TEDE Coleção:http://bibliotecatede.uninove.br/handle/tede/332024-03-28T17:47:10Z2024-03-28T17:47:10ZAnálise da expressão gênica como parâmetro da eficácia terapêutica da levotiroxina em pacientes com hipotiroidismo primárioSilva, Valdelena Alessandra dahttp://bibliotecatede.uninove.br/handle/tede/30252022-08-01T14:35:03Z2016-12-12T00:00:00ZTítulo: Análise da expressão gênica como parâmetro da eficácia terapêutica da levotiroxina em pacientes com hipotiroidismo primário
Autor: Silva, Valdelena Alessandra da
Primeiro orientador: Camacho, Cléber Pinto
Abstract: Hypothyroidism is the inadequate production of thyroid hormone or the inappropriate action of thyroid hormone on target tissues. Among thyroid dysfunctions, hypothyroidism is the most common disorder in the general population, particularly in women. Levothyroxine sodium (L-T4) is considered the drug of choice and most effective as a replacement or supplementation treatment in patients with hypothyroidism worldwide. The aim of this study was to provide a panel of gene expression to mark the therapeutic response of levothyroxine in patients with primary hypothyroidism. We selected 4 control subjects and 8 subjects with levothyroxine therapy, 4 of whom were euthyroid with adequate treatment, with serum TSH between 0.4mIU/L and 4.0mIU/L, and 4 subclinical hypothyroidism with inadequate treatment with TSH Between 4.1mIU/L and 20.0mIU/L. Samples of 5mL of venous blood were collected and stored in PAXgene RNA tubes. RNA extraction was performed with the PAXgene RNA extraction kit (Qiagen). The transcriptome library was created on an NGS platform, Ion AmpliSeq Gene human transcriptome. Mann-Whitney was used to compare the two groups. Continuous variables are presented as median, minimum and maximum values, and Kruskal-Wallis was used to compare the three groups. Correlation between transcripts, TSH and Zulewski: Spearman's method. The data analyzed using IBM SPSS Statistics. The computational data analysis was performed in software RStudio, Package EdgeR v 3.12.0 of Bioconductor. Significant genes are calculated after a False Discovery Response (FDR) setting. A p<0.05 was considered significant. Differential expression analysis revealed 179 with increase and 174 with decrease in expression, being 289 mRNA and 64 non-coding RNA. Of these, 2 genes (CXCR6 and HTR4) showed an absolute value of the reads relatively high. We constructed a panel capable of identifying patients with an inadequate response to levothyroxine treatment. We identified transcripts that could compose a panel for the evaluation of gene expression, serving as biomarkers for the diagnosis of primary hypothyroidism, even in individuals with TSH concentrations close to the reference values. In addition to marking the response to the use of levothyroxine, CXCR6 and HTR4, they may be useful in evaluating the tissue repercussion of hypothyroidism.
Instituição: Universidade Nove de Julho
Tipo do documento: Dissertação2016-12-12T00:00:00ZEfeito da vitamina 25(OH) D sobre a expressão de receptor toll-like e mediadores inflamatórios em monócitos frente ao ambiente urêmicoBrito, Rodrigo Barbosa de Oliveirahttp://bibliotecatede.uninove.br/handle/tede/30242022-08-01T14:28:30Z2017-02-10T00:00:00ZTítulo: Efeito da vitamina 25(OH) D sobre a expressão de receptor toll-like e mediadores inflamatórios em monócitos frente ao ambiente urêmico
Autor: Brito, Rodrigo Barbosa de Oliveira
Primeiro orientador: Dalboni, Maria Aparecida
Abstract: The chronic kidney disease (CRD) is characterized by an inflammatory condition caused by the presence of uremic toxins in the patients plasma. This inflammatory state is associated with a high risk of cardiovascular diseases and infections. In CKD, there is a deficiency of vitamin 25 (OH) D, which has immunomodulatory properties, and the supplementation with it can decrease inflammation present in uremia.
The aim of this study was to evaluate the effect of 25 (OH) D on inflammatory pathways such as toll like receptor 4 (TRL4), oxidative stress (ROS) and expression of vitamin D receptor (VDR), 1-α hydroxylase, 24 hydroxylase And inflammatory mediators in monocytes in the uremic environment.
The human monocytes (U937 lineage) were treated with or without 25 (OH) D 50ng / ml for 24 hours, then they were incubated with 50% serum from healthy patients or uremic patient serum for 24 hours at 37 ° C and 5% CO2. Monocytes were characterized by the expression of CD14 +. TRL4, VDR, CYP24, Cyp27 and ROS were evaluated by flow cytometry. Cell culture supernatant ELISA was performed for IL-6, TNF-α, IL-10, catatelicidin, MCP-1 and NF-KB.
We observed a high expression of TRL-4, IL-6, TNF-α, IL-10, cathelicidin and MCP-1 in monocytes incubated with uremic serum, compared when incubated with healthy serum. Treatment with 25 (OH) D was able to reduce the expression of TRL4, cathelicidin and MCP-1 against the uremic environment. There was no difference in the expression of VDR, CYP27 and CYP24 enzymes and NF-KB.
We conclude that the uremic environment induces inflammation, increasing TRL4 and inflammatory mediators, treatment with vitamin D induces an improvement in the inflammatory parameters, resulting in less inflammation in the uremic environment.
Instituição: Universidade Nove de Julho
Tipo do documento: Dissertação2017-02-10T00:00:00ZPainel de expressão gênica como biomarcador no hipotiroidismo por transcriptoma RNA-seq em indivíduos com hipotiroidismo primárioAlmeida, Robson José dehttp://bibliotecatede.uninove.br/handle/tede/30232022-08-01T14:14:11Z2016-06-14T00:00:00ZTítulo: Painel de expressão gênica como biomarcador no hipotiroidismo por transcriptoma RNA-seq em indivíduos com hipotiroidismo primário
Autor: Almeida, Robson José de
Primeiro orientador: Camacho, Cléber Pinto
Abstract: The thyroid hormone (TH), modulates directly and indirectly the primary physiological processes for the development and maintenance of the human body. The neuroendocrine activity provides an integration of complex functions of tissues, generating coordinates answers the specific needs of the body. The hypothalamus, pituitary, thyroid is the classic example of the neuroendocrine control. Hypothyroidism is defined by the thyroid gland unable to produce HT sufficient to meet the metabolic needs of the body. The plasma determination of thyroid stimulating hormone (TSH) is the first test performed on suspicion of primary hypothyroidism. The accuracy of diagnosis of TSH for Hypothyroidism detection still has limitations. Currently the specific molecular diagnostics for thyroid diseases are mostly made for thyroid carcinomas. RNA-Seq (ribonucleic acid sequencing) is currently built by technology called NGS (next generation sequencers) and performs all of the transcripts profile massively. TSH levels and free T4 set to most individuals in euthyroid may not reflect the proper amounts of hormone for the proper functioning of all tissues. The objective of this study was to identify the pattern of gene expression in peripheral blood of patients with hypothyroidism and find a gene or a panel of genes able to differentiate eutiroidianos individuals from patients with primary hypothyroidism. We have identified 5 genes (CCNJL, IMPA2, FAM129B, SLC4A11 and CDK18) that may be useful to form a panel of biomarkers for the ability to differentiate euthyroid primary hypothyroidism and also correlate them with the serum levels of TSH.
Instituição: Universidade Nove de Julho
Tipo do documento: Dissertação2016-06-14T00:00:00ZAnálise das Indicações para uso do contraste paramagnético hepatoespecífico (Gd-EOD-DTPA)Oriani, Patricia Pavesihttp://bibliotecatede.uninove.br/handle/tede/30222022-08-01T14:06:38Z2016-12-16T00:00:00ZTítulo: Análise das Indicações para uso do contraste paramagnético hepatoespecífico (Gd-EOD-DTPA)
Autor: Oriani, Patricia Pavesi
Primeiro orientador: Chojniak, Rubens
Abstract: The usual imaging diagnostic methods for the evaluation of liver difuse and focal lesions are ultrasonography (USG), computed tomography (CT) and nuclear magnetic resonance (MR). MR using gadoxic acid contrast (Gd-EOB-DTPA) is indicated for the detection and morphological characterization of hepatic lesions and may also be useful for assessing the biliary tree as well as liver function. Therefore, it can be very useful in guiding medical decisions, both surgical and clinical.
Gd-EOB-DTPA is the hepatospecific contrast recently released for clinical use in Brazil. It is a contrast medium introduced mainly in specialized centers in 2013 as in the AC Camargo Cancer Center and so far, there are very few studies in our environment, but It has been used in other countries, like Japan, USA and countries of the European Union. The differential of this contrast lies in its excretion mechanism. Approximately 50% of it is made for bile ducts and hepatic sinusoids, and the remainder through the kidneys. When used in MR studies it is performed in arterial, portal, late phases and a hepatospecific phase twenty minutes after intravenous administration.
This study aimed to evaluate the extent of utilization of Gd-EOB-DTPA in the clinical practice in a Brazilian cancer center. This is a retrospective study, approved by the institution's Ethics and Research Committee, conducted through the review of medical records and reports. All MR scans utilizing hepatospecific contrast from November 2013 to July 2015 (n = 131) were analyzed.
The mean age of the patients was 41.5 years, ranging from 13 to 90 years. Most studies 98 (74.8%) were performed in female patients. Family history of cancer was present in 29 (22.1%) patients, a history of neoplasia was present in 45 (34.3%) patients and 21 (16.0%) patients presented with chronic liver disease. In 127 (96.9%) patients. The most common indications for the use of Gd-EOD-DTPA contrast were undetermined nodules 56 (42.7%), adenoma versus FNH 43 (32.8%), detection of hepatic metastasis foci 13 (9.9%), Staging of CHC 10 (7.6%), bile duct 01 (0.8%) and other indications 08 (6.1%). The behavior of the lesion was evaluated after administration of hepatospecific intravenous contrast. We observed in this study a high number of exams indicated for the evaluation of focal liver lesions without the clear definition of the diagnostic suspicion 56 (42.7%). Regarding focal lesion vascularity most lesions 43 (79.7%) were hypervascular, and the examination contributed for clinical management in most of them 25 (58.1%). In the hypovascular nodules, the contribution rate was lower 03 (27.2%).
For all the classic indications we identified a high rate of exams that contributed to clinical decision making 41 (63.1%).
Patients with an indication for the examination are mostly young adult women, who do not have chronic liver disease and do not have an oncologic history.
The impact of the examination on clinical decision-making was greater when the indication was considered classical or for hypervascular focal liver lesions.
Instituição: Universidade Nove de Julho
Tipo do documento: Dissertação2016-12-16T00:00:00Z