP). However, they serve as an example of the
significant impact distant residues can have on receptor activation and also emphasize the
important role physical properties of residues, such as volume, can play for specific ends of the
LBP compared to chemical properties.
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Nascimento, Priscilla Marques do. "Impacto da administração das vitaminas D e E na sensibilidade insulínica, metabolismo oxidativo e aspectos da imunidade em ovelhas no período periparto." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/10/10136/tde-31072018-142817/.
Full textAbstract:
Trinta ovelhas, mestiças (Santa Inês X Dorper), adultas e hígidas foram selecionadas para avaliar o efeito da suplementação intramuscular com as vitaminas D e E no perfil bioquímico, metabolismo energético, metabolismo oxidativo, sensibilidade insulínica e imunidade no periparto. Após confirmação da gestação essas fêmeas foram distribuídas em três grupos de dez animais e no 108° dia de gestação receberam veículo oleoso (grupo controle-GC); ou 70.000 UI/kg de P.V. de vitamina D3 (colecalciferol) (grupo tratado-GD); ou 60UI/kg de P.V. de vitamina E (-tocoferol) (grupo tratado-GE). As amostras de sangue foram coletadas previamente à aplicação da vitamina (-45), quatro (-30); e duas semanas (-15) antes do parto; até duas horas do parto (0), uma (7); duas (15); e quatro semanas após o parto (30). Foram analisadas as concentrações plasmáticas de glicose, beta hidroxibutirato (BHB), ácidos graxos não esterificados (AGNEs) e as concentrações séricas de colesterol, triglicérides, ureia, creatinina, cálcio total, cálcio iônico, proteína total, ácido úrico, aspartato amino transferase (AST), gamaglutamil transferase (GGT), e ainda a creatina quinase (CK). Foram também analisadas as concentrações de insulina e cortisol. Do metabolismo oxidativo foram determinadas as atividades da superóxido dismutase (SOD) e glutationa peroxidase (GSH-Px), a habilidade de redução férrica plasmática (HRFP), substâncias reativas ao ácido tiobarbitúrico (TBARS), bem como o status antioxidante total (TAS). Para avaliar aspectos relacionados à imunidade de monócitos e neutrófilos, por método in vitro, em 24 ovelhas (seis de cada tratamento). As amostras de sangue foram coletadas nos momentos 30; 0; e 30 e avaliadas sem estímulo (burst basal) e com estímulo por DCFH-DA, SaPI e PMA. A imunofenotipagem com anticorpos monoclonais CD8, CD4, CD14, CD16, CD45R, WC1, CD206, foi realizada aos dias -30, -15,0,7 e 30. Foram determinadas as concentrações das vitaminas D e E, nos momentos pré-determinados das coletas e no dia do teste de tolerância à glicose (TTG), realizado para avaliar a sensibilidade insulínica, e foi calculado RQUICKI e RQUICKI BHB. Todas as variáveis estudadas apresentaram efeito de tempo. Houve interação tempo*tratamento em TBARS (P=0,0217) e tendência para vitamina E (0,0811), SOD (0,0886) e GSH-Px (P=0,0643). Houve efeito de tratamento no colesterol (P=0,0088) e vitamina D (P<0,0001) e tendência para TAS (P=0,0830). No TTG, com resultados de AUC de BHB e AGNE apresentaram efeito de número de fetos gestados (P=0,0006 e 0,0005 respectivamente) e o RQUICKIBHB mostrou-se melhor indicador de sensibilidade insulínica do que o RQUICKI em ovelhas. A suplementação com vitamina D influenciou os teores plasmáticos de alfa tocoferol e a resposta imune das ovelhas. A suplementação com vitamina E reduziu a peroxidação lipídica no parto e relacionou-se positivamente com a melhora oxidativa dos monócitos sem estímulo e estimulados por PMA.Thirty healthy adult ewes were selected to evaluate the effect of supplementation with intramuscular vitamins D and E in peripartum period on the biochemical profile, energetic metabolism, oxidative metabolism, insulin sensitivity and immunity. After pregnancy confirmation these females were distributed into three groups of ten animals treated with intramuscular injection containing oily vehicle (control-to-control group) on the 108th day of pregnancy, (CG); or 70,000 IU / kg of body weight of vitamin D3 (cholecalciferol) (treated group-GD); or 60 IU / kg of body weight of vitamin E (-tocopherol) (treated group-GE). Blood samples were collected before the application of the vitamins and vehicle (-45), four (-30); and two weeks (-15) before lambing; until 2 hours of lambing (0); one (7), two (15) and four weeks postpartum (30). Plasma concentrations of glucose, beta hydroxybutyrate (BHB), non-esterified fatty acids (NEFA) and serum concentrations of cholesterol, triglycerides, urea, creatinine, total calcium, ionic calcium, total protein, uric acid, aspartate amino transferase (AST), gammaglutamyl transferase (GGT), and creatine kinase (CK) were measured. The concentrations of insulin and cortisol, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), plasma ferric reduction ability (FRAP), thiobarbituric acid reactive substances (TBARS), as well as total antioxidant status (TAS) were determinate. Monocytes and neutrophils were assessed by in vitro method to identify aspects related to immunity in 24 ewes (six from each treatment) at -30, 0 and 30. Blood samples were evaluated without stimulus (basal burst), with DCFH-DA, SaPI and PMA stimulus. Immunophenotyping with monoclonal antibodies CD8, CD4, CD14, CD16, CD45R, WC1, CD206 were performed at -30, -15, 0, 7 and 30. The concentrations of vitamins D and E were determinate at the predetermined collection times and on the day of the Intravenous Glucose Tolerance Test (IVGTT), realized to evaluate the insulin sensitivity, as well as RQUICKI and RQUICKI BHB. All variables studied showed time effects. There were interaction time * treatment in TBARS (P = 0.0217) and tendency for vitamin E (0.0811), SOD (0.0886) and GSH-Px 16 (P = 0.0643). Treatment effect on cholesterol (P = 0.0088) and vitamin D (P <0.0001) and tendency for TAS (P = 0.0830) were observed. About of IVGTT, AUC results of BHB and AGNE showed number of fetuses effect (P = 0.0006 and 0.0005 respectively). RQUICKIBHB was a better indicator of insulin sensitivity than RQUICKI in ewes. Vitamin D supplementation influenced the plasma levels of alpha tocopherol and the immune response of ewes. Vitamin E supplementation reduced lipid peroxidation at parturition and was positively related to the oxidative improvement of the monocytes without stimulation and stimulated by PMA. High doses of vitamins D or E administered 45 days before parturition on healthy ewes can be beneficial; however more studies are needed about this topic.
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Lehmann, Bodo, Peter Knuschke, and Michael Meurer. "A Novel Pathway for Hormonally Active Calcitriol." Karger, 2000. https://tud.qucosa.de/id/qucosa%3A27576.
Full textAbstract:
Calcitriol [1α,25(OH)2D3], the hormonally active form of vitamin D3 (D3) is produced in both renal and extrarenal tissues. Our findings demonstrate that physiological doses of UVB radiation at 300 nm induce the conversion of 7-dehydrocholesterol (7-DHC) via preD3 and D3 into calcitriol in the pmol range in epidermal keratinocytes. The hydroxylation of photosynthesized D3 to calcitriol is strongly suppressed by ketoconazole, a known inhibitor of cytochrome P450 mixed function oxidases. The UVB-induced formation of calcitriol in human skin is demonstrable in vivo by the microdialysis technique. These results suggest that human skin is an autonomous source of hormonally active calcitriol.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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Ousley, Amanda. "Engineering the human vitamin D receptor to bind a novel small molecule: investigating the structure-function relationship between human vitamin d receptor and various ligands." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/39580.
Full textAbstract:
The human vitamin D receptor (hVDR) is a member of the nuclear receptor superfamily, involved in calcium and phosphate homeostasis; hence implicated in a number of diseases, such as Rickets and Osteoporosis. This receptor binds 1α,25-dihydroxyvitamin D3 (also referred to as 1,25(OH)2D3) and other known ligands, such as lithocholic acid. Specific interactions between the receptor and ligand are crucial for the function and activation of this receptor, as implied by the single point mutation, H305Q, causing symptoms of Type II Rickets. In this work, further understanding of the significant and essential interactions between the ligand and the receptor were deciphered, through a combination of rational and random mutagenesis. A hVDR mutant, H305F, was engineered with increased sensitivity towards lithocholic acid, with an EC50 value of 10 µM and 40 + 14 fold activation in mammalian cell assays, while maintaining wild-type activity with 1,25(OH)2D3. Furthermore, via random mutagenesis, a hVDR mutant, H305F/H397Y, was discovered to bind a novel small molecule, cholecalciferol, a precursor in the 1α,25-dihydroxyvitamin D3 biosynthetic pathway, which does not activate wild-type hVDR. This variant, H305F/H397Y, binds and activates in response to cholecalciferol concentrations as low as 100 nM, with an EC50 value of 300 nM and 70 + 11 fold activation in mammalian cell assays.
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Pedrosa-Castro, Marcia Alessandra Carneiro [UNIFESP]. "Efeitos da suplementação com vitamina D e cálcio sobre o metabolismo mineral e sobre parâmetros da função neuromuscular em idosos institucionalizados." Universidade Federal de São Paulo (UNIFESP), 2006. http://repositorio.unifesp.br/handle/11600/21492.
Full textAbstract:
Made available in DSpace on 2015-12-06T23:44:43Z (GMT). No. of bitstreams: 0
Previous issue date: 2006Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Objetivos: Avaliar os efeitos de 6 meses de suplementação com colecalciferol e cálcio sobre o metabolismo mineral e sobre os parâmetros de força muscular de membros inferiores, oscilação postural e mobilidade funcional. Desenho do Estudo: Ensaio clínico prospectivo, randomizado, duplo-cego, placebocontrolado. Local de realização: Duas instituições de longa permanência para idosos, em São Paulo - SP, Brasil. Participantes: 56 idosos de ambos os sexos (12 homens e 44 mulheres), com 60 anos de idade ou mais (mediana=77,6; limites=62-94 anos). Métodos: Os pacientes foram randomizados em Grupo-Ca (n=28) para placebo, ou Grupo-Ca+D (n=28) para colecalciferol. Todos os participantes receberam 1000 mg/dia de cálcio. O Grupo-Ca+D recebeu colecalciferol oral nas doses de 150.000 UI/ mês durante os 2 primeiros meses de estudo e 90.000 UI/mês nos 4 meses subseqüentes, correspondendo a uma dose mensal de 3670 UI/dia em média, de Dezembro-2004 a Maio-2005. Níveis séricos de 25-Hidroxivitamina D (25OHD), paratormônio intacto (PTH) e cálcio foram mensurados no início do estudo (M1), 2 meses (M2) e 6 meses (M3) após tratamento. Os testes neuromusculares foram realizados antes do início da intervenção e repetidos após o fim do tratamento. A força muscular dos membros inferiores foi avaliada através de um índice de força muscular (IFM), incluindo a força dos músculos flexores do quadril e extensores do joelho, mensurada por dinamômetro mecânico portátil. Para avaliar a oscilação postural foi criado um índice (IOP) a partir da mensuração da oscilação do corpo nos diâmetros sagital e frontal ao nível da cintura. A mobilidade funcional foi mensurada através dos testes “Timed Up&Go” (TUG) e alcance funcional (TAF). Resultados: A 25OHD sérica aumentou em ambos os grupos no M2, porém mais no Grupo-Ca+D do que no Grupo-Ca (OR=2,2; 95%IC=1,98-2,4 vs. OR=1,76; 95%IC=1.55-1.99, respectivamente). No M3, os níveis de 25OHD declinaram apenas no Grupo-Ca, contudo, o PTH sérico diminuiu no M2 (p<0.0001) e retornou aos valores basais no M3 (p<0.0001) igualmente nos dois grupos. Antes do tratamento, deficiência/insuficiência de 25OHD (<50 nmol/L) afetava 67,9% do total de participantes. No M3, nenhum paciente do Grupo-Ca+D, mas 40% dos pacientes do Grupo-Ca tinham deficiência/insuficiência de 25OHD. Hipercalcemia não foi detectada em nenhum paciente. Apenas no Grupo-Ca+D, o IFM teve um aumento de 20% no M3 (OR=1,20; 95%IC=1,12-1,29), enquanto que IOP e TAF aumentaram igualmente nos dois grupos, provavelmente porque os pacientes de ambos os grupos aumentaram sua exposição solar durante o verão. Conclusões: A suplementação com colecalciferol e cálcio foi segura e efetiva em aumentar os níveis séricos de 25OHD, reduzir a prevalência de deficiência/insuficiência de 25OHD e aumentar a força muscular de membros inferiores nos idosos do grupo tratado. Palavras-chave: 25-Hidroxivitamina D, colecalciferol, idosos, força muscular, oscilação postural, mobilidade funcional.
Objectives: To assess the effects of a 6-month supplementation with vitamin D and calcium on mineral metabolism and parameters of lower-extremity muscle-strength, body sway (BS) and functional mobility, measured by the Functional Reach Test (FRT) and Timed Up&Go test (TUG). Design: Prospective, double-blind, placebo-controlled trial. Setting: Institutionalized elderly of two long-stay geriatric care units of São Paulo-SP, Brazil. Participants: 56 elderly volunteers of both genders (12 men and 44 women) of ages 60 and older (median=77.6; range=62-94 years). Methods: Subjects were randomized into a Ca-group (n=28) to receive placebo or a Ca+D-group (n=28) to receive cholecalciferol. All participants received 1,000 mg/day of calcium. Laboratory measurements were performed at baseline (M1), 2 moths (M2) and 6 months (M3) after intervention. The Ca+D-group received oral cholecalciferol on a monthly basis (3670 IU/day on average, from December-2004 to May-2005). Neuromuscular measurements were performed at baseline and 6 months. Results: Serum 25(OH)D increased in both groups at M2, but more so in the Ca+Dgroup than in the Ca-group (OR=2.2, 95%CI=1.98-2.4 vs. OR=1.76, 95%CI=1.55- 1.99, respectively). At M3, 25(OH)D levels declined only in the Ca-group. Nevertheless, serum PTH diminished at M2 (p<0.0001) and went back to baseline levels at M3 (p<0.0001) equally in both groups. Before treatment, 25(OH)D deficiency/insufficiency (<50 nmol/liter) affected 67.9% of the entire group. At M3, no patient in the Ca+D-group, but 40% of the Ca-group patients had 25(OH)D deficiency/insufficiency. Hypercalcemia was not detected at any time. The odds of improving lower-extremity muscle strength increased by 20% (OR=1.20, 95%CI=1.12-1.29) only in the Ca+D-group, whereas BS and FRT increased equally in both groups, probably because the study was conducted during the summer. Conclusions: The supplementation with calcium and supra-physiological doses of cholecalciferol was safe and effective in enhancing 25(OH)D levels, reducing the prevalence of 25(OH)D insufficiency, and increasing lower-extremity muscle strength in institutionalized elderly.
FAPESP: 03/13194-6
BV UNIFESP: Teses e dissertações
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Colturato, Pedro Luis. "Desenvolvimento e caracterização de membranas de nanocelulose para liberação de vitamina d3. /." Araraquara, 2019. http://hdl.handle.net/11449/192623.
Full textAbstract:
Orientador: Danielle GoveiaResumo: Estudos epidemiológicos mostram que uma parcela significativa da população mundial, independente de idade, etnia e localização geográfica, apresenta baixos níveis séricos de vitamina D3. Neste contexto, a incorporação da vitamina D3 em novos sistemas de liberação de fármacos, como os sistemas transdérmicos, têm sido apontados como alternativa para a administração deste medicamento. A extração da nanocelulose de fibras vegetais e sua utilização na fabricação de insumos da área da saúde tem se destacado na medicina, pois apresenta propriedades como biocompatibilidade, biodegradabilidade e baixa toxicidade. A celulose tem um longo histórico de aplicações na área da saúde, agindo como mediador na liberação controlada de fármacos, mas sua utilização nanoestruturada em membranas, como sistema de liberação local de fármacos ainda é um desafio. Neste estudo foi desenvolvida uma membrana, pela técnica de “casting”, de nanocelulose extraída do linter de algodão e vitamina D3 acrescidos dos componentes, álcool polivinílico, glicerina e tween 80. A nanocelulose e as membranas foram caracterizadas por microscopia eletrônica de varredura de alta resolução (MEV-FEG), espectroscopia no infravermelho com transformada de Fourier (FT-IR), teste de tração no dinamômetro e a cinética de liberação do fármaco por espectroscopia molecular no ultravioleta visível (UV-Vis). A membrana apresentou reprodutibilidade na síntese, ótimas propriedades físicas como flexibilidade, transparência e elasticidade,... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Epidemiological studies show that a significant portion of the population has low serum vitamin D3 levels, regardless of age, ethnicity and geographical location. In this context, the incorporation of vitamin D3 in new drug delivery systems, such as transdermal systems, has been suggested as an alternative for the administration of this drug. The extraction of nanocellulose from plant fibers and its use in the manufacture of health inputs has been highlighted in medicine, as it has properties such as biocompatibility, biodegradability and low toxicity. Cellulose has a long history of healthcare applications, acting as a mediator in controlled drug release, but its nanostructured use in membranes as a local drug delivery system is still a challenge. In this study a membrane was developed by casting technique of nanocellulose extracted from cotton linter and vitamin D3 plus the components, polyvinyl alcohol, glycerin and tween 80. Nanocellulose and membranes were characterized by high scanning electron microscopy. resolution (SEM-FEG), Fourier transform infrared spectroscopy (FT-IR), dynamometer tensile test and drug release kinetics by visible ultraviolet molecular spectroscopy (UV-Vis). The membrane showed reproducibility in synthesis, excellent physical properties such as flexibility, transparency and elasticity, as well as adequate resistance for biomedical applications. Through the FT-IR it was observed the presence of all active components in the sample, without structura... (Complete abstract click electronic access below)
Mestre
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FRANCESCHELLI, ANTONELLA. "Hep-d3: studio pilota sull’impatto della terapia con vitamina d3, peginterferone e ribavirina nei pazienti affetti da epatite cronica da virus c, non responders a precedente trattamento." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2010. http://hdl.handle.net/2108/208736.
Full textAbstract:
Premesse: Con l’attuale schema terapeutico con interferone peghilato (PEG-IFN) e
ribavirina oltre il 20% dei pazienti naïve affetti da epatite cronica da HCV genotipo
1 (G1) sono considerati non responders (NR: assenza di risposta virologica
precoce parziale o completa (partial/complete Early Virological Response: p/cEVR)
a 12 settimane o HCV-RNA positivo a 24 settimane di terapia). Il ritrattamento è
poco efficace, specialmente negli stadi avanzati di malattia epatica. La vitamina D
(vit D) è un potente immunomodulatore, che ha migliorato le percentuali di
risposta sostenuta alla terapia i pazienti naïve G1.
Scopo dello studio: Valutare se la terapia di induzione con alte dosi di vitamina D
prima del trattamento antivirale standard aumenti le percentuali di risposta in
pazienti HCV positivi G1 NR con malattia epatica avanzata.
Metodi: Ventidue pazienti G1 (13 uomini), con fibrosi avanzata (12) o cirrosi ben
compensata (10), tutti NR ad un precedente trattamento con dose piena di PEGIFN
alfa2a/2b e di ribavirina sulla base del peso (>80% della dose prescritta e
>80% della durata del trattamento previsto) sono stati arruolati (EUDRACT
2010-019482-28). Ai pazienti è stata somministrata una terapia di induzione con
vit D per quattro settimane (colecalciferolo, 5000 UI/die), seguita da terapia con
PEG-IFN alfa2a (180 mcg/settimana), ribavirina (1000-1400 mg/die) e vitD (1500
UI/die). Sono stati misurati i livelli basali di 25(OH)vitamina D, calcio urinario,
elastografia epatica (Fibroscan) e l’indice HOMA (vedi tabella). I pazienti che
hanno ottenuto una c/pEVR ed erano HCV-RNA negativi a 24 settimane di terapia
sono stati considerati responders ed hanno proseguito il trattamento con PEG-IFN
e ribavirina per altre 24-48 settimane. I pazienti NR hanno sospeso il trattamento.
Risultati: Tutti i pazienti hanno completato le 12 settimane di terapia: 11 (50%)
hanno ottenuto una EVR (1 cEVR, 10 pEVR), 11 erano NR. A 24 settimane di
terapia, 3 pazienti erano R, 7 NR, 1 ha abbandonato lo studio. Dei 3 R, solo il
paziente che aveva ottenuto la cEVR ha completato le 48 settimane di terapia ed
ha mantenuto la negativizzazione del virus (end of treatment response: ETR).
Questo paziente aveva un basso valore di elastografia epatica ed una bassa carica
virale all’inizio del trattamento. Gli altri due pazienti stanno ultimando il
trattamento per un totale di 72 settimane. Sulla base di questi risultati poco
incoraggianti, la sperimentazione è stata interrotta. Non si sono riscontrati effetti
collaterali collegabili all’utilizzo della vitamina D.
Conclusioni: la supplementazione di vitamina D ad alte dosi si è dimostrata
sicura nei pazienti G1 HCV NR, anche in quelli con livelli basali di 25(OH)D nella
norma. La supplementazione non ha però migliorato la percentuale di risposta
alla terapia in questo gruppo particolare di pazienti con malattia epatica
avanzata, NR e con genotipo non favorevole.
Parametro Valore
Età (anni)
55±9,3
HCV-RNA (UI/ml)
6.63*106 ±10.5*106
25(OH)D (ng/ml)
64±36
Elastografia epatica (KPa)
24.5±17.3
HOMA-index
3.8±2.6
ALT (UI/ml)
98.5±66.4
GGT (Background: With current pegylated-interferon (PEG-IFN) and ribavirin (RBV) treatment, over 20% naïve patients (pts) with chronic hepatitis C virus (HCV), genotype 1 (G1), are non responders (NR, no partial or complete early virological response (p/cEVR) at 12 weeks (wks) or HCV-RNA positive at 24 wks of therapy). Re-treatment is minimally effective, especially in advanced disease. Vitamin D (vitD) is considered a potent immunomodulator, reported to improve sustained virological response (SVR) in naive G1 pts. Aim of the study: To investigate whether induction with high dose vitD before antiviral treatment improves the response in G1 HCV NR with advanced hepatic disease. Methods. Twentytwo G1 pts (13 males), with advanced fibrosis (12) or wellcompensated cirrhosis (10), all NR to full-dose weekly PEG-IFN alfa2a/2b + weightbased ribavirin (>80% of the assigned dose and >80% of treatment duration), were enrolled (EUDRACT 2010-019482-28). Pts received vitD 4 wks induction (cholecalciferol, 5000 U/day), followed by PEG-IFN alpha2a (180 mcg/weekly), RBV (1000-1400 mg/day) and vitD (1500 U/day). Baseline serum 25OH-D levels, urinary calcium, liver stiffness (Fibroscan) and HOMA index were measured (see Table). Pts achieving p/cEVR and HCV-RNA negative at 24 wks of therapy were considered responders (R) and treated with PEG-IFN and RBV for other 24-48 wks. NR pts stopped therapy. Results. All patients completed 12 wks of therapy: 11 (50%) achieved EVR (1 c/ EVR, 10 p/EVR), 11 were NR. At 24 wks of therapy, 3 were R, 7 NR, 1 dropped-out. Among 3 R, only 1 patient (with basal liver stiffness in the lower range, low viral load and who achieved cEVR) obtained end of treatment response, the other two pts are ending the 72 wks of therapy. Based on these results the study was interrupted. No pts had clinical side effects related to vitD supplementation. Conclusions. Supplementation with high dose of vitD is safe in G1 HCV NR patients, even in normal basal serum 25(OH)D levels. However, VitD supplementation did not improve the response rate to therapy in this difficult-totreat population. Age (years) 55±9,3 HCV-RNA (UI/ml) 6.63*106 ±10.5*106 25(OH)D (ng/ml) 64±36 Liver Stiffness (KPa) 24.5±17.3 HOMA-index 3.8±2.6 ALT (UI/ml) 98.5±66.4 GGT (UI/ml) 75±65 Calciuria spot (mg/dl) 9.5±3.2
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Lomri, Abderrahim. "Effets de la pth, de la 1,25(oh)2 d3 et du tgf-b sur la synthese et l'organisation du cytosquelette des osteoblastes en culture." Paris 6, 1988. http://www.theses.fr/1988PA066369.
Full text
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Molina, Vila Pablo. "Suplementación con vitamina D nativa en pacientes con enfermedad renal crónica." Doctoral thesis, Universitat Autònoma de Barcelona, 2015. http://hdl.handle.net/10803/298328.
Full textAbstract:
Introducción. Los niveles de 25(OH)-vitamina D [25(OH)D] son el mejor indicador de los depósitos de vitamina D del organismo y su déficit es muy frecuente en pacientes con enfermedad renal crónica (ERC). Más allá de su función calciotrópica como sustrato para la formación renal de 1,25(OH)2 -vitamina D, el déficit de 25(OH)D se ha relacionado con mayor prevalencia de enfermedad cardiovascular, cáncer y diabetes mellitus, y su suplementación se ha asociado a mejor supervivencia en población general. Sin embargo, el papel predictivo del déficit de 25(OH)D en la morbi-mortalidad de los pacientes con ERC necesita ser establecido en estudios prospectivos realizados en esta población. Del mismo modo, se precisan estudios controlados que confirmen que la relación descrita entre el déficit de 25(OH)D y la aparición de eventos renales y cardiovasculares no son sólo un epifenómeno, sino que presentan una relación de causalidad.
Objetivos. Los objetivos de esta tesis fueron: (1) Analizar la relación de los niveles de vitamina D sobre marcadores de riesgo cardiovascular, calcificación vascular, y la supervivencia en pacientes con ERC; (2) analizar la relación de los niveles de vitamina D sobre marcadores de progresión de la ERC; y (3) analizar el efecto de la reposición de vitamina D nativa sobre marcadores del metabolismo óseo-mineral, calcificación vascular, función cardiovascular y de progresión renal en pacientes con ERC.
Métodos. Realizamos tres tipos de estudios: (1) Dos estudios transversales de 634 y 722 pacientes, respectivamente, con ERC en estadíos 3-5 no en diálisis, donde se correlacionaron los niveles de 25(OH)D con parámetros de progresión renal y factores de riesgo cardiovascular, incluyendo proteinuria y calcificación vascular; (2) un estudio observacional prospectivo de 470 pacientes con ERC estadios 3-5 no en diálisis, seguidos durante 3 años, que analizó el poder predictivo independiente del déficit de vitamina D para la supervivencia y la aparición de eventos cardiovasculares y progresión renal en esta población; y (3) un ensayo de intervención de 101 pacientes, prospectivo y controlado, que analizó el efecto de la suplementación con vitamina D sobre marcadores de progresión renal, disfunción cardiovascular y metabolismo óseo-mineral en pacientes con ERC.
Resultados. El déficit de vitamina D fue muy frecuente en los pacientes ERC, alcanzando a cerca del 80% de esta población. Niveles disminuidos de 25(OH)D se relacionaron con mayor prevalencia de enfermedad cardiovascular (insuficiencia cardíaca y vasculopatía periférica) y con factores de riesgo cardiovascular y de progresión renal (índice tobillo-brazo disminuido, presencia de diabetes mellitus, nefropatía diabética y proteinuria). No encontramos relación de dicho déficit con la presencia calcificación vascular. Niveles de 25(OH)D inferiores a 20 ng/ml se asociaron de manera independiente con peor supervivencia y mayor progresión de la ERC tras ajustar por múltiples variables, lo que, con las limitaciones inherentes a un estudio observacional, apoya el potencial papel terapéutico de la suplementación con vitamina D en esta población. La reposición diaria con dosis moderadas de colecalciferol (600-800 UI/día) demostró ser eficaz para reducir la albuminuria en pacientes con ERC estadios 3-4, con potenciales beneficios cardiovasculares y renales a largo plazo para esta población, que deberán ser confirmados en futuros ensayos clínicos.
Conclusiones. En pacientes con ERC no en diálisis, los niveles de vitamina D no sólo se relacionaron con marcadores de función cardiovascular y renal, prediciendo la supervivencia y la progresión renal, sino que además demostraron ser una diana terapéutica para disminuir la albuminuria, lo que podría mejorar el pronóstico renal a largo plazo y la supervivencia de esta población, cuyo pronóstico sigue siendo inaceptable.Background. 25(OH)-vitamin D [25(OH)D] levels are the best indicator of vitamin D stores and its deficiency is very common in patients with chronic kidney disease (CKD). Beyond its calciotropic function as a substrate for synthesis of 1,25(OH)2-vitamin D in the kidney, 25(OH)D deficiency has been linked with higher prevalence of cardiovascular disease, cancer and diabetes mellitus. Moreover, vitamin D supplementation has been associated with better survival in the general population. Nevertheless, the independent predictor value of 25(OH) deficiency in the morbility and mortality of CKD patients needs to be established in prospective studies designed for this population. Similarly, we need controlled trials to confirm that the described relationship between 25(OH)D levels and the occurrence of renal and cardiovascular events is truly causal. Objectives. The aims of this thesis were: (1) To analyze the relationship between vitamin D levels on cardiovascular risk factors, vascular calcification, and survival in patients with CKD ; ( 2) to assess the relationship between vitamin D levels and markers of CKD progression; and (3 ) to analyze the effect of native vitamin D supplementation on bone-related parameters, vascular calcification, and markers for cardiovascular disease and renal progression in CKD patients. Methods. We perform three types of studies : (1) Two cross-sectional studies of 634 and 722 patients with stages 3-5 CKD not on dialysis, respectively, where 25(OH)D levels were correlated with renal progression parameters and cardiovascular risk factors, including proteinuria and vascular calcification; (2) a prospective, 3-year follow-up, observational study of 470 non-dialysis CKD 3-5 patients, which analyzed the ability of vitamin D deficiency to predict death, cardiovascular events and renal progression in this population; and (3) an interventional, controlled trial of 101 patients, that quantified the effect of vitamin D supplementation on markers of renal progression, cardiovascular dysfunction and bone-mineral metabolism in patients with CKD. Results. Vitamin D deficiency was highly prevalent in CKD patients, rising to up to 80% of patients. Low 25(OH)D levels were related to high prevalence of cardiovascular disease (chronic heart failure and peripheral vascular disease) and cardiovascular and renal progression risk factors (ankle-brachial pressure index, diabetes mellitus, diabetic nephropathy and proteinuria). Our data did not demonstrate an association between 25(OH)D levels and vascular calcification. After multivariate analysis, 25(OH)D level < 20 ng/ml was independently associated with worse survival and higher renal progression. Despite the inherent limitations of an observational study, this data supported the potential role of vitamin D supplementation for this population. Vitamin D repletion with daily mild doses of cholecalciferol (600-800 IU/day) was effective to reduce albuminuria in patients with CKD 3-4 stage, with potential cardiovascular and renal long-term benefits for this population that should be tested in future vitamin D supplementation trials. Conclusions / Implications. In non-dialysis CKD patients, vitamin D levels were not only related to cardiovascular and renal progression risk factors, predicting survival and renal progression, but also were demonstrate to be one of the therapeutic targets to reduce albuminuria. These findings could lead to improve the long-term renal and cardiovascular prognosis of this population, whose life expectancy continues to be unacceptable.
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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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Tatjana, Stojšić Vuksanović. "Uticaj holekalciferola na proteinuriju kod bolesnika sa tipom 2 dijabetesa mellitus." Phd thesis, Univerzitet u Novom Sadu, Medicinski fakultet u Novom Sadu, 2020. https://www.cris.uns.ac.rs/record.jsf?recordId=114771&source=NDLTD&language=en.
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Zastupljenost deficita vitamina D3 je mnogo veći kod bolesnika sa dijabetesnom bolesti tipa 2 nego u populaciji zdravih osoba. Bolesnici sa DM tipa 2 i deficitom vitamina D3 imaju veći rizik za razvoj dijabetesne nefropatije. Eksperimenti na životinjama i neka klinička istraživanja ukazuju da bi primena nižih doza vitamina D3 mogla imati renoproktektivno delovanje. Cilj istraživanja je bio da se utvrdi zastupljenost deficita vitamina D3 u populaciji bolesnika sa dijabetesnom nefropatijom koja je definisana proteinurijom ˃0,150 g/du. Drugi cilj je bio da se utvrdi da li primena holekaciferola u dozi koja predstavlja razliku između utvrđenog i optimalnog nivoa vitamina D3 dovodi do statistički značajnog smanjenja proteinurije. Bolesnici sa dijabetesom tipa 2 i proteinurijom ˃0,150 g/du su uključivani u skrining na nivo vitamina D3 (25(OH)D) nakon čega su svrstavani u grupe sa deficitom i normalnim nivoom vitamina D3. Granična vrednost za utvrđivanje deficita vitamina D3 je odreĎivana na osnovu tabele koja definiše ove vrednosti za svaki mesec tokom godine, posebno za muškarce i žene. Bolesnici sa deficitom vitamina D3 su podeljeni u 2 grupe od po 45 ispitanika. Studijska grupa je primala holekaciferol u dozi koja je izračunata na osnovu razlike između izmerene vrednosti i određenog optimalnog nivoa vitamina D3 od 90-100 nmol/L. Kontrolna grupa bolesnika je uzimala svoju uobičajenu terapiju. Istraživanje je trajalo 24 nedelje tokom koje su na drugi mesec praćeni parametri bubrežne funkcije, parametri inflamacije i koštanog metabolizma. Na početku i kraju istraživanja su odreĎeni nivo vitamina D3 u studijskoj grupi, dok su u obe grupe određivani vrednost HbA1c i lipidni profil. Analizom dobijenih podataka je utvrđeno da je zastupljenost deficita vitamina D3 kod bolesnika sa dijabetesnom nefropatijom, uzimajući u obzir sezonske varijacije u nivou ovog vitamina, bila veća od vrednosti od 30-50% koje su postavljene u radnoj hipotezi. Učestalost bolesnika sa nedostakom vitamina D3 je u ispitivanom uzorku je bila 82,56% , dok je normalne vrednosti vitamina D3 imalo 17,43% ispitanika, od toga je bilo 10 (52,63%) muškaraca i 9 (47,36%) žena. Sniženje vrednosti vitamina D3 u odnosu na donje granične vrednosti je bilo izraženije u letnjem periodu i bilo je statistički značajno kod svih ispitanika zajedno, potom u studijskoj grupi, dok je utvrđeno i u kontrolnoj grupi ali je u njoj bilo bez statisičke značajnosti. Utvrđen je porast HbA1c koji je bio veći u kontrolnoj grupi ispitanika. Suplementacija vitaminom D3 je imala povoljan efekat na lipidni profil. Registrovan je porast vrednosti ukupnog holesterola koji je bio izraženiji u kontrolnoj grupi, pad vrednosti triglicerida u grupi bolesnika koji su uzimali vitamin D3 i njihov porast u kontrolnoj grupi ispitanika. U studijskoj grupi je registrovan porast vrednosti HDL-holesterola koji je bio na granici statističke značajnosti dok je istovremeno nađeno njegovo smanjenje u kontrolnoj grupi. Vrednost LDL-holesterola je ostala bez promene pod delovanjem vitamina D3, dok je u kontrolnoj grupi došlo do njegovog porasta. Utvrđeno je snižavanje vrednosti sedimentije, CRP-a i fibrinogena koje je bilo bez statističke značajnosti. Bezbednosni profil vrednosti kalcijuma u serumu i urinu tokom dugotrajnije primene je dobar. Primenom vitamina D3 je došlo do signifikatnog smanjenja proteinurije u grupi bolesnika koji su primali holekaciferol čime je ujedno i potvrđena radna hipoteza.The prevalence of vitamin D3 deficiency is much higher in patients with type 2 diabetes than in the healthy population. Patients with type 2 DM and vitamin D3 deficiency are at increased risk for developing diabetic nephropathy. Animal experiments and some clinical studies suggest that administration of lower doses of vitamin D3 could have renoprotective effect. The aim of the study was to determine the prevalence of vitamin D3 deficiency in the population of patients with diabetic nephropathy defined by proteinuria ˃0.150 g / du. The second goal was to determine whether the use of cholecaciferol in a dose that represents the difference between the established and optimal levels of vitamin D3 leads to a statistically significant reduction in proteinuria. Patients with type 2 diabetes and proteinuria ˃0.150 g / du were screened for vitamin D3 (25 (OH) D) levels and then classified as deficient and normal vitamin D3. The limit value for determining vitamin D3 deficiency was set on the basis of a table defining these values for each month during the year, separately for men and women. Patients with vitamin D3 deficiency were divided into 2 groups of 45 subjects each. The study group received cholecaciferol at a dose calculated on the basis of the difference between the measured value and the set optimal vitamin D 3 level of 90-100 nmol/L. The control group of patients was taking their usual therapy. The study lasted 24 weeks during which the parameters of renal function, parameters of inflammation and bone metabolism were monitored every second month. At the beginning and end of the study, the levels of vitamin D3 in the study group were determined, while in both groups HbA1c and lipid profile were determined. The analysis of the obtained data showed that the prevalence of vitamin D3 deficiency in patients with diabetic nephropathy, taking into account seasonal variations in the level of this vitamin, was higher than the values of 30-50%, which were set in the working hypothesis. The frequency of patients with vitamin D3 deficiency in the study sample was 82.56%, while the normal values of vitamin D3 were in 17.43% of the subjects, of which 10 (52.63%) were men and 9 (47.36%) woman. The decrease in vitamin D3 compared to the lower limit values was more pronounced in the summer and was statistically significant in all subjects together, as well in the study group, while it was also found in the control group but was not statistically significant. An increase in HbA1c was found to be higher in the control group. Vitamin D3 supplementation had a beneficial effect on the lipid profile. An increase in the total cholesterol level that was more pronounced in the control group, a decrease in triglyceride values in the group of patients taking vitamin D3 and its increase in the control group of subjects were registered. An increase in HDL-cholesterol was reported in the study group, which was at the limit of statistical significance, while at the same time a decrease was found in the control group. LDL-cholesterol levels remained unchanged under the influence of vitamin D3, while in the control group it increased. The decrease in sedimentation, CRP and fibrinogen values was found to be of no statistical significance. The safety profile of serum and urine calcium during long-term administration is good. The use of vitamin D3 resulted in a significant decrease in proteinuria in the group of patients receiving cholecaciferol, which also confirmed the working hypothesis.
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RIAD, FOUAD. "Regulation endocrinienne de la secretion salivaire des mineraux chez les bovins." Clermont-Ferrand 2, 1986. http://www.theses.fr/1986CLF21026.
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Carmo, Luciana Simão do. "Mecanismos fisiopatológicos do remodelamento vascular associado à calcificação em camundongos com obesidade e resistência à insulina." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/5/5148/tde-15032018-111718/.
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O remodelamento vascular é uma resposta adaptativa a estímulos específicos, participando da fisiopatologia de diversas doenças cardiovasculares. Devido à intersecção de fatores de risco cardiovasculares relacionados tanto ao remodelamento vascular como à calcificação vascular (CV), propomos a investigação de mecanismos que inter-relacionam tais condições. Postulamos que camundongos ob/ob com obesidade e resistência à insulina têm resposta exacerbada de remodelamento vascular associado à CV quando comparado aos camundongos controles C57BL/6 (C57) após estímulo com vitamina D3 (VD) in vivo. Camundongos C57 e ob/ob (OB) machos foram injetados com 8x103 UI/kg de vitamina D3 intraperitoneal (IP) ou solução fisiológica (CT) durante 14 dias (n=6). Houve aumento da circunferência da lâmina elástica externa da aorta, determinando aumento da área circunferencial do vaso em camundongos OBVD. A hipervitaminose D aumentou o comprimento da lâmina elástica interna da aorta, aumentando o lúmen vascular em camundongos OBVD. Ocorreu também diminuição da espessura da parede do vaso em camundongos OBVD, caracterizando remodelamento vascular positivo hipotrófico. Observamos ainda maior deposição de colágeno na parede do vaso e elastólise em camundongos OBVD. O remodelamento vascular positivo em camundongos OBVD se correlacionou diretamente com o aumento da calcificação na aorta (R2=0,8; p < 0,003). Aortas de camundongos OBVD apresentaram aumento na expressão de espécies reativas de oxigênio (ERO), que foi associado a aumento da atividade de metaloproteinases de matriz (MMP). Estes resultados fornecem evidências que camundongos obesos, insulino-resistentes, e com diabetes tipo 2 desenvolveram remodelamento vascular positivo hipotrófico correlacionado diretamente com calcificação vascular em camundongos OBVD após estímulo com vitamina D3. O desenvolvimento de remodelamento vascular positivo hipotrófico neste modelo murino é possivelmente mediado pela ativação de MMP na parede da aorta e a geração de ERO pode ter contribuído para a ativação de MMP no nosso modeloVascular remodeling is a vessel response to mechanical and hemodynamic stimuli, which is a major determinant of changes in vessel lumen caliber. The mechanisms that influence arterial remodeling include calcification. We hypothesized that ob/ob mice develop positive vascular remodeling associated with calcification. We quantify and assess mechanisms of vascular remodeling and vascular calcification in ob/ob mice (OB) after vitamin D3 stimulation (VD) or phosphate buffered saline (CT), compared with (C57BL/6) mice. Both ob/ob (OBVD) and C57BL/6 (C57VD) mice received 8x103 IU/day of (IP) vitamin D3 for 14 days. Control ob/ob (OBCT) and C57BL/6 (C57CT) mice received IP phosphate buffered saline (PBS) for 14 days (n=6). Hypervitaminosis D increased the external and internal elastic length in aortas from OB mice, resulting in increased total vascular area and lumen vascular area respectively, which characterizes positive vascular remodeling. OBVD mice decreased the aortic wall thickness, resulting in hypotrophic vascular remodeling. We demonstrated increases in collagen deposition, elastolysis and calcification in the aortas of OBVD mice. These results showed a positive correlation between expansive vascular remodeling and vascular calcification in OBVD mice (R2=0,8; p < 0,003). Furthermore, aorta from OBVD increased oxidative stress, coincidently with augmented metalloproteinase activity. Our data provide evidence that obese type 2 diabetes mellitus and insulin-resistant mice (ob/ob) developed positive hypotrophic vascular remodeling correlated directly with increased vascular calcification in OBVD mice after chronic vitamin D3 stimulation. The development of positive hypotrophic vascular remodeling in this mouse model is possibly mediated by the activation in the aortic wall of MMP and ROS may have contributed to the activation of MMP in our model
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Wissel, Silke. "Spatial distribution of the rodent population at Boundary Stream Mainland Island and determination of the efficacy of different baits used for rodent control." Lincoln University, 2008. http://hdl.handle.net/10182/1082.
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Poison operations are a widely used technique for rodent control in the indigenous forests of New Zealand. This study examined the bait-take and rat monitoring data obtained for continuous poison operations at Boundary Stream Mainland Island (BSMI), Hawke’s Bay, between 1996 and 2007. Since the beginning of the Mainland Island project at BSMI in 1996, 800 ha of indigenous forest have been treated with an ‘Integrated Pest Management’ approach, in which rodents (primarily ship rats) have been targeted by consecutive ground poison operations. The aim of the intensive pest control was to allow the ecosystem to recover and provide a safe environment for threatened native bird species to recover or be re-introduced. Another important aim of this pest control is to provide experience and expert knowledge in management techniques especially applicable to the protection of indigenous habitat on the New Zealand mainland. This research study had two main aims: to identify spatial patterns of the rodent population at BSMI and to determine the efficacy of the different rodenticides applied for their control. The distribution of the rodent population was investigated by spatial analysis of bait-take across the reserve and through time. Visualisation of high and low bait-take areas revealed that there was a noticeable reinvasion from adjacent unmanaged native forests, but not markedly from exotic forest or pasture. Reinvasion from small and isolated adjacent forests ceased to be noticeable consistently after approximately four years of the poison operation, while a large scenic native reserve, as well as a narrow part of the treatment area surrounded by many native bush patches, were continuously affected by reinvasion through the entire project time. Bait-take was visibly higher after the bait had either been removed, or left in the field unserviced, over winter. No consistent areas of no bait-take were identified. Further statistical analysis of bait-take data revealed that bait-take was higher in bait stations within 150 m of the treatment edge than interior bait stations. Bait-take in broadleaf/tawa/podocarp forest was significantly higher than in kamahi/kanuka/rewarewa, beech and cloud-cap forest. The second aim of the study was to determine the efficacy of the various bait types with different active ingredients used during the operation. Rat monitoring data, namely rat tracking indices (RTI) obtained from tracking tunnels, were statistically modelled using Generalised Linear Models. Diphacinone cereal pellets (Pestoff® 50D, 0.05g/kg diphacinone) obtained the lowest RTI, followed by pindone cereal pellets (Pindone Pellets®, 0.5g/kg pindone), brodifacoum cereal pellets (Pestoff® 20p and Talon®, 0.02 g/kg brodifacoum), coumatetralyl paste (Racumin®, 0.375 g/kg) and diphacinone bait blocks (Ditrac®, 0.05 g/kg). Cereal pellet baits worked better than any other bait type used at this location. Season had no statistically significant effect on either RTI or bait-take estimates. The overall goal of the poison operation to decrease rat numbers, and to maintain low levels, has been met. However, the results of this study suggest that baiting needs to be done continuously and over the entire treatment area. Edge bait stations – particularly next to adjacent native forests – should be prioritised to target reinvading rodents. Poisons presented in cereal pellet baits should be preferred to other bait types. Both pindone and brodifacoum showed very good results, as well as diphacinone in cereal pellet baits.
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Hutt, Jean. "Synthese d'analogues de la vitamine d::(3) : synthese chirale de composes polyhydroxyles." Université Louis Pasteur (Strasbourg) (1971-2008), 1986. http://www.theses.fr/1986STR13326.
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La transformation de la cfarvone en quatre diastereoisomeres precurseurs du cycle a des dihydrovitamines et dihydrotachysterols est decrite dans la premiere partie. Par couplage d'un acetylure derive des cycles c/d de la vitamine d::(3) avec la cetone precurseur du cycle a, puis sa formation du systeme dienique a l'aide de titane a basse valence nous avons obtenu des dihydrotachysterols majoritairement. D'un autre cote, l'utilisation de sulfoxydes optiquement actifs dans l'intention de creer des centres hydroxyles chiraux et son application a la synthese du fragment polyhydroxyle de l'amphotericine b et du l-arabinitol est decrite dans la deuxieme partie. Les trois etapes-cles de cette methodologie sont: reduction stereospecifique d'un beta-cetosulfoxyde; condensation stereospecifique; cis-hydroxylation d'un beta-hydroxysulfoxyde
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Rouis, Mustapha. "Regulation des recepteurs membranaires par les esters de phorbol : role de la proteine kinase c." Paris 6, 1987. http://www.theses.fr/1987PA066609.
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Caracterisation de la liaison du dibutyrate de phorbol, de la lipoproteine de basse densite (ldl) et de la somatomedine (ilas) sur les cellules de la lignee u 937 (premonocytes humains). Le tpa provoque une reduction du nombre de recepteurs des ldl et une baisse de l'affinite dans le cas des ilas. Le tpa provoque une phosphorylation rapide et reversible des antigenes hla (a,b,c). Etude de la differenciation de la lignee u937 en monocytes-macrophages par la vitamine d3 et l'acide retinoique par le dibutyril-ampc (dbampc). Mise en evidence d'une synergie d'action entre le tpa et l'ionophore de ca**(2+) a 23187 dans l'inhibition de la liaison de l'insuline. Les auteurs proposent l'hypothese de l'existence d'un "pool" de recepteurs endogenes et ont mis en evidence une translocation de la proteine kinase c du cytosol vers la membrane plasmique en presence du tpa
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Morgan, David R. "Maximising the effectiveness of aerial 1080 control of possums (Trichosurus vulpecula)." Lincoln University, 2004. http://hdl.handle.net/10182/20.
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Aerial control using 1080 (sodium monofluoroacetate) baits is widely used in New Zealand for the control of introduced brushtail possums (Trichosurus vulpecula), with the aim of protecting national conservation and agricultural values from these damaging pests. This thesis integrates research, completed over 25 years, that was motivated by growing recognition in the 1970s of the extent of possum impacts and the need to improve the effectiveness and efficiency of the control operation. Field research assessed the palatability of three types of cereal-based pellet baits and carrot baits in different regions, habitat types and seasons. Palatability was assessed by the consumption of the different bait types presented independently of each other on 15-30 plots, with rotation of bait types at plots on successive nights to provide equal exposure to each bait type. There was regional variation in possums' bait preferences, possibly reflecting genotypic differences, whereas seasonal variation was less evident. Carrot bait was preferred or equally preferred to cereal bait in 14 out of 20 field trials. The proportion of possums eating baits was then investigated by, firstly, developing a technique for tracing bait acceptance using rhodamine B, a UV-fluorescent dye. In four field trials, more than 95% of possums accepted three types of dye-marked bait, eliminating bait refusal as a major reason for low kills in winter control operations. In a fifth trial, conducted in summer, only 68% of possums accepted bait suggesting that seasonal availability of favoured foods may influence bait acceptance. Since possums must encounter baits before deciding whether to eat them, field studies were undertaken to assess the coverage achieved in normal aerial baiting operations. Large gaps, up to 400 m in width, were often found between baiting swaths; these could allow some possums to survive. A controlled field experiment, using acceptance of rhodamine-dyed bait as a measure of effectiveness, showed that bait distribution was least accurate where flight paths were not marked. Where gaps of 100 m between flight paths were deliberately created, bait acceptance was slower and less than where coverage was complete. Sowing baits at 3 kg/ha was as effective as at 10 kg/ha, indicating the potential for substantially reducing operational costs by using machinery capable of faultlessly distributing baits at low rates. Navigational guidance systems were evaluated and found to improve the accuracy of bait distribution. During 1993-1997, when a lower sowing rate of 5 kg/ha was adopted operationally by regional managers, control effectiveness was unchanged but annual savings of around $9 million accrued. Because of the lack of suitable sowing machinery, a bucket was developed to permit faultless distribution of baits at lower rates, demonstrating the possibility of yet further cost-savings. The possibility of seasonal food availability affecting bait acceptance was investigated in three different forest habitats. Dyed baits were aerially distributed on 100 ha at each site in each season over two years. In each trial, fat-based condition indices of possums were calculated and the abundance of possum-preferred plant foods described. Bait acceptance was consistently high (85-100%) in the 24 trials, and was not influenced by either condition or availability of preferred foods. It seems likely that seasonal variation in operational effectiveness is caused by either the availability of sharply seasonal, scarce foods that possums may feed on intensively for brief periods, or by warmer temperatures that render 1080 less effective. The influence of 1080 on acceptance of (rhodamine-dyed) baits was investigated in a field trial. Examination of possums for dye-marking showed that 25% of possums refused to eat either a lethal quantity of bait or any bait at all, compared with 98% of possums eating non-toxic bait. This indicated that 1080 is aversive to possums, which is a potential major reason for their surviving control operations. Pen trials were therefore conducted to further examine the problem and to seek solutions. Toxic carrot baits were rejected by 27.5% of possums, equally by smell and taste aversion, whereas toxic cereal pellets were rejected by 34%, mainly by taste aversion. Orange and cinnamon were shown to be among the most preferred of 42 flavours tested and, when applied to toxic baits, 1080 was effectively masked. Bait refusal was reduced to ≤7%, the same as that recorded for possums presented with flavoured non-toxic baits. For long-term control of possum populations, aerial 1080 baiting can be used sequentially with other poisoning methods. However, the compatibility of these methods is dependent on the likelihood of possums developing bait shyness if sublethally dosed. Studies were therefore conducted to characterise and compare the four main toxicants used (1080, cyanide, cholecalciferol and brodifacoum) for induction and mitigation of bait shyness. Shyness was induced in approximately 80% of possums sublethally dosed with cyanide, 60% with 1080, 20% with cholecalciferol, and 0% with brodifacoum. Cyanide and 1080 shyness were found to persist in many possums for at least 12 and 24 months, respectively. Use of alternative bait types, and of baits containing an alternative slow-acting toxin (brodifacoum) were shown to be effective ways of overcoming shyness. This, and other related research, is reviewed to provide operational specifications that maximise the likelihood that all targeted possums will (i) encounter bait, (ii) eat it, and (iii) die. The likely future use of aerial 1080 baiting is described and the technological, economic, environmental and social constraints on its sustainability are discussed. Finally, the uptake of the research by possum managers is considered, and areas identified in the thesis where information is incomplete are summarised as prioritised topics for further research.
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Chang, Chiung-Wen, and 張瓊文. "Interactions between cholecalciferol (vitamin D3) and its polyclonal antibodies studied by surface plasmon resonance technology." Thesis, 2003. http://ndltd.ncl.edu.tw/handle/59067858363869965200.
Full textAbstract:
碩士中國醫藥學院
營養研究所
91
Vitamin D is one of the essential vitamins in the human diet and is important for normal growth and function. The recommended nutrition intake of vitamin D for an adult is 200 to 400 I.U. per day. Additional amounts of vitamin D do not confer benefits and may be toxic. However, a deficiency of this vitamin leads to inadequate absorption of calcium and phosphorus and faulty mineralization of bones and teeth. Fortified milk and milk products are major sourse of vitamin D3. Actual methods for determining vitamin D in milk are limited in term of sensitivity, rapidity and simplicity. The objective of this study was to develop a new strategy for detecting interaction between vitamin D and its polyclonal antibodies. Specific antibodies were raised in rabbits against vitamin D using the cationized bovine serum albumin (cBSA) that was reported to be a suitable carrier protein for vitamin D. Anti-vitamin D polyclonal antibodies were recovered from rabbits sera by sequential affinity chromatographies. Surface plasmon resonance (SPR) technology has been applied for analyzing of biomolecular interaction between antigen and antibody. In this study, we immobilized the anti-vitamin D polyclonal antibodies on the surface of CM5 chip and detected their interactions with vitamin D. Interaction between antigen and antibody was detected, and data collected were used to establish which were be used to vitamin D3 in food. SPR technology-based were developed to quantifity vitamin D extracted from milk. This method offers a great potential for further quantification of vitamin D in fortified milk or other dairy products.