Evaluation of Cardiometabolic Parameters among Obese Women Using Oral Contraceptives

BackgroundCombined oral contraceptive (COC) use has been associated with an unfavorable impact on carbohydrate and lipid metabolism in diverse populations of normal weight and obese women. The present study aimed to evaluate the cardiometabolic and inflammatory profiles of women in northeastern Brazil with respect to COC use and obesity.MethodsWe performed a cross-sectional study to verify cardiovascular parameters, including blood pressure (BP), fasting serum glucose, lipid, and inflammatory profile, in a population of women aged 15–45 years, considering obesity and COC use. Our sample consisted of 591 women, 481 women who were COC users, and 110 age-matched women who were COC non-users, classified as obese and non-obese according to BMI.ResultsCOC use and obesity were associated with increased systolic (p ≤ 0.001) and diastolic BP (p = 0.001), blood glucose (p ≤ 0.001), total cholesterol (p = 0.008), low-density lipoprotein cholesterol (p ≤ 0.001), very low-density lipoprotein cholesterol (p ≤ 0.001), triglycerides (p ≤ 0.001), ferritin (p = 0.006), C-reactive protein (CRP) (p ≤ 0.001), and nitric oxide metabolites (p ≤ 0.001), as well as decreased high-density lipoprotein cholesterol (HDL-c) (p ≤ 0.001) in comparison to controls. CRP and HDL-c levels in obese COC users were determined to be outside reference range values. The odds of having lower levels of HDL-c and elevated CRP increased among obese COC users. COC use was independently associated with low levels of HDL-c, especially second-generation progestins (p < 0.001; OR = 8.976; 95% CI 2.786–28.914).ConclusionObesity and COC use were associated with alterations in lipid and inflammatory cardiometabolic parameters, particularly increased CRP levels and decreased HDL-c, which are considered markers of cardiovascular disease (CVD) risk. Given the need to prevent unintended pregnancy among obese women, together with weight loss counseling, it is important to evaluate the most effective and safest contraceptive methods to avoid the potential risk of developing CVD

Age-Related Metabolic Pathways Changes in Dental Follicles: A Pilot Study

Aging is not a matter of choice; it is our fate. The “time-dependent functional decline that affects most living organisms” is coupled with several alterations in cellular processes, such as cell senescence, epigenetic alterations, genomic instability, stem cell exhaustion, among others. Age-related morphological changes in dental follicles have been investigated for decades, mainly motivated by the fact that cysts and tumors may arise in association with unerupted and/or impacted teeth. The more we understand the physiology of dental follicles, the more we are able to contextualize biological events that can be associated with the occurrence of odontogenic lesions, whose incidence increases with age. Thus, our objective was to assess age-related changes in metabolic pathways of dental follicles associated with unerupted/impacted mandibular third molars from young and adult individuals. For this purpose, a convenience sample of formalin-fixed paraffin-embedded (FFPE) dental follicles from young (<16 y.o., n = 13) and adult (>26 y.o., n = 7) individuals was selected. Samples were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS)-based untargeted metabolomics. Multivariate and univariate analyses were conducted, and the prediction of altered pathways was performed by mummichog and Gene Set Enrichment Analysis (GSEA) approaches. Dental follicles from young and older individuals showed differences in pathways related to C21-steroid hormone biosynthesis, bile acid biosynthesis, galactose metabolism, androgen and estrogen biosynthesis, starch and sucrose metabolism, and lipoate metabolism. We conclude that metabolic pathways differences related to aging were observed between dental follicles from young and adult individuals. Our findings support that similar to other human tissues, dental follicles associated with unerupted tooth show alterations at a metabolic level with aging, which can pave the way for further studies on oral pathology, oral biology, and physiology

Acidente Vascular Cerebral na Hemoglobinopatia SC (HBB glu6val e glu6lys): avaliação de marcadores de prognóstico

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2017-04-25T13:25:33Z No. of bitstreams: 1 Rayra Pereira Santiago Acidente vascular...2016.pdf: 4193213 bytes, checksum: 3e00fd40bbed978ab03470d2cfa4475e (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2017-04-25T16:39:34Z (GMT) No. of bitstreams: 1 Rayra Pereira Santiago Acidente vascular...2016.pdf: 4193213 bytes, checksum: 3e00fd40bbed978ab03470d2cfa4475e (MD5)Made available in DSpace on 2017-04-25T16:39:34Z (GMT). No. of bitstreams: 1 Rayra Pereira Santiago Acidente vascular...2016.pdf: 4193213 bytes, checksum: 3e00fd40bbed978ab03470d2cfa4475e (MD5)Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilO acidente vascular cerebral (AVC) é uma complicação clínica grave da doença falciforme (DF). Poucos estudos avaliaram a velocidade do fluxo sanguíneo cerebral utilizando o Doppler transcraniano (DTC) e marcadores preditores do AVC na hemoglobinopatia SC (HbSC) e, desta forma, as velocidades consideradas de risco para os indivíduos com esta hemoglobinopatia são baseadas em velocidades descritas para a anemia falciforme (AF) e para a Sβ talassemia (HbS/β). Assim, o objetivo do presente estudo foi identificar marcadores preditores do AVC em indivíduos com HbSC, estabelecendo subfenótipos da doença pela associação de biomarcadores genéticos, hematológicos, bioquímicos e imunológicos com o valor da velocidade do fluxo sanguíneo cerebral. Para tanto, foi realizado um estudo transversal, onde foram investigados 68 indivíduos com HbSC. A velocidade média máxima do fluxo sanguíneo cerebral nas artérias cerebral média, carótida anterior e cerebral anterior foi determinada utilizando o DTC. Os marcadores hematológicos, bioquímicos e imunológicos foram avaliados por métodos automatizados e os marcadores genéticos que pudessem estar relacionados ao AVC foram identificados pelas técnicas de reação em cadeia da polimerase e Restriction Fragment Length Polymorphism além da avaliação de polimorfismos de nucleotídeo único na plataforma Illumina. A velocidade média máxima observada nos indivíduos com HbSC apresentou correlação negativa com marcadores hematológicos (hemácias, hemoglobina, hematócrito) e bilirrubina direta e correlação positiva com monócitos e ferritina. Os indivíduos com velocidades do fluxo sanguíneo cerebral superiores a descrita por Deane e colaboradores (2008) apresentaram menores valores de Red Cell Distribution Width (RDW) e óxido nítrico (NO), já os indivíduos com velocidades do fluxo sanguíneo cerebral superiores a Vieira e colaboradores (em submissão) apresentaram níveis inferiores de hemoglobina e hematócrito e superiores de ferritina. Usando o percentil 75 da velocidade do fluxo sanguíneo cerebral foi possível verificar que os indivíduos com velocidades superiores a 125,75 cm/s possuíam valores diminuídos de hemoglobina, hematócrito, RDW e NO e valores aumentados de ferritina. O perfil genético indicou que o polimorfismo no gene da MTHFR C677T e o genótipo selvagem para a talassemia alfa -3,7kb exerciam um efeito protetor em relação ao AVC e, portanto, podem vir a ser utilizados como indicadores preditivos de AVC nos indivíduos com HbSC. A velocidade de 125,75 cm/s pode ser a mais adequada para se avaliar os indivíduos com HbSC, porém são necessários mais estudos para identificar a associação dessa velocidade com o risco de AVC. A avaliação dos dados de sequenciamento de nova geração em indivíduos com HbSC e com o perfil de DTC anormal vs normal permitiu identificar que os genes DOCK6 rs2278426, TYR rs1042602, CYP4F2 rs2108622, MST1 rs3197999, OR51B5/6 rs5006884, THADA rs7578597, FUT2 rs602662, MTHFR rs1801133, TSEN15 rs1046934, CFB rs12614 e ABCG5 rs6756629 podem ser preditores para a ocorrência do AVC. Os resultados deste trabalho sugerem que os indivíduos com HbSC e valor de DTC aumentados apresentam subfenótipo específico, caracterizado por um perfil hemolítico e inflamatório e com um perfil genético bem definido. Desse modo, sugerimos que a busca por marcadores preditores do AVC em indivíduos com HbSC é de grande relevância, uma vez que foi possível associar marcadores laboratoriais e genéticos com os resultados obtidos pelo DTCStroke is a serious clinical complication of sickle cell disease (SCD). Only few studies have evaluated the rate of cerebral blood flow by transcranial Doppler (TCD) and stroke predictor markers on hemoglobinopathy SC (HbSC), thus, velocity considered as risk for stroke that is used to diagnose HbSC individuals are based on velocities described for the sickle cell anemia (SCA) and Sβ thalassemia. The objective of this study was to identify predictors markers of stroke in individuals with HbSC, establishing subphenotypes disease by the association of genetic biomarkers, hematological, biochemical and immunological with the value of the velocity of cerebral blood flow. For that, we conducted a cross-sectional study, which were investigated 68 HbSC individuals. The average maximum rate of cerebral blood flow in the middle cerebral artery, anterior cerebral artery and anterior carotid artery was determined using the DTC. Hematological, biochemical and immunological markers were evaluated by automated methods and genetic markers that could be related to stroke were identified by polymerase chain reaction techniques and restriction fragment length polymorphism, in addition to the evaluation of single nucleotide polymorphisms was used the Illumina platform. The maximum average velocity observed in HbSC individuals, in turn, was negatively correlated with hematological markers (erythrocytes, hemoglobin, hematocrit) and direct bilirubin and positive correlation with monocytes and ferritin. Individuals with TCD velocities greater than what was described by Deane and colleagues (2008) showed lower RDW and nitric oxide, as individuals with higher TCD velocities than described by Vieira and colleagues (under submission) showed lower hemoglobin and hematocrit and higher ferritin levels. Using the 75th percentile of TCD velocity we have found that individuals with a velocities exceeding 125.75 cm / s have diminished values of hemoglobin, hematocrit, RDW and NO and ferritin increased values. The genetic profile indicated that the polymorphism in gene of MTHFR C677T and the absence of alpha thalassemia -3,7kb exert a protective effect in relation to stroke. We have found that the velocity of 125.75 cm/s was may be the most appropriate to evaluate individuals with HbSC, but more studies are needed to identify the association of this velocity with the risk of stroke. The evaluation of next-generation sequencing data in individuals with HbSC with abnormal TCD profile vs Normal identified that the DOCK6 rs2278426, TYR rs1042602, CYP4F2 rs2108622, MST1 rs3197999, OR51B5/6 rs5006884, THADA rs7578597, FUT2 rs602662, MTHFR rs1801133, TSEN15 rs1046934, CFB rs12614 and ABCG5 rs6756629 SNPs are predictors of stroke. These results suggest that individuals with HbSC and increased TCD value present specific sub-phenotype, characterized by hemolytic and inflammatory status and with a well-defined genetic profile. Thus, we suggest that the search for predictors markers for of stroke in individuals with HbSC is of great importance, since it was possible to associate laboratory and genetic markers with the results obtained from the TCD

Heme changes HIF-α, eNOS and nitrite production in HUVECs after simvastatin, HU, and ascorbic acid therapies

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-05-10T15:54:44Z No. of bitstreams: 1 Guarda CC Heme changes....pdf: 517853 bytes, checksum: 521387a5f13e3781b0af22ec40769e20 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-05-10T16:03:23Z (GMT) No. of bitstreams: 1 Guarda CC Heme changes....pdf: 517853 bytes, checksum: 521387a5f13e3781b0af22ec40769e20 (MD5)Made available in DSpace on 2016-05-10T16:03:23Z (GMT). No. of bitstreams: 1 Guarda CC Heme changes....pdf: 517853 bytes, checksum: 521387a5f13e3781b0af22ec40769e20 (MD5) Previous issue date: 2016Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, BrasilThe sickle cell disease (SCD) is a hemolytic genetic anemia characterized by free heme and hemoglobin release into intravascular spaces, with endothelial activation. Heme is a proinflammatory molecule able to directly activate vascular endothelium, thus, endothelial dysfunction and vascular disease are major chronic events described in SCD. The aim of this study was to evaluate the production of endothelial nitric oxide synthase (eNOS), nitrite and hypoxia inducible factor alpha (HIF-α) in HUVECs (human umbilical vein endothelial cells) activated by heme in response to simvastatin, hydroxyurea (HU), and ascorbic acid therapies. eNOS and HIF-α production were evaluated by ELISA and nitrite was measured by the Griess technique. The production of HIF-α increased when the cells were stimulated by heme (p b 0.01), while treatment with HU and simvastatin reduced the production (p b 0.01), and treatment with ascorbic acid increased HIF-1a production by the cells (p b 0.01). Hemeincreased eNOS production, (p b 0.01) but showed a heterogeneous pattern, and the lowest concentrations of all the treatments reduced the enzyme production (p b 0.01). The nitrite production by HUVECs was enhanced by stimulation with heme (p b 0.001) andwas reduced by treatment with HU (p b 0.001), ascorbic acid (p b 0.001) and simvastatin (p b 0.01). In summary, our results suggest that the hemolytic vascular microenvironment in SCD requires different therapeutic approaches to promote clinical improvement, and that a combination of therapies may be a viable strategy for treating patients

Evaluation of Alpha-1 Antitrypsin Levels and SERPINA1 Gene Polymorphisms in Sickle Cell Disease

Alpha-1 antitrypsin (AAT) is an inhibitor of neutrophil elastase and a member of the serine proteinase inhibitor (serpin) superfamily, and little is known about its activity in sickle cell disease (SCD). We hypothesize that AAT may undergo changes in SCD because of the high oxidative stress and inflammation associated with the disease. We have found high AAT levels in SCD patients compared to controls, while mutant genotypes of SERPINA1 gene had decreased AAT levels, in both groups. AAT showed negative correlation with red blood cells, hemoglobin (Hb), hematocrit, high-density lipoprotein cholesterol, urea, creatinine, and albumin and was positively correlated with mean corpuscular Hb concentration, white blood cells, neutrophils, Hb S, bilirubin, lactate dehydrogenase, ferritin, and C-reactive protein. Patients with higher levels of AAT had more infection episodes (OR = 1.71, CI: 1.05–2.65, p = 0.02), gallstones (OR = 1.75, CI: 1.03–2.97, p = 0.02), and had more blood transfusions (OR = 2.35, CI: 1.51–3.65, p = 0.0001). Our data on AAT association with laboratory indices of hemolysis and inflammation suggest that it may be positively associated with SCD severity; the negative correlations with renal parameters suggest a cytoprotective mechanism in SCD patients. In summary, AAT may need to be included in studies related to SCD and in the discussion of further therapeutic strategies

KRAS mutations in implant‐associated peripheral giant cell granuloma

Objectives: To investigate the molecular pathogenesis of implant‐associated peripheral giant cell granuloma (IA‐PGCG). Methods: A convenience sample of 15 IA‐PGCG cases was selected. Hotspot mutations of KRAS, FGFR1, and TRPV4 genes, previously reported in conventional giant cell lesions of the jaws, were investigated by Sanger sequencing. As these mutations could activate MAPK/ERK pathway, the expression of phospho‐ERK1/2 was also evaluated by immunohistochemistry. Results: KRAS mutations were detected in 8/15 (53.4%) samples. Similar to conventional peripheral giant cell granuloma, the KRAS mutations most frequently occurred in codon 146 (p.A146V, n = 3), followed by codon 12 (p.G12A and p.G12D, n = 1 each) and codon 14 (p.V14L, n = 1). Variants of unknown significance (VUS) were also detected in two cases, affecting codons 37 (p.E37K) and 127 (p.T127I). All samples showed wild‐type (WT) sequences for FGFR1 and TRPV4 genes. Consistent with MAPK/ERK pathway activation, all mononuclear cells of the lesion showed strong staining for phospho‐ERK1/2 protein in the immunohistochemical analysis. Conclusions: KRAS mutations and activation of the MAPK‐ERK signaling pathway occur in IA‐PGCG. This is the first study to demonstrate cancer‐associated gene mutations in a non‐neoplastic reactive condition associated with dental implants

Transcranial Doppler in hemoglobin SC disease

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2017-03-07T14:19:47Z No. of bitstreams: 1 Vieira C Transcranial doppler....pdf: 327081 bytes, checksum: ae2cda7bae0d51d9a701634aeec79d91 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2017-03-07T16:06:20Z (GMT) No. of bitstreams: 1 Vieira C Transcranial doppler....pdf: 327081 bytes, checksum: ae2cda7bae0d51d9a701634aeec79d91 (MD5)Made available in DSpace on 2017-03-07T16:06:20Z (GMT). No. of bitstreams: 1 Vieira C Transcranial doppler....pdf: 327081 bytes, checksum: ae2cda7bae0d51d9a701634aeec79d91 (MD5) Previous issue date: 2016Universidade Federal da Bahia. Hospital Universitário Professor Edgard Santos. Ambulatório Pediátrico de Doença Cerebrovascular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade Salvador. Salvador, BA, BrasilUniversidade Salvador. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, BrasilUniversidade Federal da Bahia. Hospital Universitário Professor Edgard Santos. Departamento de Hematologia. Salvador, BA, BrasilUniversidade Federal da Bahia. Hospital Universitário Professor Edgard Santos. Departamento de Hematologia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, BrasilStroke is a severe clinical disorder in sickle cell disease (SCD), and few studies have evaluated transcranial Doppler (TCD) flow velocities in hemoglobin SC disease (HbSC). The guidelines for stroke risk are based on evaluations in sickle cell anemia (SCA) or HbS/β thalassemia. Procedure: In this study, we compare cerebral blood flow in patients with SCD stratified by genotypes. A total of 1,664 pediatric patients with SCD underwent TCD velocity screening, and the time-averaged maximum mean velocity (TAMM) was determined in the middle cerebral artery (MCA), anterior cerebral artery (ACA), and distal intracranial internal carotid artery (ICA) . Results: Abnormal velocities were not identified in the ACA; therefore, we only use ICA and MCA velocities. TAMM from the left and right in the ICA andMCA was 134.3 ± 32.0 and 134.4 ± 32.6 cm/s in patients with SCA, and 105.2 ± 20.6 and 104.7 ± 20.0 cm/s in the patients with HbSC, respectively. Mean TAMM between right and left ICA/MCA was 134.5 ± 30.5 cm/s in the SCA group, and 104.9 ± 19.3 cm/s in the HbSC group.Notably, our data show that TCDvelocitieswere significantly lower among the patientswithHbSC compared to SCA. TAMMwas negatively correlated with hemoglobin and hematocrit in both genotypes. Conclusion: These results suggest that a different cut-off value for abnormal TCD velocities could be considered for patients with HbSC. Additional studies are warranted to determine the actual risk of stroke in HbSC genotype associated with this possible TCD risk value

Hydroxyurea in the management of sickle cell disease: pharmacogenomics and enzymatic metabolism

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-12-17T17:30:33Z No. of bitstreams: 1 Yahouedehou SCMA Hydroxyurea in the....pdf: 590783 bytes, checksum: bbd5c090cc7d875c0687cd3b8a0c0e4c (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-12-17T17:49:24Z (GMT) No. of bitstreams: 1 Yahouedehou SCMA Hydroxyurea in the....pdf: 590783 bytes, checksum: bbd5c090cc7d875c0687cd3b8a0c0e4c (MD5)Made available in DSpace on 2018-12-17T17:49:24Z (GMT). No. of bitstreams: 1 Yahouedehou SCMA Hydroxyurea in the....pdf: 590783 bytes, checksum: bbd5c090cc7d875c0687cd3b8a0c0e4c (MD5) Previous issue date: 2018Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemia. Departamento de Análises Clínicas. Salvador, BA, Brasil.Universidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemia. Departamento de Análises Clínicas. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemia. Departamento de Análises Clínicas. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemia. Departamento de Análises Clínicas. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemia. Departamento de Análises Clínicas. Salvador, BA, Brasil.Hydroxyurea (HU) was approved to be used in the treatment of sickle cell disease (SCD) because of its anti-sickling potential. However, there is variability in HU response among SCD patients and this can be due to physiological, socioeconomic, environmental, metabolic and/or genetic factors. The present review focuses on the latter two. Three quantitative trait loci, HBG2, BCL11A and HMIP, have been suggested as important markers for HU response. Other genes (ASS1, KLF10, HAO2, MAP3K5, PDE7B, TOX, NOS1, NOS2A, FLT1, ARG1, ARG2, UGT1A1, OR51B5/6, SIN3A, SALL2, SAR1A, UTB, OCTN1, CYP2C9, AQP9, MPO, CYP2E1, and GSTT1) have also been considered. Studies implicate catalase, urease, horseradish peroxidase and enzymes of CYP450 family in HU metabolism. However, little is known about these enzymes. Therefore, further studies are needed to elucidate the metabolic pathway of HU, which will facilitate pharmacogenomic studies and help in identification of candidate genes for predicting HU response

Association of homocysteine and inflammatory related molecules in sickle cell anemia

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-05-06T19:17:33Z No. of bitstreams: 1 Vilas-Boas W Association of....pdf: 614959 bytes, checksum: e67cd48c7a295b7265ee44271b784686 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-05-06T19:27:47Z (GMT) No. of bitstreams: 1 Vilas-Boas W Association of....pdf: 614959 bytes, checksum: e67cd48c7a295b7265ee44271b784686 (MD5)Made available in DSpace on 2016-05-06T19:27:47Z (GMT). No. of bitstreams: 1 Vilas-Boas W Association of....pdf: 614959 bytes, checksum: e67cd48c7a295b7265ee44271b784686 (MD5) Previous issue date: 2015Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade do Estado da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação de Hematologia e Hemoterapia da Bahia–Hemoba. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilObjective: Investigate the role of homocysteine (Hcy), Th17-related cytokines, and adhesion molecules in the inflammatory state seen in the sickle cell anemia (SCA). Methods: We studied the Hcy, interleukin (IL)-17, and transforming growth factor β (TGF-β) cytokine levels of 62 SCA patients, as well as the expression levels of inflammatory and endothelial activation markers. Results: We found significant associations between Hcy levels and increased expression of IL-17 and TGF-β among SCA patients, and a positive significant correlation between Hcy and soluble vascular cellular adhesion molecules (sVCAM). SCA individuals had raised IL-17 levels when compared with controls. Discussion: These results suggest a possible role of Hyc in the induction of TGF-β and IL-17. Other authors proposed that Hcy may contribute to the initiation and progression of vascular disease by monocyte activation, resulting in the secretion of cytokines that amplify the inflammatory response. The role of Hcy in cytokine production and oxidative stress in the endothelium may explain the increase of sVCAM expression and, the vascular activation currently described among the SCA individuals with the highest Hcy serum levels. The chronic inflammation was observed in hyperhomocysteinemic mice, with an increased expression of VCAM-1 and plasma levels of tumor necrosis factor-alpha, showing an association of this inflammatory molecule and vascular changes. Conclusion: Our findings suggest that the increased levels of IL-17,Hcy and sVCAM contributes contributes to the vascular inflammation and activation presented by SCA patients, which probably have an important role in vaso-occlusion. On the basis of the presented data, IL-17 and Hcy might be considered as important components in the pathogenesis of SCA

Sickle Cell Anemia Patients in Use of Hydroxyurea: Association between Polymorphisms in Genes Encoding Metabolizing Drug Enzymes and Laboratory Parameters

This study investigated associations between SNPs in genes encoding metabolizing drug enzymes and laboratory parameters in sickle cell anemia patients under hydroxyurea (SCA-HU+). We evaluated hematologic and biochemical parameters by electronic methods and SNPs by PCR-RFLP and multiplex PCR in 35 SCA-HU+ patients and 67 SCA-HU− patients. The HbS, total cholesterol, lactate dehydrogenase, aspartate aminotransferase, total bilirubin and fractions levels, and leukocyte, eosinophil, monocyte, and erythroblast counts were reduced in SCA-HU+ patients (p<0.05). Moreover, they presented higher HbF, C-reactive protein, and ferritin levels and elevated MCH and MCV values (p<0.05). Genotype frequencies of variants GA + AA of MPO −463G>A and c1c2 + c2c2 of CYP2E1 −1293G>C/−1053C>T were higher in SCA-HU+ patients (p<0.05). Independent associations were found between the variant A allele and lower total cholesterol, between c2 allele and low alpha-1 antitrypsin and between the null GSTT1 variant and high indirect and total bilirubin in SCA-HU+ patients. In SCA-HU− patients, independent associations were found between the variant A allele and high uric acid and between c2 allele and high urea. Our results suggest that SNPs MPO −463G>A, CYP2E1 −1293G>C/−1053C>T, and GSTT1 can be associated with alterations in lipid, inflammatory, renal, hemolytic, and hepatic profiles. However, further studies are needed to elucidate these associations